Patents Assigned to MITEGEN, LLC
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Publication number: 20250041871Abstract: Presented are systems, methods, and devices for provisioning controlled sample support, precision sample immersion, and/or post-cooling sample storage of cryo-electron microscopy (cryo-EM) samples and grids. A puck is presented for manual or automated storage of cryo-EM sample grids after the grids and samples have been cryocooled. The puck carries one or more cryo-EM sample grids and includes a puck top portion and a puck bottom portion, each formed with a cryogenic-temperature compatible material. The bottom portion includes multiple receptacles that each accepts and holds a sample grid. The top portion includes an array of funnels. The puck top and bottom portions are assembled together by inserting the top portion into the bottom portion. When the puck may be immersed in a liquid cryogen, each funnel guides a sample grid released into an upper portion of the funnel downward and into a grid receptacle within a bottom portion of the funnel.Type: ApplicationFiled: October 18, 2024Publication date: February 6, 2025Applicant: MiTeGen, LLCInventors: Alex Schreiber-Harris, Richard Jayne, David Closs, Robert E. Thorne
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Patent number: 12185717Abstract: A system for cryocooling biological samples includes a first chamber that holds a first amount a cryogenic liquid. A container holder, which is positioned in thermal contact with the first chamber, holds a removable container positioned therein. The container holds a second amount of the cryogenic liquid and forms a second chamber. An elongated tube holder holds a hollow elongated tube into the container. A sample wand holds and transfers a sample holder with a biological sample into the elongated tube while the elongated tube is in the container with the second amount of the cryogenic liquid.Type: GrantFiled: April 19, 2023Date of Patent: January 7, 2025Assignee: MiTeGen, LLCInventors: Robert E Thorne, David Closs, Richard Jayne, Benjamin Apker
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Publication number: 20240393215Abstract: Presented are systems, methods, and devices for provisioning sample support, controlled liquid deposition, and/or desired sample thicknesses during cryo-electron microscopy processes. A sample support for a cryo-electron microscopy process includes a support grid with multiple grid faces. The grid may be substantially rigid, flat and circular, may have a diameter of between about 2.9 and 3.1 mm, and may have a thickness of about 10 to 25 ?m. A foil covers at least one of the grid faces and includes multiple foil regions that each has a distinct thickness. The foil may be a thin and flexible metal or carbon foil. At least one of the foil regions contains an array of through-holes. A boundary between the foil regions with distinct thicknesses forms a step edge that pins thereto a receding contact line of a liquid drop deposited on the foil.Type: ApplicationFiled: December 8, 2022Publication date: November 28, 2024Applicant: MiTeGen, LLCInventors: Robert E. Thorne, An Zou
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Publication number: 20240328969Abstract: A fixed target sample holder for serial synchrotron crystallography comprising goniometer compatible base, a carrier, a sample holding insert which can be placed into the carrier. The sample holing insert comprising fiducials and windows, wherein each of the windows are respectively configured to accept a sample. The windows can also have holes and texture within each window. Additionally, a sample loading workstation for loading crystals into the sample holder and the removal of excess liquid from the sample, comprising a humidity-controlled chamber, a sample support within the chamber, a capture to place the goniometer-compatible base and a channel in communication with the chamber that allows for the flow of humidified air into the chamber.Type: ApplicationFiled: May 8, 2024Publication date: October 3, 2024Applicant: MiTeGen, LLCInventors: Robert E. Thorne, David Closs, Benjamin Apker
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Publication number: 20240319120Abstract: A fixed target sample holder for serial synchrotron crystallography comprising goniometer compatible base, a carrier, a sample holding insert which can be placed into the carrier. The sample holing insert comprising fiducials and windows, wherein each of the windows are respectively configured to accept a sample. The windows can also have holes and texture within each window. Additionally, a sample loading workstation for loading crystals into the sample holder and the removal of excess liquid from the sample, comprising a humidity-controlled chamber, a sample support within the chamber, a capture to place the goniometer-compatible base and a channel in communication with the chamber that allows for the flow of humidified air into the chamber.Type: ApplicationFiled: May 8, 2024Publication date: September 26, 2024Applicant: MiTeGen, LLCInventors: Robert E. Thorne, David Closs, Benjamin Apker
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Publication number: 20240242926Abstract: Presented are sample-supporting foils and grids for cryo-electron microscopy (cryo-EM) systems, methods for making/using disclosed cryo-EM foils, grids, devices, and/or systems, and cryo-EM systems equipped with disclosed foils, grids, and/or devices. A sample-support grid assembly may include a grid body with opposing first and second grid surfaces and multiple grid holes extending through the grid body from the first grid surface to the second grid surface. A foil sheet is seated against the first surface and covers at least a subset of the grid holes in the grid body. The foil sheet includes multiple foil regions filled with foil holes and separated from each other by multiple elongated slots. These elongated slots enable the foil regions to move with respect to each other when the grid assembly is under load. The slots of the foil sheet may be arranged in an auxetic pattern.Type: ApplicationFiled: June 3, 2022Publication date: July 18, 2024Applicant: MiTeGen, LLCInventors: Robert Thorne, Tyler Engstrom, Richard Jayne
