A DNA Fishhook Electrochemical Sensor Based on a Potassium Ferricyanide-Mediated Dual-Signal-Correlation Enhanced Electrocatalysis Reaction for a Simultaneous and Correlation Assay of Multiple Biomarkers.

Simultaneous detection and correlation analysis of multiple biomarkers in a single run are crucial to improving the detection specificity and indicate disease progression, but they remain a challenge. Herein, we propose a DNA fishhook electrochemical sensor based on the potassium ferricyanide-mediated dual-signal correlation enhanced electrocatalysis reaction (DEER). The designed T-shaped DNA fishhook scaffold has two "hooks" to recruit their respective "fish" (targets) with the help of the "fishing bait" (signal probes, Sp), resulting in the different targets and Sp being specifically captured by the DNA fishhook to the electrode interface, respectively. The proposed DEER not only effectively improves the detection sensitivity without introducing nucleic acid amplification but also can reflect the logical correlation between the targets. As proof of principle, the DNA fishhook sensor was successfully applied in the simultaneous detection of two related gene sequences of SARS-CoV-2 and the active-state assay of the PI3K/AKT signaling pathway. In general, our DNA fishhook sensor provides a meaningful potential tool for the sensitive simultaneous detection and correlation analysis of multiple targets.