Metal–Organic Framework UiO-66-Mediated Dual-Signal Ratiometric Electrochemical Sensor for microRNA Detection with DNA Walker Amplification

Electrochemical nanotags with strong signal input are necessary for a ratiometric electrochemical sensor to overcome the drawbacks of inaccurate detection results. In this paper, the metal–organic framework (MOF) UiO-66 was utilized as an electrochemical signal tag. A stable and strong current response at +0.9 V can be detected in neutral conditions. MicroRNA (miRNA) was employed as the model analyte. Herein, an enzyme-free DNA-walker-based ultrasensitive ratiometric electrochemical biosensor in combination with Zr MOF (UiO-66) signal tags to detect miRNA was demonstrated. In the presence of miRNA, the autonomous walker movement can be initiated by miRNA, leading to the release of biotin-modified fragments. Thus, streptavidin-labeled UiO-66 nanomaterials were not bound to the electrode, generating a low signal response of UiO-66 at +0.9 V. However, the current signal of electrolyte solution as reference at +0.2 V was increased due to the enhancement of electrode conductivity. This ratiometic sensor demonstrated high sensitivity, selectivity, and reproducibility. It can eliminate the disturbance of environmental factors and basic electrode characteristics, providing more accurate signals. A limit of detection (LOD) of 0.17 fM was achieved. Moreover, the method was also used to detect miRNA-21 spiked in real serum samples.