Miniaturized Laser Probe for Exosome-Based Cancer Liquid Biopsy

Exosomes have been established as a valuable tool for clinical applications for the purpose of liquid biopsy and therapy. However, the clinical practice of exosomes as cancer biopsy markers is still to a very low extent. Active mode optical microcavity with microlaser emission has aroused as a versatile approach for chemical and biological sensing due to its benefits of larger photon population, increased effective Q-factor, decreased line width, and improved sensitivity. Herein, we report a label-free and precise quantification of exosome vesicles and surface protein profiling of breast cancer exosomes using functionalized active whispering gallery mode (WGM) microlaser probes. A detection limit of 40 exosomes per microresonator was achieved. The proposed system enabled a pilot assay of quantitative exosome analysis in cancer patients' blood with only a few microliters of sample consumption, holding good potential for large-scale cancer liquid biopsy. Multiplexed functionalization of the optical microresonator allowed us to profile cancer exosomal surface markers and distinct subclasses of breast cancer-associated exosomes and monitor drug treatment outcomes. Our findings speak volumes about the advantages of the WGM microlaser sensor, including very small sample consumption, low detection limit, high specificity, and ease of operation, offering a promising means for precious clinical sample analysis.