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WO1996037797A1 - Microscope a large champ de vision et systeme de balayage utile avec ce microscope - Google Patents

Microscope a large champ de vision et systeme de balayage utile avec ce microscope Download PDF

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Publication number
WO1996037797A1
WO1996037797A1 PCT/US1996/007754 US9607754W WO9637797A1 WO 1996037797 A1 WO1996037797 A1 WO 1996037797A1 US 9607754 W US9607754 W US 9607754W WO 9637797 A1 WO9637797 A1 WO 9637797A1
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WO
WIPO (PCT)
Prior art keywords
armature
microscope
optical
scanning
detector
Prior art date
Application number
PCT/US1996/007754
Other languages
English (en)
Inventor
Jean I. Montagu
Original Assignee
General Scanning, Inc.
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 General Scanning, Inc. filed Critical General Scanning, Inc.
Priority to AU59342/96A priority Critical patent/AU5934296A/en
Publication of WO1996037797A1 publication Critical patent/WO1996037797A1/fr

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Classifications

    • 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
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/06—Means for illuminating specimens
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/361—Optical details, e.g. image relay to the camera or image sensor

Definitions

  • a driven X-Y stage is employed to take a sequence of X-Y images, in the manner of a raster scan.
  • the adjacent images, or "tiles" are joined at their edges by computer
  • processing to produce a composite image of the larger area.
  • this can be done first at a coarse resolution for panning the area to determine regions of interest, following which one can zoom to higher magnification and finer resolution to
  • microscopy is also employed to examine the 0 optical data.
  • An important example concerns fluorescence in situ hybridization (FISH) in which cytometry is performed in studies of viruses, chromosomes, DNA, etc.
  • FISH fluorescence in situ hybridization
  • flow cytometry is available in cases where one reagent is required in the study, flow cytometry is not generally useful when using multiple reagents.
  • optical microscopy is employed for fluoroscopic examination, using procedures similar to those of imaging microscopes to obtain optical data sets based on fluorescing radiation.
  • commercially available microscopes though effective, are quite slow.
  • I employ a monochromatic optical system, i.e. a lens system
  • an optical system (reflective, refractive or a combination thereof) that produces an aberration-free image at only a narrow band of a few wavelengths, which, size for size, is much less expensive than is an achromatic lens.
  • Such an optical system is made adjustable to enable selection of the particular wavelength being used at any given time, and to bring the desired focal plane at that selected wavelength into focus.
  • the system is also constructed so that at any given setting, the detector responds only to the wavelength for which the monochromatic optical system is adjusted to be in focus; in fluorescent applications, the detector is made to respond only to the wavelength of interest for the particular examination being conducted.
  • the adjustability referred to can be provided by use of a single objective lens, and adjusting the component lens elements for each selected wavelength; however, alternatively, if desired, a different objective can be provided for each wavelength as on a turret or slide, and the optical system can be adjusted by positioning the respective objective in position for each wavelength selected.
  • the resulting microscope system enables practical use of a much larger field of view, which can eliminate the need for an automated mechanical X-Y stage, or can limit the number of times the stage needs to be moved during microscopic analysis of a large specimen.
  • the need to examine the specimen at more than one wavelength is met by enabling sequential selection of each of the wavelengths of interest, and by computer control, automatically adjusting the system so that the system, in turn, is monochromatic at each of the selected wavelengths.
  • the adjustment not only adjusts the optical system to remove chromatic aberration at the wavelength selected, but also adjusts the focal plane to maintain focus at the desired height.
  • a sequence of images or optical data sets at different wavelengths is obtained, by which the desired microscopic examination can be performed.
  • the need to have a white light image or a single optical data set at a multiplicity of wavelengths beyond the capacity of the monochromatic optical system is also met.
  • the system is programmed to take a sequence of accurately delimited images of the same field of view at different selected wavelengths at the same focal plane, following which these views are calibrated, if necessary, and superposed to provide the desired multi-wavelength image or data set.
  • superposition of the images is accomplished by computer processing of the image data and correspondingly driving the color system of a high definition video display upon which the superposed images are displayed.
  • superposition of optical data is accomplished by computer processing of the optical data, and the superposed optical data is presented.
  • a microscope system samples the data at a coarse rate suitable for presenting a panned view of a large area, thus avoiding an undue demand on the memory capacity of the computer.
