Method and apparatus for automated pre-treatment and processing of biological samples

• US 7,875,245 B2
• Filed: 06/20/2005
• Issued: 01/25/2011
• Est. Priority Date: 05/14/2003
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Dako Denmark A/S (Agilent Technologies, Inc.)
• Inventors: Feingold, Gordon A., Van Bosch, John E., Rohrbacker, Dawn M., Buchanan, Kristopher S., Rau, Jeffery L., Clark, Robert M., Sweet, Douglas F., Barber, Michael T., Lathrop, Robert L., Sweda, Jonathan R., Favuzzi, John A., Martin, Merritt M. Jr., Welcher, Rosanne, Guggenheimer, Benno M., Key, Marc E., Winther, Lars, Bland, Loren L.
• Primary Examiner(s): Warden; Jill
• Assistant Examiner(s): Handy; Dwayne K
• Application Number:
  US11/156,760
• Publication Number:
  US 20060105359A1
• Time in Patent Office: 2,045 Days
• Field of Search: 435/6, 435/287.2, 422/100, 422/63, 422/67, 422/102, 702/20, 436/43, 436/46, 436/55, 436/180
• US Class Current: 422/403
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: B01L 7/00 Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• CPC Class Codes: B01L 9/06 Test-tube stands; Test-tube holders
• CPC Class Codes: G01N 1/312 for samples mounted on planar substrates
• CPC Class Codes: G01N 2035/00356 Holding samples at elevated temperature (incubation)
• CPC Class Codes: G01N 2035/00366 Several different temperatures used
• CPC Class Codes: G01N 2035/00445 Other cooling arrangements
• CPC Class Codes: G01N 2035/00455 Controlling humidity in analyser
• CPC Class Codes: G01N 2035/00534 Mixing by a special element, e.g. stirrer
• CPC Class Codes: G01N 2035/00633 logging process history of individual samples
• CPC Class Codes: G01N 2035/00673 of reagents
• CPC Class Codes: G01N 2035/00752 bar codes
• CPC Class Codes: G01N 2035/00861 printing and sticking of identifiers
• CPC Class Codes: G01N 2035/00881 network configurations
• CPC Class Codes: G01N 2035/102 Preventing or detecting loss of fluid by dripping
• CPC Class Codes: G01N 2035/1058 : for mixing
• CPC Class Codes: G01N 35/00029 : provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: G01N 35/00871 : Communications between instruments or with remote terminals
• CPC Class Codes: G01N 35/0092 : Scheduling
• CPC Class Codes: G01N 35/0095 : introducing urgent samples with priority, e.g. Short Turn Around Time Samples [STATS]
• CPC Class Codes: G01N 35/0099 : comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: G01N 35/1004 : Cleaning sample transfer devices
• CPC Class Codes: G01N 35/1011 : Control of the position or alignment of the transfer device
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/112499 : with sample on test slide
• CPC Class Codes: Y10T 436/12 : Condition responsive control
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention concerns a method and apparatus for automatic processing a biological sample on a carrier, perhaps robotically, by applying predetermined amounts of reagents in a predetermined sequence according to a processing protocol, the processing including pre-treatment steps, under the control of an adaptive processing control system using a sample process parameter input that may be independent and an independent process parameter memory that does not interrupt process operation when being used, such that samples may be added or removed without interrupting the processing of other samples. Also included is an image capture function for sample and reagent identification and process monitoring, as well as temperature regulation and environmental control functions.

Claims

1. An apparatus for automated processing of a plurality of biological samples on sample carriers having respective identifications, the processing of each sample being conducted according to a respective sequence of protocol steps, said apparatus comprising:

a frame;

a plurality of drawers within the frame, each drawer comprising a respective carrier rack for supporting at least one carrier; and

a robotic reagent dispensing head within the frame that performs ongoing robotic processing, including dispensing of reagents, according to the protocol steps; and

a sensor for reading the identifications,

wherein a first sample, in a first drawer, for which the processing is completed may be removed from the apparatus without interrupting the ongoing robotic processing of a second sample in a second drawer, and

wherein a second sample, in a second drawer, may be inserted into the apparatus without interrupting the dispensing of reagents onto a first sample, in a first drawer, with the robotic reagent dispensing head.

2. The apparatus of claim 1, further comprising a plurality of reagent containers within the frame, each reagent container containing a respective reagent for administration to the samples.

3. The apparatus of claim 2, wherein each reagent container has a respective reagent identification that may be read by the sensor.

4. The apparatus of claim 3, wherein the reagent identification comprises a two dimensional symbology.

5. The apparatus of claim 3, wherein the identification is in the form of a two-dimensional high-resolution symbology code.

