Patents by Inventor Enrico Gratton

Enrico Gratton has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 10222335
    Abstract: A label-free imaging method to monitor stem cell metabolism discriminates different states of stem cell as they differentiate in a living tissues. We use intrinsic fluorescence biomarkers and the phasor approach to Fluorescence Lifetime Imaging Microscopy (FLIM). We identify and map intrinsic fluorophores such as collagen, retinol, retinoic acid, flavins, nicotinamide adenine dinucleotide (NADH) and porphyrin. We measure the phasor values of germ cells in C. Elegans germ line. Their metabolic fingerprint cluster according to their differentiation state, reflecting changes in FAD concentration and NADH binding during the differentiation pathway. The phasor approach to lifetime imaging provides a label-free, fit-free and sensitive method to identify different metabolic state of cells during differentiation, to sense small changes in the redox state of cells and may identify symmetric and asymmetric divisions and predict cell fate.
    Type: Grant
    Filed: October 27, 2011
    Date of Patent: March 5, 2019
    Assignee: The Regents of the University of California
    Inventors: Chiara Stringari, Enrico Gratton, Michelle Digman, Peter Donovan
  • Patent number: 9874736
    Abstract: An apparatus for inclined single plane Illumination microscopy of a sample includes a laser for launching excitation light beams at a plurality of wavelengths, a laser beam expander, an injection arm optically coupled to the laser beam expander, a conventional back-to-back microscope system, a universal dichroic mirror optically coupled to the injection arm to direct the excitation light beams into the conventional back-to-back microscope onto a sample plane in an imaging plane, and to receive fluorescence light from the sample, a universal optical adaptor optically coupled to the universal dichroic mirror, a re-imaging component optically coupled to the universal optical adaptor; and a camera output connector optically coupled to the re-imaging component, where the laser beam expander, injection arm, universal optical adapter, re-imaging component, and camera are combined in a modular unit which is arranged and configured to be coupled to the conventional back-to-back microscope.
    Type: Grant
    Filed: April 29, 2013
    Date of Patent: January 23, 2018
    Assignee: The Regents of the University of California
    Inventors: Francesco Cutrale, Enrico Gratton
  • Publication number: 20160231324
    Abstract: In alternative embodiments, the invention provides high throughput, multiplexed systems or methods for detecting a biological, a physiological or a pathological maker, or a single molecule or a single cell using a droplet microfluidics system integrated with use of a sensor or a sensing system, an aptamer, or a DNAzyme. In alternative embodiments, the sensor or sensing system comprises a nucleic acid based, an antibody based, an enzyme based or a chemical based sensor or sensing system. In alternative embodiments, the invention provides methods for detecting a biological, a physiological or a pathological marker, or a single molecule or a single cell using a droplet system integrated with rapid and sensitive fluorescence detection systems including, for example, a 3D Particle Detector. In alternative embodiments, the invention provides systems comprising Integrated Comprehensive Droplet Digitial Detection (IC 3D).
    Type: Application
    Filed: September 24, 2014
    Publication date: August 11, 2016
    Inventors: Weian ZHAO, Dong-ku KANG, Kaixiang ZHANG, Md Monsur ALI, Mark A. ECKERT, Feng LI, Enrico GRATTON, MIchelle A. DIGMAN, Louai LABANIEH, Mengrou LU
  • Patent number: 9110282
    Abstract: An optical imaging method based on a feedback principle in which the specific scan pattern is adapted according to the shape of the sample. The feedback approach produces nanometer-resolved three dimensional images of very small and moving features in live cells and in a matter of seconds. Images of microvilli in live cultured opossum kidney cells expressing NaPi co-transporter proteins with different GFP constructs and images of cell protrusions in a collagen matrix are produced with a resolution of about 20 nm. Along cell protrusions in three dimensional cellular adhesions could be identified to the extracellular matrix.
