Self-referencing SPR biosensing with an ultralow limit-of-detection using long-wavelength excitation

There is an urgent need of label-free technique with low limit of detection (LOD) for biomedical research and early clinical diagnostics. Surface plasmon resonance (SPR) as a label-free approach has been exploited in DNA determination, but the LOD of most SPR sensors is inferior to labeling approaches. A novel approach for SPR biosensing with low LOD was reported in the present study. SPR for long wavelength excitation is theoretically and experimentally demonstrated to possess a high refractive index sensitivity of 11773.93 nm/RIU due to the long decay length of the electromagnetic field near the metal surface, which is optimized by an order of magnitude compared to traditional SPR sensor. Subsequently, self-referencing sensing strategy was employed to eliminate cross-sensitivity problem and further improve sensing accuracy significantly. Finally, we focused on using this sensor to measure DNA hybridization events using graphene oxide-assisted Au nanoparticle conjugates as signal amplification tags. It achieves a large dynamic range of 10(-15)-10(-11) M and a low LOD of 0.2 fM for target DNA determination. The proposed SPR sensing architecture is technologically simple, highly sensitive and extensively appropriate for existing SPR instrumentation, so it has a great potential for low LOD of various biomolecules.

Automated summary

A novel SPR biosensing approach with low LOD, high sensitivity, and extensive applicability was introduced in this study. By optimizing the SPR sensor structure and employing a self-referencing sensing strategy, the low LOD of 0.2 fM was achieved.