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Atmospheric pressure plasma jets applied to cancerology: correlating electrical configurations with in vivo toxicity and therapeutic efficiency

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 Added by Thierry Dufour
 Publication date 2019
  fields Physics
and research's language is English




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Two atmospheric pressure plasma jet devices - a plasma gun and a plasma Tesla jet - are compared in terms of safety and therapeutic efficiency to reduce the tumor volume progression of cholangiocarcinoma, i.e. a rare and very aggressive cancer emerging in biliary tree. For this, a three steps methodology is carried out. First, the two APPJ have been benchmarked in regard to their electrical and physico-chemical properties while interacting with material targets: dielectric plate, liquid sample, metal plate and an equivalent electrical circuit of human body. The propagation properties of the ionization wave interacting with these targets are discussed, in particular the profile of the related pulsed atmospheric plasma streams. In a second step, a dermal toxicity survey is performed so as to define an experimental operating window where plasma parameters can be changed without damaging healthy skin of mice during their exposure to plasma and without inducing any electrical hazards (burnings, ventricular fibrillation). Optimal conditions are identified discarding the conditions where slight alterations may be evidenced by histology (e.g. prenecrotic aspect of keratinocytes, alterations in the collagen structure). Hence, for the two APPJ plasma parameters these conditions are as follow: duty cycle=14 %, repetition frequency=30 kHz, magnitude=7 kV, gap=10 mm and exposure time=1 min. In a third step, the two plasma jets are utilized on cholangiocarcinoma xenograft tumor model developed in immunodeficient mice. The two devices are safe and a significant therapeutic efficiency is demonstrated with the plasma Tesla. In conclusion, we have developed a safe cold atmospheric plasma device with antitumoral properties in preclinical model of cholangiocarcinoma, opening the path for new anticancer treatment opportunities.



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Atmospheric pressure plasma jets (APPJ) are investigated as an efficient approach to induce antitumor effects of cancerous tissues without inducing any damage (e.g. dessication, burnings). For this, a two-steps methodology has been developed where first APPJ are calibrated and characterized on targets mimicking electrical properties of living organisms (mice, human body) and second where they are applied on murine models to demonstrate their innocuity and therapeutic efficiency.
The use of cold atmospheric plasmas (CAP) to sterilize sensitive surfaces is an interesting new field of applied plasma physics. Motivated by the shortages of face masks and safety clothing at the beginning of the corona pandemic, we conducted studies on the sterilization of FF3 face masks with CAP and the resulting material effects. Therefore, the bactericidal and sporicidal efficacy of CAP afterglow sterilization of FFP3 mask material was investigated by inoculating fabric samples with test germs Escherichia coli (E. coli) and Bacillus atrophaeus (B. atrophaeus) and subsequent CAP afterglow treatment in a surface-micro-discharge (SMD) plasma device. In addition, a detailed analysis of the changes in long-term plasma treated (15h) mask material and its individual components - ethylene vinyl acetate (EVA) and polypropylene (PP) - was carried out using surface analysis methods such as laser microscopy, contact angle measurements, X-ray photoelectron spectroscopy (XPS) as well as fabric permeability and resistance measurements. The experiments showed that E. coli and B. atrophaeus could both be effectively inactivated by plasma treatment in nitrogen mode (12 kVpp, 5 kHz). For B. atrophaeus inactivation of more than 4-log was achieved after 30 minutes. E. coli population could be reduced by 5-log within one minute of CAP treatment and after five minutes a complete inactivation (> 6-log) was achieved. Material analysis showed that long-term (> 5 h) plasma treatment affects the electrostatic properties of the fabric. From this it can be deduced that the plasma treatment of FFP3 face masks with the CAP afterglow of an SMD device effectively inactivates microorganisms on the fabric. FFP3 masks can be plasma decontaminated and reused multiple times but only to a limited extent, as otherwise the permeability levels no longer meet the DIN EN 149 specifications.
Compared to imaging in the visible and near-infrared regions below 900 nm, imaging in the second near-infrared window (NIR-II, 1000-1700 nm) is a promising method for deep-tissue high-resolution optical imaging in vivo mainly due to the reduced scattering of photons traversing through biological tissues. Herein, semiconducting single-walled carbon nanotubes with large diameters were used for in vivo fluorescence imaging in the long-wavelength NIR region (1500-1700 nm, NIR-IIb). With this imaging agent, 3-4 um wide capillary blood vessels at a depth of about 3 mm could be resolved. Meanwhile, the blood-flow speeds in multiple individual vessels could be mapped simultaneously. Furthermore, NIR-IIb tumor imaging of a live mouse was explored. NIR-IIb imaging can be generalized to a wide range of fluorophores emitting at up to 1700 nm for high-performance in vivo optical imaging.
Seeds have been packed in a dielectric barrier device where cold atmospheric plasma has been generated to improve their germinative properties. A special attention has been paid on understanding the resulting plasma electrical properties through an equivalent electrical model whose experimental validity has been demonstrated here. In this model, the interelectrode gap is subdivided into 4 types of elementary domains, according to whether they contain electric charges (or not) and according to their type of medium (gas, seed or insulator). The model enables to study the influence of seeds on the plasma electrical properties by measuring and deducing several parameters (charge per filament, gas capacitance, plasma power, ...) either in no-bed configuration (i.e. no seed in the reactor) or in packed-bed configuration (seeds in the reactor). In that second case, we have investigated how seeds can influence the plasma electrical parameters considering six specimens of seeds (beans, radishes, corianders, lentils, sunflowers and corns). The influence of molecular oxygen (0-100 sccm) mixed with a continuous flow rate of helium (2 slm) is also investigated, especially through filaments breakdown voltages, charge per filament and plasma power. It is demonstrated that such bed-packing drives to an increase in the gas capacitance, to a decrease in the beta-parameter and to variations of the filaments breakdown voltages in a seed-dependent manner. Finally, we show how the equivalent electrical model can be used to assess the total volume of the contact points, the capacitance of the seeds in the packed-bed configuration and we demonstrate that germinative effects can be induced by plasma on four of the six agronomical specimens.
448 - D. Merche , C. De Vos , J. Baneton 2018
Plasmas at atmospheric pressure are presented as a simple, fast, and versatile tool for the synthesis or/and the grafting of noble metallic NPs (Au, Pt) on substrates. In this study, noble metal NPs are generated either by the reduction of a gold salt in an aqueous medium by microplasma or either by the decomposition of a platinum or gold organometallic in the post-discharge of an atmospheric plasma torch. The latter can also be used for the grafting of NPs from a commercial colloidal solution
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