Abstract: Motility contrast imaging (MCI) is a depth-resolved holographic technique to extract cellular and subcellular motion inside tissue. The holographic basis of the measurement technique makes it highly susceptible to mechanical motion. The motility contrast application, in particular, preferably includes increased mechanical stability because the signal is based on time-varying changes caused by cellular motion, not to be confused with mechanical motion of the system. The use of the resulting spectrogram response signatures, or “fingerprint” data, of known compounds is disclosed to screen new compounds for leads as to those having potentially beneficial mechanisms of action. The “fingerprint” data of known toxic compounds can be used to screen new compounds for toxicity.

Abstract: Motility contrast imaging (MCI) is a depth-resolved holographic technique to extract cellular and subcellular motion inside tissue. The holographic basis of the measurement technique makes it highly susceptible to mechanical motion. The motility contrast application, in particular, preferably includes increased mechanical stability because the signal is based on time-varying changes caused by cellular motion, which should not be confused with mechanical motion of the system. Apparatus for motility contrast imaging that provides increased mechanical stability is disclosed. It is based on common-path configurations, in which the signal and reference beams share optical elements in their paths to the detector. The two beams share mechanical motions in common, and hence these motions do not contribute to the signal.

Abstract: A method of probing a plurality of analyzer molecules distributed about a detection platform is disclosed. The method includes contacting a test sample to the plurality of analyzer molecules, scanning the plurality of analyzer molecules at a rate relating to a carrier frequency signal, and detecting the presence or absence of a biological molecule based at least in part upon the presence or absence of a signal substantially at a sideband of the carrier frequency signal. A molecule detection platform including a substrate and a plurality of targets positioned about the substrate is also disclosed. Specific analyzer molecules adapted to bind a specific analyte are immobilized about a first set of the targets. Nonspecific analyzer molecules are immobilized about a second set of the targets. The targets positioned about the substrate along at least a segment of a scanning pathway alternate between at least one of the first set and at least one of the second set.

Abstract: A multi-modal data acquisition system for detecting target material on a biological reaction surface, the system comprising a radiation source for generating an incoming beam that impinges on the biological reaction surface at an oblique incidence angle and produces a reflected beam, an interferometric detector for detecting an interferometric signal from the illuminated surface, the reflected beam being directed to the interferometric detector, a fluorescence detector for detecting a fluorescence signal from the illuminated surface; the fluorescence detector being positioned to substantially minimize the incidence of the reflected beam; and a processing system for receiving the interferometric and fluorescence signals and determining the presence or absence of target material on the biological reaction surface. A reaction surface conditioned for the simultaneous collection of fluorescence, interferometric and other signals.

Abstract: A planar array having plurality of biological recognition molecules including at least two types of biological recognition molecules distributed about a substrate is disclosed. A first type of biological recognition molecules is distributed according to a first frequency and a second type of biological recognition molecules is distributed according to a second frequency. Another planar array having a plurality of biological recognition molecules including at least two kinds of biological recognition molecules is disclosed. The recognition molecules are distributed about a substrate with first kind of biological recognition molecules distributed at a first height or depth relative to a surface of the substrate and a second kind of biological recognition molecules distributed at a second height or depth relative to the surface.

Abstract: A system for motility contrast imaging a biological target within tissue comprising a CCD array; an illumination source for generating an incoming beam; a first beam splitter for receiving the incoming beam and producing an object beam and a reference beam; a second beam splitter for illuminating a multitude of biological targets with the object beam and for directing backscattered object beams towards the CCD array; a computer-controlled delay stage for zero-path-matching the reference beam to the backscattered object beams; a reference beam that intersects the backscattered object beams at an angle to produce a series of interference fringes that modulate Fourier-domain information; and a computer for receiving a time series of Fourier-domain information. The interference fringes between the backscattered object beam and the reference beam are recorded by the CCD array and passed to the computer which constructs a digital hologram at successive times.

Abstract: A detection system for detecting target material is provided. The system comprises a photonic structure having a reflectance-band and associated side bands; an illumination source for illuminating at a wavelength in at least one of an edge of the reflectance-band and the side bands of the photonic structure and for generating a return beam; a detector system having an intensity-sensitive channel configured to detect an in-line signal from the return beam and a phase-sensitive channel configured to detect a differential phase contrast signal from the return beam; and a processing system for receiving and adding in quadrature the in-line signal and the differential phase contrast signal to generate a joint signal, and for determining one of the presence or the absence of the target material on the photonic structure using the joint signal.

Abstract: A multi-modal data acquisition system for detecting target material on a biological reaction surface, the system comprising a radiation source for generating an incoming beam that impinges on the biological reaction surface at an oblique incidence angle and produces a reflected beam, an interferometric detector for detecting an interferometric signal from the illuminated surface, the reflected beam being directed to the interferometric detector, a fluorescence detector for detecting a fluorescence signal from the illuminated surface; the fluorescence detector being positioned to substantially minimize the incidence of the reflected beam; and a processing system for receiving the interferometric and fluorescence signals and determining the presence or absence of target material on the biological reaction surface. A reaction surface conditioned for the simultaneous collection of fluorescence, interferometric and other signals.

Abstract: 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.

