940 research outputs found
Ultrashort electric pulse induced changes in cellular dielectric properties
No full textThe interaction of nanosecond duration pulsed electric fields (nsPEFs) with biological cells, and the models describing this behavior, depend critically on the electrical properties of the cells being pulsed. Here, we used time domain dielectric spectroscopy to measure the dielectric properties of Jurkat cells, a malignant human T-cell line, before and after exposure to five 10 ns, 150 kV/cm electrical pulses. The cytoplasm and nucleoplasm conductivities decreased dramatically following pulsing, corresponding to previously observed rises in cell suspension conductivity. This suggests that electropermeabilization occurred, resulting in ion transport from the cell’s interior to the exterior. A delayed decrease in cell membrane conductivity after the nsPEFs possibly suggests long-term ion channel damage or use dependence due to repeated membrane charging and discharging. This data could be used in models describing the phenomena at work
A New Universal Gas Breakdown Theory for Classical Length Scales
No full textWhile Paschen’s law is commonly used to predict breakdown voltage, it fails at microscale gaps when field emission becomes important. Accurate breakdown voltage predictions at microscale are even more important as electronic device dimensions decrease. Developing analytic models to accurately predict breakdown at microscale is vital for understanding the underlying physics occurring within the system and to either prevent or produce a discharge, depending on the application. We first take a pre-existing breakdown model coupling field emission and Townsend breakdown and perform a matched asymptotic analysis to obtain analytic equations for breakdown voltage in argon at atmospheric pressure. Next, we extend this model to generalize for gas and further explore the independent contributions of field emission and Townsend discharge. Finally, we present analytic expressions for breakdown voltage valid for any gas at any pressure, and discuss the modified Paschen minimum at microscale. The presented models agree well with numerical simulations and experimental data when using the field enhancement factor as a fitting parameter. The work presented in this thesis is a first step in unifying gas breakdown across length scales and breakdown mechanisms. Future work will aim to incorporate other breakdown mechanisms, such as quantum effects and space charge, to provide a more complete unified model for gas breakdown
Cellular Inactivation Using Nanosecond Pulsed Electric Fields
No full textPulsed electric fields (PEFs) can induce numerous biophysical phenomena, especially perturbation of the outer and inner membranes, that may be used for applications that include nonthermal pasteurization, enhanced permeabilization of tumors to improve the transport of chemotherapeutics for cancer therapy, and enhanced membrane permeabilization of individual cells to enhance RNA and DNA delivery for gene therapy. The applied electric field and pulse duration determine the density, size, and reversibility of the created membrane pores. PEFs with durations longer than the outer membrane’s charging time will induce pore formation with the potential for application in irreversible electroporation for cancer therapy and microorganism inactivation. Shorter duration PEFs, particularly on the nanosecond timescale (nsPEFs), induce a larger density of smaller membrane pores with the potential to permeabilize intracellular membranes, such as the mitochondria, to induce programmed cell death. Thus, the PEFs can effectively kill multiple types of cells, dependent upon the cells. This thesis assesses the ability of nsPEFs to kill different cell types, specifically microorganisms with and without antibiotics as well as varying the parameters to affect populations of immortalized leukemia cells (Jurkats).Antibiotic resistance has been an acknowledged challenge since the initial development of penicillin; however, recent discoveries by the CDC and the WHO of microorganisms resistant to last line of defense drugs combined with predictions of potential infection cases reaching 50 million a year globally and the absence new drugs in the discovery pipeline highlight the need to develop novel ways to combat and overcome these resistance mechanisms. Repurposing drugs, exploring nature for new drugs, and developing enzymes to counter the resistance mechanisms may provide potential alternatives for addressing the scarcity of antibiotics effective against gramnegative infections. One may also leverage the abundance of drugs effective against gram-positive infections by using nsPEFs to make them effective against gram-negative infections, including bacterial species with multiple natural and acquired resistance mechanisms. Numerous drug and microbial combinations for different doses and pulse treatments were tested and presented here.Low intensity PEFs may selectively target cell populations at different stages of the cell cycle (quiescence and mitosis) to modify cancer cell population dynamics. Experimental studies of cancer cell growth when exposed to a low number of nsPEFs, while varying pulse duration, field intensity and number of pulses reveals a threshold beyond which cell recovery is not possible, but also a point of diminishing returns if cell death is the intention. A theory comprised of coupled differential equations representing the proliferating and quiescent cells showed how changing PEF parameters altered the behavior of these cell populations after treatment. These results may provide important information on the impact of PEFs with sub-threshold intensities and durations on cell population growth and potential recurrence
