Triple-ligand Engineered Gold Nanoclusters with Aggregation-Induced Emission for a High-Sensitivity Arginase Activity Electrochemiluminescence Biosensor

Sensitive and accurate monitoring of arginase activity is significant for clinical diagnosis. Herein, a dual-enhanced aggregation-induced electrochemiluminescence (ECL) biosensor was constructed based on triple-ligand-protected gold nanoclusters (AuNCs), sequentially coating 6-aza-2-thiothymine-capped AuNCs with L-arginine (Arg) and tetraoctylammonium bromide (TOAB). This ligand-engineering strategy restricted molecular vibrations and rotations while enhancing electron transfer efficiency, leading to a stepwise increase in ECL efficiency from 23% to 30% and finally to 71%. The hydrolysis of Arg, catalyzed by arginase, leads to dramatic quenching in the dual-enhanced ECL signal, forming the basis for quantitative detection of arginase activity. It achieved an ultra-low detection limit of 1.23 × 10-7 U mL-1 with a broad linear range from 1 × 10-6 to 0.02 U mL-1. The system showed excellent selectivity, stability, and reproducibility and was successfully applied to determine arginase activity in human serum. Triple-ligand AuNCs with dual-enhanced aggregation-induced ECL open a new avenue for constructing high-performance ECL detection platforms.