    Type: Grant
    Filed: March 30, 2012
    Date of Patent: August 18, 2015
    Assignee: The Regents of the University of California
    Inventors: Luca Lanzano, Michelle Digman, Enrico Gratton
  • Publication number: 20140320601
    Abstract: An apparatus for inclined single plane Illumination microscopy of a sample includes a laser for launching excitation light beams at a plurality of wavelengths, a laser beam expander, an injection arm optically coupled to the laser beam expander, a conventional back-to-back microscope system, a universal dichroic mirror optically coupled to the injection arm to direct the excitation light beams into the conventional back-to-back microscope onto a sample plane in an imaging plane, and to receive fluorescence light from the sample, a universal optical adaptor optically coupled to the universal dichroic mirror, a re-imaging component optically coupled to the universal optical adaptor; and a camera output connector optically coupled to the re-imaging component, where the laser beam expander, injection arm, universal optical adapter, re-imaging component, and camera are combined in a modular unit which is arranged and configured to be coupled to the conventional back-to-back microscope.
    Type: Application
    Filed: April 29, 2013
    Publication date: October 30, 2014
    Applicant: The Regents of the University of California
    Inventors: Francesco Cutrale, Enrico Gratton
  • Patent number: 8692998
    Abstract: An apparatus and method for in-depth fluorescence imaging using two-photon fluorescence imaging in turbid media. The apparatus includes a detector which can significantly enhance the use of a detection method that allows to efficiently collect scattered fluorescence photons from a wide area of the turbid sample. By using this detector it is possible to perform imaging of turbid samples, simulating brain tissue at depths up to 3 mm, where the two-photon induced fluorescence signal is too weak to be detected by previous means used in conventional two-photon microscopy. The detector separates the excitation and detection optics which allows a more efficient collection of fluorescence and enhancing the possible imaging depth.
    Type: Grant
    Filed: April 11, 2012
    Date of Patent: April 8, 2014
    Assignee: The Regents of the University of California
    Inventors: Enrico Gratton, Alexander Dvornikov, Viera Crosignani
  • Patent number: 8330123
    Abstract: A system and method is provided for improved fluorescence decay time measurement. A digital heterodyning technique is disclosed in which a photon detector is sampled at a rate slightly faster than a digitally pulsed excitation signal. A resulting cross correlation frequency is low enough to be read by inexpensive electronics such as by a field programmable gate array. Phase information in the signal provides correlation with corresponding photon detections.
    Type: Grant
    Filed: January 28, 2010
    Date of Patent: December 11, 2012
    Assignee: I.S.S. (USA), Inc.
    Inventors: Enrico Gratton, Enrico D'Amico
  • Publication number: 20120276578
    Abstract: “A label-free imaging method to monitor stem cell metabolism discriminates different states of stem cell as they differentiate in a living tissues. We use intrinsic fluorescence biomarkers and the phasor approach to Fluorescence Lifetime Imaging Microscopy (FLIM). We identify and map intrinsic fluorophores such as collagen, retinol, retinoic acid, flavins, nicotinamide adenine dinucleotide (NADH) and porphyrin. We measure the phasor values of germ cells in C. Elegans germ line. Their metabolic fingerprint cluster according to their differentiation state, reflecting changes in FAD concentration and NADH binding during the differentiation pathway. The phasor approach to lifetime imaging provides a label-free, fit-free and sensitive method to identify different metabolic state of cells during differentiation, to sense small changes in the redox state of cells and may identify symmetric and asymmetric divisions and predict cell fate.
    Type: Application
    Filed: October 27, 2011
    Publication date: November 1, 2012
    Inventors: Chiara Stringari, Enrico Gratton, Michelle Digman, Peter Donovan
  • Publication number: 20120257203
    Abstract: An apparatus and method for in-depth fluorescence imaging using two-photon fluorescence imaging in turbid media. The apparatus includes a detector which can significantly enhance the use of a detection method that allows to efficiently collect scattered fluorescence photons from a wide area of the turbid sample. By using this detector it is possible to perform imaging of turbid samples, simulating brain tissue at depths up to 3 mm, where the two-photon induced fluorescence signal is too weak to be detected by previous means used in conventional two-photon microscopy. The detector separates the excitation and detection optics which allows a more efficient collection of fluorescence and enhancing the possible imaging depth.
