Gregory Fridman

Physical and biological mechanisms of direct plasma interaction with living tissue

Mechanisms of plasma interaction with living tissues and cells can be quite complex, owing to the complexity of both the plasma and the tissue. Thus, unification of all the mechanisms under one umbrella might not be possible. However, the authors are attempting to make first steps in this direction. In this paper, analysis of interaction of floating electrode dielectric barrier discharge (FE-DBD) with living tissues and cells is presented and biological and physical mechanisms are discussed. In physical mechanisms, charged species are identified as the major contributors to the desired effect and a mechanism of this interaction is proposed. Biological mechanisms are also addressed and a hypothesis of plasma selectivity and its effects is offered.

Nonthermal Dielectric-Barrier Discharge Plasma-Induced Inactivation Involves Oxidative DNA Damage and Membrane Lipid Peroxidation in Escherichia coli

ABSTRACT Oxidative stress leads to membrane lipid peroxidation, which yields products causing variable degrees of detrimental oxidative modifications in cells. Reactive oxygen species (ROS) are the key regulators in this process and induce lipid peroxidation in Escherichia coli. Application of nonthermal (cold) plasma is increasingly used for inactivation of surface contaminants. Recently, we reported a successful application of nonthermal plasma, using a floating-electrode dielectric-barrier discharge (FE-DBD) technique for rapid inactivation of bacterial contaminants in normal atmospheric air (S. G. Joshi et al., Am. J. Infect. Control 38:293-301, 2010). In the present report, we demonstrate that FE-DBD plasma-mediated inactivation involves membrane lipid peroxidation in E. coli. Dose-dependent ROS, such as singlet oxygen and hydrogen peroxide-like species generated during plasma-induced oxidative stress, were responsible for membrane lipid peroxidation, and ROS scavengers, such as α-tocopherol (vitamin E), were able to significantly inhibit the extent of lipid peroxidation and oxidative DNA damage. These findings indicate that this is a major mechanism involved in FE-DBD plasma-mediated inactivation of bacteria.

Mechanism of Blood Coagulation by Nonthermal Atmospheric Pressure Dielectric Barrier Discharge Plasma

Mechanisms of blood coagulation by direct contact of nonthermal atmospheric pressure dielectric barrier discharge (DBD) plasma are investigated. This paper shows that no significant changes occur in the pH or Ca2+ concentration of blood during discharge treatment. Thermal effects and electric field effects are also shown to be negligible. Investigating the hypothesis that the discharge treatment acts directly on blood protein factors involved in coagulation, we demonstrate aggregation of fibrinogen, an important coagulation factor, with no effect on albumin. We conclude that direct DBD treatment triggers selective natural mechanisms of blood coagulation.

Nanosecond-Pulsed Uniform Dielectric-Barrier Discharge

The authors report a new nanosecond-pulsed dielectric-barrier discharge (DBD) for sterilization and other medical applications. In the literature, several discharges have been reported, with pulse durations on the order of hundreds of nanoseconds. In this paper, a novel pulsed DBD has been developed, with only few tens of nanosecond pulsewidths working uniformly over large range of electrode gap distance in air under atmospheric pressure.

Application of nanosecond-pulsed dielectric barrier discharge for biomedical treatment of topographically non-uniform surfaces

Antimicrobial effectiveness of a nanosecond-pulsed dielectric barrier discharge (DBD) was investigated and compared with that of a microsecond-pulsed DBD. Experiments were conducted on the Escherichia coli bacteria covering a topographically non-uniform agar surface acting as one of the DBD electrodes. They reveal that the nanosecond-pulsed DBD can inactivate bacteria in recessed areas whereas the microsecond-pulsed and conventional DBDs fail to do so. Charged species (electrons and ions) appear to play the major role in the bacteria inactivation with the nanosecond-pulsed DBD. Moreover, the nanosecond-pulsed DBD kills bacteria significantly faster than its microsecond-pulsed counterpart. (Some figures in this article are in colour only in the electronic version)

Validation of High Gradient Magnetic Field Based Drug Delivery to Magnetizable Implants Under Flow

The drug-eluting stents increasingly frequent occurrence late stage thrombosis have created a need for new strategies for intervention in coronary artery disease. This paper demonstrates further development of our minimally invasive, targeted drug delivery system that uses induced magnetism to administer repeatable and patient specific dosages of therapeutic agents to specific sites in the human body. Our first aim is the use of magnetizable stents for the prevention and treatment of coronary restenosis; however, future applications include the targeting of tumors, vascular defects, and other localized pathologies. Future doses can be administered to the same site by intravenous injection. This implant-based drug delivery system functions by placement of a weakly magnetizable stent or implant at precise locations in the cardiovascular system, followed by the delivery of magnetically susceptible drug carriers. The stents are capable of applying high local magnetic field gradients within the body, while only exposing the body to a modest external field. The local gradients created within the blood vessel create the forces needed to attract and hold drug-containing magnetic nanoparticles at the implant site. Once these particles are captured, they are capable of delivering therapeutic agents such as antineoplastics, radioactivity, or biological cells.

