Delphine Ries

ROS implication in a new antitumor strategy based on non-thermal plasma

Non‐thermal plasma (NTP) is generated by ionizing neutral gas molecules/atoms leading to a highly reactive gas at ambient temperature containing excited molecules, reactive species and generating transient electric fields. Given its potential to interact with tissue or cells without a significant temperature increase, NTP appears as a promising approach for the treatment of various diseases including cancer. The aim of our study was to evaluate the interest of NTP both in vitro and in vivo. To this end, we evaluated the antitumor activity of NTP in vitro on two human cancer cell lines (glioblastoma U87MG and colorectal carcinoma HCT‐116). Our data showed that NTP generated a large amount of reactive oxygen species (ROS), leading to the formation of DNA damages. This resulted in a multiphase cell cycle arrest and a subsequent apoptosis induction. In addition, in vivo experiments on U87MG bearing mice showed that NTP induced a reduction of bioluminescence and tumor volume as compared to nontreated mice. An induction of apoptosis was also observed together with an accumulation of cells in S phase of the cell cycle suggesting an arrest of tumor proliferation. In conclusion, we demonstrated here that the potential of NTP to generate ROS renders this strategy particularly promising in the context of tumor treatment.

Effects of a Non Thermal Plasma Treatment Alone or in Combination with Gemcitabine in a MIA PaCa2-luc Orthotopic Pancreatic Carcinoma Model

Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.

Characterization of pulsed atmospheric-pressure plasma streams (PAPS) generated by a plasma gun

An experimental study of atmospheric-pressure rare gas plasma propagation in a high-aspect-ratio capillary is reported. The plasma is generated with a plasma gun device based on a dielectric barrier discharge (DBD) reactor powered by either nanosecond or microsecond rise-time high-voltage pulses at single-shot to multi-kHz frequencies. The influence of the voltage waveform, pulse polarity, pulse repetition rate and capillary material have been studied using nanosecond intensified charge-coupled device imaging and plasma-front velocity measurements. The evolution of the plasma appearance during its propagation and the study of the role of the different experimental parameters lead us to suggest a new denomination of pulsed atmospheric-pressure plasma streams to describe all the plasma features, including the previously so-called plasma bullet. The unique properties of such non-thermal plasma launching in capillaries, far from the primary DBD plasma, are associated with a fast ionization wave travelling with velocity in the 107?108?cm?s?1 range. Voltage pulse tailoring is shown to allow for a significant improvement of such plasma delivery. Thus, the plasma gun device affords unique opportunities in biomedical endoscopic applications.

Rare gas flow structuration in plasma jet experiments

Modifications of rare gas flow by plasma generated with a plasma gun (PG) are evidenced through simultaneous time-resolved ICCD imaging and schlieren visualization. The geometrical features of the capillary inside which plasma propagates before in-air expansion, the pulse repetition rate and the presence of a metallic target are playing a key role on the rare gas flow at the outlet of the capillary when the plasma is switched on. In addition to the previously reported upstream offset of the laminar to turbulent transition, we document the reverse action leading to the generation of long plumes at moderate gas flow rates together with the channeling of helium flow under various discharge conditions. For higher gas flow rates, in the l min−1 range, time-resolved diagnostics performed during the first tens of ms after the PG is turned on, evidence that the plasma plume does not start expanding in a laminar neutral gas flow. Instead, plasma ignition leads to a gradual laminar-like flow build-up inside which the plasma plume is generated. The impact of such phenomena for gas delivery on targets mimicking biological samples is emphasized, as well as their consequences on the production and diagnostics of reactive species.

LIF and fast imaging plasma jet characterization relevant for NTP biomedical applications

In the field of biomedical application, many publications report on non-thermal plasma jet potentialities for cell behaviour modifications in cancer treatment, wound healing or sterilization. However most previous plasma jet characterizations were performed when jets expend freely in air. Only recently has the influence of the targeted surface been properly considered. In this work, modifications induced by various types of targets, mimicking the biological samples, in the plasma propagation and production of hydroxyl radicals are evidenced through time-resolved intensified charge-coupled device imaging and laser-induced fluorescence (LIF) measurements. A LIF model, also specifically dedicated to estimate air and water penetration inside the jet, is used and proves to be well adapted to characterize the plasma jet under biomedical application conditions. It is shown that the plasma produced by the plasma gun counter-propagates after impinging the surface which, for the same operating parameters, leads to an increase of almost one order of magnitude in the maximum OH density (from ~2 × 1013 cm−3 for open-air propagation to ~1 × 1014 cm−3 for a grounded metal target). The nature of the target, especially its electrical conductivity, as well as gas flow rate and voltage amplitude are playing a key role in the production of hydroxyl radicals. The strong interplay between gas flow dynamics and plasma propagation is here confirmed by air and water distribution measurements. The need for a multi-diagnostic approach, as well as great care in setting up the in situ characterization of plasma jets, is here emphasized. Special attention must not only be paid to voltage amplitude and gas flow rate but also to the nature, humidity and conductivity of the target.