6. The apparatus of claim 3, wherein the identification is in the form of a two dimensional data matrix.

7. The apparatus of claim 3, wherein the identification comprises human-readable text.

8. The apparatus of claim 2, wherein each reagent container is keyed to a mating receptacle housed within the frame, so that the container has a specific orientation.

9. The apparatus of claim 8, wherein each reagent container has more than four sides.

10. The apparatus of claim 2, wherein the probe further comprises a fluid level sensor for determining the volume of reagent within a container.

11. The apparatus of claim 2, wherein a reagent container has a cap with a septum that is penetrated by the probe upon insertion of the probe into the container and that restores to a form that inhibits reagent evaporation upon withdrawal of the probe from the container.

12. The apparatus of claim 11, wherein the septum comprises a plurality of sectors that are separated to form flaps upon first insertion of the probe into the container.

13. The apparatus of claim 2, wherein a reagent container has a cap with a septum that is penetrated by the probe upon insertion of the probe into the container and that cleans an outer surface of the probe upon withdrawal of the probe from the container.

14. The apparatus of claim 1, further comprising a washing station housed within the frame for cleaning the probe after administration of a reagent to a sample.

15. The apparatus of claim 1, further comprising a mixing station housed within the frame for mixing two or more reagents prior to administration of a mixture to a sample.

16. The apparatus of claim 1, wherein the sensor is a camera and wherein at least one identification comprises a two-dimensional arrangement of elements on a carrier, wherein an image of the identification is captured by the camera.

17. The apparatus of claim 16, wherein the identification is in the form of a two-dimensional high-resolution symbology code.

18. The apparatus of claim 16, wherein the identification is in the form of a two dimensional data matrix.

19. The apparatus of claim 16, wherein the identification comprises human-readable text.

20. The apparatus of claim 16, wherein the identification is the biological sample.

21. The apparatus of claim 16, wherein the camera further captures an image of the biological sample.

22. The apparatus of claim 1, wherein at least one carrier is a microscope slide.

23. The apparatus of claim 1, wherein at least one drawer further comprises a processing tank for immersing a carrier into a fluid used for pre-treatment of the biological sample on the carrier, the pre-treatment being administered prior to processing of the sample.

24. The apparatus of claim 23, wherein the carrier rack of the at least one drawer comprises a carrier holder that rotates the carrier into a first orientation prior to the pretreatment and that rotates the carrier into a second orientation prior to the processing.

25. The apparatus of claim 24, wherein the first orientation is substantially vertical and the second orientation is substantially horizontal.

26. The apparatus of claim 1, wherein a carrier rack comprises a temperature control element for controlling the temperature of a biological sample during processing.

27. A method of processing of a plurality of biological samples on sample carriers having respective identifications, the processing of each sample being conducted according to a respective sequence of protocol steps, comprising the steps of:

providing an apparatus comprising;

a frame;

a robotic reagent dispensing head within the frame that performs ongoing robotic processing, including dispensing of reagents; and

a plurality of drawers within the frame, each drawer comprising a respective carrier rack for supporting at least one carrier; and

inserting a first carrier having a first biological sample onto a carrier rack of a first drawer;

inserting a second carrier having a second biological sample onto a carrier rack of a second drawer;

determining the first-completed sample, being whichever one of the first biological sample and the second biological sample whose processing is completed prior to the completion of the processing of the other biological sample;

removing the first-completed sample from the apparatus without interrupting the dispensing of reagents onto the other biological sample.

28. The method of claim 27, wherein the processing includes biological staining.

29. The method of claim 27, wherein the processing includes in-situ hybridization.

30. The method of claim 27, wherein the removing step includes opening the drawer having the first-completed sample.

31. A method of processing of a plurality of biological samples on sample carriers having respective identifications, the processing of each sample being conducted according to a respective sequence of protocol steps, comprising the steps of:

providing an apparatus comprising;

a frame;

a robotic reagent dispensing head within the frame that performs ongoing robotic processing, including dispensing of reagents; and

a plurality of drawers within the frame, each drawer comprising a respective carrier rack for supporting at least one carrier; and

inserting a first carrier having a first biological sample onto a carrier rack of a first drawer;

commencing the processing of the first biological sample;

inserting a second carrier having a second biological sample onto a carrier rack of a second drawer without interrupting the dispensing of reagents onto the first biological sample with the robotic reagent dispensing head;

removing the first carrier from the carrier rack of the first drawer without interrupting the ongoing robotic processing of the second biological sample; and

commencing the processing of the second biological sample, prior to completion of the processing of the first biological sample, without interrupting the processing of the first biological sample.

32. The method of claim 31, wherein the processing includes biological staining.

33. The method of claim 31, wherein the processing includes in-situ hybridization.