Abstract: A packed bed dielectric barrier discharge (DBD) is widely used for plasma catalysis applications, but the exact plasma characteristics in between the packing beads are far from understood. Therefore, we study here these plasma characteristics by means of fluid modelling and experimental observations using ICCD imaging, for packing materials with different dielectric constants. Our study reveals that a packed bed DBD reactor in dry air at atmospheric pressure may show three types of discharges, i.e. positive restrikes, filamentary microdischarges, which can also be localized between two packing beads, and surface discharges (so-called surface ionization
waves). Restrikes between the dielectric surfaces result in the formation of filamentary microdischarges, while surface charging creates electric field components parallel to the dielectric surfaces, leading to the formation of surface discharges. A transition in discharge mode occurs from surface discharges to local filamentary discharges between the packing beads when the dielectric constant of the packing rises from 5 to 1000. This may have implications for the efficiency of plasma catalytic gas treatment, because the catalyst activation may be limited by constraining the discharge to the contact points of the beads. The production of reactive species occurs most in the positive restrikes, the surface discharges and the local microdischarges in between the beads, and is less significant in the longer filamentary microdischarges. The faster streamer propagation and discharge development with higher dielectric constant of the packing beads leads to a faster production of reactive species. This study is of great interest for plasma catalysis, where packing beads with different dielectric constants are often used as supports for the catalytic materials. It allows us to better understand how different packing materials can influence the performance of packed bed plasma reactors for environmental applications.

Abstract: A modelling study is performed of high-density low-pressure inductively coupled CF4/CHF3/H2/Cl2/O2/HBr plasmas under different gas mixing ratios. A reaction set describing the complete plasma chemistry is presented and discussed. The gas fraction of each component in this mixture is varied to investigate the sensitivity of the plasma properties, like electron density, plasma potential and species densities, towards the gas mixing ratios. This research is of great interest for microelectronics applications because these gases are often combined in two (or more)-component mixtures, and mixing gases or changing the fraction of a gas can sometimes yield unwanted reaction products or unexpected changes in the overall plasma properties due to the increased chemical complexity of the system. Increasing the CF4 fraction produces more F atoms for chemical etching as expected, but also more prominently lowers the density of Cl atoms, resulting in an actual drop in the etch rate under certain conditions. Furthermore, CF4 decreases the free electron density when mixed with Cl2. However, depending on the other gas components, CF4 gas can also sometimes enhance free electron density. This is the case when HBr is added to the mixture. The addition of H2 to the gas mixture will lower the sputtering process, not only due to the lower overall positive ion density at higher H2 fractions, but also because more H+, H2 + and H3 + are present and they have very low sputter yields. In contrast, a larger Cl2 fraction results in more chemical etching but also in less physical sputtering due to a smaller abundance of positive ions. Increasing the O2 fraction in the plasma will always lower the etch rate due to more oxidation of the wafer surface and due to a lower plasma density. However, it is also observed that the density of F atoms can actually increase with rising O2 gas fraction. This is relevant to note because the exact balance between fluorination and oxidation is important for fine-tuning the overall etch rate and for control of the sidewall profile. Finally, HBr is often used as a chemical etcher, but when mixed with F- or Cl-containing gases, HBr creates the same diluting effects as Ar or He, because a
higher fraction results in less chemical etching but more (physical) sputtering.

Abstract: Plasma‐based CO₂conversion has attracted increasing interest. However, to understand the impact of plasma operation on post‐plasma processes, we studied the effect of adding N₂, N₂/CH₄and N₂/CH₄/H₂O to a CO₂gliding arc plasmatron (GAP) to obtain valuable insights into their impact on exhaust stream composition and temperature, which will serve as feed gas and heat for post‐plasma catalysis (PPC). Adding N₂improves the CO₂conversion from 4 % to 13 %, and CH₄addition further promotes it to 44 %, and even to 61 % at lower gas flow rate (6 L/min), allowing a higher yield of CO and hydrogen for PPC. The addition of H₂O, however, reduces the CO₂conversion from 55 % to 22 %, but it also lowers the energy cost, from 5.8 to 3 kJ/L. Regarding the temperature at 4.9 cm post‐plasma, N₂addition increases the temperature, while the CO₂/CH₄ratio has no significant effect on temperature. We also calculated the temperature distribution with computational fluid dynamics simulations. The obtained temperature profiles (both experimental and calculated) show a decreasing trend with distance to the exhaust and provide insights in where to position a PPC bed.

