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.