A fast, accurate and reliable sensor applicable to chemical and biological analytes resides in an optical grating-based sensor, sensing system, and method of use. The sensor, configured for use with an illumination source and a signal detector in the system embodiment, includes first and second periodic diffraction gratings superimposed and shifted laterally relative to each other by a distance of less than one period, such that the illumination from the source is affected by both gratings before reaching the detector. An analyte recognition material disposed on a surface of the second diffraction grating. In operation, the output of the detector is first used to establish a baseline optical phase signal. The analyte recognition material is exposed to a sample, and the output of the detector is used to to determine a second optical phase signal. The baseline optical phase signal is compared to the second optical phase signal to detect the presence of the analyte, if any, in the sample. The analyte recognition material may be an antibody, nucleic acid, lectin or other substance. The sample may obtained from a mammal, including a human, plant, or the environment.