Microfluidic nanochips for rapid exosome isolation and multiplex biomarker profiling from a single blood drop: Toward sample‐to‐answer liquid biopsy

Abstract

Abstract Background Exosomes and other small extracellular vesicles carry molecular cargo that can reflect disease status, therapeutic response, and relapse dynamics. Currently, most exosome‐analysis workflows are centralized, require milliliter‐sized blood samples, involve extended isolation procedures, and depend on separate downstream assays. Single‐drop microfluidic nanochips, which can process finger‐prick blood volumes of approximately 1050 µL within a closed cartridge, offer a promising route toward integrated sample‐to‐answer liquid biopsy platforms. Main Body These systems may integrate plasma handling, exosome enrichment, cargo access, multiplex biomarker detection, and algorithmic classification. This review highlights key on‐chip enrichment techniques, including immunoaffinity, size selection, electrokinetic, acoustofluidic, and hybrid methods. It also discusses nano‐biointerface designs that improve vesicle capture efficiency while reducing fouling and shear‐induced vesicle damage. In addition, multiplex sensing architectures for optical, electrochemical, and plasmonic transduction are explored, with particular attention to challenges associated with whole‐blood measurements, including anticoagulation, sample variability, platelet activation, viscosity, and hemolysis. Conclusions Single‐drop exosome nanochips have the potential to transform liquid biopsy by enabling rapid, low‐volume, integrated analysis of extracellular vesicles. However, successful clinical translation will require clear validation requirements, standardized reporting expectations, and defined use‐case roadmaps for screening, disease monitoring, and therapeutic‐response assessment. Establishing realistic performance standards and robust engineering parameters will be essential for making single‐lab exosome nanochip platforms reproducible and clinically applicable.