Rapid identification of conditions, compounds, or compositions that inhibit, prevent, induce, modify, or reverse transitions of physical state

• US 7,108,970 B2
• Filed: 11/27/2001
• Issued: 09/19/2006
• Est. Priority Date: 01/07/2000
• Status: Expired due to Fees

• Current Assignee: TransForm Pharmaceuticals, Inc. (Johnson & Johnson)
• Original Assignee: TransForm Pharmaceuticals, Inc. (Johnson & Johnson)
• Inventors: Levinson, Douglas
• Primary Examiner(s): Wang, Andrew
• Assistant Examiner(s): Epperson, Jon D.
• Application Number:
  US09/994,585
• Publication Number:
  US 20020098518A1
• Time in Patent Office: 1,757 Days
• Field of Search: 435/6, 435/DIG.2, 435/DIG.9
• US Class Current: 435/6.11
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00484 by shaking, vibrating or oscillating of the reaction vessels
• CPC Class Codes: B01J 2219/00486 by sonication or ultrasonication
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00698 Measurement and control of process parameters
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00756 Compositions, e.g. coatings, crystals, formulations
• CPC Class Codes: C12Q 1/18 Testing for antimicrobial activity of a material
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals

Abstract

The invention concerns arrays comprising hundreds, thousands, to hundreds of thousands of samples and methods for screening thereof. These methods are useful to optimize, select, and discover compounds, compositions, or conditions that prevent, inhibit, induce, modify, or reverse physical-state transitions, particularly in-vivo physical-state transitions relating to disease causing processes. Such compounds, compositions, or conditions can be exploited to treat (e.g., reverse) or prevent the disease itself, the cause of the disease, or the symptoms of the disease.

Claims

1. A method of screening an array of at least 96 samples to identify conditions, compounds, or compositions that inhibit or prevent transitions of physical state comprising:

(a) preparing and identifying an array of at least 96 samples in tubes and support plates or in sample well plates and dispensing a liquid medium, a disease-causing substance comprising crystallized calcium oxalate in liquid form, salts of citric acid and one or more additional components into sample tubes or sample wells with an automated distribution mechanism, and wherein each sample differs with respect to the identity of one or more of the additional components;

(b) processing one or more of the samples to induce crystallization, precipitation or deposition of the disease causing substance, said processing comprising the addition of one or more additional components;

(c) analyzing the processed samples to detect the induction of said crystallization, precipitation or deposition using polarized light analysis and Raman spectroscopy; and

(d) selecting those processed samples that exhibit inhibition or prevention of a transition in physical state.

2. The method of claim 1, comprising the addition of said samples to tubes in a support plate.

3. The method of claim 2, wherein said tubes are glass tubes and said support plate is a metal support plate.

4. The method of claim 1, comprising sealing said tubes with a cap.

5. The method of claim 4, wherein said cap is pierced with a standard syringe needle and fluid aspirated through the syringe tip to remove solvent from the sample.

6. The method of claim 1, wherein said array comprises at least 1000 samples.

7. The method of claim 1, further comprising the generation of a work list for instructing an automated distribution mechanism to prepare said array of samples.

8. The method of claim 1, wherein said sample contains less than 1 milligram of said disease-causing substance.

9. The method of claim 6, comprising the piercing of said cap and aspiration of medium from said samples.

10. The method of claim 1, wherein said one or more of the additional components the is a small molecule.

11. The method of claim 1, wherein said array comprises at least 1 sub-array.

12. The method of claim 1, wherein said array comprises at least 1 sub-array with at least 24 samples.

13. The method of claim 1, wherein the processed samples are analyzed to detect a solid or an absence of a solid.

14. The method of claim 13, wherein a detected solid is analyzed to determine if the solid is amorphous or crystalline.

15. The method of claim 1, wherein at least about 100 samples are screened per day.

16. The method of claim 1, wherein at least about 1000 samples are screened per day.

17. The method of claim 1, wherein said array comprises sub-arrays, and wherein an individual sample within a sub-array is subjected to processing methods that are different from the processing methods to which another sample within the sub-array is subjected.

18. The method of claim 17, wherein said individual sample is subjected to processing methods comprising adding one or more additional components.

19. The method of claim 1, wherein said array comprises sub-arrays, and wherein an individual sub-array is subjected to processing methods that are different from the processing methods to which another sub-array is subjected.

20. The method of claim 19, wherein said individual sub-array is subjected to processing methods comprising adding one or more additional components.

21. The method of claim 1, wherein the amount of said disease-causing substance in each sample is less than about 1 milligram.

22. The method of claim 1, wherein the amount of said disease-causing substance in each sample is less than about 100 micrograms.

23. The method of claim 1, wherein the amount of said disease-causing substance in each sample is less than about 100 nanograms.

24. The method of claim 1, wherein each sample has a total volume between 5–

500 μ

l.

25. The method of claim 1, wherein each sample has a total volume between 10–

200 μ

l.