Volumetric functional imaging of transient cellular signaling and motion dynamics is often limited by hardware bandwidth and the scarcity of photons under short exposures. To overcome these challenges, we introduce squeezed light field microscopy (SLIM), a computational imaging approach that rapidly captures high-resolution three-dimensional light signals using only a single, low-format camera sensor. SLIM records over 1,000 volumes per second across a 550-µm diameter field of view and 300-µm depth, achieving 3.6-µm lateral and 6-µm axial resolution. Here we demonstrate its utility in blood cell velocimetry within the embryonic zebrafish brain and in freely moving tails undergoing high-frequency swings. Millisecond-scale temporal resolution further enables precise voltage imaging of neural membrane potentials in the leech ganglion and hippocampus of behaving mice. Together, these results establish SLIM as a versatile and robust tool for high-speed volumetric microscopy across diverse biological systems.
", "doi": "10.1038/s41592-025-02843-8", "issn": "1548-7091", "publisher": "Nature Publishing Group", "publication": "Nature Methods", "publication_date": "2025-10", "volume": "22", "pages": "2194\u20132204" }, { "id": "authors:bmska-qn168", "collection": "authors", "collection_id": "bmska-qn168", "cite_using_url": "https://authors.library.caltech.edu/records/bmska-qn168", "type": "article", "title": "A bioinspired microfluidic wearable sensor for multiday sweat sampling, transport, and metabolic analysis", "author": [ { "family_name": "Shin", "given_name": "Soyoung", "orcid": "0009-0002-3210-6427", "clpid": "Shin-Soyoung" }, { "family_name": "Liu", "given_name": "Ruixiao", "orcid": "0009-0007-4801-438X", "clpid": "Liu-Ruixiao" }, { "family_name": "Yang", "given_name": "Yiran", "orcid": "0000-0001-8770-8746", "clpid": "Yang-Yiran-Isabella" }, { "family_name": "Lasalde-Ram\u00edrez", "given_name": "Jos\u00e9 A.", "orcid": "0000-0003-2834-3120", "clpid": "Lasalde-Ramirez-Jose-A" }, { "family_name": "Kim", "given_name": "Gwangmook", "orcid": "0000-0002-7469-408X", "clpid": "Kim-Gwangmook" }, { "family_name": "Won", "given_name": "Chihyeong", "orcid": "0000-0003-2141-7983", "clpid": "Won-Chihyeong" }, { "family_name": "Min", "given_name": "Jihong", "orcid": "0000-0002-5788-1473", "clpid": "Min-Jihong" }, { "family_name": "Wang", "given_name": "Canran", "orcid": "0000-0003-3297-9041", "clpid": "Wang-Canran" }, { "family_name": "Fan", "given_name": "Kexin", "orcid": "0000-0003-3818-5891", "clpid": "Fan-Kexin" }, { "family_name": "Han", "given_name": "Hong", "orcid": "0000-0002-2852-8662", "clpid": "Han-Hong" }, { "family_name": "Uwakwe", "given_name": "Chibuike", "orcid": "0000-0002-5963-4943", "clpid": "Uwakwe-Chibuike" }, { "family_name": "Heng", "given_name": "Wenzheng", "orcid": "0009-0009-5278-0727", "clpid": "Heng-Wenzheng" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" }, { "family_name": "Li", "given_name": "Zhaoping", "orcid": "0000-0002-8662-4310" }, { "family_name": "FitzGerald", "given_name": "John D.", "orcid": "0000-0002-8419-7538" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "abstract": "Wearable sweat sensors enable noninvasive real-time biochemical monitoring, holding immense potential for personalized health care applications. However, achieving prolonged and reliable sweat sampling, along with stable biochemical analysis, remains challenging due to inconsistent secretion, rapid evaporation, and the reliance on external stimulation. Here, we present BMS3, a bioinspired microfluidic wearable sweat sensor system designed for multiday continuous metabolic monitoring. BMS3 integrates hierarchically graded microchannels and superhydrophobic-superhydrophilic Janus membranes, inspired by pitcher plant trichomes and lotus leaves to enable efficient low volume sweat collection, transport, and renewal. A miniaturized carbachol gel–based iontophoresis module autonomously induces localized sweat secretion. Furthermore, the microfluidic design sustains sweat sampling for over 2 days from a single iontophoresis session, eliminating the need for physical exertion. In vitro and in vivo studies in healthy participants and patients with gout demonstrate BMS3's capability for continuous metabolic monitoring. By simultaneously tracking uric acid, xanthine, and alcohol levels, it effectively differentiates normal and pathological states while delivering timely therapeutic feedback.
", "doi": "10.1126/sciadv.adw9024", "pmcid": "PMC12346344", "issn": "2375-2548", "publisher": "American Association for the Advancement of Science", "publication": "Science Advances", "publication_date": "2025-08-15", "series_number": "33", "volume": "11", "issue": "33", "pages": "eadw9024" }, { "id": "authors:eyfxv-sxt46", "collection": "authors", "collection_id": "eyfxv-sxt46", "cite_using_url": "https://authors.library.caltech.edu/records/eyfxv-sxt46", "type": "article", "title": "Refractive Index\u2010Corrected Light\u2010Sheet Microscopy for Macro\u2010View Cardiovascular Imaging", "author": [ { "family_name": "Zhu", "given_name": "Enbo", "orcid": "0000-0001-8600-8553" }, { "family_name": "Zhang", "given_name": "Yaran" }, { "family_name": "Zhao", "given_name": "Peng" }, { "family_name": "Cho", "given_name": "Jae Min" }, { "family_name": "Wang", "given_name": "Zhaoqiang" }, { "family_name": "Li", "given_name": "Yan\u2010Ruide" }, { "family_name": "Wang", "given_name": "Jing" }, { "family_name": "Margolis", "given_name": "Samuel" }, { "family_name": "Wang", "given_name": "Shaolei" }, { "family_name": "Yang", "given_name": "Lili" }, { "family_name": "Chu", "given_name": "Alison" }, { "family_name": "Zhang", "given_name": "Yuhua" }, { "family_name": "Gao", "given_name": "Liang" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Light\u2010sheet fluorescence microscopy (LSFM) enables rapid data acquisition with minimal phototoxicity, while optical clearing reduces light scattering by matching sample and imaging medium refractive indices (RIs). Emerging clearing methods extend from cells and organoids to entire organs and organisms, prompting macro\u2010view LSFM microscopes with macro\u2010objectives for low\u2010magnification imaging of larger specimens at adequate resolution. In cardiovascular studies, multiple organs often require imaging, yet clearing protocols optimized for different organs alter the sample RIs inconsistently. Standard\u2010size dipping objectives use correction collars for RI adaptation, but macro\u2010objectives, owing to their large size and long working distances, are typically dry lenses lacking built\u2010in RI correction. An RI\u2010corrected (rc)\u2010LSFM macro\u2010view system addresses this limitation by accommodating a broad range of RI values. By integrating axial sweeping, multi\u2010view imaging, and a closed quartz chamber, the rc\u2010LSFM improves field of view (up to ≈8.8 mm), isotropy, spatial resolution (≈3 µm), and operational safety. It effectively visualizes microvascular networks in zebrafish embryos and post\u2010natal mouse retina, traces the stem cell lineage of cardiomyocytes in mouse embryos, and reveals sympathetic nerve innervation in adult mouse aorta. The rc\u2010LSFM macro\u2010view system is compatible with various optical clearing protocols for multi\u2010scale imaging with high isotropy and spatial resolution.
", "doi": "10.1002/advs.202503684", "issn": "2198-3844", "publisher": "Wiley", "publication": "Advanced Science", "publication_date": "2025-07-13", "pages": "e03684" }, { "id": "authors:hy9gh-2je62", "collection": "authors", "collection_id": "hy9gh-2je62", "cite_using_url": "https://authors.library.caltech.edu/records/hy9gh-2je62", "type": "article", "title": "Boosting hydrogel conductivity via water-dispersible conducting polymers for injectable bioelectronics", "author": [ { "family_name": "Montazerian", "given_name": "Hossein", "orcid": "0000-0001-6972-2667" }, { "family_name": "Davoodi", "given_name": "Elham", "orcid": "0000-0001-8578-9431", "clpid": "Davoodi-Elham" }, { "family_name": "Wang", "given_name": "Canran", "orcid": "0000-0003-3297-9041", "clpid": "Wang-Canran" }, { "family_name": "Lorestani", "given_name": "Farnaz" }, { "family_name": "Li", "given_name": "Jiahong", "clpid": "Li-Jiahong" }, { "family_name": "Haghniaz", "given_name": "Reihaneh" }, { "family_name": "Sampath", "given_name": "Rohan R.", "orcid": "0009-0009-2419-0842" }, { "family_name": "Mohaghegh", "given_name": "Neda" }, { "family_name": "Khosravi", "given_name": "Safoora" }, { "family_name": "Zehtabi", "given_name": "Fatemeh" }, { "family_name": "Zhao", "given_name": "Yichao" }, { "family_name": "Hosseinzadeh", "given_name": "Negar" }, { "family_name": "Liu", "given_name": "Tianhan", "orcid": "0000-0003-3934-0785" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" }, { "family_name": "Najafabadi", "given_name": "Alireza Hassani", "orcid": "0000-0002-8215-4374" }, { "family_name": "Langer", "given_name": "Robert", "orcid": "0000-0003-4255-0492" }, { "family_name": "Anderson", "given_name": "Daniel G.", "orcid": "0000-0001-5629-4798" }, { "family_name": "Weiss", "given_name": "Paul S." }, { "family_name": "Khademhosseini", "given_name": "Ali", "orcid": "0000-0002-2692-1524" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "abstract": "Bioelectronic devices hold transformative potential for healthcare diagnostics and therapeutics. Yet, traditional electronic implants often require invasive surgeries and are mechanically incompatible with biological tissues. Injectable hydrogel bioelectronics offer a minimally invasive alternative that interfaces with soft tissue seamlessly. A major challenge is the low conductivity of bioelectronic systems, stemming from poor dispersibility of conductive additives in hydrogel mixtures. We address this issue by engineering doping conditions with hydrophilic biomacromolecules, enhancing the dispersibility of conductive polymers in aqueous systems. This approach achieves a 5-fold increase in dispersibility and a 20-fold boost in conductivity compared to conventional methods. The resulting conductive polymers are molecularly and in vivo degradable, making them suitable for transient bioelectronics applications. These additives are compatible with various hydrogel systems, such as alginate, forming ionically cross-linkable conductive inks for 3D-printed wearable electronics toward high-performance physiological monitoring. Furthermore, integrating conductive fillers with gelatin-based bioadhesive hydrogels substantially enhances conductivity for injectable sealants, achieving 250% greater sensitivity in pH sensing for chronic wound monitoring. Our findings indicate that hydrophilic dopants effectively tailor conducting polymers for hydrogel fillers, enhancing their biodegradability and expanding applications in transient implantable biomonitoring.
