Automated high volume slide processing system

• US 20050186114A1
• Filed: 04/27/2005
• Published: 08/25/2005
• 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: Showalter, Wayne, Reinhardt, Kurt, Ghusson, Andrew, Ward, Glen, Christensen, Kimberly, Lemme, Charles D., Freeman, Matthew, Ashby, Austin, Campbell, Devon C., Holubec, Miroslav, Mehta, Parula, Hendrick, Kendall B., Ambler, Brandon, Rizzo, Vince, Griebel, Rick, Borchert, Chris, Richards, William L.
• Granted Patent: US 7,468,161 B2
• Time in Patent Office: Days
• US Class Current: 422/65
• 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 apparatus for automatically treating biological specimens, comprising:

at least one slide tray holding a plurality of slides in substantially horizontal positions, wherein said biological specimens are located on said slides;

one or more workstations that receive said slide tray and perform one or more slide processing operations on said plurality of slides held in said slide tray;

a transporter that moves said slide tray into and out of said one or more workstations;

a fluidics module in fluid communication with said one or more workstations that supplies a reagent to said one or more workstations;

a pneumatics module in fluid communication with said one or more workstations and said fluidics module that supplies vacuum and/or pressurized gas to said one or more workstations and said fluidics module; and

a control module in electrical communication with said transporter, said one or more workstations, said fluidics module and said pneumatics module, wherein said control module coordinates function of components of the apparatus during treatment of said biological specimens.

2. The apparatus of claim 1, wherein said slide tray holds said plurality of slides at an angle between about 0.2 degrees and about 1.2 degrees from horizontal.

3. The apparatus of claim 1, wherein said plurality of slides held in said slide tray are arranged in two rows.

4. The apparatus of claim 1, wherein said one or more workstations dispense said reagent to said slides without a substantial amount of said reagent that contacts a first slide coming into contact with a second slide, thereby minimizing cross-contamination between slides.

5. The apparatus of claim 1, wherein said one or more workstations are arranged in one or more vertical stacks.

6. The apparatus of claim 1, wherein said one or more workstations comprise a combined de-paraffinizer/stainer or a combined de-paraffinizer/stainer/solvent exchanger.

7. The apparatus of claim 1, wherein at least one of said workstations comprises a moveable nozzle assembly, wherein said nozzle assembly includes one or more nozzles through which said reagent is delivered to a slide.

8. The apparatus of claim 7, wherein said one or more nozzles comprise dispense nozzles.

9. The apparatus of claim 7, wherein said one or more nozzles comprise rinse nozzles.

10. The apparatus of claim 7, wherein said one or more nozzles direct a stream of reagent toward a surface of a slide at an angle of between about 20 degrees and about 50 degrees relative to the surface.

11. The apparatus of claim 9, wherein said one or more nozzles comprise backward top surface rinse nozzles.

12. The apparatus of claim 7, wherein said one or more nozzles comprise jet drain nozzles.

13. The apparatus of claim 9, wherein said one or more nozzles comprise bottom surface rinse nozzles.

14. The apparatus of claim 7, wherein said one or more nozzles comprise two or more dispense nozzles, two or more forward top surface rinse nozzles, two or more backward top surface rinse nozzles, two or more jet drain nozzles, and two or more bottom surface rinse nozzles.

15. The apparatus of claim 7, wherein said nozzle assembly further comprises one or more splash guards located to reduce the amount of reagent that is delivered to said slides by said nozzle assembly that splashes out of said slide tray.

16. The apparatus of claim 6, wherein said one or more workstations further comprise an automated coverslipper.

17. The automated slide processing apparatus of claim 16, wherein said coverslipper comprises a moveable coverslipping head, wherein said coverslipping head includes an air broom.

18. The automated slide processing apparatus of claim 16, wherein said coverslipper comprises a moveable coverslipping head, wherein said coverslipping head includes one or more moveable pins that hold a coverslip in position on said slides held in said slide tray while a hook holding said coverslip is removed.

19. The apparatus of claim 1, wherein said one or more workstations comprises a solvent exchanger.

20. The apparatus of claim 19, wherein said solvent exchanger comprises a moveable nozzle assembly, wherein said nozzle assembly includes one or more nozzles through which said reagent is delivered to said slides held in said slide tray.

