Optical imaging enables visualization of biological structure and function but is fundamentally limited by several physical constraints. Spatial resolution is bounded by optical diffraction, depth penetration is curtailed by strong absorption and scattering in tissue, and image contrast-to-noise ratio is often restricted by photon shot noise in low-light conditions. This thesis advances two novel directions\u2014photoacoustic imaging and quantum imaging\u2014to address these limitations.
\r\n \r\nIn photoacoustic imaging, we design and optimize high-speed photoacoustic computed tomography systems that enable deep, volumetric visualization of vasculature. By incorporating time-gated reconstruction and image-enhancement algorithms, these systems support small-animal imaging of cardiac structure, liver morphology, and brain hemodynamics non-invasively. Building on these foundations, we explore non-invasive breast photoacoustic imaging with high spatiotemporal resolution. Through integration with learning-based feature extraction, classification, and segmentation pipelines, we demonstrate the feasibility of applying photoacoustic imaging in clinical workflows to aid the characterization of breast tissue.
\r\n \r\nIn quantum imaging, we develop two complementary architectures that extend the state of the art in opposite but synergistic directions. The scanning quantum microscope scales up existing quantum imaging approaches, achieving the largest resolvable pixel counts to date by combining entangled-photon illumination with efficient coincidence detection. This platform enables the first demonstration of whole-organism imaging and shows potential in remote sensing and sub-shot-noise imaging. In contrast, the widefield quantum microscope scales down quantum imaging to the microscopic regime, integrating single-photon\u2013sensitive cameras with a covariance-based coincidence estimation algorithm. This approach enables cellular-level imaging and demonstrates quantum-enhanced resolution beyond the classical diffraction limit, establishing a practical pathway for quantum microscopy in biological imaging.
\r\n \r\nAcross both research directions, this thesis advances system design and engineering, quantitative characterization, calibration, reconstruction, and image-enhancement methodologies. Together, these developments establish pathways from physical principles to practical imaging systems, spanning laboratory prototypes through preclinical and clinical applications in biomedical imaging.
", "doi": "10.7907/013f-vd31", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:18413", "collection": "thesis", "collection_id": "18413", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03102026-210243363", "primary_object_url": { "basename": "huang_yuxi_2026.pdf", "content": "final", "filesize": 46504173, "license": "other", "mime_type": "application/pdf", "url": "/18413/1/huang_yuxi_2026.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Signal in the Scatter: Advancing Speckle-Based Optical Sensing for Deep Cerebral Blood Flow Monitoring", "author": [ { "family_name": "Huang", "given_name": "Yu Xi (Max)", "orcid": "0009-0000-0165-2084", "clpid": "Huang-Yu-Xi-Max" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" }, { "family_name": "Liu", "given_name": "Charles", "orcid": "0000-0001-6423-8577", "clpid": "Liu-Charles-Y" }, { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents the development and application of novel, non-invasive optical techniques for monitoring cerebral blood flow (CBF) and cerebral blood volume (CBV), addressing the critical need for cost-effective and scalable solutions in cerebrovascular health assessment. The research introduces advancements in interferometric speckle visibility spectroscopy (iSVS) and speckle contrast optical spectroscopy (SCOS) to overcome the challenges of signal attenuation and noise when measuring blood flow through the scalp and skull.
\r\n\r\nThe depth sensitivity of these optical methods was first experimentally determined. Using iSVS on phantoms, rabbits, and human subjects, a two-layer decay model was observed as the source-to-detector (S-D) distance was varied, allowing for the quantification of the transition point from superficial to cerebral signal detection. Complementing this, a multi-channel SCOS system was used with temporary occlusion of the superficial temporal artery to experimentally isolate and quantify the influence of scalp blood flow, providing direct evidence of brain-to-scalp signal sensitivity and establishing optimal S-D configurations.
\r\n\r\nAnother primary focus of this work was enhancing the signal-to-noise ratio (SNR) of deep-tissue measurements. A comprehensive theoretical framework for iSVS was developed to evaluate its SNR in the presence of detector noise, confirming its superiority in photon-limited regimes and revealing relaxed constraints on the reference beam. In parallel, a compact, fiber-free SCOS device was engineered, demonstrating a 70-fold increase in signal collection over traditional fiber-based systems with enhanced stability. The SNR for SCOS was further improved through an optimization-based, adaptive noise calibration framework that mitigates artifacts from cerebral blood volume fluctuations, significantly lowering the signal detection threshold for reliable CBF measurement.
\r\n\r\nBuilding upon these foundational advancements, the research progressed to clinical applications. The technology's modularity was demonstrated by engineering a portable, six-channel SCOS system for simultaneous, real-time measurements at multiple brain locations. This system was validated in a preliminary study on a patient with traumatic brain injury, demonstrating its potential for characterizing regional cerebrovascular dysfunction by comparing blood flow dynamics against structural MRI data. Furthermore, the compact SCOS device was used to assess stroke risk in a 50-person cohort by monitoring cerebrovascular reactivity during a breath-holding task; this revealed significant discrepancies between CBF and CBV responses that correlated with risk scores.
", "doi": "10.7907/597j-zv94", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:18618", "collection": "thesis", "collection_id": "18618", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05252026-183244369", "primary_object_url": { "basename": "Zhou_Haowen_2026.pdf", "content": "final", "filesize": 101232308, "license": "other", "mime_type": "application/pdf", "url": "/18618/1/Zhou_Haowen_2026.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Synergizing Microscopy, Computation, and Artificial Intelligence to Advance Biomedical Research", "author": [ { "family_name": "Zhou", "given_name": "Haowen", "orcid": "0000-0003-0955-4010", "clpid": "Zhou-Haowen" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Bouman", "given_name": "Katherine L.", "orcid": "0000-0003-0077-4367", "clpid": "Bouman-K-L" }, { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" }, { "family_name": "Wei", "given_name": "Lu", "orcid": "0000-0001-9170-2283", "clpid": "Wei-Lu" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Over the past century, microscopy has evolved significantly through advances in hardware design. However, pushing the boundaries of imaging performance using purely optical and mechanical innovations has become increasingly challenging. Meanwhile, the rapid growth in computational power has transformed the way we process and analyze imaging data, enabling a paradigm shift in microscopy. By offloading complexity from hardware to algorithms, computational microscopy -- a rising interdisciplinary field -- offers a powerful approach to simplify system design, correct aberrations, and extract more information from data. In this thesis, I will explore how computational techniques, including artificial intelligence, can enhance modern imaging systems and image analysis for biomedical research.
\r\n\r\nThis thesis develops physics-informed computational frameworks that extend the capabilities of optical imaging systems. By embedding physics models directly into reconstruction algorithms, I show how computational approaches can overcome traditional limitations in resolution and depth-of-field, through case studies in Fourier ptychographic microscopy and single-shot volumetric fluorescence imaging.
\r\n\r\nIn addition to reconstructions, this thesis advances analytic solutions with customized optical designs that leverage physical insight to enable robust, efficient, and automated microscopy. By identifying and exploiting principles in wave optics, analytic methods are developed for high-performance autofocusing and optimization-free volumetric refractive index imaging. These approaches improve robustness across imaging modalities.
\r\n\r\nFinally, this thesis demonstrates how artificial intelligence can be integrated with microscopic imaging to enable clinically relevant inference. Deep learning models are applied to digitized histopathology slides to predict progression risk in early-stage non-small-cell lung cancer patients, achieving performance that exceeds expert-level assessment. Beyond predictive accuracy, the models are systematically analyzed to identify the spatial feature scales that drive their predictions.
", "doi": "10.7907/0d6t-py79", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:18476", "collection": "thesis", "collection_id": "18476", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04072026-143808452", "type": "thesis", "title": "Scalable Arrays From Millimeter-Wave Sensing to Microwave Wireless Power Transfer", "author": [ { "family_name": "Ayling", "given_name": "Alex Eben", "orcid": "0009-0008-5440-7785", "clpid": "Ayling-Alex-Eben" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Mirhosseini", "given_name": "Mohammad", "orcid": "0000-0002-9084-6880", "clpid": "Mirhosseini-M" }, { "family_name": "Siegel", "given_name": "Peter H.", "orcid": "0000-0002-2539-4646", "clpid": "Siegel-P-H" }, { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Wireless power transfer at a distance, long relegated to the realm of science fiction, has seen a resurgence in recent years. Chief among its promises is Space-Based Solar Power (SBSP), an ambitious project to deploy kilometer scale photovoltaic arrays in space and beam its power down to Earth using a complementary microwave phased array. The building blocks of the array are phased array tiles, which can be instantiated to produce larger apertures.
\r\n\r\nThe tile must be simultaneously lightweight and flexible for deployment in space, low-cost, high-performance, and scalable. First, the results of the MAPLE mission, which tested wireless power transfer in space using custom flexible arrays, are presented. Using the results of that mission, the design and testing of next-generation, fully flexible 8x8 element phased array tile are presented. The tile is driven by a custom 22-nm CMOS FDSOI RFIC that achieves record efficiency and performance. These results represent not only a step forward toward practical microwave wireless power transfer but offer new directions in communications and sensing driven by flexible arrays.
\r\n\r\nAdditionally, topics on maximum power point tracking in SBSP systems, transmitarrays for SBSP, and the design of a fully-integrated, scalable, and low-cost D-band (110-170GHz) radiator tile are discussed.
", "doi": "10.7907/w440-k235", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "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:16840", "collection": "thesis", "collection_id": "16840", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11072024-191407481", "primary_object_url": { "basename": "Thesis_20241208.pdf", "content": "final", "filesize": 91058226, "license": "other", "mime_type": "application/pdf", "url": "/16840/1/Thesis_20241208.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Harvesting Insights from Advanced Microscope Acquisitions: Techniques and Applications", "author": [ { "family_name": "Liang", "given_name": "Mingshu", "orcid": "0000-0001-7748-7652", "clpid": "Liang-Mingshu" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" }, { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" }, { "family_name": "Bouman", "given_name": "Katherine L.", "orcid": "0000-0003-0077-4367", "clpid": "Bouman-K-L" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Since their inception, microscopes have evolved significantly, becoming essential tools across various fields, from pathology diagnosis to biological studies. Morphological information that cannot be otherwise observed has always been regarded as the primary data a microscope could deliver. Yet microscopy data embodies further valuable information worth exploring. This thesis demonstrates extracting three types of information beyond morphology by modifying microscope systems, incorporating physical models, and applying image processing: 1) depth information, 2) object size information, and 3) object developmental information.
\r\n\r\nThe first part of the thesis describes an all-in-focus technique based on Fourier Ptychographic Microscopy (FPM) for depth information extraction. It synthesizes an all-in-focus image and depth map from an FPM-reconstructed multi-focal image stack. This technique benefits thyroid fine needle aspiration samples, relieving pathologists from the need to constantly adjust focal planes, enabling convenient data transfer, and potentially aiding machine learning tasks on cytology specimens.
\r\n\r\nThe second part of the thesis focuses on a non-destructive subvisible particle (SbVPs) analyzer for estimating size and concentrations of SbVPs in drug products. This analyzer aims to estimate the size and concentrations of SbVPs within a drug product while keeping the sample intact. Incorporating a light-sheet microscope with custom housings to compensate for container-induced astigmatism, it uses side-scattered light as a size indicator based on Mie scattering theory. Its functionality is demonstrated on polystyrene beads and biological drug products. Additionally, a new metric named the strip density is discovered from the same microscope images, which could serve as a more precise and robust size indicator beyond scattering light intensity. This new size indicator is used to train a particle detection neural network, verifying its effectiveness through good performance.
\r\n\r\nFor the final part, we focus on an embryo sex classification project, aiming to extract subtle developmental differences between male and female embryos from early development videos taken by Embryoscope. A combined convolutional and recurrent neural network structure is employed. While the prediction accuracy reaches 61%, which is not high, the deep learning model outperforms both human and random predictions, demonstrating its ability to acquire embryo developmental information from the Embryoscope videos to some extent.
", "doi": "10.7907/aysy-jg55", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:17428", "collection": "thesis", "collection_id": "17428", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06092025-053621987", "primary_object_url": { "basename": "Gray_Robert_2025.pdf", "content": "final", "filesize": 138129789, "license": "other", "mime_type": "application/pdf", "url": "/17428/1/Gray_Robert_2025.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Ultrafast Quadratic Nonlinear Dynamics and Soliton Formation in Parametric Amplifiers and Oscillators", "author": [ { "family_name": "Gray", "given_name": "Robert Matthew", "orcid": "0000-0001-5980-8774", "clpid": "Gray-Robert-Matthew" } ], "thesis_advisor": [ { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" } ], "thesis_committee": [ { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Vahala", "given_name": "Kerry J.", "orcid": "0000-0003-1783-1380", "clpid": "Vahala-K-J" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "In the more than 60 years since the invention of the laser, complementary developments in nonlinear and ultrafast optics have revolutionized fundamental science and technology, enabling the measurement of atomic and electronic motion at their native timescales, optical timekeeping with unprecedented precision, information processing offering speeds beyond those attainable in electronics, and novel spectroscopy and sensing techniques capable of parallel detection of several analytes with fast acquisition times and high sensitivity. On the one hand, pulsed sources are particularly well-suited for driving nonlinear phenomena, as the strength of nonlinear interaction depends on the peak power of the optical input. Conversely, spectral broadening, pulse shaping, and temporal sampling mechanisms enabled by nonlinearity have been critical in developing ultrafast sources and systems.
\r\n\r\nIn this thesis, we further explore this synergistic relationship between nonlinear and ultrafast optics. We specifically study nonlinear dynamical phenomena such as soliton formation and supercontinuum generation in parametric amplifiers and oscillators exhibiting a quadratic (χ(2)) nonlinearity, and we show how these processes can be leveraged for the efficient generation of ultrashort pulses and coherent broadband spectra, with direct application in sensing and information processing. We begin by exploring the formation of mid-infrared temporal simultons in a free-space optical parametric oscillator, and we exploit their formation dynamics for enhanced molecular sensing. Next, we turn to the thin-film lithium niobate platform and demonstrate pJ pulse energy, two-color soliton pulse compression to the two-cycle regime in a dispersion-engineered waveguide. We additionally show that the strong nonlinearity in such waveguides enables the on-chip characterization of ultrashort, ultra-weak pulses. Next, we demonstrate a coherent, multi-octave frequency comb from a far-above-threshold nanophotonic parametric oscillator and investigate the dynamics underpinning its formation. Finally, we show simultaneous oscillation of 70 independent time-multiplexed parametric oscillators in a dispersion-engineered nanophotonic cavity. Our results pave the way to a new generation of scalable and efficient ultrafast sources, sensors, and information processing systems powered by quadratic nonlinearity.
.", "doi": "10.7907/7zzq-4w69", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:16405", "collection": "thesis", "collection_id": "16405", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05212024-231923059", "primary_object_url": { "basename": "THESIS.pdf", "content": "final", "filesize": 153588118, "license": "other", "mime_type": "application/pdf", "url": "/16405/1/THESIS.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Oxygen-Regulating MEMS Devices for Cell Transplantation to Cure Type 1 Diabetes", "author": [ { "family_name": "Shang", "given_name": "Kuang-Ming", "orcid": "0000-0001-5065-7607", "clpid": "Shang-Kuang-Ming" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Komatsu", "given_name": "Hirotake", "orcid": "0000-0003-0876-4809", "clpid": "Komatsu-Hirotake" } ], "thesis_committee": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Komatsu", "given_name": "Hirotake", "orcid": "0000-0003-0876-4809", "clpid": "Komatsu-Hirotake" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "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" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Type 1 diabetes is an autoimmune disease in which immune cells specifically attack and destroy the insulin-producing beta cells in the pancreatic islets that regulate blood glucose levels. Traditionally managed with frequent injections of exogenous insulin, beta cell replacement therapy\u2014also known as islet transplantation\u2014has emerged as an alternative clinical option. Recently, the focus has shifted toward subcutaneous islet transplantation, offering a promising and minimally invasive therapy. However, the survival of transplanted islets has been shown to be significantly challenged by hypoxia-induced graft loss stemming from inadequate oxygen supply.
\r\n\r\nTo address this issue, we have developed innovative hollow mesh devices that regulate oxygen. These devices can either bring oxygen from the adjacent oxygen-rich tissue or draw additional oxygen from ambient air to improve oxygen delivery to the hypoxic microenvironment of islet grafts. Fabricated using MEMS techniques and biocompatible materials, these devices feature a network of unobstructed air-containing microchannels. Utilizing the property that oxygen diffuses 10,000 times faster in air than in interstitial fluids, these devices effectively overcome oxygen supply barriers when co-transplanted with islet grafts. By integrating these hollow meshes with the islet grafts, oxygen can be rapidly redistributed throughout the graft, establishing local oxygen balance and regulation. This approach significantly reduces hypoxia-induced graft loss and improves the efficacy of post-transplant blood glucose regulation in recipients.
\r\n\r\nIn this thesis, we first delved into the physiology of oxygen transport within an islet, establishing the critical oxygen threshold necessary for islet cell survival. We developed equivalent circuit models for oxygen diffusion and constructed oxygen-regulating hollow mesh MEMS devices based on these models. We investigated the effects of oxygenation through both computational models and benchtop experiments. Finally, using our device, we demonstrated enhanced survival of islet grafts in diabetic rodent models, successfully achieving a long-term cure for diabetes.
\r\n\r\nWith the preclinical success of this oxygen-regulating hollow mesh in mitigating cellular oxygen deficiency, we also explored and proposed future pathways toward clinical effectiveness. Our device holds significant therapeutic potential to revolutionize clinical outcomes in islet transplantation with the ultimate goal of curing type 1 diabetes.
", "doi": "10.7907/xf5z-0p34", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16341", "collection": "thesis", "collection_id": "16341", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03252024-002457591", "primary_object_url": { "basename": "Mingchen_Liu_PhD_Thesis_v2.2.pdf", "content": "final", "filesize": 7928964, "license": "other", "mime_type": "application/pdf", "url": "/16341/1/Mingchen_Liu_PhD_Thesis_v2.2.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Nonlinear Enhancement of Optical Spectroscopy in the Mid-infrared", "author": [ { "family_name": "Liu", "given_name": "Mingchen", "orcid": "0000-0002-0649-8976", "clpid": "Liu-Mingchen" } ], "thesis_advisor": [ { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" } ], "thesis_committee": [ { "family_name": "Okumura", "given_name": "Mitchio", "orcid": "0000-0001-6874-1137", "clpid": "Okumura-M" }, { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Optical spectroscopy has long been a cornerstone in studying material properties, playing a pivotal role in the advancement of science and technology. It remains crucial in both research and industry, particularly in the mid-infrared (MIR) region, known for its unique molecular fingerprint capabilities. The emergence of optical frequency comb technology has set the stage for dual-comb spectroscopy (DCS) to revolutionize optical spectroscopy with its potential superiority in speed, resolution, sensitivity, precision, and compactness. However, practical implementation of DCS in the MIR region faces challenges due to its demanding requirements for sources, inefficient photodetection, and dynamic range \r\nlimitations, despite an exciting prospect. \r\nThis dissertation explores the use of quadratic optical nonlinearity to tackle these challenges. By manipulating energy and information flows between photons of different \r\nfrequencies through nonlinear optics, we leverage well-developed near-infrared (NIR) sources, detectors, and optics to address difficulties in the MIR region. We first \r\ndemonstrate optical parametric oscillators in the regime of simulton (quadratic soliton pair), achieving a high-power broadband MIR frequency comb with a remarkably high NIR-to-MIR power conversion efficiency. We also introduce cross-comb spectroscopy (CCS), which upconverts the MIR frequency comb to the NIR region and allows MIR spectral analysis with NIR photodetection. This novel approach can offer superior signal-to-noise ratio (SNR), dynamic range, and detection efficiency compared to conventional DCS, while providing wavelength flexibility. Additionally, we present a new method to facilitate the detection of trace samples with short-pulse optical parametric amplifiers, which can significantly enhance SNR and limit of detection of existing methods.\r\nOverall, this research demonstrates the capabilities of quadratic nonlinearity in enabling high-performance optical sensing in spectral regions where sources, detectors, and optics are less developed.", "doi": "10.7907/ffd0-yq96", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16192", "collection": "thesis", "collection_id": "16192", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09272023-180554728", "primary_object_url": { "basename": "Ives_Craig_2024.pdf", "content": "final", "filesize": 145161062, "license": "other", "mime_type": "application/pdf", "url": "/16192/1/Ives_Craig_2024.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Subtractive Photonics in Bulk CMOS", "author": [ { "family_name": "Ives", "given_name": "Craig Edward", "orcid": "0009-0006-3893-541X", "clpid": "Ives-Craig-Edward" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Sideris", "given_name": "Constantine", "orcid": "0000-0002-3042-4889", "clpid": "Sideris-Constantine" }, { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Much of humanity's technological advancement over the last few decades may be attributed to exponentially increasing computing power, the bedrock of which is bulk CMOS technology. Exponentially increasing data rates in communications have also played an important role, facilitated by advancements in fiber optics and integrated photonics. However, efforts to capitalize on the complementary strengths of these two domains by merging them, an idea first envisioned almost 40 years ago, have so far proven inadequate. All previous attempts to integrate photonics in bulk CMOS have required either expensive process modification or resulted in waveguides with high loss.
\r\n\r\nIn this thesis, we discuss our investigations of a new method of integrating photonics into bulk CMOS, which we call the method of subtractive photonics. This method entails forming waveguides out of the back-end interconnect of an electronic chip. The interconnect metal is designed to wrap around dielectric channels such that when the metal is etched away, suspended dielectric waveguides remain. Although this method introduces a large, previously untapped design space, since there are many interconnect layers that can be used in photonic structures, it also introduces certain severe constraints. This thesis explores some of the possibilities this design space opens up, as well as some of the challenges involved in designing photonics in a process intended only for electronics. As part of this exploration, we demonstrate waveguides with an upper bound on loss that is significantly lower than the best previously published waveguide loss for unmodified bulk CMOS. We also demonstrate the first measurements of waveguide loss at visible and near-visible wavelengths in unmodified bulk CMOS, as well as the first measurements of waveguide coupled photodiodes in unmodified bulk CMOS. These proof-of-concept results may pave the way towards fully integrated electronic-photonic systems in unmodified bulk CMOS.
", "doi": "10.7907/yrz7-ds33", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16273", "collection": "thesis", "collection_id": "16273", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01032024-012340742", "primary_object_url": { "basename": "How_to_Make_Small_Things_do_Big_Things_for_PDF_v2.pdf", "content": "final", "filesize": 15527558, "license": "other", "mime_type": "application/pdf", "url": "/16273/4/How_to_Make_Small_Things_do_Big_Things_for_PDF_v2.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "How to Make Small Things Do Big Things: Exploring Engineered Disorder for Massively Scalable Metasurfaces and Metamaterials", "author": [ { "family_name": "Wray", "given_name": "Parker Ryan", "orcid": "0000-0003-3384-0826", "clpid": "Wray-Parker-Ryan" } ], "thesis_advisor": [ { "family_name": "Atwater", "given_name": "Harry Albert", "orcid": "0000-0001-9435-0201", "clpid": "Atwater-H-A" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" }, { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" }, { "family_name": "Atwater", "given_name": "Harry Albert", "orcid": "0000-0001-9435-0201", "clpid": "Atwater-H-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This work presents a collection of topics related to anomalous electromagnetic scattering, emission, and absorption states formed from random systems. The underlying motivation is to explore to what extent metasurface and metamaterial concepts could be applied at a massively large scale; by identifying emergent properties in systems that do not require careful fabrication. Emphasis is placed on exploring theoretical descriptions for systems that do not conform well to existing simpler models. Covered topics include random metasurfaces for spectral filtering and polarization invariance, random nanoparticle films for radiative cooling, broadband polarization and angle invariant absorption using random fractals, effective medium models beyond traditional assumptions, a mathematical transform to understand highly directional scattering/emission in complex systems, and optical metrology and characterization techniques for random systems.", "doi": "10.7907/kvz3-jn93", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16294", "collection": "thesis", "collection_id": "16294", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02152024-233300684", "primary_object_url": { "basename": "Ruizhi_Cao_2023_thesis_v2.pdf", "content": "final", "filesize": 33398694, "license": "other", "mime_type": "application/pdf", "url": "/16294/1/Ruizhi_Cao_2023_thesis_v2.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Dealing with Imperfections: From Aberration to Scattering", "author": [ { "family_name": "Cao", "given_name": "Ruizhi", "orcid": "0000-0003-3385-446X", "clpid": "Ruizhi-Cao" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "orcid": "0000-0003-3003-7042", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Optical imaging has gained popularity in life science, biomedical imaging, fundamental physics research, and various other fields due to its non-invasive nature. In a carefully designed optical instrument operating in an ideal environment, the resolution of the optical imaging system is defined by its numerical aperture. However, practical manufacturing issues and inaccurate lens models make it challenging to achieve high resolution across a large area. High magnification lenses introduce aberrations that degrade image quality, prompting the use of complex lens systems dedicated to mitigating such aberrations. Furthermore, when a scattering medium is introduced into the imaging system, image formation becomes infeasible as light follows a complicated trajectory. These challenges pose great obstacles to the use of optical imaging methods in various scenarios. This thesis primarily consists of two parts, one aims to deal with aberration and the other tries to solve scattering induced imaging problems.
\r\n\r\nIn the first part of my thesis, I will discuss a technique called APIC (Angular Ptychographic Imaging with Closed-form method), which enables high-resolution imaging across a large field of view. To make APIC applicable in many non-ideal cases where aberrations (such as defocus) degrade image quality, we equip APIC with a closed-form aberration correction algorithm. We will demonstrate that APIC is unprecedentedly robust against aberrations and can retrieve high-resolution complex light fields using low magnification objectives.
\r\n\r\nIn the second part, we move on to dealing with scattering induced imaging problems. To form images where a scattering medium is present, we first explore the application of ultrasound modulation in optical imaging. We show that, by using ultrasound, we can image a hidden object in a highly scattering medium with ultrasonic resolution. Although this technique helps obtain clear images in the presence of a scattering medium, its resolution is limited. We then demonstrate a method in addressing another scattering problem, namely the non-line-of-sight (NLOS) imaging problem. In a general NLOS problem, modulation mechanisms such as the aforementioned ultrasound modulation are infeasible. We demonstrate that light can be directly focused on the hidden target with an optical diffraction-limited resolution by exploring the properties of the hidden target itself. We will show that this active focusing method possess remarkably improved resolution compared to existing methods and is able to image objects with large reflectance differences.
", "doi": "10.7907/adgc-g315", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:15277", "collection": "thesis", "collection_id": "15277", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06022023-051815823", "type": "thesis", "title": "Computational Compensation for Model Imperfections in Photoacoustic Computed Tomography", "author": [ { "family_name": "Hu", "given_name": "Peng", "orcid": "0000-0002-2933-1239", "clpid": "Hu-Peng" } ], "thesis_advisor": [ { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Bouman", "given_name": "Katherine L.", "orcid": "0000-0003-0077-4367", "clpid": "Bouman-K-L" }, { "family_name": "Colonius", "given_name": "Tim", "orcid": "0000-0003-0326-3909", "clpid": "Colonius-T" }, { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Photoacoustic computed tomography (PACT) images biological tissues\u2019 optical absorption through detection of photon-absorption-induced ultrasonic waves. Various systems have been proposed for PACT and they are described by different mathematical models to reconstruct from detected ultrasonic signals the photon-absorption-induced initial pressure, the main contrast in PACT. Accurate image reconstruction has high requirements for the system and the mathematical model, which is often imperfect in practice due to multiple factors, e.g., limited transducer bandwidth, finite transducer element size, sparse spatial sampling, partial-view detection, and tissue motion. The focus of this dissertation is on using computational methods to compensate for these model imperfections.
\r\n\r\nFirst, for a human breast imaging system based on a full-ring transducer array, we incorporate the limited transducer bandwidth into the model for spatiotemporal analysis to clarify the aliasing due to sparse spatial sampling and propose (1) two methods (radius-dependent spatiotemporal antialiasing and location-dependent spatiotemporal antialiasing) to mitigate these artifacts. Second, for an isotropic-resolution 3D PACT system formed by four arc arrays, we consider both the limited transducer bandwidth and the finite transducer element size and (2) compress the system matrix through singular value decomposition and fast Fourier transform for its efficient explicit expression. Enabled by this expression, we then propose (3) fast sparsely sampling functional imaging by incorporating a densely sampled prior image into the system matrix, which maintains the critical linearity while mitigating artifacts, and (4) intra-image nonrigid motion correction by incorporating the motion as subdomain translations into the system matrix and reconstructing the translations together with the image iteratively. Finally, for a single-shot 3D PACT system based on a single ultrasonic transducer, we propose (5) a fast implementation of the forward model by connecting traditional PACT with virtual detector responses through fast Fourier transform, and we iteratively reconstruct the image from signals with extremely compressed sensing and partial-view detection.
\r\n\r\nAll these proposed methods enable image reconstruction or significantly improve image quality in numerical simulations, phantom experiments, and in vivo experiments. Although they are demonstrated only for certain PACT systems, they are directly applicable to other systems and can be extended to other tomographic imaging modalities such as X-ray computed tomography (X-ray CT) and magnetic resonance imaging (MRI).
", "doi": "10.7907/6hdm-ar41", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:15214", "collection": "thesis", "collection_id": "15214", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05272023-062623589", "primary_object_url": { "basename": "Thesis_ChengShen_v3.pdf", "content": "final", "filesize": 14315052, "license": "other", "mime_type": "application/pdf", "url": "/15214/1/Thesis_ChengShen_v3.pdf", "version": "v8.0.0" }, "type": "thesis", "title": "Computational Imaging for Phase Retrieval and Biomedical Applications", "author": [ { "family_name": "Shen", "given_name": "Cheng", "orcid": "0000-0001-7136-4715", "clpid": "Shen-Cheng" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Bouman", "given_name": "Katherine L.", "orcid": "0000-0003-0077-4367", "clpid": "Bouman-K-L" }, { "family_name": "Zernicka-Goetz", "given_name": "Magdalena", "orcid": "0000-0002-7004-2471", "clpid": "Zernicka-Goetz-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "In conventional imaging, optimizing hardware is prioritized to enhance image quality directly. Digital signal processing is viewed as supplementary. Computational imaging intentionally distorts images through modulation schemes in illumination or sensing. Then its reconstruction algorithms extract desired object information from raw data afterwards. Co-designing hardware and algorithms reduces demands on hardware and achieves the same or even better image quality. Algorithm design is at the heart of computational imaging, with model-based inverse problem or data-driven deep learning methods as approaches. This thesis presents research work from both perspectives, with a primary focus on the phase retrieval issue in computational microscopy and the application of deep learning techniques to address biomedical imaging challenges.
\r\n\r\nThe first half of the thesis begins with Fourier ptychography, which was employed to overcome chromatic aberration problems in multispectral imaging. Then, we proposed a novel computational coherent imaging modality based on Kramers-Kronig relations, aiming to replace Fourier ptychography as a non-iterative method. While this approach showed promise, it lacks certain essential characteristics of the original Fourier ptychography. To address this limitation, we introduced two additional algorithms to form a whole package scheme. Through comprehensive evaluation, we demonstrated that the combined scheme outperforms Fourier ptychography in achieving high-resolution, large field-of-view, aberration-free coherent imaging.
\r\n\r\nThe second half of the thesis shifts focus to deep-learning-based methods. In one project, we optimized the scanning strategy and image processing pipeline of an epifluorescence microscope to address focus issues. Additionally, we leveraged deep-learning-based object detection models to automate cell analysis tasks. In another project, we predicted the polarity status of mouse embryos from bright field images using adapted deep learning models. These findings highlight the capability of computational imaging to automate labor-intensive processes, and even outperform humans in challenging tasks.
", "doi": "10.7907/pahb-cx81", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:14362", "collection": "thesis", "collection_id": "14362", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09152021-000948244", "primary_object_url": { "basename": "cua_michelle_2022.pdf", "content": "final", "filesize": 30523714, "license": "other", "mime_type": "application/pdf", "url": "/14362/1/cua_michelle_2022.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Exploiting Speckle to Image Deeper in Scattering Media", "author": [ { "family_name": "Cua", "given_name": "Eunice Michelle Chua", "orcid": "0000-0002-0394-757X", "clpid": "Cua-Eunice-Michelle-Chua" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "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": "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" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Optical methods for imaging and focusing are advantageous in many scenarios as optics can provide exquisite spatial resolution, has multiple sources of contrast, and does not impart ionizing radiation. However, optical scattering remains a fundamental challenge which limits the depth at which we can perform imaging with good spatial resolution. This challenge motivated our investigations into methods that could make use of the scattered light in order to extend the depth of imaging through or within scattering media. In particular, we focus on answering: (1) Can one 'unscramble' the scattered light in order to recover information about the otherwise hidden object?; and (2) Can we preferentially detect the more forward scattered photons in an efficient manner in order to allow deeper penetration with modest resolution? These two questions are explored in the first two projects of the thesis:
\r\n\r\n1. The development of an imaging system that detects the scattered light and exploits correlations within the scattering process to enable imaging through scattering media at diffraction-limited resolution.
\r\n\r\n2. The introduction of a novel method, termed Speckle-Resolved Optical Coherence Tomography, that sensitively and preferentially detects the more forward scattered photons in a coherent, speckle-resolved fashion to allow deeper imaging at moderate resolution.
\r\n\r\nOptical methods offer the benefit of visualizing samples that would otherwise appear transparent. Using light, one is able to visualize and measure the thickness of transparent films and coatings in a non-contact manner. The third project in my thesis focuses on using light to non-destructively visualize and characterize the evenness of the silicone oil layer that typically coats the inner surface of prefilled syringes. Characterizing the evenness of this silicone oil layer is important as it impacts the functionality of the prefilled syringe and may correlate with particle formation, which is undesirable as the number of particles in a syringe is regulated due to potential health concerns.
", "doi": "10.7907/rcsj-a410", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14371", "collection": "thesis", "collection_id": "14371", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09242021-181127485", "type": "thesis", "title": "High Sensitivity Time-Varying Systems In Photonics and Electronics", "author": [ { "family_name": "Porsandeh Khial", "given_name": "Parham", "orcid": "0000-0002-3242-8541", "clpid": "Porsandeh-Khial-Parham" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" }, { "family_name": "Weinreb", "given_name": "Sander", "orcid": "0000-0002-9353-6204", "clpid": "Weinreb-S" }, { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Integrated electronics and photonics have been revolutionizing our daily lives for decades. However, the demand for high-speed communications, low-latency networks, and high-performance optical and electrical sensors continues to grow. In order to keep up with this demand as well as be able to address upcoming and unknown challenges, we need to explore unconventional solutions. Moving away from existing systems and traditional architectures allows us to take a deeper look at these challenges and potentially come up with nontrivial answers. In this thesis, unconventional approaches to implementing high-performance optical and electrical sensors and systems are investigated. Among these unorthodox solutions are time-varying architectures which led to completely new devices, sensors with dramatically improved sensitivity, and the breaking of known trade-offs.
\r\n\r\nBy developing a time-varying method that we call reciprocal sensitivity enhancement, we demonstrated a nanophotonic optical gyroscope (NOG) for the first time. The efficacy of this method is borne out by its ability to improve the performance of optical gyroscopes by two orders of magnitude. This sensitivity-enhancement method filters out reciprocal imperfections and noise, thereby increasing the overall signal-to-noise ratio. Next, the same approach is used to boost the performance of resonance-based magnetic biosensors. By merging two biosensors and taking advantage of the frequency response of magnetic beads, time-division switching cancels out most of the correlated noise. This solution pushes the sensitivity of this sensor below parts-per-million (PPM) levels for long periods of time \u2014 a property which is desirable in many biosensing applications.
\r\n\r\nAdditionally, an electrical scalable router that mitigates line-of-sight issues in next-generation wireless systems is introduced. This novel design does not require any shared timing reference to form a coherent array and uses a time-varying baseband to create a proper true-time delay. Next, we discuss how radiating elements in silicon-photonics platforms can be engineered to create a passive lensless camera. By applying a robust reconstruction algorithm, the captured image can be faithfully recovered. The same concept can be used in multi-mode nanophotonic antennas to alleviate the field-of-view (FOV)-aperture trade-off.
\r\n\r\nFinally, a hybrid photonic transmitter/receiver architecture, an electrical full-duplex transceiver with one nonreciprocal element, and a nested-ring optical modulator are presented.
", "doi": "10.7907/qzj9-rz93", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14344", "collection": "thesis", "collection_id": "14344", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08272021-165922711", "type": "thesis", "title": "Multifunctional Volumetric Metaoptics", "author": [ { "family_name": "Ballew", "given_name": "Conner Kiley", "orcid": "0000-0003-4854-8342", "clpid": "Ballew-Conner-Kiley" } ], "thesis_advisor": [ { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Bouman", "given_name": "Katherine L.", "orcid": "0000-0003-0077-4367", "clpid": "Bouman-K-L" }, { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" }, { "family_name": "Golwala", "given_name": "Sunil", "orcid": "0000-0002-1098-7174", "clpid": "Golwala-S-R" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Optical systems are often comprised of modular arrangements of components, and the improvement of these systems has historically leaned on the precise manufacturing and alignment of the comprising elements. This provides an intuitive pathway to optical design, but ultimately yields systems that are far bulkier than required by the laws of physics. It is often the case that the required degrees of freedom to achieve complex tasks is present within dielectric volumes that are only several wavelengths per side, and these degrees of freedom can be accessed by patterning the dielectric volume with subwavelength resolution. Even in such small volumes, all of the fundamental properties of light (wavelength, polarization, k-vector) can be controlled which opens the possibility for extremely multifunctional, compact image sensor elements. The determination of the refractive index distribution of these devices has historically been a challenging inverse-design problem, and the fabrication of 3D dielectric devices is a challenge unique to different regimes of the electromagnetic spectrum. This thesis utilizes current state-of-the-art optimization techniques to design multifunctional volumetric devices, and theoretically expands upon the techniques to facilitate the optimization of high index contrast structures. Multiple microwave prototypes are measured, devices operating at terahertz frequencies are fabricated using silicon micromachining, and optical devices with resolutions achievable with CMOS processing techniques are studied for next-generation camera sensors.
", "doi": "10.7907/dn7h-6r72", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:13946", "collection": "thesis", "collection_id": "13946", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09092020-162015646", "type": "thesis", "title": "Optical Light Manipulation and Imaging Through Scattering Media", "author": [ { "family_name": "Xu", "given_name": "Jian", "orcid": "0000-0002-4743-2471", "clpid": "Xu-Jian" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "orcid": "0000-0003-3003-7042", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Chen", "given_name": "Yanbei", "orcid": "0000-0002-9730-9463", "clpid": "Chen-Yanbei" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Typical optical systems are designed to be implemented in free space or clean media. However, the presence of optical scattering media scrambles light waves and becomes a problem in light field control, optical imaging, and sensing.
\r\n\r\nTo address the problem caused by optical scattering media, we discuss two types of solutions in this thesis. One type of solution is active control, where active modulators are used to modulate the light wave to compensate the wave distortion caused by optical scattering. The other type of solution is computational optics, where physical and mathematical models are built to computationally reconstruct the information from the measured distorted wavefront.
\r\n\r\nIn the part of active control, we first demonstrate coherent light focusing through scattering media by transmission matrix inversion. The transmission matrix inversion approach can realize coherent light control through scattering media with higher fidelity compared to conventional transmission matrix approaches. Then, by combining the pre-designed scattering metasurface with wavefront shaping, we demonstrate a beam steering system with large angular and high angular resolution. Next, we present optical-channel-based intensity streaming (OCIS), which uses only intensity information of light fields to realize light control through scattering media. This solution can be used to control spatially incoherent light propagating through scattering media. In the part of computational optics, we first demonstrate the idea of interferometric speckle visibility spectroscopy (ISVS) to measure the information cerebral blood flow. In ISVS, a camera records the speckle frames of diffused light from the human subject interferometrically, and the speckle statistics is used to calculate the speckle decorrelation time and consequently the blood flow index. Then, we compare the two methods of decorrelation time measurements - temporal sampling methods and spatial ensemble methods - and derive unified mathematical expressions for them in terms of measurement accuracy. Based on current technology of camera sensors and single detectors, our results indicate that spatial ensemble methods can have higher decorrelation time measurement accuracy compared to commonly used temporal sampling methods.
