Nucleic acid arrays and method for detecting nucleic acids by using nucleic acid arrays

• US 20030027154A1
• Filed: 08/31/2001
• Published: 02/06/2003
• Est. Priority Date: 01/09/2001
• Status: Abandoned Application

• Current Assignee: Hitachi, Ltd.
• Original Assignee: Hitachi, Ltd.
• Inventors: Tomita, Hiroyuki, Kato, Hirokazu, Narahara, Masatoshi, Saito, Toshiro
• Application Number:
  US09/942,563
• Publication Number:
  US 20030027154A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• 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 2219/00722 Nucleotides
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2549/125 using sterilising/blocking agents, e.g. albumin
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof

Abstract

The present invention provides nucleic acid arrays with improved sensitivity for a nucleic acid. The array comprises various kinds of nucleic acid probes, which are capable of hybridizing to the nucleic acid, immobilized at different positions on a substrate. Single-stranded nucleic acid probes are immobilized on the substrate by covalent bond, and functional groups that can have negative charge by dissociating in an aqueous solution or by hydrolysis are introduced on the surface of regions of the substrate on which no nucleic acid probe is immobilized.

Claims

1. Nucleic acid arrays comprising various kinds of single-stranded nucleic acid probes which are capable of hybridizing to nucleic acids and immobilized at different positions on a substrate, wherein said single-stranded nucleic acid probes are immobilized on the substrate by covalent bond;

and functional groups which can have negative charge by dissociating in an aqueous solution are present on the surface of regions of the substrate on which no nucleic acid probe is immobilized.

2. The nucleic acid arrays of claim 1 wherein said functional groups which can have negative charge are introduced by the steps comprising:

immobilizing single-stranded nucleic acid probes on a substrate; and

then immobilizing by covalent bond a compound with the functional groups that can have negative charge onto regions on which no single-stranded nucleic acid probe is immobilized.

3. The nucleic acid arrays of claim 2 wherein said functional group that can have negative charge is a carboxyl group.

4. The nucleic acid arrays of claim 1 wherein said functional groups that can have negative charge are introduced by the steps comprising:

immobilizing single-stranded nucleic acid probes on a substrate; and

then immobilizing by hydrophobic bond a compound with the functional groups which can have negative charge onto regions on which no single-stranded nucleic acid probe is immobilized.

5. The nucleic acid arrays of claim 4, wherein said functional group which can have negative charge is either a carboxyl group, a sulfonic acid group, or a hydrogen sulfate group.

6. Nucleic acid arrays comprising various kinds of single-stranded nucleic acid probes which are capable of hybridizing to nucleic acids and immobilized at different positions on a substrate, wherein said single-stranded nucleic acid probes are immobilized on the substrate by covalent bond;

and functional groups which are negatively charged by hydrolysis are present on the surface of regions of the substrate on which no nucleic acid probe is immobilized.

7. The nucleic acid arrays of claim 6 wherein said functional groups which are negatively charged can react with functional groups of nucleic acid probes before hydrolysis, and a reproduced by hydrolysis of regions on which no nucleic acid probe is immobilized after immobilization of nucleic acid probes.

8. The nucleic acid arrays of claim 7 wherein said functional groups are products of hydrolysis of maleimide groups.