Qingfei He, Lingjun Cheng, Yuanyuan Yang, Zhiyan Zou, Canping Su, Xuan Shi, Jiaming Chen, Weirong Huang, Zhenyu Lin, Guolin Hong
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 H 2 O 2 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 H 2 O 2 . 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.