Effects of Pulse Width on He Plasma Jets in Contact with Water Evaluated by OH(A-X) Emission and OHaq Production

Nanosecond pulsed helium plasma jets impinging on water produce hydroxyl radicals both in gas- and liquid-phase. In this study, the effects of pulse width on a repetitively pulsed plasma jet in contact with water are evaluated via OH(A-X) emission and OHaq production in water for various pulse widths ranging from 200 to 5000 ns. The maximal energy efficiency of OH(A-X) emission is obtained for pulse widths of 600-800 ns whereas the maximal efficiency of OHaq production is at 200 ns. Temporally-resolved emission spectroscopy shows that more than 40% of OH(A-X) emission is produced during the first 200 ns of the voltage pulse regardless of the pulse width. An equivalent circuit model of the plasma jet impinging on water is compiled to understand the charge transfer process, which is important for OHaq production via charge exchange reactions

In Vitro Antimicrobial Effect of a Cold Plasma Jet against Enterococcus faecalis Biofilms

The hypothesis that a cold plasma jet has the antimicrobial effect against Enterococcus faecalis biofilms was tested in vitro. 27 hydroxyapatite discs were incubated with E. faecalis for six days to form a monoculture biofilm on the disc surface. The prepared substrata were divided into three groups: the negative control, the positive control (5.25% NaOCl solution), and the plasma treatment group. Resultant colony-forming unit counts were associated with observations of bacterial cell morphology changes using scanning electron microscopy (SEM). Treatment of E. faecalis biofilm with the plasma and 5.25% NaOCl for 5 min resulted in 93.1% and 90.0% kill (P < 0.0001), respectively. SEM detected that nearly no intact bacteria were discernible for the plasma-exposed HA disc surfaces. The demonstrated bactericidal effect of the plasma with direct surface contact may be due to the enhanced oxidation by the locally produced reactive plasma species

The production of OH in a nanosecond pulsed helium plasma jet impinging on water, saline, or pigskin

Applications of plasma-induced biological effects via reactive oxygen and nitrogen species (RONS) make the non-thermal atmospheric-pressure plasma jets an appealing tool in biomedical fields. The presence of biological materials, especially as part of the electrode circuit, may change the plasma properties and impact on the production of RONS at the plasma-biomaterial interface. Effects of biomaterials on the production of hydroxyl radicals (OH) in a nanosecond pulsed, atmospheric-pressure plasma jet were investigated using a needle-to-plate electrode configuration with water, phosphate-buffered saline (PBS), or pigskin covering the ground plate. Driven by 200 ns, 7 kV pulses at 1 kHz, a helium plasma jet was generated between the hollow needle electrode and the biomaterial. Temporally resolved UV-visible imaging showed that the use of pigskin slowed down the streamer head propagation, whereas a more pronounced surface ionization wave was developed on the surface when water was used. The highest OH(A-X) emission above the biomaterial surface was observed using the PBS-covered electrode plate comparing to water or pigskin. Spatiotemporally resolved laser-induced fluorescence (LIF) showed that more OH was produced in the region near the needle electrode for both water and PBS, and the use of pigskin resulted in least OH production overall. In addition, measurements of H2O2 production in the liquid were used to determine the OH concentration in the vicinity of the biomaterial and agreed well with the relative OH-LIF measurements obtained at the gas-liquid interface for water and PBS

Moderate Heat Application Enhances the Efficacy of Nanosecond Pulse Stimulation for the Treatment of Squamous Cell Carcinoma

