A combinatorial approach to validate the surface plasmon resonance (SPR) biosensor response

Abstract One of the fundamental challenges of working with surface plasmon resonance (SPR) biosensors is their inherent lack of specificity. Being very sensitive to minute refractive index (RI) changes in their surrounding medium, SPR biosensors are highly susceptible to variations in pH, temperature, and buffer composition. Therefore, it is often necessary to include an additional validation step downstream to SPR biosensing, particularly for clinical analysis. In this proof-of-study work, we have tried to evaluate the utility of surface-enhanced Raman scattering (SERS) tags as secondary labels for validating SPR biosensor response. Accordingly, a Fibre-optic SPR (FO-SPR) biosensor set-up was fabricated by immobilizing anti-BSA antibodies on the sensor platform for capturing and sensing biotinylated-BSA as a model analyte. Subsequently, the bound analyte and the concomitant shift in SPR response were validated by employing streptavidin-functionalized SERS tags. Intriguingly, apart from validation of the SPR response, the SERS tags also significantly improved the sensitivity of the SPR response and provided semi-quantitative information on the bound analyte. Although utilizing SERS tags undermines the label-free tag of SPR biosensors, the huge improvement in sensitivity and specificity of the sensor makes it suitable for clinical analysis. Furthermore, SERS measurements with a portable Raman spectrometer utilized in this study further highlight the potential of this approach for achieving point-of-care (POC) sensing.