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.