", "doi": "10.1038/s41467-025-59045-1", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2025-04-22", "series_number": "1", "volume": "16", "issue": "1", "pages": "3755" }, { "id": "authors:knteb-fv524", "collection": "authors", "collection_id": "knteb-fv524", "cite_using_url": "https://authors.library.caltech.edu/records/knteb-fv524", "type": "article", "title": "A physicochemical-sensing electronic skin for stress response monitoring", "author": [ { "family_name": "Xu", "given_name": "Changhao", "orcid": "0000-0002-6817-3341", "clpid": "Xu-Changhao" }, { "family_name": "Song", "given_name": "Yu", "orcid": "0000-0002-4185-2256", "clpid": "Song-Yu" }, { "family_name": "Sempionatto", "given_name": "Juliane R.", "orcid": "0000-0003-2431-9019", "clpid": "Sempionatto-Juliane-R" }, { "family_name": "Solomon", "given_name": "Samuel A.", "clpid": "Solomon-Samuel-A" }, { "family_name": "Yu", "given_name": "You", "orcid": "0000-0001-7059-7023", "clpid": "Yu-You" }, { "family_name": "Nyein", "given_name": "Hnin Y. Y.", "orcid": "0000-0002-5692-6182", "clpid": "Nyein-Hnin-Y-Y" }, { "family_name": "Tay", "given_name": "Roland Yingjie", "orcid": "0000-0002-3341-0984", "clpid": "Tay-Roland-Yingjie" }, { "family_name": "Li", "given_name": "Jiahong", "clpid": "Li-Jiahong" }, { "family_name": "Heng", "given_name": "Wenzheng", "clpid": "Heng-Wenzheng" }, { "family_name": "Min", "given_name": "Jihong", "orcid": "0000-0002-5788-1473", "clpid": "Min-Jihong" }, { "family_name": "Lao", "given_name": "Alison", "orcid": "0000-0003-2634-4920", "clpid": "Lao-Alison" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" }, { "family_name": "Sumner", "given_name": "Jennifer A.", "orcid": "0000-0002-0217-7171", "clpid": "Sumner-Jennifer-A" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "abstract": "Approaches to quantify stress responses typically rely on subjective surveys and questionnaires. Wearable sensors can potentially be used to continuously monitor stress-relevant biomarkers. However, the biological stress response is spread across the nervous, endocrine and immune systems, and the capabilities of current sensors are not sufficient for condition-specific stress response evaluation. Here we report an electronic skin for stress response assessment that non-invasively monitors three vital signs (pulse waveform, galvanic skin response and skin temperature) and six molecular biomarkers in human sweat (glucose, lactate, uric acid, sodium ions, potassium ions and ammonium). We develop a general approach to prepare electrochemical sensors that relies on analogous composite materials for stabilizing and conserving sensor interfaces. The resulting sensors offer long-term sweat biomarker analysis of more than 100 h with high stability. We show that the electronic skin can provide continuous multimodal physicochemical monitoring over a 24-hour period and during different daily activities. With the help of a machine learning pipeline, we also show that the platform can differentiate three stressors with an accuracy of 98.0% and quantify psychological stress responses with a confidence level of 98.7%.
\nThe characterization of atherosclerotic plaques to predict their vulnerability to rupture remains a diagnostic challenge. Despite existing imaging modalities, none have proven their abilities to identify metabolically active oxidized low-density lipoprotein (oxLDL), a marker of plaque vulnerability. To this end, we developed a machine learning-directed electrochemical impedance spectroscopy (EIS) platform to analyze oxLDL-rich plaques, with immunohistology serving as the ground truth. We fabricated the EIS sensor by affixing a six-point microelectrode configuration onto a silicone balloon catheter and electroplating the surface with platinum black (PtB) to improve the charge transfer efficiency at the electrochemical interface. To demonstrate clinical translation, we deployed the EIS sensor to the coronary arteries of an explanted human heart from a patient undergoing heart transplant and interrogated the atherosclerotic lesions to reconstruct the 3D EIS profiles of oxLDL-rich atherosclerotic plaques in both right coronary and left descending coronary arteries. To establish effective generalization of our methods, we repeated the reconstruction and training process on the common carotid arteries of an unembalmed human cadaver specimen. Our findings indicated that our DenseNet model achieves the most reliable predictions for metabolically vulnerable plaque, yielding an accuracy of 92.59% after 100 epochs of training.
", "doi": "10.1002/btm2.10616", "issn": "2380-6761", "publisher": "Wiley", "publication": "Bioengineering & Translational Medicine", "publication_date": "2024-01", "series_number": "1", "volume": "9", "issue": "1", "pages": "e10616" }, { "id": "authors:1swh9-m9e66", "collection": "authors", "collection_id": "1swh9-m9e66", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230314-845495900.37", "type": "article", "title": "Non-invasive photoacoustic computed tomography of rat heart anatomy and function", "author": [ { "family_name": "Lin", "given_name": "Li", "orcid": "0000-0002-0517-8436", "clpid": "Lin-Li" }, { "family_name": "Tong", "given_name": "Xin", "orcid": "0000-0003-2002-5638", "clpid": "Tong-Xin" }, { "family_name": "Cavallero", "given_name": "Susana", "orcid": "0000-0001-5402-8840", "clpid": "Cavallero-Susana" }, { "family_name": "Zhang", "given_name": "Yide", "orcid": "0000-0002-9463-3970", "clpid": "Zhang-Yide" }, { "family_name": "Na", "given_name": "Shuai", "orcid": "0000-0003-2083-0047", "clpid": "Na-Shuai" }, { "family_name": "Cao", "given_name": "Rui", "orcid": "0000-0003-4444-7528", "clpid": "Cao-Rui" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" }, { "family_name": "Wang", "given_name": "Lihong V.", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong-V" } ], "abstract": "Complementary to mainstream cardiac imaging modalities for preclinical research, photoacoustic computed tomography (PACT) can provide functional optical contrast with high imaging speed and resolution. However, PACT has not been demonstrated to reveal the dynamics of whole cardiac anatomy or vascular system without surgical procedure (thoracotomy) for tissue penetration. Here, we achieved non-invasive imaging of rat hearts using the recently developed three-dimensional PACT (3D-PACT) platform, demonstrating the regulated illumination and detection schemes to reduce the effects of optical attenuation and acoustic distortion through the chest wall; thereby, enabling unimpeded visualization of the cardiac anatomy and intracardiac hemodynamics following rapidly scanning the heart within 10\u2009s. We further applied 3D-PACT to reveal distinct cardiac structural and functional changes among the healthy, hypertensive, and obese rats, with optical contrast to uncover differences in cardiac chamber size, wall thickness, and hemodynamics. Accordingly, 3D-PACT provides high imaging speed and nonionizing penetration to capture the whole heart for diagnosing the animal models, holding promises for clinical translation to cardiac imaging of human neonates.", "doi": "10.1038/s41377-022-01053-7", "pmcid": "PMC9807634", "issn": "2047-7538", "publisher": "Nature Publishing Group", "publication": "Light: Science & Applications", "publication_date": "2023-01-03", "volume": "12", "pages": "Art. No. 12" }, { "id": "authors:6e5ws-37180", "collection": "authors", "collection_id": "6e5ws-37180", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220815-112698000", "type": "article", "title": "A wearable electrochemical biosensor for the monitoring of metabolites and nutrients", "author": [ { "family_name": "Wang", "given_name": "Minqiang", "orcid": "0000-0002-7775-8341", "clpid": "Wang-Minqiang" }, { "family_name": "Yang", "given_name": "Yiran", "orcid": "0000-0001-8770-8746", "clpid": "Yang-Yiran" }, { "family_name": "Min", "given_name": "Jihong", "orcid": "0000-0002-5788-1473", "clpid": "Min-Jihong" }, { "family_name": "Song", "given_name": "Yu", "orcid": "0000-0002-4185-2256", "clpid": "Song-Yu-Med-Eng" }, { "family_name": "Tu", "given_name": "Jiaobing", "orcid": "0000-0002-7653-6640", "clpid": "Tu-Jiaobing" }, { "family_name": "Mukasa", "given_name": "Daniel", "orcid": "0000-0001-8379-3648", "clpid": "Mukasa-Daniel" }, { "family_name": "Ye", "given_name": "Cui", "orcid": "0000-0001-7689-6825", "clpid": "Ye-Cui" }, { "family_name": "Xu", "given_name": "Changhao", "orcid": "0000-0002-6817-3341", "clpid": "Xu-Changhao" }, { "family_name": "Heflin", "given_name": "Nicole", "clpid": "Heflin-Nicole" }, { "family_name": "McCune", "given_name": "Jeannine S.", "orcid": "0000-0002-0795-497X", "clpid": "McCune-Jeannine-S" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" }, { "family_name": "Li", "given_name": "Zhaoping", "clpid": "Li-Zhaoping" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "abstract": "Wearable non-invasive biosensors for the continuous monitoring of metabolites in sweat can detect a few analytes at sufficiently high concentrations, typically during vigorous exercise so as to generate sufficient quantity of the biofluid. Here we report the design and performance of a wearable electrochemical biosensor for the continuous analysis, in sweat during physical exercise and at rest, of trace levels of multiple metabolites and nutrients, including all essential amino acids and vitamins. The biosensor consists of graphene electrodes that can be repeatedly regenerated in situ, functionalized with metabolite-specific antibody-like molecularly imprinted polymers and redox-active reporter nanoparticles, and integrated with modules for iontophoresis-based sweat induction, microfluidic sweat sampling, signal processing and calibration, and wireless communication. In volunteers, the biosensor enabled the real-time monitoring of the intake of amino acids and their levels during physical exercise, as well as the assessment of the risk of metabolic syndrome (by correlating amino acid levels in serum and sweat). The monitoring of metabolites for the early identification of abnormal health conditions could facilitate applications in precision nutrition.", "doi": "10.1038/s41551-022-00916-z", "pmcid": "PMC10432133", "issn": "2157-846X", "publisher": "Nature Publishing Group", "publication": "Nature Biomedical Engineering", "publication_date": "2022-11", "series_number": "11", "volume": "6", "issue": "11", "pages": "1225-1235" }, { "id": "authors:nf9sb-7xa18", "collection": "authors", "collection_id": "nf9sb-7xa18", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220810-254276000", "type": "article", "title": "Engineering viral genomics and nano-liposomes in microfluidic platforms for patient-specific analysis of SARS-CoV-2 variants", "author": [ { "family_name": "Satta", "given_name": "Sandro", "clpid": "Satta-Sandro" }, { "family_name": "Shahabipour", "given_name": "Fahimeh", "clpid": "Shahabipour-Fahimeh" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Lentz", "given_name": "Steven R.", "clpid": "Lentz-Steven-R" }, { "family_name": "Perlman", "given_name": "Stanley", "clpid": "Perlman-Stanley" }, { "family_name": "Ashammakhi", "given_name": "Nureddin", "clpid": "Ashammakhi-Nureddin" }, { "family_name": "Hsiai", "given_name": "Tzung", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuing to spread globally, contributing to the persistence of the COVID-19 pandemic. Increasing resources have been focused on developing vaccines and therapeutics that target the Spike glycoprotein of SARS-CoV-2. Recent advances in microfluidics have the potential to recapitulate viral infection in the organ-specific platforms, known as organ-on-a-chip (OoC), in which binding of SARS-CoV-2 Spike protein to the angiotensin-converting enzyme 2 (ACE2) of the host cells occurs. As the COVID-19 pandemic lingers, there remains an unmet need to screen emerging mutations, to predict viral transmissibility and pathogenicity, and to assess the strength of neutralizing antibodies following vaccination or reinfection. Conventional detection of SARS-CoV-2 variants relies on two-dimensional (2-D) cell culture methods, whereas simulating the micro-environment requires three-dimensional (3-D) systems. To this end, analyzing SARS-CoV-2-mediated pathogenicity via microfluidic platforms minimizes the experimental cost, duration, and optimization needed for animal studies, and obviates the ethical concerns associated with the use of primates. In this context, this review highlights the state-of-the-art strategy to engineer the nano-liposomes that can be conjugated with SARS-CoV-2 Spike mutations or genomic sequences in the microfluidic platforms; thereby, allowing for screening the rising SARS-CoV-2 variants and predicting COVID-19-associated coagulation. Furthermore, introducing viral genomics to the patient-specific blood accelerates the discovery of therapeutic targets in the face of evolving viral variants, including B1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), c.37 (Lambda), and B.1.1.529 (Omicron). Thus, engineering nano-liposomes to encapsulate SARS-CoV-2 viral genomic sequences enables rapid detection of SARS-CoV-2 variants in the long COVID-19 era.", "doi": "10.7150/thno.72339", "pmcid": "PMC9254234", "issn": "1838-7640", "publisher": "Ivyspring International Publisher", "publication": "Theranostics", "publication_date": "2022-10", "series_number": "10", "volume": "12", "issue": "10", "pages": "4779-4790" }, { "id": "authors:8gchc-jax79", "collection": "authors", "collection_id": "8gchc-jax79", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211202-191325598", "type": "article", "title": "3-Dimensional