A Dual Metal–Organic Framework-Based Electrochemical Biosensor for the Capture and Detection of Cancerous Exosomes

Exosomes are emerging cancerous biomarkers, while reliable, convenient, and highly sensitive analysis remains challenging. Herein, we report a dual metal–organic framework (MOF)-based electrochemical biosensor for directly capturing and detecting cancerous exosomes in complex biological samples. This biosensor comprises three key components, that is, a pH-sensitive ZIF-8-engineered screen-printed carbon electrode for signal transduction, a pH-insensitive magnetic nanoparticle-modified copper-based MOF (MNP/Cu-BTC MOF) for exosome collection, and a DNA logic system for DNA computation. MNP/Cu-BTC MOF can directly and rapidly collect exosomes from biological media without the use of expensive antibodies or time-consuming centrifugation processes. By introduction of a DNA-based logic system, streptavidin-glucose oxidase (SA-GOx) can be chemically bonded to the surface of exosomes through the biotin–streptavidin interaction. This fabricated biosensor allows ultrasensitive detection of exosomes through the combination of magnetic enrichment, acidification of the solution around the electrode through enzymatic catalysis of glucose to gluconic acid, and ZIF-8-mediated signal transduction as an exosome capture tool. The fabricated biosensor allows label-free detection of exosomes ranging from 104 to 108 particles mL–1 with a limit of detection of 2.2 × 104 particles mL–1. With its capacity for simple exosome collection, accurate identification, and sensitive detection, the proposed biosensor may accelerate the translation of exosome analysis for routine clinical testing.