21. The apparatus of claim 20, wherein said solvent exchanger further comprises an inline mixer for combining at least two reagents before said reagents are delivered to said slides held in said slide tray.

22. The apparatus of claim 20, wherein said moveable nozzle assembly further comprises a blow-off nozzle for removing reagents from said slides held in said slide tray.

23. The apparatus of claim 6, wherein said one or more workstations further comprise a drying oven.

24. The apparatus of claim 6, wherein said one or more workstations further comprise a radiant heater.

25. The apparatus of claim 24, wherein said radiant heater has a heat profile that provider greater heating around the edges of said slide tray than in the middle of said slide tray to provide substantially uniform heating of said slides held in said slide tray when said slide tray is positioned below said radiant heater.

26. The apparatus of claim 6, wherein said one or more workstations further comprise an automated coverslipper, a drying oven and a radiant heater.

27. The apparatus of claim 1, wherein said transporter comprises an X-Y-Z transport mechanism.

28. The apparatus of claim 27, wherein said X-Y-Z transport mechanism comprises an X-Y shuttle table mounted on an elevator.

29. The apparatus of claim 28, wherein said elevator comprises a counterweight for said shuttle table.

30. The apparatus of claim 29, wherein said counterweight is driven by a lead screw and a stepping motor.

31. The apparatus of claim 30, wherein said X-Y shuttle table and said counterweight are connected by a cable.

32. The apparatus of claim 31, wherein a first end of said cable suspends the counterweight substantially at its center of gravity and a second end of said cable suspends said shuttle table substantially at its center of gravity.

33. The apparatus of claim 28, wherein said X-Y shuttle table includes a means for releaseably engaging said slide tray.

34. The apparatus of claim 28 further comprising a sensor on said elevator for sensing a vertical position of said X-Y table relative to said one or more workstations.

35. The apparatus of claim 1, wherein said reagent supplied by said fluidics module is introduced into said apparatus in a package, wherein said package is keyed to help prevent misloading of said package into said apparatus.

36. The apparatus of claim 35, wherein said package is color keyed, mechanically keyed, optically keyed and/or electronically keyed.

37. The apparatus of claim 35, wherein said package comprises a code and said apparatus further comprises a code reader located proximal to an installation location for said package.

38. The apparatus of claim 37, wherein said code is selected from the group consisting of a barcode, a character, and an RFID tag, and combinations thereof.

39. The apparatus of claim 38, wherein said code comprises an RFID tag and said code reader comprises a RFID antennae.

40. The apparatus of claim 1 further comprising a cabinet enclosing said one or more workstations and a dehumidifier that lowers humidity within said cabinet.

41. The apparatus of claim 1, wherein said control module comprises a microprocessor and one or more microcontrollers, wherein said one or more microcontrollers receive instructions from said microprocessor and separately control one or more of said one or more workstations, said fluidics module and/or said transporter.

42. The apparatus of claim 1 further comprising a sensor for detecting the presence of individual slides held in said slide tray.

43. The apparatus of claim 1, wherein said slides are marked with a code and said apparatus further comprises a code reader.

44. The apparatus of claim 43, wherein said code comprises a barcode and said code reader comprises a barcode reader.

45. The apparatus of claim 1, wherein said code comprises a character and said code reader comprises an optical character reader.

46. The apparatus of claim 44, wherein said barcode comprises a multidimensional barcode.

47. The apparatus of claim 43, wherein said code comprises an RFID tag and said code reader comprises an RFID tag antennae.

48. The apparatus of claim 1, wherein said one or more workstations comprises a workstation having a moveable nozzle assembly, wherein the moveable nozzle assembly comprises one or more dispense nozzles, one or more forward top surface rinse nozzles, one or more rearward top surface rinse nozzles, one or more jet drain nozzles, one or more bottom surface rinse nozzles, and one or more blow-off nozzles;

wherein said dispense, rinse, jet drain and blow-off nozzles are in fluid communication with one or both of said fluidics module and said pneumatics module.

