Clinical Plasma Medicine: State and Perspectives of in Vivo Application of Cold Atmospheric Plasma

Driven by extensive basic research on plasma effects on living cells and microorganisms, plasma medicine has been developed as innovative medical research field during the last years. Besides partially established applications of plasma to treat materials or devices to allow effective medical applications with respect to biocompatibility or microbiological safety, respectively, the primary focus of plasma‐medical research is the direct application of plasma as part of therapeutic concepts. Even if a huge number of atmospheric pressure plasma sources for biomedical applications are described in the literature and characterized by in vitro microbiology and cell biology, there is only a limited number of in vivo experience with animals or human beings up to now. Research in plasma medicine has been mainly focused on applications in dermatology and aesthetic surgery with the aim to support tissue regeneration to improve healing of infected and/or chronic wounds as well as to treat infective and inflamed skin diseases. In general, there are four cold atmospheric plasma sources which were tested comprehensively in animals as well as human beings with respect both to its therapeutic potential and the safety of its application. Three clinical trials with cold atmospheric pressure plasma sources have been carried out yet. All three studies realized in Germany are focused on ulcer treatment. Two cold atmospheric pressure plasma sources got a CE marking as medical device in 2013. This marks a very important step to bring plasma medicine into the clinical daily routine! In future, it will become a general practical requirement to adapt special plasma sources to specific medical applications. Consequently, it is one of the main requirements for the physical and technical field of research and development in plasma medicine to find solutions for modular and flexible plasma devices which are adaptive to some extent e.g. to variable target areas. Based on this as well as together with comprehensive basic research to get much more insight into detailed mechanisms of plasma‐induced effects on living structures and the particular role of single plasma components, further fields of plasma application in vivo will be opened or extended, respectively, with both new targets like cancer treatment or new application sites like teeth, lung, eyes, nasal cavity or gastrointestinal tract. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Impact of Electrode Design,Supply Voltage and Interelectrode Distance on Safety Aspects and Characteristics of a Medical DBD Plasma Source

In the frame of plasma source development for dermatological applications in the field of plasma medicine, operational safety of the devices is of superior priority. For sources based on the concept of dielectric barrier discharges (DBD), electric potentials with amplitudes in the range of some kV are arranged in close proximity to the skin of patients, wherein dielectric strength of the electrodes and leakage currents are crucial for electrical applicability. In this work, ceramic electrodes of 10 mm in diameter and varying ceramic thickness are operated at input powers up to 300 mW against non‐biological counter electrodes. In a combined experimental and numerical approach, electric fields inside the ceramic are determined, whereas values are well below the dielectric strength of the material. The spectrally weighted plasma emission is within limit values of exposure to human skin as long as daily treatment does not exceeded 7 h. Neutral gas temperatures of up to 310 K are determined which underline the minor thermal impact of the plasma exposure. In contrast, values for reduced electric fields are of the order of some hundred Townsend and thus the electrons can initiate various secondary effects such as chemical reaction chains. Consequently, ozone concentrations in the discharges are quantified between 230 ppm and 1140 ppm in close proximity to the actual discharge volume and the results are discussed in the frame of risk assessment for therapeutic applications in dermatology. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Plasmas for medicine

Plasma medicine is an innovative and emerging field combining plasma physics, life science and clinical medicine. In a more general perspective, medical application of physical plasma can be subdivided into two principal approaches. (i) “Indirect” use of plasma-based or plasma-supplemented techniques to treat surfaces, materials or devices to realize specific qualities for subsequent special medical applications, and (ii) application of physical plasma on or in the human (or animal) body to realize therapeutic effects based on direct interaction of plasma with living tissue. The field of plasma applications for the treatment of medical materials or devices is intensively researched and partially well established for several years. However, plasma medicine in the sense of its actual definition as a new field of research focuses on the use of plasma technology in the treatment of living cells, tissues, and organs. Therefore, the aim of the new research field of plasma medicine is the exploitation of a much more differentiated interaction of specific plasma components with specific structural as well as functional elements or functionalities of living cells. This interaction can possibly lead either to stimulation or inhibition of cellular function and be finally used for therapeutic purposes. During recent years a broad spectrum of different plasma sources with various names dedicated for biomedical applications has been reported. So far, research activities were mainly focused on barrier discharges and plasma jets working at atmospheric pressure.     