  • sampling then is done on a pixel by pixel basis, at a diffraction limited spot size, to provide the needed fine resolution of the particular regions that are to be examined in detail.
  • a lens system that does not have a highly flat field of view is employed, to take advantage of cost savings that can be made when this constraint is relaxed. This has little adverse influence because there are no flat field requirements for stitching of tiles, as is required for certain commercial microscopes, and the slight sphericity of the overall field of view can have negligible impact on the high resolution inspection of selected small regions of the image.
  • certain preferred embodiments employ relatively low cost lens systems that have significant spherical aberration.
  • wide areas of the field of view are inspected only when panning at low resolution at which inaccuracy introduced by the spherical aberration is not a drawback.
  • the field of view is much more restricted in width, and over such distance the spherical aberration is minimal.
  • the ability to adjust the focal plane readily accommodates differences in the height of the focal plane between central and peripheral parts of the spherically aberrated field.
  • the invention features an achromatic, wide field of view microscope system including a wide field of view optical system, a detector positioned to record an image of an object from the optical system, and a computer.
  • the optical system is characterized in being monochromatic and adjustable in response to the computer to focus the object at a wavelength that is selectable from a range of wavelengths.
  • the microscope system for any wavelength so selected, is constructed to limit to the selected wavelength the light delivered to the detector.
  • the invention features a photo-electric detector for delivering optical data to the computer, and the microscope system includes an optical data recorder.
  • the computer is programmed to cause the object to be imaged at a multiplicity of selected wavelengths in succession, to store image or optical data for each successive wavelength, and to present on the optical data recorder a multi-wavelength visual image or, more broadly, optical data set, free of chromatic aberration based on superposed optical data taken at the respective selected wavelengths.
  • the computer is programmed to view the object at a set of selected wavelengths in succession, the set selected to produce a white light presentation of the object, i.e. a white light image or presentation of fluorescence or luminescence activity of the object.
  • the invention features a microscope system having an objective lens that is diffraction limited and has a diameter substantially greater than 1 mm.
  • the invention is in the form of a scanning microscope including a driven scanning mirror in the optical system, and the detector is an electronic detector constructed to receive light from the optical system in scanned form and deliver scanned data to the computer.
  • the system includes X and Y scanners and the detector comprises a single detector constructed to receive light from the scanning mirrors one pixel at a time.
  • the detector comprises a linear array of detectors constructed to receive light from a scanning mirror one line of pixels at a time.
  • the detector comprises light-sensitive film.
  • the invention features a microscope system including an illuminating light source arranged to emit light into the optical system, the optical system being arranged to deliver the light to the object.
  • a light source separate from the optical system illuminates the object. With either lighting arrangement, it is advantageous to employ a set of filters mounted for selectable insertion in the light path from the light source to illuminate the object at selected wavelengths.
  • the invention also features a set of filters mounted for selectable insertion in the light path from the object to the detector to limit the light delivered to the detector to the wavelength of the filter.
  • the invention features a microscope system in which the optical system includes a set of lens elements selected and arranged to define an objective lens, a plurality of the lenses in the set being individually adjustable along the optical path in response to the computer, and the computer being so constructed, for any selected wavelength, to adjust the position of the lenses in the set to render the objective lens monochromatic for the selected wavelength while maintaining focus on a selected objective plane.
  • the objective lens has a field of view greater than 500 microns.
  • the achromatic, wide field of view microscope described above is combined with an optical scanning element disposed on a flexure-mounted armature and driven by a galvanometer to rotate about an axis, as set forth in the following summary of the novel scanning features.
  • the invention features a scanning microscope system in which one or more scanning mirrors are disposed on armatures that are supported by flexure bearing and air bearing systems.
  • the invention features a scanning system in which an optical scanning element is disposed on a flexure-mounted armature and driven by a galvanometer to rotate about an axis.
  • the armature is mounted on cross-flexures in a manner to provide high angular compliance and radial rigidity.
  • the galvanometer is of the moving magnet type having a permanent magnet rotor secured in driving relationship to the armature.
  • the optical element is part of an optical system of a scanning microscope.
