Plasma Biomedicine Research Articles

Microscopic mechanistic study of the penetration distributions for plasma reactive oxygen and nitrogen species based on sialic acid targeting on the cell membrane surface

The ability of cold atmospheric plasmas (CAPs) to produce a wide range of active constituents while maintaining a low or even room temperature of the gas has made it a novel research area of great interest. During plasma action, cancer cell membrane surface components are susceptible to oxidative modification by reactive oxygen and nitrogen species (RONS). In this study, the process of oxidative modification of membrane surface components sialic acid by RONS was investigated based on molecular dynamics simulations, and the penetration mechanism of long-lived particles ONOOH and its homolytic products at the membrane-water interface and the effect of appropriate electric field action were studied. The results showed that cancer cells with high sialic acid expression were less stable than healthy cells. Plasma treatment may promote the ONOOH homolysis process, and its homolysis product OH free radical is more likely to adsorb near sialic acid molecules by hydrogen bonding, resulting in oxidative modification. The interaction force between OH free radical and sialic acid molecules is stronger than ONOOH, which helps to further understand the oxidative modification reaction in membrane environment. At the same time, appropriate electric field stimulation can enhance the depth of penetration of RONS to more effectively treat the pathological state of biological tissues. The study proposes the use of membrane surface sialic acid as a cancer therapeutic target and provides guidance for improving the depth of RONS penetration and maximizing the survival of healthy cells, which contributes to the further clinical translation of plasma biomedicine.

Determining the Effect of Non-Thermal Plasma on the Transmembrane Kinetics of Melittin through Molecular Explorations.

Non-thermal plasma (NTP) synergistic anticancer strategies are a current hotspot of interest at the intersection of plasma biomedicine. Melittin (MEL) has been shown to inhibit cancer in many malignant tumors; however, its clinical application is controversial. Therefore, the transmembrane process and mechanism of MEL activity in different cell systems were studied and the combination of MEL and NTP was proposed in this paper. The results showed that the electrostatic attraction between MEL and the lipid bilayer contributes to the stable orientation of MEL on the membrane surface. In addition, sialic acid overexpression affects the degree to which MEL binds the membrane system and the stability of the membrane structure. The use of NTP to reduce the dosage of MEL and its related nonspecific cytolysis activity has certain clinical application value. The results of this study provide theoretical support for improving the clinical applicability of MEL and contribute to the further development of plasma biomedicine.

Flexible thin-layer plasma sterilizer based on polyimide and efficacy evaluation under bending deformation

Cold atmospheric pressure plasma is receiving attention in biomedical treatment for its non-thermal, dry-type, and high-efficiency disinfection effects on bacteria, fungi, and viruses, compared to typical sterilization methods, such as pasteurization, chemical solutions, and ultraviolet radiation. There are great demands of plasma decontamination on the surface of complex 3D objects, with the request of large coverage, convenience, and uniformity, which still remains a challenge for the current plasma devices. In this work, a flexible thin-layer plasma source for sterilization is developed based on a polyimide substrate, and its plasma generation process is characterized by experiment and simulation. The influences of bending deformation are studied and evaluated by electrical waveforms, heat radiation, and ozone production, of which the mechanisms are further explained. Results illustrate that the variation in electron impact ionization induced by different curvatures is the main cause leading to the change in microparticle production, thus affecting the macroscopic properties of plasmas. Activations of the plasma sterilizer for 30 and 120 s reduce both S. aureus and P. aeruginosa on the flat surface by around 2.5 and 5 log colony forming units (CFU). However, the plasma sterilization effect decreases with an extent of about 1 log CFU when treating the curved surface, while being regained after conforming the plasma sterilizer to the curved surface. This kind of plasma generator offers significant flexibility and efficacy, being promising for the treatment of objects with irregular surfaces in future plasma biomedicine and material processing.

Molecular dynamics simulation research on the interaction between plasma and living organisms: A comprehensive review

AbstractIn recent years, plasma biomedicine has developed into a new interdisciplinary subject. The interaction between plasma and organisms involves three aspects: “gas–liquid–living organisms.” Molecular dynamics (MD) simulation can simulate the interaction process between plasma and biological tissue with high temporal and spatial resolution. This article reviews the research on plasma biomedicine based on MD simulation and systematically summarizes the progress of MD simulation research on the interaction between plasma and water layer, cell membrane, intracellular substances, extracellular environment, and viruses. These simulations offer a unique opportunity to gain insights into the microscopic mechanisms of these interactions. This article also further looks forward to the opportunities and challenges of MD simulation research.

