@book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/101868, title ="Chemical probes for optical bio-imaging (Conference Presentation)", author = "Wei, Lu", number = "11256", pages = "Art. No. 112560E", month = "March", year = "2020", doi = "10.1117/12.2551679", isbn = "9781510632752", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200311-151708752", note = "© 2020 Society of Photo-Optical Instrumentation Engineers (SPIE).", revision_no = "5", abstract = "Innovations in novel probes have significantly push the development of new optical spectroscopy and microscopy methods for revealing new information in biological systems. In this talk, I will discuss our recent development by introducing chemical probes to stimulated Raman scattering (SRS) microscopy that could allow multi-functional imaging at sub-cellular level. Both physical and chemical principles underlying the investigation and design of new probes when coupled to the Raman imaging modalities will be presented, as well as our efforts in biomedical applications including cancer- and neuronal- metabolism.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/101862, title ="High-sensitivity stimulated Raman imaging with chemical tags (Conference Presentation)", author = "Wei, Lu", number = "11250", pages = "Art. No. 112500R", month = "March", year = "2020", doi = "10.1117/12.2548543", isbn = "9781510632639", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200311-151707376", note = "© 2020 Society of Photo-Optical Instrumentation Engineers (SPIE).", revision_no = "5", abstract = "Innovations in optical spectroscopy and microscopy have revolutionized our understanding in biological systems. In this talk, I will discuss our recent development by coupling stimulated Raman scattering (SRS) microscopy with chemical probes that could allow high-sensitivity bio-analysis with fast speed at the sub-cellular level. Both physical and chemical principles underlying the optical microscopy will be presented, as well as our efforts in biomedical applications including cancer- and neuronal- metabolism.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/101861, title ="Stimulated Raman imaging with chemical probes for subcellular bioanalysis (Conference Presentation)", author = "Wei, Lu and Miao, Kun", number = "11252", pages = "Art. No. 112521S", month = "March", year = "2020", doi = "10.1117/12.2546942", isbn = "9781510632677", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200311-151707274", note = "© 2020 Society of Photo-Optical Instrumentation Engineers (SPIE).", revision_no = "5", abstract = "Innovations in optical spectroscopy and microscopy have revolutionized our understanding in biological systems at sub-cellular levels. In this talk, I will discuss about our recent development by coupling stimulated Raman scattering (SRS) microscopy with chemical probes that could allow new subcellular bioanalysis in live cells. The introduced tags offer additional SRS contrast channel for quantification of biological contents that were previously difficult. Both physical and chemical principles underlying the optical microscopy will be presented, as well as our efforts in biomedical applications including cancer- and neuronal- metabolism.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/86921, title ="Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering microscopy", author = "Hu, Fanhao and Chen, Zhixing", number = "9723", pages = "Art. No. 97230B", month = "April", year = "2016", doi = "10.1117/12.2211787.4848770176001", isbn = "9781628419573", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180608-114633492", note = "© 2016 Society of Photo-Optical Instrumentation Engineers (SPIE). ", revision_no = "22", abstract = "Glucose is consumed as an energy source by virtually all living organisms, from bacteria to humans. Its uptake activity closely reflects the cellular metabolic status in various pathophysiological transformations, such as diabetes and cancer. Extensive efforts such as positron emission tomography, magnetic resonance imaging and fluorescence microscopy have been made to specifically image glucose uptake activity but all with technical limitations. Here, we report a new platform to visualize glucose uptake activity in live cells and tissues with subcellular resolution and minimal perturbation. A novel glucose analogue with a small alkyne tag (carbon-carbon triple bond) is developed to mimic natural glucose for cellular uptake, which can be imaged with high sensitivity and specificity by targeting the strong and characteristic alkyne vibration on stimulated Raman scattering (SRS) microscope to generate a quantitative three dimensional concentration map. Cancer cells with differing metabolic characteristics can be distinguished. Heterogeneous uptake patterns are observed in tumor xenograft tissues, neuronal culture and mouse brain tissues with clear cell-cell variations. Therefore, by offering the distinct advantage of optical resolution but without the undesirable influence of bulky fluorophores, our method of coupling SRS with alkyne labeled glucose will be an attractive tool to study energy demands of living systems at the single cell level.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/86922, title ="Optical Imaging of Vibrationally-Tagged Small molecules for Biomedicine", author = "Wei, Lu and Min, Wei", pages = "Art. No. BTh2D.2", month = "April", year = "2016", doi = "10.1364/BRAIN.2016.BTh2D.2", isbn = "978-1-943580-10-1", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180608-115332345", note = "© 2016 Optical Society of America.", revision_no = "10", abstract = "We report a novel imaging platform, by coupling stimulated Raman scattering microscopy with small vibrational tags (including isotopes and alkynes), to probe dynamics of small biomolecules in living organisms with superb sensitivity, specificity and biocompatibility.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/86928, title ="Super-nonlinear fluorescence microscopy for high-contrast deep tissue imaging", author = "Wei, Lu and Zhu, Xinxin", number = "8948", pages = "Art. No. 894825", month = "February", year = "2014", doi = "10.1117/12.2038753", isbn = "9780819498618", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180608-133651608", note = "© 2014 Society of Photo-Optical Instrumentation Engineers (SPIE).", revision_no = "11", abstract = "Two-photon excited fluorescence microscopy (TPFM) offers the highest penetration depth with subcellular resolution in light microscopy, due to its unique advantage of nonlinear excitation. However, a fundamental imaging-depth limit, accompanied by a vanishing signal-to-background contrast, still exists for TPFM when imaging deep into scattering samples. Formally, the focusing depth, at which the in-focus signal and the out-of-focus background are equal to each other, is defined as the fundamental imaging-depth limit. To go beyond this imaging-depth limit of TPFM, we report a new class of super-nonlinear fluorescence microscopy for high-contrast deep tissue imaging, including multiphoton activation and imaging (MPAI) harnessing novel photo-activatable fluorophores, stimulated emission reduced fluorescence (SERF) microscopy by adding a weak laser beam for stimulated emission, and two-photon induced focal saturation imaging with preferential depletion of ground-state fluorophores at focus. The resulting image contrasts all exhibit a higher-order (third- or fourth- order) nonlinear signal dependence on laser intensity than that in the standard TPFM. Both the physical principles and the imaging demonstrations will be provided for each super-nonlinear microscopy. In all these techniques, the created super-nonlinearity significantly enhances the imaging contrast and concurrently extends the imaging depth-limit of TPFM. Conceptually different from conventional multiphoton processes mediated by virtual states, our strategy constitutes a new class of fluorescence microscopy where high-order nonlinearity is mediated by real population transfer.", }