Vibrational kinetics in repetitively pulsed atmospheric pressure nitrogen discharges: average-power-dependent switching behaviour.

Characterisation of the vibrational kinetics in nitrogen-based plasmas at atmospheric pressure is crucial for understanding the wider plasma chemistry, which is important for a variety of biomedical, agricultural and chemical processing applications. In this study, a 0-dimensional plasma chemical-kinetics model has been used to investigate vibrational kinetics in repetitively pulsed, atmospheric pressure plasmas operating in pure nitrogen, under application-relevant conditions (average plasma powers of 0.23-4.50 W, frequencies of 1-10 kHz, and peak pulse powers of 23-450 W). Simulations predict that vibrationally excited state production is dominated by electron-impact processes at lower average plasma powers. When the average plasma power increases beyond a certain limit, due to increased pulse frequency or peak pulse power, there is a switch in behaviour, and production of vibrationally excited states becomes dominated by vibrational energy transfer processes (vibration-vibration (V-V) and vibration-translation (V-T) reactions). At this point, the population of vibrational levels up to v ⩽ 40 increases significantly, as a result of V-V reactions causing vibrational up-pumping. At average plasma powers close to where the switching behaviour occurs, there is potential to control the energy efficiency of vibrational state production, as small increases in energy deposition result in large increases in vibrational state densities. Subsequent pathways analysis reveals that energy in the vibrational states can also influence the wider reaction chemistry through vibrational-electronic (V-E) linking reactions (N + N 2 ( 40 ⩽ v ⩽ 45 ) → N ( 2 D ) + N 2 ( A ) and N + N 2 ( 39 ⩽ v ⩽ 45 ) → N + N 2 ( a ' ) ), which result in increased Penning ionisation and an increased average electron density. Overall, this study investigates the potential for delineating the processes by which electronically and vibrationally excited species are produced in nitrogen plasmas. Therefore, potential routes by which nitrogen-containing plasma sources could be tailored, both in terms of chemical composition and energy efficiency, are highlighted.

Plasma-MDS, a metadata schema for plasma science with examples from plasma technology.

A metadata schema, named Plasma-MDS, is introduced to support research data management in plasma science. Plasma-MDS is suitable to facilitate the publication of research data following the FAIR principles in domain-specific repositories and with this the reuse of research data for data driven plasma science. In accordance with common features in plasma science and technology, the metadata schema bases on the concept to separately describe the source generating the plasma, the medium in which the plasma is operated in, the target the plasma is acting on, and the diagnostics used for investigation of the process under consideration. These four basic schema elements are supplemented by a schema element with various attributes for description of the resources, i.e. the digital data obtained by the applied diagnostic procedures. The metadata schema is first applied for the annotation of datasets published in INPTDAT-the interdisciplinary data platform for plasma technology.

Biophysical characterisation of DNA origami nanostructures reveals inaccessibility to intercalation binding sites.

Intercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery.

Notch signalling is a potential resistance mechanism of progenitor cells within patient-derived prostate cultures following ROS-inducing treatments.

Low Temperature Plasma (LTP) generates reactive oxygen and nitrogen species, causing cell death, similarly to radiation. Radiation resistance results in tumour recurrence, however mechanisms of LTP resistance are unknown. LTP was applied to patient-derived prostate epithelial cells and gene expression assessed. A typical global oxidative response (AP-1 and Nrf2 signalling) was induced, whereas Notch signalling was activated exclusively in progenitor cells. Notch inhibition induced expression of prostatic acid phosphatase (PAP), a marker of prostate epithelial cell differentiation, whilst reducing colony forming ability and preventing tumour formation. Therefore, if LTP is to be progressed as a novel treatment for prostate cancer, combination treatments should be considered in the context of cellular heterogeneity and existence of cell type-specific resistance mechanisms.

Disrupting the spatio-temporal symmetry of the electron dynamics in atmospheric pressure plasmas by voltage waveform tailoring.

Single frequency, geometrically symmetric Radio-Frequency (rf) driven atmospheric pressure plasmas exhibit temporally and spatially symmetric patterns of electron heating, and consequently, charged particle densities and fluxes. Using a combination of phase-resolved optical emission spectroscopy and kinetic plasma simulations, we demonstrate that tailored voltage waveforms consisting of multiple rf harmonics induce targeted disruption of these symmetries. This confines the electron heating to small regions of time and space and enables the electron energy distribution function to be tailored.

