Bipolar Electric Pulses Research Articles

Synergistic Bipolar Irreversible Electroporation for Tumor Ablation without Muscle Contraction.

Irreversible electroporation (IRE) has emerged as a promising modality for tumor ablation, leveraging the controlled application of electrical pulses to induce cell death. However, the associated muscle contractions during the procedure pose challenges. This study introduces a novel approach, termed Synergistic Bipolar Irreversible Electroporation (SBIRE), aimed at achieving tumor ablation without the undesirable side effect of muscle contraction. SBIRE involves the simultaneous application of nanosecond bipolar electrical pulses (±1600 V per 0.2 cm or ±8000 V per 1 cm, ±500 ns, "+" to "-" delay 1 μs, "-" to "+" delay 200 μs, 5 cycles) and microsecond bipolar electrical pulses (±300 V per 0.2 cm or ±1500 V per 1 cm, ±2 μs, "+" to "-" delay 2 μs, "-" to "+" delay 1000 μs, 25 cycles), strategically designed to synergistically target tumor cells while minimizing the impact on adjacent muscle tissue. The experimental setup includes in vitro and in vivo studies utilizing tumor cells and animal models to assess the efficacy of SBIRE. Preliminary results demonstrate the effectiveness of SBIRE in inducing irreversible electroporation within the tumor, leading to cell death, and the ablation effect is better than other parameter forms (24.41±0.23 mm2 (SBIRE group) vs 12.93±0.31 mm2 (ns group), 6.55±0.23 mm2 (μs group), 19.54±0.25 mm2 (ns+μs group), p<0.0001). Notably, muscle contraction is significantly reduced compared to traditional IRE procedures, highlighting the potential of SBIRE to enhance patient comfort and procedural success. The development of SBIRE represents a significant advancement in the field of tumor ablation, addressing a fundamental limitation associated with muscle contraction during IRE. This technique not only offers a valuable and promising approach to tumor treatment but also holds promise for minimizing procedural side effects.

Electrical auricular tragus stimulation induces release of circulating cardioprotective factors in healthy human volunteers

Abstract Background Vagal activation during remote ischemic conditioning (RIC) with subsequent release of cardioprotective factors from the spleen into the circulation reduces infarct size. These humoral cardioprotective factors can be transferred with plasma-dialysate from human donors undergoing RIC to isolated recipient hearts where they reduce infarct size. Electrical auricular tragus stimulation (ATS) has been demonstrated to reduce the release of cardiac injury biomarkers and ventricular arrhythmias and to improve contractile function in patients with acute myocardial infarction. Purpose To determine whether ATS, as RIC, induces release of cardioprotective factors into the circulation. Methods Healthy volunteers (3 females, 7 males, 26±5 years) were randomized to receive ATS or RIC, respectively, with an interval of at least two weeks between protocols. ATS was induced by bipolar electrical rectangular pulses of 200 µs width and a frequency of 30 Hz. The amplitude (5.5 ± 0.81 mA) was set for each volunteer to not be perceived as uncomfortable. A microprocessor-controlled circuit periodically interrupted the stimulation signal after 5 s of stimulation for 5 s. ATS was continued over 30 min. RIC served as a reference to induce the release of cardioprotective factors by 3 x 5 min blood pressure cuff inflation at 200 mmHg on the left upper arm/ 5 min deflation. Venous blood samples were taken before and 60 min after ATS or RIC, respectively, and used to prepare plasma-dialysates (1:10 dialysis against buffer for 24 h, cut-off 12-14 kDa). Male Lewis rats were sacrificed and their hearts isolated and perfused at constant pressure with buffer. Plasma-dialysates from samples taken before and 60 min after ATS or RIC, respectively, were infused for 8 min into rat hearts followed by 2 min washout before global 30 min ischemia/ 120 min reperfusion. Infarct size was demarcated by triphenyl tetrazolium chloride staining and calculated as percent of ventricular mass. Results With infusion of plasma-dialysate before ATS, infarct size was 30.9 ± 4.5% of ventricular mass and not different from that with infusion of plasma-dialysate before RIC (35.8 ± 5.8 %). Infusion of plasma-dialysate after ATS reduced infarct size to 18.3 ± 3.9 %. This cardioprotective effect was similar to that seen with infusion of plasma-dialysate after RIC (20.1 ± 3.5 %). Conclusion ATS induces the release of cardioprotective factors into the circulation of healthy volunteers. Plasma-dialysates after ATS or RIC, respectively, reduce myocardial infarct size by the same magnitude in ex vivo isolated perfused rat hearts with global ischemia/ reperfusion.

