Duplex‐Specific DNase Signal Amplification Allows Attomolar Electrochemical Detection of MicroRNAs

Abstract Point‐of‐care biosensors for detecting blood‐circulating nucleic acids hold significant potential for disease diagnosis. However, achieving both high sensitivity and accessibility remains a challenge. Electrochemical hybridization assays offer a promising approach for detecting specific nucleic acid sequences but are typically limited to picomolar concentrations. Here, a duplex‐specific DNase‐assisted electrochemical hybridization assay is presented, enabling highly sensitive nucleic acid detection. By incorporating duplex DNase, the method achieves detection limits as low as 1 attomolar, significantly enhancing sensitivity. This work paves the way for ultrasensitive nucleic acid detection in critical point‐of‐care applications.