SBIR Phase I: 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）第一阶段项目的更广泛的影响/商业潜力将是开发用于细胞治疗制造的微流体设备。通过所提出的技术生产的细胞产品在成本和质量方面的优势应该使临床研究人员和细胞治疗学受益。此外，通过为制造过程提供高效、标准化和可扩展的方法，将实验室规模的发现转化为广泛可用的治疗性疗法的速度应该会大大加快。 在基础层面上，该项目将提高对如何将微流体技术概念应用于临床相关应用的技术理解（需要宏观流速）以实际的方式，同时还建立了一个新的医疗设备部门，该部门以一套易于实施的细胞分离设备为中心，用于细胞治疗和相关领域。该公司还将利用分离方法创建高通量概念验证原型，以帮助简化和简化细胞疗法的生产。 为了实现这一目标，将设计两级微流体模块以实现从血液样品中分离单独的富含淋巴细胞和单核细胞的亚群，同时以足以成功培养生长的水平去除不需要的红细胞和血小板。 此外，计划制造一个全规模的平行淋巴细胞/单核细胞分离模块原型系统，以实现能够在约30分钟内处理200 mL外周血、血沉棕黄层或单核细胞（MNC）白细胞来源产品的体积通量。 一旦开发出来，该技术将克服困扰当前细胞分离方法的许多缺点，包括高单位成本、费力/耗时的工作流程以及可能损害无菌性。该设备不需要昂贵或复杂的现场设备来驱动感兴趣的细胞的分离/浓缩。该奖项反映了NSF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 I project will be to develop a microfluidic device for cell therapy manufacturing. Advantages in terms of cost and quality of the cell products produced by the proposed technology should benefit clinical researchers and cell therapeutics. Further, by providing an efficient, standardized, and scalable approach to the manufacturing process, the translation of lab-scale discoveries to curative therapies that are widely-available should be significantly accelerated. On a fundamental level, this project will enhance technological understanding of how to apply microfluidic technology concepts to clinically-relevant applications (requiring macroscopic flowrates) in a practical manner, while also establishing a new medical device sector centered on a suite of easily implemented cell separation devices for use in cellular therapies and related fields.The intellectual merit of this SBIR Phase I project is to employ a cell separation approach to create a high-throughput proof-of-concept prototype to help simplify and streamline the manufacture of cellular therapies. To accomplish this objective, a two-stage microfluidic module will be designed to achieve isolation of separate lymphocyte- and monocyte-rich subpopulations from blood samples, while removing undesirable red blood cells and platelets, at levels sufficient for successful culture growth. In addition, the plan is to fabricate a full-scale prototype system of parallelized lymphocyte/monocyte isolation modules to achieve a volumetric throughput capable of processing 200mL of peripheral blood-, buffy coat-, or mononuclear cell (MNC) leukapheresis-derived product within ~30 minutes. Once developed, this technology will overcome many drawbacks that plague current cell isolation approaches including high per unit cost, laborious/time-consuming workflow, and potential to compromise sterility. This device will require no expensive or complex equipment on-site to drive the separation/concentration of the cells of interest.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.