UMD Theses and Dissertations
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Item Development of single-neuron proteomics by mass spectrometry for the mammalian brain.(2021) Choi, Bok Dong; Nemes, Peter; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Single-neuron proteomics holds the potential to advance our understanding of important biological processes during neuron maturation and development. However, to characterize proteins from single neurons, further technological advances are still required. This dissertation discusses the development and application of single-cell mass spectrometry (MS) technologies to investigate proteins and its role in different neurons. The work presented herein demonstrates the strategies to develop and advance single-neuron analysis using capillary electrophoresis (CE)-MS. In addition, this work features several contributions to our understanding of neuron-to-neuron heterogeneity, providing new information to advance cell biology and neuroscience.Item A prototype miniature mass spectrometer for in situ analysis of trace elements on planetary surfaces(2021) Farcy, Benjamin Jacob; Arevalo, Ricardo D; McDonough, William F; Geology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Interrogation of the chemical composition of rocky planets provides a deeper understanding of the history and evolution of the solar system. While laboratory studies of returned samples and remote sensing surveys of planetary surfaces can give insight into planetary history, one technique that has delivered major insights to planetary geology is in situ measurements of a planetary surface via mass spectrometry. Here, a new approach to spaceflight mass spectrometry is discussed, including an overview of the pursued scientific questions, the analytes targeted, and the prototype hardware in development. This effort constitutes the scientific and technological foundation of a landed planetary mission. This dissertation focuses on the history and evolution of the Earth-Moon system as recorded by trace elements. Specifically, the abundance and distribution of the heat producing elements (HPEs: K, Th, U) and their implications for mantle dynamics is considered. The radiogenic heat produced from K, Th, and U drives mantle convection, volcanism, and planetary dynamos. To understand better the chemical dynamics of radiogenic heat distribution in the Earth, the HPE abundance of a series of oceanic basalts was statistically analyzed. This analysis revealed the K/U ratio of the mantle and how it changes due to the enrichment or depletion of incompatible elements. The HPE abundance of the lunar interior was also discussed as a target of a future investigation, along with a series of trace element proxies meant to probe the lunar farside mantle. Further, an analysis of lunar farside craters provides a series of landing sites for an in situ mission, specifically for their surficial exposure of upper mantle material and later emplacement of lunar basalts. To access the trace element systems discussed in this dissertation, a prototype miniature inductively coupled plasma mass spectrometer (ICPMS) was developed to analyze trace elements in situ for landed planetary missions. First, the capability of the plasma to atomize and ionize input material was investigated. A plasma operating at reduced pressure can achieve 99\% ionization efficiency of most elements on the periodic table, with as much as a 50 to 100 times reduction in gas load and forward power compared to commercial systems for both He and Ar based plasma ion sources. The plasma system was integrated with a quadrupole mass spectrometer via a series of DC ion optics and vacuum housing, with its ion current and peak resolution optimized. Quantative data for an analyte spectrum of Kr demonstrates the ability for this instrument to resolve individual mass peaks, which lead to an accuracy and precision measurement of isotope ratios. This effort represents an end-to-end prototype miniature ICPMS, successfully demonstrating a viable instrument for landed planetary missions.Item COMPUTATIONAL ANALYSIS OF METABOLIC NETWORKS AND ISOTOPE TRACER EXPERIMENTS FOR METABOLIC FLUX EVALUATION IN COMPLEX SYSTEMS(2021) Lugar, Daniel James; Sriram, Ganesh; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Metabolic engineering endeavors seek to develop microorganisms as feedstocks for biofuels and commodity chemicals. Towards this, quantifying metabolic fluxes is an important step for characterizing an organism’s metabolism and designing effective engineering strategies. Metabolic fluxes are quantified using sophisticated techniques, namely flux balance analysis (FBA), an in silico technique, and isotope-assisted metabolic flux analysis (MFA), a hybrid experimental and computational technique. FBA uses a network’s stoichiometry with linear programming techniques to generate in silico flux predictions for genome-scale networks. MFA uses measurements from stable isotope (typically 13C) tracer experiments to estimate fluxes of central carbon metabolism. In MFA, fluxes are parameters to a model developed from the network’s carbon atom rearrangements, which is fit to isotope labeling data, typically acquired using mass spectrometry.We developed novel mathematical and computational techniques for quantifying and analyzing flux