Methods of generating and screening for high free energy forms in capillaries

• US 6,642,060 B2
• Filed: 12/28/2000
• Issued: 11/04/2003
• Est. Priority Date: 12/28/2000
• Status: Expired due to Term

• Current Assignee: AMRI Americium, LLC, Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Original Assignee: SSCI, Inc., Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Morris, Kenneth R., Stahly, G. Patrick
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Gakh, Yelena G.
• Application Number:
  US09/752,788
• Publication Number:
  US 20020146842A1
• Time in Patent Office: 1,041 Days
• Field of Search: 436/174, 436/180, 436/177, 422/243, 422/245.1, 422/255, 422/258, 422/260
• US Class Current: 436/174
• CPC Class Codes: C30B 29/54 Organic 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 1/40 Concentrating samples
• CPC Class Codes: G01N 1/44 Sample treatment involving radiation, e.g. heat
• CPC Class Codes: G01N 2001/4027 evaporation leaving a concentrated sample
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/25875 Gaseous sample or with change of physical state

Abstract

A method for generating and isolating a high free energy form of a compound or a mixture of compounds comprises the steps of placing a sample in a capillary tube, solidifying the sample in the capillary tube, and isolating a high free energy form of the sample. A method for searching for a high free energy form of a sample comprises the steps of placing the compound or mixture in a capillary tube, generating a solid in the capillary tube, and determining whether a high free energy form of the sample was generated. The sample may be a compound or mixture.

Claims

1. A method of generating and screening for one or more high free energy forms of an organic compound, said method comprising the steps of:

disposing a non-solid sample of the compound in a plurality of capillary tubes;

solidifying the sample in the plurality of capillary tubes, whereby a plurality of solids is generated; and

determining whether one or more high free energy forms were generated using an analytical method selected from the group consisting of visual analysis, microscopic analysis, thermal analysis, diffraction analysis, and spectroscopic analysis.

2. The method of claim 1 wherein the solidifying step comprises crystallizing the sample.

3. The method of claim 1 wherein the solidifying step comprises the use of an antisolvent.

4. The method of claim 1 wherein the solidifying step is selected from the group consisting of solvent evaporation, antisolvent addition, gel diffusion and thin-layer deposition.

5. The method of claim 1, further comprising the step of preparing the sample from a supersaturated solution of at least one compound.

6. The method of claim 1, wherein said isolated high free energy form is stabilized within the capillary tube by adding a stabilizing agent.

7. The method of claim 6, wherein said isolated high free energy form is stable within the capillary tube for at least 24 hours.

8. The method of claim 1, further comprising the step of stabilizing the high free energy form for at least 24 hours essentially by maintaining the high free energy form in the capillary tube.

9. The method of claim 1, wherein the sample is placed in at least two sets of capillary tubes, and at least one set differs from at least one other set.

10. The method of claim 9, wherein the capillary tubes of said at least one set have a different inner diameter than the capillary tubes of said at least one other set.

11. The method of claim 9, wherein the sample is placed in at least four sets of capillary tubes, and each set differs from the other set with respect to the size or surface of the capillary tubes within said sets.

12. The method of claim 1, wherein said at least one capillary tube is coated with a substance on the interior of said tube.

13. The method of claim 1, wherein the step of determining whether the high free energy form was generated comprises generating data indicative of the relative free energy of the generated form and comparing said data to data relating to a known form.

14. The method of claim 1 wherein the high energy forms exhibit different colors.

15. The method of claim 1, further comprising identifying the high free energy forms by visual analysis.

16. The method of claim 1 wherein the microscopic analysis is electron microscopy.

17. The method of claim 1 wherein the diffraction analysis is x-ray diffraction.

18. The method of claim 1 wherein the spectroscopic analysis is infrared spectroscopy.

19. The method of claim 1 further comprising analyzing the known solid form to determine the free energy.

20. The method of claim 1, wherein the step of determining whether one or more high free energy forms were generated comprises determining whether a distribution of solid forms occurred.

21. The method of claim 1, wherein the step of determining whether a high free energy form was generated comprises thermal analysis.

22. The method of claim 21 wherein the thermal analysis is determine the melting points.

23. A method of generating and screening for one or more high free energy forms of an organic compound, said method comprising the steps of:

disposing a non-solid sample of the compound in a plurality of capillary tubes;

solidifying the sample in the plurality of capillary tubes, whereby a plurality of generated solids is generated;

determining whether one or more high free energy forms were generated using an analytical method selected from the group consisting of visual analysis, microscopic analysis, thermal analysis, diffraction analysis, and spectroscopic analysis;

determining the number of occurrences of each of said solid forms; and

assigning a relative free energy to each of said solid forms based on the number of occurrences, wherein a high free energy form is associated with a lower number of occurrences.

24. The method of claim 23 wherein the plurality comprises at least 10 capillary tubes.

25. The method of claim 24 wherein the plurality comprises at least 50 or more capillary tubes.

26. The method of claim 25 wherein the plurality comprises at least about 150 capillary tubes.