• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
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    • 专利摘要:
    A slide transport device (3) for an alternative laser scanner device (1) for imaging and / or measuring fluorescent samples located on slides (8) and treated with two different fluorescent dyes is presented. In this case, this laser scanner device (1) comprises a sample table (2); at least one laser (51, 52) for providing laser beams (54, 55) of different wavelengths; a scanner device (72) having a scanner head (50) and a lens (57) for focusing the laser beams (54, 55) on the sample. The direction of movement (75) of the scanner head (50) defines a scan axis or X-axis and the sample table (2) is linearly movable in a Y-direction arranged at right angles thereto. The laser scanner device (1) additionally comprises two detectors (61, 61 ') for detecting the emission beams (59, 60) of different wavelengths coming from the samples. The slide transport device (3) according to the invention is motorized and designed to move a slide (8, 10) from a storage unit (4) of the laser scanner (1) to the sample table (2) and back. The sample table (2) is designed to be movable until immediately before the storage unit (4) and the storage unit (4) comprises an adjusting plate (11) which is designed to reversibly mount a sample part magazine (7 '). The sample compartment magazine (7 ') comprises at one of its insertion side (15) opposite corner a control opening (21) for detecting the presence or absence of a slide (8) in a specific storage location (6).
    公开号:AT14178U1
    申请号:TGM307/2013U
    申请日:2008-10-15
    公开日:2015-05-15
    发明作者:Frank Fischer；Harald Gebetsroither；Andreas Gfrörer
    申请人:Tecan Trading Ag；
    IPC主号:
    专利说明:

    Description: [0001] The invention relates to a slide transport device for a laser scanner device for imaging and / or measuring fluorescence samples located on microscope slides and treated with two different fluorescent dyes. In this case, this laser scanner device comprises a motor-driven sample stage with a receptacle for Objekt¬träger in a sample plane; at least one laser and a first optical system for providing two laser beams of different wavelengths; a scanner device comprising a scanning head movable in a moving direction and having an optical deflecting element for deflecting the laser beams toward the specimen, and an objective for focusing the laser beams on the specimen in the plane. The laser scanner apparatus further comprises a second optical system for relaying emission beams deflected by the laser beam at the sample and deflected by the lens and the deflector in a direction substantially parallel to the direction to detectors, and two detectors for detecting the emission beams of different wavelengths coming from the samples.
    Conventional optical scanning microscopes have been used for imaging microscope-based fluorescent samples for a long time. Confocal optical scanning microscopes are becoming increasingly popular because of the improved resolution. Such a microscope is known, for example, from GB 2 184 321 A.
    From US 5,304,810 and US 6,628,385 B1 microscopes are known which generate with two or more spatially separated illumination beams two or more spatially separated illumination points and to scan a sample simultaneously with these illumination points.
    WO 02/059677 A1 discloses an optical system for exciting and measuring fluorescence on or in samples treated with fluorescent dyes. This system comprises at least one laser for exciting the fluorescent dyes used, a mirror for deflecting the laser light in the direction of a sample, a deflecting element for deflecting the light from the laser onto this mirror in a Y direction of a (here Cartesian) coordinate system, an optic for forming a first focus of the laser light on the sample, a grid unit movable in the Y direction comprising the mirror and the optic, a sample table movable in the X and Z direction of the coordinate system for aligning the sample with the first focus , an optical arrangement for imaging the light emitted by the sample in a hole stop arranged in a second focal point and a detector for measuring the intensity of the light passing through the pinhole.
    These known microscopes for the highly sensitive scanning of arranged in a regular pattern (a so-called array) samples are also capable of scanning a standard standard microscope slide for light microscopy and work satisfactorily at medium resolution.
    Now, if two laser beams on a sample and in the focal plane spatially separated from each other are focused and form these laser beams when incidence on the scanning lens an angle to each other, this inevitably leads to at least one of the two laser beams before hitting the mirror element now can no longer run exactly parallel to the scan axis.
    Now, if the scanner head moves, the point of impact of the laser beam on the lens changes. The beam will still be deflected to the same focal point, but at different angles. Outside the focal plane, different positions then result according to the above-mentioned position, depending on the position of the scanner head in the X direction and depending on the deviation of the sample plane from the exact focal plane in the Z direction. The latter deviation can never be completely ruled out within the framework of realistic device tolerances, and as a random tolerance it is also not possible to control it in an arbitrary manner.
    The described effects are intrinsically small, but they are significantly noticeable in the example setup at resolutions below 5 pm. The effects described may result in the images of the two detection channels not being equal over the entire image area coverage, and the extent of the deviations varying uncontrollably across the image. Quantitative measurements of very small structures are thereby impossible or at least falsified. Visually, the errors make themselves recognizable as locally varying color fringing.
    From document DE 197 07 227 A1 a light scanning device for exciting and detecting emission light is known. The scanning device comprises a light-generating device, a deflection unit, an imaging unit and a detection unit for detection.
    The object of the present invention is to propose a slide transport device for an alternative laser scanner device for imaging and / or measuring located on slides, treated with two different fluorescent dyes, fluorescent samples.
    This object is met with a slide transport device according to claim 1. Additional preferred and inventive features emerge from the dependent claims.
    The slide transport apparatus of the present invention for an alternative laser scanner apparatus will now be explained with reference to schematic drawings, which are not intended to limit the scope of the present invention and which illustrate examples of particularly preferred embodiments. 1 shows a vertical partial section through two specimen slide magazines and a specimen stage placed in front of them during the transfer of a specimen slide from the specimen magazine to the specimen stage; [0014] FIG. 2 shows a horizontal partial section through the slide magazines and a top view of the object table placed in front of them during the transfer of a test slide from the test object magazine to the object table; [0015] FIG. 3 shows vertical views of the slide magazines with the test object magazine open, FIG. 3A showing the insertion side of the two slide magazines in a front view from FIG
    [0017] FIG. 3B shows the two slide magazines in vertical section with a view towards the stage; Fig. 4 shows vertical partial sections through the stage and its transverse device, wherein Fig. 4A shows the stage with view against the slide magazines and with a slide held double in the closed stage, and Fig. 4B shows the stage with view away from slide magazines, with open
    Object table, after removing or before inserting a slide shows; 5 shows a vertical partial section through the object table and its height adjustment and longitudinal tilting device; 6 shows a schematic diagram with essential optical elements of the laser scanner
    Apparatus with a scanner head according to a first embodiment; Fig. 7 shows schematic sketches of the scanner head, Fig. 7A showing a second embodiment of the scanner head, and Fig. 7B showing a third embodiment of the scanner head; Figure 8 is a partial horizontal section through a laser scanning device with essential optical elements, a scanner device with a scanner head and an object table with slide magazines; FIG. 9 shows a horizontal partial section through the scanner head of the laser scanner apparatus with the associated displacement sensor; FIG. 10 shows a schematic diagram of the displacement sensor for the scanner head and its nonlinear movement during scanning as an X / t diagram, which is based on the different duration of time (Ah, At2) for the detection of the fluorescence emitted by an object depending on the position of a number of pixels (Δχ) on the X-axis; Fig. 11 shows a test slide having the format of a standard microscope slide for light microscopy and comprising only light-stable test structures; Fig. 12 shows a vertical section through an eccentric for adjusting the
    Focal line.