Decontamination of Surfaces From Extremophile Organisms Using Nonthermal Atmospheric-Pressure Plasmas

We showed that nonthermal dielectric barrier discharge (DBD) plasma compromises the integrity of the cell membrane of Deinococcus radiodurans, an extremophile organism. In samples of D. radiodurans, which were dried in a laminar flow hood, we observe that DBD plasma exposure resulted in a six-log reduction in CFU (colony-forming unit) count after 30 min of treatment. When the Deinococcus radiodurans cells were suspended in distilled water and treated, it took only 15 s to achieve a four-log reduction of CFU count.

Non-thermal dielectric barrier discharge plasma treatment of endothelial cells

Non-thermal dielectric barrier discharge plasma is now being widely developed for various medical applications such as skin sterilization, blood coagulation, induction of apoptosis in malignant tissues, and wound healing among others. In this paper, we investigate the toxicity of non-thermal plasma treatment on endothelial cells, which line all blood contacting surfaces in the body. Our initial results indicate that low power non-thermal plasma is relatively non-toxic to endothelial cells at short exposure times up to 30 s, while non-thermal plasma treatment at longer exposure times is cytotoxic. Non-thermal plasma at shorter exposure times may induce proliferation in the cells.

Treatment of raw poultry with nonthermal dielectric barrier discharge plasma to reduce Campylobacter jejuni and Salmonella enterica.

Nonthermal plasma has been shown to be effective in reducing pathogens on the surface of a range of fresh produce products. The research presented here investigated the effectiveness of nonthermal dielectric barrier discharge plasma on Salmonella enterica and Campylobacter jejuni inoculated onto the surface of boneless skinless chicken breast and chicken thigh with skin. Chicken samples were inoculated with antibiotic-resistant strains of S. enterica and C. jejuni at levels of 10(1) to 10(4) CFU and exposed to plasma for a range of time points (0 to 180 s in 15-s intervals). Surviving antibiotic-resistant pathogens were recovered and counted on appropriate agar. In order to determine the effect of plasma on background microflora, noninoculated skinless chicken breast and thighs with skin were exposed to air plasma at ambient pressure. Treatment with plasma resulted in elimination of low levels (10(1) CFU) of both S. enterica and C. jejuni on chicken breasts and C. jejuni from chicken skin, but viable S. enterica cells remained on chicken skin even after 20 s of exposure to plasma. Inoculum levels of 10(2), 10(3), and 10(4) CFU of S. enterica on chicken breast and chicken skin resulted in maximum reduction levels of 1.85, 2.61, and 2.54 log, respectively, on chicken breast and 1.25, 1.08, and 1.31 log, respectively, on chicken skin following 3 min of plasma exposure. Inoculum levels of 10(2), 10(3), and 10(4) CFU of C. jejuni on chicken breast and chicken skin resulted in maximum reduction levels of 1.65, 2.45, and 2.45 log, respectively, on chicken breast and 1.42, 1.87, and 3.11 log, respectively, on chicken skin following 3 min of plasma exposure. Plasma exposure for 30 s reduced background microflora on breast and skin by an average of 0.85 and 0.21 log, respectively. This research demonstrates the feasibility of nonthermal dielectric barrier discharge plasma as an intervention to help reduce foodborne pathogens on the surface of raw poultry.

Bio-Medical Applications of Non-Thermal Atmospheric Pressure Plasma

Non-Thermal Floating Electrode Dielectric Barrier Discharge (FE-DBD) Plasma in Direct Contact with Living Tissue The focus of this work is direct application of non-thermal atmospheric pressure plasma to human tissue, where this tissue serves as a second active electrode. Such use has significant advantages over the existing technologies. Ultra Violet (UV) radiation, especially high energy Vacuum UV (VUV), does not have good penetration depth in air and VUV exists only in the discharge area. Short-lived active species and radicals (like OH, NO, O2( + Δ g 1 ) and other electronically excited species, atomic Oxygen, etc.) do not,