Inverse-designed plasmonic biosensors with LSPR-SPP-wood anomaly coupling enhanced for biomolecular analysis.

Investigating molecular interactions is crucial for advancing biological research and therapeutic discovery. Traditional analytical techniques often face limitations in sensitivity, quantification accuracy, and simplicity. Metasurfaces support resonances that are widely explored both for far-field wavefront shaping and for near-field sensing. Here, we introduce an innovative inverse-designed multilayer metasurface plasmon resonance (IDMM-SPR) sensor that overcomes these challenges. Using a double-objective optimization method that combines numerical simulations and machine learning, we developed an IDMM-SPR sensor featuring an optimized periodic nanocup array. This design yields unparalleled sensitivity and stability by harnessing collective resonances-including localized SPR, Wood's anomalies, and the Bloch wave SPR-which collectively enhance the sensing performance to enable the analysis of ultra-high affinity and low molecular weight interactions. The sensor achieves a figure of merit (FoM) of 26.3 and a detection limit (LOD) for C-reactive protein (CRP) as low as 0.84 ng/mL. Its compatibility with microplate absorbance readers and imaging detection makes it highly practical. The IDMM-SPR sensor shows exceptional promise for high-throughput direct molecular fishing, drug development, and disease diagnosis, offering a powerful tool for real-time, label-free affinity detection and quantitative analysis of biomolecular interactions.