WO2003069391A1 - Dispositif de microscopie optique confocale - Google Patents

Dispositif de microscopie optique confocale Download PDF

Info

Publication number
WO2003069391A1
WO2003069391A1 PCT/EP2003/000765 EP0300765W WO03069391A1 WO 2003069391 A1 WO2003069391 A1 WO 2003069391A1 EP 0300765 W EP0300765 W EP 0300765W WO 03069391 A1 WO03069391 A1 WO 03069391A1
Authority
WO
WIPO (PCT)
Prior art keywords
array
optical
illumination
elements
light
Prior art date
Application number
PCT/EP2003/000765
Other languages
German (de)
English (en)
Inventor
Norbert Czarnetzki
Original Assignee
Carl Zeiss Microelectronic Systems Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Carl Zeiss Microelectronic Systems Gmbh filed Critical Carl Zeiss Microelectronic Systems Gmbh
Publication of WO2003069391A1 publication Critical patent/WO2003069391A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • G01N21/6458—Fluorescence microscopy
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes
    • G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
    • G02B21/0036—Scanning details, e.g. scanning stages
    • G02B21/004—Scanning details, e.g. scanning stages fixed arrays, e.g. switchable aperture arrays
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes
    • G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
    • G02B21/0052—Optical details of the image generation
    • G02B21/0076—Optical details of the image generation arrangements using fluorescence or luminescence

