Gregor E. Morfill

A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients

Background  Bacterial colonization of chronic wounds slows healing. Cold atmospheric plasma has been shown in vitro to kill a wide range of pathogenic bacteria.

Plasma applications in medicine with a special focus on dermatology

The recent tremendous progress in understanding physical plasma phenomenon, together with the development of new plasma sources has put growing focus on the application of plasmas in health care. Active plasma components, such as molecules, atoms, ions, electrons and photons, reactive species, ultraviolet radiation, optical and infrared emission and heat have the ability of activating, controlling and catalysing reactions and complex biochemical procedures. Thermal and non‐thermal (i.e. cold) plasmas – both already widely established in medicine – are used for various therapeutic applications. Particularly in dermatology, plasma applications hold big potential, for example, in wound healing, such as efficient disinfection or sterilization, therapy of various skin infections or tissue regeneration. This review gives an overview on potential plasma applications in medicine – including the recent research on skin diseases – and summarizes possible interactions between plasmas and living tissue.

Plasma medicine: possible applications in dermatology

As a result of both the better understanding of complex plasma phenomena and the development of new plasma sources in the past few years, plasma medicine has developed into an innovative field of research showing high potential. While thermal plasmas have long been used in various medical fields (for instance for cauterization and sterilization of medical instruments), current research mainly focuses on application of non‐thermal plasmas.

Bactericidal effects of non-thermal argon plasma in vitro, in biofilms and in the animal model of infected wounds.

Non-thermal (low-temperature) physical plasma is under intensive study as an alternative approach to control superficial wound and skin infections when the effectiveness of chemical agents is weak due to natural pathogen or biofilm resistance. The purpose of this study was to test the individual susceptibility of pathogenic bacteria to non-thermal argon plasma and to measure the effectiveness of plasma treatments against bacteria in biofilms and on wound surfaces. Overall, Gram-negative bacteria were more susceptible to plasma treatment than Gram-positive bacteria. For the Gram-negative bacteria Pseudomonas aeruginosa, Burkholderia cenocepacia and Escherichia coli, there were no survivors among the initial 10(5) c.f.u. after a 5 min plasma treatment. The susceptibility of Gram-positive bacteria was species- and strain-specific. Streptococcus pyogenes was the most resistant with 17 % survival of the initial 10(5) c.f.u. after a 5 min plasma treatment. Staphylococcus aureus had a strain-dependent resistance with 0 and 10 % survival from 10(5) c.f.u. of the Sa 78 and ATCC 6538 strains, respectively. Staphylococcus epidermidis and Enterococcus faecium had medium resistance. Non-ionized argon gas was not bactericidal. Biofilms partly protected bacteria, with the efficiency of protection dependent on biofilm thickness. Bacteria in deeper biofilm layers survived better after the plasma treatment. A rat model of a superficial slash wound infected with P. aeruginosa and the plasma-sensitive Staphylococcus aureus strain Sa 78 was used to assess the efficiency of argon plasma treatment. A 10 min treatment significantly reduced bacterial loads on the wound surface. A 5-day course of daily plasma treatments eliminated P. aeruginosa from the plasma-treated animals 2 days earlier than from the control ones. A statistically significant increase in the rate of wound closure was observed in plasma-treated animals after the third day of the course. Wound healing in plasma-treated animals slowed down after the course had been completed. Overall, the results show considerable potential for non-thermal argon plasma in eliminating pathogenic bacteria from biofilms and wound surfaces.