  • the armature is elongated and the flexures are spaced apart pairs of crossed flexures, each flexure being radially rigid.
  • the flexures of each pair pass through and cross the axis of rotation.
  • the armature is balanced statically and dynamically along its axis of rotation by the cross flexures.
  • the armature has an elongated structure extending continuously between the pairs of flexures.
  • the invention features a scanning system in which a flexure-mounted armature is driven by a galvanometer to rotate about an axis.
  • the armature is mounted on cross-flexures in a manner to provide high angular compliance and radial rigidity.
  • the galvanometer is of the moving magnet type having a permanent magnet rotor secured in driving relationship to the armature, the armature being elongated.
  • the flexures are spaced apart pairs of crossed flexures, each flexure being radially rigid and passing through and crossing the axis of rotation.
  • the invention features a scanning system in which an optical scanning element is disposed on a flexure-mounted armature and driven by a galvanometer to rotate about an axis.
  • the armature is mounted on cross-flexures in a manner to provide high angular compliance and radial rigidity.
  • the galvanometer is of the moving magnet type having a permanent magnet rotor secured in driving relationship to the armature, the armature being elongated.
  • the flexures include spaced apart pairs of crossed flexures, each flexure being radially rigid. The flexures of each pair pass through a cavity within the armature and cross the axis of rotation.
  • the armature has an elongated structure extending continuously between the pairs of flexures and is balanced statically and dynamically along its axis of rotation by the cross flexures.
  • the rotor of the galvanometer is polarized into two semi-cylindrical poles on opposite sides of the axis, and the galvanometer includes coils disposed on opposite sides of the magnet, separated by a plane of symmetry that is in essential alignment with the poles of the magnet at the center of its range of rotation, whereby when a current flows through the coils the magnetic field produced applies a torque to the magnet to move it a controlled distance.
  • a sensor rotor is secured to the end of the armature opposite from the galvanometer, to determine the angular position of the armature for comparison to the command input to the system.
  • an optical element on the armature is part of an optical system of a scanning microscope.
  • the sensor rotor is used to control the galvanometer in accordance with the command input to the system.
  • Fig. 1 is a diagrammatic view an illustrative embodiment of the microscope system
  • Figs. 2, 2a, and 2b are diagrammatic views of optical arrangements of embodiments of the invention
  • Figs. 3 and 4 are a block diagram and a diagrammatic view, respectively, of another embodiment of the microscope system;
  • Figs. 5 and 6 are a block diagram and a diagrammatic view, respectively, of another embodiment of the microscope system
  • Figs. 7 and 8 are a block diagram and a diagrammatic view, respectively, of another embodiment of the microscope system.
  • Fig. 9 is a diagrammatic, exploded view of a flexure-mounted scanner, ,while Fig. 10 is a view of a scanner armature.
  • Microscope system 8 has an optical system 10 that comprises a series of lenses, two shown for example as lenses 22 and 24, and a stage elevator 20. Upon the elevator 20 and in front of the lenses 22 and 24 lies a stage 18, on which an object 12 is placed. The lenses 22 and 24 are included in the objective lens 26 of the microscope 8. Light from the object 12 is focused by the objective lens 26 along optical path 28 upon a detector 14.
  • the optical system 10 is monochromatic, made so by choice of a relatively inexpensive monochromatic lens assembly that preferably has a wide field of view.
  • a filter wheel 30 is provided having a number of filters that are selectable to restrict the light reaching the detector 14 to the selected wavelength that is in focus upon the detector 14.
  • the detector 14 receives only a monochromatic portion of the image.
  • Detector 14 is shown generically. For certain embodiments it may be composed of a large two-dimensional aggregate of sensors such as a CCD camera or a focal plane array and capture the entire field of view. In other cases, the detector may be a linear array of light sensors and the field of view may be scanned about one axis by a scanner (not shown) , to enable capture of the entire field of view. In other arrangements, the detector may comprise either a relatively small two- dimensional or one-dimensional array of sensors combined with two-dimensional scanning.
  • the detector is a single point light sensor, such as a single photon multiplier tube, and the field of view is scanned in two dimensions to enable the capture of the entire field of view.
  • Two-dimensional scanning permits focusing a diffraction limited lens with a very small spot size, on the order of a half micron.
  • the scanning proceeds pixel by pixel over the object to create a wide field of view.
  • the light beam entering the objective lens has a diameter on the order of 15 to 30 mm.
  • a large light beam is required.
  • the invention is not limited to electronic detection.
  • the detector comprises a camera which can receive a complete monochromatic image of the object 12 for exposure to a light-sensitive substance such as a photosensitive film.
