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.

Reactive oxygen and nitrogen species released by cold physical plasma are being proposed as effectors in various clinical conditions connected to inflammatory processes. As these plasmas can be tailored in a wide range, models to compare and control their biochemical footprint are desired to infer on the molecular mechanisms underlying the observed effects and to enable the discrimination between different plasma sources. Here, an improved model to trace short-lived reactive species is presented. Using FTIR, high-resolution mass spectrometry, and molecular dynamics computational simulation, covalent modifications of cysteine treated with different plasmas were deciphered and the respective product pattern used to generate a fingerprint of each plasma source. Such, our experimental model allows a fast and reliable grading of the chemical potential of plasmas used for medical purposes. Major reaction products were identified to be cysteine sulfonic acid, cystine, and cysteine fragments. Less-abundant products, such as oxidized cystine derivatives or S-nitrosylated cysteines, were unique to different plasma sources or operating conditions. The data collected point at hydroxyl radicals, atomic O, and singlet oxygen as major contributing species that enable an impact on cellular thiol groups when applying cold plasma in vitro or in vivo.

A rapid screening method for the investigation of plasma-induced chemical modifications was developed by analyzing cysteine using Fourier Transform Infrared (FTIR) spectroscopy. Cysteine is a key amino acid in proteins due to the presence of a thiol group which provides unique structural features by offering the possibility to form disulfide bonds. Its chemical composition makes cysteine a well-suited model for the investigation of plasma-induced modifications at three functional groups—the amino, the carboxyl and the thiol group—all highly abundant in proteins. FTIR spectroscopy is present in most physical laboratories and offers a fast way to assess changes in the chemical composition of cysteine substrates due to plasma treatment and to compare different treatment conditions or plasma sources with each other. Significant changes in the fingerprint spectra of cysteine samples treated with a dielectric barrier discharge (DBD) compared to untreated controls were observed using a FTIR spectrometer. The loss of the thiol signal and the simultaneous increase of bands originating from oxidized sulfur and nitrogen species indicate that the thiol group of cysteine is modified by reactive oxygen and nitrogen species during DBD treatment. Furthermore, other plasma-induced modifications, such as changes of the amino and carbonyl groups, could be observed. Complementary mass spectrometry measurements confirmed these results.

A volume and a twin surface dielectric barrier discharge (VDBD and SDBD) are generated in different nitrogen–oxygen mixtures at atmospheric pressure by applying damped sinusoidal voltage waveforms with oscillation periods in the microsecond time scale. Both electrode configurations are located inside vacuum vessels and operated in a controlled atmosphere to exclude the influence of surrounding air. The discharges are characterised with different spatial and temporal resolution by applying absolutely calibrated optical emission spectroscopy in conjunction with numerical simulations and current–voltage measurements. Plasma parameters, namely the electron density and the reduced electric field, and the dissipated power are found to depend strongly on the oxygen content in the working gas mixture. Different spatial and temporal distributions of plasma parameters and dissipated power are explained by surface and residual volume charges for different O₂ admixtures due to their effects on the electron recombination rate. Thus, the oxygen admixture is found to strongly influence the breakdown process and plasma conditions of a VDBD and a SDBD.