State of the art in nonthermal plasma processing for biomedical applications: Can it help fight viral pandemics like COVID-19?

Plasma processing finds widespread biomedical applications, such as the design of biosensors, antibiofouling surfaces, controlled drug delivery systems, and in plasma sterilizers. In the present coronavirus disease (COVID-19) situation, the prospect of applying plasma processes like surface activation, plasma grafting, plasma-enhanced chemical vapor deposition/plasma polymerization, surface etching, plasma immersion ion implantation, crosslinking, and plasma decontamination to provide timely solutions in the form of better antiviral alternatives, practical diagnostic tools, and reusable personal protective equipment is worth exploring. Herein, the role of nonthermal plasmas and their contributions toward healthcare are timely reviewed to engage different communities in assisting healthcare associates and clinicians, not only to combat the current COVID-19 pandemic but also to prevent similar kinds of future outbreaks.

Multi-nanolayer drug delivery using radiofrequency plasma technology.

BACKGROUND: It may be impossible to perform cancer surgery with free margins in the presence of an unresectable structure. Local drug treatment after surgery has been proposed to increase the rate of tumor control. METHODS: Multi-nanolayers (10-330 nm) were generated by a low-pressure (375mTorr) inductively coupled plasma (13.56 MHz) reactor for anticancer drug delivery by the deposition of polycaprolactone-polyethylene glycol multistack barrier on the collagen membrane (100 µm thickness). Carboplatin (300 µg/cm2) was used for the in vitro and in vivo investigations. Energy-dispersive X-ray spectroscopy (15 keV), scanning electron microscopy and inductively coupled plasma mass spectrometry were used to detect the presence of carboplatin in the nanolayer, the tumor sample and the culture medium. Preclinical studies were performed on ovarian (OVCAR-3NIH) and colon (CT26) cancer cell lines as xenografts (45 days) and allografts (23 days) in Swiss-nude (n = 6) and immunocompetent BALB/cByJ mice (n = 24), respectively. RESULTS: The loading of carboplatin or other drugs between the nanofilm on the collagen membrane did not modify the mesh complex architecture or the drug properties. Drugs were detectable on the membrane for more than 2 weeks in the in vitro analysis and more than 10 days in the in vivo analysis. Cytotoxic mesh decreased cell adherence (down 5.42-fold) and induced cancer cell destruction (up to 7.87-fold). Implantation of the mesh on the mouse tumor nodule modified the cell architecture and decreased the tumor size (50.26%) compared to the control by inducing cell apoptosis. CONCLUSION: Plasma technology allows a mesh to be built with multi-nanolayer anticancer drug delivery on collagen membranes.

Optimization of a low pressure plasma process for fabrication of a Drug Delivery System (DDS) for cancer treatment.

A low pressure ICP plasma setup was utilized to deposit thin organic barrier coatings on various substrates to fabricate DDS with encapsulated Carboplatin as a drug and Methylene Blue as a drug model. Choice of the substrates and optimal plasma parameters were discussed for the fabrication of DDS with required characteristics. Prepared thin films were analysed by FTIR, SEM, and the barrier properties were studied by measuring drug concentration released into the medium by UV-VIS and ICP-MS techniques.

Enhanced TiO2 nanorods photocatalysts with partially reduced graphene oxide for degrading aqueous hazardous pollutants.

Enhanced TiO2 nanorods (TNRs) with partially reduced graphene oxide (RGO) (designated as GT) were prepared for degrading aqueous hazardous pollutants. The degree of RGO oxidation had an important role in affecting the photoelectronic and photocatalytic activities of GT composites. The study examined the impact of the degree of RGO oxidation on the photocatalytic activities. The photocatalytic activity of the materials was investigated for degrading rhodamine b (RhB), methyl orange (MO), methylene blue (MB), and phenol by using ultraviolet (UV) light. The highest photocatalytic activity was observed when the atomic oxygen-to-carbon (O/C) ratio of RGO was 0.130 ± 0.003. This study suggested the photocatalytic performance was maximized by preserving a selected amount of the RGO oxygen-containing groups. The work reported in this study on optimizing the RGO-based TiO2 photocatalyst could serve as a promising approach for preparing and optimizing other types of carbon-based photocatalysts such as graphene-based CdS.

Plasma treatment of polyethersulfone membrane for benzene removal from water by air gap membrane distillation.

