Wafer-scale fabrication of transducers directly on CMOS dies can minimize device size, increase the throughput and improve uniformity. Doing so with materials sensitive to the conditions encountered during typical microfabrication processes, such as enzymes, remains a challenge.
\r\n\r\nThis thesis investigates aspects of the performance and fabrication processes of electrochemical enzyme-based glucose-sensing transducers, intended for monolithic, implantable wireless sensors. The described work builds on past efforts in the Scherer group and focuses on the transducer fabrication compatible with CMOS wafers.
\r\n\r\nIn the first part, the pre-existing, enzyme-film lift-off patterning process is analyzed. The electrochemical processes of the three glucose oxidase-platinum electrodes are first investigated for the use in sensor diagnostics. The topography of the film is then related to the geometry of the patterns and to the performance of these transducers. Modifications are then made to reduce variation and improve yield. A process to optically profile such structures was also developed to better interpret the non-uniformity from thin film interference.
\r\n\r\nThe second part of this thesis describes the development and processing for plasma etch patterning the enzyme films. This aims to separate the uniformity of the film deposition from the definition of the boundaries, as occurs in many microfabrication processes with less sensitive materials. Strategies were developed that limit the optical, thermal, and chemical degradation of the enzyme activity. The resulting process demonstrated the feasibility of dry etch patterning functional enzyme films without loss of activity. Further, it clarified that improved structural uniformity can yield improved performance uniformity.
\r\n\r\nA final, tangential section investigates a positive tone electron beam lithography process that can be entirely performed in vacuum. Myo-inositol, an electron beam sensitive material, was unexpectedly found and refined. Dry processed negative tone resists avoid pattern collapse during wet development, but analogous positive-tone processes remain elusive. Myo-inositol films, deposited with thermal evaporation, were exposed with electron beams and then developed by subsequent heating. With dry etching and plasma stripping, the full dry process could be implemented in a vacuum cluster tool. While early in development and with challenges remaining, sub 100 nm features were transferred into an underlying thin metal film with this process.
", "doi": "10.7907/b6e8-ws51", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:18542", "collection": "thesis", "collection_id": "18542", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05062026-201719589", "primary_object_url": { "basename": "caltech-thesis_Jiahong.pdf", "content": "final", "filesize": 82851522, "license": "other", "mime_type": "application/pdf", "url": "/18542/4/caltech-thesis_Jiahong.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Multimodal Implantable Bioelectronics", "author": [ { "family_name": "Li", "given_name": "Jiahong", "orcid": "0000-0001-7938-9589", "clpid": "Li-Jiahong" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Zhang", "given_name": "Anqi", "orcid": "0000-0001-6121-8095", "clpid": "Zhang-Anqi" }, { "family_name": "Abu-Mostafa", "given_name": "Yaser S.", "clpid": "Abu-Mostafa-Y-S" }, { "family_name": "Scherer", "given_name": "Axel", "orcid": "0000-0002-2160-9064", "clpid": "Scherer-A" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Advances in bioelectronic technologies are transforming healthcare by enabling continuous monitoring and active modulation of physiological functions. However, conventional electronic materials are mechanically mismatched with soft biological tissues, which can lead to poor conformal contact, unstable signal acquisition, and adverse biological responses during long-term operation. This dissertation addresses these challenges through the development of multimodal bioelectronic systems that integrate soft materials, scalable fabrication strategies, and closed-loop therapeutic functionalities for next-generation health monitoring and intervention.
\r\n\r\nFirst, scalable fabrication strategies are developed to construct flexible and multimodal sensing platforms capable of detecting diverse physiological and environmental signals. Inkjet-printed sensor arrays incorporating nanomaterial-based electrochemical and physical sensors enable simultaneous measurement of temperature, pressure, and chemical biomarkers with high sensitivity and spatial resolution. These sensing systems can be integrated onto soft electronic skins and robotic platforms to provide real-time physicochemical perception in complex environments.
\r\n\r\nSecond, conformal bioelectronic interfaces are engineered to enable stable, long-term interactions with biological tissues. By tailoring material properties and device architectures, these interfaces achieve improved mechanical compatibility with soft tissues, facilitating reliable in vivo signal acquisition and stimulation while minimizing interfacial stress and biological reactions.
\r\n\r\nFinally, closed-loop bioelectronic systems are developed that combine continuous biosensing with responsive therapeutic stimulation. Integrated platforms capable of monitoring metabolic signals and triggering neuromodulation demonstrate the potential for automated therapeutic regulation. These systems highlight the feasibility of real-time physiological monitoring coupled with intelligent intervention.
\r\n\r\nTogether, the materials, device architectures, and system-level strategies presented in this dissertation establish a framework for scalable, conformal, and multifunctional bioelectronics. These technologies provide new opportunities for wearable and implantable systems capable of continuous health monitoring, autonomous therapy, and advanced human\u2013machine interfaces.
", "doi": "10.7907/a4af-sw77", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:18576", "collection": "thesis", "collection_id": "18576", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05142026-143540945", "type": "thesis", "title": "Bioinspired Microfluidic Wearable Sensors for Continuous Sweat Sampling and Metabolic Monitoring", "author": [ { "family_name": "Shin", "given_name": "Soyoung", "orcid": "0009-0002-3210-6427", "clpid": "Shin-Soyoung" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Manthiram", "given_name": "Karthish", "orcid": "0000-0001-9260-3391", "clpid": "Manthiram-Karthish" }, { "family_name": "Dabiri", "given_name": "John O.", "orcid": "0000-0002-6722-9008", "clpid": "Dabiri-J-O" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Wearable sweat sensors have shown strong potential for noninvasive health monitoring by providing access to dynamic biochemical information. However, continuous monitoring of sweat metabolites remains challenging due to low and variable sweat rates, inefficient sampling, and signal distortion arising from evaporation, contamination, and accumulation. These limitations restrict the accuracy and practical deployment of current wearable systems.
\r\n\r\nIn this thesis, we present bioinspired microfluidic strategies to enable continuous sweat sampling, transport, and metabolic analysis under physiologically relevant conditions. We demonstrate how a Janus interface with asymmetric wettability and geometry enables directional vertical transport at the inlet and outlet, while hierarchical microchannel guides flow across the microfluidic and sensing regions. These design elements enable transport even at low sweat rates while preventing stagnation and backflow, resulting in continuous sweat transport without the need for active pumping. This extends the effective sampling window and reduces the number of sweat induction sessions required.
\r\n\r\nThe platform is integrated with electrochemical sensing modules for real-time detection of metabolites and is further extended toward multiplexed sensing of biomarkers relevant to metabolic health. The system is validated through on-body human studies under stimulated conditions, with initial evaluation during exercise-induced sweating. Overall, the works presented here establish design principles for coupling sweat induction, sampling, and sensing, advancing wearable biofluid technologies for continuous and noninvasive metabolic monitoring.
", "doi": "10.7907/kqhx-h885", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:18534", "collection": "thesis", "collection_id": "18534", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05012026-185528615", "type": "thesis", "title": "Smart Bandages for Chronic Wound Sampling, Monitoring, and Management", "author": [ { "family_name": "Wang", "given_name": "Canran", "orcid": "0000-0003-3297-9041", "clpid": "Wang-Canran" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Demirer", "given_name": "Gozde S.", "orcid": "0000-0002-3007-1489", "clpid": "Demirer-G\u00f6zde-S" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Newman", "given_name": "Dianne K.", "orcid": "0000-0003-1647-1918", "clpid": "Newman-D-K" }, { "family_name": "Mazmanian", "given_name": "Sarkis K.", "orcid": "0000-0003-2713-1513", "clpid": "Mazmanian-S-K" }, { "family_name": "Zhang", "given_name": "Anqi", "orcid": "0000-0001-6121-8095", "clpid": "Zhang-Anqi" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Chronic wounds are a major global health issue, incurring staggering economic costs and severely impacting patient well-being. Effective exudate management is crucial, yet current methods fail to balance moisture levels. Real-time analysis of biomarkers like reactive oxygen and nitrogen species could guide treatment, but existing systems lack the capacity required for continuous monitoring. Although wearable electronics have the potential to advance wound care, efficient management and analysis of wound exudate in real time remains challenging owing to its low secretion rate and complex composition. To address these issues, we introduce iCares, a wearable device for wound exudate management and continuous in situ analysis of crucial wound biomarkers. iCares contains a flexible nanoengineered sensor array that measures key reactive species such as NO, H\u2082O\u2082, and O\u2082, along with pH and temperature, providing multiparameter data to inform wound status. The device features a pump-free triad microfluidic modules with a superhydrophobic\u2013superhydrophilic Janus membrane, bioinspired wedge channels, and 3D graded micropillars for efficient unidirectional exudate collection, transport, and refreshing. The sensors demonstrate consistent response and analyte selectivity, validated in wound exudate. Rapidly manufacturable through advanced printing and laser-patterning techniques, iCares seamlessly integrates Bluetooth connectivity and enables scalable, wireless, long-term continuous reactive species monitoring without impeding daily activities. The iCares system was validated through in vivo testing in murine models of infection and fasting, where real-time monitoring was performed. In addition, clinical evaluation was conducted in 20 patients with chronic wounds, as well as in patients monitored before and after surgery, demonstrating the system\u2019s applicability across diverse wound conditions. iCares offers early infection detection and wound classification and outcome prediction using machine learning-enhanced data analysis.", "doi": "10.7907/cq9y-x940", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:18542", "collection": "thesis", "collection_id": "18542", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05062026-201719589", "primary_object_url": { "basename": "caltech-thesis_Jiahong.pdf", "content": "final", "filesize": 82851522, "license": "other", "mime_type": "application/pdf", "url": "/18542/4/caltech-thesis_Jiahong.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Multimodal Implantable Bioelectronics", "author": [ { "family_name": "Li", "given_name": "Jiahong", "orcid": "0000-0001-7938-9589", "clpid": "Li-Jiahong" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Zhang", "given_name": "Anqi", "orcid": "0000-0001-6121-8095", "clpid": "Zhang-Anqi" }, { "family_name": "Abu-Mostafa", "given_name": "Yaser S.", "clpid": "Abu-Mostafa-Y-S" }, { "family_name": "Scherer", "given_name": "Axel", "orcid": "0000-0002-2160-9064", "clpid": "Scherer-A" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Advances in bioelectronic technologies are transforming healthcare by enabling continuous monitoring and active modulation of physiological functions. However, conventional electronic materials are mechanically mismatched with soft biological tissues, which can lead to poor conformal contact, unstable signal acquisition, and adverse biological responses during long-term operation. This dissertation addresses these challenges through the development of multimodal bioelectronic systems that integrate soft materials, scalable fabrication strategies, and closed-loop therapeutic functionalities for next-generation health monitoring and intervention.