predictions obtained using MFA and FBA. FBA applications typically generate flux predictions for networks with on the order of 1000 [O(1000)] reactions and metabolites. We developed a network reduction algorithm that uses matrix algebra to reduce a large network and flux prediction to a smaller representation. From this reduced representation, a researcher may quickly gain holistic insights from the FBA model. In isotopically nonstationary MFA, time-series labeling measurements are acquired on the approach to steady state. A model consisting of a large system of typically O(1000) ordinary differential equations is fit to the measurements to estimate fluxes and pool sizes. For detailed networks, the number of parameters may be large. We developed a computationally effective framework for solving this problem having robust convergence and efficient scalability to large networks. In this approach, we formulate the problem as an equality-constrained nonlinear program (NLP), solved efficiently using a solver implemented on an algebraic modeling language. Finally, we apply this approach to a detailed model of Phaeodactylum tricornutum photoautotrophic and mixotrophic (on acetate) metabolism. Using the flux estimates, we characterized this organism’s metabolism under disparate growth conditions, which may inform future endeavors to engineer P. tricornutum as a chemical feedstock.Item Understanding the Relationships Between Architecture, Chemistry, and Energy Release of Energetic Nanocomposites(2017) DeLisio, Jeffery Brandon; Zachariah, Michael R; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Energetic nanocomposites are a class of reactive material that incorporate nanosized materials or features in order to enhance reaction kinetics and energy densities. Typically, these systems employ metal nanoparticles as the fuel source and have demonstrated reactivities orders of magnitude larger than more traditionally used micron-sized metal fuels. One drawback of using nanosized metals is that the nascent oxide shell comprises a significant weight percent as the particle size decreases. This shell also complicates the understanding of oxidation mechanisms of nanosized metal fuels. In this dissertation, I apply a two-fold approach to understanding the relationships between architecture, chemistry, and energy release of energetic nanocomposites by 1) investigating alternative metal fuels to develop a deeper understanding of the reaction mechanisms of energetic nanocomposites and 2) creating unique microstructures to tailor macroscopic properties allowing for customizability of energetic performance. In order to accurately study these systems, new analytical techniques capable of high heating rate analysis were developed. The oxidation mechanisms of tantalum nanoparticles was first probed using high heating rate TEM and Temperature-Jump Time-of-Flight Mass Spectrometry (T-Jump TOFMS) and shell crystallization was found to plan an important role in the mechanism. An air-sensitive sample holder was developed and employed to analyze the decomposition and oxidation of molecular aluminum compounds, which theoretically can achieve similar energy release rates to monomolecular explosives in addition to much higher energy densities. In order to obtain simultaneous thermal and speciation data at high heating rates, a nanocalorimeter was integrated into the TOFMS system and measurements were performed on Al/CuO nanolaminates to probe the effect of bilayer thickness on energy release. An electrospray based approach to creating energetic nanocomposites with tunable architectures is also described. An in depth study on the electrospray synthesized nAl/PVDF thin film reaction mechanism was performed using T-Jump TOFMS. The nAl/PVDF system was also studied using a Molecular Beam Sampling Time-of-Flight Mass Spectrometer designed and built primarily to investigate the reaction mechanisms of energetic nanocomposites at 1 atm in both aerobic and anaerobic environments.Item Lanthanoid Isotopic Composition of Pre and Post-Detonation Nuclear Material(2014) Sharp, Nicholas Eugene; Mignerey, Alice C; McDonough, William F; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Analysis of lanthanoid isotopic composition of pre and post-nuclear detonation materials provides information on the type of device, origin of fissile material, and in the case of spent nuclear fuel, the operating history of the reactor. Prior to analysis, the lanthanoids must be separated from bulk materials to reduce exposure to harmful radiation and to remove isobaric interferences. Trinitite and spent nuclear fuel rods are appropriate analogues for post and pre-detonation nuclear materials, respectively. Compositional analysis of trinitite glass, fused silicate material produced by the Trinity test, reveal non-normal Nd isotope composition, with deviations of -1.66 ± 0.48 e; (differences in parts in 104) in 142Nd/144Nd, +2.24 ± 0.32 e; in 145Nd/144Nd, and +1.00 ± 0.66 e; in 148Nd/144Nd (2σ) relative to natural reference materials. Greater isotopic deviations are found in Gd, with enrichments of +4.28 ± 0.72 e; in 155Gd/160Gd, +4.19 ± 0.56 e; in 156Gd/160Gd, and +3.59 ± 0.37 e; in 158Gd/160Gd. The isotopic deviations are consistent with a 239Pu based fission device with additional 235U fission contribution and a thermal neutron