Single-Cell Metabolic Activity Monitoring With Microcavity Laser Emitting Cytometry.

Abstract

Single-cell metabolism analysis is essential for understanding cellular heterogeneity. However, the ability to track it in real time, with high precision and under physiological conditions, remains a formidable challenge. Here, we introduce a microcavity laser-emitting cytometry for single-cell metabolism analysis. Single cells and the biocompatible gain medium resazurin were co-encapsulated into droplets via a microfluidic device. These droplets then flowed into the Fabry-Pérot (F-P) cavity, resulting in a 15-fold reduction in the laser pump energy, effectively alleviating phototoxicity. Capitalizing on cavity-enhanced light-matter interactions and ultra-narrow laser linewidths, subtle changes in resazurin concentration resulting from metabolic activity induced redox reactions within cells were transduced into quantifiable, ultra-sensitive shifts in the lasing wavelength. This approach achieved a sensitivity of 0.382 nM per 10 pm shift. Hence, our single-cell laser emitter enabled the quantitative characterization of metabolic kinetics at the single-cell level, facilitating applications in cytometry for metabolic heterogeneity analysis, cell-type discrimination, and drug efficacy quantification. This platform enables single-cell laser emission for cell screening and pharmacological evaluation, advancing research in areas like cancer treatment and drug discovery.