  • a computer 16 determines wavelength ⁇ to be detected by the detector 14 at a particular time. Suitable adjustment commands are delivered to the optical system 10.
  • the relative spacing of the elements of the optical system 10 are adjusted to their ⁇ position so that the system is monochromatic at that selected wavelength and is focused so that an image of the object 12 at that wavelength reaches detector 14.
  • the computer also commands stage 18 to locate object 12 to the axial position associated with ⁇ 2 and the filter wheel 30 to move the ⁇ filter into alignment with the optical axis so that only light of wavelength ⁇ reaches the detector.
  • respective monochromatic filters in the filter wheel 30 are placed in front of the opening 32 of the detector 14 for selecting the respective wavelength of light to be focused by the optical system 10.
  • filters may be placed in front of the source of white light (not shown) .
  • the image data of wavelength received by the detector 14 is sent to the memory 17 of the computer 16 for storage and processing.
  • the image data may be stored or combined in a memory buffer.
  • the computer adjusts stage 18 and the lens system to the ⁇ 2 position shown diagrammatically in dashed lines, and brings filter ⁇ into alignment with the optical axis, and so on.
  • a white light image can thus be obtained by imaging at three selected wavelengths (e.g. red, green and blue) , and causing the computer 16 to superpose those images via the color control system of the video monitor 19. This is simply done since conventional color video monitors are based upon superposed images of three colors, and thus are readily adapted to receive the image data from computer storage.
  • microscopes of the invention can be employed to form monochromatic images or data sets over a wide wavelength band, or composite images or data sets can be formed at various combined wavelengths as is commonly required for fluorescence or luminescence microscopy.
  • the elements of the optical system 10 are adjustable along the optical path 28 to permit focusing of the image at the selected wavelength.
  • the distances between the stage 18 and each of the lenses 22 and 24 are set to permit the monochromatic portion of the image of the object 12 to be focused upon the detector 14.
  • the lenses 22 and 24 are separated from the platform 20, and thus from each other, by distances O ⁇ and D 3 , respectively, which are selected to cause focusing of monochromatic light of wavelength ⁇ 2 in the optical system 10.
  • the lenses 22 and 24 are then moved to distances D 2 and D to focus monochromatic light of wavelength ⁇ 2 in the optical system 10, and so on.
  • the lenses 22 and 24 are moved on conventional threads or cams or on a linear stage (not shown) within the microscope objective 26, driven by appropriately selected stepper motors or actuators (not shown) controlled by the computer. Very fine movement of the optical elements, on the order of tens of microns, may be appropriate and can be readily realized. Advantage is taken here of existing electro-mechanical technology that is conventionally used for making lens systems automatically adjustable.
  • stage 18 itself may be moved by elevator 20 to assist in focusing the monochromatic light.
  • Figs. 2, 2a and 2b there are many important embodiments of the invention, which in each case can employ lenses of wide field of view to the extent desired.
  • the object 12 is illuminated by light source 36 at a position spaced from the optical axis.
  • the appropriately adjusted objective lens 26 then refocuses the monochromatic image of the object on an image plane 38 beyond the filter 30.
  • a scanning microscope of the conventional type (Fig. 2a) is constructed by focusing the light from an external source 36 through a condenser lens 40 onto a point on the object 12. The point on the object 12 is then refocused by the appropriately adjusted objective lens 26 through the wavelength selective filter 30 upon a point in the detector 14. In this case, the stage 18 is moved in the X-Y plane, as shown, so that the objective lens can focus on consecutive points of the object.
  • a scanning microscope In such a scanning microscope, the process of illuminating a point on the object and refocusing an image of the object at a point in the detector 14 is repeated to cover an area of the surface of the object 12, and then the individual monochromatic point images are pieced together on the screen 19 of the computer 16 for viewing either at the selected wavelength or combined with images or data sets of other wavelengths.
  • a scanning microscope can create a wide field of view upon storing a sufficient number of individual point images or data sets in the computer memory.
  • an objective lens and a collector lens both focus on the same image plane.
  • the objective lens 26 focuses the image of a point on the object 12 at the image plane 38.
  • the point image on the image plane 38 is then refocused by a collector lens 42 through the wavelength selective filter 30 upon a point in the detector 14.
  • FIGs. 3 and 4 show a wide field of view, point scanning microscope according to another embodiment of the invention.
  • Light source 52 is a mercury lamp which emits light containing a large number of different wavelengths at different intensities.
  • the light emitted from the light source 52 is focused into a beam by a collimator 54, which is adjusted automatically or manually.
  • the collimated achromatic light is first passed through a filter on a neutral density filter wheel 54 to control the intensity of the light entering the optical system.
