The advancement of pragmatic and highly-sensitive electrochemiluminescence (ECL) biosensors depends upon signal tags with high and stable signal intensity. Herein, enhanced ECL emission was obtained by encapsulating the dual-stabilizer-capped CdS QDs in a metal-organic framework (MOF), which served as a valid ECL signal tag for detecting biomarkers. Dual-stabilizer-capped CdS QDs reduce dangling bonds on the surface and improved the ECL emission. Furthermore, functionalized isoreticular metal-organic framework-3 (IRMOF-3) can not only load a large quantity of CdS QDs through the encapsulation capability but also serves as a co-reaction accelerator to promote the formation of more SO4•− from the S2O82−, further improving the ECL emission of QDs, while the integrated design of IRMOF-3 co-reaction accelerator and CdS QDs effectively shortens the electron transfer pathway and reduces the energy consumption in ECL system. Using human epithelial protein 4 (HE4) as the model of analysis, the biosensor demonstrated a broad linear range (50 fg mL−1∼50 ng mL−1) and a low detection limit (9.89 fg mL−1) under optimal operating conditions. The study provides an effective and alternative method to improve the ECL efficiency of QDs, significantly broadening their potential applications in sensing analysis, medical diagnostics, and bioimaging.
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