Muhammad Saqib, Wenxin Chen, Yun Lei, Ai‐Lin Liu
Chemiluminescence (CL) assays are often constrained by the limited availability of coreactants that combine strong signal amplification with biocompatibility. Herein, we report for the first time that sericin, a natural protein derived from silk, serves as a highly efficient coreactant in the lucigenin CL system under alkaline conditions. Impressively, this new lucigenin–sericin CL system generates an unprecedented ∼43-fold higher emission intensity compared to the traditional lucigenin–hydrogen peroxide system. Moreover, the mechanistic studies reveal that sericin, with its electron-rich functional groups, significantly promotes the generation of superoxide radicals (O 2 •– ). This, in turn, accelerates the lucigenin oxidation pathway, leading to significant enhancement in CL signal. Leveraging this enhanced system, we developed a dual-function CL platform for the ultrasensitive detection of sericin (limit of detection, LOD = 0.12 μM) and superoxide dismutase (SOD, LOD = 0.28 ng/mL), exhibiting an extended linear range spanning from 0.25 to 50 μM and 0.5 to 60 ng/mL, respectively, the latter based on CL quenching phenomena. This method offers compelling superiority in terms of simplicity, rapid analysis, enhanced sensitivity, higher selectivity, and cost-effectiveness. Moreover, this method successfully achieved the detection of sericin in cosmetics and the SOD in human serum samples. Importantly, this work represents the first chemiluminescent method for sericin detection. In addition, the system exhibited high sustainability and practical utility, as confirmed by AGREE (greenness) and BAGI (blueness) assessment tools. Furthermore, it introduces a new class of protein-based coreactants for CL systems, expanding the frontier of (bio)analytical detection.