E. Ng, G. Sun, S. Wei, M. Miller, R. DasGupta, P. Lam, C. Chen, ANALYTICAL CHEMISTRY 91, 1277–1285 (2019).
Ultrafast Single-Cell Level Enzymatic Tumor Profiling
Ee Xien Ng, Guoyun Sun, Shih-Chung Wei, Miles A. Miller, Ramanuj DasGupta, Paula Yeng Po Lam, Chia-Hung Chen*
Analytical Chemistry
In the context of tumor analysis, the implementation of precision medicine requires on-time clinical measurements, which requires rapid large-scale single-cell screening that obtains cell population distributions and functions in tumors to determine disease progression for therapeutics. In this study, a high-throughput screening (HTS) platform integrating optical fluorescence detectors and a computational method was developed as a droplet-based microfluidic flow cytometer (Droplet-mu/FG) to comprehensively analyze multiple proteolytic activities of a patient-derived tumor (with similar to 0.5-2 M cells) at single-cell resolution within 2 h. The data-driven analytical method identified distinct cell types and status through protease profiling with high precision. Multiple protease activities of single cells harvested from a tumor were thus determined with a throughput of 400 cells per second. This platform was used to screen protease activities of a wide range of cell types, forming a library. With the development of advanced computational clustering and cell mapping, rapid quantitative tumor profiling with a comprehensive description of cell population distributions and functions could be obtained for clinical treatments.