Chemical kinetics in an atmospheric pressure helium plasma containing humidity.

Atmospheric pressure plasmas are sources of biologically active oxygen and nitrogen species, which makes them potentially suitable for the use as biomedical devices. Here, experiments and simulations are combined to investigate the formation of the key reactive oxygen species, atomic oxygen (O) and hydroxyl radicals (OH), in a radio-frequency driven atmospheric pressure plasma jet operated in humidified helium. Vacuum ultra-violet high-resolution Fourier-transform absorption spectroscopy and ultra-violet broad-band absorption spectroscopy are used to measure absolute densities of O and OH. These densities increase with increasing H2O content in the feed gas, and approach saturation values at higher admixtures on the order of 3 × 1014 cm-3 for OH and 3 × 1013 cm-3 for O. Experimental results are used to benchmark densities obtained from zero-dimensional plasma chemical kinetics simulations, which reveal the dominant formation pathways. At low humidity content, O is formed from OH+ by proton transfer to H2O, which also initiates the formation of large cluster ions. At higher humidity content, O is created by reactions between OH radicals, and lost by recombination with OH. OH is produced mainly from H2O+ by proton transfer to H2O and by electron impact dissociation of H2O. It is lost by reactions with other OH molecules to form either H2O + O or H2O2. Formation pathways change as a function of humidity content and position in the plasma channel. The understanding of the chemical kinetics of O and OH gained in this work will help in the development of plasma tailoring strategies to optimise their densities in applications.

Initiating radical reactions with non-thermal plasmas.

Non-thermal plasmas were used as radical initiators in three radical chain reactions: dehalogenation, 5-exo-trig cyclisation and trifluoromethylation with the Togni II reagent. The use of non-volatile solvents (or solvent-free conditions) gave high yields in all reactions under optimised conditions. Short reaction times and mild conditions make this method an attractive alternative to conventional radical initiators.

Integration: the key to implementing the Sustainable Development Goals.

On 25 September, 2015, world leaders met at the United Nations in New York, where they adopted the Sustainable Development Goals. These 17 goals and 169 targets set out an agenda for sustainable development for all nations that embraces economic growth, social inclusion, and environmental protection. Now, the agenda moves from agreeing the goals to implementing and ultimately achieving them. Across the goals, 42 targets focus on means of implementation, and the final goal, Goal 17, is entirely devoted to means of implementation. However, these implementation targets are largely silent about interlinkages and interdependencies among goals. This leaves open the possibility of perverse outcomes and unrealised synergies. We demonstrate that there must be greater attention on interlinkages in three areas: across sectors (e.g., finance, agriculture, energy, and transport), across societal actors (local authorities, government agencies, private sector, and civil society), and between and among low, medium and high income countries. Drawing on a global sustainability science and practice perspective, we provide seven recommendations to improve these interlinkages at both global and national levels, in relation to the UN's categories of means of implementation: finance, technology, capacity building, trade, policy coherence, partnerships, and, finally, data, monitoring and accountability.

An Atmospheric Pressure Plasma Setup to Investigate the Reactive Species Formation.

Non-thermal atmospheric pressure ('cold') plasmas have received increased attention in recent years due to their significant biomedical potential. The reactions of cold plasma with the surrounding atmosphere yield a variety of reactive species, which can define its effectiveness. While efficient development of cold plasma therapy requires kinetic models, model benchmarking needs empirical data. Experimental studies of the source of reactive species detected in aqueous solutions exposed to plasma are still scarce. Biomedical plasma is often operated with He or Ar feed gas, and a specific interest lies in investigation of the reactive species generated by plasma with various gas admixtures (O2, N2, air, H2O vapor, etc.) Such investigations are very complex due to difficulties in controlling the ambient atmosphere in contact with the plasma effluent. In this work, we addressed common issues of 'high' voltage kHz frequency driven plasma jet experimental studies. A reactor was developed allowing the exclusion of ambient atmosphere from the plasma-liquid system. The system thus comprised the feed gas with admixtures and the components of the liquid sample. This controlled atmosphere allowed the investigation of the source of the reactive oxygen species induced in aqueous solutions by He-water vapor plasma. The use of isotopically labelled water allowed distinguishing between the species originating in the gas phase and those formed in the liquid. The plasma equipment was contained inside a Faraday cage to eliminate possible influence of any external field. The setup is versatile and can aid in further understanding the cold plasma-liquid interactions chemistry.

