Covalent organic framework-gold nanoparticle heterostructures amplified dynamic light scattering immunosensor for ultrasensitive detection of NT-proBNP in whole blood

Immunoassay has shown great potential in the detection of various disease protein biomarkers because of its high specificity. However, the sensitivity of conventional immunoassay is relatively limited due to its insufficient colorimetric signal transduction. Herein, we report a novel dynamic light scattering (DLS) immunosensing strategy for ultrasensitive detection of protein markers based on the covalent organic framework-gold nanoparticle ([email protected]) heterostructures combined with the gold growth. By taking advantage of the unique acid response characteristics of imine-linked COF, the [email protected] is designed as a signal amplifier to boost the release of AuNPs, and then the released AuNPs are enlarged by gold growth to amplify the DLS signal transduction and thus remarkably improve the sensitivity. Combined with the double antibody sandwich magnetic immunoassay, the [email protected] DLS immunosensor successfully achieve the highly sensitive quantitative detection of N-terminal brain-type natriuretic peptide. The limit of detection reaches up to 14 fg mL−1 with the total assay time less than 2 h. The linear detection range was from 0.32 to 1000 pg mL−1, and the coefficient of variation was below 12.5%. Briefly, this immunosensor is demonstrated with high selectivity, accuracy, reproducibility, and reliability in spiked and actual whole blood samples. The [email protected] DLS immunosensing strategy holds high promise as an alternative for detecting disease biomarkers.