Short Electrical Pulses Research Articles

Compact low‐cost high‐voltage pulse generator for biological applications

SummaryIn order to test the electroporation applied to mammalian cells (DU‐145 human prostate cancer cell line), treated with short (30 ns) intense electric pulses, a new architecture of a pulse generator is proposed. It provides a quasi‐rectangular output with nanosecond rise time and fully controlled repetition rate, which allows the control of the electric field dose applied to the cells. The system consists of a pulse generator with a high voltage gain and power efficiency, but it outputs exponential pulses. To improve that side, a pulse forming line (PFL) is used to get the final rectangular pulse. The whole device is designed using a multilayer printed circuit board (PCB) technology. That reduces the cost and increases the compactness of the generator. The output is connected to a special electroporation cuvette filled with special liquid. The impedance of such load is not well known, that is why some preliminary tests were carried out to identify the load of the generator. A number of simulations allowed to validate the design and to find out the influence of different parameters on its characteristics. Finally, a compact 4‐kV generator was built and tested. The results are discussed and compared with those obtained from simulations.

Direct observation of the processes near particle-to-particle contacts at electric pulse consolidation of titanium powder

Direct high-speed micro-video records prove the existence of highly overheated zones at the contacts of powder particles during short (~ 1 ms) electric current pulses. The value of overheating can exceed 1600 degrees and lead to the formation of liquid-phase sintering necks, the dimensions of which are well correlated with the size of the overheated zones. The micro-uniformity of the temperature field in the electric pulse heating allow understanding the unusually high consolidation rates of powder materials observed in spark plasma sintering.

Toward Ultrafast Tuning and Triggering Single-Photon Electroluminescence of Color Centers in Silicon Carbide

Electrically driven single-photon sources are essential for building compact, scalable, and energy-efficient quantum information devices. Recently, color centers in SiC emerged as promising candidates for such nonclassical light sources. However, very little is known about how to control, dynamically tune, and trigger their single-photon electroluminescence (SPEL), which is required for efficient generation of single photons on demand. Here, we propose and theoretically demonstrate a concept of a gate-tunable single-photon emitting diode (GT-SPED). We show that the SPEL rate of a single silicon antisite defect near stacking faults (SiC-SF center) in the 4H-SiC GT-SPED can be not only dynamically tuned in the range from 0.16 to 40 Mcps but also switched on and off in less than 0.2 ns. This time is shorter than the lifetime of the excited state of the SiC-SF center, which gives the possibility to trigger single-photon generation by applying short electric pulses. The high contrast ratio between the ON and OFF states combined with short characteristic times creates a solid foundation for the development of on-demand high-repetition-rate single-photon sources.

Determining velocity of detonation using high-resolution time domain reflectometry

Two methods are presented to make measurements of the length of a coaxial cable with submillimeter and submicrosecond accuracy. If the cable is destroyed by the passage of a strong shock, for instance, from the detonation of an explosive, a measure of the phase velocity of the detonation (VOD) can be obtained with high accuracy (≈0.25%). The first method introduces a series of short Gaussian electrical pulses (<300 ps) into the cable that reflect off the cable end and are compared to the time of the original outgoing pulse by using a fast digitizer (100 gigasamples per second). By curve fitting a Gaussian form to the outgoing and reflected pulses, a measurement of the cable length can be made with subsample accuracy. So, as long as the pulses do not overlap, a large number may be present in the cable at any time allowing pulse repetition rates of 40-135 MHz depending on the cable length. Averaging allows accurate VOD measurements to be made that are comparable with the best traditional techniques. The second method replaces the pulser with a wide-spectrum (0.1-10 GHz) amplified random noise source. A similar setup and digitizer are used before autocorrelating short (80-160 ns) subsamples of the total waveform to measure the reflected delay time. That is, a smaller amplitude version of the original waveform appears time shifted by twice the transit time in the cable and this time is estimated via autocorrelation. The advantage of this method is that a new subsample needs only to be selected from a time increment in which new spectral information is present for a new measure of the length to be made. In this manner, many more length estimates can be averaged to establish the VOD than with the Gaussian approach. A detailed description of the implementation of both methods is presented together with an example of the type of data collected and limitations found.

