SBIR Phase II: A New Approach for Isolating Leukocyte Sub-populations to Enable Efficient Manufacturing of Cellular Therapies

这个小企业创新研究（SBIR）二期项目的更广泛的影响/商业潜力将为目前在细胞治疗制造的几个阶段使用的现有设备提供改进和更简单的替代方案。高效、标准化和可扩展的制造方法将加速将实验室规模的发现转化为治疗性的、广泛可用的疗法。本项目也将增进对微流控技术概念在临床相关应用（需要高容量通量）中的实际应用的理解。该技术将提供一种无源（无泵、无设备，甚至无电）、高通量、连续流平台，易于保持无菌，无需正式培训即可使用，具有固有的可扩展性，从而成为一种低风险、低成本的新技术。这个小型企业创新研究（SBIR）二期项目建议采用革命性的细胞分离方法用于高通量原型设备，以帮助简化和简化细胞疗法的制造。拟议的项目将优化技术，实现仅依靠被动重力驱动流操作的规模化生产过程。原型装置的性能将根据初始血液样本中淋巴细胞的富集与红细胞、血小板、单核细胞和粒细胞的去除进行测量。预期在5 mL/min或更高的处理速率下，初始样品中保留75%或更多的淋巴细胞。此外，将测量分离的t淋巴细胞在培养中扩增和用标准细胞治疗载体转导的程度，并将其与常规分离的细胞进行比较。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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 II project will offer an improved and simpler alternative to existing equipment currently used at several stages of cell therapy manufacturing. An efficient, standardized, and scalable approach to manufacturing will accelerate the translation of lab-scale discoveries to curative, widely available therapies. This project will also enhance understanding of applications of microfluidic technology concepts to clinically relevant applications (requiring high volumetric throughput) in a practical manner. The proposed technology will offer a passive (pump-, equipment-, and even electricity-free), high-throughput, continuous-flow platform that is easily kept sterile, readily used with no formal training, and inherently scalable, thus leading to a new low-risk and inexpensive technique. This Small Business Innovation Research (SBIR) Phase II project proposes to employ a revolutionary cell separation approach for a high-throughput prototype device to help simplify and streamline the manufacture of cellular therapies. The proposed project will optimize the technology for a scaled production process relying only on passive gravity-driven flow to operate. The performance of prototype devices will be measured with respect to enrichment of lymphocytes versus removal of red cells, platelets, monocytes, and granulocytes from an initial blood sample. Retention of 75% or more of lymphocytes from the initial sample, processed at a rate of 5 mL/min or higher, is expected. Further, the degree to which the isolated T-lymphocytes expand in culture and are transduced with standard cellular therapy vectors will be measured and compared to conventionally-isolated cells.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.