    FIG. 1 shows a vertical partial section through two slide magazines and a slide placed in front of them during the transfer of a slide from the sample magazine to the slide. These two slide magazines are part of an alternative laser scanner device 1 for imaging and / or surveying fluorescently-treated fluorescence-treated glass slides. This laser scanner device comprises a sample table 2 defining a sample plane 49 and a motorized transport device 3 for moving a slide from a storage unit 4 to the sample table 2 and back. In this case, the storage unit 4 comprises a sample part 7 for sample slides 8 and test slide 9 which has at least one respective deposit 6 and is accessible to the transport device 3 during operation of the laser scanner 1. In this alternative laser scanner device the test part 9 is separated from the specimen part 7 and designed as a test part magazine 9 'fixedly connected to the laser scanner device 1 for one or more test slides 10. As a result, a test object carrier 10 which is supported in the test part 9 is not manually accessible to a user in the operating state of the laser scanner device 1. This has the advantage that a suitable test slide can be provided at any time, without such a test slide 10 can be contaminated or even damaged by improper manipulations by operators. The test part magazine 9 'depicted here comprises an open insertion side 15.
    In the embodiment shown here, the sample part 7 is arranged axially above the test part 9 and the test part 9 of the storage unit 4 is fixedly connected to a relative to the Proben¬tisch 2 of the laser scanner device 1 movable control plate 11 of the storage unit 4. Here, the setting plate 11 of the storage unit 4 is substantially perpendicular to the sample plane 49 of the sample table 2 slidably. Thus, any object carrier 8, 10 can be brought to the level of the sample plane 49 defined by the sample table 2 and provided for a linear transport onto the sample table 2.
    Notwithstanding this illustration in Fig. 1, the control plate can also stand firmly and thus provide a fixed connection between the laser scanner device 1 and the test part magazine 9 '. In such a case, the sample table 2 must be moved relative to the test part magazine 9 'if a linear transport of any slide 8,10 from a sample part magazine 7' or a test part magazine 9 'to the sample table 2 is to take place completely dispensed with an adjusting plate 11 and the test part magazine 9 'somewhere so laser scanner device 1 are attached, thereby a test object stored in the test 9 9 is not manually accessible to the operator in the operating state of the laser scanner device 1 for an operator.
    Other alternatives not shown include moving a test slide 10 already in the sample plane 49 of the sample table 2 in this sample plane 49 with respect to a stationary sample table 2, moving the sample table 2 in these samples plane 49 with respect to unmoved test part magazine 9 'or a mutual movement of sample table 2 and test part magazine 9'. In all of these cases, linear transport of any slide 8, 10 from a sample compartment magazine 7 'or a test section magazine 9' to the sample table 2 is made possible. In addition, it is conceivable to use a robot which removes a slide 8, 10 from one of the magazines 7 ', 9' and positions it on the sample table 2; In this case, the magazines 7 ', 9' and the Proben¬tisch 2 to each other occupy virtually any position.
    However, it is preferred that the sample plane 49 of the sample table 2 is arranged substantially horizontally, with the sample table 2 carrying a slide 8, 10 over itself. However, the sample table 2 can also be arranged overhead, so that the inserted slide 8,10 is arranged under the sample table. Any other position of the sample plane 49 in space is also conceivable, but is less preferred.
    The laser scanner device 1, according to the first embodiment shown in FIG. 1, preferably comprises a housing 5, wherein the sample part 7 can be used as a magazine 7 ', which can be inserted from the outside into the housing 5 of the laser scanner device 1, for a plurality of sample devices. Object slides 8 is formed. The sample part 7 is preferably reversibly mountable on the adjusting plate 11 of the storage unit 4. In the illustrated embodiment, a pluggable tine joint connects the sample compartment magazine 7 'to the vertically movable panel plate 11. Thus, the sample compartment magazine 7' can be retained on the handle 42 and lowered into the housing 5 in a substantially vertical direction and plugged into the dovetail 43 of the panel 11 , Since here the two magazines 7 ', 9' are arranged vertically one above the other, the test part magazine 9 'screwed firmly to the setting plate 11 preferably represents just the lower stop for the test part magazine 7' inserted into the dovetail 43.
    The bearings 6 in the sample compartment magazine 7 'and / or in the test cartridge magazine 9' are adapted to receive slides which are substantially the dimensions of a standard microscope slide for light microscopy. These storage compartments 6 are preferably separated from one another by support webs 12, so that these specimen slides rest on rack bars 12 each extending in each case over substantially the entire length of the microscope slides 8, 10.
    The sample table 2 shown in FIG. 1 in a vertical section is designed for the transfer of sample slides 8 or test slides 10 by means of a spindle drive 84 arranged on a suspension 83 directly in front of a storage unit 4 for such slide carriers 8, 10 , The receptacle 34 of the sample table 2 preferably comprises two opposing grooves 35 for receiving the two longitudinal edges 14 of a sample slide 8 or a test slide 10. The sample plane 49 is preferably arranged substantially horizontally. The sample table 2 comprises, for clamping a slide 8, in a direction substantially perpendicular to the surface of the slide, two fixed webs 36 and a jaw 37 movable resiliently against these webs 36 with two upstanding side walls 38, which together with the lower edges of the webs 36 define the opening width of the grooves 35 (see also Fig. 4). Preferably, a controller 40 monitors or controls a motor 87 which drives the spindle drive 84. Thus, the controller 40 controls the movements of the sample table 2.
    Figure 2 shows a horizontal partial section through the Objektträ¬germagazine shown in FIG. 1 and a plan view of the placed in front of this object table during transfer of a test slide from the test object magazine on the stage. The test piece magazine 9 'shown here comprises an open insertion side 15, which can be covered in width at least in part by a respective flap 16 that can extend individually over substantially the entire stacking height of the magazine 9'. This flap 16 is here pivoted away weg¬, so that the illustrated test slides from the insertion side 15 of the test part magazine 9 'can be pushed out without it being hindered by the wegschwenkbaren flap 16.
    In the case of the test part magazine 9 ', this swing-away flap 16 forms part of the latch, which allows a test slide 10 stored in the test part 9 to be manually inaccessible to an operator in the operating state of the laser scanner device 1. In the case of the sample compartment magazine 7 ', this swing-away flap 16 in its folded state enables handling (for example, pivoting or tilting) of a magazine 7' filled with at least one sample slide 8, without fearing that these slides will fall out , Both the sample part magazine 7 'and the test part magazine 9', but at least the sample part magazine 7 'on its side opposite the insertion side 15, preferably have a blocking plate 20 extending substantially over the entire stack height, which part the width of this page covers. This blocking plate 20 prevents falling out of slides on the other side in particular when handling the sample part magazine 7 '.
    Preferably at each magazine 7 ', 9' individually swing away flaps 16 anje a side of the magazines 7 ', 9' arranged axis 17 are rotatably mounted. These individually swing-away flaps 16 each comprise an angle plate 18, which preferably extends substantially over the entire stack height of the magazines 7 ', 9'. These swing-away flaps 16 are preferably urged against the respective magazine 7 ', 9' by a rotatable, motor-driven eccentric roller 19 to release the insertion side 15 of one of the magazines 7 ', 9'. Non-pictured variants include moving the swing-away flaps 16 with a lever, plunger, or pusher.
