Electroporation-based treatments are motivated by the response of biological membranes to high- intensity pulsed electric fields. These fields rearrange the membrane structure to enhance the membrane's diffusive permeability, or the degree to which a membrane allows molecules to diffuse through it, is impacted by the structure, composition, and environment in which the cell resides. Tracer molecules have been developed that are unable to pass through intact cell membranes yet enter permeabilized cells. This dissertation investigates the hypothesis that the flow of such molecules may be used to quantify the effects of the electrical stimulus and environmental conditions leading to membrane electroporation. Specifically, a series of electrical pulses that alternates between positive and negative pulses permeabilizes cells more symmetrically than a longer pulse with the same total on-time. However, the magnitude of this symmetric entry decreases for the shorter alternating pulses. Furthermore, a method for quantitatively measuring the permeability of the cell membrane was proposed and validated. From data near the electroporation threshold, the response of cells varies widely in the manner in which cells become permeabilized. This method is applied to study the transient cell membrane permeability induced by electroporation and is used to demonstrate that the cell membrane remains permeable beyond 30 min following treatment. To analyze these experimental findings in the context of physical mechanisms, computational models of molecular uptake were developed to simulate electroporation. The results of these simulations indicate that the cell's local environment during electroporation facilitates the degree of molecular uptake. We use these models to predict how manipulating both the environment of cells during electroporation affects the induced membrane permeability. These experimental and computational results provide evidence that supports the hypothesis of this dissertation and provide a foundation for future investigation and simulation of membrane electroporation. / PHD

State-of-Health (SoH), a specified measure of stability, is a critical parameter for determining the safe operating area of a battery cell and battery packs to avoid abuse and prevent failure and accidents. A series of experiments were performed to evaluate the performance of a 4P1S battery array using electrochemical impedance spectroscopy to identify key frequencies that may describe battery state of health at any state of charge. Using a large sample number of cells, the state of health frequency, fSoH, for these LiFePO4 26650 cells is found to be 158 Hz. Four experiments were performed to evaluate the lifetime in different configurations: single-cell at 1C (2.6A), single-cell at 10C (26A), four cells in parallel at 10C (ideal match), and four cells in parallel (manufacturer match). The lifetime for each experiment set degraded substantially, with the final parallel series reaching end of life at 400 cycles, a 75.32% reduction in life compared to operating solo. Analysis of the fSoH data for these cells revealed a change in imaginary impedance at the critical frequency that corresponded to changes in the capacity and current data, supporting the development of a single-frequency diagnostic tool. An electrochemical model of the battery was generated, and it indicated the anode material was aging faster than the SEI layer, the opposite of normal cell degradation. A post-mortem analysis of cells from three configurations (baseline, single-cell, and parallel-cell) supported the modeling, as physical damage to the copper current collector in the anode was visible in the parallel-connected cell. / Ph. D.

Shipboard MVDC power systems need to support pulsed loads, which have destabilizing ef-fects on the MVDC power transmission bus voltage. Despite the reference shipboard MVDC architecture having energy storage to buffer the large power swings of pulsed loads, a large constant power still needs to be delivered to maintain the energy storage state of charge. This recharging constant power itself introduces small signal instability to the MVDC bus voltage. This thesis investigates the advantages of adding a dynamically tuneable virtual capacitor and resistor in parallel to the pulsed load for maintaining small signal stability. The stabi-lizer is implemented in a negative load configuration in the existing reference architecture hardware, where the stabilizer negatively impacts the power quality of the downstream load. To address this, a dual use is added to existing hardware by having the energy storage also cancel out the newly introduced noise. A controller was designed to control a MVDC power converter module for providing these stability services. In addition, the controller manages its internal energy storage and stabilizes its internal DC bus that powers its downstream pulsed load. / Future ships will have a special shipboard power grid and power converters to power future electronics. Most of these power converters will have an internal battery device that provides power when the generators do not provide enough power. Generators are very slow to change their power output. Some shipboard electronics may consume very large amounts of power at very quickly changing rates, causing instability to the power system. The batteries can accomodate the instability caused by these electronics. However, the batteries need to be quickly recharged, which is also unstable to the special power grid. This thesis modifies the recharging behavior so that it does not cause this instability. Also, it is preferable that the batteries will only draw power from the power grid in one direction and send power to the power consuming electronics. This setup is called negative load. This setup is preferable, because sending power back to the power grid will require extra hardware. Ships can only carry so much equipment due to constraints in weight or room, so additonal hardware is undesireable. There already exists similar research to provide this stabilizing service, but they are not designed for a shipboard power grid supporting these quick high power electronics. This thesis also makes a controls system that manages the battery and other requirements of the power system.

