Theses and Dissertations from UMD
Permanent URI for this communityhttp://hdl.handle.net/1903/2
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
More information is available at Theses and Dissertations at University of Maryland Libraries.
Browse
108 results
Search Results
Item ENGINEERING TARGETED LIGHT ACTIVATABLE NANOPLATFORMS TO MANAGE RECURRENT CANCERS(2024) Pang, Sumiao; Huang, Huang Chiao HH; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cancer recurrence poses a significant challenge in various malignancies that adverselyaffect long-term survival and quality of life. Glioblastoma (GBM) and ovarian cancer exhibit particularly high recurrence rates. For GBM, tumor recurrence is nearly universal (90%) within 10 months post initial treatment due to its invasive characteristics, limited delivery of therapeutic agents, and persistent drug resistance, resulting in a 5-year survival rate of <10%. While standard chemotherapy and surgery can temporarily alleviate symptoms for both diseases, there has been no significant improvement in long-term disease management or survival extension over several decades. Therefore, it is critical to develop targeted therapies that integrates well with current standards of care strategies. Photomedicine is a promising treatment modality, and the two main phototherapies are photodynamic therapy (PDT) which involves photosensitizer administration followed by light activation resulting in non-thermal chemical damage and photothermal therapy (PTT) which involves exogenous or endogenous sensitizing agents followed by light activation resulting in thermal damage. Clinical applications of both modalities have shown its feasibility and safety; however, they face challenges due to (i) limited cancer selectivity, (ii) heterogenous treatment response, and (iii) low monotherapy treatment efficacy. Leveraging strategic therapeutic targets to advance the current sensitizing agents for targeted delivery is a potential solution to overcome these limitations. The overall objective of this dissertation is to advance and evaluate targeted light-activatable nanoplatforms for phototherapy delivery with considerations for the current clinical workflow of GBM and advanced ovarian cancer. This is achieved through the following goals, (1) engineering a novel Fn14 receptor-directed gold nanorods (DART-GNRs) to assess selectivity and PTT efficacy for GBM, and (2) evaluate safety and long-term efficacy of targeted light-activatable multi-agent nanoplatform (tLAMP) to deliver targeted PDT for peritoneal carcinomatosis. First, this work establishes a reproducible synthesis protocol for DART-GNRs, characterizes its photothermal properties, and demonstrate high selectivity towards the Fn14 receptor of cancer cells. Second half of this dissertation established and investigated a two-fiber tissue optical property (TOP) monitoring method for liquid phantoms and for peritoneal carcinomatosis mouse model to enable safer light dosimetry during PDT, established an irinotecan active loading method to reproducibly synthesize tLAMP, and determined tLAMP tumor nodule penetration depth for enhanced targeted PDT combination therapy with adjuvant chemotherapy to enhance long-term survival for ovarian cancer.Item PREPARATION OF A NANOSUSPENSION OF THE PHOTOSENSITIZER VERTEPORFIN FOR PHOTODYNAMIC AND LIGHT-INDEPENDENT THERAPY IN GLIOBLASTOMA(2024) Quinlan, John Andrew; Huang, Huang-Chiao; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Photodynamic therapy (PDT) using verteporfin (VP) has treated ocular disease for over 20 years, but recent interest in VP’s light-independent properties has reignited interest in the drug, particularly in glioblastoma (GBM) (NCT04590664). Separate efforts to apply PDT to GBM using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) have also garnered attention (NCT03048240), but, unfortunately, clinical trials using 5-ALA-induced PpIX-PDT have yet to yield a survival benefit. Previous studies have shown VP to be a superior PDT agent than 5-ALA-induced PpIX. Our lab has shown that 690 nm light activates VP up to 2 cm into the brain, while 635 nm light only activates PpIX at depths <1 cm into the brain. Additionally, VP is a more effective photosensitizer than PpIX because it has a higher singlet oxygen yield and is active in the vasculature as well as target tumor cells. However, the hydrophobicity of VP limits effective delivery of the drug to the brain for treatment of GBM.In this context, this thesis aims to re-evaluate the delivery method for VP. VP traditionally requires lipids for delivery as Visudyne. Recent shortages of Visudyne and potential drawbacks of liposomal carriers motivated our development of a carrier-free nanosuspension of VP, termed NanoVP. Previous work has shown that cellular uptake of VP is greater when delivered as NanoVP rather than liposomal VP, resulting in improved cell killing after light activation. This thesis builds on this previous work by (1) evaluating synthesis and storage parameters for NanoVP, (2) determining the pharmacokinetics, biodistribution, and brain bioavailability of NanoVP, and (3) evaluating the potential efficacy of NanoVP as a PDT and a chemotherapy agent, and by supporting development of a zebrafish model of the blood-brain barrier (BBB) for mechanistic studies of improved drug