Drug-induced dedifferentiation towards drug-tolerant persister states is a common mechanism cancer cells exploit to escape therapies, hindering durable responses. How early epigenomic and transcriptomic programs coordinate to initiate these reversible transitions remains largely unexplored. Here we employ high-temporal-resolution multi-omics profiling, information-theoretic approaches, and dynamic system modeling to probe these processes in BRAF-mutant melanoma models and patient specimens. We uncover a hysteretic transition trajectory in response to oncogene inhibition and subsequent release, driven by two tightly coupled transcriptional waves that orchestrate genome-scale chromatin reconfiguration. Modeling of these waves suggests NF-κB/RelA-driven chromatin remodeling as the underlying mechanism of cell-state dedifferentiation, which we validate experimentally. We identify RelA-target genes epigenetically modulated to drive this process and define a quantitative epigenome gauge of melanoma cell-state plasticity that supports targeting epigenetic machineries to potentiate oncogene inhibition. Across additional cancer models, oxidative stress-mediated NF-κB/RelA activation emerges as a common driver of transitions into drug-tolerant persister states, revealing a central role for NF-κB axis in coupling oxidative stress to cancer progression.
", "doi": "10.1038/s41467-026-71349-4", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2026-04-15", "volume": "17", "pages": "3228" }, { "id": "authors:6eyk1-dkn47", "collection": "authors", "collection_id": "6eyk1-dkn47", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230530-441187700.12", "type": "article", "title": "Stereochemical engineering yields a multifunctional peptide macrocycle inhibitor of Akt2 by fine-tuning macrocycle-cell membrane interactions", "author": [ { "family_name": "Nag", "given_name": "Arundhati", "orcid": "0000-0002-1328-1695", "clpid": "Nag-Arundhati" }, { "family_name": "Mafi", "given_name": "Amirhossein", "orcid": "0000-0002-8366-6785", "clpid": "Mafi-Amirhossein" }, { "family_name": "Das", "given_name": "Samir", "clpid": "Das-Samir" }, { "family_name": "Yu", "given_name": "Mary Beth", "clpid": "Yu-Mary-Beth" }, { "family_name": "Alvarez-Villalonga", "given_name": "Belen", "clpid": "Alvarez-Villalonga-Belen" }, { "family_name": "Kim", "given_name": "Soo-Kyung", "orcid": "0000-0002-4498-5441", "clpid": "Kim-Soo-Kyung" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Macrocycle peptides are promising constructs for imaging and inhibiting extracellular, and cell membrane proteins, but their use for targeting intracellular proteins is typically limited by poor cell penetration. We report the development of a cell-penetrant high-affinity peptide ligand targeted to the phosphorylated Ser474 epitope of the (active) Akt2 kinase. This peptide can function as an allosteric inhibitor, an immunoprecipitation reagent, and a live cell immunohistochemical staining reagent. Two cell penetrant stereoisomers were prepared and shown to exhibit similar target binding affinities and hydrophobic character but 2-3-fold different rates of cell penetration. Experimental and computational studies resolved that the ligands' difference in cell penetration could be assigned to their differential interactions with cholesterol in the membrane. These results expand the tool kit for designing new chiral-based cell-penetrant ligands.", "doi": "10.1038/s42004-023-00890-w", "pmcid": "PMC10195864", "issn": "2399-3669", "publisher": "Nature Publishing Group", "publication": "Communications Chemistry", "publication_date": "2023-05-18", "volume": "6", "pages": "Art. No. 95" }, { "id": "authors:fwdsd-77w44", "collection": "authors", "collection_id": "fwdsd-77w44", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230612-735507000.34", "type": "article", "title": "Large libraries of single-chain trimer peptide-MHCs enable antigen-specific CD8+ T cell discovery and analysis", "author": [ { "family_name": "Chour", "given_name": "William", "orcid": "0000-0003-1817-0123", "clpid": "Chour-William" }, { "family_name": "Choi", "given_name": "Jongchan", "orcid": "0000-0003-0394-9978", "clpid": "Choi-Jongchan" }, { "family_name": "Xie", "given_name": "Jingyi", "orcid": "0000-0002-8959-4268", "clpid": "Xie-Jingyi" }, { "family_name": "Chaffee", "given_name": "Mary E.", "orcid": "0000-0003-4903-0377", "clpid": "Chaffee-Mary-E" }, { "family_name": "Schmitt", "given_name": "Thomas M.", "orcid": "0000-0002-0736-4195", "clpid": "Schmitt-Thomas-M" }, { "family_name": "Finton", "given_name": "Kathryn", "orcid": "0000-0001-9673-9042", "clpid": "Finton-Kathryn" }, { "family_name": "DeLucia", "given_name": "Diana C.", "orcid": "0000-0002-1165-6799", "clpid": "DeLucia-Diana-C" }, { "family_name": "Xu", "given_name": "Alexander M.", "orcid": "0000-0003-4877-4358", "clpid": "Xu-Alexander-M" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Chen", "given_name": "Daniel G.", "orcid": "0000-0001-6660-6257", "clpid": "Chen-Daniel-G" }, { "family_name": "Zhang", "given_name": "Rongyu", "clpid": "Zhang-Rongyu" }, { "family_name": "Yuan", "given_name": "Dan", "orcid": "0000-0001-9651-8020", "clpid": "Yuan-Dan" }, { "family_name": "Hong", "given_name": "Sunga", "orcid": "0000-0003-4412-2811", "clpid": "Hong-Sunga" }, { "family_name": "Ng", "given_name": "Alphonsus H. C.", "orcid": "0000-0003-0074-4598", "clpid": "Ng-Alphonsus-H-C" }, { "family_name": "Butler", "given_name": "Jonah Z.", "orcid": "0000-0002-8694-7590", "clpid": "Butler-Jonah-Z" }, { "family_name": "Edmark", "given_name": "Rick A.", "orcid": "0000-0002-8228-8874", "clpid": "Edmark-Rick-A" }, { "family_name": "Jones", "given_name": "Lesley C.", "clpid": "Jones-Lesley-C" }, { "family_name": "Murray", "given_name": "Kim M.", "clpid": "Murray-Kim-M" }, { "family_name": "Peng", "given_name": "Songming", "orcid": "0000-0002-2742-6584", "clpid": "Peng-Songming" }, { "family_name": "Li", "given_name": "Guideng", "orcid": "0000-0003-0840-7262", "clpid": "Li-Guideng" }, { "family_name": "Strong", "given_name": "Roland K.", "orcid": "0000-0002-1338-2189", "clpid": "Strong-Roland-K" }, { "family_name": "Lee", "given_name": "John K.", "orcid": "0000-0002-6570-2180", "clpid": "Lee-John-K" }, { "family_name": "Goldman", "given_name": "Jason D.", "orcid": "0000-0002-3825-6832", "clpid": "Goldman-Jason-D" }, { "family_name": "Greenberg", "given_name": "Philip D.", "orcid": "0000-0003-3812-647X", "clpid": "Greenberg-Philip-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The discovery and characterization of antigen-specific CD8+ T cell clonotypes typically involves the labor-intensive synthesis and construction of peptide-MHC tetramers. We adapt single-chain trimer (SCT) technologies into a high throughput platform for pMHC library generation, showing that hundreds can be rapidly prepared across multiple Class I HLA alleles. We use this platform to explore the impact of peptide and SCT template mutations on protein expression yield, thermal stability, and functionality. SCT libraries were an efficient tool for identifying T cells recognizing commonly reported viral epitopes. We then construct SCT libraries to capture SARS-CoV-2 specific CD8+ T cells from COVID-19 participants and healthy donors. The immunogenicity of these epitopes is validated by functional assays of T cells with cloned TCRs captured using SCT libraries. These technologies should enable the rapid analyses of peptide-based T cell responses across several contexts, including autoimmunity, cancer, or infectious disease.", "doi": "10.1038/s42003-023-04899-8", "pmcid": "PMC10186326", "issn": "2399-3642", "publisher": "Nature Publishing Group", "publication": "Communications Biology", "publication_date": "2023-05-16", "volume": "6", "pages": "Art. No. 528" }, { "id": "authors:j7ycg-zzf59", "collection": "authors", "collection_id": "j7ycg-zzf59", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230530-441187700.19", "type": "article", "title": "Entropic analysis of antigen-specific CDR3 domains identifies essential binding motifs shared by CDR3s with different antigen specificities", "author": [ { "family_name": "Xu", "given_name": "Alexander M.", "orcid": "0000-0003-4877-4358", "clpid": "Xu-Alexander-M" }, { "family_name": "Chour", "given_name": "William", "orcid": "0000-0003-1817-0123", "clpid": "Chour-William" }, { "family_name": "DeLucia", "given_name": "Diana C.", "orcid": "0000-0002-1165-6799", "clpid": "DeLucia-Diana-C" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Pavlovitch-Bedzyk", "given_name": "Ana Jimena", "orcid": "0000-0003-1021-3635", "clpid": "Pavlovitch-Bedzyk-Ana-Jimena" }, { "family_name": "Ng", "given_name": "Rachel", "orcid": "0000-0003-3692-8524", "clpid": "Ng-Rachel-H" }, { "family_name": "Rasheed", "given_name": "Yusuf", "clpid": "Rasheed-Yusuf" }, { "family_name": "Davis", "given_name": "Mark M.", "orcid": "0000-0001-6868-657X", "clpid": "Davis-Mark-M" }, { "family_name": "Lee", "given_name": "John K.", "orcid": "0000-0003-4077-0395", "clpid": "Lee-John-K" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Antigen-specific T cell receptor (TCR) sequences can have prognostic, predictive, and therapeutic value, but decoding the specificity of TCR recognition remains challenging. Unlike DNA strands that base pair, TCRs bind to their targets with different orientations and different lengths, which complicates comparisons. We present scanning parametrized by normalized TCR length (SPAN-TCR) to analyze antigen-specific TCR CDR3 sequences and identify patterns driving TCR-pMHC specificity. Using entropic analysis, SPAN-TCR identifies 2-mer motifs that decrease the diversity (entropy) of CDR3s. These motifs are the most common patterns that can predict CDR3 composition, and we identify \"essential\" motifs that decrease entropy in the same CDR3 \u03b1 or \u03b2 chain containing the 2-mer, and \"super-essential\" motifs that decrease entropy in both chains. Molecular dynamics analysis further suggests that these motifs may play important roles in binding. We then employ SPAN-TCR to resolve similarities in TCR repertoires against different antigens using public databases of TCR sequences.", "doi": "10.1016/j.cels.2023.03.001", "pmcid": "PMC10355346", "issn": "2405-4712", "publisher": "Cell Press", "publication": "Cell Systems", "publication_date": "2023-04-19", "series_number": "4", "volume": "14", "issue": "4", "pages": "273-284" }, { "id": "authors:3x1g7-ce439", "collection": "authors", "collection_id": "3x1g7-ce439", "cite_using_url": "https://authors.library.caltech.edu/records/3x1g7-ce439", "type": "article", "title": "Non-viral precision T\u2009cell receptor replacement for personalized cell therapy", "author": [ { "family_name": "Foy", "given_name": "Susan P." }, { "family_name": "Jacoby", "given_name": "Kyle" }, { "family_name": "Bota", "given_name": "Daniela A.", "orcid": "0000-0002-9680-9060" }, { "family_name": "Hunter", "given_name": "Theresa", "orcid": "0000-0002-6494-1294" }, { "family_name": "Pan", "given_name": "Zheng" }, { "family_name": "Stawiski", "given_name": "Eric" }, { "family_name": "Ma", "given_name": "Yan" }, { "family_name": "Lu", "given_name": "William" }, { "family_name": "Peng", "given_name": "Songming" }, { "family_name": "Wang", "given_name": "Clifford L." }, { "family_name": "Yuen", "given_name": "Benjamin" }, { "family_name": "Dalmas", "given_name": "Olivier" }, { "family_name": "Heeringa", "given_name": "Katharine" }, { "family_name": "Sennino", "given_name": "Barbara" }, { "family_name": "Conroy", "given_name": "Andy" }, { "family_name": "Bethune", "given_name": "Michael T." }, { "family_name": "Mende", "given_name": "Ines" }, { "family_name": "White", "given_name": "William" }, { "family_name": "Kukreja", "given_name": "Monica" }, { "family_name": "Gunturu", "given_name": "Swetha" }, { "family_name": "Humphrey", "given_name": "Emily" }, { "family_name": "Hussaini", "given_name": "Adeel" }, { "family_name": "An", "given_name": "Duo" }, { "family_name": "Litterman", "given_name": "Adam J." }, { "family_name": "Quach", "given_name": "Boi Bryant" }, { "family_name": "Ng", "given_name": "Alphonsus H. C.", "orcid": "0000-0003-0074-4598" }, { "family_name": "Lu", "given_name": "Yue", "orcid": "0000-0001-9036-2803" }, { "family_name": "Smith", "given_name": "Chad" }, { "family_name": "Campbell", "given_name": "Katie M.", "orcid": "0000-0001-6491-4432" }, { "family_name": "Anaya", "given_name": "Daniel" }, { "family_name": "Skrdlant", "given_name": "Lindsey" }, { "family_name": "Huang", "given_name": "Eva Yi-Hsuan" }, { "family_name": "Mendoza", "given_name": "Ventura" }, { "family_name": "Mathur", "given_name": "Jyoti" }, { "family_name": "Dengler", "given_name": "Luke" }, { "family_name": "Purandare", "given_name": "Bhamini" }, { "family_name": "Moot", "given_name": "Robert" }, { "family_name": "Yi", "given_name": "Michael C." }, { "family_name": "Funke", "given_name": "Roel" }, { "family_name": "Sibley", "given_name": "Alison" }, { "family_name": "Stallings-Schmitt", "given_name": "Todd" }, { "family_name": "Oh", "given_name": "David Y." }, { "family_name": "Chmielowski", "given_name": "Bartosz", "orcid": "0000-0002-2374-3320" }, { "family_name": "Abedi", "given_name": "Mehrdad", "orcid": "0000-0003-4640-0977" }, { "family_name": "Yuan", "given_name": "Yuan", "orcid": "0000-0001-7440-8939" }, { "family_name": "Sosman", "given_name": "Jeffrey A." }, { "family_name": "Lee", "given_name": "Sylvia M.", "orcid": "0000-0002-7425-2230" }, { "family_name": "Schoenfeld", "given_name": "Adam J.", "orcid": "0000-0002-2644-1416" }, { "family_name": "Baltimore", "given_name": "David L.", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Franzusoff", "given_name": "Alex" }, { "family_name": "Ribas", "given_name": "Antoni", "orcid": "0000-0003-3669-8458" }, { "family_name": "Rao", "given_name": "Arati V." }, { "family_name": "Mandl", "given_name": "Stefanie J." } ], "abstract": "T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1,2,3. Here we developed a clinical-grade approach based on CRISPR–Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRβ). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen–HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.
", "doi": "10.1038/s41586-022-05531-1", "issn": "0028-0836", "publisher": "Nature Publishing Group", "publication": "Nature", "publication_date": "2023-03-23", "series_number": "7953", "volume": "615", "issue": "7953", "pages": "687-696" }, { "id": "authors:3nnxh-bh852", "collection": "authors", "collection_id": "3nnxh-bh852", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211210-240628000", "type": "article", "title": "HLA-A\u221702:01 restricted T cell receptors against the highly conserved SARS-CoV-2 polymerase cross-react with human coronaviruses", "author": [ { "family_name": "Nesterenko", "given_name": "Pavlo A.", "orcid": "0000-0001-9841-8170", "clpid": "Nesterenko-Pavlo-A" }, { "family_name": "McLaughlin", "given_name": "Jami", "clpid": "McLaughlin-Jami" }, { "family_name": "Tsai", "given_name": "Brandon L.", "orcid": "0000-0002-7372-3504", "clpid": "Tsai-Brandon-L" }, { "family_name": "Burton Sojo", "given_name": "Giselle", "clpid": "Burton-Sojo-Giselle" }, { "family_name": "Cheng", "given_name": "Donghui", "clpid": "Cheng-Donghui" }, { "family_name": "Zhao", "given_name": "Daniel", "orcid": "0000-0001-7779-5452", "clpid": "Zhao-Daniel" }, { "family_name": "Mao", "given_name": "Zhiyuan", "orcid": "0000-0002-5536-4691", "clpid": "Mao-Zhiyuan" }, { "family_name": "Bangayan", "given_name": "Nathanael J.", "clpid": "Bangayan-Nathanael-J" }, { "family_name": "Obusan", "given_name": "Matthew B.", "orcid": "0000-0002-9579-2308", "clpid": "Obusan-Matthew-B" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Ng", "given_name": "Rachel H.", "orcid": "0000-0003-3692-8524", "clpid": "Ng-Rachel-H" }, { "family_name": "Chour", "given_name": "William", "orcid": "0000-0003-1817-0123", "clpid": "Chour-William" }, { "family_name": "Xie", "given_name": "Jingyi", "clpid": "Xie-Jingyi" }, { "family_name": "Li", "given_name": "Yan-Ruide", "clpid": "Li-Yan-Ruide" }, { "family_name": "Lee", "given_name": "Derek", "clpid": "Lee-Derek" }, { "family_name": "Noguchi", "given_name": "Miyako", "orcid": "0000-0003-0909-7358", "clpid": "Noguchi-Miyako" }, { "family_name": "Carmona", "given_name": "Camille", "orcid": "0000-0001-7040-5773", "clpid": "Carmona-Camille" }, { "family_name": "Phillips", "given_name": "John W.", "clpid": "Phillips-John-W" }, { "family_name": "Kim", "given_name": "Jocelyn T.", "orcid": "0000-0001-8723-8190", "clpid": "Kim-Jocelyn-T" }, { "family_name": "Yang", "given_name": "Lili", "clpid": "Yang-Lili" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Boutros", "given_name": "Paul C.", "orcid": "0000-0003-0553-7520", "clpid": "Boutros-Paul-C" }, { "family_name": "Witte", "given_name": "Owen N.", "orcid": "0000-0003-4461-4533", "clpid": "Witte-Owen-N" } ], "abstract": "Cross-reactivity and direct killing of target cells remain underexplored for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific CD8\u207a T cells. Isolation of T cell receptors (TCRs) and overexpression in allogeneic cells allows for extensive T cell reactivity profiling. We identify SARS-CoV-2 RNA-dependent RNA polymerase (RdRp/NSP12) as highly conserved, likely due to its critical role in the virus life cycle. We perform single-cell TCR\u03b1\u03b2 sequencing in human leukocyte antigen (HLA)-A\u221702:01-restricted, RdRp-specific T cells from SARS-CoV-2-unexposed individuals. Human T cells expressing these TCR\u03b1\u03b2 constructs kill target cell lines engineered to express full-length RdRp. Three TCR constructs recognize homologous epitopes from common cold coronaviruses, indicating CD8\u207a T cells can recognize evolutionarily diverse coronaviruses. Analysis of individual TCR clones may help define vaccine epitopes that can induce long-term immunity against SARS-CoV-2 and other coronaviruses.", "doi": "10.1016/j.celrep.2021.110167", "pmcid": "PMC8660260", "issn": "2211-1247", "publisher": "Cell Press", "publication": "Cell Reports", "publication_date": "2021-12-28", "series_number": "13", "volume": "37", "issue": "13", "pages": "Art. No. 110167" }, { "id": "authors:p1a52-w7j03", "collection": "authors", "collection_id": "p1a52-w7j03", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211209-231124000", "type": "monograph", "title": "Stereochemical engineering of a peptide macrocycle allosteric inhibitor of phospho-Akt2 controls cell penetration by fine-tuning macrocycle-cell membrane interactions", "author": [ { "family_name": "Nag", "given_name": "Arundhati", "orcid": "0000-0002-1328-1695", "clpid": "Nag-Arundhati" }, { "family_name": "Mafi", "given_name": "Amirhossein", "orcid": "0000-0002-8366-6785", "clpid": "Mafi-Amirhossein" }, { "family_name": "Das", "given_name": "Samir", "clpid": "Das-Samir" }, { "family_name": "Yu", "given_name": "Mary Beth", "clpid": "Yu-Mary-Beth" }, { "family_name": "Alvarez-Villalonga", "given_name": "Belen", "clpid": "Alvarez-Villalonga-Belen" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report the development of a cell-penetrant cyclic loop biligand that selectively binds, in vitro, to the phosphorylated Ser474 site of Protein Kinase B (p-Akt2) with high affinity (K_D = 10 nM). The cyclic loop biligand consists of a linear peptide joined to a macrocycle peptide through triazole linkage, and it was isolated through two iterative in situ screens. This biligand allosterically inhibited kinase activity of Akt2 but it was cell-impermeable, as isolated from the screening process. Since Akt2 is an oncoprotein hyperactivated via phosphorylation at Ser474 in cancers, we sought to visualize p-Akt2 in live cancer cells using the developed biligand. To this end, we matured this biligand into a cell-penetrant reagent through systematic iterations of its chemical structure to promote cell-penetrating properties, while retaining its binding and inhibition for p-Akt2. Two retro-inverso, N-methylated versions of the macrocyclic ligand were developed which were uptaken by live cancer cells, while retaining their high affinities for pAkt2. Interestingly, the stereochemistry of two amino acid residues in the cell-penetrant ligands exhibited strong influence on their extent of cell penetration. This phenomenon of difference in cell penetration was explored through metadynamics simulations of each ligand in the cell membrane. It was found that the ligand uptaken to a greater extent by cells had more intramolecular interactions with itself and had fewer cholesterol molecules associated with it, which aided in its cell-penetration.", "doi": "10.26434/chemrxiv-2021-kldh7", "publication_date": "2021-11-24" }, { "id": "authors:92btd-ccb84", "collection": "authors", "collection_id": "92btd-ccb84", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210714-152527909", "type": "article", "title": "Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection", "author": [ { "family_name": "Jiang", "given_name": "Yonghou", "clpid": "Jiang-Yonghou" }, { "family_name": "Duffy", "given_name": "Fergal", "orcid": "0000-0002-4675-0937", "clpid": "Duffy-Fergal" }, { "family_name": "Hadlock", "given_name": "Jennifer", "orcid": "0000-0001-6103-7606", "clpid": "Hadlock-Jennifer" }, { "family_name": "Raappana", "given_name": "Andrew", "orcid": "0000-0001-5248-4172", "clpid": "Raappana-Andrew" }, { "family_name": "Styrchak", "given_name": "Sheila", "clpid": "Styrchak-Sheila" }, { "family_name": "Beck", "given_name": "Ingrid", "orcid": "0000-0001-7438-3209", "clpid": "Beck-Ingrid" }, { "family_name": "Mast", "given_name": "Fred D.", "orcid": "0000-0002-2177-6647", "clpid": "Mast-Fred-D" }, { "family_name": "Miller", "given_name": "Leslie R.", "clpid": "Miller-Leslie-R" }, { "family_name": "Chour", "given_name": "William", "orcid": "0000-0003-1817-0123", "clpid": "Chour-William" }, { "family_name": "Houck", "given_name": "John", "clpid": "Houck-John" }, { "family_name": "Armistead", "given_name": "Blair", "orcid": "0000-0001-9902-3955", "clpid": "Armistead-Blair" }, { "family_name": "Duvvuri", "given_name": "Venkata R.", "orcid": "0000-0001-7356-338X", "clpid": "Duvvuri-Venkata-R" }, { "family_name": "Yeung", "given_name": "Winnie", "orcid": "0000-0001-8083-7449", "clpid": "Yeung-Winnie" }, { "family_name": "Haglund", "given_name": "Micaela", "clpid": "Haglund-Micaela" }, { "family_name": "Wallner", "given_name": "Jackson", "clpid": "Wallner-Jackson" }, { "family_name": "Wallick", "given_name": "Julie A.", "orcid": "0000-0002-4568-4704", "clpid": "Wallick-Julie-A" }, { "family_name": "Hardy", "given_name": "Samantha", "clpid": "Hardy-Samantha" }, { "family_name": "Oldroyd", "given_name": "Alyssa", "clpid": "Oldroyd-Alyssa" }, { "family_name": "Ko", "given_name": "Daisy", "clpid": "Ko-Daisy" }, { "family_name": "Gervassi", "given_name": "Ana", "orcid": "0000-0003-0321-5632", "clpid": "Gervassi-Ana-L" }, { "family_name": "Murray", "given_name": "Kim M.", "clpid": "Murray-Kim-M" }, { "family_name": "Kaplan", "given_name": "Henry", "orcid": "0000-0001-9866-5200", "clpid": "Kaplan-Henry" }, { "family_name": "Aitchison", "given_name": "John D.", "orcid": "0000-0002-9153-6497", "clpid": "Aitchison-John-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Sather", "given_name": "D. Noah", "orcid": "0000-0002-9128-172X", "clpid": "Sather-D-Noah" }, { "family_name": "Goldman", "given_name": "Jason D.", "orcid": "0000-0002-3825-6832", "clpid": "Goldman-Jason-D" }, { "family_name": "Frenkel", "given_name": "Lisa", "orcid": "0000-0001-9566-8959", "clpid": "Frenkel-Lisa" }, { "family_name": "Harrington", "given_name": "Whitney E.", "orcid": "0000-0002-0121-978X", "clpid": "Harrington-Whitney-E" } ], "abstract": "Background: Coronavirus disease 2019 (COVID-19) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor (AT1R-Ab). \n\nMethods: We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or severe disease to age and sex matched negative controls utilizing multivariate logistic and quantile regression adjusted for comorbidities including hypertension, diabetes, and heart disease. \n\nResults: There were trends toward increased prevalence (50% vs. 33%, p = 0.1) and level of AT1R-Ab (median 9.8 vs. 6.1 U/mL, p = 0.06) in all cases versus controls. When considered by COVID-19 disease severity, there was a trend toward increased prevalence of AT1R-Ab (55% vs. 31%, p = 0.07), as well as significantly higher AT1R-Ab levels (median 10.7 vs. 5.9 U/mL, p = 0.03) amongst individuals with mild COVID-19 versus matched controls. In contrast, the prevalence (42% vs. 37%, p = 0.9) and level (both medians 6.7 U/mL, p = 0.9) of AT1R-Ab amongst those with severe COVID-19 did not differ from matched controls. \n\nConclusions: These findings support an association between COVID-19 and AT1R-Ab, emphasizing that vascular pathology may be present in individuals with mild COVID-19 as well as those with severe disease.", "doi": "10.1371/journal.pone.0259902", "pmcid": "PMC8598062", "issn": "1932-6203", "publisher": "Public Library of Science", "publication": "PLoS ONE", "publication_date": "2021-11-17", "series_number": "11", "volume": "16", "issue": "11", "pages": "Art. No. e0259902" }, { "id": "authors:m20x1-9kw24", "collection": "authors", "collection_id": "m20x1-9kw24", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200911-133137005", "type": "article", "title": "Visualizing Subcellular Enrichment of Glycogen in Live Cancer Cells by Stimulated Raman Scattering", "author": [ { "family_name": "Lee", "given_name": "Dongkwan", "clpid": "Lee-Dongkwan" }, { "family_name": "Du", "given_name": "Jiajun", "clpid": "Du-Jiajun" }, { "family_name": "Yu", "given_name": "Rona", "clpid": "Yu-Rona" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Wei", "given_name": "Lu", "orcid": "0000-0001-9170-2283", "clpid": "Wei-Lu" } ], "abstract": "Glycogen, a branched glucose polymer, helps regulate glucose homeostasis through immediate storage and release of glucose. Reprogramming of glycogen metabolism has recently been suggested to play an emerging role in cancer progression and tumorigenesis. However, regulation of metabolic rewiring for glycogen synthesis and breakdown in cancer cells remains less understood. Despite the availability of various glycogen detection methods, selective visualization of glycogen in living cells with high spatial resolution has proven to be highly challenging. Here, we present an optical imaging strategy to visualize glycogen in live cancer cells with minimal perturbation by combining stimulated Raman scattering microscopy with metabolic incorporation of deuterium-labeled glucose. We revealed the subcellular enrichment of glycogen in live cancer cells and achieved specific glycogen mapping through distinct spectral identification. Using this method, different glycogen metabolic phenotypes were characterized in a series of patient-derived BRAF mutant melanoma cell lines. Our results indicate that cell lines manifesting high glycogen storage level showed increased tolerance to glucose deficiency among the studied melanoma phenotypes. This method opens up the possibility for noninvasive study of complex glycogen metabolism at subcellular resolution and may help reveal new features of glycogen regulation in cancer systems.", "doi": "10.1021/acs.analchem.0c02348", "pmcid": "PMC10676777", "issn": "0003-2700", "publisher": "American Chemical Society", "publication": "Analytical Chemistry", "publication_date": "2020-10-06", "series_number": "19", "volume": "92", "issue": "19", "pages": "13182-13191" }, { "id": "authors:n0npk-4qf04", "collection": "authors", "collection_id": "n0npk-4qf04", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200924-122708002", "type": "article", "title": "Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells", "author": [ { "family_name": "Du", "given_name": "Jiajun", "clpid": "Du-Jiajun" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Qian", "given_name": "Chenxi", "orcid": "0000-0003-4815-5565", "clpid": "Qian-Chenxi" }, { "family_name": "Yuan", "given_name": "Dan", "clpid": "Yuan-Dan" }, { "family_name": "Miao", "given_name": "Kun", "orcid": "0000-0001-6567-3650", "clpid": "Miao-Kun" }, { "family_name": "Lee", "given_name": "Dongkwan", "clpid": "Lee-Dongkwan" }, { "family_name": "Ng", "given_name": "Alphonsus H. C.", "orcid": "0000-0003-0074-4598", "clpid": "Ng-Alphonsus-H-C" }, { "family_name": "Wijker", "given_name": "Reto S.", "orcid": "0000-0001-5104-9849", "clpid": "Wijker-Reto-S" }, { "family_name": "Ribas", "given_name": "Antoni", "orcid": "0000-0003-3669-8458", "clpid": "Ribas-Antoni" }, { "family_name": "Levine", "given_name": "Raphael D.", "clpid": "Levine-Raphael-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Wei", "given_name": "Lu", "orcid": "0000-0001-9170-2283", "clpid": "Wei-Lu" } ], "abstract": "Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.", "doi": "10.1038/s41467-020-18376-x", "pmcid": "PMC7518429", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2020-09-24", "volume": "11", "pages": "Art. No. 4830" }, { "id": "authors:pba3w-s1n51", "collection": "authors", "collection_id": "pba3w-s1n51", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201221-101511711", "type": "conference_item", "title": "Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma", "author": [ { "family_name": "Du", "given_name": "Jiajun", "clpid": "Du-Jiajun" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Heath", "given_name": "James Richard", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Wei", "given_name": "Lu", "orcid": "0000-0001-9170-2283", "clpid": "Wei-Lu" } ], "abstract": "We utilized Raman spectro-microscopy to non-invasively probe metabomics within single live cells, aiming to identify\ndruggable metabolic susceptibilities from a series of patient-derived BRAF mutant melanoma cell lines. Each cell line\nrepresents a phenotype with different characteristic level of de-differentiation and BRAFi (BRAF inhibitor) resistance.\nFirst, with single-cell Raman spectroscopy and stimulated Raman scattering (SRS) microscopy, followed by\ntranscriptomics anal., we identified lipid processes as major metabolic functional difference between different\nphenotypes. We then utilized hyperspectral-SRS imaging on intracellular single organelles to identify a previously\nunknown susceptibility of lipid desatn. within de-differentiated cell lines. Drugging this target leads to cellular apoptosis\naccompanied by phase sepd. intracellular domains. The integration of subcellular Raman spectro-microscopy with\nlipidomics and transcriptomics suggests highly heterogenous metabolic responses and possible lipid regulatory\nmechanisms underlying this pharmacol. treatment. Our method should provide a general approach in spatially-resolved\nsingle cell metabolomics studies.", "publisher": "Caltech Library", "publication_date": "2020-08" }, { "id": "authors:5haf9-91503", "collection": "authors", "collection_id": "5haf9-91503", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210305-081743845", "type": "article", "title": "Strategies to improve the sensitivity and ranking ability of neoantigen prediction methods: Report on the results of the Tumor nEoantigen SeLection Alliance (TESLA)", "author": [ { "family_name": "Wells", "given_name": "Daniel K.", "orcid": "0000-0003-2463-3139", "clpid": "Wells-Daniel-K" }, { "family_name": "Dang", "given_name": "Kristen K.", "orcid": "0000-0002-7512-4476" }, { "family_name": "Hubbard-Lucey", "given_name": "Vanessa M." }, { "family_name": "Sheehan", "given_name": "Kathleen C.", "orcid": "0000-0002-3357-8285" }, { "family_name": "Lamb", "given_name": "Andrew" }, { "family_name": "Ward", "given_name": "Jeffrey P.", "orcid": "0000-0002-9707-895X" }, { "family_name": "Sidney", "given_name": "John" }, { "family_name": "Blazquez", "given_name": "Ana B." }, { "family_name": "Rech", "given_name": "Andrew J." }, { "family_name": "Zaretsky", "given_name": "Jesse", "orcid": "0000-0002-4889-2648" }, { "family_name": "Comin-Anduix", "given_name": "Begonya" }, { "family_name": "Ng", "given_name": "Alphonsus H.", "orcid": "0000-0003-0074-4598", "clpid": "Ng-Alphonsus-H-C" }, { "family_name": "Chour", "given_name": "William", "orcid": "0000-0003-1817-0123", "clpid": "Chour-William" }, { "family_name": "Yu", "given_name": "Thomas V.", "orcid": "0000-0002-5841-0198" }, { "family_name": "Rizvi", "given_name": "Hira" }, { "family_name": "Chen", "given_name": "Jia" }, { "family_name": "Manning", "given_name": "Patrice" }, { "family_name": "Merghoub", "given_name": "Taha" }, { "family_name": "Guinney", "given_name": "Justin", "orcid": "0000-0003-1477-1888" }, { "family_name": "Kolom", "given_name": "Adam", "orcid": "0000-0003-3170-8231" }, { "family_name": "Selinsky", "given_name": "Cheryl", "orcid": "0000-0002-8792-055X" }, { "family_name": "Ribas", "given_name": "Antoni", "orcid": "0000-0003-3669-8458" }, { "family_name": "Hellmann", "given_name": "Matthew D.", "orcid": "0000-0002-2670-9777" }, { "family_name": "Schumacher", "given_name": "Ton N.", "orcid": "0000-0003-0517-8804" }, { "family_name": "Hacohen", "given_name": "Nir" }, { "family_name": "Kvistborg", "given_name": "Pia", "orcid": "0000-0002-4988-608X" }, { "family_name": "Sette", "given_name": "Alessandro" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Bhardwaj", "given_name": "Nina" }, { "family_name": "Ramsdell", "given_name": "Fred" }, { "family_name": "Schreiber", "given_name": "Robert D." }, { "family_name": "Defranoux", "given_name": "Nadine A.", "orcid": "0000-0002-6825-5531" }, { "literal": "TESLA Consortium" } ], "abstract": "Neoantigen-based therapies hold the promise of being safe, personalized anti-cancer therapies for a broad range of cancers. A crucial step for the development of effective neoantigen therapies is the identification of putative tumor specific neoantigens typically achieved through in silico analyses. In silico-based approaches have the benefit of being fast, modular and reproducible. A wide range of tools are available for variant calling, determining peptide-HLA binding affinity, peptide foreignness, agritopicity and more, and researchers are continuously adding to the lot. However, there does not currently exist a common reference data set with which these different approaches can be compared, and the key parameters for effective neoantigen identification remain elusive. Here we introduce a consortium-based initiative, the Tumor nEoantigen SeLection Alliance (TESLA), to address these needs and describe straight-forward strategies through which the sensitivity and ranking ability of neoantigen prediction methods can be improved. TESLA participants were provided with whole exome and RNA sequencing from six tumors (3 melanoma and 3 NSCLC) and in turn submitted predictions for immunogenic peptides. Twenty-five groups from academia, pharma and biotech participated to this challenge. Peptides identification and ranking across the teams were assessed and showed little overlap. The limited overlap could not be explained simply by differences in variant calling. From these predictions, 608 peptides regrouping the teams' highly ranked epitopes plus epitopes frequently called and ranked across the teams, were assessed for T-cell recognition in patient-matched samples as well as for in-vitro MHC binding affinity. Analyses showed that peptides recognized by T-cells had significantly stronger MHC binding affinity and were derived from genes with significantly higher gene expression. Concomitantly, neoantigen pipelines which prioritized epitopes with strong binding affinity and/or which filtered out those originating from genes with low tumor variant allele fraction or low gene expression were associated with improved ability to identify and rank neoantigens. Direct interventions on participant predictions using these identified traits demonstrated substantial improvement in the performance of the neoantigen predictions. Pipeline analysis indicated that there are a range of approaches to neoantigen prediction and improving upon an existing neoantigen pipeline requires assessing that pipeline for a range of characteristics, including variant detection ability, peptide filtering ability, and peptide ranking ability, and improving those areas where the pipeline performance is sub-optimal. TESLA data will be continually available and serve as a living benchmark to improve neoantigen prediction.", "doi": "10.1158/1538-7445.am2020-3210", "issn": "0008-5472", "publisher": "American Association for Cancer Research", "publication": "Cancer Research", "publication_date": "2020-08", "series_number": "16", "volume": "80", "issue": "16", "pages": "Art. No. 3210" }, { "id": "authors:abag9-n6b48", "collection": "authors", "collection_id": "abag9-n6b48", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210305-074231958", "type": "article", "title": "Systems biology for investigating drug resistance mechanism of melanoma", "author": [ { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Li", "given_name": "Guideng", "orcid": "0000-0003-0840-7262", "clpid": "Li-Guideng" }, { "family_name": "Ko", "given_name": "Melissa", "clpid": "Ko-Melissa-E" }, { "family_name": "Cheng", "given_name": "Hanjun", "clpid": "Cheng-Hanjun" }, { "family_name": "Zhu", "given_name": "Ronghui", "orcid": "0000-0001-8171-482X", "clpid": "Zhu-Ronghui" }, { "family_name": "Xue", "given_name": "Min", "clpid": "Xue-Min" }, { "family_name": "Robert", "given_name": "Lidia", "clpid": "Robert-Lidia" }, { "family_name": "Levine", "given_name": "Raphael", "clpid": "Levine-Raphael-D" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-Antoni" }, { "family_name": "Nolan", "given_name": "Garry", "clpid": "Nolan-Garry-P" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Plevritis", "given_name": "Sylvia", "clpid": "Plevritis-Sylvia-K" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Integrated proteomic and metabolic single-cell assays reveal multiple independent adaptive responses to drug tolerance in a BRAF-mutant melanoma cell line.\n\nCancers commonly develop resistance against chemotherapeutics or targeted therapies through various types of genetic or non-genetic mechanisms. Non-genetic mechanisms have been shown to occur early on and can provide a latent reservoir of cells for the emergence of various different type of mechanisms, yet very limited understanding of process were resolve main from bulk analysis. Considering the heterogeneous nature of the tumor cells, a single-cell level characterization of the process worth detailed further investigation. Using MAPK inhibition of BRAF-mutant melanomas as a model system, we resolved that cells take different paths to go from drug-sensitive to drug-resistant state. Using a microfludic-based single-cell integrated proteomic and metabolic assay, we assayed for a panel of signaling, phenotypic, and metabolic regulators at four time points during the first five days of drug treatment. Dimensional reduction of the resultant data set, coupled with information theoretic analysis, uncovered a complex cell state landscape and identified two distinct paths connecting drug-na\u00efve and drug-tolerant states. Cells are shown to exclusively traverse one of the two pathways depending on the level of the lineage restricted transcription factor MITF in the drug-na\u00efve cells. The two trajectories are associated with distinct signaling and metabolic susceptibilities, and are independently druggable. Our results update the paradigm of adaptive resistance development in an isogenic cell population and offer insight into the design of more effective combination therapies.", "doi": "10.1158/1538-7445.am2020-6585", "issn": "0008-5472", "publisher": "American Association for Cancer Research", "publication": "Cancer Research", "publication_date": "2020-08", "series_number": "16", "volume": "80", "issue": "16", "pages": "Art. No. 6585" }, { "id": "authors:gw605-vrz22", "collection": "authors", "collection_id": "gw605-vrz22", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200511-122023000", "type": "article", "title": "Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line", "author": [ { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Ko", "given_name": "Melissa E.", "clpid": "Ko-Melissa-E" }, { "family_name": "Cheng", "given_name": "Hanjun", "clpid": "Cheng-Hanjun" }, { "family_name": "Zhu", "given_name": "Ronghui", "clpid": "Zhu-Ronghui" }, { "family_name": "Xue", "given_name": "Min", "clpid": "Xue-Min" }, { "family_name": "Wang", "given_name": "Jessica", "orcid": "0000-0003-1421-4969", "clpid": "Wang-Jessica-K" }, { "family_name": "Lee", "given_name": "Jihoon W.", "orcid": "0000-0002-6749-5111", "clpid": "Lee-Jihoon-W" }, { "family_name": "Frankiw", "given_name": "Luke", "clpid": "Frankiw-L-S" }, { "family_name": "Xu", "given_name": "Alexander", "orcid": "0000-0003-4877-4358", "clpid": "Xu-Alexander-M" }, { "family_name": "Wong", "given_name": "Stephanie", "clpid": "Wong-Stephanie" }, { "family_name": "Robert", "given_name": "Lidia", "clpid": "Robert-L" }, { "family_name": "Takata", "given_name": "Kaitlyn", "orcid": "0000-0003-4864-9741", "clpid": "Takata-Kaitlyn-L" }, { "family_name": "Yuan", "given_name": "Dan", "clpid": "Yuan-Dan" }, { "family_name": "Lu", "given_name": "Yue", "orcid": "0000-0001-9036-2803", "clpid": "Lu-Yue" }, { "family_name": "Huang", "given_name": "Sui", "clpid": "Huang-Sui" }, { "family_name": "Ribas", "given_name": "Antoni", "orcid": "0000-0003-3669-8458", "clpid": "Ribas-A" }, { "family_name": "Levine", "given_name": "Raphael", "clpid": "Levine-R-D" }, { "family_name": "Nolan", "given_name": "Garry P.", "clpid": "Nolan-Garry-P" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Plevritis", "given_name": "Sylvia K.", "clpid": "Plevritis-S-K" }, { "family_name": "Li", "given_name": "Guideng", "orcid": "0000-0003-0840-7262", "clpid": "Li-Guideng" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge for understanding biological changes ranging from cellular differentiation to epigenetic responses of diseased cells upon drugging. We integrate experiments and theory to determine the trajectories that single BRAF^(V600E) mutant melanoma cancer cells take between drug-naive and drug-tolerant states. Although single-cell omics tools can yield snapshots of the cell-state landscape, the determination of individual cell trajectories through that space can be confounded by stochastic cell-state switching. We assayed for a panel of signaling, phenotypic, and metabolic regulators at points across 5 days of drug treatment to uncover a cell-state landscape with two paths connecting drug-naive and drug-tolerant states. The trajectory a given cell takes depends upon the drug-naive level of a lineage-restricted transcription factor. Each trajectory exhibits unique druggable susceptibilities, thus updating the paradigm of adaptive resistance development in an isogenic cell population.", "doi": "10.1038/s41467-020-15956-9", "pmcid": "PMC7214418", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2020-05-11", "volume": "11", "pages": "Art. No. 2345" }, { "id": "authors:wpsjb-te013", "collection": "authors", "collection_id": "wpsjb-te013", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201120-071520503", "type": "monograph", "title": "Shared Antigen-specific CD8\u207a T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants", "author": [ { "family_name": "Chour", "given_name": "William", "orcid": "0000-0003-1817-0123", "clpid": "Chour-William" }, { "family_name": "Xu", "given_name": "Alexander M.", "orcid": "0000-0003-4877-4358", "clpid": "Xu-Alexander-M" }, { "family_name": "Ng", "given_name": "Alphonsus H. C.", "orcid": "0000-0003-0074-4598", "clpid": "Ng-Alphonsus-H-C" }, { "family_name": "Choi", "given_name": "Jongchan", "clpid": "Choi-Jongchan" }, { "family_name": "Xie", "given_name": "Jingyi", "clpid": "Xie-Jingyi" }, { "family_name": "Yuan", "given_name": "Dan", "clpid": "Yuan-Dan" }, { "family_name": "Delucia", "given_name": "Diane C.", "clpid": "Delucia-Diane-C" }, { "family_name": "Edmark", "given_name": "Rick A.", "clpid": "Edmark-Rick-A" }, { "family_name": "Jones", "given_name": "Lesley C.", "clpid": "Jones-Lesley-C" }, { "family_name": "Schmitt", "given_name": "Thomas M.", "clpid": "Schmitt-Thomas-M" }, { "family_name": "Chaffee", "given_name": "Mary E.", "clpid": "Chaffee-Mary-E" }, { "family_name": "Duvvuri", "given_name": "Venkata R.", "clpid": "Duvvuri-Venkata-R" }, { "family_name": "Murray", "given_name": "Kim M.", "clpid": "Murray-Kim-M" }, { "family_name": "Peng", "given_name": "Songming", "orcid": "0000-0002-2742-6584", "clpid": "Peng-Songming" }, { "family_name": "Wallick", "given_name": "Julie", "clpid": "Wallick-Julie" }, { "family_name": "Algren", "given_name": "Heather A.", "clpid": "Algren-Heather-A" }, { "family_name": "Berrington", "given_name": "William R.", "clpid": "Berrington-William-R" }, { "family_name": "O'Mahoney", "given_name": "D. Shane", "clpid": "O'Mahoney-D-Shane" }, { "family_name": "Lee", "given_name": "John K.", "orcid": "0000-0003-4077-0395", "clpid": "Lee-John-K" }, { "family_name": "Greenberg", "given_name": "Philip D.", "clpid": "Greenberg-Philip-D" }, { "family_name": "Goldman", "given_name": "Jason D.", "orcid": "0000-0002-3825-6832", "clpid": "Goldman-Jason-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report here on antigens from the SARS-CoV-2 virus spike protein, that when presented by Class I MHC, can lead to cytotoxic CD8\u207a T cell anti-viral responses in COVID-19 patients. We present a method in which the SARS-CoV-2 spike protein is converted into a library of peptide antigen-Major Histocompatibility Complexes (pMHCs) as single chain trimers that contain the peptide antigen, the MHC HLA allele, and the \u03b2-2 microglobulin sub-unit. That library is used to detect the evolution of virus-specific T cell populations from two COVID-19 patients, at two time points over the course of infection. Both patients exhibit similar virus-specific T cell populations, but very different time-trajectories of those populations. These results can be used to track those virus-specific T cell populations over the course of an infection, thus providing deep insight into the variations in immune system trajectories observed in different COVID-19 patients.", "doi": "10.1101/2020.05.04.20085779", "publication_date": "2020-05-08" }, { "id": "authors:p7zdk-42657", "collection": "authors", "collection_id": "p7zdk-42657", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191015-074715875", "type": "article", "title": "4D electron microscopy of T cell activation", "author": [ { "family_name": "Lu", "given_name": "Yue", "orcid": "0000-0001-9036-2803", "clpid": "Lu-Yue" }, { "family_name": "Yoo", "given_name": "Byung-Kuk", "orcid": "0000-0002-2610-6685", "clpid": "Yoo-Byung-Kuk" }, { "family_name": "Ng", "given_name": "Alphonsus H. C.", "orcid": "0000-0003-0074-4598", "clpid": "Ng-Alphonsus-H-C" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Yeom", "given_name": "Sinchul", "orcid": "0000-0001-6449-0844", "clpid": "Yeom-Sinchul" }, { "family_name": "Tang", "given_name": "Jau", "orcid": "0000-0003-2078-1513", "clpid": "Tang-Jau" }, { "family_name": "Lin", "given_name": "Milo M.", "orcid": "0000-0001-8680-2685", "clpid": "Lin-Milo-M" }, { "family_name": "Zewail", "given_name": "Ahmed H.", "clpid": "Zewail-A-H" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "T cells can be controllably stimulated through antigen-specific or nonspecific protocols. Accompanying functional hallmarks of T cell activation can include cytoskeletal reorganization, cell size increase, and cytokine secretion. Photon-induced near-field electron microscopy (PINEM) is used to image and quantify evanescent electric fields at the surface of T cells as a function of various stimulation conditions. While PINEM signal strength scales with multiple of the biophysical changes associated with T cell functional activation, it mostly strongly correlates with antigen-engagement of the T cell receptors, even under conditions that do not lead to functional T cell activation. PINEM image analysis suggests that a stimulation-induced reorganization of T cell surface structure, especially over length scales of a few hundred nanometers, is the dominant contributor to these PINEM signal changes. These experiments reveal that PINEM can provide a sensitive label-free probe of nanoscale cellular surface structures.", "doi": "10.1073/pnas.1914078116", "pmcid": "PMC6825259", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2019-10-29", "series_number": "44", "volume": "116", "issue": "44", "pages": "22014-22019" }, { "id": "authors:8b757-acv48", "collection": "authors", "collection_id": "8b757-acv48", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190718-140329246", "type": "article", "title": "MATE-Seq: Microfluidic Antigen-TCR Engagement Sequencing", "author": [ { "family_name": "Ng", "given_name": "Alphonsus H. C.", "orcid": "0000-0003-0074-4598", "clpid": "Ng-Alphonsus-H-C" }, { "family_name": "Peng", "given_name": "Songming", "orcid": "0000-0002-2742-6584", "clpid": "Peng-Songming" }, { "family_name": "Xu", "given_name": "Alexander M.", "orcid": "0000-0003-4877-4358", "clpid": "Xu-Alexander-M" }, { "family_name": "Noh", "given_name": "Won Jun", "clpid": "Noh-Won-Jun" }, { "family_name": "Guo", "given_name": "Katherine", "clpid": "Guo-Katherine" }, { "family_name": "Bethune", "given_name": "Michael T.", "clpid": "Bethune-M-T" }, { "family_name": "Chour", "given_name": "William", "orcid": "0000-0003-1817-0123", "clpid": "Chour-William" }, { "family_name": "Choi", "given_name": "Jongchan", "clpid": "Choi-Jongchan" }, { "family_name": "Yang", "given_name": "Sung", "orcid": "0000-0002-6050-0993", "clpid": "Yang-Sung" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Adaptive immunity is based on peptide antigen recognition. Our ability to harness the immune system for therapeutic gain relies on the discovery of the T cell receptor (TCR) genes that selectively target antigens from infections, mutated proteins, and foreign agents. Here we present a method that selectively labels peptide antigen-specific CD8+ T cells using magnetic nanoparticles functionalized with peptide\u2013MHC tetramers, isolates these specific cells within an integrated microfluidic device, and directly amplifies the TCR genes for sequencing. Critically, the identity of the peptide recognized by the TCR is preserved, providing the link between peptide and gene. The platform requires inputs on the order of just 100\u2006000 CD8+ T cells, can be multiplexed for simultaneous analysis of multiple peptides, and performs sorting and isolation on chip. We demonstrate 1000-fold sensitivity enhancement of detecting antigen-specific TCRs relative to bulk analysis and simultaneous capture of two virus antigen-specific TCRs from a population of T cells.", "doi": "10.1039/c9lc00538b", "issn": "1473-0197", "publisher": "Royal Society of Chemistry", "publication": "Lab on a Chip", "publication_date": "2019-09-21", "series_number": "18", "volume": "19", "issue": "18", "pages": "3011-3021" }, { "id": "authors:35565-f8k34", "collection": "authors", "collection_id": "35565-f8k34", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190913-074926949", "type": "monograph", "title": "Trajectories from Snapshots: Integrated proteomic and metabolic single-cell assays reveal multiple independent adaptive responses to drug tolerance in a BRAF-mutant melanoma cell line", "author": [ { "family_name": "Su", "given_name": "Yapeng", "clpid": "Su-Yapeng" }, { "family_name": "Li", "given_name": "Guideng", "orcid": "0000-0003-0840-7262", "clpid": "Li-Guideng" }, { "family_name": "Ko", "given_name": "Melissa E.", "clpid": "Ko-Melissa-E" }, { "family_name": "Cheng", "given_name": "Hanjun", "clpid": "Cheng-Hanjun" }, { "family_name": "Zhu", "given_name": "Ronghui", "clpid": "Zhu-Ronghui" }, { "family_name": "Xue", "given_name": "Min", "clpid": "Xue-Min" }, { "family_name": "Wang", "given_name": "Jessica", "orcid": "0000-0003-1421-4969", "clpid": "Wang-Jessica-K" }, { "family_name": "Lee", "given_name": "Jihoon W.", "clpid": "Lee-Jihoon-W" }, { "family_name": "Frankiw", "given_name": "Luke", "clpid": "Frankiw-L-S" }, { "family_name": "Xu", "given_name": "Alexander", "orcid": "0000-0003-4877-4358", "clpid": "Xu-Alexander-M" }, { "family_name": "Wong", "given_name": "Stephanie", "clpid": "Wong-Stephanie" }, { "family_name": "Robert", "given_name": "Lidia", "clpid": "Robert-L" }, { "family_name": "Takata", "given_name": "Kaitlyn", "orcid": "0000-0003-4864-9741", "clpid": "Takata-Kaitlyn-L" }, { "family_name": "Huang", "given_name": "Sui", "clpid": "Huang-Sui" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-A" }, { "family_name": "Levine", "given_name": "Raphael", "clpid": "Levine-R-D" }, { "family_name": "Nolan", "given_name": "Garry P.", "clpid": "Nolan-Garry-P" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Plevritis", "given_name": "Sylvia K.", "clpid": "Plevritis-S-K" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge, with relevance towards understanding biological changes ranging from cellular differentiation to epigenetic (adaptive) responses of diseased cells to drugging. We report on a combined experimental and theoretic method for determining the trajectories that specific highly plastic BRAFV600E mutant patient-derived melanoma cancer cells take between drug-naive and drug-tolerant states. Recent studies have implicated non-genetic, fast-acting resistance mechanisms are activated in these cells following BRAF inhibition. While single-cell highly multiplex omics tools can yield snapshots of the cell state space landscape sampled at any given time point, individual cell trajectories must be inferred from a kinetic series of snapshots, and that inference can be confounded by stochastic cell state switching. Using a microfludic-based single-cell integrated proteomic and metabolic assay, we assayed for a panel of signaling, phenotypic, and metabolic regulators at four time points during the first five days of drug treatment. Dimensional reduction of the resultant data set, coupled with information theoretic analysis, uncovered a complex cell state landscape and identified two distinct paths connecting drug-naive and drug-tolerant states. Cells are shown to exclusively traverse one of the two pathways depending on the level of the lineage restricted transcription factor MITF in the drug-naive cells. The two trajectories are associated with distinct signaling and metabolic susceptibilities, and are independently druggable. Our results update the paradigm of adaptive resistance development in an isogenic cell population and offer insight into the design of more effective combination therapies.", "doi": "10.1101/767988", "publication_date": "2019-09-12" }, { "id": "authors:fqh62-czv13", "collection": "authors", "collection_id": "fqh62-czv13", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190903-130240129", "type": "article", "title": "Sensitive Detection and Analysis of Neoantigen-Specific T Cell Populations from Tumors and Blood", "author": [ { "family_name": "Peng", "given_name": "Songming", "orcid": "0000-0002-2742-6584", "clpid": "Peng-Songming" }, { "family_name": "Zaretsky", "given_name": "Jesse M.", "clpid": "Zaretsky-Jesse-M" }, { "family_name": "Ng", "given_name": "Alphonsus H. C.", "orcid": "0000-0003-0074-4598", "clpid": "Ng-Alphonsus-H-C" }, { "family_name": "Chour", "given_name": "William", "orcid": "0000-0003-1817-0123", "clpid": "Chour-William" }, { "family_name": "Bethune", "given_name": "Michael T.", "clpid": "Bethune-Michael-T" }, { "family_name": "Choi", "given_name": "Jongchan", "clpid": "Choi-Jongchan" }, { "family_name": "Hsu", "given_name": "Alice", "clpid": "Hsu-Alice" }, { "family_name": "Holman", "given_name": "Elizabeth", "orcid": "0000-0002-5158-4689", "clpid": "Holman-Elizabeth-A" }, { "family_name": "Ding", "given_name": "Xiaozhe", "clpid": "Ding-Xiaozhe-Z" }, { "family_name": "Guo", "given_name": "Katherine", "clpid": "Guo-Katherine" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Xu", "given_name": "Alexander M.", "orcid": "0000-0003-4877-4358", "clpid": "Xu-Alexander-M" }, { "family_name": "Heath", "given_name": "John E.", "clpid": "Heath-John-E" }, { "family_name": "Noh", "given_name": "Won Jun", "clpid": "Noh-Won-Jun" }, { "family_name": "Zhou", "given_name": "Jing", "clpid": "Zhou-Jing" }, { "family_name": "Su", "given_name": "Yapeng", "clpid": "Su-Yapeng" }, { "family_name": "Lu", "given_name": "Yue", "orcid": "0000-0001-9036-2803", "clpid": "Lu-Yue" }, { "family_name": "McLaughlin", "given_name": "Jami", "clpid": "McLaughlin-J" }, { "family_name": "Cheng", "given_name": "Donghui", "clpid": "Cheng-Donghui" }, { "family_name": "Witte", "given_name": "Owen N.", "orcid": "0000-0003-4461-4533", "clpid": "Witte-Owen-N" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-Antoni" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Neoantigen-specific T cells are increasingly viewed as important immunotherapy effectors, but physically isolating these rare cell populations is challenging. Here, we describe a sensitive method for the enumeration and isolation of neoantigen-specific CD8+ T cells from small samples of patient tumor or blood. The method relies on magnetic nanoparticles that present neoantigen-loaded major histocompatibility complex (MHC) tetramers at high avidity by barcoded DNA linkers. The magnetic particles provide a convenient handle to isolate the desired cell populations, and the barcoded DNA enables multiplexed analysis. The method exhibits superior recovery of antigen-specific T cell populations relative to literature approaches. We applied the method to profile neoantigen-specific T cell populations in the tumor and blood of patients with metastatic melanoma over the course of anti-PD1 checkpoint inhibitor therapy. We show that the method has value for monitoring clinical responses to cancer immunotherapy and might help guide the development of personalized mutational neoantigen-specific T cell therapies and cancer vaccines.", "doi": "10.1016/j.celrep.2019.07.106", "pmcid": "PMC6774618", "issn": "2211-1247", "publisher": "Cell Press", "publication": "Cell Reports", "publication_date": "2019-09-03", "series_number": "10", "volume": "28", "issue": "10", "pages": "2728-2738" }, { "id": "authors:xq7xw-5cp13", "collection": "authors", "collection_id": "xq7xw-5cp13", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190729-100027029", "type": "article", "title": "Inhibition of heme sequestration of histidine-rich protein 2 using multiple epitope-targeted peptides", "author": [ { "family_name": "Liang", "given_name": "JingXin", "orcid": "0000-0001-6600-8409", "clpid": "Liang-JingXin" }, { "family_name": "Bunck", "given_name": "David N.", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Mishra", "given_name": "Anvita", "clpid": "Mishra-A" }, { "family_name": "Hong", "given_name": "Sunga", "clpid": "Hong-Sunga" }, { "family_name": "Idso", "given_name": "Matthew N.", "clpid": "Idso-M-N" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Plasmodium falciparum is the most lethal species of malaria. In infected human red blood cells, P. falciparum digests hemoglobin as a nutrient source, liberating cytotoxic free heme in the process. Sequestration and subsequent conversion of this byproduct into hemozoin, an inert biocrystalline heme aggregate, plays a key role in parasite survival. Hemozoin has been a longstanding target of antimalarials such as chloroquine (CQ), which inhibit the biocrystallization of free heme. In this study, we explore heme\u2010binding interactions with histidine\u2010rich\u2010protein 2 (HRP2), a known malarial biomarker and purported player in free heme sequestration. HRP2 is notoriously challenging to target due to its highly repetitious sequence and irregular secondary structure. We started with three protein\u2010catalyzed capture agents (PCCs) developed against epitopes of HRP2, inclusive of heme\u2010binding motifs, and explored their ability to inhibit heme:HRP2 complex formation. Cocktails of the individual PCCs exhibit an inhibitory potency similar to CQ, while a covalently linked structure built from two separate PCCs provided considerably increased inhibition relative to CQ. Epitope\u2010targeted disruption of heme:HRP2 binding is a novel approach towards disrupting P. falciparum\u2010related hemozoin formation.", "doi": "10.1002/psc.3203", "issn": "1075-2617", "publisher": "Wiley", "publication": "Journal of Peptide Science", "publication_date": "2019-09", "series_number": "9", "volume": "25", "issue": "9", "pages": "Art. No. e3203" }, { "id": "authors:fhc9f-zwt87", "collection": "authors", "collection_id": "fhc9f-zwt87", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190805-155608943", "type": "monograph", "title": "Kinetic Inference Resolves Epigenetic Mechanism of Drug Resistance in Melanoma", "author": [ { "family_name": "Su", "given_name": "Yapeng", "clpid": "Su-Yapeng" }, { "family_name": "Lee", "given_name": "Jihoon W.", "clpid": "Lee-Jihoon-W" }, { "family_name": "Ng", "given_name": "Rachel", "clpid": "Ng-Rachel" }, { "family_name": "Liu", "given_name": "Victoria", "orcid": "0000-0003-1845-2497", "clpid": "Liu-Victoria" }, { "family_name": "Peng", "given_name": "Songming", "orcid": "0000-0002-2742-6584", "clpid": "Peng-Songming" }, { "family_name": "Xue", "given_name": "Min", "clpid": "Xue-Min" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Li", "given_name": "Guideng", "orcid": "0000-0003-0840-7262", "clpid": "Li-Guideng" }, { "family_name": "Wong", "given_name": "Stephanie", "clpid": "Wong-Stephanie" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" } ], "abstract": "We resolved a mechanism connecting tumor epigenetic plasticity with non-genetic adaptive resistance to therapy, with MAPK inhibition of BRAF-mutant melanomas providing the model. These cancer cells undergo multiple, reversible drug-induced cell-state transitions, ultimately yielding a drug-resistant mesenchymal-like phenotype. A kinetic series of transcriptome and epigenome data, collected over two months of drug treatment and release, revealed changing levels of thousands of genes and extensive chromatin remodeling. However, a 3-step computational algorithm greatly simplified the interpretation of these changes, and revealed that the whole adaptive process was controlled by a gene module activated within just three days of treatment, with RelA driving chromatin remodeling to