Automated high volume slide processing system

• US 9,528,918 B2
• Filed: 11/15/2013
• Issued: 12/27/2016
• Est. Priority Date: 04/15/2002
• Status: Expired due to Term

• 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 Micheil, 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:
  US14/082,092
• Publication Number:
  US 20140178858A1
• Time in Patent Office: 1,138 Days
• Field of Search: None
• US Class Current: 1/1
• 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, the method comprising:

robotically transporting a slide carrier to a stainer workstation while the slide carrier carries the plurality of slides;

staining biological samples carried by the slides by separately dispensing reagent onto individual slides of the plurality of slides via a dispense manifold, which is fluidically coupled to a first container and a second container, after robotically transporting the slide carrier to the stainer workstation, wherein separately dispensing the reagent onto the individual slides includes;

pumping a first staining solution out of the first container, through at least one line, and out the dispense manifold such that a first volume of the first staining solution is delivered onto a first one of the plurality of slides to stain a first biological sample of the biological samples,

clearing the first staining solution from the at least one line, and

pumping a second staining solution out of the second container, through the at least one line, and out the dispense manifold such that a second volume of the second staining solution is delivered onto a second one of the plurality of slides to stain a second biological sample of the biological samples; and

after staining the biological samples, robotically removing the slide carrier from the stainer workstation while the slide carrier carries the plurality of slides.

2. The method of claim 1, wherein the plurality of slides includes a first slide and a second slide, wherein the first biological sample is positioned on the first slide and the second biological sample is positioned on the second slide, and wherein staining the biological samples comprises:

performing a first set of slide processing operations on the first slide, the first set of slide processing operations includes at least

depositing the first volume of the first staining solution onto an upper surface of the first slide,

maintaining contact between the first staining solution deposited onto the upper surface of the first slide and the first biological sample for a predetermined first period of time, and

performing a second set of slide processing operations on the second slide, the second set of slide processing operations includes at least

depositing the second volume of the second staining solution onto an upper surface of the second slide, and

maintaining contact between the second staining solution deposited onto the upper surface of the second slide and the second biological sample for a predetermined second period of time.

3. The method of claim 1, wherein staining the biological samples carried by the slides includes delivering reagent towards one of the slides without contacting any other slides of the plurality of slides with the delivered reagent.

4. The method of claim 1, further comprising:

flowing the first staining solution from the first container, into the dispense manifold, and out one or more nozzles of the dispense manifold.

5. The method of claim 1, wherein separately dispensing the reagent includes sequentially delivering streams of the reagent toward upper surfaces of the slides.

6. The method of claim 1, wherein separately dispensing the reagent includes:

(a) positioning a dispense manifold relative to a slide of the plurality of slides;

(b) delivering the reagent from the dispense manifold to the slide of the plurality of slides; and

(c) repeating (a) and (b) to deliver reagent onto all the slides.

7. The method of claim 1, wherein separately dispensing the reagent includes separately dispensing hematoxylin and/or eosin to each of the slides.

8. The method of claim 1, wherein staining the biological samples includes:

removing dispensed reagent from at least one slide of the plurality of slides; and

dispensing another reagent onto the at least one slide.

9. The method of claim 8, wherein removing dispensed reagent includes delivering fluid toward the at least one slide such that the fluid causes removal of the dispensed reagent.

10. The method of claim 9, wherein the fluid is air, reagent, and/or wash solution.

11. The method of claim 1, wherein staining the biological samples includes removing reagent that has been dispensed onto at least one slide of the plurality of slides by directing air and/or reagent toward the at least one slide.

12. The method of claim 11, wherein directing air and/or reagent toward the first slide includes delivering air and/or reagent out of nozzles positioned above the slide carrier.

13. The method of claim 1, wherein robotically transporting the slide carrier to the stainer workstation includes moving the slide carrier into a chamber of the stainer workstation using a transporter mechanism.

14. The method of claim 1, wherein the slide carrier is a slide tray that holds the slides at substantially horizontal orientations.

15. The method of claim 1, wherein after robotically removing the slide carrier from the stainer workstation, the method further comprises:

transporting the slide carrier to an automated coverslipper workstation while the slide carrier carries the plurality of slides; and

coverslipping each individual slide of the plurality of slides with a respective coverslip using the automated coverslipper workstation while the individual slides are held in spatially co-planar, substantially horizontal positions in the slide carrier such that the coverslips on the slides are spaced apart from one another.

16. The method of claim 1, further comprising pumping reagents that have been dispensed by the stainer workstation out of the stainer workstation.

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

transporting a slide carrier to a stainer workstation using a transporter mechanism while the slide carrier holds the plurality of slides in a spaced apart horizontal arrangement;

after transporting the slide carrier to the stainer workstation, separately delivering reagent onto each individual slide of the plurality of slides held by the slide carrier such that a substantial amount of the reagent applied to one slide of the plurality of slides does not contact any other slides of the plurality of slides, wherein separately delivering the reagent onto each individual slide includes

pumping staining solutions from containers located outside of the stainer workstation into the stainer workstation, through a movable dispense manifold within the stainer workstation, and out of the movable dispense manifold; and

after separately delivering the reagent onto the individual slides, removing the slide carrier from the stainer workstation.