A 100-ps Pulse Laser as a Calibration Source

We have developed a pulsed laser with a pulsewidth of 70 ps in the full-width at half-maximum as a light source for calibrating photon detectors. It has a simple electric circuit that generates short electric pulses that are applied to a laser diode. By utilizing the properties of the diode, a laser beam with a pulsewidth that is one-tenth of the applied electric pulse can be generated. Since the electric circuit is a simple shaping circuit, the pulsed laser can be generated at low cost, and the device can be made compact, occupying only a few cubic centimeters. Such short-pulsed-light sources are useful in high-energy experiments and astronomical observation as the time resolution and read-out electronics of the photon detectors are being continually advanced. The performance of this pulsed laser and its application for the calibration of photon detectors are reported in this paper.

Electrodeposition of Platinum Catalyst from Ionic Liquids

The deposition of platinum from precursors dissolved in the ionic liquid 1-methyl-1-octylpyrrolidinium bis(trifluoromethylsulfonyl) imide (OMP-TFSI) was the main scope of this study. Boron doped diamond (BDD) and Au electrodes on quartz resonators were used as the substrates. A typical Pt deposition on BDD and Au was accomplished by applying short electrical pulses followed by relaxation phases for different duration in order to find optimal deposition conditions. In order to prove whether Pt was deposited on the electrode, samples were cycled in 0.1 M H2SO4 after deposition. In addition to electrochemical parameters, in the experiments on Au, the electrochemical quartz crystal microbalance permitted to monitor directly changes in the resonance frequency and damping associated with the Pt ion reduction processes.

Post-treatment analysis of irreversible electroporation waveforms delivered to human pancreatic cancer patients.

Irreversible electroporation (IRE) is a focal ablation therapy that uses high voltage, short electrical pulses to destroy tumor tissue. The success of treatment directly depends on exposure of the entire tumor to a lethal electric field magnitude. However, this exposure is difficult to predict ahead of time and it is challenging for clinicians to determine optimal treatment parameters. One method clinicians rely upon for the cessation of pulse delivery is to monitor the resistance value of the tissue, as the cells within the tissue will undergo changes during electroporation. This work presents a computational model which incorporates human pancreatic tumor conductivity, and compares predicted and measured output currents from IRE treatments of human patients. The measured currents vary widely from patient to patient, suggesting there may areas of high local conductivity in the treatment area.

Local Joule heating and electric force on biological membrane during electro-microinjection

Microinjection is one of the key technologies to introduce foreign molecules into the animal cell and embryos. Recently, a novel microinjection method for piercing relatively large egg (∼ϕ1 mm) utilizing the short electric pulse to pierce the biomembrane was developed. Although this method, electro-microinjection, was proved to be capable to pierce the stiff shell of fish egg without fatal damage, its mechanism has not been understood enough to optimize the parameter and the configuration of electro-microinjection. In this study, we have clarified the mechanism of electro-microinjection by numerically calculating the electric and thermal fields during electro-microinjection. A numerical model based on the time domain finite element method (TDFEM) with the measured reliable electric properties of fish egg was developed to calculate the intra-cell electric and thermal fields in detail. The calculation was performed in the conditions of minimal required pulse strength for piercing (227–1470 V) at various given pulse length (10 μs–1 ms) that were obtained from our previous research. The results revealed that the applied pulse generates a locally focused high temperature near the needle electrode and an electric force of 80 μN at its maximum which draws the fish egg to the injection needle. It was found that at least the local temperature of 330 K near the tip of piercing needle by Joule heating is required for electro-microinjection to decrease the rupture stress of the stiff biological shell of fish egg.

Nonlinear Dispersive Model of Electroporation for Irregular Nucleated Cells.

In this work, the electroporation phenomenon induced by pulsed electric field on different nucleated biological cells is studied. A nonlinear, non-local, dispersive, and space-time multiphysics model based on Maxwell's and asymptotic Smoluchowski's equations has been developed to calculate the transmembrane voltage and pore density on both plasma and nuclear membrane perimeters. The irregular cell shape has been modeled by incorporating in the numerical algorithm the analytical functions pertaining to Gielis curves. The dielectric dispersion of the cell media has been modeled considering the multi-relaxation Debye-based relationship. Two different irregular nucleated cells have been investigated and their response has been studied applying both the dispersive and non-dispersive models. By a comparison of the obtained results, differences can be highlighted confirming the need to make use of the dispersive model to effectively investigate the cell response in terms of transmembrane voltages, pore densities, and electroporation opening angle, especially when irregular cell shapes and short electric pulses are considered. Bioelectromagnetics. 2019;40:331-342. © 2019 Wiley Periodicals, Inc.