establish an epigenetic program encoding long-term phenotype changes. These findings were confirmed across several patient-derived cell lines and in melanoma patients under MAPK inhibitor treatment. Co-targeting BRAF and histone-modifying enzymes arrests adaptive transitions towards drug tolerance in epigenetically plastic melanoma cells and may be exploited therapeutically.", "doi": "10.1101/724740", "publication_date": "2019-08-05" }, { "id": "authors:z0vt9-b1k45", "collection": "authors", "collection_id": "z0vt9-b1k45", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190610-083058080", "type": "article", "title": "Phenotypic heterogeneity and evolution of melanoma cells associated with targeted therapy resistance", "author": [ { "family_name": "Su", "given_name": "Yapeng", "clpid": "Su-Yapeng" }, { "family_name": "Bintz", "given_name": "Marcus", "orcid": "0000-0002-4548-3953", "clpid": "Bintz-M" }, { "family_name": "Yang", "given_name": "Yezi", "clpid": "Yang-Yezi" }, { "family_name": "Robert", "given_name": "Lidia", "clpid": "Robert-L" }, { "family_name": "Ng", "given_name": "Alphonsus H. C.", "orcid": "0000-0003-0074-4598", "clpid": "Ng-Alphonsus-H-C" }, { "family_name": "Liu", "given_name": "Victoria", "orcid": "0000-0003-1845-2497", "clpid": "Liu-Victoria" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-Antoni" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" } ], "abstract": "Phenotypic plasticity is associated with non-genetic drug tolerance in several cancers. Such plasticity can arise from chromatin remodeling, transcriptomic reprogramming, and/or protein signaling rewiring, and is characterized as a cell state transition in response to molecular or physical perturbations. This, in turn, can confound interpretations of drug responses and resistance development. Using BRAF-mutant melanoma cell lines as the prototype, we report on a joint theoretical and experimental investigation of the cell-state transition dynamics associated with BRAF inhibitor drug tolerance. Thermodynamically motivated surprisal analysis of transcriptome data was used to treat the cell population as an entropy maximizing system under the influence of time-dependent constraints. This permits the extraction of an epigenetic potential landscape for drug-induced phenotypic evolution. Single-cell flow cytometry data of the same system were modeled with a modified Fokker-Planck-type kinetic model. The two approaches yield a consistent picture that accounts for the phenotypic heterogeneity observed over the course of drug tolerance development. The results reveal that, in certain plastic cancers, the population heterogeneity and evolution of cell phenotypes may be understood by accounting for the competing interactions of the epigenetic potential landscape and state-dependent cell proliferation. Accounting for such competition permits accurate, experimentally verifiable predictions that can potentially guide the design of effective treatment strategies.", "doi": "10.1371/journal.pcbi.1007034", "pmcid": "PMC6576794", "issn": "1553-7358", "publisher": "Public Library of Science", "publication": "PLOS Computational Biology", "publication_date": "2019-06-05", "series_number": "6", "volume": "15", "issue": "6", "pages": "Art. No. e1007034" }, { "id": "authors:1e3tf-49212", "collection": "authors", "collection_id": "1e3tf-49212", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181130-094846557", "type": "article", "title": "T cell antigen discovery via signaling and antigen-presenting bifunctional receptors", "author": [ { "family_name": "Joglekar", "given_name": "Alok V.", "orcid": "0000-0001-7554-7447", "clpid": "Joglekar-A-V" }, { "family_name": "Leonard", "given_name": "Michael T.", "orcid": "0000-0001-9084-2647", "clpid": "Leonard-M-T" }, { "family_name": "Jeppson", "given_name": "John D.", "clpid": "Jeppson-J-D" }, { "family_name": "Swift", "given_name": "Margaret", "clpid": "Swift-M" }, { "family_name": "Li", "given_name": "Guideng", "orcid": "0000-0003-0840-7262", "clpid": "Li-Guideng" }, { "family_name": "Wong", "given_name": "Stephanie", "clpid": "Wong-Stephanie" }, { "family_name": "Peng", "given_name": "Songming", "orcid": "0000-0002-2742-6584", "clpid": "Peng-Songming" }, { "family_name": "Zaretsky", "given_name": "Jesse M.", "clpid": "Zaretsky-J-M" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-A" }, { "family_name": "Bethune", "given_name": "Michael T.", "clpid": "Bethune-M-T" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" } ], "abstract": "CD8^+ T cells recognize and eliminate tumors in an antigen-specific manner. Despite progress in characterizing the antitumor T cell repertoire and function, the identification of target antigens remains a challenge. Here we describe the use of chimeric receptors called signaling and antigen-presenting bifunctional receptors (SABRs) in a cell-based platform for T cell receptor (TCR) antigen discovery. SABRs present an extracellular complex comprising a peptide and major histocompatibility complex (MHC), and induce intracellular signaling via a TCR-like signal after binding with a cognate TCR. We devised a strategy for antigen discovery using SABR libraries to screen thousands of antigenic epitopes. We validated this platform by identifying the targets recognized by public TCRs of known specificities. Moreover, we extended this approach for personalized neoantigen discovery.", "doi": "10.1038/s41592-018-0304-8", "pmcid": "PMC6755906", "issn": "1548-7091", "publisher": "Nature Publishing Group", "publication": "Nature Methods", "publication_date": "2019-02", "series_number": "2", "volume": "16", "issue": "2", "pages": "191-198" }, { "id": "authors:bjada-r0t26", "collection": "authors", "collection_id": "bjada-r0t26", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181130-094559783", "type": "article", "title": "T cell antigen discovery via trogocytosis", "author": [ { "family_name": "Li", "given_name": "Guideng", "orcid": "0000-0003-0840-7262", "clpid": "Li-Guideng" }, { "family_name": "Bethune", "given_name": "Michael T.", "clpid": "Bethune-M-T" }, { "family_name": "Wong", "given_name": "Stephanie", "clpid": "Wong-Stephanie" }, { "family_name": "Joglekar", "given_name": "Alok V.", "orcid": "0000-0001-7554-7447", "clpid": "Joglekar-A-V" }, { "family_name": "Leonard", "given_name": "Michael T.", "orcid": "0000-0001-9084-2647", "clpid": "Leonard-M-T" }, { "family_name": "Wang", "given_name": "Jessica K.", "orcid": "0000-0003-1421-4969", "clpid": "Wang-Jessica-K" }, { "family_name": "Kim", "given_name": "Jocelyn T.", "orcid": "0000-0001-8723-8190", "clpid": "Kim-Jocelyn-T" }, { "family_name": "Cheng", "given_name": "Donghui", "clpid": "Cheng-Donghui" }, { "family_name": "Peng", "given_name": "Songming", "orcid": "0000-0002-2742-6584", "clpid": "Peng-Songming" }, { "family_name": "Zaretsky", "given_name": "Jesse M.", "clpid": "Zaretsky-J-M" }, { "family_name": "Su", "given_name": "Yapeng", "clpid": "Su-Yapeng" }, { "family_name": "Luo", "given_name": "Yicheng", "orcid": "0000-0003-3704-2389", "clpid": "Luo-Yicheng" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-A" }, { "family_name": "Witte", "given_name": "Owen N.", "orcid": "0000-0003-4461-4533", "clpid": "Witte-O-N" } ], "abstract": "T cell receptor (TCR) ligand discovery is essential for understanding and manipulating immune responses to tumors. We developed a cell-based selection platform for TCR ligand discovery that exploits a membrane transfer phenomenon called trogocytosis. We discovered that T cell membrane proteins are transferred specifically to target cells that present cognate peptide\u2013major histocompatibility complex (MHC) molecules. Co-incubation of T cells expressing an orphan TCR with target cells collectively presenting a library of peptide\u2013MHCs led to specific labeling of cognate target cells, enabling isolation of these target cells and sequencing of the cognate TCR ligand. We validated this method for two clinically employed TCRs and further used the platform to identify the cognate neoepitope for a subject-derived neoantigen-specific TCR. Thus, target cell trogocytosis is a robust tool for TCR ligand discovery that will be useful for studying basic tumor immunology and identifying new targets for immunotherapy.", "doi": "10.1038/s41592-018-0305-7", "pmcid": "PMC6719556", "issn": "1548-7091", "publisher": "Nature Publishing Group", "publication": "Nature Methods", "publication_date": "2019-01-29", "series_number": "2", "volume": "16", "issue": "2", "pages": "183-190" }, { "id": "authors:j2fzf-ybw74", "collection": "authors", "collection_id": "j2fzf-ybw74", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180910-090801725", "type": "article", "title": "Integrated measurement of intracellular proteins and transcripts in single cells", "author": [ { "family_name": "Xu", "given_name": "Alexander M.", "orcid": "0000-0003-4877-4358", "clpid": "Xu-Alexander-M" }, { "family_name": "Liu", "given_name": "Qianhe", "orcid": "0000-0002-7517-4772", "clpid": "Liu-Qianhe" }, { "family_name": "Takata", "given_name": "Kaitlyn L.", "orcid": "0000-0003-4864-9741", "clpid": "Takata-Kaitlyn-L" }, { "family_name": "Jeoung", "given_name": "Sarah", "clpid": "Jeoung-Sarah" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Antoshechkin", "given_name": "Igor", "orcid": "0000-0002-9934-3040", "clpid": "Antoshechkin-I-A" }, { "family_name": "Chen", "given_name": "Sisi", "orcid": "0000-0001-9448-9713", "clpid": "Chen-Sisi" }, { "family_name": "Thomson", "given_name": "Matthew", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Biological function arises from the interplay of proteins, transcripts, and metabolites. An ongoing revolution in miniaturization technologies has created tools to analyze any one of these species in single cells, thus resolving the heterogeneity of tissues previously invisible to bulk measurements. An emerging frontier is single cell multi-omics, which is the measurement of multiple classes of analytes from single cells. Here, we combine bead-based transcriptomics with microchip-based proteomics to measure intracellular proteins and transcripts from single cells and defined small numbers of cells. The transcripts and proteins are independently measured by sequencing and fluorescent immunoassays respectively, to preserve their optimal measurement modes, and linked by encoding the physical address locations of the cells into digital sequencing space using spatially patterned DNA barcodes. We resolve cell-type-specific protein and transcript signatures and present a path forward to scaling the platform to high-throughput.", "doi": "10.1039/c8lc00639c", "pmcid": "PMC6752714", "issn": "1473-0197", "publisher": "Royal Society of Chemistry", "publication": "Lab on a Chip", "publication_date": "2018-11-07", "series_number": "21", "volume": "18", "issue": "21", "pages": "3251-3262" }, { "id": "authors:n12gz-wba57", "collection": "authors", "collection_id": "n12gz-wba57", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180618-082158855", "type": "article", "title": "Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL", "author": [ { "family_name": "Rossi", "given_name": "John", "clpid": "Rossi-J" }, { "family_name": "Paczkowski", "given_name": "Patrick", "clpid": "Paczkowski-P" }, { "family_name": "Shen", "given_name": "Yueh-Wei", "clpid": "Shen-Yueh-Wei" }, { "family_name": "Morse", "given_name": "Kevin", "clpid": "Morse-K" }, { "family_name": "Flynn", "given_name": "Brianna", "clpid": "Flynn-B" }, { "family_name": "Kaiser", "given_name": "Alaina", "clpid": "Kaiser-A" }, { "family_name": "Ng", "given_name": "Colin", "clpid": "Ng-Colin" }, { "family_name": "Gallatin", "given_name": "Kyle", "clpid": "Gallatin-K" }, { "family_name": "Cain", "given_name": "Tom", "clpid": "Cain-T" }, { "family_name": "Fan", "given_name": "Rong", "clpid": "Fan-Rong" }, { "family_name": "Mackay", "given_name": "Sean", "clpid": "Mackay-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Rosenberg", "given_name": "Steven A.", "clpid": "Rosenberg-S-A" }, { "family_name": "Kochenderfer", "given_name": "James N.", "clpid": "Kochenderfer-J-N" }, { "family_name": "Zhou", "given_name": "Jing", "clpid": "Zhou-Jing" }, { "family_name": "Bot", "given_name": "Adrian", "clpid": "Bot-A" } ], "abstract": "After treatment with chimeric antigen receptor (CAR) T cells, interleukin-15 (IL-15) elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines, including interferon-\u03b3, IL-17A, IL-8, and macrophage inflammatory protein 1\u03b1. A prespecified T-cell polyfunctionality strength index (PSI) applied to preinfusion CAR product was significantly associated with clinical response, and PSI combined with CAR T-cell expansion or pretreatment serum IL-15 levels conferred additional significance. Within the total product cell population, associations with clinical outcomes were greater with polyfunctional CD4+ T cells compared with CD8+ cells. Grade \u22653 cytokine release syndrome was associated with polyfunctional T cells, and both grade \u22653 neurologic toxicity and antitumor efficacy were associated with polyfunctional IL-17A\u2013producing T cells. The findings in this exploratory study show that a preinfusion CAR product T-cell subset with a definable polyfunctional profile has a major association with clinical outcomes of CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT00924326.", "doi": "10.1182/blood-2018-01-828343", "pmcid": "PMC6107882", "issn": "0006-4971", "publisher": "American Society of Hematology", "publication": "Blood", "publication_date": "2018-08-23", "series_number": "8", "volume": "132", "issue": "8", "pages": "804-814" }, { "id": "authors:65yf9-kty62", "collection": "authors", "collection_id": "65yf9-kty62", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180706-134625112", "type": "article", "title": "An Allosteric Inhibitor of KRas Identified Using a Barcoded Rapid Assay Microchip Platform", "author": [ { "family_name": "McCarthy", "given_name": "Amy Michelle", "orcid": "0000-0003-3456-0383", "clpid": "McCarthy-Amy-Michelle" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Museth", "given_name": "A. Katrine", "clpid": "Museth-A-Katrine" }, { "family_name": "Henning", "given_name": "Ryan K.", "clpid": "Henning-Ryan-K" }, { "family_name": "Heath", "given_name": "John E.", "clpid": "Heath-John-E" }, { "family_name": "Winson", "given_name": "Emma", "clpid": "Winson-Emma" }, { "family_name": "Oh", "given_name": "Joseph J.", "clpid": "Oh-Joseph-J" }, { "family_name": "Liang", "given_name": "Jingxin", "orcid": "0000-0001-6600-8409", "clpid": "Liang-JingXin" }, { "family_name": "Hong", "given_name": "Sunga", "clpid": "Hong-Sunga" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Protein catalyzed capture agents (PCCs) are synthetic antibody surrogates that can target a wide variety of biologically relevant proteins. As a step toward developing a high-throughput PCC pipeline, we report on the preparation of a barcoded rapid assay platform for the analysis of hits from PCC library screens. The platform is constructed by first surface patterning a micrometer scale barcode composed of orthogonal ssDNA strands onto a glass slide. The slide is then partitioned into microwells, each of which contains multiple copies of the full barcode. Biotinylated candidate PCCs from a click screen are assembled onto the barcode stripes using a complementary ssDNA-encoded cysteine-modified streptavidin library. This platform was employed to evaluate candidate PCC ligands identified from an epitope targeted in situ click screen against the two conserved allosteric switch regions of the Kirsten rat sarcoma (KRas) protein. A single microchip was utilized for the simultaneous evaluation of 15 PCC candidate fractions under more than a dozen different assay conditions. The platform also permitted more than a 10-fold savings in time and a more than 100-fold reduction in biological and chemical reagents relative to traditional multiwell plate assays. The best ligand was shown to exhibit an in vitro inhibition constant (IC_(50)) of \u223c24 \u03bcM.", "doi": "10.1021/acs.analchem.8b00706", "pmcid": "PMC6734936", "issn": "0003-2700", "publisher": "American Chemical Society", "publication": "Analytical Chemistry", "publication_date": "2018-08-07", "series_number": "15", "volume": "90", "issue": "15", "pages": "8824-8830" }, { "id": "authors:mfbbv-bbq20", "collection": "authors", "collection_id": "mfbbv-bbq20", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181109-142044662", "type": "conference_item", "title": "Cyclic cell state transition is associated with the adaptive resistance to BRAF inhibition in melanomas", "author": [ { "family_name": "Su", "given_name": "Yapeng", "clpid": "Su-Yapeng" }, { "family_name": "Lu", "given_name": "Xiang", "clpid": "Lu-Xiang" }, { "family_name": "Li", "given_name": "Guideng", "orcid": "0000-0003-0840-7262", "clpid": "Li-Guideng" }, { "family_name": "Robert", "given_name": "Lidia", "clpid": "Robert-L" }, { "family_name": "Ng", "given_name": "Alphonsus", "orcid": "0000-0003-0074-4598", "clpid": "Ng-Alphonsus-H-C" }, { "family_name": "Xue", "given_name": "Min", "clpid": "Xue-Min" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-A" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Levine", "given_name": "Raphael", "clpid": "Levine-R-D" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Cancers commonly develop resistance against chemotherapeutics or targeted therapies through either genetic mechanism or adaptive responses that commonly involve epigenetic reprogramming and activation of compensatory signaling pathways. Recent examples of such an adaptive response involve the treatment of BRAF mutant melanoma cancer patients with inhibitors of the BRAF/MAPK pathway. Several studies attribute it to a reversible cell state transition from a proliferative melanocytic state towards invasive neural crest-like and mesenchymal-like states. The capacity of certain BRAF mutant melanoma patient tumors, and the cell lines derived from them, to adapt to targeted therapies bears\nsome conceptual similarities to adaptive responses obsd. in other cancers. Further, the response of the cells that adapt to BRAF inhibition is highly variable depending on phenotypic plasticity of the cells, the length of drug exposure, and the dosing strategy. As such, general physiochem. approaches that provide quant., predictive models of such transitions may provide a common conceptual framework for understanding the large genome-scale gene expression level changes. Through analyzing the kinetic trajectory of the reversible, adaptive response of a highly plastic, patient-derived BRAF^(V600)\nmutant melanoma cell line to BRAFi, using genome-wide expression of these cells at 15 time points over a period that included 29 days of drug treatment, followed by either an addnl. 30 days of treatment, or 35 days of drug release, we found that the cells adapt to the drug treatment in two stages, terminating in a mesenchymal-like state after almost a month of treatment. At that stage, continued drug exposure induced no further changes in cell phenotype. Following drug release, the cells reverted back to the original, drug naive phenotype, but the reverse pathway took a different trajectory than the forward pathway. Thermodynamically-motivated Surprisal Anal. was utilized to identify two constraints\nof this cyclic cell state transition to construct a free energy surface. A kinetic ODE model of the two unbalanced processes revealed that the process assocd. with the long-term adaptive transition was driven the other process reflective of a short-term drug stress response. Such kinetic model further allowed identifying driving transcription factors and epigenetic regulations that prompt the cyclic cell state transition towards adaptive resistance.", "publisher": "Caltech Library", "publication_date": "2018-08" }, { "id": "authors:vzdhp-qh506", "collection": "authors", "collection_id": "vzdhp-qh506", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180726-081557948", "type": "article", "title": "Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding", "author": [ { "family_name": "Sibener", "given_name": "Leah V.", "clpid": "Sibener-Leah-V" }, { "family_name": "Fernandes", "given_name": "Ricardo A.", "clpid": "Fernandes-Ricardo-A" }, { "family_name": "Kolawole", "given_name": "Elizabeth M.", "clpid": "Kolawole-E-M" }, { "family_name": "Carbone", "given_name": "Catherine B.", "clpid": "Carbone-Catherine-B" }, { "family_name": "Liu", "given_name": "Fan", "clpid": "Liu-Fan" }, { "family_name": "McAffee", "given_name": "Darren", "clpid": "McAffee-Darren" }, { "family_name": "Birnbaum", "given_name": "Michael E.", "clpid": "Birnbaum-Michael-E" }, { "family_name": "Yang", "given_name": "Xinbo", "clpid": "Yang-Xinbo" }, { "family_name": "Su", "given_name": "Laura F.", "clpid": "Su-Laura-F" }, { "family_name": "Yu", "given_name": "Wong", "clpid": "Yu-Wong" }, { "family_name": "Dong", "given_name": "Shen", "clpid": "Dong-Shen" }, { "family_name": "Gee", "given_name": "Marvin H.", "clpid": "Gee-Marvin-H" }, { "family_name": "Jude", "given_name": "Kevin M.", "clpid": "Jude-Kevin-M" }, { "family_name": "Davis", "given_name": "Mark M.", "clpid": "Davis-Mark-M" }, { "family_name": "Groves", "given_name": "Jay T.", "clpid": "Groves-Jay-T" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Evavold", "given_name": "Brian D.", "clpid": "Evavold-Brian-D" }, { "family_name": "Vale", "given_name": "Ronald D.", "clpid": "Vale-Ronald-D" }, { "family_name": "Garcia", "given_name": "K. Christopher", "orcid": "0000-0001-9273-0278", "clpid": "Garcia-K-Christopher" } ], "abstract": "TCR-signaling strength generally correlates with peptide-MHC binding affinity; however, exceptions exist. We find high-affinity, yet non-stimulatory, interactions occur with high frequency in the human T cell repertoire. Here, we studied human TCRs that are refractory to activation by pMHC ligands despite robust binding. Analysis of 3D affinity, 2D dwell time, and crystal structures of stimulatory versus non-stimulatory TCR-pMHC interactions failed to account for their different signaling outcomes. Using yeast pMHC display, we identified peptide agonists of a formerly non-responsive TCR. Single-molecule force measurements demonstrated the emergence of catch bonds in the activating TCR-pMHC interactions, correlating with exclusion of CD45 from the TCR-APC contact site. Molecular dynamics simulations of TCR-pMHC disengagement distinguished agonist from non-agonist ligands based on the acquisition of catch bonds within the TCR-pMHC interface. The isolation of catch bonds as a parameter mediating the coupling of TCR binding and signaling has important implications for TCR and antigen engineering for immunotherapy.", "doi": "10.1016/j.cell.2018.06.017", "pmcid": "PMC6140336", "issn": "0092-8674", "publisher": "Cell Press", "publication": "Cell", "publication_date": "2018-07-26", "series_number": "3", "volume": "174", "issue": "3", "pages": "672-687" }, { "id": "authors:gpg9g-0bz37", "collection": "authors", "collection_id": "gpg9g-0bz37", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180412-142012478", "type": "article", "title": "Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders", "author": [ { "family_name": "Bunck", "given_name": "David N.", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Atsavapranee", "given_name": "Beatriz", "clpid": "Atsavapranee-B" }, { "family_name": "Museth", "given_name": "Anna K.", "clpid": "Museth-A-K" }, { "family_name": "VanderVelde", "given_name": "David G.", "orcid": "0000-0002-2907-0366", "clpid": "VanderVelde-D-G" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death with average survival times of 2 \u2010 5 years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a protein whose stability and aggregation propensity are affected by point mutations spanning the protein. Here, we use an epitope\u2010specific, high\u2010throughput screen to identify peptides that both stabilize the native conformation of SOD1 as well as accelerate its folding by 2.5\u2010fold. Ligands targeted to the electrostatic loop on the periphery of the protein tightened the non\u2010metalated structure and accelerated its folding. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics.", "doi": "10.1002/anie.201802269", "pmcid": "PMC6295353", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2018-05-22", "series_number": "21", "volume": "57", "issue": "21", "pages": "6212-6215" }, { "id": "authors:sm2g7-kjw72", "collection": "authors", "collection_id": "sm2g7-kjw72", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180222-123456564", "type": "article", "title": "Epitope-Targeted Macrocyclic Peptide Ligand with Picomolar Cooperative Binding to Interleukin-17F", "author": [ { "family_name": "Lai", "given_name": "Bert T.", "clpid": "Lai-Bert-T" }, { "family_name": "Wilson", "given_name": "Jer\u00e9 A.", "clpid": "Wilson-J-A" }, { "family_name": "Malette Loredo", "given_name": "Jacquie", "clpid": "J-Malette" }, { "family_name": "Pitram", "given_name": "Suresh M.", "clpid": "Pitram-S-M" }, { "family_name": "LaBerge", "given_name": "Nicole A.", "clpid": "LaBerge-N-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-H-D" } ], "abstract": "The IL-17 cytokine family is associated with multiple immune and autoimmune diseases and comprises important diagnostic and therapeutic targets. This work reports the development of epitope-targeted ligands designed for differential detection of human IL-17F and its closest homologue IL-17A. Non-overlapping and unique epitopes on IL-17F and IL-17A were identified by comparative sequence analysis of the two proteins. Synthetic variants of these epitopes were utilized as targets for in situ click screens against a comprehensive library of synthetic peptide macrocycles with 5-mer variable regions. Single generation screens yielded selective binders for IL-17F and IL-17A with low cross-reactivity. Macrocyclic peptide binders against two distinct IL-17F epitopes were coupled using variable length chemical linkers to explore the physical chemistry of cooperative binding. The optimized linker length yielded a picomolar affinity binder, while retaining high selectivity. The presented method provides a rational approach towards targeting discontinuous epitopes, similar to what is naturally achieved by many B cell receptors.", "doi": "10.1002/chem.201704752", "issn": "0947-6539", "publisher": "Wiley", "publication": "Chemistry: a European Journal", "publication_date": "2018-03-12", "series_number": "15", "volume": "24", "issue": "15", "pages": "3760-3767" }, { "id": "authors:wcgd0-5na41", "collection": "authors", "collection_id": "wcgd0-5na41", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180129-092440324", "type": "article", "title": "A kinetic investigation of interacting, stimulated T cells identifies conditions for rapid functional enhancement, minimal phenotype differentiation, and improved adoptive cell transfer tumor eradication", "author": [ { "family_name": "Zhou", "given_name": "Jing", "clpid": "Zhou-Jing" }, { "family_name": "Bethune", "given_name": "Michael T.", "clpid": "Bethune-M-T" }, { "family_name": "Malkova", "given_name": "Natalia", "clpid": "Malkova-N-V" }, { "family_name": "Sutherland", "given_name": "Alexander M.", "clpid": "Sutherland-A-M" }, { "family_name": "Comin-Anduix", "given_name": "Begonya", "clpid": "Comin-Anduix-B" }, { "family_name": "Su", "given_name": "Yapeng", "clpid": "Su-Yapeng" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-Antoni" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "For adoptive cell transfer (ACT) immunotherapy of tumor-reactive T cells, an effective therapeutic outcome depends upon cell dose, cell expansion in vivo through a minimally differentiated phenotype, long term persistence, and strong cytolytic effector function. An incomplete understanding of the biological coupling between T cell expansion, differentiation, and response to stimulation hinders the co-optimization of these factors. We report on a biophysical investigation of how the short-term kinetics of T cell functional activation, through molecular stimulation and cell-cell interactions, competes with phenotype differentiation. T cells receive molecular stimulation for a few minutes to a few hours in bulk culture. Following this priming period, the cells are then analyzed at the transcriptional level, or isolated as single cells, with continuing molecular stimulation, within microchambers for analysis via 11-plex secreted protein assays. We resolve a rapid feedback mechanism, promoted by T cell\u2014T cell contact interactions, which strongly amplifies T cell functional performance while yielding only minimal phenotype differentiation. When tested in mouse models of ACT, optimally primed T cells lead to complete tumor eradication. A similar kinetic process is identified in CD8^+ and CD4^+ T cells collected from a patient with metastatic melanoma.", "doi": "10.1371/journal.pone.0191634", "pmcid": "PMC5779691", "issn": "1932-6203", "publisher": "Public Library of Science", "publication": "PLOS ONE", "publication_date": "2018-01-23", "series_number": "1", "volume": "13", "issue": "1", "pages": "Art. No. e0191634" }, { "id": "authors:5m9xh-f4a60", "collection": "authors", "collection_id": "5m9xh-f4a60", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171211-152922263", "type": "article", "title": "Single-cell analysis resolves the cell state transition and signaling dynamics associated with melanoma drug-induced resistance", "author": [ { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Robert", "given_name": "Lidia", "clpid": "Robert-Lidia" }, { "family_name": "Xue", "given_name": "Min", "clpid": "Xue-Min" }, { "family_name": "Tsoi", "given_name": "Jennifer", "clpid": "Tsoi-Jennifer" }, { "family_name": "Garcia-Diaz", "given_name": "Angel", "clpid": "Garcia-Diaz-Angel" }, { "family_name": "Homet Moreno", "given_name": "Blanca", "clpid": "Homet-Moreno-Blanca" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Ng", "given_name": "Rachel H.", "orcid": "0000-0003-3692-8524", "clpid": "Ng-Rachel-H" }, { "family_name": "Lee", "given_name": "Jihoon W.", "orcid": "0000-0002-6749-5111", "clpid": "Lee-Jihoon-W" }, { "family_name": "Koya", "given_name": "Richard C.", "clpid": "Koya-Richard-C" }, { "family_name": "Comin-Anduix", "given_name": "Begonya", "clpid": "Comin-Anduix-Begonya" }, { "family_name": "Graeber", "given_name": "Thomas G.", "clpid": "Graeber-Thomas-G" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-Antoni" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Continuous BRAF inhibition of BRAF mutant melanomas triggers a series of cell state changes that lead to therapy resistance and escape from immune control before establishing acquired resistance genetically. We used genome-wide transcriptomics and single-cell phenotyping to explore the response kinetics to BRAF inhibition for a panel of patient-derived BRAF^(V600)-mutant melanoma cell lines. A subset of plastic cell lines, which followed a trajectory covering multiple known cell state transitions, provided models for more detailed biophysical investigations. Markov modeling revealed that the cell state transitions were reversible and mediated by both Lamarckian induction and nongenetic Darwinian selection of drug-tolerant states. Single-cell functional proteomics revealed activation of certain signaling networks shortly after BRAF inhibition, and before the appearance of drug-resistant phenotypes. Drug targeting those networks, in combination with BRAF inhibition, halted the adaptive transition and led to prolonged growth inhibition in multiple patient-derived cell lines.", "doi": "10.1073/pnas.1712064115", "pmcid": "PMC5748184", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2017-12-26", "series_number": "52", "volume": "114", "issue": "52", "pages": "13679-13684" }, { "id": "authors:w85xw-6q398", "collection": "authors", "collection_id": "w85xw-6q398", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171121-104006296", "type": "article", "title": "Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response", "author": [ { "family_name": "Xue", "given_name": "Qiong", "clpid": "Xue-Qiong" }, { "family_name": "Bettini", "given_name": "Emily", "clpid": "Bettini-Emily" }, { "family_name": "Paczkowski", "given_name": "Patrick", "clpid": "Paczkowski-Patrick" }, { "family_name": "Ng", "given_name": "Colin", "clpid": "Ng-Colin" }, { "family_name": "Kaiser", "given_name": "Alaina", "clpid": "Kaiser-Alaina" }, { "family_name": "McConnell", "given_name": "Timothy", "clpid": "McConnell-Timothy" }, { "family_name": "Kodrasi", "given_name": "Olja", "clpid": "Kodrasi-Olja" }, { "family_name": "Quigley", "given_name": "M\u00e1ire F.", "clpid": "Quigley-M\u00e1ire-F" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Fan", "given_name": "Rong", "clpid": "Fan-Rong" }, { "family_name": "Mackay", "given_name": "Sean", "clpid": "Mackay-Sean" }, { "family_name": "Dudley", "given_name": "Mark E.", "clpid": "Dudley-Mark-E" }, { "family_name": "Kassim", "given_name": "Sadik H.", "clpid": "Kassim-Sadik-H" }, { "family_name": "Zhou", "given_name": "Jing", "clpid": "Zhou-Jing" } ], "abstract": "Background:\nIt remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies.\n\nMethods:\nWe employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods.\n\nResults:\nWe demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-\u03b3, MIP-1\u03b1, TNF-\u03b1), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors.\n\nConclusions:\nSingle-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high dimensional data requires new visualization methods to further define precise polyfunctional response differences in these products. The presented biomarker capture and analysis system provides a more sensitive and comprehensive functional assessment of CAR-T pre-infusion products and may provide insights into the safety and efficacy of CAR-T cell therapy.", "doi": "10.1186/s40425-017-0293-7", "pmcid": "PMC5697351", "issn": "2051-1426", "publisher": "BioMed Central", "publication": "Journal for ImmunoTherapy of Cancer", "publication_date": "2017-11-21", "volume": "5", "pages": "Art. No. 85" }, { "id": "authors:9te3t-4tb55", "collection": "authors", "collection_id": "9te3t-4tb55", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171127-151753335", "type": "article", "title": "Future cancer research priorities in the USA: a Lancet Oncology Commission", "author": [ { "family_name": "Jaffee", "given_name": "Elizabeth M.", "clpid": "Jaffee-E-M" }, { "family_name": "Davis", "given_name": "Mark", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.", "doi": "10.1016/S1470-2045(17)30698-8", "issn": "1470-2045", "publisher": "Elsevier", "publication": "Lancet Oncology", "publication_date": "2017-11", "series_number": "11", "volume": "18", "issue": "11", "pages": "e653-e706" }, { "id": "authors:ay487-87r41", "collection": "authors", "collection_id": "ay487-87r41", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170913-105300196", "type": "conference_item", "title": "Noncovalent modulation of protien energy landscapes with targeted molecular binders", "author": [ { "family_name": "Bunck", "given_name": "David", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Atsavapranee", "given_name": "Beatriz", "clpid": "Atsavapranee-B" }, { "family_name": "Museth", "given_name": "Katrine", "clpid": "Museth-K" }, { "family_name": "Vander Velde", "given_name": "David", "orcid": "0000-0002-2907-0366", "clpid": "VanderVelde-D-G" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the deterioration of motor neurons\nthat abates essential biol. functions and exhibits survival times of 3 - 5 years after diagnosis. One driver of this\ndisease derives from inherited mutations to the protein superoxide dismutase 1 (SOD1), which hinder proper\nfolding and result in the accumulation of toxic aggregates. We identified cyclic peptides that target precise\nepitopes on SOD1 through an emerging screening platform that furnishes high-affinity binders against regions\nof a protein independent of secondary and tertiary structure. Binding these epitopes both stabilizes the native\nstate and accelerates folding. In this context, these small peptides function as mol. chaperones and mitigate\nthe impact of deleterious mutations to SOD1. They also display the traditional benefits of small mols., such as\nstraightforward chem. modifications and long-term stability. Overall, this method provides a route to rationally perturb the energy landscape of any protein through noncovalent binding, making it useful in fundamental\nstudies of protein folding as well as designing therapeutics for misfolding diseases.", "publisher": "Caltech Library", "publication_date": "2017-08" }, { "id": "authors:dxzvy-k2e29", "collection": "authors", "collection_id": "dxzvy-k2e29", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170912-074421755", "type": "conference_item", "title": "Protein-catalyzed capture agents targeting misfolded superoxide dismutase 1", "author": [ { "family_name": "Atsavapranee", "given_name": "Beatriz", "clpid": "Atsavapranee-B" }, { "family_name": "Bunck", "given_name": "David", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Museth", "given_name": "Katrine", "clpid": "Museth-K" }, { "family_name": "Vander Velde", "given_name": "David", "orcid": "0000-0002-2907-0366", "clpid": "VanderVelde-D-G" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons in the brain and\nspinal cord. Familial ALS can be caused by mutant isoforms of superoxide dismutase 1 (SOD1) that lead the\nprotein to misfold and adopt toxic conformations. Over 180 mutations in SOD1 are linked to the disease,\nmaking it a challenging therapeutic target. Protein-catalyzed capture (PCC) agents are ligands assembled\nthrough in situ click chem. that can bind a protein to stabilize its native conformation. The objective of this\nproject is to develop PCC agents that target SOD1 mutants and reduce misfolding. We used an epitope-targeted\nscreen to identify oligopeptides that bind the electrostatic loop (a region of the protein destabilized\nupon mutation) and an internal fragment (revealed upon misfolding). We anticipate that the PCC agents\nagainst the internal fragment and precleared against the electrostatic loop will bind misfolded SOD1 selectively,\nwhile the PCC agents against the electrostatic loop will detect folded SOD1. This will allow us to discriminate\nbetween the folded and misfolded species. Screens against the electrostatic loop yielded a PCC agent with\npromising ability to recognize SOD1. Ultimately, this ligand might be used to mitigate aggregation of mutant\nisoforms and treat ALS.", "publisher": "Caltech Library", "publication_date": "2017-08" }, { "id": "authors:pq3hw-g7p30", "collection": "authors", "collection_id": "pq3hw-g7p30", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180501-083541019", "type": "conference_item", "title": "High-throughput discovery of Protein catalyzed capture (PCC) agents as antibody alternatives for thermally stable biological assays", "author": [ { "family_name": "Coppock", "given_name": "Matthew", "clpid": "Coppock-M-B" }, { "family_name": "Jones", "given_name": "Curtis", "clpid": "Jones-C" }, { "family_name": "Lai", "given_name": "Bert", "clpid": "Lai-Bert-T" }, { "family_name": "Agnew", "given_name": "Heather", "clpid": "Agnew-H-D" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "There is a significant need for a rapid and streamlined method for the discovery and characterization of high performing,\nthermally stable biol. capture agents for immediate integration into fieldable detection platforms supporting applications such as\nreal-time threat, health, and biometric monitoring. Peptide-based, protein catalyzed capture (PCC) agent technol. has been\nproven to produce such viable antibody alternatives with the added advantages of extreme thermal, chem., and biol. stabilities.\nHowever current development of new PCC agents requires a few months to complete. As a result, we have accelerated the\ndiscovery time of PCC agents to a couple of weeks through the creation of an original microchip-based assay platform, use of\nautomated screening platforms, and establishment of computer modeling algorithms. The discovery method improvements\nhave been exploited to develop novel capture agents on well-characterized immune system biomarker protein targets that are\nhighly relevant for soldier performance monitoring.", "publisher": "Caltech Library", "publication_date": "2017-08" }, { "id": "authors:2szk9-x7p52", "collection": "authors", "collection_id": "2szk9-x7p52", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180108-091251718", "type": "article", "title": "Understanding cancer phenomena using a thermodynamic-based approach", "author": [ { "family_name": "Flashner-Abramson", "given_name": "E.", "clpid": "Flashner-Abramson-E" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" }, { "family_name": "Kravchenko-Balasha", "given_name": "N.", "clpid": "Kravchenko-Balasha-N" } ], "abstract": "We seek to address fundamental questions in cancer biology\nby an experimental-theoretical approach based on physicochemical laws. We have recently pioneered the application of the thermodynamic-based surprisal analysis, which has been previously applied to systems in chemistry and physics, to biological processes. We have shown that through the accurate resolution of the protein networks that deviate the cancer system from its balanced state, various biological phenotypes can be predicted. For example, we have demonstrated that using a thermodynamic-based proteomic analysis in varying cell-cell distances, the direction of movement of brain cancer cells can be predicted and experimentally manipulated. Here we present single cell and bulk proteomic methods integrated with thermodynamic-derived information theory.\nWe demonstrate how complex biological phenomena, such\nas cellular tumor architectures or inter-tumor variability can\nbe modeled using a limited number of key physical parameters.\nFurthermore we show how these parameters are used\nto predict cellular architectures or to design high-precision,\npatient-specific drug cocktails. Generally speaking, this approach\nprovides a framework that models biological systems\nin order to learn how to predict and manipulate their behavior.", "doi": "10.1007/s00249-017-1222-x", "issn": "0175-7571", "publisher": "Springer", "publication": "European Biophysics Journal", "publication_date": "2017-07", "series_number": "S1", "volume": "46", "issue": "S1", "pages": "S274" }, { "id": "authors:rjcpf-jv585", "collection": "authors", "collection_id": "rjcpf-jv585", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170508-154538447", "type": "conference_item", "title": "Noncovalent modulation of protein energy landscapes with an emerging class of cyclic-peptide chaperones", "author": [ { "family_name": "Bunck", "given_name": "David N.", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Atsavaprannee", "given_name": "Beatriz", "clpid": "Atsavapranee-B" }, { "family_name": "Museth", "given_name": "Katrine", "clpid": "Museth-K" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the deterioration of motor neurons that abates essential biol. functions and exhibits survival times of 3 - 5 years after diagnosis. One driver of this disease derives from inherited mutations to the protein superoxide dismutase 1 (SOD1), which hinder proper folding and result in the accumulation of toxic aggregates. We identified cyclic peptides that target precise epitopes on SOD1 through a new high-throughput screening platform that furnishes high-affinity binders against regions of a protein independent of secondary and tertiary structure.\nBinding these epitopes both stabilizes the native state and accelerates folding. In this context, these small peptides function as mol. chaperones and mitigate the impact of deleterious mutations to SOD1. They also display the traditional benefits of small mols., such as straightforward chem. modifications and long-term stability. Overall, this method provides a route to rationally perturb the energy landscape of any protein through noncovalent binding, making it useful in fundamental studies of protein folding as well as designing therapeutics for misfolding diseases.", "publisher": "Caltech Library", "publication_date": "2017-04" }, { "id": "authors:5wwqh-z5130", "collection": "authors", "collection_id": "5wwqh-z5130", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170509-105319622", "type": "conference_item", "title": "Development of a high-throughput immunofluorescence assay platform using a DNA-encoded streptavidin library for the rapid evaluation of protein-catalyzed capture agents", "author": [ { "family_name": "McCarthy", "given_name": "Amy", "clpid": "McCarthy-A" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Henning", "given_name": "Ryan", "clpid": "Henning-R-K" }, { "family_name": "Mishra", "given_name": "Anvita", "clpid": "Mishra-A" }, { "family_name": "Ng", "given_name": "Rachel", "clpid": "Ng-Rachel" }, { "family_name": "Museth", "given_name": "Anna", "clpid": "Museth-A-K" }, { "family_name": "Heath", "given_name": "John", "clpid": "Heath-John" }, { "family_name": "Winson", "given_name": "Emma", "clpid": "Winson-E" }, { "family_name": "Oh", "given_name": "JunHyuck", "clpid": "Oh-JunHyuck" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Protein Catalyzed Capture (PCC) Agents are an emergent class of macrocyclic peptides that selectively bind, with low NM affinities, to unique epitopes of specific proteins, such as oncoproteins and blood protein biomarkers. The development of a PCC binder is a robust process that involves screening a two million elements one-bead-one-compd. (OBOC) macrocyclic peptide library against a synthetic polypeptide representing the epitope of interest. A single generation screen is sufficient to identify\ncandidate PCC ligands. Each candidate is tested via a series of binding assays to identify a PCC with optimal avidity characteristics. Such testing requires running multiple binding curve assays in series. We report on a high-throughput, microchip-based platform for the rapid development of PCCs. Individual PCC candidates are prepd. with a biotin label, coupled onto individual members of a DNA-encoded streptavidin library (DESL), and assembled, via DNA-hybridization, onto a micropatterned DNA barcode located within a microwell of a multi-well chip. The platform allows for the simultaneous evaluation of fifteen different PCC ligands in up to sixteen different assay conditions on a single microchip. Addnl., the barcode\nsurface chem. reduces the non-specific background commonly seen in a sandwich ELISA (ELISA). We compare the barcode platform against traditional sandwich ELISA assays, and then utilize it to identify allosteric binders against the KRAS protein.", "publisher": "Caltech Library", "publication_date": "2017-04" }, { "id": "authors:exx2e-2wa03", "collection": "authors", "collection_id": "exx2e-2wa03", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170221-160921243", "type": "article", "title": "High-throughput screening of rare metabolically active tumor cells in pleural effusion and peripheral blood of lung cancer patients", "author": [ { "family_name": "Tang", "given_name": "Yin", "clpid": "Tang-Yin" }, { "family_name": "Wang", "given_name": "Zhuo", "clpid": "Wang-Zhuo" }, { "family_name": "Li", "given_name": "Ziming", "clpid": "Li-Ziming" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Deng", "given_name": "Yuliang", "clpid": "Deng-Yuliang" }, { "family_name": "Li", "given_name": "Yan", "clpid": "Li-Yan" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Lu", "given_name": "Shun", "clpid": "Lu-Shun" }, { "family_name": "Shi", "given_name": "Qihui", "clpid": "Shi-Qihui" } ], "abstract": "Malignant pleural effusion (MPE), the presence of malignant cells in pleural fluid, is often the first sign of many cancers and occurs in patients with metastatic malignancies. Accurate detection of tumor cells in pleural fluid is crucial because the presence of MPE denotes an advanced stage of disease and directs a switch in clinical managements. Cytology, as a traditional diagnostic tool, has limited sensitivity especially when tumor cells are not abundant, and may be confounded by reactive mesothelial cells in the pleural fluid. We describe a highly sensitive approach for rapid detection of metabolically active tumor cells in MPE via exploiting the altered glucose metabolism of tumor cells relative to benign cells. Metabolically active tumor cells with high glucose uptake, as evaluated by a fluorescent glucose analog (2-NBDG), are identified by high-throughput fluorescence screening within a chip containing 200,000 addressable microwells and collected for malignancy confirmation via single-cell sequencing. We demonstrate the utility of this approach through analyzing MPE from a cohort of lung cancer patients. Most candidate tumor cells identified are confirmed to harbor the same driver oncogenes as their primary lesions. In some patients, emergence of secondary mutations that mediate acquired resistance to ongoing targeted therapies is also detected before resistance is manifested in the clinical imaging. The detection scheme can be extended to analyze peripheral blood samples. Our approach may serve as a valuable complement to cytology in MPE diagnosis, helping identify the driver oncogenes and resistance-leading mutations for targeted therapies.", "doi": "10.1073/pnas.1612229114", "pmcid": "PMC5347549", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2017-03-07", "series_number": "10", "volume": "114", "issue": "10", "pages": "2544-2549" }, { "id": "authors:1xdp5-x1566", "collection": "authors", "collection_id": "1xdp5-x1566", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180117-161110844", "type": "article", "title": "Technologies for personalizing cancer immunotherapies", "author": [ { "family_name": "Peng", "given_name": "Songming", "orcid": "0000-0002-2742-6584", "clpid": "Peng-Songming" }, { "family_name": "Zaretsky", "given_name": "Jesse", "clpid": "Zaretsky-J" }, { "family_name": "Bethune", "given_name": "Michael", "clpid": "Bethune-M-T" }, { "family_name": "Hsu", "given_name": "Alice", "clpid": "Hsu-Alice" }, { "family_name": "Heath", "given_name": "John E.", "clpid": "Heath-J-E" }, { "family_name": "Noh", "given_name": "Won Jun", "clpid": "Noh-Won-Jun" }, { "family_name": "Esswein", "given_name": "Shannon", "clpid": "Esswein-S" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-Antoni" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "At the heart of most cancer immunotherapies are the specific interactions between tumor-infiltrating T cells, and the antigens that attract those T cells into the tumor. It has become increasingly apparent that (mutation containing) neoantigens likely play an important role in this regard. Putative neoantigens are identified by tumor exome analysis, but finding which of those candidates actually promote T cell tumor infiltration is challenging, as is pairing such antigens with the cognate T cell receptor (TCR) genes. Technologies that can address this challenge can help pave the way for personalized immunotherapies. For example, the active neoantigens can be engineered into personalized cell-based cancer vaccines, while the cognate TCRs represent engineered T cell therapy opportunities. I will discuss a nanotech/microchip tool that we have recently developed to address this challenge. The platform allows for the non-destructive enumeration of neoantigen specific T cell populations from either tumor infiltrating lymphocytes (TILs) or unexpanded peripheral blood mononuclear cells (PBMCs), beginning with as few as 10,000 CD8+ cells. I will discuss the application of the platform for kinetic studies of patient responses to checkpoint inhibitor therapy (via blood analysis), as well as applications for matching neoantigen-specificity with T cell receptor genes. I will also discuss how the resultant data can be used to guide the refinement of neoantigen prediction algorithms.", "doi": "10.1158/2326-6074.TUMIMM16-IA17", "issn": "2326-6066", "publisher": "American Association for Cancer Research", "publication": "Cancer Immunology Research", "publication_date": "2017-03", "series_number": "S3", "volume": "5", "issue": "S3", "pages": "IA17" }, { "id": "authors:wjh5f-zjv21", "collection": "authors", "collection_id": "wjh5f-zjv21", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160901-081827918", "type": "article", "title": "Protein Catalyzed Capture Agents with Tailored Performance for In Vitro and In Vivo Applications", "author": [ { "family_name": "Coppock", "given_name": "Matthew B.", "clpid": "Coppock-Matthew-B" }, { "family_name": "Warner", "given_name": "Candice R.", "clpid": "Warner-Candice-R" }, { "family_name": "Dorsey", "given_name": "Brandi", "clpid": "Dorsey-Brandi" }, { "family_name": "Orlicki", "given_name": "Joshua A.", "clpid": "Orlicki-Joshua-A" }, { "family_name": "Sarkes", "given_name": "Deborah A.", "clpid": "Sarkes-Deborah-A" }, { "family_name": "Lai", "given_name": "Bert T.", "clpid": "Lai-Bert-T" }, { "family_name": "Pitram", "given_name": "Suresh M.", "clpid": "Pitram-Suresh-M" }, { "family_name": "Rohde", "given_name": "Rosemary D.", "clpid": "Rohde-Rosemary-D" }, { "family_name": "Malette", "given_name": "Jacquie", "clpid": "Malette-Jacquie" }, { "family_name": "Wilson", "given_name": "Jer\u00e9 A.", "clpid": "Wilson-Jer\u00e9-A" }, { "family_name": "Kearney", "given_name": "Paul", "clpid": "Kearney-Paul" }, { "family_name": "Fang", "given_name": "Kenneth C.", "clpid": "Fang-Kenneth-C" }, { "family_name": "Law", "given_name": "Scott M.", "clpid": "Law-Scott-M" }, { "family_name": "Candelario", "given_name": "Sherri L.", "clpid": "Candelario-Sherri-L" }, { "family_name": "Farrow", "given_name": "Blake", "clpid": "Farrow-Blake" }, { "family_name": "Finch", "given_name": "Amethist S.", "clpid": "Finch-Amethist-S" }, { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-Heather-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stratis-Cullum", "given_name": "Dimitra N.", "clpid": "Stratis-Cullum-Dimitra-N" } ], "abstract": "We report on peptide-based ligands matured through the protein catalyzed capture (PCC) agent method to tailor molecular binders for in vitro sensing/diagnostics and in vivo pharmacokinetics parameters. A vascular endothelial growth factor (VEGF) binding peptide and a peptide against the protective antigen (PA) protein of Bacillus anthracis discovered through phage and bacterial display panning technologies, respectively, were modified with click handles and subjected to iterative in situ click chemistry screens using synthetic peptide libraries. Each azide-alkyne cycloaddition iteration, promoted by the respective target proteins, yielded improvements in metrics for the application of interest. The anti-VEGF PCC was explored as a stable in vivo imaging probe. It exhibited excellent stability against proteases and a mean elimination in vivo half-life (T_(1/2)) of 36 min. Intraperitoneal injection of the reagent results in slow clearance from the peritoneal cavity and kidney retention at extended times, while intravenous injection translates to rapid renal clearance. The ligand competed with the commercial antibody for binding to VEGF in vivo. The anti-PA ligand was developed for detection assays that perform in demanding physical environments. The matured anti-PA PCC exhibited no solution aggregation, no fragmentation when heated to 100\u00b0C, and \u2009>\u200981% binding activity for PA after heating at 90\u00b0C for 1 h. We discuss the potential of the PCC agent screening process for the discovery and enrichment of next generation antibody alternatives.", "doi": "10.1002/bip.22934", "pmcid": "PMC6585716", "issn": "0006-3525", "publisher": "Wiley", "publication": "Biopolymers", "publication_date": "2017-03", "series_number": "2", "volume": "108", "issue": "2", "pages": "Art. No. e22934" }, { "id": "authors:64fws-xye06", "collection": "authors", "collection_id": "64fws-xye06", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170623-103813691", "type": "article", "title": "Modulating SOD1 Folding Landscapes with Targeted Molecular Binders", "author": [ { "family_name": "Bunck", "given_name": "David N.", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Atsavapranee", "given_name": "Beatriz", "clpid": "Atsavapranee-B" }, { "family_name": "Museth", "given_name": "Katrine", "clpid": "Museth-K" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the deterioration of motor neurons that abates essential biological functions and exhibits survival times of 3 - 5 years after diagnosis. One driver of this disease derives from inherited mutations to the protein superoxide dismutase 1 (SOD1), which hinder proper folding and result in the accumulation of toxic aggregates. We identified cyclic peptides that target precise epitopes on SOD1 through an emerging screening platform that furnishes high-affinity binders against regions of a protein independent of secondary or tertiary structure. Binding these epitopes both stabilizes the native state and accelerates folding. In this context, these small peptides function as molecular chaperones and mitigate the impact of deleterious mutations to SOD1. They also display the traditional benefits of small molecules, such as straightforward chemical modifications and long-term stability. Overall, this method provides a route to rationally perturb the energy landscape of any protein through noncovalent binding, making it useful in fundamental studies of protein folding as well as designing therapeutics for misfolding diseases.", "doi": "10.1016/j.bpj.2016.11.928", "issn": "0006-3495", "publisher": "Biophysical Society", "publication": "Biophysical Journal", "publication_date": "2017-02-03", "series_number": "3, Supp. 1", "volume": "112", "issue": "3, Supp. 1", "pages": "168a" }, { "id": "authors:nwc15-6na78", "collection": "authors", "collection_id": "nwc15-6na78", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170417-132212986", "type": "article", "title": "Single cell functional proteomics and metabolomics: A conduit to physicochemical models of tumor biology", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "In this talk, I will discuss provide detail on the above described experimental platforms, and describe how analyses based on these concepts can yield insight into clinically meaningful problems associated with therapy resistance in glioblastoma and melanoma.", "doi": "10.1158/1538-7445.EPSO16-IA07", "issn": "0008-5472", "publisher": "American Association for Cancer Research", "publication": "Cancer Research", "publication_date": "2017-01", "series_number": "S2", "volume": "77", "issue": "S2", "pages": "Art. No. IA07" }, { "id": "authors:p803x-hc548", "collection": "authors", "collection_id": "p803x-hc548", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161104-095700365", "type": "article", "title": "Domain-swapped T cell receptors improve the safety of TCR gene therapy", "author": [ { "family_name": "Bethune", "given_name": "Michael T.", "clpid": "Bethune-Michael-T" }, { "family_name": "Gee", "given_name": "Marvin H.", "clpid": "Gee-Marvin-H" }, { "family_name": "Bunse", "given_name": "Mario", "clpid": "Bunse-Mario" }, { "family_name": "Lee", "given_name": "Mark S.", "clpid": "Lee-Mark-S" }, { "family_name": "Gschweng", "given_name": "Eric H.", "clpid": "Gschweng-Eric-H" }, { "family_name": "Pagadala", "given_name": "Meghana S.", "clpid": "Pagadala-Meghana-S" }, { "family_name": "Zhou", "given_name": "Jing", "clpid": "Zhou-Jing" }, { "family_name": "Cheng", "given_name": "Donghui", "clpid": "Cheng-Donghui" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Kohn", "given_name": "Donald B.", "clpid": "Kohn-Donald-B" }, { "family_name": "Kuhns", "given_name": "Michael S.", "clpid": "Kuhn-Michael-S" }, { "family_name": "Uckert", "given_name": "Wolfgang", "clpid": "Uckert-Wolfgang" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" } ], "abstract": "T cells engineered to express a tumor-specific \u03b1\u03b2 T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic \u03b1\u03b2 chains with endogenous \u03b1\u03b2 chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the \u03b1 and \u03b2 chains of a therapeutic TCR. When paired, domain-swapped (ds)TCRs assemble with CD3, express on the cell surface, and mediate antigen-specific T cell responses. By contrast, dsTCR chains mispaired with endogenous chains cannot properly assemble with CD3 or signal, preventing autoimmunity. We validate this approach in cell-based assays and in a mouse model of TCR gene transfer-induced graft-versus-host disease. We also validate a related approach whereby replacement of \u03b1\u03b2 TCR domains with corresponding \u03b3\u03b4 TCR domains yields a functional TCR that does not mispair. This work enables the design of safer TCR gene therapies for cancer immunotherapy.", "doi": "10.7554/eLife.19095", "pmcid": "PMC5101000", "issn": "2050-084X", "publisher": "eLife Sciences Publications", "publication": "eLife", "publication_date": "2016-11-08", "volume": "5", "pages": "Art. No. e19095" }, { "id": "authors:jx2e2-gz075", "collection": "authors", "collection_id": "jx2e2-gz075", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160714-113801517", "type": "article", "title": "A Thermodynamic-Based Interpretation of Protein Expression Heterogeneity in Different Glioblastoma Multiforme Tumors Identifies Tumor-Specific Unbalanced Processes", "author": [ { "family_name": "Kravchenko-Balasha", "given_name": "Nataly", "clpid": "Kravchenko-Balasha-N" }, { "family_name": "Johnson", "given_name": "Hannah", "clpid": "Johnson-Hannah" }, { "family_name": "White", "given_name": "Forest M.", "clpid": "White-F-M" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" } ], "abstract": "We describe a thermodynamic-motivated, information theoretic analysis of proteomic data collected from a series of 8 glioblastoma multiforme (GBM) tumors. GBMs are considered here as prototypes of heterogeneous cancers. That heterogeneity is viewed here as manifesting in different unbalanced biological processes that are associated with thermodynamic-like constraints. The analysis yields a molecular description of a stable steady state that is common across all tumors. It also resolves molecular