Patents by Inventor Harald F. Hess

Harald F. Hess 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).

  • Publication number: 20190355550
    Abstract: A microscopy system includes a gas cluster beam system configured for generating a beam of gas clusters directed toward a sample to irradiate a sample and mill away successive surface layers from the sample, a scanning electron microscope system configured for irradiating the successive surface layers of the sample with an electron beam and for imaging the successive surface layers of the sample in response to the irradiation of the surface layer, and a processor configured for generating a three dimensional image of the sample based on the imaging of the successive layers of the sample.
    Type: Application
    Filed: February 6, 2019
    Publication date: November 21, 2019
    Inventors: Kenneth J. Hayworth, Harald F. Hess, C. Shan Xu, David Peale
  • Publication number: 20190187053
    Abstract: Imaging a sample that includes phototransformable optical labels (“PTOLs”) with an optical system having a diffraction-limited resolution volume (DLRV), includes providing activation radiation to the PTOLs to activate a statistical subset of the PTOLs. A density of the PTOLs of the activated subset is less than an inverse of the DLRV. Excitation radiation is provided to the activated subset to excite activated PTOLs. Radiation emitted from the activated and excited PTOLs located at different focal planes of the optical system within the sample is detected with the optical system. The preceding steps are repeated one or more times, each time activating a different statistical subset of the plurality of PTOLs. Three-dimensional locations within the sample are determined, with a sub-diffraction-limited accuracy, of the activated and excited PTOLs based on the radiation emitted from the activated and excited PTOLs that is detected from the different focal planes of the optical system.
    Type: Application
    Filed: October 22, 2018
    Publication date: June 20, 2019
    Inventors: Robert Eric Betzig, Harald F. Hess
  • Patent number: 10107753
    Abstract: Imaging a sample that includes phototransformable optical labels (“PTOLs”) with an optical system having a diffraction-limited resolution volume (DLRV), includes providing activation radiation to the PTOLs to activate a statistical subset of the PTOLs. A density of the PTOLs of the activated subset is less than an inverse of the DLRV. Excitation radiation is provided to the activated subset to excite activated PTOLs. Radiation emitted from the activated and excited PTOLs located at different focal planes of the optical system within the sample is detected with the optical system. The preceding steps are repeated one or more times, each time activating a different statistical subset of the plurality of PTOLs. Three-dimensional locations within the sample are determined, with a sub-diffraction-limited accuracy, of the activated and excited PTOLs based on the radiation emitted from the activated and excited PTOLs that is detected from the different focal planes of the optical system.
    Type: Grant
    Filed: June 1, 2016
    Date of Patent: October 23, 2018
    Assignee: Hestzig LLC
    Inventors: Robert Eric Betzig, Harald F. Hess
  • Patent number: 10054518
    Abstract: A microtome includes a blade located at an end of a trough that defines a cavity for holding a liquid; a sample block in which the at least one sample is suspended, the sample block is moveable relative to the blade such that when the sample block is passed across the blade a section is cut from the sample block; a plate that includes a support frame that defines an opening, and a transparent film extending across the opening, the transparent film being transparent to electrons, a grasper being configured to receive and retain the plate, wherein the grasper is moveable relative to the blade; and a pusher section that lacks the sample pusher section.
    Type: Grant
    Filed: November 5, 2014
    Date of Patent: August 21, 2018
    Assignee: Howard Hughes Medical Institute
    Inventors: Harald F. Hess, David Peale, Patrick R. Lee
  • Publication number: 20180218878
    Abstract: A microscopy system for imaging a sample can include a scanning electron microscope system configured for imaging a surface layer of the sample and a focused ion beam system configured for generating an ion beam for milling the surface layer away from a sample after it has been imaged. A movable mechanical shutter can be configured to be moved automatically into a position between the sample and the scanning electron microscope system, so that when the electron beam is not imaging the sample the movable mechanical shutter is positioned between the sample and the scanning electron microscope system.
