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).
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Patent number: 11988604Abstract: 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: GrantFiled: May 13, 2021Date of Patent: May 21, 2024Assignee: Hestzig LLCInventors: Robert Eric Betzig, Harald F. Hess
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Publication number: 20220091038Abstract: 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: ApplicationFiled: May 13, 2021Publication date: March 24, 2022Inventors: Robert Eric Betzig, Harald F. Hess
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Patent number: 11177110Abstract: 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: GrantFiled: February 6, 2019Date of Patent: November 16, 2021Assignee: Howard Hughes Medical InstituteInventors: Kenneth J. Hayworth, Harald F. Hess, C. Shan Xu, David Peale
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Patent number: 11009460Abstract: 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: GrantFiled: October 22, 2018Date of Patent: May 18, 2021Assignee: Hestzig LLCInventors: Robert Eric Betzig, Harald F. Hess
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Patent number: 10600615Abstract: 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: GrantFiled: January 29, 2018Date of Patent: March 24, 2020Assignee: Howard Hughes Medical InstituteInventors: C. Shan Xu, Kenneth J. Hayworth, Harald F. Hess
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Publication number: 20190355550Abstract: 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: ApplicationFiled: February 6, 2019Publication date: November 21, 2019Inventors: Kenneth J. Hayworth, Harald F. Hess, C. Shan Xu, David Peale
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Publication number: 20190187053Abstract: 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: ApplicationFiled: October 22, 2018Publication date: June 20, 2019Inventors: Robert Eric Betzig, Harald F. Hess
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Patent number: 10107753Abstract: 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: GrantFiled: June 1, 2016Date of Patent: October 23, 2018Assignee: Hestzig LLCInventors: Robert Eric Betzig, Harald F. Hess
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Patent number: 10054518Abstract: 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: GrantFiled: November 5, 2014Date of Patent: August 21, 2018Assignee: Howard Hughes Medical InstituteInventors: Harald F. Hess, David Peale, Patrick R. Lee
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Publication number: 20180218878Abstract: 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: ApplicationFiled: January 29, 2018Publication date: August 2, 2018Inventors: C. Shan Xu, Kenneth J. Hayworth, Harald F. Hess
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Publication number: 20170115221Abstract: 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: ApplicationFiled: June 1, 2016Publication date: April 27, 2017Inventors: Robert Eric Betzig, Harald F. Hess
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Patent number: 9482512Abstract: 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: GrantFiled: August 7, 2015Date of Patent: November 1, 2016Assignee: Howard Hughes Medical InstituteInventor: Harald F. Hess
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Patent number: 9360426Abstract: 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: GrantFiled: October 28, 2013Date of Patent: June 7, 2016Assignee: Hestzig LLCInventors: Robert Eric Betzig, Harald F. Hess
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Publication number: 20160054112Abstract: 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: ApplicationFiled: August 7, 2015Publication date: February 25, 2016Inventor: Harald F. Hess
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Publication number: 20150135917Abstract: 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: ApplicationFiled: November 5, 2014Publication date: May 21, 2015Inventors: Harald F. Hess, David Peale, Patrick R. Lee
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Publication number: 20140293015Abstract: 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: ApplicationFiled: June 11, 2014Publication date: October 2, 2014Inventor: Harald F. Hess
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Publication number: 20140287941Abstract: 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: ApplicationFiled: October 28, 2013Publication date: September 25, 2014Applicant: Hestzig LLCInventors: Robert Eric Betzig, Harald F. Hess
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Patent number: 8780442Abstract: 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: GrantFiled: March 18, 2011Date of Patent: July 15, 2014Assignee: Howard Hughes Medical InstituteInventor: Harald F. Hess
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Patent number: 8599376Abstract: 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: GrantFiled: October 18, 2012Date of Patent: December 3, 2013Assignee: Hestzig LLCInventors: Robert Eric Betzig, Harald F. Hess
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Patent number: 8462336Abstract: 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: GrantFiled: November 30, 2010Date of Patent: June 11, 2013Assignee: Hestzig LLCInventors: Robert Eric Betzig, Harald F. Hess