Patents Assigned to Leica Microsystems CMS GmbH
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Publication number: 20190258052Abstract: A light sheet microscope or a confocal microscope includes illumination optics configured to transmit light of at least two wavelengths from at least one light source, along respective wavelength-dependent beam paths, from an illumination side of the illumination optics to a specimen side of the illumination optics. A lateral chromatic correction system comprising at least one optical lateral chromatic correction element is configured such that the beam paths of the at least two different wavelengths have, at a specimen-side output of the lateral chromatic correction element, an offset parallel to each other and/or are inclined relative to each other in relation to the illumination side, which, on the specimen side of the illumination optics, results in an offset of the foci of the at least two wavelengths transverse to an optical axis of the illumination optics.Type: ApplicationFiled: August 2, 2017Publication date: August 22, 2019Applicant: Leica Microsystems CMS GmbHInventors: Florian FAHRBACH, Werner KNEBEL
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Patent number: 10386303Abstract: A Raman microscopy imaging device (100) is described, having: a first laser light source (12) for emitting a first laser beam (16) having a first wavelength along a first light path (20); a second laser light source (44) for emitting a second laser beam (18) having a second wavelength, different from the first wavelength, along a second light path (22) physically separated from the first light path (20); a beam combining element (32) for collinearly combining the two laser beams (16, 18) in one shared light path (34) directed onto a sample; a detector (38) for sensing a measured signal on the basis of the two laser beams (16, 18) interacting with the sample; and an evaluation unit (40) for evaluating the measured signal sensed by the detector (38). According to the present invention the first laser light source (12) is embodied as a pulsed source, and the second laser light source (44) as a continuous source.Type: GrantFiled: November 19, 2014Date of Patent: August 20, 2019Assignee: Leica Microsystems CMS GmbHInventors: Vishnu Vardhan Krishnamachari, Volker Seyfried, William C. Hay
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Publication number: 20190250387Abstract: A microscope system includes a light sheet microscopic functional unit that illuminates and images a sample in a first operating state with a light sheet-like illumination light distribution, and a scanning microscopic functional unit that illuminates and images the sample in a second operating state with a point-like illumination light distribution. A first scanning element uniaxially scans the sample, in the first operating state, with the light sheet-like illumination light distribution, and uniaxially scans the sample, in the second operating state, with the point-like illumination light distribution. A second scanning element uniaxially scans the sample, in the second operating state, with the point-like illumination light distribution, such that, in the second operating state, the second scanning element generates together with the first scanning element a biaxial scanning of the sample with the point-like illumination light distribution.Type: ApplicationFiled: September 19, 2017Publication date: August 15, 2019Applicant: Leica Microsystems CMS GmbHInventor: Christian SCHUMANN
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Publication number: 20190212535Abstract: A method for the examination of a sample includes illuminating the sample in a sample plane along a sample line with an illuminating light beam. The sample is acted upon by a depletion or switching light beam, which overlaps in the sample plane in an overlap region with the illuminating light beam. Part of fluorescent light emanating from the sample plane is detected as detection light originating from a first subregion of the overlap region, in which the probability of an interaction of the sample molecules with the depletion or switching light beam is greater than 90%, and/or originating from a second subregion which is at least partially surrounded by the first sub-region and/or in which the depletion or switching light beam has a zero point, while at the same time the fluorescent light originating from outside the first subregion and the second subregion is suppressed and not detected.Type: ApplicationFiled: July 5, 2017Publication date: July 11, 2019Applicant: Leica Microsystems CMS GmbHInventors: Werner Knebel, Florian Fahrbach
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Publication number: 20190204580Abstract: A light sheet microscope includes an illuminator having a beam source which is designed to direct an illuminating beam propagating along an illumination axis onto a sample. A light-sheet generator is designed to generate a light-sheet-type illuminating light distribution illuminating the sample in one partial region. A detection unit has a detector that is designed to capture detection light originating from the section of the sample that is illuminated by the illuminating light distribution. An objective is provided for both the illuminator and the detection unit such that the objective is to be penetrated by the illuminating beam and the detection light. The illuminator has a beam modulator designed to modulate the illuminating beam perpendicular to the illumination axis.Type: ApplicationFiled: August 16, 2017Publication date: July 4, 2019Applicant: Leica Microsystems CMS GmbHInventor: Florian FAHRBACH