    Type: Application
    Filed: April 11, 2012
    Publication date: October 11, 2012
    Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
    Inventors: Enrico Gratton, Alexander Dvornikov, Viera Crosignani
  • Publication number: 20120250000
    Abstract: An optical imaging method based on a feedback principle in which the specific scan pattern is adapted according to the shape of the sample. The feedback approach produces nanometer-resolved three dimensional images of very small and moving features in live cells and in a matter of seconds. Images of microvilli in live cultured opossum kidney cells expressing NaPi co-transporter proteins with different GFP constructs and images of cell protrusions in a collagen matrix are produced with a resolution of about 20 nm. Along cell protrusions in three dimensional cellular adhesions could be identified to the extracellular matrix.
    Type: Application
    Filed: March 30, 2012
    Publication date: October 4, 2012
    Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
    Inventors: Luca Lanzano, Michelle Digman, Enrico Gratton
  • Patent number: 8256898
    Abstract: Tear film stability has an important role in the quality of vision. A system and method for performing Fluctuation Analysis of Spatial Image Correlation (FASIC) provides for a non-invasive system and method for evaluating the dynamics of the tear film surface using spatial autocorrelation analysis. With FASIC, a series of images are obtained using illumination and a camera. The spatial autocorrelation is calculated for image frames produced by the camera. A sinusoidal background appears in this correlation together with other features. The changes in the sinusoidal background of the spatial autocorrelation is extracted and monitored over time. The spatial period of this sinusoidal background correlates with the thickness of the tear film. In this regard, one is able to derive the tear film thickness from the period of this sinusoidal background.
    Type: Grant
    Filed: June 10, 2010
    Date of Patent: September 4, 2012
    Assignee: The Regents of the University of California
    Inventors: Enrico Gratton, Kaveh Azartash, Luisa Marsili
  • Publication number: 20110180726
    Abstract: A system and method is provided for improved fluorescence decay time measurement. A digital heterodyning technique is disclosed in which a photon detector is sampled at a rate slightly faster than a digitally pulsed excitation signal. A resulting cross correlation frequency is low enough to be read by inexpensive electronics such as by a field programmable gate array. Phase information in the signal provides correlation with corresponding photon detections.
    Type: Application
    Filed: January 28, 2010
    Publication date: July 28, 2011
    Applicant: I.S.S. (USA), INC.
    Inventors: Enrico Gratton, Enrico D'Amico
  • Patent number: 7973294
    Abstract: The invention provides methods and devices for detecting, identifying, classifying and characterizing particles in a fluid sample. Optical analyzers are provided having a rotating and/or translating sample container for measuring the concentrations of fluorescent particles present in very low concentrations and for characterizing fluorescent particles on the basis of size, shape, diffusion constant and/or composition. Scanning optical analyzers are provided using pattern recognitions data analysis techniques and multichannel detection.
    Type: Grant
    Filed: March 31, 2009
    Date of Patent: July 5, 2011
    Assignee: The Board of Trustees of the University of Illinois
    Inventors: Enrico Gratton, Guido Motolese, Abdel Tahari
  • Publication number: 20100315591
    Abstract: Tear film stability has an important role in the quality of vision. A system and method for performing Fluctuation Analysis of Spatial Image Correlation (FASIC) provides for a non-invasive system and method for evaluating the dynamics of the tear film surface using spatial autocorrelation analysis. With FASIC, a series of images are obtained using illumination and a camera. The spatial autocorrelation is calculated for image frames produced by the camera. A sinusoidal background appears in this correlation together with other features. The changes in the sinusoidal background of the spatial autocorrelation is extracted and monitored over time. The spatial period of this sinusoidal background correlates with the thickness of the tear film. In this regard, one is able to derive the tear film thickness from the period of this sinusoidal background.
    Type: Application
    Filed: June 10, 2010
    Publication date: December 16, 2010
    Inventors: Enrico Gratton, Kaveh Azartash, Luisa Marsili
  • Publication number: 20090230324
    Abstract: The invention provides methods and devices for detecting, identifying, classifying and characterizing particles in a fluid sample. Optical analyzers are provided having a rotating and/or translating sample container for measuring the concentrations of fluorescent particles present in very low concentrations and for characterizing fluorescent particles on the basis of size, shape, diffusion constant and/or composition. Scanning optical analyzers are provided using pattern recognitions data analysis techniques and multichannel detection.
