Surface plasmon resonance (SPR) biosensors are a key advancement in optical sensing technology for label-free biomolecular detection. Real-time analysis using these sensors is highly sensitive to changes in refractive index. Over the last two decades, in-depth research on nanofabrication and plasmonic engineering has enabled improvements in the detection limits of analytes from micromolar to femtomolar and even attomolar concentrations. However, the physical origins of these enhancements and the factors that ultimately limit sensitivity are frequently examined in isolation. This review brings together recent advances in a noise-sensitivity framework, demonstrating that the limits of detection are set by the balance between electromagnetic-field confinement and measurement stability. Existing studies highlight three main ways to improve the performance of SPR optical sensors: field engineering strategies that enhance resonance response, signal amplification strategies that amplify refractive index perturbations, and hybrid designs that combine both effects to achieve multiple benefits. The next-generation SPR platforms may get closer to detecting single molecules in normal conditions by combining wave physics, materials engineering, and computational optimization. This could change the future of label-free diagnostics with more diversified utilization of SPR-based sensing technologies for (bio)analyte detection.
Garg et al. (Thu,) studied this question.