Definitions

  • the invention relates to a device for confocal optical microanalysis, comprising an object table for receiving an object to be examined, which can be moved for optical scanning of the object in an XY plane, an illumination device with one or more light sources for illuminating an object on the object table - Conceivable object, a lighting optics arranged between the lighting device and the object table with an array of a plurality of grid-shaped, optically - namely refractive, diffractive and / or reflective - effective micro-elements for generating a grid from a multiplicity of lighting points the object to be examined, and a receiving device with a plurality of receiver cells for receiving the light coming back from the object in an individual assignment to the individual lighting points.
  • Such a device is known from DE 40 35 799 C2.
  • the object is illuminated with light points arranged in a grid.
  • the light point structure is predetermined by an aperture provided in the illumination beam path with a plurality of openings arranged in a grid.
  • the illumination grid is imaged with a grid dimension on a receiving device, namely a CCD receiver, which corresponds to the grid dimension of the light-sensitive areas of the CCD receiver or is an integral multiple thereof.
  • DE 40 35 799 C2 discloses the possibility of generating the illumination grid by means of an array from a multiplicity of lenses, which generates small light spots by means of sufficiently good imaging properties from an almost punctiform light source.
  • the object of the invention is to further improve a device of the type mentioned at the outset.
  • a device for fast analysis methods is to be made available, in which on the one hand a high efficiency of the lighting is to be ensured and on the other hand an evaluation with electronic methods is possible with a differentiated transformation of the image information from the object to be examined into an image plane.
  • a second array is assigned from a plurality of optical micro-elements arranged in a grid, which direct the light coming back from the illumination points on the object onto the receiver cells of the receiving device.
  • the optical microelements of the first array rhombically.
  • the rhombic arrangement of the optical micro-elements also favors a high luminous efficacy when lighting.
  • the proportion of the optical microelements in the area of the respective array is preferably 80% or more.
  • the receiving device is a surface camera or line camera, the object table being movable synchronously with the reading of the receiving device.
  • an area camera in the form of a structured TDI camera (TDI: Time Delayed Integration) is preferably used, the line scan rate of which is coordinated with the travel speed of the object table and which then provides a continuous, digitized image of the object to be examined. delivers the object from a large number of drawing files or single lines.
  • TDI Time Delayed Integration
  • the optical microelements of the first array can be designed, for example, as spherical or aspherical micromirrors.
  • a color-correct image of the light source (s) eg several lasers
  • the spherical aberration is smaller in the case of openings of the illuminating beam bundles that are not so large in comparison with refractive microelements of the same refractive power.
  • a vertical incidence of the illuminating beams which is advantageous for images with shaped micromirrors, can be achieved, for example, by suitable polarization-optical or dichroic splitter elements.
  • a polarizer is preferably provided in order to utilize the effect of a polarization-optical divider element.
  • one or more lasers as the light source in the lighting device, in which an intrinsic linear polarization is possible without additional loss of light output.
  • the laser light is preferably coupled into the illumination beam path via polarization-maintaining optical fibers.
  • the illumination side is preferably dimensioned such that the illumination points on the object do not exceed the size of the object structures to be resolved thereon and the illumination cones illuminate the aperture of the optical microelements of the second array that can be recorded on the image side.
  • the free diameter of the micromirrors is primarily adapted to the needs of a high area coverage, the distance between the micromirrors, however, having to take into account the requirements for confocality.
  • the ratio of the mirror diameter to the mean radius of curvature is very small for the practical applications of interest, so that the imaging via the mirror takes place in the para-axial space.
  • refractive or diffractive microelements can of course also be used, these being preferably optimized for several wavelengths (fluorescence excitation). Holographic micro-elements are also to be counted for this.
  • a color correction for imaging light sources in the image plane for two wavelengths is achieved by taking into account dispersive properties of the lens material and diffractive effects of the lens edges.
  • pinhole array between the first array and the object table, which has a large number of pinholes arranged in a grid.
  • the grid of the pinholes corresponds to the grid of the micro elements of the first array and is conjugated to it. Above all, false pin effects can be kept low by the pin holy array.
  • the neutral, optically ineffective zones between the micro-elements can be blackened or made of light-absorbing material in order to avoid reflections and to prevent an illumination background.
  • an illuminance of almost 100% can even be achieved.
  • polarization splitters or dichroic splitters in the form of preferably optical cubes are provided.
  • a ⁇ / 4 plate allows a good separation of illuminating and imaging light in the direction of illumination.
  • a steep-edged formation of the spectral separating edge of the polarization splitter layer or of the dichroic splitter layer is advantageous. This can be supplemented by suitable excitation edge filters on the part of the lighting device.
  • the lighting device generates monochromatic light or else light of defined but different wavelengths. If a white light source is used, the excitation wavelengths are fixed by suitable band filters. However, it is also possible the use of laser light sources or arc lamps with extracted lines of different wavelengths. Longitudinal color errors that may occur for different excitation waves are eliminated by focusing the object to be examined, eg. B. compensated by focusing the object table. A correction by focusing the two arrays is also possible.
  • the ends of one or more illumination fibers can also be used as point light sources, which are achromatically collimated.
  • the device explained above is particularly suitable for the optical analysis of substances arranged in an object plane which are only present in small quantities there.
  • the light in interaction with these substances is converted into light with other properties, for example changed polarization state o 'of the changed wavelength, if certain substance properties are present (eg fluorescence label).
  • the multiple illumination and imaging beam paths enable, for example, individual examinations on a large number of sample containers which are arranged on a sample carrier at a relatively large distance. The sample carrier and the sample containers then together form the imaging object to be arranged on the object table.