electrical impedance spectroscopy for in situ endoluminal mapping of metabolically active plaques", "author": [ { "family_name": "Abiri", "given_name": "Parinaz", "orcid": "0000-0002-0520-6863", "clpid": "Abiri-Parinaz" }, { "family_name": "Luo", "given_name": "Yuan", "clpid": "Luo-Yuan" }, { "family_name": "Huang", "given_name": "Zi-Yu", "clpid": "Huang-Zi-Yu" }, { "family_name": "Cui", "given_name": "Qingyu", "clpid": "Cui-Qingyu" }, { "family_name": "Duarte-Vogel", "given_name": "Sandra", "clpid": "Duarte-Vogel-Sandra" }, { "family_name": "Roustaei", "given_name": "Mehrdad", "clpid": "Roustaei-Mehrdad" }, { "family_name": "Chang", "given_name": "Chih-Chiang", "clpid": "Chang-Chih-Chiang" }, { "family_name": "Xiao", "given_name": "Xiao", "clpid": "Xiao-Xiao" }, { "family_name": "Packard", "given_name": "Rene", "orcid": "0000-0002-8520-5843", "clpid": "Packard-Ren\u00e9-Rupen-Sevag" }, { "family_name": "Cavallero", "given_name": "Susana", "orcid": "0000-0001-5402-8840", "clpid": "Cavallero-Susana" }, { "family_name": "Ebrahimi", "given_name": "Ramin", "clpid": "Ebrahimi-Ramin" }, { "family_name": "Benharash", "given_name": "Peyman", "clpid": "Benharash-Peynam" }, { "family_name": "Chen", "given_name": "Jun", "clpid": "Chen-Jun" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Electrical impedance spectroscopy (EIS) has been recognized to characterize oxidized low-density lipoprotein (oxLDL) in the metabolically active plaque. However, intravascular deployment of 3-D EIS-derived electrical impedance tomography (EIT) for endoluminal mapping of oxLDL-laden arterial walls remains an unmet clinical challenge. To this end, we designed the 6-point microelectrode arrays that were circumferentially configurated onto the balloon catheter for 15 intravascular EIS permutations. In parallel, we created the metabolically active plaques by performing partial ligation of right carotid artery in Yorkshire mini-pigs (n = 6 males), followed by demonstrating the plaque progression at baseline, 8 weeks, and 16 weeks of high-fat diet via computed tomography (CT) angiogram. Next, we deployed the 3-D EIS sensors to the right and left carotid arteries, and we demonstrated 3-D EIS mapping of metabolically active endolumen in the right but not left carotid arteries as evidenced by the positive E06 immunostaining for oxLDL-laden regions. By considering electrical conductivity (\u03c3) and permittivity (\u03b5) properties of collagen, lipid, and smooth muscle presence in the arterial wall, we further validated the 3-D EIS-derived EIT by reconstructing the histology of right and left carotid arteries for the finite element modeling of the oxLDL-laden endolumen, and we accurately predicted 3-D EIS mapping. Thus, we establish the capability of 3-D EIS-derived EIT to detect oxLDL-laden arterial walls with translational implication to predict metabolically active plaques prone to acute coronary syndromes or stroke.", "doi": "10.1016/j.snb.2021.131152", "issn": "0925-4005", "publisher": "Elsevier", "publication": "Sensors and Actuators B: Chemical", "publication_date": "2022-03-01", "volume": "354", "pages": "Art. No. 131152" }, { "id": "authors:gdjy5-n5p79", "collection": "authors", "collection_id": "gdjy5-n5p79", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220204-680191000", "type": "article", "title": "An Ex Vivo Study of Outward Electrical Impedance Tomography (OEIT) for Intravascular Imaging", "author": [ { "family_name": "Luo", "given_name": "Yuan", "orcid": "0000-0003-3153-7495", "clpid": "Luo-Yuan" }, { "family_name": "Huang", "given_name": "Dong", "clpid": "Huang-Dong" }, { "family_name": "Huang", "given_name": "Zi-Yu", "clpid": "Huang-Zi-Yu" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "Objective : Atherosclerosis is a chronic immuno-inflammatory condition emerging in arteries and considered the cause of a myriad of cardiovascular diseases. Atherosclerotic lesion characterization through invasive imaging modalities is essential in disease evaluation and determining intervention strategy. Recently, electrical properties of the lesions have been utilized in assessing its vulnerability mainly owing to its capability to differentiate lipid content existing in the lesion, albeit with limited detection resolution. Electrical impedance tomography is the natural extension of conventional spectrometric measurement by incorporating larger number of interrogating electrodes and advanced algorithm to achieve imaging of target objects and thus provides significantly richer information. It is within this context that we develop Outward Electrical Impedance Tomography (OEIT), aimed at intravascular imaging for atherosclerotic lesion characterization. \n\nMethods : We utilized flexible electronics to establish the 32-electrode OEIT device with outward facing configuration suitable for imaging of vessels. We conducted comprehensive studies through simulation model and ex vivo setup to demonstrate the functionality of OEIT. \n\nResults : Quantitative characterization for OEIT regarding its proximity sensing and conductivity differentiation was achieved using well-controlled experimental conditions. Imaging capability for OEIT was further verified with phantom setup using porcine aorta to emulate in vivo environment. \n\nConclusion : We have successfully demonstrated a novel tool for intravascular imaging, OEIT, with unique advantages for atherosclerosis detection. \n\nSignificance : This study demonstrates for the first time a novel electrical tomography-based platform for intravascular imaging, and we believe it paves the way for further adaptation of OEIT for intravascular detection in more translational settings and offers great potential as an alternative imaging tool for medical diagnosis.", "doi": "10.1109/tbme.2021.3104300", "pmcid": "PMC8837386", "issn": "0018-9294", "publisher": "IEEE", "publication": "IEEE Transactions on Biomedical Engineering", "publication_date": "2022-02", "series_number": "2", "volume": "69", "issue": "2", "pages": "734-745" }, { "id": "authors:t148b-pbx19", "collection": "authors", "collection_id": "t148b-pbx19", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201222-143554115", "type": "article", "title": "Electrical impedance tomography for non-invasive identification of fatty liver infiltrate in overweight individuals", "author": [ { "family_name": "Chang", "given_name": "Chih-Chiang", "clpid": "Chang-Chih-Chiang" }, { "family_name": "Huang", "given_name": "Zi-Yu", "clpid": "Huang-Zi-Yu" }, { "family_name": "Shih", "given_name": "Shu-Fu", "clpid": "Shih-Shu-Fu" }, { "family_name": "Luo", "given_name": "Yuan", "clpid": "Luo-Yuan" }, { "family_name": "Ko", "given_name": "Arthur", "orcid": "0000-0002-1523-7225", "clpid": "Ko-Arthur" }, { "family_name": "Cui", "given_name": "Qingyu", "clpid": "Cui-Qingyu" }, { "family_name": "Sumner", "given_name": "Jennifer", "orcid": "0000-0002-0217-7171", "clpid": "Sumner-Jennifer" }, { "family_name": "Cavallero", "given_name": "Susana", "orcid": "0000-0001-5402-8840", "clpid": "Cavallero-Susana" }, { "family_name": "Das", "given_name": "Swarna", "clpid": "Das-Swarna" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Sinsheimer", "given_name": "Janet", "orcid": "0000-0001-9540-5956", "clpid": "Sinsheimer-Janet" }, { "family_name": "Bui", "given_name": "Alex", "clpid": "Bui-Alexander" }, { "family_name": "Jacobs", "given_name": "Jonathan P.", "orcid": "0000-0003-4698-0254", "clpid": "Jacobs-Jonathan-P" }, { "family_name": "Pajukanta", "given_name": "P\u00e4ivi", "orcid": "0000-0002-6423-8056", "clpid": "Pajukanta-P\u00e4ivi" }, { "family_name": "Wu", "given_name": "Holden", "orcid": "0000-0002-2585-5916", "clpid": "Wu-Holden" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Li", "given_name": "Zhaoping", "clpid": "Li-Zhaoping" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cardiometabolic diseases in overweight individuals. While liver biopsy is the current gold standard to diagnose NAFLD and magnetic resonance imaging (MRI) is a non-invasive alternative still under clinical trials, the former is invasive and the latter costly. We demonstrate electrical impedance tomography (EIT) as a portable method for detecting fatty infiltrate. We enrolled 19 overweight subjects to undergo liver MRI scans, followed by EIT measurements. The MRI images provided the a priori knowledge of the liver boundary conditions for EIT reconstruction, and the multi-echo MRI data quantified liver proton-density fat fraction (PDFF%) to validate fat infiltrate. Using the EIT electrode belts, we circumferentially injected pairwise current to the upper abdomen, followed by acquiring the resulting surface-voltage to reconstruct the liver conductivity. Pearson's correlation analyses compared EIT conductivity or MRI PDFF with body mass index, age, waist circumference, height, and weight variables. We reveal that the correlation between liver EIT conductivity or MRI PDFF with demographics is statistically insignificant, whereas liver EIT conductivity is inversely correlated with MRI PDFF (R\u2009=\u2009\u22120.69, p\u2009=\u20090.003, n\u2009=\u200916). As a pilot study, EIT conductivity provides a portable method for operator-independent and cost-effective detection of hepatic steatosis.", "doi": "10.1038/s41598-021-99132-z", "pmcid": "PMC8494919", "issn": "2045-2322", "publisher": "Springer Nature", "publication": "Scientific Reports", "publication_date": "2021-10-06", "volume": "11", "pages": "Art. No. 19859" }, { "id": "authors:qhqv3-3eh17", "collection": "authors", "collection_id": "qhqv3-3eh17", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210203-135928428", "type": "article", "title": "In Vivo Intravascular Pacing Using a Wireless Microscale Stimulator", "author": [ { "family_name": "Abiri", "given_name": "Parinaz", "orcid": "0000-0002-0520-6863", "clpid": "Abiri-Parinaz" }, { "family_name": "Duarte-Vogel", "given_name": "Sandra", "clpid": "Duarte-Vogel-Sandra" }, { "family_name": "Chou", "given_name": "Tzu-Chieh", "orcid": "0000-0002-6074-8286", "clpid": "Chou-Tzu-Chieh" }, { "family_name": "Abiri", "given_name": "Arash", "clpid": "Abiri-Arash" }, { "family_name": "Gudapati", "given_name": "Varun", "orcid": "0000-0003-0134-7236", "clpid": "Gudapati-Varun" }, { "family_name": "Yousefi", "given_name": "Alireza", "orcid": "0000-0002-6814-4452", "clpid": "Yousefi-Alireza" }, { "family_name": "Roustaei", "given_name": "Mehrdad", "clpid": "Roustaei-Mehrdad" }, { "family_name": "Chang", "given_name": "Chih-Chiang", "clpid": "Chang-Chih-Chiang" }, { "family_name": "Cui", "given_name": "Qingyu", "clpid": "Cui-Qingyu" }, { "family_name": "Hsu", "given_name": "Jeffrey J.", "orcid": "0000-0002-9971-5916", "clpid": "Hsu-Jeffrey-J" }, { "family_name": "Bersohn", "given_name": "Malcolm", "clpid": "Bersohn-Malcolm" }, { "family_name": "Markovic", "given_name": "Dejan", "clpid": "Markovic-Dejan" }, { "family_name": "Chen", "given_name": "Jun", "clpid": "Chen-Jun" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Millions of patients worldwide are implanted with permanent pacemakers for the treatment of cardiac arrhythmias and conduction disorders. The increased use of these devices has established a growing clinical need to mitigate associated complications. Pacemaker leads, in particular, present the primary risks in most implants. While wireless power transfer holds great promise in eliminating implantable device leads, anatomical constraints limit efficient wireless transmission over the necessary operational range. We thereby developed a transmitter-centered control system for wireless power transfer with sufficient power for continuous cardiac pacing. Device safety was validated using a computational model of the system within an MRI-based anatomical model. The pacer was then fabricated to meet the acute constraints of the anterior cardiac vein (ACV) to enable intravascular deployment while maintaining power efficiency. Our computational model revealed the wireless system to operate at >\u200950 times below the tissue energy