Electrochemical sensors for in situ monitoring of reactive species during cold atmospheric plasma-based therapies

Cold atmospheric pressure plasma (CAP) is emerging as a clinically relevant therapy for dermatological conditions such as actinic keratosis, warts, and chronic wounds. However, these therapies lack strategies to monitor CAP delivery in situ and to ensure delivery of an effective CAP dose without unwanted toxicity. CAP acts as a therapeutic agent in these biomedical applications primarily (but not solely) through reactive oxygen and nitrogen species (RONS) generated at transiently high local concentrations. Here we demonstrate the use of bio-electrochemical sensors capable of real-time measurements of key CAP RONS: hydrogen peroxide and oxidation-reduction-potential (ORP). In in vitro scratch assays and in vivo murine wound models, we used these sensors to establish dose-response relationships that link CAP exposure with wound (scratch) closure dynamics, cell proliferation, oxidative stress response, and scar reduction. Our results demonstrate that CAP treatment can be continuously monitored and actively controlled in situ, providing a framework for precision plasma medicine and safer, more effective clinical translation of CAP.