\r\n\r\nFirst, scalable fabrication strategies are developed to construct flexible and multimodal sensing platforms capable of detecting diverse physiological and environmental signals. Inkjet-printed sensor arrays incorporating nanomaterial-based electrochemical and physical sensors enable simultaneous measurement of temperature, pressure, and chemical biomarkers with high sensitivity and spatial resolution. These sensing systems can be integrated onto soft electronic skins and robotic platforms to provide real-time physicochemical perception in complex environments.
\r\n\r\nSecond, conformal bioelectronic interfaces are engineered to enable stable, long-term interactions with biological tissues. By tailoring material properties and device architectures, these interfaces achieve improved mechanical compatibility with soft tissues, facilitating reliable in vivo signal acquisition and stimulation while minimizing interfacial stress and biological reactions.
\r\n\r\nFinally, closed-loop bioelectronic systems are developed that combine continuous biosensing with responsive therapeutic stimulation. Integrated platforms capable of monitoring metabolic signals and triggering neuromodulation demonstrate the potential for automated therapeutic regulation. These systems highlight the feasibility of real-time physiological monitoring coupled with intelligent intervention.
\r\n\r\nTogether, the materials, device architectures, and system-level strategies presented in this dissertation establish a framework for scalable, conformal, and multifunctional bioelectronics. These technologies provide new opportunities for wearable and implantable systems capable of continuous health monitoring, autonomous therapy, and advanced human\u2013machine interfaces.
", "doi": "10.7907/a4af-sw77", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:17644", "collection": "thesis", "collection_id": "17644", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08232025-011056106", "primary_object_url": { "basename": "Jilani_MuhammadMusab_Thesis_Revised.pdf", "content": "final", "filesize": 18310052, "license": "other", "mime_type": "application/pdf", "url": "/17644/1/Jilani_MuhammadMusab_Thesis_Revised.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Dynamics of Microfabricated Enzyme Electrodes", "author": [ { "family_name": "Jilani", "given_name": "Muhammad Musab", "orcid": "0009-0008-0739-1418", "clpid": "Jilani-Muhammad-Musab" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "orcid": "0000-0002-2160-9064", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Petillo", "given_name": "Peter A.", "orcid": "0000-0001-7516-2221", "clpid": "Petillo-Peter-A" }, { "family_name": "Scherer", "given_name": "Axel", "orcid": "0000-0002-2160-9064", "clpid": "Scherer-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This work sets out to meet some of the demands created by advancements in glucose oxidase enzyme electrode fabrication techniques. The application of microfabrication techniques to enzyme electrodes has enabled not only greater control over enzyme geometry but also the possibility of monolithic low-power fully wireless implantable biosensors with sensor-on-CMOS construction. Such efforts must be guided by a strong grasp of the theory of diffusion-limited electrochemistry of the products of enzymatically catalyzed reactions. Low power requirements demand a full understanding of sensor turn-on transients and the reduced device size impacts diffusion phenomena and increases the importance of considerations such as oxygen recycling from the reaction at the working electrode. With analytical solutions to the nonlinear differential equations involved not forthcoming, there is a need for sophisticated simulation tools that build upon other efforts in the field and deliver novel capabilities. Such simulation tools must also be complemented by robust, convenient, reproducible, and ideally automated empirical measurement tools to enable the design-test-redesign iteration process to converge quickly to the desired outcomes.
\r\n\r\nThis work presents the development of finite element simulations of enzyme electrodes incorporating full two-substrate enzyme kinetics, a dynamic simulation of the sensor environment, and a full treatment of oxygen recycling at the working electrode. While the simulations presented in this work are carried out with axisymmetric RZ meshes, they are ready for use with full 3D meshes. It additionally presents the development of an automated wafer-scale measurement system enabling the testing of up to twenty sensors in parallel, still on the wafer on which they were fabricated. We present this with the hope that the ability to attack the problem from both sides --- better in silico simulation and faster and more controlled in vitro iteration --- should assist in the development of new sensing technologies.
\r\n\r\nWe also present selected results studied through the use of these tools, in particular the determination of the impact of enzyme geometry on sensor response. These results show the promise of thin-film deposition via spin-coating and vapor deposition crosslinking to enable the kind of fast response-time high-sensitivity electrodes that are needed for achieving monolithic wireless implantable biosensors.
", "doi": "10.7907/5znv-n425", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:17212", "collection": "thesis", "collection_id": "17212", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05082025-224903418", "type": "thesis", "title": "A Path Towards Wearable Affective General Intelligence", "author": [ { "family_name": "Solomon", "given_name": "Samuel Aaron", "orcid": "0000-0001-7199-6659", "clpid": "Solomon-Samuel-Aaron" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Anandkumar", "given_name": "Anima", "orcid": "0000-0002-6974-6797", "clpid": "Anandkumar-A" }, { "family_name": "Perona", "given_name": "Pietro", "orcid": "0000-0002-7583-5809", "clpid": "Perona-P" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Artificial intelligence continues to support our daily decision-making tasks yet remains disconnected from our dynamic emotions driving these behaviors. Wearable technologies can supplement interactions with continuous emotion biofeedback, but existing models struggle to generalize across emerging biomarkers, platforms, and affective expressions. Here, we introduce a meta-analysis into embedding concurrent fragmented biosignals across 15 medical platforms, spanning five bodily locations, within a single profile that enables efficient and generalizable downstream affective analysis. We achieved this through a Lie manifold neural architecture that simultaneously reconstructs over 118,000 missing biometric details in 205 biomarkers and accurately forecasts 100 affective states across cohorts, questionnaires, and activities. We validated this framework across five datasets to propose a new skin-conformal, soft bioelectronic, affective computing platform that demonstrates closed-loop emotion modulation within thermal, audio, and visual interventions delivered through virtual, holographic, and conversational agents. Our framework establishes a new foundational bidirectional architecture for scalable, interpretable, and emotionally intelligent human-computer interactions.", "doi": "10.7907/2s0x-qq57", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:17185", "collection": "thesis", "collection_id": "17185", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04292025-233607669", "primary_object_url": { "basename": "KilYeokyoung2025Thesis.pdf", "content": "final", "filesize": 8595745, "license": "other", "mime_type": "application/pdf", "url": "/17185/1/KilYeokyoung2025Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Engineering and Computational Tools for Salivary Biomedicine", "author": [ { "family_name": "Kil", "given_name": "Yeokyoung (Anne)", "orcid": "0000-0002-1235-7379", "clpid": "Kil-Yeokyoung-Anne" } ], "thesis_advisor": [ { "family_name": "Pachter", "given_name": "Lior S.", "orcid": "0000-0002-9164-6231", "clpid": "Pachter-L" } ], "thesis_committee": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "family_name": "Wyllie", "given_name": "Anne L", "orcid": "0000-0001-6015-0279", "clpid": "Wyllie-A-L" }, { "family_name": "Pachter", "given_name": "Lior S.", "orcid": "0000-0002-9164-6231", "clpid": "Pachter-L" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Saliva is emerging as a powerful biofluid for noninvasive diagnostics, offering a window into human health through its diverse biomolecular composition. This dissertation advances the field of salivary biomedicine by addressing critical challenges in saliva collection, processing, and analysis. First, a comparative analysis of five saliva collection devices highlighted key usability factors, informing the development of SalivaStraw--a novel device designed to improve collection efficiency and minimize leakage. Next, colosseum, a low-cost, open-source fraction collector, was designed and developed to facilitate scalable saliva processing and improve biomarker isolation. Finally, a computational framework leveraging spline regression was applied to longitudinal salivary transcriptomic data, enabling the identification of temporally regulated genes and underscoring saliva\u2019s potential for dynamic health monitoring. Collectively, this work contributes new tools and methodologies that strengthen the foundation of saliva-based diagnostics, broadening its applications in precision medicine and beyond.", "doi": "10.7907/8wdh-5v36", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:16530", "collection": "thesis", "collection_id": "16530", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06292024-045659387", "type": "thesis", "title": "Computational Design of Wearable Chemical Sensors for Personalized Healthcare", "author": [ { "family_name": "Mukasa", "given_name": "Daniel", "orcid": "0000-0001-8379-3648", "clpid": "Mukasa-Daniel" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Schwab", "given_name": "Keith C.", "orcid": "0000-0001-8216-4815", "clpid": "Schwab-K-C" }, { "family_name": "Kornfield", "given_name": "Julia A.", "orcid": "0000-0001-6746-8634", "clpid": "Kornfield-J-A" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Wearable sweat sensors have the potential to revolutionize precision medicine as they can non-invasively collect molecular information closely associated with an individual\u2019s health status. However, the majority of clinically relevant biomarkers cannot be continuously detected in situ using existing wearable approaches. Molecularly imprinted polymers (MIPs) are a promising candidate to address this challenge but haven\u2019t yet gained widespread use due to their complex design and optimization process yielding variable selectivity. Despite their promise, MIPs have historically been known to be exceedingly difficult to optimize. Changes in the monomer/monomers used, polymerization solvent, and crosslinking agent have been shown to change the performance of MIP sensors significantly. This is particularly a concern in sweat-based sensors where the concentration of analytes is very low and chemical diversity is very high as a drop of sweat can contain vitamins, hormones, and amino acids. Consequentially, any sweat based sensor must exhibit high sensitivity (ability to detect low analyte concentrations) and selectivity (ability to distinguish one analyte from another). Computational methods have been introduced to design MIP sensitivity