The reflection resonance spectrum of a subwavelength diffraction-grating- coupled waveguide is used to analyze biomolecular interactions in real time. By detecting this resonance wavelength shift, the optical waveguide biosensor provides the ability to identify the kinetics of the biomolecular interaction on an on-line basis without the need for extrinsic labeling of the biomolecules. A theoretical analysis of the subwavelength optical waveguide biosensor is performed. A biosensor with a narrow reflection resonance spectrum, and hence an enhanced detection resolution, is then designed and fabricated. Currently, the detection limit of the optical waveguide sensor is approximately 10-5refractive-index units. The biosensor is successfully applied to study of the dynamic response of an antibody interaction with protein G adsorbed on the sensing surface.