Plasma–liquid interactions represent a growing interdisciplinary area of research involving plasma science, fluid dynamics, heat and mass transfer, photolysis, multiphase chemistry and aerosol science. This review provides an assessment of the state-of-the-art of this multidisciplinary area and identifies the key research challenges. The developments in diagnostics, modeling and further extensions of cross section and reaction rate databases that are necessary to address these challenges are discussed. The review focusses on non-equilibrium plasmas.

When cold atmospheric plasma comes into contact with water and biological media, antimicrobial or antitumor effects are induced, representing great potential for applications in biomedicine and agriculture. The need to control and tune the chemical composition and biomedical effects of plasma activated water/media (PAW/PAM) is emerging. By comparing two nonthermal air plasma sources, streamer corona and transient spark, interacting with water in open and closed reactors, and by enhancing the plasma–liquid interaction by water electrospray through these discharges, we demonstrate that the plasma gaseous products strongly depend on the discharge regime, its deposited power and gas flow conditions. The streamer corona strongly leads to the formation of ozone and hydrogen peroxide, while the more energetic transient spark leads to nitrogen oxides and hydrogen peroxide. The gaseous products then determine the chemical properties of the PAW and the dominant aqueous reactive oxygen and nitrogen species (RONS). The production of hydrogen peroxide depends on water evaporation and hydroxyl radical formation, which is determined by the discharge power. A transient spark produces higher concentrations of gaseous and aqueous RONS and induces stronger antibacterial effects than a streamer corona; however, the RONS production rates per joule of deposited energy are comparable for both studied discharge regimes. The net production rate per joule of gaseous nitrogen oxides strongly correlates with that of aqueous nitrites and nitrates. The antibacterial effects of the PAW tested on Escherichia coli bacteria are determined by the aqueous RONS: in the lower power streamer corona, this is ascertained mainly by the dissolved ozone and hydrogen peroxide, and in the higher power transient spark, by the combination of hydrogen peroxide, nitrite and acidic pH, while in the transient spark in the closed reactor it is determined by the acidified nitrites present.

The selective in vitro anti-tumor mechanisms of cold atmospheric plasma (CAP) and plasma-activated media (PAM) follow a sequential multi-step process. The first step involves the formation of primary singlet oxygen (¹O₂) through the complex interaction between NO₂⁻ and H₂O_2.¹O₂ then inactivates some membrane-associated catalase molecules on at least a few tumor cells. With some molecules of their protective catalase inactivated, these tumor cells allow locally surviving cell-derived, extracellular H₂O₂ and ONOO^─ to form secondary ¹O₂. These species continue to inactivate catalase on the originally triggered cells and on adjacent cells. At the site of inactivated catalase, cell-generated H₂O₂ enters the cell via aquaporins, depletes glutathione and thus abrogates the cell’s protection towards lipid peroxidation. Optimal inactivation of catalase then allows efficient apoptosis induction through the HOCl signaling pathway that is finalized by lipid peroxidation. An identical CAP exposure did not result in apoptosis for nonmalignant cells. A key conclusion from these experiments is that tumor cell-generated RONS play the major role in inactivating protective catalase, depleting glutathione and establishing apoptosis-inducing RONS signaling. CAP or PAM exposure only trigger this response by initially inactivating a small percentage of protective membrane associated catalase molecules on tumor cells.