    So that the slides 8, 10 'sit essentially free of play in the magazines 7', 9 ', each of these bearing points 6 preferably comprises a pressure spring 13, which elastically acts on a longitudinal edge 14 of an inserted slide. In addition, the respective opposite longitudinal edge 14 of the object holder 8, 10 is held in a position defined by the corresponding magazine 7 ', 9' by the spring pressure, which position is suitable for defining a reference for the origin of a coordinate system. Similarly, the sample table 2 is preferably equipped with movable pressing parts 39 in the form of rollers (see Fig. 2), which also hold the same longitudinal edge 14 in a defined position, whereby a reference for the origin of the coordinate system is again provided ,
    At least the sample compartment magazine 7 'preferably comprises, at a corner opposite the insertion side, a control opening 21 extending essentially over the entire stack height for detecting the presence or absence of a slide in a certain storage location 6. The presence or absence of a slide 8,10 in a bestimm¬ten depository 6 can be determined with different methods and devices.So example (see Fig. 2) a substantially horizontally extending light beam 23 or a light barrier of a control device 22 obliquely through the magazines 7 ', 9' wer¬den if the control opening 21 is transparent to this light beam 23. The deflection, scattering or attenuation of the light beam 23 by an object carrier 8, 10 present in a storage space 6 can be easily detected with a photosensitive sensor. In FIG. 2, a control opening 21 in the form of a "cut corner" is shown. the light beam 23 can also be transmitted through the insertion side 15 into the magazines 7 ', 9' and impinge on a sensor on the opposite, non-cut side; A biased orientation relative to the transport direction of the slides 8, 10 and / or the attachment of a deflecting mirror (both not shown) also allow detection of the slides in their magazines even with the sample stage 2 approaching.
    Other variants for determining the presence or absence of a slide in a particular bearing 6 of one of the two magazines 7 ', 9' are based for example on the basis of a capacitive approximation.
    [0045] The transport device 3 of the laser scanner device 1 preferably comprises a discharge slider 31, which engages substantially parallel to the sample plane 49 through the side opposite the insertion side 15 of the magazines 7 ', 9' and for transporting a sample. Object slide 8 or a test slide 10 is formed from its storage location 6 and from the insertion side 15 out to the sample table 2. This transport device 3 preferably also encloses a loading slider 32, which for transporting a sample slide 8 or a test slide 10 out of the sample table 2 and through the insertion side 15 into a storage space 6 in one of the magazines 7 ', 9 ' is trained. It is particularly preferred that loading slider 32 comprises a pivoting flap 33 which can be swiveled up and thus moved over the slide 8, 10 inserted in the sample table 2, without this flap 33, which can be tilted about an axis 47, touching the slide. Thus, this flap can be moved over the slide and lowered behind die¬sem, whereupon the slide can be detected by the flap 33 and pulled out of the Probentisch 2. Swinging up the flap 33 allows movement of the sample stage 2 and the slide 8, 8 inserted therein to the location of the scanner 72. This pivotal movement of the flap 33 about the tilt axis 47 thus allows free movement of the sample table 2 without the flap 33 interfering with the flap used Ob¬jektträger 8,10 may come into contact. Preferably, the drive 44 for the movable Stell¬ plate 11, the drive 45 for the discharge slide 31 and the drive 46 for the charging slide 32 each an electric motor, which is controlled and monitored by the controller 40.
    The sample table 2 shown in FIG. 2 comprises, for clamping a slide 8, in a direction substantially parallel to the surface of the slides, against at least one of the longitudinal edges 14 of the slide movable pressing parts 39 which resiliently delimit the opening width of the receptacle 34. In this case, the pressing parts 39, which are movable relative to one of the longitudinal edges 14 of the object carrier, are preferably designed as rollers, each having a substantially vertical axis. Preferably, a controller 40 monitors or controls a motor 87 which drives the spindle drive 84. As a result, the controller 40 controls the movements of the sample table 2.
    FIG. 3 shows vertical views of the slide magazines with the test object magazine open. FIG. 3A shows the insertion side of the two slide magazines in a front view from the object table. The vertically movable control plate 11 is visible on the right side and marked their mobility with a double arrow. The sample part 7 is arranged just above the test part 9, the sample part magazine 7 'with here eight sample slides 8 resting in the storage locations 6 being axially fixed above the test part magazine 9' with here two test slides 10. The swing-away flap 16 of the sample compartment magazine 7 'is closed, while the swing-away flap 16 of the test section magazine 9' is opened and releases substantially the entire width of the insertion side of the test section magazine 9 '. The pivoting away the wegschwenkbaren flap 16 of the test part magazine 9 'is accomplished here by the eccentric roller 19, which presses on the angle plate 18this flap. The eccentric roller 19 is preferably arranged at least close to the sample plane 49 defined by the sample table 2, so that despite the displacement of the storage unit 4 in height, the correct flap 16 is always pivoted away. The contact springs of the test part magazine 9 'are easy to see as they press resiliently on one side edge 14 of the test slides 10.
    FIG. 3B shows the two same slide magazines in a vertical section with a view towards the object table. The vertically movable control plate 11 is visible on the left side and marked their mobility with a double arrow.
    The sample part magazine 7 'is pushed over the dovetail 43 of the adjusting plate 11 and is held here by the test part magazine 9' in a constant position on the adjusting plate 11. The test part magazine 9 'is here firmly screwed to the control plate 11. The contactors 13 of the sample compartment magazine 7 'and the test section magazine 9' are here well visible on the right side of the slide stack.
    FIG. 4 shows vertical partial sections through the object table 2 and its transverse device or the tilting mechanism 79, which comprises a motor-driven eccentric 80 and a unilateral axis of rotation 81. This tilting mechanism 79 serves to align a specimen or slide 8, 10 with respect to a focal line 101, which runs in a detent plane 76 (see Fig. 5). The focus of the first objective 57 and the direction of movement 75 of the scanner head 50 of the laser scanner device 1 define this focal line 101. This focal line 101 itself, together with the optical deflection element 56 of the scanner head 50, defines the raster plane 76. This raster plane 76 is thereby defined by the direction of movement 75 of the scanner head 50 and its optical deflection element 56. This raster plane 76 is substantially perpendicular to the sample plane 49. This focal line 101 is defined by the direction of movement 75 of the scanner head 50 and the focal point 65 of the Scanner lens 57 and is in the correctly aligned state of the device in the sample plane 49. The axis of rotation 81 may be formed as an actual axis (not shown). However, a virtual axis of rotation 81 is preferred, which is gebil¬det by a steel spring 104. This steel spring 104 is preferably screwed by means of a respective yoke 105 on the sample table 2 or on the support part 103. This steel spring 104 causes a counterforce to the eccentric 80, so that a simple, play-free tilting mechanism for the support part 103 of the sample table 2 is provided.
    FIG. 4A shows the object table 2 of the laser scanner device 1 with a view towards the slide carriers 7 ', 9' and with a slide 8 held double in the closed slide 2. The sample table 2 comprises a tilting mechanism 79 with a motor-driven eccentric 80 and a motor one-sided rotation axis 81, with which Kippmechanis¬mus 79 a slide (8, 10) or a sample against a focal line 101 can be aligned. A section through a preferred embodiment of such Exzentervor¬richtung is shown in FIG. 12. This focal line 101 preferably lies in the sample plane 49 and in a raster plane 76 which the scanner head 50 defines with its optical deflection element 56 and its direction of movement 75. In this case, the raster plane 76 is preferably perpendicular to the sample plane 49 (see also FIG. 5). With the eccentric 80, which is preferably motor-driven, the transverse inclination of the slide 8, 8 or of the specimen slide 2 can be corrected, so that the focal line 101 of the scanner device 72 comes to rest exactly in the plane of the sample 49.