Dust in the Local Interstellar Wind

The gas-to-dust mass ratios found for interstellar dust within the solar system, versus values determined astronomically for the cloud around the solar system, suggest that large and small interstellar grains have separate histories and that large interstellar grains preferentially detected by spacecraft are not formed exclusively by mass exchange with nearby interstellar gas. Observations by the Ulysses and Galileo satellites of the mass spectrum and flux rate of interstellar dust within the heliosphere are combined with information about the density, composition, and relative flow speed and direction of interstellar gas in the cloud surrounding the solar system to derive an in situ value for the gas-to-dust mass ratio, Rg/d = 94. This ratio is dominated by the larger near-micron-sized grains. Including an estimate for the mass of smaller grains, which do not penetrate the heliosphere owing to charged grain interactions with heliosheath and solar wind plasmas, and including estimates for the mass of the larger population of interstellar micrometeorites, the total gas-to-dust mass ratio in the cloud surrounding the solar system is half this value. Based on in situ data, interstellar dust grains in the 10-14 to 10-13 g mass range are underabundant in the solar system, compared to a Mathis, Rumple, & Nordsiek mass distribution scaled to the local interstellar gas density, because such small grains do not penetrate the heliosphere. The gas-to-dust mass ratios are also derived by combining spectroscopic observations of the gas-phase abundances in the nearest interstellar clouds. Measurements of interstellar absorption lines formed in the cloud around the solar system, as seen in the direction of CMa, give Rg/d = 427 for assumed solar reference abundances and Rg/d = 551 for assumed B star reference abundances. These values exceed the in situ value suggesting either that grain mixing or grain histories are not correctly understood or that sweptup stardust is present. Such high values for diffuse interstellar clouds are strongly supported by diffuse cloud data seen toward λ Sco and 23 Ori, provided B star reference abundances apply. If solar reference abundances prevail, however, the surrounding cloud is seen to have greater than normal dust destruction compared to higher column density diffuse clouds. The cloud surrounding the solar system exhibits enhanced gas-phase abundances of refractory elements such as Fe+ and Mg+, indicating the destruction of dust grains by shock fronts. The good correlation locally between Fe+ and Mg+ indicates that the gas-phase abundances of these elements are dominated by grain destruction, while the poor correlation between Fe+ and H0 indicates either variable gas ionization or the decoupling of neutral gas and dust over parsec scale lengths. These abundances, combined with grain destruction models, indicate that the nearest interstellar material has been shocked with shocks of velocity ~150 km s-1. If solar reference abundances are correct, the low Rg/d value toward λ Sco may indicate that at least one cloud component in this direction contains dust grains that have retained their silicate mantles and are responsible for the polarization of the light from nearby stars seen in this general region. Weak frictional coupling between gas and dust in nearby low density gas permit inhomogeneities to be present.

Effects of cold atmospheric plasma on mucosal tissue culture

Thermal plasmas have been commonly used in medical applications such as plasma ablation and blood coagulation. Newer developments show that plasmas can be generated with ion temperatures close to room temperature: these non-thermal or so-called cold atmospheric plasmas (CAPs) therefore open up a wide range of further biomedical applications. Based on the understanding of the bactericidal, virucidal and fungicidal properties of CAPs, information about the effects of CAP on mucosal cells and tissue is still lacking. Therefore this study focuses on the interaction of CAP with healthy head and neck mucosal cells on a molecular level. To analyse this interaction in detail, fresh tissue samples from healthy nasal and pharyngeal mucosa were harvested during surgery, assembled to a three-dimensional tissue culture model (mini organ cultures) and treated with CAP for different treatment times. Effects on the viability, necrosis induction and mutagenic activity were evaluated with the trypan blue exclusion test, Annexin-V/PI staining and alkaline microgel electrophoresis (comet assay). Trypan blue exclusion test revealed that the CAP treatment significantly decreases the cell viability for all tested treatment times (5, 10, 30, 60 and 120s; p< 0.05), but only a treatment time of 120s showed a cytotoxic effect as the viability dropped below 90%. Annexin-V/PI staining revealed a significant increase in necrosis in CAP treated pharyngeal tissue cultures for treatment times of 60 and 120s ( p< 0.05). For nasal tissue this effect was already detected for a 30s treatment ( p< 0.05). Comet assay analysis showed no mutagenic effects after exposure to CAP. (Some figures may appear in colour only in the online journal)

Plasma chemistry model of surface microdischarge in humid air and dynamics of reactive neutral species

