Competitive immunoassay-based magneto-stress-electric coupled biosensor for ultrasensitive detection of NT-proBNP

Salivary N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a promising non-invasive biomarker for heart failure (HF); however, its ultralow concentration hinders its clinical application. In this study, a magneto-stress-electric coupled (MSEC) mechanical biosensor integrated with a competitive immunoassay (CIA) has been developed for the sensitive detection of salivary NT-proBNP. Based on the magnetostrictive effect of an Fe-Ga alloy under a uniform magnetic field, the gravitational interference on the sensor film is effectively eliminated, and the film deformation induced by specific antigen-antibody binding is significantly enhanced. Concurrently, the competitive binding between free NT-proBNP antigen and magnetic bead-NT-proBNP antigen conjugates enables the sensor to detect extremely low concentrations of free NT-proBNP with high sensitivity. The biosensor achieves an ultralow detection limit of 0.01 pg mL^-1, with excellent specificity, selectivity, stability, and batch-to-batch reproducibility. Furthermore, accurate and reproducible detection of NT-proBNP in artificial saliva samples is performed by the sensor, with recovery rates ranging from 98.0% to 103.3%. In this work, magnetic signal enhancement, stress-to-electric conversion, and competitive immunorecognition are integrated into a single sensing platform. Consequently, a novel, low-cost, and reliable strategy is established for the non-invasive and highly sensitive detection of NT-proBNP, which holds great promise for point-of-care testing and early auxiliary diagnosis of heart failure.