AC/DC voltage apparatus for detection of nucleic acids

• US 7,381,525 B1
• Filed: 06/12/1997
• Issued: 06/03/2008
• Est. Priority Date: 03/07/1997
• Status: Expired due to Fees

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Inc. (Roche Holding AG)
• Inventors: Kayyem, Jon Faiz, O'Connor, Stephen D.
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US08/873,597
• Time in Patent Office: 4,009 Days
• Field of Search: 435/6, 435/174, 422/50, 422/68.1, 536/22.1, 536/23.1, 536/24.1, 536/24.3, 536/24.33, 536/25.3, 436/501, 438/283.1
• US Class Current: 435/287.2
• 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: C12Q 1/6825 Nucleic acid detection involving sensors

Abstract

The invention relates to nucleic acids covalently coupled to electrodes via conductive oligomers. More particularly, the invention is directed to the site-selective modification of nucleic acids with electron transfer moieties and electrodes to produce a new class of biomaterials, and to methods of making and using them.

Claims

1. An apparatus for the detection of target nucleic acids in a test sample, comprising:

a) a test chamber comprising a first and a second electrode, wherein said first electrode comprises;

i. a single stranded nucleic acid covalently attached to said electrode via an insulator, wherein said insulator is an alkyl oligomer wherein each monomer of said alkyl oligomer is independently selected from the group consisting of;

—

(CH₂)_n—

, —

(CRH)_n—

, —

(CR2)_n—

, ethylene glycol and ethylene glycol derivatives using other heteroatoms in place of oxygen;

wherein n is from 1 to 16; and

wherein R is selected from the group consisting of hydrogen, alkyl, alcohol, aromatic amino, amido, nitro, ethers, esters, aldehydes, sulfonyl, silicon moieties, halogens, sulfur containing moieties, phosphorous containing moieties, and

ii. a passivation agent monolayer; and

b) an AC/DC voltage source electrically connected to said first and second electrodes.

2. An apparatus accordingly to claim 1 further comprising,

c) a second nucleic acid covalently attached to an electron transfer moiety.

5. An apparatus according to claim 1, 3 or 4, further comprising:

a processor coupled to said electrodes.

6. An apparatus according to claim 1, 3 or 4, wherein said AC/DC voltage source is capable of delivering frequencies from between about 1 Hz to about 100 kHz.

7. An apparatus according to claim 1, 3 or 4 wherein said passivation agent monolayer comprises conductive oligomers.

8. An apparatus according to claim 1, 3 or 4 wherein said passivation agent monolayer comprises insulators.

9. An apparatus according to claims 1, 3 or 4 wherein said passivation agent monolayer comprises alkyl chains.

10. An apparatus according claim 9 wherein said alkyl chains have the formula C_nH_x, where n is 1 to 30, and x is 2(n).

11. An apparatus according to claims 1, 3 or 4 wherein said passivation agent monolayer comprises terminal groups chosen from the group consisting of —

(CH₂)_n—

, —

(CRH)_n—

, —

(CR2)_n—

, ethylene glycol and ethylene glycol derivatives using other heteroatoms in place of oxygen;

wherein n is from 1 to 16, and wherein R is selected from the group consisting of hydrogen, alkyl, alcohol, aromatic amino, amido, nitro, ethers, esters, aldehydes, sulfonyl, silicon moieties, halogens, sulfur containing moieties, phosphorous containing moieties, and ethylene glycol moieties.

12. An apparatus according to claims 1, 3 or 4 wherein said passivation agent monolayer comprises both conductive oligomers and insulators.

3. An apparatus for the detection of target nucleic acids in a test sample, comprising:

a) a test chamber comprising a first and a second electrode, wherein said first electrode comprises;

i. a covalently attached single stranded nucleic acid attached to said first electrode via an insulator, wherein said insulator is an alkyl oligomer wherein each monomer of said alkyl oligomer is independently selected from the group consisting of;

—

(CH₂)_n—

, —

(CRH)_n—

, ethylene glycol and ethylene glycol derivatives using other heteroatoms in place of oxygen;

wherein n is from 1 to 16; and

wherein R is selected from the group consisting of hydrogen, alkyl alcohol, aromatic amino, amido, nitro, ethers, esters, aldehydes, sulfonyl, silicon moieties, halogens, sulfur containing moieties, phosphorous containing moieties;

ii. a passivation agent monolayer; and

iii. a covalently attached first electron transfer moiety; and

b) an AC/DC voltage source electrically connected to said test chamber.

4. An apparatus for the detection of target nucleic acids in a test sample, comprising:

a. a test chamber comprising a first and a second electrode, wherein said first electrode comprises;

i. a covalently attached first single stranded nucleic acid attached to said first electrode via an insulator, wherein said insulator is an alkyl oligomer wherein each monomer of said alkyl oligomer is independently selected from the group consisting of;

—

(CH₂)_n—

, —

(CRH)_n—

, —

(CR2)_n—

, ethylene glycol and ethylene glycol derivatives using other heteroatoms in place of oxygen;

wherein n is from 1 to 16; and

wherein R is selected from the group consisting of hydrogen, alkyl, alcohol, aromatic amino, amido, nitro, ethers, esters, aldehydes, sulfonyl, silicon moieties, halogens, sulfur containing moieties, phosphorous containing moieties; and

ii. a passivation agent monolayer; and

b) a second nucleic acid covalently attached to an electron transfer moiety; and

c) an AC/DC voltage source electrically connected to said test chamber.

13. An apparatus for the detection of target nucleic acids in a test sample, comprising:

a) a test chamber comprising an array of electrodes, each electrode comprising

i. a covalently attached single stranded nucleic acid, attached to said electrodes via an insulator, wherein said insulator is an alkyl oligomer wherein each monomer of said alkyl oligomer is independently selected from the group consisting of;

—

(CH₂)_n—

, —

(CRH)_n—

, —

(CR2)_n—

, ethylene glycol and ethylene glycol derivatives using other heteroatoms in place of oxygen;

wherein n is from 1 to 16; and

wherein R is selected from the group consisting of hydrogen, alkyl, alcohol, aromatic amino, amido, nitro, ethers, esters, aldehydes, sulfonyl, silicon moieties, halogens, sulfur containing moieties, phosphorous containing moieties; and

ii. a passivation agent monolayer; and

b) an AC/DC voltage source electrically connected to said test chamber.

14. An apparatus according to claim 13 wherein said passivation agent monolayer comprises conductive oligomers.

15. An apparatus according to claim 13 wherein said passivation agent monolayer comprises insulators.