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Publication number: 20240216906Abstract: Humidified sample preparation station for serial crystallography according to one embodiment is a humidified enclosure that delivers relative humidities above 95% and preferably above 97% in standard operation, and that can allow microscope observation of samples within. Humidified sample preparation station for serial crystallography can be used for preparation of protein crystal samples for examination using X-rays and for protein structure determination by X-ray crystallography, involving addition of liquid to the sample and removal of liquid from the sample using vacuum or suction.Type: ApplicationFiled: January 25, 2024Publication date: July 4, 2024Applicant: Mitegen, LLCInventors: Richard Jayne, David Closs, Benjamin A. Apker, Robert E. Thorne
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Patent number: 12007342Abstract: A fixed target sample holder for serial synchrotron crystallography comprising a goniometer compatible base, a carrier, a sample holding insert which can be placed into the carrier. The sample holding insert comprising fiducials and windows, wherein each of the windows are respectively configured to accept a sample. The windows can also have holes and texture within each window. Additionally, a sample loading workstation for loading crystals into the sample holder and the removal of excess liquid from the sample, comprising a humidity-controlled chamber, a sample support within the chamber, a capture to place the goniometer-compatible base, and a channel in communication with the chamber that allows for the flow of humidified air into the chamber.Type: GrantFiled: March 6, 2020Date of Patent: June 11, 2024Assignee: MiTeGen, LLCInventors: Robert E. Thorne, David Closs, Benjamin Apker
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Patent number: 11925931Abstract: Humidified sample preparation station for serial crystallography according to one embodiment is a humidified enclosure that delivers relative humidities above 95% and preferably above 97% in standard operation, and that can allow microscope observation of samples within. Humidified sample preparation station for serial crystallography can be used for preparation of protein crystal samples for examination using X-rays and for protein structure determination by X-ray crystallography, involving addition of liquid to the sample and removal of liquid from the sample using vacuum or suction.Type: GrantFiled: August 9, 2021Date of Patent: March 12, 2024Assignee: MiTeGen, LLCInventors: Richard Jayne, David Closs, Benjamin A. Apker, Robert E. Thorne
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Publication number: 20230255194Abstract: A system for cryocooling biological samples includes a first chamber that holds a first amount a cryogenic liquid. A container holder, which is positioned in thermal contact with the first chamber, holds a removable container positioned therein. The container holds a second amount of the cryogenic liquid and forms a second chamber. An elongated tube holder holds a hollow elongated tube into the container. A sample wand holds and transfers a sample holder with a biological sample into the elongated tube while the elongated tube is in the container with the second amount of the cryogenic liquid.Type: ApplicationFiled: April 19, 2023Publication date: August 17, 2023Applicant: MiTeGen, LLCInventors: Robert E Thorne, David Closs, Richard Jayne, Benjamin Apker
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Patent number: 11653644Abstract: A system for cryocooling biological samples, including a first chamber configured to hold a first amount a cryogenic liquid; a container holder positioned in thermal contact with the first chamber and configured to hold at least one removable container positioned therein, wherein the container is configured to hold a second amount of the cryogenic liquid and forms a second chamber; an elongated tube holder configured to hold at least one hollow elongated tube into the container; and a sample wand configured to hold and transfer at least one sample holder with a biological sample into the elongated tube while the elongated tube is in the container with the second amount of the cryogenic liquid therein.Type: GrantFiled: May 22, 2019Date of Patent: May 23, 2023Assignee: MITeGen, LLCInventors: Robert Thorne, David Closs, Richard Jayne, Benjamin Apker
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Patent number: 11605524Abstract: A system for storing and shipping samples for cryo-electron microscopy. The system comprising a cassette puck and support platform that accepts commercial cryo-EM sample cassettes and is compatible to a substantial extent with tools used in cryocrystallography. The system can also work with existing Cryo-EM storage and transport puck and cane systems. The cassette puck comprising a receptacle for holding one or more cassettes and a plurality of holes and grooves. The holes and grooves being configured for use with other tools such as tongs, support platforms, and canes.Type: GrantFiled: September 28, 2020Date of Patent: March 14, 2023Assignee: MiTeGen, LLCInventors: David Closs, Jessica Benitez, Benjamin Apker, Mazdak Radjainia
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Publication number: 20220412635Abstract: A cryogenic cooling manifold and methods incorporating a cryogenic cooling manifold for managing the gas layer(s) above a liquid cryogen to control cooling temperature-time profiles and ice formation for microliter and smaller samples that are plunged through the gas and into the liquid cryogen.Type: ApplicationFiled: September 1, 2022Publication date: December 29, 2022Applicant: MiTeGen, LLCInventors: David Closs, Stephen Hollabaugh, Robert E. Thorne, Robert Newman, Benjamin A. Apker
