Method for performing crystallization trials

• US 7,452,419 B1
• Filed: 12/16/2004
• Issued: 11/18/2008
• Est. Priority Date: 12/31/2003
• Status: Expired due to Fees

• Current Assignee: Takeda San Diego, Inc. (Takeda Pharmaceutical Company Limited)
• Original Assignee: Takeda San Diego, Inc. (Takeda Pharmaceutical Company Limited)
• Inventors: Martin, Laurent, Palan, John W.
• Primary Examiner(s): Hiteshew; Felisa C
• Application Number:
  US11/015,089
• Time in Patent Office: 1,433 Days
• Field of Search: 427/402, 422/252, 117/13, 117/11
• US Class Current: 117/11
• CPC Class Codes: B01D 9/0063 Control or regulation control per se G05
• CPC Class Codes: B01D 9/0077 Screening for crystallisation conditions or for crystal forms
• CPC Class Codes: Y10T 117/10 Apparatus
• CPC Class Codes: Y10T 117/1004 with means for measuring, testing, or sensing
• CPC Class Codes: Y10T 117/1008 with responsive control means
• CPC Class Codes: Y10T 117/1016 with means for treating single-crystal [e.g., heat treating]
• CPC Class Codes: Y10T 117/1024 for crystallization from liquid or supercritical state

Abstract

A method is provided for operating a crystallization system comprising identifying a screen storage plate from among the plurality of screen storage plates stored in a screen storage station, each screen storage plate having a plurality of wells that contain a screen solution and at least a portion of the screen storage plates having a selection of screen solutions that is different from the selection of screen solutions held in other screen storage plates; having a transport mechanism transport the identified screen storage plate to a screen replicator; transporting a plurality of crystallization plates to the screen replicators; and having the screen replicator transfer the screen solutions from the identified screen storage plate to the plurality of crystallization plates.

Claims

1. A method of operating a crystallization system, comprising:

(a) having a transport mechanism transport a screen storage plate to a screen replicator;

(b) having the same transport mechanism transport a plurality of crystallization plates from a crystallization plate storage station to the screen replicator; and

(c) having the screen replicator transfer the screen solutions from the screen storage plate to the plurality of crystallization plates;

wherein (a) and (b) is performed in any order prior to (c).

2. The method of claim 1, wherein the transport mechanism employed to transport the crystallization plate to the screen replicator includes a robotic arm.

3. The method of claim 1, wherein less than 250 μ

L of screen solution are transferred per well from the screen storage plate into each of the one or more well regions on each of the crystallization plates.

4. The method of claim 1, wherein the screen storage plate is transferred to a mixing station where the contents of the screen storage plate are agitated before the screen storage plate is transferred to the screen replicator.

5. The method of claim 1, wherein the screen storage station includes a housing for storing the plurality of screen storage plates, the method further comprising employing mechanics to move the screen storage plate to be transferred from the housing to a location where a transport mechanism can access the screen storage plate for transport to the screen replicator.

6. The method of claim 1, further comprising removing a cover from the screen storage plate before transferring the screen solutions from the screen storage plate to the crystallization plate.

7. The method of claim 1, the method further comprising piercing a cover over the wells of the screen storage plate that contains the screen solutions before transferring screen solutions from the screen storage plate to the crystallization plate.

8. The method of claim 1, further comprising employing a covering device to position a cover on the screen storage plate before transporting the screen storage plate from the screen storage station to the screen replicator.

9. The method of claim 1, the method further comprising transporting the screen storage plate from the screen replicator to the screen storage station after transferring screen solutions from the screen storage plate into the trial zone of the crystallization plate.

10. The method of claim 1, the method further comprising preparing one or more of the plurality of screen storage plates stored in the screen storage station outside of the system and positioning the one or more screen storage plates in the screen storage station.

11. The method of claim 1, the method further comprising preparing one or more of the plurality of screen storage plates at a screen generation station and having a transport mechanism transport the one or more plates to the screen storage station.

12. A method comprising:

storing a plurality of screen storage plates in a screen storage station;

having the screen storage station retrieve a selected screen storage plate from among the plurality of screen storage plates stored within the screen storage station;

having a transport mechanism transport the selected screen storage plate to a screen replicator; and

having a transfer mechanism of a screen replicator transfer portions of different screen solutions from the retrieved screen storage plate to a crystallization plate.

14. The method of claim 12, the method further comprising having the transport mechanism transport the crystallization plate to the screen replicator.

15. The method of claim 12, wherein the transport mechanism includes a robotic arm.

16. The method of claim 12, wherein having the transfer mechanism transfer portions of different screen solutions from the retrieved screen storage plate to the crystallization plate includes having the transfer mechanism transfer portions of different screen solutions from the retrieved screen storage plate a plurality of crystallization plates.

17. The method of claim 12, wherein having the transfer mechanism transfer portions of different screen solutions from the retrieved screen storage plate to a crystallization plate includes having the transfer mechanism transfer less than 250 μ

L of screen solution per well into each of the one or more well regions of the crystallization plate.