descriptions of unbalanced processes that are shared by several tumors, such as hyperactivated phosphoprotein signaling networks. Further, it resolves unbalanced processes that provide unique classifiers of tumor subgroups. The results of the theoretical interpretation are compared against those of statistical multivariate methods and are shown to provide a superior level of resolution for identifying unbalanced processes in GBM tumors. The identification of specific constraints for each GBM tumor suggests tumor-specific combination therapies that may reverse this imbalance.", "doi": "10.1021/acs.jpcb.6b01692", "pmcid": "PMC4937832", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2016-07-07", "series_number": "26", "volume": "120", "issue": "26", "pages": "5990-5997" }, { "id": "authors:d1zd3-z8x97", "collection": "authors", "collection_id": "d1zd3-z8x97", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160531-154453881", "type": "article", "title": "Harry Kroto (1939-2016)", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Curl", "given_name": "Robert F.", "clpid": "Curl-R-F" } ], "abstract": "Harry Kroto was part of the team that discovered buckminsterfullerene, the football-shaped carbon-60 molecule that came to be known as a buckyball. The realization that such a large molecule could self-assemble from hot carbon vapour forced a reassessment of the science of carbon. By prompting searches for other structures \u2014 carbon nanotubes and nanowires were among the materials later found \u2014 the discovery ultimately provided a foundation for nanoscience and nanotechnology.", "doi": "10.1038/533470a", "issn": "0028-0836", "publisher": "Nature Publishing Group", "publication": "Nature", "publication_date": "2016-05-25", "series_number": "7604", "volume": "533", "issue": "7604", "pages": "470-470" }, { "id": "authors:y6477-hn656", "collection": "authors", "collection_id": "y6477-hn656", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160503-072858145", "type": "article", "title": "Intercellular signaling through secreted proteins induces free-energy gradient-directed cell movement", "author": [ { "family_name": "Kravchenko-Balasha", "given_name": "Nataly", "orcid": "0000-0001-6943-7479", "clpid": "Kravchenko-Balasha-Nataly" }, { "family_name": "Shin", "given_name": "Young Shik", "orcid": "0000-0002-1097-9035", "clpid": "Shin-Young-Shik" }, { "family_name": "Sutherland", "given_name": "Alex", "clpid": "Sutherland-Alex" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-Raphael-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Controlling cell migration is important in tissue engineering and medicine. Cell motility depends on factors such as nutrient concentration gradients and soluble factor signaling. In particular, cell\u2013cell signaling can depend on cell\u2013cell separation distance and can influence cellular arrangements in bulk cultures. Here, we seek a physical-based approach, which identifies a potential governed by cell\u2013cell signaling that induces a directed cell\u2013cell motion. A single-cell barcode chip (SCBC) was used to experimentally interrogate secreted proteins in hundreds of isolated glioblastoma brain cancer cell pairs and to monitor their relative motions over time. We used these trajectories to identify a range of cell\u2013cell separation distances where the signaling was most stable. We then used a thermodynamics-motivated analysis of secreted protein levels to characterize free-energy changes for different cell\u2013cell distances. We show that glioblastoma cell\u2013cell movement can be described as Brownian motion biased by cell\u2013cell potential. To demonstrate that the free-energy potential as determined by the signaling is the driver of motion, we inhibited two proteins most involved in maintaining the free-energy gradient. Following inhibition, cell pairs showed an essentially random Brownian motion, similar to the case for untreated, isolated single cells.", "doi": "10.1073/pnas.1602171113", "pmcid": "PMC4878481", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2016-05-17", "series_number": "20", "volume": "113", "issue": "20", "pages": "5520-5525" }, { "id": "authors:yvyne-3aa19", "collection": "authors", "collection_id": "yvyne-3aa19", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160414-085615562", "type": "article", "title": "Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma", "author": [ { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Shin", "given_name": "Young Shik", "orcid": "0000-0002-1097-9035", "clpid": "Shin-Young-Shik" }, { "family_name": "Xue", "given_name": "Min", "orcid": "0000-0002-8136-6551", "clpid": "Xue-Min" }, { "family_name": "Matsutani", "given_name": "Tomoo", "clpid": "Matsutani-Tomoo" }, { "family_name": "Masui", "given_name": "Kenta", "orcid": "0000-0002-5824-6690", "clpid": "Masui-Kenta" }, { "family_name": "Yang", "given_name": "Huijun", "clpid": "Yang-Huijun" }, { "family_name": "Ikegami", "given_name": "Shiro", "clpid": "Ikegami-Shiro" }, { "family_name": "Gu", "given_name": "Yuchao", "clpid": "Gu-Yuchao" }, { "family_name": "Herrmann", "given_name": "Ken", "orcid": "0000-0002-9662-7259", "clpid": "Herrmann-Ken" }, { "family_name": "Johnson", "given_name": "Dazy", "orcid": "0000-0001-6311-8629", "clpid": "Johnson-Dazy" }, { "family_name": "Ding", "given_name": "Xiangming", "clpid": "Ding-Xiangming" }, { "family_name": "Hwang", "given_name": "Kiwook", "clpid": "Hwang-Kiwook" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Zhou", "given_name": "Jian", "clpid": "Zhou-Jian" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Li", "given_name": "Xinmin", "clpid": "Li-Xinmin" }, { "family_name": "Bonetti", "given_name": "Bruno", "orcid": "0000-0002-3944-4165", "clpid": "Bonetti-Bruno" }, { "family_name": "Chopra", "given_name": "Rajesh", "clpid": "Chopra-Rajesh" }, { "family_name": "James", "given_name": "C. David", "clpid": "James-C-David" }, { "family_name": "Cavenee", "given_name": "Webster K.", "orcid": "0000-0003-3804-9179", "clpid": "Cavenee-Webster-K" }, { "family_name": "Cloughesy", "given_name": "Timothy F.", "orcid": "0000-0002-8656-7483", "clpid": "Cloughesy-Timothy-F" }, { "family_name": "Mischel", "given_name": "Paul S.", "orcid": "0000-0002-4560-2211", "clpid": "Mischel-Paul-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Gini", "given_name": "Beatrice", "orcid": "0000-0001-6095-1500", "clpid": "Gini-Beatrice" } ], "abstract": "Intratumoral heterogeneity of signaling networks may contribute to targeted cancer therapy resistance, including in the highly lethal brain cancer glioblastoma (GBM). We performed single-cell phosphoproteomics on a patient-derived in vivo GBM model of mTOR kinase inhibitor resistance and coupled it to an analytical approach for detecting changes in signaling coordination. Alterations in the protein signaling coordination were resolved as early as 2.5 days after treatment, anticipating drug resistance long before it was clinically manifest. Combination therapies were identified that resulted in complete and sustained tumor suppression in vivo. This approach may identify actionable alterations in signal coordination that underlie adaptive resistance, which can be suppressed through combination drug therapy, including non-obvious drug combinations.", "doi": "10.1016/j.ccell.2016.03.012", "pmcid": "PMC4831071", "issn": "1535-6108", "publisher": "Cell Press", "publication": "Cancer Cell", "publication_date": "2016-04-11", "series_number": "4", "volume": "29", "issue": "4", "pages": "563-573" }, { "id": "authors:h3kp2-yjf54", "collection": "authors", "collection_id": "h3kp2-yjf54", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160222-101242946", "type": "article", "title": "Degradation of Akt using protein-catalyzed capture agents", "author": [ { "family_name": "Henning", "given_name": "Ryan K.", "clpid": "Henning-Ryan-K" }, { "family_name": "Varghese", "given_name": "Joseph O.", "clpid": "Varghese-Joseph-O" }, { "family_name": "Das", "given_name": "Samir", "clpid": "Das-Samir" }, { "family_name": "Nag", "given_name": "Arundhati", "orcid": "0000-0002-1328-1695", "clpid": "Nag-Arundhati" }, { "family_name": "Tang", "given_name": "Grace", "clpid": "Tang-Grace" }, { "family_name": "Tang", "given_name": "Kevin", "clpid": "Tang-Kevin" }, { "family_name": "Sutherland", "given_name": "Alexander M.", "clpid": "Sutherland-Alexander-M" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Abnormal signaling of the protein kinase Akt has been shown to contribute to human diseases such as diabetes and cancer, but Akt has proven to be a challenging target for drugging. Using iterative in situ click chemistry, we recently developed multiple protein-catalyzed capture (PCC) agents that allosterically modulate Akt enzymatic activity in a protein-based assay. Here, we utilize similar PCCs to exploit endogenous protein degradation pathways. We use the modularity of the anti-Akt PCCs to prepare proteolysis targeting chimeric molecules that are shown to promote the rapid degradation of Akt in live cancer cells. These novel proteolysis targeting chimeric molecules demonstrate that the epitope targeting selectivity of PCCs can be coupled with non-traditional drugging moieties to inhibit challenging targets.", "doi": "10.1002/psc.2858", "pmcid": "PMC4883657", "issn": "1075-2617", "publisher": "Wiley", "publication": "Journal of Peptide Science", "publication_date": "2016-04", "series_number": "4", "volume": "22", "issue": "4", "pages": "196-200" }, { "id": "authors:3kent-ks544", "collection": "authors", "collection_id": "3kent-ks544", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160125-133909554", "type": "article", "title": "Critical Points in Tumorigenesis: A Carcinogen-Initiated Phase Transition Analyzed via Single-Cell Proteomics", "author": [ { "family_name": "Poovathingal", "given_name": "Suresh Kumar", "clpid": "Poovathingal-Suresh-Kumar" }, { "family_name": "Kravchenko-Balasha", "given_name": "Nataly", "orcid": "0000-0001-6943-7479", "clpid": "Kravchenko-Balasha-Nataly" }, { "family_name": "Shin", "given_name": "Young Shik", "orcid": "0000-0002-1097-9035", "clpid": "Shin-Young-Shik" }, { "family_name": "Levine", "given_name": "Raphael David", "clpid": "Levine-Raphael-David" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A kinetic, single-cell proteomic study of chemically induced carcinogenesis is interpreted by treating the single-cell data as fluctuations of an open system transitioning between different steady states. In analogy to a first-order transition, phase coexistence and the loss of degrees of freedom are observed. The transition is detected well before the appearance of the traditional biomarker of the carcinogenic transformation.", "doi": "10.1002/smll.201501178", "pmcid": "PMC4886749", "issn": "1613-6810", "publisher": "Wiley", "publication": "Small", "publication_date": "2016-03-16", "series_number": "11", "volume": "12", "issue": "11", "pages": "1425-1431" }, { "id": "authors:cy9yh-gvq75", "collection": "authors", "collection_id": "cy9yh-gvq75", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160307-080722516", "type": "article", "title": "Supramolecular Probes for Assessing Glutamine Uptake Enable Semi-Quantitative Metabolic Models in Single Cells", "author": [ { "family_name": "Xue", "given_name": "Min", "orcid": "0000-0002-8136-6551", "clpid": "Xue-Min" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Johnson", "given_name": "Dazy", "orcid": "0000-0001-6311-8629", "clpid": "Johnson-Dazy" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We describe a supramolecular surface competition assay for quantifying glutamine uptake from single cells. Cy3-labeled cyclodextrins were immobilized on a glass surface as a supramolecular host/FRET donor, and adamantane-BHQ2 conjugates were employed as the guest/quencher. An adamantane-labeled glutamine analog was selected through screening a library of compounds and validated by cell uptake experiments. When integrated onto a single cell barcode chip with a multiplex panel of 15 other metabolites, associated metabolic enzymes, and phosphoproteins, the resultant data provided input for a steady-state model that describes energy potential in single cells and correlates that potential with receptor tyrosine kinase signaling. We utilize this integrated assay to interrogate a dose-dependent response of model brain cancer cells to EGFR inhibition. We find that low-dose (1 \u03bcM erlotinib) drugging actually increases cellular energy potential even as glucose uptake and phosphoprotein signaling is repressed. We also identify new interactions between phosphoprotein signaling and cellular energy processes that may help explain the facile resistance exhibited by certain cancer patients to EGFR inhibitors.", "doi": "10.1021/jacs.5b12187", "pmcid": "PMC4887079", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2016-03-09", "series_number": "9", "volume": "138", "issue": "9", "pages": "3085-3093" }, { "id": "authors:fx8vs-0vg68", "collection": "authors", "collection_id": "fx8vs-0vg68", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160404-113003421", "type": "conference_item", "title": "Rapid discovery of peptidomimetics as antibody alternatives via epitope-targeted screening", "author": [ { "family_name": "Liang", "given_name": "Jing Xin", "clpid": "Liang-Jing-Xin" }, { "family_name": "Nag", "given_name": "Arundhati", "clpid": "Nag-A" }, { "family_name": "Das", "given_name": "Samir", "clpid": "Das-S" }, { "family_name": "Bunck", "given_name": "David", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Umeda", "given_name": "Aiko", "clpid": "Umeda-Aiko" }, { "family_name": "McCarthy", "given_name": "Amy", "clpid": "McCarthy-A" }, { "family_name": "Mishra", "given_name": "Anvita", "clpid": "Mishra-A" }, { "family_name": "Heath", "given_name": "John", "clpid": "Heath-John" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on the development of peptide-based ligands as antibody alternatives for protein recognition. In\nthe developing world, antibody(Ab)-based rapid diagnostic tests (RDTs) are the preferred method of disease\ndetection for their ease-of-use and low cost relative to techniques such as microscopy and PCR. However, the\nperformance and reliability of RDTs to detect biomarkers are severely hindered by the limitations of Abs. Abs\nare expensive biomols. that have batch-to-batch variability, exhibit cross-reactivity, and target a single site on a\nprotein. As a result, Abs cannot always sensitively distinguish between disease biomarkers or detect highly\npolymorphic proteins. Peptide-based ligands are low-cost alternatives to Abs that can be engineered to bind\nspecific protein targets with high affinity. They can be adapted to simultaneously target multiple epitopes,\ndistinguish between homologous structures, and detect proteins with high sequence diversity. We employ a\nhigh throughput epitope-targeted screening protocol with combinatorial peptide libraries to rapidly discover\nligands for protein recognition. We apply our peptide-based ligands as biosensors towards challenging protein\ntargets for the development of Ab-free RDTs.", "publisher": "Caltech Library", "publication_date": "2016-03" }, { "id": "authors:11b4v-nka11", "collection": "authors", "collection_id": "11b4v-nka11", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160331-123801152", "type": "conference_item", "title": "Circle Akt In: Macrocycles against phosphorylated Akt", "author": [ { "family_name": "Nag", "given_name": "Arundhati", "clpid": "Nag-A" }, { "family_name": "Das", "given_name": "Samir", "clpid": "Das-S" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "An approach to targeting traditionally 'undruggable' target proteins using macrocyclic peptide based affinity\nreagent is demonstrated. An unbiased comprehensive Cu-catalyzed Azide Alkyne Cycloaddn. cyclized peptide\nmacrocyclic library is synthesized and screened against the phoshoS474 contg. Hydrophobic Motif (HM) peptide\nepitope of Akt2. The best macrocyclic ligand, which exhibits specificity at the peptide and protein levels, is\nfurther extended through an in situ click screen to yield bivalent macrocyclic reagent with high affinity and\nspecificity. The bivalent peptide, targeted against the phosphor-S474 region of Akt2, inhibits the Akt2 kinase in\nvitro. This ligand is being optimized, through medicinal chem. iterations, to improve its in vivo characteristics,\nso that its effects can be studied in relevant carcinoma cell lines. The optimized macrocyclic peptide can\neventually be used as an in vivo imaging probe.", "publisher": "Caltech Library", "publication_date": "2016-03" }, { "id": "authors:4cnps-xw302", "collection": "authors", "collection_id": "4cnps-xw302", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151222-085917708", "type": "article", "title": "Single-cell analysis tools for drug discovery and development", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-A" }, { "family_name": "Mischel", "given_name": "Paul S.", "clpid": "Mischel-P-S" } ], "abstract": "The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for single-cell genomic, transcriptomic and multiplex proteomic analyses. Here, we review these tools and assess their advantages and limitations. Emerging applications of single cell analysis tools in drug discovery and development, particularly in the field of oncology, are discussed.", "doi": "10.1038/nrd.2015.16", "pmcid": "PMC4883669", "issn": "1474-1776", "publisher": "Nature Publishing Group", "publication": "Nature Reviews Drug Discovery", "publication_date": "2016-03", "series_number": "3", "volume": "15", "issue": "3", "pages": "204-216" }, { "id": "authors:awnxt-03q53", "collection": "authors", "collection_id": "awnxt-03q53", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160331-090220230", "type": "conference_item", "title": "Mimicking protein functions with entropically constrained peptides", "author": [ { "family_name": "Farrow", "given_name": "Blake", "clpid": "Farrow-B" }, { "family_name": "Wang", "given_name": "Andrew", "clpid": "Wang-Andrew-G" }, { "family_name": "Deyle", "given_name": "Kaycie", "clpid": "Deyle-K-M" }, { "family_name": "Bunck", "given_name": "David", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The biol. functions of proteins, from mol. recognition to enzymic activity, depend on the thermodn. stability of a\nconformationally constrained folded structure which positions a small no. of amino acid residues in an appropriate position\nand orientation to carry out their intended function. Most proteins use many weak interactions along a long polypeptide chain\nto pay the entropic penalty of occupying the native state, though there are examples in biol. of short polypeptides which use a\nfew strong or covalent interactions to stabilize a rigid structure. We have developed a completely synthetic high throughput\nscreening platform capable of identifying conformationally constrained macrocyclic peptides with a well- defined biol.\nfunction. Proximity- catalyzed in situ click enables discovery of short constrained peptides capable of binding to a chosen site\non a protein surface with no requirements for binding pockets or naturally addressable residues in a manner analogous to\nmonoclonal antibodies. We have successfully targeted post- translational modifications, single amino acid mutations and novel\nexosites which have revealed new avenues for drug discovery. The modularity of peptide chem. and use of non- natural amino\nacid residues has enabled the engineering of superb biol., chem. and thermal stability in candidate diagnostic and therapeutic\nmols. Recently, discovery of constrained peptides capable of mimicking biol. activity on small mol. targets is made possible\nthrough the use of suicide substrate activity- based probes in our screens. Short constrained peptide motifs capable of\nactivating natural residues and non- natural cofactor mimics for nucleophilic attack and decarboxylation have been identified.", "publisher": "Caltech Library", "publication_date": "2016-03" }, { "id": "authors:8gghn-9pz16", "collection": "authors", "collection_id": "8gghn-9pz16", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160606-134847419", "type": "article", "title": "Detection of a Geographically Diverse Malarial Biomarker via Multi-Epitope Targeted Screening", "author": [ { "family_name": "Liang", "given_name": "JingXin", "orcid": "0000-0001-6600-8409", "clpid": "Liang-JingXin" }, { "family_name": "Nag", "given_name": "Arundhati", "clpid": "Nag-A" }, { "family_name": "Das", "given_name": "Samir", "clpid": "Das-S" }, { "family_name": "Bunck", "given_name": "David", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "McCarthy", "given_name": "Amy", "clpid": "McCarthy-A" }, { "family_name": "Mishra", "given_name": "Anvita", "clpid": "Mishra-A" }, { "family_name": "Heath", "given_name": "John E.", "clpid": "Heath-J-E" }, { "family_name": "Villalonga", "given_name": "Belen", "clpid": "Villalonga-B" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on the development of high affinity macrocyclic peptides as ligands for the capture and detection of PfHRP2, a protein without a defined tertiary structure. PfHRP2 is a key biomarker of the fatal falciparum strain of malaria. This intrinsically disordered protein has repeated epitopes that have inconstant occurrence over geographic regions. Thus, current antibody based diagnostic tests that target a single epitope do not account for the sequence diversity of PfHRP2 and exhibit variable performance. Ligands selected via high throughput epitope-targeted in situ click screening with combinatorial macrocylic peptide libraries yield binders with high affinity and selectivity for their protein targets. These macrocyclic peptide binders offer greater biochemical and thermal stability than antibodies. We provide a general strategy for the amplification of sensitivity in disease detection through the development of ligands that target multiple epitopes in a single and unstructured protein biomarker. We apply our macrocyclic peptide ligands towards the development of an antibody free diagnostic test for PfHRP2.", "doi": "10.1016/j.bpj.2015.11.2774", "issn": "0006-3495", "publisher": "Biophysical Society", "publication": "Biophysical Journal", "publication_date": "2016-02-16", "series_number": "3", "volume": "110", "issue": "3", "pages": "519A" }, { "id": "authors:144vr-1r916", "collection": "authors", "collection_id": "144vr-1r916", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160606-080629593", "type": "article", "title": "Mimicking Protein Functions with Entropically Constrained Peptides", "author": [ { "family_name": "Farrow", "given_name": "Blake", "clpid": "Farrow-B" }, { "family_name": "Wang", "given_name": "Andrew G.", "clpid": "Wang-Andrew-G" }, { "family_name": "Bunck", "given_name": "David N.", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The biological functions of proteins, from molecular recognition to enzymatic activity, depend on the thermodynamic stability of a conformationally constrained folded structure which positions a small number of amino acid residues in an appropriate position and orientation to carry out their intended function. Most proteins use many weak interactions along a long polypeptide chain to pay the entropic penalty of occupying the native state, though there are examples in biology of short polypeptides which use a few strong or covalent interactions to stabilize a rigid structure. We have developed a completely synthetic high throughput screening platform capable of identifying conformationally constrained macrocyclic peptides with a defined biological function. Proximity-catalyzed in situ click enables discovery of short constrained peptides capable of binding to a chosen site on a protein surface with no requirements for binding pockets or naturally addressable residues in a manner analogous to monoclonal antibodies. We have successfully targeted post-translational modifications, single amino acid mutations and allosteric sites which have revealed new avenues for drug discovery. Recently, discovery of constrained peptides capable of mimicking biological activity on small molecule targets is made possible through the use of suicide substrate activity-based probes. Short constrained peptide motifs capable of activating natural residues and cofactor mimics for nucleophilic attack and decarboxylation have been identified.", "doi": "10.1016/j.bpj.2015.11.1134", "issn": "0006-3495", "publisher": "Biophysical Society", "publication": "Biophysical Journal", "publication_date": "2016-02-16", "series_number": "3", "volume": "110", "issue": "3", "pages": "203A" }, { "id": "authors:6jn72-zbx23", "collection": "authors", "collection_id": "6jn72-zbx23", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160606-084658131", "type": "article", "title": "Molecular Modulation of Protein Energy Landscapes", "author": [ { "family_name": "Bunck", "given_name": "David N.", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-D-N" }, { "family_name": "Museth", "given_name": "Katrine", "clpid": "Museth-K" }, { "family_name": "Atsavapranee", "given_name": "Beatriz", "clpid": "Atsavapranee-B" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Protein catalyzed capture agents are an emerging class of oligopeptides that combine the benefits of small molecules and antibodies to furnish ligands with picomolar binding affinity, serum stability, and cell permeability. Their identification involves screening a synthetic, alkyne-functionalized epitope from a target protein against a library of cyclic peptides bearing terminal azides. We identified ligands that bind regions of superoxide dismutase 1 (SOD1), a protein that misfolds to cause amyotrophic lateral sclerosis (ALS), consistently destabilized upon mutation. Treatment of the disease is challenging because there are over 180 heritable mutations of SOD1 and virtually no well-defined binding sites addressable by traditional ligand identification strategies. These mutations ultimately cause the protein to adopt toxic conformations that aggregate and damage cellular functions within the central nervous system. PCC agents targeting regions consistently destabilized across several mutations bind and stabilize its native conformation. We characterized the impact of binding, both on the ground state stability of several mutants as well as the kinetics of SOD1 folding and denaturation.", "doi": "10.1016/j.bpj.2015.11.2110", "issn": "0006-3495", "publisher": "Biophysical Society", "publication": "Biophysical Journal", "publication_date": "2016-02-16", "series_number": "3", "volume": "110", "issue": "3", "pages": "391A" }, { "id": "authors:trder-31q21", "collection": "authors", "collection_id": "trder-31q21", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151124-135430326", "type": "article", "title": "Nanotechnologies for biomedical science and translational medicine", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "In 2000 the United States launched the National Nanotechnology Initiative and, along with it, a well-defined set of goals for nanomedicine. This Perspective looks back at the progress made toward those goals, within the context of the changing landscape in biomedicine that has occurred over the past 15 years, and considers advances that are likely to occur during the next decade. In particular, nanotechnologies for health-related genomics and single-cell biology, inorganic and organic nanoparticles for biomedicine, and wearable nanotechnologies for wellness monitoring are briefly covered.", "doi": "10.1073/pnas.1515202112", "pmcid": "PMC4664315", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2015-11-24", "series_number": "47", "volume": "112", "issue": "47", "pages": "14436-14443" }, { "id": "authors:4cd3j-mm213", "collection": "authors", "collection_id": "4cd3j-mm213", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150921-111839917", "type": "article", "title": "A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands", "author": [ { "family_name": "Das", "given_name": "Samir", "clpid": "Das-Samir" }, { "family_name": "Nag", "given_name": "Arundhati", "orcid": "0000-0002-1328-1695", "clpid": "Nag-Arundhati" }, { "family_name": "Liang", "given_name": "JingXin", "orcid": "0000-0001-6600-8409", "clpid": "Liang-JingXin" }, { "family_name": "Bunck", "given_name": "David N.", "orcid": "0000-0002-6246-9846", "clpid": "Bunck-David-N" }, { "family_name": "Umeda", "given_name": "Aiko", "clpid": "Umeda-Aiko" }, { "family_name": "Farrow", "given_name": "Blake", "orcid": "0000-0002-1007-7111", "clpid": "Farrow-Blake" }, { "family_name": "Coppock", "given_name": "Matthew B.", "orcid": "0000-0001-9305-3846", "clpid": "Coppock-Matthew-B" }, { "family_name": "Sarkes", "given_name": "Deborah A.", "clpid": "Sarkes-Deborah-A" }, { "family_name": "Finch", "given_name": "Amethist S.", "orcid": "0000-0002-4650-6301", "clpid": "Finch-Amethist-S" }, { "family_name": "Agnew", "given_name": "Heather D.", "orcid": "0000-0003-0010-3248", "clpid": "Agnew-Heather-D" }, { "family_name": "Pitram", "given_name": "Suresh", "clpid": "Pitram-Suresh" }, { "family_name": "Lai", "given_name": "Bert", "clpid": "Lai-Bert" }, { "family_name": "Yu", "given_name": "Mary Beth", "clpid": "Yu-Mary-Beth" }, { "family_name": "Museth", "given_name": "A. Katrine", "clpid": "Museth-A-Katrine" }, { "family_name": "Deyle", "given_name": "Kaycie M.", "clpid": "Deyle-Kaycie-M" }, { "family_name": "Lepe", "given_name": "Bianca", "clpid": "Lepe-Bianca" }, { "family_name": "Rodriguez-Rivera", "given_name": "Frances P.", "orcid": "0000-0003-0651-8639", "clpid": "Rodriguez-Rivera-Frances-P" }, { "family_name": "McCarthy", "given_name": "Amy", "orcid": "0000-0003-3456-0383", "clpid": "McCarthy-Amy-Michelle" }, { "family_name": "Alvarez-Villalonga", "given_name": "Belen", "clpid": "Alvarez-Villalonga-Belen" }, { "family_name": "Chen", "given_name": "Ann", "clpid": "Chen-Ann" }, { "family_name": "Heath", "given_name": "John", "orcid": "0000-0002-5004-2693", "clpid": "Heath-John-E" }, { "family_name": "Stratis-Cullum", "given_name": "Dimitra N.", "orcid": "0000-0002-4832-6945", "clpid": "Stratis-Cullum-Dimitra-N" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We describe a general synthetic strategy for developing high-affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope of interest is synthesized as a polypeptide, with a detection biotin tag and a strategically placed azide (or alkyne) presenting amino acid. This synthetic epitope (SynEp) is incubated with a library of complementary alkyne or azide presenting peptides. Library elements that bind the SynEp in the correct orientation undergo the Huisgen cycloaddition, and are covalently linked to the SynEp. Hit peptides are tested against the full-length protein to identify the best binder. We describe development of epitope-targeted linear or macrocycle peptide ligands against 12 different diagnostic or therapeutic analytes. The general epitope targeting capability for these low molecular weight synthetic ligands enables a range of therapeutic and diagnostic applications, similar to those of monoclonal antibodies.", "doi": "10.1002/anie.201505243", "pmcid": "PMC4890538", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2015-11-02", "series_number": "45", "volume": "54", "issue": "45", "pages": "13219-13224" }, { "id": "authors:f0emk-evp06", "collection": "authors", "collection_id": "f0emk-evp06", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160401-090255899", "type": "article", "title": "Developing integrated single-cell metabolic/proteomic assays", "author": [ { "family_name": "Xue", "given_name": "Min", "clpid": "Xue-Min" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Su", "given_name": "Yapeng", "clpid": "Su-Yapeng" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The technology boom of single-cell metabolomics and proteomics has led to exciting biological discoveries in the past decade. It has become widely acknowledged that resolving the intratumoral heterogeneity at single cell resolution can aid the understanding of cancer therapeutic response and progression, as well as facilitate the development of therapeutic interventions. Here we present an integrated assay that simultaneously quantifies the intracellular metabolites, glucose uptake, metabolic proteins and functional signaling proteins at the single-cell level. The measurement of metabolites is achieved through a series of competitive binding assays and is incorporated into the microfluidic-based single cell barcode chip platform. We demonstrate that this assay is capable of obtaining information from both protein and metabolic signaling pathways associated with tumor survival and progression, providing new insights into cancer heterogeneity and drug responsiveness.", "doi": "10.1158/1538-7445.AM2015-1995", "issn": "0008-5472", "publisher": "American Association for Cancer Research", "publication": "Cancer Research", "publication_date": "2015-08-01", "series_number": "S", "volume": "75", "issue": "S", "pages": "Art. No. 1995" }, { "id": "authors:5ypvx-68c27", "collection": "authors", "collection_id": "5ypvx-68c27", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150504-105133177", "type": "article", "title": "Epitope Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent In-Cell Inhibitor of Botulinum Neurotoxin", "author": [ { "family_name": "Farrow", "given_name": "Blake", "clpid": "Farrow-B" }, { "family_name": "Wong", "given_name": "Michelle", "clpid": "Wong-Michelle" }, { "family_name": "Malette", "given_name": "Jacquie", "clpid": "Malette-J" }, { "family_name": "Lai", "given_name": "Bert", "clpid": "Lai-Bert-T" }, { "family_name": "Deyle", "given_name": "Kaycie M.", "clpid": "Deyle-K-M" }, { "family_name": "Das", "given_name": "Samir", "clpid": "Das-S" }, { "family_name": "Nag", "given_name": "Arundhati", "clpid": "Nag-A" }, { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-H-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model.", "doi": "10.1002/anie.201502451", "pmcid": "PMC5444873", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2015-06-08", "series_number": "24", "volume": "54", "issue": "24", "pages": "7114-7119" }, { "id": "authors:38rxm-62204", "collection": "authors", "collection_id": "38rxm-62204", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161031-083900031", "type": "article", "title": "Quantitative assessments of glycolysis from single cells", "author": [ { "family_name": "Shin", "given_name": "Young Shik", "orcid": "0000-0002-1097-9035", "clpid": "Shin-Young-Shik" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Johnson", "given_name": "Dazy", "orcid": "0000-0001-6311-8629", "clpid": "Johnson-Dazy" }, { "family_name": "Dooraghi", "given_name": "Alex A.", "clpid": "Dooraghi-Alex-A" }, { "family_name": "Mai", "given_name": "Wilson X.", "clpid": "Mai-Wilson-X" }, { "family_name": "Ta", "given_name": "Lisa", "clpid": "Ta-Lisa" }, { "family_name": "Chatziioannou", "given_name": "Arion F.", "clpid": "Chatziioannou-Arion-F" }, { "family_name": "Phelps", "given_name": "Michael E.", "clpid": "Phelps-Michael-E" }, { "family_name": "Nathanson", "given_name": "David A.", "clpid": "Nathanson-David-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The most common positron emission tomography (PET) radio-labeled probe for molecular diagnostics in patient care and research is the glucose analog, 2-deoxy-2-[F-18]fluoro-D-glucose (^(18)F-FDG). We report on an integrated microfluidics-chip/beta particle imaging system for in vitro ^(18)F-FDG radioassays of glycolysis with single cell resolution. We investigated the kinetic responses of single glioblastoma cancer cells to targeted inhibitors of receptor tyrosine kinase signaling. Further, we find a weak positive correlation between cell size and rate of glycolysis.", "doi": "10.1142/S2339547815200058", "pmcid": "PMC4728151", "issn": "2339-5478", "publisher": "World Scientific Publishing", "publication": "Technology", "publication_date": "2015-06", "series_number": "4", "volume": "3", "issue": "4", "pages": "172-178" }, { "id": "authors:bz1mc-d1625", "collection": "authors", "collection_id": "bz1mc-d1625", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150323-101933830", "type": "article", "title": "The Influence of Water on the Optical Properties of Single-Layer Molybdenum Disulfide", "author": [ { "family_name": "Varghese", "given_name": "Joseph O.", "clpid": "Varghese-J-O" }, { "family_name": "Agbo", "given_name": "Peter", "clpid": "Agbo-P" }, { "family_name": "Sutherland", "given_name": "Alexander M.", "clpid": "Sutherland-A-M" }, { "family_name": "Brar", "given_name": "Victor W.", "clpid": "Brar-V-W" }, { "family_name": "Rossman", "given_name": "George R.", "orcid": "0000-0002-4571-6884", "clpid": "Rossman-G-R" }, { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Adsorbed molecules can significantly affect the properties of atomically thin materials. Physisorbed water plays a significant role in altering the optoelectronic properties of single-layer MoS_2, one such 2D film. Here we demonstrate the distinct quenching effect of adsorbed water on the photoluminescence of single-layer MoS_2 through scanning-probe and optical microscopies.", "doi": "10.1002/adma.201500555", "issn": "0935-9648", "publisher": "Wiley", "publication": "Advanced Materials", "publication_date": "2015-05-06", "series_number": "17", "volume": "27", "issue": "17", "pages": "2734-2740" }, { "id": "authors:fqaq3-f6162", "collection": "authors", "collection_id": "fqaq3-f6162", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150217-102335573", "type": "article", "title": "A protein-targeting strategy used to develop a selective inhibitor of the E17K point mutation in the PH domain of Akt1", "author": [ { "family_name": "Deyle", "given_name": "Kaycie M.", "clpid": "Deyle-Kaycie-M" }, { "family_name": "Farrow", "given_name": "Blake", "orcid": "0000-0002-1007-7111", "clpid": "Farrow-Blake" }, { "family_name": "Hee", "given_name": "Ying Qiao", "clpid": "Hee-Ying-Qiao" }, { "family_name": "Work", "given_name": "Jeremy", "orcid": "0000-0002-1677-4954", "clpid": "Work-Jeremy" }, { "family_name": "Wong", "given_name": "Michelle", "orcid": "0000-0001-6209-7475", "clpid": "Wong-Michelle" }, { "family_name": "Lai", "given_name": "Bert", "clpid": "Lai-Bert-T" }, { "family_name": "Umeda", "given_name": "Aiko", "clpid": "Umeda-Aiko" }, { "family_name": "Millward", "given_name": "Steven W.", "orcid": "0000-0002-3231-7075", "clpid": "Millward-Steven-W" }, { "family_name": "Nag", "given_name": "Arundhati", "orcid": "0000-0002-1328-1695", "clpid": "Nag-Arundhati" }, { "family_name": "Das", "given_name": "Samir", "clpid": "Das-Samir" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Ligands that can bind selectively to proteins with single amino-acid point mutations offer the potential to detect or treat an abnormal protein in the presence of the wild type (WT). However, it is difficult to develop a selective ligand if the point mutation is not associated with an addressable location, such as a binding pocket. Here we report an all-chemical synthetic epitope-targeting strategy that we used to discover a 5-mer peptide with selectivity for the E17K-transforming point mutation in the pleckstrin homology domain of the Akt1 oncoprotein. A fragment of Akt1 that contained the E17K mutation and an I19[propargylglycine] substitution was synthesized to form an addressable synthetic epitope. Azide-presenting peptides that clicked covalently onto this alkyne-presenting epitope were selected from a library using in situ screening. One peptide exhibits a 10:1 in vitro selectivity for the oncoprotein relative to the WT, with a similar selectivity in cells. This 5-mer peptide was expanded into a larger ligand that selectively blocks the E17K Akt1 interaction with its PIP3 (phosphatidylinositol (3,4,5)-trisphosphate) substrate.", "doi": "10.1038/nchem.2223", "pmcid": "PMC4408887", "issn": "1755-4330", "publisher": "Nature Publishing Group", "publication": "Nature Chemistry", "publication_date": "2015-05", "series_number": "5", "volume": "7", "issue": "5", "pages": "455-462" }, { "id": "authors:fg82r-sj650", "collection": "authors", "collection_id": "fg82r-sj650", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150324-093511464", "type": "article", "title": "Chemical Methods for the Simultaneous Quantitation of Metabolites and Proteins from Single Cells", "author": [ { "family_name": "Xue", "given_name": "Min", "orcid": "0000-0002-8136-6551", "clpid": "Xue-Min" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Su", "given_name": "Yapeng", "orcid": "0000-0002-6305-8467", "clpid": "Su-Yapeng" }, { "family_name": "Kim", "given_name": "Jungwoo", "orcid": "0000-0002-5215-2044", "clpid": "Kim-Jungwoo" }, { "family_name": "Shin", "given_name": "Young Shik", "orcid": "0000-0002-1097-9035", "clpid": "Shin-Young-Shik" }, { "family_name": "Mai", "given_name": "Wilson X.", "clpid": "Mai-Wilson-X" }, { "family_name": "Nathanson", "given_name": "David A.", "clpid": "Nathanson-David-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We describe chemical approaches for integrated metabolic and proteomic assays from single cells. Quantitative assays for intracellular metabolites, including glucose uptake and three other species, are designed as surface-competitive binding assays with fluorescence readouts. This enables integration into a microarray format with functional protein immunoassays, all of which are incorporated into the microchambers of a single-cell barcode chip (SCBC). By using the SCBC, we interrogate the response of human-derived glioblastoma cancer cells to epidermal growth factor receptor inhibition. We report, for the first time, on both the intercellular metabolic heterogeneity as well as the baseline and drug-induced changes in the metabolite\u2013phosphoprotein correlation network.", "doi": "10.1021/jacs.5b00944", "pmcid": "PMC4883658", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2015-04-01", "series_number": "12", "volume": "137", "issue": "12", "pages": "4066-4069" }, { "id": "authors:fyq7w-kpt87", "collection": "authors", "collection_id": "fyq7w-kpt87", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151020-110744228", "type": "article", "title": "Single cell phosphoproteomics identifies adaptive network dynamics of mTOR inhibitor resistance and defines effective combination therapy in glioblastoma", "author": [ { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Gini", "given_name": "Beatrice", "clpid": "Gini-B" }, { "family_name": "Mischel", "given_name": "Paul", "clpid": "Mischel-P-S" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Resistance to single-agent targeted cancer therapy is almost universal. Resistance can occur when drug-resistant tumor cell subpopulations expand to drive recurrence in a process akin to Darwinian-type evolution under the selection pressure of the drug. An alternative resistance mechanism is the one in which cancer cells targeted by the inhibitor adapt to that drug, so as to maintain the signal flux through those networks that are required for tumor maintenance and growth. The main goal of this study is to identify the mechanisms of resistance in a targeted therapy by analyzing single cells and to provide a strategy to design a more effective therapy that suppresses resistance.", "doi": "10.1158/1557-3265.PMS14-PR09", "issn": "1078-0432", "publisher": "American Association for Cancer Research", "publication": "Clinical Cancer Research", "publication_date": "2015-02-15", "series_number": "S4", "volume": "21", "issue": "S4", "pages": "Art. No. PR09" }, { "id": "authors:ssnwr-71f31", "collection": "authors", "collection_id": "ssnwr-71f31", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150604-142522878", "type": "article", "title": "Nanotechnology and single cell proteomics as a diagnostic tool", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Xue", "given_name": "Min", "clpid": "Xue-Min" }, { "family_name": "Zhou", "given_name": "Jing", "clpid": "Zhou-Jing" }, { "family_name": "Sutherland", "given_name": "Alex", "clpid": "Sutherland-A" }, { "family_name": "Yu", "given_name": "Jing", "clpid": "Yu-Jing" } ], "abstract": "Single-cell functional proteomics assays can connect genomic information to biological function through the use of quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years, and are providing approaches for directly elucidating phospho-protein signaling networks in cancer cells, or for capturing high-resolution snapshots of immune system function in cancer patients participating therapies that involve immune system engineering and manipulation. We discuss advances in single cell proteomics platforms, with an emphasis the types of data that can be obtained, and how analysis of that data can provide deep insights into either designing therapies, or understanding patient responses to therapies. I will provide illustrative examples of how microchip-based single cell functional proteomics platforms are being applied to both fundamental biology and clinical studies.", "doi": "10.1158/1538-7445.AM2014-SY23-02", "issn": "0008-5472", "publisher": "American Association for Cancer Research", "publication": "Cancer Research", "publication_date": "2014-10-01", "series_number": "19 Suppleme", "volume": "74", "issue": "19 Suppleme", "pages": "Art. No. SY23-02" }, { "id": "authors:mt6gd-qtz79", "collection": "authors", "collection_id": "mt6gd-qtz79", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140926-091054210", "type": "article", "title": "Modeling Dioxygen Reduction at Multicopper Oxidase Cathodes", "author": [ { "family_name": "Agbo", "given_name": "Peter", "clpid": "Agbo-P" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" } ], "abstract": "We report a general kinetics model for catalytic dioxygen reduction on multicopper oxidase (MCO) cathodes. Our rate equation combines Butler\u2013Volmer (BV) electrode kinetics and the Michaelis\u2013Menten (MM) formalism for enzymatic catalysis, with the BV model accounting for interfacial electron transfer (ET) between the electrode surface and the MCO type 1 copper site. Extending the principles of MM kinetics to this system produced an analytical expression incorporating the effects of subsequent intramolecular ET and dioxygen binding to the trinuclear copper cluster into the cumulative model. We employed experimental electrochemical data on Thermus thermophilus laccase as benchmarks to validate our model, which we suggest will aid in the design of more efficient MCO cathodes. In addition, we demonstrate the model's utility in determining estimates for both the electronic coupling and average distance between the laccase type-1 active site and the cathode substrate.", "doi": "10.1021/ja5077519", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2014-10-01", "series_number": "39", "volume": "136", "issue": "39", "pages": "13882-13887" }, { "id": "authors:a4683-93086", "collection": "authors", "collection_id": "a4683-93086", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140623-090712146", "type": "article", "title": "Human NK Cells Licensed by Killer Ig Receptor Genes Have an Altered Cytokine Program That Modifies CD4+ T Cell Function", "author": [ { "family_name": "Lin", "given_name": "Lin", "orcid": "0000-0001-6860-9566", "clpid": "Lin-Lin" }, { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "Wei", "given_name": "Bo", "clpid": "Wei-Bo" }, { "family_name": "Aziz", "given_name": "Najib", "clpid": "Aziz-Najib" }, { "family_name": "Rajalingam", "given_name": "Raja", "clpid": "Rajalingam-Raja" }, { "family_name": "Yusung", "given_name": "Susy", "clpid": "Yusung-Susy" }, { "family_name": "Erlich", "given_name": "Henry A.", "clpid": "Erlich-H-A" }, { "family_name": "Trachtenberg", "given_name": "Elizabeth A.", "clpid": "Trachtenberg-E-A" }, { "family_name": "Targan", "given_name": "Stephan R.", "clpid": "Targan-S-R" }, { "family_name": "McGovern", "given_name": "Dermot P. B.", "clpid": "McGovern-D-P-B" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Braun", "given_name": "Jonathan", "clpid": "Braun-Jonathan" } ], "abstract": "NK cells are innate immune cells known for their cytolytic activities toward tumors and infections. They are capable of expressing diverse killer Ig-like receptors (KIRs), and KIRs are implicated in susceptibility to Crohn's disease (CD), a chronic intestinal inflammatory disease. However, the cellular mechanism of this genetic contribution is unknown. In this study, we show that the \"licensing\" of NK cells, determined by the presence of KIR2DL3 and homozygous HLA-C1 in host genome, results in their cytokine reprogramming, which permits them to promote CD4+ T cell activation and Th17 differentiation ex vivo. Microfluidic analysis of thousands of NK single cells and bulk secretions established that licensed NK cells are more polarized to proinflammatory cytokine production than unlicensed NK cells, including production of IFN-\u03b3, TNF-\u03b1, CCL-5, and MIP-1\u03b2. Cytokines produced by licensed NK augmented CD4+ T cell proliferation and IL-17A/IL-22 production. Ab blocking indicated a primary role for IFN-\u03b3, TNF-\u03b1, and IL-6 in the augmented T cell\u2013proliferative response. In conclusion, NK licensing mediated by KIR2DL2/3 and HLA-C1 elicits a novel NK cytokine program that activates and induces proinflammatory CD4+ T cells, thereby providing a potential biologic mechanism for KIR-associated susceptibility to CD and other chronic inflammatory diseases.", "doi": "10.4049/jimmunol.1400093", "pmcid": "PMC4096688", "issn": "0022-1767", "publisher": "American Association of Immunologists", "publication": "Journal of Immunology", "publication_date": "2014-06-16", "series_number": "2", "volume": "193", "issue": "2", "pages": "940-949" }, { "id": "authors:dacct-vm711", "collection": "authors", "collection_id": "dacct-vm711", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140609-131536570", "type": "article", "title": "Microfluidics-Based Single-Cell Functional Proteomics for Fundamental and Applied Biomedical Applications", "author": [ { "family_name": "Yu", "given_name": "Jing", "clpid": "Yu-Jing" }, { "family_name": "Zhou", "given_name": "Jing", "clpid": "Zhou-Jing" }, { "family_name": "Sutherland", "given_name": "Alex", "clpid": "Sutherland-A" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Xue", "given_name": "Min", "clpid": "Xue-Min" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We review an emerging microfluidics-based toolkit for single-cell functional proteomics. Functional proteins include, but are not limited to, the secreted signaling proteins that can reflect the biological behaviors of immune cells or the intracellular phosphoproteins associated with growth factor\u2013stimulated signaling networks. Advantages of the microfluidics platforms are multiple. First, 20 or more functional proteins may be assayed simultaneously from statistical numbers of single cells. Second, cell behaviors (e.g., motility) may be correlated with protein assays. Third, extensions to quantized cell populations can permit measurements of cell\u2013cell interactions. Fourth, rare cells can be functionally identified and then separated for further analysis or culturing. Finally, certain assay types can provide a conduit between biology and the physicochemical laws. We discuss the history and challenges of the field then review design concepts and uses of the microchip platforms that have been reported, with an eye toward biomedical applications. We then look to the future of the field.", "doi": "10.1146/annurev-anchem-071213-020323", "issn": "1936-1327", "publisher": "Annual Reviews", "publication": "Annual Review of Analytical Chemistry", "publication_date": "2014-06", "volume": "7", "pages": "275-295" }, { "id": "authors:wq9k4-t5965", "collection": "authors", "collection_id": "wq9k4-t5965", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180711-141559479", "type": "book_section", "title": "Peptide-based protein capture agents with high affinity, selectivity, and stability as antibody replacements in biodetection assays", "book_title": "Smart Biomedical and Physiological Sensor Technology XI", "author": [ { "family_name": "Coppock", "given_name": "Matthew B.", "clpid": "Coppock-M-B" }, { "family_name": "Farrow", "given_name": "Blake", "clpid": "Farrow-B" }, { "family_name": "Warner", "given_name": "Candice", "clpid": "Warner-C-R" }, { "family_name": "Finch", "given_name": "Amethist S.", "clpid": "Finch-A-S" }, { "family_name": "Lai", "given_name": "Bert", "clpid": "Lai-Bert-T" }, { "family_name": "Sarkes", "given_name": "Deborah A.", "clpid": "Sarkes-D-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stratis-Cullum", "given_name": "Dimitra", "clpid": "Stratis-Cullum-D-N" } ], "contributor": [ { "family_name": "Cullum", "given_name": "Brian M.", "clpid": "Cullun-B-M" }, { "family_name": "McLamore", "given_name": "Eric S.", "clpid": "McLamore-E-S" } ], "abstract": "Current biodetection assays that employ monoclonal antibodies as primary capture agents exhibit limited fieldability, shelf life, and performance due to batch-to-batch production variability and restricted thermal stability. In order to improve upon the detection of biological threats in fieldable assays and systems for the Army, we are investigating protein catalyzed capture (PCC) agents as drop-in replacements for the existing antibody technology through iterative in situ click chemistry. The PCC agent oligopeptides are developed against known protein epitopes and can be mass produced using robotic methods. In this work, a PCC agent under development will be discussed. The performance, including affinity, selectivity, and stability of the capture agent technology, is analyzed by immunoprecipitation, western blotting, and ELISA experiments. The oligopeptide demonstrates superb selectivity coupled with high affinity through multi-ligand design, and improved thermal, chemical, and biochemical stability due to non-natural amino acid PCC agent design", "doi": "10.1117/12.2052542", "isbn": "9781628410440", "publisher": "Society of Photo-optical Instrumentation Engineers (SPIE)", "place_of_publication": "Bellingham, WA", "publication_date": "2014-05-22", "pages": "Art. no. 910711" }, { "id": "authors:m2v8v-kjj86", "collection": "authors", "collection_id": "m2v8v-kjj86", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140421-094308358", "type": "article", "title": "Glioblastoma cellular architectures are predicted through the characterization of two-cell interactions", "author": [ { "family_name": "Kravchenko-Balasha", "given_name": "Nataly", "clpid": "Kravchenko-Balasha-N" }, { "family_name": "Wang", "given_name": "Jun", "clpid": "Wang-Jun" }, { "family_name": "Remacle", "given_name": "Francoise", "clpid": "Remacle-F" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "To understand how pairwise cellular interactions influence cellular architectures, we measured the levels of functional proteins associated with EGF receptor (EGFR) signaling in pairs of U87EGFR variant III oncogene receptor cells (U87EGFRvIII) at varying cell separations. Using a thermodynamics-derived approach we analyzed the cell-separation dependence of the signaling stability, and identified that the stable steady state of EGFR signaling exists when two U87EGFRvIII cells are separated by 80\u2013100 \u03bcm. This distance range was verified as the characteristic intercellular separation within bulk cell cultures. EGFR protein network signaling coordination for the U87EGFRvIII system was lowest at the stable state and most similar to isolated cell signaling. Measurements of cultures of less tumorigenic U87PTEN cells were then used to correctly predict that stable EGFR signaling occurs for those cells at smaller cell\u2013cell separations. The intimate relationship between functional protein levels and cellular architectures explains the scattered nature of U87EGFRvIII cells relative to U87PTEN cells in glioblastoma multiforme tumors.", "doi": "10.1073/pnas.1404462111", "pmcid": "PMC4035957", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2014-04-29", "series_number": "17", "volume": "111", "issue": "17", "pages": "6521-6526" }, { "id": "authors:xz27e-wy233", "collection": "authors", "collection_id": "xz27e-wy233", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140227-222713478", "type": "article", "title": "Conversion of Danger Signals into Cytokine Signals by Hematopoietic Stem and Progenitor Cells for Regulation of Stress-Induced Hematopoiesis", "author": [ { "family_name": "Zhao", "given_name": "Jimmy L.", "clpid": "Zhao-Jimmy-L" }, { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "O'Connell", "given_name": "Ryan M.", "clpid": "O'Connell-Ryan-M" }, { "family_name": "Mehta", "given_name": "Arnav", "clpid": "Mehta-Arnav" }, { "family_name": "DiLoreto", "given_name": "Race", "clpid": "DiLoreto-Race" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" } ], "abstract": "During an infection, the body increases the output of mature immune cells to fight off the \npathogen. Despite convincing evidence that hematopoietic stem and progenitor cells (HSPCs) \ncan sense pathogens directly, how this contributes to hematopoietic cell output remains unknown. \nHere we have combined mouse models with a single cell proteomics platform to show that in \nresponse to toll-like receptor stimulation, short-term HSCs and multipotent progenitor cells \nproduce copious amount of diverse cytokines through the NF-\u03baB signaling. Interestingly, the \ncytokine production ability of HSPCs trumps mature immune cells in both magnitude and \nbreadth. Among cytokines produced by HSPCs, IL-6 is a particularly important regulator of \nmyeloid differentiation and HSPC proliferation in a paracrine manner and in mediating rapid \nmyeloid cell recovery during neutropenia. This study has uncovered a novel property of HSPCs \nthat enables them to convert danger signals into versatile cytokine signals for regulation of stress \nhematopoiesis.", "doi": "10.1016/j.stem.2014.01.007", "pmcid": "PMC4119790", "issn": "1934-5909", "publisher": "Elsevier", "publication": "Cell Stem Cell", "publication_date": "2014-04-03", "series_number": "4", "volume": "14", "issue": "4", "pages": "445-459" }, { "id": "authors:bpgv0-cwm88", "collection": "authors", "collection_id": "bpgv0-cwm88", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150312-110207059", "type": "article", "title": "Peptide-based protein capture agents with high affinity, selectivity, and stability as antibody replacements", "author": [ { "family_name": "Coppock", "given_name": "Matthew B.", "clpid": "Coppock-M-B" }, { "family_name": "Farrow", "given_name": "Blake", "clpid": "Farrow-B" }, { "family_name": "Finch", "given_name": "Amethist S.", "clpid": "Finch-A-S" }, { "family_name": "Lai", "given_name": "Bert", "clpid": "Lai-Bert-T" }, { "family_name": "Sarkes", "given_name": "Deborah", "clpid": "Sarkes-D" }, { "family_name": "Maciel", "given_name": "Jorge", "clpid": "Maciel-J" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stratis-Cullum", "given_name": "Dimitra N.", "clpid": "Stratis-Cullum-D-N" } ], "abstract": "Current biodetection assays that employ monoclonal antibodies as primary capture agents exhibit limited fieldability, shelf life,\nand performance due to batch-to-batch prodn. variability and restricted thermal stability. In order to improve upon the\ndetection of biol. threats in fieldable assays and systems for the Army, we are investigating protein catalyzed capture (PCC)\nagents as drop-in replacements for the existing antibody technol. through iterative in situ click chem. The PCC agent\noligopeptides are developed against known protein epitopes and can be mass produced using robotic methods. In this work, a\nPCC agent under development will be discussed. The performance, including affinity, selectivity, and stability of the\ncapture agent technol., is analyzed by immunopptn., western blotting, and ELISA expts. The oligopeptide demonstrates\nsuperb selectivity coupled with high affinity through multi-ligand design, and improved thermal, chem., and biochem.