SBIR Phase I: Ratcheting Cytometry Instrument for Performing Cell Therapy Quality Control Assays

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力将是开发一种工具，以解决质量控制的规模和监管挑战，这些挑战增加了成本，阻碍了细胞疗法在广泛的患者基础上的大规模部署。利用工程化人类细胞的细胞疗法已经显示出令人难以置信的潜力，作为“活药物”，为癌症患者实现个性化治疗。这些疗法的最新改进已经显示出它们在靶向和杀死特定类型的白血病方面的功效。鉴于这些成功，越来越多的研究和临床试验正在提出，以提高目前治疗血癌的疗效，并使这些疗法适应其他癌症类型。虽然在对抗癌症方面显示出希望，但人们越来越关注临床剂量的可制造性，特别是在扩大规模以满足全球需求时。此外，这些疗法的开发速度导致监管机构在质量控制和发布标准方面落后。随着细胞疗法的不断改进和需求的增加，这两个问题都需要得到解决。SBIR第一阶段项目旨在开发一种用于细胞疗法制造的集成质量控制仪器，该仪器围绕一种称为棘轮细胞术的颠覆性新技术。目前，治疗性细胞批次的质量控制仍然难以标准化和规模化，因为需要过多的独立工具来充分表征每个批次。这种模块化方法具有高的资本成本、高的经常性维护成本，并且需要熟练的技术人员。理想情况下，这些独立工具的功能可以组合到一个自动化系统中，以提供细胞治疗质量的标准化指标，而无需用户变化。利用成熟的免疫磁性细胞标记技术，棘轮细胞术能够通过单独测量磁含量和基于表面表达的门控来联合收割机结合质量控制工具的能力。利用这些优势，目标是证明集成仪器在单步测定中定量治疗性细胞批次的细胞数量、活力、表面表达和细胞因子分泌的可行性。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be the development of an instrument to address the scaling and regulatory challenges of quality control that increase cost and impede large scale deployment of cellular therapies to a wide patient base. Cellular therapies taking advantage of engineered human cells have shown incredible potential as "living drugs" that achieve personalized therapies for cancer patients. Recent improvements in these therapies have shown their efficacy in targeting and killing specific types of leukemias. In light of these successes, more and more research and clinical trials are being proposed to improve current efficacy in treating blood cancers and adapting these therapies to other cancers types. While showing promise in the fight against cancer, there is growing concern over the manufacturability of clinical doses, especially when scaling up to meet global demands. Additionally, the speed at which these therapies are being developed is causing regulatory agencies to lag behind in terms of quality control and release criteria. Both of these issues will need to be addressed as cellular therapies continue to improve and increase in demand. This SBIR Phase I project proposes to develop an integrated quality control instrument for the manufacture of cellular therapies, which centers around a disruptive new technology called ratcheting cytometry. Currently, quality control of therapeutic cell batches remains difficult to standardize and scale given the plethora of standalone tools needed to adequately characterize each batch. This modular approach has high capital cost, high recurring maintenance costs, and requires skilled technicians. Ideally, the capabilities of these standalone tools can be combined into one automated system to provide standardized metrics for cellular therapy quality without user variability. Leveraging well-established immunomagnetic cell labeling techniques, ratcheting cytometry is able combine the capabilities of quality control tools by individually measuring magnetic content and gating based on surface expression. Leveraging these advantages, the goal is to demonstrate feasibility for an integrated instrument to quantify cell number, viability, surface expression, and cytokine secretion of therapeutic cell batches in a single step assay.