Nanosecond pulse stimulation as a tumor ablation therapy has been studied for the treatment of various carcinomas in animal models and has shown a significant survival benefit. In the current study, we found that moderate heating at 43°C for 2 minutes significantly enhanced in vitro nanosecond pulse stimulation-induced cell death of KLN205 murine squamous cell carcinoma cells by 2.43-fold at 600 V and by 2.32-fold at 900 V, as evidenced by propidium iodide uptake. Furthermore, the ablation zone in KLN205 cells placed in a 3-dimensional cell-culture model and pulsed at a voltage of 900 V at 43°C was 3 times larger than in cells exposed to nanosecond pulse stimulation at room temperature. Application of moderate heating alone did not cause cell death. A nanosecond pulse stimulation electrode with integrated controllable laser heating was developed to treat murine ectopic squamous cell carcinoma. With this innovative system, we were able to quickly heat and maintain the temperature of the target tumor at 43 degrees C during nanosecond pulse stimulation. Nanosecond pulse stimulation with moderate heating was shown to significantly extend overall survival, delay tumor growth, and achieve a high rate of complete tumor regression. Moderate heating extended survival nearly 3-fold where median overall survival was 22 days for 9.8 kV without moderate heating and over 63 days for tumors pulsed with 600, 100 ns pulses at 5 Hz, at voltage of 9.8 kV with moderate heating. Median overall survival in the control groups was 24 and 31 days for mice with untreated tumors and tumors receiving moderate heat alone, respectively. Nearly 69% (11 of 16) of tumor-bearing mice treated with nanosecond pulse stimulation with moderate heating were tumor free at the completion of the study, whereas complete tumor regression was not observed in the control groups and in 9.8 kV without moderate heating. These results suggest moderate heating can reduce the necessary applied voltage for tumor ablation with nanosecond pulse stimulation

Thermal Analysis of Infrared Irradiation-Assisted Nanosecond-Pulsed Tumor Ablation

Nanosecond Pulsed Electric Fields (nsPEF) have the potential to treat a variety of cancer types including melanoma, pancreatic and lung squamous cancers. Recent studies show that nsPEF-based cancer therapy may be improved further with the assistance of moderate heating of the target. A feedbacklooped heating system, utilizing a 980-nm fiber optic laser, was integrated into nsPEF electrodes for tumor ablation. The laser beam profile was determined to be Gaussian using a knife-edge technique. Thermal properties of the biological target were evaluated based on the treatment area, penetration depth and thermal distribution due to laser irradiation with or without nsPEF. Synergistic effects between nsPEF and the moderately elevated temperature at the target was observed, resulting in enhanced overall survival tumor regression up to 50% in the treatment of lung squamous cell cancer in mice

Electroporation of Mammalian Cells by Nanosecond Electric Field Oscillations and it\u27s Inhibition by the Electric Field Reversal

The present study compared electroporation efficiency of bipolar and unipolar nanosecond electric field oscillations (NEFO). Bipolar NEFO was a damped sine wave with 140 ns first phase duration at 50% height; the peak amplitude of phases 2-4 decreased to 35%, 12%, and 7% of the first phase. This waveform was rectified to produce unipolar NEFO by cutting off phases 2 and 4. Membrane permeabilization was quantified in CHO and GH3 cells by uptake of a membrane integrity marker dye YO-PRO-1 (YP) and by the membrane conductance increase measured by patch clamp. For treatments with 1-20 unipolar NEFO, at 9.6-24 kV/cm, 10 Hz, the rate and amount of YP uptake were consistently 2-3-fold higher than after bipolar NEFO treatments, despite delivering less energy. However, the threshold amplitude was about 7 kV/cm for both NEFO waveforms. A single 14.4 kV/cm unipolar NEFO caused a 1.5-2 times greater increase in membrane conductance (p \u3c 0.05) than bipolar NEFO, along with a longer and less frequent recovery. The lower efficiency of bipolar NEFO was preserved in Ca2+ free conditions and thus cannot be explained by the reversal of electrophoretic flows of Ca2+. Instead, the data indicate that the electric field polarity reversals reduced the pore yield

Nano-Pulse Stimulation for the Treatment of Pancreatic Cancer and the Changes in Immune Profile

