Advances in microfluidic extracellular vesicle analysis for cancer diagnostics

Extracellular vesicles (EVs) secreted by cells into the bloodstream and other bodily fluids, including exosomes, have been demonstrated to be a class of significant messengers that mediate intercellular communications. Tumor-derived extracellular vesicles are enriched in a selective set of biomolecules from original cells, including proteins, nucleic acids, and lipids, and thus offer a new perspective of liquid biopsy for cancer diagnosis and therapeutic monitoring. Owing to the heterogeneity of their biogenesis, physical properties, and molecular constituents, isolation and molecular characterization of EVs remain highly challenging. Microfluidics provides a disruptive platform for EV isolation and analysis owing to its inherent advantages to promote the development of new molecular and cellular sensing systems with improved sensitivity, specificity, spatial and temporal resolution, and throughput. This review summarizes the state-of-the-art advances in the development of microfluidic principles and devices for EV isolation and biophysical or biochemical characterization, in comparison to the conventional counterparts. We will also survey the progress in adapting the new microfluidic techniques to assess the emerging EV-associated biomarkers, mostly focused on proteins and nucleic acids, for clinical diagnosis and prognosis of cancer. Lastly, we will discuss the current challenges in the field of EV research and our outlook on future development of enabling microfluidic platforms for EV-based liquid biopsy.