  • FIG.l shows a first embodiment of the inventive apparatus as' using a first array of micro-mirrors
  • Figure 2 shows a second embodiment of the inventive device with a first array of re- frepten or diffractive optical micro-elements
  • FIG. 3 shows a third exemplary embodiment of a device according to the invention with a telecentric device
  • FIG. 4 shows a fourth exemplary embodiment of a device according to the invention with a pinhole array
  • FIG. 5 shows an example of a rhombic grid of microelements in the illumination beam path
  • FIG. 6 shows an example of a rhombic grid of receiver elements in the imaging beam path.
  • FIG. 1 shows a device for optical microanalysis with confocal illumination and imaging.
  • This comprises an object table 1 for holding an object to be examined, for example a carrier with a large number of substances to be analyzed.
  • the object table 1 can be moved in the coordinates X, Y (meandering) of a coordinate system X, Y, Z, so that the object or the individual samples can be scanned point by point and can be optically scanned.
  • the device comprises an illumination device 2 with which monochromatic light is generated.
  • the lighting device 2 has a white light source 3, which is followed by a collimator 4, a polarizer 5 and a wavelength-selective filter ⁇ in the direction of illumination towards the object table 1.
  • the illuminating beam path between the illuminating device 2 and the object table 1 there is an illuminating optic with which the light from the illuminating source 2 is confocally directed onto the object table 1 in the form of a plurality of illuminating light beams running side by side, so that there is a grid in an object plane from a variety of lighting points.
  • illuminating optic with which the light from the illuminating source 2 is confocally directed onto the object table 1 in the form of a plurality of illuminating light beams running side by side, so that there is a grid in an object plane from a variety of lighting points.
  • Fig.l only a single illumination beam path and the associated imaging beam path is shown as an example.
  • the illumination optics comprises a first array 10 made up of a multiplicity of optical microelements 7 in the form of micromirrors which are arranged in a grid-like manner on a carrier plate 8.
  • all the micromirrors 7 are of the same design and are arranged rhombically to one another. Examples of rhombic structures are shown in Fig.5 and Fig.6. With such arrangements, there is a high use of space and thus a good light yield in the lighting.
  • the carrier plate 8 with the micromirrors 7 is arranged opposite the lighting device 2.
  • a polarization splitter 9 ensures the confocal illumination of the object field on the object table 1.
  • the lighting device device 2 illuminates with a collimated beam through the preferably narrow-band polarization splitter 9 through the first array 10 of micromirrors ⁇ 1, which image the light source 3 in parallel in the object plane.
  • the light reflected by the " micromirrors" 7 is deflected via the polarization splitter 9 onto the object table 1.
  • a ⁇ / 4 plate 11 is arranged between the polarization splitter 9 and the array 10 in order to achieve the 180 °.
  • the individual micromirrors 7 have a light-concentrating effect and are dimensioned such that the images of the light source 3 lie within the desired analysis volumes on the object to be examined.
  • the light of the individual illumination points reflected by the object again through the polarization splitter 9, reaches a receiving device 12 with a multiplicity of receiver cells 13 arranged in a raster pattern that individual or groups of receiver cells 13 are each assigned to an illumination point.
  • the reflected light passes through a second array 14 made up of a plurality of optical micro-elements 15 arranged in a grid.
  • the micro-elements 15 of the second array 14 are here as refractive or diffractive optical ones Elements formed and concentrate that from the lighting points' on the object emitting light onto the respectively assigned receiver cells 13 on the receiving device 12.
  • the raster of the optical microelements 15 on the second array 14 is also conjugated to the raster of the picture elements or that of the first array 10.
  • the rhombic basic arrangement is aligned in mirror image to the first array 10. Again, all the micro elements 15 are of the same design.
  • each micro-element 15 of the second array 14 transforms the fluorescent light from the assigned illumination point into the image plane of the receiving device 12 in accordance with its receiving aperture.
  • the imaging effect of the microelements 15 Due to the imaging effect of the microelements 15, only the 'illumination points of the object plane is transmitted into conjugated halftone dots of the image plane.
  • the effect is a confocal transmission, which cuts out defined thin layers from the depth and width of the transformable object space and only allows them to contribute to the composition of the image.
  • the overall picture of a certain object field is obtained by moving the object table 1 in the XY plane achieved.
  • the rhombically structured raster images are combined to form an overall image or can also be strengthened in the sum formation.
  • the complete object field is detected by the object table 1 continuing to scan in a meandering manner.
  • the step speed of the displacement of the object that can be achieved and the image formation that occurs synchronously with this by reading out the respective receiver cells depends, inter alia, on the sensitivity of the receiving device 12 or camera used, the brightness of the fluorescent examination object and the spacing of the illumination points.
  • a TDI camera is used as the receiving device 12, the receiver surface of which is rhombically structured, the structure being oriented in mirror image to the first array 10.
  • the diameters of the “light-sensitive islands” of the receiver surface preferably correspond to the Airy discs that can be focused by the microelements 15 of the array 14.
  • the image of the object runs transversely to the line direction of the TDI camera, the optoelectrically generated ones Charges of the object points are pushed across the lines at the same speed as the scanning object points, thus increasing the sensitivity of the line camera by increasing the exposure time of each image point, ie the length of time it stays on the receiving device 12.
  • a correspondingly quick image build-up follows from the current one Composition of each because completely exposed end line of the TDI camera to a picture format of virtually any length.
  • a dichroic divider in the form of a divider cube can also be provided instead of the polarization divider 9.
  • the broadband, longer-wave fluorescence radiation is transmitted by a suitable choice of the bandwidth of the polarization splitter 9 or the long-pass reflection edge of the dichroic splitter, so that a corresponding image of the longer-wave pixels is obtained at the receiving device 12.
  • a second exemplary embodiment shows in FIG. 2 a device for confocal optical microanalysis which differs from that of the first exemplary embodiment by the illumination optics.