A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to the induction of immune-mediated protection from a second tumor challenge in orthotopic mouse breast and rat liver cancer models. In the Pan02 model, there were insufficient abscopal effects (1/10) and vaccine-like protective effects (1/15) suggesting that NPS-induced immune mechanisms in this model were limited. To evaluate this further, the immune landscape was analyzed. The numbers of both T regulatory cells (Tregs) and myeloid derived suppressor cells (MDSCs) in blood were significantly reduced, but memory (CD44+) T-cells were absent. Furthermore, the numbers of Tregs and MDSCs did not reduce in spleens compared to tumor-bearing mice. Very few T-cells, but large numbers of MDSCs were present in the NPS treated tumor microenvironment (TME). The number of dendritic cells in the TME was increased and multiple activation markers were upregulated following NPS treatment. Overall, NPS treatments used here are effective for pancreatic tumor ablation, but require further optimization for induction of immunity or the need to include effective combinational NPS therapeutic strategy for pancreatic cancer

No reference quality assessment of stereo video based on saliency and sparsity

With the popularity of video technology, stereoscopic video quality assessment (SVQA) has become increasingly important. Existing SVQA methods cannot achieve good performance because the videos' information is not fully utilized. In this paper, we consider various information in the videos together, construct a simple model to combine and analyze the diverse features, which is based on saliency and sparsity. First, we utilize the 3-D saliency map of sum map, which remains the basic information of stereoscopic video, as a valid tool to evaluate the videos' quality. Second, we use the sparse representation to decompose the sum map of 3-D saliency into coefficients, then calculate the features based on sparse coefficients to obtain the effective expression of videos' message. Next, in order to reduce the relevance between the features, we put them into stacked auto-encoder, mapping vectors to higher dimensional space, and adding the sparse restraint, then input them into support vector machine subsequently, and finally, get the quality assessment scores. Within that process, we take the advantage of saliency and sparsity to extract and simplify features. Through the later experiment, we can see the proposed method is fitting well with the subjective scores

Enhanced Electric Pulse Technology for the Ablation of Pancreatic Cancer

Electric pulse based technology has been developed and studied as a non-thermal ablation method for local control of pancreatic cancer. Irreversible electroporation (IRE) has shown a significant survival benefit for local advanced pancreatic cancer in clinical trials. However, incomplete ablation with local recurrence and major complications limit the potential of this new technology. We have developed an integrated moderate heating electric pulse delivery system which consists of controllable tumor heating, multi-parameter monitoring and electric pulse delivery. The impedance of tumor is greatly decreased after moderate heating at 42°C for 1–2 min, which does not cause any cell death. Moderate heating significantly enlarges the ablation zone of tumor treated with IRE. In contrast to IRE alone, moderate heating assisted IRE results in a high rate of complete tumor regression and a significant longer median survival. Another electric pulse technology, nanosecond electric pulses, has been assessed for the treatment of pancreatic cancer as well. Nanosecond electric pulse treatment achieves more survival benefit in animals with partial tumor ablation than those treated with IRE and leads to a vaccine-like protective effect in animals with complete local ablation. More studies are needed to demonstrate the advantages and translational feasibility of the enhanced electric pulse technologies

Controllable Moderate Heating Enhances the Therapeutic Efficacy of Irreversible Electroporation for Pancreatic Cancer

Irreversible electroporation (IRE) as a non-thermal tumor ablation technology has been studied for the treatment of pancreatic carcinoma and has shown a significant survival benefit. We discovered that moderate heating (MH) at 43°C for 1-2 minutes significantly enhanced ex vivo IRE tumor ablation of Pan02 cells by 5.67-fold at 750 V/cm and by 1.67-fold at 1500 V/cm. This amount of heating alone did not cause cell death. An integrated IRE system with controllable laser heating and tumor impedance monitoring was developed to treat mouse ectopic pancreatic cancer. With this novel IRE system, we were able to heat and maintain the temperature of a targeted tumor area at 42°C during IRE treatment. Pre-heating the tumor greatly reduced the impedance of tumor and its fluctuation. Most importantly, MHIRE has been demonstrated to significantly extend median survival and achieve a high rate of complete tumor regression. Median survival was 43, 46 and 84 days, for control, IRE with 100 μs, 1 Hz, 90 pulses and electric fields 2000-2500 V/cm and MHIRE treatment respectively. 55.6% of tumor-bearing mice treated with MHIRE were tumor-free, whereas complete tumor regression was not observed in the control and IRE treatment groups