    Type: Application
    Filed: March 31, 2009
    Publication date: September 17, 2009
    Applicant: The Board of Trustees of the University of Illinois
    Inventors: Enrico GRATTON, Guido MOTOLESE, Abdel TAHARI
  • Patent number: 7528384
    Abstract: The invention provides methods and devices for detecting, identifying, classifying and characterizing particles in a fluid sample. Optical analyzers are provided having a rotating and/or translating sample container for measuring the concentrations of fluorescent particles present in very low concentrations and for characterizing fluorescent particles on the basis of size, shape, diffusion constant and/or composition. Scanning optical analyzers are provided using pattern recognitions data analysis techniques and multichannel detection.
    Type: Grant
    Filed: January 27, 2006
    Date of Patent: May 5, 2009
    Assignee: The Board of Trustees of the University of Illinois
    Inventors: Enrico Gratton, Guido Motolese, Abdel Tahari
  • Publication number: 20080300493
    Abstract: The invention is devices and related methods for detecting blood clots in a blood vessel. An optical microprobe is configured to illuminate a blood vessel with electromagnetic radiation corresponding to the near-infrared portion of the electromagnetic spectrum. The optical microprobe has a pair of fiber optic strands configured for transmission spectroscopy to obtain the absorption spectrum generated by the components within the blood vessel. Because blood clots generate a detectable and unique spectrum, the presence or absence of the blood clot is determined by examining the blood vessel absorption spectrum. A specially-designed holder is configured to stably position the optical microprobe relative to the blood vessel and is used to facilitate precise blood clot detection along a length of blood vessel.
    Type: Application
    Filed: June 6, 2008
    Publication date: December 4, 2008
    Inventors: Rodolfo Gatto, Enrico D'amico, William W. Mantulin, Enrico Gratton, Fady Charbel
  • Publication number: 20080009748
    Abstract: The illustrated embodiment is an improvement in a method of optically analyzing tissue in vivo in an individual to obtain a unique spectrum for the tissue of the individual, the improvement including the steps of optically measuring the tissue of the individual to obtain a spectrum of an optical parameter, and identifying a spectral signature specific to a metabolic or physiologic state in the tissue of the individual with a unique spectrum for the tissue by considering only the spectral differences between a first metabolic or physiologic state of the tissue of the individual and one or more other metabolic or physiologic states of the tissue of the individual such that identification of the spectral signature is self-referencing with respect to intra-individual metabolic or physiologic variations. The method also includes separating benign and malignant lesions only using the shape or a characteristic of the spectrum.
    Type: Application
    Filed: May 16, 2007
    Publication date: January 10, 2008
    Applicant: The Regents of the University of California
    Inventors: Enrico Gratton, Shwayta Kukreti, Albert Cerussi, Bruce Tromburg
  • Publication number: 20060256338
    Abstract: The invention provides methods and devices for detecting, identifying, classifying and characterizing particles in a fluid sample. Optical analyzers are provided having a rotating and/or translating sample container for measuring the concentrations of fluorescent particles present in very low concentrations and for characterizing fluorescent particles on the basis of size, shape, diffusion constant and/or composition. Scanning optical analyzers are provided using pattern recognitions data analysis techniques and multichannel detection.
    Type: Application
    Filed: January 27, 2006
    Publication date: November 16, 2006
    Applicant: The Board of Trustees of the University of IIlinois
    Inventors: Enrico Gratton, Guido Motolese, Abdel Tahari
  • Patent number: 6794659
    Abstract: A fluorescence spectrometer comprises a laser and at least one beam splitter positioned to receive a light beam from the laser and to divide it into several first light beam portions. Dichroic mirrors are positioned to separately receive the first light beam portions and to reflect the beam portions at an angle to the first light beam portions. Transparent chambers are provided for holding the samples. Objective lens systems are respectively positioned in the path of the reflected beam portions to respectively focus each reflected beam portion to a point within one of the separate transparent chambers. Lenses are positioned to receive fluorescence from a sample for testing within the transparent chambers and to respectively focus the fluorescence at pin holes in opaque partitions. The lenses are positioned to receive the fluorescence, which passes back through the objective lens system and the dichroic mirror.
    Type: Grant
    Filed: June 4, 2003
    Date of Patent: September 21, 2004
    Assignee: I.S.S. (USA) Inc.
    Inventors: Beniamino Barbieri, Enrico Gratton