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

• US 8,486,714 B2
• Filed: 04/28/2008
• Issued: 07/16/2013
• Est. Priority Date: 03/02/2004
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Dako Denmark A/S (Agilent Technologies, Inc.)
• Inventors: Bland, Lauren, Favuzzi, John A, Martin, Merritt M, Sweda, Jonathan R, Lathrop, Robert L, Van Bosch, John E, Buchanan, Kristopher S
• Primary Examiner(s): Nagpaul, Jyoti
• Application Number:
  US12/110,848
• Publication Number:
  US 20090325309A1
• Time in Patent Office: 1,905 Days
• Field of Search: 422/50, 422500-503, 436/180, 73/17.3, 73/17.4
• US Class Current: 436/180
• 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 reagent delivery system 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, comprising:

a probe for aspirating a portion of reagent from a reagent container in order to dispense a predetermined amount on a predetermined carrier element;

and a probe handling device for handling the probe, wherein the probe comprises 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 the closure of the reagent container, wherein the continuous probe tubing is provided with a spirally wound probe tubing section.

2. A reagent delivery system according to claim 1, wherein the rigid probe member is arranged to cooperate with at least one reagent container in such manner that the probe may penetrate an opening covered by a septum, aspirate reagent, and withdraw from the container, and wherein the septum is adapted so as to become substantially closed after withdrawal.

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

4. A reagent delivery system 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. A reagent delivery system according to claim 1, wherein the dispensing end of the probe comprises a conical shape.

6. A reagent delivery system according to claim 1, further comprising:

an identification on a reagent container;

a sensor element on the probe handling device that is able to acquire information from the identification; and

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

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

a reagent section comprising one or more reagent containers;

a staining section in which at least one carrier element is arranged;

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

a handling device for handling said reagent dispensing device, wherein the reagent dispensing device comprises 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. A staining apparatus 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. A staining apparatus according to claim 8, wherein said valve device is operable to provide a predetermined pressure in the tubing for aspirating or dispensing a predetermined amount of reagent in the dispensing end of the tubing.

10. A staining apparatus 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. A staining apparatus according to claim 10, wherein said washing fluid is selectable from a plurality of fluids according to the tube cleaning requirements.

12. A staining apparatus according to claim 7, wherein the handling device comprises:

a holder for holding the probe member; and

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

13. A staining apparatus according to claim 7, wherein the internal diameter of the tubing is between 1.0 mm and 2.0 mm.

14. A staining apparatus according to claim 7, wherein the length of the tubing is between 0.5 m and 2.5 m.

15. A staining apparatus according to claim 7, wherein the spirally wound probe tubing section is a coiled section.

16. A staining apparatus according to claim 15, wherein the coiled section comprises between 5 and 30 windings.

17. A staining apparatus according to claim 15, wherein the washing station comprises:

a receptacle able to accommodate a substantial portion of the dispensing end of the probe; and

an outlet to waste.

18. A staining apparatus according to claim 17 wherein the outlet to the waste is located a distance above the bottom of the receptacle so that the wash fluid ejected from the dispensing end of the probe will wash the outer surface of the dispensing end of the probe before the wash fluid is drained to waste.

19. A staining apparatus according to claim 7, further including a washing station for cleaning the reagent-dispensing device.

20. A staining apparatus 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. A staining apparatus according to claim 20, wherein the cross-section is an unsymmetrical polygon.

22. A staining apparatus according to claim 21, wherein a top wall of a reagent container is provided with a label comprising identifying information and wherein the robot head further comprises an optical sensor, able to provide the information on the label to a computer system.

23. A staining apparatus according to claim 22, wherein the computer system is connected to a plurality of staining apparatuses, wherein the computer system uses the reagent dispensing device to detect the level of reagent fluid in each reagent container, wherein the computer system maintains information about the available amount of reagent in the reagent containers in the plurality of staining apparatuses.

24. A staining apparatus according to claim 21, wherein the computer system will issue an order for a new delivery of the reagent if the level is below a predetermined limit.

25. A staining apparatus according to claim 7, wherein an electrically conducting member of the reagent dispensing device is connected to an electronic circuit adapted for capacitive level sensing.

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

a probe member having an aspirating and dispensing end, through which reagent may be aspirated and dispensed; and

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

27. A reagent dispensing device according to claim 26, wherein the internal diameter of the tubing is between 1.0 mm and 2.0 mm.

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

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

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

31. A reagent dispensing device 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.