A self-powered photoelectrochemical sensor with ultra-low background based on ZnIn2S4@CdS photoanode and Bi2WO6 photocathode for BACE1 detection.

Self-powered photoelectrochemical (PEC) sensing features no external power supply, fast response, strong anti-interference and high sensitivity, providing a powerful strategy for ultrasensitive detection of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), a key biomarker for early Alzheimer's disease (AD). In this work, a dual-photoelectrode self-powered PEC biosensor with ultralow background signal was constructed. ZnIn2S4 was grown in situ on fluorine-doped tin oxide (FTO) via hydrothermal reaction, and CdS quantum dots were loaded through successive ionic layer adsorption and reaction to fabricate ZnIn2S4@CdS/FTO photoanode. The obtained photoanode delivered a photocurrent of 279 μA, which was 2.3 times higher than pure ZnIn2S4/FTO, benefiting from superior visible light absorption and charge separation capacity. Bi2WO6@polydopamine (Bi2WO6@PDA) probes were anchored on peptide substrates in 96-well plates. When BACE1 existed, enzymatic cleavage released Bi2WO6@PDA heterojunction probes onto bare FTO photocathode to generate obvious photocurrent. In the absence of BACE1, the photocathode remained equivalent to bare FTO without Bi2WO6@PDA probe. Under visible light and zero bias, the sensor realized sensitive BACE1 detection with a linear range of 1 fg mL-1-500 pg mL-1 with a limit of detection of 0.30 fg mL-1. The biosensor possessed favorable selectivity and stability with serum sample recoveries of 96.9%-102.5%, and it could be applied to screen BACE1 inhibitors. This self-powered biosensor with near-zero background shows great application prospect in early AD clinical diagnosis.