absorption safety criteria. We further demonstrated the capacity for ex vivo pacing of pig hearts at 60 beats per minute (BPM) and in vivo pacing at 120 BPM following pacer deployment in the ACV. This work thus established the capacity for wireless intravascular pacing with the potential to eliminate complications associated with current lead-based deep tissue implants.", "doi": "10.1007/s10439-021-02729-8", "issn": "0090-6964", "publisher": "Springer", "publication": "Annals of Biomedical Engineering", "publication_date": "2021-09", "series_number": "9", "volume": "49", "issue": "9", "pages": "2094-2102" }, { "id": "authors:2ys7a-n0k22", "collection": "authors", "collection_id": "2ys7a-n0k22", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201216-100504535", "type": "article", "title": "Three-dimensional Imaging Coupled with Topological Quantification Uncovers Retinal Vascular Plexuses Undergoing Obliteration", "author": [ { "family_name": "Chang", "given_name": "Chih-Chiang", "clpid": "Chang-Chih-Chiang" }, { "family_name": "Chu", "given_name": "Alison", "clpid": "Chu-Alison" }, { "family_name": "Meyer", "given_name": "Scott", "clpid": "Meyer-Scott" }, { "family_name": "Ding", "given_name": "Yichen", "orcid": "0000-0002-6242-3506", "clpid": "Ding-Yichen" }, { "family_name": "Sun", "given_name": "Michel M.", "clpid": "Sun-Michel-M" }, { "family_name": "Abiri", "given_name": "Parinaz", "orcid": "0000-0002-0520-6863", "clpid": "Abiri-Parinaz" }, { "family_name": "Baek", "given_name": "Kyung In", "orcid": "0000-0001-9388-2070", "clpid": "Baek-Kyung-In" }, { "family_name": "Gudapati", "given_name": "Varun", "orcid": "0000-0003-0134-7236", "clpid": "Gudapati-Varun" }, { "family_name": "Ding", "given_name": "Xili", "clpid": "Ding-Xili" }, { "family_name": "Guihard", "given_name": "Pierre", "clpid": "Guihard-Pierre" }, { "family_name": "Bostrom", "given_name": "Kristina I.", "clpid": "Bostrom-Kristina-I" }, { "family_name": "Li", "given_name": "Song", "clpid": "Li-Song" }, { "family_name": "Gordon", "given_name": "Lynn K.", "clpid": "Gordon-Lynn-K" }, { "family_name": "Zheng", "given_name": "Jie J.", "clpid": "Zheng-Jie-J" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Introduction: Murine models provide microvascular insights into the 3-D network disarray seen in retinopathy and cardiovascular diseases. Light-sheet fluorescence microscopy (LSFM) has emerged to capture retinal vasculature in 3-D, allowing for assessment of the progression of retinopathy and the potential to screen new therapeutic targets in mice. We hereby coupled LSFM, also known as selective plane illumination microscopy, with topological quantification, to characterize the retinal vascular plexuses undergoing preferential obliteration. \n\nMethod and Result: In postnatal mice, we revealed the 3-D retinal microvascular network in which the vertical sprouts bridge the primary (inner) and secondary (outer) plexuses, whereas, in an oxygen-induced retinopathy (OIR) mouse model, we demonstrated preferential obliteration of the secondary plexus and bridging vessels with a relatively unscathed primary plexus. Using clustering coefficients and Euler numbers, we computed the local versus global vascular connectivity. While local connectivity was preserved (p > 0.05, n = 5 vs. normoxia), the global vascular connectivity in hyperoxia-exposed retinas was significantly reduced (p < 0.05, n = 5 vs. normoxia). Applying principal component analysis (PCA) for auto-segmentation of the vertical sprouts, we corroborated the obliteration of the vertical sprouts bridging the secondary plexuses, as evidenced by impaired vascular branching and connectivity, and reduction in vessel volumes and lengths (p < 0.05, n = 5 vs. normoxia). \n\nConclusion: Coupling 3-D LSFM with topological quantification uncovered the retinal vasculature undergoing hyperoxia-induced obliteration from the secondary (outer) plexus to the vertical sprouts. The use of clustering coefficients, Euler's number, and PCA provided new network insights into OIR-associated vascular obliteration, with translational significance for investigating therapeutic interventions to prevent visual impairment.", "doi": "10.7150/thno.53073", "issn": "1838-7640", "publisher": "Ivyspring International Publisher", "publication": "Theranostics", "publication_date": "2021-01-01", "series_number": "3", "volume": "11", "issue": "3", "pages": "1162-1175" }, { "id": "authors:e55vx-h1q02", "collection": "authors", "collection_id": "e55vx-h1q02", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200403-142831278", "type": "article", "title": "A Multi-Dimensional Analysis of a Novel Approach for Wireless Stimulation", "author": [ { "family_name": "Abiri", "given_name": "Parinaz", "orcid": "0000-0002-0520-6863", "clpid": "Abiri-Parinaz" }, { "family_name": "Yousefi", "given_name": "Alireza", "orcid": "0000-0002-6814-4452", "clpid": "Yousefi-Alireza" }, { "family_name": "Abiri", "given_name": "Arash", "orcid": "0000-0003-2656-1060", "clpid": "Abiri-Arash" }, { "family_name": "Gudapati", "given_name": "Varun", "orcid": "0000-0003-0134-7236", "clpid": "Gudapati-Varun" }, { "family_name": "Ding", "given_name": "Yichen", "orcid": "0000-0002-6242-3506", "clpid": "Ding-Yichen" }, { "family_name": "Nguyen", "given_name": "Kim-Lien", "orcid": "0000-0002-8854-2976", "clpid": "Nguyen-Kim-Lien" }, { "family_name": "Abiri", "given_name": "Ahmad", "orcid": "0000-0002-4709-5479", "clpid": "Abiri-Ahmad" }, { "family_name": "Markovic", "given_name": "Dejan", "clpid": "Markovic-Dejan" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "The elimination of integrated batteries in biomedical implants holds great promise for improving health outcomes in patients with implantable devices. However, despite extensive research in wireless power transfer, achieving efficient power transfer and effective operational range have remained a hindering challenge within anatomical constraints. Objective : We hereby demonstrate an intravascular wireless and batteryless microscale stimulator, designed for (1) low power dissipation via intermittent transmission and (2) reduced fixation mechanical burden via deployment to the anterior cardiac vein (ACV, \u223c3.8 mm in diameter). Methods : We introduced a unique coil design circumferentially confined to a 3 mm diameter hollow-cylinder that was driven by a novel transmitter-based control architecture with improved power efficiency. Results : We examined wireless capacity using heterogenous bovine tissue, demonstrating >5 V stimulation threshold with up to 20 mm transmitter-receiver displacement and 20\u00b0 of misalignment. Feasibility for human use was validated using Finite Element Method (FEM) simulation of the cardiac cycle, guided by pacer phantom-integrated Magnetic Resonance Images (MRI). Conclusion : This system design thus enabled sufficient wireless power transfer in the face of extensive stimulator miniaturization. Significance : Our successful feasibility studies demonstrated the capacity for minimally invasive deployment and low-risk fixation.", "doi": "10.1109/tbme.2020.2983443", "pmcid": "PMC8262529", "issn": "0018-9294", "publisher": "IEEE", "publication": "IEEE Transactions on Biomedical Engineering", "publication_date": "2020-12", "series_number": "12", "volume": "67", "issue": "12", "pages": "3307-3316" }, { "id": "authors:854hg-31k04", "collection": "authors", "collection_id": "854hg-31k04", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200103-111758763", "type": "article", "title": "Impact of air pollution on intestinal redox lipidome and microbiome", "author": [ { "family_name": "Feng", "given_name": "Juan", "clpid": "Feng-Juan" }, { "family_name": "Cavallero", "given_name": "Susana", "clpid": "Cavallero-S" }, { "family_name": "Hsiai", "given_name": "Tzung", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" }, { "family_name": "Li", "given_name": "Rongsong", "clpid": "Li-Rongsong" } ], "abstract": "Air pollution is a rising public health issue worldwide. Cumulative epidemiological and experimental studies have shown that exposure to air pollution such as particulate matter (PM) is linked with increased hospital admissions and all-cause mortality. While previous studies on air pollution mostly focused on the respiratory and cardiovascular effects, emerging evidence supports a significant impact of air pollution on the gastrointestinal (GI) system. The gut is exposed to PM as most of the inhaled particles are removed from the lungs to the GI tract via mucociliary clearance. Ingestion of contaminated food and water is another common source of GI tract exposure to pollutants. Recent studies have associated air pollution with intestinal diseases, including appendicitis, colorectal cancer, and inflammatory bowel disease. In addition to the liver and adipose tissue, intestine is an important organ system for lipid metabolism, and the intestinal redox lipids might be tightly associated with the intestinal and systematic inflammation. The gut microbiota modulates lipid metabolism and contributes to the initiation and development of intestinal disease including inflammatory bowel disease. Recent data support microbiome implication in air pollution-mediated intestinal and systematic effects. In this review, the associations between air pollution and intestinal diseases, and the alterations of intestinal lipidome and gut microbiome by air pollution are highlighted. The potential mechanistic aspects underlying air pollution-mediated intestinal pathology will also be discussed.", "doi": "10.1016/j.freeradbiomed.2019.12.044", "issn": "0891-5849", "publisher": "Elsevier", "publication": "Free Radical Biology and Medicine", "publication_date": "2020-05-01", "volume": "151", "pages": "99-110" }, { "id": "authors:xcbec-h2487", "collection": "authors", "collection_id": "xcbec-h2487", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191016-120329675", "type": "article", "title": "A laser-engraved wearable sensor for sensitive detection of uric acid and tyrosine in sweat", "author": [ { "family_name": "Yang", "given_name": "Yiran", "orcid": "0000-0001-8770-8746", "clpid": "Yang-Yiran" }, { "family_name": "Song", "given_name": "Yu", "orcid": "0000-0002-4185-2256", "clpid": "Song-Yu" }, { "family_name": "Bo", "given_name": "Xiangjie", "clpid": "Bo-Xiangjie" }, { "family_name": "Min", "given_name": "Jihong", "orcid": "0000-0002-5788-1473", "clpid": "Min-Jihong" }, { "family_name": "Pak", "given_name": "On Shun", "clpid": "Pak-On-Shun" }, { "family_name": "Zhu", "given_name": "Lailai", "clpid": "Zhu-Lailai" }, { "family_name": "Wang", "given_name": "Minqiang", "orcid": "0000-0002-7775-8341", "clpid": "Wang-Minqiang" }, { "family_name": "Tu", "given_name": "Jiaobing", "orcid": "0000-0002-7653-6640", "clpid": "Tu-Jiaobing" }, { "family_name": "Kogan", "given_name": "Adam", "clpid": "Kogan-Aadam" }, { "family_name": "Zhang", "given_name": "Haixia", "clpid": "Zhang-Haixia" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" }, { "family_name": "Li", "given_name": "Zhaoping", "clpid": "Li-Zhaoping" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "abstract": "Wearable sweat sensors have the potential to provide continuous measurements of useful biomarkers. However, current sensors cannot accurately detect low analyte concentrations, lack multimodal sensing or are difficult to fabricate at large scale. We report an entirely laser-engraved sensor for simultaneous sweat sampling, chemical sensing and vital-sign monitoring. We demonstrate continuous detection of temperature, respiration rate and low concentrations of uric acid and tyrosine, analytes associated with diseases such as gout and metabolic disorders. We test the performance of the device in both physically trained and untrained subjects under exercise and after a protein-rich diet. We also evaluate its utility for gout monitoring in patients and healthy controls through a purine-rich meal challenge. Levels of uric acid in sweat were higher in patients with gout than in healthy individuals, and a similar trend was observed in serum.", "doi": "10.1038/s41587-019-0321-x", "issn": "1087-0156", "publisher": "Nature Publishing Group", "publication": "Nature Biotechnology", "publication_date": "2020-02", "series_number": "2", "volume": "38", "issue": "2", "pages": "217-224" }, { "id": "authors:9fyfk-59n49", "collection": "authors", "collection_id": "9fyfk-59n49", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180816-080520317", "type": "article", "title": "Simulating Developmental Cardiac Morphology in Virtual Reality Using a Deformable Image Registration Approach", "author": [ { "family_name": "Abiri", "given_name": "Arash", "clpid": "Abiri-Arash" }, { "family_name": "Ding", "given_name": "Yichen", "orcid": "0000-0002-6242-3506", "clpid": "Ding-Yichen" }, { "family_name": "Abiri", "given_name": "Parinaz", "orcid": "0000-0002-0520-6863", "clpid": "Abiri-Parinaz" }, { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-Ren\u00e9-Rupen-Sevag" }, { "family_name": "Vedula", "given_name": "Vijay", "clpid": "Vedula-Vijay" }, { "family_name": "Marsden", "given_name": "Alison", "clpid": "Marsden-Alison-L" }, { "family_name": "Kuo", "given_name": "C.