Spatial Dependence of DNA Damage in Bacteria due to Low-Temperature Plasma Application as Assessed at the Single Cell Level.

Low temperature plasmas (LTPs) generate a cocktail of reactive nitrogen and oxygen species (RNOS) with bactericidal activity. The RNOS however are spatially unevenly distributed in the plasma. Here we test the hypothesis that this distribution will affect the mechanisms underpinning plasma bactericidal activity focussing on the level of DNA damage in situ. For the first time, a quantitative, single cell approach was applied to assess the level of DNA damage in bacteria as a function of the radial distance from the centre of the plasma jet. Salmonella enterica on a solid, dry surface was treated with two types of LTP: an atmospheric-pressure dielectric barrier discharge plasma jet (charged and neutral species) and a radio-frequency atmospheric-pressure plasma jet (neutral species). In both cases, there was an inverse correlation between the degree of DNA damage and the radial distance from the centre of the plasma, with the highest DNA damage occurring directly under the plasma. This trend was also observed with Staphylococcus aureus. LTP-generated UV radiation was eliminated as a contributing factor. Thus valuable mechanistic information can be obtained from assays on biological material, which can inform the development of LTP as a complementary or alternative therapy for (topical) bacterial infections.

Non-Thermal Plasma in Contact with Water: The Origin of Species.

Non-thermal atmospheric pressure plasma has attracted considerable attention in recent years due to its potential for biomedical applications. Determining the mechanism of the formation of reactive species in liquid treated with plasma is thus of paramount importance for both fundamental and applied research. In this work, the origin of reactive species in plasma-treated aqueous solutions was investigated by using spin-trapping, hydrogen and oxygen isotopic labelling and electron paramagnetic resonance (EPR) spectroscopy. The species originating from molecules in the liquid phase and those introduced with the feed gas were differentiated by EPR and 1 H NMR analysis of liquid samples. The effects of water vapour and oxygen admixtures in the feed gas were investigated. All the reactive species detected in the liquid samples were shown to be formed largely in the plasma gas phase. It is suggested that hydrogen peroxide (determined by UV/Vis analysis) is formed primarily in the plasma tube, whereas the radical species ⋅OOH, ⋅OH and ⋅H are proposed to originate from the region between the plasma nozzle and the liquid sample.

Low temperature plasmas as emerging cancer therapeutics: the state of play and thoughts for the future.

The field of plasma medicine has seen substantial advances over the last decade, with applications developed for bacterial sterilisation, wound healing and cancer treatment. Low temperature plasmas (LTPs) are particularly suited for medical purposes since they are operated in the laboratory at atmospheric pressure and room temperature, providing a rich source of reactive oxygen and nitrogen species (RONS). A great deal of research has been conducted into the role of reactive species in both the growth and treatment of cancer, where long-established radio- and chemo-therapies exploit their ability to induce potent cytopathic effects. In addition to producing a plethora of RONS, LTPs can also create strong electroporative fields. From an application perspective, it has been shown that LTPs can be applied precisely to a small target area. On this basis, LTPs have been proposed as a promising future strategy to accurately and effectively control and eradicate tumours. This review aims to evaluate the current state of the literature in the field of plasma oncology and highlight the potential for the use of LTPs in combination therapy. We also present novel data on the effect of LTPs on cancer stem cells, and speculatively outline how LTPs could circumvent treatment resistance encountered with existing therapeutics.

Strong ionization asymmetry in a geometrically symmetric radio frequency capacitively coupled plasma induced by sawtooth voltage waveforms.

