Automated high volume slide processing system

• US 8,663,991 B2
• Filed: 07/13/2005
• Issued: 03/04/2014
• Est. Priority Date: 04/15/2002
• Status: Active Grant

• Current Assignee: Ventana Medical Systems Incorporated (Roche Holding AG)
• Original Assignee: Ventana Medical Systems Incorporated (Roche Holding AG)
• Inventors: Reinhardt, Kurt, Lemme, Charles D., Ward, Glen, Richards, William L., Showalter, Wayne, Ambler, Brandon, Ashby, Austin, Borchert, Chris, Campbell, Devon C., Christensen, Kimberly, Freeman, Matthew, Ghusson, Andrew, Griebel, Rick, Hendrick, Kendall B., Holubec, Miroslav, Mehta, Parula, Rizzo, Vince
• Primary Examiner(s): Gordon, Brian R
• Application Number:
  US11/181,625
• Publication Number:
  US 20050250211A1
• Time in Patent Office: 3,156 Days
• Field of Search: 422/100, 422 63- 67, 422/68.1, 422/501, 422/536, 436/180, 436/43, 436/46, 436/174
• US Class Current: 436/46
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• 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 1/312 for samples mounted on planar substrates
• CPC Class Codes: G01N 1/36 Embedding or analogous mounting of samples
• CPC Class Codes: G01N 2035/00039 Transport arrangements specific to flat sample substrates, e.g. pusher blade
• CPC Class Codes: G01N 2035/00138 Slides
• CPC Class Codes: G01N 35/00029 provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: G01N 35/00732 Identification of carriers, materials or components in automatic analysers
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

An automated system is provided for performing slide processing operations on slides bearing biological samples. In one embodiment, the disclosed system includes a slide tray holding a plurality of slides in a substantially horizontal position and a workstation that receives the slide tray. In a particular embodiment, a workstation delivers a reagent to slide surfaces without substantial transfer of reagent (and reagent borne contaminants such as dislodged cells) from one slide to another. A method for automated processing of slides also is provided.

Claims

1. An automated method for processing a plurality of slides bearing biological tissue samples, comprising:

performing a set of slide processing operations on the plurality of slides in one or more workstations while the slides in the plurality are held in spatially co-planar, substantially horizontal positions in a slide tray, wherein the set of slide processing operations includes at least

staining samples on the slides in the spatially co-planar, substantially horizontal positions by flowing one or more stains from at least one reagent container, through a fluidics module, and out at least one dispense nozzle positioned above the slide tray, and

solvent-exchanging;

transporting the slide tray holding the plurality of slides to an automated coverslipper workstation after performing the set of slide processing operations that include at least staining and solvent-exchange;

coverslipping the plurality of slides held in the slide tray with separate respective coverslips using the automated coverslipper workstation while the plurality of slides are held in spatially co-planar, substantially horizontal positions in the slide tray such that the coverslips on the slides are spaced apart from one another; and

removing the slide tray holding the coverslipped slides from the automated coverslipper workstation.

2. The method of claim 1, wherein the set of slide processing operations further includes heating the plurality of slides sufficiently to adhere the biological samples to the slides.

3. The method of claim 2, wherein the set of slide processing operations further includes de-paraffinizing.

4. The method of claim 1, wherein two or more slide processing operations in the set of slide processing operations are performed in the same workstation.

5. The method of claim 1, further comprising transporting the slide tray to a drying oven to cure coverslips in place on the slides.

6. The method of claim 1, wherein the set of slide processing operations further includes de-paraffinizing and both de-paraffinizing and staining are performed in the same workstation.

7. The method of claim 1, wherein the set of slide processing operations further includes de-paraffinizing and de-paraffinizing, staining and solvent-exchanging are performed in the same workstation.

8. The method of claim 2, wherein heating comprises baking the slides with a radiant heater.

9. The method of claim 2, wherein the set of slide processing operations further includes de-paraffinizing and heating further comprises melting paraffin in the biological samples before de-paraffinizing.

10. The method of claim 3, wherein de-paraffinizing comprises treating the slides with an aqueous detergent solution.

11. The method of claim 3, wherein de-paraffinizing comprises treating the slides with an organic solvent.

12. The method of claim 11, wherein the organic solvent comprises limonene.

13. The method of claim 1, wherein staining comprises treating the slides with a hematoxylin solution and an eosin solution.

14. The method of claim 1, wherein staining comprises treating the slides with a hematoxylin solution, an Orange-G solution and an Eosin-azure solution.

15. The method of claim 14, wherein staining further comprises dehydrating the samples on the slides between treating the slides with the hematoylin solution and treating the slides with the Orange-G and Eosin-azure solutions.

16. The method of claim 1, wherein solvent exchanging comprises treating the samples with a series of two or more different solvents or solvent mixtures.

17. The method of claim 16, wherein the series of two or more different solvents or solvent mixtures comprises limonene, a limonene/alcohol mixture, alcohol and alcohol/water mixture and water.