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Patent number: 10288862Abstract: A SPIM-microscope (Selective Plane Imaging Microscopy) having a y-direction illumination light source and a z-direction detection light camera. An x-scanner generates a sequential light sheet by scanning the illumination light beam in the x-direction. By an illumination optics having a zoom optics that is provided in the beam path of the illumination light beam the focal length of the illumination light beam can be varied.Type: GrantFiled: June 1, 2015Date of Patent: May 14, 2019Assignee: Leica Microsystems CMS GmbHInventors: Werner Knebel, Wolfgang Oestreicher
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Patent number: 10215974Abstract: A selective/single plane illumination microscopy (SPIM) arrangement having an illumination device (1) for generating a light sheet (3) illuminating a sample (2); and a detection device (5), comprising a detector (4), for detected light proceeding from the sample (2), is configured and refined in the interest of efficient and low-impact sample investigation with physically simple means in such a way that the detection device (5) comprises a device (6) for allocating different focal planes of the light sheet (3) to different regions (7) of the detector (4).Type: GrantFiled: March 24, 2014Date of Patent: February 26, 2019Assignee: Leica Microsystems CMS GmbHInventors: Werner Knebel, Vishnu Vardan Krishnamachari
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Patent number: 10151675Abstract: A method for increasing the optical transparency of regions of a tissue sample (1) is proposed, in which the tissue sample (1) is introduced into a process chamber (10) and is infiltrated in the process chamber (10) with at least one process fluid (2), and in which a removal of light-scattering structures in the tissue sample (1) is carried out. The method encompasses monitoring the optical transparency of the tissue sample (1), at least during a clearing time period in which the tissue sample (1) is introduced into the process chamber (10) and in which the removal of the light-scattering structures in the tissue sample (1) is carried out, by means of an optical transparency measuring arrangement (13) associated with the process chamber (10). An apparatus (100) for carrying out the method is also a subject of the invention.Type: GrantFiled: August 26, 2014Date of Patent: December 11, 2018Assignee: Leica Microsystems CMS GmbHInventor: Bernd Sägmüller
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Patent number: 10132754Abstract: A device (10) for illuminating a sample (40) is described, having: at least one pulsed laser light source (12) for repeated emission of a first laser pulse along a first light path (14) and of a second laser pulse along a second light path (16) physically separated from the first light path; a superimposition element (32) for collinear superimposition of the two laser pulses in a shared light path (34); a delay stage (26) arranged in the first or the second light path (14, 16), for delaying one of the two laser pulses relative to the other laser pulse in such a way that the two laser pulses sent along the shared light path (34) onto the sample (40) exhibit a temporal superimposition; a shared chirp unit (36) arranged in the shared light path (34), for frequency-modifying influencing both of the first laser pulse and of the second laser pulse; and at least one separate chirp unit (18) arranged in the first light path (14), for frequency-modifying influencing only of the first laser pulse.Type: GrantFiled: November 19, 2014Date of Patent: November 20, 2018Assignee: Leica Microsystems CMS GmbHInventors: Vishnu Vardhan Krishnamachari, Volker Seyfried, William C. Hay, Manuel Kremer
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Patent number: 10132682Abstract: The invention relates to a microscope having an acousto-optic apparatus (13) that, with a mechanical wave that is characterized by a preferably adjustable frequency, removes from a polychromatic and collinear detected light bundle (18) portions of illuminated light, scattered and/or reflected at a sample, having an illuminating light wavelength associated with the frequency.Type: GrantFiled: September 3, 2014Date of Patent: November 20, 2018Assignee: Leica Microsystems CMS GmbHInventors: Volker Seyfried, Vishnu Vardhan Krishnamachari
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Patent number: 10073034Abstract: The present invention relates to a method for measuring the lifetime of an excited state in a sample, in particular a fluorescence lifetime, and to an apparatus for carrying out such a method. First, an excitation pulse is generated and a sample region is illuminated with the excitation pulse. Then, a first digital data sequence is generated which is representative of the power-time profile of the excitation pulse, and a first switching instant is determined from the first digital data sequence. Moreover, the detection light emanating from the sample region is detected by a detector, and a second digital data sequence is generated which is representative of the power-time profile of the detection light, and a second switching instant is determined from the second digital data sequence. Finally, the time difference between the first and second switching instants is calculated.Type: GrantFiled: November 14, 2012Date of Patent: September 11, 2018Assignee: Leica Microsystems CMS GmbHInventor: Bernd Widzgowski
