Metasurface Plasmon Resonance Biosensor Enhanced with Dual Gold Nanoparticles for the Ultrasensitive Quantitative Detection of C-Reactive Protein

The pursuit of cutting-edge diagnostic systems capable of detecting biomarkers with exceptional sensitivity and precision is crucial for the timely and accurate monitoring of inflammatory responses. In this study, we introduce a dual gold nanoparticle-enhanced metasurface plasmon resonance (Bi-MSPR) biosensor for the ultrasensitive detection of C-reactive protein (CRP). The Bi-MSPR sensor is constructed upon a nanocup array chip with gradient-free electron density, where an innovative metasurface structure is built using a PEI-immobilized dual-gold nanoparticle amplification system. This strategy greatly amplifies the local free electric field, resulting in a signal enhancement exceeding 10-fold, with a detection limit of 0.04 ng/mL for CRP in buffer solutions and 0.017 μg/mL for serum samples. Clinical validation demonstrates a 95.83% detection rate with no cross-reactivity, highlighting the sensor’s remarkable specificity and sensitivity for CRP detection. The Bi-MSPR biosensor thus represents a rapid, sensitive, and specific diagnostic tool for CRP detection.