\nstability due to non-natural amino acid PCC agent design.", "issn": "0065-7727", "publisher": "American Chemical Society", "publication": "Abstracts of Papers of the American Chemical Society", "publication_date": "2014-03-16", "volume": "247", "pages": "436-BIOT" }, { "id": "authors:6w2s0-sf326", "collection": "authors", "collection_id": "6w2s0-sf326", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140124-111345325", "type": "article", "title": "Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA", "author": [ { "family_name": "Nathanson", "given_name": "David A.", "clpid": "Nathanson-D-A" }, { "family_name": "Gini", "given_name": "Beatrice", "clpid": "Gini-B" }, { "family_name": "Mottahedeh", "given_name": "Jack", "clpid": "Mottahedeh-J" }, { "family_name": "Visnyei", "given_name": "Koppany", "clpid": "Visnyei-K" }, { "family_name": "Koga", "given_name": "Tomoyuki", "clpid": "Koga-Tomoyuki" }, { "family_name": "Gomez", "given_name": "German", "clpid": "Gomez-German" }, { "family_name": "Eskin", "given_name": "Ascia", "clpid": "Eskin-A" }, { "family_name": "Hwang", "given_name": "Kiwook", "clpid": "Hwang-Kiwook" }, { "family_name": "Wang", "given_name": "Jun", "clpid": "Wang-Jun" }, { "family_name": "Masui", "given_name": "Kenta", "clpid": "Masui-Kenta" }, { "family_name": "Paucar", "given_name": "Andres", "clpid": "Paucar-A" }, { "family_name": "Yang", "given_name": "Huijun", "clpid": "Yang-Huijun" }, { "family_name": "Ohashi", "given_name": "Minori", "clpid": "Ohashi-Minori" }, { "family_name": "Zhu", "given_name": "Shaojun", "clpid": "Zhu-Shaojun" }, { "family_name": "Wykosky", "given_name": "Jill", "clpid": "Wykoski-J" }, { "family_name": "Reed", "given_name": "Rachel", "clpid": "Reed-R" }, { "family_name": "Nelson", "given_name": "Stanley F.", "clpid": "Nelson-S-F" }, { "family_name": "Cloughesy", "given_name": "Timothy F.", "clpid": "Cloughesy-T-F" }, { "family_name": "James", "given_name": "C. David", "clpid": "James-C-D" }, { "family_name": "Rao", "given_name": "P. Nagesh", "clpid": "Rao-P-N" }, { "family_name": "Kornblum", "given_name": "Harley I.", "clpid": "Kornblum-H-I" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Cavenee", "given_name": "Webster K.", "clpid": "Cavenee-W-K" }, { "family_name": "Furnari", "given_name": "Frank B.", "clpid": "Furnari-F-B" }, { "family_name": "Mischel", "given_name": "Paul S.", "clpid": "Mischel-P-S" } ], "abstract": "Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring distinct cellular phenotypes to reach an optimal equilibrium for growth. Resistance to EGFR TKIs is shown to occur by elimination of mutant EGFR from extrachromosomal DNA. After drug withdrawal, reemergence of clonal EGFR mutations on extrachromosomal DNA follows. These results indicate a highly specific, dynamic, and adaptive route by which cancers can evade therapies that target oncogenes maintained on extrachromosomal DNA.", "doi": "10.1126/science.1241328", "pmcid": "PMC4049335", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2014-01-03", "series_number": "6166", "volume": "343", "issue": "6166", "pages": "72-76" }, { "id": "authors:m36yf-0d780", "collection": "authors", "collection_id": "m36yf-0d780", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131204-154453202", "type": "article", "title": "A Chemical Epitope-Targeting Strategy for Protein Capture Agents: The Serine 474 Epitope of the Kinase Akt2", "author": [ { "family_name": "Nag", "given_name": "Arundhati", "clpid": "Nag-A" }, { "family_name": "Das", "given_name": "Samir", "clpid": "Das-S" }, { "family_name": "Yu", "given_name": "Mary Beth", "clpid": "Yu-Mary-Beth" }, { "family_name": "Deyle", "given_name": "Kaycie M.", "clpid": "Deyle-K-M" }, { "family_name": "Millward", "given_name": "Steven W.", "clpid": "Millward-S-W" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Target and click: Peptide ligands targeted to the C-terminal motif of the kinase Akt2 were obtained by combining phosphate recognition of a dinuclear zinc(II) complex with in situ click chemistry to target this epitope. The peptide ligands (shown as XXXXX) selectively bind the C-terminal polypeptide of Akt2, and are selective for Akt2 relative to the Akt1 and Akt3 isoforms. The ligands differentially modulate Akt2 activity.", "doi": "10.1002/anie.201305882", "pmcid": "PMC4059071", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2013-12-23", "series_number": "52", "volume": "52", "issue": "52", "pages": "13975-13979" }, { "id": "authors:escm0-qc291", "collection": "authors", "collection_id": "escm0-qc291", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131112-112114444", "type": "article", "title": "The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas", "author": [ { "family_name": "Gini", "given_name": "Beatrice", "clpid": "Gini-B" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Purpose: mTOR pathway hyperactivation occurs in approximately 90% of glioblastomas, but the allosteric mTOR inhibitor rapamycin has failed in the clinic. Here, we examine the efficacy of the newly discovered ATP-competitive mTOR kinase inhibitors CC214-1 and CC214-2 in glioblastoma, identifying molecular determinants of response and mechanisms of resistance, and develop a pharmacologic strategy to overcome it. \n\nExperimental Design: We conducted in vitro and in vivo studies in glioblastoma cell lines and an intracranial model to: determine the potential efficacy of the recently reported mTOR kinase inhibitors CC214-1 (in vitro use) and CC214-2 (in vivo use) at inhibiting rapamycin-resistant signaling and blocking glioblastoma growth and a novel single-cell technology\u2014DNA Encoded Antibody Libraries\u2014was used to identify mechanisms of resistance. \n\nResults: Here, we show that CC214-1 and CC214-2 suppress rapamycin-resistant mTORC1 signaling, block mTORC2 signaling, and significantly inhibit the growth of glioblastomas in vitro and in vivo. EGFRvIII expression and PTEN loss enhance sensitivity to CC214 compounds, consistent with enhanced efficacy in strongly mTOR-activated tumors. Importantly, CC214 compounds potently induce autophagy, preventing tumor cell death. Genetic or pharmacologic inhibition of autophagy greatly sensitizes glioblastoma cells and orthotopic xenografts to CC214-1- and CC214-2\u2013induced cell death. \n\nConclusions: These results identify CC214-1 and CC214-2 as potentially efficacious mTOR kinase inhibitors in glioblastoma, and suggest a strategy for identifying patients most likely to benefit from mTOR inhibition. In addition, this study also shows a central role for autophagy in preventing mTOR-kinase inhibitor-mediated tumor cell death, and suggests a pharmacologic strategy for overcoming it.", "doi": "10.1158/1078-0432.CCR-13-0527", "pmcid": "PMC3815450", "issn": "1078-0432", "publisher": "American Association for Cancer Research", "publication": "Clinical Cancer Research", "publication_date": "2013-10-15", "series_number": "20", "volume": "19", "issue": "20", "pages": "5722-5732" }, { "id": "authors:7xsvm-t9n47", "collection": "authors", "collection_id": "7xsvm-t9n47", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131105-095711532", "type": "article", "title": "Fast Metabolic Response to Drug Intervention Through Analysis on a Miniaturized, Highly Integrated Molecular Imaging System", "author": [ { "family_name": "Wang", "given_name": "Jun", "clpid": "Wang-Jun" }, { "family_name": "Hwang", "given_name": "Kiwook", "clpid": "Hwang-Kiwook" }, { "family_name": "Braas", "given_name": "Daniel", "clpid": "Braas-D" }, { "family_name": "Dooraghi", "given_name": "Alex", "clpid": "Dooraghi-A" }, { "family_name": "Nathanson", "given_name": "David", "clpid": "Nathanson-D" }, { "family_name": "Campbell", "given_name": "Dean O.", "clpid": "Campbell-D-O" }, { "family_name": "Gu", "given_name": "Yuchao", "clpid": "Gu-Yuchao" }, { "family_name": "Sandberg", "given_name": "Troy", "clpid": "Sandberg-T" }, { "family_name": "Mischel", "given_name": "Paul", "clpid": "Mischel-P" }, { "family_name": "Radu", "given_name": "Caius", "clpid": "Radu-C-G" }, { "family_name": "Chatziioannou", "given_name": "Arion F.", "clpid": "Chatziioannou-A-F" }, { "family_name": "Phelps", "given_name": "Michael E.", "clpid": "Phelps-M-E" }, { "family_name": "Christofk", "given_name": "Heather", "clpid": "Christofk-H" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on a radiopharmaceutical imaging platform designed to capture the kinetics of cellular responses to drugs. Methods: A portable in vitro molecular imaging system comprising a microchip and a \u03b2-particle imaging camera permitted routine cell-based radioassays of small numbers of either suspended or adherent cells. We investigated the kinetics of responses of model lymphoma and glioblastoma cancer cell lines to ^(18)F-FDG uptake after drug exposure. Those responses were correlated with kinetic changes in the cell cycle or with changes in receptor tyrosine kinase signaling. Results: The platform enabled direct radioassays of multiple cell types and yielded results comparable to those from conventional approaches; however, the platform used smaller sample sizes, permitted a higher level of quantitation, and did not require cell lysis. Conclusion: The kinetic analysis enabled by the platform provided a rapid (\u223c1 h) drug screening assay.", "doi": "10.2967/jnumed.112.118497", "pmcid": "PMC4106462", "issn": "0161-5505", "publisher": "Society of Nuclear Medicine", "publication": "Journal of Nuclear Medicine", "publication_date": "2013-10-01", "series_number": "10", "volume": "54", "issue": "10", "pages": "1820-1824" }, { "id": "authors:78aw1-pyb42", "collection": "authors", "collection_id": "78aw1-pyb42", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131024-102505226", "type": "article", "title": "Wetting: Contact with what?", "author": [ { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Pristine graphitic surfaces seem to be more hydrophilic than previously assumed because of the unexpected\ninfluence of the quick adsorption of hydrocarbons from air.", "doi": "10.1038/nmat3763", "issn": "1476-1122", "publisher": "Nature Publishing Group", "publication": "Nature Materials", "publication_date": "2013-10", "series_number": "10", "volume": "12", "issue": "10", "pages": "872-873" }, { "id": "authors:7pazg-5e437", "collection": "authors", "collection_id": "7pazg-5e437", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131212-131040336", "type": "article", "title": "A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective Antigen", "author": [ { "family_name": "Farrow", "given_name": "Blake", "clpid": "Farrow-B" }, { "family_name": "Hong", "given_name": "Sung A.", "clpid": "Hong-Sung-A" }, { "family_name": "Romero", "given_name": "Errika C.", "clpid": "Romero-E-C" }, { "family_name": "Lai", "given_name": "Bert", "clpid": "Lai-Bert-T" }, { "family_name": "Coppock", "given_name": "Matthew B.", "clpid": "Coppock-M-B" }, { "family_name": "Deyle", "given_name": "Kaycie M.", "clpid": "Deyle-K-M" }, { "family_name": "Finch", "given_name": "Amethist S.", "clpid": "Finch-A-S" }, { "family_name": "Stratis-Cullum", "given_name": "Dimitra N.", "clpid": "Stratis-Cullum-D-N" }, { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-H-D" }, { "family_name": "Yang", "given_name": "Sung", "orcid": "0000-0002-6050-0993", "clpid": "Yang-Sung" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on a robust and sensitive approach for detecting protective antigen (PA) exotoxin from Bacillus anthracis in complex media. A peptide-based capture agent against PA was developed by improving a bacteria display-developed peptide into a highly selective biligand through in situ click screening against a large, chemically synthesized peptide library. This biligand was coupled with an electrochemical enzyme-linked immunosorbent assay utilizing nanostructured gold electrodes. The resultant assay yielded a limit of detection of PA of 170 pg/mL. (2.1 pM) in buffer, with minimal sensitivity reduction in 1% serum. The powdered capture agent could be stably stored for several days at 65 \u00b0C, and the full electrochemical biosensor showed no loss of performance after extended storage at 40 \u00b0C. The engineered stability and specificity of this assay should be extendable to other cases in which biomolecular detection in demanding environments is required.", "doi": "10.1021/nn404296k", "issn": "1936-0851", "publisher": "American Chemical Society", "publication": "ACS Nano", "publication_date": "2013-10", "series_number": "10", "volume": "7", "issue": "10", "pages": "9452-9460" }, { "id": "authors:3mgjk-t8f04", "collection": "authors", "collection_id": "3mgjk-t8f04", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131031-134624016", "type": "article", "title": "A Cocktail of Thermally Stable, Chemically Synthesized Capture Agents for the Efficient Detection of Anti-Gp41 Antibodies from Human Sera", "author": [ { "family_name": "Pfeilsticker", "given_name": "Jessica A.", "clpid": "Pfeilsticker-J-A" }, { "family_name": "Umeda", "given_name": "Aiko", "clpid": "Umeda-Aiko" }, { "family_name": "Farrow", "given_name": "Blake", "clpid": "Farrow-B" }, { "family_name": "Hsueh", "given_name": "Connie L.", "clpid": "Hsueh-Connnie-L" }, { "family_name": "Deyle", "given_name": "Kaycie M.", "clpid": "Deyle-K-M" }, { "family_name": "Kim", "given_name": "Jocelyn T.", "orcid": "0000-0001-8723-8190", "clpid": "Kim-Jocelyn-T" }, { "family_name": "Lai", "given_name": "Bert T.", "clpid": "Lai-Bert-T" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on a method to improve in vitro diagnostic assays that detect immune response, with specific application to HIV-1. The inherent polyclonal diversity of the humoral immune response was addressed by using sequential in situ click chemistry to develop a cocktail of peptide-based capture agents, the components of which were raised against different, representative anti-HIV antibodies that bind to a conserved epitope of the HIV-1 envelope protein gp41. The cocktail was used to detect anti-HIV-1 antibodies from a panel of sera collected from HIV-positive patients, with improved signal-to-noise ratio relative to the gold standard commercial recombinant protein antigen. The capture agents were stable when stored as a powder for two months at temperatures close to 60\u00b0C.", "doi": "10.1371/journal.pone.0076224", "pmcid": "PMC3792125", "issn": "1932-6203", "publisher": "Public Library of Science", "publication": "PLoS ONE", "publication_date": "2013-10", "series_number": "10", "volume": "8", "issue": "10", "pages": "Art. No. e76224" }, { "id": "authors:4tnjx-5va54", "collection": "authors", "collection_id": "4tnjx-5va54", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130906-082857317", "type": "article", "title": "Microchip platforms for multiplex single-cell functional proteomics with applications to immunology and cancer research", "author": [ { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "Wang", "given_name": "Jun", "clpid": "Wang-Jun" }, { "family_name": "Elitas", "given_name": "Meltem", "clpid": "Elitas-M" }, { "family_name": "Fan", "given_name": "Rong", "clpid": "Fan-Rong" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Single-cell functional proteomics assays can connect\ngenomic information to biological function through\nquantitative and multiplex protein measurements.\nTools for single-cell proteomics have developed rapidly\nover the past 5 years and are providing approaches for\ndirectly elucidating phosphoprotein signaling networks\nin cancer cells or for capturing high-resolution\nsnapshots of immune system function in patients\nwith various disease conditions. We discuss advances\nin single-cell proteomics platforms, with an emphasis\non microchip methods. These methods can provide\na direct correlation of morphological, functional and\nmolecular signatures at the single-cell level. We also\nprovide examples of how those platforms are being\napplied to both fundamental biology and clinical\nstudies, focusing on immune-system monitoring and\nphosphoprotein signaling networks in cancer.", "doi": "10.1186/gm479", "pmcid": "PMC3978720", "issn": "1756-994X", "publisher": "BioMed Central", "publication": "Genome Medicine", "publication_date": "2013-08-29", "volume": "5", "pages": "Art. No. 75" }, { "id": "authors:f8jyb-5d330", "collection": "authors", "collection_id": "f8jyb-5d330", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130621-101448619", "type": "article", "title": "Betabox: a beta particle imaging system based on a position sensitive avalanche photodiode", "author": [ { "family_name": "Dooraghi", "given_name": "A. A.", "clpid": "Dooraghi-A-A" }, { "family_name": "Vu", "given_name": "N. T.", "clpid": "Vu-N-T" }, { "family_name": "Silverman", "given_name": "R. W.", "clpid": "Silverman-R-W" }, { "family_name": "Farrell", "given_name": "R.", "clpid": "Farrell-R" }, { "family_name": "Shah", "given_name": "K. S.", "clpid": "Shah-K-S" }, { "family_name": "Wang", "given_name": "J.", "clpid": "Wang-J" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Chatziioannou", "given_name": "A. F.", "clpid": "Chatziioannou-A-F" } ], "abstract": "A beta camera has been developed that allows planar imaging of the spatial and temporal distribution of beta particles using a 14 \u00d7 14 mm^2 position sensitive avalanche photodiode (PSAPD). This camera system, which we call Betabox, can be directly coupled to microfluidic chips designed for cell incubation or other biological applications. Betabox allows for imaging the cellular uptake of molecular imaging probes labeled with charged particle emitters such as ^(18)F inside these chips. In this work, we investigate the quantitative imaging capabilities of Betabox for ^(18)F beta particles, in terms of background rate, efficiency, spatial resolution, and count rate. Measurements of background and spatial resolution are considered both at room temperature (21 \u00b0C \u00b1 1 \u00b0C) and at an elevated operating temperature (37 \u00b0C \u00b1 1 \u00b0C), as is often required for biological assays. The background rate measured with a 4 keV energy cutoff is below 2 cph mm^(\u22122) at both 21 and 37 \u00b0C. The absolute efficiency of Betabox for the detection of ^(18)F positron sources in contact with a PSAPD with the surface passivated from ambient light and damage is 46% \u00b1 1%. The lower detection limit is estimated using the Rose Criterion to be 0.2 cps mm^(\u22122) for 1 min acquisitions and a 62 \u00d7 62 \u00b5m^2 pixel size. The upper detection limit is approximately 21 000 cps. The spatial resolution at both 21 and 37 \u00b0C ranges from 0.4 mm FWHM at the center of the field of view (FOV), and degrades to 1 mm at a distance of 5 mm away from center yielding a useful FOV of approximately 10 \u00d7 10 mm^2. We also investigate the effects on spatial resolution and sensitivity that result from the use of a polymer based microfluidic chip. For these studies we place varying layers of low-density polyethylene (LDPE) between the detector and the source and find that the spatial resolution degrades by ~180 \u00b5m for every 100 \u00b5m of LDPE film. Sensitivity is reduced by half with the inclusion of ~200 \u00b5m of additional LDPE film. Lastly, we demonstrate the practical utilization of Betabox, with an imaging test of its linearity, when coupled to a polydimethylsiloxane microfluidic chip designed for cell based assays.", "doi": "10.1088/0031-9155/58/11/3739", "pmcid": "PMC3706465", "issn": "0031-9155", "publisher": "IOP", "publication": "Physics in Medicine and Biology", "publication_date": "2013-06-07", "series_number": "11", "volume": "58", "issue": "11", "pages": "3739-3753" }, { "id": "authors:sem89-tvs07", "collection": "authors", "collection_id": "sem89-tvs07", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140326-081558923", "type": "article", "title": "Use of iterative in situ click chemistry to develop a capture agent specific for a transforming point mutation in the pleckstrin homology domain of Akt1", "author": [ { "family_name": "Deyle", "given_name": "Kaycie M.", "clpid": "Deyle-K-M" }, { "family_name": "Hee", "given_name": "Ying Qiao", "clpid": "Hee-Ying-Qiao" }, { "family_name": "Millward", "given_name": "Steven", "clpid": "Millward-S-W" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We present an iterative in situ click chemistry approach to sequentially assemble peptide ligands that can selectively bind to and inhibit a transforming point mutation (E17K) found in the Pleckstrin Homology Domain (PHD) of the Akt1 kinase. The Akt1 kinase plays a critical role in the PI3K signaling pathway - the activation of which is closely linked to tumor development and cancer cell survival. It has recently been shown that the E17K mutation in the PHD of Akt1 results in an increased affinity of the PHD for the PIP3 substrate. Consequently, deregulated recruitment of Akt1 to the cell membrane causes constitutive activation of the PI3K pathway, which has been shown to induce leukemia in mice.", "doi": "10.1158/1538-7445.AM2013-LB-4", "issn": "0008-5472", "publisher": "American Association for Cancer Research", "publication": "Cancer Research", "publication_date": "2013-04-15", "series_number": "8", "volume": "73", "issue": "8", "pages": "Art. No. LB-4" }, { "id": "authors:yjzds-pwg31", "collection": "authors", "collection_id": "yjzds-pwg31", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130517-131724956", "type": "article", "title": "Hypoxia induces a phase transition within a kinase signaling network in cancer cells", "author": [ { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Shi", "given_name": "Qihui", "clpid": "Shi-Qihui" }, { "family_name": "Remacle", "given_name": "Francoise", "clpid": "Remacle-F" }, { "family_name": "Qin", "given_name": "Lidong", "clpid": "Qin-Lidong" }, { "family_name": "Shackelford", "given_name": "David B.", "clpid": "Shackelford-D-B" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Mischel", "given_name": "Paul S.", "clpid": "Mischel-P-S" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Hypoxia is a near-universal feature of cancer, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. In a glioblastoma multiforme (GBM) cancer cell model, we examined the response of signaling networks to targeted pathway inhibition between 21% and 1% pO_2. We used a microchip technology that facilitates quantification of a panel of functional proteins from statistical numbers of single cells. We find that near 1.5% pO_2, the signaling network associated with mammalian target of rapamycin (mTOR) complex 1 (mTORC1)\u2014a critical component of hypoxic signaling and a compelling cancer drug target\u2014is deregulated in a manner such that it will be unresponsive to mTOR kinase inhibitors near 1.5% pO2, but will respond at higher or lower pO_2 values. These predictions were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor. We attempt to understand this behavior through the use of a quantitative version of Le Chatelier's principle, as well as through a steady-state kinetic model of protein interactions, both of which indicate that hypoxia can influence mTORC1 signaling as a switch. The Le Chatelier approach also indicates that this switch may be thought of as a type of phase transition. Our analysis indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles.", "doi": "10.1073/pnas.1303060110", "pmcid": "PMC3625329", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2013-04-09", "series_number": "15", "volume": "110", "issue": "15", "pages": "E1352-E1360" }, { "id": "authors:v82fs-8mm50", "collection": "authors", "collection_id": "v82fs-8mm50", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130627-100022739", "type": "article", "title": "Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy", "author": [ { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "Cheung", "given_name": "Ann F.", "clpid": "Cheung-Ann-F" }, { "family_name": "Chodon", "given_name": "Thinle", "clpid": "Chodon-Thinle" }, { "family_name": "Koya", "given_name": "Richard C.", "clpid": "Koya-Richard-C" }, { "family_name": "Wu", "given_name": "Zhongqi", "clpid": "Wu-Zhongqi" }, { "family_name": "Ng", "given_name": "Charles", "clpid": "Ng-Charles" }, { "family_name": "Avramis", "given_name": "Earl", "clpid": "Avramis-Earl" }, { "family_name": "Cochran", "given_name": "Alistair J.", "clpid": "Cochran-Alistair-J" }, { "family_name": "Witte", "given_name": "Owen N.", "orcid": "0000-0003-4461-4533", "clpid": "Witte-O-N" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" }, { "family_name": "Chmielowski", "given_name": "Bartosz", "clpid": "Chmielowski-Bartosz" }, { "family_name": "Economou", "given_name": "James S.", "clpid": "Economou-James-S" }, { "family_name": "Comin-Anduix", "given_name": "Begonya", "clpid": "Comin-Anduix-Begonya" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-Antoni" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. These analyses revealed the coordinated functional dynamics of the adoptively transferred, as well as endogenous, T cells, and the importance of highly functional T cells in dominating the antitumor immune response. This study highlights the need to develop approaches to maintaining antitumor T-cell functionality with the aim of increasing the long-term efficacy of TCR-engineered ACT immunotherapy.\n\nSignificance: A longitudinal functional study of adoptively transferred TCR\u2013engineered lymphocytes yielded revealing snapshots for understanding the changes of antitumor responses over time in ACT immunotherapy of patients with advanced melanoma.", "doi": "10.1158/2159-8290.CD-12-0383", "pmcid": "PMC3716460", "issn": "2159-8274", "publisher": "American Association for Cancer Research", "publication": "Cancer Discovery", "publication_date": "2013-04", "series_number": "4", "volume": "3", "issue": "4", "pages": "418-429" }, { "id": "authors:4yr4g-1pw09", "collection": "authors", "collection_id": "4yr4g-1pw09", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130225-154105117", "type": "article", "title": "Catalysis of Dioxygen Reduction by Thermus thermophilus Strain HB27 Laccase on Ketjen Black Electrodes", "author": [ { "family_name": "Agbo", "given_name": "Peter", "clpid": "Agbo-P" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" } ], "abstract": "We present electrochemical analyses of the catalysis of dioxygen reduction by Thermus thermophilus strain HB27 laccase on ketjen black substrates. Our cathodes reliably produce 0.56 mA cm^(-2) at 0.0 V vs Ag|AgCl reference at 30 \u00b0C in air-saturated buffer, under conditions of nonlimiting O_(2) flux. We report the electrochemical activity of this laccase as a function of temperature, pH, time, and the efficiency of its conversion of dioxygen to water. We have measured the surface concentration of electrochemically active species, permitting the extraction of electron transfer rates at the enzyme-electrode interface: 1 s^(-1) for this process at zero driving force at 30 \u00b0C and a limiting rate of 23 s^(-1) at 240 mV overpotential at 50 \u00b0C.", "doi": "10.1021/jp309759g", "pmcid": "PMC3548030", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2013-01-17", "series_number": "2", "volume": "117", "issue": "2", "pages": "527-534" }, { "id": "authors:6pzks-kvv60", "collection": "authors", "collection_id": "6pzks-kvv60", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130117-072805253", "type": "article", "title": "In situ click chemistry: from small molecule discovery to synthetic antibodies", "author": [ { "family_name": "Millward", "given_name": "Steven W.", "orcid": "0000-0002-3231-7075", "clpid": "Millward-Steven-W" }, { "family_name": "Agnew", "given_name": "Heather D.", "orcid": "0000-0003-0010-3248", "clpid": "Agnew-Heather-D" }, { "family_name": "Lai", "given_name": "Bert T.", "clpid": "Lai-Bert-T" }, { "family_name": "Lee", "given_name": "Su Seong", "clpid": "Lee-Su-Seong" }, { "family_name": "Lim", "given_name": "Jaehong", "clpid": "Lim-Jaehong" }, { "family_name": "Nag", "given_name": "Arundhati", "orcid": "0000-0002-1328-1695", "clpid": "Nag-Arundhati" }, { "family_name": "Pitram", "given_name": "Suresh", "clpid": "Pitram-Suresh-M" }, { "family_name": "Rohde", "given_name": "Rosemary", "clpid": "Rohde-Rosemary-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Advances in the fields of proteomics, molecular imaging, and therapeutics are closely linked to the availability of affinity reagents that selectively recognize their biological targets. Here we present a review of Iterative Peptide In Situ Click Chemistry (IPISC), a novel screening technology for designing peptide multiligands with high affinity and specificity. This technology builds upon in situ click chemistry, a kinetic target-guided synthesis approach where the protein target catalyzes the conjugation of two small molecules, typically through the azide\u2013alkyne Huisgen cycloaddition. Integrating this methodology with solid phase peptide libraries enables the assembly of linear and branched peptide multiligands we refer to as Protein Catalyzed Capture Agents (PCC Agents). The resulting structures can be thought of as analogous to the antigen recognition site of antibodies and serve as antibody replacements in biochemical and cell-based applications. In this review, we discuss the recent progress in ligand design through IPISC and related approaches, focusing on the improvements in affinity and specificity as multiligands are assembled by target-catalyzed peptide conjugation. We compare the IPISC process to small molecule in situ click chemistry with particular emphasis on the advantages and technical challenges of constructing antibody-like PCC Agents.", "doi": "10.1039/C2IB20110K", "pmcid": "PMC3716466", "issn": "1757-9694", "publisher": "Royal Society of Chemistry", "publication": "Integrative Biology", "publication_date": "2013-01", "series_number": "1", "volume": "5", "issue": "1", "pages": "87-95" }, { "id": "authors:84d5x-f8g20", "collection": "authors", "collection_id": "84d5x-f8g20", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130103-153656327", "type": "article", "title": "Quantitating Cell\u2013Cell Interaction Functions with Applications to Glioblastoma Multiforme Cancer Cells", "author": [ { "family_name": "Wang", "given_name": "Jun", "clpid": "Wang-Jun" }, { "family_name": "Tham", "given_name": "Douglas", "clpid": "Tham-Douglas" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "Ahmad", "given_name": "Habib", "clpid": "Ahmad-H" }, { "family_name": "Shi", "given_name": "Qihui", "clpid": "Shi-Qihui" }, { "family_name": "Yu", "given_name": "Jenkan", "clpid": "Yu-Jenkan" }, { "family_name": "Levine", "given_name": "Raphael D.", "clpid": "Levine-R-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on a method for quantitating the distance dependence of cell\u2013cell interactions. We employ a microchip design that permits a multiplex, quantitative protein assay from statistical numbers of cell pairs, as a function of cell separation, with a 0.15 nL volume microchamber. We interrogate interactions between pairs of model brain cancer cells by assaying for six functional proteins associated with PI3k signaling. At short incubation times, cells do not appear to influence each other, regardless of cell separation. For 6 h incubation times, the cells exert an inhibiting influence on each other at short separations and a predominately activating influence at large separation. Protein-specific cell\u2013cell interaction functions are extracted, and by assuming pairwise additivity of those interactions, the functions are shown to correctly predict the results from three-cell experiments carried out under the identical conditions.", "doi": "10.1021/nl302748q", "pmcid": "PMC3680341", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2012-12", "series_number": "12", "volume": "12", "issue": "12", "pages": "6101-6106" }, { "id": "authors:346am-zg678", "collection": "authors", "collection_id": "346am-zg678", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20121213-093659505", "type": "article", "title": "Silicon Nanowire Charge-Trap Memory Incorporating Self-Assembled Iron Oxide Quantum Dots", "author": [ { "family_name": "Huang", "given_name": "Ruo-Gu", "clpid": "Huang-Ruo-Gu" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Charge-trap non-volatile memory devices based upon the precise integration of quantum dot storage elements with silicon nanowire field-effect transistors are described. Template-assisted assembly yields an ordered array of FeO QDs within the trenches that separate highly aligned SiNWs, and injected charges are reversibly stored via Fowler\u2013Nordheim tunneling into the QDs. Stored charges shift the transistor threshold voltages, providing the basis for a memory device. Quantum dot size is found to strongly influence memory performance metrics.", "doi": "10.1002/smll.201200940", "issn": "1613-6810", "publisher": "Wiley", "publication": "Small", "publication_date": "2012-11-19", "series_number": "22", "volume": "8", "issue": "22", "pages": "3417-3421" }, { "id": "authors:vajfa-bba31", "collection": "authors", "collection_id": "vajfa-bba31", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130325-093910426", "type": "article", "title": "Single Cell Proteomics Reveals Novel Cytokine-Producing Function of Hematopoietic Stem and Progenitor Cells", "author": [ { "family_name": "Zhao", "given_name": "Jimmy L.", "clpid": "Zhao-Jimmy-L" }, { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "O'Connell", "given_name": "Ryan M.", "clpid": "O'Connell-Ryan-M" }, { "family_name": "Rao", "given_name": "Dinesh S.", "orcid": "0000-0002-0794-9337", "clpid": "Rao-Dinesh-S" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" } ], "abstract": "During infection, hematopoietic stem and progenitor cells (HSPCs) are called upon to proliferate and differentiate to produce\nmore innate and adaptive immune cells to combat infection. Traditionally, HSPCs are thought to respond to depletion of\ndownstream hematopoietic cells during infection. More recent evidence suggests that HSPCs may respond directly to\ninfection and pro-inflammatory cytokines. However, little is known about the direct immune response of HSPCs and the\nmolecular signaling regulating this response upon sensing an infection. In this study, we have combined transgenic and\ngenetic knockout mouse models with a novel single cell barcode proteomics microchip technology to tackle these questions.\nWe show that although long-term hematopoietic stem cells (HSCs) (defined by Lineage-cKit+Sca1+CD150+CD48-) do not\nsecrete cytokines upon toll-like receptor (TLR) stimulation, short-term HSCs and multipotent progenitor cells (MPPs)\n(defined by Lineage-cKit+Sca1+, referred to as LKS thereafter) can produce copious amounts of cytokines upon direct\nTLR-4 and TLR-2 stimulation, indicating that LKS cells can directly participate in an immune response by producing a myriad\nof cytokines, upon a bacterial infection. Within the population of LKS cells we detect multiple functional subsets of cells,\nspecialized in producing myeloid-like, lymphoid-like or both types of cytokines. Moreover, we show that the cytokine\nproduction by LKS cells is regulated by the NF-\u03baB activity, as p50-deficient LKS cells show reduced cytokine production\nwhile microRNA-146a (miR-146a)-deficient LKS cells show significantly increased cytokine production.", "issn": "0006-4971", "publisher": "American Society of Hematology", "publication": "Blood", "publication_date": "2012-11-16", "series_number": "21", "volume": "120", "issue": "21", "pages": "26" }, { "id": "authors:p147v-7gb57", "collection": "authors", "collection_id": "p147v-7gb57", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191218-093955448", "type": "article", "title": "A microfluidic-based bubble generation platform enables analysis of physical property change in phospholipid surfactant layers by interfacial ozone reaction", "author": [ { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Choi", "given_name": "Tae Su", "clpid": "Choi-Tae-Su" }, { "family_name": "Kim", "given_name": "Hyungjun", "orcid": "0000-0001-8261-9381", "clpid": "Kim-Hyungjun" }, { "family_name": "Beauchamp", "given_name": "J. L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Kim", "given_name": "Hugh I.", "orcid": "0000-0002-6210-3107", "clpid": "Kim-Hugh-I" } ], "abstract": "The air-liquid interface filled with pulmonary surfactant is a unique feature of our lung alveoli. The mechanical properties of this interface play an important role in breathing and its malfunction induced by an environmental hazard, such as ozone, relates to various lung diseases. In order to understand the interfacial physics of the pulmonary surfactant system, we employed a microfluidic bubble generation platform with a model pulmonary surfactant composed of two major phospholipids: DPPC (1,2-dipalmitoyl-sn-phosphatidylcholine) and POPG (1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol). With fluorescence imaging, we observed the ozone-induced chemical modification of the unsaturated lipid component of the lipid mixture, POPG. This chemical change due to the oxidative stress was further utilized to study the physical characteristics of the interface through the bubble formation process. The physical property change was evaluated through the oscillatory behaviour of the monolayer, as well as the bubble size and formation time. The results presented demonstrate the potential of this platform to study interfacial physics of lung surfactant system under various environmental challenges, both qualitatively and quantitatively.", "doi": "10.1039/c2lc40940b", "pmcid": "PMC3681610", "issn": "1473-0197", "publisher": "Royal Society of Chemistry", "publication": "Lab on a Chip", "publication_date": "2012-11-13", "series_number": "24", "volume": "12", "issue": "24", "pages": "5243-5248" }, { "id": "authors:cwmf9-env95", "collection": "authors", "collection_id": "cwmf9-env95", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120417-113310153", "type": "article", "title": "Designer Reagents for Mass Spectrometry-Based Proteomics: Clickable Cross-Linkers for Elucidation of Protein Structures and Interactions", "author": [ { "family_name": "Sohn", "given_name": "Chang Ho", "clpid": "Sohn-Chang-Ho" }, { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-H-D" }, { "family_name": "Lee", "given_name": "J. Eugene", "clpid": "Lee-J-Eugene" }, { "family_name": "Sweredoski", "given_name": "Michael J.", "orcid": "0000-0003-0878-3831", "clpid": "Sweredoski-M-J" }, { "family_name": "Graham", "given_name": "Robert L. J.", "clpid": "Graham-R-L-J" }, { "family_name": "Smith", "given_name": "Geoffrey T.", "clpid": "Smith-G-T" }, { "family_name": "Hess", "given_name": "Sonja", "orcid": "0000-0002-5904-9816", "clpid": "Hess-S" }, { "family_name": "Czerwieniec", "given_name": "Gregg", "clpid": "Czerwieniec-G" }, { "family_name": "Loo", "given_name": "Joseph A.", "clpid": "Loo-Joseph-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Deshaies", "given_name": "Raymond J.", "orcid": "0000-0002-3671-9354", "clpid": "Deshaies-R-J" }, { "family_name": "Beauchamp", "given_name": "J. L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" } ], "abstract": "We present novel homobifunctional amine-reactive clickable cross-linkers (CXLs) for investigation of three-dimensional protein structures and protein\u2013protein interactions (PPIs). CXLs afford consolidated advantages not previously available in a simple cross-linker, including (1) their small size and cationic nature at physiological pH, resulting in good water solubility and cell-permeability, (2) an alkyne group for bio-orthogonal conjugation to affinity tags via the click reaction for enrichment of cross-linked peptides, (3) a nucleophilic displacement reaction involving the 1,2,3-triazole ring formed in the click reaction, yielding a lock-mass reporter ion for only clicked peptides, and (4) higher charge states of cross-linked peptides in the gas-phase for augmented electron transfer dissociation (ETD) yields. Ubiquitin, a lysine-abundant protein, is used as a model system to demonstrate structural studies using CXLs. To validate the sensitivity of our approach, biotin-azide labeling and subsequent enrichment of cross-linked peptides are performed for cross-linked ubiquitin digests mixed with yeast cell lysates. Cross-linked peptides are detected and identified by collision induced dissociation (CID) and ETD with linear quadrupole ion trap (LTQ)-Fourier transform ion cyclotron resonance (FTICR) and LTQ-Orbitrap mass spectrometers. The application of CXLs to more complex systems (e.g., in vivo cross-linking) is illustrated by Western blot detection of Cul1 complexes including known binders, Cand1 and Skp2, in HEK 293 cells, confirming good water solubility and cell-permeability.", "doi": "10.1021/ac202637n", "pmcid": "PMC3310289", "issn": "0003-2700", "publisher": "American Chemical Society", "publication": "Analytical Chemistry", "publication_date": "2012-03-20", "series_number": "6", "volume": "84", "issue": "6", "pages": "2662-2669" }, { "id": "authors:st8zx-k8x31", "collection": "authors", "collection_id": "st8zx-k8x31", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120622-114310759", "type": "article", "title": "New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer", "author": [ { "family_name": "Stroncek", "given_name": "David F.", "clpid": "Stroncek-David-F" }, { "family_name": "Berger", "given_name": "Carolina", "clpid": "Berger-Carolina" }, { "family_name": "Cheever", "given_name": "Martin A.", "clpid": "Cheever-Martin-A" }, { "family_name": "Childs", "given_name": "Richard W.", "clpid": "Childs-Richard-W" }, { "family_name": "Dudley", "given_name": "Mark E.", "clpid": "Dudley-Mark-E" }, { "family_name": "Flynn", "given_name": "Peter", "clpid": "Flynn-Peter" }, { "family_name": "Gattinoni", "given_name": "Luca", "clpid": "Gattinoni-Luca" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Kalos", "given_name": "Michael", "clpid": "Kalos-Michael" }, { "family_name": "Marincola", "given_name": "Francesco M.", "clpid": "Marincola-Francesco-M" }, { "family_name": "Miller", "given_name": "Jeffrey S.", "clpid": "Miller-Jeffrey-S" }, { "family_name": "Mostoslavsky", "given_name": "Gustavo", "clpid": "Mostoslavsky-Gustavo" }, { "family_name": "Powell", "given_name": "Daniel J., Jr.", "clpid": "Powell-Daniel-J-Jr" }, { "family_name": "Rao", "given_name": "Mahendra", "clpid": "Rao-Mahendra" }, { "family_name": "Restifo", "given_name": "Nicholas P.", "clpid": "Restifo-Nicholas-P" }, { "family_name": "Rosenberg", "given_name": "Steven A.", "clpid": "Rosenberg-Steven-A" }, { "family_name": "O'Shea", "given_name": "John", "clpid": "O'Shea-John" }, { "family_name": "Melief", "given_name": "Cornelis J. M.", "clpid": "Melief-Cornelis-J-M" } ], "abstract": "A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more na\u00efve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies.", "doi": "10.1186/1479-5876-10-48", "pmcid": "PMC3362772", "issn": "1479-5876", "publisher": "BioMed Central", "publication": "Journal of Translational Medicine", "publication_date": "2012-03-15", "volume": "10", "pages": "Art. No. 48" }, { "id": "authors:gv2sg-esh62", "collection": "authors", "collection_id": "gv2sg-esh62", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120507-073422918", "type": "article", "title": "Visualizing Local Doping Effects of Individual Water Clusters on Gold(111)-Supported Graphene", "author": [ { "family_name": "Cao", "given_name": "Peigen", "clpid": "Cao-Peigen" }, { "family_name": "Varghese", "given_name": "Joseph O.", "clpid": "Varghese-J-O" }, { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The local charge carrier density of graphene can exhibit significant and highly localized variations that arise from the interaction between graphene and the local environment, such as adsorbed water, or a supporting substrate. However, it has been difficult to correlate such spatial variations with individual impurity sites. By trapping (under graphene) nanometer-sized water clusters on the atomically well-defined Au(111) substrate, we utilize scanning tunneling microscopy and spectroscopy to characterize the local doping influence of individual water clusters on graphene. We find that water clusters, predominantly nucleated at the atomic steps of Au(111), induce strong and highly localized electron doping in graphene. A positive correlation is observed between the water cluster size and the local doping level, in support of the recently proposed electrostatic-field-mediated doping mechanism. Our findings quantitatively demonstrate the importance of substrate-adsorbed water on the electronic properties of graphene.", "doi": "10.1021/nl2041673", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2012-03", "series_number": "3", "volume": "12", "issue": "3", "pages": "1459-1463" }, { "id": "authors:zfn4t-mfm40", "collection": "authors", "collection_id": "zfn4t-mfm40", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120203-103706722", "type": "article", "title": "Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells", "author": [ { "family_name": "Shi", "given_name": "Qihui", "clpid": "Shi-Qihui" }, { "family_name": "Qin", "given_name": "Lidong", "clpid": "Qin-Lidong" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Geng", "given_name": "Feng", "clpid": "Geng-Feng" }, { "family_name": "Fan", "given_name": "Rong", "clpid": "Fan-Rong" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Guo", "given_name": "Deliang", "clpid": "Guo-Deliang" }, { "family_name": "Hood", "given_name": "Leroy", "orcid": "0000-0001-7158-3678", "clpid": "Hood-L-E" }, { "family_name": "Mischel", "given_name": "Paul S.", "clpid": "Mischel-P-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We describe a microchip designed to quantify the levels of a dozen cytoplasmic and membrane proteins from single cells. We use the platform to assess protein\u2013protein interactions associated with the EGF-receptor-mediated PI3K signaling pathway. Single-cell sensitivity is achieved by isolating a defined number of cells (n = 0\u20135) in 2 nL volume chambers, each of which is patterned with two copies of a miniature antibody array. The cells are lysed on-chip, and the levels of released proteins are assayed using the antibody arrays. We investigate three isogenic cell lines representing the cancer glioblastoma multiforme, at the basal level, under EGF stimulation, and under erlotinib inhibition plus EGF stimulation. The measured protein abundances are consistent with previous work, and single-cell analysis uniquely reveals single-cell heterogeneity, and different types and strengths of protein\u2013protein interactions. This platform helps provide a comprehensive picture of altered signal transduction networks in tumor cells and provides insight into the effect of targeted therapies on protein signaling networks.", "doi": "10.1073/pnas.1110865109", "pmcid": "PMC3258586", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2012-01-10", "series_number": "2", "volume": "109", "issue": "2", "pages": "419-424" }, { "id": "authors:qtscy-wjh21", "collection": "authors", "collection_id": "qtscy-wjh21", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120130-134629717", "type": "article", "title": "The Microscopic Structure of Adsorbed Water on Hydrophobic Surfaces under Ambient Conditions", "author": [ { "family_name": "Cao", "given_name": "Peigen", "clpid": "Cao-Peigen" }, { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Varghese", "given_name": "Joseph O.", "clpid": "Varghese-J-O" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The interaction of water vapor with hydrophobic surfaces is poorly understood. We utilize graphene templating to preserve and visualize the microscopic structures of adsorbed water on hydrophobic surfaces. Three well-defined surfaces [H\u2013Si(111), graphite, and functionalized mica] were investigated, and water was found to adsorb as nanodroplets (~10\u2013100 nm in size) on all three surfaces under ambient conditions. The adsorbed nanodroplets were closely associated with atomic-scale surface defects and step-edges and wetted all the hydrophobic substrates with contact angles < ~10\u00b0, resulting in total water adsorption that was similar to what is found for hydrophilic surfaces. These results point to the significant differences between surface processes at the atomic/nanometer scales and in the macroscopic world.", "doi": "10.1021/nl2036639", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2011-12", "series_number": "12", "volume": "11", "issue": "12", "pages": "5581-5586" }, { "id": "authors:yspe5-f1g69", "collection": "authors", "collection_id": "yspe5-f1g69", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120105-084339625", "type": "article", "title": "Iterative in Situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1", "author": [ { "family_name": "Millward", "given_name": "Steven W.", "clpid": "Millward-S-W" }, { "family_name": "Henning", "given_name": "Ryan K.", "clpid": "Henning-R-K" }, { "family_name": "Kwong", "given_name": "Gabriel A.", "clpid": "Kwong-Gabriel-A" }, { "family_name": "Pitram", "given_name": "Suresh", "clpid": "Pitram-S" }, { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-H-D" }, { "family_name": "Deyle", "given_name": "Kaycie M.", "clpid": "Deyle-K-M" }, { "family_name": "Nag", "given_name": "Arundhati", "clpid": "Nag-A" }, { "family_name": "Hein", "given_name": "Jason", "clpid": "Hein-J" }, { "family_name": "Lee", "given_name": "Su Seong", "clpid": "Lee-Su-Seong" }, { "family_name": "Lim", "given_name": "Jaehong", "clpid": "Lim-Jaehong" }, { "family_name": "Pfeilsticker", "given_name": "Jessica A.", "clpid": "Pfeilsticker-J-A" }, { "family_name": "Sharpless", "given_name": "K. Barry", "orcid": "0000-0001-6051-1599", "clpid": "Sharpless-K-B" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties.", "doi": "10.1021/ja2064389", "pmcid": "PMC3651860", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2011-11-16", "series_number": "45", "volume": "133", "issue": "45", "pages": "18280-18288" }, { "id": "authors:2bed4-70141", "collection": "authors", "collection_id": "2bed4-70141", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111213-071827066", "type": "article", "title": "High Performance Ring Oscillators from 10-nm Wide Silicon\n Nanowire Field-Effect Transistors", "author": [ { "family_name": "Huang", "given_name": "Ruo-Gu", "clpid": "Huang-Ruo-Gu" }, { "family_name": "Tham", "given_name": "Douglas", "clpid": "Tham-Douglas" }, { "family_name": "Wang", "given_name": "Dunwei", "clpid": "Wang-Dunwei" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We explore 10-nm wide Si nanowire (SiNW) field-effect transistors (FETs) for logic applications, via the fabrication\nand testing of SiNW-based ring oscillators. We report on SiNW surface treatments and dielectric annealing, for\nproducing SiNW FETs that exhibit high performance in terms of large on/off-state current ratio (~10^8), low\ndrain-induced barrier lowering (~30 mV) and low subthreshold swing (~80 mV/decade). The performance of\ninverter and ring-oscillator circuits fabricated from these nanowire FETs are also explored. The inverter\ndemonstrates the highest voltage gain (~148) reported for a SiNW-based NOT gate, and the ring oscillator\nexhibits near rail-to-rail oscillation centered at 13.4 MHz. The static and dynamic characteristics of these NW\ndevices indicate that these SiNW-based FET circuits are excellent candidates for various high-performance\nnanoelectronic applications.", "doi": "10.1007/s12274-011-0157-2", "issn": "1998-0124", "publisher": "Springer Verlag", "publication": "Nano Research", "publication_date": "2011-10", "series_number": "10", "volume": "4", "issue": "10", "pages": "1005-1012" }, { "id": "authors:wd8wb-2t351", "collection": "authors", "collection_id": "wd8wb-2t351", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111107-100516467", "type": "article", "title": "A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins", "author": [ { "family_name": "Ahmad", "given_name": "Habib", "clpid": "Ahmad-H" }, { "family_name": "Sutherland", "given_name": "Alex", "clpid": "Sutherland-A" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Hwang", "given_name": "Kiwook", "clpid": "Hwang-Kiwook" }, { "family_name": "Qin", "given_name": "Lidong", "clpid": "Qin-Lidong" }, { "family_name": "Krom", "given_name": "Russell-John", "clpid": "Krom-R-J" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells.", "doi": "10.1063/1.3636077", "pmcid": "PMC3189969", "issn": "0034-6748", "publisher": "American Institute of Physics", "publication": "Review of Scientific Instruments", "publication_date": "2011-09", "series_number": "9", "volume": "82", "issue": "9", "pages": "Art. No. 094301" }, { "id": "authors:jxyp2-pc272", "collection": "authors", "collection_id": "jxyp2-pc272", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110706-095329536", "type": "article", "title": "High-Density, Multiplexed Patterning of Cells at Single-Cell\n Resolution for Tissue Engineering and Other Applications", "author": [ { "family_name": "Vermesh", "given_name": "Udi", "clpid": "Vermesh-U" }, { "family_name": "Vermesh", "given_name": "Ophir", "clpid": "Vermesh-O" }, { "family_name": "Wang", "given_name": "Jun", "clpid": "Wang-Jun" }, { "family_name": "Kwong", "given_name": "Gabriel A.", "clpid": "Kwong-Gabriel-A" }, { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "Hwang", "given_name": "Kiwook", "clpid": "Hwang-Kiwook" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Surface chemistry meets tissue engineering: A novel surface-patterning approach for creating arrays of DNA squares is combined with a unique method for DNA-encoding of cells to construct dense arrays of distinct single cells. The cell patterns can be transferred from the substrate surface into thin hydrogel films, and these layers can be stacked to form 3D tissue constructs.", "doi": "10.1002/anie.201102249", "pmcid": "PMC3651859", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2011-08-01", "series_number": "32", "volume": "50", "issue": "32", "pages": "7378-7380" }, { "id": "authors:6enxn-b7t26", "collection": "authors", "collection_id": "6enxn-b7t26", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110621-120304768", "type": "article", "title": "A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells", "author": [ { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "Fan", "given_name": "Rong", "clpid": "Fan-Rong" }, { "family_name": "Ahmad", "given_name": "Habib", "clpid": "Ahmad-H" }, { "family_name": "Shi", "given_name": "Qihui", "clpid": "Shi-Qihui" }, { "family_name": "Comin-Anduix", "given_name": "Begonya", "clpid": "Comin-Anduix-B" }, { "family_name": "Chodon", "given_name": "Thinle", "clpid": "Chodon-T" }, { "family_name": "Koya", "given_name": "Richard C.", "clpid": "Koya-R-C" }, { "family_name": "Liu", "given_name": "Chao-Chao", "clpid": "Liu-Chao-Chao" }, { "family_name": "Kwong", "given_name": "Gabriel A.", "clpid": "Kwong-Gabriel-A" }, { "family_name": "Radu", "given_name": "Caius G.", "clpid": "Radu-C-G" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Cellular immunity has an inherent high level of functional heterogeneity. Capturing the full spectrum of these functions requires analysis of large numbers of effector molecules from single cells. We report a microfluidic platform designed for highly multiplexed (more than ten proteins), reliable, sample-efficient (~1 \u00d7 10^4 cells) and quantitative measurements of secreted proteins from single cells. We validated the platform by assessment of multiple inflammatory cytokines from lipopolysaccharide (LPS)-stimulated human macrophages and comparison to standard immunotechnologies. We applied the platform toward the ex vivo quantification of T cell polyfunctional diversity via the simultaneous measurement of a dozen effector molecules secreted from tumor antigen\u2013specific cytotoxic T lymphocytes (CTLs) that were actively responding to tumor and compared against a cohort of healthy donor controls. We observed profound, yet focused, functional heterogeneity in active tumor antigen\u2013specific CTLs, with the major functional phenotypes quantitatively identified. The platform represents a new and informative tool for immune monitoring and clinical assessment.", "doi": "10.1038/nm.2375", "pmcid": "PMC3681612", "issn": "1078-8956", "publisher": "Nature Publishing Group", "publication": "Nature Medicine", "publication_date": "2011-06", "series_number": "6", "volume": "17", "issue": "6", "pages": "738-743" }, { "id": "authors:qsskd-2xr77", "collection": "authors", "collection_id": "qsskd-2xr77", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110608-114722932", "type": "article", "title": "Protein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling", "author": [ { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Remacle", "given_name": "F.", "clpid": "Remacle-F" }, { "family_name": "Fan", "given_name": "Rong", "clpid": "Fan-Rong" }, { "family_name": "Hwang", "given_name": "Kiwook", "clpid": "Hwang-Kiwook" }, { "family_name": "Wei", "given_name": "Wei", "orcid": "0000-0002-1018-7708", "clpid": "Wei-Wei" }, { "family_name": "Ahmad", "given_name": "Habib", "clpid": "Ahmad-H" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Protein signaling networks among cells play critical roles in a host of pathophysiological processes, from inflammation to tumorigenesis. We report on an approach that integrates microfluidic cell handling, in situ protein secretion profiling, and information theory to determine an extracellular protein-signaling network and the role of perturbations. We assayed 12 proteins secreted from human macrophages that were subjected to lipopolysaccharide challenge, which emulates the macrophage-based innate immune responses against Gram-negative bacteria. We characterize the fluctuations in protein secretion of single cells, and of small cell colonies (n = 2, 3,\u00b7\u00b7\u00b7), as a function of colony size. Measuring the fluctuations permits a validation of the conditions required for the application of a quantitative version of the Le Chatelier's principle, as derived using information theory. This principle provides a quantitative prediction of the role of perturbations and allows a characterization of a protein-protein interaction network.", "doi": "10.1016/j.bpj.2011.04.025", "pmcid": "PMC3093549", "issn": "0006-3495", "publisher": "Biophysical Society", "publication": "Biophysical Journal", "publication_date": "2011-05-18", "series_number": "10", "volume": "100", "issue": "10", "pages": "2378-2386" }, { "id": "authors:taxtv-yjz75", "collection": "authors", "collection_id": "taxtv-yjz75", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110404-093933135", "type": "article", "title": "Atomic Force Microscopy Characterization of Room-Temperature Adlayers of Small Organic Molecules through Graphene Templating", "author": [ { "family_name": "Cao", "given_name": "Peigen", "clpid": "Cao-Peigen" }, { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Varghese", "given_name": "Joseph O.", "clpid": "Varghese-J-O" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on the use of graphene templating to investigate the room-temperature structure and dynamics of weakly bound adlayers at the interfaces between solids and vapors of small organic molecules. Monolayer graphene sheets are employed to preserve and template molecularly thin adlayers of tetrahydrofuran (THF) and cyclohexane on atomically flat mica substrates, thus permitting a structural characterization of the adlayers under ambient conditions through atomic force microscopy. We found the first two adlayers of both molecules adsorb in a layer-by-layer fashion, and atomically flat two-dimensional islands are observed for both the first and the second adlayers. THF adlayers form initially as rounded islands but, over a period of weeks, evolve into faceted islands, suggesting that the adlayers possess both liquid and solid properties at room temperature. Cyclohexane adlayers form crystal-like faceted islands and are immobile under the graphene template. The heights of the second adlayers of THF and cyclohexane are measured to be 0.44 \u00b1 0.02 and 0.50 \u00b1 0.02 nm, respectively, in good agreement with the layer thicknesses in the monoclinic crystal structure of THF and the Phase I \"plastic crystal\" structure of cyclohexane. The first adlayers appear slightly thinner for both molecules, indicative of interactions of the molecules with the mica substrate.", "doi": "10.1021/ja108554p", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2011-03-02", "series_number": "8", "volume": "133", "issue": "8", "pages": "2334-2337" }, { "id": "authors:h3v6n-n1a59", "collection": "authors", "collection_id": "h3v6n-n1a59", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110223-104207586", "type": "article", "title": "A solid-state switch containing an electrochemically switchable bistable poly[n]rotaxane", "author": [ { "family_name": "Zhang", "given_name": "Wenyu", "clpid": "Zhang-Wenyu" }, { "family_name": "DeIonno", "given_name": "Erica", "clpid": "DeIonno-E" }, { "family_name": "Dichtel", "given_name": "William R.", "orcid": "0000-0002-3635-6119", "clpid": "Dichtel-W-R" }, { "family_name": "Fang", "given_name": "Lei", "clpid": "Fang-Lei" }, { "family_name": "Trabolsi", "given_name": "Ali", "clpid": "Trabolsi-A" }, { "family_name": "Olsen", "given_name": "John-Carl", "clpid": "Olsen-J-C" }, { "family_name": "Ben\u00edtez", "given_name": "Diego", "clpid": "Ben\u00edtez-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "Electrochemically switchable bistable main-chain poly[n]rotaxanes have been synthesised using\na threading-followed-by-stoppering approach and were incorporated into solid-state, molecular switch\ntunnel junction devices. In contrast to single-station poly[n]rotaxanes of similar structure, the bistable\npolymers do not fold into compact conformations held together by donor\u2013acceptor interactions\nbetween alternating stacked p-electron rich and p-electron deficient aromatic systems. Films of the\npoly[n]rotaxane were incorporated into the devices by spin-coating, and their thickness was easily\ncontrolled. The switching functionality was characterised both (1) in solution by cyclic voltammetry\nand (2) in devices containing either two metal electrodes or one metal and one silicon electrode. Devices\nwith one silicon electrode displayed hysteretic responses with applied voltage, allowing the devices to be\nswitched between two conductance states, whereas devices containing two metal electrodes did not\nexhibit switching behaviour. The electrochemically switchable bistable poly[n]rotaxanes offer\nsignificant advantages in synthetic efficiency and ease of device fabrication as compared to bistable\nsmall-molecule [2]rotaxanes.", "doi": "10.1039/c0jm02269a", "issn": "0959-9428", "publisher": "Royal Society of Chemistry", "publication": "Journal of Materials Chemistry", "publication_date": "2011-02-07", "series_number": "5", "volume": "21", "issue": "5", "pages": "1487-1495" }, { "id": "authors:xyk3a-vax54", "collection": "authors", "collection_id": "xyk3a-vax54", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110301-113228946", "type": "article", "title": "Flow optimization study of a batch microfluidics PET tracer synthesizing device", "author": [ { "family_name": "Elizarov", "given_name": "Arkadij M.", "clpid": "Elizarov-A-M" }, { "family_name": "Meinhart", "given_name": "Carl", "clpid": "Meinhart-C" }, { "family_name": "Miraghaie", "given_name": "Reza", "clpid": "Miraghaie-R" }, { "family_name": "van Dam", "given_name": "R. Michael", "clpid": "van-Dam-R-M" }, { "family_name": "Huang", "given_name": "Jiang", "clpid": "Huang-Jiang" }, { "family_name": "Daridon", "given_name": "Antoine", "clpid": "Daridon-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Kolb", "given_name": "Hartmuth C.", "clpid": "Kolb-H-C" } ], "abstract": "We present numerical modeling and experimental studies of flow optimization inside a batch microfluidic micro-reactor used for synthesis of human-scale doses of Positron Emission Tomography (PET) tracers. Novel techniques are used for mixing within, and eluting liquid out of, the coin-shaped reaction chamber. Numerical solutions of the general incompressible Navier Stokes equations along with time-dependent elution scalar field equation for the three dimensional coin-shaped geometry were obtained and validated using fluorescence imaging analysis techniques. Utilizing the approach presented in this work, we were able to identify optimized geometrical and operational conditions for the micro-reactor