The use of high-powered electrical energy systems requires an efficient and capable means to move electrical energy from one location to another while reducing energy losses. This paper describes the design and construction process of a high-powered busbar system that is to be implemented in pulsed-power applications. In order to obtain a robust system capable of handling in excess of 25kJ, both mechanical and electrical analyses were performed to verify a capable design. The following methodology describes how the Lorentz force was balanced with mechanical forces during the design process and then validated after construction was completed using the fundamental Maxwell equations and computer simulations. Main focuses include handling of EMF, high current density concentrations, and overall mechanical stability of the system and how these effects determine the physical design and implementation. In the end, a repeatable methodology is presented in the form of a design process that can be implemented in any system given the design criteria. / Master of Science

The neutron diffusion parameters of water and ice were measured by the pulsed source method at two temperatures; 1.0°C. and -19°C. Neutron pulses were obtained at one millisecond intervals by modulating the beam in a Cockcroft-Walton type accelerator. The ₁H³(d,n)₂He⁴ reaction was used to generate neutrons. The samples were contained in cylindrical aluminum cans covered with cadmium. The experiment was conducted inside a large paraffin block which served as a neutron shield and thermal insulator. The temperature of the samples was maintained constant to within ±1°C. Neutrons leaving one surface of the sample were counted in a BF₃ proportional counter. The time distribution of these neutrons was recorded by an eighteen channel time analyzer. The width of each channel was 20 microseconds. The opening of the first channel was delayed 100 microseconds with respect to the start of the neutron burst to minimize harmonics in the neutron decay. A geometric buckling was calculated for each sized sample from B²=[2.405/(R+∈)]²+[π/(H+∈)]² where B² = geometric buckling 2.405 = first zero of J_o Bessel Functions R = radios of cylinder H = height of cylinder ∈ = extrapolation distance The extrapolation distance ∈ was calculated from ∈ =0.71 λ_tr where λ_tr = mean free path of neutrons in water The extrapolation distance was assumed to vary as T^½ where T is the temperature in degrees Kelvin. The measured decay constants, α, were fitted by the method of least squares to a polynomial in B² of the form α = (∑_av) ÷ D_oB² - CB⁴ where ∑_a = the macroscopic absorption cross-section v = the neutron velocity D_o = diffusion coefficient C = diffusion cooling coefficient The resultant values of (∑_av) and D_o for each temperature are below. The data did not permit a determination of C. 1.0°C. (∑_av) = 4595 ± 365 sec⁻¹ D_o = 29600 ± 840 cm²/sec -19°C. (∑_av) = 4355 ± 263 sec⁻¹ D_o = 27050 ± 630 cm²/sec / Ph. D.

Thermal neutron diffusion parameters of O, 20, 50, 80 and 100 percent D₂O in mixtures of light and heavy water were measured by the pulsed neutron technique at room temperature (21°C), near the freezing point of the mixture in the liquid state, and at -20°C in the solid state (ice). A 250-kv pulsed Cockcroft-Walton accelerator, using neutrons from the ₁H²(d,n)₂He³ reaction, was used to generate fast neutrons bursts. The values of the infinite medium decay constant, λ₀, were computed by a least squares fit of λ versus B² data to the expression: λ = λ + D₀B² - CB⁴ The parameters D₀, C, and λ𝗍ᵣ were determined from the above expression after rearranging: λ-λ₀ = D B² - CB⁴ The resulting values of D₀, C, λ, and λ𝗍ᵣ at several temperatures are tabulated. / Ph. D.

