Abstract:
A receptor is mounted on a movable stage of a microscope slide scanner, the receptor being sized and shaped to receive a slide tray having one or more microscope slides thereon. A docking station automatically locks the receptor relative to the docking station whenever a tray is inserted or removed from the receptor without transmitting force to the movable stage.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of the Invention 
         [0002]    This invention relates to the field of scanning tissue specimens on microscope slides, with particular emphasis on instrumentation and methods of changing slide trays manually, or automatically using a robotic manipulator. More particularly, this invention relates to a slide tray, receptor and docking station in which the slide tray can be manually or automatically inserted into or removed from the receptor, which is mounted on a moving stage of a microscope slide scanner. 
         [0003]    2. Background of the Invention 
         [0004]    Two general types of microscope slide loaders are known. Some slide loaders are designed for loading slides onto standard microscopes (for example the Prior Scientific PL-100) and some slide loaders integrated into pathology scanners (for example Aperio ScanScope AT) place microscope slides onto the microscope stage or insert them into the optical path. These slide loaders have the advantage of being small in size and able to handle large numbers of standard microscope slides. Disadvantages include problems that may occur when a slide breaks and the loader continues to load slides, and difficulty in handling large slides or mixing slide sizes. A second type of slide loader handles slide trays containing one or more slides, with the advantage that the slides themselves are not handled during movement of the trays, and multiple slides can be loaded into a single tray. The size of slides that can be handled is limited only by the size of the tray (our autoloader handles slide trays containing slides up to 6×8 inches in size), and slide sizes can be mixed in a single run or even in a single tray. 
       OBJECTS OF THE INVENTION 
       [0005]    It is an object of this invention to provide a slide tray, receptor and docking station such that a slide tray can be manually or automatically inserted into or removed from a receptor mounted on the moving stage of a slide-scanning microscope without transmitting force to the moving stage during insertion or removal of the slide tray. 
         [0006]    It is an object of this invention to provide a slide tray, receptor and docking station such that a slide tray can be manually or automatically inserted into the receptor (which is mounted on the moving stage of a scanning microscope) for acquisition of a preview image. The slide tray can then be removed from the receptor, and then re-inserted into the receptor at a later time for a final scan of the specimen on the microscope slide, in which the placement of the slide on the microscope stage is substantially the same after each insertion. 
         [0007]    It is a further object of this invention to provide a slide tray and receptor such that a slide tray can be manually or automatically re-inserted into the receptor (which is mounted on the moving stage of a slide-scanning microscope) for acquisition of a second image of the specimen, where the placement of the slide tray in the receptor (and thus the position of the slide on the microscope stage) is substantially the same after each insertion. 
         [0008]    It is a further object of this invention to provide a slide tray containing a permanently-mounted test and/or calibration specimen that can be used for transmission and/or reflection imaging. 
       SUMMARY OF THE INVENTION 
       [0009]    A slide tray and receptor in combination is used with one or more microscope slides located in a microscope slide scanner, the slide tray comprising an opening to removably receive the microscope slide. The receptor comprises a receiving portion that is sized and shaped to receive the tray, the receptor having at least one retainer to removably retain the tray in position when the tray is inserted into the receptor. The receptor is affixed to a movable stage of the slide scanner, the slide tray being located in substantially the same position in the receptor each time that the tray is inserted into the receptor. 
         [0010]    A slide tray, receptor and docking station in combination is used with one or more microscope slides located in a microscope slide scanner, the slide tray comprising an opening to removably receive a microscope slide. The receptor comprises a receiving portion that is sized and shaped to receive the tray, the receptor having at least one retainer to removably retain the tray in position for scanning the microscope slide when the tray is inserted into the receptor. The receptor is affixed to a movable stage of the slide scanner, the slide tray being mounted in substantially the same position in the receptor each time that it is inserted into the receptor. The receptor has at least one locking area, the locking area being sized and located to removably receive a lock located on the docking station to lock the receptor relative to the docking station when the tray is inserted into or removed from the receptor. The slide scanner has a controller to control operation of the tray, receptor and docking station so that the movable stage is not subject to external forces as a tray is inserted or removed from the receptor. 