in the absence of radioactive material commonly used in PET related tracer production platforms as well as evaluate the designed and fabricated micro-reactor using numerical and experimental validations.", "doi": "10.1007/s10544-010-9488-0", "pmcid": "PMC3028087", "issn": "1387-2176", "publisher": "Springer", "publication": "Biomedical Microdevices", "publication_date": "2011-02", "series_number": "1", "volume": "13", "issue": "1", "pages": "231-242" }, { "id": "authors:d0ds1-61402", "collection": "authors", "collection_id": "d0ds1-61402", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110310-100121704", "type": "article", "title": "Batch Fabrication of High-Performance Planar Patch-Clamp Devices in Quartz", "author": [ { "family_name": "Nagarah", "given_name": "John M.", "clpid": "Nagarah-J-M" }, { "family_name": "Paek", "given_name": "Eunsu", "clpid": "Paek-Eunsu" }, { "family_name": "Luo", "given_name": "Yi", "clpid": "Luo-Yi" }, { "family_name": "Wang", "given_name": "Pin", "clpid": "Wang-Pin" }, { "family_name": "Hwang", "given_name": "Gyeong S.", "orcid": "0000-0002-5538-9426", "clpid": "Hwang-Gyeong-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The success of the patch-clamp technique has driven an effort to create wafer-based patch-clamp platforms. We develop a lithographic/electrochemical processing scheme that generates ultrasmooth, high aspect ratio pores in quartz. These devices achieve gigaohm seals in nearly 80% of trials, with the majority exhibiting seal resistances from 20-80 G\u03a9, competing with pipette-based patch-clamp measurements.", "doi": "10.1002/adma.201001793", "issn": "0935-9648", "publisher": "Wiley", "publication": "Advanced Materials", "publication_date": "2010-11-02", "series_number": "41", "volume": "22", "issue": "41", "pages": "4622-4627" }, { "id": "authors:xxfp6-z0y74", "collection": "authors", "collection_id": "xxfp6-z0y74", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101206-111639285", "type": "article", "title": "Ultradense, Deep Subwavelength Nanowire Array Photovoltaics As Engineered Optical Thin Films", "author": [ { "family_name": "Tham", "given_name": "Douglas", "clpid": "Tham-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A photovoltaic device comprised of an array of 20 nm wide, 32 nm pitch array of silicon nanowires is modeled as an optical material. The nanowire array (NWA) has characteristic device features that are deep in the subwavelength regime for light, which permits a number of simplifying approximations. Using photocurrent measurements as a probe of the absorptance, we show that the NWA optical properties can be accurately modeled with rigorous coupled-wave analysis. The densely structured NWAs behave as homogeneous birefringent materials into the ultraviolet with effective optical properties that are accurately modeled using the dielectric functions of bulk Si and SiO_2, coupled with a physical model for the NWA derived from ellipsometry and transmission electron microscopy.", "doi": "10.1021/nl102199b", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2010-11", "series_number": "11", "volume": "10", "issue": "11", "pages": "4429-4434" }, { "id": "authors:eebc8-jjq78", "collection": "authors", "collection_id": "eebc8-jjq78", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101108-150340183", "type": "article", "title": "Chemistries for Patterning Robust DNA MicroBarcodes Enable Multiplex Assays of Cytoplasm Proteins from Single Cancer Cells", "author": [ { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Ahmad", "given_name": "Habib", "clpid": "Ahmad-H" }, { "family_name": "Shi", "given_name": "Qihui", "clpid": "Shi-Qihui" }, { "family_name": "Kim", "given_name": "Hyungjun", "orcid": "0000-0001-8261-9381", "clpid": "Kim-Hyungjun" }, { "family_name": "Pascal", "given_name": "Tod A.", "orcid": "0000-0003-2096-1143", "clpid": "Pascal-T-A" }, { "family_name": "Fan", "given_name": "Rong", "clpid": "Fan-Rong" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The optimization of chemistries to enable the patterning of miniaturized DNA barcodes using microfluidics flow channels is described (see picture). Experiment and theory reveal that solvent mixtures in which counterions are strongly associated with the negatively charged DNA oligomers may be harnessed to produce high quality, high density DNA microarray patterns over a large area.", "doi": "10.1002/cphc.201000528", "pmcid": "PMC3681607", "issn": "1439-4235", "publisher": "Wiley", "publication": "ChemPhysChem", "publication_date": "2010-10-04", "series_number": "14", "volume": "11", "issue": "14", "pages": "3063-3069" }, { "id": "authors:arxj2-tz328", "collection": "authors", "collection_id": "arxj2-tz328", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101102-075006411", "type": "article", "title": "Reduction of thermal conductivity in phononic nanomesh structures", "author": [ { "family_name": "Yu", "given_name": "Jen-Kan", "clpid": "Yu-Jen-Kan" }, { "family_name": "Mitrovic", "given_name": "Slobodan", "orcid": "0000-0001-8913-8505", "clpid": "Mitrovic-S" }, { "family_name": "Tham", "given_name": "Douglas", "clpid": "Tham-Douglas" }, { "family_name": "Varghese", "given_name": "Joseph", "clpid": "Varghese-J" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Controlling the thermal conductivity of a material independently of its electrical conductivity continues to be a goal for researchers working on thermoelectric materials for use in energy applications and in the cooling of integrated circuits. In principle, the thermal conductivity \u03ba and the electrical conductivity \u03c3 may be independently optimized in semiconducting nanostructures because different length scales are associated with phonons (which carry heat) and electric charges (which carry current). Phonons are scattered at surfaces and interfaces, so \u03ba generally decreases as the surface-to-volume ratio increases. In contrast, \u03c3 is less sensitive to a decrease in nanostructure size, although at sufficiently small sizes it will degrade through the scattering of charge carriers at interfaces. Here, we demonstrate an approach to independently controlling \u03ba based on altering the phonon band structure of a semiconductor thin film through the formation of a phononic nanomesh film. These films are patterned with periodic spacings that are comparable to, or shorter than, the phonon mean free path. The nanomesh structure exhibits a substantially lower thermal conductivity than an equivalently prepared array of silicon nanowires, even though this array has a significantly higher surface-to-volume ratio. Bulk-like electrical conductivity is preserved. We suggest that this development is a step towards a coherent mechanism for lowering thermal conductivity.", "doi": "10.1038/nnano.2010.149", "issn": "1748-3387", "publisher": "Nature Publishing Group", "publication": "Nature Nanotechnology", "publication_date": "2010-10", "series_number": "10", "volume": "5", "issue": "10", "pages": "718-721" }, { "id": "authors:8s1zt-v8g48", "collection": "authors", "collection_id": "8s1zt-v8g48", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101102-073526881", "type": "article", "title": "Achieving the Theoretical Depairing Current Limit in Superconducting Nanomesh Films", "author": [ { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Cao", "given_name": "Peigen", "clpid": "Cao-Peigen" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We show the theoretical depairing current limit can be achieved in a robust fashion in highly ordered superconductor nanomesh films having spatial periodicities smaller than both the superconducting coherence length and the magnetic penetration depth. For a niobium nanomesh film with 34 nm spatial periodicity, the experimental critical current density is enhanced by more than 17 times over the continuous film and is in good agreement with the depairing limit over the entire measured temperature range. The nanomesh superconductors are also less susceptible to thermal fluctuations when compared to nanowire superconductors. T_c values similar to the bulk film are achieved, and the nanomeshes are capable of retaining superconductivity to higher fields relative to the bulk. In addition, periodic oscillations in T_c are observed as a function of field, reflecting the highly ordered nanomesh structure.", "doi": "10.1021/nl102584j", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2010-10", "series_number": "10", "volume": "10", "issue": "10", "pages": "4206-4210" }, { "id": "authors:s44n2-a3t41", "collection": "authors", "collection_id": "s44n2-a3t41", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100920-101811136", "type": "article", "title": "Graphene Visualizes the First Water Adlayers on Mica at Ambient Conditions", "author": [ { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Cao", "given_name": "Peigen", "clpid": "Cao-Peigen" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The dynamic nature of the first water adlayers on solid surfaces at room temperature has made the direct detection of their microscopic structure challenging. We used graphene as an atomically flat coating for atomic force microscopy to determine the structure of the water adlayers on mica at room temperature as a function of relative humidity. Water adlayers grew epitaxially on the mica substrate in a layer-by-layer fashion. Submonolayers form atomically flat, faceted islands of height 0.37 \u00b1 0.02 nanometers, in agreement with the height of a monolayer of ice. The second adlayers, observed at higher relative humidity, also appear icelike, and thicker layers appear liquidlike. Our results also indicate nanometer-scale surface defects serve as nucleation centers for the formation of both the first and the second adlayers.", "doi": "10.1126/science.1192907", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2010-09-03", "series_number": "5996", "volume": "329", "issue": "5996", "pages": "1188-1191" }, { "id": "authors:vm6jg-rfd38", "collection": "authors", "collection_id": "vm6jg-rfd38", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100809-141144680", "type": "article", "title": "Time Resolved Studies of Interfacial Reactions of Ozone with Pulmonary Phospholipid Surfactants Using Field Induced Droplet Ionization Mass Spectrometry", "author": [ { "family_name": "Kim", "given_name": "Hugh I.", "orcid": "0000-0002-6210-3107", "clpid": "Kim-Hugh-Inkon" }, { "family_name": "Kim", "given_name": "Hyungjun", "orcid": "0000-0001-8261-9381", "clpid": "Kim-Hyungjun" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Beegle", "given_name": "Luther W.", "orcid": "0000-0002-4944-4353", "clpid": "Beegle-L-W" }, { "family_name": "Goddard", "given_name": "William Andrew", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Kanik", "given_name": "Isik", "orcid": "0000-0002-7912-2865", "clpid": "Kanik-Isik" }, { "family_name": "Beauchamp", "given_name": "J. L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" } ], "abstract": "Field induced droplet ionization mass spectrometry (FIDI-MS) comprises a soft ionization method to sample ions from the surface of microliter droplets. A pulsed electric field stretches neutral droplets until they develop dual Taylor cones, emitting streams of positively and negatively charged submicrometer droplets in opposite directions, with the desired polarity being directed into a mass spectrometer for analysis. This methodology is employed to study the heterogeneous ozonolysis of 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) at the air\u2212liquid interface in negative ion mode using FIDI mass spectrometry. Our results demonstrate unique characteristics of the heterogeneous reactions at the air\u2212liquid interface. We observe the hydroxyhydroperoxide and the secondary ozonide as major products of POPG ozonolysis in the FIDI-MS spectra. These products are metastable and difficult to observe in the bulk phase, using standard electrospray ionization (ESI) for mass spectrometric analysis. We also present studies of the heterogeneous ozonolysis of a mixture of saturated and unsaturated phospholipids at the air\u2212liquid interface. A mixture of the saturated phospholipid 1,2-dipalmitoyl-sn-phosphatidylglycerol (DPPG) and unsaturated POPG is investigated in negative ion mode using FIDI-MS while a mixture of 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) and 1-stearoyl-2-oleoyl-sn-phosphatidylcholine (SOPC) surfactant is studied in positive ion mode. In both cases FIDI-MS shows the saturated and unsaturated pulmonary surfactants form a mixed interfacial layer. Only the unsaturated phospholipid reacts with ozone, forming products that are more hydrophilic than the saturated phospholipid. With extensive ozonolysis only the saturated phospholipid remains at the droplet surface. Combining these experimental observations with the results of computational analysis provides an improved understanding of the interfacial structure and chemistry of a surfactant layer system when subject to oxidative stress.", "doi": "10.1021/jp102332g", "pmcid": "PMC3695605", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2010-07-29", "series_number": "29", "volume": "114", "issue": "29", "pages": "9496-9503" }, { "id": "authors:0eh1c-55676", "collection": "authors", "collection_id": "0eh1c-55676", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100521-111915396", "type": "article", "title": "Maximal entropy inference of oncogenicity from phosphorylation signaling", "author": [ { "family_name": "Graeber", "given_name": "T. G.", "clpid": "Graeber-T-G" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Skaggs", "given_name": "B. J.", "clpid": "Skaggs-B-J" }, { "family_name": "Phelps", "given_name": "M. E.", "clpid": "Phelps-M-E" }, { "family_name": "Remacle", "given_name": "F.", "clpid": "Remacle-F" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" } ], "abstract": "Point mutations in the phosphorylation domain of the Bcr-Abl fusion oncogene give rise to drug resistance in chronic myelogenous leukemia patients. These mutations alter kinase-mediated signaling function and phenotypic outcome. An information theoretic analysis of the correlation of phosphoproteomic profiling and transformation potency of the oncogene in different mutants is presented. The theory seeks to predict the leukemic transformation potency from the observed signaling by constructing a distribution of maximal entropy of site-specific phosphorylation events. The theory is developed with special reference to systems biology where high throughput measurements are typical. We seek sets of phosphorylation events most contributory to predicting the phenotype by determining the constraints on the signaling system. The relevance of a constraint is measured by how much it reduces the value of the entropy from its global maximum, where all events are equally likely. Application to experimental phospho-proteomics data for kinase inhibitor-resistant mutants shows that there is one dominant constraint and that other constraints are not relevant to a similar extent. This single constraint accounts for much of the correlation of phosphorylation events with the oncogenic potency and thereby usefully predicts the trends in the phenotypic output. An additional constraint possibly accounts for biological fine structure.", "doi": "10.1073/pnas.1001149107", "pmcid": "PMC2851899", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2010-03-30", "series_number": "13", "volume": "107", "issue": "13", "pages": "6112-6117" }, { "id": "authors:ghhq0-d7c85", "collection": "authors", "collection_id": "ghhq0-d7c85", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100407-112655335", "type": "article", "title": "Interfacial Reactions of Ozone with Surfactant Protein B in a Model Lung Surfactant System", "author": [ { "family_name": "Kim", "given_name": "Hugh I.", "orcid": "0000-0002-6210-3107", "clpid": "Kim-Hugh-Inkon" }, { "family_name": "Kim", "given_name": "Hyungjun", "orcid": "0000-0001-8261-9381", "clpid": "Kim-Hyungjun" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Beegle", "given_name": "Luther W.", "orcid": "0000-0002-4944-4353", "clpid": "Beegle-L-W" }, { "family_name": "Jang", "given_name": "Seung Soon", "orcid": "0000-0002-1920-421X", "clpid": "Jang-Seung-Soon" }, { "family_name": "Neidholdt", "given_name": "Evan L.", "clpid": "Neidholdt-Evan-Lyle" }, { "family_name": "Goddard", "given_name": "William Andrew", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Kanik", "given_name": "Isik", "orcid": "0000-0002-7912-2865", "clpid": "Kanik-Isik" }, { "family_name": "Beauchamp", "given_name": "J. L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" } ], "abstract": "Oxidative stresses from irritants such as hydrogen peroxide and ozone (O_3) can cause dysfunction of the pulmonary surfactant (PS) layer in the human lung, resulting in chronic diseases of the respiratory tract. For identification of structural changes of pulmonary surfactant protein B (SP-B) due to the heterogeneous reaction with O_3, field-induced droplet ionization (FIDI) mass spectrometry has been utilized. FIDI is a soft ionization method in which ions are extracted from the surface of microliter-volume droplets. We report structurally specific oxidative changes of SP-B_(1\u221225) (a shortened version of human SP-B) at the air\u2212liquid interface. We also present studies of the interfacial oxidation of SP-B_(1\u221225) in a nonionizable 1-palmitoyl-2-oleoyl-sn-glycerol (POG) surfactant layer as a model PS system, where competitive oxidation of the two components is observed. Our results indicate that the heterogeneous reaction of SP-B_(1\u221225) at the interface is quite different from that in the solution phase. In comparison with the nearly complete homogeneous oxidation of SP-B_(1\u221225), only a subset of the amino acids known to react with ozone are oxidized by direct ozonolysis in the hydrophobic interfacial environment, both with and without the lipid surfactant layer. Combining these experimental observations with the results of molecular dynamics simulations provides an improved understanding of the interfacial structure and chemistry of a model lung surfactant system subjected to oxidative stress.", "doi": "10.1021/ja908477w", "pmcid": "PMC2830728", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2010-02-24", "series_number": "7", "volume": "132", "issue": "7", "pages": "2254-2263" }, { "id": "authors:02t4s-vja52", "collection": "authors", "collection_id": "02t4s-vja52", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100302-092458141", "type": "article", "title": "Design and Optimization of Coin-Shaped Microreactor Chips for PET Radiopharmaceutical Synthesis", "author": [ { "family_name": "Elizarov", "given_name": "Arkadij M.", "clpid": "Elizarov-A-M" }, { "family_name": "van Dam", "given_name": "R. Michael", "clpid": "van-Dam-R-M" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Kolb", "given_name": "Hartmuth C.", "clpid": "Kolb-H-C" }, { "family_name": "Padgett", "given_name": "Henry C.", "clpid": "Padgett-H-C" }, { "family_name": "Stout", "given_name": "David", "clpid": "Stout-D" }, { "family_name": "Shu", "given_name": "Jenny", "clpid": "Shu-Jenny" }, { "family_name": "Huang", "given_name": "Jiang", "clpid": "Huang-Jiang" }, { "family_name": "Daridon", "given_name": "Antoine", "clpid": "Daridon-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "An integrated elastomeric microfluidic device, with a footprint the size of a postage stamp, has been designed and optimized for multistep radiosynthesis of PET tracers. Methods: The unique architecture of the device is centered around a 5-\u00b5L coin-shaped reactor, which yields reaction efficiency and speed from a combination of high reagent concentration, pressurized reactions, and rapid heat and mass transfer. Its novel features facilitate mixing, solvent exchange, and product collection. New mixing mechanisms assisted by vacuum, pressure, and chemical reactions are exploited. Results: The architecture of the reported reactor is the first that has allowed batch-mode microfluidic devices to produce radiopharmaceuticals of sufficient quality and quantity to be validated by in vivo imaging. Conclusion: The reactor has the potential to produce multiple human doses of ^(18)F-FDG; the most impact, however, is expected in the synthesis of PET radiopharmaceuticals that can be made only with low yields by currently available equipment.", "doi": "10.2967/jnumed.109.065946", "pmcid": "PMC3000316", "issn": "0161-5505", "publisher": "Society of Nuclear Medicine", "publication": "Journal of Nuclear Medicine", "publication_date": "2010-02-10", "series_number": "2", "volume": "51", "issue": "2", "pages": "282-287" }, { "id": "authors:harce-8k531", "collection": "authors", "collection_id": "harce-8k531", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100205-150456548", "type": "article", "title": "Accurate MALDI-TOF/TOF Sequencing of One-Bead\u2212One-Compound Peptide Libraries with Application to the Identification of Multiligand Protein Affinity Agents Using in Situ Click Chemistry Screening", "author": [ { "family_name": "Lee", "given_name": "Su Seong", "clpid": "Lee-Su-Seong" }, { "family_name": "Lim", "given_name": "Jaehong", "clpid": "Lim-Jaehong" }, { "family_name": "Tan", "given_name": "Sylvia", "clpid": "Tan-Sylvia" }, { "family_name": "Cha", "given_name": "Junhoe", "clpid": "Cha-Junhoe" }, { "family_name": "Yeo", "given_name": "Shi Yun", "clpid": "Yeo-Shi-Yun" }, { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-H-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Combinatorial one-bead\u2212one-compound (OBOC) peptide libraries are widely used for affinity screening, and the sequencing of peptides from hit beads is a key step in the process. For rapid sequencing, CNBr cleavage of the peptides from the beads, followed by de novo sequencing by MALDI-TOF/TOF, is explored. We report on a semiautomated sequencing algorithm and validate it through comparison against Edman degradation sequencing. The initial 44% sequencing success rate of the standard de novo sequencing software was improved to nearly 100%. The sequencing algorithm incorporates existing knowledge of amino acid chemistry and a new strategy for differentiating isobaric amino acids. We tested the algorithm by using MALDI-TOF/TOF to identify a peptide biligand affinity agent against the protein bovine carbonic anhydrase II, starting from comprehensive one-bead\u2212one-compound peptide libraries comprised of non-natural and artificial amino acid components and using the strategy of in situ click/OBOC library screening.", "doi": "10.1021/ac902195y", "pmcid": "PMC2829877", "issn": "0003-2700", "publisher": "American Chemical Society", "publication": "Analytical Chemistry", "publication_date": "2010-01-15", "series_number": "2", "volume": "82", "issue": "2", "pages": "672-679" }, { "id": "authors:mxbnq-xze25", "collection": "authors", "collection_id": "mxbnq-xze25", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101012-100925718", "type": "article", "title": "A self-powered, one-step chip for rapid, quantitative and multiplexed detection of proteins from pinpricks of whole blood", "author": [ { "family_name": "Wang", "given_name": "Jun", "clpid": "Wang-Jun" }, { "family_name": "Ahmad", "given_name": "Habib", "clpid": "Ahmad-H" }, { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "Shi", "given_name": "Qihui", "clpid": "Shi-Qihui" }, { "family_name": "Vermesh", "given_name": "Ophir", "clpid": "Vermesh-O" }, { "family_name": "Vermesh", "given_name": "Udi", "clpid": "Vermesh-U" }, { "family_name": "Heath", "given_name": "James", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We describe an automated, self-powered chip based on lateral flow immunoassay for rapid, quantitative, and multiplex protein detection from pinpricks of whole blood. The device incorporates on-chip purification of blood plasma by employing inertial forces to focus blood cells away from the assay surface, where plasma proteins are captured and detected on antibody \"barcode\" arrays. Power is supplied from the capillary action of a piece of adsorbent paper, and sequentially drives, over a 40 minute period, the four steps required to capture serum proteins and then develop a multiplex immunoassay. An 11 protein panel is assayed from whole blood, with high sensitivity and high reproducibility. This inexpensive, self-contained, and easy to operate chip provides a useful platform for point-of-care diagnoses, particularly in resource-limited settings.", "doi": "10.1039/C0LC00132E", "pmcid": "PMC3651856", "issn": "1473-0197", "publisher": "Royal Society of Chemistry", "publication": "Lab on a Chip", "publication_date": "2010", "series_number": "10 (22", "volume": "2010", "issue": "10 (22", "pages": "3157-3162" }, { "id": "authors:gcrc3-yeg66", "collection": "authors", "collection_id": "gcrc3-yeg66", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20091223-134117061", "type": "article", "title": "Scanning Tunneling Microscopy Characterization of the Electrical Properties of Wrinkles in Exfoliated Graphene Monolayers", "author": [ { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Cao", "given_name": "Peigen", "clpid": "Cao-Peigen" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on the scanning tunneling microscopy study of a new class of corrugations in exfoliated monolayer graphene sheets, that is, wrinkles ~10 nm in width and ~3 nm in height. We found such corrugations to be ubiquitous in graphene and have distinctly different properties when compared to other regions of graphene. In particular, a \"three-for-six\" triangular pattern of atoms is exclusively and consistently observed on wrinkles, suggesting the local curvature of the wrinkle provides a sufficient perturbation to break the 6-fold symmetry of the graphene lattice. Through scanning tunneling spectroscopy, we further demonstrate that the wrinkles have lower electrical conductance and are characterized by the presence of midgap states, which is in agreement with recent theoretical predictions. The observed wrinkles are likely important for understanding the electrical properties of graphene.", "doi": "10.1021/nl902729p", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2009-12", "series_number": "12", "volume": "9", "issue": "12", "pages": "4446-4451" }, { "id": "authors:xfs5v-afj11", "collection": "authors", "collection_id": "xfs5v-afj11", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20091012-154359037", "type": "article", "title": "Molecular Electronics", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Molecular electronics describes the field in which molecules are utilized as the active (switching, sensing, etc.) or passive (current rectifiers, surface passivants) elements in electronic devices. This review focuses on experimental aspects of molecular electronics that researchers have elucidated over the past decade or so and that relate to the fabrication of molecular electronic devices in which the molecular components are readily distinguished within the electronic properties of the device. Materials, fabrication methods, and methods for characterizing electrode materials, molecular monolayers, and molecule/electrode interfaces are discussed. A particular focus is on devices in which the molecules or molecular monolayer are sandwiched between two immobile electrodes. Four specific examples of such devices, in which the electron transport characteristics reflect distinctly molecular properties, are discussed.", "doi": "10.1146/annurev-matsci-082908-145401", "issn": "1531-7331", "publisher": "Annual Reviews", "publication": "Annual Review of Materials Research", "publication_date": "2009-08", "volume": "39", "pages": "1-23" }, { "id": "authors:q2jx4-h6041", "collection": "authors", "collection_id": "q2jx4-h6041", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090808-142501147", "type": "article", "title": "Modular Nucleic Acid Assembled p/MHC Microarrays for Multiplexed Sorting of Antigen-Specific T Cells", "author": [ { "family_name": "Kwong", "given_name": "Gabriel A.", "clpid": "Kwong-Gabriel-A" }, { "family_name": "Radu", "given_name": "Caius G.", "clpid": "Radu-C-G" }, { "family_name": "Hwang", "given_name": "Kiwook", "clpid": "Hwang-Kiwook" }, { "family_name": "Shu", "given_name": "Chengyi J.", "clpid": "Shu-Chengyi-J" }, { "family_name": "Ma", "given_name": "Chao", "clpid": "Ma-Chao" }, { "family_name": "Koya", "given_name": "Richard C.", "clpid": "Koya-R-C" }, { "family_name": "Comin-Anduix", "given_name": "Begonya", "clpid": "Comin-Anduix-B" }, { "family_name": "Hadrup", "given_name": "Sine Reker", "clpid": "Hadrup-S-R" }, { "family_name": "Bailey", "given_name": "Ryan C.", "clpid": "Bailey-R-C" }, { "family_name": "Witte", "given_name": "Owen N.", "orcid": "0000-0003-4461-4533", "clpid": "Witte-O-N" }, { "family_name": "Schumacher", "given_name": "Ton N.", "clpid": "Schumacher-T-N" }, { "family_name": "Ribas", "given_name": "Antoni", "clpid": "Ribas-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The human immune system consists of a large number of T cells capable of recognizing and responding to antigens derived from various sources. The development of peptide-major histocompatibility (p/MHC) tetrameric complexes has enabled the direct detection of these antigen-specific T cells. With the goal of increasing throughput and multiplexing of T cell detection, protein microarrays spotted with defined p/MHC complexes have been reported, but studies have been limited due to the inherent instability and reproducibility of arrays produced via conventional spotted methods. Herein, we report on a platform for the detection of antigen-specific T cells on glass substrates that offers significant advantages over existing surface-bound schemes. In this approach, called \"Nucleic Acid Cell Sorting (NACS)\", single-stranded DNA oligomers conjugated site-specifically to p/MHC tetramers are employed to immobilize p/MHC tetramers via hybridization to a complementary-printed substrate. Fully assembled p/MHC arrays are used to detect and enumerate T cells captured from cellular suspensions, including primary human T cells collected from cancer patients. NACS arrays outperform conventional spotted arrays assessed in key criteria such as repeatability and homogeneity. The versatility of employing DNA sequences for cell sorting is exploited to enable the programmed, selective release of target populations of immobilized T cells with restriction endonucleases for downstream analysis. Because of the performance, facile and modular assembly of p/MHC tetramer arrays, NACS holds promise as a versatile platform for multiplexed T cell detection.", "doi": "10.1021/ja9006707", "pmcid": "PMC2720314", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2009-07-22", "series_number": "28", "volume": "131", "issue": "28", "pages": "9695-9703" }, { "id": "authors:w8qdz-h5q57", "collection": "authors", "collection_id": "w8qdz-h5q57", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090910-091059453", "type": "article", "title": "Self-powered microfluidic chips for multiplexed protein assays from whole blood", "author": [ { "family_name": "Qin", "given_name": "Lidong", "clpid": "Qin-Lidong" }, { "family_name": "Vermesh", "given_name": "Ophir", "clpid": "Vermesh-O" }, { "family_name": "Shi", "given_name": "Qihui", "clpid": "Shi-Qihui" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report herein on a self-powered, self-contained microfluidic-based chip designed to separate plasma from whole blood, and then execute an assay of a multiplexed panel of plasma biomarker proteins. The power source is based upon a chemical reaction that is catalytically triggered by the push of a button on the chip. We demonstrate assays of a dozen blood-based protein biomarkers using this automated, self-contained device. This platform can potentially permit high throughput, accurate, multiplexed blood diagnostic measurements in remote locations and by minimally trained individuals.", "doi": "10.1039/b821247c", "pmcid": "PMC3651861", "issn": "1473-0197", "publisher": "Royal Society of Chemistry", "publication": "Lab on a Chip", "publication_date": "2009-07-21", "series_number": "14", "volume": "9", "issue": "14", "pages": "2016-2020" }, { "id": "authors:0er08-zdw15", "collection": "authors", "collection_id": "0er08-zdw15", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090828-162937053", "type": "article", "title": "The crossover from two dimensions to one dimension in granular electronic materials", "author": [ { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Qin", "given_name": "Lidong", "clpid": "Qin-Lidong" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Granular conductors1 are solids comprising densely packed nanoparticles, and have electrical properties that are determined by the size, composition and packing of the composite nanoparticles. The ability to control these properties in two- and three-dimensional granular conductors has made such systems appropriate for use as prototypes for investigating new physics1, 2, 3, 4. However, the fabrication of strictly one-dimensional granular conductors remains challenging. Here, we describe a method for the assembly of nanoparticles into granular solids that can be tuned continuously from two to one dimension, and establish how electron transport evolves between these limits. We find that the energy barriers to transport increase in the one-dimensional limit, in both the variable-range-hopping (low-voltage) and sequential-tunnelling (high-voltage) regimes. Furthermore, in the sequential-tunnelling regime we find an unexpected relationship between the temperature and the voltage at which the conductance becomes appreciable \u2014 a relationship that appears peculiar to one-dimensional systems. These results are explained by extrapolating existing granular conductor theories to one dimension.", "doi": "10.1038/NNANO.2009.81", "issn": "1748-3387", "publisher": "Nature Publishing Group", "publication": "Nature Nanotechnology", "publication_date": "2009-06", "series_number": "6", "volume": "4", "issue": "6", "pages": "368-372" }, { "id": "authors:s8mp4-7y810", "collection": "authors", "collection_id": "s8mp4-7y810", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090702-082701926", "type": "article", "title": "Fast nonlinear ion transport via field-induced hydrodynamic slip in sub-20-nm hydrophilic nanofluidic transistors", "author": [ { "family_name": "Vermesh", "given_name": "Udi", "clpid": "Vermesh-Udi" }, { "family_name": "Choi", "given_name": "Jang Wook", "orcid": "0000-0001-8783-0901", "clpid": "Choi-Jang-Wook" }, { "family_name": "Vermesh", "given_name": "Ophir", "orcid": "0000-0001-7453-3158", "clpid": "Vermesh-Ophir" }, { "family_name": "Fan", "given_name": "Rong", "clpid": "Fan-Rong" }, { "family_name": "Nagarah", "given_name": "John", "clpid": "Nagarah-J-M" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Electrolyte transport through an array of 20 nm wide, 20 \u03bcm long SiO_2 nanofluidic transistors is described. At sufficiently low ionic strength, the Debye screening length exceeds the channel width, and ion transport is limited by the negatively charged channel surfaces. At source\u2212drain biases >5 V, the current exhibits a sharp, nonlinear increase, with a 20\u221250-fold conductance enhancement. This behavior is attributed to a breakdown of the zero-slip condition. Implications for energy conversion devices are discussed.", "doi": "10.1021/nl802931r", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2009-04", "series_number": "4", "volume": "9", "issue": "4", "pages": "1315-1319" }, { "id": "authors:gghe0-sq879", "collection": "authors", "collection_id": "gghe0-sq879", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090804-133827150", "type": "article", "title": "Iterative in situ click chemistry creates antibody-like protein-capture agents", "author": [ { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-H-D" }, { "family_name": "Rohde", "given_name": "Rosemary D.", "clpid": "Rohde-R-D" }, { "family_name": "Millward", "given_name": "Steven W.", "clpid": "Millward-S-W" }, { "family_name": "Nag", "given_name": "Arundhati", "clpid": "Nag-A" }, { "family_name": "Yeo", "given_name": "Woon-Seok", "clpid": "Yeo-Woon-Seok" }, { "family_name": "Hein", "given_name": "Jason E.", "clpid": "Hein-J-E" }, { "family_name": "Pitram", "given_name": "Suresh M.", "clpid": "Pitram-S-M" }, { "family_name": "Tariq", "given_name": "Abdul Ahad", "clpid": "Tariq-A-A" }, { "family_name": "Burns", "given_name": "Vanessa M.", "clpid": "Burns-V-M" }, { "family_name": "Krom", "given_name": "Russell J.", "clpid": "Krom-R-J" }, { "family_name": "Fokin", "given_name": "Valery V.", "clpid": "Fokin-V-V" }, { "family_name": "Sharpless", "given_name": "K. Barry", "orcid": "0000-0001-6051-1599", "clpid": "Sharpless-K-B" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Iterative in situ click chemistry (see scheme for the tertiary ligand screen) and the one-bead-one-compound method for the creation of a peptide library enable the fragment-based assembly of selective high-affinity protein-capture agents. The resulting ligands are water-soluble and stable chemically, biochemically, and thermally. They can be produced in gram quantities through copper (I)-catalyzed cycloaddition.", "doi": "10.1002/anie.200900488", "pmcid": "PMC3716464", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2009-03-19", "series_number": "27", "volume": "48", "issue": "27", "pages": "4944-4948" }, { "id": "authors:y1a3t-wys49", "collection": "authors", "collection_id": "y1a3t-wys49", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090416-084420260", "type": "article", "title": "Free energy barrier for molecular motions in bistable [2]rotaxane molecular electronic devices", "author": [ { "family_name": "Kim", "given_name": "Hyungjun", "orcid": "0000-0001-8261-9381", "clpid": "Kim-Hyungjun" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Jang", "given_name": "Seung Soon", "orcid": "0000-0002-1920-421X", "clpid": "Jang-Seung-Soon" }, { "family_name": "Dichtel", "given_name": "William R.", "orcid": "0000-0002-3635-6119", "clpid": "Dichtel-W-R" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "Donor\u2212acceptor binding of the \u03c0-electron-poor cyclophane cyclobis(paraquat-p-phenylene) (CBPQT^(4+)) with the \u03c0-electron-rich tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) stations provides the basis for electrochemically switchable, bistable [2]rotaxanes, which have been incorporated and operated within solid-state devices to form ultradense memory circuits (ChemPhysChem 2002, 3, 519\u2212525; Nature 2007, 445, 414\u2212417) and nanoelectromechanical systems. The rate of CBPQT^(4+) shuttling at each oxidation state of the [2]rotaxane dictates critical write-and-retention time parameters within the devices, which can be tuned through chemical synthesis. To validate how well computational chemistry methods can estimate these rates for use in designing new devices, we used molecular dynamics simulations to calculate the free energy barrier for the shuttling of the CBPQT^4+ ring between the TTF and the DNP. The approach used here was to calculate the potential of mean force along the switching pathway, from which we calculated free energy barriers. These calculations find a turn-on time after the rotaxane is doubly oxidized of ~10^9\u22127) s (suggesting that the much longer experimental turn-on time is determined by the time scale of oxidization). The return barrier from the DNP to the TTF leads to a predicted lifetime of 2.1 s, which is compatible with experiments.", "doi": "10.1021/jp809213m", "issn": "1089-5639", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry A", "publication_date": "2009-03-12", "series_number": "10", "volume": "113", "issue": "10", "pages": "2136-2143" }, { "id": "authors:7qk36-93f40", "collection": "authors", "collection_id": "7qk36-93f40", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181114-082848785", "type": "article", "title": "Nanomedicine Targets Cancer", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" }, { "family_name": "Hood", "given_name": "Leroy", "orcid": "0000-0001-7158-3678", "clpid": "Hood-L-E" } ], "abstract": "Viewing each human body as a system of interacting molecular networks and targeting disruptions in the system with nanoscale technologies can transform how disease is understood, attacked and possibly prevented.", "doi": "10.1038/scientificamerican0209-44", "pmcid": "PMC3700418", "issn": "0036-8733", "publisher": "Scientific American", "publication": "Scientific American", "publication_date": "2009-02", "series_number": "2", "volume": "300", "issue": "2", "pages": "44-51" }, { "id": "authors:g2rjf-x3h95", "collection": "authors", "collection_id": "g2rjf-x3h95", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:SPRUacie08", "type": "article", "title": "Heterogeneous Catalysis through Microcontact Printing", "author": [ { "family_name": "Spruell", "given_name": "Jason M.", "clpid": "Spruell-J-M" }, { "family_name": "Sheriff", "given_name": "Bonnie A.", "clpid": "Sheriff-B-A" }, { "family_name": "Rozkiewicz", "given_name": "Dorota I.", "clpid": "Rozkiewicz-D-I" }, { "family_name": "Dichtel", "given_name": "William R.", "orcid": "0000-0002-3635-6119", "clpid": "Dichtel-W-R" }, { "family_name": "Rohde", "given_name": "Rosemary D.", "clpid": "Rohde-R-D" }, { "family_name": "Reinhoudt", "given_name": "David N.", "clpid": "Reinhoudt-D-N" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Here, we investigate four different chemical pathways (Scheme 1a\u2013d) relevant to the Cu-catalyzed azide\u2013alkyne cycloaddition (CuAAC) reaction.[13] Three of those pathways lead to surfaces functionalized with organic molecules.[5, 11, 14] At the outset, our practical goal was to identify surface-functionalization protocols that are capable of attaining 1) spatial selectivity, 2) high surface coverage, and 3) rapid reaction kinetics. Our ultimate goal is to achieve a fundamental understanding of how different reaction pathways influence the chemical outcome as it applies to the organic functionalization of surfaces.", "doi": "10.1002/anie.200803480", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2008-12-08", "series_number": "51", "volume": "47", "issue": "51", "pages": "9927-9932" }, { "id": "authors:7fh6m-5s297", "collection": "authors", "collection_id": "7fh6m-5s297", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:FANnb08", "type": "article", "title": "Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood", "author": [ { "family_name": "Fan", "given_name": "Rong", "clpid": "Fan-Rong" }, { "family_name": "Vermesh", "given_name": "Ophir", "clpid": "Vermesh-O" }, { "family_name": "Srivastava", "given_name": "Alok", "clpid": "Srivastava-A" }, { "family_name": "Yen", "given_name": "Brian K. H.", "clpid": "Yen-Brian-K-H" }, { "family_name": "Qin", "given_name": "Lidong", "clpid": "Qin-Lidong" }, { "family_name": "Ahmad", "given_name": "Habib", "clpid": "Ahmad-H" }, { "family_name": "Kwong", "given_name": "Gabriel A.", "clpid": "Kwong-Gabriel-A" }, { "family_name": "Liu", "given_name": "Chao-Chao", "clpid": "Liu-Chao-Chao" }, { "family_name": "Gould", "given_name": "Juliane", "clpid": "Gould-J" }, { "family_name": "Hood", "given_name": "Leroy", "orcid": "0000-0001-7158-3678", "clpid": "Hood-L-E" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "As the tissue that contains the largest representation of the human proteome [1], blood is the most important fluid for clinical diagnostics [2, 3, 4]. However, although changes of plasma protein profiles reflect physiological or pathological conditions associated with many human diseases, only a handful of plasma proteins are routinely used in clinical tests. Reasons for this include the intrinsic complexity of the plasma proteome [1], the heterogeneity of human diseases and the rapid degradation of proteins in sampled blood [5]. We report an integrated microfluidic system, the integrated blood barcode chip that can sensitively sample a large panel of protein biomarkers over broad concentration ranges and within 10 min of sample collection. It enables on-chip blood separation and rapid measurement of a panel of plasma proteins from quantities of whole blood as small as those obtained by a finger prick. Our device holds potential for inexpensive, noninvasive and informative clinical diagnoses, particularly in point-of-care settings.", "doi": "10.1038/nbt.1507", "pmcid": "PMC2775523", "issn": "1087-0156", "publisher": "Nature Publishing Group", "publication": "Nature Biotechnology", "publication_date": "2008-12", "series_number": "12", "volume": "26", "issue": "12", "pages": "1373-1378" }, { "id": "authors:5w5tv-02n02", "collection": "authors", "collection_id": "5w5tv-02n02", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAacc08", "type": "article", "title": "Superlattice Nanowire Pattern Transfer (SNAP)", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "During the past 15 years or so, nanowires (NWs) have emerged as a new and distinct class of materials. Their novel structural and physical properties separate them from wires that can be prepared using the standard methods for manufacturing electronics. NW-based applications that range from traditional electronic devices (logic and memory) to novel biomolecular and chemical sensors, thermoelectric materials, and optoelectronic devices, all have appeared during the past few years. From a fundamental perspective, NWs provide a route toward the investigation of new physics in confined dimensions. \n\nPerhaps the most familiar fabrication method is the vapor\u2212liquid\u2212solid (VLS) growth technique, which produces semiconductor nanowires as bulk materials. However, other fabrication methods exist and have their own advantages. \n\nIn this Account, I review a particular class of NWs produced by an alternative method called superlattice nanowire pattern transfer (SNAP). The SNAP method is distinct from other nanowire preparation methods in several ways. It can produce large NW arrays from virtually any thin-film material, including metals, insulators, and semiconductors. The dimensions of the NWs can be controlled with near-atomic precision, and NW widths and spacings can be as small as a few nanometers. In addition, SNAP is almost fully compatible with more traditional methods for manufacturing electronics. The motivation behind the development of SNAP was to have a general nanofabrication method for preparing electronics-grade circuitry, but one that would operate at macromolecular dimensions and with access to a broad materials set. Thus, electronics applications, including novel demultiplexing architectures; large-scale, ultrahigh-density memory circuits; and complementary symmetry nanowire logic circuits, have served as drivers for developing various aspects of the SNAP method. Some of that work is reviewed here. \n\nAs the SNAP method has evolved into a robust nanofabrication method, it has become an enabling tool for the investigation of new physics. In particular, the application of SNAP toward understanding heat transport in low-dimensional systems is discussed. This work has led to the surprising discovery that Si NWs can serve as highly efficient thermoelectric materials. Finally, we turn toward the application of SNAP to the investigation of quasi-one-dimensional (quasi-1D) superconducting physics in extremely high aspect ratio Nb NWs.", "doi": "10.1021/ar800015y", "issn": "0001-4842", "publisher": "American Chemical Society", "publication": "Accounts of Chemical Research", "publication_date": "2008-12", "series_number": "12, Sp", "volume": "41", "issue": "12, Sp", "pages": "1609-1617" }, { "id": "authors:sct47-80k08", "collection": "authors", "collection_id": "sct47-80k08", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:DICacc08", "type": "article", "title": "Kinetic and Thermodynamic Approaches for the Efficient Formation of Mechanical Bonds", "author": [ { "family_name": "Dichtel", "given_name": "William R.", "orcid": "0000-0002-3635-6119", "clpid": "Dichtel-W-R" }, { "family_name": "Miljani\u0107", "given_name": "Ognjen \u0160.", "orcid": "0000-0002-7876-9034", "clpid": "Miljani\u0107-O-\u0160" }, { "family_name": "Zhang", "given_name": "Wenyu", "clpid": "Zhang-Wenyu" }, { "family_name": "Spruell", "given_name": "Jason M.", "clpid": "Spruell-J-M" }, { "family_name": "Patel", "given_name": "Kaushik", "clpid": "Patel-Kaushik" }, { "family_name": "Aprahamian", "given_name": "Ivan", "clpid": "Aprahamian-I" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "Among the growing collection of molecular systems under consideration for nanoscale device applications, mechanically interlocked compounds derived from electrochemically switchable bistable [2]rotaxanes and [2]catenanes show great promise. These systems demonstrate dynamic, relative movements between their components, such as shuttling and circumrotation, enabling them to serve as stimuli-responsive switches operated via reversible, electrochemical oxidation\u2212reduction rather than through the addition of chemical reagents. Investigations into these systems have been intense for a number of years, yet limitations associated with their synthesis have hindered incorporation of their mechanical bonds into more complex architectures and functional materials.\n\nWe have recently addressed this challenge by developing new template-directed synthetic protocols, operating under both kinetic and thermodynamic control, for the preparation of bistable rotaxanes and catenanes. These methodologies are compatible with the molecular recognition between the \u03c0-electron-accepting cyclobis(paraquat-p-phenylene) (CBPQT4+) host and complementary \u03c0-electron-donating guests. The procedures that operate under kinetic control rely on mild chemical transformations to attach bulky stoppering groups or perform macrocyclizations without disrupting the host\u2212guest binding of the rotaxane or catenane precursors. Alternatively, the protocols that operate under thermodynamic control utilize a reversible ring-opening reaction of the CBPQT4+ ring, providing a pathway for two cyclic starting materials to thread one another to form more thermodynamically stable catenaned products. These complementary pathways generate bistable rotaxanes and catenanes in high yields, simplify mechanical bond formation in these systems, and eliminate the requirement that the mechanical bonds be introduced into the molecular structure in the final step of the synthesis.\n\nThese new methods have already been put into practice to prepare previously unavailable rotaxane architectures and novel complex materials. Furthermore, the potential for utilizing mechanically interlocked architectures as device components capable of information storage, the delivery of therapeutic agents, or other desirable functions has increased significantly as a result of the development of these improved synthetic protocols.", "doi": "10.1021/ar800067h", "issn": "0001-4842", "publisher": "American Chemical Society", "publication": "Accounts of Chemical Research", "publication_date": "2008-12", "series_number": "12, Sp", "volume": "41", "issue": "12, Sp", "pages": "1750-1761" }, { "id": "authors:19e3t-f3672", "collection": "authors", "collection_id": "19e3t-f3672", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:CAOjacs08", "type": "article", "title": "Azidation of silicon(111) surfaces", "author": [ { "family_name": "Cao", "given_name": "Peigen", "clpid": "Cao-Peigen" }, { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A two-step chlorination/azidation process was reported to prepare azide-modified silicon(111) surfaces. XPS and IR analyses show the covalent bonding of azide with silicon. In combination with scanning tunneling microscopy and spectroscopy analyses, different kinetic rates, azide coverages, and surface-area distributions were derived depending on the azidation solvent.", "doi": "10.1021/ja804448p", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2008-11-12", "series_number": "45", "volume": "130", "issue": "45", "pages": "14910-14911" }, { "id": "authors:z5ehp-cj442", "collection": "authors", "collection_id": "z5ehp-cj442", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:LEEjcc08", "type": "article", "title": "Rapid microwave-assisted CNBr cleavage of bead-bound peptides", "author": [ { "family_name": "Lee", "given_name": "Su Seong", "clpid": "Lee-Su-Seong" }, { "family_name": "Lim", "given_name": "Jaehong", "clpid": "Lim-Jaehong" }, { "family_name": "Cha", "given_name": "Junhoe", "clpid": "Cha-Junhoe" }, { "family_name": "Tan", "given_name": "Sylvia", "clpid": "Tan-Sylvia" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Large libraries of peptides, cyclic peptides, and other molecules are standard tools for the discovery of drugs, molecular probes, and affinity reagents. In particular, one-bead-one-compound (OBOC) libraries,(1) prepared by the split-and-mix method,(2) provide access to a broad chemical space with a minimum of reagents. Once such a library has been screened against the target of interest, the chemical identity of the library elements on the hit beads is identified. For peptide libraries and their variants, mass spectrometry (MS) based peptide sequencing provides the most rapid method for such analysis. OBOC libraries are constructed in a number of ways to facilitate MS analysis,(3-5) but one common feature is that the peptide must be cleaved from the bead prior to being introduced into the mass spectrometer. While a number of chemical(6) and photochemical(7) cleavage strategies have been developed, the most common strategy is to incorporate a CNBr-cleavable methionine-linker group at the C-terminus of the peptide.(8) CNBr cleavage has also been widely used in proteomics to cleave proteins.(9) With such chemistry, up to 100 beads from an OBOC peptide library can be sequenced in a 24 h period.(10) A large fraction of that time, however, is devoted to the CNBr cleavage step. Standard literature protocols describe CNBr cleavage as requiring between 12 and 24 h, using 20\u221230 \u03bcL of 0.25 M CNBr in 70% aqueous formic acid at room temperature.(11) Although the CNBr cleavage time may be reduced to 2\u22124 h at elevated temperatures (47 \u00b0C), significant side-products may be generated.(12) All reports that we have found that describe CNBr cleavage chemistry from single beads have used the same conditions as for proteomics, although the two chemical processes are not necessarily equivalent.", "doi": "10.1021/cc800113d", "pmcid": "PMC2720530", "issn": "1520-4766", "publisher": "American Chemical Society", "publication": "Journal of Combinatorial Chemistry", "publication_date": "2008-11", "series_number": "6", "volume": "10", "issue": "6", "pages": "807-809" }, { "id": "authors:xzdrr-17228", "collection": "authors", "collection_id": "xzdrr-17228", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:XUKnl08", "type": "article", "title": "Long, Highly-Ordered High-Temperature Superconductor Nanowire Arrays", "author": [ { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The preparation and electrical properties of high-temperature superconductor nanowire arrays are reported for the first time. YBa2Cu3O7\u2212\u03b4 nanowires with widths as small as 10 nm (much smaller than the magnetic penetration depth) and lengths up to 200 \u03bcm are studied by four-point electrical measurements. All nanowires exhibit a superconducting transition above liquid nitrogen temperature and a transition temperature width that depends strongly upon the nanowire dimensions. Nanowire size effects are systematically studied, and the results are modeled satisfactorily using phase-slip theories that generate reasonable parameters. These nanowires can function as superconducting nanoelectronic components over much wider temperature ranges as compared to conventional superconductor nanowires.", "doi": "10.1021/nl802264x", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2008-11", "series_number": "11", "volume": "8", "issue": "11", "pages": "3845-3849" }, { "id": "authors:jzkpq-jv156", "collection": "authors", "collection_id": "jzkpq-jv156", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:SHEacsn08", "type": "article", "title": "Complementary Symmetry Nanowire Logic Circuits: Experimental Demonstrations and in Silico Optimizations", "author": [ { "family_name": "Sheriff", "given_name": "Bonnie A.", "clpid": "Sheriff-B-A" }, { "family_name": "Wang", "given_name": "Dunwei", "clpid": "Wang-Dunwei" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Kurtin", "given_name": "Juanita N.", "clpid": "Kurtin-J-N" } ], "abstract": "Complementary symmetry (CS) Boolean logic utilizes both p- and n-type field-effect transistors (FETs) so that an input logic voltage signal will turn one or more p- or n-type FETs on, while turning an equal number of n- or p-type FETs off. The voltage powering the circuit is prevented from having a direct pathway to ground, making the circuit energy efficient. CS circuits are thus attractive for nanowire logic, although they are challenging to implement. CS logic requires a relatively large number of FETs per logic gate, the output logic levels must be fully restored to the input logic voltage level, and the logic gates must exhibit high gain and robust noise margins. We report on CS logic circuits constructed from arrays of 16 nm wide silicon nanowires. Gates up to a complexity of an XOR gate (6 p-FETs and 6 n-FETs) containing multiple nanowires per transistor exhibit signal restoration and can drive other logic gates, implying that large scale logic can be implemented using nanowires. In silico modeling of CS inverters, using experimentally derived look-up tables of individual FET properties, is utilized to provide feedback for optimizing the device fabrication process. Based upon this feedback, CS inverters with a gain approaching 50 and robust noise margins are demonstrated. Single nanowire-based logic gates are also demonstrated, but are found to exhibit significant device-to-device fluctuations.", "doi": "10.1021/nn800025q", "issn": "1936-086X", "publisher": "American Chemical Society", "publication": "ACS Nano", "publication_date": "2008-09", "series_number": "9", "volume": "2", "issue": "9", "pages": "1789-1798" }, { "id": "authors:cevwt-6vv17", "collection": "authors", "collection_id": "cevwt-6vv17", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170512-112704937", "type": "article", "title": "Peptide\u2212Nanowire Hybrid Materials for Selective Sensing of Small Molecules", "author": [ { "family_name": "McAlpine", "given_name": "Michael C.", "clpid": "McAlpine-M-C" }, { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-H-D" }, { "family_name": "Rohde", "given_name": "Rosemary D.", "clpid": "Rohde-R-D" }, { "family_name": "Blanco", "given_name": "Mario", "clpid": "Blanco-Mario" }, { "family_name": "Ahmad", "given_name": "Habib", "clpid": "Ahmad-H" }, { "family_name": "Stuparu", "given_name": "Andreea D.", "clpid": "Stuparu-A-D" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The development of a miniaturized sensing platform for the selective detection of chemical odorants could stimulate exciting scientific and technological opportunities. Oligopeptides are robust substrates for the selective recognition of a variety of chemical and biological species. Likewise, semiconducting nanowires are extremely sensitive gas sensors. Here we explore the possibilities and chemistries of linking peptides to silicon nanowire sensors for the selective detection of small molecules. The silica surface of the nanowires is passivated with peptides using amide coupling chemistry. The peptide/nanowire sensors can be designed, through the peptide sequence, to exhibit orthogonal responses to acetic acid and ammonia vapors, and can detect traces of these gases from \"chemically camouflaged\" mixtures. Through both theory and experiment, we find that this sensing selectivity arises from both acid/base reactivity and from molecular structure. These results provide a model platform for what can be achieved in terms of selective and sensitive \"electronic noses.