System for performing crystallization trials

• US 7,431,768 B1
• Filed: 12/16/2004
• Issued: 10/07/2008
• 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 CARLA
• Application Number:
  US11/016,072
• Time in Patent Office: 1,391 Days
• Field of Search: 427/402, 422/252, 117/13, 117/200, 117/204, 250/288
• US Class Current: 117/201
• 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 crystallization system is provided comprising: a screen replicator configured to transfer screen solutions from wells of a screen storage plate into well regions of multiple crystallization plates; a trial generation station configured to generate crystallization trials in the trial zones of a crystallization plate; a transport mechanism configured to transport crystallization plates from the screen replicator to the trial generation station; and a controller having logic for causing the screen replicator to transfer the screen solutions from the screen storage plate to multiple crystallization plates, logic for causing the transport mechanism to transport the crystallization plates from the screen replicator to the trial generation station and logic for causing the trial generation station to generate crystallization trials in the crystallization plates.

Claims

1. A crystallization system, comprising:

a screen replicator configured to transfer screen solutions from wells of a screen storage plate into well regions of multiple crystallization plates;

a trial generation station configured to generate crystallization trials in the trial zones of a crystallization plate;

a transport mechanism configured to transport crystallization plates from the screen replicator to the trial generation station; and

a controller having logic for causing the screen replicator to transfer the screen solutions from the screen storage plate to multiple crystallization plates, logic for causing the transport mechanism to transport the crystallization plates from the screen replicator to the trial generation station and logic for causing the trial generation station to generate crystallization trials in the crystallization plates.

2. The system of claim 1, wherein the transport mechanism includes a robotic arm.

3. The system of claim 1, wherein the trial generation station includes a head configured to move relative to a crystallization plate received from the transport mechanism, the head including a number of primary fluid dispensers in an arrangement matching an arrangement of the well regions on the crystallization plate.

4. The system of claim 3, wherein the primary fluid dispensers have a dispensing range of 50 nL to 200 nL and a CV below 10%.

5. The system of claim 3, wherein the head includes one or more secondary fluid dispensers in addition to the primary fluid dispensers.

6. The system of claim 5, wherein at least one of the one or more secondary fluid dispensers are located outside of a perimeter defined by the primary fluid dispensers.

7. The system of claim 5, wherein at least one of the one or more secondary fluid dispensers are configured to be moved vertically relative to the primary fluid dispensers.

8. The system of claim 5, wherein at least one of the one or more secondary fluid dispensers are laterally immobilized relative to the primary fluid dispensers.

9. The system of claim 3, wherein the head includes a piercer configured to pierce a material positioned over the wells of an additive plate or a molecule plate, the piercer being configured to move vertically relative to the primary fluid dispensers.

10. The system of claim 1, wherein the controller includes logic for causing the trial generation station to transfer a portion of a mother liquor in one or more trial zones of the crystallization plate from a well region of the trial zone to a sample region associated with the well region.

11. The system of claim 10, wherein the controller includes logic for causing the trial generation to transfer 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 from the well region of the trial zone to the sample region associated with the trial zone.

12. The system of claim 11, wherein the controller includes logic for causing the transport mechanism to transport the crystallization plate to a mixing station after transferring the additive solution and before transferring the mother liquor.

13. The system of claim 12, wherein the controller includes logic for causing the mixing station to mix the mother liquors in the crystallization plate and for causing the transport mechanism to transport the crystallization plate back to the trial generation station after causing the mixing station to mix the mother liquors in the crystallization plate.

14. The system of claim 10, wherein the controller includes logic for causing the trial generation station to transfer less than 1 μ

L of the mother liquor in at least one trial zone of the crystallization plate from the well region of the trial zone to the sample region associated with the trial zone.

15. The system of claim 10, wherein the controller includes logic for operating the trial generation station so as to transfer a molecule solution contained in a well of a molecule plate from the molecule plate into at least one trial zone on a crystallization plate, the molecule solution including the molecule to be crystallized by the system.

16. The system of claim 15, wherein the controller includes logic for transferring the molecule solution and the mother liquor into the sample regions associated with one or trial zones on the crystallization plate such that a total volume of the molecule solution plus the screen solution transferred into the sample region is less than 1 μ

L.