Electrochemiluminescence Biosensor Based on Dual-Signal Regulation of Gold Nanoclusters for Amyloid-β Protein Detection

Gold nanoclusters (AuNCs) are emerging electrochemiluminescence (ECL) emitters with unique luminescence and high stability. However, conventional AuNC-based ECL systems, which rely on single-signal regulation, often exhibit weak signal responses and limited stability. To address the challenge of detecting extremely low concentrations of the Alzheimer’s disease (AD) blood biomarker Aβ40, this study presents a novel ECL-based biosensing platform that leverages dual-signal regulation of AuNCs via glutathione (GSH) and H2O2 serving as ECL quenchers. Based on the peroxidase-like activity of the Aβ40–hemin complex, this system restores the ECL signal by catalyzing the consumption reaction between GSH and H2O2. Using this mechanism, a dual-regulation ECL platform was developed, demonstrating a linear detection range of 0.001–100 ng/mL for Aβ40 with a detection limit of 0.18 pg/mL (S/N = 3). This approach not only offers high sensitivity and specificity but also reduces the complexity of surface modification steps. Overall, this study advances ECL technology through dual regulation and provides a sensitive, practical, efficient, and reliable analytical method for early AD screening.