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.

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Now showing 1 - 4 of 4
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    Simplifying assay chemistry via complex sample preparation integration for point-of-care diagnostics
    (2023) Everitt, Micaela Luisa; White, Ian; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Although therapeutics are undeniably important in the fight against any disease, a crucial step in making timely and effective therapeutic choices is diagnostics. Early treatments often lead to better patient outcomes, however early treatments are only possible with accessible diagnostics. Additionally, in public health emergencies, tracking the spread of disease via diagnostic tools is crucial to slowly and stopping it. Currently, standardized diagnostic testing is typically limited to central laboratories, requiring expensive, bulky instrumentation, trained technicians to perform these diagnostic tests, and the means to collect samples from patients, deliver the samples to the central laboratory, then return the results to the patient. In resource-limited settings (e.g., rural clinics), near-patient settings (e.g., at home), and in time-sensitive settings (e.g., emergency care), where accessibility and speed to a diagnosis are critical, the current central laboratory approach to diagnostic testing slows or even prevents an informed diagnosis and thus proper treatment. Subsequently, a large sector of the diagnostic field has focused away from a central laboratory approach and instead toward a near-patient paradigm, where samples can be testing immediately at the site of the patient such that results are rapidly available, allowing for faster treatment response. The diagnostic community refers to this idea of near-patient testing as point-of-care. Although point-of-care diagnostics have seen some commercial progress, the field is still struggling to develop tests for complex sample mediums. For complex samples, it is crucial that any sample preparation steps are integrated into the overall device to be truly considered point-of-care. Specifically, a diagnostic that can produce an easy-to-interpret result with little effort exerted by the user once the sample has been input is considered to be sample-to-answer. This dissertation highlights scientific advancements in the field of sample-to-answer diagnostics through optimized approaches that integrate higher order alkanes acting as pseudo-valves with point-of-care assay techniques. These higher order alkanes are solid at ambient temperatures and liquify when warmed and these alkanes can act as either as (1) a breachable barrier to allow for hands-free, controlled reagent mixing as the alkane melts or (2) as a permeable barrier that remains in place to separate assay regions, while magnetic beads can be pulled through. The behavior can be controlled by modifying the specific geometry in which the assay is confined. Developments involving thermally responsive alkane partitions enable complex sample processing and assay integration with intervention-free operation in low-cost, easily manufacturable cartridges. The work presented in this dissertation aims to address the need for sample-to-answer diagnostics, especially for complex samples, using these alkane partitions in three sequential avenues. This dissertation first details a point-of-care method to detect proteins, specifically histones, in whole blood, which can be a biomarker for severe internal trauma. This work demonstrates a hands-free technique for temperature-controlled reagent mixing as well as automated blood separation to allow for quantitative fluorescent measurements from whole blood samples. Although this work contributes to the field of sample-to-answer diagnostics, by integrating blood sample preparation, there was a need to generalize the diagnostic device to detect not just histones, but a broader category of protein biomarkers, like antibodies. Next, this dissertation assesses a sample-to-answer immunoassay, designed to quantify antibodies from whole blood which is useful to not only help track community spread of a disease, but also aid in validating vaccines and determining immunity. Although this diagnostic device was optimized to be as sensitive as its gold standard, central laboratory equivalent, in order to branch into nucleic acid biomarker detection, there was a need to include an exponential amplification step. Thus, finally, this dissertation looks at a sample-to-answer approach to monitor viral RNA genome in an additional complex sample, wastewater, in order to monitor the spread of disease community-wide. These sample-to-answer advancements to the field of point-of-care diagnostics enable low-cost, user-friendly solutions that increase overall accessibility to healthcare.
