Mimicking of Human Body Electrical Characteristic for Easier Translation of Plasma Biomedical Studies to Clinical Applications

Abstract

Non-thermal plasma (NTP) medical applications are now well established but the translation from in vitro plasma effects to in vivo effects remains far from being intuitive. Among various possible reasons, the translation may be disturbed by a loose control over the electrical characteristics of the different targets (e.g. cell culture dish, animal models) met during the development process, a parameter generally neglected and often unmentioned in papers. The aim of this study is to raise consciousness on how target electrical parameters (e.g. conductivity, electric potential…) play a major role in determining plasma treatment conditions. This effect is of particular relevance in plasma medicine where we move from treating small in vitro samples to humans, passing by animal models. The plasma conditions on targets with different electrical characteristics are compared by means of electrical measurements, optical emission spectroscopy and basic liquid analysis. Commonly tested in vitro targets induce the generation of a plasma significantly different from that produced in contact with a human body. We demonstrate how by means of a basic and easy to implement electrical circuit it is possible to "compensate" the electrical differences between in vitro models, mice and human body and in such a way to reach more reproducible treatment conditions between in vitro and in vivo targets. The proposed method for the control of the target electrical parameters could greatly favor the transition from in vitro and in vivo models to patients for many plasma devices developed for biomedical applications.

Cell Electropermeabilisation Enhancement by Non-Thermal-Plasma-Treated PBS

“…The range of intensities of the µsPEF that was used in our study has already been demonstrated as non-cytotoxic [33,34]. The work reported in the results section was performed with a setup optimised, as described in the results section and in [31] (NTP setup 2), after establishing the proof of concept (Appendix A) with a new NTP multi-jet setup that was recently developed by our group to homogeneously treat large surfaces (NTP setup 1). The NTP setup 2 produced pPBS with reproducible characteristics due to well-controlled exposure of the PBS + / + and allowed for us to examine possible differences in the pPBS effects on the two different cell lines used in this study.…”

“…The NTP multi-jet used in this study is based on a Plasma Gun (PG) device, which was described previously [31]. Briefly, the PG is a coaxial dielectric barrier discharge (DBD) reactor that consists of a quartz capillary tube flushed with helium and a microsecond-pulses high voltage (µs-pulses HV) generator powers it.…”

“…It used a stainless steel plate as ground electrode with no compensation circuit and a three-dimensional (3D) printed spacer to fix the gap distance between the plasma output orifices and the surface of the PBS. Based on our concomitant recent work [31], the NTP multi-jet source was optimised (NTP setup 2). It consists of (i) a new and more stable reactor, (ii) a ring shaped wire electrode (stainless-steel wire Ø = 1mm) placed in the bottom of the well (instead of the plane electrode used in the setup 1), which allows for avoiding liquid leakage from the well and reducing the number of discharges that formed between the plasma jets and the grounded electrode, and (iii) a compensation circuit designed to impose the total target impedance to a reference model mimicking the human body impedance [31], which would ease the translation of the results to animal models or human body (Figure 9, note that to allow for better visualisation of the plasma multi-jets, the spacer is not represented in the simplified scheme of Figure 9a and not in use in Figure 9b).…”

“…For this purpose, we used a novel NTP setup that was able to create multiple plasma jets and, therefore, offer a larger and more homogeneous surface treatment. We also implemented a compensation circuit to change the electrical impedance of in vitro targets to that of a reference model for the human body based on our recent studies on the sample influence on plasma characteristics [31]. This setup was used for the plasma treatment of phosphate-buffered saline (PBS) with Ca 2+ /Mg 2+ (PBS + / + ).…”

Experimental Investigation on the Influence of Target Physical Properties on an Impinging Plasma Jet

“…Especially, electrical properties, such as conductivity and potential, play a major role [4,7]. During direct plasma treatment, the target becomes part of the transient electrical circuit, connecting the power supply, the plasma source, the plasma, the target and the return to ground [8,9]. This means that the target's electrical parameters (conductivity, potential, etc.)…”