delivery to the brain.Item DEVELOPMENT OF GLYCOSAMINOGLYCAN MIMICKING NANOGEL TECHNOLOGIES FOR CONTROLLED RELEASE OF THERAPEUTICS TO TREAT RETINAL DISEASES IN DIFFERENT AGE GROUPS(2024) Kim, Sangyoon; Lowe, Tao L.; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Retinal diseases, such as diabetic retinopathy, glaucoma, macular degeneration, and retinoblastoma, affect around 13 million people worldwide, with projections indicating a rise to 20 million by 2030. These conditions lead to irreversible vision loss and significant impairment in both adults and children, with an annual economic burden of $139 billion in the United States alone. Aging significantly increases the risk of certain retinal conditions, and with improvements in healthcare leading to increased life expectancy, these conditions are becoming more prevalent due to the natural aging process and associated physiological changes in the eye. Current treatments are either destructive or have low efficacy and are not optimized for the younger population. While therapeutics including small molecular drugs, proteins and antibodies show promise in treating these diseases by reducing inflammation and neuronal apoptosis, their effectiveness is hindered by short half-lives and inability to cross the blood-retinal barrier (BRB). Nanoparticles offer a potential solution by improving drug delivery across biological barriers, yet no nanoparticles have been developed to effectively transport intact proteins or small molecules across the BRB to the retina without toxicity, slow clearance and stability. Therefore, there is an unmet need to evaluate the physical and physiological property changes of the eye along development and develop nanoparticle systems that can control and sustain the release of therapeutics across the blood retinal barrier (BRB) to treat the retinal diseases. In this project, the thickness, rheological property, permeability and morphological property changes of ocular barriers including sclera, cornea and vitreous humor in the developing eye from preterm to adult were evaluated using porcine ex vivo model. Two glycosaminoglycan mimicking nanogel systems, poly(NIPAAm-co-DEXcaprolactoneHEMA) nanogels with and without positive or negative charges and β-cyclodextrin based poly(β-amino ester) (CD-p-AE) nanogels were developed for sustained release of intact proteins including insulin and anti-TNFα, and small hydrophobic drugs, respectively across the ex vivo porcine sclera and in vitro BRB models: human fetal retinal pigment epithelial (hfRPE), adult retinal pigment epithelial (ARPE-19) and human cerebral microvascular endothelial (hCMEC/D3) cell monolayers. Completion of this project will have a significant impact on developing novel personalized nanotherapeutics to treat retinal diseases in different age groups.Item HIGH PERFORMANCE NANOPHOTONIC CAVITIES AND INTERCONNECTS FOR OPTICAL PARAMETRIC OSCILLATORS AND QUANTUM EMITTERS(2024) Perez, Edgar; Srinivasan, Kartik; Hafezi, Mohammad; Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Integrated photonic devices like photonic crystals, microring resonators, and quantum emitters produce useful states of light, like solitons or single photons, through carefully engineered light-matter interactions. However, practical devices demand advanced integration techniques to meet the needs of cutting-edge technologies. High performance nanophotonic cavities and interconnects present opportunities to solve outstanding issues in the integration of nanophotonic devices. In this dissertation I develop three core tools required for the comprehensive integration of quantum emitters: wavelength-flexible excitation sources with sufficient pump power to drive down stream systems, photonic interconnects to spatially link the excitation sources to emitters, and cavities that can Purcell enhance quantum emitters without sacrificing other performance metrics. To create wavelength-flexible excitation sources, a high-performance χ(3)microring Optical Parametric Oscillator (OPO) is realized in silicon nitride. Microring OPOs are nonlinear frequency conversion devices that can extend the range of a high-quality on-chip (or off-chip) laser source to new wavelengths. However, parasitic effects normally limit the output power and conversion efficiency of χ(3)microring OPOs. This issue is resolved by using a microring geometry with strongly normal dispersion to suppress parasitic processes and multiple spatial mode families to satisfy the phase and frequency matching conditions. Our OPO achieves world-class performance with a conversion efficiency of up to 29% and an on-chip output power of over 18 mW. To create photonic interconnects, Direct Laser Writing (DLW) is used to fabricate 3-dimensional (3D) nanophotonic devices that can couple light into and out of photonic chips. In particular, polymer microlenses of 20 μm diameter are fabricated on the facet of photonic chips that increase the tolerance of the chips to misaligned input fibers by a factor of approximately 4. To do so, we develop the on-axis DLW method for photonic chips, which avoids the so-called "shadowing" effect and uses barcodes for automated alignment with machine vision. DLW is also used to fabricate Polymer Nanowires (PNWs) with diameters smaller than 1 μm that can directly couple photons from quantum emitters