  • the attenuated light passes through a filter on a broad band pass filter wheel 58, which limits the transmitted light to the chosen wavelength, before reaching a dichroic beam splitter 60.
  • the dichroic beam splitter 60 is partially transmissive and partially reflective, permitting a portion of the light to pass through it to the optical elements of the scanning microscope.
  • the optical elements of the system 50 include a relay lens 62 and an objective lens 64.
  • the optical elements focus both the light which illuminates the sample 56 and the light to be collected as an image along the same optical path.
  • the objective lens 54 is adjusted according to the principles that have been discussed above using a motor 66. This positions the optical elements of the objective 64 for color focus correction, i.e. for chromatic aberration, at the chosen wavelength of light.
  • the motor 66 rotates a portion of the objective 64 which sets the separation of the optical elements within the objective piece on the basis of instructions received from computer 68.
  • the objective lens 64 focuses light onto the location of interest on the sample 56 and collects - 17 - reflected light and directs it to the detector.
  • the relay lens system 62 may also be used for fine adjustment and to accommodate variation in the thickness of the sample 56, which may vary as much as 0.5 mm.
  • the light beam is adjusted by moving the sample 56 with respect to the objective lens 64 (for gross movements) or by adjusting the position of the lenses in the relay 62.
  • the computer 68 instructs the operation of a motorized driver (not shown) to adjust the lenses of the relay 62.
  • the scanning mechanism is configured as a paddle scanner.
  • the light path is shifted from pixel to pixel in the X and Y directions on the sample by rotating separate mirrors 70 and 72, each of which is driven by a respective limited rotation motor controlled by the computer 68.
  • the sample 56 rests on a stage 74.
  • the light focused as the image is reflected out of the incoming optical beam path by the dichroic beam splitter 60.
  • the imaged light passes though a filter on a narrow band pass filter wheel 74 that selects the monochromatic wavelength of light to be detected.
  • the narrow band pass filter 74 is selected to pass light at the fluorescent or luminescent wavelength, which differs from the wavelength selected by the broad band pass filter 58.
  • an eyepiece lens 76 focuses the monochromatic imaged light onto a point at the plane of a pinhole 78, the eyepiece 76 being adjustable manually or under computer control for fine focusing of the small spot.
  • a small pinhole 78 provides the best signal to noise ratio for a detected signal, since ambient light above and below the focal plane does not pass through the narrow pinhole 78.
  • Pinhole 78 also permits separate imaging of objects at different depths in the sample 56, such as overlapping chromosomes in a cell sample.
  • a photo-multiplier tube 80 or other optical sensor placed behind the pinhole 78 detects the focused light.
  • the electrical signal output of the photo-multiplier tube is digitized and stored in computer 68 for later recall to construct the raster scanned image. It is realized that the photo-multiplier has different gain ratios at different wavelengths that may affect the result.
  • the computer stores predetermined, stored gain ratio information, and employs this information to calibrate the recorded data at the selected wavelength of light before reconstructing the achromatic image from the monochromatic data collected by the scanning microscope of Figs. 3 and 4. Referring now to Figs. 5 and 6, a wide field of view linear array scanning microscope according to the invention is shown, adapted to produce white light images.
  • Light from a white light source 92 is focused into a beam by a collimator and spacial filter 94 before entering an optical system 90.
  • the white light is reflected from a turn mirror 96 under the stage to illuminate an area 98 of the sample 56 from below.
  • the sample is placed on an X-Y-Z stage 100 which has a robot interface with computer 68.
  • the stage 100 is moved in three directions, in the Z direction to assist in focusing the image of the sample 56 and in the X and Y directions for scanning the sample.
  • a motor 66 controlled by the computer 68 adjusts objective lens 64 for primary focusing of light at the selected wavelength, either red, blue or green. Although it is monochromatically focused, the objective lens 64 transmits a focused white light image of the sample through the optical system 90. The white light image is then reflected by a scanning mirror 102, which scans the sample and transmits the focused image along the remainder of the optical path for detection.
  • the monochromatically focused image is passed through one of the red, blue or green filters of a filter wheel 104, which is rotatable to select the appropriate monochromatic filter for the wavelength selected to be focused by the objective 64.
  • a detector lens 106 focuses the monochromatically imaged light onto a focal plane inside a linear CCD array detector 108.
  • the linear array collects a series of pixels of monochromatic data at a time. Typically, such array may have from 60 to 8,000 pixels.
  • the signal collected by the linear CCD array is subjected to signal processing 110 and proceeds to data processing 112.
