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

这个小型企业创新研究(SBIR)第一阶段项目的更广泛的影响/商业潜力将是开发一种用于细胞治疗制造的微流控设备。由拟议技术生产的细胞产品在成本和质量方面的优势应该会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，应显著加快将实验室规模的发现转化为广泛可用的根治疗法。在根本层面上，这个项目将提高对如何以实际方式将微流控技术概念应用于临床相关应用(需要宏观流量)的技术理解，同时还将建立一个新的医疗器械部门，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。这个SBIR第一阶段项目的智力优势是使用细胞分离方法来创建高通量概念验证原型，以帮助简化和精简细胞治疗的制造。为了实现这一目标，将设计一个两级微流控模块，以实现从血液样本中分离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，该计划是制造一个完整的并行淋巴细胞/单核细胞分离模块的原型系统，以实现能够在大约30分钟内处理200毫升外周血、棕黄色涂层或单核细胞(MNC)白细胞分离衍生产品的体积吞吐量。一旦开发出来，这项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，以及可能危及无菌。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/集中。该奖项反映了NSF的法定使命，并已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 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.