         [0011]    A slide tray for insertion into a receptor is used with one or more microscope slides located in a microscope slide scanner, the slide tray comprising a permanently-mounted test and/or calibration specimen that can be used for transmission and/or reflection imaging. 
         [0012]    A method of inserting or removing slide trays from a receptor is provided, the slide trays having one or more microscope slides and being located in a microscope slide scanner. The method comprises locating a receptor on a movable stage of the slide scanner, operating a docking station to releasably lock the receptor relative to the docking station whenever a tray is inserted into or removed from the receptor without transmitting force to the moving stage during the insertion or removal of the slide tray. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0013]      FIG. 1   a  shows a preferred embodiment of a slide tray used in the present invention, showing the pins which interact with the spring locking mechanism to hold the slide tray in place in the slide tray receptor shown in  FIG. 2 , and a central insert to hold a large microscope slide. 
           [0014]      FIG. 1   b  shows a slide tray with microscope slide mounted, as well as a test and calibration slide mounted near the positioning pins on the right side of the diagram. 
           [0015]      FIG. 1   b  shows the outer frame of a slide tray like that shown in  FIG. 1   a , in which a slide-holding insert will be placed. 
           [0016]      FIG. 2   a  is a perspective view of the slide tray receptor showing the spring locking mechanism used to keep the slide tray in place in the receptor. 
           [0017]      FIG. 2   b  is a perspective view of the slide tray receptor of  FIG. 2   a  with one spring locking mechanism disassembled to show its individual components. 
           [0018]      FIG. 3  shows the docking station that holds the slide tray receptor in place during insertion or removal of the slide tray. 
           [0019]      FIG. 4  shows the receptor mounted on the Z-stages that are part of a computer-controlled X-Y-Z-tilt microscope stage. 
           [0020]      FIG. 5  shows a schematic front view of an X-Y-Z-tilt stage of a scanning microscope or macroscope. 
       
    
    
     DESCRIPTION OF THE INVENTION 
       [0021]    The present invention is a practical docking station, slide tray receptor and slide tray that enables a slide tray containing one or more microscope slides to be manually or automatically inserted into and removed from a slide tray receptor mounted on a computer-controlled microscope stage without transmitting force to the microscope stage during insertion or removal, and to be re-inserted into the receptor at substantially the same position relative to the microscope stage. 
         [0022]    An example of a slide tray as used in the present invention is shown in  FIG. 1   a . A slide tray frame  100  contains a slide carrier  105  in which a microscope slide is placed, held against positioning plate  110  by a spring-loaded pusher  115 . A wedge-shaped ramp  160  (on both sides of the slide tray frame  100 ) runs under a positioning roller  224  shown in  FIG. 2   a . The slide tray shown in this diagram is designed to hold one 4×5 inch microscope slide (which is not shown loaded into this tray) above an open window  125  allowing for both transmission and reflection imaging. Indentations  130  allow fingers to be inserted under the edge of the slide to assist in removing the slide from the tray. When a tray is designed to hold multiple smaller slides, a spring-loaded pusher  115  is provided for each slide. The slide trays are designed to hold multiple 1×3 inch slides, three 2×3 inch slides, one 4×5 inch slide, one 5×7 inch slide, and one 6×8 inch slide, and trays for other slide sizes can easily be designed. Handles  140  are used for either manual or robotic handling of the tray. A barcode  150  is permanently mounted on the back edge of the tray, and is a unique identifier for that tray. There are a plurality of trays (not shown) and each tray has its own barcode or other unique identifier. Trays of the plurality of trays can be successively mounted in the receptor as desired. In addition to describing the number, size and position of each slide in the tray, the operator can store information in a database indexed by the unique tray identifier which is accessible by the scanner&#39;s control and operating system. This information enables the scanner to automatically change lasers, filters, detectors and detector gain, etc. before scanning the slides in that tray. One positioning pin  120  is shown on the right side of the tray; one more pin is at the same position along the left edge of the tray (not shown). These pins are used to align and hold the tray in the receptor as described below in the description of  FIG. 2   a.    