into Gaussian-like optical modes. Comparing the same quantum emitter system before and after the fabrication of a PNW, a (3 ± 0.7)× increase in the fiber-coupled collection efficiency is measured in the system with the PNW. To refine the design of quantum emitter cavities, a toy model is used to understand the underlying mechanisms that shape the emission profiles of Circular Bragg Gratings (CBGs). Insights from the toy model are used to guide the Bayesian optimization of high-performance CBG cavities suitable for coupling to single-mode fibers. I also demonstrate cavity designs with quality factors (Q) greater than 100000, which can be used in future experiments in cavity quantum electrodynamics or nonlinear optics. Finally, I show that these cavities can be optimized for extraction to a cladded PNW while producing a Purcell enhancement factor of 100 with efficient extraction into the fundamental PNW mode. The tools developed in this dissertation can be used to integrate individual quantum emitter systems or to build more complex systems, like quantum networks, that require the integration of multiple quantum emitters with multiple photonic devices.Item UNVEILING THE SELF-ASSEMBLY OF POLYMER-GRAFTED NANOPARTICLES IN SELECTIVE SOLVENTS(2023) Lamar, Chelsey; Nie, Zhihong; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The self-assembly of inorganic nanoparticles (NPs) has garnered considerable attention due to the potential for fabricating functional structures with unique collective properties. In recent years, polymers have emerged as valuable candidates in assisting the organization of NPs into complex architectures with multiple capabilities. Researchers have shown that polymer-grafted nanoparticles (PGNPs) facilitate the use of advanced nanostructures with tailored properties in biomedical applications. Although, continued exploration of the rational design and tailoring of PGNP assemblies is needed to expand our understanding before we can fully realize the potential of these structures in desired applications. My dissertation aims to investigate the fundamental aspects and elucidate the underlying mechanisms in the self-assembly of PGNPs for modern biomedical applications. A facile and versatile solution-based strategy was utilized to explore the individual self-assembly of PGNPs with anisotropic NPs and the co-assembly of binary PGNPs with distinct sizes. We focused on designing, characterizing, and exploring the optical properties of hierarchical assembly structures produced from inorganic NPs tethered with amphiphilic block copolymers (BCPs). Individual PNGPs with anisotropic NPs and binary mixtures of small and large PGNPs produce vesicle structures with well-defined packing arrangements. My work shows how key parameters, including polymer chain length, nanoparticle size, and concentration, influence the self-assembly behavior and the formation of vesicles in each system. Through a combination of experimental observations and theoretical considerations, I highlight the significance of polymer shell shape in dictating the self-assembly behavior of individual anisotropic PGNPs. Moreover, I demonstrate that elevated temperatures impacted the stability and optical responses of the vesicle structures. In co-assembly studies, my work describes the macroscopic segregation of PGNPs with different sizes in the vesicular membrane, which is attributed to the conformation entropy gain of the grafted copolymer ligands. This research will provide valuable insights into the self-assembly behavior and fundamental design of PGNP structures relevant to biomedical applications.Item DIRECT LASER WRITE PROCESSES FOR SPIDER INSPIRED MICROHYDRAULICS AND MULTI-SCALE LIQUID METAL DEVICES(2023) Smith, Gabriel Lewis; Bergbreiter, Sarah; Sochol, Ryan; Mechanical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Direct Laser Write (DLW) through two-photon polymerization (2PP) empowers us to delveinto the realm of genuine three-dimensional design complexity for microsystems, enabling features smaller than a single micrometer. This dissertation develops two novel fabrication processes that leverage DLW for functional fluidic microsystems. In the first process, we are inspired by arachnids that use internal hemolymph pressure to actuate extension in one or more of their leg joints. The inherent large foot displacement-to-body length ratio that arachnids can achieve through hydraulics relative to muscle-based actuators is both energy and volumetrically efficient. Until recent advances in nano/microscale 3-D printing with 2PP, the physical realization of synthetic complex ‘soft’ joints would have been impossible to replicate and fill with a hydraulic fluid into a sealed sub-millimeter system. This dissertation demonstrates the smallest scale 3D-printed hydraulic actuator 4.9 × 10^−4 mm^3 by more than an order of magnitude. The use of stiff 2PP polymers with micron-scale dimensions enable compliant membranes similar to exoskeletons seen in nature without the requirement for low-modulus materials. The bio-inspired system is designed to mimic similar hydraulic pressure-activated mechanisms in arachnid joints utilized for large displacement motions relative to body length. Using variations on this actuator design, we demonstrate the ability to transmit forces with relatively large