-C. Jay", "clpid": "Kuo-C-C-Jay" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "While virtual reality (VR) has potential in enhancing cardiovascular diagnosis and treatment, prerequisite labor-intensive image segmentation remains an obstacle for seamlessly simulating 4-dimensional (4-D, 3-D\u2009+\u2009time) imaging data in an immersive, physiological VR environment. We applied deformable image registration (DIR) in conjunction with 3-D reconstruction and VR implementation to recapitulate developmental cardiac contractile function from light-sheet fluorescence microscopy (LSFM). This method addressed inconsistencies that would arise from independent segmentations of time-dependent data, thereby enabling the creation of a VR environment that fluently simulates cardiac morphological changes. By analyzing myocardial deformation at high spatiotemporal resolution, we interfaced quantitative computations with 4-D VR. We demonstrated that our LSFM-captured images, followed by DIR, yielded average dice similarity coefficients of 0.92\u2009\u00b1\u20090.05 (n\u2009=\u2009510) and 0.93\u2009\u00b1\u20090.06 (n\u2009=\u2009240) when compared to ground truth images obtained from Otsu thresholding and manual segmentation, respectively. The resulting VR environment simulates a wide-angle zoomed-in view of motion in live embryonic zebrafish hearts, in which the cardiac chambers are undergoing structural deformation throughout the cardiac cycle. Thus, this technique allows for an interactive micro-scale VR visualization of developmental cardiac morphology to enable high resolution simulation for both basic and clinical science.", "doi": "10.1007/s10439-018-02113-z", "pmcid": "PMC6249076", "issn": "0090-6964", "publisher": "Springer", "publication": "Annals of Biomedical Engineering", "publication_date": "2018-12", "series_number": "12", "volume": "46", "issue": "12", "pages": "2177-2188" }, { "id": "authors:d9k1q-e2z70", "collection": "authors", "collection_id": "d9k1q-e2z70", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180622-101243466", "type": "article", "title": "Advanced microscopy to elucidate cardiovascular injury and regeneration: 4D light-sheet imaging", "author": [ { "family_name": "Baek", "given_name": "Kyung In", "orcid": "0000-0001-9388-2070", "clpid": "Baek-Kyung-In" }, { "family_name": "Ding", "given_name": "Yichen", "orcid": "0000-0002-6242-3506", "clpid": "Ding-Yichen" }, { "family_name": "Chang", "given_name": "Chih-Chiang", "clpid": "Chang-Chih-Chiang" }, { "family_name": "Chang", "given_name": "Megan", "clpid": "Chang-Megan" }, { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-R-R-S" }, { "family_name": "Hsu", "given_name": "Jeffrey J.", "orcid": "0000-0002-9971-5916", "clpid": "Hsu-Jeffrey-J" }, { "family_name": "Fei", "given_name": "Peng", "clpid": "Fei-Peng" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "The advent of 4-dimensional (4D) light-sheet fluorescence microscopy (LSFM) has provided an entry point for rapid image acquisition to uncover real-time cardiovascular structure and function with high axial resolution and minimal photo-bleaching/-toxicity. We hereby review the fundamental principles of our LSFM system to investigate cardiovascular morphogenesis and regeneration after injury. LSFM enables us to reveal the micro-circulation of blood cells in the zebrafish embryo and assess cardiac ventricular remodeling in response to chemotherapy-induced injury using an automated segmentation approach. Next, we review two distinct mechanisms underlying zebrafish vascular regeneration following tail amputation. We elucidate the role of endothelial Notch signaling to restore vascular regeneration after exposure to the redox active ultrafine particles (UFP) in air pollutants. By manipulating the blood viscosity and subsequently, endothelial wall shear stress, we demonstrate the mechanism whereby hemodynamic shear forces impart both mechanical and metabolic effects to modulate vascular regeneration. Overall, the implementation of 4D LSFM allows for the elucidation of mechanisms governing cardiovascular injury and regeneration with high spatiotemporal resolution.", "doi": "10.1016/j.pbiomolbio.2018.05.003", "pmcid": "PMC6226366", "issn": "0079-6107", "publisher": "Elsevier", "publication": "Progress in Biophysics and Molecular Biology", "publication_date": "2018-10", "volume": "138", "pages": "105-115" }, { "id": "authors:me54t-pk778", "collection": "authors", "collection_id": "me54t-pk778", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180716-102017991", "type": "article", "title": "Spatial and temporal variations in hemodynamic forces initiate cardiac trabeculation", "author": [ { "family_name": "Lee", "given_name": "Juhyun", "clpid": "Lee-Juhyun" }, { "family_name": "Vedula", "given_name": "Vijay", "clpid": "Vedula-V" }, { "family_name": "Baek", "given_name": "Kyung In", "orcid": "0000-0001-9388-2070", "clpid": "Baek-Kyung-In" }, { "family_name": "Chen", "given_name": "Junjie", "clpid": "Chen-Junjie" }, { "family_name": "Hsu", "given_name": "Jeffrey J.", "orcid": "0000-0002-9971-5916", "clpid": "Hsu-Jeffrey-J" }, { "family_name": "Ding", "given_name": "Yichen", "orcid": "0000-0002-6242-3506", "clpid": "Ding-Yichen" }, { "family_name": "Chang", "given_name": "Chih-Chiang", "clpid": "Chang-Chih-Chiang" }, { "family_name": "Kang", "given_name": "Hanul", "clpid": "Kang-Hanul" }, { "family_name": "Small", "given_name": "Adam", "clpid": "Small-A" }, { "family_name": "Fei", "given_name": "Peng", "clpid": "Fei-Peng" }, { "family_name": "Chuong", "given_name": "Cheng-Ming", "clpid": "Chuong-Cheng-Ming" }, { "family_name": "Li", "given_name": "Rongsong", "clpid": "Li-Rongsong" }, { "family_name": "Demer", "given_name": "Linda", "clpid": "Demer-L-L" }, { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-R-R-S" }, { "family_name": "Marsden", "given_name": "Alison L.", "clpid": "Marsden-A-L" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Hemodynamic shear force has been implicated as modulating Notch signaling-mediated cardiac trabeculation. Whether the spatiotemporal variations in wall shear stress (WSS) coordinate the initiation of trabeculation to influence ventricular contractile function remains unknown. Using light-sheet fluorescent microscopy, we reconstructed the 4D moving domain and applied computational fluid dynamics to quantify 4D WSS along the trabecular ridges and in the groves. In WT zebrafish, pulsatile shear stress developed along the trabecular ridges, with prominent endocardial Notch activity at 3 days after fertilization (dpf), and oscillatory shear stress developed in the trabecular grooves, with epicardial Notch activity at 4 dpf. Genetic manipulations were performed to reduce hematopoiesis and inhibit atrial contraction to lower WSS in synchrony with attenuation of oscillatory shear index (OSI) during ventricular development. \u03b3-Secretase inhibitor of Notch intracellular domain (NICD) abrogated endocardial and epicardial Notch activity. Rescue with NICD mRNA restored Notch activity sequentially from the endocardium to trabecular grooves, which was corroborated by observed Notch-mediated cardiomyocyte proliferations on WT zebrafish trabeculae. We also demonstrated in vitro that a high OSI value correlated with upregulated endothelial Notch-related mRNA expression. In silico computation of energy dissipation further supports the role of trabeculation to preserve ventricular structure and contractile function. Thus, spatiotemporal variations in WSS coordinate trabecular organization for ventricular contractile function.", "doi": "10.1172/jci.insight.96672", "pmcid": "PMC6124527", "issn": "2379-3708", "publisher": "American Society for Clinical Investigation", "publication": "JCI insight", "publication_date": "2018-07-12", "series_number": "13", "volume": "3", "issue": "13", "pages": "Art. No. e96672" }, { "id": "authors:wbwp2-0mz31", "collection": "authors", "collection_id": "wbwp2-0mz31", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180402-091245017", "type": "article", "title": "Light-Sheet Imaging to Elucidate Cardiovascular Injury and Repair", "author": [ { "family_name": "Ding", "given_name": "Yichen", "orcid": "0000-0002-6242-3506", "clpid": "Ding-Yichen" }, { "family_name": "Lee", "given_name": "Juhyun", "clpid": "Lee-Juhyun" }, { "family_name": "Hsu", "given_name": "Jeffrey J.", "orcid": "0000-0002-9971-5916", "clpid": "Hsu-Jeffrey-J" }, { "family_name": "Chang", "given_name": "Chih-Chiang", "clpid": "Chang-Chih-Chiang" }, { "family_name": "Baek", "given_name": "Kyung In", "orcid": "0000-0001-9388-2070", "clpid": "Baek-Kyung-In" }, { "family_name": "Ranjbarvazri", "given_name": "Sara", "clpid": "Ranjbarvazri-S" }, { "family_name": "Ardehali", "given_name": "Reza", "orcid": "0000-0003-1318-4016", "clpid": "Ardehali-R" }, { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-R-R-S" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Purpose of Review: Real-time 3-dimensional (3-D) imaging of cardiovascular injury and regeneration remains challenging. We introduced a multi-scale imaging strategy that uses light-sheet illumination to enable applications of cardiovascular injury and repair in models ranging from zebrafish to rodent hearts. \n\nRecent Findings: Light-sheet imaging enables rapid data acquisition with high spatiotemporal resolution and with minimal photo-bleaching or photo-toxicity. We demonstrated the capacity of this novel light-sheet approach for scanning a region of interest with specific fluorescence contrast, thereby providing axial and temporal resolution at the cellular level without stitching image columns or pivoting illumination beams during one-time imaging. This cutting-edge imaging technique allows for elucidating the differentiation of stem cells in cardiac regeneration, providing an entry point to discover novel micro-circulation phenomenon with clinical significance for injury and repair. \n\nSummary: These findings demonstrate the multi-scale applications of this novel light-sheet imaging strategy to advance research in cardiovascular development and regeneration.", "doi": "10.1007/s11886-018-0979-6", "pmcid": "PMC5987244", "issn": "1523-3782", "publisher": "Springer", "publication": "Current Cardiology Reports", "publication_date": "2018-05", "series_number": "5", "volume": "20", "issue": "5", "pages": "Art. No. 35" }, { "id": "authors:a2knh-myq30", "collection": "authors", "collection_id": "a2knh-myq30", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180222-083518129", "type": "article", "title": "Non-Invasive Electrical Impedance Tomography for Multi-Scale Detection of Liver Fat Content", "author": [ { "family_name": "Luo", "given_name": "Yuan", "clpid": "Luo-Yuan" }, { "family_name": "Abiri", "given_name": "Parinaz", "clpid": "Abiri-P" }, { "family_name": "Zhang", "given_name": "Shell", "clpid": "Zhang-Shell" }, { "family_name": "Chang", "given_name": "Chih-Chiang", "clpid": "Chang-Chih-Chiang" }, { "family_name": "Kaboodrangi", "given_name": "Amir H.", "clpid": "Kaboodrangi-A-H" }, { "family_name": "Li", "given_name": "Rongsong", "clpid": "Li-Rongsong" }, { "family_name": "Sahib", "given_name": "Ashish