Combination of ICCD fast imaging and image processing techniques to probe species–specific propagation due to guided ionization waves

The present report is devoted to the study of distinct ionization waves in terms of temporally-, spatially-, and wavelength-resolved analyses. The study is based on the technique of two-dimension fast imaging. However, appropriately selected ultraviolet to near infrared optical filters are employed to capture the propagation of specific species and digital image processing techniques are applied to explore the recorded snapshots. N2(SPS), (FNS), He I, OH(A–X), and O I, i.e., emissive neutral and ionic species, are investigated. On the other hand, the propagation of the NO γ species is studied by means of laser-induced fluorescence spectroscopy, since the light intensity due to spontaneous emission of this species was not readily detectable. Digital image processing techniques are also applied for the NO γ case. The crucial role of the above species in fields like plasma biomedicine and material processing is extensively recognized, and the present work: (i) provides gathered information on the propagation of these species within the atmospheric air; and (ii) introduces image processing algorithms to extract information which otherwise would remain hidden or uncorrelated with other plasma parameters. The present results unveil specific emission patterns due to the propagation of the N2(SPS), (FNS), He I, OH(A–X), and O I species. The intensity patterns consist of a first peak located in the vicinity of the reactor orifice, a second peak moving away from the reactor orifice, and a continuum which couples the two peaks. However, the detailed features of each pattern depend on the type of species considered. The fluorescence of the NO γ species also suggests the division of the area downstream of the reactor orifice into two regions where distinct ionization-excitation effects take place. Propagation speeds of the species up to about 2 × 105 m s−1 were measured. Finally, qualitative correlation between the species propagation (as it is pronounced by the emission patterns) and the local electric field (as it was numerically calculated in a similar setup) is demonstrated.

Plasma‐enhanced evaporation and its impact on plasma properties and gaseous chemistry in a pin‐to‐water pulsed discharge

AbstractThe plasma in contact with liquids has led to various novel applications such as plasma biomedicine, material synthesis, and so on. However, the phenomenon of evaporation under plasma treatment and its impact on plasma–liquid interactions has a limited understanding. In this study, the spatially and temporally resolved behavior of water vapor production and its induced influences on plasma properties and gaseous chemistry were studied in detail in an atmospheric pressure pin‐to‐water pulsed He discharge. Diagnostic methods such as laser‐induced fluorescence (LIF) and high‐resolution optical emission spectroscopy (OES) were applied to determine the water vapor and OH radical densities, as well as key plasma parameters such as the gas temperature and electron density. It shows that the physicochemical properties of plasma vary among different discharge regions due to evaporation behavior stimulated during the pulsed discharge‐on phase. In addition, using simulation based on the experimental data, the mechanisms of how water vapor affects the observed spatiotemporal behaviors of OH radicals in different discharge regions are understood. Compared to the pin‐anode and liquid‐cathode sheath regions, proper electron parameters such as density and temperature, as well as water vapor density in the plasma‐positive column, significantly enhance the production of reactive OH radical through the dominant path of electron‐stimulated H2O dissociation. However, higher levels of electron parameters in the intense discharge region near the positive‐pin boundary enhance OH dissociation and finally result in the hollow distribution of OH density. From the global kinetic plasma simulation, the production of reactive hydroxide species playing key roles in plasma medicine treatments, such as O, H, HO2, H2O2, and hydrated ions including H+(H2O)4 and H+(H2O)5, are promoted noticeably as a result of the enhanced water evaporation process.

N2O5 in air discharge plasma: energy-efficient production, maintenance factors and sterilization effects

N2O5, a reactive species produced by air discharge plasma, has recently attracted much attention. Due to its high reactivity and solubility, N2O5 is a key molecule in nitrogen fixation processes and exhibits promising prospects in plasma biomedicine. However, thus far, it is not well known how to produce N2O5 efficiently and then maintain its concentration under the action of fast removal reactions. In view of this, N2O5 production by dielectric barrier discharge (DBD) alone and by the combination of DBD and gliding arc discharge is compared in this paper. It is found that the combination method can yield over three times the concentration of N2O5 compared to the single DBD method with the optimum discharge power. Moreover, the concentration of N2O5 in the effluent gas can be maintained once O3 also exists because O3 can continually produce N2O5 to compensate for its reduction. Finally, the sterilization effects of both the plasma effluent gas and plasma-activated water have trends similar to the trend of the gaseous N2O5 concentration, implying that N2O5 plays an important role in sterilization. This paper enhances the understanding of N2O5 chemistry in air discharge plasma and provides an effective way to produce and maintain N2O5 for subsequent applications.

A boundary value problem of heat transfer within DBD-based plasma jet setups.