Electrostatic Solitary Waves in the Venusian Ionosphere Pervaded by the Solar Wind: A Theoretical Perspective

Electrostatic solitary waves (ESWs) in the Venusian ionosphere that are impinged by the solar wind are investigated using a homogeneous, collisionless, and magnetized multicomponent plasma consisting of Venusian H+ and O+ ions, Maxwellian Venusian electrons and streaming solar wind protons, and suprathermal electrons following κ − distribution. The model supports the propagation of positive potential slow O+ and H+ ion-acoustic solitons. The evolution and properties of the solitons occurring in two sectors, viz., dawn-dusk and noon-midnight sector of the Venus ionosphere at an altitude of (200–2000) km, are studied. The theoretical model predicts positive potential solitons with amplitude ∼(0.067–56) mV, width ∼(1.7–53.21) m, and velocity ∼(1.48–8.33) km s−1. The bipolar soliton electric field has amplitude ∼(0.03–27.67) mV m−1 with time duration ∼(0.34–22) ms. These bipolar electric field pulses when Fourier transformed to the frequency domain occur as a broadband electrostatic noise, with frequency varying in the range of ∼9.78 Hz–8.77 kHz. Our results can explain the observed electrostatic waves in the frequency range of 100 Hz–5.4 kHz in the Venus ionosphere by the Pioneer Venus Orbiter mission. The model can also be relevant in explaining the recent observation of ESWs in the Venus magnetosheath by the Solar Orbiter during its first gravity assist maneuver of Venus.

Electrical auricular tragus stimulation induces release of circulating cardioprotective factors in healthy human volunteers.

Background: Vagal activation during remote ischemic conditioning (RIC) with subsequent release of cardioprotective factors from the spleen into the circulation reduces infarct size. These humoral cardioprotective factors can be transferred with plasma-dialysate from donors undergoing RIC to isolated recipient hearts where they reduce infarct size. Electrical auricular tragus stimulation (ATS) has been demonstrated to reduce the cardiac injury biomarker release and the frequency of ventricular arrhythmias and to improve contractile function in patients with acute myocardial infarction. Aim: To determine whether ATS, as RIC, induces release of cardioprotective factors into the circulation. Methods: Healthy volunteers (3 females, 7 males, 26±5 years) were randomized to receive ATS or RIC, respectively, with an interval of at least two weeks between protocols. ATS was induced by bipolar electrical rectangular pulses of 200μs width at a frequency of 30 Hz (Curamed TEN630, CURAmed, Shenzen Dongdixin Technology, Shenzhen, China). The amplitude (5.5 ± 0.81 mA) was set for each volunteer to not be perceived as uncomfortable over the total stimulation period. A microprocessor-controlled circuit periodically interrupted the stimulation signal after 5 s of stimulation for 5 s. ATS was continued over 30 min. RIC served as a reference to induce the release of cardioprotective factors by 3 x 5 min blood pressure cuff inflation at 200 mmHg on the left upper arm/ 5 min deflation. Venous blood samples were taken before and 60 min after ATS or RIC, respectively, and used to prepare plasma-dialysates (1:10 dialysis against buffer for 24 h, cut-off 12-14 kDa). Male Lewis rats were sacrificed and their hearts isolated and perfused at constant pressure with buffer. Plasma-dialysates from samples taken before and 60 min after ATS or RIC, respectively, were infused for 8 min followed by 2 min washout into rat hearts before global 30 min ischemia/ 120 min reperfusion. Infarct size was demarcated by triphenyl tetrazolium chloride staining and calculated as percent of ventricular mass. Results: With infusion of plasma-dialysate before ATS infarct size was 30.9±4.5% of ventricular mass and not different from that with infusion of plasma-dialysate before RIC (35.8±5.8%). Infusion of plasma-dialysate after ATS reduced infarct size to 18.3±3.9%. This cardioprotective effect was similar to that seen with infusion of plasma-dialysate after RIC (20.1±3.5%). Conclusion: ATS induces release of cardioprotective factors into the circulation of healthy volunteers. Plasma-dialysates after ATS or RIC, respectively, reduce myocardial infarct size by the same magnitude in ex vivo isolated perfused rat hearts with global ischemia/ reperfusion. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Next generation CANCAN focusing for remote stimulation by nanosecond electric pulses

