STTR Phase I: Affinity Chromatographic Cell Sorting (AFFICS) System for Simultaneous Multiple Cell Separation

STTR 第一阶段：用于同时多细胞分离的亲和层析细胞分选 (AFFICS) 系统

• 批准号: 1622340
• 负责人: Guokui Qin
• 金额: $ 22.5万
• 依托单位: QT Holdings Corp.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1622340&HistoricalAwards=false
• 关键词: STTR; Phase; Affinity; Chromatographic; Cell

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) project will be the development of a cell sorting system to allow separation of two or more cell types to be used in cell therapies for treatment of cancer and other diseases. Purification of specific cell populations from complex materials such as blood is a critical component of cell therapy manufacturing. However, since most protocols for clinical-grade cell purification rely on binding of magnetic particles to cells, promising cell therapies face the risk of transplanting residual and potentially toxic magnetic particles to human subjects. The steps currently required to eliminate this risk add complexity, time and cost to cell therapy manufacturing, limiting the wide-scale usefulness of promising new cell therapies. This project will develop a novel cell separation technology, free of magnetic particles, that can be readily scaled to levels required to enable clinical-scale manufacturing of highly pure and highly viable cell-based therapeutics. The aim is to perform multi-target cell sorting while simultaneously leaving cells free from contaminating tags.This STTR Phase I project proposes to develop a novel affinity chromatographic cell sorting (AFFICS) system, based on proprietary dissolvable hydrogel microbeads, for efficient simultaneous separation of two and more cell types directly from heterogeneous cell environments without requiring magnetic or fluorescent tagging of cells. To achieve this, the objectives are to 1) Design a column-based affinity chromatographic system with functionalized dissolvable hydrogel microbeads for single surface marker-based cell isolation from complex cell suspensions, leading to cell capture and target cell populations with 85% purity and viability. 2) Develop tandem connection of multiple columns for sequential cell separation based on two or more surface markers on a large scale. 3) Optimize the rapid release mechanism required for efficient simultaneous separation of two and more cell subpopulations while maintaining cell phenotype and viability. The proposed system will provide multi-target cell sorting at clinical scale while simultaneously leaving cells free of residual magnetic or fluorescent affinity tags.

这一小型企业技术转移(STTR)项目的更广泛影响/商业潜力将是开发一种细胞分选系统，允许分离两种或两种以上细胞类型，用于治疗癌症和其他疾病的细胞疗法。从血液等复杂材料中提纯特定细胞群是细胞治疗制造的关键组成部分。然而，由于大多数临床级细胞纯化方案依赖于磁性颗粒与细胞的结合，有希望的细胞疗法面临着将残留的和潜在有毒的磁性颗粒移植到人体受试者身上的风险。目前消除这种风险所需的步骤增加了细胞疗法制造的复杂性、时间和成本，限制了前景看好的新细胞疗法的广泛实用性。该项目将开发一种新的细胞分离技术，不含磁性颗粒，可以很容易地扩展到能够实现临床规模生产高纯度和高度可行的基于细胞的疗法所需的水平。其目的是在进行多目标细胞分选的同时，使细胞不受污染标签的污染。这个STTR第一阶段项目建议开发一种新的基于专利可溶解水凝胶微珠的亲和层析细胞分选(AFFICS)系统，用于直接从不同的细胞环境中高效地同时分离两种或更多类型的细胞，而不需要对细胞进行磁性或荧光标记。为了实现这一目标，我们的目标是：1)设计一种柱基亲和层析系统，其中含有功能化的可溶解水凝胶微珠，用于基于单一表面标记的细胞从复杂细胞悬浮液中分离，导致细胞捕获和目标细胞群具有85%的纯度和活力。2)大规模发展基于两个或多个表面标记的多柱串联，实现细胞的顺序分离。3)优化快速释放机制，以有效地同时分离两个或更多细胞亚群，同时保持细胞表型和活力。建议的系统将提供临床规模的多目标细胞分选，同时使细胞没有残留的磁性或荧光亲和标记。