Zero-loss semiconductor material-enhanced ultrasensitive metasurface biosensor for ultrahigh-affinity assessment of antibody-drug conjugates

The pursuit of biopharmaceutical in vitro efficacy evaluation has been significantly hindered by the lack of sensitive detection technologies, particularly in the field of high-affinity drug discovery and development. In this study, we developed a novel biosensor-zero-loss semiconductor materials-enhanced ultrasensitive metasurface plasmon resonance (ZLSMSPR). A metasurface was constructed based on the nanocup array structure of the ZLSMSPR chip, and light loss was minimized due to the zero-extinction coefficient property of Nb₂O₅, thereby amplifying the local SPR effect of the chip and enhancing refractive index sensitivity by 30 times. Additionally, we successfully optimized the grafting density of carboxylated dextran on the ZLSMSPR chip. This enhancement improved the immobilized ligand loading capacity, resulting in an impressive limit of detection (LOD) of 0.018 μg/mL. Furthermore, the ZLSMSPR platform was effectively applied to accurately evaluate the affinity of antibody-drug conjugates (ADCs) to their tumor targets and to closely monitor changes in affinity changes before and after the conjugation of cytotoxic drugs to the antibody. Notably, the developed ZLSMSPR biosensor demonstrated the capability to evaluate high-affinity interactions, with a sensitivity as low as 44.5 pM, underscoring the platform's potential for efficient, label-free, and highly sensitive in vitro evaluations.