CRISPR/Cas12a
shows excellent potential in disease diagnostics.
However, insensitive signal conversion strategies hindered its application
in detecting protein biomarkers. Here, we report a metal–organic
framework (MOF)-based DNA bio-barcode integrated with the CRISPR/Cas12a
system for ultrasensitive detection of protein biomarkers. In this
work, zirconium-based MOF nanoparticles were comodified with antibodies
and bio-barcode phosphorylated DNA as an efficient signal converter,
which not only recognized the protein biomarker to form the sandwich
complex but also released the bio-barcode DNA activators after MOF
dissociation to activate the trans-cleavage activity of Cas12a. Due
to the obvious advantages, including numerous loaded oligonucleotides,
a convenient release process, and the nontoxic release reagent, this
MOF-DNA bio-barcode strategy could amplify the CRISPR/Cas12a system
to achieve simple and highly sensitive detection of tumor protein
biomarkers with detection limits of 0.03 pg/mL (PSA) and 0.1 pg/mL
(CEA), respectively. Furthermore, this platform could detect PSA directly
in clinical serum samples, offering a powerful tool for early disease
diagnosis.