Microfluidic nanochips for rapid exosome isolation and multiplex biomarker profiling from a single blood drop: Toward sample-to-answer liquid biopsy
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 1050µLwithin a closed car tridge, offer a promising route toward integrated sample-to-answer liquid biopsy platforms. Main Body: These systems may integrate plasma handling, exosome enrich ment, cargo access, multiplex biomarker detection, and algorithmic classifi cation. This review highlights key on-chip enrichment techniques, including immunoaffinity, size selection, electrokinetic, acoustofluidic, and hybrid meth ods. It also discusses nano-biointerface designs that improve vesicle capture efficiency while reducing fouling and shear-induced vesicle damage. In addi tion, 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 valida tion requirements, standardized reporting expectations, and defined use-case roadmaps for screening, disease monitoring, and therapeutic-response assess ment. Establishing realistic performance standards and robust engineering parameters will be essential for making single-lab exosome nanochip platforms reproducible and clinically applicable.