Reagent delivery system, dispensing device and container for a biological staining apparatus

• US 9,164,013 B2
• Filed: 06/17/2013
• Issued: 10/20/2015
• Est. Priority Date: 03/02/2004
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Dako Denmark A/S (Agilent Technologies, Inc.)
• Inventors: Favuzzi, John, Sweda, Jonathan, Martin, Merrit, Lathrop, Robert, Van Bosch, John, Buchanan, Kristopher, Bland, Loren
• Primary Examiner(s): Nagpaul, Jyoti
• Application Number:
  US13/919,959
• Publication Number:
  US 20140004552A1
• Time in Patent Office: 855 Days
• US Class Current: 1/1
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• 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 35/1002 Reagent dispensers
• CPC Class Codes: G01N 35/109 with two horizontal degrees of freedom
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The invention concerns reagent delivery system for an apparatus for processing of biological samples arranged on microscope slides, comprising a reagent section having one or more reagent containers; a slide section in which at least one microscope slide is arranged; a probe for dispensing a portion of reagent onto a predetermined microscope slide, and means for handling the probe. The probe comprises a continuous prove tubing element extending through a rigid probe member and connecting the probe tip to a pneumatic pressure regulation device. The reagent containers are adapted for cooperation with the probe tip. In this manner a high though-put and a very low carry over of fluid residues is achieved since there is no assembled parts making up the inside volume of the probe in which the fluid may be retained.

Claims

1. A method of reagent delivery in an apparatus for processing biological samples arranged on carrier elements, the apparatus comprising a stationary reagent section having one or more reagent containers and a stationary staining section in which at least one carrier element is arranged, the method comprising:

handling movement of a probe via a probe handling device;

aspirating a portion of reagent from a reagent container via the probe;

dispensing, via the probe, a predetermined amount of reagent on a predetermined carrier element;

the probe including a continuous probe tubing extending through a rigid probe member and providing fluid communication from a dispensing end of said probe member to a pneumatic pressure regulation device and wherein the rigid probe member is adapted for cooperation with a closure cap of the reagent container, wherein the continuous probe tubing is provided with a spirally wound probe tubing section.

2. The method of reagent delivery according to claim 1, further comprising:

penetrating an opening of at least one reagent container covered by a septum;

aspirating reagent with the rigid probe member; and

withdrawing the rigid probe member from the at least one reagent container, wherein the septum is adapted so as to become substantially dosed after withdrawal.

3. The method of reagent delivery according to claim 2, wherein the septum comprises a plurality of sectors or flaps which are free to flex upwards or downwards.

4. The method of reagent delivery according to claim 2, wherein the septum comprises a plurality of sectors or flaps, which, originally, are connected by lines of weakness such that the lines of weakness will break the first time a probe is inserted into the reagent container, and, afterwards, are free to flex upwards or downwards.

5. The method of reagent delivery according to claim 2, wherein the dispensing end of the probe comprises a conical shape.

6. The method of reagent delivery according to claim 2, further comprising:

acquiring information from an identification on a reagent container with a sensor element on the handling device; and

receiving the information with a computer electrically coupled to the sensor element.

7. A method of automated processing of biological samples arranged on carrier elements on a staining apparatus comprising:

a reagent section comprising one or more reagent containers, a staining section in which at least one carrier element is arranged, the method comprising;

dispensing a portion of reagent onto a predetermined carrier element with a reagent dispensing device; and

handling the reagent dispensing device with a handling device, the reagent dispensing device including a continuous probe tubing extending through a rigid probe member and providing fluid communication from a dispensing end of said probe member to a pneumatic pressure regulation device, wherein the continuous probe tubing is provided with a spirally wound probe tubing section.

8. The method of automated processing according to claim 7, wherein the pneumatic pressure regulation device includes a vacuum source with which the tubing may communicate via a valve device.

9. The method of automated processing according to claim 8, further comprising providing a predetermined pressure in the tubing for aspirating or dispensing a predetermined amount of reagent in the dispensing end of the tubing via the valve device.

10. The method of automated processing according to claim 8, wherein said valve device is adapted to provide a connection to a fluid source providing a wash solution or cleaning fluid for washing and or rinsing the probe tubing.

11. The method of automated processing according to claim 10, wherein said washing solution is selectable from a plurality of fluids according to the tube cleaning requirements.

12. The method of automated processing according to claim 7, further comprising:

holding the probe member with a holder of the handling device; and

moving the reagent dispensing device between predetermined locations relative to the carrier element and the reagent containers with a robotic motion system of the handling device.

13. The method of automated processing according to claim 7, wherein the internal diameter of the tubing is between 1.0 mm and 2.0 mm.

14. The method of automated processing according to claim 7, wherein the length of the tubing is between 0.5 m and 2.5 m.

17. The method of automated processing according to claim 7, further comprising cleaning the reagent-dispensing device.

18. The method of automated processing according to claim 17, wherein cleaning the reagent dispensing device is performed by a washing station including a receptacle able to accommodate a substantial portion of the dispensing end of the probe, and an outlet to waste.

19. The method of automated processing according to claim 18, further comprising ejecting the wash fluid from the dispensing end of the probe to wash the outer surface of the dispensing end of the probe before the wash fluid is drained to waste.

20. The method of automated processing according to claim 7, wherein the reagent section comprises a compartment for a reagent container wherein the cross-section of the compartment cooperates with the cross-section of the container.

21. The method of automated processing according to claim 20, wherein the cross-section is an unsymmetrical polygon.

22. The method of automated processing according to claim 21, further comprising:

identifying information of a reagent container label via an optical sensor included with the robot head;

and providing the information on the label to a computer system.

23. The method of automated processing according to claim 22, further comprising issuing an order for a new delivery of the reagent if the level is below a predetermined limit by the computer system.

24. The method of automated processing according to claim 22, further comprising:

connecting the computer system to a plurality of staining apparatuses;

detecting the level of reagent fluid in each reagent container via the reagent dispensing device; and

maintaining information about the available amount of reagent in the reagent containers in the plurality of staining apparatuses by the computer system.

25. The method of automated processing according to claim 7, further comprising connecting an electrically conducting member of the reagent dispensing device to an electronic circuit adapted for capacitive level sensing.

15. The method of automated processing 7, wherein the spirally wound probe tubing section is a coiled section.

16. The method of automated processing according to claim 15, wherein the coiled section comprises between 5 and 30 windings.

26. A reagent dispensing method for use in a staining apparatus for processing of biological samples arranged on carrier elements, the method comprising:

aspirating reagent through a dual purpose end of a probe member, the dual purpose end configured to aspirate and dispense fluid;

dispensing reagent through the dual purpose end;

wherein a continuous probe tubing is provided inside the probe member, the continuous probe tubing extending through the entire probe member from the dual purpose end to a pneumatic pressure regulation device, wherein the continuous tubing is provided with a spirally wound probe tubing section.

27. The reagent dispensing method according to claim 26, wherein the internal diameter of the tubing is between 1.0 mm and 2. 0 mm.

28. The reagent dispensing method according to claim 26, wherein the length of the tubing is between 0.5 m and 2.5 m.

29. The reagent dispensing method according to claim 26, wherein the spirally wound probe tubing section is a coiled section.

30. The reagent dispensing method according to claim 29, wherein the coiled section comprises between 5 and 30 windings.

31. The reagent dispensing method according to claim 26, wherein a mounting end of the probe member includes a fitting for mounting the probe member to a probe handling device.