Apparatus and method for high-throughput preparation and characterization of compositions

• US 20030138940A1
• Filed: 09/06/2002
• Published: 07/24/2003
• Est. Priority Date: 01/07/2000
• Status: Abandoned Application

• Current Assignee: Alasdair Y. Johnson, Anthony V. Lemmo, Christopher McNulty, Javier Gonzales-Zugasti, Michael J. Cima, Orn Almarsson, Sherry L. Morissette
• Original Assignee: Alasdair Y. Johnson, Anthony V. Lemmo, Christopher McNulty, Javier Gonzales-Zugasti, Michael J. Cima, Orn Almarsson, Sherry L. Morissette
• Inventors: Gonzales-Zugasti, Javier, Cima, Michael J., Almarsson, Orn, Lemmo, Anthony V., McNulty, Christopher, Morissette, Sherry L., Johnson, Alasdair Y.
• Application Number:
  US10/235,553
• Publication Number:
  US 20030138940A1
• Time in Patent Office: Days
• US Class Current: 435/287.1
• 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 2219/00283 Reactor vessels with top opening
• CPC Class Codes: B01J 2219/0031 the racks or blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00335 Septa
• CPC Class Codes: B01J 2219/00344 Caps
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00587 High throughput processes
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00756 Compositions, e.g. coatings, crystals, formulations
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0851 Bottom walls
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 3/5082 Test tubes per se
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C30B 29/58 Macromolecular compounds
• CPC Class Codes: C30B 7/00 Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 2035/041 : lifting items out of a rack for access
• CPC Class Codes: G01N 2035/042 : moved independently, e.g. by fork manipulator
• CPC Class Codes: G01N 2035/0425 : Stacks, magazines or elevators for plates
• CPC Class Codes: G01N 21/3577 : for analysing liquids, e.g. polluted water
• 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

Abstract

Systems and methods are described that allow the high-throughput preparation, processing, and study of arrays of samples, each of which comprises at least one compound. Particular embodiments of the invention allow a large number of experiments to be performed in parallel on samples that comprised of one or more compounds on the milligram or microgram quantities of compounds. Other embodiments of the invention encompass methods and devices for the rapid screening of the results of such experiments, as well as methods and devices for rapidly determining whether or not similarities exist among groups of samples in an array. Particular embodiments of the invention encompass methods and devices for the high-throughput preparation of different forms of compounds (e.g., different crystalline forms), for the discovery of new forms of old compounds, and for the discovery of new methods of producing such forms. Embodiments of the invention also allow for the high-throughput determination of how specific compounds or forms of compounds behave when exposed to other chemicals or environmental conditions.

Claims

1. A high throughput system for evaluating experiments, which comprises:

a) a plurality of containers, each of which contains a compound-of-interest and optionally one or more additional compounds;

b) a block having a top surface, a bottom surface, and a plurality of holes for receiving the containers, wherein each hole has a top opening on the top surface and a bottom opening on the bottom surface, wherein the top opening is of a dimension sufficient to accommodate a container and the dimension of the bottom opening is of a dimension that will not accommodate the container; and

c) a lifting mechanism which comprises a pin that when inserted in the bottom opening of the hole is of a length sufficient to at least partially push the container from the hole.

2. The system of claim 1 wherein the block is thermally conductive.

3. The system of claim 1 wherein the block is metal.

4. The system of claim 3 wherein the metal is aluminum.

5. The system of claim 1 wherein the containers are optically clear, transparent, semi-transparent, or translucent.

6. The system of claim 5 wherein the containers are made of glass or plastic.

7. The system of claim 1 wherein the containers are tubes.

8. The system of claim 1 further comprising closures for each container.

9. The system of claim 8 wherein the closures are adapted to allow the addition or extraction of fluid components.

10. The system of claim 8 wherein the closures are adapted to be pierced by a device adapted to remove or add fluid from the container.

11. The system of claim 8 wherein the closures allow light to enter the container for optical inspection of the contents of the container.

12. The system of claim 1 which further comprises an automated means of sealing the containers.

13. The system of claim 1 wherein the plurality of containers comprises at least 24 containers.

14. The system of claim 1, wherein the experiment is a salt forming experiment.

15. The system of claim 1 further comprising a robotic system for moving the blocks through the system.

16. The system of claim 1 further comprising an environmental control enclosure.

17. The system of claim 1 wherein the compound-of-interest is an active pharmaceutical ingredient and the optional additional compound is a solvent or excipient.

18. The system of claim 1 wherein the experiment is a crystallization or precipitation experiment.

19. A method of obtaining a solid form of a compound-of-interest which comprises:

a) providing a system which comprises;

i) a block having a top surface, a bottom surface, and a plurality of holes for receiving the containers, wherein each hole has a top opening on the top surface and a bottom opening on the bottom surface, wherein the top opening is of a dimension sufficient to accommodate a container and the dimension of the bottom opening is of a dimension that will not accommodate the container;

ii) a plurality of containers held in the block; and

iii) a thermal processing system for heating and cooling multiple blocks simultaneously;

b) dispensing a controlled amount of a compound-of-interest and optionally one or more additional compounds in each of the containers;

c) optionally sealing the containers; and

d) placing the block in the thermal processing system for an amount of time.

20. The method of claim 19 wherein an anti-solvent is added to at least one of the containers.

21. The method of claim 19 wherein at least one of the containers is not sealed so that any volatile compounds or solvents it contains are allowed to evaporate.

22. The method of claim 19 wherein at least one of the containers contains a compound-of-interest and a solvent, and the compound-of-interest is exposed to heat, is contacted with an anti-solvent, and/or the solvent is allowed to evaporate.

23. The method of claim 19 wherein the solid form is a crystal.