In order to obtain a durable cost-effective membrane for membrane distillation (MD) process, flat sheet polyethersulfone (PES) membranes were modified by an atmospheric pressure nonequilibrium plasma generated using a dielectric barrier discharge in a mixture of argon and hexamethyldisiloxane as the organosilicon precursor. The surface properties of the plasma-modified membranes were characterized by water contact angle (CA), liquid entry pressure, X-ray photoelectron spectroscopy, scanning electron microscopy, and atomic force microscopy. The water CA of the membrane was increased from 64° to 104° by depositing a Si(CH3)-rich thin layer. While the pristine PES membrane was not applicable in the MD process, the modified PES membrane could be applied for the first time in an air gap membrane distillation setup for the removal of benzene as a volatile organic compound from water. The experimental design using central composite design and response surface methodology was applied to study the effects of feed temperature, concentration, and flow rate as well as their binary interactions on the overall permeate flux and separation factor. The separation factor and permeation flux of the modified PES membrane at optimum conditions were comparable with those of commercial polytetrafluoroethylene membrane.

Radio-frequency plasma polymerized biodegradable carrier for in vivo release of cis-platinum.

A low pressure plasma process based on plasma deposition has been used to develop a drug delivery strategy. In this study, a drug delivery system based on different layers of plasma co-polymerized Poly ε-caprolactone-Polyethylene glycol (PCL-PEG) co-polymers was deposited on biocompatible substrates. Cis-platinum (118 µgm/cm2) was used as an anti-cancer drug and incorporated for local delivery of the chemotherapeutic agent. The co-polymer layers and their interaction with cancer cells were analyzed by scanning electron microscopy. Our study showed that the plasma-PCL-PEG coated cellophane membranes, in which the drug, was included did not modify the flexibility and appearance of the membranes. This system was actively investigated as an alternative method of controlling localized delivery of drug in vivo. The loading of the anti-cancer drug was investigated by UV-VIS spectroscopy and its release from plasma deposited implants against BALB/c mice liver tissues were analyzed through histological examination and apoptosis by TUNEL assay. The histological examination of liver tissues revealed that when the plasma-modified membranes encapsulated the cis-platinum, the Glisson's capsule and liver parenchyma were damaged. In all cases, inflammatory tissues and fibrosis cells were observed in contact zones between the implant and the liver parenchyma. In conclusion, low pressure plasma deposited uniform nano-layers of the co-polymers can be used for controlled release of the drug in vivo.

Development of silver nanoparticle loaded antibacterial polymer mesh using plasma polymerization process.

Plasma polymerized polyacrylic acid (PPAA) was deposited on a polymer substrate, namely polyethylene terephthalate (PET) mesh, for entrapment of silver nanoparticle (Ag-NP) in order to achieve antibacterial property to the material. Carboxylic groups of PPAA act as anchor as well as capping and stabilizing agents for Ag-NPs synthesized by chemical reduction method using NaBH(4) as a reducing agent. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy (XPS), and water contact angle analysis were used to characterize the PPAA coatings. The Ag-NPs loaded polymer samples were characterized by UV-visible spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray, and XPS techniques. XPS analysis showed ~1.0 at.% loading of Ag-NPs on to the PPAA-PET-mesh, which was composed of 79% zero-valent (Ag°) and 21% oxidized nano-Ag (Ag(+) ). The plasma processed PET meshes samples were tested for antibacterial activity against two bacterial strains, namely Staphylococcus aureus (Gram positive) and Escherichia coli (Gram negative). Qualitative and quantitative tests showed that silver containing PPAA-PET meshes exhibit excellent antibacterial property against the tested bacteria with percent reduction of bacterial concentration >99%, compared to the untreated PET mesh.

Catalyst-Free Plasma-Assisted Copolymerization of Poly(ε-caprolactone)-poly(ethylene glycol) for Biomedical Applications.

Catalyst-free ring-opening polymerization (ROP) strategy was developed to overcome the disadvantage of incomplete and expensive removal of catalyst used during the multistep wet chemical processes. Nano-sized biocompatible and low molecular weight poly(ε-carolactone)-poly(ethylene glycol) (PCL-PEG) copolymer coatings were deposited via a single-step, low-pressure, pulsed-plasma polymerization process. Experiments were performed at different monomer feed ratio and effective plasma power. The coatings were analyzed by XPS, as well as MALDI ToF. Ellipsometric measurement showed deposition rates ranging from 1.3 to 3 nm/min, depending on the ratio of the PCL/PEG precursors introduced in the reactor. Our results have demonstrated that plasma copolymerized PCL-PEG coatings can be tailored in such a way to be cell adherent, convenient for biomedical implants such as artificial skin substrates, or cell repellent, which can be used as antibiofouling surfaces for urethral catheters, cardiac stents, and so on. The global objective of this study is to tailor the surface properties of PCL by copolymerizing it with PEG in the pulsed plasma environment to improve their applicability in tissue engineering and biomedical science.

