Zhitong Chen, Richard Obenchain, Richard E Wirz, “Cold plasma treatment for biomedical applications: using aluminum foam to reduce risk while increasing efficacy,” arXiv preprint arXiv:2305.18349 (2023); pdf

Plasma medicine is an emerging and innovative interdisciplinary research field combining biology, chemistry, physics, engineering, and medicine. However, the safe clinical application of cold atmospheric plasma (CAP) technology is still a challenge. Here, we examine the use of aluminum (Al) foam with three pores-per-inch (PPI) ratings in clinical plasma applications. Al foams can filter sparks to avoid damage from high voltage discharge during surgery and efficiently deliver reactive species generated in CAP to the target. The sparks appear and plasma intensity increases at the foam/discharge interface, which just slightly increases the interface temperature without changing the interface microstructure during a 30-minute treatment. After CAP penetrated the Al foams, N2, N2+, *OH, O, and He emission peaks were characterized, and the highest values appeared using Al foams with 10 PPI. CAP with and without Al foam intermediating was used to treat deionized water, and the results indicate CAP in combination with 10 PPI Al foam led to much higher ROS concentration than CAP alone. For melanoma cell experiments, CAP with and without Al foam had a similar effect on cell viability after 30-second treatment, while CAP with the 10-PPI Al foam had much higher killing efficiency than CAP alone after 60-second treatment. In summary, 10-PPI Al foam can not only prevent damage to tissues resulting from high discharge voltage during clinical surgery but also increase the delivery efficiency of reactive species generated in plasma for biomedical applications.

Chen, Z., Bai, F., Jonas, S. J., & Wirz, R. E.,“Cold atmospheric plasma for addressing the COVID‐19 pandemic,” Plasma Processes and Polymers, 19(9) (2022); https://doi.org/10.1002/ppap.202200012

The coronavirus disease 2019 (COVID‐19) pandemic has greatly stressed the global community, exposing vulnerabilities in the supply chains for disinfection materials, personal protective equipment, and medical resources worldwide. Disinfection methods based on cold atmospheric plasma (CAP) technologies offer an intriguing solution to many of these challenges because they are easily deployable and do not require resource‐constrained consumables or reagents needed for conventional decontamination practices. CAP technologies have shown great promise for a wide range of medical applications from wound healing and cancer treatment to sterilization methods to mitigate airborne and fomite transfer of viruses. This review engages the broader community of scientists and engineers that wish to help the medical community with the ongoing COVID‐19 pandemic by establishing methods to utilize broadly applicable CAP technologies.

Chen, Z., Chen, G., Obenchain, R., Zhang, R., Bai, F., Fang, T., Wang, H., Lu, Y., Wirz, R. E., & Gu, Z., “Cold atmospheric plasma delivery for biomedical applications,” Materials Today, 54, 153–188 (2022); https://doi.org/10.1016/j.mattod.2022.03.001

As the fourth state of matter, plasma’s unique properties and interactions with other states of matter offer many promising opportunities for investigation and discovery. In particular, cold atmospheric plasma (CAP), operating at atmospheric pressure and room temperature, has remarkable potential for biomedical applications through various delivery methods. These biomedical applications include sterilization, wound healing, blood coagulation, oral/dental diseases treatment, cancer therapy, and immunotherapy. Effective delivery of plasma constituents is critical to its efficacy for these applications. Therefore, this review presents the key research activities related to CAP delivery (including direct CAP delivery, delivery of plasma-activated media, biomedical device-assisted plasma delivery, and CAP delivery with other therapeutics) and needs for future research. This review will be of great interest for understanding the current state-of-the-art of biomedical applications of plasma medicine while also giving researchers from a broad range of communities insight into research efforts that would benefit from their contributions. Such communities include biomedicine, physics, biochemistry, material science, nanotechnology, and medical device manufacturing.

Chen G., Chen Z., Wang Z., Obenchain R., Wen D., Li H., Wirz R.E., Gu Z., “Portable air-fed cold atmospheric plasma device for postsurgical cancer treatment ,” Science Advances, Vol 7, Issue 36 (2021); https://www.science.org/doi/10.1126/sciadv.abg5686

Surgery represents the major option for treating most solid tumors. Despite continuous improvements in surgical techniques, cancer recurrence after surgical resection remains the most common cause of treatment failure. Here, we report cold atmospheric plasma (CAP)–mediated postsurgical cancer treatment, using a portable air-fed CAP (aCAP) device. The aCAP device we developed uses the local ambient air as the source gas to generate cold plasma discharge with only joule energy level electrical input, thus providing a device that is simple and highly tunable for a wide range of biomedical applications. We demonstrate that local aCAP treatment on residual tumor cells at the surgical cavities effectively induces cancer immunogenic cell death in situ and evokes strong T cell–mediated immune responses to combat the residual tumor cells. In both 4T1 breast tumor and B16F10 melanoma models, aCAP treatment after incomplete tumor resection contributes to inhibiting tumor growth and prolonging survival.

Chen Z., Garcia G., Arumugaswami V., Wirz R.E., “Cold atmospheric plasma for SARS-CoV-2 inactivation,” Featured Article Physics of Fluids 32, 111702 (2020); https://doi.org/10.1063/5.0031332

Syndrome coronavirus 2 (SARS-CoV-2) infectious virions are viable on various surfaces (e.g., plastic, metals, and cardboard) for several hours. This presents a transmission cycle for human infection that can be broken by developing new inactivation approaches. We employed an efficient cold atmospheric plasma (CAP) with argon feed gas to inactivate SARS-CoV-2 on various surfaces including plastic, metal, cardboard, basketball composite leather, football leather, and baseball leather. These results demonstrate the great potential of CAP as a safe and effective means to prevent virus transmission and infections for a wide range of surfaces that experience frequent human contact. Since this is the first-ever demonstration of cold plasma inactivation of SARS-CoV-2, it is a significant milestone in the prevention and treatment of coronavirus disease 2019 (COVID-19) and presents a new opportunity for the scientific, engineering, and medical communities.

Chen G., Chen Z., Wen, D., Wang, Z., Li, H., Zeng., Y., Dotti, G., Wirz, R., Gu, Z., “Transdermal cold atmospheric plasma-mediated immune checkpoint blockade therapy,” Proceedings of teh National Academy of Sciences (2020); https://doi.org/10.1063/5.0031332

Despite the promise of immune checkpoint blockade (ICB) therapy against cancer, challenges associated with low objective response rates and severe systemic side effects still remain and limit its clinical applications. Here, we described a cold atmospheric plasma (CAP)-mediated ICB therapy integrated with microneedles (MN) for the transdermal delivery of ICB. We found that a hollow-structured MN (hMN) patch facilitates the transportation of CAP through the skin, causing tumor cell death. The release of tumor-associated antigens then promotes the maturation of dendritic cells in the tumor-draining lymph nodes, subsequently initiating T cell-mediated immune response. Anti-programmed death-ligand 1 antibody (aPDL1), an immune checkpoint inhibitor, released from the MN patch further augments the antitumor immunity. Our findings indicate that the proposed transdermal combined CAP and ICB therapy can inhibit the tumor growth of both primary tumors and distant tumors, prolonging the survival of tumor-bearing mice.