Micro arrays with structured and unstructured probes

• US 7,094,537 B2
• Filed: 04/30/2002
• Issued: 08/22/2006
• Est. Priority Date: 04/30/2002
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Delenstarr, Glenda C., Leproust, Eric M., Hirschberg, David L.
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US10/136,773
• Publication Number:
  US 20030203369A1
• Time in Patent Office: 1,575 Days
• Field of Search: 435/6, 435/7.1, 435/174, 435/283.1, 435/287.2, 435/288.7, 536/23.1, 530/300
• 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 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00549 2-dimensional
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential 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 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00626 Covalent
• 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 2219/00662 Two-dimensional arrays within two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 30/04 : by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 : for creating libraries

Abstract

The invention provides an apparatus and method for determining a signal produced by a micro array device. The apparatus provides an unstructured probe and structured probe. The unstructured probe binds to a target and provides a first signal that can be compared to a second signal produced by a structured probe. A more accurate level of intensity of the first signal can be determined by comparing to the second signal produced by the structured probe. A method for determining a more accurate level of signal intensity produced from the unstructured probes bound to the target is also disclosed.

Claims

1. A micro array for binding a target, comprising:

(a) a substrate surface;

(b) at least one feature of unstructured probes attached to said substrate surface for binding to said substrate surface for binding to said target and providing a first signal;

(c) nucleic acid structured probes attached to at least a portion of an interfeature area of said substrate surface in a manner that prevents binding of said target to said interfeature areas of said substrate surface, wherein said structured probes are selected from the group consisting a pseudo knot, stem-loops, bulges, hairpin, t RNA, triplex, and quadriplex and provide a second signal, and

(d) a light source for providing excitation of said unstructured and structured probes wherein said at least one feature of unstructured probes provides said first signal and said structured probes provides said second signal and wherein said first signal produced by said at least one feature of unstructured probes can be compared to said second signal produced by said structured probes.

2. A micro array as recited in claim 1, wherein said unstructured probe is a biomolecule.

3. A micro array as recited in claim 2, wherein said biomolecule is selected from the group consisting of a protein, an amino acid, an oligonucleotide, a peptide, a nucleotide, a carbohydrate, a polysaccharide, and a lipid.

4. A micro array as recited in claim 1, wherein the unstructured probe is labeled and produces said first signal.

5. A micro array as recited in claim 1, wherein the target is labeled and produces a first signal.

6. A micro array as recited in claim 1, wherein said light source is a luminescent light.

7. A micro array as recited in claim 6, wherein said luminescent source is selected from the group consisting of a fluorescent light, phosphorescent light, and a bioluminescent light.

8. A micro array as recited in claim 1, wherein said structured probe is self annealing.

9. A micro array as recited in claim 1, wherein said structured probe can fold back on itself to prevent annealing with said target.

10. A micro array as recited in claim 1, wherein said target is a biomolecule.

11. A micro array as recited in claim 10, wherein said target is selected from the group consisting of a protein, an amino acid, an oligonucleotide, a peptide, a nucleotide, a carbohydrate, a polysaccharide, and a lipid.

12. A micro array for binding a target, comprising

(a) a substrate surface;

(b) at least one feature of nucleic acid unstructured probes attached to said substrate surface for binding to said target and providing a first signal;

(c) nucleic acid structured probes comprising a nucleic acid that folds back on itself and self anneals attached to at least a portion of an interfeature area of said substrate surface and wherein said nucleic acid structured probes prevent binding of said target to said interfeature areas of said substrate surface and provide a second signal.

13. A micro array system comprising:

(a) a micro array for binding a target;

(i) at least one feature of unstructured probes attached to said substrate surface for binding a target and providing a first signal,

(ii) nucleic acid structured probes comprising a nucleic acid that folds back on itself and self anneals attached to at least a portion of an interfeature area of said substrate surface and wherein the nucleic acid structured probes prevent binding of said target to said interfeature areas of said substrate surface and provide a second signal; and

(b) a light source for providing excitation to of said unstructured and structured probes.

14. A micro array system as recited in claim 13, wherein said light source is a luminescent light.

15. A micro array system as recited in claim 14, wherein said luminescent source is selected from the group consisting of a fluorescent light, a phosphorescent light, and a bioluminescent light.