Method and apparatus for automatic staining of tissue samples

• US 8,257,968 B2
• Filed: 12/19/2003
• Issued: 09/04/2012
• Est. Priority Date: 12/20/2002
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Dako Denmark A/S (Agilent Technologies, Inc.)
• Inventors: Sweet, Doug, Key, Marc, Feingold, Gordon, Buchanan, Kristopher S., Lathrop, Bob, Favuzzi, John
• Primary Examiner(s): Beisner, William H
• Assistant Examiner(s): HENKEL, DANIELLE B
• Application Number:
  US10/538,964
• Publication Number:
  US 20060088928A1
• Time in Patent Office: 3,182 Days
• Field of Search: 435/288.7, 435/287.3, 435/286.4, 422/60, 422/63, 422/64, 422/65
• US Class Current: 435/288.7
• CPC Class Codes: G01N 1/30 Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
• CPC Class Codes: G01N 1/31 Apparatus therefor
• CPC Class Codes: G01N 1/312 for samples mounted on planar substrates
• CPC Class Codes: G01N 2035/00039 Transport arrangements specific to flat sample substrates, e.g. pusher blade
• CPC Class Codes: G01N 2035/00089 Magazines
• CPC Class Codes: G01N 2035/00306 Housings, cabinets, control panels (details)
• CPC Class Codes: G01N 2035/00326 Analysers with modular structure
• CPC Class Codes: G01N 2035/00366 Several different temperatures used
• CPC Class Codes: G01N 2035/00376 Conductive heating, e.g. heated plates
• CPC Class Codes: G01N 2035/00435 Refrigerated reagent storage
• CPC Class Codes: G01N 2035/00881 network configurations
• CPC Class Codes: G01N 2035/00891 Displaying information to the operator
• CPC Class Codes: G01N 2035/009 alarms, e.g. audible
• CPC Class Codes: G01N 2035/0091 GUI [graphical user interfaces]
• CPC Class Codes: G01N 35/00712 Automatic status testing, e.g. at start-up or periodic
• CPC Class Codes: G01N 35/00732 Identification of carriers, materials or components in automatic analysers
• CPC Class Codes: G01N 35/00871 Communications between instruments or with remote terminals
• CPC Class Codes: G01N 35/0092 Scheduling
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10S 901/02 : Arm motion controller
• CPC Class Codes: Y10S 901/41 : Tool
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/112499 : with sample on test slide
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/114165 : with step of insertion or removal from test line
• CPC Class Codes: Y10T 436/114998 : with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention concerns an apparatus (1) for staining tissue samples, said apparatus (1) including a reagent section (2) or reagent containers (3); at least one staining section or tissue samples, a robotic head (22) or robotic element (20) that may move reagent to a predetermined tissue sample, said robotic element (20) being moveable above the reagent and the staining sections, a control element (85) that may manage a staining process, a 2-D optical sensor (86) to detect two-dimensional image data of a relevant property and that can feed the captured image data to the control element (86). By providing the robotic element (20) with a 2-D optical sensor (86), a common image processor may be provided having multiple functions. By using a 2-D optical image processing system, the control system of the apparatus may easily be adapted to read various types of data presentations, just as actual images for sections of the apparatus may be identified in order to assess the condition of the apparatus. The optical sensor may be used to automatically identify the slides and the reagent containers present in the apparatus, just as the optical sensor may be used for checking if a slide is misplaced at or absent from a slide position, etc.

Claims

1. An automatic staining apparatus comprising:

at least one removable reagent container positioned on a reagent rack within a reagent section;

at least one slide positioned within a slide section;

wherein a robotic element is configured to move above the reagent section and above the slide section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the reagent section is situated to enable the at least one removable reagent container to be added to or removed from the apparatus without interrupting the movement of the robotic element during dispensing of at least one reagent during the staining process;

wherein the robotic element comprises an optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process; and

a control element to which the robotic element is responsive, the control element configured to

monitor insertion or removal of the at least one removable reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.

2. An apparatus according to claim 1, wherein the optical sensor is adapted to locate pre-selected reference features for self-calibration of the robotic element.

3. An apparatus according to claim 1, wherein a sample is placed on the at least one slide, and

wherein the optical sensor is adapted to record an image of the finalized sample after said sample has been subjected to the staining process.