fluence between 0.97 and 1.4 x 1015 neutrons/cm2. Separation and analysis of spent nuclear material is a difficult challenge in both logistics and sample handling. Lanthanoids were removed from the bulk spent nuclear fuel at Savannah River National Laboratories, while the separation of Gd, Sm and Nd was carried out at the University of Maryland. The isotopic composition of Nd and Sm were compared to predicted values calculated using two programs that were developed for modeling the burning cycle of traditional power-reactors: Oak Ridge Isotope GENeration (ORIGEN-S) and Monte Carlo N-particle transport code (MONTEBURNS). The isotopic composition of Nd agreed with predicted values within 10% with the exception of 142Nd, while only 150Sm had agreement within 10% of prediction. These results show that the typical calculation codes are not adequately modeling the intense neutron flux present in research reactors, and further work will need to be done before source reactors can be identified using reverse modeling algorithms.Item Methods and Standards for the Analysis and Imaging of Latent Fingerprints and Trace Contraband using Ambient Ionization Mass Spectrometry and Secondary Ion Mass Spectrometry(2014) Sisco, Edward; Mignerey, Alice C; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)A recent report from the National Academy of Sciences (NAS), evaluating the state of forensic science, identified the need to more rapidly, accurately, and reproducibly provide scientifically validated forensic analyses of evidence to support the criminal justice system. The NAS report also highlighted the need for the forensic science community to collaborate with universities and national laboratories, as well as to forge relationships with the National Institute of Standards and Technology (NIST) to address method development, validation, and evaluation of new analytical techniques of relevance to forensic science. This thesis was completed as part of a unique collaboration between the University of Maryland (UM), the National Institutes of Standards and Technology (NIST) and the Defense Forensic Science Center (DFSC) to address several of the existing research needs in current forensic science practice while meeting the requirements for a Department of Defense (DOD) Science Mathematics and Research for Transformation (SMART) fellowship and supporting NIST efforts in trace contraband detection. Two distinct areas of research were pursued. First, studies were conducted on method development and validation for the detection of explosives using four different ambient ionization mass spectrometry (AI-MS) techniques relevant to routine casework at DFSC and to other federal labs that screen for trace contraband. Additional method validation studies for the detection of adulterants in beverages and the analysis of bank dye are also presented. All methods were developed in accordance with the requirements specified by the International Organization of Standardization (ISO) 17025 guidelines, which is the accreditation standard for practicing forensic laboratories. The second track of this thesis involved exploration of emerging analytical methods, and several novel applications, for mass spectrometry based chemical imaging of both endogenous and exogenous components in latent fingerprints. This work was driven by a recent National Science Foundation (NSF) report that identified mass spectral imaging (MSI) as a key goal for the future development of forensic science. Both AI-MS and secondary ion mass spectrometry (SIMS) techniques were utilized and evaluated for their ability to chemically image fingerprints. To support these studies, a novel standard fingerprint test material was also developed during this research. As a result of this work there are now validated methods for the screening of trace explosives, as well as other types of forensic evidence such as adulterants and bank dye, that can be reliably employed into the casework scheme. Also, there are new applications and capabilities for MSI of fingerprints and an artificial fingerprint material that allows for the reproducible deposition of test fingerprints.Item EVALUATION OF MASS FILTERED, TIME DILATED, TIME-OF-FLIGHT MASS SPECTROMETRY(2010) Demoranville, Leonard Thomas; Mignerey, Alice C; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The Naval Research Laboratory's Trace Element Accelerator Mass Spectrometer (NRL-TEAMS) system offers a unique opportunity to develop a new type of time-of-flight (TOF) SIMS. This opportunity derives from use of a Pretzel magnet as a recombinator and mass filter in the injector to the accelerator. Mass filtering prior to time-of-flight analysis removes extraneous species, shortening the analysis time for a single beam pulse, thereby improving the duty cycle. Using this approach, it is possible to obtain an expanded portion of a narrow segment of the entire time-of-flight spectrum created by a single beam pulse. A longer flight path for greater momenta in the Pretzel magnet introduces time dilation. Potential benefits derived from time dilation and mass filtering include improved duty cycle, shorter analysis time, increased precision, and better resolution. While the NRL-TEAMS system is not designed for TOF work, it has been used as a test bed to prove the theoretical benefit of such a design. Theoretical treatments of the spectrometer have shown improved resolution is possible under certain conditions, when compared to a traditional TOF spectrometer. SIMION 8.0 computer simulations were used to model the system and provide insight to the theoretical capabilities of the Pretzel magnet. As expected, models have shown that as field decreases, and therefore path length increases, mass resolution improves. Generally, the model matched well to experimental results provided by the NRL TEAMS system. These experimental results have predicted fundamental parameters of the system accurately and consistently, and confirmed the validity of the model. This research improved the current system's performance through improved electronics and pulsing and further uses the model to predict the theoretical benefits of a system designed for use with a Pretzel magnet.Item Mass Spectrometric Analysis of Cytoplasmic Ribosomal Proteins in Drug Resistant and Drug Susceptible Human Cell Lines(2006-05-30) Hays, Faith A; Fenselau, Catherine; Biochemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This study examines changes in cytoplasmic ribosomes that accompany drug resistance in MCF-7 breast cancer cells. Differences in ribosomal protein composition between drug susceptible and drug resistant cell lines were examined. Ribosomes were isolated from mitoxantrone susceptible and mitoxantrone resistant MCF-7 cells. The acid extracted ribosomal proteins were subjected to optimized 2DGE using a "zoom" strip (pI 7-11) for the first dimension separation. Further optimization of 2DGE included the use of a 15mM DTT wick at the cathode end of the focusing tray, decreasing the protein loading amount and using large format gels for the second dimension. Forty-nine ribosomal proteins were identified in the drug susceptible cell line. Two novel protein isoforms of the proteins RPS3 and one novel isoform of RPS10 were identified in the drug resistant cell line. Methods for the extraction and detection of ribosomal proteins from the 2D gel were developed. The method of Mirza et.al. was modified and used to extract ribosomal proteins from the gel. The detection of these proteins was optimized by the use of 50% ACN/1.0% TFA to solubilize the MALDI matrix. In addition, the extracted protein solution was mixed 1:1 with 5% Triton X-100. Intact molecular weights were determined for 41 ribosomal proteins using high performance MALDI-TOF mass spectrometry. The average number of ribosomes per cell was determined for the drug susceptible, as well as the drug resistant cell line, and found to be unchanged.Item Real-Time In-Situ Chemical Sensing in AlGaN/GaN Metal-Organic Chemical Vapor Deposition Processes for Advanced Process Control(2004-08-04) Cho, Soon; Rubloff, Gary W; Material Science and Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Gallium nitride and its alloys promise to be key materials for future semiconductor devices aimed at high frequency, high power electronic applications. However, manufacturing for such high performance products is challenged by reproducibility and material quality constraints that are notably more stringent than those required for optoelectronic applications. To meet this challenge, in-situ mass spectrometry was implemented as a real-time process- and wafer-state metrology tool in AlGaN/GaN/AlN metal-organic chemical vapor deposition processes on semi-insulating SiC substrate wafers. Dynamic chemical sensing through the process cycle, carried out downstream from the wafer, revealed generation of methane and ethane reaction byproducts, as well as other residual gas species. Real-time metrics were derived based on the chemical signals to predict/control material quality and thickness of critical layers within the heterostructure in real time during growth, and corresponding metrologies were used for real-time advanced process control. Using the methane/ethane ratio, GaN epilayer crystal quality was predicted in real time to 2 5% precision, which was verified by post-process x-ray diffraction. Moreover, the same real-time metric predicted material quality as indicated by post-process photoluminescence band-edge intensities to ~5% precision. The methane/ethane ratio has a fundamental significance in terms of the intrinsic chemistry in that the two byproducts are believed to reflect two parallel reaction pathways leading to GaN-based material growth, namely the gas phase adduct formation route and the surface route for direct precursor decomposition, respectively. The fact that lower methane/ethane ratios consistently yield better material quality suggests that the surface pathway is preferred for high quality GaN growth. In addition, a metric based on methane and ethane signals integrated through the AlGaN growth period (~1 min or less) enabled prediction of the cap layer thickness (~20 nm) to within ~1% precision, which was verified by post-process x-ray reflectance. These types of real-time advanced process control activities in terms of fault detection and management, course correction, and pre-growth contamination control have made significant contributions to the GaN-based semiconductor development and manufacturing at Northrop Grumman Electronics Systems in terms of improved material quality, yield, and consequent cost reduction, and they are now in routine use.