Microfluidic systems in extracellular vesicles single analysis. A systematic review

Extracellular vesicles (EVs) are key elements in cell-to-cell communication and important circulating carriers of molecular biomarkers. There is an increasing interest in the analysis of EVs, as they can facilitate the identification and assessment of new biomarkers in liquid biopsy, allowing an earlier and more precise diagnosis of several pathologies like cancer or degenerative diseases. However, current analytical approaches are based on bulk EV analyses, being unable to provide precise information about the contents and the cells of origin of EVs. Thus, comprehensive EV research requires the analysis at a single particle level. Multiple studies have been conducted to achieve this goal, employing more sophisticated techniques such as microfluidic systems to separate single particles. In this systematic review we have identified 23 studies describing single EV analysis using different microfluidics approaches. Most of the reviewed works in this article have been performed during the last 3 years and have described several strategies for EV isolation, sorting, labeling, signal amplification, and sensing. These works provide new opportunities for further studies in the field and unravel the potential of microfluidic systems as the key to develop a single EV analysis with high sensitivity, robustness, and specificity.