", "doi": "10.7907/4hkq-dz43", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14140", "collection": "thesis", "collection_id": "14140", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05112021-170331252", "primary_object_url": { "basename": "Han_PhD_Thesis_Caltech_2021_May_11th.pdf", "content": "final", "filesize": 26607848, "license": "other", "mime_type": "application/pdf", "url": "/14140/1/Han_PhD_Thesis_Caltech_2021_May_11th.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Dielectric Metasurfaces for Integrated Imaging Devices and Active Optical Elements", "author": [ { "family_name": "Kwon", "given_name": "Hyounghan", "orcid": "0000-0002-9257-687X", "clpid": "Hyounghan-Kwon" } ], "thesis_advisor": [ { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Atwater", "given_name": "Harry Albert", "orcid": "0000-0001-9435-0201", "clpid": "Atwater-H-A" }, { "family_name": "Marandi", "given_name": "Alireza", "orcid": "0000-0002-0470-0050", "clpid": "Marandi-A" }, { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" } ], "local_group": [ { "literal": "Kavli Nanoscience Institute" }, { "literal": "div_eng" } ], "abstract": "Optical dielectric metasurfaces have shown great advances in the last two decades and become promising candidates for next-generation free-space optical elements. In addition to their compatibility with scalable semiconductor fabrication technology, metasurfaces have provided new and efficient ways to manipulate diverse characteristics of light. In this thesis, we demonstrate the potential of dielectric metastructures in the realization of compact imaging devices, reconfigurable optical elements, and multi-layer inverse-designed metasurfaces. With the metasurfaces\u2019 extreme capability to simultaneously control phase and polarization, we first showcase their potential toward optical field imaging applications. In this regard, we demonstrate a system of dielectric metasurfaces and designed random metasurfaces for single-shot phase gradient microscopes and computational complex field imaging system, respectively. Then, we propose nano-electromechanically tunable resonant dielectric metasurfaces as a general platform for active metasurfaces. For example, we demonstrate two different types of the phase and amplitude modulators. While one utilizes resonant eigenmodes in the lattice such as leaky guided mode resonances and bound-states in the continuum modes, the other is based on the high-Q Mie resonances in the dielectric nanostructures where symmetry is broken. In addition to the modulation of the phase and amplitude, we also show tuning of strong chiroptical responses in dielectric chiral metasurfaces. Next, we experimentally demonstrate inverse-designed multi-layer metasurfaces. Not only do they provide increased degree of freedom in the design space, but also overcome limits of conventional design methods of the metasurfaces. Finally, we summarize the presented works and conclude this thesis with a brief outlook on what aspects of the metasurfaces can be important for their real-world applications in the future and what challenges and opportunities remain.
", "doi": "10.7907/j08n-0q77", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:13957", "collection": "thesis", "collection_id": "13957", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09182020-074010855", "type": "thesis", "title": "Active Flat Optics Wavefront Manipulation for Imaging, Ranging, and Sensing", "author": [ { "family_name": "Fatemi", "given_name": "Seyed Mohammadreza", "orcid": "0000-0001-9081-2608", "clpid": "Fatemi-Seyed-Mohammadreza" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" }, { "family_name": "Vahala", "given_name": "Kerry J.", "orcid": "0000-0003-1783-1380", "clpid": "Vahala-K-J" }, { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The emergence and maturity of integrated photonic platforms over the past decade allowed for reliable integration of a large number of photonic components on a single substrate. This ability to process and control coherent light on a chip is a potential pathway for the realization of novel low-cost systems capable of non-conventional functionalities for optical wavefront engineering. In this thesis, integrated active flat optics architectures for generation, manipulation, and reception of optical wavefronts are investigated. In particular, the application of such systems for imaging, ranging, and sensing are studied and multiple photonic systems including a large scale transmitter, a high-sensitivity receiver, and a high-resolution transceiver are demonstrated.
\r\n\r\nFor generation of optical wavefronts, solutions for engineering a radiative optical waveform via emission by an array of nano-photonic antennas are studied and a chip-scale photonic transmitter is implemented. The transmitter forms an optical phased array with a novel architecture in a CMOS compatible silicon photonics process which not only dispenses with the limitations of previously demonstrated systems but also yields a narrower beamwidth leading to a higher resolution. Moreover, an integrated adaptive flat optical receiver architecture that collects samples of the incident light and processes it on-chip with high detection sensitivity is implemented. To detect the optical samples with a high signal to noise ratio, an optoelectronic mixer is proposed and designed that down-converts the optical signals received by each antenna to a radio frequency signal in the electronic domain, provides conversion gain, and rejects interferers. This system allows arbitrary wavefront manipulation of the received signal by adapting itself to new conditions \u2014 a capability that does not exist in conventional cameras. Using this system, we realized the first high-sensitivity optical phased array receivers with one-dimensional and two-dimensional apertures and the functionality of the chips as ultra-thin lens-less cameras were demonstrated. To achieve a high-resolution integrated photonic 3D imager with low system complexity, a double spectral sampling method is developed through a special wavefront sampling arrangement on the transmitter and receiver apertures. This transceiver architecture includes a multi-beam transmitter and a high-sensitivity receiver that can distinguish the illuminated points separately and process them simultaneously using a digital signal processor.
\r\n\r\nMoreover, novel ultra-low power architectures for generation and reception of short RF/microwave pulses are explored. Such systems have a broad range of applications including imaging and ranging. In this study, the capability of generating and receiving orthogonal Hermite pulses of various orders using a capacitor-only time-varying network is demonstrated.
", "doi": "10.7907/7e5p-9r23", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14080", "collection": "thesis", "collection_id": "14080", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02162021-124026838", "primary_object_url": { "basename": "Aroutin_Khachaturian Thesis Final.pdf", "content": "final", "filesize": 42602622, "license": "other", "mime_type": "application/pdf", "url": "/14080/1/Aroutin_Khachaturian Thesis Final.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Large-Scale Photonics Integration: Data Communications to Optical Beamforming", "author": [ { "family_name": "Khachaturian", "given_name": "Aroutin", "orcid": "0000-0001-8304-3302", "clpid": "Khachaturian-Aroutin" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Hajimiri", "given_name": "Ali", "orcid": "0000-0001-6736-8019", "clpid": "Hajimiri-A" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Vahala", "given_name": "Kerry J.", "orcid": "0000-0003-1783-1380", "clpid": "Vahala-K-J" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Integrated photonics is an emerging technology that has begun to transform our way of life with the same amount of impact that integrated CMOS electronics has. Currently, photonics integration is orders of magnitude less complicated than its electronics counterparts. Nonetheless, it serves as one of the main driving forces to meet the exponentially increasing demand for high-speed and low-cost data transfer in the Information Age. It also promises to provide solutions for next-generation high-sensitivity image sensors and precision metrology and spectroscopy instruments. In this thesis, integrated photonics architectures for solid-state photonic beamforming and processing are investigated for high-resolution and high sensitivity lens-free transceiver applications. Furthermore, high-efficiency integrated electro-optical modulators aiming to meet the demand of high-density photonic integration with improved modulation efficiency, small footprint, and lower insertion loss are investigated.
\r\n\r\nTwo integrated photonic solid-state beamforming architectures incorporating two-dimensional apertures are explored. First, a novel transceiver architecture for remote sensing, coherent imaging, and ranging applications is demonstrated. It reduces system implementation complexity and offers a methodology for very-large-scale coherent transceiver beamforming applications. Next, a transmitter beamforming architecture inspired by the diffraction pattern of the slit annular ring is analyzed and demonstrated. This transceiver architecture can be used for coherent beamforming applications such as imaging and point-to-point optical communication. Finally, a coherent imager architecture for high-sensitivity three-dimensional imaging and remote-sensing applications is present. This novel architecture can suppress undesired phase fluctuations of the optical carrier signal in the illumination and reference paths, providing higher resolution and higher acquisition speed than previous implementations.
\r\n\r\nMoreover, several compact, high-speed CMOS compatible modulators that enable high-density photonic integration are explored. Ultra-compact and low insertion loss silicon-organic-hybrid modulators are designed and implemented for high-speed beamforming and high-efficiency complex signal modulation applications. Finally, a novel integrated nested-ring assisted modulator topology is analyzed and implemented for high-density and high modulation efficiency applications.
", "doi": "10.7907/xjby-xn13", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14084", "collection": "thesis", "collection_id": "14084", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02192021-010538691", "primary_object_url": { "basename": "chour_william_2021_thesis.pdf", "content": "final", "filesize": 140220437, "license": "other", "mime_type": "application/pdf", "url": "/14084/1/chour_william_2021_thesis.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Molecular Technologies for Antigen-Based Immunity", "author": [ { "family_name": "Chour", "given_name": "William", "orcid": "0000-0003-1817-0123", "clpid": "Chour-William" } ], "thesis_advisor": [ { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" } ], "thesis_committee": [ { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Heath", "given_name": "James R.", "orcid": "0000-0001-5356-4385", "clpid": "Heath-J-R" }, { "family_name": "Rothenberg", "given_name": "Ellen V.", "orcid": "0000-0002-3901-347X", "clpid": "Rothenberg-E-V" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Thomson", "given_name": "Matthew", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "The presence and proliferation antigen-specific T cells is a defining characteristic of an adaptive immune response against various disease types (autoimmune, cancer, and infectious). The use of Class I and Class II peptide-major histocompatibility complex (pMHC) reagents to identify such cells, however, is technically difficult and expensive, and it has been challenging to refine synthesis protocols for higher yield and more efficient assembly to accommodate large-scale applications. This achievement would enable high-throughput capture of corresponding T cell receptors (TCR), which may be further used in clinical applications such as adoptive cell transfer therapies. Overcoming this hurdle requires the development and integration of various molecular technologies and analytical methods.
\r\n\r\nToward this end, the bulk of my thesis work, covered in Chapter 2, introduces these developments in the context of pMHCs, where the three subunits of each reagent are covalent linked together and expressed as a single protein. These single-chain trimer (SCT) technologies primarily consist of traditional DNA cloning and protein production techniques which have been streamlined for applications requiring output on the scale of 102-103 of reagents. This chapter serves as the foundation for much of the methodology discussed throughout the rest of my thesis, and thus should serve as a reference point. The generated constructs are also functionally validated here, and potential future research directions are outlined.
\r\n\r\nIn Chapter 3, I explore the use of this technology in the context of COVID-19 to enumerate antigen specificity of the CD8+ T cell immune response. Class I SCTs were constructed to present peptides across several SARS-CoV-2 protein domains, using various HLA alleles to match haplotyped participant blood samples. These reagents were then used to capture SARS-CoV-2-specific T cells through flow and nanoparticle cytometry to demonstrate HLA-dependent, domain-dependent immune responses. Identified TCRs were cloned into T cells for confirmation of antigen specificity and functional cytotoxicity.
\r\n\r\nIn Chapters 4 and 5, I explore potential pMHC applications in cancer antigen contexts, covering both tumor-associated and tumor-specific antigens. Through various collaborations across the west coast (UCLA, Parker Institute, Fred Hutchinson Cancer Research Center), I make use of the SCT platform to showcase new assays to discover and rank key tumor targets (Chapter 4). Finally, Chapter 5 is a reproduction of our lab\u2019s published work concerning identification of antigen-specific CD8+ T cells from melanoma cancer patients.
\r\n\r\nIn summary, the adaptation of SCTs in a high-throughput format allows for the rapid enumeration of antigen-specific T-cell receptor sequences. As demonstrated in the contexts of COVID-19 and cancer, this SCT platform enables subsequent downstream applications, such as single-cell, antigen-specific immunophenotypic mapping/analysis and target discovery for personalized immunotherapies.
", "doi": "10.7907/z20t-nq62", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:13735", "collection": "thesis", "collection_id": "13735", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05292020-131840076", "primary_object_url": { "basename": "200529_erik_jue_2020_thesis_final.pdf", "content": "final", "filesize": 13853909, "license": "other", "mime_type": "application/pdf", "url": "/13735/1/200529_erik_jue_2020_thesis_final.pdf", "version": "v9.0.0" }, "type": "thesis", "title": "Improved Tools for Point-of-Care Nucleic Acid Amplification Testing", "author": [ { "family_name": "Jue", "given_name": "Erik Bradley", "orcid": "0000-0001-7585-3794", "clpid": "Jue-Erik-Bradley" } ], "thesis_advisor": [ { "family_name": "Ismagilov", "given_name": "Rustem F.", "orcid": "0000-0002-3680-4399", "clpid": "Ismagilov-R-F" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Ismagilov", "given_name": "Rustem F.", "orcid": "0000-0002-3680-4399", "clpid": "Ismagilov-R-F" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "There is a critical need for improved diagnostic tools to detect infectious diseases, especially in low-resource regions. A sample-to-answer point-of-care nucleic acid amplification test (NAAT) would be incredibly valuable for many different applications (e.g. COVID-19, Chlamydia/Gonorrhoeae, Influenza, Ebola, Zika/Chikungunya/Dengue, etc.). However, sample preparation (purification of pure nucleic acids) is a challenging bottleneck. In Chapter 2, commercial NA extraction methods were studied and improved. In Chapter 3, commercial stocks of SARS-CoV-2 RNA used in FDA emergency-use authorizations were found to be inaccurate and were independently quantified using reverse transcription digital PCR. In Chapter 4, a 3D printed meter-mix device was developed for initial processing prior to the sample preparation device. In Chapter 5, a 3D printed sample-to-device interface was prototyped to facilitate loading multi-volume SlipChip devices with purified template mixed with LAMP reactants. In Chapters 6-7, advancements were made for image processing of commercial chips to study digital LAMP reactions. In Chapter 8, additional tools were developed towards sample-to-answer point-of-care NAAT including a sample preparation module, amplification module, cell-phone readout, and automated base station.", "doi": "10.7907/d6mf-5081", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13600", "collection": "thesis", "collection_id": "13600", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12092019-113537728", "type": "thesis", "title": "Photoacoustic Tomography: From Bench to Bedside", "author": [ { "family_name": "Lin", "given_name": "Li", "orcid": "0000-0002-0517-8436", "clpid": "Lin-Li" } ], "thesis_advisor": [ { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Photoacoustic imaging (PAI) is an emerging imaging modality that shows great potential for preclinical research and clinical practice. As a hybrid technique, PAI uniquely combines the advantages of optical excitation and of acoustic detection. Optical absorption provides a rich contrast mechanism from either endogenous chromophores or exogenous contrast agents. Because ultrasound scatters much less than light in tissue, PAI generates high-resolution images in both the optical ballistic and diffusive regimes, overcoming the limitations imposed by light scattering in deep biological tissues. PAI has led to a variety of exciting discoveries and applications from laboratory research to clinical patient care.
\r\n\r\nTo translate photoacoustic technology from the bench to the bedside, this thesis focuses on efforts to increase the imaging depth, provide clinically useful information (i.e., relevant imaging contrast), reduce system size, and improve system reliability. Assisted by powerful pulsed lasers and advanced data acquisition circuits, modern PAI has achieved applications such as functional imaging of the whole rat brain, revealing detailed angiography and functional connectivity at high spatiotemporal resolution. The advancement of deep imaging in small animal PAI has been transferred to human breast and brain imaging, showing early promise for clinical practice. To further extend the imaging depth and provide dielectric imaging contrast, microwave-based thermoacoustic tomography has been demonstrated in vivo. To map further physiological contrasts, spectroscopic PAI has been performed to image the oxygenation states of hemoglobin and myoglobin. In addition to the effort towards deep penetration and multiple contrasts, benchtop photoacoustic microscopy has been minimized to a handheld probe for human skin imaging. As a rapidly evolving imaging technology, PAI is being translated from the bench to the bedside and promises exciting and useful clinical applications.
\r\n", "doi": "10.7907/1DGY-T168", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:11569", "collection": "thesis", "collection_id": "11569", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05302019-123348477", "primary_object_url": { "basename": "Shapero_Aubrey_2019_thesis_one_sided.pdf", "content": "final", "filesize": 83602799, "license": "other", "mime_type": "application/pdf", "url": "/11569/1/Shapero_Aubrey_2019_thesis_one_sided.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Long Term Implantable Pressure Sensors", "author": [ { "family_name": "Shapero", "given_name": "Aubrey Michael", "orcid": "0000-0002-8036-3623", "clpid": "Shapero-Aubrey-Michael" } ], "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": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The benefits of implantable pressure sensors for continuous monitoring of diseases like glaucoma or hydrocephalus has been well established, but it has been difficult to achieve accurate pressure sensing in the body for more than one month. In this thesis, a general MEMS pressure sensor packaging method called parylene-oil-encapsulation is developed and analyzed in order to make commercial barometers for use in air suitable for implantation inside the body long term. Accelerated aging bench top data is presented and a wireless implantable intraocular pressure sensor has been built towards proving the viability of the packaging method in vivo.
", "doi": "10.7907/SX5J-VM54", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:11136", "collection": "thesis", "collection_id": "11136", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07262018-030251324", "type": "thesis", "title": "Periodically Disturbed Oscillators", "author": [ { "family_name": "Hong", "given_name": "Brian Daffern", "orcid": "0000-0001-8099-0312", "clpid": "Hong-Brian-Daffern" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "By controlling the timing of events and enabling the transmission of data over long distances, oscillators can be considered to generate the \"heartbeat\" of modern electronic systems. Their utility, however, is boosted significantly by their peculiar ability to synchronize to external signals that are themselves periodic in time. Although this fascinating phenomenon has been studied by scientists since the 1600s, models for describing this behavior have seen a disconnect between the rigorous, methodical approaches taken by mathematicians and the design-oriented, physically-based analyses carried out by engineers. While the analytical power of the former is often concealed by an inundation of abstract mathematical machinery, the accuracy and generality of the latter are constrained by the empirical nature of the ensuing derivations. We hope to bridge that gap here.
\r\n\r\nIn this thesis, a general theory of electrical oscillators under the influence of a periodic injection is developed from first principles. Our approach leads to a fundamental yet intuitive understanding of the process by which oscillators lock to a periodic injection, as well as what happens when synchronization fails and the oscillator is instead injection pulled. By considering the autonomous and periodically time-varying nature that underlies all oscillators, we build a time-synchronous model that is valid for oscillators of any topology and periodic disturbances of any shape. A single first-order differential equation is shown to be capable of making accurate, quantitative predictions about a wide array of properties of periodically disturbed oscillators: the range of injection frequencies for which synchronization occurs, the phase difference between the injection and the oscillator under lock, stable vs. unstable modes of locking, the pull-in process toward lock, the dynamics of injection pulling, as well as phase noise in both free-running and injection-locked oscillators. The framework also naturally accommodates superharmonic injection-locked frequency division, subharmonic injection-locked frequency multiplication, and the general case of an arbitrary rational relationship between the injection and oscillation frequencies. A number of novel insights for improving the performance of systems that utilize injection locking are also elucidated. In particular, we explore how both the injection waveform and the oscillator's design can be modified to optimize the lock range. The resultant design techniques are employed in the implementation of a dual-moduli prescaler for frequency synthesis applications which features low power consumption, a wide operating range, and a small chip area.
\r\n\r\nFor the commonly used inductor-capacitor (LC) oscillator, we make a simple modification to our framework that takes the oscillation amplitude into account, greatly enhancing the model's accuracy for large injections. The augmented theory uniquely captures the asymmetry of the lock range as well as the distinct characteristics exhibited by different types of LC oscillators. Existing injection locking and pulling theories in the available literature are subsumed as special cases of our model. It is important to note that even though the veracity of our theoretical predictions degrades as the size of the injection grows due to our framework's linearization with respect to the disturbance, our model's validity across a broad range of practical injection strengths are borne out by simulations and measurements on a diverse collection of integrated LC, ring, and relaxation oscillators. Lastly, we also present a phasor-based analysis of LC and ring oscillators which yields a novel perspective into how the injection current interacts with the oscillator's core nonlinearity to facilitate injection locking.
", "doi": "10.7907/W0A7-4258", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:11185", "collection": "thesis", "collection_id": "11185", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09172018-140652131", "primary_object_url": { "basename": "Fowler_thesis_Final_20180924.pdf", "content": "final", "filesize": 66566036, "license": "other", "mime_type": "application/pdf", "url": "/11185/12/Fowler_thesis_Final_20180924.pdf", "version": "v10.0.0" }, "type": "thesis", "title": "Silicon Neural Probes for Stimulation of Neurons and the Excitation and Detection of Proteins in the Brain", "author": [ { "family_name": "Fowler", "given_name": "Trevor Michael", "clpid": "Fowler-Trevor-Michael" } ], "thesis_advisor": [ { "family_name": "Roukes", "given_name": "Michael Lee", "orcid": "0000-0002-2916-6026", "clpid": "Roukes-M-L" } ], "thesis_committee": [ { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" }, { "family_name": "Roukes", "given_name": "Michael Lee", "orcid": "0000-0002-2916-6026", "clpid": "Roukes-M-L" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" }, { "family_name": "Moreaux", "given_name": "Laurent C.", "orcid": "0000-0003-1276-5062", "clpid": "Moreaux-Laurent-C" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "This thesis describes the development of a number of novel microfabricated neural probes for a variety of specific neuroscience applications. These devices rely on single mode waveguides and grating couplers constructed from silicon nitride thin films, which allows the use of planar lightwave circuits to create advanced device geometries and functions. These probes utilize array waveguide gratings to select an individual emitter from a large array of emitters using the wavelength of incoming light, allowing for spatial multiplexing of optical stimulation. These devices were tested in the laboratory and in living tissue to verify their efficacy. This technology was then modified to create steerable beam forming for stimulation of neurons using optical phase arrays. This technology was also tested for use in fluoresence lifetime imaging microscopy and the first application of pulsed light through the photonic circuits. Finally, this technology was again modified to create laminar illumination patterns for light sheet fluorescence microscopy applications. These devices were further improved by adding embedded microfluidics to the probes. The process of creating embedded microfluidic channels by the dig and seal method is described in detail, including modifications to the procedure that were added to address potential pitfalls in the fabrication process. Next, two projects which combine microfluidics with the optical devices described in the previous chapter are detailed. One project involves combining the use of optical emitters with microfluidic injections containing caged neurotransmitters to stimulate neurons is described. The other project involves microfluidic sampling of the extracellular space for neuropeptides which are detected using ring resonator biosensors. The sensitivity of these biosensors was analyzed in detail, determining both the physical limit of detection and the effect of biological noise due to non-specific binding on the sensors.", "doi": "10.7907/2kvw-ad56", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:11698", "collection": "thesis", "collection_id": "11698", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06062019-165907194", "primary_object_url": { "basename": "Caltech-Thesis-Anupama Lakshmanan_06062019.pdf", "content": "final", "filesize": 56790831, "license": "other", "mime_type": "application/pdf", "url": "/11698/1/Caltech-Thesis-Anupama Lakshmanan_06062019.pdf", "version": "v20.0.0" }, "type": "thesis", "title": "Engineering Acoustic Protein Nanostructures for Non-Invasive Molecular Imaging using Ultrasound", "author": [ { "family_name": "Lakshmanan", "given_name": "Anupama", "orcid": "0000-0002-6702-837X", "clpid": "Lakshmanan-Anupama" } ], "thesis_advisor": [ { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "thesis_committee": [ { "family_name": "Tirrell", "given_name": "David A.", "orcid": "0000-0003-3175-4596", "clpid": "Tirrell-D-A" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Visualizing biomolecular and cellular processes in real time within deep tissues is fundamental to our understanding of the normal and pathological activity underlying health and disease. Ultrasound provides the ability to non-invasively image deep inside biological tissues with high spatial and temporal resolution. However, this technology has limited capacity to monitor molecular and cellular processes, due to the lack of appropriate intra-cellular and endogenously producible nanoscale contrast agents, which can directly couple sound waves to the activity or concentration of physiologically relevant molecules. This problem could in principle be solved by developing genetically encodable ultrasound sensors \u2013 biomolecules that can get illuminated in ultrasound imaging in response to specific cellular or molecular activity. This thesis describes the engineering and characterization of acoustic protein nanostructures called 'gas vesicles', or 'GVs', to accomplish this task.
\r\n\r\nGVs are protein-shelled gas-filled nanostructures produced by buoyant microbes, and were recently shown to be capable of scattering sound waves to produce ultrasound contrast. Owing to this property, they were initially conceptualized as a new class of ultrasound contrast agents. However, little was known about their tunability to enable molecular ultrasound imaging for a wide range of applications. In this thesis, we leveraged the genetic encodability of GVs to modify them at the level of their DNA sequence and constituent proteins, and thereby tune their mechanical, acoustic, surface and targeting properties. We accomplished this by establishing a facile and modular molecular engineering platform, to produce GVs that provide enhanced nonlinear signals for sensitive and specific detection in deep tissues, target specific cell types such as cancer and immune cells, and also provide distinct acoustic collapse spectra for multiplexed imaging. We then extended this platform to build GV-based biosensors that modulate their nonlinear ultrasound signals in response to changes in the activity or concentration of specific molecules in their environment. Specifically, we engineered acoustic sensors for three different types of enzymes and for calcium \u2013 whose activity or flux underlie a wide range of important cellular processes. Furthermore, we succeeded in transferring the genetic code of gas vesicles from their species of origin into a variety of other microbes that do not naturally produce them, in order to unlock their potential as ultrasound reporter genes. Our results establish GVs as reliable acoustic biomolecules, and thereby extend the capabilities of ultrasound for molecular and cellular imaging in a manner analogous to green fluorescent protein (GFP) and its derivatives in optical microscopy. When combined with the advantages of ultrasound for non-invasive imaging, this work facilitates novel technology to significantly enhance our understanding of molecular and cellular processes in basic biology, as well as enable improved diagnosis, monitoring and treatment of diseases.
", "doi": "10.7907/ASX5-KB62", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:11501", "collection": "thesis", "collection_id": "11501", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05072019-120355881", "primary_object_url": { "basename": "Caltech-Thesis-LeiLi_v12.pdf", "content": "final", "filesize": 7692212, "license": "other", "mime_type": "application/pdf", "url": "/11501/1/Caltech-Thesis-LeiLi_v12.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Multi-Contrast Photoacoustic Computed Tomography", "author": [ { "family_name": "Li", "given_name": "Lei", "orcid": "0000-0001-6164-2646", "clpid": "Li-Lei" } ], "thesis_advisor": [ { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Wang", "given_name": "Lihong", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Oka", "given_name": "Yuki", "orcid": "0000-0003-2686-0677", "clpid": "Oka-Yuki" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Imaging of small animals has played an indispensable role in preclinical research by providing high dimensional physiological, pathological, and phenotypic insights with clinical relevance. Yet pure optical imaging suffers from either shallow penetration (up to ~1\u20132 mm) or a poor depth-to-resolution ratio (~3), and non-optical techniques for whole-body imaging of small animals lack either spatiotemporal resolution or functional contrast. A stand-alone single-impulse photoacoustic computed tomography (PACT) system has been built, which successfully mitigates these limitations by integrating high spatiotemporal resolution, deep penetration, and full-view fidelity, as well as anatomical, dynamical, and functional contrasts. Based on hemoglobin absorption contrast, the whole-body dynamics and large scale brain functions of rodents have been imaged in real time. The absorption contrast between cytochrome and lipid has enabled PACT to resolve MRI-like whole brain structures. Taking advantage of the distinct absorption signature of melanin, unlabeled circulating melanoma cells have been tracked in real time in vivo.
\r\n\r\nAssisted by near-infrared dyes, the perfusion processes have been visualized in rodents. By localizing single-dyed droplets, the spatial resolution of PACT has been improved by six-fold in vivo. The migration of metallic-based microrobots toward the targeted regions in the intestines has been monitored in real time. Genetically encoded photochromic proteins benefit PACT in detection sensitivity and specificity. The unique photoswitching characteristics of different photochromic proteins allow quantitative multi-contrast imaging at depths. A split version of the photochromic protein has permitted PA detection of protein-protein interactions in deep-seated tumors. The photochromic behaviors have also been utilized to guide photons to form an optical focus inside live tissue. As a rapidly evolving imaging technique, PACT promises pre-clinical applications and clinical translation.
\r\n", "doi": "10.7907/FYGX-7M29", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:11525", "collection": "thesis", "collection_id": "11525", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05202019-151055724", "primary_object_url": { "basename": "JChung_thesis_v5.pdf", "content": "final", "filesize": 35150878, "license": "other", "mime_type": "application/pdf", "url": "/11525/1/JChung_thesis_v5.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Computational Imaging: a Quest for the Perfect Image", "author": [ { "family_name": "Chung", "given_name": "Jaebum", "orcid": "0000-0003-3932-8428", "clpid": "Chung-Jaebum" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Wang", "given_name": "Lihong", "clpid": "Wang-Lihong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "clpid": "Shapiro-M-G" }, { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" }, { "family_name": "Zheng", "given_name": "Guoan", "clpid": "Zheng-Guoan" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "A physical lens is limited in its ability to capture an image that is both high- resolution and wide-field due to aberrations even with a sophisticated lens design. This thesis explores computational methods that expand on the recently developed Fourier ptychographic microscopy (FPM) to overcome the physical limitations. New algorithms and imaging methods extend the computational aberration correction to more general imaging modalities including fluorescence microscopy and incoherent bright-field imaging so as to allow even a crude lens to perform like an ideal lens. This paradigm shift from the lens design to computational algorithms democratizes high-resolution imaging by making it easier to use and less complicated to build.", "doi": "10.7907/8W3A-HE02", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:11551", "collection": "thesis", "collection_id": "11551", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05282019-104728085", "primary_object_url": { "basename": "Brake_Thesis_2019.pdf", "content": "final", "filesize": 36468307, "license": "other", "mime_type": "application/pdf", "url": "/11551/1/Brake_Thesis_2019.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Seeing Through the Fog: Using Scattered Light to Peer Deeper into Biological Tissue\r ", "author": [ { "family_name": "Brake", "given_name": "Joshua Harris", "orcid": "0000-0002-5113-6886", "clpid": "Brake-Joshua-Harris" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Wang", "given_name": "Lihong", "clpid": "Wang-Lihong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Gradinaru", "given_name": "Viviana", "clpid": "Gradinaru-V" }, { "family_name": "Chung", "given_name": "Euiheon", "clpid": "Chung-Euiheon" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Optical scattering is a fundamental problem in biomedical optics and limits most optical techniques to shallow operating depths less than 1 millimeter. However, although the scattering behavior of tissue scrambles the information it contains, it does not destroy it. Therefore, if you can unscramble the scattered light, it increases the accessible imaging depths up the absorption limit of light (several centimeters deep).
\r\n\r\nOne such way to beat optical scattering is using wavefront shaping. Borrowing ideas from adaptive optics in astronomy and phased arrays in radar and ultrasonic imaging, the basic concept of wavefront shaping is to control the phase and amplitude of the light field in order to harness scattered light. Using wavefront shaping techniques, scattered light can be used to form focal spots or transmit information through or inside optically scattering media. Furthermore, even without correcting for scattering directly by shaping the input light field, the properties of the scattered light can be analyzed to recover information about the structure and dynamic properties of a sample using methods from diffuse optics.
\r\n\r\nThe main contributions of this thesis are along these two lines of research: moving wavefront shaping toward more practical applications and developing new techniques to recover useful physiological information from scattered light. This is developed through three main projects: (1) an investigation of how dynamic samples impact the scattering process and the practical implications of these dynamics on wavefront shaping systems, (2) the development of a wavefront shaping system combining light and ultrasound to focus light inside acute brain slices to improve light delivery for optogenetics, (3) a novel method to sensitively detect the dynamics of scattered light and use it to tease out information about the flow of blood within the tissue sample of interest.
", "doi": "10.7907/0PP8-2E39", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:10380", "collection": "thesis", "collection_id": "10380", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08152017-194113650", "primary_object_url": { "basename": "Lin-Caltech-FINAL-APPROVED.pdf", "content": "final", "filesize": 9828967, "license": "other", "mime_type": "application/pdf", "url": "/10380/1/Lin-Caltech-FINAL-APPROVED.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Ultrasound Speckle Image Velocimetry: Studies on System Performance and Application to Cardiovascular Fluid Dynamics", "author": [ { "family_name": "Lin", "given_name": "Ben Albert", "clpid": "Lin-Ben-Albert" } ], "thesis_advisor": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "thesis_committee": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Dabiri", "given_name": "John O.", "orcid": "0000-0002-6722-9008", "clpid": "Dabiri-J-O" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Knowledge of detailed blood flow characteristics can be extremely valuable in a variety of settings. Examples range from studying disease processes such as\r\natherosclerosis to aiding in the design of medical devices such as prosthetic cardiac valves. For in vivo and optically inaccessible in vitro flows, accurate measurements of velocity fields and shear stresses can be difficult to obtain. Doppler ultrasound and magnetic resonance imaging are the most commonly used techniques, but have important limitations. Recently, there has been increased interest in the application of particle image velocimetry principles towards tracking of ultrasound speckle patterns to determine multidimensional flow velocities with increased temporal resolution. We refer to our implementation as ultrasound speckle image velocimetry (USIV). In this research project, our first objective was to obtain a detailed characterization of the factors unique to ultrasound imaging that can influence the accuracy of velocity measurements. By conducting in vitro experiments with uniform speckle phantom translation as well as steady tube flow, we have shown that characteristics such as transducer focal depth and beam sweep speed as well as particle motion direction and velocity can all influence USIV results. Our second objective was to demonstrate the utility of USIV for analyzing in vivo blood flows. After administering ultrasound contrast agent to anesthetized\r\npigs, we were able to obtain detailed images of both left ventricular flow and\r\nabdominal aortic flow. Velocity profiles were measured during both left ventricular filling and ejection. Our most interesting finding was the presence in certain cases of highly asymmetric retrograde flow in the infrarenal aorta. The factors that lead to such flows may have relevance to the development of atherosclerosis and abdominal aneurysms. USIV is likely to be very useful for further studies both in vivo and with in vitro elastic aorta models.", "doi": "10.7907/Z998856J", "publication_date": "2018", "thesis_type": "phd", "thesis_year": "2018" }, { "id": "thesis:10442", "collection": "thesis", "collection_id": "10442", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09202017-124555409", "primary_object_url": { "basename": "Horie_Yu_2018.pdf", "content": "final", "filesize": 59827475, "license": "other", "mime_type": "application/pdf", "url": "/10442/1/Horie_Yu_2018.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Controlling the Flow of Light Using High-Contrast Metastructures", "author": [ { "family_name": "Horie", "given_name": "Yu", "orcid": "0000-0001-7083-1270", "clpid": "Horie-Yu" } ], "thesis_advisor": [ { "family_name": "Faraon", "given_name": "Andrei", "clpid": "Faraon-A" } ], "thesis_committee": [ { "family_name": "Faraon", "given_name": "Andrei", "clpid": "Faraon-A" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "Kavli Nanoscience Institute" }, { "literal": "div_eng" } ], "abstract": "A new class of planar optical components and devices has emerged using subwavelength metastructures with a strong contrast in refractive indices. High-contrast metastructures have shown promises to manipulate optical fields in an extraordinary way and to replace conventional bulky optical elements by their low-profile analogs, typically with subwavelength-scale features. We elucidate the underlying principle, how these seemingly low-profile geometries render unique optical responses, using the coupled-mode analysis in a multimode waveguide. Moreover, strong field localization in high-index structures allows us to interpret each single element in the metastructures as a low-quality-factor resonator (or a localized scatterer), permitting us to realize designer surface that shapes phase, amplitude, and polarization of light in free space, also known as an optical metasurface. The remainder of the thesis is devoted to explore novel applications in optics using high-contrast metastructures. One of the particularly interesting applications is to use them in an optical resonator. Specifically, we demonstrate to incorporate high-contrast subwavelength grating reflectors and dielectric metasufaces in a vertical Fabry\u2013Perot cavity, and show that we can flexibly tune the resonance frequency by the subwavelength patterning. With this technique, we envision the realization of compact, on-chip spectrometers when integrating them on a photodetector array. Secondly, we investigate the use of high-contrast subwavelength gratings in visible wavelengths. We perform the optimization of their geometries and demonstrate a set of RGB color filters, down to near a micrometer in the pixel size. This platform exhibits unique performances such as high efficiency, angular insensitivity, and color tunability by the design. A novel device concept is also explored, where a high-contrast subwavelength grating reflector is integrated on a silicon platform to constitute an active resonant antenna, enabling high-speed, phase-dominant modulation by means of thermo-optic effect of silicon. We demonstrate an array of such active antennas, yielding a beam deflection capability. This justifies the robustness of our device design, enabling a large-scale integration of high-speed, phase-dominant spatial light modulators. Finally, we introduce a disorder-engineered metasurface in the context of wavefront shaping. Recently, wavefront shaping with disordered media has demonstrated optical manipulation capabilities beyond those of conventional optics, but translating this class of technology into a practical use has remained challenging due to enormous amounts of information needed to be characterized as the input-output responses. As a paradigm shift, we propose the use of disorder-engineered metasurface in wavefront shaping, where the disorder is programmatically designed and makes the system characterization-free prior to use. With this approach, we demonstrate high numerical aperture focusing in an extended volume as well as wide-field fluorescence imaging with unprecedented performances.
", "doi": "10.7907/Z94X5604", "publication_date": "2018", "thesis_type": "phd", "thesis_year": "2018" }, { "id": "thesis:11022", "collection": "thesis", "collection_id": "11022", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06042018-194533722", "primary_object_url": { "basename": "phd-thesis_June2018.pdf", "content": "final", "filesize": 71599010, "license": "cc_by_nc", "mime_type": "application/pdf", "url": "/11022/1/phd-thesis_June2018.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Silicon Integrated Arrays: From Microwave to IR", "author": [ { "family_name": "Abiri", "given_name": "Behrooz", "orcid": "0000-0002-3317-2752", "clpid": "Abiri-Behrooz" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Weinreb", "given_name": "Sander", "clpid": "Weinreb-S" }, { "family_name": "Faraon", "given_name": "Andrei", "clpid": "Faraon-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Integrated chips have enabled realization and mass production of complex systems in a small form factor. Through process miniaturization many novel applications in silicon photonics and electronic systems have been enabled. In this thesis I have provided several examples of innovations that are only enabled by integration. I have also demonstrated how electronics and photonics circuits can complement each other to achieve a system with superior performance.
", "doi": "10.7907/MNYK-Y158", "publication_date": "2018", "thesis_type": "phd", "thesis_year": "2018" }, { "id": "thesis:10178", "collection": "thesis", "collection_id": "10178", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05162017-205230203", "primary_object_url": { "basename": "Safaripour_Thesis.pdf", "content": "final", "filesize": 50078784, "license": "other", "mime_type": "application/pdf", "url": "/10178/19/Safaripour_Thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Proximal-Field Radiation Sensors for Dynamically Controllable and Self-Correcting Integrated Radiators", "author": [ { "family_name": "Safaripour Tabbalvandani", "given_name": "Amirreza", "orcid": "0000-0001-9758-6156", "clpid": "Safaripour-Tabbalvandani-Amirreza" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Weinreb", "given_name": "Sander", "clpid": "Weinreb-S" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "One of the major challenges in the design of integrated radiators at mm-wave frequencies is the generation of surface waves in the dielectric substrate by the on-chip antennas. Since dielectric substrates are excellent surface waveguides with a fundamental mode with no cutoff frequency, there is always some energy trapped in them due to the surface waves and the excited substrate modes. This phenomenon is a significant cause of reduced radiation efficiency for mm-wave integrated radiators. However, in this thesis, we use this as an opportunity. We show that the excited substrate modes in the dielectric substrate of an integrated antenna contain valuable information regarding its far-field radiation properties. We introduce Proximal-Field Radiation Sensors (PFRS) as a number of small sensing antennas that are placed strategically on the same substrate as the integrated antenna and measure electromagnetic waves in its immediate proximity. These sensors extract the existing information in the substrate modes and use it to predict the far-field radiation properties of the integrated antenna in real-time based on in-situ measurements in the close proximity of the antennas, without any need to use additional test equipment and without removing the antenna from its operating environment or interfering with its operation in a wireless system. In other words, PFRS enables self-calibration, self-correction, and self-monitoring of the performance of the integrated antennas. Design intuition and a variety of data processing schemes for these sensors are discussed. Two proof-of-concept prototypes are fabricated on printed circuit board (PCB) and integrated circuit (IC) and both verify PFRS capabilities in prediction of radiation properties solely based on in-situ measurements.
\r\n\r\nDynamically controllable integrated radiators would significantly benefit from PFRS, These radiators are capable of controlling their radiation parameters such as polarization and beam steering angle through their actuators and control units. In these cases, PFRS serves as a tool for real-time monitoring of their radiation parameters, so that without direct measurement of the far-field properties through bulky equipment the required information for the control units and the actuators are provided.
\r\n\r\nDynamically controllable integrated radiators can be designed using the additional design space provided by Multi-Port Driven (MPD) radiator methodology. After a review of advantages of MPD design over the traditional single-port design, we show that a slot-based MPD radiator would have the additional advantage of reduced exclusive use area compared to the original wire-based MPD radiator, through demonstration of a 134.5-GHz integrated slot-based MPD radiator with a measured single-element EIRP of +6.0 dBm and a total radiated power of -1.3 dBm.
\r\n\r\nWe discuss how MPD methodology enables the new concept of Dynamic Polarization Control, as a method to ensure polarization matching of the transmitter antenna to the receiver antenna, regardless of the polarization and orientation of the receiver antenna in space. A DPC antenna design using the MPD methodology is described and a 105.5-GHz 2x1 integrated DPC radiator array with a maximum EIRP of +7.8 dBm and a total radiated power of 0.9 mW is presented as the first demonstration of an integrated radiator with DPC capability. This prototype can control the polarization angle across the entire tuning range of 0 to 180 degrees while maintaining axial ratios above 10 dB, and control the axial ratio from 2.4 dB (near circular) to 14 dB (linear). We also demonstrate how simultaneous two-dimensional beam steering and DPC capabilities can even match the polarization to a mobile receiver antenna through a prototype 123-GHz 2x2 integrated DPC radiator array with a maximum EIRP of +12.3 dBm, polarization angle control across the full range of 0to 180 degrees as well as tunable axial ratio down to 1.2 dB and beam steering of up to 15 degrees in both dimensions. We also use slot-based DPC antennas to fabricate a 120-GHz integrated slot-based DPC radiator array, expected to have a maximum EIRP of +15.5 dBm.
\r\n\r\nWe also introduce a new modulation scheme called Polarization Modulation (Pol-M) as a result of DPC capability, where the polarization itself is used for encoding the data. Pol-M is a spatial modulation method and is orthogonal to the existing phase and amplitude modulation schemes. Thus, it could be added on top of those schemes to enable creation of 4-D data constellations, or it can be used as the only basis for modulation to increase the stream security by misleading the undesired receivers. We discuss how DPC antenna enables Pol-M and also present PCB prototypes for Pol-M transmitter and receiver units operating at 2.4 GHz.