Abstract: Plasma is gaining increasing interest for cancer
treatment, but the underlying mechanisms are not yet fully
understood. Using computer simulations at the molecular
level, we try to gain better insight in how plasma-generated
reactive oxygen and nitrogen species (RONS) can
penetrate through the cell membrane. Specifically, we
compare the permeability of various (hydrophilic and
hydrophobic) RONS across both oxidized and nonoxidized cell membranes. We also study pore formation,
and how it is hampered by higher concentrations of
cholesterol in the cell membrane, and we illustrate the
much higher permeability of H2O2 through aquaporin
channels. Both mechanisms may explain the selective
cytotoxic effect of plasma towards cancer cells. Finally, we
also discuss the synergistic effect of plasma-induced
oxidation and electric fields towards pore formation.
Keywords plasma medicine, cancer treatment, computer
modelling, cell membrane, reactive oxygen and nitrogen
species

Abstract: Experiments show that the etch rate of Si with SF6 inductively coupled plasma (ICP) is significantly influenced by the absolute gas flow rate in the range of 50–600 sccm, with a maximum at around 200 sccm. Therefore, we numerically investigate the effects of the gas flow rate on the bulk plasma properties and on the etch rate, to obtain more insight in the underlying reasons of this effect. A hybrid Monte Carlo—fluid model is applied to simulate an SF6 ICP. It is found that the etch rate is influenced by two simultaneous effects: (i) the residence time of the gas and (ii) the temperature profile of the plasma in the ICP volume, resulting indeed in a maximum etch rate at 200 sccm.

Abstract: A chemical kinetics model was developed to characterise the gas‐phase dynamics of H₂production in nanosecond‐pulsed CH₄plasmas. Pulsed behaviour was observed in the calculated electric field, electron temperature and species densities at all pressures. The model agrees reasonably with experimental results, showing CH₄conversion at 30% and C₂H₂and H₂as major products. The underlying mechanisms in CH₄dissociation and H₂formation were analysed, highlighting the large contribution of vibrationally excited CH₄and H₂to coupling energy from the plasma into gas‐phase heating, and revealing that H₂synthesis is not affected by applied pressure, with selectivity remaining unchanged at ~42% in the 1–5 bar range.

Abstract: Melittin (MEL), a small peptide component of bee venom, has been reported to exhibit anti-cancer effects in vitro and in vivo. However, its clinical applicability is disputed because of its non-specific cytotoxicity and haemolytic activity in high treatment doses. Plasma-treated phosphate buffered saline solution (PT-PBS), a solution rich in reactive oxygen and nitrogen species (RONS) can disrupt the cell membrane integrity and induce cancer cell death through oxidative stress-mediated pathways. Thus, PT-PBS could be used in combination with MEL to facilitate its access into cancer cells and to reduce the required therapeutic dose. The aim of our study is to determine the reduction of the effective dose of MEL required to eliminate cancer cells by its combination with PT-PBS. For this purpose, we have optimised the MEL threshold concentration and tested the combined treatment of MEL and PT-PBS on A375 melanoma and MCF7 breast cancer cells, using in vitro, in ovo and in silico approaches. We investigated the cytotoxic effect of MEL and PT-PBS alone and in combination to reveal their synergistic cytological effects. To support the in vitro and in ovo experiments, we showed by computer simulations that plasma-induced oxidation of the phospholipid bilayer leads to a decrease of the free energy barrier for translocation of MEL in comparison with the non-oxidized bilayer, which also suggests a synergistic effect of MEL with plasma induced oxidation. Overall, our findings suggest that MEL in combination with PT-PBS can be a promising combinational therapy to circumvent the non-specific toxicity of MEL, which may help for clinical applicability in the future.

