A Robust Biosensor Based on Dual Loop Constrained Antifouling Peptide for Electrochemical Detection of Human Insulin like Growth Factor 1 in Blood

Human insulin-like growth factor 1 (IGF-1) levels in human blood serve as a reliable biomarker for assessing endogenous growth hormone secretion and are also implicated in the pathogenesis of various cancers, highlighting their broad clinical diagnostic value. However, the direct detection of IGF-1 in complex blood samples with electrochemical biosensors is challenging due to the severe biofouling and the enzymes in the blood that may cause degradation of biomolecules functionalized on the sensor surfaces. Herein, a dual-loop constrained antifouling peptide (DLC-AP) was designed and constructed through the covalent cyclization of linear antifouling peptides, and it was further used for the development of an antifouling electrochemical biosensor. The DLC-AP exhibited exceptional antifouling properties in complex biological media, and its structural stability against enzymatic degradation by proteolytic enzymes in blood significantly enhanced the stability and antifouling performance of the biosensor. The DLC-AP-based biosensor demonstrated high sensitivity for IGF-1 detection in human blood samples, achieving a linear response range of 0.1 pM to 100.0 nM with a low limit of detection (7.0 fM), and its assay results of IGF-1 levels in clinical blood samples showed agreement with the ELISA results. This strategy of peptide and biosensor design offers a promising avenue for the construction of antifouling biosensing devices for biomarker monitoring in complex human blood.