Research on plasma medicine-relevant plasma-liquid interaction: What happened in the past five years?

During the last five years mechanisms of plasma-induced change of liquid chemistry have drawn huge attention in basic research in plasma medicine because liquid phase processes have been identified to be the main key to understand detailed mechanisms of atmospheric pressure plasma effects on living systems. Moreover, plasma-activated liquids are considered to be useful for several applications also in the medical field. This review gives a compilation of the work done in the past five years mainly from an analytical point of view to reveal both the actual knowledge and the still missing parts for a more complete understanding of the plasma-liquid-tissue interaction. In general, independent both on the different atmospheric pressure plasma sources (dielectric barrier discharges, plasma jets; different working gases) and the different liquid systems (water, non-buffered and buffered saline solutions, cell culture media) investigated, hydrogen peroxide (H2O2) as well as nitrite (NO2-) and nitrate (NO3-) were detected as stable reactive oxygen and nitrogen species (ROS, RNS/RONS). In non-buffered systems, pH decrease was found. It is hypothesized that the basic pathways of generation of reactive species in liquids after treatment with atmospheric pressure plasmas can be generalized. These stable and easy to detect ROS and RNS/RONS are considered to be representative for more or less complex reactions chains with the participation of other more reactive and short-lived reactive oxygen and nitrogen "precursor" species which are induced in liquids by plasma treatment and may play dominant roles in biological plasma effects. As most important precursors of hydrogen peroxide as well as nitrite and nitrate, hydroxyl radicals ((OH)-O-center dot), superoxide anion radicals (O-2(center dot-), singlet oxygen (O-1(2)), and nitric oxide ((NO)-N-center dot) were identified and partially detected in different plasma treated liquids. By combination of experimental data and theoretical considerations including modeling approaches first steps to identify reaction pathways were realized yet. Above all, peroxynitrite (ONOO-) was identified to play a crucial role for biological effects of plasma-treated liquids. In future, innovative and sophisticated analytics possibly at least partially beyond the classical chemical and pharmaceutical techniques have to found to improve the fundamental understanding of liquid phase-transmitted mechanisms of plasma effects on living cells and tissue and its consequences for complex physiological as well as pathophysiological processes in the organism. This is essential both for the consolidation of plasma medicine on a sound scientific basis and to open up innovative fields of plasma application in medicine. (C) 2015 Elsevier GmbH. All rights reserved.