\r\n", "doi": "10.7907/Z9DR2SJZ", "publication_date": "2017", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:9911", "collection": "thesis", "collection_id": "9911", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09022016-135721172", "primary_object_url": { "basename": "richard_yuhua_chen_2017_thesis.pdf", "content": "final", "filesize": 11314124, "license": "other", "mime_type": "application/pdf", "url": "/9911/1/richard_yuhua_chen_2017_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Concentration Inequalities of Random Matrices and Solving Ptychography with a Convex Relaxation", "author": [ { "family_name": "Chen", "given_name": "Yuhua Richard", "clpid": "Chen-Yuhua-Richard" } ], "thesis_advisor": [ { "family_name": "Tropp", "given_name": "Joel A.", "clpid": "Tropp-J-A" } ], "thesis_committee": [ { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" }, { "family_name": "Hou", "given_name": "Thomas Y.", "clpid": "Hou-T-Y" }, { "family_name": "Owhadi", "given_name": "Houman", "clpid": "Owhadi-H" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tropp", "given_name": "Joel A.", "clpid": "Tropp-J-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Random matrix theory has seen rapid development in recent years. In particular, researchers have developed many non-asymptotic matrix concentration inequalities that parallel powerful scalar concentration inequalities. In this thesis, we focus on three topics: 1) estimating sparse covariance matrix using matrix concentration inequalities, 2) constructing the matrix phi-entropy to derive matrix concentration inequalities, 3) developing scalable algorithms to solve the phase recovery problem of ptychography based on low-rank matrix factorization.
\r\n\r\nEstimation of covariance matrix is an important subject. In the setting of high dimensional statistics, the number of samples can be small in comparison to the dimension of the problem, thus estimating the complete covariance matrix is unfeasible. By assuming that the covariance matrix satisfies some sparsity assumptions, prior work has proved that it is feasible to estimate the sparse covariance matrix of Gaussian distribution using the masked sample covariance estimator. In this thesis, we use a new approach and apply non-asymptotic matrix concentration inequalities to obtain tight sample bounds for estimating the sparse covariance matrix of subgaussian distributions.
\r\n\r\nThe entropy method is a powerful approach in developing scalar concentration inequalities. The key ingredient is the subadditivity property that scalar entropy function exhibits. In this thesis, we construct a new concept of matrix phi-entropy and prove that matrix phi-entropy also satisfies a subadditivity property similar to the scalar form. We apply this new concept of matrix phi-entropy to derive non-asymptotic matrix concentration inequalities.
\r\n\r\nPtychography is a computational imaging technique which transforms low-resolution intensity-only images into a high-resolution complex recovery of the signal. Conventional algorithms are based on alternating projection, which lacks theoretical guarantees for their performance. In this thesis, we construct two new algorithms. The first algorithm relies on a convex formulation of the ptychography problem and on low-rank matrix recovery. This algorithm improves traditional approaches' performance but has high computational cost. The second algorithm achieves near-linear runtime and memory complexity by factorizing the objective matrix into its low-rank components and approximates the first algorithm's imaging quality.
", "doi": "10.7907/Z9M906MF", "publication_date": "2017", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:10146", "collection": "thesis", "collection_id": "10146", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04262017-114441886", "type": "thesis", "title": "Compact Microscope System for Biomedical Applications", "author": [ { "family_name": "Kim", "given_name": "Jinho", "clpid": "Kim-Jinho" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Lester", "given_name": "Henry A.", "clpid": "Lester-H-A" }, { "family_name": "Elowitz", "given_name": "Michael B.", "clpid": "Elowitz-M-B" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Demands for an imaging system which has high space-bandwidth product (SBP) are increasing in modern biomedical research as the amount of information to be dealt with is increasing. However, conventional microscopy has a limited SBP of about 10 mega pixels, and as such if a user wants an image in high resolution, the field of view (FOV) of the image is reduced, or if a wide FOV is necessary, the user needs to give up the resolution of image. A common way of overcoming this SBP limit in the conventional microscopy is to use mechanical moving stages and scan through wide sample area, however, it is time consuming to image large area using a high numerical aperture (NA) objective lens. This thesis presents compact imaging systems based on Fourier ptychographic microscopy for biomedical applications which are able to increase SBP without having any mechanical moving parts: one imaging system for an incubator embedded imaging system to be used in in-vitro cell culture monitoring, and the other for a high throughput 96 well plate imaging system for fast drug screening.
", "doi": "10.7907/Z9H9937R", "publication_date": "2017", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:9927", "collection": "thesis", "collection_id": "9927", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09292016-114827320", "type": "thesis", "title": "Electrical Impedance Based Spectroscopy and Tomography Techniques for Obesity and Heart Diseases", "author": [ { "family_name": "Zhang", "given_name": "Shell Xiaoxiao", "clpid": "Zhang-Shell-Xiaoxiao" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Hsiai", "given_name": "Tzung", "clpid": "Hsiai-Tzung" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Despite advances in diagnosis and therapy, atherosclerosis cardiovascular disease remains the leading cause of morbidity and mortality. Predicting metabolically active atherosclerotic lesions has remained an unmet clinical need. Specially, atherosclerotic plaques that are prone to rupture are of extremely high-risk and can cause detrimental heart attacks and/or strokes, leading to sudden death. It has been shown that atheroscleroses is correlated to the level of obesity of an individual [1] Usually in clinical practice, the doctor will assess a patient's \"risk factor\" based on his or her Body Mass Index (BMS), and measurement of the waist circumference. Meanwhile the level of fatty droplet deposits in the liver is an important bio-marker to assess the patient's risk factor, however the patient will need to undergo radiation imaging such as CT scan or MRI scan.
\r\n\r\nFor the vulnerable plaques that can lead to sudden rupture, the ability to distinguish them at an early stage remains largely lacking. Therefore it is of great clinical interest to find improved diagnostic techniques to identify and localize such vulnerable plaques. Meanwhile, lipid has significantly lower electrical impedance than the rest of the vessel tissues in certain frequency bands [2]. In this thesis we explore spectroscopic and tomographic methods to characterize such plaques. In addition, with the Electrical Impedance Tomography method we will propose a novel method to detect fatty liver in an early stage with non-radiating and non-invasive manner.
", "doi": "10.7907/Z9CC0XPJ", "publication_date": "2017", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:10179", "collection": "thesis", "collection_id": "10179", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05172017-103505376", "primary_object_url": { "basename": "Zhou_Edward Haojiang_2017.pdf", "content": "final", "filesize": 54748561, "license": "other", "mime_type": "application/pdf", "url": "/10179/44/Zhou_Edward Haojiang_2017.pdf", "version": "v13.0.0" }, "type": "thesis", "title": "Optical Focusing and Imaging through Scattering Media", "author": [ { "family_name": "Zhou", "given_name": "Edward Haojiang", "orcid": "0000-0001-7020-9502", "clpid": "Zhou-Edward-Haojiang" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Judkewitz", "given_name": "Benjamin", "clpid": "Judkewitz-Benjamin" }, { "family_name": "Wang", "given_name": "Lihong", "clpid": "Wang-Lihong" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Cai", "given_name": "Long", "clpid": "Cai-Long" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Optical techniques, which have been widely used in various fields including bio-medicine, remote sensing, astronomy, and industrial production, play an important role in modern life. Optical focusing and imaging, which correspond to the basic methods of utilizing light, are key to the implementation of optical techniques. In free space or a nearly transparent medium, optical imaging and focusing can be easily realized by using conventional optical elements, such as lenses and mirrors, due to the ballistic propagation of light in these media. However, in scattering media like biological tissue and fog, refractive index inhomogeneities cause diffusive propagation of light that increases with depth, which restricts the use of optical methods in thick, scattering media. Generally speaking, scattering media poses three challenges to optical focusing and imaging: wavefront aberrations, glare, and decorrelation. Wavefront aberrations can randomize light traveling through a scattering medium, disrupt the formation of focus, and break the conjugate relation in imaging. Glare caused by backscattering will largely impair the visibility of imaging, and decorrelation in dynamic media requires systems that counter the effect of scattering to operate faster than the decorrelation time. In this thesis, we explored solutions to the problem of scattering from different aspects. We presented Time Reversal by Analysis of Changing wavefronts from Kinetic targets (TRACK) technique to realize noninvasive optical focusing through a scattering medium. We showed that by taking the difference between time-varying scattering fields caused by a moving object and applying optical phase conjugation, light can be focused back to the location previously occupied by the object. To tackle the decorrelation of living tissue, we built up a fast digital optical phase conjugation (DOPC) system based on FPGA and DMD, which has a response time of 5.3 ms and was the fastest DOPC system in the world before 2017. We demonstrated that the system is fast enough to focus light through 2.3mm-thick living mouse skin. As for glare, inspired by noise canceling headphones, we invented an optical analogue termed coherence gated negation (CGN) technique. CGN can optically cancel out the glare in an active illumination imaging scenario to realize imaging through scattering media, like fog. In the experiment, we suppressed the glare by an order of magnitude and allowed improved imaging of a weak target. Finally, we demonstrated a method to image a moving target through scattering media noninvasively. Its principle roots are in the speckle-correlation-based imaging (SCI) invented by Ori Katz. We improved the technique and extended its application to bright field imaging of a moving target.
", "doi": "10.7907/Z9TX3CD1", "publication_date": "2017", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:9818", "collection": "thesis", "collection_id": "9818", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05312016-211459301", "primary_object_url": { "basename": "liu_zhao_2016_thesis.pdf", "content": "final", "filesize": 11058862, "license": "other", "mime_type": "application/pdf", "url": "/9818/55/liu_zhao_2016_thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Electromyographic Signal Processing With Application To Spinal Cord Injury", "author": [ { "family_name": "Liu", "given_name": "Zhao", "clpid": "Liu-Zhao" } ], "thesis_advisor": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Rutledge", "given_name": "David B.", "clpid": "Rutledge-D-B" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "An Electromyogram or Electromyographic (EMG) signal is the recording of the electrical activity produced by muscles. It measures the electric currents generated in muscles during their contraction. The EMG signal provides insight into the neural activation and dynamics of the muscles, and is therefore important for many different applications, such as in clinical investigations that attempt to diagnose neuromuscular deficiencies. In particular, the work in this thesis is motivated by rehabilitation for patients with spinal cord injury. The EMG signal is very important for researchers and practitioners to monitor and evaluate the effect of the rehabilitation training and the condition of muscles, as the EMG signal provides information that helps infer the neural activity in the spinal cord. Before the work in this thesis, EMG analysis required significant amounts of manual labeling of interesting signal features. The motivation of this thesis is to fully automate the EMG analysis tasks and yield accurate, consistent results.
\r\n\r\nThe EMG signal contains multiple muscle responses. The difficulty in processing the EMG signal arises from the fact that the transient muscle response is a transient signal with unknown arrival time, unknown duration, and unknown shape. In addition, the EMG signal recorded from patients with spinal cord injury during rehabilitation is very different from the EMG signal of normal healthy people undergoing the same motions. For example, some of the muscle responses are very weak and thus hard to detect. Because of this, general EMG processing tools and methods are either not applicable or insufficient.
\r\n\r\nThe primary contribution of this thesis is the development of a wavelet-based, double-threshold algorithm for the detection of transient peaks in the EMG signal. The application of wavelet transform in the detection of transient signals has been studied extensively and employed successfully. However, most of the theories assume certain knowledge about the shapes of the transient signals, which makes it hard to be generalized to the transient signals with arbitrary shapes. The proposed detection scheme focuses on the more fundamental feature of most transient signals (in particular the EMG signal): peaks, instead of the shapes. The continuous wavelet transform with Mexican Hat wavelet is employed. This thesis theoretically derived a framework for selecting a set of scales based on the frequency domain information. Ridges are identified in the time-scale space to combine the wavelet coefficients from different scales. By imposing two thresholds, one on the wavelet coefficient and one on the ridge length, the proposed detection scheme can achieve both high recall and high precision. A systematic approach for selecting the optimal parameters via simulation is proposed and demonstrated. Comparing with other state-of-the-art detection methods, the proposed method in this thesis yields a better detection performance, especially in the low Signal-to-Noise-Ratio (SNR) environment.
\r\n\r\nBased on the transient peak detection result, the EMG signal is further segmented and classified into various groups of monosynaptic Motor Evoked Potentials (MEPs) and polysynaptic MEPs using techniques stemming from Principal Component Analysis (PCA), hierarchical clustering, and Gaussian mixture model (GMM). A theoretical framework is proposed to segment the EMG signal based on the detected peaks. The scale information of the detected peak is used to derive a measure for its effective support. Several different techniques have been adapted together to solve the clustering problem. An initial hierarchical clustering is first performed to obtain most of the monosynaptic MEPs. PCA is used to reduce the number of features and the effect of the noise. The reduced feature set is then fed to a GMM to further divide the MEPs into different groups of similar shapes. The method of breaking down a segment of multiple consecutive MEPs into individual MEPs is derived.
\r\n\r\nA software with graphic user interface has been implemented in Matlab. The software implements the proposed peak detection algorithm, and enables the physiologists to visualize the detection results and modify them if necessary. The solutions proposed in this thesis are not only helpful to the rehabilitation after spinal cord injury, but applicable to other general processing tasks on transient signals, especially on biological signals.
", "doi": "10.7907/Z9QJ7F99", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9814", "collection": "thesis", "collection_id": "9814", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05312016-051759406", "primary_object_url": { "basename": "Kishore_Jaganathan_2016_Thesis.pdf", "content": "final", "filesize": 3539409, "license": "other", "mime_type": "application/pdf", "url": "/9814/1/Kishore_Jaganathan_2016_Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Convex Programming-Based Phase Retrieval: Theory and Applications", "author": [ { "family_name": "Jaganathan", "given_name": "Kishore", "clpid": "Jaganathan-Kishore" } ], "thesis_advisor": [ { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" } ], "thesis_committee": [ { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Tropp", "given_name": "Joel A.", "clpid": "Tropp-J-A" }, { "family_name": "Chandrasekaran", "given_name": "Venkat", "clpid": "Chandrasekaran-V" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Phase retrieval is the problem of recovering a signal from its Fourier magnitude. This inverse problem arises in many areas of engineering and applied physics, and has been studied for nearly a century. Due to the absence of Fourier phase, the available information is incomplete in general. Classic identifiability results state that phase retrieval of one-dimensional signals is impossible, and that phase retrieval of higher-dimensional signals is almost surely possible under mild conditions. However, there are no efficient recovery algorithms with theoretical guarantees. Classic algorithms are based on the method of alternating projections. These algorithms do not have theoretical guarantees, and have limited recovery abilities due to the issue of convergence to local optima.
\r\n\r\nRecently, there has been a renewed interest in phase retrieval due to technological advances in measurement systems and theoretical developments in structured signal recovery. In particular, it is now possible to obtain specific kinds of additional magnitude-only information about the signal, depending on the application. The premise is that, by carefully redesigning the measurement process, one could potentially overcome the issues of phase retrieval. To this end, another approach could be to impose certain kinds of prior on the signal, depending on the application. On the algorithmic side, convex programming based approaches have played a key role in modern phase retrieval, inspired by their success in provably solving several quadratic constrained problems.
\r\n\r\nIn this work, we study several variants of phase retrieval using modern tools, with focus on applications like X-ray crystallography, diffraction imaging, optics, astronomy and radar. In the one-dimensional setup, we first develop conditions, which when satisfied, allow unique reconstruction. Then, we develop efficient recovery algorithms based on convex programming, and provide theoretical guarantees. The theory and algorithms we develop are independent of the dimension of the signal, and hence can be used in all the aforementioned applications. We also perform a comparative numerical study of the convex programming and the alternating projection based algorithms. Numerical simulations clearly demonstrate the superior ability of the convex programming based methods, both in terms of successful recovery in the noiseless setting and stable reconstruction in the noisy setting.
", "doi": "10.7907/Z9C82775", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9771", "collection": "thesis", "collection_id": "9771", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05262016-142345346", "primary_object_url": { "basename": "Mooseok_Jang_2016_Thesis.pdf", "content": "final", "filesize": 53211730, "license": "other", "mime_type": "application/pdf", "url": "/9771/1/Mooseok_Jang_2016_Thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Optical Phase Conjugation and Its Applications in Biology", "author": [ { "family_name": "Jang", "given_name": "Mooseok", "orcid": "0000-0003-1977-9539", "clpid": "Jang-Mooseok" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Vellekoop", "given_name": "Ivo", "clpid": "Vellekoop-I" }, { "family_name": "Gradinaru", "given_name": "Viviana", "clpid": "Gradinaru-V" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Optical phase conjugation is a process where an incoming electromagnetic wave is reflected with a reversed phase. The propagation direction of an incoming beam (equivalently, local phase gradient) can thereby be precisely reversed by the phase conjugate beam. This intriguing effect, so called \"time-reversal of electromagnetic waves,\" allows cancellation of spatial distortion introduced into the incoming beam. Recently, this concept has provided a new avenue to overcome or utilize random scattering in the field of biophotonics.
\r\n\r\nThis thesis discusses a number of interrelated topics regarding optical phase conjugation and its applications in biology. First, two examples of exploiting optical phase conjugation for light focusing are presented. The first example shows that the axial resolution can be improved based on the counter-propagating property of the phase-conjugate beam, and the second example demonstrates how the random scattering media can be used to enhance the flexibility in focusing range. We then discuss a new class of techniques that involves the use of guidestars in the phase conjugation process for deep tissue (> 1mm) light focusing and imaging. In the context of in vivo application, we model and estimate the penetration depth limit of one prominent example of this approach, time-reversed ultrasonically encoded (TRUE) optical focusing. Based on the analysis, we show that the iteration of phase conjugation operation can improve the contrast and resolution of the focal spot created inside deep tissue. We also present a new kind of guidestar-assisted method, time-reversed ultrasound microbubble encoded (TRUME) light focusing, which can focus light with sub-ultrasound wavelength resolution. At last, the effect of dynamic scatterers on time-reversal fidelity is studied to explore the possibility of applying the optical phase conjugation techniques in living tissue.
", "doi": "10.7907/Z99G5JSN", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9688", "collection": "thesis", "collection_id": "9688", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04282016-051723211", "primary_object_url": { "basename": "Xiaoze_Thesis_Caltech_04282016.pdf", "content": "final", "filesize": 13112405, "license": "other", "mime_type": "application/pdf", "url": "/9688/1/Xiaoze_Thesis_Caltech_04282016.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Computational Microscopy: Breaking the Limit of Conventional Optics", "author": [ { "family_name": "Ou", "given_name": "Xiaoze", "orcid": "0000-0001-9918-0221", "clpid": "Ou-Xiaoze" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "clpid": "Shapiro-M-G" }, { "family_name": "Cai", "given_name": "Long", "clpid": "Cai-Long" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Computational imaging is flourishing thanks to the recent advancement in array photodetectors and image processing algorithms. This thesis presents Fourier ptychography, which is a computational imaging technique implemented in microscopy to break the limit of conventional optics. With the implementation of Fourier ptychography, the resolution of the imaging system can surpass the diffraction limit of the objective lens's numerical aperture; the quantitative phase information of a sample can be reconstructed from intensity-only measurements; and the aberration of a microscope system can be characterized and computationally corrected. This computational microscopy technique enhances the performance of conventional optical systems and expands the scope of their applications.", "doi": "10.7907/Z9M32SRZ", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9231", "collection": "thesis", "collection_id": "9231", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10202015-173005082", "primary_object_url": { "basename": "thesis_final_10-20-15.pdf", "content": "final", "filesize": 38189479, "license": "other", "mime_type": "application/pdf", "url": "/9231/1/thesis_final_10-20-15.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Computational Microscopy: Turning Megapixels into Gigapixels", "author": [ { "family_name": "Horstmeyer", "given_name": "Roarke William", "orcid": "0000-0002-2480-9141", "clpid": "Horstmeyer-Roarke-William" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tropp", "given_name": "Joel A.", "clpid": "Tropp-J-A" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" }, { "family_name": "Zheng", "given_name": "Guoan", "clpid": "Zheng-Guoan" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The layout of a typical optical microscope has remained effectively unchanged over the past century. Besides the widespread adoption of digital focal plane arrays, relatively few innovations have helped improve standard imaging with bright-field microscopes. This thesis presents a new microscope imaging method, termed Fourier ptychography, which uses an LED to provide variable sample illumination and post-processing algorithms to recover useful sample information. Examples include increasing the resolution of megapixel-scale images to one gigapixel, measuring quantitative phase, achieving oil-immersion quality resolution without an immersion medium, and recovering complex\r\nthree dimensional sample structure.", "doi": "10.7907/Z95Q4T1W", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:8982", "collection": "thesis", "collection_id": "8982", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06042015-065451017", "primary_object_url": { "basename": "MEMS for Diabetic Retinopathy_Dongyang_06122015_Final.pdf", "content": "final", "filesize": 15903015, "license": "other", "mime_type": "application/pdf", "url": "/8982/1/MEMS for Diabetic Retinopathy_Dongyang_06122015_Final.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "MEMS for Diabetic Retinopathy", "author": [ { "family_name": "Kang", "given_name": "Dongyang", "clpid": "Kang-Dongyang" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Mark", "clpid": "Humayun-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "As the worldwide prevalence of diabetes mellitus continues to increase, diabetic retinopathy remains the leading cause of visual impairment and blindness in many developed countries. Between 32 to 40 percent of about 246 million people with diabetes develop diabetic retinopathy. Approximately 4.1 million American adults 40 years and older are affected by diabetic retinopathy. This glucose-induced microvascular disease progressively damages the tiny blood vessels that nourish the retina, the light-sensitive tissue at the back of the eye, leading to retinal ischemia (i.e., inadequate blood flow), retinal hypoxia (i.e., oxygen deprivation), and retinal nerve cell degeneration or death. It is a most serious sight-threatening complication of diabetes, resulting in significant irreversible vision loss, and even total blindness.
\r\n\r\nUnfortunately, although current treatments of diabetic retinopathy (i.e., laser therapy, vitrectomy surgery and anti-VEGF therapy) can reduce vision loss, they only slow down but cannot stop the degradation of the retina. Patients require repeated treatment to protect their sight. The current treatments also have significant drawbacks. Laser therapy is focused on preserving the macula, the area of the retina that is responsible for sharp, clear, central vision, by sacrificing the peripheral retina since there is only limited oxygen supply. Therefore, laser therapy results in a constricted peripheral visual field, reduced color vision, delayed dark adaptation, and weakened night vision. Vitrectomy surgery increases the risk of neovascular glaucoma, another devastating ocular disease, characterized by the proliferation of fibrovascular tissue in the anterior chamber angle. Anti-VEGF agents have potential adverse effects, and currently there is insufficient evidence to recommend their routine use.
\r\n\r\nIn this work, for the first time, a paradigm shift in the treatment of diabetic retinopathy is proposed: providing localized, supplemental oxygen to the ischemic tissue via an implantable MEMS device. The retinal architecture (e.g., thickness, cell densities, layered structure, etc.) of the rabbit eye exposed to ischemic hypoxic injuries was well preserved after targeted oxygen delivery to the hypoxic tissue, showing that the use of an external source of oxygen could improve the retinal oxygenation and prevent the progression of the ischemic cascade.
\r\n\r\nThe proposed MEMS device transports oxygen from an oxygen-rich space to the oxygen-deficient vitreous, the gel-like fluid that fills the inside of the eye, and then to the ischemic retina. This oxygen transport process is purely passive and completely driven by the gradient of oxygen partial pressure (pO2). Two types of devices were designed. For the first type, the oxygen-rich space is underneath the conjunctiva, a membrane covering the sclera (white part of the eye), beneath the eyelids and highly permeable to oxygen in the atmosphere when the eye is open. Therefore, sub-conjunctival pO2 is very high during the daytime. For the second type, the oxygen-rich space is inside the device since pure oxygen is needle-injected into the device on a regular basis.
\r\nTo prevent too fast or too slow permeation of oxygen through the device that is made of parylene and silicone (two widely used biocompatible polymers in medical devices), the material properties of the hybrid parylene/silicone were investigated, including mechanical behaviors, permeation rates, and adhesive forces. Then the thicknesses of parylene and silicone became important design parameters that were fine-tuned to reach the optimal oxygen permeation rate.
\r\n\r\nThe passive MEMS oxygen transporter devices were designed, built, and tested in both bench-top artificial eye models and in-vitro porcine cadaver eyes. The 3D unsteady saccade-induced laminar flow of water inside the eye model was modeled by computational fluid dynamics to study the convective transport of oxygen inside the eye induced by saccade (rapid eye movement). The saccade-enhanced transport effect was also demonstrated experimentally. Acute in-vivo animal experiments were performed in rabbits and dogs to verify the surgical procedure and the device functionality. Various hypotheses were confirmed both experimentally and computationally, suggesting that both the two types of devices are very promising to cure diabetic retinopathy. The chronic implantation of devices in ischemic dog eyes is still underway.
\r\nThe proposed MEMS oxygen transporter devices can be also applied to treat other ocular and systemic diseases accompanied by retinal ischemia, such as central retinal artery occlusion, carotid artery disease, and some form of glaucoma.
\r\n", "doi": "10.7907/Z97D2S34", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8763", "collection": "thesis", "collection_id": "8763", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01302015-101318815", "primary_object_url": { "basename": "Han_Chao_2015_Thesis.pdf", "content": "final", "filesize": 5996704, "license": "other", "mime_type": "application/pdf", "url": "/8763/1/Han_Chao_2015_Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Wide Field-of-View Microscopes and Endoscopes for Time-Lapse Imaging and High-Throughput Screening", "author": [ { "family_name": "Han", "given_name": "Chao", "clpid": "Han-Chao" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Ismagilov", "given_name": "Rustem F.", "clpid": "Ismagilov-R-F" }, { "family_name": "Lai", "given_name": "Lily L.", "clpid": "Lai-Lily-L" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Wide field-of-view (FOV) microscopy is of high importance to biological research and clinical diagnosis where a high-throughput screening of samples is needed. This thesis presents the development of several novel wide FOV imaging technologies and demonstrates their capabilities in longitudinal imaging of living organisms, on the scale of viral plaques to live cells and tissues.
\r\n\r\nThe ePetri Dish is a wide FOV on-chip bright-field microscope. Here we applied an ePetri platform for plaque analysis of murine norovirus 1 (MNV-1). The ePetri offers the ability to dynamically track plaques at the individual cell death event level over a wide FOV of 6 mm \u00d7 4 mm at 30 min intervals. A density-based clustering algorithm is used to analyze the spatial-temporal distribution of cell death events to identify plaques at their earliest stages. We also demonstrate the capabilities of the ePetri in viral titer count and dynamically monitoring plaque formation, growth, and the influence of antiviral drugs.
\r\n\r\nWe developed another wide FOV imaging technique, the Talbot microscope, for the fluorescence imaging of live cells. The Talbot microscope takes advantage of the Talbot effect and can generate a focal spot array to scan the fluorescence samples directly on-chip. It has a resolution of 1.2 \u03bcm and a FOV of ~13 mm2. We further upgraded the Talbot microscope for the long-term time-lapse fluorescence imaging of live cell cultures, and analyzed the cells\u2019 dynamic response to an anticancer drug.
\r\n \r\nWe present two wide FOV endoscopes for tissue imaging, named the AnCam and the PanCam. The AnCam is based on the contact image sensor (CIS) technology, and can scan the whole anal canal within 10 seconds with a resolution of 89 \u03bcm, a maximum FOV of 100 mm \u00d7 120 mm, and a depth-of-field (DOF) of 0.65 mm. We also demonstrate the performance of the AnCam in whole anal canal imaging in both animal models and real patients. In addition to this, the PanCam is based on a smartphone platform integrated with a panoramic annular lens (PAL), and can capture a FOV of 18 mm \u00d7 120 mm in a single shot with a resolution of 100\u2500140 \u03bcm. In this work we demonstrate the PanCam\u2019s performance in imaging a stained tissue sample.
", "doi": "10.7907/Z9SF2T49", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8970", "collection": "thesis", "collection_id": "8970", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06022015-141742970", "type": "thesis", "title": "Scalable Methods for Deterministic Integration of Quantum Emitters in Photonic Crystal Cavities", "author": [ { "family_name": "Homyk", "given_name": "Andrew P.", "clpid": "Homyk-Andrew-P" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Choo", "given_name": "Hyuck", "orcid": "0000-0002-8903-7939", "clpid": "Choo-Hyuck" }, { "family_name": "Walavalkar", "given_name": "Sameer S.", "clpid": "Walavalkar-S-S" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "We investigated four unique methods for achieving scalable, deterministic integration of quantum emitters into ultra-high Q{V photonic crystal cavities, including selective area heteroepitaxy, engineered photoemission from silicon nanostructures, wafer bonding and dimensional reduction of III-V quantum wells, and cavity-enhanced optical trapping. In these areas, we were able to demonstrate site-selective heteroepitaxy, size-tunable photoluminescence from silicon nanostructures, Purcell modification of QW emission spectra, and limits of cavity-enhanced optical trapping designs which exceed any reports in the literature and suggest the feasibility of capturing- and detecting nanostructures with dimensions below 10 nm. In addition to process scalability and the requirement for achieving accurate spectral- and spatial overlap between the emitter and cavity, these techniques paid specific attention to the ability to separate the cavity and emitter material systems in order to allow optimal selection of these independently, and eventually enable monolithic integration with other photonic and electronic circuitry.
\r\n\r\nWe also developed an analytic photonic crystal design process yielding optimized cavity tapers with minimal computational effort, and reported on a general cavity modification which exhibits improved fabrication tolerance by relying exclusively on positional- rather than dimensional tapering. We compared several experimental coupling techniques for device characterization. Significant efforts were devoted to optimizing cavity fabrication, including the use of atomic layer deposition to improve surface quality, exploration into factors affecting the design fracturing, and automated analysis of SEM images. Using optimized fabrication procedures, we experimentally demonstrated 1D photonic crystal nanobeam cavities exhibiting the highest Q/V reported on substrate. Finally, we analyzed the bistable behavior of the devices to quantify the nonlinear optical response of our cavities.
", "doi": "10.7907/Z9D50JXC", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8970", "collection": "thesis", "collection_id": "8970", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06022015-141742970", "type": "thesis", "title": "Scalable Methods for Deterministic Integration of Quantum Emitters in Photonic Crystal Cavities", "author": [ { "family_name": "Homyk", "given_name": "Andrew P.", "clpid": "Homyk-Andrew-P" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Choo", "given_name": "Hyuck", "orcid": "0000-0002-8903-7939", "clpid": "Choo-Hyuck" }, { "family_name": "Walavalkar", "given_name": "Sameer S.", "clpid": "Walavalkar-S-S" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "We investigated four unique methods for achieving scalable, deterministic integration of quantum emitters into ultra-high Q{V photonic crystal cavities, including selective area heteroepitaxy, engineered photoemission from silicon nanostructures, wafer bonding and dimensional reduction of III-V quantum wells, and cavity-enhanced optical trapping. In these areas, we were able to demonstrate site-selective heteroepitaxy, size-tunable photoluminescence from silicon nanostructures, Purcell modification of QW emission spectra, and limits of cavity-enhanced optical trapping designs which exceed any reports in the literature and suggest the feasibility of capturing- and detecting nanostructures with dimensions below 10 nm. In addition to process scalability and the requirement for achieving accurate spectral- and spatial overlap between the emitter and cavity, these techniques paid specific attention to the ability to separate the cavity and emitter material systems in order to allow optimal selection of these independently, and eventually enable monolithic integration with other photonic and electronic circuitry.
\r\n\r\nWe also developed an analytic photonic crystal design process yielding optimized cavity tapers with minimal computational effort, and reported on a general cavity modification which exhibits improved fabrication tolerance by relying exclusively on positional- rather than dimensional tapering. We compared several experimental coupling techniques for device characterization. Significant efforts were devoted to optimizing cavity fabrication, including the use of atomic layer deposition to improve surface quality, exploration into factors affecting the design fracturing, and automated analysis of SEM images. Using optimized fabrication procedures, we experimentally demonstrated 1D photonic crystal nanobeam cavities exhibiting the highest Q/V reported on substrate. Finally, we analyzed the bistable behavior of the devices to quantify the nonlinear optical response of our cavities.
", "doi": "10.7907/Z9D50JXC", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8944", "collection": "thesis", "collection_id": "8944", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05302015-005943888", "primary_object_url": { "basename": "Pai_Alex_2015_06_12_thesis.pdf", "content": "final", "filesize": 35439405, "license": "other", "mime_type": "application/pdf", "url": "/8944/1/Pai_Alex_2015_06_12_thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Sensing and Actuation from Biology to Electronics", "author": [ { "family_name": "Pai", "given_name": "Alex Hao-Yu", "clpid": "Pai-Alex-Hao-Yu" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Rutledge", "given_name": "David B.", "clpid": "Rutledge-D-B" }, { "family_name": "Weinreb", "given_name": "Sander", "clpid": "Weinreb-S" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "We introduce an in vitro diagnostic magnetic biosensing platform for immunoassay and nucleic acid detection. The platform has key characteristics for a point-of-use (POU) diagnostic: portability, low-power consumption, low cost, and multiplexing capability. As a demonstration of capabilities, we use this platform for the room temperature, amplification-free detection of a 31 bp DNA oligomer and interferon-gamma (a protein relevant for tuberculosis diagnosis). Reliable assay measurements down to 100 pM for the DNA and 1 pM for the protein are demonstrated. We introduce a novel \"magnetic freezing\" technique for baseline measurement elimination and to enable spatial multiplexing. We have created a general protocol for adapting integrated circuit (IC) sensors to any of hundreds of commercially available immunoassay kits and custom designed DNA sequences.
\r\n\r\nWe also introduce a method for immunotherapy treatment of malignant gliomas. We utilize leukocytes internalized with immunostimulatory nanoparticle-oligonucleotide conjugates to localize and retain immune cells near the tumor site. As a proof-of-principle, we develop a novel cell imaging and incubation chamber for in vitro magnetic motility experiments. We use the apparatus to demonstrate the controlled movement of magnetically loaded THP-1 leukocytes.
\r\n\r\nFinally, we introduce an IC transmitter and power ampli er (PA) that utilizes electronic digital infrastructure, sensors, and actuators to self-heal and adapt to process, dynamic, and environmental variation. Traditional IC design has achieved incredible degrees of reliability by ensuring that billions of transistors on a single IC die are all simultaneously functional. Reliability becomes increasingly difficult as the size of a transistor shrinks. Self-healing can mitigate these variations.
", "doi": "10.7907/Z9NC5Z5M", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8994", "collection": "thesis", "collection_id": "8994", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06052015-084726649", "primary_object_url": { "basename": "Thesis.pdf", "content": "final", "filesize": 3194374, "license": "other", "mime_type": "application/pdf", "url": "/8994/1/Thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Microelectrode Implants for Spinal Cord Stimulation in Rats ", "author": [ { "family_name": "Nandra", "given_name": "Mandheerej Singh", "clpid": "Nandra-Mandheerej-Singh" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Paralysis is a debilitating condition afflicting millions of people across the globe, and is particularly deleterious to quality of life when motor function of the legs is severely impaired or completely absent. Fortunately, spinal cord stimulation has shown great potential for improving motor function after spinal cord injury and other pathological conditions. Many animal studies have shown stimulation of the neural networks in the spinal cord can improve motor ability so dramatically that the animals can even stand and step after a complete spinal cord transaction.
\r\n\r\nThis thesis presents work to successfully provide a chronically implantable device for rats that greatly enhances the ability to control the site of spinal cord stimulation. This is achieved through the use of a parylene-C based microelectrode array, which enables a density of stimulation sites unattainable with conventional wire electrodes. While many microelectrode devices have been proposed in the past, the spinal cord is a particularly challenging environment due to the bending and movement it undergoes in a live animal. The developed microelectrode array is the first to have been implanted in vivo while retaining functionality for over a month. In doing so, different neural pathways can be selectively activated to facilitate standing and stepping in spinalized rats using various electrode combinations, and important differences in responses are observed.
\r\n\r\nAn engineering challenge for the usability of any high density electrode array is connecting the numerous electrodes to a stimulation source. This thesis develops several technologies to address this challenge, beginning with a fully passive implant that uses one wire per electrode to connect to an external stimulation source. The number of wires passing through the body and the skin proved to be a hazard for the health of the animal, so a multiplexed implant was devised in which active electronics reduce the number of wires. Finally, a fully wireless implant was developed. As these implants are tested in vivo, encapsulation is of critical importance to retain functionality in a chronic experiment, especially for the active implants, and it was achieved without the use of costly ceramic or metallic hermetic packaging. Active implants were built that retained functionality 8 weeks after implantation, and achieved stepping in spinalized rats after just 8-10 days, which is far sooner than wire-based electrical stimulation has achieved in prior work.
", "doi": "10.7907/Z9930R3G", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8494", "collection": "thesis", "collection_id": "8494", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06062014-102704108", "primary_object_url": { "basename": "POC MDx FOR HUMANITY.pdf", "content": "final", "filesize": 12308510, "license": "other", "mime_type": "application/pdf", "url": "/8494/1/POC MDx FOR HUMANITY.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Point of Care Molecular Diagnostics for Humanity", "author": [ { "family_name": "Malik", "given_name": "Imran Raouf", "clpid": "Malik-Imran-Raouf" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Rutledge", "given_name": "David B.", "clpid": "Rutledge-D-B" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tombrello", "given_name": "Thomas A.", "clpid": "Tombrello-T-A" }, { "family_name": "Joyce", "given_name": "Gerald", "clpid": "Joyce-G" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Diagnostics of disease at POC (point of care) has been declared one of the Grand Challenge by the Bill and Melina Gates Foundation (BMGF). Infectious diseases constitute a major cause of disease burden and cause more than half a billion Disability-Adjusted Life Years (DALYs) and millions of deaths each year. They have an especially large effect on children under 5 years of age. We have analyzed data from the GBD 2010 (Global Burden of Disease) project to emphasize the damage caused by infectious diseases, and highlight the opportunity of using diagnostic tools to rapidly identify and treat diseases. To motivate the work of this thesis, we quantify the expected impact of appropriate diagnostic technologies.
\r\n\r\nWe have also analyzed the requirements that a diagnostic tool should meet to generate the maximal global impact. We present various existing TPPs (Target Product Profiles) from different organizations and suggest some additions to these existing TPPs. We explain the particular molecular pathology technologies which have the potential to allow deployment of functional products in the developing world for point-of-care pathogen detection, especially in low-resource settings.
\r\n \r\nWe perform a detailed analysis on existing polymerase chain reaction (PCR) systems and describe the problems caused with thermal performance and optical interrogation. We list the requirements that disposable cartridges for such instruments should meet and suggest a metal base design with polymer top. After detailed FEA simulations, we demonstrate that the thermal response can be modeled using a one-dimensional (1D) lumped element system. We show improvements in thermal response due to using a metal base and the effect of fluid height. We also performed thermal-structural simulations to quantify the stresses on the adhesive bonds of metal/polymer cartridges.\r\nNext, we explain fabrication of these cartridges. We show methods to dispense adhesive using a robot and a custom made jig to spread the adhesive during curing. The cartridge was tested with different PCR reagents and we obtained reaction efficiencies approaching those of the commercial real time PCR machines. Our fabrication technique is useful to join dissimilar materials and is production friendly. By developing custom software, we observed the cartridge performance in a continuous manner. We could see the thermal response of cartridges by continuous fluorescence monitoring, and used reflective aluminum which increase light collection efficiency.
\r\n\r\nWe then present a simple and robust new way for thermal cycling. Robust thermal cycling has been a major challenge conducting PCR, especially in point of care situations. Here, we suggest a contact cooling approach, in which the cartridge rests on a thin metal plate with an integrated thin heater constructed from flexible printed circuit board (PCB) material. We use a solenoid to move a metal plate to cool down the sample cartridge during cycling. The metal plate then rests on a larger heat sink to disperse the shuttled heat. Our design is dust and water proof and was verified on a bench-top prototype.
\r\n\r\nA novel optical design for fluorescence detection during qPCR is also described. We suggest a lateral illumination waveguide geometry with prism coupling that eliminates lenses and is integrated into an injection molded cartridge. The light is homogenized using a light guide, and we quantify the sources of scattered stray light from the chamber edge by performing ray tracing simulations to optimize the precise geometry. The design is tolerant to misalignments and enables easy coupling of LED light into the chamber. As the light collection efficiency is high, the size of the chamber can be very small. We tested real PCR reactions using this concept and observed a rapid integration time, enabling very fast reading.
\r\n\r\nSample preparation has been another challenge for all point-of-care (POC) lab-on-chip devices for many years. Here, we propose a new design which is robust, fast, flexible and simple, and uses a sliding seal to move the collected sample between various reservoir chambers. The sample moves on a slider sandwiched between seals that shuttles a DNA binding membrane between different reactions. Thus, size and volumes of reagents can be increased without increasing dead volumes. This design is easily automated, and positive displacement of fluids can work with many reagents without worrying about their characteristics such as foaming. The speed of the sample preparation protocols is high and complex protocols can be ported on this design concept, which we tested on real clinical samples and obtained impressive results. We designed and injection molded devices to test and verify this concept.