18. The method of claim 12, wherein having a transport mechanism transport the selected screen storage plate to a screen replicator includes having the transport mechanism transport the selected screen storage plate to a mixing station before transporting the identified screen storage plate to the screen replicator.

19. The method of claim 18, wherein the selected screen storage is transported from the screen storage station to the mixing station.

20. The method of claim 12, the method further comprising removing a cover from the retrieved screen storage plate before having the transfer mechanism transfer portions of different screen solutions from the retrieved screen storage plate to the crystallization plate.

21. The method of claim 12, further comprising piercing a cover over the wells of the screen storage plate that contain the screen solutions before having the transfer mechanism transfer portions of different screen solutions from the retrieved screen storage plate to the crystallization plate.

22. The method of claim 12, the method further comprising having a covering device position a cover on the selected screen storage plate before having the screen storage station retrieve the selected screen storage plate from among the plurality of screen storage plates.

23. The method of claim 12, the method further comprising having a controller identify the selected screen storage plate as containing a particular screen before having the screen storage station retrieve the selected screen storage plate.

24. The method of claim 23, wherein having the controller identify the selected screen storage plate includes comparing a screen identifier associated with the particular screen against screen identifiers listed in a tracking database, the tracking database including the screen identifiers associated with screen storage plates stored in the screen storage station.

25. The method of claim 23, the method further comprising having the transport mechanism transport the selected screen storage plate to the screen storage station after having the transfer mechanism transfer portions of different screen solutions.

13. The method of 12, wherein having the screen storage station retrieve a selected screen storage plate includes causing the selected screen storage plate to be moved from a position within the screen storage station where the transport mechanism cannot access the selected screen storage plate to a position where the transport mechanism can access the selected screen storage plate.

26. A method of operating a crystallization system, comprising:

having a screen replicator transfer screen solutions from wells of a screen storage plate to a plurality of crystallization plates;

having a transport mechanism transport the plurality of crystallization plates from the screen replicator to a trial generation station; and

having the trial generation station generate crystallization trials in the plurality of crystallization plates.

27. The method of claim 26, wherein the transport mechanism includes a robotic arm.

28. The method of claim 26, wherein having the trial generation station generate crystallization trials includes having the trial generation station transfer an additive solution from an additive plate to the crystallization plate before having the trial generation station generate crystallization trials.

29. The method of claim 28, further comprising having the transport mechanism transport the crystallization plate to a mixing station and transport the crystallization plate back to the trial generation station after having the trial generation station transfer the additive solution.

30. The method of claim 28, the method further comprising mixing the mother liquors in the crystallization plate after having the trial generation station transfer the additive solution and before having the trial generation station generate the crystallization trials.

31. The method of claim 28, wherein having the trial generation station generate crystallization trials includes piercing a material on the additive plate before having the trial generation station transfer the additive solution.

32. The method of claim 28, wherein having the trial generation station generate crystallization trials includes having the trial generation station transfer a molecule solution from a molecule plate to the crystallization plate.

33. The method of claim 32, wherein the molecule solution includes a protein to be crystallized by the system.

34. The method of claim 32, wherein having the trial generation station generate crystallization trials includes transferring the molecule solution and the screen solutions to sample regions of the crystallization plate such that a total combined volume of molecule solution and screen solution transferred to a given sample region is less than 1 μ

L.

35. The method of claim 32, wherein having the trial generation station generate crystallization trials includes piercing a material on the molecule plate before having the trial generation station transfer the molecule solution.

36. A method, comprising:

transferring screen solutions from wells of a screen storage plate to wells of a plurality of crystallization plates;

transporting the crystallization plates to a trial generation station; and

generating crystallization trials in the crystallization plates transported to the trial generation station;

wherein the method is performed in a single, automated system.

37. The method of claim 36, wherein the transport mechanism includes a robotic arm.

38. The method of claim 36, wherein generating crystallization trials includes transferring a portion of a mother liquor in one or more trial zones of a crystallization plate from a well region of the trial zone to a sample region associated with the trial zone.

39. The method of claim 38, wherein less than 1 μ

L of the mother liquor are transferred into the sample regions of one or more trial zone on the crystallization plate.

40. The method of claim 38, wherein generating crystallization trials includes transferring an additive solution from an additive plate to the well regions of one or more trial zones on the crystallization plate before transferring the mother liquor.

41. The method of claim 40, the method further comprising transporting the crystallization plate to a mixing station and back to the trial generation station after transferring the additive solution and before transferring the mother liquor.

42. The method of claim 40, the method further comprising mixing the mother liquors in the crystallization plate after transferring the additive solution and before transferring the mother liquor.

43. The method of claim 40, wherein generating crystallization trials includes piercing a material on the additive plate before transferring the additive solution.

44. The method of claim 38, wherein generating crystallization trials includes transferring a molecule solution from a molecule plate to the sample regions of one or trial zones on the crystallization plate, the molecule solution including the molecule to be crystallized by the system.

45. The method of claim 44, wherein the molecule solution and the mother liquor are transferred into the sample regions such that a total volume of the molecule solution plus the screen solution transferred into the sample region is less than 1 μ

L.

46. The method of claim 44, wherein generating crystallization trials includes piercing a material on the molecule plate before the molecule solution.