A coaxial solid state nonlinear pulse forming line with an exponentially tapered ferrite composite core.

The need to optimize size, weight, and power of high-power microwave (HPM) systems has motivated the development of solid-state HPM sources, such as nonlinear transmission lines (NLTLs), which utilize gyromagnetic precession or dispersion to generate RF. One recent development implemented the NLTL as a pulse forming line (PFL) to form a nonlinear pulse forming line (NPFL) system that substantially reduced the system's size by eliminating the need for a separate PFL; however, matching standard loads can be challenging. This paper describes the development of a tapered NPFL using an exponentially tapered composite based ferrite core containing 60% nickel zinc ferrite (by volume) encased in polydimethylsiloxane (PDMS) and encapsulated in a 5% barium strontium titanate shell.

Maps of Membrane Pore Dynamics From Picosecond to Millisecond Pulse Durations.

Electroporation occurs when cells are exposed to an electric pulse of sufficient intensity E and pulse duration τ. Many studies have attempted to develop universal scaling laws to predict membrane pore dynamics for pulsed electric fields (PEFs) of different durations; however, the differences in pore dynamics across these parameters makes this difficult both experimentally and numerically. This study uses the asymptotic Smoluchowski equation (ASME) to quantify the number of pores, average pore radius, and fractional pore area (FPA) during exposure to PEFs with durations from hundreds of picoseconds to a millisecond.

The transition from field emission to collisional space-charge limited current with nonzero initial velocity.

Multiple electron emission mechanisms often contribute in electron devices, motivating theoretical studies characterizing the transitions between them. Previous studies unified thermionic and field emission, defined by the Richardson-Laue-Dushman (RLD) and Fowler-Nordheim (FN) equations, respectively, with the Child-Langmuir (CL) law for vacuum space-charge limited current (SCLC); another study unified FN and CL with the Mott-Gurney (MG) law for collisional SCLC. However, thermionic emission, which introduces a nonzero injection velocity, may also occur in gas, motivating this analysis to unify RLD, FN, CL, and MG.

Selective Electroporation of Tumor Cells Under AC Radiofrequency Stimulation - A Numerical Study.

Self-consistent evaluations of membrane electroporation along with local heating in single spherical cells arising from external AC radiofrequency electrical stimulation have been carried out. The present numerical study seeks to determine whether healthy and malignant cells exhibit separate electroporative responses with regards to operating frequency. It is shown that cells of Burkitt's lymphoma would respond to frequencies >4.

Space-charge-limited current density for nonplanar diodes with monoenergetic emission using Lie-point symmetries.

Understanding space-charge-limited current density (SCLCD) is fundamentally and practically important for characterizing many high-power and high-current vacuum devices. Despite this, no analytic equations for SCLCD with nonzero monoenergetic initial velocity have been derived for nonplanar diodes from first principles. Obtaining analytic equations for SCLCD for nonplanar geometries is often complicated by the nonlinearity of the problem and over constrained boundary conditions.

Infrared Laser-Based Single Cell Permeabilization by Plasma Membrane Temperature Gradients.

Single cell microinjection provides precise tuning of the volume and timing of delivery into the treated cells; however, it also introduces workflow complexity that requires highly skilled operators and specialized equipment. Laser-based microinjection provides an alternative method for targeting a single cell using a common laser and a workflow that may be readily standardized. This paper presents experiments using a 1550 nm, 100 fs pulse duration laser with a repetition rate of 20 ns for laser-based microinjection and calculations of the hypothesized physical mechanism responsible for the experimentally observed permeabilization.

Nonlinear transmission line implemented as a combined pulse forming line and high-power microwave source.

Nonlinear transmission lines (NLTLs) are typically driven by pulse forming lines (PFLs) or Marx generators to generate high repetition rate, high power microwaves (HPMs) with fewer auxiliary systems than conventional sources. This paper reports the development of an even more compact HPM system that utilizes a composite-based hybrid NLTL as the PFL and HPM generator in a single device. We designed the following three different combinations of nickel zinc ferrite (NZF) and barium strontium titanate (BST) inclusion volume loads in a polydimethylsiloxane host material to provide magnetic field dependent permeability and electric field dependent permittivity, respectively: 25% NZF, 10% BST/15% NZF, and 15% BST/10% NZF.

Electrical stimulation of whole blood for growth factor release and potential clinical implications.

