Shoulong Dong

FPGA-Controlled All-Solid-State Nanosecond Pulse Generator for Biological Applications

In vivo studies of tumor-cell apoptosis induced by nanosecond pulsed electric field require high-voltage nanosecond pulses delivered to the biological tissues. In this paper, a newly developed all-solid-state nanosecond pulse generator based on the Marx generator concept is proposed for this application. The generator comprises four parts: a dc charging power, a solid-state Marx circuit using metal-oxide-semiconductor field-effect transistors, a control circuit using a field-programmable gate array, and the load. This generator has the capability of producing repetitive pulses with a voltage up to 8 kV, pulsewidth of 200-1000 ns, rise time of 35 ns, and repetition rate of 1-1000 Hz with various resistive loads and 1-kV dc input voltage. The all-solid-state design makes the generator compact and reliable. Initial experiments were carried out to verify the performances of the proposed generator.

Bipolar Microsecond Pulses and Insulated Needle Electrodes for Reducing Muscle Contractions During Irreversible Electroporation

Objective: To minimize the effect of muscle contractions during irreversible electroporation (IRE), this paper attempts to research the ablation effect and muscle contractions by applying high-frequency IRE (H-FIRE) ablation to liver tissue in vivo. Methods: An insulated needle electrode was produced by painting an insulating coating on the outer surface of the needle electrode tip. A series of experiments were conducted using insulated needle electrodes and traditional needle electrodes to apply H-FIRE pulses and traditional monopolar IRE pulses to rabbit liver tissues. The finite element model of the rabbit liver tissue was established to determine the lethal thresholds of H-FIRE in liver tissues. Muscle contractions were measured by an accelerometer. Results: With increased constitutive pulse width and pulse voltage, the ablation area and muscle contraction strength are also increased, which can be used to optimize the ablation parameters of H-FIRE. Under the same pulse parameters, the ablation areas are similar for the two types of electrodes, and the ablation region has a clear boundary. H-FIRE and insulated needle electrodes can mitigate the extent of muscle contractions. The lethal thresholds of H-FIRE in rabbit liver tissues were determined. Conclusion: This paper describes the relationships between the ablation area, muscle contractions, and pulse parameters; the designed insulated needle electrodes can be used in IRE for reducing muscle contraction. Significance: The study provides guidance for treatment planning and reducing muscle contractions in the clinical application of H-FIRE.

A Novel Configuration of Modular Bipolar Pulse Generator Topology Based on Marx Generator With Double Power Charging

A bipolar pulse has been proved to be more advanced in the treatment of tumor because of the elimination of muscle contractions and the effect for ablating nonuniform tissue. In this paper, a new type of modular bipolar pulsed-power generator based on Marx generator with double power charging is proposed. The concept of this generator is charging the two series of capacitors in parallel by two power sources, respectively, and then connecting the capacitors in series through solid-state switches with different control strategies. Utilizing a number of fast solid-state switches, the capacitors can be connected in series with different polarities, so that a positive or negative polarity pulse will be delivered to the load. The simulated models of this generator have been investigated in a PSPICE platform, and a laboratory prototype has been implemented in a laboratory. The simulation and test results verify the operation of the proposed topology in different switching modes. The development of this pulse generator can provide the hardware foundation for the research on biological effect without muscle contraction when the tumors are applied with bipolar pulse electric field.

Irreversible electroporation ablation area enhanced by synergistic high- and low-voltage pulses

Irreversible electroporation (IRE) produced by a pulsed electric field can ablate tissue. In this study, we achieved an enhancement in ablation area by using a combination of short high-voltage pulses (HVPs) to create a large electroporated area and long low-voltage pulses (LVPs) to ablate the electroporated area. The experiments were conducted in potato tuber slices. Slices were ablated with an array of four pairs of parallel steel electrodes using one of the following four electric pulse protocols: HVP, LVP, synergistic HVP+LVP (SHLVP) or LVP+HVP. Our results showed that the SHLVPs more effectively necrotized tissue than either the HVPs or LVPs, even when the SHLVP dose was the same as or lower than the HVP or LVP doses. The HVP and LVP order mattered and only HVPs+LVPs (SHLVPs) treatments increased the size of the ablation zone because the HVPs created a large electroporated area that was more susceptible to the subsequent LVPs. Real-time temperature change monitoring confirmed that the tissue was non-thermally ablated by the electric pulses. Theoretical calculations of the synergistic effects of the SHLVPs on tissue ablation were performed. Our proposed SHLVP protocol provides options for tissue ablation and may be applied to optimize the current clinical IRE protocols.

Characterization of Conductivity Changes During High-Frequency Irreversible Electroporation for Treatment Planning

For irreversible-electroporation (IRE)-based therapies, the underlying electric field distribution in the target tissue is influenced by the electroporation-induced conductivity changes and is important for predicting the treatment zone. Objective: In this study, we characterized the liver tissue conductivity changes during high-frequency irreversible electroporation (H-FIRE) treatments of widths 5 and 10 μs and proposed a method for predicting the ablation zones. Methods: To achieve this, we created a finite-element model of the tissue treated with H-FIRE and IRE pulses based on experiments conducted in an in-vivo rabbit liver study. We performed a parametric sweep on a Heaviside function that captured the tissue conductivity versus electric field behavior to yield a model current close to the experimental current during the first burst/pulse. A temperature module was added to account for the current increase in subsequent bursts/pulses. The evolution of the electric field at the end of the treatment was overlaid on the experimental ablation zones determined from hematoxylin and eosin staining to find the field thresholds of ablation. Results: Dynamic conductivity curves that provided a statistically significant relation between the model and experimental results were determined for H-FIRE. In addition, the field thresholds of ablation were obtained for the tested H-FIRE parameters. Conclusion: The proposed numerical model can simulate the electroporation process during H-FIRE. Significance: The treatment planning method developed in this study can be translated to H-FIRE treatments of different widths and for different tissue types.