Assessing Effective Medium Theories for Designing Composites for Nonlinear Transmission Lines
No full textNonlinear transmission lines (NLTLs) are of great interest for high power microwave (HPM) generation because they can sharpen pulses to create an electromagnetic shockwave to produce oscillations from 100 MHz to low GHz. NLTLs provide frequency agility, compactness, durability and reliability, providing a solid-state radiofrequency (RF) source for producing HPM. The essential component of NLTLs is the nonlinear material, typically a dielectric that varies with voltage or a magnetic material whose permeability varies with current, incorporated in the transmission line in various topologies. This thesis presents an alternative approach involving designing composites comprised of nonlinear dielectric inclusions (barium strontium titanate (BST)) and/or nonlinear inductive inclusions (nickel zinc ferrites (NZF)) in a polymer base host material, analogous to electromagnetic interference designs that incorporate stainless steel inclusions of various shapes in a plastic to tune the composite’s electromagnetic properties at GHz. Appropriately designing NLTL composites requires predicting these effective properties both in linear (for a fixed and low voltage and current) and nonlinear regions (permittivity and permeability become voltage dependent and current dependent, respectively) prior to designing HPM systems comprised of them. As a first step, this thesis evaluates and benchmarks composites models in the commercial software CST Microwave Studios (CST MWS) to various effective medium theories (EMTs) to predict the permittivity and permeability of composites of BST and/or NZF inclusions in the linear regime, compared with experimental measurements. The manufacturing and measurement of the nonlinear composites will be briefly discussed with an analysis of the homogeneity of a composite sample using 3D X-ray scan. Long-term application of these approaches to predicting the effective nonlinear composite permittivity and permeability and future work will be discussed
Nanosecond Electric Pulse Induced Changes of Mammalian Cell Suspension Conductivity in Real Time
No full textElectric pulses (EPs) have been used for many biological applications from electrochemotherapy to wound healing. While conventional techniques use microsecond to millisecond pulses, more recent techniques use nanosecond EPs (NSEPs) with a much higher amplitude. Generally, the longer duration pulses fully charge the plasma membrane to permeabilize it in a process called electroporation. NSEPs fully charge the smaller intracellular organelles to enable the manipulation of intracellular function; however, they still partially charge the membrane to permeabilize it to facilitate the transport of smaller ions. Experiments have demonstrated this motion using dyes and long-term (on the order of minutes) electrical measurements. This thesis studies the net motion of ions during one or more NSEPs to establish the direction the ions flow, into or out of the cell, to better understand the mechanisms involved with electroporation. This was done by examining the change in electrical conductivity of a Jurkat cell suspension by measuring the voltage and current for three different energy densities determined at two pulse durations (60 ns and 300 ns), three buffer solutions (growth media, Hank’s balanced salt solution (HBSS), and a low conductivity buffer (LCB)), and pulse trains of one, five, and fifteen pulses. A simulation coupling the asymptotic Smoluchowski equation for EP induced membrane pore formation and the Nernst-Planck equation for ion motion due to diffusion and electrophoresis elucidated the contribution of various electrically driven mechanisms for ion motion. The electrical conductivity increased for each pulse duration for cell suspensions in growth media or HBSS, indicating net ion motion from the intracellular to extracellular fluid. Applying 300 ns pulses also increased suspension conductivity for the LCB; however, suspension conductivity decreased during the 60 ns pulse, indicating net ion motion into the cell. The simulations indicated that EP induced electrophoresis would reduce suspension conductivity, as observed for the 60 ns EPs in LCB. Thus, a nonelectrical mechanism, such as EP induced shock waves or cell membrane temperature gradients, which are both mitigated by shorter durations and lower buffer conductivity, or colloid-osmotic swelling, must drive the increased suspension conductivity for other conditions. Similar results arose during the final pulse during cell treatment using one, five, and fifteen EPs. These results elucidate ion motion during the NSEP and provide a means for future studies on the efficacy of bipolar pulses to better optimize electroporation pulse parameters for various medical treatments
Assessing Novel Bioelectric Effects of Nanosecond Pulsed Electric Fields on Cell Stimulation, Proliferation and Microorganism Inactivation
