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Oral SARS-CoV-2 reduction by local treatment: A plasma technology application?

2022, von Woedtke, Thomas, Gabriel, Gülsah, Schaible, Ulrich E., Bekeschus, Sander

The SARS-CoV-2 pandemic reemphasized the importance of and need for efficient hygiene and disinfection measures. The coronavirus' efficient spread capitalizes on its airborne transmission routes via virus aerosol release from human oral and nasopharyngeal cavities. Besides the upper respiratory tract, efficient viral replication has been described in the epithelium of these two body cavities. To this end, the idea emerged to employ plasma technology to locally reduce mucosal viral loads as an additional measure to reduce patient infectivity. We here outline conceptual ideas of such treatment concepts within what is known in the antiviral actions of plasma treatment so far.

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From patent to product? 50 years of low-pressure plasma sterilization

2018-10-18, Fiebrandt, Marcel, Lackmann, Jan-Wilm, Stapelmann, Katharina

The development of new sterilization methods is still a major topic. The need for new techniques arises from the development of new instruments and the usage of different materials. Especially in the case of plastics with their beneficial properties, for example, in the field of implantology, plasma sterilization is seen as a promising alternative to the standard methods. However, 50 years after the first patent and although low-pressure plasmas show excellent inactivation performance (>log 6 reduction), only one commercial system is available on the market for a distinct application. We will give a short review about known plasma sterilization mechanisms, the different plasma sterilization systems in use, analyze possible challenges for an industrial process and comment on possible solutions for a broader acceptance and utilization of low-pressure plasma sterilization.

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Nonspherical Nanoparticle Shape Stability Is Affected by Complex Manufacturing Aspects: Its Implications for Drug Delivery and Targeting

2019, Haryadi, Bernard Manuel, Hafner, Daniel, Amin, Ihsan, Schubel, Rene, Jordan, Rainer, Winter, Gerhard, Engert, Julia

The shape of nanoparticles is known recently as an important design parameter influencing considerably the fate of nanoparticles with and in biological systems. Several manufacturing techniques to generate nonspherical nanoparticles as well as studies on in vitro and in vivo effects thereof have been described. However, nonspherical nanoparticle shape stability in physiological-related conditions and the impact of formulation parameters on nonspherical nanoparticle resistance still need to be investigated. To address these issues, different nanoparticle fabrication methods using biodegradable polymers are explored to produce nonspherical nanoparticles via the prevailing film-stretching method. In addition, systematic comparisons to other nanoparticle systems prepared by different manufacturing techniques and less biodegradable materials (but still commonly utilized for drug delivery and targeting) are conducted. The study evinces that the strong interplay from multiple nanoparticle properties (i.e., internal structure, Young's modulus, surface roughness, liquefaction temperature [glass transition (Tg) or melting (Tm)], porosity, and surface hydrophobicity) is present. It is not possible to predict the nonsphericity longevity by merely one or two factor(s). The most influential features in preserving the nonsphericity of nanoparticles are existence of internal structure and low surface hydrophobicity (i.e., surface-free energy (SFE) > ≈55 mN m−1, material–water interfacial tension <6 mN m−1), especially if the nanoparticles are soft (<1 GPa), rough (Rrms > 10 nm), porous (>1 m2 g−1), and in possession of low bulk liquefaction temperature (<100 °C). Interestingly, low surface hydrophobicity of nanoparticles can be obtained indirectly by the significant presence of residual stabilizers. Therefore, it is strongly suggested that nonsphericity of particle systems is highly dependent on surface chemistry but cannot be appraised separately from other factors. These results and reviews allot valuable guidelines for the design and manufacturing of nonspherical nanoparticles having adequate shape stability, thereby appropriate with their usage purposes. Furthermore, they can assist in understanding and explaining the possible mechanisms of nonspherical nanoparticles effectivity loss and distinctive material behavior at the nanoscale. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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Plasma-Assisted Immobilization of a Phosphonium Salt and Its Use as a Catalyst in the Valorization of CO2

2020, Hu, Yuya, Peglow, Sandra, Longwitz, Lars, Frank, Marcus, Epping, Jan Dirk, Breser, Volker, Werner, Thomas

