Session GT1: Biological and Medical Applications

Cold Atmospheric Plasma Jet Diagnostic for Tumour Growth Control and Bacteria Inactivation

Bone cancer incidence is on the rise in Canada, and treatments for these tumors rely on heavy doses of chemotherapeutic agents and invasive surgical procedures, which usually extend onto healthy tissue. The introduction of a cold plasma treatment promises to be a novel therapy to aid surgical intervention. While empirical plasma medicine shows promising results, the reaction mechanism between plasma and tissues and proper treatment dosage are still unknown at large. We therefore propose a plasma-bio interaction platform which combines a 3D-bioprinted tissue model to an automated cold plasma source as a controled way to study plasma tumor interaction in a realistic tissue model. To ensure biocompatibility, highly sensitive diagnostic techniques are necessary. With the thermo-optic effect on a fibre Bragg grating, gas temperature measurements were made. This technique, coupled to the plasma jet, brings a novel approach for temperature characterization. It accurately shows its capability to attain a maximum temperature of 40 °C while interacting with a dielectric surface. Similarly, spatially and time resolved colorimetric assays for nitrite and hydrogen peroxide detection have confirmed that these long-lived species can be tailored through the electric pulse duration, the distance and the duration of treatment. These results, combined with promising 2D in vitro treatment of MDA-MB-231 breast cancer cell line, show great potential toward tailoring of the plasma for personalized medicine.   

Electrical Monitoring during Non-Thermal Plasma Treatment of Cell Suspensions

The current understanding of the effects of nonthermal plasma (NTP) on living cells extends beyond plasma induced chemistry to include physical effects such as electric and electromagnetic fields. In addition, there is a growing recognition of the feedback effects of the treated cell suspensions on the properties of the applied NTP. The concept of adaptive plasma that changes as it both alters the substrate and adjusts in response to the properties of the treated material, has been suggested as a way to control plasma applications. In this study we explore the changes in the properties of the applied NTP depending on the type and the viability of cells during an in vitro treatment of cell suspensions. Cell suspensions are treated with NTP produced by a floating electrode dielectric barrier discharge and therefore become a part of the overall electrical circuit. Operando electrical measurements are used to determine the load impedance and changes thereof for various cell suspensions. We compare the changes in the impedance of cell media, live Viro cells, and cells of reduced viability, since these changes affect the properties of the NTP during treatment. This study confirms that the control of the power input conditions and treatment time are insufficient for the control of NTP dose in biomedical applications.   

The temporal electric field strength in skin during a plasma jet treatment: a new door for electroporation

Electroporation has been widely used for cancer treatment, drug delivery, and so on. When a plasma is applied topically on a human being, it might also induce electroporation effect on the skin. However, such electric field strength in the skin induced by plasma has never been measured. In this paper, a helium plasma jet driven by a pulsed direct current (DC) power supply is in contact with a skin which is placed on a Bi₄Ge₃O₁₂ (BGO) crystal. The time-resolved electric field strength in the skin including in the stratum corneum (SC) and in the viable epidermis and dermis layer is measured by Pockels effect. It is found that the maximum electric field strength in the SC reaches 43 kV/cm while the electric field in the viable epidermis and dermis layer reaches about 1.8 kV/cm. Such electric field strength is within the typical required strength of electroporation but it does not induce any painful sensation, which is the unavoidable side effect of the traditional electroporation. Thus, this “plasmaporation” might open a new door for electroporation.   

The role of short- and long-lived reactive species on the anti-cancer action of plasma-treated liquids: in vitro and in vivo applications

In this study, we investigated two modes of plasma cancer treatment (direct vs indirect) and unveiled the role of different reactive oxygen and nitrogen species (RONS) on the selective nature and anti-cancer action of plasma-treated PBS (pPBS). In vitro, we used 2 models of cancer cells and 3 normal cell lines [1]. We observed a selective anti-cancer action of the indirect plasma treatment and an anti-selective action of the direct plasma treatment. We demonstrated that the hypersensitivity of normal cells to direct plasma treatment cannot be explained only by the action of long-lived RONS, but it also requires the participation of short/intermediate-lived RONS [1]. Considering the selective nature of the indirect plasma treatment, we decided to use pPBS as an anti-cancer drug both in vitro and in vivo in combination with electrochemotherapy (ECT). We showed in vitro that the combined treatment opens the possibility to reduce the amplitude of the microsecond-pulsed electric fields (µsPEFs), allowing an ECT treatment with reduced side-effects. Finally, we observed in vivo on mice that the combination of pPBS and µsPEFs delays the tumour growth and increases the probability of survival compared to µsPEFs or ECT treatments alone.   

Biomedical applications of plasma-activated solutions

We have previously developed plasma-activated medium (PAM) and plasma-activated Ringer’s lactate solution (PAL). We have identified some components including 2,3-dimetyl tartrate, glyoxylate, pyruvate, formate, and acetate in PAL using NMR and mass spectrometry analysis. We further found that 2,3-dimetyl tartrate exhibited selective killing effect on cancer cells against normal cells, glyoxylate exhibited cytotoxicity on both cancer and normal cells, while pyruvate, formate, and acetate did not exhibit cytotoxicity. Microarray analysis of PAM-treated glioblastoma cells revealed that PAM induced oxidative stress-dependent cell death through the GADD45 signal transduction pathway. Meanwhile, PAL did not activate GADD45 signal transduction pathway on the glioblastoma cells, which suggest that PAL induced cell death through different intracellular molecular mechanisms. We further performed microarray analysis of PAL-treated glioblastoma cells, and we found that PAL upregulated histone cluster genes. In this meeting, we will report our progress in elucidating intracellular molecular mechanisms of selective killing of cancer cells by plasma-activated solutions.