Preclinical Characterization of Dielectric Barrier Discharge as a Complementary Plasma Technology for Low-Thermal Argon Plasma Devitalization of Cervical Intraepithelial Neoplasia.

Cold atmospheric plasma (CAP) has emerged as a promising tool in biomedical applications, including the treatment of precancerous neoplasias. The clinical application of low-thermal argon plasma devitalization (ltAPD) using electrosurgical argon plasma coagulation (APC) probes demonstrated significant clinical efficacy in the treatment of cervical intraepithelial neoplasia (CIN) across several prospective clinical trials. Building on the previously demonstrated antineoplastic efficacy of ltAPD treatment, we investigated a prototype dielectric barrier discharge (DBD) plasma source as an alternative plasma generation principle for the treatment of larger areas under preclinical conditions. Both devices were characterized regarding their electrical properties, reactive oxygen and nitrogen species (RONS) generation, biological efficacy, and penetration depth. Electrical measurements revealed a significantly lower current and reduced energy output for the DBD compared to the clinically approved APC probe. Reactive species analysis demonstrated comparable hydrogen peroxide generation between both devices in argon atmospheres, while the APC probe generated higher levels of ·OH and NO2- in argon atmosphere. As the gas composition is defined entirely by the externally supplied mixture, the DBD allowed the working gas to be tuned systematically by adding small fractions of air (87.5% argon/12.5% air) which strongly enhanced nitrogen-species formation and biological efficacy. Implementation of nitrogen or air to the APC could likewise lead to an increase in nitrogen species. Ex vivo treatment of human cervical tissue displayed staining for the DNA damage marker γ-H2AX throughout the epithelial layer for both devices, without detectable structural tissue damage. Agarose gel experiments under controlled laboratory atmospheres revealed greater reactive species penetration depth for the APC probe, whereas the DBD prototype provided a larger treatment area. While DBD efficacy was demonstrated under defined laboratory gas conditions in a controlled chamber setup, these findings establish a first preclinical rationale for DBD as a complementary plasma geometry.