  • the detection process is repeated for the two remaining monochromatic filters on the filter wheel 104 so that the computer may reconstruct a white light image from the data for the three stored monochromatic images.
  • Figs. 7 and 8 show a wide field of view scanning microscope employing two dimensional array detection according to another embodiment of the invention.
  • White light enters the optical system 120 from a source (not shown) above the sample 56.
  • a motor 66 adjusts the objective lens 64 to focus a white light image of a wide area of the sample 56 with respect to only one wavelength.
  • the focused light is limited to the chosen wavelength by passing the white light image through the selected sector of a red-green-blue filter wheel 124.
  • a detector lens 106 focuses the monochromatic imaged light onto a focal plane inside a two-dimensional array detector 122.
  • the detector 122 contains a two-dimensional CCD array at the focal plane of the detector lens 106, which detects an image of a planar area of the sample 56.
  • the signals collected by the two dimensional array are processed in the detector 122 and sent to the computer 68 for storage and data processing 112 so that a white light image can be reconstructed from stored data for the red, green and blue monochromatic images.
  • the detector comprises a limited dimension two-dimensional array of detectors, such as a two-dimensional miniature CCD array, to collect image data from a small region of the sample.
  • This miniature array is raster scanned across the sample.
  • the image can be selected and collected by the miniature array with a high level of detail, without raster scanning every point on the sample.
  • Software for utilizing miniature CCD array image data is known in the television industry and can readily be adapted for this microscope scanning function.
  • a turret or slide carrying a number of monochromatic objective lenses can be brought into selected position for each selected wavelength to form the monochromatic images or optical data sets.
  • the microscope system is constructed to be extremely stable, particularly with respect to the high speed scanning mirrors of embodiments involving scanning.
  • a flexure mounted armature 136 driven by a galvanometer 150 achieves sufficient repeatability and stability in driving the high speed X-axis scanning mirror, so that successive monochromatic images can be superposed to produce useful microscope images.
  • An armature 136 comprising the rotor is extremely rigid and is balanced statically and dynamically along its axis of rotation by cross flexures 138.
  • Each cross flexure is securely held in place by a flexure support 139 mounted to a stable surface.
  • the flexures pass through and cross the armature 136 along its axis of rotation which creates a very rigid structure and permits large rotational movement of the armature about that axis.
  • the flexures have high angular compliance while maintaining high radial rigidity, to provide a high radial mode resonant frequency.
  • the armature 136 is rotated by the movement of a cylindrical magnet 130 attached to one end of the armature.
  • the magnet 130 is polarized into two essentially semi-cylindrical poles (N and S) on opposite sides of its axis.
  • the magnet 130 is disposed inside the shell 134 of a driver 135.
  • Coils 132 are disposed on opposite sides of the magnet, separated by a plane of symmetry that is in essential alignment with the poles of the magnet 130 at the center of its range of motion.
  • An output shaft 142 connected to the X-axis mirror 144 and a "butterfly" sensor rotor 140 are securely attached to the other end of the armature 136.
  • the plates of the sensor rotor 140 are suspended between the stationary capacitive plates of a position sensor (not shown) so that the capacitance varies between the capacitive plates as the armature rotates, such as in a variable capacitance transducer.
  • the sensor rotor 140 being disposed on the end of the armature opposite from the drive, is thermally isolated from the driver 135 to minimize the effects of temperature on transducer measurements.
  • the capacitance signals produced between the plates of the position sensor are amplified and processed into a sum and difference signal.
  • the difference signal determines the angular position of the armature 136 and is compared to the transducer's command input.
  • the sum signal is used as a reference to compensate for the temperature dependence of some of the parameters of the rotor system.
  • Mirror drivers of this description are preferably employed from the X and Y scanning stages of X-Y scanners. It is presently preferred to employ flexure mounted moving magnet scanners that are available from General Scanning Incorporated, models FM2 and FM3. In certain other instances, other high accuracy bearing systems, such as the known air bearing systems, may support armatures of scanners that are utilized.
  • the microscopes of the present invention achieve a high resolution with respect to the size of the field of view. For example, for single point detection using the raster scanning technique, a 0.5 micron spot size is focused over a 5 mm diameter field of view. For a linear array detector, a 1 micron spot size is focused over an 8 millimeter square field of view. For a full imaging device, the resolution achieved is a 2 micron spot size focused over a 30 mm field of view.
  • the images or optical data sets may be recorded and presented by any of a wide variety of optical data recorders, including video monitors, printers, floppy discs for computerized presentation and film recorders.