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Patent number: 10025081Abstract: An objective and an illumination unit for selectable generation of an orthoscopic beam path proceeding through the objective for pointlike scanning illumination, and of a conoscopic beam path proceeding through the objective for evanescent illumination of an object are disclosed. The illumination unit has a light source for generating illuminating rays along an illuminating beam path; a displacement unit for deflecting the illuminating beam path; a scanning eyepiece, placed after the displacement unit for focusing the illuminating rays into an image plane of the scanning eyepiece; and a mirror surface arranged in the image plane of the scanning eyepiece, having a transparent region for generating the orthoscopic beam path and having an at least partly reflective region facing toward the scanning eyepiece for generating the conoscopic beam path from the illuminating beam path, the image plane is located in a plane conjugated with the exit pupil.Type: GrantFiled: October 30, 2014Date of Patent: July 17, 2018Assignee: Leica Microsystems CMS GmbHInventors: Peter Euteneuer, Christian Schumann
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Patent number: 10012826Abstract: A method, in which a sample is manipulated with manipulation light, includes imaging the sample using a single plane illumination microscopy SPIM technique under illumination with illumination light being an illumination light sheet of fluorescent excitation light. Both the manipulation light and the illumination light are focused by an objective brought to an objective working position. Either the manipulation light or the illumination light are diverted after passing through the objective by use of a diverting device to propagate the manipulation light or the illumination light at an angle different from zero degrees with respect to an optical axis of the objective.Type: GrantFiled: March 20, 2014Date of Patent: July 3, 2018Assignee: Leica Microsystems CMS GmbHInventors: Werner Knebel, Wernher Fouquet, Frank Sieckmann
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Patent number: 9952155Abstract: A method for illumination and detection in RESOLFT microscopy using a pulsed or continuous light source for excitation light and switching light is characterized in that the excitation light (4) is irradiated in pulses and in that the pulse of the excitation light (4) is longer than 150 picoseconds, preferably up to a few hundred picoseconds, and even up to a few nanoseconds. A corresponding apparatus uses the method according to the present invention.Type: GrantFiled: November 5, 2012Date of Patent: April 24, 2018Assignee: Leica Microsystems CMS GmbHInventor: Jonas Foelling
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Patent number: 9933686Abstract: The invention relates to an acousto-optic main beam splitter for a scanning microscope, which is embodied and intended to direct illuminating light having a preselected or preselectable illuminating light wavelength into an illumination beam path for illumination of a sample, and to direct detected light coming from a sample into a detection beam path.Type: GrantFiled: September 3, 2014Date of Patent: April 3, 2018Assignee: Leica Microsystems CMS GmbHInventor: Vishnu Vardhan Krishnamachari
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Patent number: 9909976Abstract: The invention relates to a method for investigating a sample, the sample being impinged upon by illuminating light, and detected light emerging from the sample being directed to a detector, and the illuminating light being directed through an acousto-optic component with which the impingement upon the sample by illuminating light can be temporarily interrupted.Type: GrantFiled: September 3, 2014Date of Patent: March 6, 2018Assignee: Leica Microsystems CMS GmbHInventor: Vishnu Vardhan Krishnamachari
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Publication number: 20180031420Abstract: A method for improving dynamic range of a device for detecting light includes providing at least two detection regions. The detection regions are each formed by an array of a plurality of single-photon avalanche diodes (SPADs) and the detection regions each comprise at least one signal output. A characteristic curve is determined for each of the detection regions. The characteristic curves are combined with one another and/or offset against one another in order to obtain a correction curve and/or a correction factor.Type: ApplicationFiled: February 24, 2016Publication date: February 1, 2018Applicant: Leica Microsystems CMS GmbHInventor: Marcus Dyba
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Patent number: 9772485Abstract: A method for light-microscopy imaging of a sample structure (2, 34) is described, having the following steps: preparing the sample structure (2, 34) with markers that are transferrable into a state imageable by light microscopy, generating a sequence of individual-image data sets by sequential imaging of the sample structure (2, 34), in such a way that for each image, only a subset of the totality of the markers is in each case transferred into the state imageable by light microscopy, the markers of the respective subset having an average spacing from one another which is greater than the resolution limit of light-microscopy imaging which determines the extent of a light distribution representing one of the respectively imaged markers, generating at least two data blocks in which multiple successive individual-image data sets are respectively combined, superposing the individual-image data sets contained in the respective data block to yield a superposed-image data set, identifying an image offset betweenType: GrantFiled: June 27, 2011Date of Patent: September 26, 2017Assignee: Leica Microsystems CMS GmbHInventors: Marcus Dyba, Volker Seyfried
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Patent number: D799576Type: GrantFiled: November 5, 2014Date of Patent: October 10, 2017Assignee: Leica Microsystems CMS GmbHInventor: Christophe Apothéloz
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Patent number: D824445Type: GrantFiled: February 18, 2015Date of Patent: July 31, 2018Assignee: Leica Microsystems CMS GmbHInventor: Christophe Apothéloz