No full textBioelectrics is the application of electric fields to cells in a conducting media, treating the cell as a circuit comprising resistors and capacitors (membranes and intracellular fluids respectively). Recent advancements in construction of nanosecond pulse generators allow for construction of low cost devices capable of generating nanosecond pulsed electric fields (nsPEFs). These fields are capable of forming pores on the extra and intra cellular membranes, while also affecting intracellular organelles, DNA and the nucleus. With the first generation of nano-signalling devices set to enter the medical field for treatments ranging from carcinomas to regenerative therapy, the intent of this study was to examine their effect on the growth dynamics of cancer cells under treatment and the potential to stimulate stem cells for use in regenerative healing therapies. A novel application to combat antibiotic resistance in microorganisms was explored. While pulsed electric fields (PEFs) can control cell population in vitro, the ability to specifically predict the types of cells (dividing or resting) targeted and optimize the PEF parameters remain critical challenges for potential cancer treatment applications. Mathematical models of cancer cell population dynamics based on coupled differential equations can predict the transition of cells between the proliferating, quiescent, and dead states to predict the progression of cell population over time. Chapter 2 of this dissertation will experimentally assess the impact of pulse duration, field intensity, and number of pulses on cell population dynamics and fit the mathematical model to assess the transition between proliferating, quiescent, and dead states. These results demonstrate the tenability of nsPEFs for controlling cell number, suggesting the potential impact of sublethal PEFs on cell populations, which may impact cancer therapy. Low intensity electric fields can induce changes in cardiomyocyte (heart muscle) differentiation, increasing the number of beating foci. These fields can also induce cytoskeletal stresses that facilitate manipulation of osteoblasts and mesenchymal stem cells. While effective, low intensity DC or AC electric fields require long (tens of minutes) application times, which are on the order of physiological mechanisms that can complicate the consistency of the treatments. We hypothesized that intense nanosecond pulsed electric fields (nsPEFs) can overcome these side effects by inducing similar stresses on a timescale shorter than physiological processes while additionally inducing plasma membrane nanoporation, ion transport, and intracellular structure manipulation. Chapter 3 of this dissertation examines the impact of pulse duration, field intensity and number of pulses on muscle stem cell population dynamics, demonstrating increased proliferation on a photospectrometer and observed increased differentiation under fluorescent microscopy. The increasing prevelance of antibiotic resistance mechanisms that render current antibiotics ineffective while requiring greater cytotoxicity and concentrations of newer and more powerful drugs to treat infections necessitates the design of new treatments by combining nsPEFs with antibiotics and combinations of antibiotics. This dissertation demonstrates the synergistic inactivation of clinically relevant gram negative Escherichia coli and gram positive Stapphylococcus aureus. Low electric fields which have no effect on gram positive microorganism populations by themselves, produced a 2.5 log reduction of bacterial colony forming units when combined with 1/20th of the clinical dose of certain antibiotics. This synergistic effect was magnified with an increase in drug concentration and an increase in field strength, individually. In combination, this leads to complete sterilization (a 9-log reduction) in colony forming units
Optical emission spectroscopy of high voltage cold atmospheric plasma generated using dielectric barrier discharges
No full textWhile numerous experiments have demonstrated the efficacy of high voltage cold atmospheric pressure plasmas for extending food shelf-life and sterilizing medical instrumentation in sealed packages, the influence of the packaging material and gas composition on the reactive gas species generated by the high voltage atmospheric cold plasma is poorly understood. This study elucidates the impact of these parameters on plasma generation in sealed packages for four gases (ambient air, commercial grade compressed air, and high purity helium and nitrogen) placed in commercially available transparent plastic containers and bags. After adequate gas flushing, we observed that the container and bag individually reduced signal intensity by 63% and 45% across the measured wavelengths of 200 nm to 1100 nm, demonstrating that they acted as broadband absorbers. Neither the container nor bag influenced the wavelengths of the peak emissions, only the amplitude, indicating no significant effect on the types of species generated. Lissajous diagrams showed that the power dissipated by the nitrogen and ambient air plasma generated at 72 ± 3.7 kV RMS were comparable to the compressed dry air discharge generated at 80 ± 3.7 kV RMS.^ The helium discharge at 37 ± 3.7 kV RMS absorbed approximately 92% more power than these gases. We observed translational temperatures ranging from 1088 K for nitrogen to 1421 K for compressed air and rotational temperatures ranging from 285 K for helium to 479 K for compressed air. These results indicate that packaging materials have minimal effect on the most dominant peaks although further studies are required to elucidate the impact on less intense peaks observed.^ We next assessed the effect of voltage on species generation using a helium air plasma generated using the Phenix system with applied voltages of 36.4, 44.8, 58.1, and 71.0 kV. The light from the plasma was collected using a fiber optic cable that was provided with the SP2500 spectrometer. The N2 Second Positive system of a helium air plasma generated at 36.4 kV was observed using the 1800 g/mm grating of a spectrometer. SPECAIR fits for the spectra show no real correlation to voltage. Higher voltage did not necessarily translate to higher plasma temperature although the relative intensities for the observed peaks increased with increasing voltage. This clearly showed that the increased voltage did not directly correlate to increased temperature of the bulk gas.