Microwave Plasmas at Atmospheric Pressure

Microwave plasmas at atmospheric pressure are used for surface treatments like for example cleaning, sterilization or decontamination purposes, for a pre‐treatment to increase the adhesion of lacquer, paint, or glue, and for the deposition of different kind of layers and coatings. Micro plasma jets can also be applied for biomedical applications and for treatment of small and complex geometries like for example the inside of capillaries. Larger plasma torches which exhibit higher gas temperatures can also be used for chemical syntheses like waste gas decomposition, methane pyrolysis, or carbon dioxide dissociation and for plasma spraying purposes. In the present publication an overview on the development and the investigation of the operating principle of two atmospheric pressure microwave plasma torches at frequencies of 2.45 GHz and 915 MHz will be presented. The plasma sources are based on a cylindrical resonator combined with coaxial structures. To explain how these plasma sources work, simulations of the electric field distribution will be discussed. Furthermore, some physical characteristics of an air and an Ar/H2 atmospheric plasma like gas temperatures, excitation temperatures and densities as well as the heating of the plasma by the microwave will be investigated. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Laser Ablation Inductively Coupled Plasma Mass Spectrometry: Principles and Applications

Abstract

The application of laser ablation inductively plasma mass spectrometry (LA‐ICP‐MS) to the determination of major, minor, and trace elements as well as isotope‐ratio measurements offers superior technology for direct solid sampling in analytical chemistry. The advantages of LA‐ICP‐MS include direct analysis of solids; no chemical dissolution is necessary, reduced risk of contamination, analysis of small sample mass, and determination of spatial distributions of elemental compositions. This review aims to summarize recent research to apply LA‐ICP‐MS, primarily in the field of environmental chemistry. Experimental systems, fractionation, calibration procedures, figures of merit, and new applications are discussed. Selected applications highlighting LA‐ICP‐MS are presented.     

我国等离子体工艺研究进展

扼要综述了我国等离子体材料工艺研究的新近进展。内容包括：热等离子体源,等离子冶金、化工,超细粉合成,喷涂;低气压非平衡等离子体源,镀膜,表面改性,等离子浸没离子注入,电晕放电,介质阻挡放电,滑动弧等及其应用,当前,各类薄膜制备和表面改性的研究工作更为活跃。     

Recent Advances in Microwave Induced Plasma Atomic Emission Spectrometry with Okamoto‐Cavity

Abstract

Microwave induced plasmas with an Okamoto‐cavity (Okamoto‐cavity MIP) are noted as a new excitation source in atomic emission spectrometry. The Okamoto‐cavity MIP can be sustained with various plasma gases, and can produce each stable plasma with a high robustness against loading of various types of samples. For example, the oxygen‐containing MIP becomes an effective atomization and excitation source for direct injection of organic solvents analysis because they are completely burned in the plasma. In this review, the fundamental structure of the microwave cavity, the spectrochemical characteristics, and the analytical applications are summarized from reference papers.     

Dispersion properties of electron acoustic waves in degenerate and non‐degenerate quantum plasmas

The longitudinal response functions are used to generalize the dispersion properties of electron acoustic waves (EAWs) in the presence of quantum recoil, for isotropic, non‐relativistic, degenerate/non‐degenerate plasmas. In order to study the EAWs, the constituents of non‐degenerate (thermal) plasma are considered to be of two groups of electrons having different number density and temperature, namely the cold electrons and the hot electrons. Similarly in degenerate (Fermi) plasma the two population of electrons are considered to be the thinly populated and the thickly populated electrons. The sparsely populated electrons are termed as cold electrons while the densely populated ones are termed as hot electrons. The ions are stationary which form the neutralizing background. The absorption coefficients for Landau damping with the inclusion of the quantum recoil in both plasmas are calculated and discussed. The results are discussed in the context of laser‐produced plasma.     

Laser-driven electron beam and radiation sources for basic,medical and industrial sciences

To date active research on laser-driven plasma-based accelerators have achieved great progress on production of high-energy, high-quality electron and photon beams in a compact scale. Such laser plasma accelerators have been envisaged bringing a wide range of applications in basic, medical and industrial sciences. Here inheriting the groundbreaker’s review article on “Laser Acceleration and its future” [Toshiki Tajima, (2010)],¹⁾ we would like to review recent progress of producing such electron beams due to relativistic laser-plasma interactions followed by laser wakefield acceleration and lead to the scaling formulas that are useful to design laser plasma accelerators with controllability of beam energy and charge. Lastly specific examples of such laser-driven electron/photon beam sources are illustrated.     