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  • Analytical Chemistry (AREA)
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Abstract

Le système décrit (8) de microscope achromatique à large champ de vision comprend un système optique à large champ de vision (10), un détecteur (14) positionné afin d'enregistrer une image d'un objet (12) observé à travers le système optique, et un ordinateur (16). Le système optique est relativement monochromatique et ajustable en réponse aux signaux fournis par l'ordinateur afin de focaliser l'image de l'objet à une longueur d'onde sélectionnable dans une plage de longueurs d'ondes alors que la lumière qui atteint le détecteur est limitée à la longueur d'onde sélectionnée. En superposant des images successives à différentes longueurs d'ondes sélectionnées, on obtient une image ou une série de données composites à des longueurs d'ondes multiples. L'invention concerne différents types importants de microscopes qui présentent les caractéristiques décrites. Particulièrement importants sont les microscopes à balayage qui comprennent des miroirs de balayage montés sur des armatures soutenues par des systèmes flexibles de support ou par des systèmes pneumatiques de support.
PCT/US1996/007754 1995-05-26 1996-05-28 Microscope a large champ de vision et systeme de balayage utile avec ce microscope WO1996037797A1 (fr)

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AU59342/96A AU5934296A (en) 1995-05-26 1996-05-28 Wide field of view microscope and scanning system useful in the microscope

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US45212395A 1995-05-26 1995-05-26
US08/452,123 1995-05-26

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999035527A1 (fr) * 1998-01-12 1999-07-15 Wallac Oy Microscope confocal a plusieurs faisceaux de balayage
WO2001057576A3 (fr) * 2000-02-04 2002-01-17 Inspectech Ltd Microscope a source d'eclairage couleur
EP1209504A2 (fr) * 2000-11-23 2002-05-29 Leica Microsystems Heidelberg GmbH Méthode et dispositif pour balayer des objets microscopiques avec un système de balayage
WO2002077694A1 (fr) * 2001-03-28 2002-10-03 Gnothis Holding S.A. Ensemble microscope pour la spectroscopie de fluorescence, notamment pour la spectroscopie a correlation de fluorescence
EP1273878A2 (fr) * 2001-07-02 2003-01-08 Leica Microsystems Semiconductor GmbH Procédé et microscope pour détecter un objet
WO2004086117A1 (fr) * 2003-03-28 2004-10-07 Carl Zeiss Jena Gmbh Dispositif d'eclairage d'objets avec une lumiere de differentes longueurs d'ondes
DE102007001010A1 (de) * 2007-01-02 2008-07-10 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Verfahren und Bilderfassungssystem zur achromatisierten Bildaufnahme von Objekten
US8320637B2 (en) 2009-08-04 2012-11-27 Chemimage Corporation System and method for hyperspectral imaging of treated fingerprints
DE102011083847A1 (de) * 2011-09-30 2013-04-04 Carl Zeiss Microscopy Gmbh Mikroskop für die Weitfeldmikroskopie
EP2051051A3 (fr) * 2007-10-16 2013-06-12 Cambridge Research & Instrumentation, Inc. Système d'imagerie spectrale avec correction optique dynamique
US9046476B2 (en) 2010-06-01 2015-06-02 Vbact Ltd. Method and system for the detections of biological objects
EP3145171A1 (fr) * 2015-09-15 2017-03-22 Mitutoyo Corporation Correction d'aberration chromatique dans un système d'imagerie à lentille à longueur focale variable

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61281211A (ja) * 1985-06-07 1986-12-11 Olympus Optical Co Ltd カラ−画像撮影用照明装置
US4720804A (en) * 1984-08-08 1988-01-19 Moore Sidney D Electrically addressable opto-electronic indicator for making dynamic evaluations of microscopic or larger subjects
US4758727A (en) * 1986-02-12 1988-07-19 Ohio State University Research Foundation Method and apparatus for the measurement of low-level laser-induced fluorescence
US5097356A (en) * 1990-06-01 1992-03-17 General Scanning, Inc. Optical scanner with damped coupling
US5225923A (en) * 1992-07-09 1993-07-06 General Scanning, Inc. Scanning microscope employing improved scanning mechanism
US5247384A (en) * 1989-11-13 1993-09-21 Fuji Photo Film Co., Ltd. Method of stabilizing resonant frequency and resonant scanner using the same
US5340981A (en) * 1989-08-28 1994-08-23 Stm (Societe D'investissement Dans La Microscopie) S.A. Rear field reflection microscopy process and apparatus
US5532874A (en) * 1992-12-18 1996-07-02 Morphometrix Inc. Multiscanning confocal microscopy

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4720804A (en) * 1984-08-08 1988-01-19 Moore Sidney D Electrically addressable opto-electronic indicator for making dynamic evaluations of microscopic or larger subjects
JPS61281211A (ja) * 1985-06-07 1986-12-11 Olympus Optical Co Ltd カラ−画像撮影用照明装置
US4758727A (en) * 1986-02-12 1988-07-19 Ohio State University Research Foundation Method and apparatus for the measurement of low-level laser-induced fluorescence
US5340981A (en) * 1989-08-28 1994-08-23 Stm (Societe D'investissement Dans La Microscopie) S.A. Rear field reflection microscopy process and apparatus
US5247384A (en) * 1989-11-13 1993-09-21 Fuji Photo Film Co., Ltd. Method of stabilizing resonant frequency and resonant scanner using the same
US5097356A (en) * 1990-06-01 1992-03-17 General Scanning, Inc. Optical scanner with damped coupling
US5225923A (en) * 1992-07-09 1993-07-06 General Scanning, Inc. Scanning microscope employing improved scanning mechanism
US5532874A (en) * 1992-12-18 1996-07-02 Morphometrix Inc. Multiscanning confocal microscopy