18. The method of claim 1, wherein a plurality of slide trays holding slides are simultaneously processed.

19. The method of claim 18 further comprising prioritizing any given slide tray, thereby completing all operations on that slide tray first.

20. The method of claim 18, wherein slide tray status is communicated to a laboratory information system.

21. The method of claim 1, wherein the biological samples comprise cytological samples.

22. The method of claim 1, wherein said biological samples comprise tissue sections.

23. The method of claim 1, wherein each individual slide in the plurality is treated separately with fresh reagent during a slide processing operation that employs a reagent.

24. The method of claim 1, wherein a substantial amount of a reagent that contacts a first slide does not contact a second slide, thereby minimizing cross contamination between slides processed by the apparatus.

25. The method of claim 1, wherein the set of slide processing operations is performed in two or more workstations and further comprising transporting the slide tray between the two or more workstations.

26. The method of claim 1, further comprising:

moving a coverlipping head carrying a first one of the coverslips over a first one of the slides held in the slide tray;

placing the first one of the coverslips on the first one of the slides;

after placing the first one of the coverslips on the first one of the slides, moving the coverslipping head carrying a second one of the coverslips over a second one of the slides held in the slide tray; and

placing the second one of the coverslips on the second one of the slides held in the slide tray.

27. The method of claim 1, wherein coverslipping the plurality of slides includes applying the respective coverslips to the slides using a coverslipping head that is movable through the automated coverslipper workstation and adapted to carry and release the coverslips onto the slides.

28. The method of claim 1, wherein the at least one reagent container includes a plurality of reagent containers, and wherein staining the samples includes mixing reagents from two of the reagent containers using the fluidics module and delivering the mixture out of the dispense nozzles and onto the samples.

29. The method of claim 1, wherein staining the samples includes individually delivering the one or more stains onto the samples.

30. The method of claim 1, further comprising replacing a first reagent container of the at least one reagent container with a second reagent container while staining the samples on the slides.

31. The method of claim 30, wherein replacing the first reagent container includes fluidically disconnecting the first reagent container from the fluidics module and fluidically connecting the second reagent container to the fluidics module.

32. The method of claim 1, wherein staining the samples on the slides comprises simultaneously applying reagents to samples on two of the slides.

33. The method of claim 1, wherein staining the samples on the slides includes individually delivering a series of stains onto the samples while the at least one dispense nozzle is kept positioned generally above the slide tray.

34. An automated method for processing a plurality of slides bearing biological tissue samples, wherein the slides are held in spatially co-planar, substantially horizontal positions in a slide tray, comprising:

de-paraffinizing, staining and solvent exchanging the samples on the slides in the slide tray in a single modular workstation, wherein staining the samples includes flowing one or more stains out of at least one reagent container, through a fluidics module, and out at least one dispense nozzle positioned above the slide tray;

transporting the slide tray to an automated coverslipper; and

applying separate glass coverslips over the samples on the slides in the automated coverslipper, wherein the slides are held in spatially co-planar, substantially horizontal positions in the slide tray as the glass coverslips are applied such that the glass coverslips on the slides are spaced apart from one another.

35. The method of claim 34, wherein a substantial amount of a reagent that contacts a first slide held in the slide tray does not contact a second slide held in the slide tray, thereby minimizing cross contamination between slides.

36. An automated method for processing a plurality of slides bearing biological tissue samples, wherein the slides are held in spatially co-planar, substantially horizontal positions in a slide tray during processing, comprising:

(i) baking the samples under a radiant heater;

(ii) de-paraffinizing the samples;

(iii) staining the samples by delivering one or more stains through one or more fluidic components and out one or more nozzles positioned generally above the slide tray, wherein the one or more fluidic components fluidically connect at least one reagent container holding the one or more stains to the one or more nozzles;

(iv) solvent-exchanging the samples; and

(v) coverslipping the samples with separate coverslips, wherein the aforementioned steps are automatically performed by an apparatus comprising two or more workstations between which the slide tray holding the slides is moved during processing.

37. The method of claim 36, wherein steps (ii) and (iii) are performed in a single workstation.

38. The method of claim 36, wherein steps (ii)-(iv) are performed in a single workstation.

39. An automated method for processing a plurality of slides bearing biological samples, comprising:

performing a set of slide processing operations on the plurality of slides in one or more workstations while the slides in the plurality are held in substantially horizontal positions in a slide tray, wherein the set of slide processing operations includes at least staining and solvent-exchanging, wherein staining comprises treating the slides with a hematoxylin solution and an eosin solution by flowing the hematoxylin solution and the eosin solution from one or more reagent containers to at least one dispense nozzle via a fluidics module;

transporting the slide tray holding the plurality of slides to an automated coverslipper workstation; and

,

coverslipping the plurality of slides held in the slide tray with respective coverslips using the automated coverslipper workstation while the plurality of slides are held in the substantially horizontal positions by the slide tray such that the coverslips on the slides are spaced apart from one another.

