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: 10179915
• 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/10179915
• 关键词: Address; Antibodies; Bacteria; Benchmarking; Biological; Bioreactors; Biotechnology; COVID-19 pandemic; Caliber; Categories; Cell Culture Techniques; Cell Line; Chemicals; Clinical; Containment; Dangerousness; Development; Disease; Disinfectants; Electromagnetic Fields; Electromagnetics; 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; 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; flexibility; fundamental research; improved; innovation; irradiation; magnetic field; manufacturing process; 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 生物药物或“生物制剂”是开发中最重要的药物之一 今天，他们的安全制造对于人类健康至关重要。运营商面临的一个主要问题 在实验室规模和工业规模上，生物反应器的构成者都是微生物污染，这是不可或缺的风险 从活细胞系派生的任何过程。根本关注的是确保受污染的生物制剂 没有注入人体。为了保证无污染的无污染物制剂，终末灭菌通常是 必要的。此步骤中的核心挑战是灭活或去除微生物污染物而没有 对宝贵的生物制剂造成伤害。这项工作的重点是抗体作为代表性生物制剂。尤其 对于病毒和支原体污染，末端灭菌步骤由于小而挑战 病原体的大小。当今的行业标准通过使用过滤机制通过被动过滤去除 孔直径较小或与病毒颗粒相同。但是，这种方法需要很长的时间 与高成本相关的处理时间。此外，超滤可以诱导抗体自我关联 并且与新兴的柔性，小规模的护理生物制造技术不兼容。 需要新的选择性微生物灭活策略的需求也不仅限于生物制造领域。这 Covid19大流行最近说明了对可靠的病毒灭活策略的必要性，这些策略有选择地作用 例如，在组织中的病毒上，而不是蛋白质上的病毒，以允许对感染样品进行免疫学评估 在高遏制实验室之外。光具有灭菌特性，紫外线长期以来一直用于 灭活广泛的微生物病原体。不幸的是，它缺乏特殊性，也损害了珍贵 通过反应性光化学的生物制剂，由分子滥用器驱动的紫外线范围 电磁频谱。为了克服超滤清和紫外线的缺点，作为微生物 灭活策略，该提案开发了一种塑料增强的光子灭活方法， 利用近红外（NIR）光的选择性灭活病毒和支原体。就像NIR辐射一样 并非与分子滥用的重叠，而是对生物制剂的附带损害很小。拟议的工作将 揭示浆液病原体失活的基本工作原理并实施磁性 等离子体纳米颗粒（NP），可以轻松，无接触的纳米材料从 灭菌后样品。本应用程序的具体目的是： 目标1：通过血浆增强实现NIR光的可靠病毒灭活 AIM 2：用NIR Light展示支原体灭活的等离子体增强策略 AIM 3：用磁性等离子体NPS证明病毒和支原体的可扩展清除率