49. The apparatus of claim 48, wherein said workstation further comprises a tilt pan that receives said slide tray in substantially a single position.

50. The apparatus of claim 1 further comprising a cabinet enclosing said transporter, said one or more workstations, said fluidics module, said pneumatics module and said control module, said cabinet also enclosing said slide tray during treatment of said biological specimens.

51. The apparatus of claim 50 further comprising a powered exhaust for exhausting fumes from said cabinet.

52. The apparatus of claim 50 further comprising a portal formed in a wall of said cabinet through which said slide trays are introduced to and retrieved from said apparatus, said portal located proximal to said transporter.

53. An automated slide processing apparatus, comprising:

at least one slide tray holding a plurality of slides in substantially horizontal positions;

a plurality of workstations arranged in a vertical stack that receive said slide tray, the plurality of workstations comprising a combined de-paraffinizer/stainer, a solvent exchanger, a drying oven and an automated coverslipper;

a transporter proximal to said plurality of workstations that moves said slide tray into and out of said plurality of workstations, wherein said transporter comprises an X-Y-Z mechanism, wherein the X-Y-Z mechanism comprises an X-Y shuttle table that releaseably engages said slide tray and an elevator in an elevator space;

a garage proximal to said elevator space for storing said at least one slide tray;

a radiant heater located in said garage;

a fluidics module in fluid communication with said combined de-paraffinizer/stainer, and said solvent exchanger, that supplies reagents thereto;

a pneumatics module in fluid communication with said combined de-paraffinized/stainer, said solvent exchanger and said fluidics module that supplies vacuum and/or pressurized gas to said combined de-paraffinizer/stainer, said solvent exchanger and said fluidics module;

a control module in electrical communication with said transporter, said combined de-paraffinizer/stainer, said solvent exchanger, said fluidics module and said pneumatics module, wherein said control module coordinates function of the aforementioned components of the apparatus; and

a cabinet enclosing substantially all of the aforesaid elements during operation of said apparatus, said cabinet further including a dehumidifier for lowering humidity within said cabinet and a portal through which said at least one slide tray can be introduced to or removed from said apparatus.

54. The automated slide processing apparatus of claim 53, wherein said combined de-paraffinizer/stainer and said solvent exchanger is configured to deliver a reagent to slides in said slide tray without a substantial amount of said reagent that contacts a first slide contacting a second slide, thereby minimizing cross-contamination between slides.

56. The automated slide processing apparatus of claim 53, wherein said combined de-paraffinizer/stainer/solvent exchanger is configured to deliver a reagent to slides in said slide tray without a substantial amount of said reagent that contacts a first slide contacting a second slide, thereby minimizing cross-contamination between slides.

55. An automated slide processing apparatus, comprising:

at least one slide tray holding a plurality of slides in substantially horizontal positions;

a plurality of workstations arranged in a vertical stack that receive said slide tray, the plurality of workstations comprising a combined de-paraffinizer/stainer/solvent exchanger;

a drying oven and an automated coverslipper;

a transporter proximal to said plurality of workstations that moves said slide tray into and out of said plurality of workstations, wherein said transporter comprises an X-Y-Z mechanism, wherein the X-Y-Z mechanism comprises an X-Y shuttle table that releaseably engages said slide tray and an elevator in an elevator space;

a garage proximal to said elevator space for storing said at least one slide tray;

a radiant heater located in said garage;

a fluidics module in fluid communication with said combined de-paraffinizer/stainer/solvent exchanger that supplies reagents thereto;

a pneumatics module in fluid communication with said combined de-paraffinizer/stainer/solvent exchanger and said fluidics module that supplies vacuum and/or pressurized gas to said combined de-paraffinizer/stainer/solvent exchanger and said fluidics module;

a control module in electrical communication with said transporter, said combined de-paraffinizer/stainer/solvent exchanger, said fluidics module and said pneumatics module, wherein said control module coordinates function of the aforementioned components of the apparatus; and

a cabinet enclosing substantially all of the aforesaid elements during operation of said apparatus, said cabinet further including a dehumidifier for lowering humidity within said cabinet and a portal through which said at least one slide tray can be introduced to or removed from said apparatus.