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装置。该技术在成本和质量方面的优势将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一种高效、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方法应该会大大加快。在基础层面上，本项目将加强对如何将微流体技术概念以实际方式应用于临床相关应用（需要宏观流量）的技术理解，同时也将建立一个新的医疗器械部门，以一套易于实现的细胞分离设备为中心，用于细胞治疗和相关领域。这个SBIR一期项目的智力优势在于采用细胞分离方法来创建高通量概念验证原型，以帮助简化和简化细胞疗法的制造。为了实现这一目标，将设计一个两级微流体模块，以实现从血液样本中分离淋巴细胞和单核细胞丰富亚群，同时去除不需要的红细胞和血小板，其水平足以成功培养生长。此外，该计划是制造一个平行淋巴细胞/单核细胞分离模块的全尺寸原型系统，以实现能够在30分钟内处理200mL外周血、灰白色被或单核细胞（MNC）白血病衍生产品的体积吞吐量。一旦开发成功，该技术将克服困扰当前细胞分离方法的许多缺点，包括单位成本高，工作流程费力/耗时，以及可能影响无菌性。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 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.