Patents Assigned to Leica Mikrosysteme GmbH
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Patent number: 11940362Abstract: A method including one or more steps of a procedure for preparing a microscopic sample for a high-pressure freezing process is provided, wherein the sample is provided using an arrangement comprising a middle plate of a high-pressure freezing cartridge and an incubation chamber, wherein the middle plate is attached to a lower surface of a bottom of the incubation chamber by an adhesive and detachable from the incubation chamber by effecting a relative movement between the middle plate and the incubation chamber, wherein the sample is provided on an enclosing element which is fitted into an opening of the middle plate, and wherein, when the sample is to be subjected to the high-pressure freezing process, the relative movement between the middle plate and the incubation chamber is effected, thereby detaching the middle plate with the sample from the incubation chamber. Means to implement the method are also part of the present disclosure.Type: GrantFiled: August 30, 2021Date of Patent: March 26, 2024Assignee: Leica Mikrosysteme GmbHInventors: Rainer Wogritsch, Paul Wurzinger, Joose Kreutzer
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Patent number: 11828692Abstract: A device for preparing a microscopic sample for a high-pressure freezing process in which the sample is provided using an arrangement having a middle plate of a high-pressure freezing cartridge and an incubation chamber, the middle plate being attached to and detachable from the incubation chamber by effecting a relative movement between the middle plate and the incubation chamber, and the sample being provided on an enclosing element which is fitted into an opening of the middle plate, wherein the device includes an engagement structure adapted to engage with the middle plate and to restrict a movement of the middle plate while the incubation chamber is moved, such as to effect the relative movement between the middle plate and the incubation chamber and to thereby detach the middle plate from the incubation chamber.Type: GrantFiled: August 30, 2021Date of Patent: November 28, 2023Assignee: Leica Mikrosysteme GmbHInventors: Rainer Wogritsch, Paul Wurzinger
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Patent number: 11764031Abstract: The present invention concerns a method and a system for imaging at least a part of a specimen by means of two microscopy imaging methods, where a surface (11) of the specimen (10) is imaged by means of a first microscopy imaging method, where a replica (25) of the surface (11) to be imaged by means of the first microscopy imaging method is produced and this replica (25) is simultaneously imaged by means of a second microscopy imaging method, where the images produced by means of the first and the second microscopy imaging methods are overlaid at the correct scale.Type: GrantFiled: January 30, 2020Date of Patent: September 19, 2023Assignee: Leica Mikrosysteme GmbHInventor: Peer Oliver Kellermann
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Patent number: 11754477Abstract: A high pressure freezing cartridge (300, 400, 500) for use in vitrification of a biological sample (10) is provided, the cartridge (300, 400, 500) being adapted to fixedly hold a sample chamber (216, 218, 220) at a sample chamber position (320, 420, 520) in the cartridge (300, 400, 500), a refrigerant channel arrangement comprising at least one refrigerant channel (208, 308, 408, 462, 464, 466, 468, 508, 562, 564, 566, 569) being provided in the cartridge (300, 400, 500) and extending from a surface of the cartridge (300, 400, 500) to the sample chamber position, and the cartridge (300, 400, 500) comprising a baffle structure (350, 450, 550, 571) at a baffle position being adapted to interact with a refrigerant stream in the refrigerant channel arrangement before the refrigerant of the refrigerant stream reaches the sample chamber position in the cartridge (300, 400, 500). A corresponding method in which the high pressure freezing cartridge (300, 400, 500) is used is also part of the present disclosure.Type: GrantFiled: August 10, 2021Date of Patent: September 12, 2023Assignee: Leica Mikrosysteme GmbHInventors: Paul Wurzinger, Rainer Wogritsch, Ricardo Vizcaya Benavides, Julia König
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Patent number: 11311886Abstract: The invention relates to a holding apparatus (100) for sample carriers (200) for use in cryomicroscopy, encompassing: a body having at least one sample carrier receptacle that comprises at least one sample carrier support surface against which at least one sample carrier (200) is abuttable; at least one first sample carrier holding means (121); and at least one second sample carrier holding means (131) that is configured to impinge upon the sample carrier (200) with force against the first sample carrier holding means (121); and to an arrangement having a manipulation container and such a holding apparatus (100), and to methods for introducing and withdrawing a sample carrier (200).Type: GrantFiled: April 3, 2018Date of Patent: April 26, 2022Assignee: LEICA MIKROSYSTEME GMBHInventors: Reinhard Lihl, Leander Gaechter, Saskia Mimietz-Oeckler