    Type: Application
    Filed: January 29, 2018
    Publication date: August 2, 2018
    Inventors: C. Shan Xu, Kenneth J. Hayworth, Harald F. Hess
  • Publication number: 20170115221
    Abstract: Imaging a sample that includes phototransformable optical labels (“PTOLs”) with an optical system having a diffraction-limited resolution volume (DLRV), includes providing activation radiation to the PTOLs to activate a statistical subset of the PTOLs. A density of the PTOLs of the activated subset is less than an inverse of the DLRV. Excitation radiation is provided to the activated subset to excite activated PTOLs. Radiation emitted from the activated and excited PTOLs located at different focal planes of the optical system within the sample is detected with the optical system. The preceding steps are repeated one or more times, each time activating a different statistical subset of the plurality of PTOLs. Three-dimensional locations within the sample are determined, with a sub-diffraction-limited accuracy, of the activated and excited PTOLs based on the radiation emitted from the activated and excited PTOLs that is detected from the different focal planes of the optical system.
    Type: Application
    Filed: June 1, 2016
    Publication date: April 27, 2017
    Inventors: Robert Eric Betzig, Harald F. Hess
  • Patent number: 9482512
    Abstract: A method includes sequentially acquiring phase-shifted images of an optical source in a plurality of predetermined positions in the z plane to form a plurality of image frame sequences; determining from the plurality of image frame sequences at least one phase-related characteristic associated with each predetermined position of the optical source in the z plane; and storing the at least one phase-related characteristic and the predetermined positions of the optical source in the z plane.
    Type: Grant
    Filed: August 7, 2015
    Date of Patent: November 1, 2016
    Assignee: Howard Hughes Medical Institute
    Inventor: Harald F. Hess
  • Patent number: 9360426
    Abstract: Imaging a sample that includes phototransformable optical labels (“PTOLs”) with an optical system having a diffraction-limited resolution volume (DLRV), includes providing activation radiation to the PTOLs to activate a statistical subset of the PTOLs. A density of the PTOLs of the activated subset is less than an inverse of the DLRV. Excitation radiation is provided to the activated subset to excite activated PTOLs. Radiation emitted from the activated and excited PTOLs located at different focal planes of the optical system within the sample is detected with the optical system. The preceding steps are repeated one or more times, each time activating a different statistical subset of the plurality of PTOLs. Three-dimensional locations within the sample are determined, with a sub-diffraction-limited accuracy, of the activated and excited PTOLs based on the radiation emitted from the activated and excited PTOLs that is detected from the different focal planes of the optical system.
    Type: Grant
    Filed: October 28, 2013
    Date of Patent: June 7, 2016
    Assignee: Hestzig LLC
    Inventors: Robert Eric Betzig, Harald F. Hess
  • Publication number: 20160054112
    Abstract: A method includes sequentially acquiring phase-shifted images of an optical source in a plurality of predetermined positions in the z plane to form a plurality of image frame sequences; determining from the plurality of image frame sequences at least one phase-related characteristic associated with each predetermined position of the optical source in the z plane; and storing the at least one phase-related characteristic and the predetermined positions of the optical source in the z plane.
    Type: Application
    Filed: August 7, 2015
    Publication date: February 25, 2016
    Inventor: Harald F. Hess
  • Publication number: 20150135917
    Abstract: A microtome includes a blade located at an end of a trough that defines a cavity for holding a liquid; a sample block in which the at least one sample is suspended, the sample block is moveable relative to the blade such that when the sample block is passed across the blade a section is cut from the sample block; a plate that includes a support frame that defines an opening, and a transparent film extending across the opening, the transparent film being transparent to electrons, a grasper being configured to receive and retain the plate, wherein the grasper is moveable relative to the blade; and a pusher section that lacks the sample pusher section.
    Type: Application
    Filed: November 5, 2014
    Publication date: May 21, 2015
    Inventors: Harald F. Hess, David Peale, Patrick R. Lee
  • Publication number: 20140293015
    Abstract: In one embodiment, an apparatus comprises an optical system with multiple detectors and a processor. The optical system is configured to produce images of an optical source in a first dimension and a second dimension substantially orthogonal to the first dimension at each detector at a given time. Each image from the images is based on an interference of an emission from the optical source in a first direction and an emission from the optical source in a second direction different from the first direction. The processor is configured to calculate a position in a third dimension based on the images. The third dimension is substantially orthogonal to the first dimension and the second dimension.