    Preferably, the sample plane 49 is arranged substantially horizontally. The receptacle 34 of the sample table 2 comprises two mutually opposite grooves 35 (see Fig. 4B) for receiving the two longitudinal edges 14 of the sample slide 8 shown or a (not shown) test slide 10th
    The sample table 2 comprises for clampingly holding a slide 8,10 in a direction substantially perpendicular to the surface of the slide preferably a Auflage¬teil 103 with two fixed webs 36. In addition, the sample table 2 includes a resiliently against these webs 36 movable jaws 37 with two upstanding side walls 38. These side walls 38 define together with the lower edges of the webs 36, the opening width of the grooves 35. The movable jaw 37 is resiliently supported by springs 30 against the support portion 103 of the sample table 2, so that these springs 30, the two upstanding Seiten¬wände 38 of the movable Press jaw 37 resiliently against the underside of the slide 8. As a result, a sample slide or a test slide 10, which preferably has at least approximately the mass of a glass slide for light microscopy, is clamped in the sample table 2 in an inverted direction.
    The sample table 2 comprises for clampingly holding a slide 8, 10 in substantially parallel direction to the surface of the slides against at least one of the longitudinal edges 14 of the slide 8 movable pressing parts 39, which limit the opening width of the receptacle 34 resiliently. These pressing parts 39, which are movable relative to at least one of the longitudinal edges 14 of the object carrier 8, are preferably designed as rollers, each having a substantially vertical axis. The groove 35 facing the rollers 39 defines a stop of the sample slides 8 and test slides 10 suitable for defining the axis of a coordinate system of the laser scanner device 1.
    Submerging in a recess 98, a lowering mandrel 88 is also shown here, which penetrates into the sample table 2 when approaching the sample table 2 to the storage unit 4 and with this penetration pulls the jaws 37 and the side walls 38 away from the webs 36 of the support part 103.
    FIG. 4B shows the object table 2 with a view away from the slide magazines 7 ', 9', with the object table 2 open, after the removal or before the insertion of a slide 8, 8. Because there is currently no slide 8,10 in the sample table 2, the roller-shaped Anpressteile 39 are in their extreme position. From this extreme position, the roller-shaped pressing parts 39 are displaced against the pressure of spring elements as soon as a slide 8, 8 is pushed into the sample table 2. Also clearly visible here is how the Senk¬ thorn 88 runs on a ramp 89 so that the movable jaws 37 of the sample table 2 pulled down a bit and so the insertion of a slide 8,10 in the receptacle 34 of the sample table 2 is made possible.
    FIG. 5 shows a vertical partial section through the object table as well as its height adjustment and longitudinal tilting device. The sample plane 49 defined by the sample table 2 is adjustable in substantially the Z-direction (here in the vertical direction), in that the sample table 2 linearly mounted on a suspension 83 and linearly displaceable rests together with this suspension 83 on a motor-driven eccentric 106 and pivotally mounted on a frame 82 on one side. A section through a preferred embodiment of such an eccentric device is shown in FIG. If the eccentric 106 is turned slightly, the suspension 83 raises or lowers correspondingly with the sample table 2. With this movement, the plane of the sample table 2, ie the sample plane 49, can be aligned with the plane of a bearing 6 in the sample compartment magazine 7 'or in the Test magazine 9 'of the storage unit 4 are brought into agreement so that a linear transfer between one of these magazines 7', 9 'and the sample table can be done. Preferably, the corresponding magazine in the Z direction is provided by a displacement of the movable control plate 11, so that only a possible fine tuning must be done with the eccentric 106 of the sample table 83. With the eccentric 106, which is preferably driven by a motor, the longitudinal inclination of the object carrier 8, 10 or of the sample table 2 can be corrected so that the focal line 101 of the scanner device 72 comes exactly into the sample plane 49. In fact, with the correction of the longitudinal inclination, there is also a shift in the height, ie along a Z-axis.
    For the purpose of such a slide transfer, the sample table 2 is preferably approached as far as possible to the storage unit 4 in the substantially horizontal Y direction. As the sample table 2 approaches the storage unit 4, a dowel 88 penetrates into the sample table 2, thereby lowering a support of the receptacle 34 of the sample table 2 for receiving a slide. Thereby, the sample table 2 for receiving a slide 8, 10 is provided. This approach is preferably done by means of a spindle drive 84 mounted on the suspension 83 and along a linear guide 85. The spindle drive 84 is connected to the motor 87 via a flexible coupling 86, so that an exact linear guidance of the sample table 2 in substantially the Y direction is also possible can take place when the sample plane 49 includes a small angle of inclination to Horizonta¬len. The aim of the adjustability of the sample table 2 with the eccentric 80 is mainly the alignment of the sample plane 49 to a focal line 101, which is defined by a scanning head 50 of the laser scanner device 1 oscillating in the X direction (in this case perpendicular to the plane of the drawing) , This scanner head 50 moves very quickly in the X direction and on the upper side of a separating plate 99. This separating plate has a raster opening 90. Preferably, the scanner head 50 is recessed into this raster aperture 90 so that the light beams emanating from it strike the sample a short distance and the scanner head 50 receives the fluorescence emission coming from the sample as effectively as possible and to one or more detectors 61 Detectors 61,61 'forward.
    FIG. 6 shows a schematic diagram with essential optical elements of the laser scanner device 1 with a scanner head 50 according to a first embodiment. The laser
    Scanner apparatus 1 for imaging and / or measuring fluorescent samples treated on microscope slides treated with two different fluorescent dyes comprises a motorized sample stage 2 with a receptacle for a sample slide 10 in a sample plane 49. A first laser 51 and a second laser 52 and a first optical system 53 provide two laser beams 54, 55 of different wavelengths aligned parallel to one another and parallel to this antenna 49. A scanner device 72 includes a scanner head 50 reciprocable parallel to this plane 49 and having an optical deflector 56 for deflecting the laser beams 54, 55 toward the sample. A first objective 57 focuses the laser beams 54, 55 on the sample in the plane 49. This first objective 57 has a main plane 107, which is preferably arranged parallel to the sample plane 49.
    A second optical system 58 guides the emission beams 59, 60 deflected by the laser beams 54, 55 on the sample and deflected by the first objective 57 and the deflection element 56 in a direction substantially parallel to plane 49 to detectors 61, 61 '. , Two such detectors 61, 61 'detect the emission beams 59, 60 of different wavelengths coming from the samples. The apertures of the apertures 48 preferably have a larger diameter than the focused emission beams 59, 60, but may also substantially correspond to the dimensions of the focused emission beams 59, 60, thereby providing a confocal laser scanner apparatus 1.
    The optical deflection element 56 of the alternative laser scanner device 1 preferably comprises a wedge-shaped dichroic mirror 62 with front and rear dichroic surfaces 63, 64 arranged at an intermediate angle β to one another. In this case, the wedge-shaped dichroic mirror 62 is adjusted so that the two laser beams 54, 55 are reflected on one of the surfaces 63, 64. The wedge-shaped dichroic mirror 62 causes, by the intermediate angle β, a spatial separation of the two resulting focus points 65 and the two emission beams 59, 60 guided in the direction of the detectors 61, 61 '. The two resulting focus points 65, 65 'are arranged at a distance 5 to one another in the sample plane 49. In this first embodiment shown in Figure 6, the optical deflector 56 is a wedge-shaped dichroic mirror 62. Preferred is the rear dichroic surface 64 of the wedge-shaped dichroic mirror 62 for mirroring a first laser beam 54 and its front dichroic surface 63 for mirroring a second laser beam 55 and formed two emission beams 59,60.
