Spotting pattern for placement of compounds in an array

• US 20040091941A1
• Filed: 08/08/2003
• Published: 05/13/2004
• Est. Priority Date: 08/13/2002
• Status: Abandoned Application

• Current Assignee: Discovery Partners International, Inc. (Infinity Pharmaceuticals, Inc.)
• Original Assignee: Discovery Partners International, Inc. (Infinity Pharmaceuticals, Inc.)
• Inventors: Ewing, William R., Neeper, Robert K., Affleck, Rhett L., Lillig, John E.
• Application Number:
  US10/638,275
• Publication Number:
  US 20040091941A1
• Time in Patent Office: Days
• US Class Current: 435/7.1
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals

Abstract

A plurality of samples of different substances are tested for their ability to enhance or inhibit a biological process. The samples are deposited on a supporting surface, such as a ChemCard, in an array comprising at least two dots of each sample, wherein at least one of the dots of each sample is at least a predetermined distance from at least one of the dots of each of the plurality of samples. One or more assay reagents in a gel sheet, for example, are then brought in contact with the compounds and reactions with certain of the compounds are evident as the active compounds diffuse into the one or more assay reagents. The concept of having unique neighbors for each occurrence of a dot allows the definitive correlation of active compounds with the dot (and the compound) that caused the biological activity.

Claims

1. An array of n unique materials, each of which appears in the array at least two times and which has a plurality of neighboring materials, wherein for each of the n materials in the array, the neighboring materials in one occurrence of the material are different from the neighboring materials of all other occurrences of the material, wherein n is greater than 25:

2. The array of claim 1 wherein said materials are considered neighboring materials of a particular material if they are within a predetermined radius around said particular material.

3. The array of claim 2 wherein said predetermined radius is in the range of about 1 mm to 1 cm.

4. The array of claim 2 wherein said predetermined radius is about 3 mm.

5. The array of claim 1 wherein said materials are considered neighboring materials of a particular material if they are within a predetermined dot-pitch distance from said particular material.

6. The array of claim 4, wherein said predetermined dot-pitch distance is 1 dot pitch.

7. The array of claim 4, wherein said predetermined dot-pitch distance is between 1 and 5 dot pitch distances.

8. The array of claim 4, wherein said predetermined dot-pitch distance is greater than 5 dot pitch distances.

9. The array of claim 1, wherein n is greater than 300.

10. The array of claim 1, wherein n is greater than 4000.

11. The array of claim 1, wherein n is greater than 9000.

12. The array of claim 1, further in combination with a planar porous assay matrix, such that a surface of the porous assay matrix is in contact with each of the n materials of the array in such a manner that the materials can diffuse into the porous assay matrix.

13. The array of claim 12 further comprising a substantially non porous assay matrix in contact with said porous assay matrix and containing at least one assay reagent capable of interacting with any of the materials on the porous assay matrix.

14. The array of claim 12, in which the porous assay matrix contains at least one assay reagent capable of interacting with any of the materials in the array that is active in a test assay, wherein the test assay displays positive results (if any) within a time period t, during which time t the materials diffuse within the porous assay matrix to form a spot of diameter d, and wherein “

neighboring materials”

are within a predetermined distance of the center of the spot.

15. The array of claim 12 further comprising a second porous assay matrix in contact with said porous assay matrix and containing at least one assay reagent capable of interacting with any of the materials in the array that is active in a test assay, wherein the test assay displays positive results (if any) within a time period t, during which time t the materials diffuse within the porous assay matrix and the second porous assay matrix to form a spot of diameter d on the second porous assay matrix and wherein “

neighboring materials”

are within a predetermined distance of the center of the spot.

16. The array of claim 12, wherein “

neighboring materials”

include materials within a radius of about 3.5 mm.

17. A method of testing a plurality of samples of different substances for their ability to enhance or inhibit a biological process, the method comprising:

providing an array of at least two dots of each of said samples on a planar matrix such that each of said at least two dots is centered at its own distinct site, wherein at least one of said at least two dots of each of said samples is at least a predetermined distance from at least one of said dots of each of said plurality of samples;

transferring the array from the planar matrix into a uniformly dispersed assay reagent; and

observing the interaction of each of said substances with said assay reagent and correlating said interaction with an ability of each of said substances to enhance or inhibit said biological process.

18. The method of claim 17, further comprising:

providing a second array of at least two dots of each of said samples on a second planar matrix such that each of said at least two dots is centered at its own distinct site, wherein at least one of said at least two dots of each of said samples is at least a predetermined distance from at least one of said dots of each of said plurality of samples, and a pattern of placement of said dots on said second array is different than a pattern of placement of said dots on said first array;

placing said uniformly dispersed assay reagent on said second planar matrix; and

observing the interaction of each of said substances with said assay reagent and correlating said interaction with an ability of each of said substances to enhance or inhibit said biological process.

