Simultaneous Detection of Ovarian Cancer-Concerned HE4 and CA125 Markers Based on Cu Single-Atom-Triggered CdS QDs and Eu MOF@Isoluminol ECL

Simultaneous detection of different disease markers is significant for clinical diagnosis. In this work, a dual-signal electrochemiluminescence (ECL) immunosensor was constructed for the simultaneous detection of carbohydrate antigen 125 (CA125) and human epithelial protein 4 (HE4) markers of ovarian cancer. The results showed that the Eu metal–organic framework-loaded isoluminol–Au nanoparticles (Eu MOF@Isolu–Au NPs) could generate a strong anodic ECL signal through synergistic interaction; as cathodic luminophore, the composite of carboxyl-functionalized CdS quantum dots and N-doped porous carbon-anchored Cu single-atom catalyst could catalyze H₂O₂ co-reactant to produce a large amount of ^•OH and O₂^•–, making the anodic and cathodic ECL signals significantly increase and become stable. Based on the enhancement strategy, a sandwich immunosensor was constructed for the simultaneous detection of ovarian cancer-associated CA125 and HE4 markers by combining antigen–antibody specific recognition and magnetic separation technique. The resulting ECL immunosensor displayed high sensitivity, a wide linear response range of 0.005∼500 ng mL^–1, and low detection limits of 0.37 and 1.58 pg mL^–1 for CA125 and HE4, respectively. Furthermore, it had excellent selectivity, stability, and practicability in the detection of real serum samples. This work establishes a framework for in-depth design and application of single-atom catalysis in ECL sensing.