A coupled waveguide-surface plasmon resonance (CWSPR) biosensor constructed with sub-wavelength grating structure is developed and used to analyze biomolecular interaction in real time. The normal incident white light is coupled into the waveguide layer through the sub-wavelength grating, and hence it has an enhanced wave vector to excite the localized surface plasmons on the metal grating surface. The CWSPR biosensor with the surface plasmon resonance (SPR) mode and the waveguide mode not only retains the same sensing sensitivity as that of a conventional SPR device, but also yields sharper dips in the reflectivity spectrum and therefore provides an improved measurement precision. Moreover, without the limitation of a conventional attenuated total reflection coupler and with the help of
normal incidence, the system is more flexible and feasible for protein microarray and imaging applications.