The first plasma-assisted immobilization of an organocatalyst, namely a bifunctional phosphonium salt in an amorphous hydrogenated carbon coating, is reported. This method makes the requirement for prefunctionalized supports redundant. The immobilized catalyst was characterized by solid-state 13C and 31P NMR spectroscopy, SEM, and energy-dispersive X-ray spectroscopy. The immobilized catalyst (1 mol %) was employed in the synthesis of cyclic carbonates from epoxides and CO2. Notably, the efficiency of the plasma-treated catalyst on SiO2 was higher than those of the SiO2 support impregnated with the catalyst and even the homogeneous counterpart. After optimization of the reaction conditions, 13 terminal and four internal epoxides were converted with CO2 to the respective cyclic carbonates in yields of up to 99 %. Furthermore, the possibility to recycle the immobilized catalyst was evaluated. Even though the catalyst could be reused, the yields gradually decreased from the third run. However, this is the first example of the recycling of a plasma-immobilized catalyst, which opens new possibilities in the recovery and reuse of catalysts. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

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Surface modification of the laser sintering standard powder polyamide 12 by plasma treatments

2018-6-7, Almansoori, Alaa, Masters, Robert, Abrams, Kerry, Schäfer, Jan, Gerling, Torsten, Majewski, Candice, Rodenburg, Cornelia

Polyamide 12 (PA12) powder was exposed for up to 3 h to low pressure air plasma treatment (LP-PT) and several minutes by two different atmospheric pressure plasma jets (APPJ) i.e., kINPen (K-APPJ) and Hairline (H-APPJ). The chemical and physical changes resulting from LP-PT were observed by a combination of Scanning Electron Microscopy (SEM), Hot Stage Microscopy (HSM) and Fourier transform infrared spectroscopy (FTIR), which demonstrated significant changes between the plasma treated and untreated PA12 powders. PA12 exposed to LP-PT showed an increase in wettability, was relatively porous, and possessed a higher density, which resulted from the surface functionalization and materials removal during the plasma exposure. However, it showed poor melt behavior under heating conditions typical for Laser Sintering. In contrast, brief PJ treatments demonstrated similar changes in porosity, but crucially, retained the favorable melt characteristics of PA12 powder.

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Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice

2021, Clemen, Ramona, Freund, Eric, Mrochen, Daniel, Miebach, Lea, Schmidt, Anke, Rauch, Bernhard H., Lackmann, Jan‐Wilm, Martens, Ulrike, Wende, Kristian, Lalk, Michael, Delcea, Mihaela, Bröker, Barbara M., Bekeschus, Sander

Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken ovalbumin (Ova vs oxOva). Dynamic light scattering and circular dichroism spectroscopy reveal structural modifications in oxOva compared to Ova. T cells from Ova-specific OT-II but not from C57BL/6 or SKH-1 wild type mice presents enhanced activation after Ova addition. OxOva exacerbates this activation when administered ex vivo or in vivo, along with an increased interferon-gamma production, a known anti-melanoma agent. OxOva vaccination of wild type mice followed by inoculation of syngeneic B16F10 Ova-expressing melanoma cells shows enhanced T cell number and activation, decreased tumor burden, and elevated numbers of antigen-presenting cells when compared to their Ova-vaccinated counterparts. Analysis of oxOva using mass spectrometry identifies three hot spots regions rich in oxidative modifications that are associated with the increased T cell activation. Using Ova as a model protein, the findings suggest an immunomodulating role of multi-ROS/RNS modifications that may spur novel research lines in inflammation research and for vaccination strategies in oncology.

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Making Sense of Complex Carbon and Metal/Carbon Systems by Secondary Electron Hyperspectral Imaging

2019, Abrams, Kerry J., Dapor, Maurizio, Stehling, Nicola, Azzolini, Martina, Kyle, Stephan J., Schäfer, Jan, Quade, Antje, Mika, Filip, Kratky, Stanislav, Pokorna, Zuzana, Konvalina, Ivo, Mehta, Danielle, Black, Kate, Rodenburg, Cornelia

Carbon and carbon/metal systems with a multitude of functionalities are ubiquitous in new technologies but understanding on the nanoscale remains elusive due to their affinity for interaction with their environment and limitations in available characterization techniques. This paper introduces a spectroscopic technique and demonstrates its capacity to reveal chemical variations of carbon. The effectiveness of this approach is validated experimentally through spatially averaging spectroscopic techniques and using Monte Carlo modeling. Characteristic spectra shapes and peak positions for varying contributions of sp2-like or sp3-like bond types and amorphous hydrogenated carbon are reported under circumstances which might be observed on highly oriented pyrolytic graphite (HOPG) surfaces as a result of air or electron beam exposure. The spectral features identified above are then used to identify the different forms of carbon present within the metallic films deposited from reactive organometallic inks. While spectra for metals is obtained in dedicated surface science instrumentation, the complex relations between carbon and metal species is only revealed by secondary electron (SE) spectroscopy and SE hyperspectral imaging obtained in a state-of-the-art scanning electron microscope (SEM). This work reveals the inhomogeneous incorporation of carbon on the nanoscale but also uncovers a link between local orientation of metallic components and carbon form.

