Liquid chemical distribution method and apparatus

• US 6,372,185 B1
• Filed: 01/11/1999
• Issued: 04/16/2002
• Est. Priority Date: 05/16/1997
• Status: Expired due to Term

• Current Assignee: Aurora Biotechnologies, Inc. (Azenta, Inc.)
• Original Assignee: Aurora Biosciences Corporation (Vertex Pharmaceuticals Incorporated)
• Inventors: Shumate, Christopher Bentley, Coassin, Peter J.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K.
• Application Number:
  US09/228,258
• Time in Patent Office: 1,191 Days
• Field of Search: 422/99-104, 422/62-65, 436/43, 436/47, 436/174, 436/179, 436/180, 738/63, 738/630.1, 738/633.1, 738/633.2, 738/633.3, 738/64, 738/640.1
• US Class Current: 422/510
• CPC Class Codes: B01J 19/00 Chemical, physical or physico-chemical processes in general; Their relevant apparatus
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00011 Laboratory-scale plants
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00328 Movement by linear translation
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/007 Simulation or vitual synthesis
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: B01L 9/523 for multisample carriers, e.g. used for microtitration plates
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2035/00326 Analysers with modular structure
• CPC Class Codes: G01N 2035/042 moved independently, e.g. by fork manipulator
• CPC Class Codes: G01N 2035/0422 carried on a linear conveyor
• CPC Class Codes: G01N 2035/0425 Stacks, magazines or elevators for plates
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/110833 : Utilizing a moving indicator strip or tape
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/114165 : with step of insertion or removal from test line
• CPC Class Codes: Y10T 436/114998 : with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A chemical solution distribution system and method that includes or employs a plurality of liquid handlers where each of the liquid handlers includes a movable table that engages a sample multiwell plate and can align pipettes of the station with different subsets of wells of the multiwell plate where the number of wells of the multiwell plate is a multiple of the number of pipettes of the head of the pipette station. The system further includes and employs four different pumps to enable the system and method to supply four different solutions to wash stations of each of the four liquid handlers.

Claims

1. A chemical solution distribution system for distributing chemical solutions to a plurality of multiwell plates having N wells with I subsets of M wells, I being an integer and greater than one, the system comprising:

a plurality of liquid handlers, each said liquid handler including;

a head capable of moving in a Z-direction, said head having M pipettes; and

a table configured to engage one of said plurality of multiwell plates and movable in an X-Y plane relative to Z, said table capable of moving to at least I different positions,

wherein at each of said at least I different positions, said M pipettes of said head are aligned with a different one of said I subsets of M wells of said one of said plurality of multiwell plates, and with the proviso that M is about 864 or less.

2. The chemical solution distribution system of claim 1, wherein said system has I liquid handlers.

3. The chemical solution distribution system of claim 1, wherein each of said plurality of said liquid handlers further includes a wash station below said head, wherein said head is capable of moving said M pipettes into contact with solution in said wash station.

4. The chemical solution distribution system of claim 2, said system further including a computational unit to reformat from a first density to a second higher density multiwell plate.

5. The chemical solution distribution system of claim 1, said system further comprising at least one stacker, said stacker capable of storing said plurality of multiwell plates.

6. The chemical solution distribution system of claim 1, said system further including a conveyor belt, said conveyor belt capable of moving at least one of said plurality of multiwell plates between said plurality of said liquid handlers and at least one stacker.

7. The chemical solution distribution system of claim 5, wherein each of said plurality of multiwell plates has a lid, said system further including a delidder, said delidder capable of removing and replacing a lid on each of said plurality of multiwell plates and said conveyor belt further capable of moving said at least one of said plurality of multiwell plates between said plurality of said liquid handlers, said at least one stacker, and said delidder.

8. A chemical solution distribution system of claim 1, wherein M is equal to 96, N is equal to 384, and there are four liquid handlers.

9. The chemical solution distribution system of claim 1, where M is equal to 96.

10. The chemical solution distribution system of claim 1, where M is equal to 96 and N is equal to one of 384 or 864.

11. A chemical solution distribution system for distributing chemical solutions between at least one first multiwell plate having N wells with I subsets of M wells, I being an integer and greater than one and at least one solid substrate or at least one second multiwell plate having M sites or wells, the system comprising:

a plurality of liquid handlers, each liquid handling station including;

a head capable of moving in a Z-direction, said head having M pipettes; and

a table configured to engage one of said at least one first multiwell plate having N wells or said at least one second multiwell plate having M wells or said solid substrate and movable in an X-Y plane relative to Z, said table capable of moving to at least I different positions,

wherein at least at I different positions, said M pipettes of said head are aligned with a different one of the I subsets of M wells of the at least one multiwell plate having N wells or at least at one position said M pipettes of said head are aligned with said M wells of said at least one solid substrate or at least one second multiwell plate having M sites or wells, and with the proviso that M is about 864 or less.

