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In this study we investigated the synergistic antimicrobial effect of a dual protocol combining cold atmospheric pressure plasma (CAP) and antimicrobial photodynamic therapy (aPDT) against different planktonic bacterial and yeast species including methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Escherichia coli, extended-spectrum β-lactamase-positive Escherichia coli and Candida albicans. A DBD plasma device was used for CAP treatment while for aPDT, toluidine blue O (TBO) was the photosensitizer (PS) of choice and a radiator emitting visible and water-filtered-Infrared A light (VIS-wIRA) was used as irradiation source.
Microbial suspensions were either exposed to CAP treatment alone, aPDT treatment alone or aPDT followed by CAP exposure in a dual treatment protocol. Aliquots from each suspension were plated on agar plates and the number of colonies surviving after each treatment was counted. Under the experimental conditions conducted in this study, combining sub-lethal exposure doses of CAP and aPDT treatment showed significantly higher antimicrobial efficacy (P<0.0001) compared to single treatments against all tested microorganisms suggesting a synergistic effect which yielded at least 3.3 log microbial reduction corresponding to 99.6 % microbial death. In the dual CAP-aPDT approach, aPDT did not interfere with CAP-induced acidification of solution, a crucial feature for CAP antimicrobial efficiency, which further confirms the promising clinical potential of this combination regime.
We believe that the CAP-aPDT dual approach described in this study holds great potential as a successful novel antimicrobial and healing-supporting strategy especially when directed for the management of acute and chronic wounds and possibly other skin and soft tissue infections. The use of a VIS-wIRA light source in treating skin infections is preferential, due to the additional therapeutic effects of wIRA in wound healing. Furthermore, the enhanced antimicrobial effects of aPDT when combined with CAP as shown in this study may grant for a reduction in treatment times and costs as well as improving patient compliance.
Particle and heat transport in fusion devices often exceed the neoclassical prediction. This anomalous transport is thought to be produced by turbulence caused by microinstabilities such as ion and electron-temperature-gradient (ITG/ETG) and trapped-electron-mode (TEM) instabilities, the latter ones known for being strongly influenced by collisions. Additionally, in stellarators, the neoclassical transport can be important in the core, and therefore investigation of the effects of collisions is an important field of study. Prior to this thesis, however, no gyrokinetic simulations retaining collisions had been performed in stellarator geometry. In this work, collisional effects were added to EUTERPE, a previously collisionless gyrokinetic code which utilizes the δ f method. To simulate the collisions, a pitch-angle scattering operator was employed, and its implementation was carried out following the methods proposed in [Takizuka & Abe 1977, Vernay Master's thesis 2008]. To test this implementation, the evolution of the distribution function in a homogeneous plasma was first simulated, where Legendre polynomials constitute eigenfunctions of the collision operator. Also, the solution of the Spitzer problem was reproduced for a cylinder and a tokamak. Both these tests showed that collisions were correctly implemented and that the code is suited for more complex simulations. As a next step, the code was used to calculate the neoclassical radial particle flux by neglecting any turbulent fluctuations in the distribution function and the electric field. Particle fluxes in the neoclassical analytical regimes were simulated for tokamak and stellarator (LHD) configurations. In addition to the comparison with analytical fluxes, a successful benchmark with the DKES code was presented for the tokamak case, which further validates the code for neoclassical simulations. In the final part of the work, the effects of collisions were investigated for slab and toroidal ITGs and TEMs in a tokamak configuration. The results show that collisions reduce the growth rate of slab ITGs in cylinder geometry, whereas they do not affect ITGs in a tokamak, which are mainly curvature-driven. However it is important to note that the pitch-angle scattering operator does not conserve momentum, which is most critical in the parallel direction. Therefore, the damping found in a cylinder could be the consequence of this missing feature and not a physical result [Dimits & Cohen 1994]. Nonetheless, the results are useful to determine whether the instability is mainly being driven by a slab or toroidal ITG mode. EUTERPE also has the feature of including kinetic electrons, which made simulations of TEMs with collisions possible. The combination of collisions and kinetic electrons made the numerical calculations extremely time-consuming, since the time step had to be small enough to resolve the fast electron motion. In contrast to the ITG results, it was observed that collisions are extremely important for TEMs in a tokamak, and in some special cases, depending on whether they were mainly driven by density or temperature gradients, collisions could even suppress the mode (in agreement with [Angioni et al. 2005, Connor et al. 2006]). In the case of stellarators it was found that ITGs are highly dependent on the device configuration. For LHD it was shown that collisions slightly reduce the growth rate of the instability, but for Wendelstein 7-X they do not affect it and the growth rate showed a similar trend with collisionality to that of the tokamak case. Collisions also tend to make the ballooning structure of the modes less pronounced.