alone, however these prior methods do not cover all aspects essential for using a sensor in a wearable device such as selectivity optimization, detection of non-electroactive analytes, and scalable manufacturing. Here, we introduce a full computational method that allows for high throughput materials discovery for wearable devices. We will describe how to design novel sensing materials with QuantumDock, an automated computational framework for universal MIP development toward wearable applications. Then we delve into further technical details on signal transduction and scalable manufacturing approaches for these wearable devices. We present a number of novel devices designed with these computational methods including a wearable non-invasive phenylalanine monitoring system (the first of its kind), a wearable nutritional tracker \u2018Nutritrek\u2019 capable of monitoring a range of metabolic disorders, and an implantable pharmaceutical drug monitoring system for cancer patients.", "doi": "10.7907/r46k-sw73", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:17069", "collection": "thesis", "collection_id": "17069", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03172025-234845488", "type": "thesis", "title": "Smart Masks for in situ Exhaled Breath Condensate Harvesting and Analysis", "author": [ { "family_name": "Heng", "given_name": "Wenzheng", "orcid": "0009-0009-5278-0727", "clpid": "Heng-Wenzheng" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Zhang", "given_name": "Anqi", "orcid": "0000-0001-6121-8095", "clpid": "Zhang-Anqi" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "With the growing focus on personalized breath health management and early detection of chronic pulmonary diseases, there is an urgent demand for noninvasive wearable technologies capable of continuous breath molecular monitoring during daily activities. Existing respiratory monitoring systems remain limited to physical signal tracking and lack the capability for real-time biochemical analysis of exhaled biomarkers. To address this critical gap, we developed EBCare, a fully integrated smart mask platform for automated in situ analysis of exhaled breath condensate (EBC) biomarkers. The system combines tandem passive cooling strategies (hydrogel evaporation and radiative metamaterials) with bioinspired microfluidics to enable sustainable breath condensation and efficient sample transport under real-world conditions. A multiplexed electrochemical sensor array functionalized with nanoengineered interfaces achieves selective detection of key inflammatory markers (nitrite, pH) and metabolic indicators (ammonia, alcohol), while an embedded wireless module facilitates continuous data transmission. System validation through controlled breathing experiments and field trials demonstrates reliable operation across diverse environments (10-35\u00b0C, 30-80% humidity). Clinical evaluations involving healthy subjects, COPD/asthma patients, and post-COVID cohorts reveal EBCare's ability to dynamically track airway inflammation patterns and metabolic shifts during daily tasks. This wearable EBC analysis platform bridges the gap between laboratory-based breath testing and real-world respiratory monitoring, offering a scalable solution for home-based management of chronic respiratory conditions and post-infection recovery tracking. The modular design and automated operation framework further support future expansion to monitor airborne pathogens and systemic metabolic disease biomarkers through exhaled breath.", "doi": "10.7907/7kzx-ee44", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:16751", "collection": "thesis", "collection_id": "16751", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09222024-230441454", "primary_object_url": { "basename": "HeatherLukas_PhDThesis.pdf", "content": "final", "filesize": 48618608, "license": "other", "mime_type": "application/pdf", "url": "/16751/1/HeatherLukas_PhDThesis.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Engineering Bioaffinity Sensors toward Continuous Electrochemical Biosensing", "author": [ { "family_name": "Lukas", "given_name": "Heather Lauren", "orcid": "0000-0002-8160-9066", "clpid": "Lukas-Heather-Lauren" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The rise of wearable sensing through smartwatches and continuous glucose monitors has made health data more widely accessible. Advances in machine learning have also been pivotal in identifying personalized health insights from biometric data streams. However, continuous biochemical data has been limited in sensor design by the availability of oxidoreductases (e.g., glucose oxidase, lactate dehydrogenase) to a given target. The challenge in engineering diverse oxidoreductase enzymes has led to the exploration of other generalized approaches to continuous electrochemical biosensing. To meet this need, we have explored a variety of bioaffinity sensing schemes using broad bioreceptor classes including antibodies, nucleic acids, and periplasmic binding proteins. We present a case study in electrochemical sensor design utilizing high-affinity antibodies for the rapid diagnosis of COVID-19 disease states. We then investigate the potential of nucleic acid-based electrochemical sensors for continuous sensing with a focus on structure-switching nucleic acid aptamers. The utility of aptamer sensors is demonstrated in the development of a serotonin aptamer sensor embedded in an ingestible capsule for continuous biosensing in the gastrointestinal tract. Applying the principles of electrochemical aptamer-based sensing, we explored the development of an electrochemical protein-based sensor for nicotine, which exploits the hinge-like binding motion of periplasmic binding proteins while also capitalizing on decades of protein evolution and characterization research. With the goal of continuous, noninvasive biochemical sensing, we evaluate the design considerations and translatability of these sensors for wearable sweat analysis. These biosensing techniques may enable the future hardware necessary to expand accessible biomedical data for the next wave of personalized health monitoring.", "doi": "10.7907/2c89-k924", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:16239", "collection": "thesis", "collection_id": "16239", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11062023-050222447", "type": "thesis", "title": "Wearable Sweat Sensors for Disease Monitoring and Management", "author": [ { "family_name": "Tu", "given_name": "Jiaobing", "orcid": "0000-0002-7653-6640", "clpid": "Tu-Jiaobing" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Dabiri", "given_name": "John O.", "orcid": "0000-0002-6722-9008", "clpid": "Dabiri-J-O" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "With the emphasis of healthcare shifting towards prevention and early detection of diseases and monitoring of chronic conditions, there is a growing need for hassle\u2010free telemedicine sensor technologies that can be seamlessly integrated into daily life. While significant progress has been made in the development of wearable sweat and salivary biosensors to meet this need for rapid, real-time collection of physiological information, the majority of current epidermal sensing systems are unable to detect trace-level disease-relevant biomarkers accurately in biofluids and cannot be mass produced. To meet this demand for low-cost, mass-producible mHealth devices for at-home settings, we developed several fully integrated laser-engraved graphene-based biosensors for the detection of low-concentration sweat and saliva analytes including hormones (cortisol) and proteins (C-reactive protein). Several graphene surface engineering strategies are investigated for the sensitive and selective detection of targets. System-level engineering and microfluidic designs are explored to achieve on-demand sweat induction and harvesting under sedentary settings and automated sweat and reagent routing and in situ signal correction and analysis for facile operation on the skin. The utility of these fully integrated flexible mHealth systems is evaluated through multiple human studies involving healthy and various patient subgroups towards stress assessment, as well as the monitoring and management of various chronic conditions including chronic obstructive pulmonary disease, heart failure, and inflammatory bowel diseases. These fully integrated mHealth devices demonstrate a technology that can be easily adapted to monitor a broad spectrum of disease-specific proteins, cytokines, and hormones, thus advancing future applications in personalized disease diagnosis, management, and prevention.", "doi": "10.7907/7jdg-z479", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16297", "collection": "thesis", "collection_id": "16297", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02182024-070645738", "primary_object_url": { "basename": "changhao_xu_2024_thesis.pdf", "content": "final", "filesize": 61292483, "license": "other", "mime_type": "application/pdf", "url": "/16297/1/changhao_xu_2024_thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Electronic Skin in Robotics and Healthcare: Towards Multimodal Sensing and Intelligent Analysis", "author": [ { "family_name": "Xu", "given_name": "Changhao", "orcid": "0000-0002-6817-3341", "clpid": "Xu-Changhao" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Yue", "given_name": "Yisong", "orcid": "0000-0001-9127-1989", "clpid": "Yue-Yisong" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Skin-interfaced electronics is gradually transforming robotic and medical fields by enabling noninvasive and continuous monitoring of physiological and biochemical information. Despite their promise, current wearable technologies face challenges in several disciplines: Physical sensors are prone to motion-induced noise and lack the capability for effective disease detection, while existing wearable biochemical sensors suffer from operational instability in biofluids, limiting their practicality. Conventional electronic skin contains only a limited category of sensors that are not sufficient for practical applications, and conventional data processing methods for these wearables necessitate manual intervention to filter noise and decipher health-related information.
\r\n\r\nThis thesis presents advances in electronic skin within robotics and healthcare, emphasizing multimodal sensing and data analysis through machine intelligence. Chapter 1 introduces the concept of electronic skin, outlining the emerging sensor technologies and a general machine learning pipeline for data processing. Chapter 2 details the development of multimodal physiological and biochemical sensors that enable long-term continuous monitoring with high sensitivity and stability. Chapter 3 explores the application of integrated electronic skin in robotics, prosthetics, and human machine interactions. Chapter 4 showcases practical implementations of integrated electronic skin with robust sensors for wound monitoring and treatment. Chapter 5 highlights the transformative deployment of artificial intelligence in deconvoluting health profiles on mental health. The last chapter, Chapter 6, delves into the challenges and prospects of artificial intelligence-powered electronic skins, offering predictions for the evolution of smart electronic skins. We envision that multimodal sensing and machine intelligence in electronic skin could significantly advance the field of human machine interactions and personalized healthcare.
