Ultrasensitive Detection of Extracellular Vesicles Based on Metal–Organic Framework DNA Biobarcodes Triggered G-Quadruplex Coupled with Rolling Circle Amplification Assay

Extracellular vesicles (EVs), as liquid biopsy markers for accurate tumor diagnosis, are considered to hold great promise. However, effectively isolating and sensitively detecting EVs with convenience still face challenges. Herein, we propose a highly sensitive and specific platform for EV detection by integrating a metal–organic framework (MOF)-based DNA biobarcodes strategy with a rolling circle amplification (RCA)/G-quadruplex system. In this study, first, Zr-MOFs act as signal converters by comodification with DNA barcodes and antibodies, converting and amplifying the abundance of EVs into DNA barcodes. Second, the released DNA can trigger RCA, followed by G-quadruplex formation to further amplify the signal. Consequently, this approach significantly enhances the sensitivity for EV biomarker detection, achieving a low limit of detection of 100 EVs mL–1. Furthermore, the strategy offers high sensitivity, specificity, accuracy, and simplicity, highlighting its potential for clinical applications in noninvasive EV detection.