    The second optical system 58 comprises elements known per se, such as a second objective 57 ', which focuses the incoming emission beams 59, 60 in one point at a time. The second optical system 58 further comprises a diaphragm 48, the openings of which are preferably substantially larger than those these openings, focused emission beam bundles 59,60. According to a particularly preferred embodiment, the laser scanner device 1 is thus based on a non-confocal imaging principle. These focused emissive radiation beams 59, 60 then impinge on a respective detector 61, 61 ', which measures the intensity of the respective emission beam 59, 60. This second objective 57 'can be designed as an automatic or as a simple lens.
    FIG. 7 shows schematic diagrams of the scanner head of the laser scanner device according to the invention. In this case, FIG. 7A shows a second embodiment of the scanner head 50, in which the optical deflection element 56 is designed as a pentagonal mirror arrangement 66 with a wedge-shaped dichroic mirror 62 and a simple mirror 67. As in the first embodiment (see Fig. 6), the rear dichroic surface 64 of the wedge-shaped dichroic mirror 62 for mirroring a first laser beam 54 and its front dichroic surface 63 is for mirroring a second laser beam 55 and the two emission beams 59, 60 educated.
    FIG. 7B shows a third embodiment of the scanner head 50, in which the optical deflection element 56 is likewise designed as a pentagonal seal arrangement 66 with a wedge-shaped
    Dichroid mirror 62 and a simple mirror 67 is formed. Unlike the second embodiment (see Fig. 7A), the arrangement of the dichroic mirror 62 and the simple mirror 67 are reversed. In this case, the rear dichroic surface 64 of the wedge-shaped dichroic mirror 62 is designed to mirror a first laser beam 54 and its front-dichroic surface 63 to mirror a second laser beam 55 and the first and second emission beams 59, 60.
    In a further alternative embodiment of the scanner head 50 (not shown), the optical deflecting element 56 is also designed as a pentagonal seal arrangement 66 with a wedge-shaped dichroic mirror 62 and a simple mirror 67. In this case, the rearedichroid surface 64 of the wedge-shaped dichroic mirror 62 is designed to mirror a first laser beam 54 and the two emission beams 59, 60 and its front dichroic surface 63 to mirror a second laser beam 55.
    According to a further alternative embodiment, not shown, the optical deflecting element 56 is likewise designed as a pentagonal mirror arrangement 66. In contrast to the similar embodiment shown in FIG. 7A, the wedge-shaped dichroid mirror 62 is replaced by a first simple dichroic mirror which replaces the other surface 63. In place of the rear surface 64 of the wedge-shaped dichroic mirror 62, a second simple dichroic mirror or a full mirror occurs. The second simple dichroic mirror or the full mirror each include a corresponding intermediate angle with the first simple dichroic mirror. These variations of the reflection and Transmis-sionseigenschaften the Pentaspiegelanordnung 66 apply in principle for Ausführungsfor¬men with simple, arranged substantially at 45 ° mirrors.
    8 shows a horizontal partial section through a laser scanner device 1 with essential optical elements of a first optical system 53 for providing excitation light and a second optical system 58 for detecting the triggered Fluo¬zenzzenzemission of the samples, a scanner device 72 with Scanner head 50 and a Objekttisch 2 with a slide magazines 7 ', 9' comprehensive storage unit 4. Be¬vorzugt are all essential optical elements and the scanner device 72 on a common partition plate 99 and the sample table 2 below this partition plate 99 (vgl.Fig. 5) arranged.
    The essential optical elements of the first optical system 53 are arranged in a housing 5 and comprise at least a first laser 51 and optionally a second laser 52, filter wheels 97 for the laser beams 54, 55 emanating from the one or more lasers 51, 52 a number of dichroic mirrors 62 and simple mirrors 67 for deflecting the laser beams 54, 55 from the lasers 51, 52 in a direction parallel to the X direction.
    The essential optical elements of the second optical system 58 are arranged in the same housing 5 and comprise one or more detectors 61, 61 'of these upstream filter wheels 97 and diaphragms 48 for the emission beam bundles 59 emanating from the samples. 60 and a number of dichroic mirrors 62 and simple mirrors 67 for deflecting the emission beams 59, 60 from a direction parallel to the X direction in the direction of the detectors 61, 6T.
    The scanner device 72 comprises a drive 71, the scanner head 50 and preferably a counter-oscillator 73 with a mass equal to or at least equivalent to the scanner head 50 for pulse compensation. Scanner head and counter-oscillator are connected by means of connecting rods 70,70 'to the drive 71 and each fixed to a precise linear guide (not shown). The drive 71 brings the scanner head 50 into rapid reciprocation in a direction of movement 75 (see filled double arrows) which simultaneously defines the scan axis 75. In this case, the counteroscillator 73 always performs an opposite movement, which makes it possible to keep the partition plate 99 and thus the whole laser scanner device 1 quiet despite the preferably high scanning speed of the scanner head 50. The scan axis 75 is parallel to or coincident with the X axis. The scanner head 50 includes an optical deflector 56 which is e.g. when
    Dichroid mirror 62 is formed. This deflection element 56 can be embodied as a full mirror, prism, pentaprism, pentagonal mirror configuration or as a combination of these elements listed here. On the one hand, this deflecting element 56 directs the laser beams 54, 55 of the first optical system 53 onto the specimens on the specimen stage 2 and, on the other hand, guides the emission beams 59, 60 emitted by the specimens in the direction of the second optical system 58.
    Perpendicular to the X axis and scan axis 75, the direction of movement of the sample table 2 arranged below the partition plate 99 runs in the direction of the Y axis. Preferably, in a region outside of the separating plate 99, the storage unit 4 is arranged with the sample slides 8 mounted in a sample magazine 7 'and the test slides 10 mounted in a test part magazine 9'. The presence of a slide 8, 8 in a specific bearing 6 of these magazines 7 ', 9' is preferably checked by means of a control device 22. This control device preferably comprises a light beam 23, which penetrates a control opening 21 for these control purposes.
    Preferably, the laser scanner device 1 comprises a vent 24 having a fan 25, an air inlet 26 with an activated carbon filter 27, and an air outlet 28 to allow exposure of the fluorescent dyes to or in the samples stored in the sample compartment magazine 7 'to ozone to reduce. Particularly preferably, the ventilation device 24 comprises an additional housing 29, which encloses the sample part 7 with the sample slides 8 substantially. This additional housing 29 is preferably arranged within the housing 5 of the laser scanner device 1 and designed as a pivotable away, at least in the public closed area. In this case, it is particularly preferred that the ventilation device 24 is accommodated in this additional housing 29 and is independent of the ventilation of the laser scanner device 1.
    For example, a service person may open this additional housing 29 and, if necessary, insert or replace one or more test slides in the otherwise inaccessible test section magazine 9 '. Preferably, this additional housing 29 is formed swingably away from the partition plate 99 and has a loading opening 100, through which a respective object carrier 8, 10 can be transported onto the sample table 2 or into a magazine 7 ', 9'. Preferably, the sample portion 7 is axially disposed over the test portion 9 of the storage unit 4 and is pivoted away, along with the additional housing 29 or at least along with a portion of this additional housing (thus opened to the service person skilled in the art). Should a sample slide 8 become jammed or broken during transport between the sample table 2 and the storage unit 4, the operator can remove the defective sample slide 8 without access to the test slides 10.
