Current-decoupling electrochemical-photoelectrochemical biosensors for the simultaneous detection of coexisting cancer biomarkers miR-155 and miR-451.

Electrochemical (EC) and photoelectrochemical (PEC) biosensors offer accuracy, convenience, and affordability, making them ideal for early cancer screening. However, in conventional EC and PEC biosensors, signal crosstalk between the photocurrent and redox currents poses a significant challenge for the simultaneous detection of multiple biomarkers, as it prevents their independent readout. Here, we present an interference-free EC-PEC biosensor that simultaneously detects the early-stage cancer biomarkers miR-155 and miR-451 using a direct hybridization method, and enhances the EC-mode signal via a hybridization chain reaction. Through ingenious design, the photocurrent generated by the poly(o-phenylenediamine) (PoPD)/WSe2 heterojunction is decoupled from the redox peak current of methylene blue, effectively avoiding signal interference and enabling separate quantification of miR-155 and miR-451. Moreover, the PEC mode employs a photocurrent polarity-switching strategy to effectively eliminate false-positive results. This current-decoupled biosensor exhibits excellent analytical performance for miR-155 and miR-451 over the range of 1.0×10°-1.0 × 105 fM, with detection limits as low as 9.0 × 10-2 fM and 3.7 × 10-1 fM, respectively. This work not only provides a new approach for early cancer screening but also offers an easy-to-use electrochemical platform for multiplexed detection of coexisting targets.