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Patent number: 11238626Abstract: A method is proposed for generating a series of sections of a microscopic sample (10), in which the sections are detached from the sample (10) by means of a blade (21), collected, and placed onto a transfer device. A sequence in which the sections are detached from the sample is detected; detachment of the sections from the sample (10) and/or collection of the sections and/or placement of the sections onto the transfer device is monitored by means of one or several observation cameras, accompanied by the acquisition of moving-image data; the sections are tracked in the moving-image data; and positions of the sections on the transfer device are correlated, on the basis of the tracking in the moving-image data, with the sequence in which they were detached from the sample.Type: GrantFiled: December 9, 2019Date of Patent: February 1, 2022Assignee: LEICA MIKROSYSTEME GMBHInventor: Peer Oliver Kellermann
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Patent number: 10901196Abstract: In a light microscope (1) for cryomicroscopy, encompassing at least an objective (2) and a sample stage (3) having a cutout (7) for a coolable holder (8) for a sample carrier mount, the cutout (7) being covered by a cover (6), the sample stage (3) is displaceable in two horizontal directions (4). The cover (6) rests floatingly on the sample stage (3), and the objective (2) passes through a cutout (12), corresponding to the objective (2), in the cover (6). The method for cooling a holder (8) for a sample carrier mount in a light microscope (1) for cryomicroscopes, by means of a flow of liquid nitrogen through a cooling conduit (15), open at at least one end, in the holder (8), is notable for the fact that the quantity of liquid nitrogen is dimensioned so that all of the nitrogen is present in gaseous form at at least one open end (16) of the cooling conduit (15).Type: GrantFiled: July 15, 2015Date of Patent: January 26, 2021Assignees: LEICA MIKROSYSTEME GMBH, EUROPEAN MOLECULAR BIOLOGY LABORATORYInventors: Reinhard Lihl, John Briggs, Martin Schorb, Leander Gaechter
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Patent number: 10809211Abstract: A modular specimen holder (10?) for high pressure freezing and/or X-ray crystallography of a specimen has a specimen holding element (100?) and an extension element (200?) connectable with and separable from each other; the specimen holding element (100?) including a tubule (120?) adapted to hold the specimen and a base element (110?) adapted to hold the tubule (120?), wherein a distance from a bottom of the base element (110?) to a top of the tubule (120?) is a first distance (d1); the extension element (200?) being connectable with the base element (110?), wherein, when the extension element (200?) and the base element (110?) are connected with each other, a second distance (d2) from a bottom of the extension element (200?) to the top of the tubule (120?) is larger than the first distance (d1).Type: GrantFiled: July 13, 2017Date of Patent: October 20, 2020Assignee: Leica Mikrosysteme GmbHInventors: Rainer Wogritsch, Cveta Tomova, Paul Wurzinger, Heinz Plank, Siegfried Tanki
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Patent number: 10551285Abstract: The invention relates to a sample transfer device (10) for reception of a sample, having a transfer rod (4) that is configured for reception of a sample holder, the sample holder to be arranged in a chamber (1) of the sample transfer device (10) for the purpose of transferring the sample to a processing unit or analytical unit (200), at least one measurement device (3, 8) for measuring a physical variable being arranged inside the sample transfer device (10).Type: GrantFiled: January 14, 2016Date of Patent: February 4, 2020Assignee: Leica Mikrosysteme GmbHInventors: Leander Gaechter, Günther Bock, Thomas Pfeifer
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Patent number: 10539360Abstract: The invention relates to a freezing machine (150) for freezing samples, encompassing: a freezing device (140) for freezing a sample received in the freezing machine (150); a container (100) for receiving the frozen sample, having a reservoir (105) for liquid nitrogen; and a transfer apparatus for transferring the frozen sample from the freezing device (140) into the container (100), the container (100) comprising at least two receiving devices (104), separated from one another, each for at least one frozen sample; a selection apparatus being provided for selecting one of the receiving devices (104) for a frozen sample that is to be transferred into the container (100), the freezing machine (150) being configured to carry out the transfer of the frozen sample, by means of the transfer apparatus, into the respectively selected receiving device (104) of the container (100); and to a method for transferring frozen samples into a container provided therefor.Type: GrantFiled: November 13, 2014Date of Patent: January 21, 2020Assignee: Leica Mikrosysteme GmbHInventors: Robert Lange, Cveta Tomova