19. The method of claim 17, further comprising placing a second uniformly dispersed assay reagent on said uniformly dispersed assay reagent, observing a second interaction of each of said substances with said second uniformly dispersed assay reagent, and correlating said second interaction with an ability of each of said substances to enhance or inhibit said biological process.

20. The method of claim 19, further comprising placing a third uniformly dispersed assay reagent on said second uniformly dispersed assay reagent, observing a third interaction of each of said substances with said third uniformly dispersed assay reagent, and correlating said third interaction with an ability of each of said substances to enhance or inhibit said biological process.

21. The method of claim 17, wherein said planar matrix comprises a plurality of alignment dots configured to diffuse into said uniformly dispersed assay reagent;

said alignment dots on said uniformly dispersed assay reagent providing reference points for aligning said uniformly dispersed assay reagent with said planar matrix so that each particular interaction is correlated with each particular substance from which each interaction resulted.

22. The method of claim 20, wherein said planar matrix comprises a plurality of alignment dots configured to diffuse into said uniformly dispersed assay reagent, said second uniformly dispersed assay reagent, and said third uniformly dispersed assay reagent;

said alignment dots on said third uniformly dispersed assay reagent providing reference points for aligning said third uniformly dispersed assay reagent with said planar matrix so that each particular third interaction is correlated with each particular substance from which each third interaction resulted.

23. A method of testing a plurality of samples of different substances for their ability to enhance or inhibit a biological process, the method comprising:

depositing in an array at least one dot of each of said samples onto a plurality of planar matrixes such that each of said at least one dot is centered at its own distinct site, wherein at least one of said dots of each of said samples is at least a predetermined distance from at least one of said dots of each of said plurality of samples;

transferring the array of samples from the plurality of planar matrixes into a uniformly dispersed assay reagent; and

observing the interaction of each of said substances with said assay reagent and correlating said interaction with an ability of each of said substances to enhance or inhibit said biological process.

24. A system for creating an array of sample compounds comprising:

a relatively flat carrier configured to support a plurality of samples; and

a dispensing mechanism configured to dispense at least two dots of each of said plurality of samples of different compounds on said flat carrier such that each of said at least two dots of each of said plurality of samples has a different set of neighboring compounds within a predetermined distance.

25. The system of claim 24, wherein said samples are chemically bonded to said relatively flat carrier.

26. The system of claim 24, wherein said samples are free to diffuse from said relatively flat carrier.

27. The system of claim 24, wherein said dispensing mechanism simultaneously dispenses a portion of said plurality of samples in a first relative orientation on at least two locations on said flat container.

28. The system of claim 27, wherein none of said samples in said portion of said plurality of samples are neighboring compounds.

29. The system of claim 27, wherein said portion of said plurality of samples comprises twelve samples.

30. The system of claim 24, wherein said flat carrier comprises a plurality of alignment dots configured to diffuse into a material brought into contact with the flat carrier and provide reference points for aligning said material brought into contact with the flat carrier with said flat carrier so that each particular diffused dot is correlated with each particular dot on said flat carrier from which said diffused dot resulted.

31. An array of samples in which each sample appears at least twice and there are at least 768 dispenses of groups of 12 samples.

32. An array of samples in which each sample appears at least twice and there are at least 4608 samples, wherein the array comprises 144 columns and 64 rows and the samples are arranged substantially according to the relative coordinates shown in Table 1.

33. A method for performing an assay, comprising:

providing a substantially planar substrate having an array of at least two dots of each of a plurality of test materials, wherein each of said dots has a plurality of neighboring test materials and is placed such that the neighboring materials in one occurrence of the material are different from the neighboring materials of all other occurrences of the material; and

transferring the array of test materials into a uniformly-dispersed assay reagent that participates in indicating which of the test materials are active in the assay while maintaining the relative positioning of the test materials vis-a-vis each other.

34. The method of claim 33, wherein transferring the array of test materials comprises contacting the array with the assay reagent and allowing the materials to diffuse into the assay reagent.

35. The method of claim 33, wherein transferring the array of test materials comprises contacting the array with a non-porous surface carrying said uniformly dispersed assay reagent and allowing the materials to have surface reactions with said assay reagent.

36. The method of claim 33, wherein transferring the array comprises transferring the materials into a first matrix, and then contacting the first matrix with the assay reagent.

37. The method of claim 33, wherein transferring the array comprises contacting the array with a gel into which the materials can diffuse.