Focusing electric pulse effects away from electrodes is a challenge because the electric field weakens with distance. Previously we introduced a remote focusing method based on bipolar cancellation, a phenomenon of low efficiency of bipolar nanosecond electric pulses (nsEP). Superpositioning two bipolar nsEP into a unipolar pulse canceled bipolar cancellation (“CANCAN” effect), enhancing bioeffects at a distance despite the electric field weakening. Here, we introduce the next generation (NG) CANCAN focusing with unipolar nsEP packets designed to produce bipolar waveforms near electrodes (suppressing electroporation) but not at the remote target. NG-CANCAN was tested in CHO cell monolayers using a quadrupole electrode array and labeling electroporated cells with YO-PRO-1 dye. We routinely achieved 1.5–2 times stronger electroporation in the center of the quadrupole than near electrodes, despite a 3–4-fold field attenuation. With the array lifted 1–2 mm above the monolayer (imitating a 3D treatment), the remote effect was enhanced up to 6-fold. We analyzed the role of nsEP number, amplitude, rotation, and inter-pulse delay, and showed how remote focusing is enhanced when re-created bipolar waveforms exhibit stronger cancellation. Advantages of NG-CANCAN include the exceptional versatility of designing pulse packets and easy remote focusing using an off-the-shelf 4-channel nsEP generator.

Development of Bipolar Pulse Power Supply Based on Peak Closed-Loop Control Method

With the wide application of pulsed power technology in tumor ablation, sewage treatment, and other related fields, researchers have found that bipolar electrical pulses are more effective than unipolar electrical pulses. In this article, a new bipolar pulse generator is proposed, which combines the features of boost circuit and Marx circuit to significantly improve the boost ratio of output pulse and the tunability of pulse peak. In order to improve the load regulation rate and peak stability of bipolar pulse power supply, a bipolar pulse power supply based on peak closed-loop control method is designed in this article. The high-voltage pulse is attenuated, and its peak is sampled by the pulse peak sampling circuit, and the pulse peak voltage is fed back to the DSP controller for comparison with the set peak value, and the proportional integral differential (PID) adjustment is performed according to the voltage deviation, and the boost ratio of the pulse generator is changed to realize the constant peak output of the bipolar pulse. In order to verify the feasibility of the proposed bipolar pulse generator with peak closed-loop control scheme, simulation and experimental studies of the bipolar pulse power supply with five-stage peak closed-loop control were conducted. The results show that the output repetition frequency of 5 kHz, pulsewidth of 5– <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$10~\mu \text{s}$ </tex-math></inline-formula> , and peak pulse value within ±2.0 kV can be stabilized when the input voltage is 100 V.

Response of Human Malignant Glioma Cells to Asymmetric Bipolar Electrical Impulses

Electric and electromagnetic pulses have been shown to enhance the endocytosis rate, with all-or-nothing responses beyond a field strength threshold and linear responses as a function of field strength and treatment duration utilizing bipolar symmetrical and monopolar pulses, respectively. Malignant glioma (MG) is resistant to chemotherapy. The present study looked for a new electrical impulse that can aid electrochemotherapy to deliver anticancer drugs while using less electrical energy. Bipolar asymmetric electric pulses were applied to U251MG cells suspended in physiologically conductive media in the presence of molecular probes, including Bleomycin. The delivered electric pulses with a pulse duration range of 180-500 µs and a frequency range of 100-400 Hz had a low field intensity ranging from 1.5 V/cm to 7.3 V/cm. Spectrophotometric and spectrofluorometric measurements were used to investigate the impact of these variables on cancer cell survival and the molecular probe uptake induced by the electric pulses. An all-or-nothing response was observed above a specified threshold of electric field intensity of 4 V/cm. This threshold was unaffected by changes in repetition frequency or pulse duration. It was not a temperature effect that caused the molecular probe uptake to increase. When bipolar asymmetric electric pulses were applied just before electroporation, the effectiveness of the cytotoxic impact of bleomycin was increased from 80%, when employing electroporation pulses alone, to 100%.

