An OR-logic-gated polarity-switching biosensor for multiplexed dual-mode thalassemia screening

The concurrent detection of multiple thalassemia mutations remains challenging due to the limitations of conventional single-readout biosensors in terms of reliability and sensitivity. Herein, we report an intelligent photoelectrochemical (PEC)/colorimetric dual-mode biosensor that integrates an OR logic gate with a DNAzyme Walker cascade amplification strategy, built on a proposed Z-scheme Bi₂S₃/Bi-BiOI heterojunction whose proposed Z-scheme charge-transfer pathway is supported by Mott-Schottky and photovoltage measurements. The OR logic gate enables parallel recognition of CD142 and CD41-42 mutations, outputting a unified trigger to initiate a nicking enzyme-assisted DNAzyme Walker. This autonomous machinery releases abundant G-quadruplex/hemin (G4-hemin) complexes, serving as a bifunctional signal transducer. Notably, the specific binding of G4-hemin to the electrode interface induces a distinct anodic-to-cathodic photocurrent polarity switching, which, coupled with its intrinsic peroxidase-mimicking activity, allows for self-validated dual-signal output. The platform achieves limits of detection down to 28.7 aM (PEC) and 2.6 fM (colorimetric) across a wide linear range (0.1 fM-0.1 μM). Furthermore, the dual-mode design effectively eliminates false positives through signal cross-validation. Practical application in human serum yielded satisfactory recoveries (94.1-107.8%), highlighting the platform's potential for high-precision genetic screening in resource-limited settings.