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In this paper, we present a waveguide-surface plasmon resonance biosensor. A 450nm period sub-wavelength metallic gratings (SWMGs) were fabricated by nanoimprint, which was then applied to detect the protein layer capping on the grating. Both our measurement and simulation results indicate that the resonance does exist for 450nm pitched gratings. A resonance shift in surface plasmon resonance (SPR) curves of protein films with different refractive indices were investigated, which would be promisingly applied in protein, DNA or drug test. Moreover, a novel angle of incidence (AOI) based detection method was developed to help reduce the cost of the expensive detecting devices.