Purdue Research Foundation

Other

International Business Machines Corporation

Hrl Laboratories, LLC

Hughes Electronics Corporation

David D Nolte

John J Turek

Manoj Varma

Fred E Regnier

Ming Zhao

Kwan Jeong

Ran An

Leilei Peng

Xuefeng Wang

David M Pepper

Gilmore Joseph Dunning

Marvin E Klein

G David Bacher

Brian Weichel

Timothy Norwood

Fouad Sayegh

Jerry M Woodall

Peter Daniel Kirchner

Rodney T Hodgson

John Lawrence Freeouf

Marvin B Klein

Michael R Melloch

John Anthony Coy

Nicholas Nolte

Meng P Chiao

Kenneth Bacher

Laura Pyrak-Nolte

Zoltan Machaty

Indrajit Lahiri

Maria Josef Lopera

Apparatuses and methods for investigating the inside of a tissue cell are disclosed. Embodiments include diffusely scattering light off a target sample, producing two crossing beams from the scattered light, and using a camera to create an image from the light. Some embodiments utilize a Fourier lens and a Fresnel biprism, and optionally include a long-coherence light source, a delay plate (which can be a polarization rotator or an optical flat), and/or a beam expander. Still further embodiments utilize a diffraction grating, a spatial filter (which may include two differently sized apertures), and a Fourier lens, and optionally include differently sized apertures in the spatial filter. Some embodiments include a transparent support and illuminating the target at an oblique angle through the transparent support. Still further embodiments utilize a low-coherence light source and/or immobilizing the sample tissue using surface bonding chemistry.

Apparatuses and methods for examining the movement of constituents within tissue cells

A system for determining a fingerprint of a structure is provided. The system includes a plurality of granules inserted in a structure having a plurality of fissures, fractures, and cracks (collectively apertures), each granule comprising a membrane, and at least one bubble of compressed gas formed in the membrane, the membrane selectively dissolving in presence of a predetermined fluid and thereby selectively bursting the at least one bubble, thereby generating a concussing vibration, at least at least i) three detection devices for two-dimensional mapping or ii) four detection devices for three-dimensional mapping placed proximate to the structure according to a predetermined placement schedule, and a computing device comprising a processor configured to receive data from the at least three or four detection devices and to determine location of the at least one bubble of each of the plurality of the granules at the time of bursting by triangulating the concussive vibration in order to determine location of the at least one bubble.

System and method of mapping topology

An apparatus for viewing a biological sample that functions as both a microscope and an interferometer. A short-coherence light source directs light onto the sample. A Fourier transform lens and a pixel-array detector are positioned to collect light scattered by the sample. An optic fiber assembly conveys a reference beam from the short-coherence light source. The detector collects the reference beam and the signal beam and uses coherence gating to acquire interferometric image data. In some embodiments the axis of the incident light striking the sample and the axis of collected scattered signal light form an angle of less than 180 degrees and advantageously an angle between 120 and 150 degrees. A method of converting a microscope into an interferometer is also disclosed.

Biodynamic microscopes and methods of use thereof

A phenotypic profiling method for drug/dose physiological response of living bodies utilizes feature recognition to segment the information in time-frequency tissue-response spectrograms to construct N-dimensional feature vectors. The feature vectors are used to generate a correlation matrix among a large number of different stimuli in the form of drugs, doses and conditions. Multi-dimensional scaling is applied to the correlation matrix to form a two-dimensional map of response relationships that retains rank distances from the higher-dimensionality feature matrix. The two-dimensional phenotypic profile space displays compact regions indicative of particular physiological responses, such as regions of enhanced active transport, membrane undulations and blebbing.

Using differential time-frequency tissue-response spectroscopy to evaluate living body response to a drug

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 are 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 those motions do not contribute to the signal.

Digital holographic method of measuring cellular activity and measuring apparatus with improved stability

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.

Method and apparatus for motility contrast imaging

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.

Digital holographic method of measuring cellular activity and of using results to screen compounds

A method and system is provided for evaluating viability of oocytes and embryos comprising imaging an oocyte or embryo using motility contrast imaging; generating temporal contrast and spatial contrast data for the cells; generating a cell viability value as a function of the temporal and spatial contrast data; and comparing the cell viability value to a predetermined value indicative of a cell suitable for use in an in vitro fertilization program.

Motility-contrast imaging for oocyte and embryo viability assessment

In a method for ex vivo evaluation of tissue response, a target biological sample is placed in a chamber of a sample holder. Biodynamic imaging (BDI) is performed on the sample to extract BDI data of the entire sample, optical coherence imaging (OCI) data is generated from the BDI data; and then motility contrast imaging (MCI) data is generated from the OCI data. The MCI data is used to select an area of the ex vivo sample having the highest normalized standard deviation (NSD) value, indicative of a region of desirable responsiveness to a stimuli. The sample is subjected to a perturbation or external condition and an MCI analysis is performed on the selected area to determine the tissue response to the perturbation or external condition. In one aspect, the selected area or region of interest is obtained using a gradient descent method.

Ex vivo motility contrast imaging

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.

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. A method including providing a substrate for supporting biological analyzer molecules the substrate including at least one scanning pathway is also disclosed. The scanning pathway includes a plurality of scanning targets. Specific biological analyzer molecules adapted to detect a specific target analyte are distributed about a first set of the targets which alternate in groups of at least one with a second set of the targets the second set of the targets not including the specific biological analyzer molecules.

Differentially encoded biological analyzer planar array apparatus and methods

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. A multi-modal data acquisition system for collecting and processing additional modes, including multiple interferometric, fluorescence and scattering channels.

System with extended range of molecular sensing through integrated multi-modal data acquisition

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. An apparatus including a surface normal interferometry platform including a scanning pathway and a plurality of analyzer molecules adapted to detect the presence or absence of a plurality of target analytes is also disclosed. The plurality of analyzer molecules are distributed about the scanning pathway according to a multiplexing scheme. A method including multiplexing a plurality of kinds of capture molecules about a detection pathway is further disclosed. The method also includes contacting a biological sample to the array, detecting the presence or absence of binding of the plurality of kinds of capture molecules and a plurality of target analytes using interferometry.

Multiplexed biological analyzer planar array apparatus and methods

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.

Growing community of inventors

Lafayette, IN, United States of America

David D Nolte