    It is particularly preferred that a service specialist inserts one or more test slides 10 individually into a sample magazine 7 'and inserts this sample magazine 7' in the proper way into the laser scanner device 1. A correspondingly programmed firmware in the controller 40 of the laser scanner device 1 is then preferably activated by entering a personal identification number (PIN) of the service specialist or by entering a code for the service professionals. The thus-activated firmware enables the controller 40 of the laser scanner apparatus 1 to control the automatic transport of each of these test slides 10 from the sample compartment magazine 7 'onto the sample table 2 and further into a storage location 6 of the test section magazine 9'. According to this particularly preferred method, any manual intervention in the test part magazine 9 'is made impossible. Only in special emergencies could a service person using suitable tools retrieve the test object carrier 10, preferably enclosed in the additional housing 29. Preferably, the controller 40 of the alternative laser scanner device 1 is designed to control an automated, internal test performed on test slides 10.
    Preferably, the sample table 2 is designed to be driven by a motor until immediately before the storage unit 4 and its position and movement are controlled by the controller 40. The same also applies to the setting plate 11 of the storage unit 4 for selecting the object holder 8, 10 to be examined and for the rotatable eccentric roller 19 for swinging the flaps 16. It is also preferred that the unloading slide 31 also be used to transport a slide 8, 10 to the sample table 2 for the automated selection and provision of a sample slide 8 or test slide 10 formed on the sample stage 2 driven by a motor and whose position and movement are controlled by the control 40. The same applies to the loading slider 32 for transporting a slide 8, 8 to the storage unit 4 when it is put back into a storage area 6 of the sample compartment magazine 7 'or the test part magazine 9'.
    FIG. 9 shows a horizontal partial section through the scanner head 50 of the laser scanner device 1 with the associated displacement sensor 91. A linear guide 68, to which the scanner head 50 in the X-axis is attached, is fastened to a frame 82. Direction and dipping into a Rasteröff- 90, is arranged to move. In this case, the X-axis coincides with the direction of movement 75 of the scanner head 50, this movement direction 75, together with the first and second laser beams 54, 55 deflected to the sample (not shown) arranged below the scanner head 50, being a raster plane 76 defined. This scanner plane 76 is preferably perpendicular to the sample plane 49. The scanner head 50 encloses a scale 77, which is arranged at a distance from a fixed, linear measuring system 78 of the laser scanner device 1 and in this raster plane 76. The sample table 2 is preferably linearly movable in a Y-direction of a Cartesian coordinate system arranged at right angles to the X-axis 75 and is driven by a motor.
    The scanner head with all its optical elements, fasteners, scale 77 and part of the linear guide has a center of mass 74. This center of mass 74 is arranged in the direction of movement 75 of the scanner head 50 on a line with a connecting point 69 which connects the connecting rod 70 of the scanner head 50 to the drive 71. This connecting point 69 can be e.g. be designed as an axle; However, it is preferred to form the Pleuelangriffspunkt as a cross-spring joint.
    FIG. 10 shows a schematic diagram of the displacement sensor 91 for the scanner head 50 and its non-linear movement when scanning as an X / t diagram. This X / t diagram indicates the different time duration (Δ ^ At2) for the detection of a pixel (Δχ) depending on the position on the X-axis. The Weggeber signal 92 corresponds approximately to a sine curve, which has their maxima at the extreme points (end points) of a scan line of the laser head 50. Because of the reversal of the scan direction in these endpoints and the resulting slowed motion, the scanner head needs a longer time (At2) for the same distance (Δχ) near these inflection points than the maximum achievable speed of the scanner head in one Middle position between the turning points, in which the same Wegstrecke (Δχ) in a much shorter time (Δ ^) is traversed. The pixel (Δχ) and the corresponding location and time are correlated with one another and assigned to the intensity measured at this time. The sum of all measured pixels then yields a zweidimensiona¬les image. The correlation of the location of these pixels in the sample plane 49 with the intensity of the fluorescence intensity measured at this location, in combination with the pixel size, ultimately determines the resolution of the laser scanner device 1.
    FIG. 11 shows a test slide 10, which has the format of a standard microscope slide for light microscopy and which comprises only substantially light-stable test structures 41. As "substantially light stable" For example, a test structure is referred to when used under normal use, i. no measurable damage is suffered during the radiation exposure usually occurring during test procedures. Exposing a test slide 10 for a minute or even hours to a laser beam 54, 55, or leaving a test slide 10 in an unprotected location for a long time (exposed to ambient light, for example) is not referred to as "normal use".
    The following Table 1 gives an overview of the most common glass slides for light microscopy:
    The exemplary test slide 10 shown in Figure 11 has an area of 75 mm in length A having a width B of 25 mm and a thickness C of 1 mm. One half of the surface A / 2 is frosted (for example by means of grinding). The other half has a preferred line pattern with a width D of 20 mm. This line pattern preferably consists of a masked vapor deposited chromium layer. The capital letters E, F, G denote a certain number of line pairs per millimeter (Ip / mm) and the lower case letters I, m, η, o denote certain mass as follows: E = 50 lp / mm; F = 100 lp / mm; G = 10 lp / mm; I = 0.5 mm; m = 2 mm; n = 1 mm; o = 7 mm.
    All these test structures 41 are preferably exclusively light-stable and non-fluorescent.
    FIG. 12 shows a vertical section through an eccentric device 80, 106 for adjusting the focal line 101 determined by the scanner head 50 relative to the specimen plane 49 on the specimen stage 2. Each eccentric device 80, 106 is preferably motor-driven and comprises a ball bearing, which has a stationary outer ring 108, a rotatable inner ring 109 and a number of rolling elements or balls 110 includes. Preferably, such a roller bearing also includes a cage, which was omitted because of the clarity of Darstel¬lung in Fig. 12. The rotatable inner ring 109 of the especially preferred rolling bearing has an eccentric bore 111, in which a motor-driven drive shaft 112 is fixed non-rotatably relative to the inner ring 109. If now this An¬triebsachse 112, which is stationary and rotatably mounted on a suspension (not shown), rotated by a certain angle, the standing, on the moving component befes¬tigte outer ring 108 is raised or lowered. This raising or lowering depends on the eccentric mass 113, which defines the distance of the center of the drive shaft 112 from the center of rotation 114 of the ball bearing, the instantaneous mutual arrangement of these two centers and the direction of rotation of the drive axle. The advantage of these eccentric arrangements 80, 106 is, inter alia, that a virtually stepless and friction-free height adjustment is made possible. It is clear that a smaller eccentric mass 113 allows a lower maximum adjustability of the eccentric devices 80, 106, but increases the fineness of this adjustability. The outer ring 108 may be fixed immovably to the device 83, 103 to be moved; however, this is not mandatory, so that the outer ring 108 can also be movably arranged relative to the device 83, 103 to be moved. The eccentric mass 113 can be arranged in any spatial direction, so that it does not necessarily define a horizontal deviation, as shown in FIG. 12.
    The alternative laser scanner device 1 is designed for imaging and measuring zweidi¬mensionalen objects. Accordingly, a sensitivity calibration must be accurate for this " flat " Objects be valid. However, two-dimensional fluorescence probes that are stable to light as well as chemically stable for long periods of time are not or only very difficult to produce.
