The potential of cold plasma as a food processing aid has been demonstrated for a range of processes and products. The potential applications of plasma technology are extensive and include: microbial decontamination, pest control, toxin elimination, food and package functionalisation and many others. However, studies reported to date have principally been at laboratory scale. This paper discusses the status and challenges of transferring the technology to the industry. The major challenges discussed for adoption of atmospheric plasma as a food processing tool by industry are: 1) demonstration of product/process specific efficacies; 2) development of process compatible technology designs and scale-up; 3) effective process control and validation; 4) regulatory approval and 5) consumer acceptance.

cold atmospheric plasma (cAp) enhances uptake and accumulation of nanoparticles and promotes synergistic cytotoxicity against cancer cells. However, the mechanisms are not well understood. In this study, we investigate the enhanced uptake of theranostic nanomaterials by CAP. Numerical modelling of the uptake of gold nanoparticle into U373MG Glioblastoma multiforme (GBM) cells predicts that CAP may introduce a new uptake route. We demonstrate that cell membrane repair pathways play the main role in this stimulated new uptake route, following non-toxic doses of dielectric barrier discharge CAP. CAP treatment induces cellular membrane damage, mainly via lipid peroxidation as a result of reactive oxygen species (ROS) generation. Membranes rich in peroxidised lipids are then trafficked into cells via membrane repairing endocytosis. We confirm that the enhanced uptake of nanomaterials is clathrindependent using chemical inhibitors and silencing of gene expression. Therefore, CAP-stimulated membrane repair increases endocytosis and accelerates the uptake of gold nanoparticles into U373MG cells after CAP treatment. We demonstrate the utility of CAP to model membrane oxidative damage in cells and characterise a previously unreported mechanism of membrane repair to trigger nanomaterial uptake. This knowledge will underpin the development of new delivery strategies for theranostic nanoparticles into cancer cells. Cold atmospheric plasma (CAP) is increasingly studied in a growing number of clinical trials for cancer treatment 1,2 and research is ongoing to explore the combination of CAP with other therapies, including nanoparticles, radiotherapy and chemotherapy 3-5. Gold nanoparticles (AuNPs) are known to be weakly-toxic to human cells and be readily manufactured and designed for targeting delivery of various therapeutic compounds into cells. Citrate-capped cationic AuNPs may adsorb serum proteins onto their surface and thereby stimulate receptor-mediated endocytosis 6. Without special surface functionalisation, AuNPs enter cells and become trapped in vesicles 6-8 or enter the nucleus, depending on their size/shape 9,10. Meanwhile, AuNPs with functionalised surface chemistries/ligands can directly penetrate the membrane and enter the cytoplasm 11 .

A large gap pin‐to‐plate, atmospheric‐pressure plasma reactor is demonstrated as means of in vitro study of plasma species interactions with cell cultures. By employing optical emission and optical absorption spectroscopy, we report that the pin‐to‐pate plasma array had an optimal discharge frequency for cell death of 1000 Hz in ambient air for the target cancer cell line, human glioblastoma multiform (U‐251MG). The detected plasma chemistry contained reactive oxygen and nitrogen species including OH, N2, N2+ and O3. We show that by varying the plasma discharge frequency, the plasma chemistry can be tailored to contain up to 8.85 times higher levels of reactive oxygen species (ROS) as well as a factor increase of up to 2.86 for levels of reactive nitrogen species (RNS). At higher frequencies, ROS are more dominant than RNS, which allows for a more dynamic and controlled environment for sample study without modifying the inducer gas conditions. When used for treatment of culture media and cell cultures, variation of the plasma discharge frequency over the range 1000–2500 Hz demonstrated a clear dependence of the responses, with the highest cytotoxic responses observed for 1000 Hz. We propose that the reactor offers a means of studying plasma–cell interactions and possible cofactors such as pro‐drugs and nanoparticles for a large volume of samples and conditions due to the use of well plates.

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