Detection of biomolecular binding by fourier-transform SPR

Surface plasmon resonance (SPR) is a widely used label-free detection technique that has many applications in drug discovery, pharmacokinetics, systems biology and food science. The SPR technique measures the dynamics of a biomolecular interaction at a surface, yielding kinetic association and dissociation constants. Present SPR systems measure the step response of the interaction in time domain hence are subject to time-varying noise disturbances and drifts that limit the minimum-detectable mass changes. This paper presents a new synchronous SPR technique that measures the biomolecular interaction not in time domain, but in frequency domain with a high degree of rejection to uncorrelated spurious signals. The new technique was implemented using a PDMS microfluidic chemical signal modulator chip connected to a set of on-chip functionalized Au SPR sensing sites. Preliminary experimental spectral data for a model system of carbonic anhydrase binding demonstrates the feasibility of the new spectral technique.