Clinicians have increasingly applied platelet-rich plasma (PRP) for wound healing treatments. Topical treatments commonly require biochemical agents such as bovine thrombin to activate PRP ex vivo for clotting and growth factor release to facilitate healing upon application to the wound of interest. Recent studies have explored electrical stimulation as an alternative to bovine thrombin for PRP activation due to the former's cost, workflow complexity and potentially significant side effects; however, both approaches require separating the PRP from whole blood (WB) prior to activation.

Nanosecond electric pulses rapidly enhance the inactivation of Gram-negative bacteria using Gram-positive antibiotics.

Physically disrupting microorganism membranes to enable antibiotics to overcome resistance mechanisms that inhibit or excrete antibiotics has great potential for reducing antibiotic doses and rendering resistance mechanisms inert. We demonstrate the synergistic inactivation of a Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria by combining 222 30 kV/cm electric pulses (EPs) or 500 20 kV/cm EPs with 300-ns EP duration with various antibiotics with different mechanisms of action is demonstrated. Doses of antibiotics that produced no inactivation in 10 min of exposure in solution with bacteria induced several log reductions under the influence of nanosecond EPs.

Pulsed electric field inactivation of microorganisms: from fundamental biophysics to synergistic treatments.

The growth of antibiotic resistant microorganisms and the increasing demand for nonthermal antimicrobial treatment in the food and beverage industry motivates research into alternative inactivation methods. Pulsed electric fields (PEFs) provide an athermal method for inactivating microorganisms by creating nanometer-sized membrane pores in microorganisms, inducing cell death when the PEF duration and intensity are sufficient such that the pores cannot reseal after the PEFs through a process referred to as irreversible electroporation. While PEF inactivation has been studied for several decades, recent studies have focused on extending the technique to various liquids in the food industry and optimizing microorganism inactivation while minimizing adverse effects to the treated sample.

Nanosecond pulsed electric field induced proliferation and differentiation of osteoblasts and myoblasts.

Low-intensity electric fields can induce changes in cell differentiation and cytoskeletal stresses that facilitate manipulation of osteoblasts and mesenchymal stem cells; however, the application times (tens of minutes) are of the order of physiological mechanisms, which can complicate treatment consistency. Intense nanosecond pulsed electric fields (nsPEFs) can overcome these challenges by inducing similar stresses on shorter timescales while additionally inducing plasma membrane nanoporation, ion transport and intracellular structure manipulation. This paper shows that treating myoblasts and osteoblasts with five 300 ns PEFs with intensities from 1.

The Transition to Paschen's Law for Microscale Gas Breakdown at Subatmospheric Pressure.

The decrease in electronic device size necessitates greater understanding of gas breakdown and electron emission at microscale to optimize performance. While traditional breakdown theory using Paschen's law (PL), driven by Townsend avalanche, fails for gap distance d [Formula: see text] 15 μm, recent studies have derived analytic equations for breakdown voltage when field emission and Townsend avalanche drive breakdown. This study derives a new analytic equation that predicts breakdown voltage V within 4% of the exact numerical results of a previously derived theory and new experimental results at subatmospheric pressure for gap distances from 1-25 μm.

Using extracellular calcium concentration and electric pulse conditions to tune platelet-rich plasma growth factor release and clotting.

Platelet-rich plasma (PRP) is an emerging autologous biologic method for wound healing. Clinicians apply PRP either topically (where it is activated ex-vivo before treatment by adding an external agent to trigger clotting and the release of growth factors that facilitate wound healing) or through injection (where it is activated in vivo at the injury site with no prior activation before injection). Because topical PRP activation typically utilizes bovine thrombin, which has significant potential side effects and high costs, recent studies have assessed the efficacy of combining extracellular calcium (EC) and electric pulses (EPs) to activate PRP.

Synergistic bacterial inactivation by combining antibiotics with nanosecond electric pulses.

Antibiotic resistance mechanisms render current antibiotics ineffective, requiring higher concentrations of existing drugs or the development of more powerful drugs for infection treatment. This study demonstrates the synergistic inactivation of a gram-positive (Staphylococcus aureus) and a gram-negative (Escherichia coli) bacteria by combining either tobramycin or rifampicin with 300-ns electric pulses (EPs). For EPs depositing the same total energy density into the sample with no drug, higher electric fields induced greater inactivation, indicating a threshold for irreversible electroporation at these fields and membrane recovery in between lower intensity EPs.

