Theses and Dissertations at Montana State University (MSU)
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Item Development and characterization of a novel isothermal DNA amplification reaction(Montana State University - Bozeman, College of Engineering, 2021) Ozay, Burcu; Chairperson, Graduate Committee: Scott McCalla; This is a manuscript style paper that includes co-authored chapters.Isothermal nucleic acid amplification chemistries are gaining popularity as nucleic acid detection tools that can replace the current gold standard methods, PCR and its derivatives, with their simplicity, speed and applicability to point-of-care applications. In this work, we have developed and characterized a novel isothermal amplification chemistry, ultrasensitive DNA amplification reaction (UDAR). UDAR differs from similar chemistries with its unique, biphasic response with a high-gain output that can be captured with a cell-phone camera. The switch-like, nonlinear characteristics provide a definitive on/off signal for potential use in applications such as molecular diagnostics and DNA circuits. Tunability of the reaction was explored and the relationship between thermodynamic properties of the reaction templates and the reaction output was established. Limitations on fluorescent staining of reaction components by two popular commercial nucleic acid stains, SYBR Green II and SYBR Gold, were determined for a more accurate evaluation of the reaction output and reaction product analysis. A mathematical model of the reaction output was built and outputs from three different UDAR templates were successfully simulated. This model revealed important information on reaction pathways and helped identify the impact of individual reaction events. A comprehensive literature review of enhancement strategies for isothermal amplification reactions was conducted to serve as a guide to improve and modify these reactions according to different needs and applications. Lastly, UDAR was applied to microRNA detection, which are putative biomarkers for diseases such as cancer, malaria, and traumatic brain injury. Five different miRNAs were successfully detected by UDAR, down to 10 fM concentration. UDAR-based miRNA quantification is possible, with linear calibration curves provided between 10fM and 1 nM. This work has significant contributions to the growing field of isothermal nucleic acid amplification based-molecular detection systems by introducing a unique isothermal amplification chemistry, establishing design and manipulation techniques, and guiding improvement efforts of these technologies.Item Analysis of transport in the brain(Montana State University - Bozeman, College of Engineering, 2021) Ray, Lori Ann; Chairperson, Graduate Committee: Jeffrey Heys; Jeffrey J. Heys was a co-author of the article, 'Fluid flow and mass transport in brain tissue: a literature review' in the journal 'Fluids' which is contained within this dissertation.; Jeffrey J. Iliff and Jeffrey J. Heys were co-authors of the article, 'Analysis of convective and diffusive transport in the brain interstitium' in the journal 'Fluids and barriers of the CNS' which is contained within this dissertation.; Martin Pike, Jeffrey J. Iliff and Jeffrey J. Heys were co-authors of the article, 'Quantification of transport in the whole mouse brain' which is contained within this dissertation.Neurodegeneration is one of the most significant medical challenges facing our time, yet the gap between therapies and understanding of the inner workings of the brain is great. Impairment of waste clearance has been identified as one key underlying factor in the vulnerability of the brain to neurodegeneration, stimulating research towards understanding transport of molecules in the brain. Based on experimental findings, a unique-to-the-brain circulation has been proposed, the glymphatic system, where cerebrospinal fluid surrounding the brain moves into the brain along the periarterial space that surrounds cerebral arteries, flows through the interstitial space between brain cells, where cellular wastes reside, and carries waste out of the brain tissue along perivenous routes. However, current gaps in knowledge about the driving force for fluid flow have generated scientific skepticism, and an independent method for quantifying transport and demonstrating the presence or absence of convection is desirable. In this work, computational transport models are developed and used to analyze published experimental data to determine fundamental transport parameters for different aspects of the glymphatic circulation. Calculated transport parameters are compared to the known diffusivity of tracers through brain tissue to draw conclusions about the presence and significance of bulk flow, or convection. Based on these analyses, transport in the periarterial spaces surrounding major arteries is over 10,000 times faster than diffusion and in brain tissue, containing both periarterial and interstitial space, transport is around 10 times faster than diffusion alone (for characteristic transport lengths around 1 mm). Interstitial velocity is determined to be on the order of 0.01 mm/min, making convection in the interstitial spaces of the brain critical to the transport of large, slow-to-diffuse molecules implicated in neurodegeneration. Convection is demonstrated to be a significant mechanism of transport throughout the brain. Observations and analyses from this work contribute further evidence to a circulatory-like system in the brain with relatively rapid convection along periarterial space, branching throughout the brain tissue and slower convection across that tissue, in the interstitial spaces of the brain. Transport models developed in this work are demonstrated to be useful tools for gleaning further information from experimental data.Item Kinetic modeling of gold nanoparticle formation for radiation dose prediction(Montana State University - Bozeman, College of Engineering, 2017) Akar, Burak; Chairperson, Graduate Committee: Jeff Heys; James Wilking (co-chair)Nanoparticles have numerous uses in the biomedical sciences, and this study focused on use of gold nanoparticles (GNPs) for measuring ionizing radiation dose. GNPs synthesized at various radiation doses were experimentally characterized and two mathematical models were developed to simulate the synthesis process. The first is based on the Finke-Watzky model and predicts the rate of soluble gold salt conversion to GNPs, and the second model is based on a population balance model and predicts nanoparticle concentration and size distribution. The model parameters that provided an optimal fit to experimentally gathered data were determined, and both models were able to capture the experimental absorbance time trends. The population balance model, however, had the greater predictive power as it was able to capture mean particle size trends that were consistent with experimental measurement.Item Computer calculations for binary electrolyte vapor-liquid equilibrium(Montana State University - Bozeman, College of Engineering, 1969) Nelson, Gary DaleItem Control of microbial souring of oil in a porous media column(Montana State University - Bozeman, College of Engineering, 1995) Reinsel, Mark AndrewItem Mathematical models for inorganic processes found in a zinc plant(Montana State University - Bozeman, College of Engineering, 1973) James, Rodney Allen