I-Corps: Generalization Platform for Single Cell Characterization

这个i-Corps项目的更广泛的影响/商业潜力将是改进药物发现和医学的技术开发。在细胞制造中，人类细胞被设计用于治疗损伤或疾病，这项技术可能被用来有效地测试细胞的安全性和效力，这反过来将有助于更有效、更低成本和更安全的细胞疗法。在药物开发中，这项技术可能提供一种方法，在筛选药物化合物时获得高度特征化的信息，从而导致新的疗法。在医疗诊断、个性化医学和伴随诊断中，该技术可能为分析患者细胞和预测患者对治疗的反应提供更好、更快的方法。总体而言，该项目将通过改进疾病治疗的开发和制造方式产生广泛的社会影响。这个i-Corps项目是基于技术的开发，以实现信息丰富、快速和一次性的大规模单细胞表征分析。正在研究的技术是一种微流控设备，用于单细胞的高通量和高含量成像测量。该装置由密集的陷阱阵列组成，数百个单独的细胞可以在几分钟内确定性地加载和捕获。一旦细胞排列好，就可以使用现成的试剂和基于成像的测量来测量细胞的表型和功能。以前的工作已经优化了该设备的设计，以实现快速、确定性和高密度的细胞捕获。该装置已被应用于许多不同的领域，用于研究细胞、细胞团、胚胎和类器官的生物学，例如利用高分辨率成像研究T细胞的信号动力学以及T细胞和抗原提呈细胞之间的相互作用。这些研究的结果为免疫系统细胞的功能提供了重要的见解，这对更好地了解人类健康和治疗疾病具有重要意义。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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 I-Corps project will be the development of technology to improve drug discovery and medicine. In cell manufacturing, where human cells are engineered to treat injury or disease, the technology may be used to efficiently test the safety and potency of the cells, which will in turn contribute to more effective, less costly, and safer cell therapies. In drug development, the technology may provide a way to obtain highly characterized information when screening pharmaceutical compounds, leading to novel therapies. In medical diagnostics, personalized medicine, and companion diagnostics, the technology may provide better and faster methods for analyzing patient cells and predicting patient responses to treatment. Overall, this project will have broad societal impacts by improving how treatments for diseases are developed and manufactured. This I-Corps project is based on the development of technologies to enable information-rich, fast, and disposable assays for large-scale single-cell characterization. The technology under investigation is a microfluidic device for high-throughput and high-content imaging-based measurements of single cells. The device consists of a dense array of traps into which hundreds of individual cells can be deterministically loaded and trapped within a few minutes. Once cells are arrayed, measurements of cell phenotype and function can be made using readily available reagents and imaging-based measurements. Previous work has optimized the design of the device for fast, deterministic, and high density trapping of cells. The device has been applied in a number of different contexts for studying the biology of cells, cell aggregates, embryos, and organoids, such as studying the signaling dynamics of T cells and the interactions between T cells and antigen presenting cells using high-resolution imaging. The results of these studies have provided important insights into how cells of the immune system function, which has implications for better understanding human health and treating disease.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.