\r\n\r\nFinally, we focus on instrumentation and software required to allow our technology to be used at the POC. We describe our embedded electronics and describe the powerful micro-controller and various high performance ICs that are used to construct a fully functional for sample to answer instrument. We developed various versions of software. The developer software allows us to control our system and bench top setup. Our end user product includes a tablet and cell phone software interface. Software was developed for a windows 8 tablet, windows 8 phone and an Android based devices.
\r\n\r\nTo conclude, we very briefly describe the POC systems that are under development: A portable qPCR system with a separate cartridge design, and a universal sample to answer system that performs qPCR, sample preparation and sample to answer protocols in one box depending on the cartridge.
\r\n\r\nAs per best of our knowledge the cost of this technology is much lower than any other option in its class. The sample to answer instrument is expected to cost less than $500. The test cost is expected to be less than $5. The performance is not compromised. We hope that this work can help bring a transformative change in the practice of pathology especially in the developing world.
\r\n", "doi": "10.7907/Z9HH6H2D", "publication_date": "2014", "thesis_type": "phd", "thesis_year": "2014" }, { "id": "thesis:8227", "collection": "thesis", "collection_id": "8227", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05102014-143921707", "type": "thesis", "title": "Innovations of Wide-Field Optical-Sectioning Fluorescence Microscopy: Toward High-Speed Volumetric Bio-Imaging with Simplicity", "author": [ { "family_name": "Yu", "given_name": "Jiun-Yann", "clpid": "Yu-Jiun-Yann" } ], "thesis_advisor": [ { "family_name": "Guo", "given_name": "Chin-Lin", "clpid": "Guo-Chin-Lin" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Blake", "given_name": "Geoffrey A.", "clpid": "Blake-G-A" }, { "family_name": "Fraser", "given_name": "Scott E.", "clpid": "Fraser-S-E" }, { "family_name": "Guo", "given_name": "Chin-Lin", "clpid": "Guo-Chin-Lin" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Optical microscopy has become an indispensable tool for biological researches since its invention, mostly owing to its sub-cellular spatial resolutions, non-invasiveness, instrumental simplicity, and the intuitive observations it provides. Nonetheless, obtaining reliable, quantitative spatial information from conventional wide-field optical microscopy is not always intuitive as it appears to be. This is because in the acquired images of optical microscopy the information about out-of-focus regions is spatially blurred and mixed with in-focus information. In other words, conventional wide-field optical microscopy transforms the three-dimensional spatial information, or volumetric information about the objects into a two-dimensional form in each acquired image, and therefore distorts the spatial information about the object. Several fluorescence holography-based methods have demonstrated the ability to obtain three-dimensional information about the objects, but these methods generally rely on decomposing stereoscopic visualizations to extract volumetric information and are unable to resolve complex 3-dimensional structures such as a multi-layer sphere.
\r\n\r\nThe concept of optical-sectioning techniques, on the other hand, is to detect only two-dimensional information about an object at each acquisition. Specifically, each image obtained by optical-sectioning techniques contains mainly the information about an optically thin layer inside the object, as if only a thin histological section is being observed at a time. Using such a methodology, obtaining undistorted volumetric information about the object simply requires taking images of the object at sequential depths.
\r\n\r\nAmong existing methods of obtaining volumetric information, the practicability of optical sectioning has made it the most commonly used and most powerful one in biological science. However, when applied to imaging living biological systems, conventional single-point-scanning optical-sectioning techniques often result in certain degrees of photo-damages because of the high focal intensity at the scanning point. In order to overcome such an issue, several wide-field optical-sectioning techniques have been proposed and demonstrated, although not without introducing new limitations and compromises such as low signal-to-background ratios and reduced axial resolutions. As a result, single-point-scanning optical-sectioning techniques remain the most widely used instrumentations for volumetric imaging of living biological systems to date.
\r\n\r\nIn order to develop wide-field optical-sectioning techniques that has equivalent optical performance as single-point-scanning ones, this thesis first introduces the mechanisms and limitations of existing wide-field optical-sectioning techniques, and then brings in our innovations that aim to overcome these limitations. We demonstrate, theoretically and experimentally, that our proposed wide-field optical-sectioning techniques can achieve diffraction-limited optical sectioning, low out-of-focus excitation and high-frame-rate imaging in living biological systems. In addition to such imaging capabilities, our proposed techniques can be instrumentally simple and economic, and are straightforward for implementation on conventional wide-field microscopes. These advantages together show the potential of our innovations to be widely used for high-speed, volumetric fluorescence imaging of living biological systems.
", "doi": "10.7907/4V14-HW42", "publication_date": "2014", "thesis_type": "phd", "thesis_year": "2014" }, { "id": "thesis:8095", "collection": "thesis", "collection_id": "8095", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02212014-174719213", "primary_object_url": { "basename": "Thesis_final_SALee.pdf", "content": "final", "filesize": 3968641, "license": "other", "mime_type": "application/pdf", "url": "/8095/1/Thesis_final_SALee.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Bright-Field and Fluorescence Chip-Scale Microscopy for Biological Imaging", "author": [ { "family_name": "Lee", "given_name": "Seung Ah", "clpid": "Lee-Seung-Ah" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Ismagilov", "given_name": "Rustem F.", "clpid": "Ismagilov-R-F" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" } ], "local_group": [ { "literal": "Kavli Nanoscience Institute" }, { "literal": "div_eng" } ], "abstract": "Optical microscopy is an essential tool in biological science and one of the gold standards for medical examinations. Miniaturization of microscopes can be a crucial stepping stone towards realizing compact, cost-effective and portable platforms for biomedical research and healthcare. This thesis reports on implementations of bright-field and fluorescence chip-scale microscopes for a variety of biological imaging applications. The term \u201cchip-scale microscopy\u201d refers to lensless imaging techniques realized in the form of mass-producible semiconductor devices, which transforms the fundamental design of optical microscopes.
\r\n\r\nOur strategy for chip-scale microscopy involves utilization of low-cost Complementary metal Oxide Semiconductor (CMOS) image sensors, computational image processing and micro-fabricated structural components. First, the sub-pixel resolving optofluidic microscope (SROFM), will be presented, which combines microfluidics and pixel super-resolution image reconstruction to perform high-throughput imaging of fluidic samples, such as blood cells. We discuss design parameters and construction of the device, as well as the resulting images and the resolution of the device, which was 0.66 \u00b5m at the highest acuity. The potential applications of SROFM for clinical diagnosis of malaria in the resource-limited settings is discussed.
\r\n\r\nNext, the implementations of ePetri, a self-imaging Petri dish platform with microscopy resolution, are presented. Here, we simply place the sample of interest on the surface of the image sensor and capture the direct shadow images under the illumination. By taking advantage of the inherent motion of the microorganisms, we achieve high resolution (~1 \u00b5m) imaging and long term culture of motile microorganisms over ultra large field-of-view (5.7 mm \u00d7 4.4 mm) in a specialized ePetri platform. We apply the pixel super-resolution reconstruction to a set of low-resolution shadow images of the microorganisms as they move across the sensing area of an image sensor chip and render an improved resolution image. We perform longitudinal study of Euglena gracilis cultured in an ePetri platform and image based analysis on the motion and morphology of the cells. The ePetri device for imaging non-motile cells are also demonstrated, by using the sweeping illumination of a light emitting diode (LED) matrix for pixel super-resolution reconstruction of sub-pixel shifted shadow images. Using this prototype device, we demonstrate the detection of waterborne parasites for the effective diagnosis of enteric parasite infection in resource-limited settings.
\r\n\r\nThen, we demonstrate the adaptation of a smartphone\u2019s camera to function as a compact lensless microscope, which uses ambient illumination as its light source and does not require the incorporation of a dedicated light source. The method is also based on the image reconstruction with sweeping illumination technique, where the sequence of images are captured while the user is manually tilting the device around any ambient light source, such as the sun or a lamp. Image acquisition and reconstruction is performed on the device using a custom-built android application, constructing a stand-alone imaging device for field applications. We discuss the construction of the device using a commercial smartphone and demonstrate the imaging capabilities of our system.
\r\n\r\nFinally, we report on the implementation of fluorescence chip-scale microscope, based on a silo-filter structure fabricated on the pixel array of a CMOS image sensor. The extruded pixel design with metal walls between neighboring pixels successfully guides fluorescence emission through the thick absorptive filter to the photodiode layer of a pixel. Our silo-filter CMOS image sensor prototype achieves 13-\u00b5m resolution for fluorescence imaging over a wide field-of-view (4.8 mm \u00d7 4.4 mm). Here, we demonstrate bright-field and fluorescence longitudinal imaging of living cells in a compact, low-cost configuration.
\r\n", "doi": "10.7907/HNWJ-J182", "publication_date": "2014", "thesis_type": "phd", "thesis_year": "2014" }, { "id": "thesis:8508", "collection": "thesis", "collection_id": "8508", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06092014-120248372", "primary_object_url": { "basename": "Final_Thesis_Yu Zhao_2014_Submit_06102014.pdf", "content": "final", "filesize": 10633193, "license": "other", "mime_type": "application/pdf", "url": "/8508/1/Final_Thesis_Yu Zhao_2014_Submit_06102014.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Flexible Microimplants for In Vivo Sensing", "author": [ { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Yu" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Hsiai", "given_name": "Tzung", "clpid": "Hsiai-Tzung" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Dabiri", "given_name": "John O.", "clpid": "Dabiri-J-O" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The work in this thesis develops two types of microimplants for the application of cardiovascular in vivo biomedical sensing, one for short-term diagnosis and the other for long-term monitoring.
\r\n\r\nDespite advances in diagnosis and therapy, atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in the Western world. Predicting metabolically active atherosclerotic plaques has remained an unmet clinical need. A stretchable impedance sensor manifested as a pair of quasi-concentric microelectrodes was developed to detect unstable intravascular. By integrating the impedance sensor with a cardiac catheter, high-resolution Electrochemical Impedance Spectroscopy (EIS) measurements can be conducted during cardiac catheterization. An inflatable silicone balloon is added to the sensor to secure a well-controlled contact with the plaque under test in vivo. By deploying the device to the explants of NZW rabbit aorta and live animals, distinct EIS measurements were observed for unstable atherosclerotic plaques that harbored active lipids and inflammatory cells.
\r\n\r\nOn the other hand, zebrafish (Danio rerio) is an emerging genetic model for heart regenerative medicine. In humans, myocardial infarction results in the irreversible loss of cardiomyocytes. Zebrafish hearts can fully regenerate after two months with 20% ventricular resection. Long-term electrocardiogram (ECG) recording can characterize the heart regeneration in a functional dimension. A flexible microelectrode membrane was developed to be percutaneously implanted onto a zebrafish heart and record epicardial ECG signals from specific regions on it. Region-specific aberrant cardiac signals were obtained from injured and regenerated hearts. Following that, in order to achieve continuous and wireless recording from non-sedated and non-restricted small animal models, a wireless ECG recording system was designed for the microelectrode membrane, prototyped on a printed circuit board and demonstrated on a one-day-old neonatal mouse. Furthermore, a flexible and compact parylene C printed circuit membrane was used as the integration platform for the wireless ECG recording electronics. A substantially miniature wireless ECG recording system was achieved.
", "doi": "10.7907/SHYA-5Y51", "publication_date": "2014", "thesis_type": "phd", "thesis_year": "2014" }, { "id": "thesis:7166", "collection": "thesis", "collection_id": "7166", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06252012-171451630", "primary_object_url": { "basename": "Thesis_Wendian.pdf", "content": "final", "filesize": 9564483, "license": "other", "mime_type": "application/pdf", "url": "/7166/1/Thesis_Wendian.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Blood Cell Count On-a-Chip", "author": [ { "family_name": "Shi", "given_name": "Wendian (Leo)", "clpid": "Shi-Wendian-Leo" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Dabiri", "given_name": "John O.", "clpid": "Dabiri-J-O" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "White blood cell (WBC) count is one of the most frequently ordered clinical tests in hospitals. There are five types of WBCs in the circulating blood, including lymphocyte, monocyte, neutrophil, eosinophil and basophil. The WBC count test enumerates not only the total number of WBCs in per volume blood, but also the percentage of each WBC type. A portable instrument for the WBC count test is currently in demand by the NASA human spaceflight, and also by the on-earth telemedicine application. However, the commercially available tests do not meet the requirement of the portable applications, because of their large instrument size and the large reagent volume consumed per test.
\r\n\r\nThis study describes the development of a WBC count technology optimized for portable applications. First, a sheathless microfluidic cytometer is developed for WBC count. This technology consumes only a small amount of blood (5 microlitre) and a minimal volume of reagents (50 microlitre). Second, fluorescent dye assays are developed for the WBC differential count by measuring fluorescent emissions on the microfluidic cytometer. Based on this technology, a portable instrument is built with high test accuracy (maximum error less than 10%).
\r\n \r\nFurthermore, this study explores two key components for future integrating this technology into a self-contained chip. First, a microvalve actuated by thermal blood clogging is developed. This valve has a simple structure suitable for on-chip integration. Second, a micromixer is used to demonstrate the staining of blood with dye assays, and the following fluorescent detection of WBCs on the cytometer.
\r\n", "doi": "10.7907/6YF1-WR04", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7705", "collection": "thesis", "collection_id": "7705", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05142013-075702623", "type": "thesis", "title": "Parylene-C as a New Piezoelectric Material", "author": [ { "family_name": "Kim", "given_name": "Justin Young-Hyun", "clpid": "Kim-Justin-Young-Hyun" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The goal of this thesis is to develop a proper microelectromechanical systems (MEMS) process to manufacture piezoelectric Parylene-C (PA-C), which is famous for its chemical inertness, mechanical and thermal properties and electrical insulation. Furthermore, piezoelectric PA-C is used to build miniature, inexpensive, non-biased piezoelectric microphones.
\r\n \r\nThese piezoelectric PA-C MEMS microphones are to be used in any application where a conventional piezoelectric and electret microphone can be used, such as in cell phones and hearing aids. However, they have the advantage of a simplified fabrication process compared with existing technology. In addition, as a piezoelectric polymer, PA-C has varieties of applications due to its low dielectric constant, low elastic stiffness, low density, high voltage sensitivity, high temperature stability and low acoustic and mechanical impedance. Furthermore, PA-C is an FDA approved biocompatible material and is able to maintain operate at a high temperature.
\r\n\r\nTo accomplish piezoelectric PA-C, a MEMS-compatible poling technology has been developed. The PA-C film is poled by applying electrical field during heating. The piezoelectric coefficient, -3.75pC/N, is obtained without film stretching.
\r\n\r\nThe millimeter-scale piezoelectric PA-C microphone is fabricated with an in-plane spiral arrangement of two electrodes. The dynamic range is from less than 30 dB to above 110 dB SPL (referenced 20 \u00b5Pa) and the open-circuit sensitivities are from 0.001 \u2013 0.11 mV/Pa over a frequency range of 1 - 10 kHz. The total harmonic distortion of the device is less than 20% at 110 dB SPL and 1 kHz.
", "doi": "10.7907/1VEH-EP90", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7902", "collection": "thesis", "collection_id": "7902", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06172013-155313179", "primary_object_url": { "basename": "Thesis_JianRen_2013.pdf", "content": "final", "filesize": 20121522, "license": "other", "mime_type": "application/pdf", "url": "/7902/13/Thesis_JianRen_2013.pdf", "version": "v11.0.0" }, "type": "thesis", "title": "Endoscopic Optical Coherence Tomography: Design and Application", "author": [ { "family_name": "Ren", "given_name": "Jian", "clpid": "Ren-Jian" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Humayun", "given_name": "Mark", "clpid": "Humayun-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents an investigation on endoscopic optical coherence tomography (OCT). As a noninvasive imaging modality, OCT emerges as an increasingly important diagnostic tool for many clinical applications. Despite of many of its merits, such as high resolution and depth resolvability, a major limitation is the relatively shallow penetration depth in tissue (about 2\u223c3 mm). This is mainly due to tissue scattering and absorption. To overcome this limitation, people have been developing many different endoscopic OCT systems. By utilizing a minimally invasive endoscope, the OCT probing beam can be brought to the close vicinity of the tissue of interest and bypass the scattering of intervening tissues so that it can collect the reflected light signal from desired depth and provide a clear image representing the physiological structure of the region, which can not be disclosed by traditional OCT. In this thesis, three endoscope designs have been studied. While they rely on vastly different principles, they all converge to solve this long-standing problem.
\r\n\r\nA hand-held endoscope with manual scanning is first explored. When a user is holding a hand- held endoscope to examine samples, the movement of the device provides a natural scanning. We proposed and implemented an optical tracking system to estimate and record the trajectory of the device. By registering the OCT axial scan with the spatial information obtained from the tracking system, one can use this system to simply \u2018paint\u2019 a desired volume and get any arbitrary scanning pattern by manually waving the endoscope over the region of interest. The accuracy of the tracking system was measured to be about 10 microns, which is comparable to the lateral resolution of most OCT system. Targeted phantom sample and biological samples were manually scanned and the reconstructed images verified the method.
\r\n\r\nNext, we investigated a mechanical way to steer the beam in an OCT endoscope, which is termed as Paired-angle-rotation scanning (PARS). This concept was proposed by my colleague and we further developed this technology by enhancing the longevity of the device, reducing the diameter of the probe, and shrinking down the form factor of the hand-piece. Several families of probes have been designed and fabricated with various optical performances. They have been applied to different applications, including the collector channel examination for glaucoma stent implantation, and vitreous remnant detection during live animal vitrectomy.
\r\n\r\nLastly a novel non-moving scanning method has been devised. This approach is based on the EO effect of a KTN crystal. With Ohmic contact of the electrodes, the KTN crystal can exhibit a special mode of EO effect, termed as space-charge-controlled electro-optic effect, where the carrier electron will be injected into the material via the Ohmic contact. By applying a high voltage across the material, a linear phase profile can be built under this mode, which in turn deflects the light beam passing through. We constructed a relay telescope to adapt the KTN deflector into a bench top OCT scanning system. One of major technical challenges for this system is the strong chromatic dispersion of KTN crystal within the wavelength band of OCT system. We investigated its impact on the acquired OCT images and proposed a new approach to estimate and compensate the actual dispersion. Comparing with traditional methods, the new method is more computational efficient and accurate. Some biological samples were scanned by this KTN based system. The acquired images justified the feasibility of the usage of this system into a endoscopy setting.\r\nMy research above all aims to provide solutions to implement an OCT endoscope. As technology evolves from manual, to mechanical, and to electrical approaches, different solutions are presented. Since all have their own advantages and disadvantages, one has to determine the actual requirements and select the best fit for a specific application.
", "doi": "10.7907/Z9445JF5", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7614", "collection": "thesis", "collection_id": "7614", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04132013-185824588", "primary_object_url": { "basename": "Pang_Shuo_Thesis.pdf", "content": "final", "filesize": 12182996, "license": "other", "mime_type": "application/pdf", "url": "/7614/1/Pang_Shuo_Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Fluorescence Optofluidic Microscopy and Fluorescence Microscopy Based on the Talbot Effect", "author": [ { "family_name": "Pang", "given_name": "Shuo", "clpid": "Pang-Shuo" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Sternberg", "given_name": "Paul W.", "clpid": "Sternberg-P-W" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Light microscopy has been one of the most common tools in biological research, because of its high resolution and non-invasive nature of the light. Due to its high sensitivity and specificity, fluorescence is one of the most important readout modes of light microscopy. This thesis presents two new fluorescence microscopic imaging techniques: fluorescence optofluidic microscopy and fluorescent Talbot microscopy. The designs of the two systems are fundamentally different from conventional microscopy, which makes compact and portable devices possible. The components of the devices are suitable for mass-production, making the microscopic imaging system more affordable for biological research and clinical diagnostics.
\r\n\r\nFluorescence optofluidic microscopy (FOFM) is capable of imaging fluorescent samples in fluid media. The FOFM employs an array of Fresnel zone plates (FZP) to generate an array of focused light spots within a microfluidic channel. As a sample flows through the channel and across the array of focused light spots, a filter-coated CMOS sensor collects the fluorescence emissions. The collected data can then be processed to render a fluorescence microscopic image. The resolution, which is determined by the focused light spot size, is experimentally measured to be 0.65 \u03bcm.
\r\n\r\nFluorescence Talbot microscopy (FTM) is a fluorescence chip-scale microscopy technique that enables large field-of-view (FOV) and high-resolution imaging. The FTM method utilizes the Talbot effect to project a grid of focused excitation light spots onto the sample. The sample is placed on a filter-coated CMOS sensor chip. The fluorescence emissions associated with each focal spot are collected by the sensor chip and are composed into a sparsely sampled fluorescence image. By raster scanning the Talbot focal spot grid across the sample and collecting a sequence of sparse images, a filled-in high-resolution fluorescence image can be reconstructed. In contrast to a conventional microscope, a collection efficiency, resolution, and FOV are not tied to each other for this technique. The FOV of FTM is directly scalable. Our FTM prototype has demonstrated a resolution of 1.2 \u03bcm, and the collection efficiency equivalent to a conventional microscope objective with a 0.70 N.A. The FOV is 3.9 mm \u00d7 3.5 mm, which is 100 times larger than that of a 20X/0.40 N.A. conventional microscope objective. Due to its large FOV, high collection efficiency, compactness, and its potential for integration with other on-chip devices, FTM is suitable for diverse applications, such as point-of-care diagnostics, large-scale functional screens, and long-term automated imaging.
", "doi": "10.7907/WWFF-7S14", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7812", "collection": "thesis", "collection_id": "7812", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05312013-213433052", "primary_object_url": { "basename": "JS_Thesis.pdf", "content": "final", "filesize": 8183664, "license": "other", "mime_type": "application/pdf", "url": "/7812/1/JS_Thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "On-Chip Integrated Label-Free Optical Biosensing", "author": [ { "family_name": "Sendowski", "given_name": "Jacob Benjamin", "clpid": "Sendowski-Jacob-Benjamin" } ], "thesis_advisor": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "thesis_committee": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis investigates the design and implementation of a label-free optical biosensing system utilizing a robust on-chip integrated platform. The goal has been to transition optical micro-resonator based label-free biosensing from a laborious and delicate laboratory demonstration to a tool for the analytical life scientist. This has been pursued along four avenues: (1) the design and fabrication of high-$Q$ integrated planar microdisk optical resonators in silicon nitride on silica, (2) the demonstration of a high speed optoelectronic swept frequency laser source, (3) the development and integration of a microfluidic analyte delivery system, and (4) the introduction of a novel differential measurement technique for the reduction of environmental noise.
\r\n\r\nThe optical part of this system combines the results of two major recent developments in the field of optical and laser physics: the high-$Q$ optical resonator and the phase-locked electronically controlled swept-frequency semiconductor laser. The laser operates at a wavelength relevant for aqueous sensing, and replaces expensive and fragile mechanically-tuned laser sources whose frequency sweeps have limited speed, accuracy and reliability. The high-$Q$ optical resonator is part of a monolithic unit with an integrated optical waveguide, and is fabricated using standard semiconductor lithography methods. Monolithic integration makes the system significantly more robust and flexible compared to current, fragile embodiments that rely on the precarious coupling of fragile optical fibers to resonators. The silicon nitride on silica material system allows for future manifestations at shorter wavelengths. The sensor also includes an integrated microfluidic flow cell for precise and low volume delivery of analytes to the resonator surface. We demonstrate the refractive index sensing action of the system as well as the specific and nonspecific adsorption of proteins onto the resonator surface with high sensitivity. Measurement challenges due to environmental noise that hamper system performance are discussed and a differential sensing measurement is proposed, implemented, and demonstrated resulting in the restoration of a high performance sensing measurement.
\r\n\r\nThe instrument developed in this work represents an adaptable and cost-effective platform capable of various sensitive, label-free measurements relevant to the study of biophysics, biomolecular interactions, cell signaling, and a wide range of other life science fields. Further development is necessary for it to be capable of binding assays, or thermodynamic and kinetics measurements; however, this work has laid the foundation for the demonstration of these applications.
", "doi": "10.7907/2H9Y-AB63", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7640", "collection": "thesis", "collection_id": "7640", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04282013-103938118", "type": "thesis", "title": "Deep Tissue Fluorescence Imaging with Time-Reversed Light", "author": [ { "family_name": "Wang", "given_name": "Ying Min", "clpid": "Wang-Ying-Min" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Guo", "given_name": "Chin-Lin", "clpid": "Guo-Chin-Lin" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Fraser", "given_name": "Scott E.", "clpid": "Fraser-S-E" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Gradinaru", "given_name": "Viviana", "clpid": "Gradinaru-V" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Advances in optical techniques have enabled many breakthroughs in biology and medicine. However, light scattering by biological tissues remains a great obstacle, restricting the use of optical methods to thin ex vivo sections or superficial layers in vivo. In this thesis, we present two related methods that overcome the optical depth limit\u2014digital time reversal of ultrasound encoded light (digital TRUE) and time reversal of variance-encoded light (TROVE). These two techniques share the same principle of using acousto-optic beacons for time reversal optical focusing within highly scattering media, like biological tissues. Ultrasound, unlike light, is not significantly scattered in soft biological tissues, allowing for ultrasound focusing. In addition, a fraction of the scattered optical wavefront that passes through the ultrasound focus gets frequency-shifted via the acousto-optic effect, essentially creating a virtual source of frequency-shifted light within the tissue. The scattered ultrasound-tagged wavefront can be selectively measured outside the tissue and time-reversed to converge at the location of the ultrasound focus, enabling optical focusing within deep tissues. In digital TRUE, we time reverse ultrasound-tagged light with an optoelectronic time reversal device (the digital optical phase conjugate mirror, DOPC). The use of the DOPC enables high optical gain, allowing for high intensity optical focusing and focal fluorescence imaging in thick tissues at a lateral resolution of 36 \u00b5m by 52 \u00b5m. The resolution of the TRUE approach is fundamentally limited to that of the wavelength of ultrasound. The ultrasound focus (~ tens of microns wide) usually contains hundreds to thousands of optical modes, such that the scattered wavefront measured is a linear combination of the contributions of all these optical modes. In TROVE, we make use of our ability to digitally record, analyze and manipulate the scattered wavefront to demix the contributions of these spatial modes using variance encoding. In essence, we encode each spatial mode inside the scattering sample with a unique variance, allowing us to computationally derive the time reversal wavefront that corresponds to a single optical mode. In doing so, we uncouple the system resolution from the size of the ultrasound focus, demonstrating optical focusing and imaging between highly diffusing samples at an unprecedented, speckle-scale lateral resolution of ~ 5 \u00b5m. Our methods open up the possibility of fully exploiting the prowess and versatility of biomedical optics in deep tissues.", "doi": "10.7907/YNSN-8960", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7234", "collection": "thesis", "collection_id": "7234", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10102012-101657790", "primary_object_url": { "basename": "Zheng_Guoan_Final_Thesis_12_17_2012.pdf", "content": "final", "filesize": 20784687, "license": "other", "mime_type": "application/pdf", "url": "/7234/4/Zheng_Guoan_Final_Thesis_12_17_2012.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Innovations in Imaging System Design: Gigapixel, Chip-Scale and MultiFunctional Microscopy", "author": [ { "family_name": "Zheng", "given_name": "Guoan", "clpid": "Zheng-Guoan" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Elowitz", "given_name": "Michael B.", "clpid": "Elowitz-M-B" }, { "family_name": "Fraser", "given_name": "Scott E.", "clpid": "Fraser-S-E" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Microscopy imaging is of fundamental importance in diverse disciplines of science and technology. In a typical microscopy imaging platform, the light path can be generalized to the following steps: photons leave the light source, interact with the sample, and finally are detected by the image sensor. Based on such a light path, this thesis presents several new microscopy imaging techniques from three aspects: illumination design, sample manipulation, and imager modification.
\r\n \r\nThe first design strategy involves the active control of the illumination sources. Based on this strategy, we demonstrate a simple and cost-effective imaging method, termed Non-interferometric Aperture-synthesizing Microscopy (NAM), for breaking the spatial-bandwidth product barrier of a conventional microscope. We show that the NAM method is capable of providing two orders of magnitude higher throughput for most existing bright-field microscopes without involving any mechanical scanning. Based on NAM, we report the implementation of a 1.6 gigapixel microscope with a maximum numerical aperture of 0.5, a field-of-view of 120 mm2, and a resolution-invariant imaging depth of 0.3 mm. This platform is fast (acquisition time of ~ 3 minutes), free from chromatic aberration, capable for phase imaging, and, most importantly, compatible with most existing microscopes. High quality color images of histology slides were acquired by using such a platform for demonstration. The proposed NAM method provides a robust way to transform the problem of high-throughput microscopy from one that is tied to physical limitations of the optics to one that is computationally solvable. The active control of illumination sources can also be adapted for chip-scale microscopy imaging. To this end, we present a lensless microscopy solution termed ePetri-dish. This ePetri-dish platform can automatically perform high resolution (~ 0.66 micron) microscopy imaging over a large field-of-view (6 mm \u00d7 4 mm). This new approach is fully capable of working with cell cultures or any samples in which cells/bacteria may be contiguously connected, and thus, it can significantly improve Petri-dish-based cell/bacteria culture experiments. With this approach providing a low-cost and disposable microscopy solution, we can start to transit Petri-dish-based experiments from the traditionally labor-intensive process to an automated and streamlined process.
\r\n\r\nThe second strategy in design considerations is to manipulate the sample. We present a fully on-chip, lensless, sub-pixel resolving optofluidic microscope (SROFM). This device utilizes microfluidic flow to deliver specimens directly across an image sensor to generate a sequence of low-resolution projection images, where resolution is limited by the sensor\u2019s pixel size. This image sequence is then processed to reconstruct a single high-resolution image, where features beyond the Nyquist rate of the LR images are resolved. We demonstrate the device\u2019s capabilities by imaging microspheres, protist Euglena gracilis, and Entamoeba invadens cysts with sub-cellular resolution.
\r\n\r\nThe third accessing point in design considerations is the image sensor. Imager modification is an emerging technique that performs pre-detection light field manipulation. We present two novel optical structure designs: surface-wave-enabled darkfield aperture (SWEDA) and light field sensor. These structures can be directly incorporated onto optical sensors to accomplish pre-detection background suppression and wavefront sensing. We further demonstrate SWEDA\u2019s ability to boost the detection sensitivity, with a contrast enhancement of 27 dB.
\r\n", "doi": "10.7907/SF6E-S775", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7820", "collection": "thesis", "collection_id": "7820", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06032013-060508409", "primary_object_url": { "basename": "Arseny_Vasilyev_Thesis_CompleteThesis.pdf", "content": "", "filesize": 10762891, "license": "other", "mime_type": "application/pdf", "url": "/7820/1/Arseny_Vasilyev_Thesis_CompleteThesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "The Optoelectronic Swept-Frequency Laser and Its Applications in Ranging, Three-Dimensional Imaging, and Coherent Beam Combining of Chirped-Seed Amplifiers", "author": [ { "family_name": "Vasilyev", "given_name": "Arseny", "clpid": "Vasilyev-Arseny" } ], "thesis_advisor": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "thesis_committee": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Schwab", "given_name": "Keith C.", "clpid": "Schwab-K-C" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis explores the design, construction, and applications of the optoelectronic swept-frequency laser (SFL). The optoelectronic SFL is a feedback loop designed around a swept-frequency (chirped) semiconductor laser (SCL) to control its instantaneous optical frequency, such that the chirp characteristics are determined solely by a reference electronic oscillator. The resultant system generates precisely controlled optical frequency sweeps. In particular, we focus on linear chirps because of their numerous applications. We demonstrate optoelectronic SFLs based on vertical-cavity surface-emitting lasers (VCSELs) and distributed-feedback lasers (DFBs) at wavelengths of 1550 nm and 1060 nm. We develop an iterative bias current predistortion procedure that enables SFL operation at very high chirp rates, up to 10^16 Hz/sec. We describe commercialization efforts and implementation of the predistortion algorithm in a stand-alone embedded environment, undertaken as part of our collaboration with Telaris, Inc. We demonstrate frequency-modulated continuous-wave (FMCW) ranging and three-dimensional (3-D) imaging using a 1550 nm optoelectronic SFL.
\r\n\r\nWe develop the technique of multiple source FMCW (MS-FMCW) reflectometry, in which the frequency sweeps of multiple SFLs are \"stitched\" together in order to increase the optical bandwidth, and hence improve the axial resolution, of an FMCW ranging measurement. We demonstrate computer-aided stitching of DFB and VCSEL sweeps at 1550 nm. We also develop and demonstrate hardware stitching, which enables MS-FMCW ranging without additional signal processing. The culmination of this work is the hardware stitching of four VCSELs at 1550 nm for a total optical bandwidth of 2 THz, and a free-space axial resolution of 75 microns.
\r\n\r\nWe describe our work on the tomographic imaging camera (TomICam), a 3-D imaging system based on FMCW ranging that features non-mechanical acquisition of transverse pixels. Our approach uses a combination of electronically tuned optical sources and low-cost full-field detector arrays, completely eliminating the need for moving parts traditionally employed in 3-D imaging. We describe the basic TomICam principle, and demonstrate single-pixel TomICam ranging in a proof-of-concept experiment. We also discuss the application of compressive sensing (CS) to the TomICam platform, and perform a series of numerical simulations. These simulations show that tenfold compression is feasible in CS TomICam, which effectively improves the volume acquisition speed by a factor ten.
\r\n\r\nWe develop chirped-wave phase-locking techniques, and apply them to coherent beam combining (CBC) of chirped-seed amplifiers (CSAs) in a master oscillator power amplifier configuration. The precise chirp linearity of the optoelectronic SFL enables non-mechanical compensation of optical delays using acousto-optic frequency shifters, and its high chirp rate simultaneously increases the stimulated Brillouin scattering (SBS) threshold of the active fiber. We characterize a 1550 nm chirped-seed amplifier coherent-combining system. We use a chirp rate of 5*10^14 Hz/sec to increase the amplifier SBS threshold threefold, when compared to a single-frequency seed. We demonstrate efficient phase-locking and electronic beam steering of two 3 W erbium-doped fiber amplifier channels, achieving temporal phase noise levels corresponding to interferometric fringe visibilities exceeding 98%.
", "doi": "10.7907/YD38-BT07", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7800", "collection": "thesis", "collection_id": "7800", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05312013-151934307", "primary_object_url": { "basename": "Thesis.pdf", "content": "final", "filesize": 9140424, "license": "other", "mime_type": "application/pdf", "url": "/7800/1/Thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "High-Coherence Hybrid Si/III-V Semiconductor Lasers", "author": [ { "family_name": "Santis", "given_name": "Christos Theodoros", "orcid": "0000-0001-8636-1613", "clpid": "Santis-Christos-Theodoros" } ], "thesis_advisor": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "thesis_committee": [ { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The relentlessly increasing demand for network bandwidth, driven primarily by Internet-based services such as mobile computing, cloud storage and video-on-demand, calls for more efficient utilization of the available communication spectrum, as that afforded by the resurging DSP-powered coherent optical communications. Encoding information in the phase of the optical carrier, using multilevel phase modulationformats, and employing coherent detection at the receiver allows for enhanced spectral efficiency and thus enables increased network capacity. The distributed feedback semiconductor laser (DFB) has served as the near exclusive light source powering the fiber optic, long-haul network for over 30 years. The transition to coherent communication systems is pushing the DFB laser to the limits of its abilities. This is due to its limited temporal coherence that directly translates into the number of different phases that can be imparted to a single optical pulse and thus to the data capacity. Temporal coherence, most commonly quantified in the spectral linewidth \u0394\u03bd, is limited by phase noise, result of quantum-mandated spontaneous emission of photons due to random recombination of carriers in the active region of the laser.
\r\n\r\nIn this work we develop a generically new type of semiconductor laser with the requisite coherence properties. We demonstrate electrically driven lasers characterized by a quantum noise-limited spectral linewidth as low as 18 kHz. This narrow linewidth is result of a fundamentally new laser design philosophy that separates the functions of photon generation and storage and is enabled by a hybrid Si/III-V integration platform. Photons generated in the active region of the III-V material are readily stored away in the low loss Si that hosts the bulk of the laser field, thereby enabling high-Q photon storage. The storage of a large number of coherent quanta acts as an optical flywheel, which by its inertia reduces the effect of the spontaneous emission-mandated phase perturbations on the laser field, while the enhanced photon lifetime effectively reduces the emission rate of incoherent quanta into the lasing mode. Narrow linewidths are obtained over a wavelength bandwidth spanning the entire optical communication C-band (1530-1575nm) at only a fraction of the input power required by conventional DFB lasers. The results presented in this thesis hold great promise for the large scale integration of lithographically tuned, high-coherence laser arrays for use in coherent communications, that will enable Tb/s-scale data capacities.
", "doi": "10.7907/M4KJ-8H56", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7058", "collection": "thesis", "collection_id": "7058", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05212012-132419705", "primary_object_url": { "basename": "Dempsey_2012_Thesis.pdf", "content": "final", "filesize": 75958490, "license": "other", "mime_type": "application/pdf", "url": "/7058/22/Dempsey_2012_Thesis.pdf", "version": "v11.0.0" }, "type": "thesis", "title": "Establishing a Genetic and Exogenous Toolbox for Studying Multiple Stages of Vertebrate Development in vivo", "author": [ { "family_name": "Dempsey", "given_name": "William P.", "clpid": "Dempsey-William-P" } ], "thesis_advisor": [ { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" } ], "thesis_committee": [ { "family_name": "Phillips", "given_name": "Robert B.", "orcid": "0000-0003-3082-2809", "clpid": "Phillips-R" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Understanding of cell behavior during vertebrate development and repair has been greatly facilitated by advances in biological imaging. Importantly, more powerful tools to generate contrast within the tissue make in vivo analyses of these processes in time and space more tractable. Here, I present my efforts to develop and refine an imaging toolbox to study in vivo cell shape, dynamics, structure, and behavior in the zebrafish vertebrate model system. Mosaic analysis and targeted photoconversion illuminate fine morphological details as cells migrate during gastrulation, revealing cell connections that span several cell diameters across the embryo. These intercellular bridges link cells between lineage boundaries and allow cells to share membrane components on a developmentally relevant time scale. The PhOTO zebrafish transgenic lines combine the strengths of sparse and global cell labeling to monitor cell dynamics and morphology at any stage in the lifetime of the zebrafish. I demonstrate targeted and instantaneous sparse cell tracking in the context of global cell behavior in the embryo, and I also isolate a subset of slowly dividing cells populating a regenerating adult tail fin. Combining fluorescence and endogenous second harmonic generation (SHG) imaging as a tool to study early muscle structure and organization within whole zebrafish muscle compartments uncovers the source of vernier-patterned signal in highly ordered myosin arrays. Instead of being physical distortions in muscle sarcomeres, these patterns may result from an optical artifact of SHG imaging, since comparable signal is not visible in both the SHG and fluorescence channels. To complement the aforementioned genetic labeling and endogenous contrast tools, barium titanate SHG nanoprobes \u2014 exogenous and nontoxic SHG-capable nanomaterial tags \u2014 are refined for cell labeling in the zebrafish. Silane functionalization acts as a platform for further surface modifications, including: multistep chemical additions, non-reactive surface coating modifications, and antibody linkages for cell targeting applications. The power of each of these tools lies in their compatibility with one another: combining the fluorescence and SHG contrast approaches described here may enable high-resolution imaging at a variety of developmental stages to appreciate the multifaceted cell behaviors governing vertebrate developmental programs more completely.", "doi": "10.7907/Z98S4MVS", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:7074", "collection": "thesis", "collection_id": "7074", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05242012-174045229", "primary_object_url": { "basename": "Thesis_HsiChunLiu.pdf", "content": "final", "filesize": 2427683, "license": "other", "mime_type": "application/pdf", "url": "/7074/1/Thesis_HsiChunLiu.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Theory and Experiment of Slow-Light Coupled-Resonator Structures", "author": [ { "family_name": "Liu", "given_name": "Hsi-Chun", "clpid": "Liu-Hsi-Chun" } ], "thesis_advisor": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "thesis_committee": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Slow light has been an inter-disciplinary topic and a rapidly growing area, especially over the last decade with the improvement of fabrication technology. The ability to slow down and control the group velocity of light may find applications such as optical buffers, optical delay lines, and enhanced light-matter interaction in optical modulator, amplifier, detectors, lasers, and nonlinear optics. The spirit of slow light is to replace a bulky device with a much shorter, compact structure.
\r\n\r\nThis thesis explores the design and experiment of coupled-resonator optical waveguides (CROWs), which consist of arrays of optical resonators in which light propagates through the coupling between resonators. The group velocity of light is dictated by the inter-resonator coupling strength. Light can be significantly slowed down if the inter-resonator coupling is weak. CROWs can be realized with various types of resonators. This thesis focuses on grating resonators in silicon waveguides, including grating-defect resonators and bandgap-modulated resonators. With the strong gratings, the grating resonators are only a few microns long. We control the inter-resonator coupling via the number of holes between adjacent resonators.
\r\n\r\nThe major limitations in the realization of CROWs have been various kinds of transmission losses, including the resonator losses, the discontinuity between CROWs and the coupling waveguides, and the fabrication disorder. These transmission losses limit the achievable group velocity and the maximum number of resonators. We address these transmission losses throughout this thesis. The resonator losses are overcome with the design and optimized fabrication of tapered grating-defect resonators and bandgap-modulated resonators. The discontinuity between CROWs and waveguides is reduced by tailoring the coupling along the CROW for adiabatic conversion. The optimization of the CROW response leads to the study of filter design based on CROW. Filter design formalism based on coupled-mode theory is presented. The effect of fabrication disorder on CROWs is analyzed, and the Butterworth filters are shown to be more robust against fabrication disorder. The fabrication and measurement of grating CROWs are presented, featuring high-Q (Q=105) grating resonators, coupling of up to 50 resonators, control of group velocity between c/13 and c/49, and Butterworth filters.