  • the object table 1, the lighting device 2 and the receiving device 12 can be designed as in the first exemplary embodiment, so that only the differences in the lighting optics need to be explained in more detail here.
  • This in turn comprises a first array 17 for generating an illumination point grid in an object field.
  • this first array 17 has a plurality of refractive or diffractive optical microelements 18 instead of micromirrors.
  • holographic micro-elements 18 are also possible.
  • the optical micro-elements 18 are configured in a rhombic arrangement with respect to one another on a carrier plate, the distance and aperture being selected such that the light from the illuminating device 2 is multiplied directly into the object plane.
  • a divider element 19 is provided for this purpose, which directs the light coming from the lighting device 2 and passing through the first array 17 onto the object table 1. The light reflected by the object is reflected by the divider element 19 onto the receiving device 12 without being deflected.
  • the divider element 19 is followed by a second array 20 made up of a large number of optical microelements 21 which act refractive or also diffractive.
  • the optical microelements 21 in the imaging beam path are in turn formed on a carrier plate 22 and have a mirror-image rhombic basic arrangement to the first array 17. All micro-elements 21 are designed in the same way. In particular, they all have the same focal length and the same specific diameter.
  • the divider element 19 can also be designed as a narrow-band polarization splitter, in particular for fluorescence applications, as a result of which the illumination beam path and the imaging beam path can be separated well. Alternatively, the use of a dichroic divider is also possible. In connection with a polarization divider, a ⁇ / 4 plate 27 can again be provided between the divider element 19 and the object table 1.
  • the third exemplary embodiment shows in FIG. 3 a further device for confocal optical microanalysis in the form of a confocal microanalysis device with telecentric partial beam paths.
  • the object table 1, the lighting device 2 and the receiving device 12 can be designed in the same way as in the first two exemplary embodiments. However, there are deviations for the lighting optics.
  • the collimated light coming from the lighting device 2 is directed onto the object table 1 via a divider element 23.
  • the divider element 23 is provided with a first array 24 ′′ in the direction of the object table 1 with a multiplicity of optical microelements 25, in particular refractive or diffractive micro- elements downstream.
  • These micro-elements 25 are formed on a carrier plate 26 which is adjustable in the direction of the optical axis for the purpose of focusing. If necessary, depending on the purpose of the analysis, a ⁇ / 4 plate 27 is again provided in the illumination beam path between the dividing element 23 and the object table 1.
  • the second array 28 in turn comprises a multiplicity of optical microelements 29 which are formed on a carrier plate 30.
  • This carrier plate is arranged between the divider element 23 and the receiving device 12.
  • the microelements 25 and 29 can in turn be arranged rhombically, with the receiving device 12 then likewise structuring the receiver cells 13 accordingly.
  • the telecentric arrangement enables simple adjustment of the two arrays 24 and 28, which can be moved in the direction of the optical axis for the purpose of focusing.
  • the image scale can be easily changed.
  • the illumination is carried out with a white light source, this can be designed as a modified Köhler illumination, so that a large number of images of a uniformly illuminated light field diaphragm through the optical micro elements 25 of the first array 24 in the object plane arise.
  • An achromatic correction for two lines is achieved by a suitable choice of the dispersive properties of the material of the refractive optical microelements 25 in relation to their diffractive lens edges.
  • the object plane or the object table 1 is preferably focused in the direction of the optical axis, ie. H. here in the Z direction.
  • the imaging beams which arise at the rear pass through the optical microelements 25 of the first array 24 and are approximately collimated in the process.
  • the telecentric imaging beam is imaged onto the receiving device 12 via this.
  • the second array 28 is finely focused in the direction of the optical axis by moving the second array 28 relative to the receiving device 12. A movement of the arrays 24 and 28 transversely to the optical axis for the purpose of scanning different pixels is not provided. Rather, the scanning is carried out solely by moving the object table 1 and the synchronous reading of the receiver cells assigned to the object points.
  • the two arrays 24 and 28 are firmly connected to the divider element 23, so that these components together form an advantageous technical unit.
  • the stage 1, illumination device 2 and receive device 12 may be formed as already explained above.
  • the parallel confocal illumination beam path is generated before the divider element 31.
  • a collimated illuminated first array 32 with a large number of refractive or diffractive optical microelements 33 generates a rhombically screened confocal bundle, which is sharply confocally imaged onto a pinhole array 34 similarly screened to the first array 33.
  • the illuminating light passes through a second array 36 with a large number of optical microelements 37 to the object table 1.
  • the second array 36 has a dual task here, namely the task of mapping the pinhole array 34 into the object plane and further the task of the lighting points to be analyzed on the object in to map a receiver level, ie on the receiving device 12.
  • Axial color aberrations occurring for different illumination wavelengths are compensated for by focusing the receiving device 12 relative to the object table 1.
  • An overall image is then generated from a multiplicity of raster images as already described above.
  • FIG. 5 shows an example of a pinhole array 34 with a plurality of pinholes 35.
  • Their rhombic arrangement is based on a right-sided displacement of the confocal pinhole rows by one pinhole radius each.
  • the displacement of the object table 1 takes place in adaptation to these distances, so that after such a length, ie a scanning period, the scanning of the line-shaped object has been carried out completely once in the example on which this is based.
  • the 10 * 10 rhombic pinhole grid can be periodically multiplied in length and width in order to dimension the desired object scanning width or length and the number of scanning processes.
  • n 10 is chosen, which corresponds to a degree of coverage with pinhole areas of approx. 3%.
  • FIG. 6 shows the associated second array 36 with the micro-elements 37.
  • the rhombic grid structure of the micro-elements 37 is a mirror image of that of the pinholes 35.
  • R radius of a 'micro-element
  • the devices described are particularly suitable for examining fluorescence properties. By dividing the illuminating light into a large number of independent analysis beam paths, a large number of samples can be examined simultaneously. Besugsseichenliste
  • optical micro elements 30 carrier plate 31 divider elements 32 first array 33 optical micro-elements 34 pinhole array 35 pinhole 36 second array 37 optical micro-elements