    Type: Application
    Filed: June 11, 2014
    Publication date: October 2, 2014
    Inventor: Harald F. Hess
  • Publication number: 20140287941
    Abstract: Imaging a sample that includes phototransformable optical labels (“PTOLs”) with an optical system having a diffraction-limited resolution volume (DLRV), includes providing activation radiation to the PTOLs to activate a statistical subset of the PTOLs. A density of the PTOLs of the activated subset is less than an inverse of the DLRV. Excitation radiation is provided to the activated subset to excite activated PTOLs. Radiation emitted from the activated and excited PTOLs located at different focal planes of the optical system within the sample is detected with the optical system. The preceding steps are repeated one or more times, each time activating a different statistical subset of the plurality of PTOLs. Three-dimensional locations within the sample are determined, with a sub-diffraction-limited accuracy, of the activated and excited PTOLs based on the radiation emitted from the activated and excited PTOLs that is detected from the different focal planes of the optical system.
    Type: Application
    Filed: October 28, 2013
    Publication date: September 25, 2014
    Applicant: Hestzig LLC
    Inventors: Robert Eric Betzig, Harald F. Hess
  • Patent number: 8780442
    Abstract: In one embodiment, an apparatus comprises an optical system with multiple detectors and a processor. The optical system is configured to produce images of an optical source in a first dimension and a second dimension substantially orthogonal to the first dimension at each detector at a given time. Each image from the images is based on an interference of an emission from the optical source in a first direction and an emission from the optical source in a second direction different from the first direction. The processor is configured to calculate a position in a third dimension based on the images. The third dimension is substantially orthogonal to the first dimension and the second dimension.
    Type: Grant
    Filed: March 18, 2011
    Date of Patent: July 15, 2014
    Assignee: Howard Hughes Medical Institute
    Inventor: Harald F. Hess
  • Patent number: 8599376
    Abstract: An apparatus includes a position-sensitive detector to detect intensities of radiation as a function of position on the detector, and an optical system, characterized by a diffraction-limited resolution volume, adapted for imaging light emitted from activated and excited phototransformable optical labels (“PTOLs”) in a sample onto the position sensitive-detector. A first light source provides activation radiation to the sample to activate a subset of the PTOLs that are distributed in the sample with a density greater than an inverse of the diffraction-limited resolution volume of the optical system. A second light source provides excitation radiation to the sample to excite a portion of the PTOLs in the subset of the PTOLs. A controller controls one both of the activation radiation and the excitation radiation provided to the sample such that a density of PTOLs in the portion of the PTOLs is less than the inverse of the diffraction-limited resolution volume.
    Type: Grant
    Filed: October 18, 2012
    Date of Patent: December 3, 2013
    Assignee: Hestzig LLC
    Inventors: Robert Eric Betzig, Harald F. Hess
  • Patent number: 8462336
    Abstract: An apparatus includes a position-sensitive detector to detect intensities of radiation as a function of position on the detector, and an optical system, characterized by a diffraction-limited resolution volume, adapted for imaging light emitted from activated and excited phototransformable optical labels (“PTOLs”) in a sample onto the position sensitive-detector. A first light source provides activation radiation to the sample to activate a subset of the PTOLs that are distributed in the sample with a density greater than an inverse of the diffraction-limited resolution volume of the optical system. A second light source provides excitation radiation to the sample to excite a portion of the PTOLs in the subset of the PTOLs. A controller controls one both of the activation radiation and the excitation radiation provided to the sample such that a density of PTOLs in the portion of the PTOLs is less than the inverse of the diffraction-limited resolution volume.