Fabrication and characterization of implantable flushable electrodes for electric field-mediated drug delivery in a brain tissue-mimic agarose gel.

Every forty minutes, one person dies in the USA due to glioblastoma multiforme; a deadly form of brain cancer with an average five-year survival rate less than 3%. The current standard of care for treatment involves surgical resection of the accessible tumor followed by radiation therapy and concomitant chemotherapy. Despite their potency, delivering chemotherapeutic agents to the brain is limited by the highly selective blood-brain barrier, which prevents molecules >500 Da from reaching the brain.

Design, characterization and experimental validation of a compact, flexible pulsed power architecture for ex vivo platelet activation.

Electric pulses can induce various changes in cell dynamics and properties depending upon pulse parameters; however, pulsed power generators for in vitro and ex vivo applications may have little to no flexibility in changing the pulse duration, rise- and fall-times, or pulse shape. We outline a compact pulsed power architecture that operates from hundreds of nanoseconds (with the potential for modification to tens of nanoseconds) to tens of microseconds by modifying a Marx topology via controlling switch sequences and voltages into each capacitor stage. We demonstrate that this device can deliver pulses to both low conductivity buffers, like standard pulsed power supplies used for electroporation, and higher conductivity solutions, such as blood and platelet rich plasma.

Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma.

Background: Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin.

Plasma membrane temperature gradients and multiple cell permeabilization induced by low peak power density femtosecond lasers.

Calculations indicate that selectively heating the extracellular media induces membrane temperature gradients that combine with electric fields and a temperature-induced reduction in the electropermeabilization threshold to potentially facilitate exogenous molecular delivery. Experiments by a wide-field, pulsed femtosecond laser with peak power density far below typical single cell optical delivery systems confirmed this hypothesis. Operating this laser in continuous wave mode at the same average power permeabilized many fewer cells, suggesting that bulk heating alone is insufficient and temperature gradients are crucial for permeabilization.

Platelet activation using electric pulse stimulation: growth factor profile and clinical implications.

Background: Autologous platelet gel therapy using platelet-rich plasma has emerged as a promising alternative for chronic wound healing, hemostasis, and wound infection control. A critical step for this therapeutic approach is platelet activation, typically performed using bovine thrombin (BT) and calcium chloride. However, exposure of humans to BT can stimulate antibody formation, potentially resulting in severe hemorrhagic or thrombotic complications.

Nonthermal atmospheric plasma rapidly disinfects multidrug-resistant microbes by inducing cell surface damage.

Plasma, a unique state of matter with properties similar to those of ionized gas, is an effective biological disinfectant. However, the mechanism through which nonthermal or "cold" plasma inactivates microbes on surfaces is poorly understood, due in part to challenges associated with processing and analyzing live cells on surfaces rather than in aqueous solution. Here, we employ membrane adsorption techniques to visualize the cellular effects of plasma on representative clinical isolates of drug-resistant microbes.

Nanosecond electric pulses penetrate the nucleus and enhance speckle formation.

Nanosecond electric pulses generate nanopores in the interior membranes of cells and modulate cellular functions. Here, we used confocal microscopy and flow cytometry to observe Smith antigen antibody (Y12) binding to nuclear speckles, known as small nuclear ribonucleoprotein particles (snRNPs) or intrachromatin granule clusters (IGCs), in Jurkat cells following one or five 10ns, 150kV/cm pulses. Using confocal microscopy and flow cytometry, we observed changes in nuclear speckle labeling that suggested a disruption of pre-messenger RNA splicing mechanisms.

Ultrashort electric pulse induced changes in cellular dielectric properties.

The 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 10ns, 150kV/cm electrical pulses. The cytoplasm and nucleoplasm conductivities decreased dramatically following pulsing, corresponding to previously observed rises in cell suspension conductivity.

Leukemic cell intracellular responses to nanosecond electric fields.

Intense, nanosecond (ns) pulsed electric fields (PEFs) are known to affect the intracellular structures of cells. The probability of preferentially inducing subcellular effects increases with decreasing pulse length while effects on the plasma membrane are diminished. This has been demonstrated by applying electrical pulses of 60 and 10 ns duration with electric field intensities of up to 6.