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A phase contrast quadrature interferometric method and apparatus for determining the presence or absence of a target analyte in a sample. The method includes probing a substrate exposed to the sample with a laser beam. The substrate includes a reflecting surface with a first region having recognitio

A phase contrast quadrature interferometric method and apparatus for determining the presence or absence of a target analyte in a sample. The method includes probing a substrate exposed to the sample with a laser beam. The substrate includes a reflecting surface with a first region having recognition molecules specific to the target analyte and a second region without recognition molecules. The method also includes probing the first and second region, and measuring time dependent intensity on a photodetector at one or both of a pair of quadrature angles of a reflected diffraction signal. The apparatus includes a laser source, a platform for receiving the planar array, an objective lens offset from the platform by approximately a focal length, and a split photodetector means for measuring a first quadrature and a second quadrature in a signal resulting from reflection of the laser beam.

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What is claimed is: 1. 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

What is claimed is: 1. 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 w0 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/2w0). 2. The method of claim 1, further comprising inverting an output of the split-photodetector at one of the pair of quadrature angles and summing the inverted output with an output of the split-photodetector at the other of the pair of quadrature angles. 3. The method of claim 2, further comprising passing the reflected signal through an objective lens prior to measuring intensity using the split-photodetector. 4. The method of claim 3, wherein intensity measurement of the far-field diffraction pattern of the reflected beam is done in a Fourier plane. 5. The method of claim 1, wherein the substrate is a disk and scanning of the substrate is done by rotating the disk. 6. A quadrature interferometric method for determining the presence or absence of a target analyte in a sample, comprising: using a laser beam having a wavelength λ and a waist wo to probe at least a portion of a substrate having a reflecting surface that has been exposed to the sample, the reflecting surface including at least a first region having a layer of recognition molecules specific to the target analyte and a second region that does not include a layer of recognition molecules specific to the target analyte; and measuring a time dependent intensity on a photodetector of a substantially only first quadrature at one of a pair of quadrature angles ⊖q of a reflected diffraction signal of the probe beam while probing the first region and the second region. 7. The method of claim 6, wherein the time dependence arises from a relative motion of the incident laser beam with respect to the substrate. 8. The method of claim 7, wherein the substrate is a disk and the relative motion of the disk with respect to the incident laser beam is generated by rotating the disk. 9. The method of claim 8, wherein the reflected diffraction signal of the laser beam is measured using a split-photodetector configuration, further comprising inverting a first output portion of the reflected signal corresponding to the one of the pair of quadrature angles, and summing the inverted first output with a second output of the reflected signal corresponding to the other of the pair of quadrature angles. 10. The method of claim 9, wherein the substrate is a disk and the reflected diffraction signal is passed through an objective lens prior to measuring the intensity. 11. The method of claim 7, further comprising passing the reflected diffraction signal of the probe beam through a π/2 phase mask prior to measuring the intensity. 12. The method of claim 6, wherein the reflecting surface is substantially flat and the quadrature angles are defined from a ray normal to the substrate by a formula: ⊖q=sin−1(λ/2wo). 13. The method of claim 6, wherein the substrate is a disk and the reflecting surface of the disk includes a plurality of lands and a plurality of ridges, the ridges having a height h, and the quadrature angles are defined from a ray normal to the substrate by a formula: ⊖q=sin−1[(λ/2−4h)/wo]. 14. A phase-contrast quadrature interferometric step-detection method of determining the presence or absence of a target analyte in a sample, comprising: measuring time dependent intensity of a far-field diffraction pattern of a reflected light signal resulting from a probe laser beam incident on a disk having a spatial pattern of recognition molecules using a split photodetector configuration, and summing contributions from a first quadrature and a second opposing quadrature of the resulting light signal, the summing of the contributions being preceded by inversion of the contribution of the first quadrature. 15. The method of claim 14, wherein intensity is measured of the resulting light signal that is reflected from a reflecting surface of the disk. 16. The method of claim 15, wherein the split photodetector configuration is a split-ring photodetector. 17. The method of claim 15, wherein the split photodetector configuration is a quadrant photodetector. 18. The method of claim 15, wherein the split photodetector configuration includes a first and a second photodetector, the probe beam having a wavelength λ and a waist wo incident on the disk, the first and second photodetectors measuring intensity at substantially a pair of quadrature angles ⊖q, the quadrature angles being defined from a ray normal to the disk by a formula ⊖q=sin−1(λ/2wo). 19. The method of claim 15, wherein time dependent intensity is measured by rotating the disk. 20. The method of claim 19, wherein the disk is rotating at about 80 Hz. 21. A phase-contrast quadrature interferometric step-detection method of determining the presence or absence of a target analyte in a sample, comprising: measuring a time dependent difference at substantially a first quadrature interference angle of a first portion of a reflected light signal of a substantially only first quadrature, the reflected light signal resulting from tracing a laser beam across alternating regions of a specific antibody and a non-specific antibody on a planar array. 22. The method of claim 21, further comprising measuring a time dependent difference at substantially a second quadrature interference angle of a second portion of the reflected light signal of a substantially only second quadrature resulting from the tracing of the laser beam across alternating regions of the planar array. 23. The method of claim 22, further comprising inverting a first output of the first portion of the reflected light signal; and summing the inverted first output with a second output of the second portion of the reflected light signal. 24. A scale free label free quadrature interferometric step-detection method of determining the presence or absence of a target analyte in a sample, comprising: using a focused laser beam having an incident waist wo and a wavelength λ to scan a disk having a spatially patterned layer of receptor molecules specific to the target analyte, the layer having a substantially sharp layer edge; and detecting intensity change in a far-field diffraction pattern caused by scanning the substantially sharp layer edge using a split photodetector configuration, the split photodetector configuration providing an output of the far-field diffraction pattern at substantially at least one of a pair of quadrature interference angles defined from a ray normal to the disk. 25. A quadrature interferometric method of determining the presence or absence of a target analyte in a sample, comprising: measuring an output of a first photodetector aligned in an optical train to receive a substantially only first quadrature of a reflected light signal resulting from observing at substantially a first quadrature angle the reflected light signal resulting from a probe laser beam having a wavelength λ and a waist wo incident on a planar array having at least one ridge defined by a layer of receptor molecules specific to the target analyte, wherein quadrature angles ⊖q are defined from a ray normal to the planar array by a formula: ⊖q =sin−1(λ/2wo). 26. The method of claim 25, further comprising measuring an output of a second photodetector aligned in the optical train to receive a substantially only second opposing quadrature resulting from observing at substantially a second quadrature angle the reflected light signal. 27. The method of claim 26, further comprising inverting the output of the first photodetector; and summing the inverted output of the first photodetector with the output of the second photodetector. 28. The method of claim 26, wherein the optical train includes an objective lens. 29. The method of claim 28, wherein the first and second photodetectors are measuring the far-field diffraction pattern of the reflected light signal in a Fourier plane.