", "doi": "10.7907/en0a-ep72", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16163", "collection": "thesis", "collection_id": "16163", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08212023-211243186", "type": "thesis", "title": "Additive Manufacturing of 3D Micro-Architected Materials for Device Applications", "author": [ { "family_name": "Deng", "given_name": "Weiting", "orcid": "0000-0003-0984-8027", "clpid": "Deng-Weiting" } ], "thesis_advisor": [ { "family_name": "Greer", "given_name": "Julia R.", "orcid": "0000-0002-9675-1508", "clpid": "Greer-J-R" } ], "thesis_committee": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Faber", "given_name": "Katherine T.", "orcid": "0000-0001-6585-2536", "clpid": "Faber-K-T" }, { "family_name": "Greer", "given_name": "Julia R.", "orcid": "0000-0002-9675-1508", "clpid": "Greer-J-R" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Natural cellular biomaterials typically consist of hard and soft constituent materials that are hierarchically ordered to achieve outstanding mechanical properties, e.g., light weight, mechanical resilience, multi-functionality, etc. Architected materials are a new class of engineered materials with meticulously controlled internal structures that produce properties that differ from or exceed those of their constituent materials. Recent developments in additive manufacturing offer an extraordinary opportunity to rationally design the structure and chemical composition of architected materials to optimize properties and functionalities for a wide range of device applications. Here we first present a framework that combines an artificial intelligence tool and two-photon lithography in order to design and fabricate optimal porous structure with the desired anisotropic mechanical properties. The biomimetic and extremely tunable natural of the structures generated by the framework enables the great potential to be used as the bone scaffold design strategy which meets the requirements of complex anisotropic and heterogeneous mechanical properties of the vivo environment. The designed the architectures are meticulously verified by in situ Nanomechanics. These theory-informed experiments revealed close agreement between experimental data and artificial intelligence-predicted stiffness anisotropy, which opens a pathway for uncovering previous unattainable design space of elasticity vs. 3D architecture mapping in quantifiable and deterministic way. Besides, we explore the structural and material effects of additively manufactured microrobots which is powered by external physical fields for complex therapeutic assignments. The excellent movability and controllability permit the microrobots to be used as minimal invasive instruments for precise application in healthcare. The synergistically optimized microstructures and chemical composition enables the microrobots great potential to be applied to in vivo clinical applications.", "doi": "10.7907/74dt-4442", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16255", "collection": "thesis", "collection_id": "16255", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12052023-185529151", "primary_object_url": { "basename": "Thesis - Jihong Min.pdf", "content": "final", "filesize": 9341850, "license": "other", "mime_type": "application/pdf", "url": "/16255/11/Thesis - Jihong Min.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Innovations in Wireless Bioelectronics for Precision Medicine, from Sustainable Sweat Sensing to Ingestible Gut Monitoring", "author": [ { "family_name": "Min", "given_name": "Jihong", "orcid": "0000-0002-5788-1473", "clpid": "Min-Jihong" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Biofluids, constituting about 60% of the human body, serve as treasure troves of biomarkers such as metabolites and electrolytes, shedding light on individual health conditions. Although blood and urine tests have been routinely utilized, they are limited by their invasive and episodic nature. However, the promise of continuous and noninvasive access to other biofluids like sweat, GI fluids, and saliva paves the way for real-time, onsite health monitoring. This thesis delves into the untapped potential of wearable sensors and noninvasive biofluid analysis, emphasizing the importance of continuous and sustainable monitoring for predictive personal healthcare. Chapter 1 introduces the paradigm of biofluid sensing, focusing on sweat as a key candidate for personalized healthcare applications. Chapter 2 delves into the physiology of sweat glands, highlighting the composition of sweat and the mechanisms behind sweat extraction, either through natural exercise or iontophoretic stimulation. Chapter 3 embarks on the development of innovative sensors designed for detecting clinically pertinent biomarkers in sweat, a step forward in predictive health analytics. In Chapter 4, the spotlight is on system integration, as the study emphasizes the need for miniaturized and reliable wireless sensor devices that ensure minimal discomfort and maximum reliability. Chapters 5 and 6 delve into strategies for sustainably powering wearable devices from energy harvested from body motions and from ambient light, respectively. The final chapter, Chapter 7, extrapolates the aforementioned technologies for the realm of ingestible devices, adapting them for electrochemical sensing in alternate media, primarily gastrointestinal fluids. This allows for enhanced detection of gastrointestinal diseases and a deeper understanding of the intricate gut-brain axis. The ultimate vision of this research is to equip individuals with wearable and ingestible sensors that can seamlessly monitor a broad spectrum of clinically relevant biomarkers. This continuous monitoring, coupled with data analytics, will potentially catalyze a shift from reactive to predictive healthcare, ushering in an era of personalized therapeutic interventions. As wearable sweat and ingestible sensors become mainstream, a confluence of biosensing mechanisms, materials science, and flexible electronics is anticipated enable continuous and unobtrusive acquisition of clinically relevant biomarkers over prolonged periods and large populations, further refining the nexus between health monitoring and precision medicine.", "doi": "10.7907/kcm7-wz71", "publication_date": "2024-06-14", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:15252", "collection": "thesis", "collection_id": "15252", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06012023-001712615", "primary_object_url": { "basename": "Tamborini_Alessio_2023_redacted.pdf", "content": "final", "filesize": 14813490, "license": "other", "mime_type": "application/pdf", "url": "/15252/9/Tamborini_Alessio_2023_redacted.pdf", "version": "v8.0.0" }, "type": "thesis", "title": "A Novel Approach to Cardiac Health Assessment Using a Redesign of the Brachial Cuff Device", "author": [ { "family_name": "Tamborini", "given_name": "Alessio", "orcid": "0000-0001-7651-3505", "clpid": "Tamborini-Alessio" } ], "thesis_advisor": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Dabiri", "given_name": "John O.", "orcid": "0000-0002-6722-9008", "clpid": "Dabiri-J-O" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Current diagnostic methodologies in cardiology face large tradeoffs between procedure invasiveness and diagnostic reliability, ultimately requiring individuals to undergo cardiac catheterization for accurate diagnosis. Given the current societal burden of cardiovascular disease, there is a need for translational medical devices that bridge the accuracy gap between invasive and non-invasive measurements in the assessment of heart health. This thesis focuses on the development and validation of a high-resolution cuff-based system for assessment of central cardiovascular health.
\r\n\r\nTraditional pressure cuffs suffer low signal resolution when applied to non-invasive pulse waveform acquisition. In the first section of this thesis, we develop a cuff-based device with a pneumatic filter for high fidelity pulse waveform acquisition. This work discusses the design and functionality of the cuff-device, and investigates the repeatability of the cuff-based measurement. Furthermore, the derived mathematical model of the pneumatic filter is shown to have an equivalent behavior to an electrical low-pass filter inclusive of a time constant and a frequency response curve.
\r\n\r\nThe accuracy and reliability of the pulse waveform features from the cuff-device are evaluated with human study data. Firstly, an IRB study is performed at Caltech on a young and healthy population showing that the cuff-device data lies within a narrow distribution indicative of the healthy nature of the population. Secondly, data from a clinical trial collecting simultaneous invasive catheter, cuff, and ECG is analyzed. The first analysis compared waveform parameters from the cuff in sSBP hold pressure with simultaneous aortic catheter, showing strong correlations between the two measurement modalities for both magnitude and fluctuations thereof.
\r\n\r\nLastly, this work investigated the relationship between cuff-based parameters and left ventricular functions. We introduced a cuff-based method for extraction of the pressure-sound waveform, a pressure based surrogate of heart sounds. The results from this analysis showed that the pressure-sound features correlate with the strength of the left ventricular isovolumetric contraction and relaxation. Other important results from this work demonstrated the correlations between the heart-lung interactions in the left ventricle and cuff parameters: breathing fluctuations proportionally affect LV pressures and cuff sSBP waveform parameters. Overall these results support the accuracy and reliability of a cuff-based device for central cardiovascular health assessments.
", "doi": "10.7907/rp22-me93", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:15215", "collection": "thesis", "collection_id": "15215", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05272023-093432414", "primary_object_url": { "basename": "MPAbundo_05272023.pdf", "content": "final", "filesize": 11712317, "license": "other", "mime_type": "application/pdf", "url": "/15215/1/MPAbundo_05272023.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Ultrasound Controlled Drug Delivery by Acoustically Switchable Hydrogels", "author": [ { "family_name": "Abundo", "given_name": "Maria Paulene Bernal", "orcid": "0000-0002-5122-6937", "clpid": "Abundo-Maria-Paulene-Bernal" } ], "thesis_advisor": [ { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "thesis_committee": [ { "family_name": "Brady", "given_name": "John F.", "orcid": "0000-0001-5817-9128", "clpid": "Brady-J-F" }, { "family_name": "Daraio", "given_name": "Chiara", "orcid": "0000-0001-5296-4440", "clpid": "Daraio-C" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Not only is ultrasound widely used as a diagnostic imaging modality, it can also be focused into deep tissues to perform non-invasive actuation of cells, implants and delivery vehicles and other biological targets. With the addition of gas vesicles (GV), generic hydrogel materials gain the ability to communicate with ultrasound, equipping them with in vivo tracking, targeting and actuation capabilities to safely transport biomolecular cargo. This is possible as GVs function simultaneously as ultrasound contrast agents and steric blockers that can be \"erased\" by an increase in ultrasound pressure to trigger a rapid outflow diffusion of the payload from within the material. We evaluate this concept through in vitro measurements of ultrasound-modulated diffusion and drug release and targeted in vivo release in the lower gastrointestinal tract. Then we demonstrate the use of orally administered hydrogel particles to deliver etanercept in the duodenum to treat gastrointestinal inflammation in a rat model of colitis. Finally, we explore new directions and applications of GV-hydrogel systems, showcasing their potential for deployment in a wide range of biomedical applications.
", "doi": "10.7907/5rr6-q625", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:15216", "collection": "thesis", "collection_id": "15216", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05272023-161541041", "primary_object_url": { "basename": "2023-05-26_Xiong_Thesis.pdf", "content": "final", "filesize": 68354418, "license": "other", "mime_type": "application/pdf", "url": "/15216/1/2023-05-26_Xiong_Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Expanding the Toolbox for Thermal Control of E. coli: Cold-Activated Transcription with Applications in Temperature Self-Regulation", "author": [ { "family_name": "Xiong", "given_name": "Lealia Li", "orcid": "0000-0001-7636-5936", "clpid": "Xiong-Lealia-Li" } ], "thesis_advisor": [ { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Kornfield", "given_name": "Julia A.", "orcid": "0000-0001-6746-8634", "clpid": "Kornfield-J-A" } ], "thesis_committee": [ { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Kornfield", "given_name": "Julia A.", "orcid": "0000-0001-6746-8634", "clpid": "Kornfield-J-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Temperature can be used to control engineered E. coli \u2014 for example, the living component of an engineered living material (ELM) - through the use of thermolabile transcription factors. Sharp induction of gene expression with heat has been established using these bacteria- and phage-derived proteins. Here, we expand the toolbox for thermal control of E. coli through both direct cold-induced gene expression and through the construction of genetic circuits to invert heat-induced gene expression.
\r\n\r\nWe accomplish direct induction at low temperatures through the use of temperature-sensitive mutants of Lambda repressor as transcriptional activators. In addition, we show that a temperature-sensitive mutant of Lambda repressor can serve as an activator and a repressor of different genes simultaneously in one genetic circuit, leading to opposite thermal responses and serving as a temperature switch.
\r\n\r\nNext, we demonstrate inversion of a temperature-sensitive repressor using a temperature insensitive repressor. We apply this multicomponent switch to engineer a temperature self-regulation circuit for E. coli-based ELMs. Seasonal variation in ambient temperature presents a challenge in deploying ELMs outside of a laboratory environment, because E. coli growth rate is impaired both below and above 37\u00b0C. Our construct enables E. coli to produce a light-absorptive pigment in response to environmental temperature below 36\u00b0C with the goal of allowing the cells to absorb sunlight and locally warm to their optimal growth temperature. We demonstrate the efficacy of our pigment temperature switch in a model flat ELM growing at 32\u00b0C and 42\u00b0C in a home-built illuminated growth chamber. Below 36\u00b0C, our engineered E. coli increase in pigmentation, causing an increase in sample temperature and growth rate above non-pigmented bacteria. On the other hand, above 36\u00b0C, they decrease in pigmentation, protecting their growth compared to bacteria with temperature- independent high pigmentation. Integrating our temperature homeostasis circuit into an ELM has the potential to improve ELM performance by optimizing growth and protein production in the face of seasonal temperature changes.
