Detection of analytes using reorganization energy

• US 6,013,170 A
• Filed: 06/12/1998
• Issued: 01/11/2000
• Est. Priority Date: 06/12/1997
• Status: Expired due to Term

• Current Assignee: Osmetech Technology Inc. (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Inc. (Roche Holding AG)
• Inventors: Meade, Thomas J.
• Primary Examiner(s): Achutamurthy, Ponnathapu
• Application Number:
  US09/096,504
• Time in Patent Office: 578 Days
• Field of Search: 435/4, 435/5, 435/6, 435/7.1, 435/7.71, 435/7.72, 435/7.8, 435/7.9, 435/7.91, 435/7.93, 435/7.6, 435/7.4, 205/793.5, 205/777.5, 205/778, 204/418, 204/415, 204/290, 204/403
• US Class Current: 205/777.5
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

The invention relates to novel methods and compositions for the detection of analytes using the nuclear reorganization energy, λ, of an electron transfer process.

Claims

1. A composition comprising an electrode comprising a covalently attached binding ligand that will bind a target analyte and a covalently attached solvent accessible transition metal complex comprising a metal selected from the group consisting of manganese, technetium, rhenium, iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium, platinum, copper, silver and gold, such that upon binding of said target analyte, a solvent inhibited transition metal complex is formed.

2. A composition according to claim 1 wherein said solvent accessible transition metal complex has at least two coordination sites occupied by polar coordination groups.

3. A composition according to claim 1 wherein said solvent accessible transition metal complex has at least one coordination site occupied by a water molecule.

4. A composition according to claim 1 wherein said electrode further comprises a self-assembled monolayer.

5. A composition according to claim 1 wherein said solvent accessible transition metal complex is covalently attached to said electrode via a conductive oligomer.

6. A composition according to claim 1 wherein said solvent accessible transition metal complex is linked to said binding ligand to form a redox active complex.

7. A composition according to claim 1 wherein said binding ligand is covalently attached to said electrode via a conductive oligomer.

12. A composition according to claim 1 wherein said binding ligand will bind a protein.

13. A composition according to claim 1 wherein said binding ligand will bind a nucleic acid.

14. A composition according to claim 1 wherein said binding ligand is a protein.

16. A composition according to claim 1 wherein said solvent accessible transition metal complex is attached to said binding ligand.

17. A composition according to claim 5 or 7 wherein said conductive oligomer has the formula, ##STR9## 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 the group consisting of oxygen, sulfur, nitrogen and phosphorus.

18. A composition according to claim 17 wherein said aromatic group is phenyl, g is 1, and B--D is an acetylene linkage.

19. A composition according to claim 5 or 7 wherein said conductive oligomer has the formula:

##STR10## wherein n is an integer from 1 to 50;

m is zero or 1;

C is carbon;

J is carbonyl or a heteroatom moiety, wherein the heteroatom is selected from the group consisting of oxygen, nitrogen, silicon, phosphorus and sulfur; and

G is bond selected from alkane, alkene or acetylene.

20. A composition according to claim 1 wherein said metal is ruthenium.

21. A composition according to claim 1 wherein said metal is osmium.

22. A composition according to claim 1 wherein said metal is iron.

23. A composition according to claim 1 wherein said metal is platinum.

24. A composition according to claim 1 wherein said metal is palladium.

25. A composition according to claim 1 wherein said metal is manganese.

26. A composition according to claim 1 wherein said metal is technetium.

27. A composition according to claim 1 wherein said metal is rhenium.

28. A composition according to claim 1 wherein said metal is cobalt.

29. A composition according to claim 1 wherein said metal is rhodium.

30. A composition according to claim 1 wherein said metal is iridium.

31. A composition according to claim 1 wherein said metal is nickel.

32. A composition according to claim 1 wherein said metal is copper.

33. A composition according to claim 1 wherein said metal is silver.

34. A composition according to claim 1 wherein said metal is gold.

57. A composition according to claim 1 wherein said solvent accessible transition metal complex has a solvent reorganization energy of greater than about 1000 meV.