The ionization dynamics in geometrically symmetric parallel plate capacitively coupled plasmas driven by radio frequency tailored voltage waveforms is investigated using phase resolved optical emission spectroscopy (PROES) and particle-in-cell (PIC) simulations. Temporally asymmetric waveforms induce spatial asymmetries and offer control of the spatiotemporal dynamics of electron heating and associated ionization structures. Sawtooth waveforms with different rise and fall rates are employed using truncated Fourier series approximations of an ideal sawtooth. Experimental PROES results obtained in argon plasmas are compared with PIC simulations, showing excellent agreement. With waveforms comprising a fast voltage drop followed by a slower rise, the faster sheath expansion in front of the powered electrode causes strongly enhanced ionization in this region. The complementary waveform causes an analogous effect in front of the grounded electrode.

Low temperature plasma: a novel focal therapy for localized prostate cancer?

Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially novel approach for the treatment of early onset prostate cancer: low temperature plasma. The rapidly evolving plasma technology has the potential to deliver a wide range of promising medical applications via the delivery of plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect of low temperature plasma on cell lines and xenografts have demonstrated DNA damage leading to apoptosis and reduction in cell viability. However, there have been no studies on prostate cancer, which is an obvious candidate for this novel therapy. We present here the potential of low temperature plasma as a focal therapy for prostate cancer.

Low Temperature Plasma Causes Double-Strand Break DNA Damage in Primary Epithelial Cells Cultured from a Human Prostate Tumour.

Research in the new field of plasma medicine continues to demonstrate the efficacy of low temperature plasmas for numerous biomedical applications. Responses such as reduction in cell viability and cell death for cancer therapy, cell proliferation for wound healing, and bacterial inactivation have been observed as a result of plasma treatment. In this study we applied low temperature plasma to prostate cancer primary cells and tissue to inflict irreparable DNA damage.

Eradication of Pseudomonas aeruginosa biofilms by atmospheric pressure non-thermal plasma.

Bacteria exist, in most environments, as complex, organised communities of sessile cells embedded within a matrix of self-produced, hydrated extracellular polymeric substances known as biofilms. Bacterial biofilms represent a ubiquitous and predominant cause of both chronic infections and infections associated with the use of indwelling medical devices such as catheters and prostheses. Such infections typically exhibit significantly enhanced tolerance to antimicrobial, biocidal and immunological challenge. This renders them difficult, sometimes impossible, to treat using conventional chemotherapeutic agents. Effective alternative approaches for prevention and eradication of biofilm associated chronic and device-associated infections are therefore urgently required. Atmospheric pressure non-thermal plasmas are gaining increasing attention as a potential approach for the eradication and control of bacterial infection and contamination. To date, however, the majority of studies have been conducted with reference to planktonic bacteria and rather less attention has been directed towards bacteria in the biofilm mode of growth. In this study, the activity of a kilohertz-driven atmospheric pressure non-thermal plasma jet, operated in a helium oxygen mixture, against Pseudomonas aeruginosa in vitro biofilms was evaluated. Pseudomonas aeruginosa biofilms exhibit marked susceptibility to exposure of the plasma jet effluent, following even relatively short (≈ 10's s) exposure times. Manipulation of plasma operating conditions, for example, plasma operating frequency, had a significant effect on the bacterial inactivation rate. Survival curves exhibit a rapid decline in the number of surviving cells in the first 60 seconds followed by slower rate of cell number reduction. Excellent anti-biofilm activity of the plasma jet was also demonstrated by both confocal scanning laser microscopy and metabolism of the tetrazolium salt, XTT, a measure of bactericidal activity.

Application of atmospheric pressure nonthermal plasma for the in vitro eradication of bacterial biofilms.

The use of atmospheric pressure nonthermal plasma represents an interesting and novel approach for the decontamination of surfaces colonized with microbial biofilms that exhibit enhanced tolerance to antimicrobial challenge. In this study, the influence of an atmospheric pressure nonthermal plasma jet, operated in a helium and oxygen gas mixture under ambient pressure, was evaluated against biofilms of Bacillus cereus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Within < 4 min of plasma exposure, complete eradication of the two gram-positive bacterial biofilms was achieved. Although gram-negative biofilms required longer treatment time, their complete eradication was still possible with 10 min of exposure. Whilst this study provides useful proof of concept data on the use of atmospheric pressure plasmas for the eradication of bacterial biofilms in vitro, it also demonstrates the critical need for improved understanding of the mechanisms and kinetics related to such a potentially significant approach.