    On the other hand, objects having a three-dimensional extent can be measured. However, because the intensities measured on such three-dimensional objects are highly dependent on the depth of focus of the laser scanner device and on the particular positioning in focus (i.e., in the Z direction), such three-dimensional objects are not directly suitable for calibrating signal intensity or sensitivity. As so-called "bulk material", however, there are materials 102, such as, for example, fluorescent dyes embedded in plastic or doped glasses which are largely light-stable and chemically resistant.
    The orientation of the sample table 2 and the storage unit of the laser scanner device 1 in space is actually arbitrary. The same applies to the well-balanced or counter-oscillator 73 pulse-compensated scanner device 72.
    Also, the sample plane 49 of the sample table 2 may be arranged substantially horizontally overhead but hanging. However, a standing arrangement of the sample table according to FIGS. 1 and 2 or 4 to 7 is preferred.
    Identical features or elements of the alternative laser scanner device 1 are each given the same reference numerals, although these elements are not described in detail in all cases.
    Also disclosed is a method of operating such a laser scanner apparatus 1 for imaging and / or measuring slide-coated fluorescent samples on slide glass. This method is characterized in that a wedge-shaped dichroic mirror 62 with front and rear dichroic surfaces 63, 64 arranged at an intermediate angle β is preferably used as the optical deflection element 56, the wedge-shaped dichroic mirror 62 being set such that the two laser beams 54, 55 each of the surfaces 63, 64 are reflected, and the wedge-shaped dichroic mirror 62 effects, by the intermediate angle β, both a spatial separation of the two resulting focus points 65 and of the two emission beams 59, 60 directed in the direction of the detectors 61, 61 '.
    In this method, an optical Umlen¬kelement 56 is preferably used as Pentaspiegelanordnung 66 with a wedge-shaped Dichroidspiegel 62 and a simple mirror 67, said pentaseal assembly 66 tilts the scanner head 50 to a scan axis 75th rectified Y-axis is corrected so that the resulting focus points 65 do not change their current position in the sample plane 49.
    It is especially preferred that the scanner head 50 with its optical deflection element 56 and its movement direction 75 defines a raster plane 76 which is perpendicular to the sample plane 49, wherein the deflection of the scanner head 50 in the X-axis 75 is measured at a scale 77, which is arranged at a distance from a linear measuring system 78 of the laser scanner device 1 and in this raster plane 76. This scale 77 is preferably arranged in the raster plane 76 or at least in the immediate vicinity of this raster plane 76. This scale 77 is preferably also arranged in the main plane 107 of the first objective 57 (see FIGS. 6 and 7) or at least in the immediate vicinity of this main plane 107. Reference numbers: 1 laser scanner device 38 upstanding side walls 2 sample table 39 movable pressing parts 3 transporting device 40 control 4 storage unit 41 lightfast test structures 5 housing 42 handle 6 bearing 43 dovetail 7 sample part 44 drive to 11 7 'sample part magazine 45 drive to 31 8 sample Slide 46 Drive to 32 9 Test part 47 Tilting axis of 33 9 'Test part magazine 48 Aperture 10 Test slides 49 Plane, sample plane 11 Movable positioning plate 50 Scanner head 12 Bearings 51 First laser 13 Contact spring 52 Second laser 14 Long edge Slide 53 First optical system 15 insertion side 54 first laser beam 16 swing-away flap 55 second laser beam 17 axis 56 optical deflecting element 18 angle plate 57 first objective 19 eccentric roller 57 'second objective 20 blocking plate 58 second optical system 21 control aperture 59 first 22 control device "" emission beam 60 second 23 light beam emission beam 24 Ventilation device 61 First detector 25 Fan 61 'Second detector 26 Air inlet 62 Dichroic mirror 27 Activated carbon filter 63 Front surface 28 Air outlet 64 Rear surface 29 Additional housing 65 Resulting focus points 30 Spring 66 Penta mirror arrangement 31 Discharge slide 67 Simple mirror 32 Charging slide 68 Linear guide 33 Swiveling flap 69, 69 'Connecting point 34 Receptacle 70, 70' Connecting rod, connecting rod 35 Opposite grooves 71 Actuator 36 Fixed webs 72 Scanner device 37 movable jaws 73 Counteroscillator 74 Mass center of gravity 75 Direction of movement X-axis, scanning axis 76 Raster plane 77 Scale 78 Linear measuring system 79 Tilting mechanism 80 eccentrics,
    Eccentric device 81 Rotary axis 82 Frame 83 Suspension 84 Spindle drive 85 Linear guide 86 Coupling 87 Motor 88 Countersink 89 Ramp 90 Raster opening 91 Displacement transmitter 92 Displacement signal 97 Filter wheel 98 Recess 99 Divider 100 Charging opening 101 Focus line 102 Flat materials 103 Support part of 2 104 Steel spring 105 Yoke 106 Eccentric .
    Eccentric device 107 Main plane of the objective 57 108 Outer ring 109 Inner ring 110 Rolling elements, balls 111 Eccentric bore 112 Drive shaft 113 Eccentric dimension 114 Center of rotation of the ball bearing
    权利要求:
    Claims (6)
    [1]
    Claims 1. A slide transport device (3) for a laser scanner device (1) for imaging and / or measuring fluorescent samples located on slides in a sample plane (49) and treated with two different fluorescent dyes, wherein the laser scanner device (1) comprises: (a) a motorized sample stage (2) with a receptacle (34) for slides (8, 10) in a sample plane (49); (b) at least one laser (51, 52) and a first optical system (53) for providing two laser beams (54, 55) of different wavelengths; (C) a scanner device (72) having a in a direction of movement (75) reciprocable scanner head (50) with an optical deflecting element (56) for deflecting the laser beams (54,55) towards a sample wherein the direction of movement (75) of the scanner head (50) defines a scan axis or X axis, and wherein the sample table (2) can be moved linearly in a Y direction of a Cartesian coordinate system arranged at right angles thereto; (d) a first objective (57) for focusing the laser beams (54, 55) on the sample in the plane (49); (E) a second optical system (58) for passing through the laser beams (54,55) triggered on the sample and through the first lens (57) and the Umlen¬kelement (56) in one to the plane (49) substantially parallel deflected emission beam (59,60) to detectors (61,6T), and (f) two detectors (61,6T) for detecting the coming of the samples emission beam (59,60) of different wavelengths, characterized in that the slide transport device (3) of the laser scanner device (1) is motorized and designed to move a slide (8, 10) from a storage unit (4) of the laser scanner device (1) to the sample table (2) and back is; - Wherein the sample table (2) for transfer of slides (8,10) to just before the storage unit (4) or in front of a loading opening (100) of an additional housing (29) is designed to be movable; - wherein the storage unit (4) comprises a setting plate (11), which is designed for reversible mounting a sample part magazine (7 '); - Wherein the sample part magazine (7) has an open insertion side (15) for storing Ob¬jektträgern (8) in certain bearings (6) and a stack height; and - wherein the sample compartment magazine (7 ') at a corner opposite the insertion side (15) has a control opening (21) extending essentially over the entire stack height for detecting the presence or absence of a slide (8) in one certain bearing (6) includes.
    [2]
    2. slide transport device (3) according to claim 1, characterized in that the adjusting plate (11) of the storage unit (4) relative to the sample table (2) of the La¬ser scanner device (1) is designed to be displaceable, whereby any slide ( 8) can be brought to the level of the sample plane (49) defined by the sample table (2) and provided for linear transport to the sample table (2).
    [3]
    3. slide transport device (3) according to claim 1 or 2, characterized in that the sample part magazine (7 ') as from the outside in a housing (5) of the laser scanner device (1) insertable magazine (7') for a plurality of sample slides (8) is formed and comprises a handle (42) to which it can be held and inserted into the housing (5) of the laser scanner device (1).