         [0023]      FIG. 1   b  shows a slide tray containing a permanently-mounted test and/or calibration slide  145  which is mounted above an open window (not shown) in the slide holder frame so either transmission or reflection test and/or calibration slides can be used. Slide trays containing test or calibration slides can be used for several different purposes, including calibrating the instrument (often done daily or before scanning a large number of similar slides); for standardizing fluorescence by measuring fluorescence from a well-characterized calibration slide; for testing instrument resolution; and many others. The barcode  150  on the back edge of the slide tray includes information describing the calibration and/or test slide mounted on that tray.  FIG. 1   b  also shows a large microscope slide  135  in position in the slide tray, held against positioning plate  110  by pressure from spring loaded pusher  115 . The edges of both positioning plate  110  and spring loaded pusher  115  that push on the slide are beveled to apply a downward force component to the edge of the slide. The positioning of indentations  130  relative to the edge of slide  135  allows a finger of a user to be inserted in one of the indentations to aid in removing the slide from the tray. The slide tray shown in  FIG. 1   b  has two positioning pins ( 120  and  121 ) on each side of the tray. In this embodiment, the positioning rollers  224  shown in  FIG. 2   a  roll over pin  120  and settle into the the space between pins  120  and  121  (the same thing happens on the other side of the tray), holding the tray in place. In this arrangement, the trays are held in position by the rollers pushing down on the two pins on each side of the tray. The tray and receptor can be designed with one retainer to retain the tray in the receptor other than the two retainers (i.e. pins  121 ). 
         [0024]    A slide tray frame  100  for very large slides is shown in  FIG. 1   c , which has a window opening large enough to accommodate a slide carrier (not shown in this diagram) designed to hold one very large slide or several small slides. 
         [0025]      FIG. 2   a  shows a slide tray receptor  200  for receiving and holding a microscope slide tray like that shown in  FIG. 1   a  or  1   b . The slide tray receptor is a component of the microscope stage {i.e. the instrument is rigidly mounted to two Z-stages that enable focus and tilt on the scanner (see  FIG. 4 ), part of the X-Y-Z-tilt stage (see FIG.  5 )}. The slide tray receptor  200  is comprised of a frame  201  on which there are two guides  230  containing bushings  210  and two spring-loaded rocker arms  220  pivoted on axle  222  to push positioning rollers  224  downward. The arms  220  are spring-loaded by springs  221  (only one of which is shown). The arms  220  can be spring-loaded in various other ways, including a spring-loaded axle. When a slide tray like that shown in  FIG. 1   a  is loaded from the open end of the receptor, it slides on the base plate of frame  201  between guide walls  231  and the wedge-shaped ramps  160  move under positioning rollers  224 . When the tray is fully inserted, the positioning rollers pass over the pins just before full insertion of the slide tray, and the tray is held firmly by pressure from the rollers on single pins on each side of the tray holding the tray against end plate  240  at the back of slide tray receptor  200 . When a slide tray like that shown in  FIG. 1   b  is loaded, positioning rollers  224  pass over pin  120  on both sides of the tray, and the spring-loaded rollers settle down between and on top of pins  120  and  121  and these pairs of pins on both sides of the tray hold the tray in position. Two bushings  210  at the front of the slide tray receptor are used during docking as will be described later. 
         [0026]      FIG. 2   b  shows an exploded view of the spring-loaded rocker arm on the left side of receptor  200 . Rocker arm  220  pivots about axle  222 , pushed by spring  221 . At the other end of the rocker arm, roller  224  is mounted on axle  226  with spacer  228  holding the roller away from the end of the rocker arm. Bushing  210 , which is inserted in the top of guide  230 , is also shown. 