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Supercritical fluid extraction-supercritical fluid chromatography of saliva: Single-quadrupole mass spectrometry monitoring of caffeine for gastric emptying studies†

2021, Hofstetter, Robert K., Schulig, Lukas, Bethmann, Jonas, Grimm, Michael, Sager, Maximilian, Aude, Philipp, Keßler, Rebecca, Kim, Simon, Weitschies, Werner, Link, Andreas

Saliva is an attractive sampling matrix for measuring various endogenous and exogeneous substances but requires sample treatment prior to chromatographic analysis. Exploiting supercritical CO2 for both extraction and chromatography simplifies sample preparation, reduces organic solvent consumption, and minimizes exposure to potentially infectious samples, but has not yet been applied to oral fluid. Here, we demonstrate the feasibility and benefits of online supercritical fluid extraction coupled to supercritical fluid chromatography and single-quadrupole mass spectrometry for monitoring the model salivary tracer caffeine. A comparison of 13C- and 32S-labeled internal standards with external standard calibration confirmed the superiority of stable isotope-labeled caffeine over nonanalogous internal standards. As proof of concept, the validated method was applied to saliva from a magnetic resonance imaging study of gastric emptying. After administration of 35 mg caffeine via ice capsule, salivary levels correlated with magnetic resonance imaging data, corroborating caffeine's usefulness as tracer of gastric emptying (R2 = 0.945). In contrast to off-line methods, online quantification required only minute amounts of organic solvents and a single manual operation prior to online bioanalysis of saliva, thus demonstrating the usefulness of CO2-based extraction and separation techniques for potentially infective biomatrices.

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Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

2020, Bekeschus, Sander, Clemen, Ramona, Nießner, Felix, Sagwal, Sanjeev Kumar, Freund, Eric, Schmidt, Anke

Medical technologies from physics are imperative in the diagnosis and therapy of many types of diseases. In 2013, a novel cold physical plasma treatment concept was accredited for clinical therapy. This gas plasma jet technology generates large amounts of different reactive oxygen and nitrogen species (ROS). Using a melanoma model, gas plasma technology is tested as a novel anticancer agent. Plasma technology derived ROS diminish tumor growth in vitro and in vivo. Varying the feed gas mixture modifies the composition of ROS. Conditions rich in atomic oxygen correlate with killing activity and elevate intratumoral immune-infiltrates of CD8+ cytotoxic T-cells and dendritic cells. T-cells from secondary lymphoid organs of these mice stimulated with B16 melanoma cells ex vivo show higher activation levels as well. This correlates with immunogenic cancer cell death and higher calreticulin and heat-shock protein 90 expressions induced by gas plasma treatment in melanoma cells. To test the immunogenicity of gas plasma treated melanoma cells, 50% of mice vaccinated with these cells are protected from tumor growth compared to 1/6 and 5/6 mice negative control (mitomycin C) and positive control (mitoxantrone), respectively. Gas plasma jet technology is concluded to provide immunoprotection against malignant melanoma both in vitro and in vivo.

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Understanding Surface Modifications Induced via Argon Plasma Treatment through Secondary Electron Hyperspectral Imaging

2021, Farr, Nicholas, Thanarak, Jeerawan, Schäfer, Jan, Quade, Antje, Claeyssens, Frederik, Green, Nicola, Rodenburg, Cornelia

Understanding the effects that sterilization methods have on the surface of a biomaterial is a prerequisite for clinical deployment. Sterilization causes alterations in a material's surface chemistry and surface structures that can result in significant changes to its cellular response. Here we compare surfaces resulting from the application of the industry standard autoclave sterilisation to that of surfaces resulting from the use of low-pressure Argon glow discharge within a novel gas permeable packaging method in order to explore a potential new biomaterial sterilisation method. Material surfaces are assessed by applying secondary electron hyperspectral imaging (SEHI). SEHI is a novel low-voltage scanning electron microscopy based characterization technique that, in addition to capturing topographical images, also provides nanoscale resolution chemical maps by utilizing the energy distribution of emitted secondary electrons. Here, SEHI maps are exploited to assess the lateral distributions of diverse functional groups that are effected by the sterilization treatments. This information combined with a range of conventional surface analysis techniques and a cellular metabolic activity assay reveals persuasive reasons as to why low-pressure argon glow discharge should be considered for further optimization as a potential terminal sterilization method for PGS-M, a functionalized form of poly(glycerol sebacate) (PGS).