Action spectra and mechanisms of (in) efficiency of bipolar electric pulses at electroporation

The reversal of the electric field direction inhibits various biological effects of nanosecond electric pulses (nsEP). This feature, known as “bipolar cancellation,” enables interference targeting of nsEP bioeffects remotely from stimulating electrodes, for prospective applications such as precise cancer ablation and non-invasive deep brain stimulation. This study was undertaken to achieve the maximum cancellation of electroporation, by quantifying the impact of the pulse shape, duration, number, and repetition rate across a broad range of electric field strengths. Monolayers of endothelial cells (BPAE) were electroporated in a non-uniform electric field. Cell membrane permeabilization was quantified by YO-PRO-1 (YP) dye uptake and correlated to local electric field strength. For most conditions tested, adding an opposite polarity phase reduced YP uptake by 50–80 %. The strongest cancellation, which reduced YP uptake by 95–97 %, was accomplished by adding a 50 % second phase to 600-ns pulses delivered at a high repetition rate of 833 kHz. Strobe photography of nanosecond kinetics of membrane potential in single CHO cells revealed the temporal summation of polarization by individual unipolar nsEP applied at sub-MHz rate, leading to enhanced electroporation. In contrast, there was no summation for bipolar pulses, and increasing their repetition rate suppressed electroporation. These new findings are discussed in the context of bipolar cancellation mechanisms and remote focusing applications.

Bipolar Electric Field Pulses in the Martian Magnetosheath and Solar Wind; Their Implication and Impact Accessed by System Scale Size.

The scale size of the plasma boundary region between the sheath and ionosphere in the Martian system is often similar to the gyro‐radii of sheath protons, ∼200 km. As a result, ion energization via kinetic structures may play an important role in modifying the ion trajectories and thus be important when evaluating the large‐scale dynamics of the Martian system. In this paper, we report observations made with the MAVEN Langmuir Probe and Waves instrument of solitary bipolar electric field structures, and assess their potential role in ion energization in the Martian system. The observed structures appear as short duration (∼0.5 ms) bipolar electric field pulses of ∼1–25 mV/m, and are frequently observed in the upstream solar wind and inside the sheath. The study presented in this paper suggests that the bipolar electric field structures observed at Mars have an average electrostatic potential drop of ∼0.07 V. The estimated upper rate at which these structures could further energize the protons is estimated, assuming the protons gain the full 0.07 eV, to be ∼0.13 eV per gyration, or a change in proton energy of ∼0.3%, and a corresponding change in the gyroradius of ∼0.3 km. These numbers imply that to first order the bipolar structures are not a significant source of ion energization in the Martian magnetosheath.

Cardiac impact of high-frequency irreversible electroporation using an asymmetrical waveform on liver in vivo

BackgroundHigh-Frequency Irreversible Electroporation (H-FIRE) is a novel technology for non-thermal ablation. Different from Irreversible electroporation (IRE), H-FIRE delivers bipolar electrical pulses without muscle contraction and does not cause electrolysis. Currently, little is known regarding the cardiac safety during the administration of H-FIRE on liver. The aim of this study was to evaluate the changes of electrocardiogram (ECG) and biomarkers of cardiac damage during asymmetrical waveform of H-FIRE therapy in vivo.MethodsThe swines (n = 7) in IRE group, which used 100 pulses (2200 V, 100–100 μs configuration), were administrated with muscle relaxant under anesthesia. In the absence of muscle relaxant, 7 swines in H-FIRE group were performed with 2400 pulses (3000 V, 5–3–3–5 μs configuration). Midazolam (0.5 mg/kg) and xylazine hydrochloride (20 mg/kg) were given to induce sedation, followed by Isoflurane (2.5%, 100% oxygen, 3 L/min) to maintain sedation in all the swines. Limb lead ECG recordings were analyzed by two electrophysiologists to judge the arrhythmia. Cardiac and liver tissue was examined by pathology technique.ResultsThe ablation zones were larger in H-FIRE than IRE. Both IRE and H-FIRE did not affect the autonomous cardiac rhythm. Even when the electrical signal of IRE and H-FIRE fell on ventricular vulnerable period. Moreover, cTnI in IRE group showed an increase in 4 h after ablation, and decreased to baseline 72 h after ablation. However, cTnI showed no significant change during the administration of H-FIRE.ConclusionsThe study suggests an asymmetrical waveform for H-FIRE is a promising measure for liver ablation. The results were based on normal liver and the swines without potential cardiac diseases. With the limitations of these facts, asymmetrical waveform for H-FIRE of liver tissue seems relatively safe without major cardiac complications. The safety of asymmetrical waveform for H-FIRE needs to evaluate in future.

