Plasma, the fourth and most pervasive state of matter in the visible universe, is a fascinating medium that is connected to the beginning of our universe itself. Man-made plasmas are at the core of many technological advances that include the fabrication of semiconductor devices, which enabled the modern computer and communication revolutions. The introduction of low temperature, atmospheric pressure plasmas to the biomedical field has ushered a new revolution in the healthcare arena that promises to introduce plasma-based therapies to combat some thorny and long-standing medical challenges. This paper presents an overview of where research is at today and discusses innovative concepts and approaches to overcome present challenges and take the field to the next level. It is written by a team of experts who took an in-depth look at the various applications of plasma in hygiene, decontamination, and medicine, made critical analysis, and proposed ideas and concepts that should help the research community focus their efforts on clear and practical steps necessary to keep the field advancing for decades to come.

The application of atmospheric pressure plasmas in medicine is increasingly gaining attention in recent years, although very little is currently known about the plasma-induced processes occurring on the surface of living organisms. It is known that most bio-organisms, including bacteria, are coated by a liquid film surrounding them, and there might be many interactions between plasma species and the liquid layer before the plasma species reach the surface of the bio-organisms. Therefore, it is essential to study the behaviour of the reactive species in a liquid film, in order to determine whether these species can travel through this layer and reach the biomolecules, or whether new species are formed along the way. In this work, we investigate the interaction of reactive oxygen species (i.e. O, OH, HO2 and H2O2) with water, which is assumed as a simple model system for the liquid layer surrounding biomolecules. Our computational investigations show that OH, HO2 and H2O2 can travel deep into the liquid layer and are hence in principle able to reach the bio-organism. Furthermore, O, OH and HO2 radicals react with water molecules through hydrogen-abstraction reactions, whereas no H-abstraction reaction takes place in the case of H2O2. This study is important to gain insight into the fundamental operating mechanisms in plasma medicine, in general, and the interaction mechanisms of plasma species with a liquid film, in particular.

We report on multi-level atomistic simulations for the interaction of reactive oxygen species (ROS) with the head groups of the phospholipid bilayer, and the subsequent effect of head group and lipid tail oxidation on the structural and dynamic properties of the cell membrane. Our simulations are validated by experiments using a cold atmospheric plasma as external ROS source. We found that plasma treatment leads to a slight initial rise in membrane rigidity, followed by a strong and persistent increase in fluidity, indicating a drop in lipid order. The latter is also revealed by our simulations. This study is important for cancer treatment by therapies producing (extracellular) ROS, such as plasma treatment. These ROS will interact with the cell membrane, first oxidizing the head groups, followed by the lipid tails. A drop in lipid order might allow them to penetrate into the cell interior (e.g., through pores created due to oxidation of the lipid tails) and cause intracellular oxidative damage, eventually leading to cell death. This work in general elucidates the underlying mechanisms of ROS interaction with the cell membrane at the atomic level.