Direct plasma stimuli including electrostimulation and OH radical induce transient increase in intracellular Ca2+ and uptake of a middle‐size membrane‐impermeable molecule

Despite the promising potential of medical treatments based on non‐equilibrium atmospheric‐pressure plasma, most of the underlying mechanisms remain unknown. Here we report that direct plasma irradiation (DPI) can induce transient increase in intracellular calcium (Ca2+) concentrations, thereby playing key roles in many cellular processes as well as the uptake of middle‐size membrane‐impermeable molecules, which did not occur with indirect plasma irradiation (IPI). Experimental measurements using a Pockels voltage probe and gelling chemical reagent showed that electric field of 150 kV/cm and hydroxyl radical (OH) supply to cell cultures were induced by DPI under a typical condition compared with IPI. In addition, significant inhibition of the OH scavenger D‐mannitol indicated involvement of OH in those DPI‐induced cellular responses. These results facilitate the elucidation of plasma‐cell interaction and the development of plasma devices for medical treatments. Direct plasma irradiation (DPI) can induce intracellular Ca2+ response as well as the uptake of middle‐size membrane‐impermeable molecules YOYO‐1, which does not occur with indirect plasma irradiation. The DPI‐derived complex stimuli, including the electrostimulation and the reactive species supply, could be used for a novel medical treatment.