\r\n\r\nFinally, an optical analog of electromagnetically induced transparency is presented. The structure consists of two co-spatial gratings imposed on a three-mode waveguide. One of the supermodes, the Dark mode, possesses a group velocity which depends on the ratio of the grating strengths. The group velocity can be nearly zero if the two grating strengths are nearly identical.
\r\n", "doi": "10.7907/GVBF-4T29", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:7130", "collection": "thesis", "collection_id": "7130", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06042012-135440197", "primary_object_url": { "basename": "Full_Thesis-v5.pdf", "content": "final", "filesize": 16190173, "license": "other", "mime_type": "application/pdf", "url": "/7130/1/Full_Thesis-v5.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Biomimetic Accommodating Intraocular Lens", "author": [ { "family_name": "DeBoer", "given_name": "Charles Meno Theodore", "clpid": "DeBoer-Charles-Meno-Theodore" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Mark", "clpid": "Humayun-M" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The crystalline lens allows the eye to focus on near and far objects. During the aging process, it loses its ability to focus and often becomes cloudy during cataract formation. At this point, traditional medical therapy replaces the lens with an artificial replacement lens. Although replacement lenses for the crystalline lens have been implanted since 1949 for cataract surgery, none of the FDA-approved lenses mimic the anatomy of the natural lens. Hence, they are not able to focus in a manner similar to the youthful lens. Instead, they function in a manner similar to the aged lens and only provide vision at a single distance or at a very limited range of focal distances. Patients with the newest implants are often obliged to use reading glasses when using near vision, or suffer from optical aberrations, halos, or glare. Therefore, there is a need to provide youthful vision after lens surgery in terms of focusing ability, accurate optical power, and sharp focus without distortion or optical aberrations.
\r\n\r\nThis thesis presents an approach to restoring youthful vision after lens replacement. An intraocular lens (IOL) that can provide accurate visual acuity along with focusing ability is proposed. This IOL relies on the natural anatomy and physiology of the eye, and therefore is actuated in a manner identical to the natural lens. In addition, the lens has the capability for adjustment during or after implantation to provide high-acuity vision throughout life.
\r\n\r\nThe natural anatomy and physiology of the eye is described, along with lens replacement surgery. A lens design is proposed to address the unmet need of lens-replacement patients. Specific care in the design is made for small surgical incisions, high visual acuity, adjustable acuity over years, and the ability to focus similar to the natural lens. Methods to test the IOL using human donor tissue are developed based upon prior experiments on the ex vivo natural lens. These tools are used to demonstrate efficacy of the newly developed accommodating intraocular lens.
\r\n\r\nTo further demonstrate implant feasibility, materials and processes for building the lens are evaluated for biocompatibility, endurance, repeatable manufacture, and stability. The lens biomechanics are determined after developing an artificial anatomy testing setup inspired by the natural anatomy of the human focusing mechanism. Finally, based upon a mechanical and optical knowledge of the lens, several improved lens concepts are proposed and demonstrated for efficacy.
", "doi": "10.7907/Z9B56GQH", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:6998", "collection": "thesis", "collection_id": "6998", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05022012-003225468", "primary_object_url": { "basename": "Bo_Lu_PhD_Thesis_2012.pdf", "content": "final", "filesize": 15579488, "license": "other", "mime_type": "application/pdf", "url": "/6998/1/Bo_Lu_PhD_Thesis_2012.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Parylene as a New Membrane Material for Biomems Applications", "author": [ { "family_name": "Lu", "given_name": "Bo", "clpid": "Lu-Bo" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Guo", "given_name": "Chin-Lin", "clpid": "Guo-Chin-Lin" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The work in this thesis aims to use MEMS and microfabrication technologies to develop two types of parylene membrane devices for biomedical applications. The first device is the parylene membrane filter for cancer detection. The presence of circulating tumor cells (CTC) in patient blood is an important sign of cancer metastasis. However, currently there are two big challenges for CTC detection. First, CTCs are extremely rare, especially at the early stage of cancer metastasis. Secondly, CTCs are very fragile, and are very likely to be damaged during the capturing process. By using size-based membrane filtration through the specially designed parylene filters, together with a constant-pressure filtration system, we are able to capture the CTCs from patient blood with high capture efficiency, high viability, moderate enrichment, and high throughput. Both immunofluorescence enumeration and telomerase activity detection have been used to detect and differentiate the captured CTCs. The feasibility of further cell culture of the captured CTCs has also been demonstrated, which could be a useful way to increase the number of CTCs for future studies. Models of the time-dependent cell membrane damage are developed to predict and prevent CTC damage during this detection process. The results of clinical trials further demonstrate that the parylene membrane filter is a promising device for cancer detection.
\r\n\r\nThe second device is the parylene artificial Bruch\u2019s membrane for age-related macular degeneration (AMD). AMD is usually characterized by an impaired Bruch\u2019s membrane with much lowered permeability, which impedes the transportation of nutrients from choroid vessels to nourish the retinal pigment epithelial (RPE) cells and photoreceptors. Parylene is selected as a substitute material because of its good mechanical properties, transparency, biocompatibility, and machinability. More importantly, it is found that the permeability of submicron parylene is very similar to that of healthy human Bruch\u2019s membrane. A mesh-supported submicron parylene membrane structure has been designed and its feasibility as an artificial Bruch\u2019s membrane has been demonstrated by diffusion experiments, cell perfusion culture, and pressure deflection tests. RPE cells are able to adhere, proliferate and develop into normal in vivo-like morphology and functions. Currently this artificial membrane is under clinical trials.
\r\n", "doi": "10.7907/DPDC-9E57", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:7008", "collection": "thesis", "collection_id": "7008", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05062012-225422868", "primary_object_url": { "basename": "J_Huang_2012.pdf", "content": "final", "filesize": 37734443, "license": "other", "mime_type": "application/pdf", "url": "/7008/1/J_Huang_2012.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Wavelength-Scale Confinement of Light and Its Applications in On-Chip Photonic Devices", "author": [ { "family_name": "Huang", "given_name": "Jingqing", "clpid": "Huang-Jingqing" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" }, { "family_name": "Atwater", "given_name": "Harry Albert", "clpid": "Atwater-H-A" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "We present design and experimental work toward building room temperature, continuous-wave (CW) lasers with a cavity that confines light to a volume of \u2264 (\u03bb/n)3. We begin with the mechanisms of strong optical confinement using dispersive metals and photonic crystals. Finite-difference time-domain methods (FDTD) are used to simulate the behavior of electromagnetic fields in the cavity; fast Fourier transform from FDTD-generated near-field data calculates the far-field radiation pattern from the microcavity laser.
\r\n\r\nWe then present our investigations into designs where metals are incorporated into microdisk and photonic crystal optical cavities to curb or redirect radiation loss. The significant effects of boundary conditions and substrate feedback on far-field radiation directionality are studied. We evaluate the threshold gain required to achieve room temperature lasing in these metallo-dielectric cavities.
\r\n\r\nWhile studying the confinement mechanism of photonic crystals on metal substrate, it became clear that room temperature lasing can be achieved in optically-thick photonic crystal cavities, where the thicker semiconductor layer would give us more freedom in designing the vertical p-i-n doping profile within, for a less resistive and leaky electrical path for current injection operation. We fabricate and demonstrate single-mode room temperature lasing by optical pumping in an optically- thick single-defect cavity.
\r\n\r\nWe move on to present our design and characterization of coupled-cavity photonic crystal lasers operating with CW, high output power, and directional emission. Single-mode stable emission with output power on the order of 10 \u03bcW and linear polarization was achieved. Moreover, we switched from the commonly used InGaAsP quantum well material to the lesser-known InAsP quantum wells in InP cladding, and found that the large band-edge offset between InAsP and InP made a world of difference in achieving high power operation despite the large thermal resistance in the device.
\r\nFor a microcavity laser with directional radiation, Purcell-enhanced spontaneous emission, and diminished effects due to feedback from surrounding structures such as the substrate, nanobeam photonic crystal lasers are analyzed, fabricated, and characterized. Despite thermal resistance an order of magnitude higher than their 2D counterparts, quasi-CW operation with a soft threshold turn-on was achieved.
\r\n\r\nMuch work was done to optimize fabrication techniques in order to realize the optical cavity designs with little fabrication error. We detail the high-contrast hydrogen silsesquioxane (HSQ) electron-beam lithography and deep vertical dry etch procedures especially developed for this work.
\r\n\r\nLastly, related projects on nonlinear silicon photonic devices are presented. Synthetic nonlinear polymer is integrated on to the silicon photonic platform to achieve low half-wave voltage electro-optic modulation. Causes and magnitude of the nonlinear loss particular to silicon waveguides with sub-\u03bcm2 cross-section are evaluated.
", "doi": "10.7907/6F0A-TD74", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:7143", "collection": "thesis", "collection_id": "7143", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06072012-004925615", "primary_object_url": { "basename": "StephaneLintner_Thesis_2012.pdf", "content": "final", "filesize": 8490042, "license": "other", "mime_type": "application/pdf", "url": "/7143/1/StephaneLintner_Thesis_2012.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "High-Order Integral Equation Methods for Diffraction Problems Involving Screens and Apertures", "author": [ { "family_name": "Lintner", "given_name": "St\u00e9phane Karl", "clpid": "Lintner-St\u00e9phane-Karl" } ], "thesis_advisor": [ { "family_name": "Bruno", "given_name": "Oscar P.", "clpid": "Bruno-O-P" } ], "thesis_committee": [ { "family_name": "Bruno", "given_name": "Oscar P.", "clpid": "Bruno-O-P" }, { "family_name": "Meiron", "given_name": "Daniel I.", "clpid": "Meiron-D-I" }, { "family_name": "Owhadi", "given_name": "Houman", "clpid": "Owhadi-H" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents a novel approach for the numerical solution of problems of diffraction by infinitely thin screens and apertures. The new methodology relies on combination of weighted versions of the classical operators associated with the Dirichlet and Neumann open-surface problems. In the two-dimensional case, a rigorous proof is presented, establishing that the new weighted formulations give rise to second-kind Fredholm integral equations, thus providing a generalization to open surfaces of the classical closed-surface Calderon formulae. High-order quadrature rules are introduced for the new weighted operators, both in the two-dimensional case as well as the scalar three-dimensional case. Used in conjunction with Krylov subspace iterative methods, these rules give rise to efficient and accurate numerical solvers which produce highly accurate solutions in small numbers of iterations, and whose performance is comparable to that arising from efficient high-order integral solvers recently introduced for closed-surface problems. Numerical results are presented for a wide range of frequencies and a variety of geometries in two- and three-dimensional space, including complex resonating structures as well as, for the first time, accurate numerical solutions of classical diffraction problems considered by the 19th-century pioneers: diffraction of high-frequency waves by the infinitely thin disc, the circular aperture, and the two-hole geometry inherent in Young's experiment.\r\n", "doi": "10.7907/VP8P-DP74", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:7158", "collection": "thesis", "collection_id": "7158", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06112012-145654043", "type": "thesis", "title": "Silicon-Based Terahertz Circuits and Systems", "author": [ { "family_name": "Sengupta", "given_name": "Kaushik", "clpid": "Sengupta-Kaushik" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Weinreb", "given_name": "Sander", "clpid": "Weinreb-S" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The Terahertz frequency range, often referred to as the `Terahertz' gap, lies wedged between microwave at the lower end and infrared at the higher end of the spectrum, occupying frequencies between 0.3-3.0 THz. For a long time, applications in THz frequencies had been limited to astronomy and chemical sciences, but with advancement in THz technology in recent years, it has shown great promise in a wide range of applications ranging from disease diagnostics, non-invasive early skin cancer detection, label-free DNA sequencing to security screening for concealed weapons and contraband detection, global environmental monitoring, nondestructive quality control and ultra-fast wireless communication. Up until recently, the terahertz frequency range has been mostly addressed by high mobility compound III-V processes, expensive nonlinear optics, or cryogenically cooled quantum cascade lasers. A low cost, room temperature alternative can enable the development of such a wide array of applications, not currently accessible due to cost and size limitations. In this thesis, we will discuss our approach towards development of integrated terahertz technology in silicon-based processes. In the spirit of academic research, we will address frequencies close to 0.3 THz as 'Terahertz'.
\r\n\r\nIn this thesis, we address both fronts of integrated THz systems in silicon: THz power generation, radiation and transmitter systems, and THz signal detection and receiver systems. THz power generation in silicon-based integrated circuit technology is challenging due to lower carrier mobility, lower cut-o frequencies compared to compound III-V processes, lower breakdown voltages and lossy passives. Radiation from silicon chip is also challenging due to lossy substrates and high dielectric constant of silicon. In this work, we propose novel ways of combining circuit and electromagnetic techniques in a holistic design approach, which can overcome limitations of conventional block-by-block or partitioned design methodology, in order to generate high-frequency signals above the classical definition of cut-off frequencies (\u0192t/\u0192max). We demonstrate this design philosophy in an active electromagnetic structure, which we call Distributed Active Radiator. It is inspired by an Inverse\r\nMaxwellian approach, where instead of using classical circuit and electromagnetic blocks to generate and radiate THz frequencies, we formulate surface (metal) currents in silicon chip for a desired THz field prole and develop active means of controlling different harmonic\r\ncurrents to perform signal generation, frequency multiplication, radiation and lossless filtering, simultaneously in a compact footprint. By removing the articial boundaries between circuits, electromagnetics and antenna, we open ourselves to a broader design space. This\r\nenabled us to demonstrate the rst 1 mW Eective-isotropic-radiated-power(EIRP) THz (0.29 THz) source in CMOS with total radiated power being three orders of magnitude more than previously demonstrated. We also proposed a near-field synchronization mechanism, which is a scalable method of realizing large arrays of synchronized autonomous radiating sources in silicon. We also demonstrate the first THz CMOS array with digitally controlled beam-scanning in 2D space with radiated output EIRP of nearly 10 mW at 0.28 THz.
\r\n\r\nOn the receiver side, we use a similar electronics and electromagnetics co-design approach to realize a 4x4 pixel integrated silicon Terahertz camera demonstrating to the best of our knowledge, the most sensitive silicon THz detector array without using post-processing,\r\nsilicon lens or high-resistivity substrate options (NEP < 10 pW √ Hz at 0.26 THz). We put the 16 pixel silicon THz camera together with the CMOS DAR THz power generation arrays and demonstrated, for the first time, an all silicon THz imaging system with a CMOS source.
", "doi": "10.7907/MBXB-6R29", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:6719", "collection": "thesis", "collection_id": "6719", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10192011-190918785", "primary_object_url": { "basename": "Thesis_Lap_Man_Lee.pdf", "content": "final", "filesize": 4822758, "license": "other", "mime_type": "application/pdf", "url": "/6719/1/Thesis_Lap_Man_Lee.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "The Implementation of Optofluidic Microscopy on a Chip Scale and Its Potential Applications in Biology", "author": [ { "family_name": "Lee", "given_name": "Lap Man", "clpid": "Lee-Lap-Man" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Guo", "given_name": "Chin-Lin", "clpid": "Guo-Chin-Lin" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents an effort to miniaturize conventional optical microscopy to a chip level using microfluidic technology. Modern compound microscopes use a set of bulk glass lenses to form magnified images from biological objects. This limits the possibility of shrinking the size of a microscope system. The invention of micro/nanofabrication technology gives hope to engineers who want to rethink the way we build optical microscopes. This advancement can fundamentally reform the way clinicians and biologists conduct microscopy. Optofluidic microscopy (OFM) is a miniaturized optical imaging method which utilizes a microfluidic flow to deliver biological samples across a 1-D or 2-D array of sampling points defined in a microfluidic channel for optical scanning. The optical information of these sampling points is collected by a CMOS imaging sensor on the bottom of the microfluidic channel. Although the size of the OFM device is as small as a US dime, it can render high resolution images of less than 1 \u03bcm with quality comparable to that of a bulky, standard optical microscope. OFM has a good potential in various biological applications. For example, the integration of an OFM system with high-speed hydrodynamic focusing technology will allow very large scale imaging-based analysis of cells or microorganisms; the compactness and low cost nature of OFM systems can enable portable or even disposable biomedical diagnostic tools for future telemedicine and personalized health care. ", "doi": "10.7907/GKW9-QR51", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:7053", "collection": "thesis", "collection_id": "7053", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05192012-003206031", "primary_object_url": { "basename": "MEMS_for_Glaucoma_Lin_2012.pdf", "content": "final", "filesize": 7792333, "license": "other", "mime_type": "application/pdf", "url": "/7053/1/MEMS_for_Glaucoma_Lin_2012.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "MEMS for Glaucoma", "author": [ { "family_name": "Lin", "given_name": "Jeffrey Chun-Hui", "clpid": "Lin-Jeffrey-Chun-Hui" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Choo", "given_name": "Hyuck", "clpid": "Choo-Hyuck" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Glaucoma is an eye disease that gradually steals vision. Open angle glaucoma is one of the most common glaucoma forms, in which eye fluid (aqueous humor) produced by the ciliary body cannot be drained away normally by patients\u2019 eyes. The accumulated eye fluid inside the anterior chamber causes high intraocular pressure (IOP), which is transmitted onto the retina in the back of the eyeball (globe), continuously suppressing and damaging the patient\u2019s optic nerves; this may lead to total blindness if not treated properly.
\r\n\r\nThe current most-popular IOP monitoring technique is to use applanation tonometry, which applies applanation force onto the cornea and measures the resulting deformation in order to calculate the IOP. Even though applanation tonometry can provide quite useful information about patients\u2019 IOP, continuous monitoring of IOP is required for ophthalmologists to understand the IOP fluctuation of the patients, something which still cannot be achieved via current applanation approach. In addition, applanation tonometry requires skillful operation performed by well-trained professionals, such as ophthalmologists, making continuous IOP monitoring impractical. In this work, we have developed a telemetric IOP sensor that is capable of monitoring IOP wirelessly and continuously. As the quality factor drops when a telemetric IOP sensor is implanted in the anterior chamber, due to the high loss tangent of the saline-based aqueous humor (~ 0.2) compared to air (0.0), a modified IOP sensor is developed to monitor IOP with sensing coil that is left exposed after implantation in order to avoid interruption from the eye fluid. Another approach is also proposed and tested to demonstrate that the quality factor can also be recovered by covering the sensing coil with low loss tangent materials.
\r\n\r\nCurrently glaucoma is treated mostly by taking oral medications or applying eye drops. However, some glaucoma patients do not respond to those medications. Therefore, another physical approach, using a glaucoma drainage device (GDD), is necessary in order to drain out excessive eye fluid and serve as a long-term way to manage the increased IOP. Current commercially available glaucoma drainage devices do not have reliable valve systems to stop the drainage when the IOP falls into the normal range. Therefore, we have developed a dual-valved GDD to fulfill the \u201cband-pass\u201d flow regulation which drains out eye fluid only when IOP is higher than 20 mmHg, and stops drainage (closes the valve) when IOP is lower than 20 mmHg to prevent hypotony. The key component of GDD is a normally closed (NC) check-valve, which only opens to drain away the excess fluid when the pressure is higher than 20 mmHg. The proposed paradigm of our NC check-valve is to have a couple of parylene-C pre-stressed slanted tethers to provide the desired cracking pressure. The slanted tethers are achieved in this thesis by: 1) slanted photoresist generated by gray-scale photolithography, 2) pop-up mechanism, and 3) self-stiction bonding mechanism. The built-in residual tensile stress can be controlled by mechanical stretching or thermal annealing. The protecting mechanism preventing the unwanted drainage when the eyes experience sudden unpredicted high IOP is achieved by utilizing a normally open (NO) check-valve. A \"minimally invasive implantation\" procedure is proposed in the thesis to implant the GDD subconjunctivally. The small size of the device allows its insertion using a #19-gauge needle.
\r\n\r\nTo accurately design the desired cracking pressure and also predict the lifetime of the NC check-valve, parylene-C\u2019s mechanical, thermal, and polymer properties are investigated. The results show that the properties of parylene-C are highly process-temperature-dependent and therefore can be tailored by adjusting the thermal annealing process.
", "doi": "10.7907/4XD2-SP34", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:6364", "collection": "thesis", "collection_id": "6364", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04292011-221312708", "type": "thesis", "title": "Optoelectronic Control of the Phase and Frequency of Semiconductor Lasers", "author": [ { "family_name": "Satyan", "given_name": "Naresh", "clpid": "Satyan-Naresh" } ], "thesis_advisor": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "thesis_committee": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" }, { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis explores the precise control of the phase and frequency of the output of semiconductor lasers (SCLs), which are the basic building blocks of most modern optical communication networks. Phase and frequency control is achieved by purely electronic means, using SCLs in optoelectronic feedback systems, such as optical phase-locked loops (OPLLs) and optoelectronic swept-frequency laser (SFL) sources. Architectures and applications of these systems are studied.
\r\n\r\nOPLLs with single-section SCLs have limited bandwidths due to the nonuniform SCL frequency modulation (FM) response. To overcome this limitation, two novel OPLL architectures are designed and demonstrated, viz. (i) the sideband-locked OPLL, where the feedback into the SCL is shifted to a frequency range where the FM response is uniform, and (ii) composite OPLL systems, where an external optical phase modulator corrects excess phase noise. It is shown, theoretically and experimentally, and in the time and frequency domains, that the coherence of the master laser is \u201ccloned\u201d onto the slave SCL in an OPLL. An array of SCLs, phase-locked to a common master, therefore forms a coherent aperture, where the phase of each emitter is electronically controlled by the OPLL. Applications of phase-controlled apertures in coherent power-combining and all-electronic beam-steering are demonstrated.
\r\n\r\nAn optoelectronic SFL source that generates precisely linear, broadband, and rapid frequency chirps (several 100 GHz in 0.1 ms) is developed and demonstrated using a novel OPLL-like feedback system, where the frequency chirp characteristics are determined solely by a reference electronic oscillator. Results from high-sensitivity biomolecular sensing experiments utilizing the precise frequency control are reported. Techniques are developed to increase the tuning range of SFLs, which is the primary requirement in high-resolution three-dimensional imaging applications. These include (i) the synthesis of a larger effective bandwidth for imaging by \"stitching\" measurements taken using SFLs chirping over different regions of the optical spectrum; and (ii) the generation of a chirped wave with twice the chirp bandwidth and the same chirp characteristics by nonlinear four-wave mixing of the SFL output and a reference monochromatic wave. A quasi-phase-matching scheme to overcome dispersion in the nonlinear medium is described and implemented.
\r\n", "doi": "10.7907/24DM-VW62", "publication_date": "2011", "thesis_type": "phd", "thesis_year": "2011" }, { "id": "thesis:6273", "collection": "thesis", "collection_id": "6273", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03242011-165209307", "type": "thesis", "title": "Surface Optofluidic Implementations towards the Development of a Biosensor", "author": [ { "family_name": "Choi", "given_name": "Jae-Woo", "clpid": "Choi-Jae-Woo" } ], "thesis_advisor": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" } ], "thesis_committee": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" }, { "family_name": "Willis", "given_name": "Peter", "clpid": "Willis-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Microfluidics is a multidisciplinary field that uses minute volumes of liquids to attempt complex functionalities. These complicated functionalities often require manipulating interfaces through external forces. In addition, optics have become a fundamental necessity for most microfluidic devices. We combine these two concepts and call it surface optofluidics. Here, we focus on the advantages of surface optofluidics for the development of a biosensor, specifically focusing on the flexibility and adaptability offered by these techniques.
\r\n\r\nTo introduce the advantages presented by surface optofluidics, devices using droplet electrowetting techniques are discussed. We then discuss biosensing through structured electrodes on surfaces. The electrodes are used to align asymmetric bacteria. The aligned bacteria are detected optically. This method of detection is improved by incorporating two different surface optofluidic methods. Concentration and motion control of the bacterium is demonstrated with electric fields on three dimensionally structured electrodes and an optothermal nanoparticle carpet. Finally, we show preliminary work in the study of single bacterium behavior using nanoparticles as labels to detect its specific alignment in space.
\r\n", "doi": "10.7907/KYZG-3503", "publication_date": "2011", "thesis_type": "phd", "thesis_year": "2011" }, { "id": "thesis:5970", "collection": "thesis", "collection_id": "5970", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07092010-104142755", "primary_object_url": { "basename": "Ray_Huang_PhD_Thesis.pdf", "content": "final", "filesize": 5798296, "license": "other", "mime_type": "application/pdf", "url": "/5970/1/Ray_Huang_PhD_Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Flexible Neural Implants", "author": [ { "family_name": "Huang", "given_name": "Ray Kui-Jui", "clpid": "Huang-Ray-Kui-Jui" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Andersen", "given_name": "Richard A.", "clpid": "Andersen-R-A" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Despite recent development in integration technologies for biomedical implantable devices, current state-of-the-art prosthetic platforms still lack a reliable and convenient packaging scheme to integrate high-density signal-driving chips, wireless telemetry circuitries and noise-canceling amplifiers, mainly due to the limitations in fabrication technology, material compatibility and interconnect reliability. In this dissertation, new packaging technologies are developed and presented to enable a new generation of flexible neural implants. These technologies can also house integrated circuit chips and provide high-density electrical connection to it.
\r\n\r\nThis packaging scheme utilizes the parylene-metal-parylene skin structure and can be totally integrated and be monolithically fabricated with existing functional devices. The size and the electrode patterns can be modified to suit different chips and applications. Integration with flexible cable integrated silicon probes for neural prosthesis, implantable muscle stimulators and implantable RFID tagging technology are all successfully demonstrated in this dissertation. Other discrete components can also be integrated to achieve high level functionality.
\r\n\r\nIn order to ensure the long-term stability of such packaging scheme, accelerated hot saline soaking test is conducted on the overall structure and its components. Detailed adhesion enhancement techniques are also presented to improve its performances. A physical model of the flexible retinal implant is then tested in vivo during the course of the experiment. Finally, the high-density squeegee bonding technique is introduced, which allows the integration of a 256-channel chip. Functionality of the chip has been demonstrated. As a result, this technology has the potential to achieve ultra high lead count connection and can facilitate future research in flexible implantable biodevices.
\r\n", "doi": "10.7907/VMZB-0N20", "publication_date": "2011", "thesis_type": "phd", "thesis_year": "2011" }, { "id": "thesis:6281", "collection": "thesis", "collection_id": "6281", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04082011-064907780", "primary_object_url": { "basename": "HSIEH_PhD_thesis_2011.pdf", "content": "final", "filesize": 5320736, "license": "other", "mime_type": "application/pdf", "url": "/6281/1/HSIEH_PhD_thesis_2011.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Imaging with Second-Harmonic Generation Nanoparticles", "author": [ { "family_name": "Hsieh", "given_name": "Chia-Lung", "clpid": "Hsieh-Chia-Lung" } ], "thesis_advisor": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" } ], "thesis_committee": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" }, { "family_name": "Rutledge", "given_name": "David B.", "clpid": "Rutledge-D-B" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" }, { "family_name": "Daraio", "given_name": "Chiara", "clpid": "Daraio-C" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Second-harmonic generation nanoparticles show promise as imaging probes due to their coherent and stable signal with a broad flexibility in the choice of excitation wavelength. In this thesis, we developed and demonstrated barium titanate nanoparticles as second-harmonic radiation imaging probes. We studied the absolute second-harmonic generation efficiency of the nanoparticles on single-particle level. The polarization dependent second-harmonic signal of single nanoparticles was studied in detail. From the measured polar response, we were able to find the orientation of the nanoparticle. We developed a biochemical interface for using the second-harmonic nanoprobes as biomarkers, including in vitro cellular imaging and in vivo live animal imaging. The nanoparticles were surface functionalized with primary amine groups for stable colloidal dispersion. We achieved specific labeling of the second-harmonic nanoprobes via immunostaining where the antibodies were covalently conjugated onto the nanoparticles. We observed no toxicity of the functionalized nanoparticles to biological cells. The coherent second-harmonic signal radiated from the nanoparticles offers opportunities for new imaging techniques. Using interferometric detection, namely harmonic holography, both amplitude and phase of the second-harmonic field can be captured. Through digital beam propagation, three-dimensional field distribution, reflecting three-dimensional distribution of the nanoparticles, can be reconstructed. We achieved a scan-free three-dimensional imaging of nanoparticles in biological cells with sub-micron spatial resolution by using the harmonic holographic microscope. We further exploited the coherent second-harmonic signal for imaging through scattering media by performing optical phase conjugation of the second-harmonic signal. We demonstrated an all-digital optical phase conjugation of the second-harmonic signal originated from a nanoparticle by combining harmonic holography and dynamic computer generated holography using a spatial light modulator. The phase-conjugated second-harmonic scattered field retraced the scattering trajectory and formed a clean focus on the nanoparticle placed inside a scattering medium. The nanoparticle acted as a beacon of light; it helped us find the tailored wavefront for concentrating light at the nanoparticle inside the scattering medium. We also demonstrated imaging through a thin scattering medium by raster-scanning the phase-conjugated focus in the vicinity of the beacon nanoparticle, in which a clear image of a target placed behind a ground glass diffuser was obtained.", "doi": "10.7907/WCS2-FD82", "publication_date": "2011", "thesis_type": "phd", "thesis_year": "2011" }, { "id": "thesis:6222", "collection": "thesis", "collection_id": "6222", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01102011-204907918", "primary_object_url": { "basename": "Electrolytic_Inchworms.pdf", "content": "final", "filesize": 12433844, "license": "other", "mime_type": "application/pdf", "url": "/6222/1/Electrolytic_Inchworms.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "MEMS Electrolytic Inchworms for Movable Neural Probe Applications", "author": [ { "family_name": "Giacchino", "given_name": "Luca", "clpid": "Giacchino-Luca" } ], "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": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Kornfield", "given_name": "Julia A.", "clpid": "Kornfield-J-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Over decades of cortical neural prosthesis, it was found that \"movable\" neural probes are important to track neurons for long-term, reliable prostheses. This is challenging because the ideal movable probes require low voltage, small power, bidirectional/latchable movement, and large total traveling distance. The device should also be small enough to entirely fit under the skull after implantation. Many different devices have been demonstrated to move neural probes, but none of them satisfies all the actuation and size requirements.
\r\n\r\nThis thesis presents our work on actuators for movable neural probes that combine MEMS technology with an electrolytic actuation mechanism. Each inchworm is based on two electrolytic balloon actuators. The actuators rely on gas generation by electrolysis inside a sealed balloon, which causes its expansion. When electrolysis is stopped, gas recombination and permeation across the balloon membrane cause the balloon to relax. Electrolytic actuation, although slow, has several advantages: low power, low voltage, and ability to provide large force and displacement. The balloons have been characterized and their behavior mathematically modeled. Innovative salt-shell-based and hydrogel-based processes have been developed to fabricate the balloons and to allow their replenishment by osmosis.
\r\n\r\nTwo balloons are combined into a bidirectional inchworm mechanism. Large traveling distance can be obtained in multiple cycles, the only constraint being the probe length. Displacement of a silicon probe and of a commercial metal probe have been demonstrated in both directions, with a displacement per cycle between 0.5 um and 75 um. The voltage required to drive electrolysis is typically around 3.5 V, with peak power per balloon around 100 uW. The devices were tested in air, water, and saline.
\r\n\r\nClosed-loop control of the inchworm may be needed for accurate positioning of the probe, and monitoring of the pressure inside the balloons represents a possible source of feedback from the inchworm. Parylene-membrane pressure sensors that are suitable for integration inside balloon actuators have been demonstrated.
", "doi": "10.7907/GQYY-BM80", "publication_date": "2011", "thesis_type": "phd", "thesis_year": "2011" }, { "id": "thesis:5733", "collection": "thesis", "collection_id": "5733", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04222010-082435622", "type": "thesis", "title": "Chemical Synthesis in Elastomer-Based Integrated Microfluidics", "author": [ { "family_name": "Lee", "given_name": "Cheng-Chung", "clpid": "Lee-Cheng-Chung" } ], "thesis_advisor": [ { "family_name": "Quake", "given_name": "Stephen R.", "clpid": "Quake-S-R" } ], "thesis_committee": [ { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Quake", "given_name": "Stephen R.", "clpid": "Quake-S-R" }, { "family_name": "Stoltz", "given_name": "Brian M.", "clpid": "Stoltz-B-M" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "There is wide interest in using the unique properties of microfluidic environments for the production of fine chemicals and pharmaceuticals. Compared to bench top synthesis, microfluidic systems engender the significant advantage of superior control of chemical state functions. The ability to tune reagent concentration, reaction temperature, mixing time, and residence time allows reactions to run more efficiently thus generating products of higher yield and purity. While several microfluidic platforms are actively developed in both academic and industrial laboratories, vast majority are based in rigid materials and have only demonstrated improvements in yield for single reaction steps.
\r\n\r\nMultilayer Soft Lithography has already found much use in the biological field. For example, several complex devices based upon functional modules have been developed for protein crystallography, nucleic acid processing, FACS, enzyme screening tools, and PCR. Because of the many similarities between operations in organic synthesis and biochemistry, there is widespread interest in extending these newfound successes in the realm of biology to the realm of automated chemical synthesis.
\r\n\r\nThis thesis focuses on the application of Multilayer Soft Lithography to the development and adaptation of microfluidic tools for chemical synthesis. The first successful demonstration of multistep organic synthesis in integrated microfluidics was the production of a molecular image probe, 2-deoxy-2-[18F]fluoro-d-glucose. The nanogram level dosage for imaging probes makes them attractive candidates for small scale synthesis of microfluidics. The reduced synthesis time achieved by using a microfluidic device is especially important because of the relatively short half-life of the radioactive fluoride.
\r\n\r\nWhile PDMS remains the material of choice for devices in biological applications, its incompatibility with many nonpolar organic solvents limits the types of reactions that can be performed with it. Through collaboration with Joseph DeSimone\u2019s group at the University of North Carolina at Chapel Hill, a suitable substitute for PDMS was found in perfluoropolyethers (PFPE). A solvent-resistant integrated microfluidic device was developed for solid-phase oligonucleotide synthesis using conventional phosphoramidite chemistry. To confirm that the microfluidic platform in development can indeed become a valuable tool in the field of synthetic biology, a 16 column parallel oligonucleotide synthesizer was manufactured that is capable of producing 16 distinct sequences up to 40 bases in length to be used in gene assembly. Successful construction of a gene fragment was completed from a mixture of unpurified and unamplified oligonucleotides synthesized on the device.
", "doi": "10.7907/8603-G150", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:5343", "collection": "thesis", "collection_id": "5343", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11012009-234712901", "primary_object_url": { "basename": "McDowell_Thesis_Final.pdf", "content": "final", "filesize": 54950750, "license": "other", "mime_type": "application/pdf", "url": "/5343/1/McDowell_Thesis_Final.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Low Optical Signal Detection in Biological Materials: SNR Considerations and Novel Techniques", "author": [ { "family_name": "McDowell", "given_name": "Emily Jayne", "clpid": "McDowell-Emily-Jayne" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Dabiri", "given_name": "John O.", "orcid": "0000-0002-6722-9008", "clpid": "Dabiri-J-O" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" }, { "family_name": "Phillips", "given_name": "Robert B.", "orcid": "0000-0003-3082-2809", "clpid": "Phillips-R" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Light scattering poses significant challenges for biomedical optical imaging techniques. Diffuse scattering scrambles wavefront information, confounding easy analysis of signals reflected from or transmitted through biological tissues. For optical imaging techniques that employ only unscattered light components, the penetration depth is severely limited. In this thesis, we develop and discuss two general methods for dealing with large levels of light scattering in tissue. The first involves optimization of the signal-to-noise ratio (SNR) of coherence domain optical tomography techniques. The majority of the signal measured in these techniques is singly scattered. Thus, an improvement in SNR will improve the penetration depth of the system by picking out the weak signal contribution from increasing depths that would otherwise be buried in noise. We show that the SNR can be optimized in terms of image reconstruction algorithms, and in terms of detection parameters. An important detection parameter, the integration time, determines the dominant noise source of the measurement, and can be varied to obtain the maximal SNR. A second general method that will be discussed involves the time-reversal of scattered light components in tissues through the process of optical phase conjugation (OPC). OPC has long been used to remove optical aberrations and distortions, but has never before been applied to light scattering in tissues. We show that we are capable of time reversing light scattering in both chicken tissue sections and tissue phantoms, and characterize both the amplitude and resolution trends of the process. Finally, we provide the first successful results of OPC in living tissues.", "doi": "10.7907/7Q7B-1E27", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:5873", "collection": "thesis", "collection_id": "5873", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05272010-215001543", "primary_object_url": { "basename": "thesis-uday-full.pdf", "content": "final", "filesize": 18604069, "license": "cc_by_nc_sa", "mime_type": "application/pdf", "url": "/5873/1/thesis-uday-full.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Photon Confinement in Photonic Crystal Cavities", "author": [ { "family_name": "Khankhoje", "given_name": "Uday Kiran", "clpid": "Khankhoje-Uday-Kiran" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "van Zyl", "given_name": "Jakob J.", "clpid": "van-Zyl-J-J" }, { "family_name": "Kim", "given_name": "Se-Heon", "clpid": "Kim-S-H" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "In this thesis, the use of photonic crystal cavities for experiments in cavity quantum-electrodynamics is described. To this end, the propagation of light in photonic crystals, and the creation of cavities by making defects in the photonic crystal lattice, is discussed. By drawing an analogy with Fabry-Perot etalons, the mechanism of light confinement in these cavities is explained. It is shown that by engineering the immediate cavity neighborhood, the mirror reflectivities can be increased, resulting in a very high quality factor (Q) and low mode volume. Photonic crystal cavity designs used in this thesis are introduced, along with numerically computed data of their performance.
\r\n\r\nDevice fabrication in gallium arsenide wafers is described in detail, with special attention to address factors that lead to a lack of reproducibility. Over the course of this thesis effort, several thousand cavities were fabricated, and a wide range of Qs were recorded. Careful experiments were performed to determine the causes of low Qs, both at the wafer growth level, and at the fabrication level. Technological improvements in wafer growth are reported, as well as fabrication techniques to improve cavity Q.
\r\n\r\nThese cavities contain indium arsenide quantum dots (QDs) as internal light sources. Cavity-induced enhancement of QD light emission is discussed, along with interferometric measurements of photon correlations. It is found that light emission from coupled QD-cavity systems is highly non-classical, and this quantum nature is characterized by means of a second order correlation function.
\r\n\r\nTo conclude, a novel application of high-Q cavities is discussed, that of an electrically-pumped laser fabricated in a 1D nanobeam cavity. The salient feature of such a geometry is that a high Q is retained even with the introduction of gold in the cavity vicinity. Finally, approaches to improve cavity Q by material system optimizations are explored. In the first approach, QD growth in III-V material systems with light emission wavelengths in the telecommunications wavelength range (\u03bb \u2248 1.55 \u03bcm) is discussed, and in the second, the growth of III-V-based active media in silicon structures is considered.
", "doi": "10.7907/CZBG-5917", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:5443", "collection": "thesis", "collection_id": "5443", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12142009-145646250", "primary_object_url": { "basename": "20100331_thesis_with_new_coverpage.pdf", "content": "final", "filesize": 2461346, "license": "other", "mime_type": "application/pdf", "url": "/5443/2/20100331_thesis_with_new_coverpage.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "A Parylene Real Time PCR Microdevice", "author": [ { "family_name": "Quach", "given_name": "Quoc Chan (Brandon)", "clpid": "Quach-Quoc-Chan-Brandon" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "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": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The polymerase chain reaction (PCR) is a powerful biochemical assay that is used in virtually all biochemical labs. By specifically amplifying a small sample of DNA, this technique is useful in the fields of paternity testing, forensics, and virus detection, just to name a few. A useful advancement of PCR involves monitoring the fluorescence generated by an increase in DNA during the amplification. This so called real time (RT)PCR allows quantification of the initial sample amount and allows for shorter assay times by stopping the reaction when enough fluorescence has been detected.
\r\n\r\nTechnology in the field of micro-electro-mechanical systems (MEMS) has advanced from the academic laboratory level to a handful of commercially successful devices. Work on adapting MEMS to biochemical applications, however, is still at the laboratory research stage. Recent breakthroughs in the use of more biocompatible materials in MEMS devices have helped to advance bio-MEMS. In particular, the polymer Parylene has superior properties that present a promising new platform for this field.
\r\n\r\nThis work presents the design, fabrication, and testing of a parylene-based MEMS RTPCR device. By combining advancements in both biology and MEMS engineering, this work demonstrates the feasibility of such a device along with quantitative analysis and data that serve as a guide for its future development.
\r\n", "doi": "10.7907/YC9S-0R15", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:5938", "collection": "thesis", "collection_id": "5938", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06082010-074917811", "primary_object_url": { "basename": "mkelzenberg_thesis.pdf", "content": "final", "filesize": 50336230, "license": "other", "mime_type": "application/pdf", "url": "/5938/1/mkelzenberg_thesis.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Silicon Microwire Photovoltaics", "author": [ { "family_name": "Kelzenberg", "given_name": "Michael David", "clpid": "Kelzenberg-Michael-David" } ], "thesis_advisor": [ { "family_name": "Atwater", "given_name": "Harry Albert", "clpid": "Atwater-H-A" } ], "thesis_committee": [ { "family_name": "Atwater", "given_name": "Harry Albert", "clpid": "Atwater-H-A" }, { "family_name": "Lewis", "given_name": "Nathan Saul", "clpid": "Lewis-N-S" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The favorable bandgap and natural abundance of Si, combined with the large expertise base for semiconductor wafer processing, have led to the use of wafer-based crystalline Si in the vast majority of photovoltaic cells and modules produced worldwide. However the high cost of purifying, crystallizing, and sawing Si wafers has inhibited these photovoltaic energy sources from approaching cost parity with fossil fuels. Crystalline Si microwires, grown by the catalytic vapor-liquid-solid (VLS) chemical vapor deposition process, have recently emerged as promising candidate materials for thin-film photovoltaics--combining low-cost Si deposition techniques with mechanically flexible, high-performance device geometries.
