Recent Advances in Microfluidics for Nucleic Acid Analysis of Small Extracellular Vesicles in Cancer

Small extracellular vesicles (sEVs) are membranous vesicles released from cellular structures through plasma membrane budding. These vesicles contain cellular components such as proteins, lipids, mRNAs, microRNAs, long-noncoding RNA, circular RNA, and double-stranded DNA, originating from the cells they are shed from. Ranging in size from ≈25 to 300 nm and play critical roles in facilitating cell-to-cell communication by transporting signaling molecules. The discovery of sEVs in bodily fluids and their involvement in intercellular communication has revolutionized the fields of diagnosis, prognosis, and treatment, particularly in diseases like cancer. Conventional methods for isolating and analyzing sEVs, particularly their nucleic acid content face challenges including high costs, low purity, time-consuming processes, limited standardization, and inconsistent yield. The development of microfluidic devices, enables improved precision in sorting, isolating, and molecular-level separation using small sample volumes, and offers significant potential for the enhanced detection and monitoring of sEVs associated with cancer. These advanced techniques hold great promise for creating next-generation diagnostic and prognostic tools given their possibility of being cost-effective, simple to operate, etc. This comprehensive review explores the current state of research on microfluidic devices for the detection of sEV-derived nucleic acids as biomarkers and their translation into practical point-of-care and clinical applications.