A Scandium-Doped Gold Nanocluster with Enhanced Electrochemiluminescence Triggered by Low Potentials for Ultrasensitive Detection of an Alzheimer’s Biomarker in Urine

The development of high-performance electrochemiluminescence (ECL) systems operating at low triggering potentials remains a critical challenge for advancing their practical applications in bioassays. In this study, a novel ECL system based on a scandium-doped gold nanocluster (Sc@AuNC) and <i>N</i>,<i>N</i>-diisopropylethylamine (DIPEA) had been designed for ultrasensitive detection of urinary Alzheimer's disease-associated neuronal thread protein (AD7c-NTP). By using DIPEA as a low-oxidation-potential coreactant and synergistic doping of Sc to promote free radical generation in the coreactant through accelerated electron transfer, the Sc@AuNC/DIPEA system achieved a 40.89-fold enhancement in ECL intensity and a higher ECL quantum yield (Φ_ECL) of 35.19% at 0.75 V, surpassing conventional AuNC systems. Utilizing this system, a sandwich-type ECL immunoassay (ECLIA) platform was developed, demonstrating a linear detection range of 0.001 to 100 ng/mL for AD7c-NTP with a detection limit of 0.45 pg/mL (S/N = 3). Owing to the low triggering potential, the ECL system exhibited inherent anti-interference capability by minimizing electrochemical side reactions and preserving biomolecular integrity, as evidenced by stable signals in complex urine matrices. Critically, the satisfactory recovery of clinical urine samples and high correlation with ELISA kits confirmed the utility of the constructed detection platform. This work not only advances ECL technology through coreaction acceleration but also provides a practical, scalable strategy for early Alzheimer's disease screening.