Electrochemical Quantification of miRNA Based on Strain-Promoted Azide–Alkyne Cycloaddition Ligated Tetrahedral DNA Nanotags

Highly sensitive and accurate detection of disease biomarkers is of great importance for diagnosis, staging, and treatment of certain diseases. Herein, we report a novel electrochemical method for the quantification of miRNA biomarkers with DNA tetrahedrons as the signal reporters. Upon the initiation of DNA hairpin opening by miRNA at the electrode interface, the hidden click reaction group is exposed for the bioconjugation with a tetrahedral DNA nanostructure, which carries multiple electrochemical species. Strand displacement polymerization and reductant-mediated amplification are integrated for improved analytical performance. The established method achieves accurate quantitative detection of miRNA in the range from 100 aM to 10 pM. More importantly, it exhibits exceptional selectivity and stability, making it a highly convenient approach to monitor miRNA biomarkers, meeting the requirements of point-of-care testing.