We claim an analytical solution for the thermal boundary value problem that arises in DBD-based plasma jet systems as a preliminary and consistent approach to a simplified geometry. This approach involves the outline of a coaxial plasma jet reactor and the consideration of the heat transfer to the reactor solids, namely, the dielectric barrier and the grounded electrode. The non-homogeneous initial and boundary value thermal problem is solved analytically, while a simple cut-off technique is applied to deal with the appearance of infinite series relationships, being the outcome of merging dual expressions. The results are also implemented numerically, supporting the analytical solution, while a Finite Integration Technique (FIT) is used for the validation. Both the analytical and numerical data reveal the temperature pattern at the cross-section of the solids in perfect agreement. This analytical approach could be of importance for the optimization of plasma jet systems employed in tailored applications where temperature-sensitive materials are involved, like in plasma biomedicine.

Investigation of different solutions activated by air plasma jet and their anticancer effect

In the field of plasma biomedicine, research on a plasma-activated medium (PAM) has attracted increasing attention in recent years because of its excellent characteristics. In this study, we used an atmospheric pressure air plasma jet to treat four different solutions: de-ionized water, RPMI 1640 medium, phosphate buffered saline (PBS), and saline. In order to investigate the property differences of different PAM, we mainly analyzed the physical and chemical properties and liquid-phase active species of different PAM and evaluated the inactivation of A549 lung cancer cells. The results show that the concentrations of long-lived reactive species (H2O2, NO2−, and NO3−) in different PAM increased with increasing treatment time. Biological experiments showed that the antitumor effects were in the order of PBS > saline > RPMI 1640 medium, and the best inactivation effect of plasma-activated PBS for 12 min was 89%. Meanwhile, plasma-activated PBS effectively promoted apoptosis in A549 cells, and the highest apoptosis rate was 91.3%. Therefore, this study demonstrates the medical application of different PAM in killing cancer cells and promotes the understanding of plasma–liquid interaction.

1D fluid model of the interaction between helium APPJ and deionized water

Atmospheric pressure plasma jets (APPJs) are widely used for the treatment of water-containing substances such as human tissue, leading to a necessity of understanding the interaction between APPJs and water solutions for the development of plasma biomedicine. The reported two- or three-dimensional fluid models are shown to be an effective method for this study. However, owing to the complex chemistry in APPJ-water interaction, little of them could provide a quantitative estimation of reactive species, which are difficult to be measured but of much interest in the applications. In this paper, a one-dimensional fluid model is developed to simulate the interaction between a helium APPJ and deionized water, which incorporates a relatively comprehensive chemistry both in gas and liquid phases but with a moderate computational load. The composition and distribution of reactive species are quantified during a plasma treatment time of 6 min, which is typical in practice. By considering the sidewise loss inside the quartz tube, the air mixing outside the quartz tube, the conductivity of deionized water, and the chlorine evolution reaction, the simulation results agree well with the experiments. It is found that the plasma could be divided into three regions with much different physicochemical properties, mainly due to the sidewise loss, the air mixing and the water evaporation. In plasma-activated water, H2O2aq and HNO2aq/NO2aq − are the dominant reactive species, and OHaq is the key intermediate species for the transformation among other reactive species. Finally, the chemical pathways for the production of aqueous reactive species are elucidated.

Modeling study of the indirect treatment of phosphate buffered saline in surface air plasma

Phosphate buffered saline (PBS) is a commonly used medium for in vitro experiments in plasma biomedicine; however, the mechanism for changes in PBS in response to plasma treatment is not well understood. Many kinds of reactive species are produced in plasma-activated PBS, but to date only a few of them can be quantified. In this paper, therefore, we aim to develop a fully coupled model for the interaction between surface air plasma and PBS, primarily to quantify its plasma-induced aqueous reactive species, as well as to elucidate their production mechanism. This model consists of a 0D sub-model for the surface plasma in air, and two 1D sub-models: for the PBS, and for the air gap between the plasma and the PBS. Similar models have been reported by our group fwith respect to the plasma treatment of deionized water. Here, by comparison, an additional 24 chlorine compounds, 17 phosphorous species and 123 chemical reactions are incorporated in our model. Our results indicate that the main aqueous reactive species are H2O2aq, O3aq, NO2aq −, NO3aq −, HClOaq, ClO2aq and ClO3aq −. During plasma treatment, the oxidation reduction potential of most reactive species increases within the first 50 s, then remains almost constant. The chemical profile of the plasma-activated PBS is also plotted, from which it can be observed that some reactive oxygen species, such as OHaq, H2O2aq, and O3aq play a crucial role in the production of chlorine compounds such as HClOaq and ClO3aq −.

