Dual-Polarity Switching Photoelectrochemical Biosensor Based on Z-Scheme Bi ₂ S ₃ /Bi ₂ WO ₆ Heterojunction for Clinical Thalassemia Screening: Cascade Signal Amplification via 3D DNA Walker and Target Recycling

The simultaneous detection of CD142 and CD41–42 mutations is critical for accurate diagnosis and precision medicine but remains challenging due to the ultralow target abundance in early stage screening. Here, we develop a dual-polarity switching photoelectrochemical biosensor based on a photocurrent polarity-switching strategy, achieving ultrasensitive dual-target detection of thalassemia genes CD142 and CD41–42 through a “cathodic-anodic-cathodic” tristate conversion. This sensor innovatively integrates a Z-scheme Bi 2 S 3 /Bi 2 WO 6 heterojunction substrate with an Ag 2 S quantum dots (anodic)/Cu 2 O (cathodic) labeling system, combined with a target-triggered cascaded nucleic acid amplification strategy: target-driven toehold-mediated strand displacement reaction with exonuclease III-assisted target cycling (TSDR-EATC) and 3D DNA walker, converting background interference into characteristic signals with self-calibration capability. Experiments demonstrate that the sensor exhibits excellent linear response in the range of 0.1 fM-0.1 μM, with detection limits of 30.9 aM (CD142) and 27.8 aM (CD41–42). Clinical sample validation shows a recovery rate of 98.0–107.9% and an RSD of ≤4.8%, and the correct rate in double-blind tests exceed 93%. This work establishes a new paradigm for polarity-switchable PEC systems by integrating heterojunction engineering with nucleic acid amplification, providing a highly reliable solution for the community screening of thalassemia.