Abstract

L'invention concerne un dispositif de microscopie optique confocale comprenant les éléments suivants : une platine porte-objet (1), mobile dans un plan X-Y pour le balayage optique d'un objet ; un dispositif d'éclairage (2) pour éclairer l'objet ; un instrument optique d'éclairage disposé entre la platine porte-object (1) et le dispositif d'éclairage (2), cet instrument optique comportant un premier ensemble (10) composé d'une pluralité de microéléments (7) optiques pour créer une trame à partir d'une pluralité de points d'éclairage sur l'objet à examiner ; un dispositif de réception (12) doté d'une pluralité de cellules réceptrices (13) pour réceptionner la lumière émise par l'objet après interférence et en correspondance avec les points d'éclairage individuels. Au dispositif de réception (12) est associé un deuxième ensemble (14) composé de microéléments (15) optiques disposés en forme de trame, lesquels dirigent la lumière reflétée sur l'objet vers les cellules réceptrices (13). Le dispositif de l'invention permet de saisir de grands champs d'objet avec optimisation de la résolution latérale et en profondeur. Il est particulièrement adapté à l'analyse de substances fluorescentes, une pluralité d'échantillons pouvant être examinée simultanément.
PCT/EP2003/000765 2002-02-14 2003-01-25 Dispositif de microscopie optique confocale WO2003069391A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2002106004 DE10206004A1 (de) 2002-02-14 2002-02-14 Vorrichtung zur konfokalen optischen Mikroanalyse
DE10206004.5 2002-02-14