12. The chemical solution distribution system of claim 11, wherein said table is movable to I plus one positions.

13. The chemical solution distribution system of claim 12, wherein M is equal to 96.

14. The chemical solution distribution system of claim 13, wherein N is equal to one of 384 or 864.

15. The chemical solution distribution system of claim 13, wherein there are I liquid handlers.

16. A method of distributing chemical solutions between a plurality of plates having N wells with I subsets of M wells, I being an integer and greater than one, said method comprising the steps of:

aligning a subset of M wells of a first one of said plurality of plates with M pipettes of a first pipette station;

lowering said M pipettes of said first pipette station to engage said subset of M wells and aspirating solution from M wells into said M pipettes and dispensing solution from said M pipettes into a first set of M wells;

aligning a subset of M wells of a second one of the plurality of plates with M pipettes of a second pipette station; and

lowering said M pipettes of said second pipette station to engage said subset of M wells of said second one of the plurality of plates and one of aspirating solution from M wells into said M pipettes and dispensing solution from said M pipettes into a second set of M wells, and with the proviso that M is about 864 or less.

17. The method of claim 16, wherein said samples are chemicals and said plurality of multiwell plates are used to store test chemicals.

18. The method of claim 17, wherein said chemicals comprise polynucleotides.

19. The method of claim 17, further comprising the step of providing a different solution to wash stations of the first liquid handler and said second liquid handler.

20. The method of claim 16, further comprising the steps of:

aligning a subset of M wells of a third one of said plurality of plates with M pipettes of a third pipette station;

lowering said M pipettes of said third pipette station to engage the subset of M wells of said third one of said plurality of plates and one of aspirating solution from M wells into said M pipettes and dispensing solution from said M pipettes into a third set of M wells;

aligning a subset of M wells of a fourth one of said plurality of plates with M pipettes of a fourth pipette station; and

lowering said M pipettes of said fourth pipette station to engage the subset of M wells of said fourth one of said plurality of plates and one of aspirating solution from M wells into said M pipettes and dispensing solution from said M pipettes into a fourth set of M wells.

21. A method of distributing chemical solutions to a first plate having N wells with I subsets of M wells, I being an integer and greater than one and at least one second plate with about N/I wells, the method comprising the steps of:

aligning a first subset of N/I wells of said first plate with M pipettes of a first pipette station;

lowering said M pipettes of said first pipette station to engage said first subset of N/I wells and aspirating solution from said N/I wells into said M pipettes and dispensing solution from said M pipettes into a subset of M wells;

aligning a second set of N/I wells a second plate with M pipettes of a second pipette station; and

lowering said M pipettes of said second pipette station to engage said second set of N/I wells of said second plate and aspirating solution from said N/I wells of said second plate into said M pipettes and dispensing solution from said M pipettes into a second subset of M wells and with the proviso that M is about 864 or less.

22. The method of claim 21, further comprising the steps of:

aligning a third set of N/I wells of one of said plurality of plates with M pipettes of a third pipette station;

lowering said M pipettes of said third pipette station to engage said third set of N/I wells and aspirating solution from M wells into said M pipettes and dispensing solution from said M pipettes into a third set of M wells;

aligning a fourth subset of N/I wells of one of said plurality of plates with M pipettes of a fourth pipette station; and

lowering said M pipettes of said fourth pipette station to engage said fourth set of N/I wells of one of said plurality of plates and aspirating solution from M wells into said M pipettes and dispensing solution from said M pipettes into a fourth set of M wells.

23. The method of claim 22, further comprising the step of providing a different solution to wash stations of said first liquid handler, said second liquid handler, said third liquid handler, and said fourth liquid handler.

24. The method of claim 23, wherein M is equal to 96.

25. The method of claim 24, wherein N is equal to one of 384 or 864.

26. A chemical solution distribution system for distributing chemical solutions into multiwell plates having at least 384 wells, the system comprising:

a) at least one liquid handler comprising 48 or more, but less than 384, tips, said tips having a dynamic range of liquid dispensation of 100 to 2000 nanoliters, and

b) an orthogonal positioner, said liquid handler comprising a tip dispensing matrix with about 96 or more tips, being capable of moving said at least one multiwell plate with an X-Y location accuracy of at least ±

0.09 mm in X and Y.

27. The device of claim 26, wherein said liquid handler comprises a tip dispensing matrix with about 96 or more tips.

28. The device of claim 27, wherein said tip dispensing matrix comprises no more than 96 tips.

29. A test chemicals distribution system for distributing test chemicals to a plurality of multiwell plates used to store chemical libraries having N wells with I subsets of M wells, I being an integer and greater than one, the system comprising:

a plurality of liquid handlers containing test chemicals, each said liquid handler including;

a head capable of moving in a Z-direction, said head having M pipettes; and

a table configured to engage one of said plurality of multiwell plates and movable in an X-Y plane relative to Z, said table capable of moving to at least I different positions,

wherein at each of said at least I different positions, said M pipettes of said head are aligned with a different one of said I subsets of M wells of said one of said plurality of multiwell plates, and with the proviso that M is about 864 or less.

30. A chemical solution distribution system for distributing chemical solutions comprising polynucleotides to a plurality of multiwell plates having N wells with I subsets of M wells, I being an integer and greater than one, the system comprising:

a plurality of liquid handlers containing chemical solutions comprising polynucleotides, each said liquid handler including;

a head capable of moving in a Z-direction, said head having M pipettes; and

a table configured to engage one of said plurality of multiwell plates and movable in an X-Y plane relative to Z, said table capable of moving to at least I different positions,

wherein at each of said at least I different positions, said M pipettes of said head are aligned with a different one of said I subsets of M wells of said one of said plurality of multiwell plates, and with the proviso that M is about 864 or less.