Abstract: 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.

Abstract: 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.

Abstract: Biodynamic imaging (BDI) performs Doppler spectroscopy of intracellular motion in living samples. The present disclosure describes novel methods and systems to perform: 1) BDI of living 3D tissue culture exposed to bacteria; 2) BDI of living biopsies exposed to bacteria; 3) BDI of infected tissues responding to antibiotics. A novel new element is the use of immortalized cancer cells to generate tissues that act as “biosensors” or “reporters” of bacterial infection, for cells as found directly in aqueous samples and cells that have been concentrated through filtration, centrifugation or a combination while maintaining them in a viable form. Pathogenicity is assessed through the spectral Doppler signatures of the changes in tissue dynamics induced by the bacteria.

Abstract: 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.

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 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A method is provided to translate from tissue dynamics spectroscopy (TDS) data formats into high-content analysis (HCA) data formats. The method utilizes TDS feature vectors and HCA feature vectors obtained from a shared set of compounds and cell lines to generate a translation matrix. The translator is applied to the unique data format of TDS that carries information from deep inside 3D tissue to convert the data into a standard data 2D HCA data format that fits into the standard workflow of potential customers.

Abstract: Systems and methods for imaging small (˜1 mm thick) living biological specimen is provided to enable the generation of functional 3D images of living tissue for evaluating the effect of an external perturbation on the health of the specimen. A fluctuation power spectrum is constructed for each pixel of a holographic 3D image of the specimen over time and subject to the external perturbation. A normalized spectrum of dynamic intensity as a function of frequency is generated for each pixel. The normalized spectra for each pixel is filtered according to a selected frequency range from among characteristic frequencies corresponding to dynamic activity of naturally occurring biological events within the specimen to provide data corresponding only to the dynamic activity associated with the selected frequency range.

Abstract: 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.

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 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 method is provided for automatically applying named styles to existing documents including word processing documents. The existing document is scanned and parsed into style regions of uniform style. The style attributes of each uniform style region are identified, and these identified style attributes are used to create style groups containing style regions having identical or substantially identical style attributes. These style attributes can be expressed in set or vector form. Named styles are then associated with the identified style group by either comparing the style attributes of a given style group to the attributes of a pre-defined named style or by extracting a named style from the style group. Once associated with a named style, the style regions within a given style group can be modified to be consistent with the named style associated with the style group.

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 method is provided for automatically applying named styles to existing documents including word processing documents. The existing document is scanned and parsed into style regions of uniform style. The style attributes of each uniform style region are identified, and these identified style attributes are used to create style groups containing style regions having identical or substantially identical style attributes. These style attributes can be expressed in set or vector form. Named styles are then associated with the identified style group by either comparing the style attributes of a given style group to the attributes of a pre-defined named style or by extracting a named style from the style group. Once associated with a named style, the style regions within a given style group can be modified to be consistent with the named style associated with the style group.

Abstract: A system is provided in which first data associated with a user and owned by a first data owner is received, second data associated with the user and owned by a second data owner is received, and a service to provide to the user is determined based on the first data and the second data. As a result, a seller may spontaneously offer an appropriate service to a user, thereby increasing both the user's satisfaction with the seller and the seller's chance of profit.