Rapid X-ray diffraction screening method of polymorph libraries created in multi-well plates

• US 6,507,636 B1
• Filed: 02/10/2000
• Issued: 01/14/2003
• Est. Priority Date: 02/10/2000
• Status: Expired due to Fees

• Current Assignee: Freeslate Inc. (Unchained Labs Inc.)
• Original Assignee: Studiengesellschaft Kohle MBH
• Inventors: Lehmann, Christian W.
• Primary Examiner(s): Kim, Robert H.
• Assistant Examiner(s): Yun, Jurie
• Application Number:
  US09/501,634
• Time in Patent Office: 1,069 Days
• Field of Search: 378/73, 378/79, 378/208
• US Class Current: 506/12
• CPC Class Codes: B01J 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01L 2300/168 Specific optical properties, e.g. reflective coatings
• CPC Class Codes: B01L 2300/185 using a liquid as fluid
• CPC Class Codes: B01L 3/50853 with covers or lids
• 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: G01N 23/20 by using diffraction of the radiation by the materials, e.g. for investigating crystal structure; by using scattering of the radiation by the materials, e.g. for investigating non-crystalline materials; by using reflection of the radiation by the materials

Abstract

Method and device for rapid characterization of arrays of crystalline, polycrystalline or amorphous materials; in particular for the formation and X-ray diffraction analysis of polymorph libraries and the discovery of new crystal forms. According to one aspect, a multi-well plate comprising a masking plate with an array of openings and a removable base plate is used to crystallize precipitates. X-ray diffraction analysis is performed by scanning an X-ray beam over the base plate and recording diffractograms of the crystalline precipitates.

Claims

1. A method for characterizing crystalline, polycrystalline or amorphous materials in an array of said materials comprising:

a) providing a multi-well plate comprising;

i) a base plate; and

ii) a masking plate with an array of openings;

wherein said base plate is separable from said masking plate;

b) forming said materials through crystallization or precipitation, on said multi-well plate so that each material is located in a predefined area of said base plate;

c) separating said base plate from said masking plate; and

d) characterizing said materials using X-ray diffraction, analyzing each predefined location of said array in subsequent steps directly on the base plate.

2. The method of claim 1, wherein said material consists of a single chemical compound, and wherein the conditions of crystallization or precipitation are varied depending on the position of the predefined area on the base plate.

3. The method of claim 2, wherein the single chemical compound is an organic compound or natural product.

4. The method of claim 2, wherein the single chemical compound is a pharmaceutical drug substance.

5. The method of claim 1, wherein the said material found on the base plate is placed in reflection geometry into the X-ray beam of an X-ray diffractometer and is moved by means of a translation mechanism into the X-ray beam.

6. The method of claim 1, wherein the said material found on the base plate is placed in transmission geometry into the X-ray beam of an X-ray difractometer and is moved by means of a translation mechanism into the X-ray beam.

7. A multi-well plate for the formation and X-ray diffractometric analysis of an array of crystalline, polycrystalline or amorphous materials comprising:

a) a base plate; and

b) a masking plate with an array of openings;

said base plate being separable from aid masking plate.

8. The multi-well plate of claim 7, wherein the masking plate is made from metal.

9. The multi-well plate of claim 7, further comprising channels connecting adjoining openings pairwise in such way to enable an exchange of gas but not liquid between said openings.

10. The multi-well plate of claim 7, wherein the openings are coated with a chemically inert polymer, or wherein said openings are lined with chemically inert polymer sleeves.

11. The multi-well plate of claim 10, wherein said chemically inert polymer is polytetrafluoroethylene.

12. The multi-well plate of claim 7, wherein the base plate is made from a single crystal plate.

13. The multi-well plate of claim 12, wherein the single crystal plate is made from silicon or quartz.

14. The multi-well plate of claim 7, wherein the base plate is made from an optically transparent plate of sapphire.

15. The multi-well plate of claim 7, wherein the base plate is made from a polymer film which is transparent for X-rays with a wavelength in the range between 0.45 and 2.5 Å

, and which is chemically resistant to organic solvents and water.

16. The multi-well plate of claim 15, wherein the polymer film is made from polyacetate with a thickness between 0.1 μ

m and 100 μ

m.

17. The multi-well plate of claim 7, further comprising a pressurising plate with an array of openings matching the pattern of the openings of the masking plate, wherein said pressurising plate is connected removably to the multi-well plate assembly.

18. The multi-well plate of claim 7, further comprising one or more connectors for fitting heat-exchangers to the masking plate.

19. The multi-well plate of 18, wherein said heat-exchangers comprise metal rods through which a liquid flows.