A Comparative Approach to Assess the Particle Size Effect on Performance of Immunoaffinity Surface Plasmon Sensor

Abstract This study investigates the impact of silica nanoparticle (SiNP) size on optimizing surface plasmon resonance (SPR) sensor performance, a highly sensitive technology for biological detection. Although metallic nanoparticles enhance SPR through localized plasmon generation, they can obscure the specific influence of nanoparticle size. To isolate this effect, optically transparent and non‐conductive SiNPs, which do not support localized plasmon resonance, were chosen to minimize perturbations in evanescent light propagation and ensure that observed enhancements arise solely from nanoparticle size variations. SiNPs with diameters of 57, 65, and 80 nm were synthesized via the Stöber method and integrated into SPR chips. Comprehensive characterization, including zeta potential, contact angle analysis, FTIR, and SEM, confirmed successful nanoparticle integration. Real‐time immunoaffinity detection using immunoglobulin G (IgG) as the model analyte showed the SiNP57@anti‐IgG sensor exhibited superior sensitivity and detection limits. This improvement is attributed to the higher surface area‐to‐volume ratio of smaller SiNPs, which enhances analyte capture density, leading to a greater local refractive index change and a more pronounced resonance angle shift (∆R). Kinetic and equilibrium studies showed enhanced binding affinity for sensors with smaller SiNPs, underscoring the crucial role of nanoparticle size in improving SPR sensor performance and optical biosensing technologies.