No abstract

The kINPen ®4,5 plasma jet was developed from laboratory prototype to commercially available non-equilibrium cold plasma jet for various applications in materials research, surface treatment and medicine. It has proven to be a valuable plasma source for industry as well as research and commercial use in plasma medicine, leading to very successful therapeutic results and its certification as a medical device. This topical review presents the different kINPen plasma sources available. Diagnostic techniques applied to the kINPen are introduced. The review summarizes the extensive studies of the physics and plasma chemistry of the kINPen performed by research groups across the world, and closes with a brief overview of the main application fields.

Plasma medicine means the direct application of cold atmospheric plasma (CAP) on or in the human body for therapeutic purposes. Further, the field interacts strongly with results gained for biological decontamination. Experimental research as well as first practical application is realized using two basic principles of CAP sources: dielectric barrier discharges (DBD) and atmospheric pressure plasma jets (APPJ). Originating from the fundamental insights that the biological effects of CAP are most probably caused by changes of the liquid environment of cells, and are dominated by reactive oxygen and nitrogen species (ROS, RNS), basic mechanisms of biological plasma activity are identified. It was demonstrated that there is no increased risk of cold plasma application and, above all, there are no indications for genotoxic effects. The most important biological effects of cold atmospheric pressure plasma were identified: (1) inactivation of a broad spectrum of microorganisms including multidrug resistant ones; (2) stimulation of cell proliferation and tissue regeneration with lower plasma treatment intensity (treatment time); (3) inactivation of cells by initialization of programmed cell death (apoptosis) with higher plasma treatment intensity (treatment time). In recent years, the main focus of clinical applications was in the field of wound healing and treatment of infective skin diseases. First CAP sources are CE-certified as medical devices now which is the main precondition to start the introduction of plasma medicine into clinical reality. Plasma application in dentistry and, above all, CAP use for cancer treatment are becoming more and more important research fields in plasma medicine. A further in-depth knowledge of control and adaptation of plasma parameters and plasma geometries is needed to obtain suitable and reliable plasma sources for the different therapeutic indications and to open up new fields of medical application.

Non-thermal atmospheric-pressure plasma, also named cold plasma, is defined as a partly ionized gas. Therefore, it cannot be equated with plasma from blood; it is not biological in nature. Non-thermal atmospheric-pressure plasma is a new innovative approach in medicine not only for the treatment of wounds, but with a wide-range of other applications, as e.g. topical treatment of other skin diseases with microbial involvement or treatment of cancer diseases. This review emphasizes plasma effects on wound healing. Non-thermal atmospheric-pressure plasma can support wound healing by its antiseptic effects, by stimulation of proliferation and migration of wound relating skin cells, by activation or inhibition of integrin receptors on the cell surface or by its pro-angiogenic effect. We summarize the effects of plasma on eukaryotic cells, especially on keratinocytes in terms of viability, proliferation, DNA, adhesion molecules and angiogenesis together with the role of reactive oxygen species and other components of plasma. The outcome of first clinical trials regarding wound healing is pointed out.

No abstract

A novel approach combining experimental and numerical methods for the study of reaction mechanisms in a cold atmospheric Ar plasma jet is introduced. The jet is operated with a shielding gas device that produces a gas curtain of defined composition around the plasma plume. The shielding gas composition is varied from pure N 2 to pure O 2 .The density of metastable argon ( ) Ar 4s, P

Treatment of aqueous liquids by surface‐DBD in atmospheric air resulted in bactericidal activity of the liquid itself. A 7 min treatment of sodium chloride (NaCl) solution and its immediate addition to Escherichia coli resulted in a complete bacteria inactivation (≥7 log) after 15 min exposure time. With a 30 min delay between plasma treatment of liquid and its addition to the bacteria, bactericidal effect was reduced but still detectable. Nitrate (${\rm NO}_{2}^{{-} } $), nitrite (${\rm NO}_{2}^{{-} } $), and hydrogen peroxide (H2O2), respectively, as well as strong acidification are detected in plasma treated liquids and can explain this bactericidal activity partially. Combination of 1.5 mg · L−1 ${\rm NO}_{2}^{{-} } $ and 2.5 mg · L−1 H2O2 at pH 3 results in maximum 3.5 log E. coli reduction within 60 min. Plasma diagnostics and liquid analytics are combined with theoretical considerations to focus possible reaction channels of plasma–water interactions. Using FT‐IR, stable molecules like nitrous oxide (N2O), ozone (O3), carbon dioxide (CO2), and traces of nitric acid (HNO3) and/or peroxynitrous acid (ONOOH) were measured. Reactions of these molecules from the plasma/gas phase with the aqueous liquid can result in acidification and generation of H2O2, ${\rm NO}_{2}^{{-} } $, and ${\rm NO}_{3}^{{-} } $ or peroxynitrite (ONOO−), respectively, via reactions which are associated with the occurrence of several more or less stable but biologically active chemical intermediates like ${\rm NO}^{ \bullet } $ or nitrogen dioxide (${\rm NO}_{2}^{ \bullet } $). On the other hand, H2O2, ${\rm NO}_{2}^{{-} } $, and ${\rm NO}_{3}^{{-} } $/ONOO− could serve as starting reaction partners to generate ${\rm NO}^{ \bullet } $, ${\rm HO}^{ \bullet } $, ${\rm NO}_{2}^{ \bullet } $, or hydroxyl radicals (${\rm HOO}^{ \bullet } $) in the liquid.

Physical plasmas generate unique mixes of reactive oxygen and nitrogen species (RONS or ROS). Only a bit more than a decade ago, these plasmas, operating at body temperature, started to be considered for medical therapy with considerably little mechanistic redox chemistry or biomedical research existing on that topic at that time. Today, a vast body of evidence is available on physical plasma-derived ROS, from their spatiotemporal resolution in the plasma gas phase to sophisticated chemical and biochemical analysis of these species once dissolved in liquids. Data from in silico analysis dissected potential reaction pathways of plasma-derived reactive species with biological membranes, and in vitro and in vivo experiments in cell and animal disease models identified molecular mechanisms and potential therapeutic benefits of physical plasmas. In 2013, the first medical plasma systems entered the European market as class IIa devices and have proven to be a valuable resource in dermatology, especially for supporting the healing of chronic wounds. The first results in cancer patients treated with plasma are promising, too. Due to the many potentials of this blooming new field ahead, there is a need to highlight the main concepts distilled from plasma research in chemistry and biology that serve as a mechanistic link between plasma physics (how and which plasma-derived ROS are produced) and therapy (what is the medical benefit). This inevitably puts cellular membranes in focus, as these are the natural interphase between ROS produced by plasmas and translation of their chemical reactivity into distinct biological responses.