Measurement of nitrogen dioxide and nitric oxide densities by using CEAS (cavity‐enhanced absorption spectroscopy) in nonthermal atmospheric pressure air plasma

AbstractNonthermal atmospheric pressure plasmas are widely used in biomedicine and agriculture. Currently, radical density is used as an important parameter for the development of plasma biomedicine and agriculture. Especially, nitrogen dioxide (NO2) and nitric oxide (NO) radicals are significant species in these applications. These could be measured by using the cavity‐enhanced absorption spectroscopy (CEAS) technique. For the NO2 and NO radical density measurement, we used a visible LED (light‐emitting diode) of 660 nm and a mid‐infrared LD (laser diode) of 5238.6 nm, respectively. Radical densities can be calculated with the transmission ratio using Beer–Lambert law, which is obtained by the absorbed amount of laser intensity passed through the gas from the plasma jet in an optical cavity of CEAS.

Atmospheric pressure plasma treatments protect neural cells from ischemic stroke‐relevant injuries by targeting mitochondria

AbstractMost studies regarding plasma biomedicine applications mainly focus on the oxidative and/or nitrative stress on bacteria, cancer cells, and other treatment objects. In this study, we evaluate the protective effect of appropriate atmospheric pressure plasma jet (APPJ) treatments on oxygen and glucose deprivation (OGD)‐induced neural cell apoptosis, which is a major pathological process during ischemic stroke, based on the physiological functions of NO. Results show that APPJ treatment reduces the OGD‐induced apoptosis by weakening typical OGD injury consequences including loss of mitochondrial membrane potential, the release of cytochrome c from the mitochondria into the cytoplasm, lower antiapoptotic Bcl‐2 expression, and upregulating the proapoptotic protein Bax. Furthermore, APPJ increased intracellular NO production, which is closely related to the cytoprotective effect of APPJ.

Development of a portable cold air plasma jet device and observation of its photo ionization process

Photo ionization plays a critical role in the formation and propagation of atmospheric pressure plasma jet plumes. But in experiments, it is very difficult to observe the photo ionization due to its relative lower density of photo electrons. In the present study, we develop a portable cold air plasma jet device and observe the ionization wave in a dc spark air plasma jet. The discharge images acquired by an ICCD camera show that the ionization wave front performs as a quickly moving bright ball. Breakdown could take place at another side of the quartz plate or pork tissue layer (6 mm thick), which suggests that the ionization should be attributed to photo ionization. The laser schlieren images indicate there is propagation of a shock wave along with the plasma bullet. Based on the photo ionization theory and the photo-electric measurement, the direct photo ionization and multistage photo ionization are the main factors in charge of generating the cold air plasma jet. In addition, the plasma jet outside of the cathode nozzle is colder than 320 K and can be touched safely by a human. In view of the plasma jet including a large amount of active particles, such as NO, O, OH, emitted photons, etc, the proposed portable cold air plasma jet device could be qualified for plasma bio-medicine applications.

Interfacial current distribution between helium plasma jet and water solution

The plasma–liquid interaction holds great importance for a number of emerging applications such as plasma biomedicine, yet a main fundamental question remains about the nature of the physiochemical processes occurring at the plasma–liquid interface. In this paper, the interfacial current distribution between helium plasma jet and water solution was measured for the first time by means of the splitting electrode method, which was borrowed from the field of arc plasma. For a plasma plume in continuous mode, it was found that the mean absolute current distribution at the plasma–liquid interface typically had an annular shape. This shape could be affected by regulating the air doping from the surrounding atmosphere, the gas flow rate, the applied voltage and the conductivity of the water solution. However, only the air doping fraction and the water conductivity could fundamentally change the interfacial current distribution from the annular shape to the central maximum shape. It was deduced that a certain amount of ambient air doping (mainly N2 and O2) and a low conductivity (typically <300 μS cm−1) of the treated water were essential for the formation of the annular current distribution at the plasma–liquid interface.

