Signal on-off ratiometric electrochemical immunosensor based on Au@C-COFs and Thi@aCOFs for ultrasensitive IGF-1 detection.

Insulin-like growth factor-1 (IGF-1) is a critical biomarker linked to various human diseases, necessitating sensitive and reliable detection methods. Herein, we report a novel sandwich-type ratiometric electrochemical immunosensor with signal on-off capability for the ultrasensitive measurement of IGF-1. The sensor was constructed using gold nanoparticle-engineered carbonized covalent organic frameworks (Au@C-COFs) as the sensing platform and thionine-enriched alkynyl COFs (Thi@aCOFs) as the signal amplification probe. Au@C-COFs exhibited excellent electrocatalytic activity toward hydroquinone (HQ) oxidation, providing a stable internal reference signal, while Thi@aCOFs generated a concentration-dependent reporter signal upon specific recognition of IGF-1 via the immobilized aptamer. The ratiometric strategy effectively eliminated external interferences, significantly enhancing accuracy and reliability. Under optimal conditions, the biosensor displayed a wide linear range from 10 fM to 1 nM, a low detection limit of 0.45 fM (S/N = 3), good specificity, stability, and satisfactory reproducibility. Furthermore, the sensor performed well for measuring IGF-1 in diluted human serum, achieving satisfactory recoveries. This work presents a robust and adaptable platform toward ratiometric electrochemical biosensing, holding great promise to achieve clinical diagnosis and management treatment of IGF-1-related disorders.