", "doi": "10.7907/5w59-0667", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:15102", "collection": "thesis", "collection_id": "15102", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02082023-162753604", "primary_object_url": { "basename": "Thesis-YiranYang-final.pdf", "content": "final", "filesize": 31535477, "license": "other", "mime_type": "application/pdf", "url": "/15102/1/Thesis-YiranYang-final.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Laser-Engraved Wearable Sweat Sensor for Metabolic Monitoring", "author": [ { "family_name": "Yang", "given_name": "Yiran (Isabella)", "orcid": "0000-0001-8770-8746", "clpid": "Yang-Yiran-Isabella" } ], "thesis_advisor": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Wearable sensors have shown great potential in health diagnostics and monitoring. Continuous monitoring of metabolites in sweat could potentially offer great insight into a person\u2019s health, but current sweat sensing technology faces challenges in different realms: The sensing strategies are limited and there is a need to achieve high sensitivity for low-concentration targets and widen the detection spectrum of chemical targets. The lack of efficient sweat sampling creates inaccurate sensing results from sweat mixing with skin contaminants or sensing byproducts. Moreover, the lack of evaluation of sweat metabolites with respect to relevant clinical conditions and the lack of scalable fabrication technique pose hurdles in the eventual applications of non-invasive sweat monitoring. In this thesis, efforts advancing progress in these fronts are presented. Chapter 1 establishes a brief topical overview of the sweat-sensing background. In Chapter 2, we demonstrate how to utilize laser-engraving technique to achieve high-performance graphene sensors for electroactive metabolite sensing and vital signs detection. Chapter 3 describes subsequent efforts built on laser-engraved graphene sensors to improve sensing selectivity and widen the detection spectrum to detect non-electroactive targets in sweat. In Chapter 4, design and performance of our laser-engraved microfluidics are described and shown to improve sweat sampling in both exercise-induced and iontophoresis-induced sweating individuals. Chapter 5 presents our endeavors in evaluating sweat biomarkers with clinical conditions in pilot studies involving individuals with gout and metabolic syndrome. In total, the works summarized here expand biology, chemistry, material science, and mechanical engineering, and could potentially facilitate future applications in precision nutrition.", "doi": "10.7907/5yfm-tt16", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:16057", "collection": "thesis", "collection_id": "16057", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06022023-145117270", "primary_object_url": { "basename": "Thesis_Caltech_Thesis_LaTeX_Template__with_logo____Amylynn_Chen (1).pdf", "content": "final", "filesize": 15428051, "license": "other", "mime_type": "application/pdf", "url": "/16057/1/Thesis_Caltech_Thesis_LaTeX_Template__with_logo____Amylynn_Chen (1).pdf", "version": "v4.0.0" }, "type": "thesis", "title": "3D in situ Chemical Synthesis: Additive Manufacturing of Functional Polymeric Materials via Vat Photo-polymerization", "author": [ { "family_name": "Chen", "given_name": "Amylynn C.", "orcid": "0000-0002-8112-5862", "clpid": "Chen-Amylynn-C" } ], "thesis_advisor": [ { "family_name": "Greer", "given_name": "Julia R.", "orcid": "0000-0002-9675-1508", "clpid": "Greer-J-R" } ], "thesis_committee": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Faber", "given_name": "Katherine T.", "orcid": "0000-0001-6585-2536", "clpid": "Faber-K-T" }, { "family_name": "Wang", "given_name": "Zhen-Gang", "orcid": "0000-0002-3361-6114", "clpid": "Wang-Zhen-Gang" }, { "family_name": "Greer", "given_name": "Julia R.", "orcid": "0000-0002-9675-1508", "clpid": "Greer-J-R" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "As additively manufacturing gains popularity in rapid-prototyping, manufacturing and customized production, there is a continuous demand in seeking for new materials with advanced functionalities to satisfy the wide range of applications in aerospace, construction, optics, actuation, dentistry, biomedical practices and even food industry. Vat photopolymerization (VP), a light-enabled AM technique, is particularly promising due to its ability to achieve good surface quality, high resolution, and large volumetric throughput. The vast majority of materials obtained by VP are covalently-crosslinked thermosets with nondegradable carbon backbones. This highly crosslinked molecular structure gives rise to stiff and brittle materials, limiting the structural functionality in desired applications.
\r\n\r\nThis thesis explores a variety of molecular structures for new VP photopolymers: a) dynamically-crosslinked compliant polymer, b) interpenetrating network (IPN) hydrogel, and c) covalently-crosslinked polymer with labile group (ex. ester) insertion to polymer backbone. With the dynamic crosslinking system, we demonstrate tunable mechanical behaviors of the metal-coordinated supramolecular polymers. These materials display a range of failure strain of 450% - 940% and ultimate tensile strength of 12.4 - 2.2 MPa with varying resin compositions. To incorporate multifunctionality, we design thermoresponsive IPN hydrogels by fabricating a hydrophilic host polymer network via VP and a subsequent formation a thermoresponsive 2nd network (poly(N-Isopropylacrylamide)). The architected IPNs consistently display strong polymer-liquid phase separation behavior and a tunable water release behavior with volumetric shrinkage between 30% and 70% upon heating at 50oC. Finally, to promote the degradability of the acylate-based photoresin, we demonstrated successful incorporation for ester functional groups into the polymer backbone via radical ring opening polymerization of cyclic ketene acetals. The obtained polymer undergoes 84% mass loss within 7 hours under hydrolytic degradation condition. Overall, we demonstrated VP as a powerful technique to achieve one-pot synthesis and fabrication of functional materials. Our explorations on the development of degradable photopolymers, thermoresponsive double-network hydrogels, and metal-coordinated supramolecular polymers provide valuable insights into the impact of resin formulation on mechanical properties. From analyzing the molecular weight of 3DP materials to finetuning of phase separation behavior and degradability, we demonstrate that VP provides a new platform to inspire advanced photoresin design strategies for desirable mechanical performance.
", "doi": "10.7907/ca3e-rc06", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:13621", "collection": "thesis", "collection_id": "13621", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01152020-143207091", "primary_object_url": { "basename": "TzuChiehChou2022thesis.pdf", "content": "final", "filesize": 24486732, "license": "other", "mime_type": "application/pdf", "url": "/13621/2/TzuChiehChou2022thesis.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Wearable Inductive Damping Sensors for Skin Edema Quantification", "author": [ { "family_name": "Chou", "given_name": "Tzu-Chieh", "orcid": "0000-0002-6074-8286", "clpid": "Chou-Tzu-Chieh" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "orcid": "0000-0003-3003-7042", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The electrical conductivity of human organs is closely related to the physiological or pathological changes occurring within the organ. For example, metastatic liver tumors significantly increase electrical conductivity compared to healthy liver tissues over a wide frequency range. Therefore, knowing when and where these conductivity changes happen within an organ is highly valuable for disease monitoring.
\r\n \r\nSkin is the largest human organ by surface area, and under its large surface, there are numerous tiny blood and lymphatic vessels that circulate body fluid and dissipate heat. Therefore, it contains critical information about systemic circulation. Diseases such as congestive heart failure, acute renal injury, and liver failure disturb the systemic circulation and allow extra interstitial fluid to accumulate in the form of peripheral skin edema. As the interstitial fluid is highly conductive, the overall skin conductivity significantly increases when edema occurs.
\r\n\r\nConsequently, quantification of skin edema allows us to track the progression of these diseases and is the main goal to pursue in this study. The current clinical standard uses a 0-to-4 grade system to quantify the severity of edema based on how the skin responds to a pressing force. However, it requires in-person examination and has relatively large inter-examiner variations, making it less suitable for real-time edema monitoring.
\r\n\r\nTo solve the unmet need to quantify edema in real-time, I present a skin edema model that relates skin conductivity to the interstitial fluid volume fraction. The latter is used to quantify the severity of edema. Furthermore, I developed a wearable coil sensor that provides accurate real-time conductivity measurements on subcutis, a significant portion of the skin where edema typically occurs. The coil sensor uses alternating magnetic fields to induce eddy currents in the skin and measures the skin conductivity as a function of coil resistance change. The experimental results suggested that when grade-1 edema occurs, the subcutis conductivity increases from the average value of 0.09 S/m to 0.25 S/m. This change corresponds to an increase of interstitial volume fraction from 10% to 20% in the subcutis. These quantitative results are consistent with finite element simulations and allow direct comparison with ultrasonography measurements. Due to its high accuracy and portability, the proposed wearable sensor opens a new possibility for continuous monitoring of skin edema.