Synergistic combinations of short high-voltage pulses and long low-voltage pulses enhance irreversible electroporation efficacy

Irreversible electroporation (IRE) uses ~100 μs pulsed electric fields to disrupt cell membranes for solid tumor ablation. Although IRE has achieved exciting preliminary clinical results, implementing IRE could be challenging because of volumetric limitations at the ablation region. Combining short high-voltage (SHV: 1600V, 2 μs, 1 Hz, 20 pulses) pulses with long low-voltage (LLV: 240–480 V, 100 μs, 1 Hz, 60–80 pulses) pulses induces a synergistic effect that enhances IRE efficacy. Here, cell cytotoxicity and tissue ablation were investigated. The results show that combining SHV pulses with LLV pulses induced SKOV3 cell death more effectively, and compared to either SHV pulses or LLV pulses applied alone, the combination significantly enhanced the ablation region. Particularly, prolonging the lag time (100 s) between SHV and LLV pulses further reduced cell viability and enhanced the ablation area. However, the sequence of SHV and LLV pulses was important, and the LLV + SHV combination was not as effective as the SHV + LLV combination. We offer a hypothesis to explain the synergistic effect behind enhanced cell cytotoxicity and enlarged ablation area. This work shows that combining SHV pulses with LLV pulses could be used as a focal therapy and merits investigation in larger pre-clinical models and microscopic mechanisms.

Dielectric variations of potato induced by irreversible electroporation under different pulses based on the cole-cole model

To investigate dielectric property variations induced by electric pulses, equivalent doses of conventional irreversible electroporation (IRE) and high-frequency IRE were used to treat potato slices. The dielectric property of the potatoes were measured before and after treatment in the frequency band of 0.1 Hz-10 MHz, and then the Cole-Cole model was used to fit the experimental data in the frequency band of 1 kHz-10 MHz to explain the β dispersion mechanism. The Cole-Cole model parameters showed that under an equivalent dose, the conventional IRE pulses were more efficient than the high-frequency IRE pulses for electroporation. After treatment with conventional IRE pulses, the DC conductivity greatly increased at time 0 after the pulses and showed little recovery over time. The electroporation effect of the high-frequency IRE pulses improved with increasing pulse duration. This study presents a potential new method for evaluating the effects of IRE during and immediately after the treatment process.

Investigation of condition monitoring of transformer winding based on detection simulated transient overvoltage response

In order to keep the original connection of transformer, a novel method and apparatus is proposed for condition monitoring of transformer winding based on the detection of transient overvoltage signals. Firstly, a lumped parameter model of transformer winding is established to verify the equivalence in frequency response analysis between the overvoltage and sweep frequency voltage. Then experimental study is conducted on different types of winding faults, to conform the capability to identify the winding fault types. And the investigation of condition monitoring of 110 kV transformer is conducted. The over-voltage frequency response method is verified and can be applied to online monitoring of field windings.

Development and Simulation of a Compact Picosecond Pulse Generator Based on Avalanche Transistorized Marx Circuit and Microstrip Transmission Theory

The new biological effect of picosecond pulsed electric fields (psPEFs) has elicited the interest of researchers. A pulse generator based on an avalanche transistorized Marx circuit has been proposed. However, the problem of reflection in the transmission of the generated picosecond pulse based on this circuit has not received much attention and remains unresolved. In this paper, a compact picosecond pulse generator based on microstrip transmission theory was developed. A partial matching model based on microstrip transmission line theory was also proposed to eliminate reflection, and a series inductor was utilized to optimize pulse waveform. Through simulation studies and preliminary experimental tests, a pulse optimized with 1015 V amplitude, 620-ps width, and 10-kHz high stability repetition rate was generated. This pulse generator can be used with microelectrodes in cell experiments to explore the biological effect mechanism of psPEF.

Differences in the Effects of Duty Cycle and Interval on Cell Response Induced by High-Frequency Pulses Under Different Pulse Durations

High-frequency pulses constitute a new method for tumor treatment and have been proposed to solve the problems of muscle contraction and tumor recurrence caused by the nonuniform distribution of the electric field. However, the killing mechanism of high-frequency pulses remains unclear. Different pulse parameters have varying influences on the killing effect on cells. We studied the influence of the pulse duty cycle and the interval between pulses on the cellular response, including the transmembrane potential (TMP), pore radii, and the pore density, using finite-element simulation. Results showed that, given a pulse duration of 5 μs, the pulse duty cycle has an insignificant effect on the cellular response, and the cellular responses under monopolar pulses and bipolar pulses are similar. Given a bipolar pulse duration of 300 ns, the TMP and the pulse radii become larger if the interval between pulses is longer under bipolar pulses. Given a pulse duration of 300 ns, the TMP and pore radii under the monopolar pulse are larger than those under the bipolar pulse. Normal human epidermal cells (Hacat) and tumor cells (Gll19) are used to verify the simulation results, which show that the duty has an insignificant effect on cell killing. The simulation with the duration of 300 ns is verified using an experiment reported in the literature.