Constraint Coupling of Redox Cascade and Electron Transfer Synchronization on Electrode‐Nanosensor Interface for Repeatable Detection of Tumor Biomarkers

Abstract Quantitative analysis of up‐regulated biomarkers in pathological tissues is helpful to tumor surgery yet the loss of biomarker extraction and time‐consuming operation limited the accurate and quick judgement in preoperative or intraoperative diagnosis. Herein, an immobilization‐free electrochemical sensing platform is developed by constraint coupling of electron transfer cascade on electrode‐nanosensor interface. Specifically, electrochemical indicator (Ri)‐labeled single‐stranded DNA on electroactive nanodonor (polydopamine, PDA) can be responsively detached by formation of DNA complex through the recognition and binding with targets. By applying the oxidation potential of Ri, nanosensor collisions on electrode surface trigger a cascade redox cycling of PDA and Ri through synchronous electron transfer, which boost the amplification of current signal output. The developed nanosensor exhibit excellent linear response toward up‐regulated biomarkers (miRNA‐21, ATP, and VEGF) with low detection limits (32 fM, 386 pM, and 2.8 pM). Moreover, background influence from physiological interferent is greatly reduced by restricted electron transfer coupling on electrode. The practical applicability is illustrated in sensitive and highly repeatable profiling of miRNA‐21 in lysate of tumor cells and tumor tissue, beneficial for more reliable diagnosis. This electrochemical platform by employing electron transfer cascades at heterogeneous interfaces offers a route to anti‐interference detection of biomarkers in tumor tissues.