Plasmonic Inactivation of Virus and Mycoplasma Contaminants

病毒和支原体污染物的等离子体灭活

• 批准号: 10640258
• 负责人: SHYAMSUNDER ERRAMILLI
• 金额: $ 33万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640258
• 关键词: Address; Antibodies; Bacteria; Benchmarking; Biological; Biological Products; Bioreactors; Biotechnology; COVID-19 pandemic; Categories; Cell Culture Techniques; Cell Line; Cells; Chemicals; Clinical; Containment; Dangerousness; Development; Diameter; Disease; Disinfectants; Electromagnetic Fields; Electromagnetics; Electronics; Endotoxins; Ensure; Excision; Filtration; Generations; Goals; Gold; Guidelines; Health; Human; Human body; Immunology procedure; Industrialization; Industry; Industry Standard; Infrared Rays; Investigation; Laboratories; Lasers; Light; Magnetism; Mediating; Membrane; Methods; Microbe; Molecular; Monoclonal Antibodies; Mycoplasma; Nanostructures; Nanotechnology; Nucleosome Core Particle; Optics; Pathway interactions; Patient-Focused Outcomes; Pharmaceutical Preparations; Pharmacologic Substance; Photochemistry; Principal Investigator; Process; Production; Property; Proteins; Public Health; Radiation; Reactive Oxygen Species; Reproducibility; Risk; Sampling; Scheme; Shapes; Specificity; Sterilization; Technology; Temperature; Time; Tissue Sample; Tissues; Treatment Efficacy; Ultrafiltration; Ultraviolet Rays; Viral; Virion; Virus; Virus Inactivation; Work; absorption; bactericide; cost; emerging antibiotic resistance; fabrication; flexibility; fundamental research; improved; innovation; irradiation; magnetic field; manufacture; manufacturing process; manufacturing technology; microbial; monoclonal antibody production; nanomaterials; nanoparticle; nanoplasmonic; pathogen; pathogenic microbe; photonics; plasmonics; point of care; pressure; prevent; programs; response; superparamagnetism; ultraviolet irradiation

SUMMARY Biological pharmaceuticals, or “biologics”, are among the most important pharmaceuticals in development today, and their safe manufacture is absolutely crucial for human health. A major problem faced by operators of bioreactors, at both the laboratory scale and industrial scale, is microbial contamination as an integral risk of any process that derives from live cell lines. The fundamental concern is to ensure that contaminated biologics are not injected into the human body. To warrant contamination free biologics a terminal sterilization is often necessary. The central challenge in this step is the inactivation or removal of microbial contaminates without causing harm to the precious biologics. This work focuses on antibodies as representative biologics. Especially for viral and mycoplasma contaminations the terminal sterilization step remains challenging due to the small size of the pathogens. The industry standard today is removal through passive filtration using filter membranes with pore diameters smaller or of the same size as the virus particles. This approach requires, however, long processing times associated with high costs. Furthermore, ultrafiltration can induce antibody self-association and is not compatible with emerging flexible, small-scale, point-of-care biologics fabrication technologies. The need for new selective microbe inactivation strategies is also not limited to the field of biologics fabrication. The Covid19 pandemic has recently illustrated the need for reliable virus inactivation strategies that selectively act on the virus in tissues but not on proteins, for instance, to allow immunological assays of infected samples outside of high containment laboratories. Light has sterilization properties, and UV-light has long been used to inactivate a broad range of microbial pathogens. Unfortunately, it lacks specificity and also damages precious biologics through reactive photochemistries driven by molecular absorptions in the UV range of the electromagnetic spectrum. To overcome the shortcomings of both ultrafiltration and UV-irradiation as microbe inactivation strategies, this proposal develops a plasmonically enhanced photonic inactivation method that utilizes near-infrared (NIR) light for the selective inactivation of viruses and mycoplasma. As NIR radiation does not overlap with molecular absorptions, the collateral damage on biologics is minimal. The proposed work will reveal the fundamental working principles underlying plasmonic pathogen inactivation and implement magnetic plasmonic nanoparticles (NPs) that allow for an easy, contact-free removal of the nanomaterials from the samples after sterilization. The specific aims of this application are to: Aim 1: Achieve Reliable Virus Inactivation with NIR Light through Plasmonic Enhancement Aim 2: Demonstrate a Plasmon-Enhancement Strategy for Mycoplasma Inactivation with NIR Light Aim 3: Demonstrate Scalable Clearance of Virus and Mycoplasma with Magnetic Plasmonic NPs

概括 生物药品或“生物制剂”是开发中最重要的药品之一 如今，它们的安全生产对于人类健康来说绝对至关重要，这是运营商面临的一个主要问题。 无论是在实验室规模还是工业规模的生物反应器中，微生物污染都是生物反应器的一个整体风险 任何源自活细胞系的过程最根本的问题是确保生物制品受到污染。 不注射到人体中，为了保证无污染的生物制剂，通常需要进行最终灭菌。 此步骤的主要挑战是在不进行任何处理的情况下灭活或去除微生物污染物。 这项工作特别关注作为代表性生物制品的抗体。 对于病毒和支原体污染，由于微小的污染，最终灭菌步骤仍然具有挑战性。 当今的行业标准是通过使用滤膜的被动过滤来去除。 然而，这种方法需要较长的孔径。 处理时间长且成本高。此外，超滤可诱导抗体自缔合。 并且与新兴的灵活、小规模、即时护理生物制剂制造技术不兼容。 对新的选择性微生物灭活策略的需求也不仅限于生物制剂制造领域。 最近的 Covid19 大流行表明需要有选择性地采取可靠的病毒灭活策略 例如，作用于组织中的病毒而不是蛋白质，以便对受感染的样本进行免疫分析 在高密闭实验室之外，光具有灭菌特性，而紫外线长期以来一直被用来灭菌。 不幸的是，它缺乏特异性并且还会损害珍贵的微生物。 通过由紫外线范围内的分子吸收驱动的反应光化学来制备生物制剂 克服了超滤和紫外线照射作为微生物的缺点。 失活策略，该提案开发了一种等离子体增强光子失活方法， 利用近红外 (NIR) 光选择性灭活病毒和支原体，就像近红外辐射一样。 与分子吸收不重叠，对生物制品的附带损害是最小的。 揭示等离子体病原体灭活的基本工作原理并实施磁性 等离激元纳米粒子 (NP)，可以轻松、无接触地从表面去除纳米材料 该应用的具体目的是： 目标 1：通过等离子体增强，利用近红外光实现可靠的病毒灭活 目标 2：展示近红外光灭活支原体的等离激元增强策略 目标 3：展示利用磁性等离子纳米颗粒可大规模清除病毒和支原体

项目成果

Thermal transport across membranes and the Kapitza length from photothermal microscopy

跨膜热传输和光热显微镜的 Kapitza 长度

• DOI: 10.1007/s10867-023-09636-0
• 发表时间: 2023
• 期刊: Journal of Biological Physics
• 影响因子: 1.8
• 作者: Samolis, Panagis D.;Sander, Michelle Y.;Hong, Mi K.;Erramilli, Shyamsunder;Narayan, Onuttom
• 通讯作者: Narayan, Onuttom