1D fluid model of RF-excited cold atmospheric plasmas in helium with air gas impurities

Cold atmospheric plasmas (CAPs) in helium with air gas impurities (He+Air for abbreviation) compromise the discharge stability of helium and the chemical reactivity of air, having great prospects for various applications such as plasma biomedicine. However, different kinds of reactive species are produced in He+Air CAPs but only a few of them could be measured, and the plasma chemistry is so complex that the reported simulation models are simplified to a large extent, such as neglecting the space variation of CAPs by using a 0D model. As a result, much remains unknown for He+Air CAPs, which hinders the development of their applications. For that reason, a 1D fluid model of He+Air CAPs is developed in this paper, incorporating 48 chemical species and 118 volume reactions, which are extracted from a complex chemistry set by a reported 0D model, and then the density distribution of reactive species, the power dissipation pathways, and the chemistry pathways among the reactive species are obtained as a function of air concentration from 500 to 10 000 ppm. It is found that O and NO are the dominant reactive oxygen species (ROS) and reactive nitrogen species (RNS), respectively. Taking the ROS as a whole, it is mainly produced by the electron impact dissociation and excitation of O2; taking the RNS as a whole, it is mainly produced by the oxidation of atomic nitrogen [N and N(2D)], and NO is the precursor for all the other RNS.

Discharge characteristics of pin-micron droplet-pin system driven by DC pulse voltage

The multi-phase discharge with the gas-liquid interface has attracted a lot of interest and especially the plasma biomedicine application has become the research hotpot in recent years. Considering the size effect of the gas and liquid phases, this paper focuses on the discharge processes based on the micron droplet system with a pin-to-pin electrode excited by the high DC pulse voltage with 30 ns rising time. The main innovation of this article is the droplet diameters varying from 300 μm to 600 μm. The image shows that the discharge always develops along the surface of the droplet, and the droplet appears to have the effect of guiding the ionizing wave. And the discharge affects the shape of the droplet. When the applied voltage (UA) is different, the difference between with droplet and without droplet inside the electrodes shows reverse characteristics. When UA is 10 kV, the emission duration time and area of the without droplet case is larger than that with the droplet while the result is the opposite for when UA is 40 kV. There is a pre-breakdown channel before the ellipsoidal discharge and the pre-breakdown channel is related to the electrode-droplet position. And the pre-breakdown channel always propagates along the droplet surface.

Cold plasma bullet influence on the water contact angle of human skin surface

Skin wettability is determinant factor for skin protection, adhesion to substances or patches, and molecule absorption, which are subsequently important for the overall health, the application of cosmetic formulation, as well as transdermal drug delivery. The present work is devoted to a novel way of human skin wettability enhancement by making use of atmospheric pressure helium plasma in the form of “bullets”. Although there exists extended bibliography as well as active research on both stratum corneum wettability and atmospheric pressure plasmas, their interacting relation had never been considered in the field of plasma biomedicine until recently. Herein, we demonstrate the chemical reactivity of helium plasma “bullets” produced by a sinusoidally driven reactor. It is demonstrated that their application to human stratum corneum yields hydrophilic skin surface. Water contact angle values as low as those reported following conventional treatments of skin, are obtained. The role of the reactive neutral and charged species in the stratum corneum modification is discussed, based on the experimental findings.

Investigation on the effects of the operating conditions on electron energy in the atmospheric-pressure helium plasma jet

This work presents a numerical investigation on the effects of the operating conditions on electron energy in the atmospheric-pressure helium plasma jets based on a needle-plane discharge system. The investigation is carried out by using a 2-D fluid model. The considered operating conditions refer to the needle radius, the gap width, and both the inner diameter and the relative permittivity of the dielectric tube. The mechanisms governing the operating condition effects of electron energy have also been analyzed in detail. This work gives the following significant results. The needle radius has only a slight effect on the averaged electron energy whether in the entire plasma jet or in the plasma bullet. The averaged electron energy decreases obviously with the increase in the gap width. The effect of the dielectric tube on electron energy becomes evident only when its inner diameter is smaller than 4 mm in the present simulation. The relative permittivity of the dielectric tube slightly affects electron energy. In particular, the present work shows that the plasma bullet has a substantial contribution to high-energy electrons in contrast to the other region in the plasma jet. This is of importance for the study on the mass transfer of the reactive species in the aqueous solutions in plasma biomedicine because in the mass transfer, the penetration depth of the reactive species can be improved via the dissociative electron attachment to water molecules when increasing the electron energy in plasmas, which helps deliver the reactive species to the surface of living matter and even into its interior for inducing the expected biomedical effects.

A Microwave-Induced Room-Temperature Atmospheric-Pressure Plasma Jet

A 2450-MHz microwave-induced room-temperature atmospheric-pressure plasma jet (RTAPPJ) based on a coaxial structure is proposed for applications of plasma biomedicine. This device is a simple structure with small size, low-power requirement and high controllability. It can induce an argon discharge at atmospheric pressure with as low as 15-W microwave power. The optical emission spectrum of the RTAPPJ shows various highly reactive radicals such as OH and O. The appropriate operation condition can reduce the temperature at the downstream of the flame to be around 30 °C. This portable device is designed to be suitable to manipulate different medical treatments.