\"", "doi": "10.1021/ja802506d", "pmcid": "PMC3716463", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2008-07-23", "series_number": "29", "volume": "130", "issue": "29", "pages": "9583-9589" }, { "id": "authors:cc0ax-e9k25", "collection": "authors", "collection_id": "cc0ax-e9k25", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:ZHApnas08a", "type": "article", "title": "Folding of a donor\u2013acceptor polyrotaxane by using noncovalent bonding interactions", "author": [ { "family_name": "Zhang", "given_name": "Wenyu", "clpid": "Zhang-Wenyu" }, { "family_name": "Dichtel", "given_name": "William R.", "orcid": "0000-0002-3635-6119", "clpid": "Dichtel-W-R" }, { "family_name": "Steig", "given_name": "Adam Z.", "clpid": "Steig-A-Z" }, { "family_name": "Benitez", "given_name": "Diego", "clpid": "Benitez-D" }, { "family_name": "Gimsewski", "given_name": "James K.", "clpid": "Gimzewski-J-K" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "Mechanically interlocked compounds, such as bistable catenanes and bistable rotaxanes, have been used to bring about actuation in nanoelectromechanical systems (NEMS) and molecular electronic devices (MEDs). The elaboration of the structural features of such rotaxanes into macromolecular materials might allow the utilization of molecular motion to impact their bulk properties. We report here the synthesis and characterization of polymers that contain \u03c0 electron-donating 1,5-dioxynaphthalene (DNP) units encircled by cyclobis(paraquat-p-phenylene) (CBPQT4+), a \u03c0 electron-accepting tetracationic cyclophane, synthesized by using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The polyrotaxanes adopt a well defined \"folded\" secondary structure by virtue of the judicious design of two DNP-containing monomers with different binding affinities for CBPQT4+. This efficient approach to the preparation of polyrotaxanes, taken alongside the initial investigations of their chemical properties, sets the stage for the preparation of a previously undescribed class of macromolecular architectures.", "doi": "10.1073/pnas.0711072105", "pmcid": "PMC2373343", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2008-05-06", "series_number": "18", "volume": "105", "issue": "18", "pages": "6514-6519" }, { "id": "authors:ezhsa-jrp60", "collection": "authors", "collection_id": "ezhsa-jrp60", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170719-065012335", "type": "article", "title": "Hall Mobility Measurements and Chemical Stability of Ultrathin, Methylated Si(111)-on-Insulator Films", "author": [ { "family_name": "Green", "given_name": "Jonathan E.", "clpid": "Green-J-E" }, { "family_name": "Wong", "given_name": "Shelley J.", "clpid": "Wong-Shelley-J" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The chemical and electronic properties of 10\u221220 nm thick, methylated Si(111)-on-insulator (CH_3/Si(111)_(SOI)) thin films, prepared using a wet chemical chlorination/methylation procedure, are investigated. X-ray photoelectron spectroscopy reveals that CH_3/Si(111)_(SOI) is resistant to oxidation upon exposure to air and to various device fabrication schemes and associated chemicals. Temperature-dependent Hall mobility measurements yield results that are dependent upon the duration of the chlorination step. For short-time chlorination steps, bulklike mobilities are observed, and the dominant scattering mechanism arises from ionized impurities. For longer time chlorination steps, surface roughness or neutral impurity scattering limit the carrier mobilities.", "doi": "10.1021/jp710482t", "issn": "1932-7447", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry C", "publication_date": "2008-04-03", "series_number": "13", "volume": "112", "issue": "13", "pages": "5185-5189" }, { "id": "authors:eekcr-vyk41", "collection": "authors", "collection_id": "eekcr-vyk41", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAarm08", "type": "article", "title": "Nanotechnology and cancer", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Davis", "given_name": "Mark E.", "orcid": "0000-0001-8294-1477", "clpid": "Davis-M-E" } ], "abstract": "The biological picture of cancer is rapidly advancing from models built from phenomenological descriptions to network models derived from systems biology, which can capture the evolving pathophysiology of the disease at the molecular level. The translation of this (still academic) picture into a clinically relevant framework can be enabling for the war on cancer, but it is a scientific and technological challenge. In this review, we discuss emerging in vitro diagnostic technologies and therapeutic approaches that are being developed to handle this challenge. Our discussion of in vitro diagnostics is guided by the theme of making large numbers of measurements accurately, sensitively, and at very low cost. We discuss diagnostic approaches based on microfluidics and nanotechnology. We then review the current state of the art of nanoparticle-based therapeutics that have reached the clinic. The goal of the presentation is to identify nanotherapeutic strategies that are designed to increase efficacy while simultaneously minimizing the toxic side effects commonly associated with cancer chemotherapies.", "doi": "10.1146/annurev.med.59.061506.185523", "pmcid": "PMC3706454", "issn": "0066-4219", "publisher": "Annual Reviews", "publication": "Annual Review of Medicine", "publication_date": "2008-02", "volume": "59", "pages": "251-265" }, { "id": "authors:kcg0q-0vv45", "collection": "authors", "collection_id": "kcg0q-0vv45", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170807-071416246", "type": "article", "title": "Controlled Fabrication and Electrical Properties of Long Quasi-One-Dimensional Superconducting Nanowire Arrays", "author": [ { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report a general method for reliably fabricating quasi-one-dimensional superconducting nanowire arrays, with good control over nanowire cross section and length, and with full compatibility with device processing methods. We investigate Nb nanowires with individual nanowire cross sectional areas that range from bulklike to 10 \u00d7 11 nm, and with lengths from 1 to 100 \u03bcm. Nanowire size effects are systematically studied. In particular, a comprehensive investigation of influence of nanowire length on superconductivity is reported for the first time. All results are interpreted within the context of phase-slip models.", "doi": "10.1021/nl072227z", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2008-01", "series_number": "1", "volume": "8", "issue": "1", "pages": "136-141" }, { "id": "authors:94jjp-maj15", "collection": "authors", "collection_id": "94jjp-maj15", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170614-082601399", "type": "article", "title": "The Emergence of a Coupled Quantum Dot Array in a Doped Silicon Nanowire Gated by Ultrahigh Density Top Gate Electrodes", "author": [ { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Green", "given_name": "Jonathan E.", "clpid": "Green-J-E" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Remacle", "given_name": "F.", "clpid": "Remacle-F" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" } ], "abstract": "The electrical characteristics of Si nanowire gated by an array of very closely spaced nanowire gate electrodes are experimentally determined and theoretically modeled. Qualitative and quantitative changes in the transport characteristics of these devices, as a function of gate-array voltage, are described. Experiments are reported for two widths of Si nanowires, 40 and 17 nm, and for a varying number of gate electrodes, all spaced at a pitch of 33 nm. We find that these top nanowire gate electrodes can be utilized to locally deplete the carriers in the underlying Si nanowire and thus define an array of coupled quantum dots along the nanowire. Reproducible Coulomb blockade is observed, and clear diamond features are obtained when the conductance is plotted in the plane of the source-drain and gate voltages. The regularity of the diamond diagrams is imposed by the regularity of the SNAP top gate electrodes. Model computations of the electronic structure starting from a tight-biding Hamiltonian in the atomic basis suggest that the control made possible by the top gate voltage induces the emergence (and reversible submergence) of a coupled quantum dot structure in an otherwise homogenously doped Si nanowire.", "doi": "10.1021/jp071353o", "issn": "1932-7447", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry C", "publication_date": "2007-12-06", "series_number": "48", "volume": "111", "issue": "48", "pages": "17852-17860" }, { "id": "authors:ktn5z-41766", "collection": "authors", "collection_id": "ktn5z-41766", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170426-150614423", "type": "article", "title": "Structural and Co-conformational Effects of Alkyne-Derived Subunits in Charged Donor\u2212Acceptor [2]Catenanes", "author": [ { "family_name": "Miljani\u0107", "given_name": "Ognjen \u0160.", "orcid": "0000-0002-7876-9034", "clpid": "Miljani\u0107-O-\u0160" }, { "family_name": "Dichtel", "given_name": "William R.", "orcid": "0000-0002-3635-6119", "clpid": "Dichtel-W-R" }, { "family_name": "Khan", "given_name": "Saeed I.", "clpid": "Khan-S-I" }, { "family_name": "Mortezaei", "given_name": "Shahab", "clpid": "Mortezaei-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "Four donor\u2212acceptor [2]catenanes with cyclobis(paraquat-p-phenylene) (CBPQT^(4+)) as the \u03c0-electron-accepting cyclophane and 1,5-dioxynaphthalene (DNP)-containing macrocyclic polyethers as \u03c0-electron donor rings have been synthesized under mild conditions, employing Cu^+-catalyzed Huisgen 1,3-dipolar cycloaddition and Cu^(2+)-mediated Eglinton coupling in the final steps of their syntheses. Oligoether chains carrying terminal alkynes or azides were used as the key structural features in template-directed cyclizations of [2]pseudorotaxanes to give the [2]catenanes. Both reactions proceed well with precursors of appropriate oligoether chain lengths but fail when there are only three oxygen atoms in the oligoether chains between the DNP units and the reactive functional groups. The solid-state structures of the donor\u2212acceptor [2]catenanes confirm their mechanically interlocked nature, stabilized by [\u03c0\u00b7\u00b7\u00b7\u03c0], [C\u2212H\u00b7\u00b7\u00b7\u03c0], and [C\u2212H\u00b7\u00b7\u00b7\u039f] interactions, and point to secondary noncovalent contacts between 1,3-butadiyne and 1,2,3-triazole subunits and one of the bipyridinum units of the CBPQT^(4+) ring. These contacts are characterized by the roughly parallel orientation of the inner bipyridinium ring system and the 1,2,3-triazole and 1,3-butadiyne units, as well as by the short [\u03c0\u00b7\u00b7\u00b7\u03c0] distances of 3.50 and 3.60 \u00c5, respectively. Variable-temperature ^1H NMR spectroscopy has been used to identify and quantify the barriers to the conformationally and co-conformationally dynamic processes. The former include the rotations of the phenylene and the bipyridinium ring systems around their substituent axes, whereas the latter are confined to the circumrotation of the CBPQT^(4+) ring around the DNP binding site. The barriers for the three processes were found to be successively 14.4, 14.5\u221217.5, and 13.1\u221215.8 kcal mol^(-1). Within the limitations of the small dataset investigated, emergent trends in the barrier heights can be recognized:\u2009 the values decrease with the increasing size of the \u03c0-electron-donating macrocycle and tend to be lower in the sterically less encumbered series of [2]catenanes containing the 1,3-butadiyne moiety.", "doi": "10.1021/ja071319n", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2007-07-04", "series_number": "26", "volume": "129", "issue": "26", "pages": "8236-8246" }, { "id": "authors:eke2e-b0m66", "collection": "authors", "collection_id": "eke2e-b0m66", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200929-143508496", "type": "article", "title": "Designing bistable [2]rotaxanes for molecular electronic devices", "author": [ { "family_name": "Dichtel", "given_name": "William R.", "orcid": "0000-0002-3635-6119", "clpid": "Dichtel-W-R" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "The development of molecular electronic components has been accelerated by the promise of increased circuit densities and reduced power consumption. Bistable rotaxanes have been assembled into nanowire crossbar devices, where they may be switched between low- and high-conductivity states, forming the basis for a molecular memory. These memory devices have been scaled to densities of 10\u00b9\u00b9\u200abits\u200acm\u207b\u00b2, the 2020 node for memory of the International Technology Roadmap for Semiconductors. Investigations of the kinetics and thermodynamics associated with the electromechanical switching processes of several bistable [2]rotaxane derivatives in solution, self-assembled monolayers on gold, polymer electrolyte gels and in molecular switch tunnel junction devices are consistent with a single, universal switching mechanism whose speed is dependent largely on the environment, as well as on the structure of the switching molecule. X-ray reflectometry studies of the bistable rotaxanes assembled into Langmuir monolayers also lend support to an oxidatively driven mechanical switching process. Structural information obtained from Fourier transform reflection absorption infrared spectroscopy of rotaxane monolayers taken before and after evaporation of a Ti top electrode confirmed that the functionality responsible for switching is not affected by the metal deposition process. All the considerable experimental data, taken together with detailed computational work, support the hypothesis that the tunnelling current hysteresis, which forms the basis of memory operation, is a direct result of the electromechanical switching of the bistable rotaxanes.", "doi": "10.1098/rsta.2007.2034", "issn": "1364-503X", "publisher": "Royal Society of London", "publication": "Philosophical Transactions A: Mathematical, Physical and Engineering Sciences", "publication_date": "2007-06-15", "series_number": "1855", "volume": "365", "issue": "1855", "pages": "1607-1625" }, { "id": "authors:v0ygg-h3s83", "collection": "authors", "collection_id": "v0ygg-h3s83", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150317-125849636", "type": "article", "title": "Highly ordered nanowire arrays on plastic substrates for ultrasensitive flexible chemical sensors", "author": [ { "family_name": "McAlpine", "given_name": "Michael C.", "clpid": "McAlpine-M-C" }, { "family_name": "Ahmad", "given_name": "Habib", "clpid": "Ahmad-Habib" }, { "family_name": "Wang", "given_name": "Dunwei", "clpid": "Wang-Dunwei" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The development of a robust method for integrating high-performance semiconductors on flexible plastics could enable exciting avenues in fundamental research and novel applications. One area of vital relevance is chemical and biological sensing, which if implemented on biocompatible substrates, could yield breakthroughs in implantable or wearable monitoring systems. Semiconducting nanowires (and nanotubes) are particularly sensitive chemical sensors because of their high surface-to-volume ratios. Here, we present a scalable and parallel process for transferring hundreds of pre-aligned silicon nanowires onto plastic to yield highly ordered films for low-power sensor chips. The nanowires are excellent field-effect transistors, and, as sensors, exhibit parts-per-billion sensitivity to NO_2, a hazardous pollutant. We also use SiO_2 surface chemistries to construct a 'nano-electronic nose' library, which can distinguish acetone and hexane vapours via distributed responses. The excellent sensing performance coupled with bendable plastic could open up opportunities in portable, wearable or even implantable sensors.", "doi": "10.1038/nmat1891", "pmcid": "PMC3695594", "issn": "1476-1122", "publisher": "Nature Publishing Group", "publication": "Nature Materials", "publication_date": "2007-05", "series_number": "5", "volume": "6", "issue": "5", "pages": "379-384" }, { "id": "authors:2ga1b-jnt26", "collection": "authors", "collection_id": "2ga1b-jnt26", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170607-143656605", "type": "article", "title": "A Clicked Bistable [2]Rotaxane", "author": [ { "family_name": "Aprahamian", "given_name": "Ivan", "clpid": "Aprahamian-I" }, { "family_name": "Dichtel", "given_name": "William R.", "orcid": "0000-0002-3635-6119", "clpid": "Dichtel-W-R" }, { "family_name": "Ikeda", "given_name": "Taichi", "clpid": "Ikeda-Taichi" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "A universal diazide-terminated polyether, incorporating tetrathiafulvalene (TTF, green) and 1,5-dioxynaphthalene (DNP, red) units, was prepared and subsequently employed in the template-directed synthesis of a switchable donor/acceptor [2]rotaxane. The triazole rings (magenta), which are introduced into the rotaxane during requisite click reactions, do not present themselves as competing recognition sites for the tetracationic cyclophane (blue) as it is induced to switch between the TTF unit, when it becomes dicationic (green adorned with yellow extremities), and the DNP unit.", "doi": "10.1021/ol070052u", "issn": "1523-7060", "publisher": "American Chemical Society", "publication": "Organic Letters", "publication_date": "2007-03-29", "series_number": "7", "volume": "9", "issue": "7", "pages": "1287-1290" }, { "id": "authors:x472p-wna24", "collection": "authors", "collection_id": "x472p-wna24", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170424-134958078", "type": "article", "title": "DNA-Encoded Antibody Libraries: A Unified Platform for Multiplexed Cell Sorting and Detection of Genes and Proteins", "author": [ { "family_name": "Bailey", "given_name": "Ryan C.", "clpid": "Bailey-R-C" }, { "family_name": "Kwong", "given_name": "Gabriel A.", "clpid": "Kwong-Gabriel-A" }, { "family_name": "Radu", "given_name": "Caius G.", "clpid": "Radu-C-G" }, { "family_name": "Witte", "given_name": "Owen N.", "orcid": "0000-0003-4461-4533", "clpid": "Witte-O-N" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Whether for pathological examination or for fundamental biology studies, different classes of biomaterials and biomolecules are each measured from a different region of a typically heterogeneous tissue sample, thus introducing unavoidable sources of noise that are hard to quantitate. We describe the method of DNA-encoded antibody libraries (DEAL) for spatially multiplexed detection of ssDNAs and proteins as well as for cell sorting, all on the same diagnostic platform. DEAL is based upon the coupling of ssDNA oligomers onto antibodies which are then combined with the biological sample of interest. Spotted DNA arrays, which are found to inhibit biofouling, are utilized to spatially stratify the biomolecules or cells of interest. We demonstrate the DEAL technique for (1) the rapid detection of multiple proteins within a single microfluidic channel, and, with the additional step of electroless amplification of gold-nanoparticle labeled secondary antibodies, we establish a detection limit of 10 fM for the protein IL-2, 150 times more sensitive than the analogue ELISA; (2) the multiplexed, on-chip sorting of both immortalized cell lines and primary immune cells with an efficiency that exceeds surface-confined panning approaches; and (3) the co-detection of ssDNAs, proteins, and cell populations on the same platform.", "doi": "10.1021/ja065930i", "pmcid": "PMC3677962", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2007-02-21", "series_number": "7", "volume": "129", "issue": "7", "pages": "1959-1967" }, { "id": "authors:p7drv-mek86", "collection": "authors", "collection_id": "p7drv-mek86", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150317-085943330", "type": "article", "title": "Synergy in a superlattice", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Put two types of crystal together in one lattice, and the resulting material can have properties greater than the sum of those of its individual components. Until now, that's been a difficult trick to pull off on a large scale.", "doi": "10.1038/445492a", "issn": "0028-0836", "publisher": "Nature Publishing Group", "publication": "Nature", "publication_date": "2007-02-01", "series_number": "7127", "volume": "445", "issue": "7127", "pages": "492-493" }, { "id": "authors:8w6kc-06a42", "collection": "authors", "collection_id": "8w6kc-06a42", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180402-144708576", "type": "book_section", "title": "Label-Free Nanowire and Nanotube Biomolecular Sensors for In-Vitro Diagnosis of Cancer and other Diseases", "book_title": "Nanobiotechnology II", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "contributor": [ { "family_name": "Mirkin", "given_name": "Chad A.", "clpid": "Mirkin-C-A" }, { "family_name": "Niemeyer", "given_name": "Christof M.", "clpid": "Niemeyer-C-M" } ], "abstract": "[no abstract]", "doi": "10.1002/9783527610389.ch12", "isbn": "9783527316731", "publisher": "Wiley", "place_of_publication": "Weinheim", "publication_date": "2007-01-26", "pages": "213-232" }, { "id": "authors:qa6yj-aky02", "collection": "authors", "collection_id": "qa6yj-aky02", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150318-084609166", "type": "article", "title": "A 160-kilobit molecular electronic memory patterned at 10^(11) bits per square centimetre", "author": [ { "family_name": "Green", "given_name": "Jonathan E.", "clpid": "Green-J-E" }, { "family_name": "Choi", "given_name": "Jang Wook", "orcid": "0000-0001-8783-0901", "clpid": "Choi-Jang-Wook" }, { "family_name": "Boukai", "given_name": "Akram", "clpid": "Boukai-Akram" }, { "family_name": "Bunimovich", "given_name": "Yuri", "clpid": "Bunimovich-Y-L" }, { "family_name": "Johnston-Halperin", "given_name": "Ezekiel", "clpid": "Johnston-Halperin-E" }, { "family_name": "Delonno", "given_name": "Erica", "clpid": "Delonno-E" }, { "family_name": "Luo", "given_name": "Yu", "clpid": "Luo-Yu" }, { "family_name": "Sheriff", "given_name": "Bonnie A.", "clpid": "Sheriff-B-A" }, { "family_name": "Xu", "given_name": "Ke", "clpid": "Xu-Ke" }, { "family_name": "Shin", "given_name": "Younk Shik", "clpid": "Shin-Younk-Shik" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The primary metric for gauging progress in the various semiconductor integrated circuit technologies is the spacing, or pitch, between the most closely spaced wires within a dynamic random access memory (DRAM) circuit. Modern DRAM circuits have 140nm pitch wires and a memory cell size of 0.0408 \u03bcm^2. Improving integrated circuit technology will require that these dimensions decrease over time. However, at present a large fraction of the patterning and materials requirements that we expect\nto need for the construction of new integrated circuit technologies in 2013 have 'no known solution'. Promising ingredients for advances in integrated circuit technology are nanowires, molecular electronics and defect-tolerant architectures, as demonstrated by reports of single devices and small circuits. Methods of extending these approaches to large-scale, high-density circuitry are largely undeveloped. Here we describe a 160,000-bit molecular electronic memory circuit, fabricated at a density of 10^(11) bits cm^(-2) (pitch 33 nm; memory cell size 0.0011 mm^2), that is, roughly analogous to the dimensions of a DRAM circuit projected to be available by 2020. A monolayer of bistable, [2]rotaxane molecules 10 served as the data storage elements. Although the circuit has large numbers of defects, those defects could be readily identified through electronic testing and isolated using software coding. The working bits were then configured to form a fully functional random access memory circuit for storing and retrieving information.", "doi": "10.1038/nature05462", "issn": "0028-0836", "publisher": "Nature Publishing Group", "publication": "Nature", "publication_date": "2007-01-25", "series_number": "7126", "volume": "445", "issue": "7126", "pages": "414-417" }, { "id": "authors:7g2wx-8zh55", "collection": "authors", "collection_id": "7g2wx-8zh55", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170512-171548636", "type": "article", "title": "Quantitative Real-Time Measurements of DNA Hybridization with Alkylated Nonoxidized Silicon Nanowires in Electrolyte Solution", "author": [ { "family_name": "Bunimovich", "given_name": "Yuri L.", "clpid": "Bunimovich-Y-L" }, { "family_name": "Shin", "given_name": "Young Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Yeo", "given_name": "Woon-Seok", "clpid": "Yeo-Woon-Seok" }, { "family_name": "Amori", "given_name": "Michael", "clpid": "Amori-M" }, { "family_name": "Kwong", "given_name": "Gabriel", "clpid": "Kwong-Gabriel-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The quantitative, real-time detection of single-stranded oligonucleotides with silicon nanowires (SiNWs) in physiologically relevant electrolyte solution is demonstrated. Debye screening of the hybridization event is circumvented by utilizing electrostatically adsorbed primary DNA on an amine-terminated NW surface. Two surface functionalization chemistries are compared:\u2009 an amine-terminated siloxane monolayer on the native SiO2 surface of the SiNW, and an amine-terminated alkyl monolayer grown directly on a hydrogen-terminated SiNW surface. The SiNWs without the native oxide exhibit improved solution-gated field-effect transistor characteristics and a significantly enhanced sensitivity to single-stranded DNA detection, with an accompanying 2 orders of magnitude improvement in the dynamic range of sensing. A model for the detection of analyte by SiNW sensors is developed and utilized to extract DNA-binding kinetic parameters. Those values are directly compared with values obtained by the standard method of surface plasmon resonance (SPR) and demonstrated to be similar. The nanowires, however, are characterized by higher detection sensitivity. The implication is that SiNWs can be utilized to quantitate the solution-phase concentration of biomolecules at low concentrations. This work also demonstrates the importance of surface chemistry for optimizing biomolecular sensing with silicon nanowires.", "doi": "10.1021/ja065923u", "pmcid": "PMC3695614", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2006-12-20", "series_number": "50", "volume": "128", "issue": "50", "pages": "16323-16331" }, { "id": "authors:rr1c9-5xn80", "collection": "authors", "collection_id": "rr1c9-5xn80", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170524-111153989", "type": "article", "title": "Scanning Tunneling Microscopy and Spectroscopy of Wet-Chemically Prepared Chlorinated Si(111) Surfaces", "author": [ { "family_name": "Cao", "given_name": "Peigen", "clpid": "Cao-Peigen" }, { "family_name": "Yu", "given_name": "Hongbin", "clpid": "Yu-Hongbin" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Chlorine-terminated Si(111) surfaces prepared through the wet-chemical treatment of H-terminated Si(111) surfaces with PCl_5 (in chlorobenzene) were investigated using ultrahigh vacuum scanning tunneling microscopy (UHV cryo-STM) and tunneling spectroscopy. STM images, collected at 77 K, revealed an unreconstructed 1\u2009\u00d7\u20091 structure for the chlorination layer, consistent with what has been observed for the gas phase chlorination of H-terminated Si(111). However, the wet-chemical chlorination is shown to generate etch pits in the Si(111) surface, with an increase in etch pit density correlating with increasing PCl_5 exposure temperatures. These etch pits were assumed to stabilize the edge structure through the partial removal of the \u3008112\u0304\u3009 step edges. Tunneling spectroscopy revealed a nonzero density of states at zero bias. This is in contrast to the cases of H-, methyl-, or ethyl-terminated Si(111), in which similar measurements have revealed the presence of a large conductance gap.", "doi": "10.1021/jp064342o", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2006-11-30", "series_number": "47", "volume": "110", "issue": "47", "pages": "23615-23618" }, { "id": "authors:fqv9h-z9w54", "collection": "authors", "collection_id": "fqv9h-z9w54", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170609-082013306", "type": "article", "title": "Scanning Tunneling Microscopy of Ethylated Si(111) Surfaces Prepared by a Chlorination/Alkylation Process", "author": [ { "family_name": "Yu", "given_name": "Hongbin", "clpid": "Yu-Hongbin" }, { "family_name": "Webb", "given_name": "Lauren J.", "orcid": "0000-0001-9999-5500", "clpid": "Webb-L-J" }, { "family_name": "Solares", "given_name": "Santiago D.", "orcid": "0000-0003-0895-8160", "clpid": "Solares-S-D" }, { "family_name": "Cao", "given_name": "Peigen", "clpid": "Cao-Peigen" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Lewis", "given_name": "Nathan S.", "orcid": "0000-0001-5245-0538", "clpid": "Lewis-N-S" } ], "abstract": "Scanning tunneling microscopy (STM) and computational modeling have been used to study the structure of ethyl-terminated Si(111) surfaces. The ethyl-terminated surface was prepared by treating the H-terminated Si(111) surface with PCl_5 to form a Cl-terminated Si(111) surface with subsequent exposure to C_2H_5MgCl in tetrahydrofuran to produce an alkylated Si(111) surface. The STM data at 77 K revealed local, close-packed, and relatively ordered regions with a nearest-neighbor spacing of 0.38 nm as well as disordered regions. The average spot density corresponded to \u224885% of the density of Si atop sites on an unreconstructed Si(111) surface. Molecular dynamics simulations of a Si(111) surface randomly populated with ethyl groups to a total coverage of \u224880% confirmed that the ethyl-terminated Si(111) surface, in theory, can assume reasonable packing arrangements to accommodate such a high surface coverage, which could be produced by an exoergic surface functionalization route such as the two-step chlorination/alkylation process. Hence, it is possible to consistently interpret the STM data within a model suggested by recent X-ray photoelectron spectroscopic data and infrared absorption data, which indicate that the two-step halogenation/alkylation method can provide a relatively high coverage of ethyl groups on Si(111) surfaces.", "doi": "10.1021/jp063655g", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2006-11-30", "series_number": "47", "volume": "110", "issue": "47", "pages": "23898-23903" }, { "id": "authors:b4mdd-n1e23", "collection": "authors", "collection_id": "b4mdd-n1e23", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170427-112457768", "type": "article", "title": "Efficient Templated Synthesis of Donor\u2212Acceptor Rotaxanes Using Click Chemistry", "author": [ { "family_name": "Dichtel", "given_name": "William R.", "orcid": "0000-0002-3635-6119", "clpid": "Dichtel-W-R" }, { "family_name": "Miljani\u0107", "given_name": "Ognjen \u0160.", "orcid": "0000-0002-7876-9034", "clpid": "Miljani\u0107-O-\u0160" }, { "family_name": "Spruell", "given_name": "Jason M.", "clpid": "Spruell-J-M" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "The mild reaction conditions, remarkable functional group compatibility, and complete regioselectivity of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition (\"click chemistry\") between organic azides and terminal alkynes have led to a threading-followed-by-stoppering approach to the synthesis of donor\u2212acceptor rotaxanes incorporating cyclobis(paraquat-p-phenylene) (CBPQT^(4+)) as the \u03c0-accepting ring component. Rotaxane formation is initiated by reacting azide-functionalized pseudorotaxanes containing \u03c0-donating 1,5-dioxynaphthalene (DNP) recognition units with appropriate alkyne-functionalized stoppers. The high yields obtained in this efficient, kinetically controlled post-assembly covalent modification, as well as the excellent convergence of the synthetic protocol, are demonstrated by the preparation of [2]-, [3]-, and [4]rotaxanes containing multiple DNP/CBPQT^(4+) donor\u2212acceptor recognition motifs.", "doi": "10.1021/ja063127i", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2006-08-16", "series_number": "32", "volume": "128", "issue": "32", "pages": "10388-10390" }, { "id": "authors:9c3qp-vkw22", "collection": "authors", "collection_id": "9c3qp-vkw22", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:WANcc06", "type": "article", "title": "Electrochemical fabrication of conducting polymer nanowires in an integrated microfluidic system", "author": [ { "family_name": "Wang", "given_name": "Jun", "clpid": "Wang-Jun" }, { "family_name": "Bunimovich", "given_name": "Yuri L.", "clpid": "Bunimovich-Y-L" }, { "family_name": "Sui", "given_name": "Guodong", "clpid": "Sui-Guodong" }, { "family_name": "Savvas", "given_name": "Stavros", "clpid": "Savvas-S" }, { "family_name": "Wang", "given_name": "Jinyi", "clpid": "Wang-Jinyi" }, { "family_name": "Guo", "given_name": "Yaoyao", "clpid": "Guo-Yaoyao" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" } ], "abstract": "In this paper, we introduce a new approach for the in situ electrochemical fabrication of an individually addressable array of conducting polymer nanowires (CPNWs) positioned within an integrated microfluidic device and also demonstrate that such an integrated device can be used as a chemical sensor immediately after its construction.", "doi": "10.1039/b604426c", "issn": "1359-7345", "publisher": "Royal Society of Chemistry", "publication": "Chemical Communications", "publication_date": "2006-08-04", "series_number": "29", "volume": "2006", "issue": "29", "pages": "3075-3077" }, { "id": "authors:eqahq-s0z83", "collection": "authors", "collection_id": "eqahq-s0z83", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170509-155331656", "type": "article", "title": "A Non-Oxidative Approach toward Chemically and Electrochemically Functionalizing Si(111)", "author": [ { "family_name": "Rohde", "given_name": "Rosemary D.", "clpid": "Rohde-R-D" }, { "family_name": "Agnew", "given_name": "Heather D.", "clpid": "Agnew-H-D" }, { "family_name": "Yeo", "given_name": "Woon-Seok", "clpid": "Yeo-Woon-Seok" }, { "family_name": "Bailey", "given_name": "Ryan C.", "clpid": "Bailey-R-C" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A general method for the non-oxidative functionalization of single-crystal silicon(111) surfaces is described. The silicon surface is fully acetylenylated using two-step chlorination/alkylation chemistry. A benzoquinone-masked primary amine is attached to this surface via Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (\"click\" chemistry). The benzoquinone is electrochemically reduced, resulting in quantitative cleavage of the molecule and exposing the amine terminus. Molecules presenting a carboxylic acid have been immobilized to the exposed amine sites. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), cyclic voltammetry (CV), and contact angle goniometry were utilized to characterize and quantitate each step in the functionalization process. This work represents a strategy for providing a general platform that can incorporate organic and biological molecules on Si(111) with minimal oxidation of the silicon surface.", "doi": "10.1021/ja062012b", "pmcid": "PMC3695602", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2006-07-26", "series_number": "29", "volume": "128", "issue": "29", "pages": "9518-9525" }, { "id": "authors:70mtn-aj483", "collection": "authors", "collection_id": "70mtn-aj483", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:YUHapl06", "type": "article", "title": "Scanning tunneling spectroscopy of methyl- and ethyl-terminated Si(111) surfaces", "author": [ { "family_name": "Yu", "given_name": "Hongbin", "clpid": "Yu-Hongbin" }, { "family_name": "Webb", "given_name": "Lauren J.", "orcid": "0000-0001-9999-5500", "clpid": "Webb-L-J" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Lewis", "given_name": "Nathan S.", "orcid": "0000-0001-5245-0538", "clpid": "Lewis-N-S" } ], "abstract": "Methyl- and ethyl-terminated Si(111) surfaces prepared by a two-step chlorination/alkylation method were characterized by low temperature scanning tunneling spectroscopy (STS). The STS data showed remarkably low levels of midgap states on the CH3- and C2H5-terminated Si surfaces. A large conductance gap relative to the Si band gap was observed for both surfaces as well as for the hydrogen-terminated Si(111) surface. This large gap is ascribed to scanning tunneling microscope tip-induced band bending resulting from a low density of midgap states which avoid pinning of the Fermi levels on these passivated surfaces.", "doi": "10.1063/1.2203968", "issn": "0003-6951", "publisher": "American Institute of Physics", "publication": "Applied Physics Letters", "publication_date": "2006-06-19", "series_number": "25", "volume": "88", "issue": "25", "pages": "Art. No. 252111" }, { "id": "authors:prsa7-4zt41", "collection": "authors", "collection_id": "prsa7-4zt41", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170803-093630552", "type": "article", "title": "Silicon p-FETs from Ultrahigh Density Nanowire Arrays", "author": [ { "family_name": "Wang", "given_name": "Dunwei", "clpid": "Wang-Dunwei" }, { "family_name": "Sheriff", "given_name": "Bonnie A.", "clpid": "Sheriff-B-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Statistical numbers of field-effect transistors (FETs) were fabricated from a circuit of 17-nm-wide, 34-nm-pitch Si nanowires boron doped at a level of 10^(18) cm^(-3). Top-gated 4-\u03bcm-wide Si nanowire p-FETs yielded low off-currents (\u223c10^(-12) A), high on/off ratios (10^5\u221210^6), good on current values (30 \u03bcA/\u03bcm), high mobilities (\u223c100 cm^2/V\u2212s), and low subthreshold swing values (\u223c80 mV/decade between 10^(-12) and 10^(-10) A increasing to 200 mV/decade between 10^(-10)\u221210^(-8) A).", "doi": "10.1021/nl052558g", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2006-06", "series_number": "6", "volume": "6", "issue": "6", "pages": "1096-1100" }, { "id": "authors:dcjyb-ywc65", "collection": "authors", "collection_id": "dcjyb-ywc65", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170711-110702121", "type": "article", "title": "Infrared Spectroscopic Characterization of [2]Rotaxane Molecular Switch Tunnel Junction Devices", "author": [ { "family_name": "DeIonno", "given_name": "Erica", "clpid": "DeIonno-E" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" }, { "family_name": "Harvey", "given_name": "Desmond D.", "clpid": "Harvey-D-D" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Langmuir\u2212Blodgett monolayers of a bistable [2]rotaxane were prepared at packing densities of 118, 73, and 54 \u00c5^2/molecule. The monolayers were both characterized via infrared spectroscopy before and after evaporation of a 2 nm film of titanium and incorporated into molecular switch tunnel junction devices. The study suggests that the evaporation process primarily affects portions of the molecule exposed to the metal atom source. Thus, in tightly packed monolayers (73 and 54 \u00c5^2/molecule), only the portions of the [2]rotaxane that are present at the molecule/air interface are clearly affected, leaving key functionality necessary for switching intact. Monolayers transferred at a lower pressure (118 \u00c5^2/molecule) exhibit nonspecific damage and poor switching behavior following Ti deposition. These results indicate that tightly packed monolayers and sacrificial functionality displayed at the molecule/air interface are important design principles for molecular electronic devices.", "doi": "10.1021/jp0607723", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2006-04-20", "series_number": "15", "volume": "110", "issue": "15", "pages": "7609-7612" }, { "id": "authors:q0vn3-zrr98", "collection": "authors", "collection_id": "q0vn3-zrr98", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170512-133830648", "type": "article", "title": "Chlorination\u2212Methylation of the Hydrogen-Terminated Silicon(111) Surface Can Induce a Stacking Fault in the Presence of Etch Pits", "author": [ { "family_name": "Solares", "given_name": "Santiago D.", "orcid": "0000-0003-0895-8160", "clpid": "Solares-S-D" }, { "family_name": "Yu", "given_name": "Hongbin", "clpid": "Yu-Hongbin" }, { "family_name": "Webb", "given_name": "Lauren J.", "orcid": "0000-0001-9999-5500", "clpid": "Webb-L-J" }, { "family_name": "Lewis", "given_name": "Nathan S.", "orcid": "0000-0001-5245-0538", "clpid": "Lewis-N-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" } ], "abstract": "Recently, we reported STM images of the methylated Si(111) surface [prepared through chlorination\u2212alkylation of the Si(111)\u2212H surface] taken at 4.7 K, indicating that the torsion angle of the methyl group with respect to the subsurface silicon layer is \u03c6 = 23 \u00b1 3\u00b0. Repulsions between H atoms in adjacent methyl groups are minimized at 30\u00b0, while repulsions between H atoms and second layer Si atoms are minimized at 60\u00b0. The experimental result of 23\u00b0 is surprising because it suggests a tendency of the methyl group toward the eclipsed configuration (0\u00b0) rather than staggered (60\u00b0). In contrast, extensive fully periodic quantum mechanical Density Functional Theory studies of this surface give an equilibrium torsion angle of 37.5\u00b0, indicating a tendency toward the staggered configuration. This discrepancy can be resolved by showing that the CH_3 on the step edges and etch pits interacts repulsively with the CH_3 on the surface terraces unless a stacking fault is introduced between the first and second silicon layers of the Si(111)\u2212CH_3 surface terraces. We propose that this could occur during the chlorination\u2212alkylation of the Si(111)\u2212H surface. This stacking fault model predicted \u03c6 = 22.5\u00b0 measured with respect to the bulk (corresponding to \u03c6 = 37.5\u00b0 with respect to the second layer Si atoms). This model can be tested by measuring the orientation of the CH_3 within the etch pits, which should have \u03c6 = 37.5\u00b0, or by making a surface without etch pits, which should have \u03c6 = 37.5\u00b0.", "doi": "10.1021/ja055408g", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2006-03-29", "series_number": "12", "volume": "128", "issue": "12", "pages": "3850-3851" }, { "id": "authors:6xjwt-7ba93", "collection": "authors", "collection_id": "6xjwt-7ba93", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170801-152203233", "type": "article", "title": "Circuit Fabrication at 17 nm Half-Pitch by Nanoimprint Lithography", "author": [ { "family_name": "Jung", "given_name": "Gun-Young", "clpid": "Jung-Gun-Young" }, { "family_name": "Johnston-Halperin", "given_name": "Ezekiel", "clpid": "Johnston-Halperin-E" }, { "family_name": "Wu", "given_name": "Wei-Li", "orcid": "0000-0003-2610-1881", "clpid": "Wu-Wei-Li" }, { "family_name": "Yu", "given_name": "Zhaoning", "clpid": "Yu-Zhaoning" }, { "family_name": "Wang", "given_name": "Shih-Yuan", "clpid": "Wang-Shih-Yuan" }, { "family_name": "Tong", "given_name": "William M.", "clpid": "Tong-W-M" }, { "family_name": "Li", "given_name": "Zhiyong", "clpid": "Li-Zhiyong" }, { "family_name": "Green", "given_name": "Jonathan E.", "clpid": "Green-J-E" }, { "family_name": "Sheriff", "given_name": "Bonnie A.", "clpid": "Sheriff-B-A" }, { "family_name": "Boukai", "given_name": "Akram", "clpid": "Boukai-A" }, { "family_name": "Bunimovich", "given_name": "Yuri", "clpid": "Bunimovich-Y-L" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Williams", "given_name": "R. Stanley", "clpid": "Williams-R-S" } ], "abstract": "High density metal cross bars at 17 nm half-pitch were fabricated by nanoimprint lithography. Utilizing the superlattice nanowire pattern transfer technique, a 300-layer GaAs/AlGaAs superlattice was employed to produce an array of 150 Si nanowires (15 nm wide at 34 nm pitch) as an imprinting mold. A successful reproduction of the Si nanowire pattern was demonstrated. Furthermore, a cross-bar platinum nanowire array with a cell density of approximately 100 Gbit/cm^2 was fabricated by two consecutive imprinting processes.", "doi": "10.1021/nl052110f", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2006-03", "series_number": "3", "volume": "6", "issue": "3", "pages": "351-354" }, { "id": "authors:85eer-v5e76", "collection": "authors", "collection_id": "85eer-v5e76", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:BECfd06", "type": "article", "title": "Spiers Memorial Lecture: Molecular mechanics and molecular electronics", "author": [ { "family_name": "Beckman", "given_name": "Robert", "clpid": "Beckman-R-A" }, { "family_name": "Beverly", "given_name": "Kris", "clpid": "Beverly-K-C" }, { "family_name": "Boukai", "given_name": "Akram", "clpid": "Boukai-Akram" }, { "family_name": "Bunimovich", "given_name": "Yuri", "clpid": "Bunimovich-Y-L" }, { "family_name": "Choi", "given_name": "Jang Wook", "orcid": "0000-0001-8783-0901", "clpid": "Choi-Jang-Wook" }, { "family_name": "DeIonno", "given_name": "Erica", "clpid": "DeIonno-E" }, { "family_name": "Green", "given_name": "Johnny", "clpid": "Green-J-E" }, { "family_name": "Johnston-Halperin", "given_name": "Ezekiel", "clpid": "Johnston-Halperin-E" }, { "family_name": "Luo", "given_name": "Yi", "clpid": "Luo-Yi" }, { "family_name": "Sheriff", "given_name": "Bonnie", "clpid": "Sheriff-B-A" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We describe our research into building integrated molecular electronics circuitry for a diverse set of functions, and with a focus on the fundamental scientific issues that surround this project. In particular, we discuss experiments aimed at understanding the function of bistable [2]rotaxane molecular electronic switches by correlating the switching kinetics and ground state thermodynamic properties of those switches in various environments, ranging from the solution phase to a Langmuir monolayer of the switching molecules sandwiched between two electrodes. We discuss various devices, low bit-density memory circuits, and ultra-high density memory circuits that utilize the electrochemical switching characteristics of these molecules in conjunction with novel patterning methods. We also discuss interconnect schemes that are capable of bridging the micrometre to submicrometre length scales of conventional patterning approaches to the near-molecular length scales of the ultra-dense memory circuits. Finally, we discuss some of the challenges associated with fabricated ultra-dense molecular electronic integrated circuits.", "doi": "10.1039/b513148k", "issn": "1359-6640", "publisher": "Royal Society of Chemistry", "publication": "Faraday Discussions", "publication_date": "2006", "volume": "131", "pages": "9-22" }, { "id": "authors:k4388-gn295", "collection": "authors", "collection_id": "k4388-gn295", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141119-084459417", "type": "article", "title": "Multistep Synthesis of a Radiolabeled Imaging Probe Using Integrated Microfluidics", "author": [ { "family_name": "Lee", "given_name": "Chung-Cheng", "clpid": "Lee-Chung-Cheng" }, { "family_name": "Sui", "given_name": "Guodong", "clpid": "Sui-Guodong" }, { "family_name": "Elizarov", "given_name": "Arkadij", "clpid": "Elizarov-A-M" }, { "family_name": "Shu", "given_name": "Chengyi Jenny", "clpid": "Shu-Chengyi-Jenny" }, { "family_name": "Shin", "given_name": "Young-Shik", "clpid": "Shin-Young-Shik" }, { "family_name": "Dooley", "given_name": "Alek N.", "clpid": "Dooley-A-N" }, { "family_name": "Huang", "given_name": "Jiang", "clpid": "Huang-Jiang" }, { "family_name": "Daridon", "given_name": "Antoine", "clpid": "Daridon-A" }, { "family_name": "Wyatt", "given_name": "Paul", "clpid": "Wyatt-P" }, { "family_name": "Stout", "given_name": "David", "clpid": "Stout-D" }, { "family_name": "Kolb", "given_name": "Hartmuth C.", "clpid": "Kolb-H-C" }, { "family_name": "Witte", "given_name": "Owen N.", "orcid": "0000-0003-4461-4533", "clpid": "Witte-O-N" }, { "family_name": "Satyamurthy", "given_name": "Nagichettiar", "clpid": "Satyamurthy-N" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Phelps", "given_name": "Michael E.", "clpid": "Phelps-M-E" }, { "family_name": "Quake", "given_name": "Stephen R.", "clpid": "Quake-S-R" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" } ], "abstract": "Microreactor technology has shown potential for optimizing synthetic efficiency, particularly in preparing sensitive compounds. We achieved the synthesis of an [^(18)F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-d-glucose ([^(18)F]FDG), in an integrated microfluidic device. Five sequential processes\u2014[^(18)F]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection\u2014proceeded with high radio-chemical yield and purity and with shorter synthesis time relative to conventional automated synthesis. Multiple doses of [^(18)F]FDG for positron emission tomography imaging studies in mice were prepared. These results, which constitute a proof of principle for automated multistep syntheses at the nanogram to microgram scale, could be generalized to a range of radiolabeled substrates.", "doi": "10.1126/science.1118919", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2005-12-16", "series_number": "5755", "volume": "310", "issue": "5755", "pages": "1793-1796" }, { "id": "authors:8jy2h-8c492", "collection": "authors", "collection_id": "8jy2h-8c492", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170516-102144211", "type": "article", "title": "Molecular Dynamics Simulation of Amphiphilic Bistable [2]Rotaxane Langmuir Monolayers at the Air/Water Interface", "author": [ { "family_name": "Jang", "given_name": "Seung Soon", "orcid": "0000-0002-1920-421X", "clpid": "Jang-Seung-Soon" }, { "family_name": "Jang", "given_name": "Yun Hee", "orcid": "0000-0002-6604-5813", "clpid": "Jang-Yun-Hee" }, { "family_name": "Kim", "given_name": "Yong-Hoon", "orcid": "0000-0001-5209-4908", "clpid": "Kim-Yong-Hoon" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Choi", "given_name": "Jang Wook", "orcid": "0000-0001-8783-0901", "clpid": "Choi-Jang-Wook" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Laursen", "given_name": "Bo W.", "orcid": "0000-0002-1120-3191", "clpid": "Laursen-B-W" }, { "family_name": "Flood", "given_name": "Amar H.", "orcid": "0000-0002-2764-9155", "clpid": "Flood-A-H" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "N\u00f8rgaard", "given_name": "Kasper", "orcid": "0000-0002-7784-7985", "clpid": "N\u00f8rgaard-Kasper" }, { "family_name": "Bj\u00f8rnholm", "given_name": "Thomas", "orcid": "0000-0002-8908-1657", "clpid": "Bj\u00f8rnholm-Thomas" } ], "abstract": "Bistable [2]rotaxanes display controllable switching properties in solution, on surfaces, and in devices. These phenomena are based on the electrochemically and electrically driven mechanical shuttling motion of the ring-shaped component, cyclobis(paraquat-p-phenylene) (CBPQT^(4+)), between a monopyrrolotetrathiafulvalene (mpTTF) unit and a 1,5-dioxynaphthalene (DNP) unit located along a dumbbell component. The most stable state of the rotaxane (CBPQT^(4+)@mpTTF) is that in which the CBPQT^(4+) ring encircles the mpTTF unit, but a second less favored metastable co-conformation with the CBPQT^(4+) ring surrounding the DNP (CBPQT^(4+)@DNP) can be formed experimentally. For both co-conformations of an amphiphilic bistable [2]rotaxane, we report here the structure and surface pressure\u2212area isotherm of a Langmuir monolayer (LM) on a water subphase as a function of the area per molecule. These results from atomistic molecular dynamics (MD) studies are validated by comparing with experiments based on similar amphiphilic rotaxanes. For both co-conformations, we found that as the area per molecule increases the thickness of the LM decreases while the molecular tilt increases. Both co-conformations led to similar LM thicknesses at the same packing area. From the simulated LM systems, we calculated the electron density profiles of the monolayer as a function of area per molecule, which show good agreement with experimental analyses from synchrotron X-ray reflectivity measurements of related systems. Decomposing the overall electron density profiles into component contributions, we found distinct differences in molecular packing in the film depending upon the co-conformation. Thus we find that the necessity of allowing the tetracationic ring to become solvated by water leads to differences in the structures for the two co-conformations in the LM. At the same packing area, the value of the overall tilt angle does not seem to be sensitive to whether the CBPQT^(4+) ring is encircling the mpTTF or the DNP unit. However, the conformation of the dumbbell does depend on the location of the CBPQT^(4+) ring, which is reflected in the segmental tilt angles of the mpTTF and DNP units. Using the Kirkwood\u2212Buff formula in conjunction with MD calculations, we find the surface pressure\u2212area isotherms for each co-conformation in which the CBPQT^(4+)@mpTTF form has smaller surface tension and therefore larger surface pressure than the CBPQT^(4+)@DNP at the same packing area, differences that decreases with increasing area per molecule, which is verified experimentally.", "doi": "10.1021/ja0531531", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2005-10-26", "series_number": "42", "volume": "127", "issue": "42", "pages": "14804-14816" }, { "id": "authors:5m4et-bff72", "collection": "authors", "collection_id": "5m4et-bff72", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141121-102628290", "type": "article", "title": "Bridging Dimensions: Demultiplexing Ultrahigh-Density Nanowire Circuits", "author": [ { "family_name": "Beckman", "given_name": "Robert", "clpid": "Beckman-R-A" }, { "family_name": "Johnston-Halperin", "given_name": "Ezekiel", "clpid": "Johnston-Halperin-E" }, { "family_name": "Luo", "given_name": "Yi", "clpid": "Luo-Yi" }, { "family_name": "Green", "given_name": "Jonathan E.", "clpid": "Green-J-E" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A demultiplexer is an electronic circuit designed to separate two or more combined signals. We report on a demultiplexer architecture for bridging from the submicrometer dimensions of lithographic patterning to the nanometer-scale dimensions that can be achieved through nanofabrication methods for the selective addressing of ultrahigh-density nanowire circuits. Order log_2(N) large wires are required to address N nanowires, and the demultiplexer architecture is tolerant of low-precision manufacturing. This concept is experimentally demonstrated on submicrometer wires and on an array of 150 silicon nanowires patterned at nanowire widths of 13 nanometers and a pitch of 34 nanometers.", "doi": "10.1126/science.1114757", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2005-10-21", "series_number": "5747", "volume": "310", "issue": "5747", "pages": "465-468" }, { "id": "authors:xqqr4-5nt64", "collection": "authors", "collection_id": "xqqr4-5nt64", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170516-174653680", "type": "book_section", "title": "Molecular mechanics and molecular electronics", "book_title": "5th IEEE Conference on Nanotechnology, 2005", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Electronic devices containing molecules as either passive or active (switching) components present the opportunity for scaling electronic circuitry down to near-molecular dimensions. In this paper the kinetic and thermodynamic properties of bistable molecular mechanical switches known as catenanes and rotaxanes are discussed. A defect-tolerant, binary tree demultiplexer architecture using Order log/sub 2/N submicron (lithographically patterned) wires to address TV nanowires are developed. Apart from traditional applications of memory, logic, and routing, new opportunities that include actuation, sensing, energy management, and possibly even peptide sequencing are enabled by these nanofabrication approaches.", "doi": "10.1109/NANO.2005.1500634", "isbn": "0-7803-9199-3", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2005-07" }, { "id": "authors:ypm8y-skv80", "collection": "authors", "collection_id": "ypm8y-skv80", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:REMpnas05", "type": "article", "title": "Electrical addressing of confined quantum systems for quasiclassical computation and finite state logic machines", "author": [ { "family_name": "Remacle", "given_name": "F.", "clpid": "Remacle-F" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" } ], "abstract": "Conduction spectroscopy measures the current I through a nanosystem as a function of the voltage V between two electrodes. The differential conductance, dI/dV, has peaks that can be assigned to resonance conditions with different electronic levels of the system. Between these increments, the current has roughly constant plateaus. We discuss how measurements of the current vs. voltage can be used to perform Boolean operations and hence construct finite state logic machines and combinational circuits. The inputs to the device are the source\u2013drain voltage, including its sign, and a gate voltage applied in a manner analogous to optical Stark spectroscopy. As simple examples, we describe a two-state set\u2013reset machine (a machine whose output depends on the input and also on its present state) and a full adder circuit (a circuit that requires three inputs and provides two outputs).", "doi": "10.1073/pnas.0501623102", "pmcid": "PMC556307", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2005-04-19", "series_number": "16", "volume": "102", "issue": "16", "pages": "5653-5658" }, { "id": "authors:n4prf-7ps09", "collection": "authors", "collection_id": "n4prf-7ps09", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170420-084322252", "type": "article", "title": "Structures and Properties of Self-Assembled Monolayers of Bistable [2]Rotaxanes on Au (111) Surfaces from Molecular Dynamics Simulations Validated with Experiment", "author": [ { "family_name": "Jang", "given_name": "Seung Soon", "orcid": "0000-0002-1920-421X", "clpid": "Jang-Seung-Soon" }, { "family_name": "Jang", "given_name": "Yun Hee", "orcid": "0000-0002-6604-5813", "clpid": "Jang-Yun-Hee" }, { "family_name": "Kim", "given_name": "Yong-Hoon", "orcid": "0000-0001-5209-4908", "clpid": "Kim-Yong-Hoon" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Flood", "given_name": "Amar H.", "orcid": "0000-0002-2764-9155", "clpid": "Flood-A-H" }, { "family_name": "Laursen", "given_name": "Bo W.", "orcid": "0000-0002-1120-3191", "clpid": "Laursen-B-W" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "orcid": "0000-0003-0942-5905", "clpid": "Tseng-Hsian-Rong" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Jeppesen", "given_name": "Jan O.", "orcid": "0000-0002-3088-2994", "clpid": "Jeppesen-J-O" }, { "family_name": "Choi", "given_name": "Jang Wook", "orcid": "0000-0001-8783-0901", "clpid": "Choi-Jang-Wook" }, { "family_name": "Steuerman", "given_name": "David W.", "orcid": "0000-0002-3464-7932", "clpid": "Steuerman-D-W" }, { "family_name": "DeIonno", "given_name": "Erica", "clpid": "DeIonno-Erica" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Bistable [2]rotaxanes display controllable switching properties in solution, on surfaces, and in devices. These phenomena are based on the electrochemically and electrically driven mechanical shuttling motion of the ring-shaped component, cyclobis(paraquat-p-phenylene) (CBPQT^(4+)) (denoted as the ring), between a tetrathiafulvalene (TTF) unit and a 1,5-dioxynaphthalene (DNP) ring system located along a dumbbell component. When the ring is encircling the TTF unit, this co-conformation of the rotaxane is the most stable and thus designated the ground-state co-conformer (GSCC), whereas the other co-conformation with the ring surrounding the DNP ring system is less favored and so designated the metastable-state co-conformer (MSCC). We report here the structure and properties of self-assembled monolayers (SAMs) of a bistable [2]rotaxane on Au (111) surfaces as a function of surface coverage based on atomistic molecular dynamics (MD) studies with a force field optimized from DFT calculations and we report several experiments that validate the predictions. On the basis of both the total energy per rotaxane and the calculated stress that is parallel to the surface, we find that the optimal packing density of the SAM corresponds to a surface coverage of 115 \u00c5^2/molecule (one molecule per 4 \u00d7 4 grid of surface Au atoms) for both the GSCC and MSCC, and that the former is more stable than the latter by 14 kcal/mol at the optimum packing density. We find that the SAM retains hexagonal packing, except for the case at twice the optimum packing density (65 \u00c5^2/molecule, the 3 \u00d7 3 grid). For the GSCC and MSCC, investigated at the optimum coverage, the tilt of the ring with respect to the normal is \u03b8 = 39\u00b0 and 61\u00b0, respectively, while the tilt angle of the entire rotaxane is \u03c8 = 41\u00b0 and 46\u00b0, respectively. Although the tilt angle of the ring decreases with decreasing surface coverage, the tilt angle of the rotaxane has a maximum at 144 \u00c5^2/molecule (the 4 \u00d7 5 grid/molecule) of 50\u00b0 and 51\u00b0 for the GSCC and MSCC, respectively. The hexafluorophosphate counterions (PF_6^-) stay localized around the ring during the 2 ns MD simulation. On the basis of the calculated density profile, we find that the thickness of the SAM is 40.5 \u00c5 at the optimum coverage for the GSCC and 40.0 \u00c5 for MSCC, and that the thicknesses become less with decreasing surface coverage. The calculated surface tension at the optimal packing density is 45 and 65 dyn/cm for the GSCC and MSCC, respectively. This difference suggests that the water contact angle for the GSCC is larger than for the MSCC, a prediction that is verified by experiments on Langmuir\u2212Blodgett monolayers of amphiphilic [2]rotaxanes.", "doi": "10.1021/ja044530x", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2005-02-09", "series_number": "5", "volume": "127", "issue": "5", "pages": "1563-1575" }, { "id": "authors:fw6t8-9n070", "collection": "authors", "collection_id": "fw6t8-9n070", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170524-143033911", "type": "article", "title": "Low-Temperature STM Images of Methyl-Terminated Si(111) Surfaces", "author": [ { "family_name": "Yu", "given_name": "Hongbin", "clpid": "Yu-Hongbin" }, { "family_name": "Webb", "given_name": "Lauren J.", "orcid": "0000-0001-9999-5500", "clpid": "Webb-L-J" }, { "family_name": "Ries", "given_name": "Ryan S.", "clpid": "Ries-R-S" }, { "family_name": "Solares", "given_name": "Santiago D.", "orcid": "0000-0003-0895-8160", "clpid": "Solares-S-D" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Lewis", "given_name": "Nathan S.", "orcid": "0000-0001-5245-0538", "clpid": "Lewis-N-S" } ], "abstract": "Low-temperature scanning tunneling microscopy (STM) has been used to image CH3-terminated Si(111) surfaces that were prepared through a chlorination/alkylation procedure. The STM data revealed a well-ordered structure commensurate with the atop sites of an unreconstructed 1 \u00d7 1 overlayer on the silicon (111) surface. Images collected at 4.7 K revealed bright spots, separated by 0.18 \u00b1 0.01 nm, which are assigned to adjacent H atoms on the same methyl group. The C\u2212H bonds in each methyl group were observed to be rotated by 7 \u00b1 3\u00b0 away from the center of an adjacent methyl group and toward an underlying Si atom. Hence, the predominant interaction that determines the surface structure arises from repulsions between hydrogen atoms on neighboring methyl groups, and secondary interactions unique to the surface are also evident.", "doi": "10.1021/jp047672m", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2005-01-20", "series_number": "2", "volume": "109", "issue": "2", "pages": "671-674" }, { "id": "authors:j279b-tpg28", "collection": "authors", "collection_id": "j279b-tpg28", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:FENapl05", "type": "article", "title": "Probing the size and density of silicon nanocrystals in nanocrystal memory device applications", "author": [ { "family_name": "Feng", "given_name": "Tao", "clpid": "Feng-Tao-Applied-Physics" }, { "family_name": "Yu", "given_name": "Hongbin", "clpid": "Yu-Hongbin" }, { "family_name": "Dicken", "given_name": "Matthew", "clpid": "Dicken-M-J" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Atwater", "given_name": "Harry