A digital microfluidic integrated SiNW array FET for amplification-free detection of extracellular vesicle-derived miRNAs

Abstract

Extracellular vesicles (EVs) and EV-derived microRNAs (EV–miRNAs) are emerging as valuable nanoscale circulating biomarkers for tumor progression and immune responses. Conventional detection methods, such as quantitative reverse transcription polymerase chain reaction (qRT-PCR), require large sample volumes and labor-intensive purification, limiting the analysis of EV–miRNAs from scarce samples. In this work, we present an integrated DropFET device that combines a high-density active-matrix digital microfluidic (AM-DMF) chip with a silicon nanowire array field-effect transistor (SiNW array FET) sensor for fully integrated EV–miRNA detection. Based on a bio-cascade strategy, EVs are efficiently captured with dual-antibody-functionalized magnetic beads, lysed in situ on-chip, and the released miRNAs are directionally delivered to the SiNW sensor for electrical sensing. With a detection limit of 10⁻¹⁷ M, the device discriminates single-base mismatches and reliably distinguishes EV–miRNA expression differences between normal and M1 disease states. This integrated approach enables low-volume EV enrichment and ultrasensitive EV–miRNA detection, offering a promising platform for clinical analysis of rare samples.