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公开(公告)号：US11314068B2
公开(公告)日：2022-04-26
申请号：US16574437
申请日：2019-09-18
摘要： The invention relates to an illumination apparatus for a microscope, a microscope and a method for operating the illumination apparatus. The illumination apparatus has a sample space for holding a sample that is to be illuminated, and at least one laser light source. An objective for the directional emission of laser radiation of a first wavelength along a first optical axis that is directed into the sample space, and with a cover of the sample space by which the sample space is delimited at least on one of its sides. The cover further has a layer that is either impenetrable for the laser radiation over a blocking angle range of the illumination angle and is transmissive for radiation of a second wavelength over a transmitted light angle range, or has a controllable layer that, in a first control state, is transparent for radiation of the second wavelength and, in a second control state, is impenetrable for the laser radiation of the first wavelength.
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2.发明授权公开(公告)号：US11300770B2
公开(公告)日：2022-04-12
申请号：US16312517
申请日：2017-06-29
摘要： A method for adjusting a specimen holder in the beam path of a microscope, in which at least one beam of an illumination radiation is directed onto the specimen holder; a component of the illumination radiation reflected by the specimen holder is captured by means of a detector and measurement values of the captured illumination radiation are ascertained. A current actual manner of positioning of the specimen holder in relation to the beam path is established depending on the measurement values; the established actual manner of positioning is compared to an intended manner of positioning, and control commands for modifying the actual manner of positioning are produced, the execution of which causes the specimen holder to be moved into the intended manner of positioning.
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3.发明申请公开(公告)号：US20220057329A1
公开(公告)日：2022-02-24
申请号：US17309510
申请日：2019-12-02
发明人： Thomas Kalkbrenner
IPC分类号： G01N21/64 , G01N33/542 , G02B21/00 , G02B27/00 , G02B26/06
摘要： The disclosure relates to a detection method for optical signals in a three-dimensional region of a sample, and a detection method for marked antibodies and/or antigens on a biological surface. In the process, signals with a depth of field that is extended in relation to an original depth of field are captured and evaluated. Also, an apparatus includes an optical element in a detection beam path, a depth of field that is extended in relation to an original depth of field being generated by the effect of said optical element.
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公开(公告)号：US11194144B2
公开(公告)日：2021-12-07
申请号：US16310870
申请日：2017-06-21
发明人： Ralf Netz , Thomas Kalkbrenner , Tiemo Anhut
摘要： A microscopy method, and related microscope, including producing illumination radiation and directing it at a focus. The illumination radiation is switched temporally between at least two modes, such that focus modulation is effected at which temporally varying and mutually different mode fields of the illumination radiation are produced in the focus. The focus is guided at least over regions of a sample to be examined, wherein detection radiation in the sample is or may be brought about by the illumination radiation in the focus at least at a point of origin. The detection radiation is captured in a manner assigned to the at least one point of origin. In addition to the illumination radiation, at least one disexcitation beam of rays of disexcitation radiation is directed at the focus. The disexcitation radiation prevents the detection radiation from being brought about in the region that is illuminated by the disexcitation radiation.
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公开(公告)号：US20200300765A1
公开(公告)日：2020-09-24
申请号：US16826058
申请日：2020-03-20
发明人： Thomas Kalkbrenner , Yauheni Novikau , Martin Beck
摘要： The invention relates to a localization microscopy method for localizing signal sources. Here, at least once for each pixel of a detector, values of an error parameter are ascertained and stored in a calibration data record in a manner assigned to the relevant pixel. Captured image data are used to identify regions of origin of signal sources and fit a point spread function to the pixel values of the respective regions of origin. The respective signal source is localized on the basis of the point spread function. The pixel-specific error parameter of each pixel can be compared to a threshold. If the threshold is exceeded, these pixels are either ignored or replaced by means of interpolation when fitting the point spread function. In addition or as an alternative thereto, the real noise performance of the pixels is ascertained and corrected on the basis of derived pixel-specific error parameters.
