Bioinspired rational spatial-arrangement of antigens enables the accurate and rapid detection of anti-p53 autoantibody.

A highly sensitive antibody detection strategy is presented that leverages the rational spatial arrangement of antigens at the sensing interface. Specifically, we employed rigid benzene ring-based coupling agents, carefully controlling their density and orientation on the biosensing interface to establish a well-defined spatial arrangement of receptor molecules, thereby enhancing antibody binding efficiency. Additionally, we utilized Au-decorated MoS2 nanosheets as an effective electrode modification, which also function as contact points for regulating the coupling agents. By optimizing both the electrode materials and the spatial arrangement of receptor molecules, our strategy enabled the precise and rapid detection of anti-p53 autoantibodies (anti-p53aAbs) in spiked plasma samples, achieving a broad linear range from 0.05 to 10 ng/mL and a low detection limit of 16.67 pg/mL, surpassing the performance of most existing methods. Notably, we introduce a biomimetic strategy for the spatial arrangement of antigens, inspired by the bionic recognition mechanism. This design effectively reduces steric hindrance between antibody molecules, enhances binding efficiency, and provides a novel approach for the rapid and sensitive detection of macromolecules, such as antibodies.