magnitudes (milliNewtons) in 3D space, as well as the ability to direct motion that is useful towards microrobotics and medical applications. Microscale hydraulic actuation provides a promising approach to the transmission of large forces and 3D motions at small scales, previously unattainable in wafer-level 2D microelecromechanical systems (MEMS). The second fabrication process focuses on incorporating functionality through the use of liquid metals in 3D DLW structures. Room temperature eutectic Gallium Indium (eGaIn)- based liquid metal devices with stretchable, conductive, and reconfigurable behavior show great promise across many areas of technology, including robotics, communications, and medicine. Microfluidics provide one means of creating eGaIn devices and circuits, but these devices are typically limited to larger feature sizes. Developments in 3D printing via DLW have enabled sub-100 µm complex microfluidic devices, though interfacing microfluidic devices manufactured with DLW to larger millimeter-scale systems is difficult. The reduced channel diameter creates challenges for removing resist from the channels, filling microchannels with eGaIn, and electrically integrating them to larger channels or other circuitry. These challenges have prevented microscale liquid metal devices from being used more widely. In this dissertation, we demonstrate a facile, low-cost multiscale process for printing DLW microchannels and devices onto centimeter-scale custom fluidic channel substrates fabricated via stereolithography (SLA). This work demonstrates a robust interface between the two independently printed materials and greatly simplifies the filling of eGaIn microfluidic channels down to 50 µm in diameter, with the potential to achieve even smaller feature sizes of liquid metals. This work also demonstrates eGaIn coils with resistance of 43-770 mΩ and inductance of 2-4 nH. As a result, this process empowers us to manufacture interfaces that are not only low-temperature but also conductive and flexible. These interfaces find their application in connecting with sensors, actuators, and integrated circuits, thereby opening new avenues in the field of 3D electronics. Furthermore, our approach extends the lower limits of size-dependent properties for passive electronic components like resistors, capacitors, and inductors crafted from liquid metal, expanding the frontiers of possibilities in miniature electronic design.Item PERFORMANCE ENHANCEMENTS OF MICRO CORIOLIS VIBRATORY GYROSCOPES THROUGH LINEARIZED TRANSDUCTION AND TUNING MECHANISMS(2023) Knight, Ryan; DeVoe, Don L; Mechanical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)A quadruple mass Microelectromechanical System (MEMS) Coriolis vibratory gyroscope has been re-engineered with the singular focus of minimizing nonlinear transduction mechanisms, thereby allowing for angle random walk (ARW) noise reduction when operating at amplitudes higher than 2 μm. The redesign involved six primary steps: (i) the creation of an aspect-ratio independent deep reactive ion etch with minimal notching on 100 μm thick silicon-on-insulator device layer, (ii) the creation of micro-torr vacuum packaging capability, enabling operation at the thermoelastic dissipation limit of silicon, (iii) the redesign of Coriolis mass folded flexures and shuttle springs, (iv) the linearization of the antiphase coupler spring rate while maintaining parasitic modal separation, (v) the substitution of parallel plate transducers with linear combs, and (vi) the implementation of dedicated force-balanced electrostatic frequency tuners. Cross-axis stiffness is also reduced through folded-flexure moment balancing to further reduce ARW. By balancing positive and negative Duffing frequency contributions, net fractional frequency nonlinearity was reduced to -20 ppm. The gyroscope presented in this research has achieved, a first reported of its kind, an ARW of 0.0005 °/√hr, with an uncompensated bias instability of 0.08 °/hr. These advancements hold promise for enhancing navigation and North-finding applications. In tandem with gyroscope performance enhancements, vacuum packaging of ceramic chip carrier physics packages has achieved pressure levels below 1 micro-torr, a first in the field and remains state-of-the-art. Besides high-performance MEMS inertial sensors, ultrahigh vacuum packaging proves beneficial for chip scale atomic clocks, which require micro-torr vacuum levels to maintain fractional frequencies less than 10^-12. Finally, an approach to tuning the quality factor mismatch between degenerate modes in as-fabricated gyroscopes has demonstrated a reduction in gyroscope bias instability. This tuning can be achieved by incorporating lead zirconate titanate into regions where the trade-off between mechanical Q, tuning Q, and bias instability reduction is balanced. Both modeling and empirical frequency data justify this approach, suggesting, for typical MEMS foundry Q mismatch of 7%, a 70× reduction in bias instability.Item Functionalized Nanoparticles for the Controlled Modulation of Cellular Behavior(2023) Pendragon, Katherine Evelyn; Fisher, John; Delehanty, James; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The ability to control cellular behavior at the single-cell level is of great importance for gaining a nuanced understanding of cellular