\r\n\r\nThis thesis presents several achievements that have helped to establish the viability of high-performance Si microwire photovoltaics. We begin by developing a comprehensive numerical model of Si microwire-array solar cells, combining finite-element device physics simulations with time-domain optical methods to predict that these devices can exceed 17% solar energy conversion efficiency. We then turn our attention to the optical properties of Si microwire arrays, concerned that the sparsely packed wires might not absorb enough sunlight. However our experiments reveal that simple light-trapping techniques can dramatically improve their absorption, not only permitting them to effectively absorb sunlight using 1/100th as much Si as a wafer, but also leading to an unexpected and fundamentally advantageous absorption enhancement over classical light trapping in planar materials. Techniques are then presented to characterize the material quality of VLS-grown Si wires. Although the growth of these wires is catalyzed by notoriously undesirable metal impurities for crystalline Si (e.g., Au, Ni, and Cu), we find it is nonetheless possible to synthesize high-quality material with remarkable diffusion lengths. By combining these materials with effective surface-passivation and a novel junction-fabrication technique, we realize single-wire solar cells that achieve open-circuit voltages of ~600 mV and with fill factors exceeding 80%. These observations suggest that Si microwires may offer a promising alternative to wafers for cost-effective crystalline Si photovoltaics.
", "doi": "10.7907/99RA-7Z65", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:5415", "collection": "thesis", "collection_id": "5415", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12032009-160213018", "type": "thesis", "title": "Optofluidic Microscopy and Wavefront Microscopy: Innovations in Biological Imaging", "author": [ { "family_name": "Cui", "given_name": "Xiquan", "clpid": "Cui-Xiquan" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Fraser", "given_name": "Scott E.", "clpid": "Fraser-S-E" }, { "family_name": "Atwater", "given_name": "Harry Albert", "clpid": "Atwater-H-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents two new microscopic imaging techniques: the optofluidic microscopy (OFM) and the wavefront microscopy (WM). By integrating optical functionalities onto a single semiconductor chip, these inventions could reduce the cost and improve the efficiency and quality of microscopic imaging in biological research and clinical diagnostics. First, OFM utilizes a microfluidic flow to deliver cellular samples across array(s) of micron-sized apertures defined on a metal-coated CMOS image sensor to acquire direct projection images of the samples. Although the OFM prototype is as small as a dime, it can render high resolution images (~1 \u00b5m) with comparable quality to those of a bulky standard optical microscope. OFM has great potential in revolutionizing the way we use microscopes. For example, the availability of tens or even hundreds of microscopes on a single chip will allow massively paralleled imaging of large populations of cells or microorganisms; the compactness and low cost of the OFM can enable portable and even disposable biomedical diagnostic tools for future telemedicine and personalized health care. Second, we present a new microscopy concept - WM. Wavefront image sensor (WIS) is the enabling component of WM. By monitoring the tightly confined transmitted light spots through a 2D aperture grid (spacing = 11 \u00b5m, diameter = 6 \u00b5m) fabricated on a CMOS image sensor in a high Fresnel number regime, we can accurately measure both intensity and phase front variations (a measured normalized phase gradient sensitivity of 0.1 mrad under the typical working condition - 1.0 second total signal accumulation time and 9.2 \u00b5W/cm^2 light intensity on the sensor) of a wavefront separately and quantitatively. Therefore, researchers and clinicians can incorporate pure phase imaging into their current microscope systems by simply adding the WIS in place of the conventional camera. When combined with adaptive optics strategies, this technology will facilitate deep tissue imaging using multiphoton microscopy. ", "doi": "10.7907/BJY0-NJ69", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:5921", "collection": "thesis", "collection_id": "5921", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06072010-060526366", "primary_object_url": { "basename": "ChrisWalkerThesis.pdf", "content": "final", "filesize": 6757454, "license": "other", "mime_type": "application/pdf", "url": "/5921/1/ChrisWalkerThesis.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Fabrication of Microfluidic Structures by Automated Laser Ablation and Automation of Optical Testing", "author": [ { "family_name": "Walker", "given_name": "Christopher", "clpid": "Walker-Christopher" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Bridges", "given_name": "William B.", "clpid": "Bridges-W-B" }, { "family_name": "Kartalov", "given_name": "Emil P.", "clpid": "Kartalov-E-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "A versatile, semi-automated instrument to fabricate embedded devices by laser ablation was designed, built, and tested. The expertise required for this came partially from the development of an optical testing system. This system and its utility in testing silicon on oxide waveguide structures are briefly explored. Processes for reproducibly fabricating microfluidic channels and vias were developed. Using one of these processes, design rules for more complex features were developed, and fully three dimensional structures realized. The phenomenon of nonlinear fluidic resistance in deformable channels was explored; a simple analytical model was designed, and compared favorably to measured data. Finally, using this effect, fully embedded valves were developed. With the combination of large scale accurate feature placement, a developed process for three dimensional features, and the development of valves, this instrument is capable of fabricating complex systems of devices, and should prove a useful tool in the future.", "doi": "10.7907/PEET-AM61", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:5300", "collection": "thesis", "collection_id": "5300", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10162009-053129363", "primary_object_url": { "basename": "thesis_mikeliu.pdf", "content": "final", "filesize": 14346681, "license": "other", "mime_type": "application/pdf", "url": "/5300/1/thesis_mikeliu.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Integrated Microfluidic Devices for Cell Culture and Assay", "author": [ { "family_name": "Liu", "given_name": "Mike Chia-Chung", "clpid": "Liu-Mike-Chia-Chung" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Dabiri", "given_name": "John O.", "clpid": "Dabiri-J-O" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents the development of three-dimensional (3-D) microfluidic devices for cellular studies, with focus on applications for high-throughput cell culture and cell-based assay. Microfluidic devices provide potential inexpensive platforms for high-throughput screening with the advantages of precise liquid handling, ability to control cell culture microenvironment, and reduced reagents and cells.
\r\n \r\nBecause a mixture of drugs or chemical compounds can often treat diseases more effectively or act synergistically in certain cellular pathways, a device capable of screening the combinatorial effects of multiple compound exposures on cells is highly desirable. To this end, a novel method to monolithically fabricate 3-D microfluidic networks was developed, and based on this fabrication technology, the first cell culture device with an integrated combinatorial mixer was constructed. The proof-of-concept chip having a three-input combinatorial mixer and eight individually isolated micro culture chambers was fabricated on silicon utilizing the surface micromachining of Parylene C (poly(chloro-p-xylylene)). Unlike other 3-D microfluidic fabrications, multilayer bonding process was favorably obviated. By incorporating several microfluidic overpass structures to allow one microfluidic channel to cross over other microfluidic channels, the combinatorial mixer generated all the combinations of the input fluidic streams. Cell culturing on-chip was successful, and the ability to simultaneously treat arrays of cells with different combinations of compounds was demonstrated.
\r\n\r\nTo facilitate cell-based assay, another combinatorial cell array device was fabricated on glass with incorporated membrane. Characterization of the combined compound concentration profile at each chamber with a fluorescence method was developed. We demonstrated functionality of the quantitative cell-based assay by screening three different compounds\u2019 ability to reduce cytotoxicity of hydrogen peroxide on neuron cells and also assaying combinatorial exposures of three chemotherapeutic agents on breast cancer cells. The 3-D microfluidic fabrication process was extended to construct multilayer microfluidic device with integrated membrane. Applications of microfluidic devices for marine microbiology were demonstrated. Based on the capabilities demonstrated in this work, devices with high-density cell array and integrated high-input combinatorial mixer can be constructed. At the same time, the technology has general applicability for building complex 3-D microfluidic devices, which can broaden the applications for current lab-on-a-chip systems.
\r\n", "doi": "10.7907/D43B-D825", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:4949", "collection": "thesis", "collection_id": "4949", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-12112008-102138", "primary_object_url": { "basename": "JigangWuThesis.pdf", "content": "final", "filesize": 1620248, "license": "other", "mime_type": "application/pdf", "url": "/4949/1/JigangWuThesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Coherence Domain Optical Imaging Techniques", "author": [ { "family_name": "Wu", "given_name": "Jigang", "clpid": "Wu-Jigang" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Fraser", "given_name": "Scott E.", "clpid": "Fraser-S-E" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Coherence domain optical imaging techniques have been developing quickly in the past few decades after the invention of laser. In this thesis, I will report the imaging methods that constitute my research projects during these years of graduate studies, including paired-angle-rotation scanning (PARS) forward-imaging probe for optical coherence tomography (OCT), full-field phase imaging technique based on harmonically matched diffraction grating (G1G2 grating), and Fresnel zone plate (FZP) based optifluidic microscopy (OFM). Compared with conventional optical microscopy, the coherence domain optical imaging has many advantages and greatly extends the application of imaging techniques.
\r\n\r\nOCT, based on low-coherence interferometry, is a high-resolution imaging technique that has been successfully applied to many biomedical applications. The development of various probes for OCT further made this technique applicable to endoscopic imaging. In the project of PARS-OCT probe, I have developed a forward-imaging probe based on two rotating angle-cut GRIN lenses. The diameter of the first prototype PARS-OCT probe that I made is 1.65 mm. My colleagues further built a probe with diameter of 0.82 mm. To our knowledge, this is the smallest forward-imaging probe that has been reported. The first prototype probe was characterized and successfully used to acquire OCT images of a Xenopus laevis tadpole.
\r\n\r\nFull-field phase imaging techniques are important for metrology and can also obtain high-resolution images for biological samples, especially transparent samples such as living cells. We have developed a novel full-field phase imaging technique based on the G1G2 grating. The G1G2 interferometry uses the G1G2 grating as a beam splitter/combiner and can confer nontrivial phase shift between output interference signals. Thus the phase and intensity information of the sample can be obtained by processing the two direct CCD images acquired at the output ports of the G1G2 grating. The details of this technique are explained in this thesis, and the phase imaging results for standard phase objects and biological samples are also shown.
\r\n\r\nOFM is a novel high-resolution and low-cost chip-level microscope developed by our group several years ago. Combining the unique imaging concept and microfluidic techniques, OFM system can be potentially useful to many biomedical applications, such as cytometry, blood parasite diagnosis, and water quality inspection. In the project of FZP-OFM, I applied the FZP to project the OFM aperture array onto an imaging sensor for OFM imaging. In this way, the sensor and the aperture array can be separated and will be useful for some situations. To demonstrate its capability, the FZP-OFM system was used to acquire OFM images of the protist Euglena gracilis.
\r\n\r\nThe studies in my research show the possibility of the application of various coherence domain optical imaging techniques in biomedical area, which is the primary objective of this thesis.
", "doi": "10.7907/6H07-PA44", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:2466", "collection": "thesis", "collection_id": "2466", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06052009-131714", "primary_object_url": { "basename": "thesis_Raviv_Perahia_single_sided.pdf", "content": "final", "filesize": 6057922, "license": "other", "mime_type": "application/pdf", "url": "/2466/1/thesis_Raviv_Perahia_single_sided.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Investigation and Application of Microscale Semiconductor Lasers and Cavities", "author": [ { "family_name": "Perahia", "given_name": "Raviv", "clpid": "Perahia-Raviv" } ], "thesis_advisor": [ { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "As optical, active, semiconductor devices are miniaturized to the wavelength scale, many applications of cavities, lasers, and detectors become possible. In order to make such devices useful in real-world applications one must first understand how these devices behave when they are reduced in size and what technological barriers must be overcome.
\r\n\r\nIn this dissertation several thrusts are presented toward the investigation and application of microscale active semiconductor cavities. Work is divided into four thrusts: fluid sensing based on surface sensitive quantum cascade lasers, hybridization of surface plasmon modes and waveguide modes as well as lasing in near-infrared subwavelength microdisks, quantum dot based cavities for strong coupling, and nascent work on optomechanical tuning of active cavities. In all four thrusts design and fabrication techniques are used to overcome challenges and capitalize on reduced scale.
\r\n\r\nProgress in fabrication, design, and testing of surface sensitive quantum cascade lasers is presented. Work focuses on increasing surface sensitivity by modifying the metal contacts on top of active material originally intended to be used with a surface plasmon waveguide. An experiment where isopropyl and ethyl alcohol is differentiated based on laser behavior is carried out. Work toward integration of semiconductor lasers with fluidic delivery systems is explored.
\r\n\r\nWork then turns to the intimate and advantageous inclusion of metal into subwavelength strained quantum well microdisk lasers in the near-infrared. Optical and thermal characteristics are simulated. Hybridization of surface plasmon mode and waveguide whispering-gallery modes is simulated and experimentally verified. Lasing behavior of such small devices is investigated.
\r\n\r\nIn parallel, work toward improving the probability of achieving a strongly coupled quantum dot microdisk cavity system is carried out. Improvements in fabrication techniques and potential metal integration makes this project a natural extension of the subwavelength microdisk laser project.
\r\n\r\nFinally, a new project is discussed where the above projects are combined with investigation of optomechanical systems currently ongoing in our lab. Work toward the combination of active optical cavities with optomechanical devices will lead to wide band wavelength tuning functionality.
\r\n", "doi": "10.7907/TVHA-6D03", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:5233", "collection": "thesis", "collection_id": "5233", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06102009-164232", "primary_object_url": { "basename": "Thesis.pdf", "content": "final", "filesize": 10103965, "license": "other", "mime_type": "application/pdf", "url": "/5233/1/Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Precision Frequency and Phase Synthesis Techniques in Integrated Circuits for Biosensing, Communication and Radar", "author": [ { "family_name": "Wang", "given_name": "Hua", "orcid": "0000-0003-4952-5505", "clpid": "Wang-Hua" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Weinreb", "given_name": "Sander", "clpid": "Weinreb-S" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Today\u2019s CMOS technology provides circuit designers with a powerful implementation platform that supports innovation opportunities on both circuit-topology and system-architecture levels. Moreover, the versatility of CMOS implementation opens the door for a plethora of challenging and exciting interdisciplinary research.
\r\n\r\nThis dissertation focuses on investigating novel techniques and applications for precision frequency and phase synthesis in CMOS. It consists of two parts: a CMOS compatible molecular-level biosensor and a multiple-beam/multi-band scalable CMOS phased array receiver system.
\r\n\r\nIn the first part, a frequency shift based magnetic biosensing scheme is introduced to address the Point-of-Care (PoC) biomolecular diagnosis for high-sensitivity, portable and cost low applications. Compared with existing biosensing schemes, the proposed scheme achieves a competitive sensitivity without using optical devices, external biasing fields or expensive post-processing steps. A discrete implementation first verifies the sensing mechanism and reveals several design insights. An integrated implementation based on standard 130nm CMOS process is then designed with differential sensing and temperature controlling schemes. Overall, with a differential uncertainty of 0.13ppm for relative frequency shift, the sensor achieves reliable detection of one single micron-size magnetic particle (D=4.5um, 2.4um and 1um) as well as 1n-Molar real DNA samples labeled by magnetic nanoparticles (D=50nm).
\r\n\r\nIn the second part, a high-resolution compensation technique is proposed to address mismatch and offset issues encountered by practical phased array system. It employs a dense Cartesian interpolation scheme with an easily scalable architecture and a wide operation bandwidth. As an implementation example, a 6-to-18GHz dual-band quad-beam phased array CMOS receiver is presented, which is capable of forming four spatially independent beams at two different frequencies across the tritave bandwidth. With the mismatch compensation, the array element has achieved a maximum RMS phase error of 0.5\u02da with an RMS amplitude variation less than 1.5dB for the 360\u02da interpolation over the full operation bandwidth. For a 4-element phased array receiver system based on the designed CMOS chip, the electrical array pattern is measured at 6GHz, 10.4GHz and 18GHz, with the worst case peak-to-null ratio of 21.5dB. In addition, a broadband inductorless design methodology based on Cherry-Hooper topology is proposed for chip area saving. As implementation examples, we will show a DC-19GHz 10dB gain broadband buffer amplifier, a DC-12GHz broadband phase rotator with 10-bit resolution and a beam-forming network in a 10.4GHz to 18GHz phased array receiver chip with dual-beam capability.
", "doi": "10.7907/T4EC-TX97", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:5238", "collection": "thesis", "collection_id": "5238", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-07202008-164745", "type": "thesis", "title": "Integration of Dye Lasers and Microfluidics for Biochemical Analysis", "author": [ { "family_name": "Chen", "given_name": "Yan", "clpid": "Chen-Yan-Bioengineering" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Guo", "given_name": "Chin-Lin", "clpid": "Guo-Chin-Lin" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This dissertation describes the study of two important aspects of integration in microfluidics: optics and biochemistry. In optics integration, two types of miniaturized dye lasers, namely the solid-state polymer dye lasers and optofluidic dye lasers were demonstrated. Both of the dye lasers possess a resonant cavity with circular grating geometry, and they are suitable to serve as low-threshold, surface-emitting coherent light source in microfluidic networks. The mass production and large scale fabrication of such low-cost dye laser arrays can be realized by the well developed nanoimprint and soft lithography, making this technology attractive for various biochemical applications. In biochemistry integration, a microfluidic system was developed to fully utilize the complexity of microfluidic circuits to process single cells and extract gene expression information in a parallel manner. The work presented here explored both the optics and biochemistry integration in microfluidics, which are the key issues for further development of complete \u201clab-on-a-chip\u201d systems. ", "doi": "10.7907/2E06-0W63", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:3747", "collection": "thesis", "collection_id": "3747", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09242008-151715", "primary_object_url": { "basename": "Chapter_all.pdf", "content": "final", "filesize": 18608108, "license": "other", "mime_type": "application/pdf", "url": "/3747/1/Chapter_all.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Thin Film Silicon for Implantable Electronics", "author": [ { "family_name": "Lo", "given_name": "Hsi-Wen", "clpid": "Lo-Hsi-Wen" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng E-F-C" }, { "family_name": "Bockrath", "given_name": "Marc William", "clpid": "Bockrath-M-W" }, { "family_name": "Weinreb", "given_name": "Sander", "clpid": "Weinreb-S" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The implantable electronic systems have changed our life greatly and provided crucial support for people who previously could not live an independent life otherwise. However, current implantable electronic systems are based on technologies more than 50 years old and more medical problems require advanced implantable electronic systems with small form factors and multiple electrodes. This work explores and evaluates possible alternatives of implantable electronic systems.
\r\n\r\nParylene, a widely used MEMS/CMOS process compatible material, is the cornerstone of this work. Parylene has been an ISO10933 and USP Class VI certi\ufb01ed biocompatible material. Parylene serves as the substrate and protective coating of the implantable electronic systems developed in this work.
\r\n\r\nThin \ufb01lm pentacene is studied in this work and thin \ufb01lm pentacene transistors are developed. The thin \ufb01lm pentacene transistor uses Parylene as the \ufb02exible substrate, the gate insulator and the protective coating. Studies of parylene surface are carried out. And based on this study, pentacene hole mobility is improved using spin-cast smoothing layers and top-contact con\ufb01gurations. To evaluate the long term reliability and stability of the thin \ufb01lm pentacene transistors, saline soaking tests are performed. The results are less than satisfactory.
\r\n\r\nIn addition, thin \ufb01lm amorphous silicon is studied and thin \ufb01lm amorphous silicon transistors are developed. This thin-\ufb01lm amorphous silicon uses Parylene HT\u00ae, a Parylene variant with high temperature stability, as the \ufb02exible substrate. To evaluate the long term reliability and stability of the thin \ufb01lm amorphous silicon transistor, room temperature saline soaking tests and 80\u25e6 C accelerated saline soaking tests are carried out. The thin \ufb01lm amorphous silicon transistors show excellent stability in saline soaking. The thin \ufb01lm amorphous silicon transitor shows no degradations after more than 90 days in 80\u25e6 C saline solution.
\r\n\r\nIn summary, thin \ufb01lm pentacene transistors and thin \ufb01lm amorphous silicon transistors are developed and their performances are optimized. The long-term stability and reliability of these transistors are evaluated via saline soaking tests. While thin \ufb01lm pentacene transistors show only less than satisfactory results, thin \ufb01lm amorphous silicon transistors exhibit stable and reliable performances.
", "doi": "10.7907/DBDE-PQ14", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:648", "collection": "thesis", "collection_id": "648", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-02162009-095558", "primary_object_url": { "basename": "Dissertation_Wen.pdf", "content": "final", "filesize": 9878128, "license": "other", "mime_type": "application/pdf", "url": "/648/1/Dissertation_Wen.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Integrated Retinal Implants", "author": [ { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Integrated wireless implants have always been the ultimate goal for neural prostheses. However, technologies are still in development and few have actually been transferred to clinical practice due to constraints in material biocompatibility, device miniaturization and flexibility. In this dissertation, emphasis is placed on the development of Parylene devices for neural prostheses, and particularly, for retinal prostheses that partially restore lost vision for patients suffering from outer retina degeneration.
\r\n\r\nA basic Parylene-metal-Parylene skin technology for making planar Parylene micro-electro-mechanical systems (MEMS) devices, such as electrode arrays and radio-frequency (RF) coil, is first discussed, followed by accelerated lifetime soaking tests to investigate the long term stability of such skins in hot saline under both passive and active electrical stressing. Discussion is further expanded on a detailed description of the design, fabrication, and testing procedure of two types of MEMS coils, which serve as receiver coils for wireless power and data transfer in a retinal implant system. After that, an embedded chip integration technology is presented, which allows the integration of complementary metal-oxide-semiconductor (CMOS) integrated circuit (IC) chips with other MEMS devices and discrete components so as to achieve high-level system functionality. Finally, an integrated wireless neural stimulator is designed and successfully fabricated using a test chip.
\r\n", "doi": "10.7907/AMK6-TA42", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:3312", "collection": "thesis", "collection_id": "3312", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09022008-113511", "primary_object_url": { "basename": "Thesis_PJChen_2008.pdf", "content": "final", "filesize": 15588540, "license": "other", "mime_type": "application/pdf", "url": "/3312/1/Thesis_PJChen_2008.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Implantable Wireless Intraocular Pressure Sensors", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng E-F-C" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The work in this thesis aims to develop a suite of biomedical microdevice implants, with an intense focus on pressure sensors, for glaucoma study and management featuring the enabling micro-electro-mechanical-system (MEMS) technologies and the use of parylene (poly-para-xylene) as a biocompatible MEMS material. The problems of the debilitating eye disease glaucoma threaten tens of millions of people worldwide with loss of vision, and are not completely resolved using the current non-optimal clinical procedures. Given the relation of neuropathy and the physiological parameter of intraocular pressure (IOP) in glaucoma from clinical findings, such parylene-based MEMS implants are investigated to realize physical IOP monitoring and regulation, and further to accomplish continuous, direct, accurate, reliable, and more effective glaucoma detection and treatment.
\r\n \r\nMiniaturized parylene-based passive pressure sensors are presented in this thesis for IOP monitoring. Complete design, fabrication, characterization, and analysis of such MEMS implants are described to demonstrate their feasibility, covering both engineering and surgical/biological aspects of the proposed applications. Their passive behaviors, based on the comprised micromechanical structures, facilitate unpowered device operations. In addition, such devices are microfabricated in suitable form factors so that minimally invasive suture-less implantation procedures are possible, minimizing time and complexity of the surgeries. Two types of micromachined wireless pressure sensors are developed utilizing optical and electrical sensing methodologies, respectively, to explore the possibility of the proposed implant approach. On-bench experimental results verify that wireless pressure sensing with 1 mmHg accuracy in the 0\u2013100 mmHg range can be achieved using both types of devices. Surgical studies, including ex vivo and in vivo animal tests, confirm the bioefficacy and biostability of the device implants in the intraocular environment. With the attempt of providing implementation concepts of the MEMS implant approaches for ultimate glaucoma study and management in practice, system-level designs and configurations involving such microdevice implants are briefly described as well. Micromachined passive-valved flow-control devices with designed surgical and engineering features are also developed (experimentally achieving 0\u2013100 mmHg and 0\u201310 uL/min pressure and flow rate regulation ranges) to investigate the feasibility and possibility of such implant approach for unpowered physical IOP regulation in glaucoma treatment.
\r\n", "doi": "10.7907/46T7-0P24", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:2284", "collection": "thesis", "collection_id": "2284", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05292009-172708", "primary_object_url": { "basename": "08_Thesis_Ostby.pdf", "content": "final", "filesize": 44426206, "license": "other", "mime_type": "application/pdf", "url": "/2284/9/08_Thesis_Ostby.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Photonic Whispering-Gallery Resonators in New Environments", "author": [ { "family_name": "Ostby", "given_name": "Eric Paul", "clpid": "Ostby-Eric-Paul" } ], "thesis_advisor": [ { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" } ], "thesis_committee": [ { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Atwater", "given_name": "Harry Albert", "clpid": "Atwater-H-A" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Optical whispering-gallery devices, like the microtoroid or microdisk, confine light at resonant frequencies and in ultra-small volumes for long periods of time. Such ultra-low loss resonators have been applied in diverse areas of scientific research, including low-threshold lasers on-chip, biological sensing, and quantum computing. In this thesis, novel ultra-low loss microstructures are studied for their unique characteristics and utility. The author investigates the interaction between microcavities and various environments in order to quantify the results and lay the foundation for future applications.
\r\n\r\nThe first optical cavity studied is the microtoroid, which possesses ultra-high quality factor (Q) on account of its nearly atomic smooth surface, produced by surface-tension induced laser reflow. Ytterbium-doped silica microtoroids are fabricated by a sol-gel technique. The ytterbium microtoroid laser achieves record-low laser threshold (2 \u00b5W) in air, and produces the first laser output for a solid-state laser in water. This laser in water can be developed as an ultra-sensitive biological sensor, with potentially record sensitivity enabled by gain-narrowed linewidth. Also, a novel CO2 laser reflow and microtoroid testing vacuum system is demonstrated. Fabrication and testing of microtoroids is performed in a vacuum chamber to study the effect of atmospheric water and upper limit of Q in microtoroids.
\r\n\r\nThe selective reflow of microtoroids presents difficulties for integration of on-chip optical waveguides. As an alternative, dimension-preserving low-loss optical structures are researched for their unique applications. A gold-coated silica microdisk is fabricated, and demonstrates record and nearly-ideal quality factor (1,376) as a surface-plasmon polariton resonator. The hybrid optical-plasmonic mode structure is studied in simulation and experiment. The plasmonic resonator has ultra-low mode volume and high field confinement, making it suitable for short-range optical communication or sensing. Finally, a novel whispering-gallery optical delay line in a spiral geometry is designed and experimentally demonstrated. The center transition region of the spiral is optimized for low transmission loss by beam propagation simulation. A 1.4 m long spiral waveguide within a 1 cm^2 area is presented. The spiral waveguide structure is being developed as a real-time optical delay line with fiber-like loss, important for optical communication and signal processing.
", "doi": "10.7907/ER2J-WT93", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:1719", "collection": "thesis", "collection_id": "1719", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05102009-103332", "type": "thesis", "title": "Plasmonic Nanoparticles for Optofluidic Applications", "author": [ { "family_name": "Adleman", "given_name": "James Richard", "clpid": "Adleman-James-Richard" } ], "thesis_advisor": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" } ], "thesis_committee": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Erickson", "given_name": "David", "clpid": "Erickson-D" }, { "family_name": "Goodwin", "given_name": "David G.", "clpid": "Goodwin-D-G" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis discusses the application of colloidal particles to optofluidic systems. Colloidal particles can be added as a \"dopant\" to the liquids in these devices to provide functionality that cannot be obtained with homogenous fluids. We examine electrooptic effects in liquid suspensions asymmetric metallic nanoparticles. The theoretical optical properties of gold nanorods and noble metal nanohalfshells are computed and compared with those of actual colloidal dispersions. We discuss the design and fabrication of electro-optic waveguides utilizing these suspensions as the active material. We also study the dynamics of photothermal holograms recorded by nanosecond laser pulses in suspensions of silver nanospheres. Unexpected transients in the grating diffraction efficiency correspond to the nanoscale inhomgeneity of the colloid. Longer timescale decay can be used to measure the thermal conductivity of the liquid as predicted by the established theory of heat conduction. This technique is extended to perform spatial imaging of the thermal diffusivity of immiscible binary liquids. Gold nanosphere coated substrates for microfluidic devices are employed to enable optical actuation of fluids. Nanoparticle absorption of continuous wave laser light was used to trap air bubbles inside partially filled microfluidic channels. Light focused on the array near one side of the trapped bubble will drive a mass flow across the bubble. This evaporative bubble assisted mass transport mechanism can be operated as a pump powered by a stationary laser beam. In addition, the process efficiently separates volatile and non-volatile materials and can concentrate and purify specimens in solution.
\r\n\r\nFinally, several schemes for storing and extracting data from subwavelength volumes using spectral multiplexing of semiconductor quantum dots are explored. We demonstrate microfluidic composition and delivery of cocktails of several colors of quantum dots to act as information packets for optical storage. In addition we analyze imaging at the subwavelength level using a patterned surface of quantum dots. The theoretical performance of such a surface is compared to imaging through nanoapertures as is currently implemented in optofluidic microscopy.
\r\n", "doi": "10.7907/QB6E-2Q64", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:1879", "collection": "thesis", "collection_id": "1879", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05192008-132422", "primary_object_url": { "basename": "Thesis.pdf", "content": "final", "filesize": 9566604, "license": "other", "mime_type": "application/pdf", "url": "/1879/1/Thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Microfabricated High-Performance Liquid Chromatography (HPLC) System with Closed-Loop Flow Control", "author": [ { "family_name": "Shih", "given_name": "Jason J.", "clpid": "Shih-Jason-J" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Emami", "given_name": "Azita", "clpid": "Emami-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" }, { "family_name": "Lee", "given_name": "Terry D.", "clpid": "Lee-T-D" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents the development of a microfabricated high-performance liquid chromatography (HPLC) system. The design, fabrication, and characterization of individual HPLC components such as high-pressure pumps, mixers, flow sensors, composition sensors, separation columns, filters, and detectors is presented. These individual components were then integrated to create robust, feedback-driven separation systems capable of performing gradient, reverse-phase, nanoscale HPLC. Two separate separation systems were created. The first integrated system was a microfluidic device for HPLC tandem mass spectrometry (HPLC-MS/MS) designed for proteomic applications. The second system was a portable HPLC conductivity detection (HPLC-CD) system designed for point-of-care applications such as biodetection. Both systems demonstrated good performance and repeatability. The performance of these systems is largely attributable to the development of HPLC-compatible sensors that could provide precise control over the elution profiles. These microfluidic closed-loop flow control systems represent an important advancement in the microfluidics field, where open-loop flow control is universally used, and risks becoming inadequate with the increasing complexity of microfluidic systems.", "doi": "10.7907/8A6W-2X34", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:448", "collection": "thesis", "collection_id": "448", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-02012008-150234", "primary_object_url": { "basename": "Thesis_all.pdf", "content": "final", "filesize": 4616612, "license": "other", "mime_type": "application/pdf", "url": "/448/11/Thesis_all.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Quantitative Three-dimensional Imaging of Droplet Convection and Cardiac Cell Motions Based on Micro DDPIV", "author": [ { "family_name": "Lu", "given_name": "Jian", "clpid": "Lu-Jian" } ], "thesis_advisor": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "thesis_committee": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Hove", "given_name": "Jay R.", "clpid": "Hove-J-R" }, { "family_name": "Lansford", "given_name": "Rusty", "orcid": "0000-0002-2159-3699", "clpid": "Lansford-R" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Biomechanical forces such as blood flow induced shear stress as well as genetic programming are widely acknowledged as critical factors regulating vertebrate heart development. While mechanisms of genetic regulation have been well studied, effects of biomechanics are poorly understood due to the lack of proper imaging tools with sufficient spatial and temporal resolutions for quantitative analysis of the mechanical stimuli in complex three-dimensional (3D) living systems. 3D quantitative flow visualization by tracking microscale particles has become an invaluable tool in microfluid mechanics. Defocusing digital particle image velocimetry (DDPIV) can recover depth coordinates by calculating the separation between defocused images generated by an aperture mask with a plurality of pinholes forming an equilateral triangle. In this thesis, a novel high-speed 3D micro-PTV system was developed based on this technique with laser-induced fluorescence to achieve microscale velocity field measurements. Application of this technique to microscale imaging was validated by calibration of targets spread over the image field. A micro volume of 400x300 \u00b5m2 with 100 \u00b5m depth has been mapped using an inverted microscope equipped with a 20X objective lens. The proposed technique was successfully applied to 3D tracking of 2-\u00b5m fluorescent particles inside an evaporating water droplet, exhibiting convective flow induced by Marangoni effects.
\r\n\r\nThe microscopic imaging system was then utilized to acquire 3D time series data of highly dynamic cell motions in living embryonic zebrafish hearts. 1-\u00b5m and 500-nm fluorescent tracer particles were injected into the blood stream of developing zebrafish embryos at 32 hours post fertilization (hpf) to 59 hpf to help describe cardiac cell motions. Microinjection was delicately performed at the fish tail to minimize the influence to normal cardiovascular functions. The measurable depth in an embryonic heart is about 40 \u00b5m. 3D velocities of cardiovascular blood flow and trajectories of heart-wall motions were obtained, showing dynamic changes of the flow field and phase differences of wall movements between the atrium and the ventricle during heart beating. Endocardial ventricular strains were calculated based on the reconstructed coordinates of two particles adhered to the endocardium.
\r\n", "doi": "10.7907/4JFZ-AG10", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:4671", "collection": "thesis", "collection_id": "4671", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-11262007-125539", "primary_object_url": { "basename": "PhDThesisFinalChanglinPang.pdf", "content": "final", "filesize": 10839101, "license": "other", "mime_type": "application/pdf", "url": "/4671/1/PhDThesisFinalChanglinPang.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Parylene Technology for Neural Probes Applications", "author": [ { "family_name": "Pang", "given_name": "Changlin", "clpid": "Pang-Changlin" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Andersen", "given_name": "Richard A.", "clpid": "Andersen-R-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Neural probes are important tools in detecting and studying neuron activities. Although people have been working on neural probe development for a long time, the current neural probes (including metal-wire probes and silicon neural probes) are still far from being satisfactory. An ideal neural probe array should have good biocompatibility, high-density electrodes with high signal-to-noise ratio, flexible cables for interconnections, integrated electronics, and even integrated actuators to track neuron movement.
\r\n\r\nThe work of this thesis focused on applying parylene technology to neural probes development to make a new generation of neural probes with better functions. With the properties of high electrical resistivity, mechanical flexibility, biocompatibility, low coefficient of friction, and an easy deposition/etching process, parylene is a good material for neural probe applications. In this thesis, we have designed, fabricated, and characterized a new parylene neural probe with a long, flexible parylene cable for a neural prosthesis system. Parylene layers are first used on the silicon probe shank with multiple electrodes as insulation and protective layers. And long parylene flexible cables are first monolithically integrated with silicon neural probes. A 96-electrode high-density, 3-D neural probe array for chronic implantation has been demonstrated. Different types of electrolysis actuators (including a silicon diaphragm actuator and a parylene balloon actuator) have been made and tested. The research on electrolysis-based actuators shows their great potential to be used for movable neural probes.
\r\n\r\nCompared with the traditional silicon neural probes (e.g., the Michigan probes, the Utah electrode arrays), our microfabricated neural probes have much longer and stronger probe shanks (8 or 12 mm long, able to penetrate the human pia) and much longer flexible parylene cable (about 7 or 12 cm, long enough to go through a percutaneous connector and the human skull). At the same time, our new probe arrays are shown to have better biocompatibility (being totally covered with parylene material), lower stress, better penetration ability, and greater flexibility for making high-density 3-D arrays and for use in chronic neural signal recording implantation.
\r\n", "doi": "10.7907/GH99-K875", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:5057", "collection": "thesis", "collection_id": "5057", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-12182007-163333", "primary_object_url": { "basename": "Thesis_v2_combined_new_v2.pdf", "content": "final", "filesize": 4563403, "license": "other", "mime_type": "application/pdf", "url": "/5057/1/Thesis_v2_combined_new_v2.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Optofluidic Microscopy: Technology Development and Its Applications in Biology", "author": [ { "family_name": "Heng", "given_name": "Xin", "clpid": "Heng-Xin" } ], "thesis_advisor": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "thesis_committee": [ { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Psaltis", "given_name": "Demetri", "orcid": "0000-0003-4684-8800", "clpid": "Psaltis-D" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" }, { "family_name": "Troian", "given_name": "Sandra M.", "orcid": "0000-0003-1224-6377", "clpid": "Troian-S-M" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The Optofluidic Microscope (OFM) is a new imaging platform based upon nanoapertures that are fabricated on planar metallic film, whilst microfluidic delivery technology is used to transport the objects-of-interest. The planar nature of OFM makes it ideal to integrate with other micro total analysis systems, such as cell sorters or cell culturing chambers. Furthermore, a variety of imaging functionalities, such as differential phase contrast, fluorescence, and Raman spectroscopy can potentially fit into a single OFM device.
\r\n\r\nThis thesis reports on the early technology development of Optofluidic Microscopy. I have built a variety of off-chip prototypes of OFM that all possess different functionalities. These OFM prototypes include 1D array OFM, hydraulically pumped OFM, 2D nanoaperture grid OFM, super high-resolution OFM, OFM coupled with optical tweezer actuation, fluorescent OFM, electrokinetic enabled OFM, etc.
\r\n\r\nI applied the first OFM prototype in imaging Caenorhabditis elegans (C. elegans) larvae and characterizing different genotypes. Later on, the microscopy properties of OFM, such as the optical resolution and the depth of field, were thoroughly investigated both experimentally and theoretically. More recently, I successfully combined optical tweezers with a grid-based OFM prototype, which was then used in high-resolution imaging of microspheres and a few biological samples. In addition, preliminary results on fluorescence OFM imaging were also demonstrated.
\r\n\r\nI trust that these functionalities, after being demonstrated off-chip, can be readily fabricated and then assembled as a complete on-chip OFM. It will eventually enable a real \"microscale microscope on a chip\".
\r\n", "doi": "10.7907/JAYF-RX26", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:5214", "collection": "thesis", "collection_id": "5214", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05292008-064614", "primary_object_url": { "basename": "Dissertation.pdf", "content": "final", "filesize": 15784387, "license": "other", "mime_type": "application/pdf", "url": "/5214/1/Dissertation.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Detection of Aerobic Bacterial Endospores: From Air Sampling, Sterilization Validation to Astrobiology", "author": [ { "family_name": "Yung", "given_name": "Pun To (Douglas)", "orcid": "0000-0002-2005-9478", "clpid": "Yung-Pun-To-Douglas" } ], "thesis_advisor": [ { "family_name": "Ponce", "given_name": "Adrian", "clpid": "Ponce-A" } ], "thesis_committee": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Ponce", "given_name": "Adrian", "clpid": "Ponce-A" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Bacterial endospores are formed in genera such as Bacillus and Clostridium in times of incipient stresses. Derivative of their remarkable resistance and ubiquity, endospores are delivery vehicles for anthrax attack, biological indicators for checking sterilization efficacy, and candidates for Panspermia and potential extraterrestrial life, thereby underscoring the significance of their rapid detection. In this thesis project, spectroscopy and microscopy methods are studied to measure the release of a unique constituent, dipicolinic acid (DPA), via germination as a proxy for endospore viability. In particular, a luminescence time-gated microscopy technique (called microscopy endospore viability assay, acronym: \u03bcEVA) has been developed to enumerate germination-capable aerobic endospores rapidly based on energy transfer from DPA to terbium ions doped on a solid matrix upon UV excitation. The distinctive emission and millisecond lifetime enable \r\ntime-resolved imaging to achieve a sensitivity of one endospore.
\r\n\r\nEffective air sampling of endospores is crucial in view of the potential catastrophe caused by the dissemination of airborne anthrax endospores. Based on time-gated spectroscopy of terbium-DPA luminescence, the Anthrax Smoke Detector has been built to provide real-time surveillance of air quality for timely mitigation and decontamination. This technology also finds application in the monitoring of airborne endospore bioburden as an indicator of total biomass in a closed spacecraft system in order to safeguard the health of astronauts.
\r\n\r\nSterilization validation is of prime concern in the medical field and planetary protection to prevent cross-contaminations among patients and planets. \u03bcEVA has yielded faster and comparable results compared with the culture-based NASA standard assay in assessing surface endospore bioburden on spacecraft materials and clean rooms surfaces. The current analysis time has been expedited from 3 days to within an hour in compliance with planetary protection requirements imposed on landers and probes designed for life detection missions.