Nanostructure protein repellant amphiphilic copolymer coatings with optimized surface energy by Inductively Excited Low Pressure Plasma.

Statistically designed amphiphilic copolymer coatings were deposited onto Thermanox, Si wafer, and quartz crystal microbalance (QCM) substrates via Plasma Enhanced Chemical Vapor Deposition of 1H,1H,2H,2H-perfluorodecyl acrylate and diethylene glycol vinyl ether in an Inductively Excited Low Pressure Plasma reactor. Plasma deposited amphiphilic coatings were characterized by Field Emission Scanning Electron Microscopy, X-ray Photoelectron Spectroscopy, Atomic Force Microscopy, and Water Contact Angle techniques. The surface energy of the coatings can be adjusted between 12 and 70 mJ/m(2). The roughness of the coatings can be tailored depending on the plasma mode used. A very smooth coating was deposited with a CW (continuous wave) power, whereas a rougher surface with R(a) in the range of 2 to 12 nm was deposited with the PW (pulsed wave) mode. The nanometer scale roughness of amphiphilic PFDA-co-DEGVE coatings was found to be in the range of the size of the two proteins namely BSA and lysozyme used to examine for the antifouling properties of the surfaces. The results show that the statistically designed surfaces, presenting a surface energy around 25 mJ/m(2), present no adhesion with respect to both proteins measured by QCM.

Ammonia plasma treated polyethylene films for adsorption or covalent immobilization of trypsin: quantitative correlation between X-ray photoelectron spectroscopy data and enzyme activity.

The ammonia plasma process was used for generating reactive groups, particularly primary amine functions on the surface of polyethylene (PE) films, to immobilize the enzyme trypsin. The attachment of the enzyme was achieved by directly applying an aqueous solution of trypsin to the plasma-activated surface or by using glutaraldehyde as a chemical linker. In both cases, the utilization of sodium cyanoborohydride efficiently stabilized the immobilization. The surfaces were analyzed by X-ray photoelectron spectroscopy (XPS) and enzymatic activity measurements. Active trypsin was successfully immobilized on the surface with a mean activity of 0.09 ± 0.02 U/cm(2). The study of the stability of the immobilized enzyme during repetitive assays showed that some activity could be maintained during several months. An original quantitative correlation between the immobilized enzyme activity and the XPS signal intensity of the S 2p electrons present in the sulfur-containing amino acid residues was evidenced.

Determination of amine and aldehyde surface densities: application to the study of aged plasma treated polyethylene films.

The aim of this work was to test and to compare different methods reported in the literature to quantify amine and aldehyde functions on the surface of polyethylene (PE) films treated by ammonia plasma and to specify their stability against time. A low pressure ammonia plasma reactor was used to functionalize PE films with amine groups, which could be subsequently used for further immobilization of biomolecules. In order to determine the density of amine groups on the surface of treated films, various molecule probes and spectrophotometric analytical methods have been investigated. Two methods using (i) sulfosuccinimidyl 6-[3'-(2-pyridyldithio)-propionamido] hexanoate (sulfo-LC-SPDP) and (ii) 2-iminothiolane (ITL) associated with bicinchoninic acid (BCA) have been proved to be reliable and sensitive enough to estimate the surface concentration of primary amine functions. The amount of primary amino groups on the functionalized polyethylene films was found to be between 1.2 and 1.4 molecules/nm2. In a second step, the surface concentration of glutaraldehyde (GA), which is currently used as a spacer arm before immobilization of biomolecules, has been assessed: two methods were used to determine the surface density of available aldehyde functions, after the reaction of GA with the aminated polyethylene film. The concentration of GA was found to be in the same range as primary amine concentration. The influence of aging time on the density of available amino and aldehyde groups on the surfaces were evaluated under different storage conditions. The results showed that 50% of the initial density of primary amine functions remained available after storage during 6 days of the PE samples in PBS (pH 7.6) at 4 degrees C. In the case of aldehyde groups, the same percentage of the initial density (50%) remained active after storage in air at RT over a longer period, i.e., 15 days.

Stable modification of PDMS surface properties by plasma polymerization: application to the formation of double emulsions in microfluidic systems.

We describe a method based on plasma polymerization for the modification and control of the surface properties of poly(dimethylsiloxane) (PDMS) surfaces. By depositing plasma polymerized acrylic acid coatings on PDMS, we succeeded to fabricate stable (several days) hydrophilic and patterned hydrophobic/hydrophilic surfaces. We used this approach to generate direct and (for the first time in this material) double emulsions in PDMS microchannels.