40. The method of claim 39, wherein the biological samples are tissue samples and wherein said tissue samples comprise cytological samples or tissue sections.

41. The method of claim 39, wherein said solvent exchanging comprises treating the samples with the organic solvent limonene.

42. The method of claim 39, wherein a substantial amount of a reagent that contacts a first slide does not contact a second slide, thereby minimizing cross contamination between slides processed by the apparatus.

43. The method of claim 39, wherein the set of slide processing operations further comprises heating the plurality of slides sufficiently to adhere the biological samples to the slides, wherein heating comprises baking the slides with a radiant heater.

44. The method of claim 39, wherein the set of slide processing operations further comprises de-paraffinizing, and de-paraffinizing, staining and solvent-exchanging are performed in the same workstation.

45. An automated method for processing a plurality of slides bearing biological samples, comprising:

performing a set of slide processing operations on the plurality of slides in one or more workstations while the slides in the plurality are held in substantially horizontal positions in a slide tray, wherein the set of slide processing operations includes at least staining and solvent-exchanging, wherein staining comprises treating the slides with a hematoxylin solution, an Orange-G solution and an Eosin-azure solution by delivering the hematoxylin solution, the Orange-G solution and the Eosin-azure solution through a fluidics module which controls delivery of the hematoxylin solution, the Orange-G solution and the Eosin-azure solution to one or more dispense nozzles positioned above the slide tray;

transporting the slide tray holding the plurality of slides to an automated coverslipper workstation; and

,

coverslipping the plurality of slides held in the slide tray with separate respective coverslips using the automated coverslipper workstation while the plurality of slides are held in substantially horizontal positions by the slide tray such that the coverslips on the slides are spaced apart from one another.

46. The method of claim 45, wherein the biological samples are cell samples and wherein said cell samples comprise cytological samples or tissue sections.

47. The method of claim 45, wherein said solvent-exchanging comprises treating the samples with the organic solvent limonene.

48. The method of claim 45, wherein a substantial amount of a reagent that contacts a first slide does not contact a second slide, thereby minimizing cross contamination between slides processed by the apparatus.

49. The method of claim 45, wherein the set of slide processing operations further comprises heating the plurality of slides sufficiently to adhere the biological samples to the slides, wherein heating comprises baking the slides with a radiant heater.

50. The method of claim 45, wherein the set of slide processing operations further comprises de-paraffinizing, and de-paraffinizing, staining and solvent-exchanging are performed in the same workstation.

51. An automated method for processing a plurality of slides bearing biological samples, comprising:

performing a set of slide processing operations on the plurality of slides in one or more workstations while the slides in the plurality are held in substantially horizontal positions in a slide tray, wherein the set of slide processing operations includes at least

staining samples on the slides by flowing one or more stains from at least one reagent container, through a fluidics module, and out at least one dispense nozzle, and

solvent-exchanging;

transporting the slide tray holding the plurality of slides to an automated coverslipper workstation;

coverslipping the plurality of slides held in the slide tray with separate respective coverslips using the automated coverslipper workstation while the plurality of slides are held in the substantially horizontal positions by the slide tray such that the coverslips on the slides are spaced apart from one another; and

,

processing simultaneously the plurality of slide trays holding slides wherein said processing comprises prioritizing any given slide tray and wherein all operations on a prioritized slide tray are completed first.

52. The method of claim 51, wherein the biological samples are cell samples and wherein said cell samples comprise cytological samples or tissue sections.

53. The method of claim 51, wherein said solvent-exchanging comprises treating the samples with the organic solvent limonene.

54. The method of claim 51, wherein a substantial amount of a reagent that contacts a first slide does not contact a second slide, thereby minimizing cross contamination between slides processed by the apparatus.

55. The method of claim 51, wherein the set of slide processing operations further comprises heating the plurality of slides sufficiently to adhere the biological samples to the slides, wherein heating comprises baking the slides with a radiant heater.

56. The method of claim 51, wherein the set of slide processing operations further comprises de-paraffinizing, and de-paraffinizing, staining and solvent-exchanging are performed in the same workstation.

57. The method of claim 51, wherein the at least one reagent container includes a plurality of reagent containers, wherein staining the samples on the slides includes mixing reagents from two of the reagent containers and delivering the mixture onto the samples.

58. An automated method for processing a plurality of slides bearing biological tissue samples, comprising:

positioning a slide tray carrying a plurality of slides in a staining workstation, wherein the slide tray holds the slides in spatially co-planar, substantially horizontal positions, wherein a fluidics module fluidically connects a plurality of reagent containers to the staining workstation;

sequentially staining samples on the slides held in the spatially co-planar, substantially horizontal positions by flowing one or more stains out of one or more of the reagent containers, through the fluidics module, and out at least one dispense nozzle of the staining workstation positioned generally above the slide tray;

transporting the slide tray holding the slides to an automated coverslipper workstation after performing the staining; and

coverslipping the plurality of slides held in the slide tray with separate respective coverslips using the automated coverslipper workstation.