Publications (1)

Publication Number Publication Date
WO2003069391A1 true WO2003069391A1 (fr) 2003-08-21

Family

ID=27634920

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2003/000765 WO2003069391A1 (fr) 2002-02-14 2003-01-25 Dispositif de microscopie optique confocale

Country Status (2)

Country Link
DE (1) DE10206004A1 (fr)
WO (1) WO2003069391A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7369227B2 (en) 2005-01-18 2008-05-06 Roche Diagnostics Operations, Inc. Imaging fluorescence signals using telecentricity
WO2008119964A1 (fr) * 2007-03-30 2008-10-09 University Of Strathclyde Système imageur non ionisant
EP2148188A1 (fr) 2008-07-25 2010-01-27 F. Hoffmann-Roche AG Excitation et imagerie optique pour la détection de fluorescence
US7687260B2 (en) 2005-01-18 2010-03-30 Roche Diagnostics Operations, Inc. Imaging fluorescence signals using telecentric optics
WO2013020663A1 (fr) * 2011-08-06 2013-02-14 Carl Zeiss Microscopy Gmbh Microscope à balayage laser comportant un réseau d'éclairement
JP2020515828A (ja) * 2017-04-07 2020-05-28 ヴェリリー ライフ サイエンシズ エルエルシー 落射蛍光集光用のパターン形成光学系

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102007009550B4 (de) 2007-02-27 2008-12-18 Ludwig-Maximilian-Universität Verfahren und Mikroskopvorrichtung zur Beobachtung einer bewegten Probe

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5248876A (en) * 1992-04-21 1993-09-28 International Business Machines Corporation Tandem linear scanning confocal imaging system with focal volumes at different heights
US5579157A (en) * 1991-10-31 1996-11-26 Yokogawa Electric Corporation Confocal optical scanner
DE19632594A1 (de) * 1996-08-13 1998-02-19 Johannes Prof Dr Schwider Konfokales Mikroskop unter Anwendung von refraktiven Mikrolinsen-Feldern
WO1998030889A1 (fr) * 1997-01-13 1998-07-16 Medispectra, Inc. Mesures optiques obtenues par procede a resolution spatiale
WO2001001112A1 (fr) * 1999-06-26 2001-01-04 Packard Instrument Company, Inc. Lecteur pour microplaques

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19811202C2 (de) * 1998-03-09 2002-01-17 Gf Mestechnik Gmbh Konfokales Scanmikroskop
US6248988B1 (en) * 1998-05-05 2001-06-19 Kla-Tencor Corporation Conventional and confocal multi-spot scanning optical microscope

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5579157A (en) * 1991-10-31 1996-11-26 Yokogawa Electric Corporation Confocal optical scanner
US5248876A (en) * 1992-04-21 1993-09-28 International Business Machines Corporation Tandem linear scanning confocal imaging system with focal volumes at different heights
DE19632594A1 (de) * 1996-08-13 1998-02-19 Johannes Prof Dr Schwider Konfokales Mikroskop unter Anwendung von refraktiven Mikrolinsen-Feldern
WO1998030889A1 (fr) * 1997-01-13 1998-07-16 Medispectra, Inc. Mesures optiques obtenues par procede a resolution spatiale
WO2001001112A1 (fr) * 1999-06-26 2001-01-04 Packard Instrument Company, Inc. Lecteur pour microplaques

