UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
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 given thesis/dissertation in DRUM.
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Item SAMPLE-TO-ANSWER POINT-OF-CARE VIRUS DIAGNOSTIC SYSTEM USING THERMALLY RESPONSIVE ALKANE PARTITIONS(2024) Boegner, David John; White, Ian M; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Many viral infections can be accurately diagnosed using today’s most sophisticated detection systems. Unfortunately, many of these detection systems fail to benefit society as a whole, but rather favor select areas of the world that are able to install and maintain the infrastructure such diagnostics require. Thus, in an effort to eliminate the barrier of access to diagnosis and treatment in low-and-middle-income areas, portable point-of-care devices are fabricated such that rapid results can be obtained without the need for bulky lab equipment or skilled technicians. An ideal point-of-care diagnostic device can easily collect an untampered sample and limits a patient’s encounter with a clinician to a single visit for both the diagnosis and the treatment. Many so-called point-of-care diagnostics for blood-borne viruses first require blood sample preparation (e.g. centrifugation) prior to testing in the device. Other point-of-care devices sacrifice diagnostic accuracy in favor of speed and portability. Both cases demonstrate our inability to properly distribute the benefits of sophisticated diagnostics worldwide.I present a solution in the form of an affordable handheld diagnostic device with the sensitivity and specificity of benchtop lab equipment and built-in automatic sample preparation. Automatic sample preparation will be achieved using thermally responsive alkane partitions, which are solid at ambient temperatures and liquid at moderately elevated temperatures. When liquid, the alkane partitions allow passage of magnetically activated microbeads coated with material that captures viruses. Despite magnetic beads with virus particles passing through, the alkane partition continues to prevent unwanted sample components (e.g. blood cells, DNases, etc.) from interfering with the virus-detecting mechanism on the other side. To address the lack of sensitivity in many point-of-care diagnostics, the virus-detecting mechanism will feature isothermal amplification which enables detection of attomolar concentrations of virus within 30 minutes without expensive thermo-cycling equipment that standard detection systems require. The novel technology described here is demonstrated in a platform which detects SARS-CoV-2 from blood, a capability currently unachievable in point-of-care settings.Item ISOTHERMAL DNA DETECTION UTILIZING BICYCLIC AMPLIFICATION OF PADLOCK PROBES(2019) Zimmermann, Alessandra C.; Kahn, Jason D; White, Ian M; Biochemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)As healthcare worldwide changes to more patient-centric models, medical diagnostics need to adapt to being used in settings outside of the central lab. Current strategies to bring diagnostics to the patient’s bedside involve miniaturizing complicated amplification techniques, such as polymerase chain reaction, or building convoluted microfluidic assays that are difficult to operate. Ideally, a patient-centric diagnostic would require little instrumentation or training to operate, for which isothermal amplification techniques are ideal. Recent developments in catalytic DNA have enabled novel ways of iterating on amplification strategies to detect medically-relevant target sequences in systems that require little manipulation to operate. In this thesis we improve upon the body of research on DNAzymes, catalytic DNAs that can self-cleave in the presence of a cofactor, used in concert with amplification techniques. We create a one-pot, bicyclic amplification assay capable of detecting single-stranded oligonucleotides, with straightforward extensions to double-stranded targets, multiplexing, and integration into advanced detection platforms. The target is detected through its hybridization to a circle template, using the sequence specificity of DNA to splint the ligation of this ‘Template I,’ with minimal detection of off-target sequences. The circular Template I is copied through rolling circle amplification (RCA), with the amplicon containing a DNAzyme that will self-cleave in the presence of copper ions. This generates a second primer in situ that can be used to prime a second, pre-ligated, Template II to elevate the RCA amplification scheme from a linear method to a polynomial one. This Circle II template can then be used in a variety of detection modalities. The second amplicon can be used to cleave a hybridized FRET probe through the same copper ion cleavage mechanism as the primer generation, resulting in real-time fluorescence tracking. Alternatively, the RCA of the second circle can produce G-quadruplexes, which can be visualized with ABTS as a colorimetric endpoint that can be seen by eye, reducing the need for peripheral electronics. Finally, this thesis demonstrates the performance of the bicyclic RCA system in a phase-change system providing sequential mixing of components separated by wax layers, allowing the assay to proceed without any user interaction other than heating.Item Novel Emittance Measurement Through Experimental Study of Envelope Mode Resonance in a High-Intensity Particle Beam(2015) Stem, William Durst; Koeth, Timothy W; O'Shea, Patrick G; Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)On-line monitoring of beam quality for high-intensity particle beams requires non-invasive transverse phase space diagnostics. Such diagnostics are in high demand for use in heavy ion accelerators and free-electron lasers (FELs). A technique to measure emittance using multi-turn resonant excitation of the quadrupole envelope mode has been demonstrated at the University of Maryland Electron Ring (UMER). The rms Kapchinsky-Vladimirsky (KV) equations predict the time-evolution of particle beam envelopes. Linear perturbations to the matched envelope solution of these equations excite normal modes at space-charge-dependent natural frequencies. This experiment employs periodic, impulsed perturbations to drive resonant excitations of these modes. Steady state resonance structure in the form of a lattice is predicted using analytic solutions of a delta-kicked simple harmonic oscillator (SHO). Numerical simulations of this SHO along with simulations from the WARP envelope solver and particle-in-cell (PIC) codes are documented. This dissertation presents the first proof-of-principle experimental resonant excitation of the quadrupole envelope mode in a high-intensity particle beam. To excite the mode experimentally, an rf-driven electric quadrupole is constructed and installed in UMER. The quadrupole fields are driven by a tunable resonant tank circuit designed and built for this experiment. After resonant excitation, the knockout imaging method is used to collect 3 ns synchronized transverse time slice images of the beam. Image moments are analyzed and show good agreement with simulation. Emittance can then be inferred from the measured natural frequencies of the envelope modes utilizing a conversion obtained through simulation. A direct emittance measurement is performed using a conventional pinhole scan at injection as an experimental validation of the envelope resonance method.