Radio Frequency Oscillations in Gyrotropic Nonlinear Transmission Lines

The paper considers the quasi-monochromatic radio frequency oscillations that are observable in transmission lines of doubly connected cross-sections, partially filled with a magnetized ferrite. The frequencies and amplitudes of the oscillations appearing under the impact of short carrier-free electric pulses are determined by dispersive and non-linear properties of the line’s structure. The dispersion characteristics are governed by the geometry and size of the line and the spatial arrangement in the line of the ferromagnetic material with its intrinsic dispersion. The dependences shown by the oscillation parameters in real physical experiments are reproduced and analyzed via numerical simulation within models which account separately for different physical properties of the material and the structure.

Low-Voltage Irreversible Electroporation Using a Comb-Shaped Contact Electrode.

Irreversible electroporation (IRE) is a less invasive therapy to ablate tumor cells by delivering short intensive electric pulses more than a few kV via needle-like electrodes. For reducing the required voltage for the IRE, a durable comb-shaped miniature electrode was designed to use in contact with the lesion surface for a new method named contact IRE. A miniature electrode was newly fabricated by a fine inkjet patterning and the subsequent etching of a copper-clad polyimide film. A train of 10-μs or 100-μs long electric pulses were applied 90 times at the interval of 1 s to a tissue phantom, and its cross section was observed to measure the necrotized area. Cell experiments showed that the maximum ablation depth increased as a function of the applied voltage and reached 400 μm at 20 V. Furthermore, insulation of the lateral space between electrode teeth with a resin and administration of adjuvants to reduce the IRE threshold of the cell membrane did increase the ablation depth by 26% and the ablation area by 40%. The miniature electrode developed in this study successfully necrotized cells in a tissue phantom 400 μm deep from the surface with the electric pulses of only 20 V. The contact IRE for the surface of skin and gastrointestinal tract will ablate cutaneous and subcutaneous tumors by applying only several tens of volts.

Analysis of Optical and Electrical Responses of $\boldsymbol{\mu}$ -OLED With Metallized ITO Coplanar Waveguide Electrodes Submitted to Nanosecond Electrical Pulses

In this paper, the optical and electrical pulse responses of an optimized high-speed organic light-emitting diode (OLED) is investigated as a function of the pulse duration. The original design is based on the coplanar waveguide electrodes that are implemented on a transparent and conductive oxide thin film. The designed electrodes with reduced serial resistances (13 $\Omega $ ) allow to maximize the pulse energy delivery and to feed the organic device with short electrical pulses of few nanoseconds for the first time. This is achieved by designing the electrodes to have 50- $\Omega $ characteristic impedance, thanks to microwave techniques, and by implementing small values of capacitance (4.5 pF). The experimental results demonstrate $\boldsymbol \mu $ -OLED electrical and optical responses to electrical excitation pulses as short as 2.5 ns, for the first time, and state-of-the-art current densities above 1.7 kA/cm2. Moreover, and rather unexpectedly, the developed characterization procedure to extract the reported results demonstrated the first direct measurement of the electroluminescence lifetime of organic materials in the nanosecond time scale.

Effect of high-rate annealing on microstructure, martensitic transformation and shape memory behavior of TiNiCu melt-spun ribbons

The amorphous rapidly quenched quasi-binary TiNi–TiCu alloys containing 30–38 at.% Cu were crystallized by isothermal annealing at 500 °C for 300 s and by exposing to short electric pulse with a duration of 10 ms to study the effect of the annealing rate on their properties. The results obtained showed that electropulse crystallization fundamentally changed the microstructure of the alloys due to almost completely hindering the formation of brittle Ti-Cu phases. This leads to a significant increase in the enthalpy of the martensitic transformation and a considerable shift of the transformation range towards higher temperatures. It was found that reducing the crystallization time dramatically increases the plasticity and shape memory effect of the alloys.