machinery. This dissertation focuses on the development of novel hard nanoparticle (NP) bioconjugate materials, specifically gold nanoparticles (AuNPs) and quantum dots (QDs), for the controlled modulation of cellular behavior. These hard NPs offer advantages such as small size on the order of 1 – 100 nm, high stability, unique optical properties, and the ability to load cargo on a large surface area to volume ratio, making them ideal tools for understanding and controlling cell behavior. In Aim 1, we demonstrate the use of AuNPs to manipulate cellular biological functions, specifically the modulation of membrane potential. We present the conception of anisotropic-shaped AuNPs, known as gold nanoflowers (AuNFs), which exhibit broad absorption extending into the near-infrared region of the spectrum. We demonstrate the effectiveness of utilizing the plasmonic properties AuNFs for inducing plasma membrane depolarization in rat adrenal medulla pheochromocytoma (PC-12) neuron-like cells. Importantly, this is achieved with temporal control and without negatively impacting cellular viability. Aim 2 explores the use of QDs as an optical, trackable scaffold for the multivalent display of growth factors, specifically erythropoietin (EPO), for the enhanced induction of protein expression of aquaporin-4 (AQPN-4) within human astrocytes. This results in enhanced cellular water transport within human astrocytes, a critical function in the brain's glymphatic system. We show that EPO-QD-induced augmented AQPN-4 expression does not negatively impact astrocyte viability and augments the rate of water efflux from astrocytes by approximately two-fold compared to cells treated with monomeric EPO, demonstrating the potential of EPO-NP conjugates as research tools and prospective therapeutics for modulating glymphatic system function. Overall, the body of work presented in this dissertation develops new NP tools, namely solid anisotropic AuNFs and growth factor-delivering QDs, for the understanding and control of cell function. These new functional nanomaterials pave the way for the continued development of novel NP-based tools for the precise modulation of cellular physiology.Item Ultra-high impedance superconducting circuits(2023) Mencia, Raymond; Manucharyan, Vladimir E; Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Chains of Josephson junctions are known to produce some of the largest kinetic per unit-length inductance, which can exceed the conventional geometric one by about 104. However, the maximum total inductance is still limited by the stray capacitance of the chain, which results in parasitic self-resonances. This stray capacitance is unnecessarily large in most circuits due to the high dielectric constant of silicon or sapphire substrates used. Here, we explore a regime of ultra-high impedance superconducting circuits by introducing the technique of releasing the Josephson chain off the substrate. The ultra-high impedance regime (Z > 4xRQ ~ 25.8 kOhms) is realized by combining a maximal per-unit-length inductance with a minimal stray capacitance and demonstrating the highest impedance electromagnetic structures available today. We begin with suspended “telegraph” transmission lines, composed of 30,000+ junctions, and show that the wave impedance can exceed 5 x RQ (33 kOhms) while the line still maintains a negligible DC resistance. To quantify the effects of parasitic chain modes in ultra-high impedance circuits, we use high-inductance fluxonium qubits. We show that chain modes are ultra-strongly coupled to the qubit but can be moved to a higher frequency with the Josephson chain releasing technique. Finally, we create a superconducting quasicharge qubit (blochnium), dual of transmon, whose impedance reaches over 30 x RQ (200 kOhms) with no evidence of parasitic modes below 10 GHz. This qubit completes the periodic table of superconducting atoms and demonstrates the dual nature of a small Josephson junction in ultra-high impedance circuits, which we probe in a DC experiment in the final chapter.Item MONOLAYER MOLYBDENUM DISULFIDE IN SEMICONDUCTOR ELECTRONICS(2023) Mazzoni, Alexander; Daniels, Kevin M; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Two-dimensional (2D) semiconductors are a new class of materials being researched due to their unique electrical, optical, and mechanical properties compared to their bulk counterparts. Here I investigate the use of the 2D semiconductor molybdenum disulfide (MoS2) as the active channel material in various electronic devices and circuits. Motivation is provided for 2D materials in general and monolayer MoS2 in particular, followed by an overview of the material properties of MoS2 and a relevant literature review. Back-gated field-effect transistors (FETs) were fabricated and characterized to investigate the impact of growth conditions on material properties, and to study the performance of different contact metals. A top-gated fabrication process was developed to make RF transistors and simple amplifier circuits on rigid and flexible substrates. Finally, device operating characteristics were modeled using simple transistor current-voltage equations, and Monte Carlo electron transport simulations were performed to demonstrate the importance of device operating temperature and intervalley separation in the conduction band.