Electrolytic Microsystems for Biomedical Applications
No full textWith an American dying each minute due to cancer and with a global burden of over $170 billion by 2020, there is a critical need for alternate solutions, especially for deep-seated, inoperable tumors in the liver and brain. Systemic chemotherapy has side effects and radiation is expensive. Challenges of current technologies for treating the liver include poor performance near vascular structures and the inability to treat multiple nodular tumors. Brain tumor treatment suffers from inadequate intra-cerebral drug concentration and uncontrollable drug delivery. These difficulties motivate the development of low-cost solutions that have fractionated application and are localized, monitored, and compatible with intra-operative imaging. This research presents two alternative systems based on electrolytic mechanisms: an ultrasound- powered micro-ablator for electrochemical treatment of deep-seated liver tumors and an implantable electrophoretic flushable-electrode system for controllable drug delivery to brain tumors. The micro-ablator leverages pH change, below six and above nine for tumor tissue destruction. Using ultrasound to energize the ablator provides advantages of deep penetration, omni-directionality, device miniaturization and possible wireless telemetry for data communication, which are all attractive for implementation in a clinical setting. The use of direct current enables delivery of charged therapeutic substances through electrophoresis to increase their intra-tumoral concentration and penetration. The facile fabrication of novel fluidic-flushable channel electrodes enables their conformability with soft tissue. Together, these two technologies enable the low-cost development of customized and localized treatment protocols for practical applicability with a potential to reduce tumor burden
The rise and fall of the Labour league of youth
No full textThis thesis charts the rise and fall of the Labour Party’s first and most enduring youth organisation, the Labour League of Youth. The history of the League, from its birth in the early nineteen twenties to its demise in the late nineteen fifties, is placed in the context of the Labour Party’s subsequent fruitless attempts to establish and maintain a vibrant and functional youth organisation. A narrative is incorporated that illuminates the culture, organisation and political activism of the League and establishes it as a predominantly working class radical organisation. The reluctance on the part of the Labour Party to grant autonomy to its youth sections resulted in the history of the League of Youth being one of control, suppression and tension. This state of affairs ensured that subsequent youth groups, the Young Socialists and Young Labour, would be established in an atmosphere of reservation and scepticism.
The thesis places the prime responsibility for the failure of the party’s youth organisations with the party leadership but also considers the contributory factors of changing social and political circumstances. A number of themes are explored which include the impact of structure and agency factors, the power of the Parliamentary Labour Party, the political socialisation of leading figures within the party, the social context in which each of the groups emerged and the extent to which the youth groups were prey to intra-party factionalism.
The thesis redresses the balance of research where most accounts have focussed on the Young Socialists and traces the common characteristics that are prevalent in the way the party leadership has approached its relationship with its youth organisations. Use has been made of previously unpublished primary source material, the major source being the League of Youth members themselves whose recollections have helped to demonstrate the arguments put forward in this thesis
Darwin (Buffs) Football Club
No full textDarwin (Buffs) Football Club, A grade, 1964-65 Premiers. Back row, L-R: V. Birch (coach); J. Muir; J. Kelly; G. Tilmouth; C. McKarlie; W. Birch; K. Goldie (trainer); J. De La Cruz (president). Middle row, L-R: F. Perez; J. Tutton; D. Stokes; R. Garner; P. Patten; R. Cummings; G. Brown; I. McLeod. Front row, L-R: J. Angeles; J. McLeod; J. Anderson (capt); H. Brown; W. Dempsey; R. Woodroffe; T. Allen. Mascots: J. Cardona; T. Nickels.Lorman, Steve
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