Sensor surfaces for detecting analytes

1. A sensor surface for detecting the interaction of a biological binding pair, said sensor surface comprising:

a substrate coated with a free electron metal;

a matrix layer disposed on said free electron metal, said matrix layer comprising an organic compound, wherein said organic compound has a boronic acid complexing moiety;

a boronic acid moiety complexed to said boronic acid complexing moiety; and

a first member of said binding pair conjugated to said boronic acid moiety, wherein said first member binds to a second member of said binding pair such that a detectable response is elicited.

2. The sensor surface of claim 1 , wherein said matrix is a self-assembled monolayer, a mixed self-assembled monolayer, or combinations thereof.

3. The sensor surface of claim 2 , wherein said matrix is a mixed self-assembled monolayer.

4. The sensor surface of claim 2 , wherein said free electron metal is a member selected from the group consisting of copper, silver, aluminum, platinum and gold.

5. The sensor surface of claim 4 , wherein said free electron metal is gold.

6. The sensor surface of claim 1 , wherein said organic compound having said boronic acid complexing moiety is of the formula:

X—R—Y  (I)

wherein:

X is an anchor group that forms a complex with said free-electron metal;

R is an optionally substituted alkylene group optionally interrupted by one or more members selected from the group consisting of a heteroatom, an amido group and combinations thereof; and

Y is a boronic acid complexing moiety.

7. The sensor surface of claim 6 , wherein said organic compound having said boronic acid complexing moiety is of the formula:

X(CH 2 ) n C(O)NHR′-(NSBI) m-Y   (IIa)

X(CH 2 ) n NHC(O)R′-(NSBI) m-Y   (IIb)

wherein:

n is an integer from about 1 to 5;

R′ is an optionally substituted alkylene group optionally interrupted by a heteroatom;

NSBI is a nonspecific binding inhibitor;

m is 0 or 1; and

Y is a boronic acid complexing moiety.

8. The sensor surface of claim 7 , wherein R′ is an optionally substituted alkylene group, which is optionally interrupted by a heteroatom and which is at least about 8 carbon atoms in length.

9. The sensor surface of claim 7 , wherein said nonspecific binding inhibitor is a member selected from the group consisting of an oligo(ethylene glycol), a poly(ethylene glycol), a branched OEG, a branched PEG, an oligo(peptide), an oligo(propylene sulfoxide), a sugar, a sugar alcohol, and a dendrimer.

10. The sensor surface of claim 7 , wherein R is an optionally substituted alkylene group, which is optionally interrupted by a heteroatom and which is between about 8 carbon atoms to about 40 carbon atoms in length.

11. The sensor surface of claim 7 , wherein m is 1.

12. The sensor surface of claim 7 , wherein Y has the formula:

wherein:

W is a member selected from the group consisting of H, OH, NH 2 , NHCH 3 , NHOH and NHOCH 3 ;

Q is a member selected from the group consisting of O, S and NH;

X is a member selected from the group consisting of H or OH; and

p is 0 to 3.

13. The sensor surface of claim 12 , wherein said organic compound having said boronic acid complexing moiety is of the formula

HS(CH 2) n C(O)NHR′-(NSBI)-SHA  (IV)

wherein:

n is an integer from 1 to about 5;

R′ is an optionally substituted alkylene group, which is optionally interrupted by a heteroatom;

NSBI is a nonspecific binding inhibitor;

x is 0 or 1; and

SHA is a salicyihydroxamic acid.

14. The sensor surface of claim 13 , wherein R′ is an optionally substituted alkylene group, which is optionally interrupted by a heteroatom and which is at least about 8 carbon atoms in length.

15. The sensor surface of claim 13 , wherein said nonspecific binding inhibitor is a member selected from the group consisting of an oligo(ethylene glycol), a poly(ethylene glycol), a branched OEG, a branched PEG, an oligo(peptide), an oligo(propylene sulfoxide), a sugar, a sugar alcohol, and a dendrimer.

16. The sensor surface of claim 13 , wherein R′ is an optionally substituted alkylene group, which is optionally interrupted by a heteroatom and which is between about 8 carbon atoms to about 40 carbon atoms in length.

17. The sensor surface of claim 12 , wherein said organic compound having said boronic acid complexing moiety is of the formula:

HS(CH 2 ) 2 C(O)NHR′-(NSBI)-DHBHA  (V)

wherein:

n is an integer from 1 to about 5;

R′ is an optionally substituted alkylene group, which is optionally interrupted by a heteroatom;

NSBI is a nonspecific binding inhibitor; and

DHBHA is a dihydroxybenzohydroxamic acid.

18. The sensor surface of claim 3 , wherein said matrix comprises an organic compound of the formula:

X—(CH 2 ) n C(O)NHR′-(NSBI) m -Z  (VIa)

or

X—(CH 2 ) n C(O)NHR′-(NSBI) m -Z  (VIb)

wherein:

X is an anchor group that forms a complex with a free electron metal;

n is an integer from 1 to 5;

R′ is an optionally substituted alkylene group, which is optionally interrupted by a heteroatom;

NSB is a nonspecific binding inhibitor;

m is 0 or 1; and

Z is an unreactive, uncharged chain-terminating group.

