Cathodic electrochemiluminescence biosensing based on In₂Se₃/Ag₃PO₄ composite for sensitive detection of p-Tau181...

This study presents a highly sensitive cathodic electrochemiluminescence (ECL) biosensor for the detection of p-Tau181 protein, a critical biomarker for Alzheimer's disease. The biosensor utilizes a novel In₂Se₃/Ag₃PO₄ composite as the ECL emitter. By doping Ag₃PO₄ with In₂Se₃, the band structure is precisely modulated, which significantly enhances the ECL intensity and stability by improving charge separation efficiency and electron transfer rates. CeO₂@polydopamine (PDA) core-shell nanoparticles serve as an efficient energy acceptor, quenching the ECL signal via an ECL resonance energy transfer (ECL-RET) mechanism. The biosensor was constructed in a sandwich immunoassay format, where the specific binding of the target p-Tau181 protein brings the CeO₂@PDA-Ab₂ conjugate into close proximity with the In₂Se₃/Ag₃PO₄-modified electrode, resulting in a concentration-dependent signal quenching. Under optimal conditions, the biosensor demonstrated a wide linear detection range from 10 pg/mL to 150 ng/mL (R² = 0.997) and an ultralow detection limit of 3.2 pg/mL (S/N = 3). It exhibited excellent specificity against potential interferents, outstanding stability, and was successfully applied to the detection of p-Tau181 in spiked human serum samples with satisfactory recovery rates. This work provides a promising and reliable platform for the early diagnosis and monitoring of Alzheimer's disease.