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7369227B2 (en) 2005-01-18 2008-05-06 Roche Diagnostics Operations, Inc. Imaging fluorescence signals using telecentricity
US7687260B2 (en) 2005-01-18 2010-03-30 Roche Diagnostics Operations, Inc. Imaging fluorescence signals using telecentric optics
WO2008119964A1 (fr) * 2007-03-30 2008-10-09 University Of Strathclyde Système imageur non ionisant
US9084535B2 (en) 2007-03-30 2015-07-21 King's College London Non-ionizing imager
EP2148188A1 (fr) 2008-07-25 2010-01-27 F. Hoffmann-Roche AG Excitation et imagerie optique pour la détection de fluorescence
EP2148187A1 (fr) 2008-07-25 2010-01-27 Roche Diagnostics GmbH Optique d'excitation et de représentation pour la détection de fluorescence
US7906767B2 (en) 2008-07-25 2011-03-15 Roche Molecular Systems, Inc. Excitation and imaging optics for fluorescence detection
WO2013020663A1 (fr) * 2011-08-06 2013-02-14 Carl Zeiss Microscopy Gmbh Microscope à balayage laser comportant un réseau d'éclairement
DE102011109653B4 (de) 2011-08-06 2021-11-25 Carl Zeiss Microscopy Gmbh Laser-Scanning-Mikroskop mit einem Beleuchtungsarray
JP2020515828A (ja) * 2017-04-07 2020-05-28 ヴェリリー ライフ サイエンシズ エルエルシー 落射蛍光集光用のパターン形成光学系

Also Published As

Publication number Publication date
DE10206004A1 (de) 2003-08-28

Similar Documents

Publication Publication Date Title
EP2948810B1 (fr) Microscope optique et procédé de microscopie
DE10004191B4 (de) Fluoreszenz-Scanmikroskop
DE69728572T2 (de) Mikroabbildungssystem
EP2860566B1 (fr) Microscopie à balayage haute résolution
EP3033645B1 (fr) Microscopie à balayage haute résolution
DE102013015931B4 (de) Mikroskop und Verfahren zur hochauflösenden Scanning-Mikroskope
LU101084B1 (de) Verfahren und Vorrichtung zum punktförmigen Beleuchten einer Probe in einem Mikroskiop
EP2904442B1 (fr) Microscope à foyer commun avec balayage d'échantillon librement réglable
DE69635628T2 (de) Konfokales Mikroskop
DE102011055294B4 (de) Mikroskopische Einrichtung und Verfahren zur dreidimensionalen Lokalisierung von punktförmigen Objekten in einer Probe
EP0898783A2 (fr) Microscope a balayage dans lequel un echantillon est excite optiquement simultanement en plusieurs points
EP3177957A1 (fr) Microscopie à balayage à haute résolution distinguant au moins deux plages de longueurs d'onde
WO1998038542A1 (fr) Dispositif de balayage lumineux
DE102016119730A1 (de) Optikgruppe für Detektionslicht für ein Mikroskop, Verfahren zur Mikroskopie und Mikroskop
DE102011109653A1 (de) Laser-Scanning-Mikroskop mit einem Beleuchtungsarray
DE102006009831A1 (de) Verfahren und Mikroskop zur räumlich hochauflösenden Untersuchung von Proben
EP3283917B1 (fr) Procédé et dispositif d'analyse d'un échantillon
DE102020209889A1 (de) Mikroskop und Verfahren zur mikroskopischen Bildaufnahme mit variabler Beleuchtung
EP1927026B1 (fr) Microscope confocal et procede pour detecter un microscope confocal
EP1664887A1 (fr) Microscope confocal a balayage laser
DE102018127281A1 (de) Mikroskop und Verfahren zur Mikroskopie
WO2003069391A1 (fr) Dispositif de microscopie optique confocale
LU93022B1 (de) Verfahren und Mikroskop zum Untersuchen einer Probe
WO2024012878A1 (fr) Appareil de mesure confocale chromatique de distances
DE102006011277A1 (de) Laser-Scanning-Mikroskop und Laser-Scanning-Mikroskopierverfahren

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT SE SI SK TR

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP