Electrospray is an atomization method subject to intense study recently due to its monodispersity and the wide size range of droplets it can produce, from nanometers to hundreds of micrometers. This thesis focuses on the numerical and theoretical modeling of the interaction of charged droplets from the single and multiplexed electrospray. We studied two typical scenarios: large area film depositions using multiplexed electrospray and fine pattern printings assisted by linear electrostatic quadrupole focusing. Due to the high computation power requirement in the unsteady n-body problem, graphical processing unit (GPU) which delivers 10 Tera flops in computation power is used to dramatically speed up the numerical simulation both efficiently and with low cost. For large area film deposition, both the spray profile and deposition number density are studied for different arrangements of electrospray and electrodes. Multiplexed electrospray with hexagonal nozzle configuration can not give us uniform deposition though it has the highest packing density. Uniform film deposition with variation < 5% in thickness was observed with the linear nozzle configuration combined with relative motion between ES source and deposition substrate. For fine pattern printing, linear quadrupole is used to focus the droplets in the radial direction while maintaining a constant driving field at the axial direction. Simulation shows that the linear quadrupole can focus the droplets to a resolution of a few nanometers quickly when the interdroplet separation is larger than a certain value. Resolution began to deteriorate drastically when the inter-droplet separation is smaller than that value. This study will shed light on using electrospray as a scalable nanomanufacturing approach.

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No description available.

No description available.

Accelerator Mass Spectrometry (AMS) studies of rare isotopes with abundant isobars that form negative ions often require the use of large accelerators to achieve high sensitivity measurements. The Isobar Separator for Anions (ISA) is a radiofrequency quadrupole (RFQ) reaction cell system that provides selective isobar suppression for many of these isotopes in the low energy system, prior to injection into an accelerator. The ISA can then facilitate the measurement of these ions using smaller accelerators. A commercial version from Isobarex Corp. was installed in a separate low energy injection line of the 3 MV accelerator system at the A. E. Lalonde AMS Laboratory in the University of Ottawa and was tested using the measurement of 36Cl, suppressing its stable isobar 36S. The ISA includes a DC deceleration region, a combined cooling and reaction cell, and a DC acceleration region. The deceleration region reduces the beam energy from the ion source (20-35 keV) to a level that chemical reactions can occur, scattering is minimized, and that the reaction cell can accept and contain. RFQ segments along the length of the cell create a potential well, which limits the divergence of the traversing ions. DC offset voltages on these RFQ segments maintain a controlled ion velocity through the cell. Helium was used as a cooling gas to further decelerate the ions, facilitating charge exchange between 36S and a reaction gas. Helium provided the highest transmission of 30-80% for chlorine anions. The reaction gas NO2 was chosen to preferentially react with sulfur. Over seven orders of magnitude reduction of sulfur to chlorine was observed. After exiting the cell, the beam is reaccelerated prior to injection into the tandem accelerator for AMS analysis. Using 36Cl reference materials, it was determined that linear transmission results could be obtained for a 36Cl/Cl ratio ranging from 10−11 to 10−15. The measurements were stable over more than 24 hours of continuous measurement. A blank level on the order of 10−15 was observed. The ISA was used to measure unknown 36Cl /Cl ratio groundwater samples and the results are compared to external AMS measurements.

Gastroparesis is a disorder characterized by delayed gastric emptying due to chronic abnormal gastric motility. Prokinetic agents such as domperidone and metoclopramide are the cornerstone in treatment of gastroparesis. Although these medications have been used for decades, essential information about their metabolism is not available. Lack of knowledge about the metabolites formed in the body upon administration of the aforementioned medications as well as the enzymes involved in their metabolism limits key information needed to make sound medical decisions. Accurate and comprehensive identification of the metabolites along with reaction phenotyping of prokinetic agents will ensure safe and effective use of these drugs and hence enhance the clinical outcome. The thesis starts with an introductory chapter which comprises a comprehensive literature review on gastroparesis and the available pharmacological treatment options. The chapter also emphasizes the importance of metabolic profiling of prokinetic agents (domperidone and metoclopramide) and its impact on enhancing the safety and efficacy of these medications. Chapter 2 of this project was aimed to determine phase oxidative and conjugative metabolites of domperidone in the plasma and urine of gastroparesis patients using tandem mass spectrometry. First, the metabolites were identified in in-vitro human subcellular fractions. The knowledge gained in this experiment helped identifying the metabolites in the biological fluids of patients. In total, 12 metabolites including 7 new metabolites were identified, 5 of which were not reported previously. Chapter 3 aimed to identify the cytochrome P450 (CYP) enzymes responsible for the metabolism of metoclopramide. The parent depletion approach was used and a novel LC-MS/MS method was developed and validated to enable metoclopramide quantification. CYP2D6 was showed to the predominant isoform in metoclopramide metabolism; other isoforms also contribute to a minor extent. Chapter 4 discusses the possibility of potential drug-drug interaction (DDI) in the current management practice of gastroparesis. We identified and investigated some frequently used drug combinations that are known to share common metabolic pathways. Domperidone in combination with pioglitazone and ondansetron was evaluated. Results showed that pioglitazone inhibited domperidone metabolism in-vitro. Our experiments did not predict a DDI for the domperidone - ondansetron combination. In summary, the ultimate goal of this thesis was to improve the management of gastroparesis by increasing information about the metabolic disposition of prokinetic agents and to investigate the magnitude of putative drug combinations. The knowledge provided by this work will help in making more effective and less hazardous clinical decisions which will ultimately lead to more successful gastroparesis management. / Pharmaceutical Sciences

Phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxylase (Pepc) are two important CO₂-fixation enzymes which share a similar reaction mechanism. Both operate through a lid-gated active site and have a hypothesized enol-pyruvate intermediate in their catalytic pathway. While PEPCK is an important metabolic enzyme in animals and plays a broad role in cataplerosis, gluconeogenesis and glyceroneogenesis, Pepc reaction in plants catalyzes the first committed step in CO₂ fixation in CAM and C₄ plants via Rubisco. We are studying the structure-function aspects of both enzymes, with a goal of discovering new elements in these enzymes which can modulate catalysis. We have undertaken an interdisciplinary approach for this work and have shown that a combination of experimental and computational techniques can be complementary and can provide novel information. We have determined that in human PEPCK, Tyr235 forms an anion-quadrupole interaction with the carboxylate of PEP and thus positions the latter with respect to the enzyme-bound Mn²+ for optimal phosphoryl transfer and catalysis. We have also identified Pro82 as a catalytically influential residue in this enzyme. Using molecular dynamics simulations we have noted that absence of ligands induces active-site lid opening in GTP-PEPCKS and we have made the first observation of the intermediary structures of the lid opening event, the dynamics of which is an important element that controls GTP-PEPCK catalysis. We have determined the first three-dimensional crystal structure of an archaeal-type Pepc, i.e. C. perfringens PepcA. Our experimental data also provide information about the oligomerization of PepcAs and reveal that aspartate inhibits the C. perfringens enzyme competitively compared to the allosteric inhibition in Pepcs. Structure-based modeling has led to the identification of putative aspartate- and bicarbonate-binding residues in C. perfringens PepcA, of which Arg82, His11, Ser201, Arg390, Lys340, Arg342 and Arg344 probably play an important role. / Ph. D.

To accurately solve the general nuclear spin state function in Nuclear Magnetic Resonance (NMR), a rotation wave approach was employed, allowing the reference frame to rotate in sync with the oscillating magnetic field. The spin state system was analogously treated as a Rubik's Cube, ensuring the diagonalization of only the time-dependent part of the state function. Although Gottfried's equation (1966) aligns with transitions between specific spin states m and m′, his second rotation contradicts the conservation of angular momentum, resulting in inaccuracies for spin states with initial phase shifts or entangled states. Contrarily, Schwinger (1937) efficiently computed the coefficients for each spin state in a frequency range opposite to the Larmor frequency, using an unorthodox approach in quantum mechanics, which unfortunately led to the oversight of his work in subsequent citations. This methodology was also applied to derive the general electron spin state function in Nuclear Magnetic Resonance (NMR) and Electron Paramagnetic Resonance (EPR), enabling the construction of a doubly rotated ground state for time-dependent perturbation theory. This was particularly relevant as the Hamiltonians for magnetic dipole, electric quadrupole, and magnetic octupole moments incorporate powers of I · J terms, necessitating the calculation of sub-state energy levels for perturbation, including those of molecules 14N7 and 7Li3. Furthermore, the study expanded to the general Lie group for 3D rotations along three linearly independent axes, resulting in 12 distinct methods to achieve rotations in any arbitrary direction using these axes, yielding wave function with only one spin operator in each exponent. The ongoing research is now concentrated on generating NMR spectra for 14N7 in amino acids, furthering the understanding of nuclear spin dynamics in complex molecular systems.

This thesis is a numerical study of fields within ion traps having segmented electrodes1. The focus is on two cylindrical ion trap structures, two Orbit rap structures and one planar structure which mimics the field of the Orbit rap. In all these geometries, the segments which comprise the electrodes are easily Machin able rings and plates. By applying suitable potential to the different segments, the fields within these geometries are made to mimic the fields in the respective ideal structures. This thesis is divided into 6 chapters. Chapter 1 presents introduction and background information relevant to this work. A brief description of the Quadrupole Ion Trap (QIT) and the Orbit rap is given. The role of numerical simulations in the design of an ion trap geometry is briefly outlined. The motivation of this thesis is presented. The chapter ends by describing the scope of the thesis. Chapter 2 presents a general description of computational methods used throughout this work. The Boundary Element Methods (BEM) is first described. Both 2D and 3D BEM are used in this work. The software for 3D BEM is newly developed and hence 3D BEM is described in more detail. A verification of 3D BEM is presented with a few examples. The Runge-Kutta method used to compute the trajectory of ion is presented. A brief overview of the Nelder-Mead method of function minimization is given. The computational techniques specifically used to obtain the results in Chapter 3, 4 and 5 are presented in the respective chapters. Chapter 3 presents segmented electrode geometries of the Cylindrical Ion Trap (CIT). In these geometries, the electrodes of the CIT are split into number of mini-electrodes and different voltages are applied to these segmented electrodes to achieve the desired field. Two geometries of the segmented electrode CIT will be investigated. In the first, we retain the flat end cap electrodes of the CIT but split the ring electrode into five mini-rings. In the second configuration, we split the ring electrode of the CIT into three mini-rings and 1The term ‘segmented electrode’ used in this thesis has the same connotation as the term ‘split-electrode’ used in Sonalikar and Mohanty (2013). also divide the end caps into two mini-discs. By applying different potentials to the mini-rings and mini-discs of these geometries we will show that the field within the trap can be optimized to desired values. Two different types of fields will be targeted. In the first, potentials are adjusted to obtain a linear electric field and, in the second, a controlled higher order even multipole field are obtained by adjusting the potential. It will be shown that the different potentials to the segmented electrodes can be derived from a single RF generator by connecting appropriate capacitor terminations to segmented electrodes. The field within the trap can be modified by changing the value of the external capacitors. Chapter 4 presents segmented electrode geometries which are possible alternatives for the Orbitrap. Two segmented-electrode structures, ORB1 and ORB2, to mimic the electric field of the Orbitrap, will be investigated. In the ORB1, the inner spindle-like electrode and the outer barrel-like electrode of the Orbitrap are replaced by rings and discs of fixed radii, respectively. In this structure two segmented end cap electrodes are added. In this geometry, different potentials are applied to the different electrodes keeping top-bottom symmetry intact. In the second geometry, ORB2, the inner and outer electrodes of the Orbitrap are replaced by an approximate step structure which follows the profile of the Orbitrap electrodes. For the purpose of comparing the performance of ORB1 and ORB2 with that of the Orbitrap, the following studies will be undertaken: (1) variation of electric potential, (2) computation of ion trajectories, (3) measurement of image currents. These studies will be carried out using both 2D and 3D Boundary Element Method (BEM), the 3D BEM is developed specifically for this study. It will be seen in these investigations that ORB1 and ORB2 have performance similar to that of the Orbitrap, with the performance of the ORB1 being seen to be marginally superior to that of the ORB2. It will be shown that with proper optimization, geometries containing far fewer electrodes can be used as mass analysers. A novel technique of optimization of the electric field is proposed with the objective of minimizing the dependence of axial frequency of ion motion on the initial position of an ion. The results on the optimization of 9 and 15 segmented-electrode trap having the same design as ORB1 show that it can provide accurate mass analysis. Chapter 5 presents a segmented electrode planar geometry named as PORB used to mimic the electric field of the Orbit rap. This geometry has two planes, each plane consisting of 30 concentric ring electrodes. Although the geometry of PORB does not have conventional inner and outer electrodes of the Orbit rap, it will be shown that by selecting appropriate geometry parameters and suitable potentials for the ring electrodes, this geometry can trap the ions into an orbital motion similar to that in the Orbit rap. The performance of the planar geometry is studied by comparing the variation of potential, ion trajectories and image current in this geometry with that in the Orbit rap. The optimization of applied potentials is performed to correct the errors in the electric field so that the variation of axial frequency of ions with their initial position is minimized. Chapter 6 presents the summary and a few concluding remarks

The interaction of active molybdenum field emission microcathode arrays with oxygen, water, carbon dioxide, methane, hydrogen and helium gases was studied. Experiments were setup to measure the emission characteristics as a function of gas exposures. The resulting changes in the surface work function of the tips were determined from the Fowler-Nordheim plots. The kinetics of the FEA-gas interaction were studied by observing the ion species originating from the array during and after gas exposures with a high resolution quadrupole mass spectrometer. With the work function data and the mass spectrometry information, the mechanisms responsible for emission degradation and subsequent device recovery after exposures have been determined. The data obtained was used in estimating the device lifetimes under various vacuum environments. Also it was found that the gas exposure effects are similar in dc and pulsed modes of operation of the arrays, thus permitting the use of dc mode testing as an effective acceleration method in establishing the device lifetimes under various vacuum conditions. The vacuum conditions required for the long term emission current stability and reliability of vacuum microelectronic devices employing FEAs are established. Exposure of Mo field emitter arrays to oxygen bearing species like oxygen, water and carbon dioxide resulted in serious emission current degradation. Whereas, exposure to methane and hydrogen caused a significant increase in emission current. The control of residual gases like 02, C02 and H20 in the vacuum envelope is essential for the emission current stability and long term reliability of vacuum microelectronic devices employing field emission microcathode technology.