58. A composition according to claim 1 wherein said solvent accessible transition metal complex has a solvent reorganization energy of greater than about 500 meV.

59. A composition according to claim 1 wherein the solvent reorganization energy of said solvent accessible transition metal complex decreases by at least 100 meV upon binding of said analyte to form said solvent inhibited transition metal complex.

60. A composition according to claim 1 wherein the solvent reorganization energy of said solvent accessible transition metal complex decreases to result in a decrease in the E₀ by at least 100 meV upon binding of said analyte to form said solvent inhibited transition metal complex.

8. An apparatus for the detection of target analytes in a test sample, comprising:

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

i) a covalently attached solvent accessible transition metal comprising a metal selected from the group consisting of manganese, technetium, rhenium, iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium, platinum, copper, silver and gold; and

ii) a covalently attached binding ligand that will bind said target analyte;

such that upon binding of said target analyte a solvent inhibited transition metal complex is formed;

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

9. An apparatus according to claim 8 wherein said covalent attachment is via a spacer.

10. An apparatus according to claim 8 further comprising a processor coupled to said AC/DC voltage source.

11. An apparatus according to claim 8 wherein said electrode further comprises a self-assembled monolayer.

15. An apparatus according to claim 9 wherein said spacer is a conductive oligomer.

35. An apparatus according to claim 8 wherein said solvent accessible transition metal complex attached to said binding ligand.

36. An apparatus according to claim 15 therein said conductive oligomer has the formula:

##STR11## 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 the group consisting of oxygen, sulfur, nitrogen and phosphorus.

37. An apparatus according to claim 36 wherein said aromatic group is phenyl, g is 1, and B--D is an acetylene linkage.

38. An apparatus according to claim 15 wherein said conductive oligomer has the formula. ##STR12## wherein n is an integer from 1 to 50;

m is zero or 1;

C is carbon,

J is carbonyl or a heteroatom moiety, wherein the heteroatom is selected from the group consisting of oxygen, nitrogen, silicon, phosphorus and sulfur; and

G is bond selected from alkane, alkene or acetylene.

39. An apparatus according to claim 8 wherein said metal is ruthenium.

40. An apparatus according to claim 8 wherein said metal is osmium.

41. An apparatus according to claim 8 wherein said metal is iron.

42. An apparatus according to claim 8 wherein said metal is platinum.

43. An apparatus according to claim 8 wherein said metal is palladium.

44. An apparatus according to claim 8 wherein said metal is manganese.

45. An apparatus according to claim 8 wherein said metal is technetium.

46. An apparatus according to claim 8 wherein said metal is rhenium.

47. An apparatus according to claim 8 wherein said metal is cobalt.

48. An apparatus according to claim 8 wherein said metal is rhodium.

49. An apparatus according to claim 8 wherein said metal is iridium.

50. An apparatus according to claim 8 wherein said metal is nickel.

51. An apparatus according to claim 8 wherein said metal is copper.

52. An apparatus according to claim 8 wherein said metal is silver.

53. An apparatus according to claim 8 wherein said metal is gold.

54. An apparatus according to claim 8 wherein said solvent accessible transition metal complex has at least one coordination site occupied by a polar coordination group.

55. An apparatus according to claim 8 wherein said solvent accessible transition metal complex has at least one coordination site occupied by a water molecule.

56. An apparatus according to claim 8 wherein said solvent accessible transition metal complex has at least one coordination site occupied by a water molecule.

61. An apparatus according to claim 8 wherein said solvent accessible transition metal complex has a solvent reorganization energy of greater than about 1000 meV.

62. An apparatus according to claim 8 wherein said solvent accessible transition metal complex has a solvent reorganization energy of greater than about 500 meV.

63. An apparatus according to claim 8 wherein the solvent reorganization energy of said solvent accessible transition metal complex decreases by at least 100 meV upon binding of said analyte to form said solvent inhibited transition metal complex.

64. An apparatus according to claim 8 wherein the solvent reorganization energy of said solvent accessible transition metal complex decreases to result in a decrease in the E₀ by at least 100 meV upon binding of said analyte to form said solvent inhibited transition metal complex.