K.", "clpid": "Sahib-A-K" }, { "family_name": "Bui", "given_name": "Alex", "clpid": "Bui-Alexander" }, { "family_name": "Kumar", "given_name": "Rajesh", "clpid": "Kumar-Rajesh" }, { "family_name": "Woo", "given_name": "Mary", "clpid": "Woo-Mary" }, { "family_name": "Li", "given_name": "Zhaoping", "clpid": "Li-Zhaoping" }, { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-R-R-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements. \n\nMethods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI < 25 kg/m\u00b2) and 0.286 S/m for high BMI (> 25 kg/m\u00b2). \n\nConclusion: We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome.", "doi": "10.7150/thno.22233", "pmcid": "PMC5858172", "issn": "1838-7640", "publisher": "Ivyspring International Publisher", "publication": "Theranostics", "publication_date": "2018-02-08", "series_number": "6", "volume": "8", "issue": "6", "pages": "1636-1647" }, { "id": "authors:9e5ks-ffk97", "collection": "authors", "collection_id": "9e5ks-ffk97", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170925-081332206", "type": "article", "title": "Flow-Responsive Vascular Endothelial Growth Factor Receptor-Protein Kinase C Isoform Epsilon Signaling Mediates Glycolytic Metabolites for Vascular Repair", "author": [ { "family_name": "Baek", "given_name": "Kyung In", "orcid": "0000-0001-9388-2070", "clpid": "Baek-Kyung-In" }, { "family_name": "Li", "given_name": "Rongsong", "clpid": "Li-Rongsong" }, { "family_name": "Jen", "given_name": "Nelson", "clpid": "Jen-Nelson" }, { "family_name": "Choi", "given_name": "Howard", "clpid": "Choi-Howard" }, { "family_name": "Kaboodrangi", "given_name": "Amir", "clpid": "Kaboodrangi-A" }, { "family_name": "Ping", "given_name": "Peipei", "clpid": "Ping-Peipei" }, { "family_name": "Liem", "given_name": "David", "clpid": "Liem-D-A" }, { "family_name": "Beebe", "given_name": "Tyler", "clpid": "Beebe-T" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Aims: Hemodynamic shear stress participates in maintaining vascular redox status. Elucidating flow-mediated endothelial metabolites enables us to discover metabolic biomarkers and therapeutic targets. We posited that flow-responsive vascular endothelial growth factor receptor (VEGFR)-protein kinase C isoform epsilon (PKC\u025b)-6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) signaling modulates glycolytic metabolites for vascular repair.\nResults: Bidirectional oscillatory flow (oscillatory shear stress [OSS]: 0.1\u2009\u00b1\u20093 dyne\u00b7cm^(\u22122) at 1\u2009Hz) upregulated VEGFR-dependent PKC\u025b expression to a greater degree than did unidirectional pulsatile flow (pulsatile shear stress [PSS]: 23\u2009\u00b1\u20098 dyne\u00b7cm^(\u22122) at 1\u2009Hz) in human aortic endothelial cells (p\u2009<\u20090.05, n\u2009=\u20093). PSS and OSS further upregulated PKC\u025b-dependent PFKFB3 expression for glycolysis (p\u2009<\u20090.05, n\u2009=\u20094). Constitutively active PKC\u025b increased, whereas dominant-negative PKC\u025b reduced both basal and maximal extracellular acidification rates for glycolytic flux (p\u2009<\u20090.01, n\u2009=\u20094). Metabolomic analysis demonstrated an increase in PKC\u025b-dependent glycolytic metabolite, dihydroxyacetone (DHA), but a decrease in gluconeogenic metabolite, aspartic acid (p\u2009<\u20090.05 vs. control, n\u2009=\u20096). In a New Zealand White rabbit model, both PKC\u025b and PFKFB3 immunostaining was prominent in the PSS- and OSS-exposed aortic arch and descending aorta. In a transgenic Tg(flk-1:EGFP) zebrafish model, GATA-1a morpholino oligonucleotide injection (to reduce viscosity-dependent shear stress) impaired vascular regeneration after tail amputation (p\u2009<\u20090.01, n\u2009=\u200920), which was restored with PKC\u025b messenger RNA (mRNA) rescue (p\u2009<\u20090.05, n\u2009=\u20095). As a corollary, siPKC\u025b inhibited tube formation and vascular repair, which were restored by DHA treatment in our Matrigel and zebrafish models.\nInnovation and Conclusion: Flow-sensitive VEGFR-PKC\u025b-PFKFB3 signaling increases the glycolytic metabolite, dihydroxyacetone, to promote vascular repair.", "doi": "10.1089/ars.2017.7044", "pmcid": "PMC5695747", "issn": "1523-0864", "publisher": "Mary Ann Liebert", "publication": "Antioxidants and Redox Signaling", "publication_date": "2018-01", "series_number": "1", "volume": "28", "issue": "1", "pages": "31-43" }, { "id": "authors:rwb15-cfa66", "collection": "authors", "collection_id": "rwb15-cfa66", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171212-085409495", "type": "article", "title": "Integrating light-sheet imaging with virtual reality to recapitulate developmental cardiac mechanics", "author": [ { "family_name": "Ding", "given_name": "Yichen", "orcid": "0000-0002-6242-3506", "clpid": "Ding-Yichen" }, { "family_name": "Abiri", "given_name": "Arash", "clpid": "Abiri-A" }, { "family_name": "Abiri", "given_name": "Parinaz", "clpid": "Abiri-P" }, { "family_name": "Li", "given_name": "Shuoran", "clpid": "Li-Shuoran" }, { "family_name": "Chang", "given_name": "Chih-Chiang", "clpid": "Chang-Chih-Chiang" }, { "family_name": "Baek", "given_name": "Kyung In", "orcid": "0000-0001-9388-2070", "clpid": "Baek-Kyung-In" }, { "family_name": "Hsu", "given_name": "Jeffrey J.", "orcid": "0000-0002-9971-5916", "clpid": "Hsu-Jeffrey-J" }, { "family_name": "Sideris", "given_name": "Elias", "clpid": "Sideris-E" }, { "family_name": "Li", "given_name": "Yilei", "clpid": "Li-Yilei" }, { "family_name": "Lee", "given_name": "Juhyun", "clpid": "Lee-Juhyun" }, { "family_name": "Segura", "given_name": "Tatiana", "clpid": "Segura-T" }, { "family_name": "Nguyen", "given_name": "Thao P.", "clpid": "Nguyen-Thao-P" }, { "family_name": "Bui", "given_name": "Alexander", "clpid": "Bui-Alexander" }, { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-R-R-S" }, { "family_name": "Fei", "given_name": "Peng", "clpid": "Fei-Peng" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Currently, there is a limited ability to interactively study developmental cardiac mechanics and physiology. We therefore combined light-sheet fluorescence microscopy (LSFM) with virtual reality (VR) to provide a hybrid platform for 3D architecture and time-dependent cardiac contractile function characterization. By taking advantage of the rapid acquisition, high axial resolution, low phototoxicity, and high fidelity in 3D and 4D (3D spatial + 1D time or spectra), this VR-LSFM hybrid methodology enables interactive visualization and quantification otherwise not available by conventional methods, such as routine optical microscopes. We hereby demonstrate multiscale applicability of VR-LSFM to (a) interrogate skin fibroblasts interacting with a hyaluronic acid\u2013based hydrogel, (b) navigate through the endocardial trabecular network during zebrafish development, and (c) localize gene therapy-mediated potassium channel expression in adult murine hearts. We further combined our batch intensity normalized segmentation algorithm with deformable image registration to interface a VR environment with imaging computation for the analysis of cardiac contraction. Thus, the VR-LSFM hybrid platform demonstrates an efficient and robust framework for creating a user-directed microenvironment in which we uncovered developmental cardiac mechanics and physiology with high spatiotemporal resolution.", "doi": "10.1172/jci.insight.97180", "pmcid": "PMC5752380", "issn": "2379-3708", "publisher": "American Society for Clinical Investigation", "publication": "JCI Insight", "publication_date": "2017-11-16", "series_number": "22", "volume": "2", "issue": "22" }, { "id": "authors:fjccx-0kw71", "collection": "authors", "collection_id": "fjccx-0kw71", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170706-155341835", "type": "article", "title": "3-D Electrochemical Impedance Spectroscopy Mapping of Arteries to Detect Metabolically Active but Angiographically Invisible Atherosclerotic Lesions", "author": [ { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-R-R-S" }, { "family_name": "Luo", "given_name": "Yuan", "clpid": "Luo-Yuan" }, { "family_name": "Abiri", "given_name": "Parinaz", "clpid": "Abiri-P" }, { "family_name": "Jen", "given_name": "Nelson", "clpid": "Jen-Nelson" }, { "family_name": "Aksoy", "given_name": "Olcay", "clpid": "Aksoy-O" }, { "family_name": "Suh", "given_name": "William M.", "clpid": "Suh-William-M" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "We designed a novel 6-point electrochemical impedance spectroscopy (EIS) sensor with 15 combinations of permutations for the 3-D mapping and detection of metabolically active atherosclerotic lesions. Two rows of 3 stretchable electrodes circumferentially separated by 120\u00b0 were mounted on an inflatable balloon for intravascular deployment and endoluminal interrogation. The configuration and 15 permutations of 2-point EIS electrodes allowed for deep arterial penetration via alternating current (AC) to detect varying degrees of lipid burden with distinct impedance profiles (\u03a9). By virtue of the distinctive impedimetric signature of metabolically active atherosclerotic lesions, a detailed impedance map was acquired, with the 15 EIS permutations uncovering early stages of disease characterized by fatty streak lipid accumulation in the New Zealand White rabbit model of atherosclerosis. Both the equivalent circuit and statistical analyses corroborated the 3-D EIS permutations to detect small, angiographically invisible, lipid-rich lesions, with translational implications for early atherosclerotic disease detection and prevention of acute coronary syndromes or strokes.", "doi": "10.7150/thno.19184", "pmcid": "PMC5525747", "issn": "1838-7640", "publisher": "Ivyspring International Publisher", "publication": "Theranostics", "publication_date": "2017-06-22", "series_number": "9", "volume": "7", "issue": "9", "pages": "2431-2442" }, { "id": "authors:nd92m-gz466", "collection": "authors", "collection_id": "nd92m-gz466", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170522-145005144", "type": "article", "title": "A Rapid Capillary-Pressure Driven Micro-Channel to Demonstrate Newtonian Fluid Behavior of Zebrafish Blood at High Shear Rates", "author": [ { "family_name": "Lee", "given_name": "Juhyun", "clpid": "Lee-Juhyun" }, { "family_name": "Chou", "given_name": "Tzu-Chieh", "orcid": "0000-0002-6074-8286", "clpid": "Chou-Tzu-Chieh" }, { "family_name": "Kang", "given_name": "Dongyang", "clpid": "Kang-Dongyang" }, { "family_name": "Kang", "given_name": "Hanul", "clpid": "Kang-Hanul" }, { "family_name": "Chen", "given_name": "Junjie", "orcid": "0000-0002-1493-2189", "clpid": "Chen-Junjie" }, { "family_name": "Baek", "given_name": "Kyung In", "orcid": "0000-0001-9388-2070", "clpid": "Baek-Kyung-In" }, { "family_name": "Wang", "given_name": "Wei", "orcid": "0000-0002-5257-7675", "clpid": "Wang-Wei" }, { "family_name": "Ding", "given_name": "Yichen", "orcid": "0000-0002-6242-3506", "clpid": "Ding-Yichen" }, { "family_name": "Carlo", "given_name": "Dino Di", "clpid": "Carlo-Dino-Di" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Blood viscosity provides the rheological basis to elucidate shear stress underlying developmental cardiac mechanics and physiology. Zebrafish is a high throughput model for developmental biology, forward-genetics, and drug discovery. The micro-scale posed an experimental challenge to measure blood viscosity. To address this challenge, a microfluidic viscometer driven by surface tension was developed to reduce the sample volume required (3\u03bcL) for rapid (<2\u2009min) and continuous viscosity measurement. By fitting the power-law fluid model to the travel distance of blood through the micro-channel as a function of time and channel configuration, the experimentally acquired blood viscosity was compared with a vacuum-driven capillary viscometer at high shear rates (>500\u2009s^(\u22121)), at which the power law exponent (n) of zebrafish blood was nearly 1 behaving as a Newtonian fluid. The measured values of whole blood from the micro-channel (4.17cP) and the vacuum method (4.22cP) at 500\u2009s^(\u22121) were closely correlated at 27\u2009\u00b0C. A