Surface-plasmon optical-heterodyne clock biosensor

Surface-plasmon resonance (SPR) sensors represent a formidable technology for molecular biology and bioanalytics applications. Here, we devise a new interrogation architecture that transforms a standard SPR chip into an optical-heterodyne clock detector comparable with the best SPR instruments. The key ingredients are (i) the conversion of refractive-index changes on the SPR chip into frequency shifts of an oscillatory electronic signal (ii) a differential probe & reference optical-cavity scheme that cancels out most source/detector noise contributions. A rigorous characterization of the sensor performance with the integration time demonstrates a refractive-index resolution on the 10−8-RIU level over a 1-s timescale using a bare, unstabilized SPR element. A bio-sensing test with a functionalized surface interfaced with a microfluidic flow-cell is carried out, showing detection of streptavidin via covalent bond down to concentrations of 90 fg/mm2.