         [0027]      FIG. 3  shows a docking station  300  for holding the slide tray receptor firmly in place when inserting or removing a slide tray such that no force is transmitted to the microscope stage. When energized, solenoid  310  pulls control arm  320  downwards, compressing springs  325  and causing pins  330  to move downwards and be inserted into the bushings  210  at the front of tray receptor  200 . At the same time, the front of tray receptor  200  is pushed down onto pads  340 , and the tray receptor is held firmly by pins  330  and the pressure on pads  340 . When solenoid  310  is turned off, springs  325  push control arm  320  upwards, retracting pins  330  and moving solenoid  310  back to its unenergized state. The frame  350  of docking station  300  is rigidly attached to the microscope frame (not shown in  FIG. 3 ) to keep it from moving with respect to the microscope frame and stage during insertion and removal of a slide tray. 
         [0028]      FIG. 4  shows the relative positions of docking station  300 , slide tray receptor  200  {mounted on two Z-stages which can be used for specimen focus and tilt, which are themselves mounted on an X-Y stage (not shown)} and with an empty slide tray frame  100  in the fully inserted position. Optical sensor  410  confirms whether a slide tray is in the slide tray receptor or not. 
         [0029]    When a slide tray is to be inserted or removed, a series of stage movements are made under computer control. First, the Z stages  400  level the tray receptor  200  and then move it vertically until the front edge of the receptor is just above pads  340  (which cannot be seen in this view). Next, the X and Y stages center the tray receptor so that bushings  210  at the front of receptor  200  are aligned with pins  330  in docking station  300 . Solenoid  310  is energized, pulling pins  330  down into bushings  210  and pushing the bottom of receptor  200  against pads  340 . At the same time, power is removed from the Z stages so that the receptor is now held firmly by the docking station, and no force is transmitted to the stages. If power is not removed from the Z stage, there is the possibility that the solenoid and Z stages will compete, which may cause the control program to shut down the stages. Depending on the motors used in the X and Y stages and the controller used, it may be necessary to remove power from these stage motors when docked, but in practice it has been found that this not necessary for the particular stages used. Optical sensor  410  confirms whether a slide tray is in the receptor. If a slide tray is in the receptor, it can now be removed either manually or using a robotic tray handler. If the optical sensor  410  does not find a tray in the receptor, one can now be loaded manually or by a robotic tray handler. After a new slide tray has been loaded, solenoid  310  is powered off, pins  340  retract, at the same time the Z stage is activated, and then the X, Y and two Z stages move the new specimen into position to start preview scanning, tissue finding, focusing, setting system gain, etc., and scanning. Because the combination of slide tray, slide tray receptor and docking station described in this patent have been designed so that a tray can be removed from the instrument and then loaded again with the specimen in substantially the same position relative to the microscope stage, when a number of slides are to be scanned in the same run using a robotic tray loader, the operator can perform a rapid preview of specimens on all of the slides, check to make sure focus and exposure are correct, and that instrument settings are correct for each slide, before starting batch scanning of a number of slide trays. This is particularly useful when a batch scan can take several hours, and can most conveniently be done overnight. The bushings  210  are each a locking area on the receptor. The pistons are locks to lock the receptor relative to the locking mechanism. 
         [0030]      FIG. 5  shows a schematic front view of the X-Y-Z-tilt stage used in our instrument. Slide tray receptor  200  is attached to two positioners  400  that move in the Z direction. The focus of the microscope (or macroscope) is changed by moving these two positioners equal distances in the Z-direction, and the tilt of the slide tray receptor can be changed by moving only one positioner. The two positioners  400  are attached to a Y-stage  510  which is moved by Y-stage motor  511 , and Y-stage  510  is mounted on an X-stage  500  which is moved by X-stage motor  501 . In this diagram, the Y-direction is into the page. This combination comprises an X-Y-Z-tilt stage that is computer controlled when in operation. 
         [0031]    Having described preferred embodiments of a new apparatus and method for changing slide trays in a Microscope Slide Scanner for imaging microscopic and macroscopic specimens, constructed in accordance with the present invention, it is believed that other modifications, variations, and changes will be suggested to those skilled in the art in view of the teachings set forth herein. It is therefore to be understood that all such variations, modifications, and changes are believed to fall within the scope of the present invention as defined by the appended claims.