Electrodes linked via conductive oligomers to nucleic acids
AssigneeClinical Micro Sensors, Inc.
InventorsJon F. Kayyem, Stephen D. O'Connor, Michael Gozin, Changjun Yu
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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.
Claims41
A composition comprising:
- a) an electrode;
- b) at least one nucleoside;
- and
- c) a conductive oligomer covalently attached to both said electrode and said nucleoside, wherein said conductive oligomer has the formula:
- 38
- wherein
- Y is an aromatic group;
- n is an integer from 1 to 50;
- g is either 1 or zero;
- e is an integer from zero to 10;
- and
- m is zero or 1;
- wherein when g is 1, B-D is a conjugated bond;
- and
- wherein when g is zero, e is 1 and D is preferably carbonyl, or a heteroatom moiety, wherein the heteroatom is selected from oxygen, sulfur, nitrogen or phosphorus.
A composition comprising:
- a) an electrode;
- b) at least one nucleoside;
- and
- c) a conductive oligomer covalently attached to both said electrode and said nucleoside, wherein said conductive oligomer has the formula:
- 39
- wherein
- n is an integer from 1 to 50;
- m is O or 1;
- C is carbon;
- J is carbonyl or a heteroatom moeity, wherein the heteroatom is selected from the group consisting of nitrogen, silicon, phosphorus, sulfur;
- and
- G is a bond selected from alkane, alkene or acetylene.
A composition comprising:
- a) a first electron transfer moiety comprising an electrode;
- b) a nucleic acid;
- c) a second electron transfer moiety covalently attached to said nucleic acid;
- and
- d) a conductive oligomer covalently attached to both said electrode and said nucleic acid.
A method of detecting a target sequence in a nucleic acid sample comprising
- a) hybridizing a probe nucleic acid to said target sequence, if present, to form a hybridization complex, wherein said probe nucleic acid comprises:
- i) a conductive oligomer covalently attached to a first electron transfer moiety comprising an electrode and to a single stranded nucleic acid capable of hybridizing to said target sequence, said single stranded nucleic acid comprising a covalently attached second electron transfer moiety, wherein said conductive oligomer has the formula:
- 42
- wherein
- Y is an aromatic group;
- n is an integer from 1 to 50;
- g is either 1 or zero;
- e is an integer from zero to 10;and
- m is zero or 1;
- wherein when g is 1, B-D is a conjugated bond;
- and
- wherein when g is zero, e is 1 and D is preferably carbonyl, or a heteroatom moiety, wherein the heteroatom is selected from oxygen, sulfur, nitrogen or phosphorus;
- and
- b) detecting electron transfer between said electrode and said second electron transfer moiety, if present, as an indicator of the present or absence of said target sequence.
A method of detecting a target sequence in a nucleic acid sample comprising
- a) hybridizing a probe nucleic acid to said target sequence, if present, to form a hybridization complex, wherein said probe nucleic acid comprises:
- i) a conductive oligomer covalently attached to a first electron transfer moiety comprising an electrode and to a single stranded nucleic acid capable of hybridizing to said target sequence, said single stranded nucleic acid comprising a covalently attached second electron transfer moiety, wherein said conductive oligomer has the formula:
- 43
- wherein
- n is an integer from 1 to 50;
- m is 0 or 1;
- C is carbon;
- J is carbonyl or a heteroatom moeity, wherein the heteroatom is selected from the group consisting of nitrogen, silicon, phosphorus, sulfur;
- and
- G is a bond selected from alkane, alkene or acetylene;
- and
- b) detecting electron transfer between said electrode and said second electron transfer moiety, if present, as an indicator of the present or absence of said target sequence.
A method of detecting a target sequence in a nucleic acid wherein said target sequence comprises a first target domain and a second target domain, said method comprising:
- a) hybridizing a first probe nucleic acid to said first target domain, if present, to form a hybridization complex, wherein said first probe nucleic acid comprises:
- i) a conductive oligomer covalently attached to a first electron transfer moiety comprising an electrode and to a single stranded nucleic acid capable of hybridizing to said target sequence, wherein said conductive oligomer has the formula:
- 44
- wherein
- Y is an aromatic group;
- n is an integer from 1 to 50;
- g is either 1 or zero;
- e is an integer from zero to 10;
- and
- m is zero or 1;
- wherein when g is 1, B-D is a conjugated bond;
- and
- wherein when g is zero, e is 1 and D is preferably carbonyl, or a heteroatom moiety, wherein the heteroatom is selected from oxygen, sulfur, nitrogen or phosphorus;
- b) hybridizing a second single stranded nucleic acid comprising a covalently attached electron transfer moiety to said second target domain;
- and
- c) detecting electron transfer between said electrode and said second electron transfer moiety, if present, as an indicator of the present or absence of said target sequence.
