Microfluidic size-based chromatography as a promising label-free tool for isolation and purification of extracellular vesicles

Extracellular vesicles (EVs) are anticipated to make a paradigm shift in early diagnosis and treatment modalities across a broad spectrum of diseases in the coming decade. Successful use hinges on effective isolation and purification protocols. Despite the existence of several approaches since their discovery in 1985, the lack of a standardized, efficient, cost-effective, and rapid isolation method has limited the clinical translation of EVs. Recently, microfluidic systems have emerged as a promising technology for developing standardized methods for EV isolation, purification, and detection. Along with the size-exclusion chromatography (SEC) that has produced encouraging outcomes in isolating undamaged and pure EV populations, microfluidic-based size-exclusion chromatography (microSEC) could be an effective starting approach for EV deployment. This review aims to examine these new techniques and discuss a more practical approach that integrates the microfluidic system with SEC in a way that is automated, less time-consuming, and less labor-intensive, while also being highly functional and cost-effective, thereby minimizing the damage caused during EV isolation. The optimized platform allows for swift identification of tumor-specific EVs at the point of care, as well as the creation of innovative drug delivery systems, personalized medicines, and vaccine vectors, thus successfully linking broad-scale processing with precision medicine.