19. The sensor surface of claim 18 , wherein said nonspecific binding inhibitor is a member selected from the group consisting of an oligo(ethylene glycol), a poly(ethylene glycol), a branched OEG, a branched PEG, an oligo(peptide), an oligo(propylene sulfoxide), a sugar, a sugar alcohol, and a dendrimer.

20. The sensor surface of claim 18 , wherein Z is a member selected from the group consisting of H, CH 3 , OH, OCH 3 , CO 2 CH 3 , C(O)NH 2 , C(O)NHCH 3 , C(O)N(CH 3 ) 2 or SO 2 NH 2 .

21. The sensor surface of claim 18 , wherein said matrix layer comprises a combination of polymers having the formula:

SCH 2 C(O)NH(CH 2 ) 11 (OCH 2 CH 2 ) 11 OC(O)Y (Polymer A), wherein Y is a boronic acid complexing moiety; and —SCH 2 C(O)NH—(CH 2 ) 11 (COCH 2 CH 2 ) 3 OH (Polymer B).

22. The sensor surface of claim 21 , wherein the mole percent of Polymer A is less than about 10% of the total mole percent of Polymer A and Polymer B.

23. The sensor surface of claim 21 , wherein the mole percent of the Polymer A is less than about 5% of the total mole percent of Polymer A and Polymer B.

24. The sensor surface of claim 18 , wherein R′ is an optionally substituted alkylene group, which is optionally interrupted by a heteroatom and which is at least about 8 carbon atoms in length.

25. The sensor surface of claim 18 , wherein R′ is an optionally substituted alkylene group, which is optionally interrupted by a heteroatom and which is between about 8 carbon atoms to about 40 carbon atoms in length.

26. The sensor surface of claim 1 , wherein said boronic acid moiety comprises a bioactive species.

27. The sensor surface of claim 26 , wherein said boronic acid moiety is of the formula:

wherein:

BAS is a bioactive species, selected from the group consisting of a protein, a polypeptide, a polypeptide fragment, a nucleic acid, a carbohydrate, a receptor, a hormone, a toxin, a vesicle, a liposome and a cell;

Z 1 is a member selected from the group consisting of a saturated or unsaturated aliphatic chain up to about 0 to 6 carbon equivalents in length, an unbranched saturated or unsaturated aliphatic chain of from about 6 to 18 carbon equivalents in length with at least one intermediate amide or disulfide moiety, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length;

Q 1 is a member selected from the group consisting of an amide, methyl amide, methylene, ether, thioether, methylene ether and methylene thioether moieties; and

t is an integer from 1 to 3.

28. The sensor surface of claim 27 wherein said protein is selected from the group consisting of a capture protein, an antigen, an antibody, protein A, protein G, protein A/G, an enzyme, a lectin, and avidin.

29. The sensor surface of claim 27 , wherein said boronic acid moiety has the formula:

wherein:

BAS is a protein;

Z 1 is C 1 –C 4 alkylene; and

Q 1 is an amide.

30. The sensor surface of claim 27 , wherein said boronic acid moiety has the formula:

wherein:

BAS is a protein;

Z 1 is C 1 –C 4 alkylene; and

Q 1 is an amide.

31. The sensor surface of claim 27 , wherein said boronic acid moiety has the formula:

wherein:

BAS is a protein;

Z 1 is C 1 –C 4 alkylene; and

Q 1 is an amide.

32. The sensor surface of claim 1 , wherein said sensor surface is an array of sensor surfaces.

33. The sensor surface of claim 1 , wherein said sensor surface is part of a surface plasmon resonance sensing apparatus or a potentiometric sensing apparatus.

34. A sensor surface, said sensor surface comprising:

a substrate coated with a free electron metal;

a matrix layer disposed on said free electron metal, said matrix layer comprising an organic compound, wherein said organic compound has the formula

wherein:

Y 1 is a member selected from the group consisting of a boronic acid complexing moiety, a binding partner, a cell, a receptor, a liposome, a vesicle, an artificial membrane, a protein, a polypeptide, a protein fragment, a polypeptide fragment, a peptide hormone, a nucleic acid, a toxin, a hapten, a hormone, a sugar, biotin, a vitamin, and combinations thereof.

35. A process for immobilizing a ligand on a sensor surface, said process comprising:

admixing a boronic acid reagent having a reactive group with a ligand to form a boronic acid-ligand conjugate; and

incubating said boronic acid-ligand conjugate with said sensor surface wherein said sensor surface comprises:

a substrate coated with a free electron metal;

a matrix layer disposed on said free electron metal, said matrix layer comprising an organic compound, wherein said organic compound has a boronic acid complexing moiety complexed to the boronic acid-ligand conjugate, thereby immobilizing said ligand.

36. The process for immobilizing a ligand of claim 35 , further comprising washing said boronic acid-ligand conjugate complexed to said boronic acid complexing moiety.

37. The process for immobilizing a ligand of claim 35 , wherein said sensor surface comprises an array of sensor surfaces.