Apparatus and method for high-throughput preparation, visualization and screening of compositions

• US 20030106492A1
• Filed: 09/06/2002
• Published: 06/12/2003
• Est. Priority Date: 09/07/2001
• Status: Abandoned Application

• Current Assignee: TransForm Pharmaceuticals, Inc. (Johnson & Johnson)
• Original Assignee: TransForm Pharmaceuticals, Inc. (Johnson & Johnson)
• Inventors: Gonzalez-Zugasti, Javier P., Cima, Michael J., Almarsson, Orn, Lemmo, Anthony V., McNulty, Christopher, Levinson, Douglas, Johnson, Alasdair Y., Morissette, Sherry Lynn
• Application Number:
  US10/235,554
• Publication Number:
  US 20030106492A1
• Time in Patent Office: Days
• US Class Current: 117/200
• 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 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01J 2219/00283 Reactor vessels with top opening
• CPC Class Codes: B01J 2219/00308 interchangeably mounted in racks or blocks
• CPC Class Codes: B01J 2219/0031 the racks or blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00333 Closures attached to the reactor vessels
• CPC Class Codes: B01J 2219/00335 Septa
• CPC Class Codes: B01J 2219/00344 Caps
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• 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 2001/4027 : evaporation leaving a concentrated sample
• CPC Class Codes: G01N 2021/651 : Cuvettes therefore
• 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 21/65 : Raman scattering
• 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
• CPC Class Codes: Y10T 117/10 : Apparatus
• CPC Class Codes: Y10T 117/1004 : with means for measuring, testing, or sensing
• CPC Class Codes: Y10T 117/1012 : with a window or port for visual observation or examination

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 processing samples and screening for solid forms of a compound-of-interest, which comprises:

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

b) a block made of a thermally conductive material having an array of holes, each hole having a top and a bottom, the top having an opening for receiving the removable container and the bottom having an access hole;

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

d) an imaging device for detecting solid forms.

2. The system of claim 1 wherein the imaging device comprises a CCD camera.

3. The system of claim 1 which further comprises a computer configured to recognize images of solids.

4. 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.

5. A method for the high-throughput processing and screening of samples, which comprises:

a) providing a system for processing a sample comprising;

i) removable containers; and

ii) a block having an array of holes, each hole having a top and a bottom, the top having an opening for receiving a container and the bottom having an access hole;

b) placing the containers in the holes;

c) dispensing a controlled amount of a compound-of-interest and optionally one or more additional compounds in each container to provide an array of samples;

d) processing the array; and

e) screening the samples for the presence or absence of solid forms using an imaging device.

6. The method of claim 5 wherein the compound-of-interest is an active pharmaceutical ingredient and the optional additional compound is a solvent or excipient.

7. The method of claim 5 wherein the screening comprises:

a) imaging the contents of the containers; and

b) analyzing the images for a desired experimental result.

8. The method of claim 5 which further comprises prescreening containers prior to the processing of the array.

9. The method of claim 8 wherein the prescreening comprises:

a) imaging the contents of the containers; and

b) analyzing the images for a desired experimental result.

10. The method of claim 5 which further comprising re-arraying the containers which contain the desired experimental results into an output block.

11. The method of claim 5 wherein processing comprises raising or lowering the temperature of containers in the array.

12. An automated high throughput method for screening for solid forms of a compound-of-interest, wherein the compound-of-interest is a biologically active small organic molecule, which comprises:

a) preparing an array of samples, each of which comprises the compound-of-interest and optionally one or more additional compounds;

b) processing the array so as to generate solid forms;

c) prescreening the array for solid formation using a digital imaging camera;

d) identifying samples with solid formations for further analysis;

e) rearranging and reprocessing samples with solids, and optionally repeating steps (b) to (d).

13. A method of evaluating experiments which comprises:

a) providing a system for evaluating experiments comprising;

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

ii) a block containing an array of holes for receiving the containers; and

iii) an imaging device;

b) positioning the block near the imaging device;

c) producing images of the contents of each of the containers;

d) analyzing the images for the presence of a desired experimental result; and

e) identifying containers with the desired experimental result.

14. The method of claim 13 wherein the contents of the containers are analyzed for birefringence.

15. The method of claim 13 wherein the contents of the containers are analyzed for the scattering of laser light.

16. The method of claim 13 wherein the contents of the containers are subjected to processing.

17. The method of claim 16, wherein the processing is heating, cooling, mixing, changing pH, changing pressure, changing the concentration of the compound-of-interest, or placing the compound-of-interest in contact with one or more additional compounds.

18. The method of claim 16 wherein the containers without the desired result are subjected to further processing.

19. The method of claim 13 wherein the identified containers having the desired experimental result are re-arrayed to an output block for further analysis.

20. The method of claim 13 wherein the compound-of-interest is an active pharmaceutical ingredient and the optional additional compound is a solvent, excipient, or additive.

21. The method of claim 13, wherein the experiment is a crystallization or precipitation experiment.