Oxide materials display a wide range of physical properties. Recently, doped complex oxides have drawn considerable attention for various applications including thermoelectrics. Doped complex oxide materials have high Seebeck coefficients (S) and electrical conductivities (o) comparable to other doped semiconductors but low thermoelectric figure of merit ZT values due to their poor thermal conductivities. For example, niobium doped strontium titanate (SrNbxTi_1-xO₃ or simply Nb:STO) has a power factor comparable to that of bismuth telluride. Semiconductor nanostructures have demonstrated a decrease in thermal conductivity (κ) resulting in an increase in the thermoelectric figure of merit (ZT). Nanostructures of doped oxides like niobium doped strontium titanate, may also lead to decreased κ and a corresponding increase in ZT. The major impediment to nanostructured oxide thermoelectric materials is the lack of suitable fabrication techniques for testing and eventual use. Electron Beam Lithography (EBL) was used to pattern poly-methyl-methacrylate (PMMA) resists on undoped single crystalline SrTiO₃ (STO) substrates which were then filled with Nb:STO using Pulsed Laser Deposition (PLD) at room temperature. This technique produced nanowires and nanodots with critical dimensions below 100 nm, and a yield of approximately 95%. In addition to scanning electron microscopy and atomic force microscopy morphological studies of the patterned oxide, thin film analogues were used to study composition, crystallinity and electrical conductivity of the material in response to a post deposition heat treatment. Since the thin films were grown under similar experimental parameters as the oxide nanostructres, the patterned oxides are believed to be stoichiometric and highly crystalline. The study found that using a combination of EBL and PLD, it is possible to produce highly crystalline, doped complex oxide nanostructures with excellent control over morphology. Furthermore, the technique is applicable to nearly all materials and provides the capability of patterning doped oxide materials without the requirement of etching or multiple lithography steps makes this approach especially interesting for future fundamental materials research and novel device fabrication. / Master of Science

No description available.