", "doi": "10.7907/q77f-me73", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14635", "collection": "thesis", "collection_id": "14635", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05272022-085102678", "primary_object_url": { "basename": "Thesis FINAL - Vincenzo Costanza.pdf", "content": "final", "filesize": 74433912, "license": "other", "mime_type": "application/pdf", "url": "/14635/1/Thesis FINAL - Vincenzo Costanza.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Thermally Responsive Polymers for Wearable Calorimeters", "author": [ { "family_name": "Costanza", "given_name": "Vincenzo", "orcid": "0000-0002-2409-0632", "clpid": "Costanza-Vincenzo" } ], "thesis_advisor": [ { "family_name": "Daraio", "given_name": "Chiara", "orcid": "0000-0001-5296-4440", "clpid": "Daraio-C" } ], "thesis_committee": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Daraio", "given_name": "Chiara", "orcid": "0000-0001-5296-4440", "clpid": "Daraio-C" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The measurement of the body core temperature (BCT) can provide insightful health information spanning from hypothermia and heat stroke to inflammations and infections. In addition, the continuous monitoring of the BCT can unlock new possibilities for people\u2019s well-being such counting of burnt calories, prediction of the ovulation period in the female population, and for the assessment of mental health issues. However, the integration of a BCT sensor in wearable devices is extremely challenging, since standard methods cannot combine minimal invasiveness with high measurement accuracy. Dual heat flux (DHF) thermometry is a novel technique that allows the precise estimation of BCT from the measurement of skin temperature. Nevertheless, the limited precision of currently available temperature sensors has not favored the wide spread of devices based on this architecture. In this thesis, we present the fabrication of a fully wearable DHF thermometer realized by integrating new polymers with a remarkable temperature sensitivity. In these particular polymers, an increase in temperature results in a change of the ionic conductivity. In the first part of this work, we focus on the understanding of the ion transport mechanism in these polymers and, in particular, on the nature of the interaction between the functional groups present on the polymer backbone and the conducting species (i.e. metal cations and water molecules). We show that the ion\u2019s coordinating environment is the key to make these materials highly sensitive to temperature. The second part of the thesis tackles the fabrication of a BCT sensor, integrating these temperature responsive polymers in an ultrathin DHF thermometer. Building on the understanding of the nature of the temperature response, we optimize the polymer\u2019s composition to obtain a thermal sensitivity that allows a good precision when measuring the BCT. Finally, we characterize the performance of the fabricated DHF thermometer in different conditions, assessing the sensor\u2019s accuracy and response time.", "doi": "10.7907/0hf9-8m62", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14399", "collection": "thesis", "collection_id": "14399", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10172021-215439860", "primary_object_url": { "basename": "Dobreva_Tatyana_2021_v7.pdf", "content": "final", "filesize": 10892340, "license": "other", "mime_type": "application/pdf", "url": "/14399/1/Dobreva_Tatyana_2021_v7.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Engineering Tools to Probe and Manipulate the Immune System at Single-Cell Resolution", "author": [ { "family_name": "Dobreva", "given_name": "Tatyana", "orcid": "0000-0002-2625-8873", "clpid": "Dobreva-Tatyana" } ], "thesis_advisor": [ { "family_name": "Thomson", "given_name": "Matthew", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" } ], "thesis_committee": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" }, { "family_name": "Thomson", "given_name": "Matthew", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "My thesis focuses on developing experimental and computational tools to probe and manipulate cellular transcriptomes in the context of human health and disease. Chapter 1 and 2 focus on published work where we leverage single-cell RNA sequencing (scRNA-seq) to understand human immune variability, characterize cell-type specific biases of multiple viral variants within an animal, and assess temporal immune response in the brain to delivery of genetic cargo via an adeno-associated virus (AAV). Chapter 3 and 4 present progress I have made on tools for exporting RNA extracellularly and engineering of a transcription factor for modulating macrophage state.
\r\n\r\nFor probing cellular transcriptome states, we have developed a platform using multiplexed single-cell sequencing and out-of-clinic capillary blood extraction to understand temporal and inter-individual variability of gene expression within immune cell types. Our platform enables simplified, cost-effective profiling of the human immune system across subjects and time at single-cell resolution. To demonstrate the power of our platform, we performed a three day time-of-day study of four healthy individuals, generating gene expression data for 24,087 cells across 22 samples. We detected genes with cell type-specific time-of-day expression and identified robust genes and pathways particular to each individual, all of which could have been missed if analyzed with bulk RNA-sequencing. Also, using scRNA-seq, we have developed a method to screen and characterize cellular tropism of multiple AAV variants. Additionally, I have looked at AAV-mediated transcriptomic changes in animals injected with AAV-PHP.eB three days and twenty-five days post-injection. I have found that there is an upregulation of genes involved in p53 signaling in endothelial cells three days post-injection.
\r\n\r\nIn the context of manipulating cellular transcriptomic states, I demonstrate that a fusion between RNA targeting enzyme, dCas13, and capsid-forming neuronal protein, Arc, is able to form a capsid-like structure capable of encapsulating RNA. I also present methods and preliminary data for tuning macrophage states through mutations in transcription factor EB (TFEB) using scRNA-seq as a readout.
", "doi": "10.7907/n3rs-ft69", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14506", "collection": "thesis", "collection_id": "14506", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02182022-230421298", "type": "thesis", "title": "Nanophotonic Application to Biomedical Devices", "author": [ { "family_name": "Hanania", "given_name": "Haeri Park", "orcid": "0000-0002-2206-5732", "clpid": "Hanania-Haeri-Park" } ], "thesis_advisor": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "thesis_committee": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Scherer", "given_name": "Axel", "orcid": "0000-0002-2160-9064", "clpid": "Scherer-A" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "orcid": "0000-0003-3003-7042", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Choo", "given_name": "Hyuck", "orcid": "0000-0002-8903-7939", "clpid": "Choo-Hyuck" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Nanophotonics is the study of interactions between nanoscale structures and light. It has greatly expanded the fields of application over the past decades, taking advantage of the advancement in MEMS technology. The most common nanophotonic structures consist of either dielectrics, metals, or both. When a nanophotonic structure contains metals, it is considered as a plasmonic structure. Plasmonics is a field of light-metal interactions. Due to the negative permittivity of metals, the electromagnetic energy of light is focused at the metal-dielectric interface and creates plasmons-a collective motion of electrons in the conduction band of metals. By shaping metals into different structures to achieve a desired performance, plasmonics have been successfully applied to many fields including photovoltaics, spectroscopy, and biomedical devices.
\r\n\r\nThis thesis provides 3 different applications of biomedical devices in which nanophotonics-articularly plasmonics-was applied. Chapter 1 discusses the application of nanophotonics to molecular sensing. In this chapter, an open-top, tapered waveguide that serves as a 3-dimensional plasmon cavity is demonstrated and achieves a near or single molecular detection. Chapter 2 discusses the application of nanophotonics to an implantable intraocular pressure sensor. In this chapter, an array of gold nanodots are introduced on a flexible membrane to optimize the performance of the sensor. Chapter 3 discusses the application of nanophotonics to angle-and-polarization independent pressure or strain sensing, which reduces the need for precise alignment or a trained technician, and therefore can be easily applied to moving subjects in diverse environments. Inspired by the geometry and optical principles of butterfly corneas, an array of gold paraboloids is designed to support a surface plasmon resonance that is angle-and-polarization independent. This array is integrated onto a hermetically sealed cavity with a flexible membrane and enables angle-and-polarization independent pressure/strain sensing.
", "doi": "10.7907/tzpw-pt75", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14454", "collection": "thesis", "collection_id": "14454", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12202021-172349636", "primary_object_url": { "basename": "Zi-Yu_Huang_Thesis.pdf", "content": "final", "filesize": 198300068, "license": "other", "mime_type": "application/pdf", "url": "/14454/1/Zi-Yu_Huang_Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Electrical Impedance Spectroscopy-Derived 3D Conductivity Tomography for Atherosclerosis Detection", "author": [ { "family_name": "Huang", "given_name": "Zi-Yu", "orcid": "0000-0001-5998-3097", "clpid": "Huang-Zi-Yu" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Electrical impedance tomography (EIT) utilizes voltage/current data measured from the surface of interest to reconstruct the electrical conductivity distribution. This results in a noninvasive medical imaging procedure with many applications. Some examples would be: lung ventilation monitoring, breast cancer detection, and fatty liver detection. Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cardiometabolic diseases in overweight individuals. The gold standard for NAFLD diagnosis is a liver biopsy which is a risky and invasive procedure. A non-invasive and cost effective method to detect fatty liver is an important unmet clinical need. Due to the distinct electrical properties of fatty tissue versus normal tissue, EIT can be applied to detect the fat infiltrate in the liver. We conducted EIT measurements and reconstructions on 19 subjects where the fat infiltrate was validated by MRI proton-density fat fraction (PDFF). The liver EIT conductivity was shown to be inversely correlated with MRI PDFF, demonstrating the ability of EIT to detect fatty infiltrate in the liver.
\r\n\r\nThis thesis also extends the EIT reconstruction to detect atherosclerosis, which is a build-up of fatty tissue in the arteries (plaque). Some plaques are prone to rupture and the current gold standard has a false negative rate of 20 % when distinguishing between vulnerable plaque and stable plaque. We sought to use EIT to detect the fatty content (mainly oxidize LDL) inside these vulnerable plaques. Therefore, the reconstruction method was modified into an outward setting that can measure from the inner surface of interest. Ex vivo experiments have demonstrated the ability to detect the location of fatty tissue in swine aorta. This technique has the potential to detect vulnerable plaque. However, the dimension of the device and the required electrode number limits the application from in vivo animal artery experiments.
\r\n\r\nFinally EIS-derived EIT, a new method we proposed, utilizes impedance values at a fixed frequency to solve for the conductivity distribution. This approach circumvents the mathematically ill-posed problem found when performing traditional EIT methods. We designed a 6-point EIS electrode array that was circumferentially configured to a balloon catheter and deployed in Yorkshire mini-pigs with induced stenosis in the right carotid artery. The EIS spectra demonstrated an elevated impedance in the right carotid arteries and the EIS-derived EIT mappings were reconstructed. The low conductivity regions in the EIS-derived EIT mappings were correlated with the positive E06 immunostaining for oxLDL-laden regions. Thus, we establish the capability of 3D EIS-derived EIT to detect oxLDL-laden arterial walls with translational implication to predict metabolically active plaques prone to acute coronary syndromes.
", "doi": "10.7907/n0md-h379", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14055", "collection": "thesis", "collection_id": "14055", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01132021-224837966", "type": "thesis", "title": "Eddy Current Damping Stroke Sensor", "author": [ { "family_name": "Shahrestani", "given_name": "Shane Shayan", "orcid": "0000-0001-7561-4590", "clpid": "Shahrestani-Shane-Shayan" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Zada", "given_name": "Gabriel", "clpid": "Zada-Gabriel" } ], "local_group": [ { "literal": "3MT Competition (Caltech)" }, { "literal": "div_eng" } ], "abstract": "Existing paradigms for stroke diagnosis typically involve computed tomography (CT) or magnetic resonance (MR) imaging to classify ischemic versus hemorrhagic stroke variants, as treatment for these subtypes varies widely. Delays in diagnosis and issues related to transport of unstable patients may worsen neurological status. As such, translational medical devices that accelerate time to treatment in the field or hospital setting have the potential to lower morbidity and mortality in stroke patients. We demonstrated feasibility of rapid and accurate bedside stroke detection using a novel, handheld portable eddy current damping imaging device in laboratory benchtop as well as live human clinical ischemic and hemorrhagic stroke settings. We show that diagnosis of stroke may potentially be reduced from several hours to minutes, with additional spatial localization of intracranial hemorrhage, thereby rapidly guiding time-sensitive medical decisions for clinical intervention such as tissue plasminogen activator (tPA). The sensor additionally detects ischemic and hemorrhagic lesions located deep inside the brain, and its range can be selectively tuned during sensor design and fabrication.