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Patent number: 10520398Abstract: A microtome system has a cryomicrotome with a sectioning device in which is provided a preparation holder and a knife edge that are guided past one another inside a working space during a sectioning operation, in order to produce thin sections of a preparation retained in the preparation holder. A micromanipulator is operable outside the working space. With the micromanipulator, a tool for retention of a specimen support is positioned proximate the knife edge during a sectioning operation in order to receive the sections that are produced, preferably for substantially stationary retention of the specimen support.Type: GrantFiled: January 8, 2016Date of Patent: December 31, 2019Assignee: Leica Mikrosysteme GmbHInventors: Reinhard Lihl, Michael Zimmermann
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Patent number: 10217603Abstract: A loading station (100, 200) for translocating a frozen sample for electron microscopy, encompassing a chamber (104, 204), open toward the top, that is fillable at least partly with a coolant, the chamber (104, 204) comprising in its side wall at least two ports (101a, 102a, 103a) each for different sample transfer devices (101, 102, 103), the ports (101a, 102a, 103a) permitting introduction of a frozen sample into the chamber (104, 204) via a selected sample transfer device and withdrawal of a frozen sample from the chamber via a respective different sample transfer device; and wherein a receptacle (108, 208) for at least two differently configured sample holders (109, 110) is arranged in the chamber (104, 204), the at least two sample holders (109, 110) being detachably fastenable to at least one of the sample transfer devices (101) for introduction of the frozen sample into the chamber (104, 204) and for withdrawal of the frozen sample from the chamber (104, 204).Type: GrantFiled: July 15, 2015Date of Patent: February 26, 2019Assignee: Leica Mikrosysteme GmbHInventors: Reinhard Lihl, Leander Gaechter
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Patent number: 10144010Abstract: In a manipulation container (1) for cryomicroscopy, having at least one holder (9) for a sample carrier mount (7) and at least one manipulation opening (2) for manipulating sample carriers or sample carrier mounts (7), the holder (9) for a sample carrier mount (7) is movable into a displacement path (11), passing completely through the manipulation container (1), of a displacement apparatus (3) for the sample carrier mount (7).Type: GrantFiled: July 21, 2015Date of Patent: December 4, 2018Assignees: Leica Mikrosysteme GmbH, European Molecular Biology LaboratoryInventors: Reinhard Lihl, Leander Gaechter, John Briggs, Martin Schorb
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Patent number: 10073016Abstract: A freeze fracture machine (100) comprises a vacuum chamber (110); a sample receptacle (160) for receiving a sample to be processed and a knife receptacle (150) for receiving a knife (110) for processing of the sample arranged in the vacuum chamber (155); a transfer lock (130) on the vacuum chamber (110) through which a sample and a knife (155) are introducible into the vacuum chamber (155) and positionable in the vacuum chamber (110) by means of a positioning apparatus (135); the sample and the sample receptacle (160) being positionable with respect to one another such that the sample is mountable on the sample receptacle (160) by means of the positioning apparatus (135); and the knife (155) and the knife receptacle (150) being positionable with respect to one another such that the knife (155) is mountable on the knife receptacle (150) by means of the positioning apparatus (135).Type: GrantFiled: November 28, 2015Date of Patent: September 11, 2018Assignee: Leica Mikrosysteme GmbHInventors: Reinhard Lihl, Michael Zimmermann
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Publication number: 20170227752Abstract: In a light microscope (1) for cryomicroscopy, encompassing at least an objective (2) and a sample stage (3) having a cutout (7) for a coolable holder (8) for a sample carrier mount, the cutout (7) being covered by a cover (6), the sample stage (3) is displaceable in two horizontal directions (4). The cover (6) rests floatingly on the sample stage (3), and the objective (2) passes through a cutout (12), corresponding to the objective (2), in the cover (6). The method for cooling a holder (8) for a sample carrier mount in a light microscope (1) for cryomicroscopes, by means of a flow of liquid nitrogen through a cooling conduit (15), open at at least one end, in the holder (8), is notable for the fact that the quantity of liquid nitrogen is dimensioned so that all of the nitrogen is present in gaseous form at at least one open end (16) of the cooling conduit (15).Type: ApplicationFiled: July 15, 2015Publication date: August 10, 2017Applicants: Leica Mikrosysteme GmbH, European Molecular Biology LaboratoryInventors: Reinhard LIHL, John BRIGGS, Martin SCHORB, Leander GAECHTER
