System for performing crystallization trials

• US 7,435,379 B1
• Filed: 12/16/2004
• Issued: 10/14/2008
• 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): Hitewshew; Felisa C
• Application Number:
  US11/015,100
• Time in Patent Office: 1,398 Days
• Field of Search: 427/402, 422/252, 117/13, 117/200, 117/206, 117/11
• US Class Current: 422/25
• 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 trial generation station is provided comprising: a deck configured to receive a crystallization plate from a transport mechanism, the crystallization plate including a plurality of trial zones where crystallization trials are generated; and a head configured to be moved relative to the stage, the head including a plurality of primary fluid dispensers, each fluid dispenser being configured to transfer a portion of a mother liquor from the well region of a trial zone to a sample region associated with the trial zone, and one or more secondary fluid dispensers configured to dispense a molecule solution into the sample regions of the wells, the molecule solution including the molecule to be crystallized by the system and at least one of the secondary fluid dispenser being laterally immobilized relative to one or more of the fluid dispensers.

Claims

1. A trial generation station, comprising:

a deck configured to receive a crystallization plate from a transport mechanism, the crystallization plate including a plurality of trial zones where crystallization trials are generated; and

a head including

a plurality of primary fluid dispensers, each fluid dispenser being configured to transfer a portion of a mother liquor from a well region of a trial zone to a sample region associated with the trial zone, and

one or more secondary fluid dispensers configured to dispense a molecule solution into the sample regions of the wells, the molecule solution including the molecule to be crystallized by the system and at least one of the secondary fluid dispensers being laterally immobilized relative to one or more of the fluid dispensers;

wherein the head and deck are configured to move relative to each other.

2. The station of claim 1, wherein the secondary fluid dispenser is laterally immobilized relative to all of the primary fluid dispensers.

3. The station of claim 1, wherein a number and arrangement of the primary fluid dispensers on the head matches a number and arrangement of well regions on the crystallization plate.

4. The station of claim 1, wherein the primary fluid dispensers have a dispensing range of 50 nL to 200 nL and a CV below 10%.

5. The station of claim 1, wherein at least one of the one or more secondary fluid dispensers are configured to be moved vertically relative to the primary fluid dispensers.

6. The station of claim 1, wherein at least one of the one or more secondary dispensers is positioned outside a perimeter defined by the primary fluid dispensers.

7. The station of claim 1, wherein at least one of the one or more secondary fluid dispensers is laterally immobilized relative to the primary fluid dispensers.

8. The station of claim 1, wherein the head includes a piercer configured to move relative to the fluid dispensers and shaped so as to pierce a material positioned over the wells of an additive plate or a molecule plate.

9. The station of claim 1, wherein the head is configured to be moved vertically relative to the deck.

10. A crystallization system, comprising:

a trial generation station having a deck configured to receive a crystallization plate from a transport mechanism, the crystallization plate including a plurality of trial zones that each have a well region and a crystallization trial region, the trial generation station including a head that includes

a plurality of primary fluid dispensers, each fluid dispenser configured to transfer a portion of a mother liquor from the well region of a well to the sample region of the well, and

one or more secondary fluid dispensers configured to dispense a molecule solution into the crystallization trial regions of the wells, the molecule solution including the molecule to be crystallized by the system and the secondary fluid dispenser being laterally immobilized relative to the primary fluid dispensers; and

a controller having logic for causing the trial generation station to generate crystallization trials in the crystallization plate;

wherein the head and deck are configured to move relative to each other.

11. The system of claim 10, 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 trial zone.

12. The system of claim 11, 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 well of the crystallization plate from the well region of the well to the sample region of the same well.

13. The system of claim 11, 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 well of a crystallization plate, the molecule solution including the molecule to be crystallized by the system.

14. The system of claim 10, wherein the controller includes logic for causing the trial generation to transfer an additive solution in a well of an additive plate from the additive plate to the well regions of one or more wells on the crystallization plate before transferring the mother liquor from the well region of the well to the sample region of the well.

15. The system of claim 14, 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.

16. The system of claim 15, 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.

17. The system of claim 14, wherein the controller includes logic for transferring the molecule solution and the mother liquor into the sample region of one or more wells on the crystallization plate such that a total volume of the molecule solution plus the mother liquor transferred into the sample region is less than 1 μ

L, the molecule solution including the molecule to be crystallized by the system.