18. The method of claim 17, wherein separately delivering the reagent onto the slides includes directing reagent streams of reagent toward respective slides.

19. The method of claim 18, wherein

the plurality of slides includes a first slide and a second slide, and

directing reagent streams of reagent toward the respective slides includes:

directing a first reagent stream toward the first slide; and

directing a second reagent stream toward the second slide.

20. The method of claim 17, wherein separately delivering the reagent onto the slides includes flowing the staining solutions from at least one of the containers, through a fluidics module, and out at least one dispense nozzle positioned above the slide carrier.

21. The method of claim 17, further comprising:

performing a first stain protocol on a first slide of the plurality of slides; and

performing a second stain protocol on a second slide of the plurality of slides, wherein the first stain protocol is different from the second stain protocol.

22. The method of claim 17, wherein separately delivering the reagent includes delivering hematoxylin and/or eosin onto two or more of the slides.

23. The method of claim 17, wherein the slide carrier is a slide tray that holds the slides at substantially horizontal orientations.

24. The method of claim 17, further comprising:

after delivering the reagent onto a first slide of the plurality of slides, removing the reagent from the first slide, and

after removing the reagent from the first slide, dispensing another reagent onto the first slide.

25. The method of claim 17, wherein separately delivering the reagent onto the individual slides includes delivering a first reagent onto a first slide of the plurality of slides, and the method further comprises:

removing at least a portion of the first reagent from the first slide; and

delivering a second reagent onto the first slide.

26. The method of claim 25, wherein delivering the second reagent onto the first slide includes dispensing hematoxylin and/or eosin onto the first slide.

27. The method of claim 17, wherein separately delivering the reagent onto the individual slides includes delivering a first reagent onto a first slide of the plurality of slides, and the method further comprises:

after delivering the first reagent onto the first slide, delivering a second reagent onto the first slide.

28. The method of claim 27, further comprising removing at least a portion of the first reagent prior to delivering the second reagent.

29. The method of claim 17, wherein the dispense manifold is fluidically coupled to a first container located outside of the stainer workstation and the dispense manifold is fluidically coupled to a second container located outside of the stainer workstation, and wherein the method further comprises:

pumping a first stain solution out of the first container, through at least one fluid line of a fluidics module, and through the dispense manifold such that the stainer workstation dispenses the first stain solution onto a first one of the plurality of slides; and

pumping a second stain solution out of the second container, through the fluidics module, and through the dispense manifold such that the dispense manifold dispenses the second stain solution onto a second one of the plurality of slides.

30. The method of claim 17, further comprising

pumping reagents, which have been dispensed by the stainer workstation, away from the slide carrier positioned within the stainer workstation;

and

delivering the reagents out of the stainer workstation.

31. The method of claim 17, wherein the plurality of slides includes a first slide and a second slide, wherein a first biological sample is positioned on the first slide and a second biological sample is positioned on the second slide, and wherein the method further comprises:

dispensing reagent out of an array of spaced apart dispense nozzles of the dispense manifold to deliver the reagent toward different locations along the first slide; and

dispensing reagent out of the array of spaced apart dispense nozzles of the dispense manifold to deliver the reagent toward different locations along the second slide.

32. An automated method for processing a plurality of slides, the method comprising:

robotically transporting a slide carrier into a stainer workstation while the slide carrier carries the plurality of slides;

separately dispensing staining solutions onto individual slides of the plurality of slides by pumping staining solutions from containers located outside of the stainer workstation into the stainer workstation, through a movable dispense manifold within the stainer workstation, and out of the movable dispense manifold;

delivering staining solution, which has been dispensed by the movable dispense manifold, out of the stainer workstation; and

robotically removing the slide carrier from the stainer workstation.

33. The method of claim 32, further comprising:

combining the staining solutions from the containers using a mixing manifold in fluid communication with the containers to produce the staining solutions that are delivered onto the individual slides, and

wherein the containers include

a first container containing hematoxylin solution,

a second container containing eosin solution, and

a third container containing a solvent.

34. The method of claim 32, wherein the containers include a first container and a second container, the method further comprising:

pumping a first staining solution out of the first container, through at least one line, and out the dispense manifold such that the first staining solution is delivered onto a first one of the plurality of slides to stain a first biological sample;

clearing the first staining solution from the at least one line;

pumping a second staining solution out of the second container, through the at least one line, and out the dispense manifold such that the second staining solution is delivered onto a second one of the plurality of slides to stain a second biological sample; and

delivering the first staining solution and/or the second staining solution, which has been delivered out of the dispense manifold, out of the stainer workstation.

35. The method of claim 32, wherein the staining solutions include a hematoxylin solution and an eosin solution, and wherein all of the staining solutions dispensed onto the plurality of slides are pumped from the containers and through fluid lines in fluid communication with the dispense manifold.

36. The method of claim 32, wherein the staining solutions include hematoxylin solution and eosin solution, the method further comprising delivering the hematoxylin solution and the eosin solution onto each of the plurality of slides.