", "doi": "10.7907/zxdh-ej95", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14048", "collection": "thesis", "collection_id": "14048", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01082021-041336404", "type": "thesis", "title": "Stimuli Responsive Micro-Architected Materials", "author": [ { "family_name": "Elliott", "given_name": "Luizetta Vadimovna", "orcid": "0000-0002-6411-0239", "clpid": "Elliott-Luizetta-Vadimovna" } ], "thesis_advisor": [ { "family_name": "Greer", "given_name": "Julia R.", "orcid": "0000-0002-9675-1508", "clpid": "Greer-J-R" } ], "thesis_committee": [ { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Daraio", "given_name": "Chiara", "orcid": "0000-0001-5296-4440", "clpid": "Daraio-C" }, { "family_name": "Greer", "given_name": "Julia R.", "orcid": "0000-0002-9675-1508", "clpid": "Greer-J-R" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Shape memory polymers (SMPs) respond to heat by generating programmable movement useful in devices that require substantial deformation and operate at transient temperatures, including stents, embolization coils, and robotic grippers. Transitioning these materials to the microscale can result in expanded potential applications, such as clot removal from retinal vasculature, neural probe delivery, and responsive metamaterials. To achieve these goals, shape transformation must occur in SMPs with complex 3D geometries and nanoscale features.
\r\n\r\nThis thesis describes the synthesis and sculpting of a benzyl methacrylate-based SMP into 3D structures with <800nm characteristic critical dimensions via two photon lithography. The glass transition based shape memory mechanism of these materials is explored through dynamic nanomechanical analysis of 8\u00b5m-diameter cylindrical pillars, which revealed the initiation of a tunable glass transition at 60\u00b0C not present in highly crosslinked materials. Shape memory programming of the characterized pillars as well as complex 3D architectures, including flowers with 500nm thick petals and cubic lattices with 2.5\u00b5m unit cells and overall dimensions of 4.5\u00b5m x 4.5\u00b5m x 10\u00b5m, demonstrated an 86 +/- 4% characteristic shape recovery ratio. These results reveal a pathway towards SMP devices with nanoscale features and arbitrary 3D geometries changing shape in response to temperature.
\r\n\r\nThis thesis subsequently focuses on a particular potential application for such materials: neural probes designed for deployment in primate brains. Architected shape memory structures have the potential to create favorable long-term recording environments through softening triggered by biological conditions, deployment to beyond tissue damage during initial electrode positioning, and architectural features designed for optimal scaffold-tissue interactions. This thesis addresses one of the barriers to the deployment of such structures: the high loading during centimeter scale insertions required for primate brain targeting is incompatible with buckling free-insertion of low stiffness and/or cross sectional area probes required for minimizing the foreign body response.
\r\n\r\nLamb brain tissue model experiments with 280\u00b5m diameter platinum coated carbon fiber probes demonstrate that 59+/- 3% of the work during 3cm probe insertion is attributable to friction, suggesting that friction reduction is a favorable approach to load minimization. A phosphorylcholine-based ~100nm low friction coating is used to reduce the shear stress at the probe-brain interface by 20+/-7 %, demonstrating a facile method for friction reduction that has minimal impacts on probe cross sectional area. Surgical validation of probe insertion in a porcine head model reveals that these probes are suitable for whole brain penetration of brains at the primate scale (~10\u00b2g). These results show that loading requirements during whole brain penetration can be reduced through addressing the contribution of friction and introduce a viable vehicle for recording electrode delivery to large scale brains.
\r\n\r\nIn summary, this thesis provides the foundation for developing stimuli responsive microscale devices and materials and, in the case of deep brain neural recording, the building blocks for the design of an integrated shape memory/ low friction carbon fiber electrode delivery device. Future research on the scalable fabrication of architected shape memory polymers could enable the widespread application of such materials.
", "doi": "10.7907/bnfv-9c75", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:13980", "collection": "thesis", "collection_id": "13980", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10182020-133113205", "type": "thesis", "title": "Therapeutic Microparticles and Biolistic Drug-Delivery to the Cornea", "author": [ { "family_name": "Laccetti", "given_name": "Benjamin Joseph", "orcid": "0000-0002-0399-1204", "clpid": "Laccetti-Benjamin-Joseph" } ], "thesis_advisor": [ { "family_name": "Kornfield", "given_name": "Julia A.", "orcid": "0000-0001-6746-8634", "clpid": "Kornfield-J-A" } ], "thesis_committee": [ { "family_name": "Flagan", "given_name": "Richard C.", "orcid": "0000-0001-5690-770X", "clpid": "Flagan-R-C" }, { "family_name": "Kornfield", "given_name": "Julia A.", "orcid": "0000-0001-6746-8634", "clpid": "Kornfield-J-A" }, { "family_name": "Ravichandran", "given_name": "Guruswami", "orcid": "0000-0002-2912-0001", "clpid": "Ravichandran-G" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The ability to deliver therapeutic compounds to the cornea using high-velocity microparticles is assessed and a method to synthesize therapeutic particles suitable for the cornea is demonstrated. Using a commercial gene gun (BioRad; PDS1000), a pneumatic capillary gun, and custom biolistic technology, microparticles were accelerated and made to embed in target materials: either homogeneous gels or corneal tissue. In homogeneous gels, penetration was shown to be directly proportional to particle size and density. In contrast, penetration of microparticles into the cornea is insensitive to particle size and density: varying the sectional density by 680% failed to penetrate beyond the epithelium (ca. 50 microns). The corneal epithelium exhibits two distinct kinetic energy thresholds that must be exceeded to first embed particles in the epithelium (rather than stopping on its anterior surface) and second to embed particles in the stroma (rather than stopping at the posterior surface of the epithelium). Penetration profiles show that the stroma is a highly effective stopping medium for high velocity microparticles. Despite the high water content of corneal tissue (76 w%) compared to the stratum corneum of skin (40 w%), the resistance to penetration of the cornea is comparable to literature values for skin. Ideal particles for drug delivery to the cornea would dissolve away completely, leaving no residue that might scatter light. With a vibrating orifice aerosol generator and a temperature-controlled column, 30-50 \u00b5m particles were composed of 1% Eosin Y with poly(ethylene glycol). Using low density polymer particles with a therapeutic agent payload, it was demonstrated that bulk material can be ballistically delivered to the central 1 cm\u00b2 of the corneal epithelium rapidly, in an even, quantifiable layer.", "doi": "10.7907/nf29-gy82", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:13722", "collection": "thesis", "collection_id": "13722", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05252020-134146453", "primary_object_url": { "basename": "Thesis Draft_v1.3.pdf", "content": "final", "filesize": 32451964, "license": "other", "mime_type": "application/pdf", "url": "/13722/12/Thesis Draft_v1.3.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Additive Manufacturing of 3D Nano-Architected Metals and Ceramics", "author": [ { "family_name": "Vyatskikh", "given_name": "Andrey", "orcid": "0000-0002-6917-6931", "clpid": "Vyatskikh-Andrey" } ], "thesis_advisor": [ { "family_name": "Greer", "given_name": "Julia R.", "clpid": "Greer-J-R" } ], "thesis_committee": [ { "family_name": "Shapiro", "given_name": "Mikhail G.", "clpid": "Shapiro-M-G" }, { "family_name": "Faber", "given_name": "Katherine T.", "clpid": "Faber-K-T" }, { "family_name": "Gao", "given_name": "Wei", "clpid": "Gao-Wei" }, { "family_name": "Greer", "given_name": "Julia R.", "clpid": "Greer-J-R" } ], "local_group": [ { "literal": "Resnick Sustainability Institute" }, { "literal": "Rosen Bioengineering Center" }, { "literal": "div_eng" } ], "abstract": "Additive manufacturing (AM) represents a set of manufacturing processes that create complex 3D parts out of polymers, metals, and ceramics. AM of metals and ceramics is widely used to produce parts for aerospace, automotive, and medical applications. At the micro- and nano-scales, AM is poised to become the enabling technology for efficient 3D microelectromechanical systems (MEMS), 3D micro-battery electrodes, 3D electrically small antennae, micro-optical components, and photonics. Today, the minimum feature size for most commercially available metal and ceramic AM is limited to ~20-50 \u03bcm. Currently, no established processes can reliably produce complex 3D metal and ceramic parts with sub-micron features.
\r\n\r\nIn this thesis, we first demonstrate a nanoscale metal AM process that can produce ~300 nm features out of nanocrystalline, nanoporous nickel using synthesized hybrid organic-inorganic materials, two-photon lithography, and pyrolysis. We study microstructure and mechanical properties of as-fabricated nickel architectures and compare their structural strength to established AM processes. We then show how this process can be extended to other metals and metalloids, including Mg, Ge, Si, and Ti.
\r\n\r\nThis study extends further into nanoscale AM of transparent, high refractive index materials for micro-optics and photonic crystals. We develop an AM process to 3D print fully dense nanocrystalline rutile titanium dioxide (TiO\u2082) with feature dimensions down to ~120 nm. We carefully study and model the relationship between feature dimensions and process parameters to achieve a <2% variation in critical dimensions. We then use this understanding of the process to fabricate and study 3D dielectric photonic crystals with a full photonic bandgap in the infrared.
\r\n\r\nFinally, a microscale AM process of titanium dioxide is demonstrated for photocatalytic water treatment. We show how synthesized hybrid organic-inorganic materials can be applied for stereolithography to print TiO\u2082 architectures with 100 \u03bcm features. We use the developed 3D printing process to investigate the effect of 3D architecture on the efficiency of photocatalytic water treatment.
\r\n\r\nThis work establishes a versatile and efficient pathway to create three-dimensional nano-architected metals and ceramics and to investigate their properties for applications in 3D MEMS, micro-optics, photonics, and photocatalysis.
