Wide dynamic range phase-sensitive surface plasmon resonance biosensor based on measuring the modulation harmonics

In this study, a novel phase-sensitive surface plasmon resonance (SPR) setup, based on temporal modulation of a pumping beam by a photoelastic modulator, and subsequent extraction of phase information at the second and the third harmonics of the modulation frequency, has been developed to study biomolecular interactions on SPR-supporting gold. We demonstrated that the design setup provides ultra-high phase sensitivity, together with a wide dynamic range of measurements. In particular, the proposed scheme was used to study real-time interaction of biotin–protein and streptavidin–BSA complexes. We have found that the proposed technique has a detection limit as high as 2.89 × 10−7 in terms of refractive index units (RIU). In terms of biosensing performance, a detection sensitivity of 1.3 nM from the streptavidin–maleimide/thiolated BSA complex binding reaction has also been demonstrated.