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6.发明申请公开(公告)号：US20200096752A1
公开(公告)日：2020-03-26
申请号：US16574437
申请日：2019-09-18
摘要： The invention relates to an illumination apparatus for a microscope, a microscope and a method for operating the illumination apparatus. The illumination apparatus has a sample space for holding a sample that is to be illuminated, and at least one laser light source. An objective for the directional emission of laser radiation of a first wavelength along a first optical axis that is directed into the sample space, and with a cover of the sample space by which the sample space is delimited at least on one of its sides. The cover further has a layer that is either impenetrable for the laser radiation over a blocking angle range of the illumination angle and is transmissive for radiation of a second wavelength over a transmitted light angle range, or has a controllable layer that, in a first control state, is transparent for radiation of the second wavelength and, in a second control state, is impenetrable for the laser radiation of the first wavelength.
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公开(公告)号：US20190094512A1
公开(公告)日：2019-03-28
申请号：US16144839
申请日：2018-09-27
发明人： Thomas Ohrt , Thomas Kalkbrenner
摘要： The invention relates to an immersion matrix (5), designed for adjusting optical properties at interfaces of optical arrangements, having a porosity with pores of at least one pore size selected from a range from >20 nm to 200 μm and/or nanopores in the material of the immersion matrix (5), wherein the nanopores have at least one average pore size selected from a range of 0.5 nm to 20 nm, and an elasticity modulus E selected from a range of 0.1-100 MPa. The invention furthermore relates to the use of the immersion matrix (5), an arrangement with the immersion matrix and an immersion device.
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8.发明授权公开(公告)号：US10234667B2
公开(公告)日：2019-03-19
申请号：US15573429
申请日：2016-05-09
摘要： A method for evaluating signals of fluorescence scanning microscopy with simultaneous excitation and detection of fluorescence in different focal planes of a sample by means of confocal laser scanning microscopy. The invention evaluates signals of fluorescence scanning microscopy without the signal losses usually taking place with a confocal aperture, by coupling an illumination beam into a microscope observation beam path which images a measuring volume on a detector array arranged in the image plane, focusing the illumination beam which passes through a beam-forming phase mask for generating an elongated focus in the measuring volume, collecting and collimating fluorescent light generated in the measuring volume and routing it to diffractive optics which split the light beams into different diffraction orders and impress a different spherical phase on the light beams, imaging the different diffraction orders on detector regions of the detector array so that fluorescent light from focal planes at different depths of the measuring volume are associated with different diffraction orders, and associating the fluorescence signals on which crosstalk is superposed from different focal planes of the measuring volume with defined focal planes by means of correlation-based association based on distinguishable blinking behavior of fluorescing dyes.
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公开(公告)号：US10042153B2
公开(公告)日：2018-08-07
申请号：US14889417
申请日：2014-04-25
发明人： Thomas Kalkbrenner
IPC分类号： G02B21/36 , G02B5/30 , G02B21/00 , G02B21/16 , G02B21/18 , G01N21/64 , H04N13/20 , H04N13/271
摘要： A microscope for high-resolution imaging of a sample in a depth direction and transversely thereto has an excitation beam path for illuminating a sample,—an imaging beam path with an objective and two detectors,—and a phase element. The phase element is situated in a pupil of the imaging beam path and has a different influence on two halves of the pupil cross section. The imaging beam path is split into two partial imaging beam paths downstream of the pupil as seen in the imaging direction, which partial imaging beam paths each lead to one of the two detectors. The two partial imaging beam paths have imaging lengths that differ by a specific wavelength difference such that the two detectors record images of the sample from two different focal planes, which are spaced apart by a distance in the depth direction.
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公开(公告)号：US09983395B2
公开(公告)日：2018-05-29
申请号：US14432858
申请日：2013-09-27
发明人： Thomas Kalkbrenner
IPC分类号： G02B21/00
CPC分类号： G02B21/0032 , G02B6/04 , G02B21/0036 , G02B21/004 , G02B21/0052
摘要： A microscope for raster-free, confocal imaging of a sample arranged in a sample space has an illumination arrangement comprising a light source group having light sources which can be switched on individually, a detector arrangement, a pinhole arrangement which comprises a pinhole array and which has a plurality of pinhole elements which are adjacent to one another, wherein there is one pinhole element provided for each light source, and optics which irradiate each pinhole element with radiation of an individual light source of the light source group and confocally illuminate an individual spot located in the sample space, wherein one of the individual spots is associated with each pinhole element, and the individual spots are adjacent to one another in the sample space with respect to an incidence direction of the radiation, and the optics image the individual spots through the pinhole arrangement confocally on the detector arrangement.
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