High-frequency irreversible electroporation brain tumor ablation: exploring the dynamics of cell death and recovery

Improved therapeutics for malignant brain tumors are urgently needed. High-frequency irreversible electroporation (H-FIRE) is a minimally invasive, nonthermal tissue ablation technique, which utilizes high-frequency, bipolar electric pulses to precisely kill tumor cells. The mechanisms of H-FIRE-induced tumor cell death and potential for cellular recovery are incompletely characterized. We hypothesized that tumor cells treated with specific H-FIRE electric field doses can survive and retain proliferative capacity. F98 glioma and LL/2 Lewis lung carcinoma cell suspensions were treated with H-FIRE to model primary and metastatic brain cancer, respectively. Cell membrane permeability, apoptosis, metabolic viability, and proliferative capacity were temporally measured using exclusion dyes, condensed chromatin staining, WST-8 fluorescence, and clonogenic assays, respectively. Both tumor cell lines exhibited dose-dependent permeabilization, with 1,500 V/cm permitting and 3,000 V/cm inhibiting membrane recovery 24 h post-treatment. Cells treated with 1,500 V/cm demonstrated significant and progressive recovery of apoptosis and metabolic activity, in contrast to cells treated with higher H-FIRE doses. Cancer cells treated with recovery-permitting doses of H-FIRE maintained while those treated with recovery-inhibiting doses lost proliferative capacity. Taken together, our data suggest that H-FIRE induces reversible and irreversible cellular damage in a dose-dependent manner, and the presence of dose-dependent recovery mechanisms permits tumor cell proliferation.

A Multiplexed Microfluidic Device to Measure Blood-Brain Barrier Disruption by Pulsed Electric Fields.

Local disruption of the blood-brain barrier (BBB) by pulsed electric fields shows significant potential for treating neurological conditions. Microfluidic BBB models can provide low-cost, controlled experiments with human cells and test a range of parameters for preclinical studies. We developed a multiplexed BBB device that can test a three-fold range of electric field magnitudes. A tapered channel creates a linear gradient of the electric field within the device, and an asymmetric branching channel enables an on-chip control. We monitored BBB permeability in real-time using the diffusion of a fluorescent marker across an endothelial monolayer to determine BBB disruption after high-frequency bipolar electrical pulses (HFIRE). We show that HFIRE pulses can transiently open the BBB. Unexpectedly, electrofusion of cells resulted in decreased permeability for some conditions. Our multiplexed device can efficiently probe treatment variables for efficient preclinical testing of optimal parameters for reversible BBB disruption.Clinical Relevance-This in vitro model of the BBB can inform preclinical studies by investigating a range of electroporation parameters for BBB disruption.

On the molecular mechanisms implicated in the bipolar cancellation of membrane electroporation

Bipolar cancellation is the phenomenon in which the permeability of cell membranes subjected to high intensity short pulsed electric field (ns-μs range) is reduced or eliminated when the system is subjected to bipolar instead of monopolar pulses. Although several studies have tried to explain bipolar cancellation, the underlying mechanisms remain unclear. Very few articles study bipolar cancellation by means of molecular dynamics (MD) simulation. In this paper, we investigated the molecular mechanisms underlying the difference in electroporation induced by bipolar and monopolar picosecond electric pulses (EPs) using MD simulation. The electric field gradients and electric forces on water molecules of the two pulses were analyzed in detail for the first time. For a certain pulse width, when the field intensity is relatively small, the direction of bipolar electric force on the interfacial water molecule reverses as the bipolar EPs reverse, while the electric force on interfacial water molecules of the cathode side remains in the same direction as that of applied monopolar EPs. The bipolar electric force reversal delays the water protrusion and increases the pore formation time. Therefore, this phenomenon could correspond to bipolar cancellation. When the field intensity is relatively large, although the bipolar electric force direction still reverses, half of the total time of the monopolar EPs has no electric fields. The electric forces of monopolar no-field half-cycles are much smaller than those of the bipolar EPs. Therefore, the pore formation time of bipolar EPs reduces, and this phenomenon is called bipolar enhancement. The occurrence of bipolar cancellation or bipolar enhancement depends on conditions such as the width and intensity of the pulse.

