Array compositions and methods of making same

• US 6,770,441 B2
• Filed: 08/16/2001
• Issued: 08/03/2004
• Est. Priority Date: 02/10/2000
• Status: Expired due to Term

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Carlson, Edward, Coblentz, Kenneth D., Dickinson, Todd
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US09/931,271
• Publication Number:
  US 20020102578A1
• Time in Patent Office: 1,083 Days
• Field of Search: 435/6, 435/7.1, 435/283.1, 435/287.2, 435/287.8, 435/288.2, 435/288.3, 435/288.4, 435/288.5, 422/68, 422/102
• US Class Current: 435/6.11
• 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 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00628 Ionic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00662 Two-dimensional arrays within two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 : Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0654 : Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0822 : Slides
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates

Abstract

The invention relates to sensor compositions comprising a composite array of individual arrays, to allow for simultaneous processing of a number of samples. The invention further provides methods of making and using the composite arrays. The invention further provides a hybridization chamber for use with a composite array.

Claims

1. An array composition comprising:

(a) a rigid support;

(b) a molded layer with at least a first assay location comprising discrete sites, wherein each of said discrete sites is configured to hold a single microsphere, and wherein said molded layer is adhered to said rigid support;

(c) an adhesive layer disposed between said rigid support and said molded layer; and

(d) a population of microspheres comprising at least a first and a second subpopulation, wherein said first subpopulation comprises a first bioactive agent and said second subpopulation comprises a second bioactive agent wherein said microspheres are randomly distributed on said sites.

2. An array composition according to claim 1, wherein said sites are separated by a distance of at least about 5 μ

m.

3. An array composition according to claim 1, wherein said sites are separated by a distance of at most about 100 μ

m.

4. An array composition according to claim 1, wherein said rigid support is formatted to the dimensions of a microscope slide.

5. An array composition according to claim 1, wherein said molded layer comprises at least a second assay location comprising discrete sites.

6. An array composition according to claim 5, wherein said first and second assay locations are separated by a fluid barrier.

7. An array composition according to claim 6, wherein said fluid barrier is a physical fluid barrier.

8. An array composition according to claim 7, wherein said physical fluid barrier comprises a material that is added to said molded layer.

9. An array composition according to claim 8, wherein said molded layer comprises said physical fluid barrier.

10. An array composition according to claim 6, wherein said fluid barrier comprises a physico-chemical surface coating.

11. An array composition according to claim 1, wherein said first and second bioactive agents comprise nucleic acids.

12. An array composition according to claim 1, wherein said first and second bioactive agents comprise proteins.

13. A method for making an array composition containing at least a first assay location having discrete sites comprising the steps of:

(a) contacting a surface of a template structure, said surface comprising one or more sets of projections, with a moldable material;

(b) removing said moldable material from said surface of said template structure, whereby said removed moldable material forms a molded layer with at least a first assay location comprising discrete sites, wherein each of said discrete sites is configured to hold a single microsphere;

(c) applying a layer of adhesive to adhere said molded layer to a rigid support in order to maintain the molded layer in a planar configuration; and

(d) randomly distributing microspheres on said molded layer such that individual discrete sites comprise microspheres, wherein said microspheres comprise at least a first and a second subpopulation, wherein said first subpopulation comprises a first bioactive agent and said second subpopulation comprises a second bioactive agent.

14. The method according to claim 13, wherein the projections in said one or more sets of projections are separated by a distance of at least about 5 μ

m.

15. The method according to claim 13, wherein the projections in said one or more sets of projections are separated by a distance of at most about 100 μ

m.

16. The method according to claim 13, wherein said template structure is cylindrical, and steps (a) and (b) are carried out by a continuous process of rolling said cylindrical template structure wherein at a first portion of the cylinder, the cylinder is contacted with a moldable material and at a second portion of the cylinder, solidified moldable material is removed from the cylinder as a molded layer.

17. The method according to claim 13, wherein said molded layer is flexible.

18. The method according to claim 17, wherein prior to step (c), said flexible molded layer is stored in rolled form.

19. The method according to claim 13, wherein said molded layer comprises at least a second assay location comprising discrete sites.

20. The method according to claim 19, wherein said first and second assay locations are separated by a fluid barrier.

21. The method according to claim 19, further comprising the step of adding a fluid barrier to said molded layer, which fluid barrier separates said first and second assay locations.

22. The method according to claim 13, wherein said rigid support is formatted to at least one dimension of a microscope slide.

23. The method according to claim 13, further comprising a step of applying a releasing agent to said surface of said template structure prior to said contacting step.

24. The method according to claim 13, further comprising the step of coating the back surface of said molded layer with an adhering agent.

25. An array composition comprising:

(a) a molded layer having an upper surface and a planar lower surface, wherein said upper surface comprises a first assay location comprising discrete sites, each of which is configured to hold a single microsphere;

(b) a rigid support adhered to said planar lower surface and adapted to maintain said molded layer in a planar configuration; and

(c) a population of microspheres comprising at least a first and a second subpopulation, wherein said first subpopulation comprises a first bioactive agent and said second subpopulation comprises a second bioactive agent, and wherein said microspheres are randomly distributed on said sites.

26. An array composition according to claim 25, wherein said sites are separated by a distance of at least about 5 μ

m.

27. An array composition according to claim 25, wherein said sites are separated by a distance of at most about 100 μ

m.

28. An array composition according to claim 25, wherein said molded layer comprises at least a second assay location comprising discrete sites.

29. An array composition according to claim 28, wherein said first and second assay locations are separated by a fluid barrier.

30. An array composition according to claim 29, wherein said fluid barrier is a physical fluid barrier.

31. An array composition according to claim 30, wherein said physical fluid barrier comprises a material that is added to said molded layer.

32. An array composition according to claim 31, wherein said molded layer comprises said physical fluid barrier.

33. An array composition according to claim 29, wherein said fluid barrier comprises a physico-chemical surface coating.

34. An array composition according to claim 25, wherein said first and second bioactive agents comprise nucleic acids.

35. An array composition according to claim 25, wherein said first and second bioactive agents comprise proteins.

36. An array composition according to claim 25, wherein said moldable layer is between 50 μ

m-1 mm in thickness.

37. An array composition according to claim 25, wherein said moldable layer is approximately 1 mm in thickness.

38. An array composition according to claim 25, wherein the rigid structure has optical properties.

39. An array composition according to claim 38, wherein the optical properties are selected from the group consisting of:

having low autofluorescence, being transparent, being selectively transparent, being absorptive, being selectively absorptive, being opaque and being reflective.

40. An array composition according to claim 25, wherein the rigid support is composed of a material selected from the group consisting of:

aluminum, iron, steel, an alloy, a ceramic, fiberglass, silicon, semiconductor materials, glass, rigid plastics, and rigid polymers.