\r\n\r\nFrom the perspective of astrobiology, endospores are time capsules preserving geological history and may exist as dormant lives in analogous extraterrestrial environments. \u03bcEVA has successfully recovered ancient endospores in cold biospheres (Greenland ice core, Antarctic Lake Vida, polar permafrost) and hyper-arid biospheres (Atacama Desert) on Earth as templates for determining life longevity and the search of extinct or extant life on Mars and other icy celestial bodies. Result authenticity has been validated by a comprehensive suite of experiments encompassing culture-based and culture-independent techniques such as epifluorescence microscopy, flow cytometry, fluorometry, bioluminescence and 16s rRNA analysis. In conclusion, \u03bcEVA is a sensitive analytical tool that opens a new realm in microbiology to provide insights into air sampling, sterility assessment and exobiology.
\r\n", "doi": "10.7907/9GJ2-FV58", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:5214", "collection": "thesis", "collection_id": "5214", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05292008-064614", "primary_object_url": { "basename": "Dissertation.pdf", "content": "final", "filesize": 15784387, "license": "other", "mime_type": "application/pdf", "url": "/5214/1/Dissertation.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Detection of Aerobic Bacterial Endospores: From Air Sampling, Sterilization Validation to Astrobiology", "author": [ { "family_name": "Yung", "given_name": "Pun To (Douglas)", "orcid": "0000-0002-2005-9478", "clpid": "Yung-Pun-To-Douglas" } ], "thesis_advisor": [ { "family_name": "Ponce", "given_name": "Adrian", "clpid": "Ponce-A" } ], "thesis_committee": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Ponce", "given_name": "Adrian", "clpid": "Ponce-A" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Bacterial endospores are formed in genera such as Bacillus and Clostridium in times of incipient stresses. Derivative of their remarkable resistance and ubiquity, endospores are delivery vehicles for anthrax attack, biological indicators for checking sterilization efficacy, and candidates for Panspermia and potential extraterrestrial life, thereby underscoring the significance of their rapid detection. In this thesis project, spectroscopy and microscopy methods are studied to measure the release of a unique constituent, dipicolinic acid (DPA), via germination as a proxy for endospore viability. In particular, a luminescence time-gated microscopy technique (called microscopy endospore viability assay, acronym: \u03bcEVA) has been developed to enumerate germination-capable aerobic endospores rapidly based on energy transfer from DPA to terbium ions doped on a solid matrix upon UV excitation. The distinctive emission and millisecond lifetime enable \r\ntime-resolved imaging to achieve a sensitivity of one endospore.
\r\n\r\nEffective air sampling of endospores is crucial in view of the potential catastrophe caused by the dissemination of airborne anthrax endospores. Based on time-gated spectroscopy of terbium-DPA luminescence, the Anthrax Smoke Detector has been built to provide real-time surveillance of air quality for timely mitigation and decontamination. This technology also finds application in the monitoring of airborne endospore bioburden as an indicator of total biomass in a closed spacecraft system in order to safeguard the health of astronauts.
\r\n\r\nSterilization validation is of prime concern in the medical field and planetary protection to prevent cross-contaminations among patients and planets. \u03bcEVA has yielded faster and comparable results compared with the culture-based NASA standard assay in assessing surface endospore bioburden on spacecraft materials and clean rooms surfaces. The current analysis time has been expedited from 3 days to within an hour in compliance with planetary protection requirements imposed on landers and probes designed for life detection missions.
\r\n\r\nFrom the perspective of astrobiology, endospores are time capsules preserving geological history and may exist as dormant lives in analogous extraterrestrial environments. \u03bcEVA has successfully recovered ancient endospores in cold biospheres (Greenland ice core, Antarctic Lake Vida, polar permafrost) and hyper-arid biospheres (Atacama Desert) on Earth as templates for determining life longevity and the search of extinct or extant life on Mars and other icy celestial bodies. Result authenticity has been validated by a comprehensive suite of experiments encompassing culture-based and culture-independent techniques such as epifluorescence microscopy, flow cytometry, fluorometry, bioluminescence and 16s rRNA analysis. In conclusion, \u03bcEVA is a sensitive analytical tool that opens a new realm in microbiology to provide insights into air sampling, sterility assessment and exobiology.
\r\n", "doi": "10.7907/9GJ2-FV58", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:5251", "collection": "thesis", "collection_id": "5251", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09142007-143251", "primary_object_url": { "basename": "thesis_zhenyu.pdf", "content": "final", "filesize": 12717987, "license": "other", "mime_type": "application/pdf", "url": "/5251/1/thesis_zhenyu.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Optofluidic Dye Lasers", "author": [ { "family_name": "Li", "given_name": "Zhenyu", "orcid": "0000-0002-7752-6225", "clpid": "Li-Zhenyu" } ], "thesis_advisor": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" } ], "thesis_committee": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Libbrecht", "given_name": "Kenneth George", "clpid": "Libbrecht-K-G" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Optofluidic dye lasers refer to a class of liquid dye lasers, usually on a microfabricated device, in which the adaptive nature of the liquid gain medium allows the dynamical control of the laser properties. Miniaturizing liquid dye lasers onto a microfluidic device not only results in compact, easy-to-maintain and safe dye laser systems, but also provides unprecedented optical performances such as precise spatial mode control, low threshold, and automatic fluidic tuning. Equally important, such on-chip liquid laser sources represent an important component for \"lab-on-a-chip\" systems.
\r\n\r\nThis thesis studies the implementations of optofluidic dye lasers on polydimethylsiloxane (PDMS) based microfluidic devices. Replica molding soft lithography was used to fabricate monolithic PDMS devices which contain both wavelength-scale optical structures and large-sized microfluidic channels. We have demonstrated narrow linewidth single mode DFB lasers, simultaneous operation of integrated DFB laser arrays with a single pump, multiple color lasing from the same DFB cavity, continuous mechanical wavelength tuning over a 60nm range, microfluidic wavelength tuning, single mode liquid-core microring lasers using Vernier effect, liquid-cladding evanescent gain DFB lasers, and monolithic integration with PDMS microfluidic circuits. Typical laser thresholds achieved are well within the reach of commercial high power laser diodes, thus enabling the implementations of compact tunable laser sources for portable \u201clab-on-a-chip\u201d devices. The impressive performances, diverse geometries and applications clearly demonstrate the power of optofluidic integration and adaptation.
\r\n\r\n", "doi": "10.7907/AQQR-QG80", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:2215", "collection": "thesis", "collection_id": "2215", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05282008-162123", "primary_object_url": { "basename": "linzhu_thesis.pdf", "content": "final", "filesize": 5368793, "license": "other", "mime_type": "application/pdf", "url": "/2215/1/linzhu_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Photonic Crystal Bragg Lasers: Design, Fabrication, and Characterization", "author": [ { "family_name": "Zhu", "given_name": "Lin", "clpid": "Zhu-Lin" } ], "thesis_advisor": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "thesis_committee": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "On-chip, single mode semiconductor lasers are usually fabricated using conventional distributed feedback (DFB) structures. Due to the limitation of index guiding in the transverse direction, the width of these lasers has to be less than a few microns. Meanwhile, the laser output power is limited by catastrophic optical damage (COD) at the facets and thus large optical cavities are necessary for high power semiconductor lasers. Therefore, high power, single mode applications are challenging, due to the conflicting requirements for large modal volume (to prevent COD by reducing optical power density) and narrow width (to obtain the single mode operation). Increasing the width of single mode semiconductor lasers is fundamentally important for obtaining high spectral and spatial optical power densities.
\r\n\r\nThis thesis reports on achieving the single mode operation of large area, edge emitting semiconductor lasers, using the photonic crystal Bragg structure (two dimensional distributed feedback structure). Both theoretical and experimental results are presented. Two dimensional coupled mode approaches and transfer matrix methods are developed to analyze and design the photonic crystal Bragg structure. It is shown that the single mode lasing can be obtained by satisfying both the transverse and longitudinal Bragg conditions and a single lobe, diffraction limited far field can be obtained by optimizing the coupling coefficient of the photonic crystal.
\r\n\r\nElectrically pumped, large-area (100 um x 500 um), single mode semiconductor photonic crystal Bragg lasers are experimentally demonstrated in pulsed and continuous wave conditions with single lobe, diffraction limited far fields. Two dimensional lasing wavelength tuning is demonstrated, which proves that the lasing mode is truly defined by the photonic crystal lattice. Furthermore, a wavelength tuning sensitivity about 80 times smaller than a conventional DFB laser is also achieved, allowing for more accurate control of the lasing wavelength.
\r\n\r\nPhotonic crystal lasers based on effective index guiding are also studied. Single mode operation is achieved by combining the transverse confinement provided by an effective index guiding mechanism with the longitudinal mode selection provided by the Bragg reflection from the photonic crystal cladding. These devices represent an important first step toward using photonic crystals in a different way for the modal control of semiconductor lasers in planar optical circuits.
\r\n\r\n\r\n", "doi": "10.7907/7MMN-7Q15", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:958", "collection": "thesis", "collection_id": "958", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-03142008-155402", "primary_object_url": { "basename": "Princess_Imoukhuede.pdf", "content": "final", "filesize": 5887662, "license": "other", "mime_type": "application/pdf", "url": "/958/1/Princess_Imoukhuede.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Visualizing the Membrane Confinement, Trafficking and Structure of the GABA Transporter, GAT1", "author": [ { "family_name": "Imoukhuede", "given_name": "Princess Ikhianosen Uerenikhosen", "orcid": "0000-0002-4257-1085", "clpid": "Imoukhuede-Princess-Ikhianosen-Uerenikhosen" } ], "thesis_advisor": [ { "family_name": "Lester", "given_name": "Henry A.", "clpid": "Lester-H-A" } ], "thesis_committee": [ { "family_name": "Lester", "given_name": "Henry A.", "clpid": "Lester-H-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Chow", "given_name": "Robert", "clpid": "Chow-Robert" }, { "family_name": "Fraser", "given_name": "Scott E.", "clpid": "Fraser-S-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Transporter trafficking regulators can play an important role in maintaining the transporter density necessary for effective function. I determine interactions that confine GAT1 at the membrane by investigating GAT1 lateral mobility through fluorescence recovery after photobleaching (FRAP). I find that the mobility of GAT1 can be increased by depolymerizing actin or by blocking the GAT1 PDZ interacting domain. I also identify ezrin as the GAT1 adaptor to actin. Through fluorescence resonance energy transfer (FRET), the distance between GAT1-YFP and Ezrin-CFP is calculated as 64--68 \u00c5, and it can be significantly increased by disrupting the actin cytoskeleton. Altogether, my data reveals that actin confines GAT1 to the plasma membrane via ezrin, an interaction mediated through the GAT1-PDZ interaction domain.
\r\n\r\nDiscoveries in the field of vesicle fusion provide direct ties to translational research. While the study of vesicle fusion classically has been applied to neurotransmitter and neuropeptide containing vesicles; there is evidence that secretory vesicles physiologically differ from vesicles trafficking membrane protein. For instance, GAT1 resides on a vesicle lacking neurotransmitter but containing some v-SNARE proteins. These differences in the vesicle composition suggest inherent differences in trafficking mechanisms, which can only be confirmed through further study of membrane protein trafficking. To this end, I apply total internal reflection fluorescence microscopy (TIRFM) to quantify the number of GAT1 molecules on vesicles and to observe the movement of vesicles containing fluorescently tagged GAT1 into the plasma membrane. I determine that these vesicles contain 3--7 molecules of GAT1 and uncover a population of GAT1 vesicles with ATP-dependent lateral displacement.
\r\n\r\nThe protein-protein interactions, trafficking, and oligomerization of mouse GAT1 were studied using fourteen different fusions of mGAT1 with fluorescent protein. We determine that a natural PDZ-interacting motif is minimally required for wild-type GAT1 behavior. Fusions with wild-type function yielded up to 21% FRET efficiency, indicating efficient GAT1 oligomerization. Additionally, 45% FRET was observed between a GAT1 construct and YFP-syntaxin-1A. Inserting XFP between R565 and L566, resulted in 33% FRET but impaired function, which indicated the \"RL\" motif in the proximal C terminus governs export from the endoplasmic reticulum but not transporter oligomerization.
", "doi": "10.7907/3Q8S-CV89", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:1667", "collection": "thesis", "collection_id": "1667", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05072008-204627", "primary_object_url": { "basename": "mchale_thesis.pdf", "content": "final", "filesize": 4874716, "license": "other", "mime_type": "application/pdf", "url": "/1667/1/mchale_thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Feedback Tracking and Correlation Spectroscopy of Fluorescent Nanoparticles and Biomolecules", "author": [ { "family_name": "McHale", "given_name": "Kevin L.", "clpid": "McHale-Kevin-L" } ], "thesis_advisor": [ { "family_name": "Mabuchi", "given_name": "Hideo", "clpid": "Mabuchi-H" } ], "thesis_committee": [ { "family_name": "Pierce", "given_name": "Niles A.", "clpid": "Pierce-N-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Mabuchi", "given_name": "Hideo", "clpid": "Mabuchi-H" }, { "family_name": "Wang", "given_name": "Zhen-Gang", "clpid": "Wang-Zhen-Gang" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The best way to study dynamic fluctuations in single molecules or nanoparticles is to look at only one particle at a time, and to look for as long as possible. Brownian motion makes this difficult, as molecules move along random trajectories that carry them out of any fixed field of view. We developed an instrument that tracks the Brownian motion of single fluorescent molecules in three dimensions and in real-time while measuring fluorescence with nanosecond time resolution and single-photon sensitivity. The apparatus increases observation times by approximately three orders of magnitude while improving data-collecting efficiency by locking tracked objects to a high-intensity region of the excitation laser.
\r\n\r\nAs a first application of our technique, we tracked and studied the fluorescence statistics of semiconductor quantum dots. Our measurements were well resolved at 10ns correlation times, allowing measurement of photon anti-bunching on single particles in solution for the first time. We observed variations of (34 \u00b1 16)% in the fluorescence lifetimes and (23 \u00b1 18)% in the absorption cross-sections within an aqueous quantum dot sample, confirming that these variations are real, not artifacts of the immobilization methods previously used to study them. Additionally, we studied quantum dot fluorescence intermittency and its dependence on 2-mercaptoethanol, finding evidence that the chemical suppresses blinking on short time-scales (<1s) by reducing the lifetime of the dark state.
\r\n\r\nFinally, we studied the translational and intramolecular Brownian motion of \u03bb-phage DNA molecules. Our apparatus decouples these motions almost completely, and yielded a translational diffusion coefficient estimate D=(0.71 \u00b1 0.05)\u03bcm\u00b2/s lying between previous measurements for this molecule under identical solution conditions but with less precise techniques. Our measurements show clear evidence of intramolecular motion of the polymer chain in the form of statistical correlations on time-scales up to 1s, but we have not yet been able to determine the influence of solvent interactions on these dynamics.
\r\n", "doi": "10.7907/6YYA-9T10", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:5188", "collection": "thesis", "collection_id": "5188", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05162007-123028", "primary_object_url": { "basename": "Thesis_comprehensive_20070515.pdf", "content": "final", "filesize": 4330174, "license": "other", "mime_type": "application/pdf", "url": "/5188/11/Thesis_comprehensive_20070515.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Towards Functional Miniaturized Lasers", "author": [ { "family_name": "Zhang", "given_name": "Zhaoyu", "clpid": "Zhang-Zhaoyu" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Bockrath", "given_name": "Marc William", "clpid": "Bockrath-M-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "In this thesis, nanometer scale semiconductor lasers and micrometer scale polymer based dye lasers are our focus in bringing the miniaturized lasers to applications in data transmission; ultra-small chemical / biological sensors; and ultra-compact spectroscopic sources. Combining the advantage of electrically driven semiconductor lasers and the advantage of a broad emission spectrum of dye molecules would utilize the highly dense multi-functional lab-on-a-chip by integrating microfluidic PCR, microfluidic fluorescent detection system, and compact visible and NIR detectors which are commercially available. On the other hand, in the meantime of pushing the size limit of the laser cavities, new phenomena with the nanoscale lasers enable further exploration and understanding in fundamental physics. \r\n\r\nIn the first part of this thesis, two sub-micron scale semiconductor lasers are presented. The smallest lasers utilizing the disk structures\u2014with diameters of approximately 600 nm\u2014were realized in the InGaP/InGaAlP quantum well material system at room temperature, featuring ultra-small mode volumes of approximately 0.03 cubic?microns, and exhibiting single-mode operation at low threshold powers. And the first visible photonic crystal ultra-small mode volume lasers, with cavity volumes of approximately 0.01 cubic?microns, are realized in the same material system. They are ideally suited for use as spectroscopic sources and both of them can be lithographically tuned from 650 \u2013 690 nm. \r\n\r\nIn the second part of this thesis, two sub-millimeter-scale polymer-based dye lasers\u2014a poly(dimethylsiloxane) (PDMS)-based mechanically tunable DFB dye laser and a poly(methylmethacrylate) (PMMA)-based second-order circular grating distributed feedback dye laser\u2014are presented. Both of them are compatible with microfluidic technology, which gives freedom in integrating the lasers with the microfluidic chips. Compared to the soft lithography used in the PDMS-based dye laser, the nanoimprint lithography used in the PMMA-based dye laser would be more useful for fabricating ultra-small dye lasers and enabling mass production in the near future. \r\n\r\nAt the end of the thesis, a nano-linewidth metal grating mask pattern transferred transient grating (MPT-TG) technique is described as a potential technique using the ultra-small lasers for molecular-dynamics study in solutions.", "doi": "10.7907/C2WY-TG62", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:5213", "collection": "thesis", "collection_id": "5213", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05292007-002034", "primary_object_url": { "basename": "FengXL-2007-Thesis.pdf", "content": "final", "filesize": 8654797, "license": "other", "mime_type": "application/pdf", "url": "/5213/1/FengXL-2007-Thesis.pdf", "version": "v9.0.0" }, "type": "thesis", "title": "Ultra-High Frequency Nanoelectromechanical Systems with Low-Noise Technologies for Single-Molecule Mass Sensing", "author": [ { "family_name": "Feng", "given_name": "Philip Xiao-Li", "orcid": "0000-0002-1083-2391", "clpid": "Feng-Philip-Xiao-Li" } ], "thesis_advisor": [ { "family_name": "Roukes", "given_name": "Michael Lee", "clpid": "Roukes-M-L" } ], "thesis_committee": [ { "family_name": "Roukes", "given_name": "Michael Lee", "clpid": "Roukes-M-L" }, { "family_name": "Hajimiri", "given_name": "S. Ali", "clpid": "Hajimiri-S-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Bockrath", "given_name": "Marc W.", "clpid": "Bockrath-M-W" }, { "family_name": "Lifshitz", "given_name": "Ron", "clpid": "Lifshitz-R" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Advancing today's very rudimentary nanodevices toward functional nanosystems with considerable complexity and advanced performance imposes enormous challenges. This thesis presents the research on ultra-high frequency (UHF) nanoelectromechanical systems (NEMS) in combination with low-noise technologies that enable single-molecule mass sensing and offer promises for NEMS-based mass spectrometry (MS) with single-Dalton sensitivity. The generic protocol for NEMS resonant mass sensing is based on real-time locking and tracking of the resonance frequency as it is shifted by the mass-loading effect. This has been implemented in two modes: (i) creating an active self-sustaining oscillator based on the NEMS resonator, and (ii) a higher-precision external oscillator phase-locking to and tracking the NEMS resonance.
\r\n\r\nThe first UHF low-noise self-sustaining NEMS oscillator has been demonstrated by using a 428MHz vibrating NEMS resonator as the frequency reference. This stable UHF NEMS oscillator exhibits ~0.3ppm frequency stability and ~50zg (1zg = 10-21 g) mass resolution with its excellent wideband-operation (~0.2MHz) capability. Given its promising phase noise performance, the active NEMS oscillator technology also offers important potentials for realizing NEMS-based radio-frequency (RF) local oscillators, voltage-controlled oscillators (VCOs), and synchronized oscillators and arrays that could lead to nanomechanical signal processing and communication. The demonstrated NEMS oscillator operates at much higher frequency than conventional crystal oscillators and their overtones do, which opens new possibilities for the ultimate miniaturization of advanced crystal oscillators.
\r\n\r\nLow-noise phase-locked loop (PLL) techniques have been developed and engineered to integrate with the resonance detection circuitry for the passive UHF NEMS resonators. Implementations of the NEMS-PLL mode with generations of low-loss UHF NEMS resonators demonstrate improving performance, namely, reduced noise and enhanced dynamic range. Very compelling frequency stability of ~0.02ppm and unprecedented mass sensitivity approaching 1zg has been achieved with a typical 500MHz device in the narrow-band NEMS-PLL operation.
\r\n\r\nRetaining high quality factors (Q's) while scaling up frequency has become crucial for UHF NEMS resonators. Extensive measurements, together with theoretical modeling, have been performed to investigate various energy loss mechanisms and their effects on UHF devices. This leads to important insights and guidelines for device Q-engineering.
\r\n\r\nThe first VHF/UHF silicon nanowire (NW) resonators have been demonstrated based on single-crystal Si NWs made by bottom-up chemical synthesis nanofabrication. Pristine Si NWs have well-faceted surfaces and exhibit high Q's (Q \u2248 13100 at 80MHz and Q \u2248 5750 at 215MHz). Given their ultra-small active mass and very high mass responsivity, these Si NWs also offer excellent mass sensitivity in the ~10?50zg range.
\r\n\r\nThese UHF NEMS and electronic control technologies have demonstrated promising mass sensitivity for kilo-Dalton-range single-biomolecule mass sensing. The achieved performance roadmap, and that extended by next generations of devices, clearly indicates realistic and viable paths toward the single-Dalton mass sensitivity. With further elaborate engineering, prototype NEMS-MS is optimistically within reach.
", "doi": "10.7907/Z9NC5Z62", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:5201", "collection": "thesis", "collection_id": "5201", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05252007-220130", "primary_object_url": { "basename": "PhDThesisSiyangZheng.pdf", "content": "final", "filesize": 15402284, "license": "other", "mime_type": "application/pdf", "url": "/5201/1/PhDThesisSiyangZheng.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "On-Chip Blood Count", "author": [ { "family_name": "Zheng", "given_name": "Siyang", "orcid": "0000-0002-0616-030X", "clpid": "Zheng-Siyang" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "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": "Psaltis", "given_name": "Demetri", "orcid": "0000-0003-4684-8800", "clpid": "Psaltis-D" }, { "family_name": "Kasdan", "given_name": "Harvey L.", "clpid": "Kasdan-H-L" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Blood count is one of the most common medical laboratory tests performed today. It provides information on patient\u2019s oxygen carrying capacity, immune system functionality, and the overall hemapoiesis process for disease diagnosis and drug side-effect monitoring. Traditionally blood count is performed either manually or by conventional automated blood analyzers. With the advance of microfabrication, on-chip blood count has become a target for miniaturization aiming at providing cost-effective, functional, capable point-of-care devices and systems that use less than 100 nL of blood sample and generate measurement results within minutes. The focus of this thesis is on investigation of erythrocyte/leukocyte counting and leukocyte differential, which are the two key components in blood count, in microdevices.
\r\n\r\nDue to the large number ratio of erythrocytes to leukocytes and their property overlap, conventional automated blood analyzers accomplish blood count in several different channels by measuring different parameters. Similarly, in microdevices, it is desirable that erythrocytes and leukocytes can be separated before further analysis. Two types of hydrodynamic separation devices were investigated to continuously separate erythrocytes and leukocytes based on size. The principle of the device exploits the laminar flow in microdevices and design of streamlines which particles follow. Pillar-shaped devices with single geometrical design demonstrate a binary separation profile. With proper design, separation efficiency over 90% can be achieved. Channel-shaped devices, an improved design, can achieve similar separation efficiency with the added benefits of a smaller footprint, fewer requirements on flow control, and easier integration with downstream components.
\r\n\r\nErythrocyte and leukocyte count is accomplished with electrical impedance sensing, which is one of the most accurate ways to measure particle volume. The well-known problem of small double-layer capacitance inherent to micro impedance sensors is solved by two methods: platinum black electroplating on the electrode surface and inductor-induced resonance sensing. In the first method, platinum black is electroplated in situ on the electrode surfaces, which increases the effective surface area by two orders of magnitude and thus increases the double-layer capacitance significantly. The other innovative way, inductor-induced resonance sensing, nullifies the capacitive components in the system at the resonance frequency by connecting a parallel inductor to the system. In this way the sensitivity can be greatly improved and the optimal sensing frequency can be chosen from the inductance value. For both methods, polystyrene beads of different diameters were used for validation, while diluted blood samples and leukocyte-rich plasma were used to successfully demonstrate the feasibility.
\r\n\r\nTwo-part leukocyte differential is demonstrated in microflow cytometers with fluorescence sensing. Unlike methods used in conventional blood analyzers, undiluted blood samples are stained with nucleic acid stain acridine orange. Lymphocytes and granulocytes emit fluorescent light at different peak frequency after interaction with the dye due to the difference in cellular composition. Using the undiluted sample greatly minimizes sample preparation procedure, and reduces the overall measurement time, the reagent, and the waste volume. These benefits make it a practical method for implementation in microdevices. A throughput of one thousand leukocytes per second was demonstrated, which means the leukocyte differential could be accomplished in a couple of seconds.
", "doi": "10.7907/SJ43-XM11", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:5200", "collection": "thesis", "collection_id": "5200", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05252007-140239", "primary_object_url": { "basename": "Thesis_submitted_2007-05-26.pdf", "content": "final", "filesize": 72916510, "license": "other", "mime_type": "application/pdf", "url": "/5200/1/Thesis_submitted_2007-05-26.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "On the Development of Defocusing Digital Particle Image Velocimetry with Full Characterization", "author": [ { "family_name": "Graff", "given_name": "Emilio Casta\u00f1o", "clpid": "Graff-Emilio-Casta\u00f1o" } ], "thesis_advisor": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "thesis_committee": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Ravichandran", "given_name": "Guruswami", "orcid": "0000-0002-2912-0001", "clpid": "Ravichandran-G" }, { "family_name": "Shepherd", "given_name": "Joseph E.", "orcid": "0000-0003-3181-9310", "clpid": "Shepherd-J-E" } ], "local_group": [ { "literal": "GALCIT" }, { "literal": "div_eng" } ], "abstract": "Defocusing Digital Particle Image Velocimetry is the first volumetric, three-dimensional PIV method ever put into practice. This manuscript contains the details of its development, a detailed analysis of its performance (both through simulation and real measurements), and a series of experimental demonstrations of the capability of the technique. The system is capable of resolving upwards of 7,000 vectors per pair with an absolute error on the order of 0.03% of the volume size.", "doi": "10.7907/Z9HM56F8", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:2021", "collection": "thesis", "collection_id": "2021", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05242007-121638", "primary_object_url": { "basename": "Jeff_Fingler_0_Thesis_complete.pdf", "content": "final", "filesize": 21365542, "license": "other", "mime_type": "application/pdf", "url": "/2021/1/Jeff_Fingler_0_Thesis_complete.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Motion Contrast Using Optical Coherence Tomography", "author": [ { "family_name": "Fingler", "given_name": "Jeffrey Paul", "clpid": "Fingler-Jeffrey-Paul" } ], "thesis_advisor": [ { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" } ], "thesis_committee": [ { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Vahala", "given_name": "Kerry J.", "orcid": "0000-0003-1783-1380", "clpid": "Vahala-K-J" }, { "family_name": "Phillips", "given_name": "Robert B.", "orcid": "0000-0003-3082-2809", "clpid": "Phillips-R" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Diagnosis of ophthalmic diseases like age-related macular degeneration is very important for treatment of the disease as well as the development of future treatments. Optical coherence tomography (OCT) is an optical interference technique which can measure the three-dimensional structural information of the reflecting layers within a sample. In retinal imaging, OCT is used as the primary diagnostic tool for structural abnormalities such as retinal holes and detachments. The contrast within the images of this technique is based upon reflectivity changes from different regions of the retina.
\r\n\r\nThis thesis demonstrates the developments of methods used to produce additional contrast to the structural OCT images based on the tiny fluctuations of motion experienced by the mobile scatterers within a sample. Motion contrast was observed for motions smaller than 50 nm in images of a variety of samples. Initial contrast method demonstrations used Brownian motion differences to separate regions of a mobile Intralipid solution from a static agarose gel, chosen in concentration to minimize reflectivity contrast.
\r\n\r\nZebrafish embryos in the range of 3-4 days post fertilization were imaged using several motion contrast methods to determine the capabilities of identifying regions of vascular flow. Vasculature identification was demonstrated in zebrafish for blood vessels of all orientations as small as 10 microns in diameter. Mouse retinal imaging utilized the same motion contrast methods to determine the contrast capabilities for motions associated with vasculature within the retina. Improved contrast imaging techniques demonstrated comparable images to fluorescein angiography, the gold standard of retinal vascular imaging. Future studies can improve the demonstrated contrast analysis techniques and apply them towards human retinal motion contrast imaging for ophthalmic diagnostic purposes.
", "doi": "10.7907/8W4X-Z041", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:2020", "collection": "thesis", "collection_id": "2020", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05242007-105741", "primary_object_url": { "basename": "PoonThesis.pdf", "content": "final", "filesize": 3158864, "license": "other", "mime_type": "application/pdf", "url": "/2020/1/PoonThesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Active and Passive Coupled-Resonator Optical Waveguides", "author": [ { "family_name": "Poon", "given_name": "Joyce Kai See", "clpid": "Poon-Joyce-Kai-See" } ], "thesis_advisor": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "thesis_committee": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Bockrath", "given_name": "Marc William", "clpid": "Bockrath-M-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Coupled-Resonator Optical Waveguides (CROWs) are chains of resonators in which light propagates by virtue of the coupling between the resonators. The dispersive properties of these waveguides are controllable by the inter-resonator coupling and the geometry of the resonators. If the inter-resonator coupling is weak, light can be engineered to propagate slowly in these structures. The small group velocities possible in CROWs may enable applications in and technologies for optical delay lines, interferometers, buffers, nonlinear optics, and lasers.
\r\n\r\nThis thesis reports on achieving and controlling the optical delay in passive and active CROWs. Both theoretical and experimental results are presented. Transfer matrices, tight-binding models, and coupled-mode approaches are developed to analyze and design a variety of coupled resonator systems in the space, frequency, and time domains. Although each analytical method is fundamentally different, in the limit of weak inter-resonator coupling these approaches are consistent with each other. From these formalisms, simple expressions for the delay, loss, bandwidth, and a figure of merit are derived to compare the performance of CROW delay lines. Using a time-domain tight-binding model, we examine the resonant gain enhancement and spontaneous emission noise in amplifying CROWs to find that the net amplification of a propagating wave does not always vary with the group velocity but instead depends on the termination and excitation of the CROW.
\r\n\r\nCROWs in the form of high-order (> 10) weakly coupled passive polymer microring resonators were fabricated and measured. The measured transmission, group delay, and dispersive properties of the CROWs agreed with the theoretical results. Delays in excess of 100 ps and slowing factors of about 25 over bandwidths of about 20 GHz were observed. The main limitation of the passive CROWs was the optical losses. To overcome the losses and to enable electrical integration, we demonstrated active CROWs in the form of current injection InP-InGaAsP Fabry-Perot laser arrays. Even though the losses could be completely compensated, the transmission spectra and signal-to-noise ratio depended strongly on the injection current and resonator position. The signal-to-noise ratio degraded rapidly away from the input. Our results highlight possible avenues to operate laser arrays as loss-compensated or amplifying CROWs.
", "doi": "10.7907/MX8K-9V82", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:2367", "collection": "thesis", "collection_id": "2367", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06012007-130844", "primary_object_url": { "basename": "Arun_Natarajan_Thesis.pdf", "content": "final", "filesize": 42998359, "license": "other", "mime_type": "application/pdf", "url": "/2367/1/Arun_Natarajan_Thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Millimeter-Wave Phased Arrays in Silicon", "author": [ { "family_name": "Natarajan", "given_name": "Arun Sridhar", "clpid": "Natarajan-Arun-Sridhar" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Rutledge", "given_name": "David B.", "clpid": "Rutledge-D-B" }, { "family_name": "D'Addario", "given_name": "Larry R.", "clpid": "D'Addario-L-R" }, { "family_name": "Weinreb", "given_name": "Sander", "clpid": "Weinreb-S" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Integration of mm-wave multiple-antenna systems on silicon-based processes enables complex, low-cost systems for high-frequency communication and sensing applications. While individual silicon devices struggle to achieve the same performance as III-V semiconductor-based transistors at mm-wave frequencies, the benefits of integration, such as good component matching and near-zero incremental device cost, can be leveraged to achieve good system performance. This dissertation presents different techniques and architectures for integrating mm-wave phased arrays on commercial silicon process technologies by demonstrating phased-array transmitters and receivers at 24GHz, 60GHz, and 77GHz, in CMOS and SiGe BiCMOS processes.
\r\n\r\nInitially, the tradeoffs of high-frequency systems are discussed in the context of Shannon capacity and the benefits of integrating phased arrays at such high frequencies are discussed in detail. An analysis of the output noise in a phased-array receiver in the presence of antenna coupling and input noise correlation is carried out and measurements on a discrete two-element array demonstrate the dependence of output noise on the phase-shift setting.
\r\n\r\nThe design of the first fully-integrated 24GHz phased-array transmitter using mainly 0.18[mu]m CMOS transistors is described. The four-element array adopts a centralized LO-path phase-shifting approach using a multi-phase VCO. The on-chip 19.2GHz VCO generates 16 equally spaced LO phases leading to 7 degree beam resolution for radiation normal to the array. The transmitter includes four on-chip CMOS power amplifiers, with outputs matched to 50 Ohms, that are each capable of generating up to 14.5dBm of output power at 24GHz. The array achieves a peak-to-null ratio of 23dB with four elements active and can support data rates of 500Mb/s on each channel (with BPSK modulation) while occupying 6.8mm x 2.1mm of die area.
\r\n\r\nA high-resolution local LO-path phase-shifting architecture is presented as part of the first fully-integrated 77GHz phased-array transceiver in a SiGe BiCMOS process. The SiGe transceiver includes four transmit and four receive elements (including 77GHz LNA and PA), along with the LO frequency generation and distribution circuitry. The local LO-path phase-shifting scheme enables a robust distribution network that scales well with increasing frequency and/or number of elements, while providing high-resolution phase shifts. Each transmit element of the heterodyne transmitter generates +12.5dBm of output power at 77GHz, with a bandwidth of 2.5GHz leading to a four-element EIRP of 24.5dBm. Each on-chip PA has a maximum saturated power of +17.5dBm at 77GHz while the on-chip VCO achieves a phase noise of -95dBc/Hz@1MHz offset at 54GHz. The phased-array performance is measured using an internal test option and achieves 12dB peak-to-null ratio with two transmit and receive elements active.
\r\n\r\nWhile the 24GHz and 77GHz array are multiple-input single-output systems, higher-order phase-shifting and combining techniques can be used to achieve arrays with multiple outputs, with beams focused on different directions concurrently. Toward this end, a 60GHz bidirectional RF-combined phased array front-end is implemented in SiGe BiCMOS, using a hybrid parallel/series phase-shift approach that reduces the requirements of the on-chip phase shifters, enabling RF signal combining. The four-element array enables simultaneous illumination of two angles of incidence and includes amplitude control, as well as continuous phase adjustment. The front-end has a noise figure lower than 6.9dB at 60GHz and the array achieves full spatial coverage with peak-to-null ratio higher than 25dB. The four-element front-end consumes 265mW and occupies 4.6mm2 of die area.
", "doi": "10.7907/SGZC-FD54", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:2203", "collection": "thesis", "collection_id": "2203", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05282007-203227", "primary_object_url": { "basename": "Thesis_Komijani.pdf", "content": "final", "filesize": 9579874, "license": "other", "mime_type": "application/pdf", "url": "/2203/1/Thesis_Komijani.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Microwave Integrated Phased-Array Transmitters in Silicon", "author": [ { "family_name": "Komijani", "given_name": "Abbas", "clpid": "Komijani-Abbas" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Bruck", "given_name": "Jehoshua", "clpid": "Bruck-J" }, { "family_name": "D'Addario", "given_name": "Larry R.", "clpid": "D'Addario-L-R" }, { "family_name": "Weinreb", "given_name": "Sander", "clpid": "Weinreb-S" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Phased-array systems, a special case of multiple-input-multiple-output (MIMO) systems, take advantage of spatial directivity and array gain to increase spectral efficiency. Implementing a phased-array system at high frequency in a commercial silicon process technology presents several challenges. This thesis focuses on the architectural and circuit-level trade-offs involved in the design of the silicon-based fully integrated phased-array transmitters.
\r\n \r\nAs the first implementation, a four-element 24GHz 0.18\u00b5m CMOS phased-array transmitter with integrated power amplifiers is presented. On-chip power amplifiers use substrate-shielded slow-wave transmission lines for impedance matching and can generate up to 14dBm of output power. The transmitter employs a two-step upconversion architecture with 4.8GHz as the intermediate frequency (IF) and uses a single 19.2GHz synthesizer serving as the local oscillator (LO) generator. The phased-array, employing the LO phase shifting architecture, achieves 23dB of peak to null-ratio when all four elements are used, demonstrates a beam steering range covering all signal incident angles, and can support a data rate of 500Mbps with a quadrature phase-shift keying (QPSK) baseband signal.
\r\n\r\nAs the second implementation with a modified phase shifting architecture, an integrated 4-element 77GHz Silicon-Germanium (SiGe) phased-array transceiver is presented. Two-step conversion, envisioning a dual-mode 77GHz/24GHz operation, is used at both the receiver and the transmitter paths. A differential phase of 52GHz is generated by the on-chip voltage-controlled oscillator (VCO) and is distributed to all radio frequency (RF) paths. The phase shifting is performed at the LO ports of the RF mixers with continuous analog phase shifters. The quadrature signal of the second LO, at the IF frequency of 26GHz, is generated by dividing the VCO frequency by a factor of 2 using a cross-coupled injection-locked frequency divider. The on-chip 77GHz power amplifier with an output power of 17.5dBm and peak power added efficiency (PAE) of 14% achieves the best performance demonstrated in silicon. A single transmitter path achieves a 40dB conversion gain at 77GHz with 2.5GHz of bandwidth and a maximum output power of 12.5 dBm.
\r\n\r\nThe measured results demonstrate the feasibility of using silicon-based integrated phased-arrays for wireless communication and vehicular radar applications.
", "doi": "10.7907/EW67-RX66", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:1863", "collection": "thesis", "collection_id": "1863", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05182007-171118", "primary_object_url": { "basename": "Thesis.pdf", "content": "final", "filesize": 20600038, "license": "other", "mime_type": "application/pdf", "url": "/1863/1/Thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Development of Biocompatible Parylene Neurocages for Action Potential Stimulation and Recording", "author": [ { "family_name": "Tooker", "given_name": "Angela Colleen", "clpid": "Tooker-Angela-Colleen" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Pine", "given_name": "Jerome", "clpid": "Pine-J" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng E-F-C" }, { "family_name": "Pine", "given_name": "Jerome", "clpid": "Pine-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Neurons, and the neural networks they form, are at the heart of our biological and cognitive functions. Traditional in vitro techniques for studying neural networks use two-dimensional multi-electrode arrays. While furthering the study of neural networks, the inherent mobility of the neurons and the lack of specificity between neurons and electrodes can limit the use of these arrays. Initial work, the neuro-well, eliminated these problems by physically trapping individual neurons in wells. While neural networks were formed and action potentials recorded with arrays of neuro-wells, the bulk micromachining techniques required a complex fabrication process, with limited scalability and a low yield, thus inhibiting their further development.
\r\n\r\nParylene neurocages counteract these difficulties by using surface micromachined structures to trap neurons in close proximity to electrodes, without inhibiting their growth. The use of surface micromachining techniques minimizes the fabrication and scaling complexities, improving the device yield. The neurocages can be fabricated on either glass or silicon substrates, with a variety of electrical insulation materials, including Parylene and silicon-nitride. Parylene is a biocompatible polymer that is non-toxic, extremely inert, and resistant to moisture and most chemicals. Its conformal deposition makes it easy to fabricate 3D structures like the neurocage. Parylene is transparent, allowing the neurons to be easily seen.
\r\n\r\nIndividual neurons are placed into the neurocages, either manually with a pressure-driven micropipette or automatically with a laser tweezers system. The neurocages have openings to allow the neurites to extend out of the neurocages and form synaptic connections with their neighboring neurons. Each neurocage has its own electrode, which is platinized to increase its capacitance. Successful growth of neural networks has been achieved using arrays of neurocages with Parylene and silicon-nitride insulation on both silicon and glass substrates. These neurocages have a long-term cell survival rate of ~ 50% after 3 weeks and have proven 99% effective in trapping neurons. The neurons inside the neurocages have been successfully stimulated, with both current and voltage pulses. Action potentials, both spontaneous and resulting from a current stimulus, have been recorded from neurons comprising the neural networks.
", "doi": "10.7907/9M7Q-ZM04", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:2368", "collection": "thesis", "collection_id": "2368", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06012007-143736", "primary_object_url": { "basename": "Thesis_final.pdf", "content": "final", "filesize": 8166633, "license": "other", "mime_type": "application/pdf", "url": "/2368/1/Thesis_final.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Measurement and Analysis of Structure and Function of Myocardium in Embryonic and Adult Heart", "author": [ { "family_name": "Nasiraei Moghaddam", "given_name": "Abbas", "orcid": "0000-0002-6423-3458", "clpid": "Nasiraei-Moghaddam-Abbas" } ], "thesis_advisor": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "thesis_committee": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Barr", "given_name": "Alan H.", "clpid": "Barr-A-H" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Wen", "given_name": "Han", "clpid": "Wen-Han" }, { "family_name": "Tyszka", "given_name": "Julian Michael", "clpid": "Tyszka-J-M" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Congestive heart failure is the most common and costly medical problem in the modern world. Current disease management procedures are mostly limited to treating the symptoms of this disease. The effective treatment, however, needs a deep understanding of the normal structure-function relationships of the myocardium.
