Patent ID: 7663092

Claim:
A label-free phase-contrast quadrature interferometric method of detecting the presence or absence of a target analyte in a biological sample, comprising: exposing a reflecting surface of a substrate to the biological sample, the reflecting surface having a spatial pattern of coatings of receptor molecules, each coating specific to a particular target analyte; and using a split-photodetector to measure intensity in a far-field diffraction pattern of a reflected signal resulting from a focused probe laser beam having a wavelength λ that is incident with waist w 0 on the spatial pattern of coatings of receptor molecules while scanning at least a portion of the substrate; wherein intensity is measured of a portion of the reflected signal in a substantially quadrature condition by measuring intensity with the split-photodetector of at least one of two observation angles substantially equal to a pair of quadrature angles, the quadrature angles ⊖ q being defined from a ray normal to the substrate by a formula: ⊖ q =sin −1 (λ/2 w 0 ).