Single-Cell Laser Emitting Cytometry for Label-Free Nucleolus Fingerprinting

Abstract Nucleolus, a recognized biomolecular condensate, serves as the hub for ribosome biogenesis within the cell nucleus. Its number and morphology act as discernible indicators of cellular functional states, particularly under stress conditions. However, precise identification and quantification of nucleolus remains challenging without specific labeling, particularly for suspended cells and high-throughput applications. Here we introduce a single-cell laser emitting cytometry (SLEC) for label-free nucleolus differentiation through light-matter interactions within a Fabry-Perot photonic resonator. The laser emission image provides insights into the structural inhomogeneity and the temporal fluid-like dynamics within the nucleolus. Lasing spectral fingerprint depicts the quantity and size of nucleoli within a single cell, showcasing the viability of nucleolus flow cytometry on a biochip. This approach holds promise for nucleolus-guided cell screening and drug evaluation, advancing the study of diseases such as cancer and neurodegenerative disorders.