An electrochemical biosensor for exosome detection based on covalent organic frameworks conjugated with DNA and horseradish peroxidase.

• Covalent organic frameworks conjugated with DNA and horseradish peroxidase (HRP-DNA-COFs, HDCs) are successfully prepared. • The prepared HDCs can recognize exosomes and catalyze the oxidation of 1, 3, 5-trimethylbenzene (TMB) substrate. • An HDCs-based electrochemical biosensor is constructed for exosome detection. • The HDCs-based biosensor achieves good performance to detect exosomes with simplicity and sensitivity. Quantification of trace exosomes in biofluids is helpful for the early diagnosis of cancers. Electrochemical biosensors have attracted special attentions for exosome detection, while the employment of nanoconjugates in the construction of electrochemical biosensors can achieve better performance. So, in this work, we have designed and fabricated HRP-DNA-COF nanoconjugates (HDCs) that involve covalent organic frameworks (COFs) as the scaffold, cholesterol-tagged DNA to recognize exosomes and horseradish peroxidase (HRP) to amplify the signal readout. The successful preparation of HDCs have been verified experimentally, based on which an electrochemical biosensor has been constructed for exosome detection. Attributed to the specific recognition ability and excellent catalytic ability of HDCs, the biosensor achieves good performance to detect exosomes with simplicity and sensitivity in the linear range from 104 to 107 particles/μL. Besides, the strategy proposed in this work to construct COF-based nanoconjugates may promote the wider application of COFs in biomedical research. [ABSTRACT FROM AUTHOR]