Abstract: Despite modern therapeutic advances, the survival prospects of pancreatic cancer patients remain poor, due to chemoresistance and dysregulated oncogenic kinase signaling networks. We applied a novel kinome activitymapping approach using biological peptide targets as phospho-sensors to identify vulnerable kinase de­pendencies for therapy sensitization by physical plasma. Ser/Thr-kinome specific activity changes were mapped upon induction of ferroptotic cell death in pancreatic tumor cells exposed to reactive oxygen and nitrogen species of plasma-treated water (PTW). This revealed a broad kinome activity response involving the CAMK, the AGC and CMGC family of kinases. This systems-level kinome network response supports stress adaptive switches between chemoresistant anti-oxidant responses of Kelch-like ECH-associated protein 1 (KEAP1)/Heme Oxy­genase 1 (HMOX1) and ferroptotic cell death sensitization upon suppression of Nuclear factor (erythroid derived 2)-like 2 (NRF2) and Glutathione peroxidase 4 (GPX4). This is further supported by ex vivo experiments in the chicken chorioallantoic membrane assay, showing decreased GPX4 and Glutathione (GSH) expression as well as increased lipid peroxidation, along with suppressed BxPC-3 tumor growth in response to PTW. Taken all together, we demonstrate that plasma treated water-derived oxidants sensitize pancreatic cancer cells to fer­roptotic cell death by targeting a NRF2-HMOX1-GPX4 specific kinase signaling network.

Abstract: There is a growing body of literature that recognizes the importance of plasma treated water (PTW)for inactivation of microorganism. However, very little attention has been paid to the role of reactive nitrogen species (RNS) in deactivation of bacteria. The aim of this study is to explore the role of RNS in bacterial killing, and to develop a plasma system with increased sterilization efficiency. To increase the concentration of reactive oxygen and nitrogen species (RONS) in solution, we have used vapor systems (DI water/HNO3 at different wt%) combined with plasma using N2 as working gas. The results show that the addition of the vapor system yields higher RONS contents. Furthermore, PTW produced by N2 + 0.5 wt% HNO3 vapor comprises a large amount of both RNS and ROS, while PTW created by N2 + H2O vapor consists of a large amount of ROS, but much less RNS. Interestingly, we observed more deactivation of E. Coli with PTW created by N2 + 0.5 wt% HNO3 vapor plasma as compared to PTW generated by the other plasma systems. This work provides new insight into the role of RNS along with ROS for deactivation of bacteria.

Abstract: Gap junctions (GJs), essential structures for cell-cell communication, are made of two hemichannels (commonly called connexons), one on each adjacent cell. Found in almost all cells, GJs play a pivotal role in many physi­ological and cellular processes, and have even been linked to the progression of diseases, such as cancer. Modulation of GJs is under investigation as a therapeutic strategy to kill tumor cells. Furthermore, GJs have also been studied for their key role in activating anti-cancer immunity and propagating radiation- and oxidative stress-induced cell death to neighboring cells, a process known as the bystander effect. While, gap junction (GJ)based therapeutic strategies are being developed, one major challenge has been the paradoxical role of GJs in both tumor progression and suppression, based on GJ composition, cancer factors, and tumoral context. Therefore, understanding the mechanisms of action, regulation, and the dual characteristics of GJs in cancer is critical for developing effective therapeutics. In this review, we provide an overview of the current under­ standing of GJs structure, function, and paradoxical pro- and anti-tumoral role in cancer. We also discuss the treatment strategies to target these GJs properties for anti-cancer responses, via modulation of GJ function.

Abstract: The unique capabilities of microsecond dwell time (DT) single-particle inductively coupled plasma mass spectrometry (spICPMS) were utilized to characterize the cloud of ions generated from the introduction of suspensions of gold nanoparticles (AuNPs) into the plasma. A set of narrowly distributed particles with diameters ranging from 15.4 to 100.1 nm was synthesized and characterized according to established protocols. Statistically significant numbers of the short transient spICPMS events were evaluated by using 50 μs DT for their summed intensity, maximum intensity, and duration, of which all three were found to depend on the particle diameter. The summed intensity increases from 10 to 1661 counts and the maximum intensity from 6 to 309 counts for AuNPs with diameters from 15.4 to 83.2 nm. The event duration rises from 322 to 1007 μs upon increasing AuNP diameter. These numbers represent a comprehensive set of key data points of the ion clouds generated in ICPMS from AuNPs. The extension of event duration is of high interest to appoint the maximum possible particle number concentration at which separation of consecutive events in spICPMS can still be achieved. Moreover, the combined evaluation of all above-mentioned ion cloud characteristics can explain the regularly observed prolonged single-particle events. The transport and ionization behavior of AuNPs in the ICP was also computationally modeled to gain insight into the size-dependent signal generation. The simulated data reveals that the plasma temperature, and therefore the point of ionization of the particles, is the same for all diameters. However, the maximum number density of Au+, as well as the extent of the ion cloud, depends on the particle diameter, in agreement with the experimental data, and it provides an adequate explanation for the observed ion cloud characteristics.