    Type: Grant
    Filed: November 30, 2010
    Date of Patent: June 11, 2013
    Assignee: Hestzig LLC
    Inventors: Robert Eric Betzig, Harald F. Hess
  • Publication number: 20110170200
    Abstract: In one embodiment, an apparatus comprises an optical system with multiple detectors and a processor. The optical system is configured to produce images of an optical source in a first dimension and a second dimension substantially orthogonal to the first dimension at each detector at a given time. Each image from the images is based on an interference of an emission from the optical source in a first direction and an emission from the optical source in a second direction different from the first direction. The processor is configured to calculate a position in a third dimension based on the images. The third dimension is substantially orthogonal to the first dimension and the second dimension.
    Type: Application
    Filed: March 18, 2011
    Publication date: July 14, 2011
    Applicant: HOWARD HUGHES MEDICAL INSTITUTE
    Inventor: Harald F. Hess
  • Publication number: 20110102787
    Abstract: An apparatus includes a position-sensitive detector to detect intensities of radiation as a function of position on the detector, and an optical system, characterized by a diffraction-limited resolution volume, adapted for imaging light emitted from activated and excited phototransformable optical labels (“PTOLs”) in a sample onto the position sensitive-detector. A first light source provides activation radiation to the sample to activate a subset of the PTOLs that are distributed in the sample with a density greater than an inverse of the diffraction-limited resolution volume of the optical system. A second light source provides excitation radiation to the sample to excite a portion of the PTOLs in the subset of the PTOLs. A controller controls one both of the activation radiation and the excitation radiation provided to the sample such that a density of PTOLs in the portion of the PTOLs is less than the inverse of the diffraction-limited resolution volume.
    Type: Application
    Filed: November 30, 2010
    Publication date: May 5, 2011
    Applicant: HESTZIG LLC
    Inventors: Harald F. Hess, Robert Eric Betzig
  • Patent number: 7924432
    Abstract: A statistically sparse subset of switchable optical sources in a sample is activated, and the activated switchable optical sources are excited such that optical beams are emitted from the activated switchable optical sources along at least two optical paths. A first wavefront modification in a first optical beam emitted from the activated switchable optical sources along a first optical path is introduced and a second wavefront modification in a second optical beam emitted from the activated switchable optical sources along a second optical path is introduced, the second wavefront modification being distinct from the first wavefront modification. The first and second optical beams are interfered with each other to produce a plurality of output beams, and three-dimensional position information of the optical sources is determined based on an intensity of each output beam from the plurality of output beams.
    Type: Grant
    Filed: September 10, 2009
    Date of Patent: April 12, 2011
    Assignee: Howard Hughes Medical Institute
    Inventors: Harald F. Hess, Gleb Shtengel
  • Patent number: 7916304
    Abstract: In one embodiment, an apparatus comprises an optical system with multiple detectors and a processor. The optical system is configured to produce images of an optical source in a first dimension and a second dimension substantially orthogonal to the first dimension at each detector at a given time. Each image from the images is based on an interference of an emission from the optical source in a first direction and an emission from the optical source in a second direction different from the first direction. The processor is configured to calculate a position in a third dimension based on the images. The third dimension is substantially orthogonal to the first dimension and the second dimension.
    Type: Grant
    Filed: December 20, 2007
    Date of Patent: March 29, 2011
    Assignee: Howard Hughes Medical Institute
    Inventor: Harald F. Hess
  • Patent number: 7864314
    Abstract: An apparatus includes a position-sensitive detector to detect intensities of radiation as a function of position on the detector, and an optical system, characterized by a diffraction-limited resolution volume, adapted for imaging light emitted from activated and excited phototransformable optical labels (“PTOLs”) in a sample onto the position sensitive-detector. A first light source provides activation radiation to the sample to activate a subset of the PTOLs that are distributed in the sample with a density greater than an inverse of the diffraction-limited resolution volume of the optical system. A second light source provides excitation radiation to the sample to excite a portion of the PTOLs in the subset of the PTOLs. A controller controls one both of the activation radiation and the excitation radiation provided to the sample such that a density of PTOLs in the portion of the PTOLs is less than the inverse of the diffraction-limited resolution volume.
    Type: Grant
    Filed: December 22, 2009
    Date of Patent: January 4, 2011
    Assignee: Hestzig LLC
    Inventors: Robert Eric Betzig, Harald F. Hess