Microfluidic technologies for extracellular vesicle isolation and analysis: Implications for translational...

Extracellular vesicles (EVs) are emerging as pivotal mediators of tumor progression, metastasis, and therapy resistance, reflecting the dynamic complexity of the tumor microenvironment. Their stability in biofluids makes EVs promising candidates for both tailored cancer therapies and liquid biopsy-based cancer diagnostics. However, their nanoscale size and molecular heterogeneity continue to challenge standardized isolation and analysis. Recent advances in microfluidic and organ-on-chip technologies are transforming EV research by enabling high-resolution separation, label-free detection, and real-time monitoring within physiologically relevant microenvironments. These platforms not only enhance analytical precision but also recapitulate tumor-stromal interactions that govern EV biogenesis, trafficking, and uptake. When coupled with complementary methods (such as immunoaffinity capture, size-exclusion chromatography, and viscoelastic or magnetophoretic sorting) microfluidic systems offer unprecedented control over EV isolation and characterization. Moreover, emerging wearable microfluidic devices and metabolic labeling strategies open new avenues for personalized EV delivery and nascent vesicle tracking in cancer models. Real-time monitoring of EV transfer between cancer and stromal cells within microfluidic environments further deepens our understanding of EV-mediated communication and its role in metastatic niche formation. In this review, we highlight the latest technological innovations and translational perspectives in EV isolation and analysis, emphasizing how microfluidic platforms are reshaping cancer diagnostics and therapy. Thanks to microfluidics, these integrated systems hold promise for accelerating the clinical deployment of EVs as functional biomarkers and therapeutic agents in precision oncology and nanomedicine-based cancer treatment.