Sandwich arrays of biological compounds

• US 6,268,210 B1
• Filed: 02/17/1999
• Issued: 07/31/2001
• Est. Priority Date: 05/27/1998
• Status: Expired due to Fees

• Current Assignee: Callida Genomics, Inc. (SBH Genomics, Inc.)
• Original Assignee: Hyseq, Inc. (Arca Biopharma, Inc.)
• Inventors: Hauser, Brian, Drmanac, Radoje T., Baier, Joerg
• Primary Examiner(s): Jones, W. Gary
• Assistant Examiner(s): FORMAN, BETTY J
• Application Number:
  US09/251,303
• Time in Patent Office: 895 Days
• Field of Search: 422/50, 422/58, 435/287.2, 435/6, 435/288.4, 435/288.5, 435/287.3
• US Class Current: 435/288.5
• 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 2219/00542 Alphanumeric characters
• CPC Class Codes: B01J 2219/00547 Bar codes
• 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 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00626 Covalent
• 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 2219/00659 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 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 3/508 : rigid containers not provided for above
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 9/52 : Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes

Abstract

The present invention relates to spatially-addressable sandwich arrays of compounds, particularly biological compounds such as peptides and polynucleotide probes, and methods of making and using the same. The present invention also relates to a method and device for holding together the substrates of the sandwich array, more particularly, a clamping device for securely yet safely holding substrates of a sandwich array together during assembly, use, storage, and/or transport of the sandwich array.

Claims

1. A sandwich array comprising:

a first substrate comprising a spatially addressable array of biological compounds immobilized thereon;

a second substrate comprising a spatially addressable array of compounds immobilized thereon; and

a spacer disposed between the first and second substrates thereby forming one or more chambers between the substrates;

wherein the first and second substrates are positioned with respect to each other such that when an assay solution is applied to the sandwich array, the assay solution contacts at least one compound from the first array and at least one compound from the second array.

2. The sandwich array of claim 1, wherein the substrates and the spacer form a plurality of chambers.

3. The sandwich array of claim 1, wherein at least one of the substrates comprises a glass slide or a plastic sheet.

4. The sandwich array of claim 1, wherein the arrays are two-dimensional arrays.

5. The sandwich array of claim 1, wherein the immobilized compounds are polynucleotides.

6. The sandwich array of claim 5, wherein the polynucleotides are covalently attached to the substrate, optionally by way of a linker.

7. The sandwich array of claim 6, wherein the polynucleotide is covalently attached via a terminal nucleotide.

8. The sandwich array of claim 1, wherein each array comprises 10 to 10⁶ unique compounds.

9. The sandwich array of claim 6, wherein each immobilized polynucleotide is independently 6 to 20 nucleotides in length.

10. The sandwich array of claim 6, wherein each immobilized polynucleotide is 6-20 nucleotides is length.

11. The sandwich array of claim 1, wherein at least one of the arrays comprises all possible polynucleotides 6-10 nucleotides in length.

12. The sandwich array of claim 1, wherein at least one of the arrays comprises a subset of polynucleotides 6-10 nucleotides in length.

13. The sandwich array of claim 5, wherein at least one spatial address has immobilized thereto a mixture of polynucleotides.

14. The sandwich array of claim 13, wherein the mixture is of the formula:

N_xB_yN_z, wherein N represents any of the four bases and varies for the polynucleotides in a given mixtures, B represents any of the four bases but is the same for each of the polynucleotides in a given mixture, and x, y, and z are integers.

15. The sandwich array of claim 13, wherein each spatial address of at least one array immobilized thereto a mixture of polynucleotides of the formula:

N_xB_yN_z, wherein N represents any of the four bases and varies for the polynucleotides in a given mixtures, B represents any of the four bases but is the same for each of the polynucleotides in a given mixture, and x, y, and z are integers.

16. The sandwich array of claim 1 further comprising:

a first clamping bar comprising first and second arms spaced apart when in a neutral configuration to permit insertion of said first and second substrates there between, said clamping bar arms being biased together to clamp said first and second substrates there between to maintain said first and second substrates in a desired position with respect to each other.

17. The sandwich array of claim 16, wherein said first and second substrates and said clamping bar have the same widths.

18. The sandwich array of claim 16, wherein said first and second substrates have a first height and said clamping bar arms have a second height, said second height being half of said first height.

19. The sandwich array of claim 16, wherein:

said first and second substrates have bottom edges and top edges,

said first clamping bar is positioned over said bottom edges of said first and second substrates; and

said sandwich array further comprises a second clamping bar with first and second clamping arms positioned over said top edges of said first and second substrates.

20. The sandwich array of claim 19, wherein:

said first and second substrates have a first height;

said arms of said first and second clamping bars have a second height; and

said second height is half of said first height;

whereby said substrate is covered by said arms of said first and second clamping bars when said first and second clamping bars are positioned respectively over said top and bottom edges of said first and second substrates.

21. The sandwich array of claim 1, wherein said biological compounds are synthetic polynucleotides.