An integrated device for preparation of plasma-activated media with bactericidal properties: An in vitro and in vivo study

Plasma-activated media (PAM), the product of cold atmospheric plasma (CAP) acting on aqueous media, has similarly strong biological activity and some unique advantages compared with CAP for biomedical targets. However, no reliable PAM-preparing device with high safety for medical uses has yet been developed, limiting the advancement of PAM clinical trials. Herein, an integrated device for PAM preparation with a maximum yield of 4.8 L/hr is reported in detail. A large-area CAP is generated by the plasma-generating module based on the surface dielectric barrier discharge. Several sensors and controllers are applied in this device to stabilize the discharge environment and PAM consistency. In the in vitro experiments, PAM prepared in this device exhibits the bactericidal property of up to 6 logs reduction against various clinical pathogens with multi-drug resistance. The high bactericidal effect of PAM can be preserved for ∼10 min. After constructing the mice model by cecal ligation and puncture, it is found that the abdominal injection of PAM can effectively relieve sepsis-induced systemic toxicity and maintain homeostasis, which is mainly attributed to the anti-infective efficacy of PAM. The third-party testing confirms that the soaking bactericidal rates of PAM to S. aureus and E. coli are respectively higher than 99.99% and 99.999%, while the acute oral toxicity, skin irritation, and oral genotoxicity of PAM are negligible. This study provides a practical approach for preparing PAM with high reliability, which shows an excellent prospect of clinical applications and commercialization.