Electrochemotherapy: A Review of Current Status, Alternative IGP Approaches, and Future Perspectives.

The efficiency of electroporation (EP) has made it a widely used therapeutic procedure to transfer cell killing substances effectively to the target site. A lot of researches are being done on EP-based cancer treatment techniques. Electrochemotherapy (ECT) is the first EP-based application in the field of drug administration. ECT is a local and nonthermal treatment of cancer that combines the use of a medical device with pharmaceutical agents to obtain local tumor control in solid cancers. It involves the application of eight, 100µs, pulses at 1 or 5000 Hz frequency and specified electric field (V/cm) with a median duration of 25 minutes. The efficacy of chemotherapeutic drugs increases by applying short and intense electrical pulses. Several clinical studies proposed ECT as a safe and complementary curative or palliative treatment option (curative intent of 50% to 63% in the treatment of Basal Cell Carcinoma (BCC)) to treat a number of solid tumors and skin malignancies, which are not suitable for conventional treatments. It is used currently for treatment of cutaneous and subcutaneous lesions, without consideration of their histology. On the contrary, it is also becoming a practical method for treatment of internal, deep-seated tumors and tissues. A review of this method, needed instruments, alternative image-guided procedures (IGP) approaches, and future perspectives and recommendations are discussed in this paper.

Chemical Enhancement of Irreversible Electroporation: A Review and Future Suggestions.

Irreversible electroporation has raised great interest in the past decade as a means of destroying cancers in a way that does not involve heat. Irreversible electroporation is a novel ablation technology that uses short high-voltage electrical pulses to enhance the permeability of tumor cell membranes and generate irreversible nano-sized structural defects or pores, thus leading to cell death. Irreversible electroporation has many advantages over thermal therapies due to its nonthermal mechanism: (1) reduced risk of injury to surrounding organs and (2) no “heat-sink” effect due to nearby blood vessels. However, so far, it has been difficult for irreversible electroporation to completely ablate large tumors (eg, >3 cm in diameter). In order to overcome this problem, many preclinical and clinical studies have been performed to improve the efficacy of IRE in the treatment of large size of tumors through a chemical perspective. Due to the distribution of electric field, irreversible electroporation region, reversible electroporation region, and intact region can be found in the treatment of irreversible electroporation. Thus, 2 types of chemical enhancements of irreversible electroporation were discussed in the article, such as the reversible electroporation region enhanced and the irreversible electroporation region enhanced. Specifically, the state-of-the-art results regarding the following approaches that have the potential to be used in the enhancement of irreversible electroporation were systematically reviewed in the article, including (1) combination with cytotoxic drugs, (2) calcium electroporation, (3) modification of cell membrane, and (4) modification of the tumor cell microenvironment. In the end, we concluded with 4 issues that should be addressed in the future for improving irreversible electroporation further in a chemical way.

Ultra-high selectivity pulsed plasmachemical deposition reaction pathways.

Glycidyl methacrylate pulsed plasmas have been investigated using time-resolved in situ mass spectrometry. At low pulsed plasma duty cycles, monomer fragmentation leading to the formation of polymerisation initiator species occurs within each short electrical discharge pulse (ton = microseconds timescale). This is followed by conventional step-wise monomer addition polymerisation occurring during the subsequent extended off-period (toff = milliseconds timescale), culminating in the growth of well-defined poly(glycidyl methacrylate) chains. Key attributes associated with this high selectivity pulsed plasmachemical functional thin film synthesis approach are the absence of the requirement for any additional chemicals (catalyst, solvent, etc.) in combination with very low power consumption (mW) and ambient temperature.