Development of an atmospheric nonthermal multineedle dielectric barrier discharge jet for large area treatment of skin diseases

Nonthermal plasma is suitable for applications in the biomedical field because of the large amounts of active species and a low gas temperature that does not injure the human body. A plasma jet of the typical pen type is applied in most biomedical applications, but it is difficult to apply such jets to treat skin diseases that generally have wide affected areas. In this study, nonthermal multineedle dielectric barrier discharge (DBD) jet was developed for the treatment of large area lesions and used to verify its effectiveness in treating psoriasis as a representative skin disease. Stable discharge was maintained using the developed plasma jet with a multineedle electrode structure by utilizing various discharge gases. Electrical and optical analyses were performed to determine the characteristics of the plasma. The effectiveness of psoriasis treatment using this approach was confirmed by performing in vitro and in vivo experiments with the multineedle DBD jet.     

Effect of nonthermal atmospheric pressure plasma on plasma coagulation in healthy persons and patients under treatment with Warfarin

Recently, nonthermal atmospheric pressure plasma has been used in medical devices for sterilization, blood coagulation, induction of apoptosis in cancer cells, etc. The purpose of this study is to evaluate the impact of cold atmospheric plasma on coagulation time in patients under treatment with warfarin as an anticoagulant agent (group A) and to compare this impact in healthy persons (group B). To measure the coagulation time, Clotting Time (CT) is used. After obtaining informed consent from each subject, two venous blood samples are taken to check CT. One sample is processed with plasma (case sample) and the other sample is not processed with plasma. CT in both samples is measured by a physician and recorded in a form in addition to demographic characteristics and drug history. The data are analysed using Statistical Package for the Social Sciences (SPSS) software. The Mann–Whitney test is used for comparison between groups and the Wilcoxon signed‐ranks test is used to compare the difference between CT before and after plasma processing. The results show the significant effect of plasma on the reduction of plasma coagulation time, and this reduction is higher in the warfarin‐treated group.     

脉冲射频容性耦合氩等离子体的发射探针诊断

利用工作在浮点模式下的发射探针,对500 Hz脉冲调制的27.12 MHz容性耦合氩气等离子体的空间电位和电子温度的时变特性进行了诊断.等离子体空间电位是通过测量强热状态下的发射探针电位获得的,而电子温度则是由发射探针在冷、热状态下的电位差来估算得到.测量结果表明:脉冲开启时,空间电位会快速上升并在300μs内趋于饱和;当脉冲关断后,空间电位经历了快速下降后趋于稳定的过程.电子温度在脉冲开启时存在过冲并趋于稳定的特征;而在脉冲关断期间,电子温度在300μs内则快速下降到0.45 e V后略有上升.无论在脉冲开启或关断期间,空间电位基本上都随功率和气压的变化存在有线性的依赖关系;而放电功率对脉冲开启期间过冲电子温度与稳态电子温度差异的影响较大.针对空间电位和电子温度在各阶段及不同放电条件下的时变特性,给出了相应的解释.     

冷等离子体强化制备金属催化剂研究进展

冷等离子体属于非热平衡等离子体,具有较高的电子能量和较低的气体温度,是一种制备金属催化剂的绿色新方法.等离子体强化制备金属催化剂包含复杂的物理和化学多相反应.一方面,等离子体提供的高活性环境不但可以加速化学反应,使反应时间从数小时缩短至数分钟,还可以使热力学或者动力学上不可行的反应发生,实现非常规制备;另一方面,等离子体强化制备过程中,在介观尺度上等离子体对相接触行为的影响,可使获得的金属催化剂结构区别于传统方法制备的催化剂.本综述总结了冷等离子体制备金属催化剂的反应器结构、物理化学机理、获得金属催化剂的结构特性、制备面临的挑战,并对未来发展进行了展望.重点阐述了冷等离子体反应器、制备机制及其对金属催化剂结构和性能的影响.     

两种温度电子对稳态等离子体鞘层的影响

建立包含冷热电子的无碰撞等离子体鞘层的流体模型,利用数值模拟研究含有两种温度电子时等离子体鞘层的产生.结果表明:对于含有两种不同温度电子的稳态等离子体,冷电子的温度越低或者冷电子的含量越多,鞘边离子的马赫数临界值就越小,鞘层的宽度就变得越窄,沉积器壁的离子动能流也就越少.此外,研究不同种类的等离子体(Ar、Ke、Xe),鞘层厚度和离子沉积器壁动能流受冷电子的影响.     