Analytical properties of switching current transients in ferroelectrics

The increasing application of ferroelectrics in technological applications such as nonvolatile ferroelectric random access memories, capacitors, and energy harvesters highlights the importance of investigating how the characteristics of switching current transients change in response to variation of factors that affect it. This work presents a completely analytical approach based on the Landau-Devonshire (LD) model of phase transitions to quickly study the changes to the properties of switching current transients and back-switching currents in ferroelectric material. The non-linear nature of polarization decay is analyzed based on an exact solution of the Landau-Khalatnikov equation. Exact expressions of the temporal changes in polarization and back-switching current that incorporate the cubic polarization are derived. Comparison of differences between the exact non-linear model of polarization decay phenomena from the linearized model of polarization decay are discussed. This work shows that the characteristics of the critical switching time phenomenon in partial switching current experiments can be explained by the analytical LD model. Many features of complete and partial switching current transients produced by bipolar electric pulses are successfully modeled analytically by varying factors such as temperature, electric field amplitude, pulse-width and off-time. This work shows that pulse powered switching current behaviour in ferroelectric material can be modeled analytically instead of relying only on numerical approaches to the Landau-Khalatnikov equation.

Interference targeting of bipolar nanosecond electric pulses for spatially focused electroporation, electrostimulation, and tissue ablation

Stimulation and electroporation by nanosecond electric pulses (nsEP) are distinguished by a phenomenon of bipolar cancellation, which stands for a reduced efficiency of bipolar pulses compared to unipolar ones. When two pairs of stimulating electrodes are arrayed in a quadrupole, bipolar cancellation inhibits nsEP effects near the electrodes, where the electric field is the strongest. Two properly shaped and synchronized bipolar nsEP overlay into a unipolar pulse towards the center of the electrode array, thus canceling the bipolar cancellation (a “CANCAN effect”). High efficiency of the re-created unipolar nsEP outweighs the weakening of the electric field with distance and focuses nsEP effects to the center. In monolayers of CHO, BPAE, and HEK cells, CANCAN effect achieved by the interference of two bipolar nsEP enhanced electroporation up to tenfold, with a peak at the quadrupole center. Introducing a time interval between bipolar nsEP prevented the formation of a unipolar pulse and eliminated the CANCAN effect. Strong electroporation by CANCAN stimuli killed cells over the entire area encompassed by the electrodes, whereas the time-separated pulses caused ablation only in the strongest electric field near the electrodes. The CANCAN approach is promising for uniform tumor ablation and stimulation targeting away from electrodes.

Design of Rehabilitation Training System for Pelvic Floor Dysfunction

Pelvic floor dysfunction has caused pain to the lives of the majority of female patients, and repeated visits to the hospital for treatment have also caused inconvenience to patients. Therefore, a portable pelvic floor dysfunction rehabilitation training system is designed to help female patients with personalized and private treatment. The pelvic floor dysfunction rehabilitation system realizes the independent training mode selection through the APP client, assists the pelvic floor muscle rehabilitation training through the electrical stimulation module, and can realize the recovery situation of the pelvic floor muscle strength in real time through the AD acquisition module. The experimental results show that the pelvic floor dysfunction rehabilitation training system implements bipolar electrical stimulation pulses, and the EMG signals collected at the same time clearly show the EMG signal strength and strength maintenance time.