A.", "orcid": "0000-0001-9435-0201", "clpid": "Atwater-H-A" } ], "abstract": "Structural characterization via transmission electron microscopy and atomic force microscopy of arrays of small Si nanocrystals embedded in SiO2, important to many device applications, is usually difficult and fails to correctly resolve nanocrystal size and density. We demonstrate that scanning tunneling microscopy (STM) imaging enables a much more accurate measurement of the ensemble size distribution and array density for small Si nanocrystals in SiO2, estimated to be 2-3 nm and 4 x 10^(12) - 3 x 10^(13) cm^(-2), respectively, in this study. The reflection high energy electron diffraction pattern further verifies the existence of nanocrystallites in SiO2. The present STM results enable nanocrystal charging characteristics to be more clearly understood: we find the nanocrystal charging measurements to be consistent with single charge storage on individual Si nanocrystals. Both electron tunneling and hole tunneling processes are suggested to explain the asymmetric charging/ discharging processes as a function of bias.", "doi": "10.1063/1.1852078", "issn": "0003-6951", "publisher": "American Institute of Physics", "publication": "Applied Physics Letters", "publication_date": "2005-01-17", "series_number": "3", "volume": "86", "issue": "3", "pages": "Art. No. 033103" }, { "id": "authors:yj4hk-2qh86", "collection": "authors", "collection_id": "yj4hk-2qh86", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190516-090336142", "type": "article", "title": "The Role of Physical Environment on Molecular Electromechanical Switching", "author": [ { "family_name": "Flood", "given_name": "Amar H.", "clpid": "Flood-A-H" }, { "family_name": "Peters", "given_name": "Andrea J.", "clpid": "Peters-A-J" }, { "family_name": "Vignon", "given_name": "Scott A.", "clpid": "Vignon-S-A" }, { "family_name": "Steuerman", "given_name": "David W.", "clpid": "Steuerman-D-W" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" }, { "family_name": "Kang", "given_name": "Seogshin", "clpid": "Kang-Seogshin" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "The influences of different physical environments on the thermodynamics associated with one key step in the switching mechanism for a pair of bistable catenanes and a pair of bistable rotaxanes have been investigated systematically. The two bistable catenanes are comprised of a cyclobis(paraquat\u2010p\u2010phenylene) (CBPQT^(4+)) ring, or its diazapyrenium\u2010containing analogue, that are interlocked with a macrocyclic polyether component that incorporates the strong tetrathiafulvalene (TTF) donor unit and the weaker 1,5\u2010dioxynaphthalene (DNP) donor unit. The two bistable rotaxanes are comprised of a CBPQT^(4+) ring, interlocked with a dumbbell component in which one incorporates TTF and DNP units, whereas the other incorporates a monopyrrolotetrathiafulvalene (MPTTF) donor and a DNP unit. Two consecutive cycles of a variable scan rate cyclic voltammogram (10\u20131500 mV\u2009s^(\u22121)) performed on all of the bistable switches (\u223c1\u2009mM) in MeCN electrolyte solutions (0.1\u2009M tetrabutylammonium hexafluorophosphate) across a range of temperatures (258\u2013303 K) were recorded in a temperature\u2010controlled electrochemical cell. The second cycle showed different intensities of the two features that were observed in the first cycle when the cyclic voltammetry was recorded at fast scan rates and low temperatures. The first oxidation peak increases in intensity, concomitant with a decrease in the intensity of the second oxidation peak. This variation changed systematically with scan rate and temperature and has been assigned to the molecular mechanical movements within the catenanes and rotaxanes of the CBPQT^(4+) ring from the DNP to the TTF unit. The intensities of each peak were assigned to the populations of each co\u2010conformation, and the scan\u2010rate variation of each population was analyzed to obtain kinetic and thermodynamic data for the movement of the CBPQT^(4+) ring. The Gibbs free energy of activation at 298 K for the thermally activated movement was calculated to be 16.2 kcal\u2009mol^(\u22121) for the rotaxane, and 16.7 and 19.2 kcal\u2009mol^(\u22121) for the bipyridinium\u2010 and diazapyrenium\u2010based bistable catenanes, respectively. These values differ from those obtained for the shuttling and circumrotational motions of degenerate rotaxanes and catenanes, respectively, indicating that the detailed chemical structure influences the rates of movement. In all cases, when the same bistable compounds were characterized in an electrolyte gel, the molecular mechanical motion slowed down significantly, concomitant with an increase in the activation barriers by more than 2 kcal\u2009mol^(\u22121). Irrespective of the environment\u2014solution, self\u2010assembled monolayer or solid\u2010state polymer gel\u2014and of the molecular structure\u2014rotaxane or catenane\u2014a single and generic switching mechanism is observed for all bistable molecules.", "doi": "10.1002/chem.200401052", "issn": "0947-6539", "publisher": "John Wiley & Sons", "publication": "Chemistry: a European Journal", "publication_date": "2004-12-17", "series_number": "24", "volume": "10", "issue": "24", "pages": "6558-6564" }, { "id": "authors:6efa2-qfj13", "collection": "authors", "collection_id": "6efa2-qfj13", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-155141637", "type": "article", "title": "Whence Molecular Electronics?", "author": [ { "family_name": "Flood", "given_name": "Amar H.", "clpid": "Flood-A-H" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Steuerman", "given_name": "David W.", "clpid": "Steuerman-D-W" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The drive toward yet further miniaturization of silicon-based electronics has led to a revival of efforts to build devices with molecular-scale components. The field of molecular electronics is teeming with results, rationalizations, and speculations [HN1]. Some claims may have been exaggerated, but news stories of a crisis in the field (1) are premature. Reports of passive molecular electronics devices, such as tunnel junctions and rectifiers, as well as of active devices, for example, single-molecule transistors and molecular switch tunnel junctions, have withstood scientific scrutiny. Simple molecular electronic devices usually consist of organic molecules sandwiched between conducting electrodes. According to early predictions, such devices could show electron tunneling (2) [HN2] or one-way flow of current (rectification) [HN3] through the molecule (3). In most tunneling junctions, linear alkanes are sandwiched between metal electrodes. Measurements over the past 25 years (4, 5) have largely validated McConnell's prediction (2) that the tunnel current depends exponentially on the length of the molecules between conducting electrodes [HN4]. In rectifiers, a molecule composed of an electron donor, a bridge, and an electron acceptor is extended between two electrodes (see the first figure, top panel). Experiments (6, 7) have again validated the early prediction by Aviram and Ratner (3) [HN5].", "doi": "10.1126/science.1106195", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2004-12-17", "series_number": "5704", "volume": "306", "issue": "5704", "pages": "2055-2056" }, { "id": "authors:cweyh-wt464", "collection": "authors", "collection_id": "cweyh-wt464", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190516-094412309", "type": "article", "title": "Molecular-Mechanical Switch-Based Solid-State Electrochromic Devices", "author": [ { "family_name": "Steuerman", "given_name": "David W.", "clpid": "Steuerman-D-W" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" }, { "family_name": "Peters", "given_name": "Andrea J.", "clpid": "Peters-A-J" }, { "family_name": "Flood", "given_name": "Amar H.", "clpid": "Flood-A-H" }, { "family_name": "Jeppesen", "given_name": "Jan O.", "clpid": "Jeppesen-J-O" }, { "family_name": "Nielsen", "given_name": "Kent A.", "clpid": "Nielsen-K-A" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "You only need eyes to appreciate the color change that occurs in a polymer matrix when the bistable rotaxane shown is switched between its ground\u2010state (green) and metastable\u2010state (red) co\u2010conformers. Not only is an electrochromic device within reach, but a universal switching mechanism seems to be on the cards.", "doi": "10.1002/anie.200461723", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2004-12-03", "series_number": "47", "volume": "43", "issue": "47", "pages": "6486-6491" }, { "id": "authors:w0n4f-dhj34", "collection": "authors", "collection_id": "w0n4f-dhj34", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170427-110128445", "type": "article", "title": "Electrochemically Programmed, Spatially Selective Biofunctionalization of Silicon Wires", "author": [ { "family_name": "Bunimovich", "given_name": "Yuri L.", "clpid": "Bunimovich-Y-L" }, { "family_name": "Ge", "given_name": "Guanglu", "clpid": "Ge-Guanglu" }, { "family_name": "Beverly", "given_name": "Kristen C.", "clpid": "Beverly-K-C" }, { "family_name": "Ries", "given_name": "Ryan S.", "clpid": "Ries-R-S" }, { "family_name": "Hood", "given_name": "Leroy", "orcid": "0000-0001-7158-3678", "clpid": "Hood-L-E" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A method for the spatially selective biofunctionalization of silicon micro- and nanostructures is reported, and results are presented for both single-crystal silicon (111) or (100) surfaces. An electroactive monolayer of hydroquinone was formed on the surface of H-terminated silicon working electrodes via an olefin reaction with UV-generated surface radicals. Molecules presenting either cyclopentadiene or a thiol group can be immobilized onto the regions where the hydroquinone has been oxidized. Molecular size and crystal orientation are evaluated as important factors that dictate the electrode stability in aqueous solution under anodic potentials. Monolayers composed of smaller molecules on (111) surfaces exhibit the highest packing density and are more effective in preventing anodic oxidation of the underlying substrate. Voltammetry, X-ray photoelectron spectroscopy, and atomic force and fluorescence microscopy are utilized to interrogate the kinetic rates of biofunctionalization, the extent of surface coverage, monolayer quality, and the spatial selectivity of the process.", "doi": "10.1021/la047913h", "issn": "0743-7463", "publisher": "American Chemical Society", "publication": "Langmuir", "publication_date": "2004-11-23", "series_number": "24", "volume": "20", "issue": "24", "pages": "10630-10638" }, { "id": "authors:wbg7w-jxp14", "collection": "authors", "collection_id": "wbg7w-jxp14", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:BECjap04", "type": "article", "title": "Fabrication of conducting Si nanowire arrays", "author": [ { "family_name": "Beckman", "given_name": "R. A.", "clpid": "Beckman-R-A" }, { "family_name": "Johnston-Halperin", "given_name": "E.", "clpid": "Johnston-Halperin-E" }, { "family_name": "Melosh", "given_name": "N. A.", "clpid": "Melosh-N-A" }, { "family_name": "Luo", "given_name": "Y.", "clpid": "Luo-Yi" }, { "family_name": "Green", "given_name": "J. E.", "clpid": "Green-J-E" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The recent development of the superlattice nanowire pattern transfer technique allows for the fabrication of arrays of nanowires at a diameter, pitch, aspect ratio, and regularity beyond competing approaches. Here, we report the fabrication of conducting Si nanowire arrays with wire widths and pitches of 10\u201320 and 40\u201350 nm, respectively, and resistivity values comparable to the bulk through the selection of appropriate silicon-on-insulator substrates, careful reactive-ion etching, and spin-on glass doping. These results promise the realization of interesting nanoelectronic circuits and devices, including chemical and biological sensors, nanoscale mosaics for electronics, and ultradense field-effect transistor arrays.", "doi": "10.1063/1.1801155", "issn": "0021-8979", "publisher": "American Institute of Physics", "publication": "Journal of Applied Physics", "publication_date": "2004-11-15", "series_number": "10", "volume": "96", "issue": "10", "pages": "5921-5923" }, { "id": "authors:c2k3t-e4563", "collection": "authors", "collection_id": "c2k3t-e4563", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-154357028", "type": "article", "title": "Systems Biology and New Technologies Enable Predictive and Preventative Medicine", "author": [ { "family_name": "Hood", "given_name": "Leroy", "orcid": "0000-0001-7158-3678", "clpid": "Hood-L-E" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Phelps", "given_name": "Michael E.", "clpid": "Phelps-M-E" }, { "family_name": "Lin", "given_name": "Biaoyang", "clpid": "Lin-Biaoyang" } ], "abstract": "Systems approaches to disease are grounded in the idea that disease-perturbed protein and gene regulatory networks differ from their normal counterparts; we have been pursuing the possibility that these differences may be reflected by multiparameter measurements of the blood. Such concepts are transforming current diagnostic and therapeutic approaches to medicine and, together with new technologies, will enable a predictive and preventive medicine that will lead to personalized medicine.", "doi": "10.1126/science.1104635", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2004-10-22", "series_number": "5696", "volume": "306", "issue": "5696", "pages": "640-643" }, { "id": "authors:crr05-rqq30", "collection": "authors", "collection_id": "crr05-rqq30", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170408-135725447", "type": "article", "title": "Silicon chip-based patch-clamp electrodes integrated with PDMS microfluidics", "author": [ { "family_name": "Pantoja", "given_name": "Rigo", "clpid": "Pantoja-R" }, { "family_name": "Nagarah", "given_name": "John M.", "clpid": "Nagarah-J-M" }, { "family_name": "Starace", "given_name": "Dorine M.", "clpid": "Starace-D-M" }, { "family_name": "Melosh", "given_name": "Nicholas A.", "clpid": "Melosh-N-A" }, { "family_name": "Blunck", "given_name": "Rikard", "orcid": "0000-0003-4484-2907", "clpid": "Blunck-R" }, { "family_name": "Bezanilla", "given_name": "Francisco", "clpid": "Bezanilla-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on a silicon wafer-based device that can be used for recording macroscopic ion channel protein activities across a diverse group of cell-types. Gigaohm seals were achieved for CHO-K1 and RIN m5F cells, and both cell-attached and whole-cell mode configurations were also demonstrated. Two distinct intrinsic potassium ion channels were recorded in whole-cell mode for HIT-T15 and RAW 264.7 cells. Polydimethylsiloxane (PDMS) microfluidics were also coupled with the micromachined silicon chips in order to demonstrate that a single cell could be selectively directed to a micropore, and membrane protein currents could subsequently be recorded. These silicon chip-based devices have significant advantages over traditional micropipette approaches, and may serve as combinatorial tools for investigating membrane biophysics, pharmaceutical screening, and other bio-sensing tasks.", "doi": "10.1016/j.bios.2004.02.020", "issn": "0956-5663", "publisher": "Elsevier", "publication": "Biosensors and Bioelectronics", "publication_date": "2004-10-15", "series_number": "3", "volume": "20", "issue": "3", "pages": "509-517" }, { "id": "authors:rq8jv-p3890", "collection": "authors", "collection_id": "rq8jv-p3890", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170524-141911014", "type": "article", "title": "Black Lipid Membranes: Visualizing the Structure, Dynamics, and Substrate Dependence of Membranes", "author": [ { "family_name": "Ries", "given_name": "Ryan S.", "clpid": "Ries-R-S" }, { "family_name": "Choi", "given_name": "Hyeon", "clpid": "Choi-Hyeon" }, { "family_name": "Blunck", "given_name": "Rikard", "orcid": "0000-0003-4484-2907", "clpid": "Blunck-R" }, { "family_name": "Bezanilla", "given_name": "Francisco", "clpid": "Bezanilla-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The structure and long-time dynamics of suspended lipid bilayers made of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (SOPE) in the gel phase was interrogated using electrical measurements co-recorded with second harmonic generation (SHG) micrographs. SHG microscopy was shown to be an efficient method for distinguishing between the regions of bilayer and annulus as well as probing structural and dynamical variations within a single bilayer. Micromachined silicon chips and two types of plastic partitions, delrin and polyethylene, were investigated as substrate materials. Silicon chips yielded the most stable bilayers, lasting for 1 or 2 days. The membrane characteristics, including the amount of incorporated solvent within the bilayer, the dynamics of bilayer formation, and the stability of the bilayer, were found to be strongly substrate-dependent. In a second set of experiments, SHG-active membrane dyes, di-8-ANEPPS and di-4-ANEPPS, were used to interrogate the domain structure of the same suspended bilayers using scanning two-photon fluorescence (2PF) and SHG microscopy, again correlated with capacitance measurements. Using these dyes, an enhancement in the SHG signal due to membrane potential was recorded, and the rates of molecular diffusion for di-4-ANEPPS through the membrane were investigated. Polarization-resolved SHG imaging was used to determine the orientation of the dye molecules within the membrane.", "doi": "10.1021/jp048098h", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2004-10-14", "series_number": "41", "volume": "108", "issue": "41", "pages": "16040-16049" }, { "id": "authors:psvk5-ge032", "collection": "authors", "collection_id": "psvk5-ge032", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170710-153242193", "type": "article", "title": "Electrochemically Fabricated Polyaniline Nanoframework Electrode Junctions that Function as Resistive Sensors", "author": [ { "family_name": "Wang", "given_name": "Jun", "clpid": "Wang-Jun" }, { "family_name": "Chan", "given_name": "Samuel", "clpid": "Chan-Samuel" }, { "family_name": "Carlson", "given_name": "Richard R.", "clpid": "Carlson-R-R" }, { "family_name": "Luo", "given_name": "Yi", "clpid": "Luo-Yi" }, { "family_name": "Ge", "given_name": "Guanglu", "clpid": "Ge-Guanglu" }, { "family_name": "Ries", "given_name": "Ryan S.", "clpid": "Ries-R-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" } ], "abstract": "In this paper, we demonstrate a template-free, site-specific, and scalable electrochemical method for the fabrication of individually addressable polyaniline nanoframework electrode junctions in a parallel-oriented array. These polyaniline nanoframeworks, which are composed of numerous intercrossing polyaniline nanowires that have uniform diameters ranging from 40 to 80 nm, can be used for the chemical sensing of HCl and NH_3 gases and ethanol vapor and for sensing the pH of aqueous NaCl solutions.", "doi": "10.1021/nl049114p", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2004-09", "series_number": "9", "volume": "4", "issue": "9", "pages": "1693-1697" }, { "id": "authors:y2f50-43342", "collection": "authors", "collection_id": "y2f50-43342", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141120-075859561", "type": "article", "title": "More on Molecular Electronics", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Williams", "given_name": "R. Stanley", "clpid": "Williams-R-S" } ], "abstract": "Two recent news stories by Robert Service (\"Next-generation technology hits an early midlife crisis,\" 24 Oct., News Focus, p. 556; \"Nanodevices make fresh strides toward reality,\" 21 Nov., News of the Week, p. 1310) provide the impression that the field of molecular electronics stalled and then suddenly revived. The specific contributions described in the 21 Nov. news story are just two of a large number of breakthroughs that have been reported by many research groups over the past several years. Progress in the field has been continuous and is accelerating dramatically.", "doi": "10.1126/science.303.5661.1136c", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2004-02-20", "series_number": "5661", "volume": "303", "issue": "5661", "pages": "1136-1137" }, { "id": "authors:m35za-ygb58", "collection": "authors", "collection_id": "m35za-ygb58", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170426-103832302", "type": "article", "title": "Gating the Conductivity of Arrays of Metallic Quantum Dots", "author": [ { "family_name": "Remacle", "given_name": "F.", "clpid": "Remacle-F" }, { "family_name": "Beverly", "given_name": "K. C.", "clpid": "Beverly-K-C" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" } ], "abstract": "Experimental and computational studies demonstrating that the conduction of compressed, two-dimensional arrays of hexagonally ordered Ag quantum dots (QDs) may be varied through the influence of applied electric fields are reported and discussed. Monolayers of Ag QDs are incorporated into three-terminal (gated) devices, in which temperature, source-drain voltage (V_(sd)), gating voltage (V_g), compression of the array, and QD size distribution may all be varied. Experimental and computational results are compared in an effort to construct a physical picture of the system. Current vs V_(sd) plots at low temperatures exhibit systematic nonlinearities that change over to an ohmic-like behavior at higher temperatures and/or higher V_(sd). The voltage-induced transition is discussed as a transition of the conducting states from domain localized to delocalized. Such a transition was previously observed in the temperature dependence of the resistance. The computational model reveals that this transition is also highly sensitive to both the compression of the array and the size-distribution of the dots. We calculate the influence of V_g on the conductivity of the QD array, using the same computational model. In both the experiment and the model, we find a significant voltage gating effect and we observe hole-type conductivity of the array. Overall, the results demonstrate that low-temperature transport measurements provide a spectroscopic-like probe of the electronic states of the QD lattice. The theoretical approach further suggests that quite different gating behavior can be observed for electrodes with a different Fermi energy than the gold electrodes used in the experiment.", "doi": "10.1021/jp036357h", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2003-12-18", "series_number": "50", "volume": "107", "issue": "50", "pages": "13892-13901" }, { "id": "authors:sm3k4-e4k06", "collection": "authors", "collection_id": "sm3k4-e4k06", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190516-092658172", "type": "article", "title": "Single-Walled Carbon Nanotube Based Molecular Switch Tunnel Junctions", "author": [ { "family_name": "Diehl", "given_name": "Michael R.", "clpid": "Diehl-M-R" }, { "family_name": "Steuerman", "given_name": "David W.", "clpid": "Steuerman-D-W" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" }, { "family_name": "Vignon", "given_name": "Scott A.", "clpid": "Vignon-S-A" }, { "family_name": "Star", "given_name": "Alexander", "clpid": "Star-A" }, { "family_name": "Celestre", "given_name": "Paul C.", "clpid": "Celestre-P-C" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "This article describes two\u2010terminal molecular switch tunnel junctions (MSTJs) which incorporate a semiconducting, single\u2010walled carbon nanotube (SWNT) as the bottom electrode. The nanotube interacts noncovalently with a monolayer of bistable, nondegenerate [2]catenane tetracations, self\u2010organized by their supporting amphiphilic dimyristoylphosphatidyl anions which shield the mechanically switchable tetracations from a two\u2010micrometer wide metallic top electrode. The resulting 0.002 \u03bcm^2 area tunnel junction addresses a nanometer wide row of \u22482000 molecules. Active and remnant current\u2013voltage measurements demonstrated that these devices can be reconfigurably switched and repeatedly cycled between high and low current states under ambient conditions. Control compounds, including a degenerate [2]catenane, were explored in support of the mechanical origin of the switching signature. These SWNT\u2010based MSTJs operate like previously reported silicon\u2010based MSTJs, but differently from similar devices incorporating bottom metal electrodes. The relevance of these results with respect to the choice of electrode materials for molecular electronics devices is discussed.", "doi": "10.1002/cphc.200300871", "issn": "1439-4235", "publisher": "Wiley", "publication": "ChemPhysChem", "publication_date": "2003-12-15", "series_number": "12", "volume": "4", "issue": "12", "pages": "1335-1339" }, { "id": "authors:1kt33-z4z96", "collection": "authors", "collection_id": "1kt33-z4z96", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190516-093543949", "type": "article", "title": "The Molecule-Electrode Interface in Single-Molecule Transistors", "author": [ { "family_name": "Yu", "given_name": "Hongbin", "clpid": "Yu-Hongbin" }, { "family_name": "Luo", "given_name": "Yi", "clpid": "Luo-Yi" }, { "family_name": "Beverly", "given_name": "Kristen", "clpid": "Beverly-K-C" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "What's in the middle matters little! Differential conductance measurements made on single\u2010molecule rotaxanes and their precursor dumbbells in transistors with platinum electrodes reflect the molecule\u2013electrode contacts rather than the middle section of the molecules (see diagram; the color reflects the conductance, with dark corresponding to zero current). Interface states dominate electron transport. Molecular signatures are masked and even constitutional asymmetry in the molecule is difficult to detect.", "doi": "10.1002/anie.200352352", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2003-12-01", "series_number": "46", "volume": "42", "issue": "46", "pages": "5706-5711" }, { "id": "authors:3kv5p-3c945", "collection": "authors", "collection_id": "3kv5p-3c945", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190516-085234738", "type": "article", "title": "NanoSystems biology", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Phelps", "given_name": "Michael E.", "clpid": "Phelps-M-E" }, { "family_name": "Hood", "given_name": "Leroy", "orcid": "0000-0001-7158-3678", "clpid": "Hood-L-E" } ], "abstract": "Systems biology is an approach in which the digital information of the genome, acted upon by environmental cues, generates the many molecular signatures of gene and protein expression, as well as other, more phenomenological experimental observations. These data may be integrated together to form a testable hypothesis of how a biological organism functions as a system. The central components of systems biology are genetically programmed networks (circuits) within cells and networks of cells. These components establish the organization and function of individual cells and tissues in response to environmental signals such as cell-to-cell communication within organ systems and whole organisms. Within this context, disease is considered as a genetic or environmental reprogramming of cells to gain or lose specific functions that are characteristics of disease. This paper is a combination of three tutorials with an outlined series of technologies, including microfluidics, nanotechnologies, and molecular imaging methods, and we describe how their development should be driven by the needs of systems biology. We also discuss how these technologies can enable a systems biology approach through a pathway from single cells to mouse models of disease and finally to patients. Within this technology base are approaches to develop, use and test molecules as probes that target proteins, DNA and mRNA to test systems biology models, as well as provide molecular diagnostics and molecular therapeutics within a systems biology framework.", "doi": "10.1016/j.mibio.2003.10.001", "issn": "1536-1632", "publisher": "Springer", "publication": "Molecular Imaging and Biology", "publication_date": "2003-09", "series_number": "5", "volume": "5", "issue": "5", "pages": "312-325" }, { "id": "authors:dgj0r-1fd64", "collection": "authors", "collection_id": "dgj0r-1fd64", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161102-163632579", "type": "book_section", "title": "A Systems Approach to Molecular Electronics", "book_title": "ISLPED '03 Proceedings of the 2003 international symposium on Low power electronics and design", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "contributor": [ { "family_name": "Verbauwhede", "given_name": "Ingrid", "clpid": "Verbauwhede-I" }, { "family_name": "Roh", "given_name": "Hyung", "clpid": "Roh-Hyung" } ], "abstract": "Molecular electronics is an area of research in which molecules are employed to yield the active and passive device components (switches, diodes, resistors) of an electronic circuit or integrated circuit. Consider the crossbar circuits of nanowires in the electron micrograph at the left [1]. The smallest (100 element) crossbar in this image is patterned at a density approach 10^12/cm^2, and the wire diameter is approximately 8 nm. At a doping level (with species like Boron or Arsenic) of 10^18/cm^3, a similar 8 nm diameter, micrometer-long segment of silicon wires would have 20-30 dopant atoms, and a junction of two crossed wires would contain approximately 0.1-0.2 dopant atoms. Thus, field-effect transistors fabricated at these wiring densities might exhibit non-statistical, and perhaps non-predictable behavior. Related arguments, such as the gate oxide thickness, power consumption, (just from leakage currents through the gate oxide), fabrication costs, and others also highlight the difficulty of scaling standard electronics materials to molecular dimensions [2]. The point is that at device areas of a few tens of square nanometers, molecules have a certain fundamental attractiveness because of their size, because they represent the ultimate in terms of atomic control over physical properties, and because of the diversity of properties, such as switching, dynamic organization and recognition that can be achieved through such control.Molecular electronics circuits based on crossbar architectures can be utilized for both logic and memory applications [3], but in order to realize such applications, many things must be simultaneously considered. These include the design of the molecule, the molecule electrode interface, electronically configurable and defect tolerant circuit architectures, methods for bridging the nanometer-scale densities of these circuits to the sub-micrometer densities achievable with lithography, etc. [4] In this talk I will treat such circuits as a system, and discuss how all of these various properties are interrelated. I will also present experimental results of working random-access memory and configurable logic circuits, and FET-based multiplexers capable of bridging length scales.In these circuits the active device elements are molecular mechanical complexes organized at each of the junctions within the crossbar, as shown at left in the drawing. The molecules are switched via 1 or 2 electron process that results in a mechanical isomerization of the molecule, and thereby a change in the tunneling characteristics of the junction. Detailed electrical measurements on single molecule, three-terminal devices are revealing substantial information concerning how these types of devices can be better designed and optimized, and such measurements will also be presented and discussed.", "doi": "10.1145/871506.871596", "isbn": "1-58113-682-X", "publisher": "ACM", "place_of_publication": "New York, NY", "publication_date": "2003-08", "pages": "359" }, { "id": "authors:ebfx3-2jv75", "collection": "authors", "collection_id": "ebfx3-2jv75", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141119-115412847", "type": "article", "title": "Ultrahigh-Density Nanowire Lattices and Circuits", "author": [ { "family_name": "Melosh", "given_name": "Nicholas A.", "clpid": "Melosh-N-A" }, { "family_name": "Boukai", "given_name": "Akram", "clpid": "Boukai-A" }, { "family_name": "Diana", "given_name": "Frederic", "clpid": "Diana-F" }, { "family_name": "Gerardot", "given_name": "Brian", "clpid": "Gerardot-B" }, { "family_name": "Badolato", "given_name": "Antonio", "clpid": "Badolato-A" }, { "family_name": "Petroff", "given_name": "Pierre M.", "clpid": "Petroff-P-M" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We describe a general method for producing ultrahigh-density arrays of aligned metal and semiconductor nanowires and nanowire circuits. The technique is based on translating thin film growth thickness control into planar wire arrays. Nanowires were fabricated with diameters and pitches (center-to-center distances) as small as 8 nanometers and 16 nanometers, respectively. The nanowires have high aspect ratios (up to 10^6), and the process can be carried out multiple times to produce simple circuits of crossed nanowires with a nanowire junction density in excess of 10^(11) per square centimeter. The nanowires can also be used in nanomechanical devices; a high-frequency nanomechanical resonator is demonstrated.", "doi": "10.1126/science.1081940", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2003-04-04", "series_number": "5616", "volume": "300", "issue": "5616", "pages": "112-115" }, { "id": "authors:e5pyv-efv42", "collection": "authors", "collection_id": "e5pyv-efv42", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190516-095057730", "type": "article", "title": "Starched Carbon Nanotubes", "author": [ { "family_name": "Star", "given_name": "Alexander", "clpid": "Star-A" }, { "family_name": "Steuerman", "given_name": "David W.", "clpid": "Steuerman-D-W" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "Common\u2010or\u2010garden starch can render single\u2010walled carbon nanotubes (SWNTs) readily soluble in water. The secret is to preorganize the linear amylose component in the starch into a helix with iodine prior to bringing the SWNTs on the scene. The SWNTs displace the iodine molecules in a \"pea\u2010shooting\" type of mechanism (see scheme). After some physical cajoling of the aqueous solution containing the starch\u2013SWNT complex, a fine \"bucky paper\" is formed. Spitting in the aqueous solution, followed by sitting around for a few hours, also enables equally fine \"bucky paper\" to be harvested.", "doi": "10.1002/1521-3773(20020715)41:14<2508::aid-anie2508>3.0.co;2-a", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2002-07-15", "series_number": "14", "volume": "41", "issue": "14", "pages": "2508-2512" }, { "id": "authors:j2256-grp46", "collection": "authors", "collection_id": "j2256-grp46", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190516-102504910", "type": "article", "title": "Two-Dimensional Molecular Electronics Circuits", "author": [ { "family_name": "Luo", "given_name": "Yi", "clpid": "Luo-Yi" }, { "family_name": "Collier", "given_name": "C. Patrick", "clpid": "Collier-C-P" }, { "family_name": "Jeppesen", "given_name": "Jan O.", "clpid": "Jeppesen-J-O" }, { "family_name": "Nielsen", "given_name": "Kent A.", "clpid": "Nielsen-K-A" }, { "family_name": "DeIonno", "given_name": "Erica", "clpid": "DeIonno-E" }, { "family_name": "Ho", "given_name": "Greg", "clpid": "Ho-Greg" }, { "family_name": "Perkins", "given_name": "Julie", "clpid": "Perkins-J" }, { "family_name": "Tseng", "given_name": "Hsian-Rong", "clpid": "Tseng-Hsian-Rong" }, { "family_name": "Yamamoto", "given_name": "Tohru", "clpid": "Yamamoto-Tohru" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Addressing an array of bistable [2]rotaxanes through a two\u2010dimensional crossbar arrangement provides the device element of a current\u2010driven molecular electronic circuit. The development of the [2]rotaxane switches through an iterative, evolutionary process is described. The arrangement reported here allows both memory and logic functions to use the same elements.", "doi": "10.1002/1439-7641(20020617)3:6<519::aid-cphc519>3.0.co;2-2", "issn": "1439-4235", "publisher": "Wiley", "publication": "ChemPhysChem", "publication_date": "2002-06-17", "series_number": "6", "volume": "3", "issue": "6", "pages": "519-525" }, { "id": "authors:606yg-x8j83", "collection": "authors", "collection_id": "606yg-x8j83", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190516-100847454", "type": "article", "title": "Photochemical Response of Electronically Reconfigurable Molecule-Based Switching Tunnel Junctions", "author": [ { "family_name": "Collier", "given_name": "Charles P.", "clpid": "Collier-C-P" }, { "family_name": "Ma", "given_name": "Bin", "clpid": "Ma-Bin" }, { "family_name": "Wong", "given_name": "Eric W.", "clpid": "Wong-Eric-W" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Wudl", "given_name": "Fred", "clpid": "Wudl-F" } ], "abstract": "Robust molecular devices may be based on the photo\u2010switching between spiropyran and merocyanine isomers (see Scheme). The equilibrium has been investigated in a Langmuir\u2013Blodgett film and then succesfully sandwiched into a solid\u2010state tunnel junction.", "doi": "10.1002/1439-7641(20020517)3:5<458::aid-cphc458>3.0.co;2-x", "issn": "1439-4235", "publisher": "Wiley", "publication": "ChemPhysChem", "publication_date": "2002-05-17", "series_number": "5", "volume": "3", "issue": "5", "pages": "458-461" }, { "id": "authors:apb74-mnp68", "collection": "authors", "collection_id": "apb74-mnp68", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:BEVpnas02", "type": "article", "title": "Quantum dot artificial solids: Understanding the static and dynamic role of size and packing disorder", "author": [ { "family_name": "Beverly", "given_name": "K. C.", "clpid": "Beverly-K-C" }, { "family_name": "Sample", "given_name": "J. L.", "clpid": "Sample-J-L" }, { "family_name": "Sampaio", "given_name": "J. F.", "clpid": "Sampaio-J-F" }, { "family_name": "Remacle", "given_name": "F.", "clpid": "Remacle-F" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Levine", "given_name": "R. D.", "clpid": "Levine-R-D" } ], "abstract": "This perspective examines quantum dot (QD) superlattices as model systems for achieving a general understanding of the electronic structure of solids and devices built from nanoscale components. QD arrays are artificial two-dimensional solids, with novel optical and electric properties, which can be experimentally tuned. The control of the properties is primarily by means of the selection of the composition and size of the individual QDs and secondly, through their packing. The freedom of the architectural design is constrained by nature insisting on diversity. Even the best synthesis and separation methods do not yield dots of exactly the same size nor is the packing in the self-assembled array perfectly regular. A series of experiments, using both spectroscopic and electrical probes, has characterized the effects of disorder for arrays of metallic dots. We review these results and the corresponding theory. In particular, we discuss temperature-dependent transport experiments as the next step in the characterization of these arrays.", "doi": "10.1073/pnas.251537898", "pmcid": "PMC128549", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2002-04-30", "series_number": "suppl. 2", "volume": "99", "issue": "suppl. 2", "pages": "6456-6459" }, { "id": "authors:4wjrc-b0462", "collection": "authors", "collection_id": "4wjrc-b0462", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-095529176", "type": "article", "title": "Interactions between Conjugated Polymers and Single-Walled Carbon Nanotubes", "author": [ { "family_name": "Steuerman", "given_name": "David W.", "clpid": "Steuerman-D-W" }, { "family_name": "Stark", "given_name": "Alexander", "clpid": "Stark-A" }, { "family_name": "Narizzano", "given_name": "Riccardo", "clpid": "Narizzano-R" }, { "family_name": "Choi", "given_name": "Hyeon", "clpid": "Choi-Hyeon" }, { "family_name": "Ries", "given_name": "Ryan S.", "clpid": "Ries-R-S" }, { "family_name": "Nicolini", "given_name": "Claudio", "clpid": "Nicolini-C" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The chemical interactions between single walled carbon nanotubes (SWNTs) and two structurally similar polymers, poly{(m-phenylenevinylene)-co-[(2,5-dioctyloxy-p-phenylene)vinylene]}, or PmPV, and poly{(2,6-pyridinylenevinylene)-co-[(2,5-dioctyloxy-p-phenylene)vinylene]}, or PPyPV, are investigated. The fundamental difference between these two polymers is that PPyPV is a base and is readily protonated via the addition of HCl. Both polymers promote chloroform solubilization of SWNTs. We find that the SWNT/PPyPV interaction lowers the pKa of PPyPV. Optoelectronic devices, fabricated from single polymer-wrapped SWNT structures, reveal a photogating effect on charge transport which can rectify or amplify current flow through the tubes. For PmPV wrapped tubes, the wavelength dependence of this effect correlates to the absorption spectrum of PmPV. For PPyPV, the wavelength dependence correlates with the absorption spectrum of protonated PPyPV, indicating that SWNTs assist in charge stabilization.", "doi": "10.1021/jp014326l", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2002-03-28", "series_number": "12", "volume": "106", "issue": "12", "pages": "3124-3130" }, { "id": "authors:1m43n-th783", "collection": "authors", "collection_id": "1m43n-th783", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170619-072243967", "type": "article", "title": "The Structure of a Tetraazapentacene Molecular Monolayer", "author": [ { "family_name": "Choi", "given_name": "H.", "clpid": "Chi-H" }, { "family_name": "Yang", "given_name": "X.", "clpid": "Yang-X" }, { "family_name": "Mitchell", "given_name": "G. W.", "clpid": "Mitchell-G-W" }, { "family_name": "Collier", "given_name": "C. P.", "clpid": "Collier-C-P" }, { "family_name": "Wudl", "given_name": "F.", "clpid": "Wudl-F" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Langmuir molecular monolayers of a unique tetraazapentacene zwitterionic amphiphile were found to form stripe-like domains that responded strongly to an applied magnetic field. These stripe domains were transferred as Langmuir\u2212Blodgett (LB) films to glass substrates, where they were structurally characterized using five complementary imaging techniques, including scanning second-harmonic generation (SHG) microscopy and capacitance force microscopy. The molecular orientations of adjacent single striped domains of a tetraazapentacene monolayer were determined by SHG polarization measurements. Those structures were shown to be consistent across the various imaging techniques.", "doi": "10.1021/jp0155415", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2002-02-28", "series_number": "8", "volume": "106", "issue": "8", "pages": "1833-1839" }, { "id": "authors:xt51j-dvc66", "collection": "authors", "collection_id": "xt51j-dvc66", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190516-100255802", "type": "article", "title": "Self-Assembled, Deterministic Carbon Nanotube Wiring Networks", "author": [ { "family_name": "Diehl", "given_name": "Michael R.", "clpid": "Diehl-M-R" }, { "family_name": "Yaliraki", "given_name": "Sophia N.", "clpid": "Yaliraki-S-N" }, { "family_name": "Beckman", "given_name": "Robert A.", "clpid": "Beckman-R-A" }, { "family_name": "Barahona", "given_name": "Mauricio", "orcid": "0000-0002-1089-5675", "clpid": "Barahona-M" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A \"minimal\u2010lithography\" technique for chemically assembling small deterministic crossbars of single\u2010walled carbon nanotube (SWNT) ropes: The formation of electrically conducting crossbar circuits with 8 to 14 junctions (see picture) from a suspension of SWNTs is described. The critical structural parameters of the circuits were controlled by chemically directed self\u2010assembly, rather than lithographic patterning, and all steps were carried out under ambient conditions.", "doi": "10.1002/1521-3773(20020118)41:2<353::aid-anie353>3.0.co;2-y", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2002-01-18", "series_number": "2", "volume": "41", "issue": "2", "pages": "353-356" }, { "id": "authors:wyhmz-mvn72", "collection": "authors", "collection_id": "wyhmz-mvn72", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-082756149", "type": "article", "title": "Molecular-Based Electronically Switchable Tunnel Junction Devices", "author": [ { "family_name": "Collier", "given_name": "C. Patrick", "clpid": "Collier-C-P" }, { "family_name": "Jeppesen", "given_name": "Jan O.", "clpid": "Jeppesen-J-O" }, { "family_name": "Luo", "given_name": "Yi", "clpid": "Luo-Yi" }, { "family_name": "Perkins", "given_name": "Julie", "clpid": "Perkins-J" }, { "family_name": "Wong", "given_name": "Eric W.", "clpid": "Wong-Eric-W" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" } ], "abstract": "Solid-state tunnel junction devices were fabricated from Langmuir Blodgett molecular monolayers of a bistable [2]catenane, a bistable [2]pseudorotaxane, and a single-station [2]rotaxane. All devices exhibited a (noncapacitive) hysteretic current\u2212voltage response that switched the device between high- and low-conductivity states, although control devices exhibited no such response. Correlations between the structure and solution-phase dynamics of the molecular and supramolecular systems, the crystallographic domain structure of the monolayer film, and the room-temperature device performance characteristics are reported.", "doi": "10.1021/ja0114456", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2001-12-19", "series_number": "50", "volume": "123", "issue": "50", "pages": "12632-12641" }, { "id": "authors:5g1h3-90284", "collection": "authors", "collection_id": "5g1h3-90284", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-153906998", "type": "article", "title": "Bilayer Reconstitution of Voltage-Dependent Ion Channels using a Microfabricated Silicon Chip", "author": [ { "family_name": "Pantoja", "given_name": "Rigo", "clpid": "Pantoja-R" }, { "family_name": "Sigg", "given_name": "Daniel", "clpid": "Sigg-D" }, { "family_name": "Blunck", "given_name": "Rikard", "orcid": "0000-0003-4484-2907", "clpid": "Blunck-R" }, { "family_name": "Bezanilla", "given_name": "Francisco", "clpid": "Bezanilla-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Painted bilayers containing reconstituted ion channels serve as a well defined model system for electrophysiological investigations of channel structure and function. Horizontally oriented bilayers with easy solution access to both sides were obtained by painting a phospholipid:decane mixture across a cylindrical pore etched into a 200-\u03bcm thick silicon wafer. Silanization of the SiO_2 layer produced a hydrophobic surface that promoted the adhesion of the lipid mixture. Standard lithographic techniques and anisotropic deep-reactive ion etching were used to create pores with diameters from 50 to 200 \u03bcm. The cylindrical structure of the pore in the partition and the surface treatment resulted in stable bilayers. These were used to reconstitute Maxi K channels in the 100- and 200-\u03bcm diameter pores. The electrophysiological characteristics of bilayers suspended in microchips were comparable with that of other bilayer preparations. The horizontal orientation and good voltage clamping properties make the microchip bilayer method an excellent system to study the electrical properties of reconstituted membrane proteinssimultaneously with optical probes.", "doi": "10.1016/s0006-3495(01)75885-7", "pmcid": "PMC1301709", "issn": "0006-3495", "publisher": "Biophysical Society", "publication": "Biophysical Journal", "publication_date": "2001-10", "series_number": "4", "volume": "81", "issue": "4", "pages": "2389-2394" }, { "id": "authors:vd06b-7vq79", "collection": "authors", "collection_id": "vd06b-7vq79", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-111919529", "type": "article", "title": "Crystalline, Shape, and Surface Anisotropy in Two Crystal Morphologies of Superparamagnetic Cobalt Nanoparticles by Ferromagnetic Resonance", "author": [ { "family_name": "Diehl", "given_name": "Michael R.", "clpid": "Diehl-M-R" }, { "family_name": "Yu", "given_name": "Jae-Young", "clpid": "Yu-Jae-Young" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Held", "given_name": "Glenn A.", "clpid": "Held-G-A" }, { "family_name": "Doyle", "given_name": "Hugh", "clpid": "Doyle-H" }, { "family_name": "Sun", "given_name": "Shouheng", "clpid": "Sun-Shouheng" }, { "family_name": "Murray", "given_name": "Christopher B.", "clpid": "Murray-C-B" } ], "abstract": "Ferromagnetic resonance (FMR) techniques are used to investigate superparamagnetic cobalt nanoparticles (NP's) with different crystalline structures and sizes ranging from 4 to 9 nm in diameter. Magnetic contributions from NC shape, crystallographic structure, defects, and surface structure are discussed. An independent-superparamagnetic-grain model is employed to simulate the FMR measurements. The results from both single crystalline and polycrystalline cobalt NP's reveal that a particle's effective anisotropy, and thus its magnetic properties, are extremely sensitive to internal structure as well as overall particle shape. Finally, surface chemical properties were found to yield unique FMR signatures for NP's at low temperatures.", "doi": "10.1021/jp004252y", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2001-08-23", "series_number": "33", "volume": "105", "issue": "33", "pages": "7913-7919" }, { "id": "authors:f3kfn-btm40", "collection": "authors", "collection_id": "f3kfn-btm40", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-073433919", "type": "article", "title": "Switching Devices Based on Interlocked Molecules", "author": [ { "family_name": "Pease", "given_name": "Anthony R.", "clpid": "Pease-A-R" }, { "family_name": "Jeppesen", "given_name": "Jan O.", "clpid": "Jeppesen-J-O" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Luo", "given_name": "Yi", "clpid": "Luo-Yi" }, { "family_name": "Collier", "given_name": "C. Patrick", "clpid": "Collier-C-P" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "An architectural rationale and an experimental program aimed at the development of molecular electronics switching devices for memory and computing applications are discussed. Two-terminal molecular switch tunnel junctions are identified as the critical device components of molecular electronics-based circuitry. They can be tiled in two dimensions and are tolerant of manufacturing defects. Singly and multiply configurable solid-state switching devices that are based upon electrochemically switchable molecular and supramolecular systems are discussed in terms of both the synthesis of the molecular components and the fabrication and performance of the devices.", "doi": "10.1021/ar000178q", "issn": "0001-4842", "publisher": "American Chemical Society", "publication": "Accounts of Chemical Research", "publication_date": "2001-06", "series_number": "6", "volume": "34", "issue": "6", "pages": "433-444" }, { "id": "authors:gwvhs-xpr35", "collection": "authors", "collection_id": "gwvhs-xpr35", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-152930277", "type": "article", "title": "Preparation and Properties of Polymer-Wrapped Single-Walled Carbon Nanotubes", "author": [ { "family_name": "Star", "given_name": "Alexander", "clpid": "Star-A" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Steuerman", "given_name": "David", "clpid": "Steuerman-D-W" }, { "family_name": "Diehl", "given_name": "Mike", "clpid": "Diehl-M" }, { "family_name": "Boukai", "given_name": "Akram", "clpid": "Boukai-A" }, { "family_name": "Wong", "given_name": "Eric W.", "clpid": "Wong-Eric-W" }, { "family_name": "Yang", "given_name": "Xin", "orcid": "0000-0001-5111-2959", "clpid": "Yang-Xin" }, { "family_name": "Chung", "given_name": "Sung-Wook", "clpid": "Chung-Sung-Wook" }, { "family_name": "Choi", "given_name": "Hyeon", "clpid": "Choi-Hyeon" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Intimate electrical contact occurs between a substituted poly(metaphenylenevinylene) (PmPV) and bundles of single\u2010walled nanotubes (SWNT) as evidenced by atomic force microscopy, optical, and electronic measurements carried out on single, isolated SWNT/PmPV structures (see picture). PmPV may provide a useful route toward \"functionalizing\" the SWNT without destroying their electrical character.", "doi": "10.1002/1521-3773(20010504)40:9<1721::aid-anie17210>3.0.co;2-f", "issn": "1433-7851", "publisher": "Wiley", "publication": "Angewandte Chemie International Edition", "publication_date": "2001-05-04", "series_number": "9", "volume": "40", "issue": "9", "pages": "1721-1725" }, { "id": "authors:ne76h-52p62", "collection": "authors", "collection_id": "ne76h-52p62", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-113220292", "type": "article", "title": "How the news that we were not the first to conceive of soccer ball C_(60) got to us", "author": [ { "family_name": "Curl", "given_name": "Robert F.", "clpid": "Curl-R-F" }, { "family_name": "Smalley", "given_name": "Richard E.", "clpid": "Smalley-R-E" }, { "family_name": "Kroto", "given_name": "Harold W.", "clpid": "Kroto-H-W" }, { "family_name": "O'Brien", "given_name": "Sean", "clpid": "O'Brien-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "[no abstract]", "doi": "10.1016/s1093-3263(00)00107-8", "issn": "1093-3263", "publisher": "Elsevier", "publication": "Journal of Molecular Graphics and Modelling", "publication_date": "2001-04", "series_number": "2", "volume": "19", "issue": "2", "pages": "185-186" }, { "id": "authors:nprwe-8q064", "collection": "authors", "collection_id": "nprwe-8q064", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-111259764", "type": "article", "title": "Silicon Nanowires: Preparation, Device Fabrication, and Transport Properties", "author": [ { "family_name": "Yu", "given_name": "Jae-Young", "clpid": "Yu-Jae-Young" }, { "family_name": "Chung", "given_name": "Sung-Wook", "clpid": "Chung-Sung-Wook" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The preparation of 20 \u00b1 5 nm diameter Si nanowires and the electrical characterization of Si nanowire devices are presented. The nanowires were grown at 450\u2212500 \u00b0C on solid substrates via the vapor\u2212liquid\u2212solid mechanism using Au or Zn nucleation catalysts and SiH4 as the silicon source. The wires were investigated by high-resolution transmission electron microscopy. Two types of wires were found, as characterized by different growth directions (\u3008111\u0304\u3009 and \u3008211\u3009). Several types of devices, including crossed nanowire devices, four- and six-terminal devices, and three-terminal (gated) devices, were fabricated. For certain devices, various electrode compositions were also studied. The measured resistivity of these nanowires was separated from the contact resistance and could be varied from >10^5 \u03a9 cm to \u223c10^(-3) \u03a9 cm. The wide variation in resistivity was related to the nature of the electrical contact to the wires (Schottky or Ohmic) and to the doping level of the wires. Doping of the nanowires was performed by the thermal diffusion of metal catalyst into the nanowires at 750\u2212850 \u00b0C. Au nucleated nanowires exhibited resistivity values much lower than those of similarly treated Zn nucleated nanowires. This result is attributed to the much larger relative solid solubility of gold in silicon.", "doi": "10.1021/jp002595q", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2000-12-21", "series_number": "50", "volume": "104", "issue": "50", "pages": "11864-11870" }, { "id": "authors:3aaxa-qf230", "collection": "authors", "collection_id": "3aaxa-qf230", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-152218119", "type": "article", "title": "A [2]Catenane-Based Solid State Electronically Reconfigurable Switch", "author": [ { "family_name": "Collier", "given_name": "Charles P.", "clpid": "Collier-C-P" }, { "family_name": "Mattersteig", "given_name": "Gunter", "clpid": "Mattersteig-G" }, { "family_name": "Wong", "given_name": "Eric W.", "clpid": "Wong-Eric-W" }, { "family_name": "Luo", "given_name": "Yi", "clpid": "Luo-Yi" }, { "family_name": "Beverly", "given_name": "Kristen", "clpid": "Beverly-K-C" }, { "family_name": "Sampaio", "given_name": "Jos\u00e9", "clpid": "Sampaio-J" }, { "family_name": "Raymo", "given_name": "Fran\u00e7isco M.", "clpid": "Raymo-F-M" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A solid state, electronically addressable, bistable [2]catenane-based molecular switching device was fabricated from a single monolayer of the [2]catenane, anchored with phospholipid counterions, and sandwiched between an n-type polycrystalline silicon bottom electrode and a metallic top electrode. The device exhibits hysteretic (bistable) current/voltage characteristics. The switch is opened at +2 volts, closed at \u22122 volts, and read at \u223c0.1 volt and may be recycled many times under ambient conditions. A mechanochemical mechanism for the action of the switch is presented and shown to be consistent with temperature-dependent measurements of the device operation.", "doi": "10.1126/science.289.5482.1172", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2000-08-18", "series_number": "5482", "volume": "289", "issue": "5482", "pages": "1172-1175" }, { "id": "authors:9fpnz-n3237", "collection": "authors", "collection_id": "9fpnz-n3237", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:CHOjvsta00", "type": "article", "title": "Fabrication of bismuth nanowires with a silver nanocrystal shadowmask", "author": [ { "family_name": "Choi", "given_name": "S. H.", "clpid": "Choi-S-H" }, { "family_name": "Wang", "given_name": "K. L.", "clpid": "Wang-K-L" }, { "family_name": "Leung", "given_name": "M. S.", "clpid": "Leung-M-S" }, { "family_name": "Stupian", "given_name": "G. W.", "clpid": "Stupian-G-W" }, { "family_name": "Presser", "given_name": "N.", "clpid": "Presser-N" }, { "family_name": "Morgan", "given_name": "B. A.", "clpid": "Morgan-B-A" }, { "family_name": "Robertson", "given_name": "R. E.", "clpid": "Robertson-R-E" }, { "family_name": "Abraham", "given_name": "M.", "clpid": "Abraham-M" }, { "family_name": "King", "given_name": "E. E.", "clpid": "King-E-E" }, { "family_name": "Tueling", "given_name": "M. B.", "clpid": "Tueling-M-B" }, { "family_name": "Chung", "given_name": "S. W.", "clpid": "Shung-S-W" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Cho", "given_name": "S. L.", "clpid": "Cho-S-L" }, { "family_name": "Ketterson", "given_name": "J. B.", "clpid": "Ketterson-J-B" } ], "abstract": "We fabricated bismuth (Bi) nanowires with low energy electron beam lithography using silver (Ag) nanocrystal shadowmasks and a subsequent chlorine reactive ion etching. Submicron-size metal contacts on the single Bi nanowire were successfully prepared by in situ focused ion beam metal deposition for transport measurements. The temperature dependent resistance measurements on the 50 nm wide Bi nanowires showed that the resistance increased with decreasing temperature, which is characteristic of semiconductors and insulators.", "doi": "10.1116/1.582348", "issn": "0734-2101", "publisher": "American Vacuum Society", "publication": "Journal of Vacuum Science and Technology A", "publication_date": "2000-07", "series_number": "4", "volume": "18", "issue": "4", "pages": "1326-1328" }, { "id": "authors:4hmqm-pg053", "collection": "authors", "collection_id": "4hmqm-pg053", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-081722324", "type": "article", "title": "Fabrication and Transport Properties of Single-Molecule-Thick Electrochemical Junctions", "author": [ { "family_name": "Wong", "given_name": "Eric W.", "clpid": "Wong-Eric-W" }, { "family_name": "Collier", "given_name": "Charles P.", "clpid": "Collier-C-P" }, { "family_name": "B\u011bhloradsk\u00fd", "given_name": "Martin", "clpid": "B\u011bhloradsk\u00fd-M" }, { "family_name": "Raymo", "given_name": "Fran\u00e7isco M.", "clpid": "Raymo-F-M" }, { "family_name": "Stoddart", "given_name": "J. Fraser", "orcid": "0000-0003-3161-3697", "clpid": "Stoddart-J-F" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A V-shaped compound incorporating two bipyridinium units, which emanate from a central hydrophilic core and bear hydrophobic tetraarylmethane-based stoppers at each end, was designed and synthesized. In a thermodynamically controlled self-assembly process in solution, either one or two 1,4-dioxybenzene-based macrocyclic polyethers can be slipped over the bulky stoppers of the V-shaped compound, affording either a [2]rotaxane or a [3]rotaxane, respectively. The parent V-shaped compound and the two rotaxanes incorporate two redox-active bipyridinium units that can be reduced reversibly and two redox-active phenoxy groups in the stoppers that can be oxidized irreversibly. Furthermore, these three compounds have amphiphilic character and, as a result, form stable monolayers at the air/water interface. Langmuir\u2212Blodgett monolayers of these compounds were sandwiched between two electrodes to afford molecule-based solid-state switches. In forward bias mode, the I\u2212V characteristics of the junction are reversible, but upon application of a sufficient reverse bias the junction resistance is irreversibly decreased, thereby switching the device. As a result, the current flowing through the device at forward bias voltages is lowered by a factor of 60\u221280. The behavior of the solid-state devices can be interpreted on the basis of the redox properties determined in solution for the three compounds. Initially, current flow at forward bias is determined by resonant tunneling through the molecular LUMO states associated with the bipyridium units. The irreversible decrease in current that occurs at reverse biases suggests a similarity to the solution-phase oxidation of the phenoxy groups.", "doi": "10.1021/ja993890v", "issn": "0002-7863", "publisher": "American Chemical Society", "publication": "Journal of the American Chemical