The Development and Application of Low Temperature Plasma Technology

The development and applications of low temperature plasma technology used in surface modification of materials are presented in this paper. Based on plasma sources and ion sources technology, multi-functions ion implantation and deposition technologies were developed and the related processes are also used to treat different products. The related technologies were translated into industrial productions supported by national research projects. Following the last development of international plasma researches, the standardization and internationalization processes of plasma technologies are executed in our center.     

Effects of electron‐absorbing boundaries on the plasma parameters of a hot‐filament discharge

In this paper we investigate theoretically and experimentally the plasma parameters in a double‐plasma device in the presence of an additional electron‐absorbing boundary. The latter is formed by an electrode of variable size immersed in the plasma. It is found that, depending on its size and bias potential, such an anode can considerably influence the plasma parameters. Good qualitative and fair quantitative agreement between theoretical predictions and laboratory measurements of the plasma parameters is found for various discharge conditions. In addition we discuss the consequences of our results with respect to the existence conditions of anode‐type double layers in double‐plasma devices.     

Characterisation of a Simple Non‐Thermal Atmospheric Pressure Plasma Source for Biomedical Research Applications

The recent progress in plasma medicine as well as biomedical aspects of plasma physics over the last years have enhanced the need for experimental plasma devices which are capable of producing non‐thermal atmospheric pressure plasmas. These plasma sources are used for studying the effect of non‐thermal plasmas on biological samples of different nature. In this paper we present such an easy to build low cost apparatus that can be used for scientific as well as for educational purposes. Directions for the construction of the device are given and the basic plasma parameters are investigated. The characterisation of the experiment was done by electrical diagnostics for the measurements of the plasma potential in combination with optical emission spectroscopy. The latter is used for the determination of the excitation temperature of the plasma and the electron density. Furthermore the influence of the produced plasma on yeast cells is demonstrated. The produced plasma is characterised in different ways and it was found that the feeding gas has also a considerable impact on the radio frequency wave form of the source. It is also demonstrated that the constructed plasma source is capable of producing non‐thermal plasma that hinder cell growth of yeast colonies on a agar substrate. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Self‐focusing of a cosh‐Gaussian laser beam in magnetized plasma under relativistic‐ponderomotive regime

The combined effect of relativistic and ponderomotive nonlinearities on the self‐focusing of an intense cosh‐Gaussian laser beam (CGLB) in magnetized plasma have been investigated. Higher‐order paraxial‐ray approximation has been used to set up the self‐focusing equations, where higher‐order terms in the expansion of the dielectric function and the eikonal are taken into account. The effects of various lasers and plasma parameters viz. laser intensity (a₀), decentred parameter (b), and magnetic field (ω_c) on the self‐focusing of CGLB have been explored. The results are compared with the Gaussian profile of laser beams and relativistic nonlinearity. Self‐focusing can be enhanced by optimizing and selecting the appropriate laser‐plasma parameters. It is observed that the focusing of CGLB is fast in a nonparaxial region in comparison with that of a Gaussian laser beam and in a paraxial region in magnetized plasma. In addition, strong self‐focusing of CGLB is observed at higher values of a₀, b, and ω_c. Numerical results show that CGLB can produce ultrahigh laser irradiance over distances much greater than the Rayleigh length, which can be used for various applications.     

Efficient and Rapid Synthesis of Radioactive Gold Nanoparticles by Dielectric Barrier Discharge

A compact bench‐top system based on a dielectric barrier plasma discharge (DBD), enables the rapid, automatable, and continuous‐flow synthesis of gold nanoparticles (AuNPs) and radioactive gold nanoparticles (¹⁹⁸AuNPs). AuNPs are used as radiosensitizers in oncology, and ¹⁹⁸AuNPs (half‐life: 2.7 d) have been suggested as potential cancer brachytherapy sources. Plasma applied at the surface of a liquid containing gold ions (AuCl₄^?) and dextran induces the production of AuNPs directly in water. This synthesis is monitored in real time by UV–visible spectrometry: the change of absorbance of the solution provides new insights on the growth dynamics of AuNPs by plasma synthesis. By balancing gold ions and surfactant molecules, particles with a diameter lying in the optimal range for radiosensitizing applications (28 ± 9 nm) are produced. The method yields a reduction of more than 99% of the gold ions within only 30 min of plasma treatment. A postsynthesis ripening of the AuNPs is revealed, monitored by UV–visible spectrometry, and quantified within the first few hours following plasma treatment. Radioactive ¹⁹⁸AuNPs are also produced by DBD synthesis and characterized by electron microscopy and single‐photon emission computed tomography imaging. The results confirm the efficiency of DBD reactors for AuNPs synthesis in oncology applications.