Electro-thermal therapy: Microsecond duration pulsed electric field tissue ablation with dynamic temperature control algorithms

Electro-thermal therapy (ETT) is a new cancer treatment modality which combines the use of high voltage pulsed electric fields, dynamic energy delivery rates, and closed loop thermal control algorithms to rapidly and reproducibly create focal ablations. This study examines the ablative potential and profile of pulsed electric field treatments delivered in conjunction with precise temperature control algorithms. An ex vivo perfused liver model was utilized to demonstrate the capability of 5000 V 2 μs duration bipolar electrical pulses and dynamic temperature control algorithms to produce ablations. Using a three applicator array, 4 cm ablation zones were created in under 27 min. In this configuration, the algorithms were able to rapidly achieve and maintain temperatures of 80 °C at the tissue-electrode interface. A simplified single applicator and grounding pad approach was used to correlate the measured ablation zones to electric field isocontours in order to determine lethal electric field thresholds of 708 V/cm and 867 V/cm for 45 °C and 60 °C treatments, respectively. These results establish ETT as a viable method for hepatic tumor treatment with ablation profiles equivalent to other energy based techniques. The single applicator and multi-applicator approaches demonstrated may enable the treatment of complex tumor geometries. The flexibility of ETT temperature control yields a malleable intervention which gives clinicians robust control over the ablation modality, treatment time, and safety profile.

Numerical Study of Mach Number on Solutions in a Warm Negative Ion Plasma With Flat-Topped Electron Distribution

The influence of the Mach number on the localized ion acoustic solitons is investigated in a collisionless one-dimensional unmagnetized plasma system. The plasma model used here is a negative ion plasma having electrons complying flat-topped distribution. Using the basic fluid equations and applying proper boundary conditions we derive the energy integral equations containing the Sagdeev potential. The Sagdeev potential obtained, depends on various parameters out of which the effect of Mach number on the highly nonlinear structures is studied. It is found that depth of the Sagdeev potential, amplitude of the solitary structures and bipolar electric field pulses rises with rise in the values of M . Also narrower solitons starts appearing with increase in the solitary speed.

Orientational Effects Observed During the Passage of Electrons Induced by an Electric Field in Low-Concentration Aqueous Solutions of Liquid Crystals

The features of the emission and passage of electrons in structured aqueous solutions of low-concentration liquid crystals are studied. The investigated materials are low-concentration aqueous solutions of molecular complexes of the surface-active substance cetyltrimethyl ammonium bromide. The weighted droplets of an aqueous solution are studied, electron emission from the surface and from the volume of which was stimulated by bipolar electrical pulses. Analysis of the results showed that at surfactant concentrations of up to about 1.5 × 10–4 mol % the isotropic emission of electrons from the surface of the aqueous solution is observed. At high concentrations of long-chain molecules, the surfactants form aggregates (micelles) ordered along the four directions. This ensures the formation of channels of the facilitated anisotropic emission of electrons from the volume of the solution. The obtained experimental data make it possible to determine the shape of the molecular complexes, their spatial orientation and the nature of the ordering.

High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity

BackgroundDespite promising treatments for breast cancer, mortality rates remain high and treatments for metastatic disease are limited. High-frequency irreversible electroporation (H-FIRE) is a novel tumor ablation technique that utilizes high-frequency bipolar electric pulses to destabilize cancer cell membranes and induce cell death. However, there is currently a paucity of data pertaining to immune system activation following H-FIRE and other electroporation based tumor ablation techniques. MethodsHere, we utilized the mouse 4T1 mammary tumor model to evaluate H-FIRE treatment parameters on cancer progression and immune system activation in vitro and in vivo. FindingsH-FIRE effectively ablates the primary tumor and induces a pro-inflammatory shift in the tumor microenvironment. We further show that local treatment with H-FIRE significantly reduces 4T1 metastases. H-FIRE kills 4T1 cells through non-thermal mechanisms associated with necrosis and pyroptosis resulting in damage associated molecular pattern signaling in vitro and in vivo. Our data indicate that the level of tumor ablation correlates with increased activation of cellular immunity. Likewise, we show that the decrease in metastatic lesions is dependent on the intact immune system and H-FIRE generates 4T1 neoantigens that engage the adaptive immune system to significantly attenuate tumor progression. InterpretationCell death and tumor ablation following H-FIRE treatment activates the local innate immune system, which shifts the tumor microenvironment from an anti-inflammatory state to a pro-inflammatory state. The non-thermal damage to the cancer cells and increased innate immune system stimulation improves antigen presentation, resulting in the engagement of the adaptive immune system and improved systemic anti-tumor immunity.