Splitting and Mixing of High-Velocity Ionization-Wave-Sustained Atmospheric-Pressure Plasmas Generated With a Plasma Gun

The nanosecond imaging of high-velocity ionization-wave-generated plasmas using a plasma gun is presented. A circular glass pipe is used to study the splitting, the propagation, and the mixing of atmospheric-pressure plasma streams ensuing from a single dielectric-barrier-discharge reactor.

Unexpected Plasma Plume Shapes Produced by a Microsecond Plasma Gun Discharge

The plasma plume shapes produced at the outlet of a 1 mm inner diameter plasma gun capillary are investigated over an extended range of both neon flow rates and pulse repetition rate (prr). Various complex, but stable, plume shapes are observed. It appears first that for a given flow rate, the plume shape can be modulated with prr sweeping, revealing fascinating multidart shape when discharge is triggered at a fundamental frequency and up to the sixth harmonic. Second, reproducible similar plume patterns, either multidarts or conical shaped, can be obtained for given appropriate flow rate/prr parameter couples. These phenomena tend to show the effect of the force exchange between the neutral gas flow and the discharge species resulting in plume patterning.

Analysis of NO x production in an RF kINPen and a µs driven plasma gun

Summary form only given. NOx and associated acids are investigated with regards to their role for biomedical application. NOx are produced by two different plasma sources, a RF kINPen and a μS Plasma gun, both are cold atmospheric pressure plasma jets. The first one is powered by a radio frequency voltage [1, 2] of 1 MHz, the second one is a dielectric barrier discharge powered by a μs pulse voltage [3, 4]. For these two sources, NOx are produced by many complex chemicals reactions occurring in the interaction of the active plume with surrounding air. With the mid infrared quantum cascade laser absorption spectroscopy [1], we are able to measure the absolute density of NO2 and O3 produced by both plasma sources. Correlating the measurements in situ with optical emission spectroscopy, great differences in the excitation processes of fundamental species such as O, N2, OH, N2 and N2+ can be observed. With a parametrical study, varying the voltage and the pulse repetition frequency, we are able to modulate the NO2 densities production from a few tens to a few hundreds of ppb. Such parametric analysis also shows that large variations in the population of the different molecular bands of the NO gamma system, are associated with the plasma gun operation regime. These physical parameters play a major role in the NOx production and yield vital clues to discriminate major kinetic reactions involved in the NO production and in relation with future numerical simulations.

Pulsed atmospheric pressure plasma streams: Characterization and role of critical experimental parameters

Summary form only given. This work reports on the investigation of neon and helium atmospheric pressure plasma generation and propagation in high aspect ratio capillaries, either in straight or branched assemblies. ICCD imaging on ns and sub-ns time scales, together with measurement of the speed of the plasma ionization front reveal the specific features of such plasmas. The plasmas are ignited with DBD electrodes and launched into a tube flushed with a moderate flow (a few sccm) of rare gas and powered with high voltage pulses delivered in single shot or repetitive mode up to a few kHz. The plasma expands in a wall hugging mode in the vicinity of the DBD electrodes gradually switching to a much more homogenous plasma volume during its propagation before inducing a plasma plume in ambient air at the outlet of the capillary. This plasma pattern is associated with two ionization front velocity regimes during which the plasma experiences an order of magnitude deceleration from a few 108 cm/s to a few 107 cm/s in the wall hugging mode and then gradually slows over distances of up to a few tens of cm in the homogenous mode. The influence of pulse repetition rate, dielectric wall permittivity, voltage rising front (either µs or ns) and voltage polarity, will be discussed, while accounting for the roles of the impedance of plasma tail behind the ionization front region and the wall charging processes. For our conditions, photoionization appears to be of minor importance.

Antitumoral effects of combined non thermal plasma and gemcitabine treatments on a MIA PaCa-luc orthotopic pancreatic carcinoma model

Summary form only given. Cancer of the exocrine pancreas, especially ductal adenocarcinoma, the most common pancreatic cancer1, is rarely curable and has an overall survival rate of less than 4%. Moreover, chemotherapy and radiotherapy of pancreatic cancer are only, up to now, palliative treatments. New therapeutic approaches are then necessary. Recent results were obtained on the treatment of glioblastoma and colon carcinoma2,3 using non thermal plasma (NTP). They led us to assess the antitumoral effect of NTP alone or in combination with Gemcitabine, a, reference chemotherapeutic agent with radiosensitizing properties, on pancreatic cancer.