Abstract: A multi-modal data acquisition system for detecting target material on a biological reaction surface, the system comprising a radiation source for generating an incoming beam that impinges on the biological reaction surface at an oblique incidence angle and produces a reflected beam, an interferometric detector for detecting an interferometric signal from the illuminated surface, the reflected beam being directed to the interferometric detector, a fluorescence detector for detecting a fluorescence signal from the illuminated surface; the fluorescence detector being positioned to substantially minimize the incidence of the reflected beam; and a processing system for receiving the interferometric and fluorescence signals and determining the presence or absence of target material on the biological reaction surface. A reaction surface conditioned for the simultaneous collection of fluorescence, interferometric and other signals.

Abstract: A method of probing a plurality of analyzer molecules distributed about a detection platform is disclosed. The method includes contacting a test sample to the plurality of analyzer molecules, scanning the plurality of analyzer molecules at a rate relating to a carrier frequency signal, and detecting the presence or absence of a biological molecule based at least in part upon the presence or absence of a signal substantially at a sideband of the carrier frequency signal. A molecule detection platform including a substrate and a plurality of targets positioned about the substrate is also disclosed. Specific analyzer molecules adapted to bind a specific analyte are immobilized about a first set of the targets. Nonspecific analyzer molecules are immobilized about a second set of the targets. The targets positioned about the substrate along at least a segment of a scanning pathway alternate between at least one of the first set and at least one of the second set.

Abstract: A molecular interferometric imaging system for detecting an analyte in a sample, that includes an illumination source providing a beam of radiation; a pixel array for detecting radiation in an image plane; a biolayer designed to react to the analyte when it comes in contact with the sample; a substrate designed to convert phase modulation into intensity modulation which can be detected and imaged directly by the pixel array, the biolayer being on the substrate; a reference surface; an image switching means for switching between a first position for collecting a sample image of the biolayer, and a second position for collecting a reference image of the reference surface; and a processing means for producing a composite image using the sample image and the reference image for illumination normalization.

Abstract: A detection system for detecting target material is provided. The system comprises a photonic structure having a reflectance-band and associated side bands; an illumination source for illuminating at a wavelength in at least one of an edge of the reflectance-band and the side bands of the photonic structure and for generating a return beam; a detector system having an intensity-sensitive channel configured to detect an in-line signal from the return beam and a phase-sensitive channel configured to detect a differential phase contrast signal from the return beam; and a processing system for receiving and adding in quadrature the in-line signal and the differential phase contrast signal to generate a joint signal, and for determining one of the presence or the absence of the target material on the photonic structure using the joint signal.

Abstract: A multi-modal data acquisition system for detecting target material on a biological reaction surface, the system comprising a radiation source for generating an incoming beam that impinges on the biological reaction surface at an oblique incidence angle and produces a reflected beam, an interferometric detector for detecting an interferometric signal from the illuminated surface, the reflected beam being directed to the interferometric detector, a fluorescence detector for detecting a fluorescence signal from the illuminated surface; the fluorescence detector being positioned to substantially minimize the incidence of the reflected beam; and a processing system for receiving the interferometric and fluorescence signals and determining the presence or absence of target material on the biological reaction surface. A reaction surface conditioned for the simultaneous collection of fluorescence, interferometric and other signals.

Abstract: A device for identifying analytes in a biological sample, including a substrate configured to bind the analyte and a detection system to determine the presence or absence of the analyte in the biological sample.

Abstract: A molecular interferometric imaging system for detecting an analyte in a sample, that includes an illumination source providing a beam of radiation; a pixel array for detecting radiation in an image plane; a biolayer designed to react to the analyte when it comes in contact with the sample; a substrate designed to convert phase modulation into intensity modulation which can be detected and imaged directly by the pixel array, the biolayer being on the substrate; a reference surface; an image switching means for switching between a first position for collecting a sample image of the biolayer, and a second position for collecting a reference image of the reference surface; and a processing means for producing a composite image using the sample image and the reference image for illumination normalization.

Abstract: A device for identifying analytes in a biological sample, including a substrate configured to bind the analyte and a detection system to determine the presence or absence of the analyte in the biological sample.

Abstract: A device for identifying analytes in a biological sample, including a substrate having a surface lying substantially in a first plane, a plurality of targets, each having a wall lying substantially in a second plane offset from the first plane, and a receptor coating applied to one of the surface and the target walls for binding analytes present in the biological sample when the biological sample is applied to the substrate. A laser beam is sequentially directed onto each of the plurality of target, the laser being positioned relative to the substrate such that when the beam is directed onto a target, a first half of the beam is reflected back to the laser from the wall of the target and a second half of the beam is reflected back to the laser from the surface of the substrate adjacent the target.

Abstract: A device for identifying analytes in a biological sample, including a substrate having a surface lying substantially in a first plane, a plurality of targets, each having a wall lying substantially in a second plane offset from the first plane, and a receptor coating applied to one of the surface and the target walls for binding analytes present in the biological sample when the biological sample is applied to the substrate. A laser beam is sequentially directed onto each of the plurality of target, the laser being positioned relative to the substrate such that when the beam is directed onto a target, a first half of the beam is reflected back to the laser from the wall of the target and a second half of the beam is reflected back to the laser from the surface of the substrate adjacent the target.

Abstract: Faults, dimensions and other characteristics of a material or structure are sensed by a coherent beam's reflection from the material during ultrasonic or very fast vibration. The reflected beam acquires a phase substantially different from its original phase and from the phase of a reference beam split from the common source beam. The reflected beam and the reference beam are superimposed by diffraction in a multiple quantum well adaptive holographic beamsplitter, and the superimposed beams are detected by a photodetector capable of detecting small interference changes from ultrasonic surface displacements or perturbations. An apparatus and method defining an improved homodyne interferometer for performing the method is described.