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
APPLIED OPTICS, Volume 12, No. 10, issued 01 October 1973, J.S. COURTNEY-PRATT et al., "Microscope with Enhanced Depth of Field and 3-D Capability", pages 2509-2519. *

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999035527A1 (fr) * 1998-01-12 1999-07-15 Wallac Oy Microscope confocal a plusieurs faisceaux de balayage
WO2001057576A3 (fr) * 2000-02-04 2002-01-17 Inspectech Ltd Microscope a source d'eclairage couleur
EP1209504A3 (fr) * 2000-11-23 2004-04-21 Leica Microsystems Heidelberg GmbH Méthode et dispositif pour balayer des objets microscopiques avec un système de balayage
EP1209504A2 (fr) * 2000-11-23 2002-05-29 Leica Microsystems Heidelberg GmbH Méthode et dispositif pour balayer des objets microscopiques avec un système de balayage
DE10058100B4 (de) * 2000-11-23 2017-07-13 Leica Microsystems Cms Gmbh Verfahren und eine Anordnung zur Abtastung mikroskopischer Objekte mit einer Scaneinrichtung
US6852964B2 (en) 2000-11-23 2005-02-08 Leica Microsystems Heidelberg Gmbh Method and arrangement for scanning microscopic specimens with a scanning device
WO2002077694A1 (fr) * 2001-03-28 2002-10-03 Gnothis Holding S.A. Ensemble microscope pour la spectroscopie de fluorescence, notamment pour la spectroscopie a correlation de fluorescence
US6924900B2 (en) 2001-07-02 2005-08-02 Leica Microsystems Semiconductor Gmbh Method and microscope for detection of a specimen
EP1273878A2 (fr) * 2001-07-02 2003-01-08 Leica Microsystems Semiconductor GmbH Procédé et microscope pour détecter un objet
EP1273878A3 (fr) * 2001-07-02 2003-11-19 Leica Microsystems Semiconductor GmbH Procédé et microscope pour détecter un objet
JP2003066337A (ja) * 2001-07-02 2003-03-05 Leica Microsystems Semiconductor Gmbh 被検試料検出方法及び顕微鏡
US7416313B2 (en) 2003-03-28 2008-08-26 Carl Zeiss Microimaging Gmbh Assembly for illuminating objects with light of different wavelengths
WO2004086117A1 (fr) * 2003-03-28 2004-10-07 Carl Zeiss Jena Gmbh Dispositif d'eclairage d'objets avec une lumiere de differentes longueurs d'ondes
DE102007001010A1 (de) * 2007-01-02 2008-07-10 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Verfahren und Bilderfassungssystem zur achromatisierten Bildaufnahme von Objekten
EP2051051A3 (fr) * 2007-10-16 2013-06-12 Cambridge Research & Instrumentation, Inc. Système d'imagerie spectrale avec correction optique dynamique
US8320637B2 (en) 2009-08-04 2012-11-27 Chemimage Corporation System and method for hyperspectral imaging of treated fingerprints
US9046476B2 (en) 2010-06-01 2015-06-02 Vbact Ltd. Method and system for the detections of biological objects
DE102011083847A1 (de) * 2011-09-30 2013-04-04 Carl Zeiss Microscopy Gmbh Mikroskop für die Weitfeldmikroskopie
US9435992B2 (en) 2011-09-30 2016-09-06 Carl Zeiss Microscopy Gmbh Microscope for widefield microscopy
EP3145171A1 (fr) * 2015-09-15 2017-03-22 Mitutoyo Corporation Correction d'aberration chromatique dans un système d'imagerie à lentille à longueur focale variable
CN107071258A (zh) * 2015-09-15 2017-08-18 株式会社三丰 包括可变焦距透镜的成像系统中的色差校正
US9774765B2 (en) 2015-09-15 2017-09-26 Mitutoyo Corporation Chromatic aberration correction in imaging system including variable focal length lens
CN107071258B (zh) * 2015-09-15 2020-09-22 株式会社三丰 包括可变焦距透镜的成像系统中的色差校正

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