Advanced Technologies in Extracellular Vesicle Biosensing: Platforms, Standardization, and Clinical Translation.

Recently, extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication that reflect physiological homeostasis and pathological alterations. By encapsulating diverse biomolecules, including proteins, nucleic acids, and lipids, EVs mirror the molecular signatures of their parent cells, thereby positioning EV-based biosensing as a transformative platform for noninvasive diagnostics, prognostic prediction, and therapeutic monitoring. This review provides a comprehensive overview of the current state and clinical translation of EV biosensing technologies. Herein, we have discussed ongoing efforts toward standardization and analytical validation (e.g., MISEV2023 and EV-TRACK) and evaluated advances in sensing modalities such as surface plasmon resonance (SPR), electrochemical, fluorescence, and magnetic detection systems, which have significantly improved analytical performance in terms of sensitivity and specificity. Furthermore, we highlight recent developments in multiplexed and multiomics integration at the single-EV level and the application of machine learning to enhance diagnostic accuracy and interpret biological heterogeneity. The clinical relevance of EV biosensing has been explored across multiple disease domains, including oncology, neurology, and cardiometabolic and infectious diseases, with an emphasis on translational progress toward standardized, regulatory-compliant, and scalable platforms. Finally, this review identifies key challenges in manufacturing scale-up, quality control, and point-of-care deployment and proposes a unified framework to accelerate the adoption of EV biosensing as a cornerstone of next-generation precision diagnostics and personalized medicine.