Electrochemical generation of microbubbles by carbon nanotube interdigital electrodes to increase the permeability and material uptakes of cancer cells

Artificial cavitation as a prerequisite of sonoporation, plays an important role on the ultrasound (US) assisted drug delivery systems. In this study, we have proposed a new method of microbubble (MB) generation by local electrolysis of the medium. An integrated interdigital array of three-electrode system was designed and patterned on a nickel-coated quartz substrate and then, a short DC electrical pulse was applied that consequently resulted in distributed generation of microbubbles at the periphery of the electrodes. Growth of the carbon nanotube (CNT) nanostructures on the surface of the electrodes approximately increased the number of generated microbubbles up to 7-fold and decreased their average size from ∼20 µm for bare to ∼7 µm for CNT electrodes. After optimizing the three-electrode system, biocompatibility assays of the CNT electrodes stimulated by DC electrical micropulses were conducted. Finally, the effect of the proposed method on the sonoporation efficiency and drug uptake of breast cells were assessed using cell cycle and Annexin V/PI flow cytometry analysis. These results show the potential of electrochemical generation of MBs by CNT electrodes as an easy, available and promising technique for artificial cavitation and ultrasound assisted drug delivery.

Practical Constraints on Nonlinear Transmission Lines for RF Generation

Previous research has shown the applicability of nonlinear transmission lines (NLTLs) in high speed and wide bandwidth systems. These applications involve techniques for forming and sharpening a short electrical pulse to achieve pulse compressors, frequency multipliers, phase shifters, and, in addition, radio frequency (RF) generation, holding, in this case, a great potential for replacing vacuum electron tubes with a low cost and fully solid-state technology. Based on the analysis of relevant experimental results of different types of NLTLs reported in the literature, this paper presents an investigation about the correlation between the performance limits of NLTLs and specific characteristics of the materials used in their construction, concluding that there is a pressing demand for the development of high-performance dielectric and magnetic materials with special characteristics such as highly nonlinear behavior, low losses at microwave frequencies, and thermal stability that would allow for an improvement in the performance of NLTLs, enabling their operation at higher frequencies and with better electrical-to-RF conversion efficiency. The achievement of a stable behavior over a broader operating temperature range would allow the application of NLTLs in military and aerospace devices.

Cas9-guide RNA ribonucleoprotein-induced genome editing in the industrial green alga Coccomyxa sp. strain KJ

BackgroundOxygen-evolving photosynthetic microorganisms, collectively termed as microalgae, are gaining attention as alternative fuel sources. The unicellular alga Coccomyxa sp. strain KJ that belongs to the class Trebouxiophyceae can grow rapidly in minimal mineral media and accumulate triacylglycerols at levels > 60% (w/w) of its dry weight under nitrogen depletion conditions. Thus, the strain can be a good candidate for biofuel production. Still, substantial improvements in lipid productivity and other traits of this strain are needed to meet commercial production requirements. Consequently, the development of new genetic tools including genome editing that are applicable to this strain is highly desired.ResultsIn this paper, we report successful genome editing of strain KJ by intracellular delivery of a ribonucleoprotein complex comprising recombinant Cas9 protein and guide RNA. For introduction of Cas9-guide RNA ribonucleoprotein into strain KJ cells, we used an electroporator with a short (2.5 ms) electric pulse at a high field strength (7500 V cm−1) followed by multiple 50-ms electric pulses at low field strength (250 V cm−1). Under these conditions, we successfully isolated several knockout lines of the FTSY gene of strain KJ, encoding a signal recognition particle-docking protein at a frequency of 0.01%.ConclusionsOur study shows applicability of DNA-free genome editing in Coccomyxa, which may be applicable in other Trebouxiophyceae species.

Switchable Two‐Terminal Transparent Optoelectronic Devices Based on 2D Perovskite

AbstractA switch‐like structure that can be turned on/off with photons is considered necessary for most optoelectronic devices, such as phototransistors and photodetectors. However, developing a single device whose photoresponse can be modulated without changing the measuring voltage or illuminating light is challenging, and yet to be achieved. In this work, a conceptually new 2D perovskite‐based fully transparent two‐terminal optoelectronic device that can be turned on/off with a short electric pulse without any further change in the measuring conditions, such as the illuminating photon or applied voltage is proposed and demonstrated. The device exhibits loop opening in the current–voltage characteristics, which is utilized to design the novel electrically triggered optoelectronic device. The photocurrent of the device can be modulated from zero to 2.2 mA using a simple voltage pulse. Further, a responsivity of 550 mA W−1 and detectivity of 2.16 × 1010 Jones are measured in the on‐state. Potentially, the approach opens a new avenue for the design of two‐terminal advanced highly transparent optoelectronic devices, such as smart windows and transparent image sensors.