Society", "publication_date": "2000-06-21", "series_number": "24", "volume": "122", "issue": "24", "pages": "5831-5840" }, { "id": "authors:1wspm-w0932", "collection": "authors", "collection_id": "1wspm-w0932", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-113215705", "type": "article", "title": "Josephson Coupled Quantum Dot Artificial Solids", "author": [ { "family_name": "Weitz", "given_name": "Iris S.", "clpid": "Weitz-I-S" }, { "family_name": "Sample", "given_name": "Jennifer L.", "clpid": "Sample-J-L" }, { "family_name": "Ries", "given_name": "Ryan", "clpid": "Ries-R-S" }, { "family_name": "Spain", "given_name": "Eileen M.", "clpid": "Spain-E-M" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Josephson coupled quantum dot artificial solids were prepared from 20 \u00b1 4 nm diameter organically functionalized Pb particles. Interparticle separation distances were varied from approximately 26 to 11 \u00c5 by varying the passivating organic ligand. Isolated particles were too small to exhibit a Meisner effect by themselves, and so it was possible to employ SQUID magnetometry as a zero-background probe for Cooper pair delocalization in these solids. As the interparticle separation distance was decreased, the quantum dot solids progressed from a Mott insulator to a strongly localized superfluid, and finally to a superfluid.", "doi": "10.1021/jp000238+", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "2000-05-11", "series_number": "18", "volume": "104", "issue": "18", "pages": "4288-4291" }, { "id": "authors:77sk5-1z553", "collection": "authors", "collection_id": "77sk5-1z553", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:CHUapl00", "type": "article", "title": "Silicon nanowire devices", "author": [ { "family_name": "Chung", "given_name": "Sung-Wook", "clpid": "Chung-Sung-Wook" }, { "family_name": "Yu", "given_name": "Jae-Young", "clpid": "Yu-Jae-Young" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Transport measurements were carried out on 15\u201335 nm diameter silicon nanowires grown using SiH4 chemical vapor deposition via Au or Zn particle-nucleated vapor-liquid-solid growth at 440\u00b0C. Both Al and Ti/Au contacts to the wires were investigated. The wires, as produced, were essentially intrinsic, although Au nucleated wires exhibited a slightly higher conductance. Thermal treatment of the fabricated devices resulted in better electrical contacts, as well as diffusion of dopant atoms into the nanowires, and increased the nanowire conductance by as much as 10^4. Three terminal devices indicate that the doping of the wires is p type.", "doi": "10.1063/1.126257", "issn": "0003-6951", "publisher": "American Institute of Physics", "publication": "Applied Physics Letters", "publication_date": "2000-04-10", "series_number": "15", "volume": "76", "issue": "15", "pages": "2068-2070" }, { "id": "authors:eayc5-m9v81", "collection": "authors", "collection_id": "eayc5-m9v81", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120113-073602025", "type": "article", "title": "Electrochemical Characterization of Films of Single-Walled Carbon Nanotubes and Their Possible Application in Supercapacitors", "author": [ { "family_name": "Liu", "given_name": "Chong-yang", "clpid": "Liu-Chong-yang" }, { "family_name": "Bard", "given_name": "Allen J.", "clpid": "Bard-A-J" }, { "family_name": "Wudl", "given_name": "Fred", "clpid": "Wudl-F" }, { "family_name": "Weitz", "given_name": "Iris", "clpid": "Weitz-I" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Films of single-wall carbon nanotubes (SWCNTs) were cast from suspensions in several solvents on the surface of a Pt or Au electrode. Cyclic voltammetry of the films in MeCN did not show well-resolved waves (as distinct from films of C_(60) prepared in a similar manner). However, the increase in the effective capacitance of the electrode with a SWCNT film at 0.5 V vs. an AgQRE was 283 F/g, which is about twice that of carbon electrodes in nonaqueous solvents.", "doi": "10.1149/1.1390910", "issn": "1099-0062", "publisher": "Electrochemical Society", "publication": "Electrochemical and Solid-State Letters", "publication_date": "1999-11", "series_number": "11", "volume": "2", "issue": "11", "pages": "577-578" }, { "id": "authors:e66e2-eqy45", "collection": "authors", "collection_id": "e66e2-eqy45", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120110-132111493", "type": "article", "title": "Fabrication of nanometer size photoresist wire patterns with a silver nanocrystal shadowmask", "author": [ { "family_name": "Choi", "given_name": "S. H.", "clpid": "Choi-S-H" }, { "family_name": "Wang", "given_name": "K. L.", "clpid": "Wang-K-L" }, { "family_name": "Leung", "given_name": "M. S.", "clpid": "Leung-M-S" }, { "family_name": "Stupian", "given_name": "G. W.", "clpid": "Stupian-G-W" }, { "family_name": "Presser", "given_name": "N.", "clpid": "Presser-N" }, { "family_name": "Chung", "given_name": "S. W.", "clpid": "Shung-S-W" }, { "family_name": "Markovich", "given_name": "G.", "clpid": "Markovich-G" }, { "family_name": "Kim", "given_name": "S. H.", "clpid": "Kim-S-H" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "In this article, we present a new method for fabricating precisely defined nanometer scale photoresist wire patterns. The Langmuir technique was utilized to form high aspect ratio lamellae, or wire patterns, of Ag nanocrystals at the air/water interface, and these patterns were transferred onto resist-coated substrates as a Langmuir\u2013Schaeffer film and as a shadowmask. The wire patterns were transferred to the photoresist material by spatially selective electron beam exposure on the Ag nanocrystal wire shadowmask. Monte Carlo simulation was done to estimate the electron stopping power for the Ag nanocrystal shadowmask at low voltage.", "doi": "10.1116/1.581831", "issn": "0734-2101", "publisher": "American Vacuum Society", "publication": "Journal of Vacuum Science and Technology A", "publication_date": "1999-07", "series_number": "4", "volume": "17", "issue": "4", "pages": "1425-1427" }, { "id": "authors:vy8vx-rj127", "collection": "authors", "collection_id": "vy8vx-rj127", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:SEApre99", "type": "article", "title": "Spontaneous patterning of quantum dots at the air-water interface", "author": [ { "family_name": "Sear", "given_name": "Richard P.", "clpid": "Sear-R-P" }, { "family_name": "Chung", "given_name": "Sung-Wook", "clpid": "Chung-Sung-Wook" }, { "family_name": "Markovich", "given_name": "Gil", "clpid": "Markovich-G" }, { "family_name": "Gelbart", "given_name": "William M.", "clpid": "Gelbart-W-M" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Nanoparticles deposited at the air-water interface are observed to form circular domains at low density and stripes at higher density. We interpret these patterns as equilibrium phenomena produced by a competition between an attraction and a longer-ranged repulsion. Computer simulations of a generic pair potential with attractive and repulsive parts of this kind, reproduce both the circular and stripe patterns. Such patterns have a potential use in nanoelectronic applications.", "doi": "10.1103/PhysRevE.59.R6255", "issn": "1063-651X", "publisher": "American Physical Society", "publication": "Physical Review E", "publication_date": "1999-06", "series_number": "6", "volume": "59", "issue": "6", "pages": "R6255-R6258" }, { "id": "authors:gjrk8-t1r33", "collection": "authors", "collection_id": "gjrk8-t1r33", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-093117451", "type": "article", "title": "Positive and Negative Contrast Lithography on Silver Quantum Dot Monolayers", "author": [ { "family_name": "Henrichs", "given_name": "Sven E.", "clpid": "Henrichs-S-E" }, { "family_name": "Sample", "given_name": "Jennifer L.", "clpid": "Sample-J-L" }, { "family_name": "Shiang", "given_name": "Joe J.", "clpid": "Shiang-Joe-J" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Collier", "given_name": "Charles P.", "clpid": "Collier-C-P" }, { "family_name": "Saykally", "given_name": "Richard J.", "clpid": "Saykally-R-J" } ], "abstract": "Scanning nonlinear optical microscopy, at a resolution of \u223c2 \u03bcm, was utilized to examine monolayers of alkylthiol-passivated silver nanocrystals. Selected regions of the monolayers were irradiated with a pulse train of picosecond 1064 nm laser pulses, and then the second harmonic generation (SHG) response of those monolayers was recorded in a second scan. Two lithographic processesone leading to a negative contrast SHG image (observed for particles <4 nm diameter) and a second leading to a positive contrast SH G image (observed for larger particles)were found. These processes are explained within the context of literature models that account for particle size dependent energy partitioning.", "doi": "10.1021/jp990080x", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "1999-05-06", "series_number": "18", "volume": "103", "issue": "18", "pages": "3524-3528" }, { "id": "authors:3b61e-ys479", "collection": "authors", "collection_id": "3b61e-ys479", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-064905258", "type": "article", "title": "Nanoscale Materials", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Few terms in the chemical and physical sciences have seen more use (and abuse) in recent years than \"nanoscience\" or, even worse, \"nanotechnology\". Why all the interest and hype? Explaining the interest in this subject is relatively easy. The past 15 years or so have witnessed an explosion of relatively inexpensive analytical tools, such as scanning probe microscopies, for interrogating and manipulating materials on the nanometer length scale. At the same time, several previously unrelated fields have begun to focus on understanding and controlling physical and chemical phenomena on nanometer length scales. In electrical engineering, complimentary metal oxide semiconductor (CMOS) based transistors have been fabricated with gate widths of 50 nm. The same lithographic techniques that defined the features of that transistor have been utilized to attach two electrodes to a single molecule. In biology, experiments that probe the dynamics of single cells, single proteins, and single DNA strands have been carried out, and the operational mechanisms of certain biomolecular motors and gears have been elucidated. At the same time that scientists and engineers are planning to build terabit (1012 cm-2) memories, the sequencing of the human genome is nearing completion. In addition, nanoscale materials have truly come of age. Physical scientists have learned how to manipulate crystallization processes such that nanometer- or even angstrom-level control over size and shape is now possible for a wide variety of materials. Nanocrystals that are of the quality of high-grade electronic materials are now prepared by routine synthetic procedures, and single-walled carbon nanotubes have been demonstrated to be stronger fibers with better electronic properties than anything previously known.", "doi": "10.1021/ar990059e", "issn": "0001-4842", "publisher": "American Chemical Society", "publication": "Accounts of Chemical Research", "publication_date": "1999-05", "series_number": "5", "volume": "32", "issue": "5", "pages": "388-388" }, { "id": "authors:80j62-dnb98", "collection": "authors", "collection_id": "80j62-dnb98", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-080943418", "type": "article", "title": "Architectonic Quantum Dot Solids", "author": [ { "family_name": "Markovich", "given_name": "Gil", "clpid": "Markovich-G" }, { "family_name": "Collier", "given_name": "C. Patrick", "clpid": "Collier-C-P" }, { "family_name": "Henrichs", "given_name": "Sven E.", "clpid": "Henrichs-S-E" }, { "family_name": "Remacle", "given_name": "Fran\u00e7oise", "clpid": "Remacle-F" }, { "family_name": "Levine", "given_name": "Raphael D.", "clpid": "Levine-R-D" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Three things largely determine the electronic properties of a crystal:\u2009 the energy levels of the atoms or lattice sites, the coupling between adjacent sites, and the symmetry of the solid. Imagine being able to control each of these properties separately, and therefore being able to \"design\" a solid with a prescribed set of electronic properties. For an atomic solid, this would amount to being able to tune the electronegativity of an atom, to control the strength of the covalent interactions within the lattice, and to choose the crystal structure. While the chemistry of the periodic table does not permit such control, the chemistry of \"artificial atoms\",1 or quantum dots (QDs), does. In this Account, we will discuss one example of \"designing\" a unique electronic property into a QD solid. This property, which is the ability of the solid to reversibly pass through a metal\u2212insulator (MI) transition under ambient conditions, is something that has not been previously demonstrated for a more traditional solid. A two-dimensional (2D) hexagonal superlattice of organically passivated silver QDs was fabricated as a Langmuir monolayer. Selecting a particular size of QD controlled the (super)lattice site energies. The coupling between adjacent QDs was coarsely controlled by selection of the organic surface passivant, and precisely controlled by compressing the superlattice using the Langmuir technique. By using the title \"Architectonic2 Quantum Dot Solids\", we emphasize that many of the collective properties of the superlattice were rationally designed into the material.", "doi": "10.1021/ar980039x", "issn": "0001-4842", "publisher": "American Chemical Society", "publication": "Accounts of Chemical Research", "publication_date": "1999-05", "series_number": "5", "volume": "32", "issue": "5", "pages": "415-423" }, { "id": "authors:h10ak-e4m52", "collection": "authors", "collection_id": "h10ak-e4m52", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:MEDprb99", "type": "article", "title": "Rehybridization of electronic structure in compressed two-dimensional quantum dot superlattices", "author": [ { "family_name": "Medeiros-Ribeiro", "given_name": "G.", "clpid": "Medeiros-Ribeiro-G" }, { "family_name": "Ohlberg", "given_name": "D. A. A.", "clpid": "Ohlberg-D-A-A" }, { "family_name": "Williams", "given_name": "R. Stanley", "clpid": "Williams-R-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Two-dimensional superlattices of organically passivated 2.6-nm silver quantum dots were prepared as Langmuir monolayers and transferred to highly oriented pyrolytic graphite substrates. The structural and electronic properties of the films were probed with variable temperature scanning tunneling microscopy. Particles passivated with decanethiol (interparticle separation distance of \u223c1.1\u00b10.2\u2002nm) exhibited Coulomb blockade and staircase. For particles passivated with hexanethiol or pentanethiol (interparticle separation distance of \u223c0.5\u00b10.2\u2002nm), the single-electron charging was quenched, and the redistribution of the density of states revealed that strong quantum mechanical exchange, i.e., wave-function hybridization, existed among the particles in these films.", "doi": "10.1103/PhysRevB.59.1633", "issn": "0163-1829", "publisher": "American Physical Society", "publication": "Physical Review B", "publication_date": "1999-01-15", "series_number": "3", "volume": "59", "issue": "3", "pages": "1633-1636" }, { "id": "authors:2pge7-3xm19", "collection": "authors", "collection_id": "2pge7-3xm19", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:KIMapl99", "type": "article", "title": "Tunnel diodes fabricated from CdSe nanocrystal monolayers", "author": [ { "family_name": "Kim", "given_name": "S.-H.", "clpid": "Kim-S-H" }, { "family_name": "Markovich", "given_name": "G.", "clpid": "Markovich-G" }, { "family_name": "Rezvani", "given_name": "S.", "clpid": "Rezvani-S" }, { "family_name": "Choi", "given_name": "S. H.", "clpid": "Choi-S-H" }, { "family_name": "Wang", "given_name": "K. L.", "clpid": "Wang-K-L" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A parallel approach for fabricating nanocrystal-based semiconductor\u2013insulator\u2013metal tunnel diodes is presented. The devices consisted of a Au electrode, a monolayer of 38 \u00c5 CdSe nanocrystals, an insulating bilayer of eicosanoic acid (C19H39CO2H), and an Al electrode. Each device was approximately 100 \u00b5m^2. Conductance measurements at 77 K reveal strong diode behavior and evidence of Coulomb blockade and staircase structure. A single barrier model was found to reproduce the electronic characteristics of these devices.", "doi": "10.1063/1.123035", "issn": "0003-6951", "publisher": "American Institute of Physics", "publication": "Applied Physics Letters", "publication_date": "1999-01-11", "series_number": "2", "volume": "74", "issue": "2", "pages": "317-319" }, { "id": "authors:r7e7x-9f666", "collection": "authors", "collection_id": "r7e7x-9f666", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:VOSjap98", "type": "article", "title": "Combinatorial approaches toward patterning nanocrystals", "author": [ { "family_name": "Vossmeyer", "given_name": "T.", "clpid": "Vossmeyer-T" }, { "family_name": "Jia", "given_name": "S.", "clpid": "Jia-S" }, { "family_name": "Delonno", "given_name": "E.", "clpid": "Delonno-E" }, { "family_name": "Diehl", "given_name": "M. R.", "clpid": "Diehl-M-R" }, { "family_name": "Kim", "given_name": "S.-H.", "clpid": "Kim-S-H" }, { "family_name": "Peng", "given_name": "X.", "clpid": "Peng-X" }, { "family_name": "Alivisatos", "given_name": "A. P.", "orcid": "0000-0001-6895-9048", "clpid": "Alivisatos-A-P" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A scheme for generating complex, spatially separated patterns of multiple types of semiconducting and/or metallic nanocrystals is presented. The process is based on lithographic patterning of organic monolayers that contain a photolabile protection group and are covalently bound to SiO2 surfaces. The process results in spatially and chemically distinct interaction sites on a single substrate. Nanocrystal assembly occurs with a high selectivity on just one type of site. We report on the production of binary, tertiary, and quatemary patterns of nanocrystals. We highlight and discuss the differences between nanocrystal/substrate assembly and molecule/substrate assembly. Finally, we investigate the assembled structures using photoluminescence and absorption spectroscopy.", "doi": "10.1063/1.368542", "issn": "0021-8979", "publisher": "American Institute of Physics", "publication": "Journal of Applied Physics", "publication_date": "1998-10-01", "series_number": "7", "volume": "84", "issue": "7", "pages": "3664-3670" }, { "id": "authors:0a2w8-sgp89", "collection": "authors", "collection_id": "0a2w8-sgp89", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-144234145", "type": "article", "title": "Nanocrystal Superlattices", "author": [ { "family_name": "Collier", "given_name": "C. P.", "clpid": "Collier-C-P" }, { "family_name": "Vossmeyer", "given_name": "T.", "clpid": "Vossmeyer-T" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Ordered arrays, or superlattices, of metallic, insulating, or semiconducting quantum dots, represent an exciting new class of materials. These superlattices are often referred to as artificial solids, in which the nanocrystals take the place of atoms in traditional solids, and the packing arrangement of the nanocrystals determines the unit cell parameters of the superstructure. In this review, we discuss various approaches toward assembling nanocrystal superlattices and we discuss their physical properties.", "doi": "10.1146/annurev.physchem.49.1.371", "issn": "0066-426X", "publisher": "Annual Reviews", "publication": "Annual Review of Physical Chemistry", "publication_date": "1998-10", "volume": "49", "pages": "371-404" }, { "id": "authors:xz3ea-1f376", "collection": "authors", "collection_id": "xz3ea-1f376", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:MARprl98b", "type": "article", "title": "Reversible Metal-Insulator Transition in Ordered Metal Nanocrystal Monolayers Observed by Impedance Spectroscopy", "author": [ { "family_name": "Markovich", "given_name": "Gil", "clpid": "Markovich-G" }, { "family_name": "Collier", "given_name": "Charles P.", "clpid": "Collier-C-P" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Low frequency impedance spectroscopy was applied on a Langmuir monolayer of alkylthiol passivated 35 \u00c5 diameter silver quantum dots, as a function of interparticle separation distance. As interparticle spacing decreases below 30% of particle diameter, a reduction in interparticle charge tunneling time is observed. On further compression, the complex impedance of the films undergoes a transition from a parallel RC equivalent circuit to an inductive circuit. Optical reflectance changes in the films are consistent with the deduced metal-insulator transition.", "doi": "10.1103/PhysRevLett.80.3807", "issn": "0031-9007", "publisher": "American Physical Society", "publication": "Physical Review Letters", "publication_date": "1998-04-27", "series_number": "17", "volume": "80", "issue": "17", "pages": "3807-3810" }, { "id": "authors:7hbr3-cnz15", "collection": "authors", "collection_id": "7hbr3-cnz15", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:WALapl98", "type": "article", "title": "Solid-state metathesis reactions under pressure: A rapid route to crystalline gallium nitride", "author": [ { "family_name": "Wallace", "given_name": "Charles H.", "clpid": "Wallace-C-H" }, { "family_name": "Kim", "given_name": "Sang-Ho", "clpid": "Kim-Sang-Ho" }, { "family_name": "Rose", "given_name": "Garry A.", "clpid": "Rose-G-A" }, { "family_name": "Rao", "given_name": "Lin", "clpid": "Rao-Lin" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Nicol", "given_name": "Malcolm", "clpid": "Nicol-M" }, { "family_name": "Kaner", "given_name": "Richard B.", "clpid": "Kaner-R-B" } ], "abstract": "High pressure chemistry has traditionally involved applying pressure and increasing temperature until conditions become thermodynamically favorable for phase transitions or reactions to occur. Here, high pressure alone is used as a starting point for carrying out rapid, self-propagating metathesis reactions. By initiating chemical reactions under pressure, crystalline phases, such as gallium nitride, can be synthesized which are inaccessible when initiated from ambient conditions. The single-phase gallium nitride made by metathesis reactions under pressure displays significant photoluminescence intensity in the blue/ultraviolet region. The absence of size or surface-state effects in the photoluminescence spectra show that the crystallites are of micron dimensions. The narrow lines of the x-ray diffraction patterns and scanning electron microscopy confirm this conclusion. Brightly luminescent thin films can be readily grown using pulsed laser deposition.", "doi": "10.1063/1.120818", "issn": "0003-6951", "publisher": "American Institute of Physics", "publication": "Applied Physics Letters", "publication_date": "1998-02-02", "series_number": "5", "volume": "72", "issue": "5", "pages": "596-598" }, { "id": "authors:m0t5f-gz625", "collection": "authors", "collection_id": "m0t5f-gz625", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:MARapl97", "type": "article", "title": "Parallel fabrication and single-electron charging of devices based on ordered, two-dimensional phases of organically functionalized metal nanocrystals", "author": [ { "family_name": "Markovich", "given_name": "Gil", "clpid": "Markovich-G" }, { "family_name": "Leff", "given_name": "Daniel V.", "clpid": "Leff-D-V" }, { "family_name": "Chung", "given_name": "Sung-Wook", "clpid": "Chung-Sung-Wook" }, { "family_name": "Soyez", "given_name": "Hermes M.", "clpid": "Soyez-Hermes-M" }, { "family_name": "Dunn", "given_name": "Bruce", "orcid": "0000-0001-5669-4740", "clpid": "Dunn-Bruce-S" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "A parallel technique for fabricating single-electron, solid-state capacitance devices from ordered, two-dimensional closest-packed phases of organically functionalized metal nanocrystals is presented. The nanocrystal phases were prepared as Langmuir monolayers and subsequently transferred onto Al-electrode patterned glass substrates for device construction. Alternating current impedance measurements were carried out to probe the single-electron charging characteristics of the devices under both ambient and 77 K conditions. Evidence of a Coulomb blockade and step structure reminiscent of a Coulomb staircase is presented.", "doi": "10.1063/1.119105", "issn": "0003-6951", "publisher": "American Institute of Physics", "publication": "Applied Physics Letters", "publication_date": "1997-06-09", "series_number": "23", "volume": "70", "issue": "23", "pages": "3107-3109" }, { "id": "authors:caz74-bm055", "collection": "authors", "collection_id": "caz74-bm055", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120125-113307747", "type": "article", "title": "Theory of size-dependent resonance Raman intensities in InP nanocrystals", "author": [ { "family_name": "Shiang", "given_name": "J. J.", "clpid": "Shiang-J-J" }, { "family_name": "Wolters", "given_name": "R. H.", "clpid": "Wolters-R-H" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "The resonance Raman spectrum of InP nanocrystals is characterized by features ascribable to both longitudinal (LO) and transverse (TO) optical modes. The intensity ratio of these modes exhibits a strong size dependence. To calculate the size dependence of the LO and TO Raman cross sections, we combine existing models of Raman scattering, the size dependence of electronic and vibrational structure, and electron vibration coupling in solids. For nanocrystals with a radius >10 \u00c5, both the LO and TO coupling strengths increase with increasing radius. This, together with an experimentally observed increase in the electronic dephasing rate with decreasing size, allows us to account for the observed ratio of LO/TO Raman intensities.", "doi": "10.1063/1.474031", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1997-06-08", "series_number": "22", "volume": "106", "issue": "22", "pages": "8981-8994" }, { "id": "authors:cy33v-95y22", "collection": "authors", "collection_id": "cy33v-95y22", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-090743290", "type": "article", "title": "Pressure/Temperature Phase Diagrams and Superlattices of Organically Functionalized Metal Nanocrystal Monolayers: The Influence of Particle Size, Size Distribution, and Surface Passivant", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Knobler", "given_name": "Charles M.", "clpid": "Knobler-C-M" }, { "family_name": "Leff", "given_name": "Daniel V.", "clpid": "Leff-D-V" } ], "abstract": "The phase behavior of organically passivated 20\u221275 \u00c5 diameter Ag and Au nanocrystals is investigated by examining surface\u2212area isotherms of Langmuir monolayers and transmission electron micrographs of Langmuir\u2212Blodgett (LB) films. The effects of temperature, organic passivant chain length, and nanocrystal size and composition are studied. Three distinct types of phase behavior are observed and may be classified in terms of the extra (conical) volume (V_e) available to the alkyl capping group as it extends from a nearly spherical metal core. For V_e > 350 \u00c5^3, the phase diagram is dominated by extended, low-dimensional structures that, at high pressures, compress into a two-dimensional foamlike phase. This behavior is rationalized as originating from the interpenetration of the ligand shells of adjacent particles. For V_e < 350 \u00c5^3, dispersion attractions between the metal cores dominate particle condensation. For 350 \u00c5^3 > V_e > 150 \u00c5^3, the particles condense to form closest packed structures, which, for sufficiently narrow particle size distributions, are characterized by crystalline phases. For V_e \u2248 30 \u00c5^3, the particles irreversibly aggregate into structures similar to those expected from a diffusion-limited-aggregation (DLA) model. Optical properties of certain LB films of the closest packed phases are reported.", "doi": "10.1021/jp9611582", "issn": "1520-6106", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry B", "publication_date": "1997-01-09", "series_number": "2", "volume": "101", "issue": "2", "pages": "189-197" }, { "id": "authors:0g38d-tsh90", "collection": "authors", "collection_id": "0g38d-tsh90", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:KIMjcp96", "type": "article", "title": "Photophysics of size-selected InP nanocrystals: Exciton recombination kinetics", "author": [ { "family_name": "Kim", "given_name": "S.-H.", "clpid": "Kim-S-H" }, { "family_name": "Wolters", "given_name": "R. H.", "clpid": "Wolters-R-H" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report here on the size-dependent kinetics of exciton recombination in a III\u2013V quantum dot system, InP. The measurements reported include various frequency dependent quantum yields as a function of temperature, frequency dependent luminescence decay curves, and time-gated emission spectra. This data is fit to a three-state quantum model which has been previously utilized to explain photophysical phenomena in II\u2013VI quantum dots. The initial photoexcitation is assumed to place an electron in a (delocalized) bulk conduction band state. Activation barriers for trapping and detrapping of the electron to surface states, as well as activation barriers for surface-state radiationless relaxation processes are measured as a function of particle size. The energy barrier to detrapping is found to be the major factor limiting room temperature band-edge luminescence. This barrier increases with decreasing particle size. For 30 \u00c5 particles, this barrier is found to be greater than 6 kJ/mol\u2014a barrier which is more than an order of magnitude larger than that previously found for 32 \u00c5 CdS nanocrystals.", "doi": "10.1063/1.472703", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1996-11-08", "series_number": "18", "volume": "105", "issue": "18", "pages": "7957-7963" }, { "id": "authors:fs58m-28j72", "collection": "authors", "collection_id": "fs58m-28j72", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-112552752", "type": "article", "title": "Synthesis and Characterization of Hydrophobic, Organically-Soluble Gold Nanocrystals Functionalized with Primary Amines", "author": [ { "family_name": "Leff", "given_name": "Daniel V.", "clpid": "Leff-D-V" }, { "family_name": "Brandt", "given_name": "Lutz", "clpid": "Brandt-L" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "We report on the synthesis and characterization of 25\u221270 \u00c5 diameter amine-capped gold nanocrystals. In particular, we show how these particles can be prepared by a simple procedure and confirm the particle composition (including the identity of the amine surface passivant) through several materials characterization techniques that include infrared spectroscopy, nuclear magnetic resonance spectroscopy, ultraviolet\u2212visible spectroscopy, mass spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, X-ray diffraction analysis, differential scanning calorimetry, thermogravimetric analysis, and elemental analysis. All physical characterizations are consistent with a charge\u2212neutral amine/gold surface interaction described by a weak covalent bond. The stability of the particles appears to be largely kinetic, rather than thermodynamic, in nature. Comparison of these nanocrystals to amines adsorbed onto bulk Au surfaces indicates that the stability of the nanocrystal/amine system is a finite-size effect.", "doi": "10.1021/la960445u", "issn": "0743-7463", "publisher": "American Chemical Society", "publication": "Langmuir", "publication_date": "1996-10-02", "series_number": "20", "volume": "12", "issue": "20", "pages": "4723-4730" }, { "id": "authors:qana9-h1068", "collection": "authors", "collection_id": "qana9-h1068", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:OHAprl95", "type": "article", "title": "Crystallization of opals from polydisperse nanoparticles", "author": [ { "family_name": "Ohara", "given_name": "Pamela C.", "clpid": "Ohara-P-C" }, { "family_name": "Leff", "given_name": "Daniel V.", "clpid": "Leff-D-V" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Gelbart", "given_name": "William M.", "clpid": "Gelbart-W-M" } ], "abstract": "We report the reversible formation of crystals of nanoparticles (opals) from solutions of polydisperse gold nanocrystals. The structures are identified by transmission electron microscopy, and are characterized by hexagonal domains of large particles at the center, surrounded radially by successively smaller particles. Simulated annealing Monte Carlo calculations are used to demonstrate that these configurations correspond to minimization of the mesoscopic van der Waals energy of polydisperse particles, and the driving force for ordering is the size dependence of dispersional attractions.", "doi": "10.1103/PhysRevLett.75.3466", "issn": "0031-9007", "publisher": "American Physical Society", "publication": "Physical Review Letters", "publication_date": "1995-11-06", "series_number": "19", "volume": "75", "issue": "19", "pages": "3466-3469" }, { "id": "authors:m35zd-sc186", "collection": "authors", "collection_id": "m35zd-sc186", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-083634276", "type": "article", "title": "Thermodynamic Control of Gold Nanocrystal Size: Experiment and Theory", "author": [ { "family_name": "Leff", "given_name": "Daniel V.", "clpid": "Leff-D-V" }, { "family_name": "Ohara", "given_name": "Pamela C.", "clpid": "Ohara-P-C" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Gelbart", "given_name": "William M.", "clpid": "Gelbart-W-M" } ], "abstract": "We present an experimental demonstration and a corresponding statistical thermodynamic formulation of\nsurfactant-mediated size control of Au nanocrystals. In particular, we show how particle size-over a range of diameters from 15 to 200 A-can be sensitively controlled by simply varying the gold-to-thiol ratio. The agreement between theory and experiment is confirmed by X-ray line-broadening measurements of the nanocrystal products from a room-temperature synthesis in which the gold-thiol composition is systematically varied.", "doi": "10.1021/j100018a041", "issn": "0022-3654", "publisher": "American Chemical Society", "publication": "Journal of Physical Chemistry", "publication_date": "1995-05-04", "series_number": "18", "volume": "99", "issue": "18", "pages": "7036-7041" }, { "id": "authors:8bzgp-mam76", "collection": "authors", "collection_id": "8bzgp-mam76", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-110240062", "type": "article", "title": "Toward the detection of pure carbon clusters in the ISM", "author": [ { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Van Orden", "given_name": "A.", "clpid": "Van-Orden-A" }, { "family_name": "Hwang", "given_name": "H. J.", "clpid": "Hwang-H-J" }, { "family_name": "Kuo", "given_name": "E. W.", "clpid": "Kuo-E-W" }, { "family_name": "Tanaka", "given_name": "K.", "clpid": "Tanaka-K" }, { "family_name": "Saykally", "given_name": "R. J.", "clpid": "Saykally-R-J" } ], "abstract": "The questions of how and in what form that carbon is distributed in the Universe are critical ones for understanding the evolution of dust and planets, and for elucidating the origin of life on Earth and the prospects for discovering it elsewhere in the cosmos. While the abundant CI and CII atoms and CO molecule, which together account for a large fraction of the total carbon budget, have been thoroughly studied in many sources, and a large number of organic molecules have been detected in cold dust clouds, two potentially large reservoirs of carbon remain essentially unexplored. These are the PAH's and pure carbon clusters. The former are strongly suspected to be important components of interstellar dust, while the latter have essentially been ignored. Most probably, this simply reflects the fact that relatively little information exists regarding the structures, properties, and in particular, on the transition frequencies of pure carbon clusters that would permit their study by astrophysical methods. The work described below is designed to mitigate these deficiencies through the study of pure carbon clusters (C_n) in the size range n=3-20 by high resolution infrared (350-3000 cm(-1)) and far infrared (10-350 cm^(-1)) laser spectroscopy. The specific goal of this work is to provide a precise inventory of laboratory frequencies and physical properties for these carbon clusters, such that a serious effort can be made to detect them in cold interstellar sources by far-IR astronomy.", "doi": "10.1016/s0273-1177(99)80060-x", "issn": "0273-1177", "publisher": "Elsevier", "publication": "Advances in Space Research", "publication_date": "1995-03", "series_number": "3", "volume": "15", "issue": "3", "pages": "25-33" }, { "id": "authors:4q1b6-9ea06", "collection": "authors", "collection_id": "4q1b6-9ea06", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAjcp94", "type": "article", "title": "Germanium quantum dots: Optical properties and synthesis", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Shiang", "given_name": "J. J.", "clpid": "Shiang-J-J" }, { "family_name": "Alivisatos", "given_name": "A. P.", "orcid": "0000-0001-6895-9048", "clpid": "Alivisatos-A-P" } ], "abstract": "Three different size distributions of Ge quantum dots (>~200, 110, and 60 \u00c5) have been synthesized via the ultrasonic mediated reduction of mixtures of chlorogermanes and organochlorogermanes (or organochlorosilanes) by a colloidal sodium/potassium alloy in heptane, followed by annealing in a sealed pressure vessel at 270 \u00b0C. The quantum dots are characterized by transmission electron microscopy, x-ray powder diffraction, x-ray photoemission, infrared spectroscopy, and Raman spectroscopy. Colloidal suspensions of these quantum dots were prepared and their extinction spectra are measured with ultraviolet/visible (UV/Vis) and near infrared (IR) spectroscopy, in the regime from 0.6 to 5 eV. The optical spectra are correlated with a Mie theory extinction calculation utilizing bulk optical constants. This leads to an assignment of three optical features to the E(1), E(0'), and E(2) direct band gap transitions. The E(0') transitions exhibit a strong size dependence. The near IR spectra of the largest dots is dominated by E(0) direct gap absorptions. For the smallest dots the near IR spectrum is dominated by the Gamma25-->L indirect transitions.", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1994-07-15", "series_number": "2", "volume": "101", "issue": "2", "pages": "1607-1615" }, { "id": "authors:2bz7n-p7r35", "collection": "authors", "collection_id": "2bz7n-p7r35", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAapl94", "type": "article", "title": "Nanocrystal seeding: A low temperature route to polycrystalline Si films", "author": [ { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Gates", "given_name": "S. M.", "clpid": "Gates-S-M" }, { "family_name": "Chess", "given_name": "C. A.", "clpid": "Chess-C-A" } ], "abstract": "A novel method is presented for growth of polycrystalline silicon films on amorphous substrates at temperatures of 540\u2013575 \u00b0C. Grain nucleation and grain growth are performed in two steps, using Si nanocrystals as nuclei (\"seeds\"). The nanocrystal seeds are produced by excimer laser photolysis of disilane in a room temperature flow cell. Film (grain) growth occurs epitaxially on the seeds in a separate thermal chemical vapor deposition (CVD) step, with growth rates 10\u2013100 times higher than similar CVD growth rates on crystal Si. Grain size and CVD growth rates are dependent on seed coverage, for seed coverage <0.2 monolayers.", "doi": "10.1063/1.111200", "issn": "0003-6951", "publisher": "American Institute of Physics", "publication": "Applied Physics Letters", "publication_date": "1994-06-27", "series_number": "26", "volume": "64", "issue": "26", "pages": "3569-3571" }, { "id": "authors:v2bmh-fwn17", "collection": "authors", "collection_id": "v2bmh-fwn17", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:BATprl93", "type": "article", "title": "Electron energy loss spectroscopy of single silicon nanocrystals: The conduction band", "author": [ { "family_name": "Batson", "given_name": "P. E.", "clpid": "Batson-P-E" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Spatially resolved electron energy loss spectroscopy has been performed on single, H-terminated, Si nanocrystals in the size range 25\u2013500 \u00c5. The particles were prepared via the gas-phase photolysis of a dilute Si2H6/He mixture in a gas flow cell, and deposited on a holey carbon grid for analysis. Energy loss within a few eV of the core 2p ionization edge reveals information about the conduction band states at \u03941 and L1 in the Brillouin zone. The conduction band edge is observed to shift to higher energy as the inverse square of the particle radius. In addition, a strong increase in the oscillator strength for these transitions is observed for decreasing particle sizes below 60 \u00c5.", "doi": "10.1103/PhysRevLett.71.911", "issn": "0031-9007", "publisher": "American Physical Society", "publication": "Physical Review Letters", "publication_date": "1993-08-09", "series_number": "6", "volume": "71", "issue": "6", "pages": "911-914" }, { "id": "authors:e8ms5-9jp45", "collection": "authors", "collection_id": "e8ms5-9jp45", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-105329896", "type": "article", "title": "Infrared laser spectroscopy of jet-cooled carbon clusters: Structure of triplet C_6", "author": [ { "family_name": "Hwang", "given_name": "H. J.", "clpid": "Hwang-H-J" }, { "family_name": "Van Orden", "given_name": "A.", "clpid": "Van-Orden-A" }, { "family_name": "Tanaka", "given_name": "K.", "clpid": "Tanaka-K" }, { "family_name": "Kuo", "given_name": "E. W.", "clpid": "Kuo-E-W" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Saykally", "given_name": "R. J.", "clpid": "Saykally-R-J" } ], "abstract": "We report the first structural characterization of the triplet isomer of C_6. Forty-one rovibrational/fine structure transitions in the v_4(\u03c3_u) antisymmetric stretch fundamental of the C_6 cluster have been measured by diode laser absorption spectroscopy of a supersonic carbon cluster beam. The observed spectrum is characteristic of a centrosymmetric linear triplet state with cumulene-type bonding. The measured ground state rotational constant B_0 = 0\u00b7048 479 (10) cm^(-1) and the effective bond length r_(eff) = 1\u00b72868 (1) \u00c5 are in good agreement with ab initio predictions for the linear triplet (^3\u03a3^-_g) state of C_6.", "doi": "10.1080/00268979300101611", "issn": "0026-8976", "publisher": "Taylor & Francis", "publication": "Molecular Physics", "publication_date": "1993-07", "series_number": "4", "volume": "79", "issue": "4", "pages": "769-776" }, { "id": "authors:k6p30-vqp60", "collection": "authors", "collection_id": "k6p30-vqp60", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:GATapl93", "type": "article", "title": "Epitaxial Si films on Ge(100) grown via H/Cl exchange", "author": [ { "family_name": "Gates", "given_name": "S. M.", "clpid": "Gates-S-M" }, { "family_name": "Koleske", "given_name": "D. D.", "clpid": "Koleske-D-D" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Copel", "given_name": "M.", "clpid": "Copel-M" } ], "abstract": "Thin Si films have been grown isothermally on Ge(100) substrates using alternating exposures of Si2H6 and Si2Cl6, maintaining chlorine and hydrogen surface termination. At 465 \u00b0C, film growth rate is roughly 2 monolayer per cycle (one cycle equals 1 Si2H6 and 1 Si2Cl6 exposure). At 475 \u00b0C a uniform epitaxial film is obtained, while islanding is observed at higher T. This process is thermally activated and is not strictly self-limiting, but has certain desirable characteristics of atomic layer epitaxy growth.", "doi": "10.1063/1.108895", "issn": "0003-6951", "publisher": "American Institute of Physics", "publication": "Applied Physics Letters", "publication_date": "1993-02-01", "series_number": "5", "volume": "62", "issue": "5", "pages": "510-512" }, { "id": "authors:7xdxf-4hr31", "collection": "authors", "collection_id": "7xdxf-4hr31", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-094051482", "type": "book_section", "title": "Synthesis of C_(60) from Small Carbon Clusters", "book_title": "Fullerenes", "author": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "contributor": [ { "family_name": "Hammond", "given_name": "George S.", "clpid": "Hammond-G-S" }, { "family_name": "Kuck", "given_name": "Valerie J.", "clpid": "Kuck-V-J" } ], "abstract": "A model based on experiment and ab initio theory for the high-yield carbon-arc synthesis of C_(60) and other fullerenes is presented. Evidence that is given indicates that the synthesis must start with the smallest units of carbon (atoms, dimers, etc.). The model is then broken into four steps: (1) the growth of carbon chains up to length C_(10) from initial reactants present in the carbon vapor, (2) growth from chains into monocyclic rings (C_(10)\u2014C_(20)), (3) production and growth of three-dimensional reactive carbon networks (C_(21)\u2014C_x, x = 30\u201440), and (4) growth of small fullerene cages via a closed-shell mechanism that exclusively produces C_(60), C_(70), and the higher fullerenes as the stable products.", "doi": "10.1021/bk-1992-0481.ch001", "isbn": "9780841221826", "publisher": "American Chemical Society", "place_of_publication": "Washington, DC", "publication_date": "1992-01-06", "pages": "1-23" }, { "id": "authors:n04t6-5y473", "collection": "authors", "collection_id": "n04t6-5y473", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAjcp91b", "type": "article", "title": "The structure of the C4 cluster radical", "author": [ { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Saykally", "given_name": "R. J.", "clpid": "Saykally-R-J" } ], "abstract": "The first infrared spectrum of gas phase, jet-cooled C4 has been measured by high resolution diode laser absorption spectroscopy. Twelve rovibrational transitions are assigned to the nu3(sigmau) antisymmetric stretch of linear 3Sigma - g C4. No evidence is observed for the bent structure of triplet C4 recently observed in a matrix study by Cheung and Graham [J. Chem. Phys. 91, 6664 (1989)]. Indeed, the measured band origin (1548.9368(21) cm^\u20131) and effective ground state C\u2013C bond length [1.304 31(21)A] are consistent with several ab initio predictions of a rigid, linear, cumulenic structure for this cluster radical.", "doi": "10.1063/1.459797", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1991-02-15", "series_number": "4", "volume": "94", "issue": "4", "pages": "3271-3273" }, { "id": "authors:rmzed-8sp52", "collection": "authors", "collection_id": "rmzed-8sp52", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAjcp91a", "type": "article", "title": "Infrared laser absorption spectroscopy of the nu4(sigmau) fundamental and associated nu11(piu) hot band of C7: Evidence for alternating rigidity in linear carbon clusters", "author": [ { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Saykally", "given_name": "R. J.", "clpid": "Saykally-R-J" } ], "abstract": "The first characterization of the bending potential of the C7 cluster is reported via the observation of the v=11 and v=20 levels of the nu11(piu) bend as hot bands associated with the nu4(sigmau) antisymmetric stretch fundamental. The lower state hot band rotational constants are measured to be 1004.4(1.3) and 1123.6(9.0) MHz, constituting a 9.3% and 22% increase over the ground state rotational constant [918.89(41) MHz]. These large increases are strong evidence for extremely large amplitude, anharmonic bending modes in this cluster. In addition, quartic and sextic centrifugal distortion constants determined for the ground and nu4=1 states are found to be anomalously large and negative, evidencing strong perturbations between stretching and bending modes.", "doi": "10.1063/1.459945", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1991-02-01", "series_number": "3", "volume": "94", "issue": "3", "pages": "1724-1729" }, { "id": "authors:a91s1-zqt84", "collection": "authors", "collection_id": "a91s1-zqt84", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180302-084837776", "type": "article", "title": "Organic Chemistry of C_(60) (Buckminsterfullerene): Chromatography and Osmylation", "author": [ { "family_name": "Hawkins", "given_name": "Joel M.", "clpid": "Hawkins-J-M" }, { "family_name": "Lewis", "given_name": "Timothy A.", "clpid": "Lewis-T-A" }, { "family_name": "Loren", "given_name": "Stefan D.", "clpid": "Loren-S-D" }, { "family_name": "Meyer", "given_name": "Axel", "clpid": "Meyer-A" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Shibato", "given_name": "Yoko", "clpid": "Shibato-Yoko" }, { "family_name": "Saykally", "given_name": "Richard J.", "clpid": "Saykally-R-J" } ], "abstract": "Treatment of CG0 with osmium tetroxide and pyridine gives the osmate ester (2.1 adduct) establishing that oxygen functionality can be added to C_(60) without disrupting the carbon framework.", "doi": "10.1021/jo00313a009", "issn": "0022-3263", "publisher": "American Chemical Society", "publication": "Journal of Organic Chemistry", "publication_date": "1990-12-21", "series_number": "26", "volume": "55", "issue": "26", "pages": "6250-6252" }, { "id": "authors:w9gxc-pkd67", "collection": "authors", "collection_id": "w9gxc-pkd67", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAjcp90", "type": "article", "title": "The C9 cluster: Structure and infrared frequencies", "author": [ { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Saykally", "given_name": "R. J.", "clpid": "Saykally-R-J" } ], "abstract": "The high resolution infrared spectrum of the C9 cluster has been measured in direct absorption by infrared diode laser spectroscopy of a pulsed supersonic carbon cluster jet. Fifty-one rovibrational transitions have been assigned to the nu6 (sigmau ) antisymmetric stretch fundamental of the 1Sigma + 9 linear ground state of C9. The measured rotational constant [429.30(50) MHz] is in good agreement with ab initio calculations and indicates an effective bond length of 1.278 68(75) \u00c5, consistent with cumulenic bonding in this cluster. Several perturbations are observed in the upper state, and the upper- and lower-state centrifugal distortion constants are observed to be anomolously large, evidencing a high degree of Coriolis mixing of the normal modes.", "doi": "10.1063/1.459271", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1990-12-01", "series_number": "11", "volume": "93", "issue": "11", "pages": "8392-8394" }, { "id": "authors:x8k0z-fbw33", "collection": "authors", "collection_id": "x8k0z-fbw33", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAprb89", "type": "article", "title": "Size-dependent surface-plasmon resonances of bare silver particles", "author": [ { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "abstract": "Surface-plasmon resonances of silver microparticle aerosols have been measured as a function of average particle size. Resonance line shapes are modeled as a function of particle size and complex refractive index. The surface-plasmon frequency is found to exhibit a red shift from 3.8 to 3.4 eV as the average particle diameter is decreased by approximately a factor of 3 in contrast to the blue shift observed for matrix-isolated silver particles.", "doi": "10.1103/PhysRevB.40.9982", "issn": "0163-1829", "publisher": "American Physical Society", "publication": "Physical Review B", "publication_date": "1989-11-15", "series_number": "14", "volume": "40", "issue": "14", "pages": "9982-9985" }, { "id": "authors:mf2qf-v7649", "collection": "authors", "collection_id": "mf2qf-v7649", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:OBRjcp88", "type": "article", "title": "Photophysics of buckminsterfullerene and other carbon cluster ions", "author": [ { "family_name": "O'Brien", "given_name": "S. C.", "clpid": "O'Brien-S-C" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Curl", "given_name": "R. F.", "clpid": "Curl-R-F" }, { "family_name": "Smalley", "given_name": "R. E.", "clpid": "Smalley-R-E" } ], "abstract": "The laser-induced fragmentation behavior of positive carbon cluster ions has been investigated by tandem time-of-flight techniques for the jet-cooled clusters up to 80 atoms in size. Two distinct photophysical regimes were found. The first applies to clusters with 34 atoms or more, all of which dissociate to produce even numbered fragments. Large even clusters fragment by the loss of the high energy species C2, odd ones lose a C atom. The second regime applies to clusters composed of 31 or less atoms, all of which fragment by the loss of C3. These two regimes are sharply separated by C + 32 which fragments to produce small cluster ions in the 10\u201319 atom size range. Fragmentation of the large clusters occurs on a microsecond or faster time scale only at very high levels of excitation (>12.8 eV). These photophysical results are interpreted as consequences of the large even clusters having edgeless, spheroidal cage structures while the small ones have linear chain or ring structures.", "doi": "10.1063/1.454640", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1988-01-01", "series_number": "1", "volume": "88", "issue": "1", "pages": "220-230" }, { "id": "authors:rb80s-9c626", "collection": "authors", "collection_id": "rb80s-9c626", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAjcp87", "type": "article", "title": "The UV absorption spectrum of C60 (buckminsterfullerene): A narrow band at 3860 \u00c5", "author": [ { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Curl", "given_name": "R. F.", "clpid": "Curl-R-F" }, { "family_name": "Smalley", "given_name": "R. E.", "clpid": "Smalley-R-E" } ], "abstract": "The absorption spectrum of the special C60 cluster buckminsterfullerene has been studied in a supersonic beam by laser depletion of the cold van der Waals complexes of C60 with benzene and methylene chloride. Both complexes were found to display a single, isolated absorption band in the near ultraviolet superimposed on a structureless absorption continuum. For the methylene chloride complex this feature is centered at 3860 \u00c5, and is roughly 50 cm\u22121 wide. In the benzene van der Waals cluster, the corresponding feature is located at 3863 \u00c5, and has a similar width. This spectrum is tentatively assigned to the 0\u20130 band of the lowest 1T1u<--1Ag (LUMO+1<--HOMO) transition of a truncated icosahedral carbon shell structure, broadened by coupling to the underlying quasicontinuum of ground state vibrational levels.", "doi": "10.1063/1.452879", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1987-10-01", "series_number": "7", "volume": "87", "issue": "7", "pages": "4236-4238" }, { "id": "authors:km5p6-ze291", "collection": "authors", "collection_id": "km5p6-ze291", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:OBRjcp86", "type": "article", "title": "Supersonic cluster beams of III\u2013V semiconductors: GaxAsy", "author": [ { "family_name": "O'Brien", "given_name": "S. C.", "clpid": "O'Brien-S-C" }, { "family_name": "Liu", "given_name": "Y.", "clpid": "Liu-Y" }, { "family_name": "Zhang", "given_name": "Q.", "clpid": "Zhang-Q" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Tittel", "given_name": "F. K.", "clpid": "Tittel-F-K" }, { "family_name": "Curl", "given_name": "R. F.", "clpid": "Curl-R-F" }, { "family_name": "Smalley", "given_name": "R. E.", "clpid": "Smalley-R-E" } ], "abstract": "Supersonic beams of semiconductor clusters with the formula GaxAsy were generated by laser vaporization of a disc of pure GaAs mounted on the side of a pulsed supersonic nozzle. These cluster beams were characterized by laser photoionization with various fixed-frequency lasers followed by time-of-flight mass spectrometry. Mass analysis of the clusters with x+y>10 showed all clusters in the composition range from Gax+y through GaxAsy to Asx+y to be present in roughly the amount expected from a binomial distribution. In the smaller clusters strong variations were observed from this expected binomial distirbution as a result of kinetic effects in the cluster formation process. Photoionization with an ArF excimer laser at very low pulse energy revealed a pronounced even/odd alternation in the photoionization cross section of the GaxAsy clusters, depending only on the total number of atoms in the cluster. Clusters in the 5\u201321 atom range with an odd number of atoms were one-photon ionized by the 6.4 eV ArF excimer laser photons. This even/odd alternation in ionization properties of the clusters supports the view that the even clusters have fully paired singlet ground states with no dangling bonds. At higher ArF excimer laser fluences, the observed mass spectrum became increasingly affected by fragmentation. As is true with bulk GaAs surfaces, these GaxAsy clusters evaporate largely by the loss of arsenic (probably As2) when heated by the laser, leaving behind clusters which are richer in gallium.", "doi": "10.1063/1.450069", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1986-04-01", "series_number": "7", "volume": "84", "issue": "7", "pages": "4074-4079" }, { "id": "authors:0j1yf-0tk16", "collection": "authors", "collection_id": "0j1yf-0tk16", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEAjcp85", "type": "article", "title": "Semiconductor cluster beams: One and two color ionization studies of Six and Gex", "author": [ { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Liu", "given_name": "Yuan", "clpid": "Liu-Yuan" }, { "family_name": "O'Brien", "given_name": "S. C.", "clpid": "O'Brien-S-C" }, { "family_name": "Zhang", "given_name": "Qing-Ling", "clpid": "Zhang-Qing-Ling" }, { "family_name": "Curl", "given_name": "R. F.", "clpid": "Curl-R-F" }, { "family_name": "Tittel", "given_name": "F. K.", "clpid": "Tittel-F-K" }, { "family_name": "Smalley", "given_name": "R. E.", "clpid": "Smalley-R-E" } ], "abstract": "Supersonic beams of clusters of Si and Ge atoms have been produced by laser vaporization followed by supersonic expansion in a helium carrier. The cluster beams were characterized by F2(7.9 eV) and ArF(6.4 eV) excimer laser ionization accompanied by time-of-flight mass analysis. In addition, the feasibility of a resonant two-photon ionization (R2PI) spectroscopic study was explored by two-color experiments involving initial excitation with the second (2.36 eV) and third (3.54 eV) harmonics of the Nd:YAG followed by excimer laser ionization. All two-photon ionization processes were found to produce extensive fragmentation of the larger clusters. The observed fragmentation pattern for the silicon and germanium clusters were remarkably similar to each other, but drastically different from that seen for metal clusters in the same apparatus. Unlike metal clusters, which tend to lose one atom at a time, these semiconductor clusters appear to fragment by a fission process, the daughter ions falling almost exclusively in the size range from 6 to 11 atoms. Time delay studies in the two-color experiments established that clusters of both Si and Ge have excited electronic states with lifetimes of approximately 100 ns. This again is dramatically different from the behavior found with metal clusters, and indicates the feasibility of R2PI spectroscopy on these cold semiconductor particles. The existence of such long-lived excited states indicates that there is probably an energy gap between the band of electronic states being excited and the ground electronic state.", "doi": "10.1063/1.449673", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1985-12-01", "series_number": "11", "volume": "83", "issue": "11", "pages": "5520-5526" }, { "id": "authors:7vqj0-c8x06", "collection": "authors", "collection_id": "7vqj0-c8x06", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:MORjcp85", "type": "article", "title": "Surface reactions of metal clusters. II. Reactivity surveys with D2, N2, and CO", "author": [ { "family_name": "Morse", "given_name": "M. D.", "clpid": "Morse-M-D" }, { "family_name": "Gausic", "given_name": "M. E.", "clpid": "Gausic-M-E" }, { "family_name": "Heath", "given_name": "J. R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Smalley", "given_name": "R. E.", "clpid": "Smalley-R-E" } ], "abstract": "Reactions on the surface of a variety of transition metal clusters have been studied in the gas phase at near room temperature using a newly developed fast-flow reaction device. Initial examples of the use of this device are provided by survey studies of the reactivity of iron, cobalt, nickel, copper, and niobium clusters in contact with low concentrations of D2, N2 and CO. Dissociative chemisorption of D2 is found to occur with dramatic sensitivity to cluster size in the cases of iron, cobalt, and niobium clusters, the detailed pattern of reactivity differing markedly for each metal. The corresponding reaction is also observed with nickel clusters, but here the reactivity shows only a slow, steady increase with cluster size. Copper clusters are found to be completely unreactive to H2 chemisorption under these conditions. Molecular nitrogen is found to chemisorb readily to clusters of cobalt and niobium, with a reactivity pattern very similar to that observed with D2. Iron clusters are found to show slight reactivity with N2; only a small amount of chemisorption is observed on the most reactive clusters at high N2 concentration, but the pattern of this reactivity with cluster size is consistent with that observed in D2 chemisorption. In contrast to these highly structured reactivity patterns of D2 and N2, carbon monoxide is found to show only a slow, monotonic increase in reactivity with cluster size. It is suggested that these dramatic reactivity patterns for chemisorption on metal clusters provide stringent tests for future theories as to the nature of chemisorption on metal surfaces at a detailed, molecular level.", "doi": "10.1063/1.449321", "issn": "0021-9606", "publisher": "American Institute of Physics", "publication": "Journal of Chemical Physics", "publication_date": "1985-09-01", "series_number": "5", "volume": "83", "issue": "5", "pages": "2293-2304" } ]