I-Corps: A label-free, autofluorescence lifetime flow cytometer for in-line monitoring of T cell function

I-Corps：一种无标记、自发荧光寿命流式细胞仪，用于在线监测 T 细胞功能

• 批准号: 2319225
• 负责人: Melissa Skala
• 金额: $ 5万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2319225&HistoricalAwards=false
• 关键词: Corps; label; free; autofluorescence; lifetime

The broader impact/commercial potential of this I-Corps project is the development of a label-free method for cell therapy manufacturing process optimization and product characterization prior to clinical use. Cell-based therapies have the potential to treat, or even cure, a myriad of diseases. However, these complex biological products display intrinsic variability within a tightly regulated industry and standard quality assessments require labels to characterize functional subsets of cells. Current methods of assessment are laborious, time-consuming, susceptible to reagent quality variability, and may alter cell function. The proposed technology may provide a solution for cell manufacturing that is critical for the continued development of cell-based therapies.This I-Corps project is based on the development of a label-free, non-destructive optical detection technology with single-cell resolution to quantify cell function, viability, and metabolism including machine learning methods that predict later cell quality. The proposed hardware, optics, and analytical algorithms may be readily integrated into a variety of geometries, such as flow cytometry and microscopy, enabling non-destructive assessment for rapid, label-free diagnostics and biomanufacturing process optimization. The inherent flexibility of the proposed technology enables non-destructive assessment for rapid, label-free biomanufacturing process optimization. In addition, a prototype has been engineered that was purpose-built to integrate with biomanufacturing workflows at reduced cost and footprint compared to commercial instruments. Software also has been developed to detect functional biomarker changes at the cell level along with machine learning models that predict later cell function, neither of which are commercially available. The proposed technology operates on intrinsic universal cellular signals, enabling utility across all cell types. Previous results demonstrated that the technology is sensitive to functional response from T cells that predict activation within minutes, preceding expression of activation surface marker at 1 hour.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.

该I-Corps项目的更广泛的影响/商业潜力是开发一种无标签的方法，用于临床使用之前的细胞治疗过程优化和产品表征。基于细胞的疗法有可能治疗甚至治愈无数疾病。但是，这些复杂的生物产品在严格调节的行业内显示出内在的可变性，标准质量评估需要标签以表征细胞的功能子集。当前的评估方法是费力的，耗时的，容易受到试剂质量变异性的影响，并且可能会改变细胞功能。所提出的技术可以为细胞制造提供解决方案，这对于基于细胞的疗法的持续开发至关重要。此I-Corps项目基于具有单细胞分辨率的无标签，无损的光学检测技术的开发，以量化细胞功能，生存能力和代谢，包括预测后期细胞质量的机器学习方法。提出的硬件，光学和分析算法可以容易地集成到各种几何形状中，例如流式细胞术和显微镜，从而实现了无限制评估，以进行快速，无标签的诊断和生物制造过程优化。所提出的技术的固有灵活性使得无限制的评估可以进行快速，无标签的生物制造过程优化。此外，与商业仪器相比，已经设计了一个专门设计的原型，该原型是专为与生物制造工作流相结合的。 还开发了软件，以检测细胞级别的功能生物标志物以及预测较晚的细胞功能的机器学习模型，这些模型均未市售。该提出的技术在固有的通用细胞信号上运行，从而使所有细胞类型的效用。 先前的结果表明，该技术对T细胞的功能响应敏感，该T细胞在几分钟内预测激活，此前1小时表达激活表面标记。该奖项反映了NSF的法定任务，并认为值得通过基金会的智力优点评估来支持，并具有更广泛的影响。