We present a numerical model of a surface microdischarge (SMD) in humid air at atmospheric pressure. Our model includes over 50 species and 600 elementary reactions and consists of two, coupled well-mixed regions: a discharge layer with both charged and neutral species and an afterglow region consisting only of neutral species. Multiple time steps employed in our model enable capturing rapid dynamic behaviour in the discharge layer as well as the relatively slow diffusion and reaction in the afterglow. A short duration, high electric field is assumed to be excited at 10 kHz in the discharge region with power density maintained at 0.05 W cm−2. Among the predicted dominant species in the afterglow are O3, N2O5, N2O, HNO3, H2, NO3, H2O2, HNO2 and NO2. The results are in qualitative agreement with Fourier transform infrared absorption spectroscopy. Our simulation results show that density of those reactive species continues to evolve significantly in time, even after ~15 min of SMD exposure. This result suggests that SMD treatments on the order of minutes or less may involve significant neutral species concentration and flux transients, potentially affecting interpretation of results.

Cold atmospheric air plasma sterilization against spores and other microorganisms of clinical interest

ABSTRACT Physical cold atmospheric surface microdischarge (SMD) plasma operating in ambient air has promising properties for the sterilization of sensitive medical devices where conventional methods are not applicable. Furthermore, SMD plasma could revolutionize the field of disinfection at health care facilities. The antimicrobial effects on Gram-negative and Gram-positive bacteria of clinical relevance, as well as the fungus Candida albicans, were tested. Thirty seconds of plasma treatment led to a 4 to 6 log10 CFU reduction on agar plates. C. albicans was the hardest to inactivate. The sterilizing effect on standard bioindicators (bacterial endospores) was evaluated on dry test specimens that were wrapped in Tyvek coupons. The experimental D 23 ° C values for Bacillus subtilis, Bacillus pumilus, Bacillus atrophaeus, and Geobacillus stearothermophilus were determined as 0.3 min, 0.5 min, 0.6 min, and 0.9 min, respectively. These decimal reduction times (D values) are distinctly lower than D values obtained with other reference methods. Importantly, the high inactivation rate was independent of the material of the test specimen. Possible inactivation mechanisms for relevant microorganisms are briefly discussed, emphasizing the important role of neutral reactive plasma species and pointing to recent diagnostic methods that will contribute to a better understanding of the strong biocidal effect of SMD air plasma.

The Galileo Dust Detector

The Galileo Dust Detector is intended to provide direct observations of dust grains with masses between 10−19 and 10−9 kg in interplanetary space and in the Jovian system, to investigate their physical and dynamical properties as functions of the distances to the Sun, to Jupiter and to its satellites, to study its interaction with the Galilean satellites and the Jovian magnetosphere. Surface phenomena of the satellites (like albedo variations), which might be effects of meteoroid impacts will be compared with the dust environment. Electric charges of particulate matter in the magnetosphere and its consequences will be studied; e.g., the effects of the magnetic field on the trajectories of dust particles and fragmentation of particles due to electrostatic disruption. The investigation is performed with an instrument that measures the mass, speed, flight direction and electric charge of individual dust particles. It is a multicoincidence detector with a mass sensitivity 106 times higher than that of previous in-situ experiments which measured dust in the outer solar system. The instrument weighs 4.2 kg, consumes 2.4 W, and has a normal data transmission rate of 24 bits s−1 in nominal spacecraft tracking mode. On December 29, 1989 the instrument was switched-on. After the instrument had been configured to flight conditions cruise science data collection started immediately. In the period to May 18, 1990 at least 168 dust impacts have been recorded. For 81 of these dust grains masses and impact speeds have been determined. First flux values are given.

Complex Plasmas and Colloidal Dispersions: Particle-resolved Studies of Classical Liquids and Solids

Interdisciplinary Research: Scientific Background Basic Properties of Complex Plasmas and Colloidal Dispersions: Charging, Interactions, Major Forces Examples of Particle-Resolved Studies: Static Liquid Structure Liquid-Solid Phase Transitions Kinetics of Liquids Hydrodynamics and Rheology at the Discreteness Limit Nonequilibrium Phase Transitions Binary Mixtures Tunable Interactions Anisotropic Particles.