Improving the performance of integrated PEC biosensors by photocarrier transfer function layers with tandem nanostructure.

Improving the resolution of photoelectrochemical (PEC) sensors is vital for reliable detection in complex biomedical environments. Here, we report an integrated PEC biosensor featuring a tandem nanostructured photoelectrode composed of BiVO4 (BVO), TiO2, NiCrOx, and Ti2CO2 MXene (BTNCM), designed to enhance photocarrier transfer and surface reaction kinetics thereby improving sensor resolution. This multilayered architecture acts as a photocarrier transfer function layer, where the NiCrOx cocatalyst facilitates interfacial charge transport, while TiO2 and MXene respectively contribute to efficient charge separation and aptamer immobilization. Benefiting from these synergistic effects, the BTNCM biosensor enables ultra-sensitive detection of Alzheimer's disease (AD) biomarkers, including amyloid β40 (Aβ40), amyloid β42 (Aβ42), and tau protein, achieving detection limits down to approximately 0.03 fg/mL (S/N = 3) for Aβ40 and Aβ42, together with a high signal resolution of about 40 μA cm-2 dec-1. Mechanistic analysis reveals that small-molecular-weight analytes, like Aβ40 and Aβ42, enhance photocurrent through redox reactions, while larger molecules, such as tau protein, induce steric hindrance, resulting in suppressed PEC sensing responses. Notably, validation using clinical cerebrospinal fluid and plasma samples showed strong agreement with SimoA, a commercial ultra-sensitive immunoassay platform, demonstrating the sensor's reliability and clinical relevance. This work offers a scalable and cost-effective PEC biosensing strategy for early and precise AD diagnosis, offering a promising foundation for future applications in non-invasive precision medicine.