A method of detecting a target sequence in a nucleic acid wherein said target sequence comprises a first target domain and a second target domain, said method comprising:
- a) hybridizing a first probe nucleic acid to said first target domain, if present, to form a hybridization complex, wherein said first probe nucleic acid comprises:
- i) a conductive oligomer covalently attached to a first electron transfer moiety comprising an electrode and to a single stranded nucleic acid capable of hybridizing to said target sequence, wherein said conductive oligomer has the formula:
- 45
- wherein
- n is an integer from 1 to 50;
- m is 0 or 1;
- C is carbon;
- J is carbonyl or a heteroatom moeity, wherein the heteroatom is selected from the group consisting of nitrogen, silicon, phosphorus, sulfur;
- and
- G is a bond selected from alkane, alkene or acetylene;
- and
- b) hybridizing a second single stranded nucleic acid comprising a covalently attached electron transfer moiety to said second target domain;
- and
- c) detecting electron transfer between said electrode and said second electron transfer moiety, if present, as an indicator of the present or absence of said target sequence.
A method for attaching a conductive oligomer to a gold electrode comprising
- a) adding an ethyl pyridine protecting group to a sulfur atom attached to a first subunit of said conductive oligomer.
A conductive oligomer with a ethyl-pyridine protected sulfur atom.
A composition comprising a conductive oligomer covalently attached to a nucleoside, wherein said conductive oligomer has the formula:
- 46
- wherein
- Y is an aromatic group;
- n is an integer from 1 to 50;
- g is either 1 or zero;
- e is an integer from zero to 10;
- and
- m is zero or 1;
- wherein when g is 1, B-D is a conjugated bond;
- and
- wherein when g is zero, e is 1 and D is preferably carbonyl, or a heteroatom moiety, wherein the heteroatom is selected from oxygen, sulfur, nitrogen or phosphorus.
A composition comprising a conductive oligomer covalently attached to a nucleoside, wherein said conductive oligomer has the formula:
- 47
- wherein
- n is an integer from 1 to 50;
- m is 0 or 1;
- C is carbon;
- J is carbonyl or a heteroatom moeity, wherein the heteroatom is selected from the group consisting of nitrogen, silicon, phosphorus, sulfur;
- and
- G is a bond selected from alkane, alkene or acetylene
A composition comprising a conductive oligomer covalently attached to a phosphoramidite nucleoside, wherein said conductive oligomer has the formula:
- 48
- wherein
- Y is an aromatic group;
- n is an integer from 1 to 50;
- g is either 1 or zero;
- e is an integer from zero to 10;
- and
- m is zero or 1;
- wherein when g is 1, B-D is a conjugated bond;
- and
- wherein when g is zero, e is 1 and D is preferably carbonyl, or a heteroatom moiety, wherein the heteroatom is selected from oxygen, sulfur, nitrogen or phosphorus.
A composition comprising a conductive oligomer covalently attached to a phosphoramidite nucleoside, wherein said conductive oligomer has the formula:
- 49
- wherein
- n is an integer from 1 to 50;
- m is 0 or 1;
- C is carbon;
- J is carbonyl or a heteroatom moeity, wherein the heteroatom is selected from the group consisting of nitrogen, silicon, phosphorus, sulfur;
- and
- G is a bond selected from alkane, alkene or acetylene
A composition comprising a conductive oligomer covalently attached to a CPG-nucleoside.
A composition comprising a nucleoside covalently linked to a metallocene.
A composition comprising:
- a) an electrode;
- b) at least one metallocene;
- and
- c) a conductive oligomer covalently attached to both said electrode and said metallocene, wherein said conductive oligomer has the formula:
- 50
- wherein
- n is an integer from 1 to 50;
- m is 0 or 1;
- C is carbon;
- J is carbonyl or a heteroatom moeity, wherein the heteroatom is selected from the group consisting of nitrogen, silicon, phosphorus, sulfur;
- and
- G is a bond selected from alkane, alkene or acetylene
A composition comprising:
- a) an electrode;
- b) at least one metallocene;
- and
- c) a conductive oligomer covalently attached to both said electrode and said metallocene, wherein said conductive oligomer has the formula:
- 51
- wherein
- Y is an aromatic group;
- n is an integer from 1 to 50;
- g is either 1 or zero;
- e is an integer from zero to 10;
- and
- m is zero or 1;
- wherein when g is 1, B-D is a conjugated bond;
- and
- wherein when g is zero, e is 1 and D is preferably carbonyl, or a heteroatom moiety, wherein the heteroatom is selected from oxygen, sulfur, nitrogen or phosphorus.
Dependencies are inferred from the claim text.