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Patent number: 11473826Abstract: A cryogenic cooling manifold and methods incorporating a cryogenic cooling manifold for managing the gas layer(s) above a liquid cryogen to control cooling temperature-time profiles and ice formation for microliter and smaller samples that are plunged through the gas and into the liquid cryogen.Type: GrantFiled: July 27, 2016Date of Patent: October 18, 2022Assignee: MiTeGen, LLCInventors: David Closs, Stephen Hollabaugh, Robert E. Thorne, Robert Newman, Benjamin A. Apker
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Publication number: 20220291098Abstract: Sample support design and sample cooling devices for single-particle cryo-electron microscopy that simplify sample preparation and handling, dramatically reduce errors and improve outcome reproducibility, and dramatically reduce overall costs. The system consisting of grid based sample support system, grid handling tools, grid blotting tools, a plunge cooling system, and jet cooling systems.Type: ApplicationFiled: October 5, 2020Publication date: September 15, 2022Applicant: MiTeGen, LLCInventors: David Closs, Benjamin Apker, Robert E. Thorne
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Publication number: 20220146441Abstract: A fixed target sample holder for serial synchrotron crystallography comprising a goniometer compatible base, a carrier, a sample holding insert which can be placed into the carrier. The sample holding insert comprising fiducials and windows, wherein each of the windows are respectively configured to accept a sample. The windows can also have holes and texture within each window. Additionally, a sample loading workstation for loading crystals into the sample holder and the removal of excess liquid from the sample, comprising a humidity-controlled chamber, a sample support within the chamber, a capture to place the goniometer-compatible base, and a channel in communication with the chamber that allows for the flow of humidified air into the chamber.Type: ApplicationFiled: March 6, 2020Publication date: May 12, 2022Applicant: MITEGEN, LLCInventors: Robert E. Thorne, David Closs, Benjamin Apker
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Publication number: 20220040685Abstract: Humidified sample preparation station for serial crystallography according to one embodiment is a humidified enclosure that delivers relative humidities above 95% and preferably above 97% in standard operation, and that can allow microscope observation of samples within. Humidified sample preparation station for serial crystallography can be used for preparation of protein crystal samples for examination using X-rays and for protein structure determination by X-ray crystallography, involving addition of liquid to the sample and removal of liquid from the sample using vacuum or suction.Type: ApplicationFiled: August 9, 2021Publication date: February 10, 2022Applicant: Mitegen, LLCInventors: Richard Jayne, David Closs, Benjamin A. Apker, Robert E. Thorne
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Publication number: 20210195889Abstract: A system for cryocooling biological samples, including a first chamber configured to hold a first amount a cryogenic liquid; a container holder positioned in thermal contact with the first chamber and configured to hold at least one removable container positioned therein, wherein the container is configured to hold a second amount of the cryogenic liquid and forms a second chamber; an elongated tube holder configured to hold at least one hollow elongated tube into the container; and a sample wand configured to hold and transfer at least one sample holder with a biological sample into the elongated tube while the elongated tube is in the container with the second amount of the cryogenic liquid therein.Type: ApplicationFiled: May 22, 2019Publication date: July 1, 2021Applicant: Mitegen, LLCInventors: Robert Thorne, David Closs, Richard Jayne, Benjamin Apker
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Publication number: 20210098226Abstract: A system for storing and shipping samples for cryo-electron microscopy. The system comprising a cassette puck and support platform that accepts commercial cryo-EM sample cassettes and is compatible to a substantial extent with tools used in cryocrystallography. The system can also work with existing Cryo-EM storage and transport puck and cane systems. The cassette puck comprising a receptacle for holding one or more cassettes and a plurality of holes and grooves. The holes and grooves being configured for use with other tools such as tongs, support platforms, and canes.Type: ApplicationFiled: September 28, 2020Publication date: April 1, 2021Applicant: Mitegen, LLCInventors: David Closs, Jessica Benitez, Benjamin Apker, Mazdak Radjainia
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Patent number: 10241015Abstract: A method and a cryogenic sample positioning system are provided which include: a sample holder cassette that is vertically coupled to a carousel gear through a first shaft. Each sample holder cassette has a first degree of rotation about the first shaft. A first planet drive gear underlies and is vertically coupled to the carousel gear through a second shaft that extends from the carousel gear through the first planet drive gear. The carousel gear has a second degree of rotation about the second shaft that is different from the first degree of rotation. A planet gear that is laterally connected to a second planet drive gear is interposed between each of the carousel gear and the first planet drive gear. Each of the planet gear and the second planet drive gear selectively define the first degree of rotation, without affecting the second degree of rotation of the carousel gear.Type: GrantFiled: July 24, 2017Date of Patent: March 26, 2019Assignee: Mitegen, LLCInventors: Stephen Hollabaugh, Robert Newman, David Closs