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Patent number: 9097632Abstract: In a device (1) for rapid pressure-freezing an aqueous sample (3), such as a biological specimen, a pressurized cooling medium can be fed into a high-pressure chamber (11) into which a sample holder (30) containing a sample (3) is inserted and which is sealed with a pressure-tight seal, to the location of the sample holder (30) held therein. The high-pressure chamber (11) comprises a viewing window structure (2) with a pressure-tight window (20), through which light can be directed from the outside onto the sample (3) located in the sample holder (30). The window (20) can comprise a transparent window element made of a high-pressure-resistant material, wherein the window element (20) is held by a pressure- and temperature-resistant window bearing provided in the high-pressure chamber.Type: GrantFiled: February 27, 2013Date of Patent: August 4, 2015Assignee: LEICA MIKROSYSTEME GMBHInventors: Reinhard Lihl, Rainer Wogritsch, Heinz Plank
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Patent number: 8648316Abstract: The invention relates to a cooling apparatus (101) for a sample in an ion beam etching process, including, a sample stage (102) for arranging the sample, a coolant receptacle (120) containing a coolant, at least one thermal conduction element (106a, 106b) that connects the sample stage (102) to the coolant, a cooling finger (105) connected to the thermal conduction element (106a, 106b), the cooling finger (105) comprising a conduit (130, 131) through which coolant can flow and which is connectable to the coolant receptacle (120). The invention further relates to a method of adjusting the temperature of a sample in an ion beam etching process, including mounting a sample on a coolable sample stage (102), aligning the sample on the sample stage (102), and cooling the sample by coolant directed through a conduit (130, 131) of a cooling finger.Type: GrantFiled: December 21, 2011Date of Patent: February 11, 2014Assignee: Leica Mikrosysteme GmbHInventors: Thomas Pfeifer, Rainer Wogritsch
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Patent number: 8585985Abstract: An apparatus for staining sample sections, comprising: a chamber that is adapted for fastening sample sections therein; and a pump that is adapted for pumping liquids through the chamber. The chamber has an inlet and an outlet. The inlet can be connected to at least one reservoir of a staining liquid via inlet lines that are controllable by valves. The inlet lines are formed at least in the region of the associated valves by means of elastic hose lines, and the valves are formed as hose pinch valves. This apparatus minimizes or eliminates contaminations arising from staining processes for thin sections that are in particular prepared for examination in an electron microscope.Type: GrantFiled: July 21, 2008Date of Patent: November 19, 2013Assignee: Leica Mikrosysteme GmbHInventors: Reinhard Lihl, Heinz Plank, Siegfried Tanki
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Patent number: 8555758Abstract: The present invention relates to a method for positioning a cutting knife of a microtome or ultramicrotome equipped with motors for moving the cutting knife. The method may include determining/defining at least two segments of the cutting knife according to a division of the previously defined width of the cutting knife, selecting a segment of the cutting knife, and positioning the cutting knife in an operational position by motorized movement of the cutting knife, the selected segment of the cutting knife being positioned to cut the specimen.Type: GrantFiled: July 26, 2010Date of Patent: October 15, 2013Assignee: Leica Mikrosysteme GmbHInventors: Robert Ranner, Andreas Loydold
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Publication number: 20130227970Abstract: In a device (1) for rapid pressure-freezing an aqueous sample (3), such as a biological specimen, a pressurized cooling medium can be fed into a high-pressure chamber (11) into which a sample holder (30) containing a sample (3) is inserted and which is sealed with a pressure-tight seal, to the location of the sample holder (30) held therein. The high-pressure chamber (11) comprises a viewing window structure (2) with a pressure-tight window (20), through which light can be directed from the outside onto the sample (3) located in the sample holder (30). The window (20) can comprise a transparent window element made of a high-pressure-resistant material, wherein the window element (20) is held by a pressure- and temperature-resistant window bearing provided in the high-pressure chamber.Type: ApplicationFiled: February 27, 2013Publication date: September 5, 2013Applicant: LEICA MIKROSYSTEME GMBHInventors: Reinhard LIHL, Rainer WOGRITSCH, Heinz PLANK