Abstract: This paper discusses our recent results on plasma-based CO2 conversion, obtained by a combination of experiments and modeling, for a dielectric barrier discharge (DBD), a microwave plasma and a packed bed DBD reactor. The results illustrate that plasma technology is quite promising for CO2 conversion, but more research is needed to better understand the underlying mechanisms and to further improve the capabilities.

Abstract: It is well established that lipid aldehydes (LAs) are able to increase the permeability of cell membranes and induce their rupture. However, it is not yet clear how LAs are distributed in phase-separated membranes (PSMs), which are responsible for the transport of selected molecules and intracellular signaling. Thus, we investigate here the distribution of LAs in a PSM by coarse-grained molecular dynamics simulations. Our results reveal that LAs derived from mono-unsaturated lipids tend to accumulate at the interface between the liquid-ordered/liquiddisordered domains, whereas those derived from poly-unsaturated lipids remain in the liquid-disordered domain. These results are important for understanding the effects caused by oxidized lipids in membrane structure, properties and organization.

Abstract: Utilizing ammonia as a storage medium for hydrogen is currently receiving increased attention. A possible method to retrieve the hydrogen is by plasma-catalytic decomposition. In this work, we combined an experimental study, using a dielectric barrier discharge plasma reactor, with a plasma kinetic model, to get insights into the decomposition mechanism. The experimental results revealed a similar effect on the ammonia conversion when changing the flow rate and power, where increasing the specific energy input (higher power or lower flow rate) gave an increased conversion. A conversion as high as 82 % was achieved at a specific energy input of 18 kJ/Nl. Furthermore, when changing the discharge volume from 31 to 10 cm3, a change in the plasma distribution factor from 0.2 to 0.1 was needed in the model to best describe the conversions of the experiments. This means that a smaller plasma volume caused a higher transfer of energy through micro-discharges (non-uniform plasma), which was found to promote the decomposition of ammonia. These results indicate that it is the collisions between NH3 and the high-energy electrons that initiate the decomposition. Moreover, the rate of ammonia destruction was found by the model to be in the order of 1022 molecules/(cm3 s) during the micro-discharges, which is 5 to 6 orders of magnitude higher than in the afterglows. A considerable re-formation of ammonia was found to take place in the afterglows, limiting the overall conversion. In addition, the model revealed that implementation of packing material in the plasma introduced high concentrations of surface-bound hydrogen atoms, which introduced an additional ammonia re-formation pathway through an Eley-Rideal reaction with gas phase NH2. Furthermore, a more uniform plasma is predicted in the presence of MgAl2O4, which leads to a lower average electron energy during micro-discharges and a lower conversion (37 %) at a comparable residence time for the plasma alone (51 %).

Abstract: Reactive oxygen and nitrogen species (RONS) are involved in many biochemical processes, including nitrooxidative stress that causes cancer cell death, observed in cancer therapies such as photodynamic therapy and cold atmospheric plasma. However, their mechanisms of action and selectivity still remain elusive due to the complexity of biological cells. For example, it is not well known how RONS generated by cancer therapies permeate the cell membrane to cause nitro-oxidative damage. There are many studies dedicated to the perme­ation of RONS across native and oxidized membranes, but not across nitrated membranes, another lipid product also generated during nitro-oxidative stress. Herein, we performed molecular dynamics (MD) simulations to calculate the free energy barrier of RONS permeation across nitrated membranes. Our results show that hy­drophilic RONS, such as hydroperoxyl radical (HO2) and peroxynitrous acid (ONOOH), have relatively low barriers compared to hydrogen peroxide (H2O2) and hydroxyl radical (HO), and are more prone to permeate the membrane than for the native or peroxidized membranes, and similar to aldehyde-oxidized membranes. Hy­drophobic RONS like molecular oxygen (O2), nitrogen dioxide (NO2) and nitric oxide (NO) even have insignif­icant barriers for permeation. Compared to native and peroxidized membranes, nitrated membranes are more permeable, suggesting that we must not only consider oxidized membranes during nitro-oxidative stress, but also nitrated membranes, and their role in cancer therapies.