calibration curve was established for viscosity as a function of hematocrits to predict a rise and fall in viscosity during embryonic development. Thus, our rapid capillary pressure-driven micro-channel revealed the Newtonian fluid behavior of zebrafish blood at high shear rates and the dynamic viscosity during development.", "doi": "10.1038/s41598-017-02253-7", "pmcid": "PMC5434032", "issn": "2045-2322", "publisher": "Nature Publishing Group", "publication": "Scientific Reports", "publication_date": "2017-05-16", "volume": "7", "pages": "Art. No. 1980" }, { "id": "authors:5mjgb-1t695", "collection": "authors", "collection_id": "5mjgb-1t695", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160915-082808353", "type": "article", "title": "Ultrasonic transducer-guided electrochemical impedance spectroscopy to assess lipid-laden plaques", "author": [ { "family_name": "Ma", "given_name": "Jianguo", "orcid": "0000-0002-7522-1014", "clpid": "Ma-Jianguo" }, { "family_name": "Luo", "given_name": "Yuan", "orcid": "0000-0003-3153-7495", "clpid": "Luo-Yuan" }, { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-Ren\u00e9-Rupen-Sevag" }, { "family_name": "Ma", "given_name": "Teng", "clpid": "Ma-Teng" }, { "family_name": "Ding", "given_name": "Yichen", "orcid": "0000-0002-6242-3506", "clpid": "Ding-Yichen" }, { "family_name": "Abiri", "given_name": "Parinaz", "orcid": "0000-0002-0520-6863", "clpid": "Abiri-Parinaz" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Zhou", "given_name": "Qifa", "orcid": "0000-0003-1527-3020", "clpid": "Zhou-Qifa" }, { "family_name": "Shung", "given_name": "Kirk K.", "clpid": "Shung-Kirk-K" }, { "family_name": "Li", "given_name": "Rongsong", "orcid": "0000-0002-8247-5258", "clpid": "Li-Rongsong" }, { "family_name": "Hsiai", "given_name": "Tzung", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Plaque rupture causes acute coronary syndromes and stroke. Intraplaque oxidized low density lipoprotein (oxLDL) is metabolically unstable and prone to induce rupture. We designed an intravascular ultrasound (IVUS)-guided electrochemical impedance spectroscopy (EIS) sensor to enhance the detection reproducibility of oxLDL-laden plaques. The flexible 2-point micro-electrode array for EIS was affixed to an inflatable balloon anchored onto a co-axial double layer catheter (outer diameter = 2 mm). The mechanically scanning-driven IVUS transducer (45 MHz) was deployed through the inner catheter (diameter = 1.3 mm) to the acoustic impedance matched-imaging window. Water filled the inner catheter to match acoustic impedance and air was pumped between the inner and outer catheters to inflate the balloon. The integrated EIS and IVUS sensor was deployed into the ex vivo aortas dissected from the fat-fed New Zealand White (NZW) rabbits (n = 3 for fat-fed, n = 5 normal diet). IVUS imaging was able to guide the 2-point electrode to align with the plaque for EIS measurement upon balloon inflation. IVUS-guided EIS signal demonstrated reduced variability and increased reproducibility (p < 0.0001 for magnitude, p < 0.05 for phase at <15 kHz) as compared to EIS sensor alone (p < 0.07 for impedance, p < 0.4 for phase at <15 kHz). Thus, we enhanced topographic and EIS detection of oxLDL-laden plaques via a catheter-based integrated sensor design to enhance clinical assessment for unstable plaque.", "doi": "10.1016/j.snb.2016.04.179", "pmcid": "PMC5068578", "issn": "0925-4005", "publisher": "Elsevier", "publication": "Sensors and Actuators B: Chemical", "publication_date": "2016-11-01", "volume": "235", "pages": "154-161" }, { "id": "authors:rpate-snn12", "collection": "authors", "collection_id": "rpate-snn12", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160217-102637017", "type": "article", "title": "Two-Point Stretchable Electrode Array for Endoluminal Electrochemical Impedance Spectroscopy Measurements of Lipid-Laden Atherosclerotic Plaques", "author": [ { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-R-R-S" }, { "family_name": "Zhang", "given_name": "Xiaoxiao", "clpid": "Zhang-Xiaoxiao" }, { "family_name": "Luo", "given_name": "Yuan", "clpid": "Luo-Yuan" }, { "family_name": "Ma", "given_name": "Teng", "clpid": "Ma-Teng" }, { "family_name": "Jen", "given_name": "Nelson", "clpid": "Jen-Nelson" }, { "family_name": "Ma", "given_name": "Jianguo", "clpid": "Ma-Jianguo" }, { "family_name": "Demer", "given_name": "Linda L.", "clpid": "Demer-L-L" }, { "family_name": "Zhou", "given_name": "Qifa", "clpid": "Zhou-Qifa" }, { "family_name": "Sayre", "given_name": "James W.", "clpid": "Sayre-J-W" }, { "family_name": "Li", "given_name": "Rongsong", "clpid": "Li-Rongsong" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Four-point electrode systems are commonly used for electric impedance measurements of biomaterials and tissues. We introduce a 2-point system to reduce electrode polarization for heterogeneous measurements of vascular wall. Presence of endoluminal oxidized low density lipoprotein (oxLDL) and lipids alters the electrochemical impedance that can be measured by electrochemical impedance spectroscopy (EIS). We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in New Zealand White rabbits. An array of 2 flexible round electrodes, 240 \u00b5m in diameter and separated by 400 \u00b5m was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of the oxLDL-rich lesions developed as a result of high-fat diet-induced hyperlipidemia. Upon balloon inflation, the 2-point electrode array conformed to the arterial wall to allow deep intraplaque penetration via alternating current (AC). The frequency sweep from 10 to 300 kHz generated an increase in capacitance, providing distinct changes in both impedance (\u03a9) and phase (\u03d5) in relation to varying degrees of intraplaque lipid burden in the aorta. Aortic endoluminal EIS measurements were compared with epicardial fat tissue and validated by intravascular ultrasound and immunohistochemistry for plaque lipids and foam cells. Thus, we demonstrate a new approach to quantify endoluminal EIS via a 2-point stretchable electrode strategy.", "doi": "10.1007/s10439-016-1559-9", "pmcid": "PMC5403741", "issn": "0090-6964", "publisher": "Springer", "publication": "Annals of Biomedical Engineering", "publication_date": "2016-09", "series_number": "9", "volume": "44", "issue": "9", "pages": "2695-2706" }, { "id": "authors:98tef-eb097", "collection": "authors", "collection_id": "98tef-eb097", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160225-130847631", "type": "article", "title": "Blood flow modulation of vascular dynamics", "author": [ { "family_name": "Lee", "given_name": "Juhyun", "clpid": "Lee-Juhyun" }, { "family_name": "Packard", "given_name": "Ren\u00e9 R. Sevag", "orcid": "0000-0002-8520-5843", "clpid": "Packard-R-R-S" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Purpose of review: Blood flow is intimately linked with cardiovascular development, repair and dysfunction. The current review will build on the fluid mechanical principle underlying haemodynamic shear forces, mechanotransduction and metabolic effects. \n\nRecent findings: Pulsatile flow produces both time (\u2202\u03c4/\u2202t) and spatial-varying shear stress (\u2202\u03c4/\u2202x) to modulate vascular oxidative stress and inflammatory response with pathophysiological significance to atherosclerosis. The characteristics of haemodynamic shear forces, namely, steady laminar (\u2202\u03c4/\u2202t\u200a=\u200a0), pulsatile shear stress (PSS: unidirectional forward flow) and oscillatory shear stress (bidirectional with a near net 0 forward flow), modulate mechano-signal transduction to influence metabolic effects on vascular endothelial function. Atheroprotective PSS promotes antioxidant, anti-inflammatory and antithrombotic responses, whereas atherogenic oscillatory shear stress induces nicotinamide adenine dinucleotide phosphate oxidase\u2013JNK signalling to increase mitochondrial superoxide production, protein degradation of manganese superoxide dismutase and post-translational protein modifications of LDL particles in the disturbed flow-exposed regions of vasculature. In the era of tissue regeneration, shear stress has been implicated in reactivation of developmental genes, namely, Wnt and Notch signalling, for vascular development and repair. \n\nSummary: Blood flow imparts a dynamic continuum from vascular development to repair. Augmentation of PSS confers atheroprotection and reactivation of developmental signalling pathways for regeneration.", "doi": "10.1097/MOL.0000000000000218", "pmcid": "PMC4626080", "issn": "0957-9672", "publisher": "Lippincott, Williams & Wilkins", "publication": "Current Opinion in Lipidology", "publication_date": "2015-10", "series_number": "5", "volume": "26", "issue": "5", "pages": "376-383" }, { "id": "authors:qred9-5kn97", "collection": "authors", "collection_id": "qred9-5kn97", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150717-091904516", "type": "article", "title": "Flexible and waterproof micro-sensors to uncover zebrafish circadian rhythms: The next generation of cardiac monitoring for drug screening", "author": [ { "family_name": "Zhang", "given_name": "Xiaoxiao", "clpid": "Zhang-Xiaoxiao" }, { "family_name": "Beebe", "given_name": "Tyler", "clpid": "Beebe-T" }, { "family_name": "Jen", "given_name": "Nelson", "clpid": "Jen-Nelson" }, { "family_name": "Lee", "given_name": "Chia-An", "clpid": "Lee-Chia-An" }, { "family_name": "Tai", "given_name": "Yuchong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Flexible electronics are the next generation of sensors for mobile health and implantation. Zebrafish (Danio rerio) is an emergent strategy for pre-clinical drug development and toxicity testing. To address the confounding effects from sedation of fish and removal from the aquatic habitat for micro-electrocardiogram (\u00b5ECG) measurements, we developed waterproof and wearable sensors to uncover the circadian variation in heart rate (HR) and heart rate variability (HRV) ( Massin et al., 2000). The parylene-C based ECG sensor consisted of an ultra-soft silicone integrated jacket designed to wrap around the fish during swimming. The Young's modulus of this silicone jacket matched with the fish surface, and an extended parylene cable connected the underwater chest electrodes with the out-of water electronics. In addition, embedded micro-glass spheres in the silicone effectively reduced the effective density of the jacket to ~1 g cm^(\u22123). These innovations enabled physiological ECG telemetry in the fish's natural habitat without the need for sedation. Furthermore, a set of non-linear signal processing techniques filtered out the breathing and electromagnetic artifacts from the recorded signals. We observed a reduction in mean HR and an increase in HRV over 24 h at 10 dpa, accompanied by QT prolongation as well as diurnal variations, followed by normalization in mean HR and QT intervals at 26 days post ventricular amputation (dpa). We revealed Amiodarone-mediated QTc prolongation, HR reduction and HRV increase otherwise masked by sedation. The novel features of the flexible silicon jacket for \u00b5ECG telemetry unraveled the biological clock and normalization of QT intervals at 26 dpa, providing the first evidence of new physiological phenomena during cardiac injury and repair as well as cardiac drug-mediated aberrant rhythms. Thus, the light weight and waterproof design holds promise to advance the next generation of mobile health and drug discovery.", "doi": "10.1016/j.bios.2015.04.027", "pmcid": "PMC4457543", "issn": "0956-5663", "publisher": "Elsevier", "publication": "Biosensors and Bioelectronics", "publication_date": "2015-09-15", "volume": "71", "pages": "150-157" }, { "id": "authors:2sn1z-9ay67", "collection": "authors", "collection_id": "2sn1z-9ay67", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150420-153441058", "type": "article", "title": "Dry-contact microelectrode membranes for wireless detection of electrical phenotypes in neonatal mouse hearts", "author": [ { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Yu" }, { "family_name": "Cao", "given_name": "Hung", "clpid": "Cao-Hung" }, { "family_name": "Beebe", "given_name": "Tyler", "clpid": "Beebe-T" }, { "family_name": "Zhang", "given_name": "Hemin", "clpid": "Zhang-Hemin" }, { "family_name": "Zhang", "given_name": "Xiaoxiao", "clpid": "Zhang-Xiaoxiao" }, { "family_name": "Chang", "given_name": "Honglong", "clpid": "Chang-Honglong" }, { "family_name": "Scremin", "given_name": "Oscar", "clpid": "Scremin-O" }, { "family_name": "Lien", "given_name": "Ching-Ling", "clpid": "Lien-Ching-Ling" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Continuous monitoring of aberrant electrical rhythms during heart injury and repair requires prolonged data acquisition. We hereby developed a wearable microelectrode membrane that could be adherent to the chest of neonatal mice for in situ wireless recording of electrocardiogram (ECG) signals. The novel dry-contact membrane with a meshed parylene-C pad adjacent to the microelectrodes and the expandable meandrous strips allowed for varying size of the neonates. The performance was evaluated at the system level; specifically, the ECG signals (\u03bcV) acquired from the microelectrodes underwent two-stage amplification, band-pass filtering, and optical data transmission by an infrared Light Emitting Diode (LED) to the data-receiving unit. The circuitry was prototyped on a printed circuit board (PCB), consuming less than 300 \u03bcW, and was completely powered by an inductive coupling link. Distinct P waves, QRS complexes, and T waves of ECG signals were demonstrated from the non-pharmacologically sedated neonates at ~600 beats per minutes. Thus, we demonstrate the feasibility of both real-time and wireless monitoring cardiac rhythms in a neonatal mouse (17\u201320 mm and <1 g) via dry-contact microelectrode membrane; thus, providing a basis for diagnosing aberrant electrical conduction in animal models of cardiac injury and repair.", "doi": "10.1007/s10544-014-9912-y", "issn": "1387-2176", "publisher": "Springer", "publication": "Biomedical Microdevices", "publication_date": "2015-04", "series_number": "2", "volume": "17", "issue": "2", "pages": "Art. No. 40" }, { "id": "authors:2ctm0-act93", "collection": "authors", "collection_id": "2ctm0-act93", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140902-083854858", "type": "article", "title": "Wearable multi-channel microelectrode membranes for elucidating electrophysiological phenotypes of injured myocardium", "author": [ { "family_name": "Cao", "given_name": "Hung", "clpid": "Cao-Hung" }, { "family_name": "Yu", "given_name": "Fei", "clpid": "Yu-Fei" }, { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Yu" }, { "family_name": "Zhang", "given_name": "Xiaoxiao", "clpid": "Zhang-Xiaoxiao" }, { "family_name": "Tai", "given_name": "Joyce", "clpid": "Tai-Joyce" }, { "family_name": "Lee", "given_name": "Juhyun", "clpid": "Lee-Juhyun" }, { "family_name": "Darehzerenski", "given_name": "Ali", "clpid": "Darehzereshki-A" }, { "family_name": "Bersohn", "given_name": "Malcolm", "clpid": "Bersohn-M" }, { "family_name": "Lien", "given_name": "Ching-Ling", "clpid": "Lien-Ching-Ling" }, { "family_name": "Chi", "given_name": "Neil C.", "clpid": "Chi-Neil-C" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Understanding the regenerative capacity of small vertebrate models has provided new insights into the plasticity of injured myocardium. Here, we demonstrate the application of flexible microelectrode arrays (MEAs) in elucidating electrophysiological phenotypes of zebrafish and neonatal mouse models of heart regeneration. The 4-electrode MEA membranes were designed to detect electrical signals in the aquatic environment. They were micro-fabricated to adhere to the non-planar body surface of zebrafish and neonatal mice. The acquired signals were processed to display an electrocardiogram (ECG) with high signal-to-noise-ratios, and were validated via the use of conventional micro-needle electrodes. The 4-channel MEA provided signal stability and spatial resolution, revealing the site-specific electrical injury currents such as ST-depression in response to ventricular cryo-injury. Thus, our polymer-based and wearable MEA membranes provided electrophysiological insights into long-term conduction phenotypes for small vertebral models of heart injury and regeneration with a translational implication for monitoring cardiac patients.", "doi": "10.1039/c4ib00052h", "pmcid": "PMC4124744", "issn": "1757-9694", "publisher": "Royal Society of Chemistry", "publication": "Integrative Biology", "publication_date": "2014-08", "series_number": "8", "volume": "6", "issue": "8", "pages": "789-795" }, { "id": "authors:grxx3-tqk26", "collection": "authors", "collection_id": "grxx3-tqk26", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140425-092221534", "type": "article", "title": "Stretchable electrochemical impedance sensors for intravascular detection of lipid-rich lesions in New Zealand White rabbits", "author": [ { "family_name": "Cao", "given_name": "Hung", "clpid": "Cao-Hung" }, { "family_name": "Yu", "given_name": "Fei", "clpid": "Yu-Fei" }, { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Yu" }, { "family_name": "Scianmarello", "given_name": "Nick", "clpid": "Scianmarello-N" }, { "family_name": "Lee", "given_name": "Juhyun", "clpid": "Lee-Juhyun" }, { "family_name": "Dai", "given_name": "Wangde", "clpid": "Dai-Wangde" }, { "family_name": "Jen", "given_name": "Nelson", "clpid": "Jen-Nelson" }, { "family_name": "Beebe", "given_name": "Tyler", "clpid": "Beebe-T" }, { "family_name": "Li", "given_name": "Rongsong", "clpid": "Li-Rongsong" }, { "family_name": "Ebrahimi", "given_name": "Ramin", "clpid": "Ebrahimi-R" }, { "family_name": "Chang", "given_name": "Donald S.", "clpid": "Chang-Donald-S" }, { "family_name": "Mody", "given_name": "Freny V.", "clpid": "Mody-F-V" }, { "family_name": "Pacella", "given_name": "John", "clpid": "Pacella-J" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Flexible electronics have enabled catheter-based intravascular sensing. However, real-time interrogation of unstable plaque remains an unmet clinical challenge. Here, we demonstrate the feasibility of stretchable electrochemical impedance spectroscopy (EIS) sensors for endoluminal investigations in New Zealand White (NZW) rabbits on diet-induced hyperlipidemia. A parylene C (PAC)-based EIS sensor mounted on the surface of an inflatable silicone balloon affixed to the tip of an interrogating catheter was deployed (1) on the explants of NZW rabbit aorta for detection of lipid-rich atherosclerotic lesions, and (2) on live animals for demonstration of balloon inflation and EIS measurements. An input peak-to-peak AC voltage of 10 mV and sweeping-frequency from 300 kHz to 100 Hz were delivered to the endoluminal sites. Balloon inflation allowed EIS sensors to be in contact with endoluminal surface. In the oxidized low-density-lipoprotein (oxLDL)-rich lesions from explants of fat-fed rabbits, impedance magnitude increased significantly by 1.5-fold across the entire frequency band, and phase shifted ~5\u00b0 at frequencies below 10 kHz. In the lesion-free sites of the normal diet-fed rabbits, impedance magnitude increased by 1.2-fold and phase shifted ~5\u00b0 at frequencies above 30 kHz. Thus, we demonstrate the feasibility of stretchable intravascular EIS sensors for identification of lipid rich lesions, with a translational implication for detecting unstable lesions.", "doi": "10.1016/j.bios.2013.11.059", "issn": "0956-5663", "publisher": "Elsevier", "publication": "Biosensors and Bioelectronics", "publication_date": "2014-04-15", "volume": "54", "pages": "610-616" }, { "id": "authors:27jc1-3s702", "collection": "authors", "collection_id": "27jc1-3s702", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130711-105746475", "type": "article", "title": "Implantable micro-Electrode Array for Long-term ECG Recording in Zebrafish", "author": [ { "family_name": "Cobo", "given_name": "Angelica Maria", "clpid": "Cobo-A-M" }, { "family_name": "Yu", "given_name": "Fei", "clpid": "Yu-Fei" }, { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Yu" }, { "family_name": "Gu", "given_name": "Jie", "clpid": "Gu-Jie" }, { "family_name": "Cao", "given_name": "Hung", "clpid": "Cao-Hung" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "Zebrafish is an emerging model for cardiac electromechanical coupling owing to\nits regenerative capacity after 20% ventricular amputation. We hereby developed a\nmicro-electrode array (MEA) for both long-term and real-time monitoring of\nzebrafish electrocardiogram (ECG) in response to injury and regeneration. The gold\nsputtered 5-lead MEA was formed on a parylene base by micro-fabrication\nprocesses (Fig. 1A). To test the MEA, we sedated Zebrafish in 0.04% tricaine\nmethanesulfonate, followed by a 2-mm-long horizontal incision at 0.5 mm\ncaudally to the heart. The MEA was embedded into the incision site so that the four\nworking electrodes (WE) were close to the heart and the reference electrode (RE)\npositioned on the fish body. The entire device was then secured by medical epoxy\n(Fig. 1B). The ECG signal recording was performed by connecting the MEA to a\ndifferential amplifier and a computer loaded with Labview. The signal was\nprocessed using wavelet transform and thresholding algorithm. The ECG obtained\nfrom the top working electrode is shown in Fig. 1C. The processed data were\ncomparable with ECG recorded by conventional electrodes in terms of signal-tonoise\nratio (SNR) and patterns. The implantable devices remained attached to\nzebrafish for several days, allowing for reliable long-term and multi-site\nrecordings for heart regeneration research.", "issn": "0892-6638", "publisher": "Federation of American Societies for Experimental Biology", "publication": "FASEB Journal", "publication_date": "2013-04", "volume": "27", "pages": "Art. No. 706.9" }, { "id": "authors:6hjfw-wad54", "collection": "authors", "collection_id": "6hjfw-wad54", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120417-091746701", "type": "article", "title": "Flexible microelectrode arrays to interface epicardial electrical signals with intracardial calcium transients in zebrafish hearts", "author": [ { "family_name": "Yu", "given_name": "Fei", "clpid": "Yu-Fei" }, { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Yu" }, { "family_name": "Gu", "given_name": "Jie", "clpid": "Gu-Jie" }, { "family_name": "Quigley", "given_name": "Katherine L.", "clpid": "Quigley-K-L" }, { "family_name": "Chi", "given_name": "Neil C.", "clpid": "Chi-Neil-C" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Hsiai", "given_name": "Tzung K.", "orcid": "0000-0003-1734-0792", "clpid": "Hsiai-Tzung-K" } ], "abstract": "The zebrafish (Danio rerio) is an emerging genetic model for regenerative medicine. In humans, myocardial infarction results in the irreversible loss of cardiomyocytes. However, zebrafish hearts fully regenerate after a 20% ventricular resection, without either scarring or arrhythmias. To study this cardiac regeneration, we developed implantable flexible multi-microelectrode membrane arrays that measure the epicardial electrocardiogram signals of zebrafish in real-time. The microelectrode electrical signals allowed for a high level of both temporal and spatial resolution (~20 \u03bcm), and the signal to noise ratio of the epicardial ECG was comparable to that of surface electrode ECG (7.1 dB vs. 7.4 dB, respectively). Processing and analysis of the signals from the microelectrode array demonstrated distinct ECG signals: namely, atrial conduction (P waves), ventricular contraction (QRS), and ventricular repolarization (QT interval). The electrical signals were in synchrony with optically measured Calcium concentration gradients in terms of d[Ca^(2+)]/dt at both whole heart and tissue levels. These microelectrodes therefore provide a real-time analytical tool for monitoring conduction phenotypes of small vertebral animals with a high temporal and spatial resolution.", "doi": "10.1007/s10544-011-9612-9", "pmcid": "PMC3322508", "issn": "1387-2176", "publisher": "Springer", "publication": "Biomedical Microdevices", "publication_date": "2012-04", "series_number": "2", "volume": "14", "issue": "2", "pages": "357-366" } ]