    [4]
    A slide transport device (3) according to any one of the preceding claims, characterized in that the bearing points (6) of the sample compartment magazine (7 ') each comprise a pressure spring (13) which elastically engages a longitudinal edge (14) of an inserted slide (8). so that the slides (8) sit substantially free of play in the test tube magazine (7 ').
    [5]
    5. slide transport device (3) according to any one of the preceding claims, characterized in that the sample part magazine (7 ') of the laser scanner device (1) extending substantially over the entire stack height of the magazine (7'), In¬dividuell wegschwenkbaren flap (16), with which the open insertion side (15) of the sample part magazine (7 ') is at least partially coverable, thereby falling out of slides (8) when handling a with at least one sample slide (8) filled magazine (7 ') is prevented.
    [6]
    6. slide transport device (3) according to any one of the preceding claims, da¬durch in that the sample part magazine (T) on its insertion side (15) opposite side of the laser scanner device (1) is a substantially over the Whole stack height of the magazine (7 ') extending blocking plate (20) which covers part of the width of this page, thereby falling out of slides (8) when handling a filled with at least one specimen slide (8) Maga¬zins (T) is prevented. 4 sheets of drawings
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    同族专利:
    公开号 | 公开日
    CN101419335A|2009-04-29|
    JP5269858B2|2013-08-21|
    JP5149766B2|2013-02-20|
    EP2053447A1|2009-04-29|
    DE502008001877D1|2011-01-05|
    AT489655T|2010-12-15|
    US20100301232A1|2010-12-02|
    DE202008018428U1|2013-10-09|
    US20090101839A1|2009-04-23|
    EP2259125B1|2017-07-26|
    US8013313B2|2011-09-06|
    EP2259125A2|2010-12-08|
    JP2011100136A|2011-05-19|
    EP2259125A3|2011-03-16|
    EP2053447B1|2010-11-24|
    US7777200B2|2010-08-17|
    CN101419335B|2013-06-12|
    JP2009104136A|2009-05-14|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE20221635U1|1977-08-02|2006-09-21|Tecan Trading Ag|Optical system for stimulating, measuring fluorescence on/in specimens treated with fluorescent paint has geometric axis at least partly identical with optic axis between mirror and detector|
    DE19707227A1|1997-02-24|1998-08-27|Bodenseewerk Perkin Elmer Co|Light scanner|
    US20060109432A1|2004-11-24|2006-05-25|Patrick Guiney|System and method for calibrating position of microscope slide within storage receptacle|
    FR2427017B1|1978-05-24|1982-11-19|Onera |
    FR2551886B1|1983-09-09|1986-09-26|Sopelem|DEVICE FOR COUPLING OPTICAL FIBER CABLES|
    GB8531011D0|1985-12-17|1986-01-29|Medical Res Council|Confocal scanning microscope|
    GB9015793D0|1990-07-18|1990-09-05|Medical Res Council|Confocal scanning optical microscope|
    US5225893A|1990-12-10|1993-07-06|Hughes Aircraft Company|Two-color focal plane array sensor arrangement|
    JPH05210868A|1992-01-30|1993-08-20|Hitachi Ltd|Multibeam separation type optical head|
    US6628385B1|1999-02-05|2003-09-30|Axon Instruments, Inc.|High efficiency, large field scanning microscope|
    US6864097B1|2000-09-27|2005-03-08|Agilent Technologies, Inc.|Arrays and their reading|
    JP4209679B2|2001-01-26|2009-01-14|テカン・トレーディング・アクチェンゲゼルシャフト|Holding device|
    CH697814B1|2001-01-26|2009-02-27|Tecan Trading Ag|Optical system and method for exciting and measuring fluorescence on or in samples treated with fluorescent dyes.|
    US7589891B2|2003-11-26|2009-09-15|Olympus Corporation|Laser scanning type fluorescent microscope|
    CH708797B1|2007-08-17|2015-05-15|Tecan Trading Ag|Sample part magazine for a slide transport device of a laser scanner device.|JP5718329B2|2009-07-09|2015-05-13|ホワルド フグヘス メドイクアル インストイトウテ|Microscopy with adaptive optics|
    JP5338573B2|2009-08-31|2013-11-13|ソニー株式会社|Fluorescent image acquisition method, fluorescent image acquisition device, and fluorescent image acquisition program|
    FR2960689B1|2010-05-28|2013-05-10|Univ Bordeaux 1|METHODS OF WRITING AND READING DATA BY FLUORESCENCE ON A PHOTOSENSITIVE MEDIUM, MEDIA AND ASSOCIATED DEVICES|
    JP5537615B2|2011-08-10|2014-07-02|ウルトラテックインク|System and method for forming a time-averaged line image|
    US8399808B2|2010-10-22|2013-03-19|Ultratech, Inc.|Systems and methods for forming a time-averaged line image|
    EP2732326B1|2011-07-14|2020-11-18|Howard Hughes Medical Institute|Microscopy with adaptive optics|
    JP2014029395A|2012-07-31|2014-02-13|Hitachi Media Electoronics Co Ltd|Luminous flux scanning device and luminous flux scanning type image projection device|
    CN103063628A|2012-12-13|2013-04-24|公安部第一研究所|Excitation method for multiple fluorescent dyes|
    TWI498990B|2012-12-19|2015-09-01|Genesis Photonics Inc|Splitting apparatus|
    EP2951982B1|2013-01-29|2019-10-09|Hewlett-Packard Development Company, L.P.|Single-facet spindle implementation for a laser scanner system|
    DE102013022026A1|2013-12-19|2015-06-25|Carl Zeiss Microscopy Gmbh|Multi-Color scanning microscope|
    US9599572B2|2014-04-07|2017-03-21|Orbotech Ltd.|Optical inspection system and method|
    US10083843B2|2014-12-17|2018-09-25|Ultratech, Inc.|Laser annealing systems and methods with ultra-short dwell times|
    CN107003508B|2014-12-23|2020-07-10|通用电气医疗集团生物科学公司|Selective planar illumination microscopy instrument|
    US10317663B2|2015-02-27|2019-06-11|General Electric Company|Determination of deflection of a microscope slide|
    CN104729996B|2015-04-17|2017-10-31|江苏天瑞仪器股份有限公司|Reflective laser on-line gas analysis instrument light path device|
    CN105527231A|2015-12-30|2016-04-27|聚光科技股份有限公司|An off-axis type gas remote measurement device and a method|
    WO2017130770A1|2016-01-29|2017-08-03|学校法人明治大学|Laser scanning system, laser scanning method, moving laser scanning system, and program|
    CN107479310B|2016-06-07|2021-06-25|海信集团有限公司|Wavelength conversion device and projection light source|
    US10371626B2|2016-08-17|2019-08-06|Kla-Tencor Corporation|System and method for generating multi-channel tunable illumination from a broadband source|
    DE102016119727A1|2016-10-17|2018-04-19|Carl Zeiss Microscopy Gmbh|Device for beam manipulation for a scanning microscope and microscope|
    US10684124B1|2017-07-20|2020-06-16|Michael Hanchett|Scanning and measurement system for repair of structures|
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    法律状态:
    2018-06-15| MM01| Lapse because of not paying annual fees|Effective date: 20171031 |
    优先权:
    申请号 | 申请日 | 专利标题
    CH16412007|2007-10-22|
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