\r\n", "doi": "10.7907/pdz2-dd59", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13636", "collection": "thesis", "collection_id": "13636", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02062020-145031701", "type": "thesis", "title": "Facilitating Miniaturized Bioanalytical Assays in Microfluidic Devices", "author": [ { "family_name": "Zhukov", "given_name": "Dmitriy Vladimirovich", "orcid": "0000-0002-4834-3147", "clpid": "Zhukov-Dmitriy-Vladimirovich" } ], "thesis_advisor": [ { "family_name": "Ismagilov", "given_name": "Rustem F.", "clpid": "Ismagilov-R-F" } ], "thesis_committee": [ { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Ismagilov", "given_name": "Rustem F.", "clpid": "Ismagilov-R-F" }, { "family_name": "Guttman", "given_name": "Mitchell", "clpid": "Guttman-M" }, { "family_name": "Gao", "given_name": "Wei", "clpid": "Gao-Wei" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This work describes several efforts in making microfluidic lab-on-a-chip technology more convenient to use for bioanalysis in limited-resource settings (Chapters 2-3), and describes a device for miniaturized multistep process execution (Chapter 4). One underlying theme of these projects is the streamlining of the 'chip-to-world' interfacing to help bring this technology from specialized labs of its developers into more widespread utilization by potential users in other disciplines. Chapter 2 outlines a portable method for achieving stable fluid pumping for sample loading and flow control in microfluidic devices. Chapter 3 details a method for digital nucleic acid test readout with unmodified smartphone cameras. Chapter 4 demonstrates a lab-on-a-chip platform capable of carrying out complex multiplexed biochemical reactions requiring multiple sequential additions of reagents by performing RNA barcoding for multiplexed cDNA library generation.
", "doi": "10.7907/x9wq-h920", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13608", "collection": "thesis", "collection_id": "13608", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12122019-162434400", "primary_object_url": { "basename": "Jinglin_Huang_2020_Thesis.pdf", "content": "final", "filesize": 13253785, "license": "other", "mime_type": "application/pdf", "url": "/13608/1/Jinglin_Huang_2020_Thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Investigations of Different Methods to Promote Drug Mixing in the Eye", "author": [ { "family_name": "Huang", "given_name": "Jinglin Alice", "orcid": "0000-0003-0760-4950", "clpid": "Huang-Jinglin-Alice" } ], "thesis_advisor": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Gao", "given_name": "Wei", "orcid": "0000-0002-8503-4562", "clpid": "Gao-Wei" }, { "family_name": "Petrasek", "given_name": "Danny", "clpid": "Petrasek-Danny" }, { "family_name": "Schwartz", "given_name": "Daniel M.", "clpid": "Schwartz-Daniel-M" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "local_group": [ { "literal": "Resnick Sustainability Institute" }, { "literal": "3MT Competition (Caltech)" }, { "literal": "div_eng" } ], "abstract": "Age-related macular degeneration (AMD) is the leading cause of central vision loss in the developed world. In the case of wet AMD, it can be managed through serial intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. However, sometimes the treatment is ineffective. Given that half-life time of the drug is limited, one possible cause of the ineffective treatment is inefficient drug mixing in the eye. Here, we focus on the understanding of drug mixing in vitreous chamber and parameters that could potentially influence mixing profiles. Both movement-driven method and thermal-driven method are explored. The in-vitro study outcomes will not only be useful for achieving fundamental understandings of fluid dynamics in the eye, but also helpful in developing a better strategy for intravitreal injection and improving the quality of care for patients.", "doi": "10.7907/741T-MN38", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:11548", "collection": "thesis", "collection_id": "11548", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05282019-074707723", "primary_object_url": { "basename": "Full_Thesis_Final.pdf", "content": "final", "filesize": 13376941, "license": "other", "mime_type": "application/pdf", "url": "/11548/1/Full_Thesis_Final.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Oxygen Transporter and Generator Devices to Treat Diabetic Retinopathy", "author": [ { "family_name": "Scianmarello", "given_name": "Nicholas E.", "orcid": "0000-0002-1207-4029", "clpid": "Scianmarello-Nicholas-E" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Mark", "clpid": "Humayun-M" }, { "family_name": "Gao", "given_name": "Wei", "clpid": "Gao-Wei" }, { "family_name": "Wang", "given_name": "Lihong", "clpid": "Wang-Lihong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "In recent years, Micro-Electrical Mechanical Systems (MEMS) have opened new areas of the human body to non-pharmacological treatment. Miniaturized implants have started to appear in volume or power constrained areas, such as the eye and the heart. In particular, the eye benefits from miniaturization, as it is very sensitive to pressure and volumetric changes, which can affect eyesight and blood flow.
\r\n\r\nDiabetic retinopathy is the worldwide leading cause of blindness among working age adults. As the numbers of diabetics increases, so does the number of retinopathies. By 2030, 191 million people are expected to be affected by the disease. As a patient\u2019s retinopathy progresses, the chronic hyperglycemia from diabetes causes permanent changes to the vasculature; vessels become leaky and occluded, tissue becomes hypoxic due to this ischemia and begins to release vascular endothelial growth factor (VEGF) to promote angiogenesis.
\r\n\r\nCurrently, treatments exist only for severe non-proliferative or proliferative DR, and rely on blocking VEGF (vascular endothelial growth factor) or panretinal laser photocoagulation to reduce retinal metabolic demand. VEGF antagonists are expensive; costing up to $164k per quality life adjusted year and must be administered by intravitreal injections monthly. Laser photocoagulation also requires retreatment and is known to reduce peripheral vision\u2014up to 20% of the peripheral retina is ablated. Another treatment approach may be to supply oxygen. Oxygen is a strong vasoconstrictor and suppresses the hypoxic signaling that leads to release of VEGF. These two effects reduce the plasma volume leaked into tissue, which in turn reduces edema, and may help prevent ischemic related cell death. Literature supports this assertion. A study of nasally inspired oxygen in patients with macular edema showed a reduction of edema and improvement of visual acuity following 3 months of treatment. Another study on rabbits with an induced ischemia demonstrated that intravitreal oxygenation maintained the retina to a near healthy condition.
\r\n\r\nIn this thesis, two devices, the oxytransporter and oxygenerator, that treat diabetic retinopathy are designed and tested. The former shuttles oxygen from areas of high concentration to the ischemic retina. The latter generates oxygen by electrolysis.
\r\n\r\nThis thesis is grounded on a computational model of oxygen consumption in the retina. To estimate the oxygen consumption, the model accounts for the anatomical distribution of tissue and vasculature in the retina. Previous models in literature averaged over the effects in the inner retina. The model estimates that the devices must supply 0.25nmol/s of oxygen to the human macula with an oxygen tension dependent on the degree of ischemia.
\r\n\r\nA nanoporous filler material was developed and integrated into the oxytransporter to allow this device to operate in the high humidity environment of the eye. The material is capable of withstanding an environment with water vapor 1.4 times the bulk saturation pressure. Theory behind the material was tested and compared to simulation. Benchtop testing over a month demonstrated the stability of the device in conditions similar to the eye. This oxytransporter was implanted in rabbits and the diffusor, or output membrane, reached the favorable mark of 100mmHg in the vitreous humor from atmospheric oxygen alone. This is estimated to be sufficient to treat a mild to moderate ischemia in humans.
\r\n\r\nThe oxygenerator is powered from a coil up to 3cm away, and can provide 0.25nmol/s continuously with an oxygen tension of up to 300mmHg for a human sized diffusor. A steady state test demonstrated the capability of maintaining the oxygen tension in the device by modulating the input power. The device is replenished through osmosis from the vitreous humor, and can absorb moisture at a rate comparable to the required oxygen consumption. One week implantation in vivo in rabbits demonstrated that the oxygen tension exceeded 200mmHg at the diffusor, which is estimated to be sufficient to treat severe ischemia.\r\nFuture work should involve a study of the long term effects of oxygen in an ischemic animal model.
", "doi": "10.7907/JCS2-8E12", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:11337", "collection": "thesis", "collection_id": "11337", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01102019-190818557", "primary_object_url": { "basename": "Phototherapeutic Devices for the Treatment of Diabetic Retinopathy_Colin Andrew Cook_2019_Caltech.pdf", "content": "final", "filesize": 94243327, "license": "other", "mime_type": "application/pdf", "url": "/11337/1/Phototherapeutic Devices for the Treatment of Diabetic Retinopathy_Colin Andrew Cook_2019_Caltech.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Phototherapeutic Devices for the Treatment of Diabetic Retinopathy", "author": [ { "family_name": "Cook", "given_name": "Colin Andrew", "orcid": "0000-0002-6283-5105", "clpid": "Cook-Colin-Andrew" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Shapiro", "given_name": "Mikhail G.", "clpid": "Shapiro-M-G" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Gao", "given_name": "Wei", "clpid": "Gao-Wei" }, { "family_name": "Martinez-Camarillo", "given_name": "Juan Carlos", "clpid": "Martinez-Camarillo-Juan-Carlos" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Diabetic retinopathy is a microvascular disease of the retina and a leading cause of vision loss worldwide. In the non-proliferative phase, diabetes-induced degradation of the retinal blood supply leads to edema and progressive tissue hypoxia. In response, the retinal tissue expresses proangiogenic growth factors (e.g. vascular endothelial growth factor), which drive proliferation of aberrant blood vessels within the eye. These poorly formed vessels leak fluid and blood cells into the eye and grow into the vitreous, which puts traction on the retina and leads to detachment. Given the hypoxic etiology, retinal oxygen tension and metabolism have received considerable attention. Dark-adapted conditions drive the retina to a significantly lower oxygen tension compared to light- adapted conditions as rod cells consume more energy in order to boost sensitivity. While tolerable in the healthy retina, it has been hypothesized that increased nightly metabolism overwhelms the compromised oxygen supply in the diabetic retina, leading to hypoxia and pathological vascular endothelial growth factor expression.
\r\n\r\nThis thesis develops ocular devices that shine light onto the retina to modulate rod metabolism, reducing oxygen demand and mitigating nightly hypoxia. The phototherapeutic effect is characterized through mathematical modeling of retinal metabolism and in vivo testing. Implantable phototherapy devices are designed, fabricated, and evaluated. This thesis also develops overnight phototherapeutic contact lenses utilizing radioluminescence, chemiluminescence, and electroluminescence approaches. Phototherapy holds promise as a non-invasive, preventative therapy for the treatment of hypoxic retinal diseases such as diabetic retinopathy.
", "doi": "10.7907/62R5-RF78", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" } ]