\r\n\r\nThe research of this study is concerned with the relationship between the structure and function of the myocardium in both embryonic and adult hearts. This relationship was investigated through an in-depth analysis of the spatial distribution of the local contractile function in the myocardium. The analysis is based on the heart kinematics captured through the tissue tracking of the myocardium.
\r\n\r\nAdvanced imaging techniques, such as DENSE MRI and confocal microscopy, were used for tissue tracking in adult and embryonic myocardium, respectively. The acquired data, together with continuum mechanics concepts and computational methods, were exploited in a Lagrangian framework to measure appropriate characteristic parameters that describe local contribution of the myocardium in its global functionality.
\r\n\r\nThis method resulted in novel understandings of the local and global functions in each of these hearts. In particular, it was observed in the adult heart that the left ventricle functionality is not uniformly distributed. Instead, the regions with higher effect on the pumping process form a helical band which wraps around the heart. This is the first time that such a myocardium macro-structure, which is supported by the established histological evidence, is revealed from its function in a beating heart. It can be considered as a landmark in connecting the structure and function of the heart through imaging. Furthermore, the compatibility of this model with microscopic observations about the fiber direction is investigated.
\r\n \r\nA similar approach was applied to embryonic zebrafish heart with GFP labeled myocytes. It identified distribution of regions that play an active role in functionality of the heart tube. This new understanding has provided better insights into the pumping mechanism of the embryonic heart.
", "doi": "10.7907/RQE4-MA23", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:2368", "collection": "thesis", "collection_id": "2368", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06012007-143736", "primary_object_url": { "basename": "Thesis_final.pdf", "content": "final", "filesize": 8166633, "license": "other", "mime_type": "application/pdf", "url": "/2368/1/Thesis_final.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Measurement and Analysis of Structure and Function of Myocardium in Embryonic and Adult Heart", "author": [ { "family_name": "Nasiraei Moghaddam", "given_name": "Abbas", "orcid": "0000-0002-6423-3458", "clpid": "Nasiraei-Moghaddam-Abbas" } ], "thesis_advisor": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "thesis_committee": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Barr", "given_name": "Alan H.", "clpid": "Barr-A-H" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" }, { "family_name": "Wen", "given_name": "Han", "clpid": "Wen-Han" }, { "family_name": "Tyszka", "given_name": "Julian Michael", "clpid": "Tyszka-J-M" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Congestive heart failure is the most common and costly medical problem in the modern world. Current disease management procedures are mostly limited to treating the symptoms of this disease. The effective treatment, however, needs a deep understanding of the normal structure-function relationships of the myocardium.
\r\n\r\nThe research of this study is concerned with the relationship between the structure and function of the myocardium in both embryonic and adult hearts. This relationship was investigated through an in-depth analysis of the spatial distribution of the local contractile function in the myocardium. The analysis is based on the heart kinematics captured through the tissue tracking of the myocardium.
\r\n\r\nAdvanced imaging techniques, such as DENSE MRI and confocal microscopy, were used for tissue tracking in adult and embryonic myocardium, respectively. The acquired data, together with continuum mechanics concepts and computational methods, were exploited in a Lagrangian framework to measure appropriate characteristic parameters that describe local contribution of the myocardium in its global functionality.
\r\n\r\nThis method resulted in novel understandings of the local and global functions in each of these hearts. In particular, it was observed in the adult heart that the left ventricle functionality is not uniformly distributed. Instead, the regions with higher effect on the pumping process form a helical band which wraps around the heart. This is the first time that such a myocardium macro-structure, which is supported by the established histological evidence, is revealed from its function in a beating heart. It can be considered as a landmark in connecting the structure and function of the heart through imaging. Furthermore, the compatibility of this model with microscopic observations about the fiber direction is investigated.
\r\n \r\nA similar approach was applied to embryonic zebrafish heart with GFP labeled myocytes. It identified distribution of regions that play an active role in functionality of the heart tube. This new understanding has provided better insights into the pumping mechanism of the embryonic heart.
", "doi": "10.7907/RQE4-MA23", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:636", "collection": "thesis", "collection_id": "636", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-02142007-151137", "primary_object_url": { "basename": "Choi_jm_2007.pdf", "content": "final", "filesize": 2712042, "license": "other", "mime_type": "application/pdf", "url": "/636/1/Choi_jm_2007.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Design, Fabrication, and Characterization of Semiconductor Transverse Bragg Resonance Lasers", "author": [ { "family_name": "Choi", "given_name": "John Myun", "clpid": "Choi-John-Myun" } ], "thesis_advisor": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" } ], "thesis_committee": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Crosignani", "given_name": "Bruno", "clpid": "Crosignani-B" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Bockrath", "given_name": "Marc William", "clpid": "Bockrath-M-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Controlling the spatial modes of a laser cavity is fundamental for improving the beam quality of a laser and achieving highly efficient coupling of power into an optical system. High-power applications are particularly challenging due to the conflicting requirements for large modal volume, to prevent facet damage by reducing energy density, and narrow width, for single-mode operation of an index-guided waveguide. By replacing traditional index confinement with Bragg reflection in the transverse direction, single-mode operation can be achieved even for large modal volumes. These grating confined structures, transverse Bragg resonance (TBR) waveguides, have the unique ability to support localized modes above the light line. Such modes normally couple to radiation modes of the cladding when the confinement mechanism is total-internal-reflection and are too lossy to be considered guided modes. However, for Bragg resonance confined modes, the modal loss can be designed by careful optical mode engineering to introduce a large loss discrimination that can favor a single spatial, low-loss mode. Semiconductor TBR lasers in an InP/InGaAsP/InGaAs material system were designed, fabricated, and characterized to investigate this property. Two regions of operation are identified for TBR waveguides, and, while transverse mode selection is provided by a grating, longitudinal mode control is found to be also necessary to restrict operation to the region that supports modes above the light line.", "doi": "10.7907/NG25-BN55", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:1408", "collection": "thesis", "collection_id": "1408", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-04182006-162552", "primary_object_url": { "basename": "thesis.pdf", "content": "final", "filesize": 7175762, "license": "other", "mime_type": "application/pdf", "url": "/1408/1/thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Temperature-Controlled Microchip Liquid Chromatography System", "author": [ { "family_name": "Shih", "given_name": "Victor-Chi-Yuan", "clpid": "Shih-Victor-Chi-Yuan" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Lee", "given_name": "Terry D.", "clpid": "Lee-T-D" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "High-performance liquid chromatography (HPLC) is one of the most important analytical tools heavily used in the fields of chemistry, biotechnology, pharmaceutics, and the food industry. The power of liquid chromatography comes from its ability to achieve molecular separation with extremely high efficiency and its great flexibility of incorporating versatile sensors for detecting a broad range of analytes. In the past decades, great efforts have been put into liquid chromatography instrumentation and methods, aiming to further improve separation efficiency, sensitivity, repeatability, throughput, and costs. The contribution of this thesis is to illustrate with real examples the great potential of MEMS microchip liquid chromatography systems with on-chip temperature control for replacing and improving the conventional desktop HPLC systems.
\r\n\r\nThis thesis is composed of seven chapters. Chapter 1 gives an introduction to MEMS technology and its application in making lab-on-a-chip systems. Chapter 2 describes the theoretical background and the evolution of HPLC technology. Chapter 3 demonstrates how to use state-of-the-art MEMS technology to make high-pressure microfluidic channels, which will be used for constructing microchip HPLC systems later. Chapter 4 describes a temperature-controlled microchip HPLC system that uses a temporal temperature gradient to achieve analyte elution. Separation of amino acids and low density lipoproteins was successfully demonstrated using the proposed system. Chapter 5 describes a novel embedded HPLC system, which demonstrated a record high pressure capacity (> 1000 psi) among microchip HPLC systems. High quality separation results of trace-level daunorubicin and doxorubicin were obtained using the proposed system and laser-induced fluorescence detection. A novel C4D sensor together with the RISE sensitivity enhancement method was proposed and investigated for the first time for microchip HPLC analyte detection. Chapter 6 describes the first work to pack 30 nm gold nanoparticles into the HPLC separation column as the stationary phase with the assistance of in-situ molecular self-assembly between nanoparticles and thiolated molecules. Preliminary results demonstrated the possibility of building fully filled nanoparticle HPLC columns for extremely high separation efficiency application. Chapter 7 then gives the conclusions of this thesis.
", "doi": "10.7907/ZDK5-Q871", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:3698", "collection": "thesis", "collection_id": "3698", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09222006-151349", "primary_object_url": { "basename": "Terrell_D_Neal.pdf", "content": "final", "filesize": 1463952, "license": "other", "mime_type": "application/pdf", "url": "/3698/1/Terrell_D_Neal.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Surface Plasmon Enhanced Light Emission from Organic Light Emitters", "author": [ { "family_name": "Neal", "given_name": "Terrell Demetris", "clpid": "Neal-Terrell-Demetris" } ], "thesis_advisor": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" } ], "thesis_committee": [ { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "We have experimentally verified that visible light emission for various organic light emitters can be enhanced through the use of surface plasmon coupling layers. By matching the plasmon frequency of a thin unpatterned silver film to the emission of a dye-doped polymer deposited onto this metal surface, we have observed an 11-fold enhancement of light emission. By patterning the silver layer, we estimate that the plasmon frequency can be tuned to match dye-doped polymer emission frequencies, and even larger emission enhancements as well as extraction efficiencies are expected. Carrier dynamics of such plasmon-enhanced organic light emitters were studied and a recombination rate increase due to surface plasmon polaritons was experimentally observed. Internal quantum efficiency data from the polyfluorenes studied follow the trend supported by the time-resolved photoluminescence measurements. Also, we have presented a way to extend the lifetime of organic light emitters by reducing the photodegredation effects from photo-oxidation using surface plasmon coupling.", "doi": "10.7907/DH6C-2C59", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:1594", "collection": "thesis", "collection_id": "1594", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05032006-154541", "primary_object_url": { "basename": "thesis.pdf", "content": "final", "filesize": 3011002, "license": "other", "mime_type": "application/pdf", "url": "/1594/1/thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Classical and Quantum Nonlinear Optical Information Processing", "author": [ { "family_name": "Tsang", "given_name": "Mankei", "orcid": "0000-0001-7173-1239", "clpid": "Tsang-Mankei" } ], "thesis_advisor": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" } ], "thesis_committee": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Hong", "given_name": "John Hyunchul", "clpid": "Hong-J-H" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis is a theoretical investigation of the classical and quantum information processing enabled by the advent of modern ultrafast nonlinear optics.
\r\n\r\nChapter 2 and 3 study the propagation of ultrashort optical pulses in optical fibers, and propose two methods of compensating the linear and nonlinear distortions experienced by the pulses, namely, reverse propagation and spectral phase conjugation. Chapter 4 and 5 suggest different schemes that implement spectral phase conjugation.
\r\n\r\nChapter 6 and 7 establish the connection between classical spectral phase conjugation and quantum coincident frequency entanglement. Chapter 6 shows how a spectral phase conjugator can create coincident frequency entangled photon pairs, and Chapter 7 in turn demonstrates how a coincident frequency entanglement generator can perform spectral phase conjugation.
\r\n\r\nThe next three chapters, 8, 9, and 10, focus on quantum spatiotemporal information processing. Chapter 8 studies the temporal properties of entangled photon pair propagation and proposes the concept of quantum temporal imaging. Chapter 9 investigates how optical solitons can be used to perform quantum timing jitter reduction and temporal entanglement, while Chapter 10 applies the same idea to the spatial domain for quantum spatial information processing tasks, such as spatial beam displacement uncertainty reduction and quantum lithography.
\r\n\r\nThe final two chapters return to a couple of miscellaneous problems in classical optics. Chapter 11 shows how a pair of dielectric slabs can amplify the near field of an optical image. Chapter 12 explores the similarities between nonlinear optics and fluid dynamics, and speculates on the possibility of using nonlinear optics experiments to simulate fluid dynamics problems.
", "doi": "10.7907/BG6Y-VX33", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:3671", "collection": "thesis", "collection_id": "3671", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09202008-110124", "primary_object_url": { "basename": "McGarvey_t_2006.pdf", "content": "final", "filesize": 8270442, "license": "other", "mime_type": "application/pdf", "url": "/3671/1/McGarvey_t_2006.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Ultra-Sensitive Absorption Measurements through Cavity-Enhanced Spectroscopy", "author": [ { "family_name": "McGarvey", "given_name": "Raymond Timothy James", "clpid": "McGarvey-Raymond-Timothy-James" } ], "thesis_advisor": [ { "family_name": "Mabuchi", "given_name": "Hideo", "clpid": "Mabuchi-H" } ], "thesis_committee": [ { "family_name": "Rees", "given_name": "Douglas C.", "clpid": "Rees-D-C" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Lester", "given_name": "Henry A.", "clpid": "Lester-H-A" }, { "family_name": "Mabuchi", "given_name": "Hideo", "clpid": "Mabuchi-H" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "The desire to increase the sensitivity of solution-based absorption spectroscopy is motivated by the need for label-free biosensing (which provides a more authentic indication of the state of a biological system) and by the usefulness of characterizing the kinetics of biologically-relevant reactions (which may not be accurately characterizable at reagent concentrations required by standard methods. There are a number of techniques by which such increasingly sensitive measurements have been made, including cavity ringdown spectroscopy, incoherent cavity-enhanced spectroscopy, microsphere-based whispering-gallery mode sensing,and our cavity-enhanced measurements, which are the most sensitive to date and which can be conducted in real time with high bandwidth. Our current device has a demonstrated detection threshold of 1.7x 10^{-7}/sqrt{Hz} (4.36x10^{-6}cm^{-1}), which could with further technical work be improved to a shot-noise limited sensitivity of 1.93x 10^{-10}/sqrt{Hz} (1.06x10^{-8}cm^{-1}). The latter would correspond to an average of 700 strong absorbers (epsilon = 10^5 M^{-1}cm^{-1}) in the optical beam volume. The shot-noise limited detection threshold of our measurement method could potentially be improved by up to two orders of magnitude by incorporating state-of-the-art optical mirrors. With such mirrors, cavity-enhanced absorption experiments performed with gas-phase samples have previously demonstrated single molecule sensitivity. We have established that solution-based cavity-enhanced absorption measurements are more sensitive than standard single-pass measurements by the predicted enhancement factor for our present device (~ 20,000). These measurements provide the proof-of-principle for solution-based, cavity-enhanced spectroscopy and serve as the intermediate step towards the attainment of the theoretical sensitivity of this technique. We believe that this device will be of broad interest to the scientific community, because it is presently the most sensitive solution-based spectroscopic device. It can make real-time absorption measurements which would allow monitoring of the kinetics of chemical reactions in which the spectral properties of reactants change by even a small amount, and, near its theoretical limit of sensitivity (given currently available mirrors), such a device could potentially resolve single-molecule absorption events on the sub-millisecond timescale and below.\r\n", "doi": "10.7907/CGYD-6J27", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:2885", "collection": "thesis", "collection_id": "2885", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-07142005-013255", "primary_object_url": { "basename": "Thesis_QingHe.pdf", "content": "final", "filesize": 29811978, "license": "other", "mime_type": "application/pdf", "url": "/2885/1/Thesis_QingHe.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Integrated Nano Liquid Chromatography System On-a-Chip", "author": [ { "family_name": "He", "given_name": "Qing", "clpid": "He-Qing" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Pickar", "given_name": "Kenneth A.", "clpid": "Pickar-K-A" }, { "family_name": "Lee", "given_name": "Terry D.", "clpid": "Lee-T-D" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Integrated liquid chromatography (LC) chips are valued because of their significant advantages over conventional systems. However, they are very challenging to build due to the high complexity of LC systems and the need for high-level integration of many discrete microfluidic devices.
\r\n\r\nThe goal of this thesis is to develop technologies and devices towards a totally integrated LC system on-a-chip. Using parylene microfluidics technology, all of the devices are integrated on silicon wafers with CMOS-compatible batch processes. Due to the small size of the on-chip LC columns, the chips all perform nano LC, which means that the flow rates are on the scale of nano liters per minute.
\r\n\r\nThe thesis starts with the solution of the problem of bead integration, since most LC columns are packed with micro-beads. A wafer-scale batch process is developed to integrate beads into micromachined devices. The technology is applied to make an LC-ESI (Electro-Spray Ionization) chip with an integrated bead column packed with 5 \u00b5m diameter C18 silica beads. The integrated ESI nozzle allows direct coupling to a mass spectrometer (MS).
\r\n\r\nDue to the high-pressure nature of LC operations, a complete LC chip must be able to both withstand and generate high pressures on-chip. Therefore, an anchoring technique is developed to dramatically increase the pressure rating of parylene devices from about 30 psi to 1000 psi. In addition, on-chip high-pressure generation is achieved with electrolysis-based micro-actuators.
\r\n\r\nAn integrated ion liquid chromatography chip is demonstrated, which has on-chip column, filters, injection structure, and conductivity detector. The column is packed with 7 \u00b5m anion-exchange beads with a slurry packing technique. On-chip sample injection, separation, and detection of seven common anions are successfully demonstrated with a sensitivity of 1 ppm.
\r\n\r\nFinally, a microchip that demonstrates high-pressure LC with integrated ESI coupling to MS is presented. The capacity of the column, which is 6.5 cm long and packed with 5 \u00b5m C18 silica beads, is the highest of all the devices in the thesis. Gradient separation at a pressure of 450 psi and on-line MS detection of digested cytochrome c protein is successfully performed.
", "doi": "10.7907/NQVA-F827", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:2061", "collection": "thesis", "collection_id": "2061", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05252006-221314", "primary_object_url": { "basename": "MichelaMunozTH.pdf", "content": "final", "filesize": 4113829, "license": "other", "mime_type": "application/pdf", "url": "/2061/1/MichelaMunozTH.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Coherent Optical Array Receiver for PPM Signals Under Atmospheric Turbulence", "author": [ { "family_name": "Mu\u00f1oz Fern\u00e1ndez", "given_name": "Michela", "orcid": "0000-0001-8028-2156", "clpid": "Mu\u00f1oz-Fern\u00e1ndez-M" } ], "thesis_advisor": [ { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" } ], "thesis_committee": [ { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Elachi", "given_name": "Charles", "clpid": "Elachi-C" }, { "family_name": "Mabuchi", "given_name": "Hideo", "clpid": "Mabuchi-H" }, { "family_name": "Mukai", "given_name": "Ryan", "clpid": "Mukai-R" }, { "family_name": "Vilnrotter", "given_name": "Victor", "clpid": "Vilnrotter-V" }, { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The performance of a coherent free-space optical communications system operating in the presence of turbulence is investigated. Maximum Likelihood Detection techniques are employed to optimally detect Pulse Position Modulated signals with a focal-plane detector array and to reconstruct the turbulence-degraded signals.
\r\n\r\nLaboratory equipment and experimental setup used to carry out these experiments at the Jet Propulsion Laboratory are described. The key components include two lasers operating at 1064 nm wavelength for use with coherent detection, a 16 element (4 X 4) InGaAs focal-plane detector array, and a data-acquisition and signal-processing assembly needed to sample and collect the data and analyze the results. The detected signals are combined using the least-mean-square (LMS) algorithm. In the first part of the experimental results we show convergence of the algorithm for experimentally obtained signal tones in the presence of atmospheric turbulence. The second part of the experimental results shows adaptive combining of experimentally obtained heterodyned pulse position modulated (PPM) signals with pulse-to-pulse coherence in the presence of simulated spatial distortions resembling atmospheric turbulence. The adaptively combined PPM signals are phased up via an LMS algorithm suitably optimized to operate with PPM in the presence of additive shot noise. A convergence analysis of the algorithm is presented, and results with both computer-simulated and experimentally obtained PPM signals are analyzed.
\r\n\r\nThe third part of the experimental results, in which the main goal of this thesis is achieved, includes an investigation of the performance of the Coherent Optical Receiver Experiment (CORE) at JPL. Bit Error Rate (BER) results are presented for single and multichannel optical receivers where quasi shot noise-limited performance is achieved under simulated turbulence conditions using noncoherent postdetection processing techniques. Theoretical BER expressions are compared with experimentally obtained BER results, and array combining gains are presented. BER results are shown as a function of signal-to-noise ratio (SNR), photons per symbol, and photons per bit (PPB).
", "doi": "10.7907/VDSA-SA42", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:3841", "collection": "thesis", "collection_id": "3841", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09302005-174955", "primary_object_url": { "basename": "thesisweb.pdf", "content": "final", "filesize": 3522270, "license": "other", "mime_type": "application/pdf", "url": "/3841/1/thesisweb.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Uncooled Carbon Microbolometer Imager", "author": [ { "family_name": "Liger", "given_name": "Matthieu", "clpid": "Liger-Matthieu" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng E-F-C" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The discovery of infrared radiation two centuries ago and the theory of blackbody radiation one century later have given birth to the field of thermal imaging. Since then, researchers have devised numerous ways to detect infrared radiation. From World War II to the 1980s, semiconductor-based cooled photon detector arrays have reigned over the field of thermal imaging. Albeit limited to expensive, bulky systems used for military applications due to their cooling requirement they have been . The emergence of micromachining techniques in the 1980s however, have allowed for the development of uncooled, thermal detector arrays. Uncooled systems are expected to find more and more applications, especially in the civilian world.
\r\n\r\nHere we present a novel and simple way to fabricate uncooled infrared detectors suitable for integration into large-area arrays. The design is based on carbon obtained by means of polymer pyrolysis. We demonstrate how some electrical and thermal properties can be adjusted by process parameters, and then present the first micromachined carbon uncooled bolometer made of two-layers of self-supporting pyrolyzed-parylene carbon having different process-tuned properties.
\r\n\r\nFinally, based on this unique design and fabrication process, we develop a carbon bolometer array and demonstrate the thermal imaging capability by taking thermal images. Measurements show that the sensitivity to target temperature can be as low as 31mK and 44mK for 100us and 12us electrical signal integration time, respectively. This matches the current state of the art which is very promising considering the fact that this is the first time pyrolytic carbon has been used to fabricate a microbolometer array.
\r\n", "doi": "10.7907/R7HB-GF96", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:3834", "collection": "thesis", "collection_id": "3834", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09302005-024349", "primary_object_url": { "basename": "thesis_xiang_final.pdf", "content": "final", "filesize": 3505176, "license": "other", "mime_type": "application/pdf", "url": "/3834/1/thesis_xiang_final.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Microwave Integrated Phased Array Receivers in Silicon", "author": [ { "family_name": "Guan", "given_name": "Xiang", "clpid": "Guan-Xiang" } ], "thesis_advisor": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" } ], "thesis_committee": [ { "family_name": "Hajimiri", "given_name": "Ali", "clpid": "Hajimiri-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Rutledge", "given_name": "David B.", "clpid": "Rutledge-D-B" }, { "family_name": "D'Addario", "given_name": "Larry R.", "clpid": "D'Addario-L-R" }, { "family_name": "Weinreb", "given_name": "Sander", "clpid": "Weinreb-S" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Microwave integrated systems in silicon provide a low cost, low power and high yield solution for wideband data communication, radar, and many other applications. Phased-array systems are capable of steering the radiation beam by electronic means, emulating the behavior of a directional antenna. This dissertation is dedicated to presenting various techniques to implement microwave integrated phased-array receivers in silicon-based technologies in the context of three design examples.
\r\n\r\nA 24-GHz 0.18-\u00b5m complementary metal oxide semiconductor (CMOS) front-end was demonstrated. The front-end consists of a low noise amplifier (LNA) and a mixer. The LNA utilizes a novel topology common-gate with resistive feedthrough to obtain low-noise performance. The entire front-end achieves a 7.7dB noise figure and a 27.5dB power gain.
\r\n\r\nA fully integrated 8-element 24-GHz silicon germanium (SiGe) phased array receiver was implemented. The receiver uses two-step downconversion and local oscillator (LO) phase shifting with 4-bit resolution. The signal is combined at the 4.8-GHz intermediate frequency. The 16 phases of 19.2-GHz LO signal are generated with a voltage controlled oscillator (VCO) and symmetrically distributed to the phase selectors at all path. Appropriate phase sequence is applied to the phase distribution transmission lines to minimize mismatch. An integrated frequency synthesizer locks the 19.2-GHz VCO output to a 75-MHz external reference. Measured array patterns show a peak-to-null ratio of more than 20dB and a beam steering range covering all signal incident angles.
\r\n\r\nAn integrated 4-element 77-GHz SiGe wideband phased-array transceiver was implemented. Two-step conversion is used at both the receiver and the transmitter. A differential phase of 52 GHz is generated by the VCO and distributed to all RF paths at the transmitter and receiver. The phase shifting is performed at the LO ports of the RF mixers using continuous analog phase shifters. The quadrature signal of the second LO frequency is generated by dividing the VCO frequency by a factor of 2 using a cross-coupled injection-locked frequency divider. The signal combining is performed at IF with an active combining amplifier. The receiver achieves a 41dB gain at 80 GHz with 3 GHz of bandwidth. The 52-GHz-to-50MHz frequency divider chain obtains 7% locking range.
", "doi": "10.7907/E5GE-EP91", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:845", "collection": "thesis", "collection_id": "845", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-03032005-135900", "primary_object_url": { "basename": "thesis-junxie.pdf", "content": "final", "filesize": 14013724, "license": "other", "mime_type": "application/pdf", "url": "/845/1/thesis-junxie.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Integrated Parylene LC-ESI on a Chip", "author": [ { "family_name": "Xie", "given_name": "Jun", "clpid": "Xie-Jun" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Scherer", "given_name": "Axel", "clpid": "Scherer-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Lee", "given_name": "Terry D.", "clpid": "Lee-T-D" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "In this thesis, several microfluidic devices will be introduced to demonstrate the integration capability of a multilayer parylene surface micromachining technology. Due to its flexibility and versatility, various devices have been developed and integrated onto a single ship. Based on the technology, on-chip LC-ESI was successfully demonstrated.
\r\n\r\nBased on the technology, an electrostatically actuated micro peristaltic pump has been developed. An AC actuation voltage combined with a peristaltic actuation was used to demonstrate fluid pumping. A reasonable flow rate and pumping pressure were achieved. The pump dynamics and performance were then addressed further by an analysis based on a lumped-parameter model of the system.
\r\n\r\nBased on the same technology, an entirely surface micromachined electrostatically actuated valve has been demonstrated. A thermal flow sensor was integrated with the valve to be used for feedback control. Two modes, actuation voltage adjustment and PWM were investigated in characterizing the valve to control air flow. The testing results show that PWM has better linearity and performance.
\r\n\r\nThree types of capacitive fluidic sensors were demonstrated in several microfluidic applications. These include sensors for fluid pressure, flow rate, volume, and composition measurement. The sensors showed great promise for microfluidic applications because of their high sensitivity and easy integration capabilities. The integration of these sensors with abovementioned devices was achieved.
\r\n\r\nA novel electrochemical pumping system for on-chip LC gradient generation was demonstrated. This pump was able to deliver significant flow rates under high back pressures that are sufficient for many LC applications. On-chip gradient formation with integrated electrospray ionization was demonstrated.
\r\n\r\nFinally, a complete LC-ESI system was integrated in a chip format. Typical nano-LC reversed-phase gradient elution was demonstrated using on-chip electrolysis pump. Separated analytes from on-chip column were then sprayed into MS for analysis through an integrated ESI-nozzle. Separation results are comparable to those of commercial system. Peptide identification performance using the LC-ESI chip with MS was also very close to those achieved by the commercial system.
", "doi": "10.7907/00KQ-V723", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:1717", "collection": "thesis", "collection_id": "1717", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05102005-112605", "primary_object_url": { "basename": "GTPaloczi_PhD_Thesis.pdf", "content": "final", "filesize": 7131872, "license": "other", "mime_type": "application/pdf", "url": "/1717/1/GTPaloczi_PhD_Thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Polymer Integrated Optics: Device Architectures and Fabrication Methods", "author": [ { "family_name": "Paloczi", "given_name": "George T.", "clpid": "Paloczi-George-T" } ], "thesis_advisor": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" } ], "thesis_committee": [ { "family_name": "Yariv", "given_name": "Amnon", "clpid": "Yariv-A" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Bockrath", "given_name": "Marc William", "clpid": "Bockrath-M-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Polymer materials are becoming increasingly important for integrated photonic circuits in optical communications networks. The optical and mechanical properties of polymers for integrated optics are explored in this thesis and it is shown that the manipulation of these properties leads to developments that in other optical materials could not be achieved as quickly or as easily, or not achieved at all.
\r\n\r\nSo that the benefits of a large range of operating wavelengths due to low material dispersion in polymers, are not lost to the wavelength dependence of optical couplers, we design wavelength-invariant couplers using a geometrical representation of coupled mode theory. Simulations of the resulting couplers confirm a virtually constant response over a large range of input wavelengths.
\r\n\r\nThe direct-write ability of electron beam sensitive polymers enables rapid fabrication of high-precision optical devices. Microring resonator optical filters and a compact microring-based inline reflector are fabricated by this method and characterized. Chaining multiple rings together results in the coupled resonator optical waveguide (CROW). A CROW-Mach-Zehnder interferometer is fabricated and the measured response corresponds well with the predictions based on the matrix theory.
\r\n\r\nPolymer materials can be patterned by a variety of methods not possible with traditional optical materials. Soft-stamp replica molding presents a means to further reduce the costs of implementing polymer materials. Demonstrating the potential of the method, microring resonators are fabricated, with excellent agreement between the responses of the original and the replica. To further demonstrate the effectiveness of the process, it is applied in the fabrication of Mach-Zehnder modulators. The modulators exhibit excellent properties, with single-arm modulation voltages of 8 V and extinction ratios better than 19 dB. Successive repetition of the molding process allows for multilayer polymer optical devices. Finally, the flexible properties of polymers are exploited for pliable, all-polymer freestanding optical circuits.
", "doi": "10.7907/W41G-2374", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:2423", "collection": "thesis", "collection_id": "2423", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06032005-115306", "primary_object_url": { "basename": "Yang_l_2005.pdf", "content": "final", "filesize": 10395220, "license": "other", "mime_type": "application/pdf", "url": "/2423/3/Yang_l_2005.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Fabrication and Characterization of Microlasers by the Sol-Gel Method", "author": [ { "family_name": "Yang", "given_name": "Lan", "orcid": "0000-0002-9052-0450", "clpid": "Yang-Lan" } ], "thesis_advisor": [ { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" } ], "thesis_committee": [ { "family_name": "Vahala", "given_name": "Kerry J.", "clpid": "Vahala-K-J" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Rutledge", "given_name": "David B.", "clpid": "Rutledge-D-B" }, { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Painter", "given_name": "Oskar J.", "clpid": "Painter-O" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The present study explores the application of new materials systems for low threshold microlasers, and characterization of the microcavities. The sol-gel method is used for gain functionalization of high-Q microcavities. A detailed procedure for preparation of the sol-gel films by the spin-on or dip-coating method is presented. The effect of different process conditions on the properties and microstructure of the thin films is investigated through Fourier Transform Infrared (FTIR) Spectroscopy, Scanning Electron Microscopy (SEM), and etching rate test.
\r\n\r\nSurface gain functionalization of microsphere cavities is fabricated by coating the microsphere with a thin layer of Er\u00b3\u207a-doped sol-gel films. The optical gain is due to the population inversion of rare earth ions in the sol-gel films. A fiber taper is used to both couple the pump power into and extract the laser power out of the microsphere laser. The laser dynamics change between continuous-wave and pulsating operation by varying the doping concentration and the thickness of the sol-gel films outside the microsphere.
\r\n\r\nSurface functionalization is also achieved on the microtoroid on a single silicon chip, which can be fabricated in parallel using wafer-scale processing and has characteristics that are more easily controlled than microsphere. The microtoroid can be selectively coated only at the periphery by making use of the variation of etching rate (in buffered HF) of sol-gel films with different degrees of densification. The laser performance of the gain functionalized microtoroids is investigated. Highly confined whispering gallery modes make possible single-mode microlasers. This work also shows that the high Q microtoroid laser has a linewidth much lower than 300 kHz.
\r\n\r\nThe thesis explores fabrication of high Q microcavities directly from the sol-gel silica films deposited on a single silicon wafer. Quality factor as high as 2.5 x 10\u2077 at 1561 nm is obtained in toroidal microcavities formed of silica sol-gel, which allows Raman lasing at absorbed pump power below 1 mW. Additionally, Er\u00b3\u207a-doped microlasers are fabricated from Er\u00b3\u207a-doped sol-gel layers with control of the laser dynamics possible by varying the erbium concentration of the starting sol-gel material. Continuous lasing with a record threshold of 660 nW for erbium-doped microlaser on a silicon wafer is also obtained.
\r\n\r\nAnalytic formulas are derived to predict the laser performance, such as the laser output power, the threshold power, and the differential quantum efficiency, under different loading condition, i.e. the air gap between the fiber-taper coupler and the cavities. The effect of Er3+ concentration on the minimum threshold is also investigated. In addition, we present a theoretical model in which we include paired ions as the saturable absorber. It shows that self-pulsing operation can be expected with paired-ions-induced quenching in the system. The pulsation frequency increases linearly with the square root of the pumping level, which is consistent with the experimental observation.
", "doi": "10.7907/HHQ8-VC25", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:1621", "collection": "thesis", "collection_id": "1621", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05052005-131822", "primary_object_url": { "basename": "ThesisTeTe.pdf", "content": "final", "filesize": 2013868, "license": "other", "mime_type": "application/pdf", "url": "/1621/1/ThesisTeTe.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Operation of Holographic Elements with Broadband Light Sources", "author": [ { "family_name": "Hsieh", "given_name": "Hung-Te", "clpid": "Hsieh-Hung-Te" } ], "thesis_advisor": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" } ], "thesis_committee": [ { "family_name": "Psaltis", "given_name": "Demetri", "clpid": "Psaltis-D" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Hong", "given_name": "John Hyunchul", "clpid": "Hong-J-H" }, { "family_name": "Buse", "given_name": "Karsten", "clpid": "Buse-K" }, { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents the theoretical and experimental investigation of volume holography operated with broadband/polychromatic light sources, i.e., in both continuous-wave (linear) and femtosecond-pulse (nonlinear) regimes.
\r\n\r\nThe first chapter reviews the concept of volume holography and provides a tacit introduction to some basic properties of volume holograms and compares the operation of holograms in the spatial and temporal domains, preparing the readers for later chapters.
\r\n\r\nThe second chapter introduces a powerful theoretical tool for the analysis of volume holograms in the reflection geometry: the matrix formulation, laying the foundation for the application of holographic gratings utilized as WDM filters.
\r\n\r\nThe third chapter takes into consideration the effects of the practically inevitable finite beam-widths. By means of Fourier decomposition, the deviation of the filtering properties of volume holographic gratings from the ideal plane-wave case can be satisfactorily explained and predicted. Experiments and simulations are performed and compared to confirm the validity of the theory.
\r\n\r\nVolume holographic gratings in the reflection geometry serve as excellent WDM filters for telecommunication purposes thanks to their low cross-talk and readily engineered filtering properties. The theoretical design and experimental realization of athermal holographic filters are presented in the fourth chapter. By incorporating a passive, thermally actuated MEMS mirror, the temperature dependence of the Bragg wavelength of a holographic filter can be compensated.
\r\n\r\nThe analysis of holographic gratings in the 90 degree geometry requires a two dimensional theory. The relevant boundary conditions give rise to some peculiar behaviors in this configuration. Theory, simulations and some experimental results of the 90-degree holography are presented in chapter five.
\r\n\r\nThe sixth chapter delves into the subject of instantaneous Kerr index grating established by two intense, interfering femtosecond (pump) pulses at 388 nm owing to the omnipresent third-order nonlinearity. The coupled-mode equations describing the incident and diffracted (probe) pulses at 776 nm are written down; the solution is experimentally corroborated. It is further demonstrated that the temporal resolution in such a holographic pump-probe configuration does not degrade appreciably as the angular separation between pump pulses increases.
\r\n\r\nChapter seven investigates the nonlinear absorption processes in lithium niobate crystals with femtosecond pulses. The model of two-photon absorption well explains and anticipates the transmission coefficients of single pulses over a wide range of intensity. Collinear pump-probe transmission experiments are then carried out to look into the nonlinear absorption suffered by the probe pulse at 776 nm owing to the pump pulse at 388 nm; the dependence of the probe pulse transmission coefficient on the time delay between pump and probe pulses is characterized by a dip and a long-lasting plateau, which are attributed, respectively, to direct two-photon transitions involving pump and probe photons and the existence of free carriers.
\r\n\r\nBuilding on the experimental experience and theoretical understanding of the previous two chapters, the results of holographic pump-probe experiments in lithium niobate crystals are presented in the final chapter. The behavior is much more complicated because it encompasses all phenomena explored in the two preceding chapters, i.e., both the real and imaginary parts of the third-order susceptibility come into play in the instantaneous material response; furthermore, another mixed grating due to excited charge carriers exists long after the pump pulses pass through. Valuable information on the grating formation process is obtained thanks to the sub-picosecond temporal resolution of such configurations.
", "doi": "10.7907/9R5R-JT19", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:5228", "collection": "thesis", "collection_id": "5228", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06092005-112430", "primary_object_url": { "basename": "JustinBoland.pdf", "content": "final", "filesize": 12677604, "license": "other", "mime_type": "application/pdf", "url": "/5228/1/JustinBoland.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Micro Electret Power Generators", "author": [ { "family_name": "Boland", "given_name": "Justin Scott", "clpid": "Boland-Justin-Scott" } ], "thesis_advisor": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" } ], "thesis_committee": [ { "family_name": "Tai", "given_name": "Yu-Chong", "clpid": "Tai-Yu-Chong" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" }, { "family_name": "Rutledge", "given_name": "David B.", "clpid": "Rutledge-D-B" }, { "family_name": "Pickar", "given_name": "Kenneth A.", "clpid": "Pickar-K-A" }, { "family_name": "Hunt", "given_name": "Melany L.", "clpid": "Hunt-M-L" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The taming of electricity and its widespread use allows people to see in the dark, to speak to one another instantaneously across the earth, and it allows retrieval of data from instruments sent out of the solar system. It is right to expect that the uses and demand for electricity will continue to grow, and to extend the ability to generate electricity; here two new micromachined devices for converting mechanical energy into electrical energy are presented. Aided by the wealth of micromachining process technology, generators that use an oscillatory motion to modify the physical structure of a capacitor with a built-in electric field provided by a permanent electret have been designed, built, and tested. The electret creates an electric field inside the capacitor structure, which induces mirror charge at some potential. The modification of the capacitor then generates an alternating displacement current through an external circuit, which provides useful electrical power. The electret microphone is a similar well known device for converting pressure waves into electrical signals by varying the distance between two charged capacitive plates. This work explores and proves feasible the ability to use mechanical forces to change the overlapping area of a charged capacitor structure and using mechanical forces to move a liquid into the gap of a charged capacitor structure, changing its permittivity to produce electricity. This work demonstrates 2.5mW of power from a 2cm diameter rotary generator at 12kRPM and 10[micro]w for a 0.1cm3 linear shaking generator at 60Hz.\r\n", "doi": "10.7907/B16C-NT21", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:7307", "collection": "thesis", "collection_id": "7307", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12062012-091333466", "primary_object_url": { "basename": "Hsu_hs_1993.pdf", "content": "final", "filesize": 17852866, "license": "other", "mime_type": "application/pdf", "url": "/7307/1/Hsu_hs_1993.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Properties of the first genetically engineered neuron.", "author": [ { "family_name": "Hsu", "given_name": "Hsiaolan S.", "clpid": "Hsu-Hsiaolan-S" } ], "thesis_advisor": [ { "family_name": "Lester", "given_name": "Henry A.", "clpid": "Lester-H-A" } ], "thesis_committee": [ { "family_name": "Davidson", "given_name": "Norman R.", "clpid": "Davidson-N-R" }, { "family_name": "Yang", "given_name": "Changhuei", "clpid": "Yang-Changhuei" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "Electrically excitable channels were expressed in Chinese hamster ovary cells using a vaccinia virus vector system. In cells expressing rat brain IIA Na^+ channels, brief pulses (< 1ms) of depolarizing current resulted in action potentials with a prolonged (0.5-3s) depolarizing plateau; this plateau was caused by slow and incomplete Na^+ channel inactivation. In cells expressing both Na^+ and Drosophila Shaker H4 transient K^+ channels, there were neuron-like action potentials. In cells with appropriate Na^+/K^+ current ratios, maintained stimulation produced repetitive firing over a 10-fold range of frequencies but eventually led to \"lockup\" of the potential at a positive value after several seconds of stimulation; the latter effect was due primarily to slow inactivation of the K^+ currents. Numerical simulations of modified Hodgkin-Huxley equations describing these currents, using parameters from voltage-clamp kinetics studied in the same cells, accounted for most features of the voltage trajectories. The present study shows that insights into the mechanisms for generating action potentials and trains of action potentials in real excitable cells can be obtained from the analysis of synthetic excitable cells that express a controlled repertoire of ion channels. This model system provides a direct control of complexity of neuronal behavior, and a tool for studying various forms of neural modulation at molecular and cellular levels.
", "doi": "10.7907/svss-ye57", "publication_date": "1993", "thesis_type": "phd", "thesis_year": "1993" } ]