Magnetic Sorter Channels for Stem Cells

描述（由申请人提供）： SHOT建议开展研究，以实施从人脐带血和外周血液分离产品细胞中磁性分离造血干细胞的技术。骨髓移植（BMT）是治疗某些类型的白血病和其他血液病的一种既定疗法。同种异体BMT的高治愈潜力受到对紧密匹配的组织相容性供体的要求的限制，以最大限度地减少移植物抗宿主病（GvHD）的可能性。分离干细胞的能力开辟了一种新的临床方法，旨在设计最合适的移植物。SHOT在克利夫兰临床基金会的合作者已经确定，四极磁流分选满足成功选择血液干细胞的大部分要求。建议测试这种方法，因为它比大多数其他方法具有更高的产量和容量。要做到这一点，需要一个重要的研究步骤，这非常适合SBIR范式，即设计一个一次性的磁性流动通道，具有足够的精度和再现性，最终有资格在临床环境中分离人类造血干细胞。SHOT将（1）从克利夫兰诊所基金会转移现有的磁流通道技术，（2）通过研究确定高精度色谱柱制造的最佳大规模生产工艺，该工艺最终符合cGMP资格，以及（3）通过在克利夫兰诊所进行的实验测试此类色谱柱的有效性。拟定的第一阶段可交付成果是在克利夫兰诊所进行的至少五次实验中测试的制造原型流道。第二阶段的活动预计将包括将可制造的流动通道集成到一个完整的磁流分离器中，SHOT将组装成一个上市前的原型，用于继续实验室研究。

DESCRIPTION (provided by applicant): SHOT proposes to perform research leading to the implementation of technology for the magnetic isolation of hematopoietic stem cells from human umbilical cord blood and peripheral apheresis product cells. Bone marrow transplantation (BMT) is an established therapy for certain types of leukemia and other hematologic diseases. The high cure potential of allogeneic BMT is limited by the requirement for closely-matched, histocompatible donors to minimize the possibility of graft-versus-host disease (GvHD). The ability to isolate stem cells opens a new clinical approach aimed at engineering a most suitable graft. SHOT's collaborators at The Cleveland Clinic Foundation have established that quadrupole magnetic flow sorting fulfills most of the requirements for successful hematologic stem cell selection. It is proposed to test this method owing to its much higher yield and capacity than most other methods. To do this requires an important research step, which fits well into the SBIR paradigm, namely the design of a disposable magnetic flow channel with sufficient precision and reproducibility to qualify ultimately for the isolation of human hematopoietic stem cells in the clinical setting. SHOT will (1) transfer existing magnetic flow channel technology from the Cleveland Clinic Foundation, (2) determine, through research, the optimum mass-production processes for high precision column manufacture, this process being ultimately eligible for cGMP qualification, and (3) test, through experimentation to be performed at The Cleveland Clinic, the efficacy of such columns. The proposed Phase I deliverable is a manufactured prototype flow channel tested in at least five experiments at The Cleveland Clinic. Phase II activities are expected to include integrating the manufacturable flow channels into a complete magnetic flow separator that SHOT will assemble into a pre-market prototype for continued laboratory research.