Low-temperature plasma-processing technologies are essential for material synthesis and device fabrication. Not only the utilization but also the development of plasma-related products and services requires an understanding of the multiscale hierarchies of complex behaviors of plasma-related phenomena, including plasma generation in physics and chemistry, transport of energy and mass through the sheath region, and morphology- and geometry-dependent surface reactions. Low-temperature plasma science and technology play a pivotal role in the exploration of new applications and in the development and control of plasma-processing methods. Presently, science-based and data-driven approaches to control systems are progressing with the state-of-the-art deep learning, machine learning, and artificial intelligence. In this review, researchers in material science and plasma processing, review and discuss the requirements and challenges of research and development in these fields. In particular, the prediction of plasma parameters and the discovery of processing recipes are asserted by outlining the emerging science-based, data-driven approaches, which are called plasma informatics.

Hepatocellular carcinoma (HCC) is a major histological subtype of primary liver cancer. Ample evidence suggests that the pathological properties of HCC originate from hepatic cancer stem cells (CSCs), which are responsible for carcinogenesis, recurrence, and drug resistance. Cold atmospheric-pressure plasma (CAP) and plasma-activated medium (PAM) induce apoptosis in cancer cells and represent novel and powerful anti-cancer agents. This study aimed to determine the anti-cancer effect of CAP and PAM in HCC cell lines with CSC characteristics. We showed that the air-based CAP and PAM selectively induced cell death in Hep3B and Huh7 cells with CSC characteristics, but not in the normal liver cell line, MIHA. We observed both caspase-dependent and -independent cell death in the PAM-treated HCC cell lines. Moreover, we determined whether combinatorial PAM therapy with various anti-cancer agents have an additive effect on cell death in Huh7. We found that PAM highly increased the efficacy of the chemotherapeutic agent, cisplatin, while enhanced the anti-cancer effect of doxorubicin and the targeted-therapy drugs, trametinib and sorafenib to a lesser extent. These findings support the application of CAP and PAM as anti-cancer agents to induce selective cell death in cancers containing CSCs, suggesting that the combinatorial use of PAM and some specific anti-cancer agents is complemented mechanistically.

The effects of argon plasma (ArP) and helium plasma (HeP) jets on E-cadherin protein function have been tested in order to choose the working gas for a better plasma-mediated transdermal drug delivery. The plasma-mediated changes of the E-cadherin function and the skin penetration efficacies of epidermal growth factor (EGF) were monitored in vitro using HaCaT human keratinocytes and in vivo using hairless mice. The ArP showed higher efficacy for E-cadherin regulation and EGF absorption than HeP under the same applied voltage and the same gas flow rate. The ArP generates higher volume power density, higher discharge current peak, and more reactive species than HeP, especially for OH with the same operating parameters. Moreover, the effect of ArP on E-cadherin function was blocked by the use of a grounded metal mesh. Taken together, this study presents the possibility that the synergetic effect of negative charges with radicals plays an important role in plasma-mediated E-cadherin regulation, which leads to enhanced transdermal drug delivery.

Many key aspects of low-temperature plasmas include nonlinear, transient, and kinetic effects related to the spatio-temporal variation of electron energy distribution function (EEDF) which cannot be treated in a fluid simulation model. The particle-in-cell (PIC) simulation calculates kinetic effects through the statistical representation of the EEDF using many particles and thus gives accurate results. However, the computational cost is very expensive to resolve all aspects in a plasma discharge with millions of computational particles as well as hundreds of thousands of grids during millions of time steps. Additionally, the simulation of discharge plasmas should handle the collision processes and the rapid increase in the total number of simulation particles. In this presentation, details of a two-dimensional PIC simulation parallelized with graphics processing units (GPUs) are explained for the improvement of computation speed. The resulting GPU-PIC code executes aggregate time steps in two-dimensional geometry from 80 to 140 times faster than a conventional single CPU-PIC code with the same numerical scheme modelling a standard capacitively coupled plasma (CCP) reactor.

To achieve rapid, uniform deposition of an amorphous hydrogenated silicon (a-Si:H) film, a capacitively coupled plasma (CCP) is often used at an intermediate pressure (>100 Pa), with a silane (SiH ₄ )-based mixture. At these pressures, heavy particle interactions (such as ion–ion, ion–neutral, and neutral–neutral reactions) contribute significantly to the formation of precursor radicals. By adding a consideration of the thermal diffusion effects to the neutral transport equation, the chemical processes have been numerically analyzed with variation in the number fraction of SiH ₄ and electrode spacing using a two-dimensional fluid model of radio frequency discharges in a cylindrically symmetric CCP reactor. The non-uniformity of the deposition rate profiles increases consistently as electrode spacing increases, although the non-uniformity of the plasma parameters decreases with the increase of electrode spacing. The simulated deposition rate profiles match well with the experimental data for the change of electrode spacing. Based on the validation of our model, we propose predictive designs to potentially improve the reactor and process by modifying the thermal and electrical surface conditions.

Cold atmospheric pressure plasma (CAP) and plasma-activated medium (PAM) induce cell death in diverse cancer cells and may function as powerful anti-cancer agents. The main components responsible for the selective anti-cancer effects of CAP and PAM remain elusive. CAP or PAM induces selective cell death in hepatocellular carcinoma cell lines Hep3B and Huh7 containing populations with cancer stem cell markers. Here, we investigated the major component(s) of CAP and PAM for mediating the selective anti-proliferative effect on Hep3B and Huh7 cells. The anti-proliferative effect of CAP was mediated through the medium; however, the reactive oxygen species scavenger N-acetyl cysteine did not suppress PAM-induced cell death. Neither high concentrations of nitrite or nitrite/nitrate nor a low concentration of H₂O₂ present in the PAM containing sodium pyruvate affected the viability of Hep3B and Huh7 cells. Inhibitors of singlet oxygen, superoxide anions, and nitric oxide retained the capacity of PAM to induce anti-cancer effects. The anti-cancer effect was largely blocked in the PAM prepared by placing an aluminum metal mesh, but not a dielectric PVC mesh, between the plasma source and the medium. Hence, singlet oxygen, hydrogen peroxide, nitric oxide, and nitrite/nitrate are not the main factors responsible for PAM-mediated selective death in Hep3B and Huh7 cells. Other factors, such as charged particles including various ions in CAP and PAM, may induce selective anti-cancer effects in certain cancer cells.