4. An apparatus according to claim 3, further comprising:

at least one element provided on the at least one removable reagent container and the at least one slide;

wherein at least one element comprises an element selected from a group consisting of;

a two-dimensional high-resolution symbology code, a datamatrix code, a bar code, an adhesive label, a two dimensional symbology zone, and a human readable text zone.

5. An apparatus according to claim 3, wherein the optical sensor is configured to identify a feature selected from a group consisting of:

the texture of the sample, the outline of the sample, a visual property of the sample, and an individual identification feature of the sample.

6. A method of identifying at least one property in an automatic staining apparatus comprising the steps of:

providing at least one sample on a slide positioned within a slide section;

providing at least one reagent container positioned on a reagent rack within a reagent section;

wherein a robotic element is configured to move above the slide section and above the reagent section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the at least one reagent container is added to or removed from the apparatus without interrupting dispensing of at least one reagent during the staining process;

providing the robotic element with an optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process;

recording relevant image data;

recording calibration reference points of the apparatus; and

feeding said image data to a control element to which said robotic element is responsive, the control element configured to monitor insertion or removal of the at least one reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.

7. A method of staining samples in an automatic staining apparatus comprising the steps of:

providing at least one sample on a slide, the slide being positioned in a slide section within slide racks;

providing at least one reagent container positioned on a reagent rack within a reagent section;

wherein a robotic element is configured to move above the slide section and above the reagent section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the at least one reagent container is added to or removed from the apparatus without interrupting dispensing of at least one reagent during the staining process;

providing the robotic element with an optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process;

recording relevant image data;

recording calibration reference positions for said slide racks; and

feeding said image data to a control element to which said robotic element is responsive, the control element configured to monitor insertion or removal of the at least one reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.

8. An automatic staining apparatus comprising:

at least one reagent container positioned on a reagent rack within a reagent section;

at least one sample on a slide, the slide being positioned within a slide section;

wherein a robotic element is configured to move above the reagent section and above the slide section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the reagent section is situated to enable the at least one reagent container to be added to or removed from the apparatus without interrupting the movement of the robotic element during dispensing of at least one reagent during the staining process;

wherein the robotic element comprises an optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process and locate pre-selected reference features for self-calibration of the robotic element; and

a control element to which the robotic element is responsive, the control element configured to monitor insertion or removal of the at least one reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.

9. An automatic staining apparatus comprising:

at least one reagent container on a reagent rack in a reagent section;

at least one first sample contained on a slide in a first slide section;

at least one second sample contained on a slide in a second slide section, wherein said first slide section and said second slide section are separated by said reagent section;

wherein a robotic element is configured to move above the reagent section and above the first and second slide sections during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the reagent section is situated to enable the at least one reagent container to be added to or removed from the apparatus without interrupting the movement of the robotic element during dispensing of at least one reagent during the staining process; and

a control element to which said robotic element is responsive, the control element configured to monitor insertion or removal of the at least one reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.

10. An automatic staining apparatus comprising:

at least one reagent container positioned on a reagent rack within a reagent section;

at least one sample placed on a slide, the slide being positioned within a slide section;

wherein a robotic element is configured to move above the reagent section and above the slide section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the reagent section is situated to enable the at least one reagent container to be added to or removed from the apparatus without interrupting the movement of the robotic element during dispensing of at least one reagent during the staining process;

wherein the robotic element comprises an optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process and image at least one optical identification element; and

a control element to which the robotic element is responsive, the control element configured to monitor insertion or removal of the at least one reagent container during the-staining process using the optical identification element and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.

11. An apparatus according to claim 10 wherein the optical identification element has reiterated information, said reiterated information comprises multiple reiterated information.

12. An apparatus according to claim 11 wherein said reiterated information comprises redundant information.

13. An apparatus according to claim 11 wherein said optical identification element comprises a two-dimensional high-resolution symbology code.

14. An apparatus according to claim 11 wherein said optical identification element comprises a datamatrix code.

15. An apparatus according to claim 11 wherein said optical identification element comprises a bar code.

16. An automatic staining apparatus comprising:

at least one reagent container positioned on a reagent rack within a reagent section;

at least one sample on a slide, the slide being positioned within a slide section;

wherein a robotic element is configured to move above the reagent section and above the slide section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the reagent section is situated to enable the at least one reagent container to be added to or removed from the apparatus without interrupting the movement of the robotic element during dispensing of at least one reagent during the staining process;

wherein the robotic element comprises an optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process;

a computer image biological analysis element; and

a control element to which the robotic element is responsive, the control element configured to monitor insertion or removal of the at least one reagent container during the staining process,

wherein the optical sensor records a first image of the at least one sample before staining and records a second image of the sample after staining and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.

