Method and apparatus for phase contrast quadrature interferometric detection of an immunoassay

摘要

A phase contrast quadrature interferometric method for determining the presence or absence of a target analyte in a sample. The method comprises using a laser beam having a wavelength lambda and a waist w_o to probe at least a portion of a substrate having a reflecting surface that has been exposed to the sample. The reflecting surface includes 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. The method further comprises 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. An apparatus for phase-contrast quadrature interferometric detection of the presence or absence of a target molecule on a planar array, comprises a laser source for generating a probe beam. The apparatus includes a platform for receiving the planar array and a first optical train for directing the probe beam at the platform in a substantially surface normal manner. The apparatus also includes an objective lens having a first side and a second side and having a focal length, the objective lens being offset on the first side of the lens from the platform by a first distance approximately equal to the focal length. The apparatus further includes split photodetector means for measuring a first quadrature and a second quadrature in a signal resulting from reflection of the probe laser beam.