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

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.