Cell-level and tissue-level mechanical properties are key to healthy biological functions, and many diseases and disorder arise or progress due to altered cell and tissue mechanics. Pulse electric field (PEFs), which employ intense external electric fields to cause electroporation, a phenomenon characterized by increased cell membrane permeability, also can cause significant changes to cell and tissue mechanics. Here, we investigate the mechanics of brain and brain cancer cells, specifically focusing on how PEFs impact cell mechanics and PEF-induced blood-brain barrier disruption. In our first study, we investigate single-cell mechanical disruption of glioblastoma cells after reversible electroporation using Nanonet Force Microscopy (NFM). A precise network of extracellular-matrix mimicking nanofibers enabled cell attachment and contraction, resulting in measurable fiber deflections. Cell contractile forces were shown to be temporarily disrupted after reversible electroporation, in an orientation and field-dependent manner. Furthermore, we found that cell response is often a multi-stage process involving a cell-rounding stage, biphasic stage, and a cell re-spreading stage. Additionally, cell viability post-PEFs was orientation-dependent. In another study, we investigated the mechanical properties of brain cancer for various-grade glioma cells (healthy astrocytes, grade II, grade III, and grade IV (glioblastoma) cells). A microfluidic constriction channel caused cell deformation as cells, driven by hydrostatic pressure, entered a narrow constriction. Finite element models of cell deformation and a neural network were used to convert experimental results (cell entry time and cell elongation within the channel) into elastic modulus values (kPa). We found that the that low-grade glioma cells showed higher stiffnesses compared to healthy and grade IV glioma cells, which both showed similar values. These results warrant future studies to investigate these trends further. PEFs can induce Blood-brain barrier (BBB) disruption, an effect we studied using a multiplexed, PDMS microdevice. A monolayer of human cerebral endothelial cells on a semi-permeable membrane was used to model the BBB, and permeability was assessed by the diffusion of a fluorescent dye from an upper to lower channel. A custom tapered channel and branching channel design created a linear gradient in the electric field within the device that enabled six electric field strengths to be tested at once against two unexposed (control) channels. Normalization of permeability by the control channels significantly removed experimental noise. We found that after high-frequency bipolar irreversible electroporation (HFIRE) electric pulses, permeability transiently increased within the first hour after electroporation, in a voltage- and pulse-number dependent manner. However, we found significant electrofusion events after pulsing at high voltages, which reduced monolayer permeability below baseline values. This device enables efficient exploration of a wide range of electroporation parameters to identify the optimal conditions for blood-brain barrier disruption. In another blood-brain barrier study, we incorporate dense, polystyrene nanofiber networks to create ultra-thin, ultra-porous basement-membrane-mimics for In vitro blood-brain barrier models. Fiber networks are fabricated using the non-electrospinning Spinneret-based Tunable Engineered Parameters (STEP) technique. Endothelial cells cultured on one side of the fiber network are in close contact with supporting cell types (pericytes) cultured on the backside of the fibers. Contact-orientation co-cultures have been shown to increase blood-brain barrier integrity, and our nanofiber networks increase the physiological realism of basement-membrane mimics for improve modeling. Finally, we investigate how cell viability post-electroporation is impacted by cell morphology. The impact of cell morphology (shape and cytoskeletal structure) on cell survival after electroporation is not well understood. Linking specific morphological characteristics with cell susceptibility to electroporation will enhance fundamental knowledge and will be widely useful for improving electroporation techniques where cell viability is desirable (gene transfection, electrofusion, electrochemotherapy) or where cell viability is undesirable (tumor ablation, cardiac ablation). Precise control of cell shape and orientation enabled by nanofiber scaffolds provides a convenient and expedient platform for investigating a wide variety of factors (morphological and experimental) on cell viability. Altogether, these investigations shed new light on cell mechanical changes due to disease and pulsed electric fields, and suggest opportunities for improving brain cancer therapies. / Doctor of Philosophy / In biology, structure and function are interrelated. Cells and tissue have structures that enable them to perform their proper function. In the case of disease, cell and tissue properties are altered, leading to dysfunction. Alternatively, healthy structures sometime hinder effective treatments, and therefore can be therapeutically disrupted to improve treatments. In this study, we investigate single-cell and multi-cellular mechanical change due to disease or after pulsed electric fields (PEFs), with a specific focus on the brain. Pulsed electric fields (PEFs) use electrodes to deliver short, intense pulses of electrical energy to disrupt cell membranes and change cell mechanics. We studied as single-cell contractility, cancer cell stiffness, and blood-brain barrier (BBB) disruption by PEFs. We found that PEFs cause significant change to cell shape and mechanics, and can disrupt the BBB. By studying several grades of brain cancers, we found that low-grade brain cancer (gliomas) showed increased stiffness compared to healthy and highly diseased (grade IV) cells. To mimic the BBB, we used microfluidic devices to grow specialized brain cells (endothelial cells) on permeable membranes and nanofibers networks and showed that these devices can mimic structures found in animals/humans. Finally, we studied how cell properties (such as shape) determine whether cells will survive PEFs. Taken together, our investigations improve the understanding of brain mechanics during disease and after PEFs, and suggest the usefulness of PEFs for improved brain cancer therapies.

Layered transition metal dichalcogenides (TMDs) are potentially ideal semiconducting materials due to their in-plane carrier transport and tunable bandgaps, which are favorable properties for electrical and optoelectronic applications. However, the ability to make p-n junctions is the foundation of semiconductor devices, and therefore the ability to achieve reproducible p- and n-type doping in TMD semiconducting materials is critical. In this work, p-type substitutional doping of pulsed laser deposited WS2 films with niobium is reported. The synthesis technique of the PLD target with dopant incorporation which also ensures host material stoichiometry is presented. Hall electrical measurements confirmed stable p-type conductivity of the grown films. Structural characterization revealed that there was no segregation phase of niobium in the fabricated films and x-ray phtoelectron spectroscopy (xps) characterization suggest that the p-type doping is due to Nb4+ which results in p-type behavior. Stable hole concentrations as high as 10E21(cm-3) were achieved. The target fabrication and thin film deposition technique reported here can be used for substitutional doping of other 2D materials to obtain stable doping for device applications.