SBIR Phase I: Microparticle reagents for clonal selection of producer cell lines

这个小型企业创新研究(SBIR)第一阶段项目的更广泛的影响/商业潜力是开发一种易于分布和采用的方法来寻找用于制造抗体的细胞。今天用于诊断和治疗的许多抗体都是使用细胞系生产的。需要选择以稳定的方式产生最多抗体的细胞，以更快和更低的成本将新的诊断和治疗产品推向市场。然而，今天用于识别和挑选细胞的工具和方法极其缓慢和/或昂贵，通常需要昂贵的定制设备。该项目的目标是开发一种产品，使用户能够利用实验室现有的设备识别产生最多抗体的单个细胞。这将使更多的小型制药公司、生物技术公司和研究实验室能够开发稳定的抗体生产细胞系，并可能在流行病期间实现分布式开发和抗体生产的直接影响，例如COVID-19。这个小型企业创新研究(SBIR)第一阶段项目旨在开发一种基于试剂的工作流程，以执行用户友好且易于分发的单细胞抗体分泌检测。根据分泌物分析和选择单个细胞的能力对于单抗疗法的快速发展至关重要。一个关键的挑战是筛选生产性细胞系，这可能需要几个月的时间和精力。试图解决这一问题的现有系统需要专业知识或商业设备，而这些专业知识或商业设备并不广泛使用，因此可以分析的细胞数量仍然很少。该项目致力于开发一种基于试剂的微粒产品，该产品可以分离单个细胞，浓缩和分析它们的分泌物，并使用标准的流式细胞仪高通量地根据分泌物对单个细胞进行分选。该项目的主要技术目标是：开发最适合用于生产大量抗体的标准细胞的微粒产品配方，将系统性能与当前方法进行比较，并使用该系统创建产生大量潜在SARS-CoV-2疗法的细胞系。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact /commercial potential of this Small Business Innovation Research (SBIR) Phase I project is the development of an easily distributed and adopted approach to find cells used to manufacture antibodies. Many of the antibodies used today for diagnostics and therapies are produced using cell lines. Selection of the cells that produce the most antibodies in a stable manner is required to bring new diagnostic and therapeutic products to market faster and with lower costs. However, the tools and approaches used to identify and pick cells today are extremely slow and/or expensive, often requiring costly custom equipment. The goal of this project is to develop a product that enables a user to identify individual cells that produce the most antibodies with equipment already present in their labs. This would enable more small pharmaceutical companies, biotechnology companies, and research labs to develop stable cell lines for antibody production and could have immediate impact in enabling distributed development and production of antibodies during pandemics, such as COVID-19.This Small Business Innovation Research (SBIR) Phase I project aims to develop a reagent-based workflow to perform single-cell antibody secretion assays that is user-friendly and easily distributed. The ability to analyze and select out single cells based on secretions is critical for the rapid development of monoclonal antibody therapies. A key challenge is the screening of producer cell lines for productivity, which can take months and require significant time and effort. Existing systems that try and address this problem require specialized expertise or commercial equipment that is not widely available, so the number of cells that can be analyzed remains small. This project focuses on developing a microparticle, reagent-based product that can isolate single cells, concentrate and analyze their secreted products, and sort individual cells based on secretions in high-throughput using standard flow cytometers. The key technical objectives of this project are to: develop microparticle product formulations optimal for standard cells used to produce high quantities of antibodies, compare the system performance to current approaches, and use the system to create a cell line producing high amounts of a potential SARS-CoV-2 therapeutic.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.