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    ANALYSIS AND IMPEDANCE-BASED DETECTION OF ELECTROMAGNETIC COIL INSULATION DEGRADATION
    (2019) Jameson, Noel Jordan; Pecht, Michael; Azarian, Michael H; Mechanical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Electromagnetic induction coils are widely used in a variety of applications, such as motors, solenoid valves, and relays. Many of these applications are safety-critical. Failure of the insulation that protects the windings in electromagnetic coils is a significant cause of coil failure and can have severe implications for system reliability. An effective insulation health monitoring program can reduce maintenance and replacement costs, predict the useful lifetime of the coil, and improve the operational availability of the system in which the coil is used. Impedance monitoring of coils has emerged as a promising approach for non-invasive, in-situ insulation health assessments of electromagnetic coils. Yet, little was understood about the relationship between coil impedance and traditional insulation health metrics, such as insulation capacitance and insulation resistance. Furthermore, relating the impedance measurements to chemical and mechanical characteristics of the insulation material is important to understanding the relationship between impedance measurements and the state of the insulation at failure. This study describes the development an improved method of electromagnetic coil insulation health monitoring and shows the uncovered relationships between coil impedance and the insulation electrical, chemical, and mechanical properties.
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    The Performance of Balance Diagnostics for Propensity-Score Matched Samples in Multilevel Settings
    (2019) Burnett, Alyson; Stapleton, Laura M; Measurement, Statistics and Evaluation; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The purpose of the study was to assess and demonstrate the use of covariate balance diagnostics for samples matched with propensity scores in multilevel settings. A Monte Carlo simulation was conducted that assessed the ability of different balance measures to identify the correctly specified propensity score model and predict bias in treatment effect estimates. The balance diagnostics included absolute standardized bias (ASB) and variance ratios calculated across the pooled sample (pooled balance measures) as well as the same balance measures calculated separately for each cluster and then summarized across the sample (within-cluster balance measures). The results indicated that overall across conditions, the pooled ASB was most effective for predicting treatment effect bias but the within-cluster ASB (summarized as a median across clusters) was most effective for identifying the correctly specified model. However, many of the within-cluster balance measures were not feasible with small cluster sizes. Empirical illustrations from two distinct datasets demonstrated the different approaches to modeling, matching, and assessing balance in a multilevel setting depending on the cluster size. The dissertation concludes with a discussion of limitations, implications, and topics for further research.
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    THERMOPLASTIC MICROFLUIDIC PCR TECHNOLOGIES FOR NEAR-PATIENT DIAGNOSTICS
    (2017) Sposito, Alex J.; DeVoe, Don L; Mechanical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Microfluidic technologies have great potential to help create portable, scalable, and cost-effective devices for rapid polymerase chain reaction (PCR) diagnostics in near patient settings. Unfortunately, current PCR diagnostics have not reached ubiquitous use in such settings because of instrumentation requirements, operational complexity, and high cost. This dissertation demonstrates a novel platform that can provide reduced assay time, simple workflow, scalability, and integration in order to better meet these challenges. First, a disposable microfluidic chip with integrated Au thin film heating and sensing elements is described herein. The system employs capillary pumping for automated loading of sample into the reaction chamber, combined with an integrated hydrophilic valve for precise self-metering of sample volumes into the device. With extensive multiphysics modeling and empirical testing we were able to optimize the system and achieve cycle times of 14 seconds and completed 35 PCR cycles plus HRMA in a total of 15 minutes, for successful identification of a mutation in the G6PC gene indicative of von Gierke’s disease. Next, a scalable sample digitization method that exploits the controlled pinning of fluid at geometric discontinuities within an array of staggered microfluidic traps is described. A simple geometric model is developed to predict the impact of device geometry on sample filling and discretization, and validated experimentally using fabricated cyclic olefin polymer devices. Finally, a 768-element staggered trap array is demonstrated, with highly reliable passive loading and discretization achieved within 5 min. Finally, a technique for reagent integration by pin spotting affords simplified workflow, and the ability to perform multiplexed PCR. Reagent printing formulations were optimized for stability and volume consistency during spotting. Paraffin wax was demonstrated as a protective layer to prevent rehydration and reagent cross contamination during sample loading. Deposition was accomplished by a custom pin spotting tool. A staggered trap array device with integrated reagents successfully amplified and validated a 2-plex assay, showing the potential of the platform for a multiplexed antibiotic resistance screening panel.