DNA‐Enabled Self‐Resetting Electrochemical Sensor for microRNA Detection

Abstract Nucleic acids, such as microRNA and circulating tumor DNA, are widely utilized potential biomarkers for early disease diagnosis. Electrochemical sensors with high sensitivity play a significant role in quantitative bioanalysis, however, target molecules during detection usually bind to probes and limit their reusability. Powered by DNA/RNA fuel and enzyme‐based fuel consumption unit, dissipative DNA systems can perform periodic tasks in a self‐resettable manner. Here, a self‐resetting electrochemical sensor is reported for miRNA detection based on dissipative DNA networks. The target microRNA‐21 (miRNA‐21) invades the incumbent strand and activates the strand displacement process. Released ferrocene‐modified strands bind to the probe on the electrode surface for accurate detection. The miRNA within RNA/DNA heteroduplex will then be digested by RNase H to free the incumbent strand which replaces the ferrocene strand and restores the probe to the initial state. It is found that the detection limit of this self‐resetting electrochemical sensor is 0.35 p M for the third cycle. The self‐resetting electrochemical sensor can not only achieve lower detection limits, and maintain repeatability and stability in complex matrices, but also reduce the detection cost of electrochemical sensors. It is envisioned that many real‐life applications can be initiated such as analyzing various oligonucleotide biomarkers during early cancer diagnosis and bioanalysis.