38. The method of claim 33, wherein the uniformly-dispersed assay reagent is surface bound on a non-porous surface so that transferring the array comprises contacting the array with said non-porous surface.

39. An algorithm for formulating an array S having A elements (S_A), wherein the value of each element S_A represents a dispense position on a card, wherein a dispensing mechanism dispenses a plurality of compounds at each dispense position, the algorithm comprising:

(a) setting each of the A elements of the array S to a random, non-repeating value from 1- A, wherein each S_A is set to a preliminary dispense position;

(b) providing an array C having A elements (C_A), wherein each of said A elements of the array C comprises J representations of compounds;

(c) setting a counter x to zero;

(d) incrementing x by 2;

(e) determining whether each of said J compounds in C_X satisfy a placement constraint with respect to certain other compounds in the array C;

(f) if step (e) determines that there in a constraint violation with one or more of said J compounds in C_x;

(1) decrementing x by 2;

(2) determining if there are remaining dispense positions that have not been tested in S_X against the constraints of step (e);

(3) if step (2) determines that there are no remaining dispense positions that have not been tested in S_X against the constraints of step (e), repeating steps (1) and (2);

(4) changing the value of S_X to a remaining dispense position that has not been tested in S_X against the constraints of step (e);

(5) return to step (e);

(g) if step (e) determines that there is not a constraint violation with any of said J compounds in C_X, return to step (d).

40. The array of claim 39, wherein C_x and C_x+1 are equal and wherein x=any odd integer<

A.

41. A method for creating an array of a plurality of materials, each material occurring at least twice within the array and having different neighboring materials in each occurrence, the method comprising:

(a) creating a candidate arrangement of materials containing pairs of n said materials in a spatial relationship;

(b) testing whether a first occurrence and a second occurrence of each of said materials have different neighbors;

(c) if the criteria of (b) is not satisfied, changing said spatial relationship of at least some of n said materials; and

(d) repeating steps (b) and (c) until the criteria of (b) is satisfied.

42. The method of claim 41, wherein said candidate arrangement created in step (a) comprises each of said plurality of materials such that when the criteria of (b) is satisfied, the array is complete.

43. The method of claim 41, wherein said candidate arrangement created in step (a) comprises a portion of said plurality of materials, the method further comprising:

(e) expanding said candidate arrangement of materials by increasing n by a predetermined number;

(f) repeating steps (b)-(e) until a final candidate arrangement is created containing each of said plurality of materials.

44. The method of claim 43, wherein said changing said spatial relationship of at least some of n said materials comprises:

determining whether a placement of a nth material in every open location within said candidate arrangement fails to satisfy the criteria of (b);

decrementing n if said nth material fails to satisfy the criteria of (b) in every open location within said candidate arrangement; and

changing said spatial relationship of at least some of n said materials.

45. A method for formulating an array S having A elements (S_A), wherein the value of each element of S_A represents a dispense position for one or more materials on a substrate, wherein each material occurs at least two times (C₁ and C₂) in S_A, with the constraint that when the distance from one of C₁ and C₂ to any occurrence of any other material is less than or equal to a minimum value D, then the distance from the other of C₁ and C₂ to any occurrence of such other material is greater than D, comprising:

tentatively assigning a plurality of elements to S_A;

for each first occurrence of a material, determining a set of Q materials that are within a distance of D;

for each second occurrence of a material, ascertaining whether each of the Q materials are within a distance of D and, if so, changing the location of at least one material.

46. A method for formulating an array containing pairs of materials, wherein each member of the pair has different neighboring materials than the other member of the pair, comprising:

(a) tentatively assigning a plurality of materials to array locations;

(b) testing to ascertain whether a first member of a pair has different neighboring materials than a second member of a pair, and if not, then

(c) sequentially repeating step (a) with at least one altered material location and repeating step (b), until each member of each pair has different neighboring materials.

47. The method of claim 46, wherein the testing step comprises measuring the distance from the first member of the pair to the tentative array locations of some or all of the other materials in the array, measuring the distance from the second member of the pair to the tentative array locations of some or all of the other materials in the array, and performing a comparison of data resulting from the measurements.

48. The method of claim 47, wherein the data resulting from the measurements comprises a first set of materials located within a predetermined distance of the first member of the pair.

49. The method of claim 48, wherein the data resulting from the measurements further comprises a second set of materials located within a predetermined distance of the first member.

50. A method of creating an array of sample compounds comprising:

providing a relatively flat carrier configured to support a plurality of samples; and

dispensing at least two dots of each of said plurality of samples of different compounds on said flat carrier such that each of said at least two dots of each of said plurality of samples has a different set of neighboring compounds within a predetermined distance.