17. An apparatus according to claim 16 wherein said optical sensor comprises a camera.

18. An apparatus according to claim 17, wherein said camera comprises a CCD element.

19. A method of identifying at least one property in an automatic staining apparatus comprising the steps of:

providing at least one sample, the sample being placed on a slide in a removable slide rack, the slide rack being positioned within a slide section;

providing at least one reagent container positioned on a reagent rack within a reagent section;

wherein a robotic element is configured to move above the reagent section and above the slide section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the at least one reagent container is added to or removed from the apparatus without interrupting dispensing of at least one reagent during the staining process;

providing the robotic element with an optical sensor configured to automatically identify new slides and regent bottles loaded into the apparatus during the staining process;

recording relevant image data;

feeding said image data to a control element to which said robotic element is responsive, the control element configured to monitor insertion or removal of the at least one reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container; and

biologically analysing image data of said at least one sample with a computer.

20. A method according to claim 19, wherein said optical sensor comprises a camera.

21. A method according to claim 20, wherein said camera comprises a CCD element.

22. A method of staining tissue samples in an automatic staining apparatus comprising the steps of:

providing at least one removable sample on at least one slide positioned within a slide section;

providing at least one reagent container positioned on a reagent rack within a reagent section;

wherein a robotic element is configured to move above the reagent section and above the slide section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the at least one reagent container is be added to or removed from the apparatus without interrupting dispensing of at least one reagent during the staining process;

providing the robotic element with an optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process;

recording relevant image data;

feeding said image data to a control element to which said robotic element is responsive, the control element configured to monitor insertion or removal of the at least one reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container; and

biologically analysing image data of said at least one sample with a computer.

23. A method according to claim 22, wherein said optical sensor comprises a camera.

24. A method according to claim 22, wherein said optical sensor comprises a CCD element.

25. A method according to claim 22, further comprising a step of storing an image relevant to the staining process.

26. An automatic staining apparatus comprising:

at least one reagent container positioned on a reagent rack within a reagent section;

at least one sample, the sample being placed on a slide positioned within a slide section;

wherein a robotic element is configured to move above the reagent section and above the slide section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the reagent section is situated to enable the at least one reagent container to be added to or removed from the apparatus without interrupting the movement of the robotic element during dispensing of at least one reagent during the staining process;

wherein the robotic element comprises a multifunction optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process;

a computer image biological analysis element; and

a control element to which the robotic element is responsive, the control element configured to monitor insertion or removal of the at least one reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.

27. An apparatus according to claim 26, wherein said optical sensor comprises a camera.

28. An apparatus according to claim 26, wherein said optical sensor comprises a CCD element.

29. An apparatus according to claim 26, further comprising a stored image relevant to the staining process.

30. An automatic staining apparatus comprising:

at least one removable reagent container positioned on a reagent rack within a reagent section;

at least two staining sections separated by the reagent section;

at least one sample placed on a slide in a slide rack, the slide rack being positioned within the staining sections;

wherein a robotic element is configured to move above the reagent section and above the staining sections during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the reagent section is situated to enable the at least one reagent container to be added to or removed from the apparatus without interrupting the movement of the robotic element during dispensing of at least one reagent during the staining process;

wherein the robotic element comprises an optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process; and

a control element to which the robotic element is responsive, the control element configured to monitor insertion or removal of the at least one removable reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.

31. A method of staining tissue samples in an automatic staining apparatus comprising the steps of:

providing at least one slide positioned within a slide section;

providing at least one removable reagent container positioned on a reagent rack within a reagent section;

wherein a robotic element is configured to move above the reagent section and above the slide section during a staining process and wherein the reagent rack is removable below the plane of the robotic element;

wherein the at least one reagent container is be added to or removed from the apparatus without interrupting dispensing of at least one reagent during the staining process;

providing the robotic element with an optical sensor configured to automatically identify new slides and reagent bottles loaded into the apparatus during the staining process;

recording relevant image data; and

feeding said image data to a control element to which said robotic element is responsive, the control element configured to monitor insertion or removal of the at least one removable reagent container during the staining process and to continue movement of the robotic element and dispensing of at least one reagent during insertion or removal of the at least one removable reagent container.