There is a growing interest in the application of non-thermal atmospheric pressure plasma for the treatment of wounds. Due to the generation of various ROS and RNS, UV radiation and electric fields plasma is a very promising tool which can stimulate skin and immune cells. However, not much is known about the mammalian cell responses after plasma treatments on a molecular level. The present work focusses on the impact of plasma on cell signaling in the human keratinocyte cell line HaCaT by using the methods DNA microarray, qPCR, ELISA and flow cytometry. Here, cell signaling mediators such as cytokines and growth factors which could promote wound healing by enhancing angiogenesis, reepithelization, migration and proliferation were of major interest. Additionally, the crosstalk between keratinocytes and monocytes was studied using a co-culture. For the first time extensive investigations on the impact of plasma on cell signaling in human keratinocytes were conducted. The most prominent cytokines and growth factors which were regulated by plasma at gene and protein level were VEGF-A, GM-CSF, HB-EGF, IL-8, and IL-6. The latter was not activated due to the JAK/STAT-pathway but probably by a combined activation of MAPK- and PI3K/Akt-pathways. By the use of conditioned medium it was found out that ROS and RNS generated directly after plasma treatment induced larger effects on cell signaling in keratinocytes than the subsequently secreted growth factors and cytokines. Furthermore, monocytes and keratinocytes hardly altered their secretion profiles in co-culture. From these results it is deduced that the plasma generated reactive species are the main actors during cell signaling. In order to differentiate the impact of ROS and RNS on the cellular response the ambience of the plasma effluent was controlled, varying the ambient gas composition from pure nitrogen to pure oxygen. Thereby a first step towards the attribution of the cellular response to specific plasma generated reactive species was achieved. While IL-6 expression correlated with ROS generated by the plasma source, the cell signaling mediators VEGF-A, GM-CSF and HB-EGF were significantly changed by RONS. Above all hydrogen peroxide was found to play a dominant role for observed cell responses. In summary, plasma activates wound healing related cell signaling mediators as cytokines and growth factors in keratinocytes. It was also shown that the generated reactive species mainly induced cell signaling. For the first time cell responses can be correlated to ROS and RONS in plasma treated cells. These results underline the potential of non-thermal atmospheric pressure plasma sources for their applications in wound treatment.
The main issue of this thesis was the investigation of dusty plasmas in magnetic fields. We made use of spherical paramagnetic as well as non-magnetic plastic particles in the micrometer range, so-called dust particles. The particles were then trapped in the sheath region of the driven lower electrode of an rf discharge. The plasma chamber was surrounded by coils to apply a horizontal magnetic field with field strengths of up to B=50mT at the particles’ position. In this configuration the sheath electric field and the external magnetic field were perpendicular to each other. Only the electrons could be magnetized but this leads to several forces acting on the dust particles. In some aspects the dust clusters with the magnetic particles show a behavior that is in complete contrast to those consisting of the standard non-magnetic plastic particles. Both types of particles have in common that the dust clusters were found to move either towards the positive or negative ExB-direction as a reaction to the magnetic field. Whether the positive or negative direction was preferred depended on the experimental conditions. The forces that lead to this transport are plasma-based forces induced by the magnetic field. These investigations were performed on two-dimensional horizontal particle systems. Vertically aligned dust particles due to the ion focus interaction have also been studied to determine the influence of horizontal magnetic fields on the stability of such dust pairs. Under certain conditions the vertical alignment can be broken up by the magnetic field. Some additional experiments on the interaction of non-magnetic dust particles in a plasma with UV irradiation were performed, but a significant decrease of dust charge due to a photoelectric effect was not detected. In summary, even relatively weak horizontal magnetic fields have a strong influence on dust particle systems.