Sensor chips

• US 20060194343A1
• Filed: 01/06/2006
• Published: 08/31/2006
• Est. Priority Date: 07/08/2003
• Status: Active Grant

• Current Assignee: Tacnia Pty., Ltd.
• Original Assignee: Tacnia Pty., Ltd.
• Inventors: Johnson, Daniel Luke, Martin, Lisandra Lorraine
• Granted Patent: US 7,759,114 B2
• Time in Patent Office: Days
• US Class Current: 436/518
• CPC Class Codes: B01J 2219/00572 Chemical means
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00738 Organic catalysts
• CPC Class Codes: B01J 2219/00745 Inorganic compounds
• CPC Class Codes: B01J 2219/0075 Metal based compounds
• CPC Class Codes: B05D 1/185 applying monomolecular layers B05D1/204 takes precedence
• CPC Class Codes: B05D 2202/40 based on other transition elements
• CPC Class Codes: B05D 3/105 Intermediate treatments
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/18 Libraries containing only inorganic compounds or inorganic materials
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393

Abstract

A method for selectively orienting molecules on a surface of a solid support. The method includes the steps of: (a) attaching a linker molecule to the surface of the solid support, the linker molecule including a head group that is capable of binding to the solid support, and a tail group that is capable of chelating to a metal ion; (b) subsequently treating the solid support with a solution containing the metal ion; (c) attaching a metal ion chelating tag to the molecules to form tagged molecules; and (d) capturing the tagged molecules on the solid support by contacting it with the tagged molecules to form a monolayer of molecules on the surface of the solid support in which a majority of the molecules are held in the same orientation with respect to the surface. The invention also provides a sensor chip formed using the methods of the invention.

Claims

1. A method for selectively orienting and immobilizing molecules on a surface of a solid support, the method comprising:

attaching a linker molecule to the surface of the solid support, the linker molecule including a head group that is capable of binding to the solid support, and a tail group that is capable of chelating to a metal ion;

treating the solid support with a solution containing the metal ion so that the metal ion is chelated to the tail group;

attaching a metal ion chelating tag to the molecules to form tagged molecules; and

capturing the tagged molecules on the solid support by contacting it with the tagged molecules to form a monolayer of molecules on the surface of the solid support in which a majority of the molecules are held in the same orientation with respect to the surface.

2. The method of claim 1 wherein the tail group of the linker molecule is a cyclic ligand containing three or more atoms that are capable of coordinating to the metal ion.

3. The method of claim 2 wherein the tail group of the linker molecule is a macrocycle that is capable of chelating with the metal ion.

4. The method of claim 3 wherein the macrocycle is a multidentate macrocycle.

5. The method of claim 4 wherein the macrocycle is a derivative of 1,4,7-triazacyclononane.

6. The method of claim 5 wherein the macrocycle is 1-acetato-4-benzyl-1,4,7-triazacyclononane.

7. The method of claim 1 wherein the metal ion is selected from the group consisting of zinc, copper, cobalt, nickel, sodium, potassium, magnesium, calcium and lithium.

8. The method of claim 1 wherein the tag is a peptide chain containing one or more chelate forming amino acids independently selected from the group consisting of cysteine, lysine, histidine, and arginine.

9. The method of claim 8 wherein the tag is a peptide containing four to six histidine residues.

10. The method of claim 1 wherein the solid support onto which the linker molecule is attached comprises a noble metal selected from the group consisting of silver, gold, platinum and palladium.

11. The method of claim 1 wherein the solid support includes a gold surface onto which the head group of the linker molecule binds.

12. The method of claim 1 wherein the linker molecule includes a spacer between the head and tail groups.

13. The method of claim 12 wherein the spacer is a carbon-based chain between the head and tail groups.

14. The method of claim 13 wherein the carbon-based chain is two to fifteen atoms in length.

15. The method of claim 14 wherein the carbon-based chain is two to six atoms in length.

16. The method of claim 1 wherein the head group is sulphur, oxygen or selenium.

17. The method of claim 1 wherein the molecule is a peptide or a protein.

18. The method of claim 17 wherein the tag in the tagged molecule is covalently bound to the protein at a position on the protein that is separated from the active site or recognition region of the protein.

19. The method of claim 1 wherein the solid support is an electrode.

20. A biosensor comprising:

a solid support having a surface;

a linker molecule attached to a surface of the solid support, the linker molecule including a head group that is bound to the solid support, and a multidentate macrocylic tail group that is chelated to a metal ion;

a monolayer of molecules on the surface of the solid support, wherein each molecule contains a metal ion chelating tag and is held on the surface of the solid support by coordination between of the tag and the metal ion such that a majority of the molecules are held in the same orientation with respect to the surface.

21. The biosensor of claim 20 wherein the multidentate macrocyclic tail group is a tetradentate macrocycle.

22. The biosensor of claim 21 wherein the tetradentate macrocycle is a derivative of 1,4,7-triazacyclononane.

23. The biosensor of claim 22 wherein the macrocycle is 1-acetato-4-benzyl-1,4,7-triazacyclononane.

24. The biosensor of claim 23 wherein the metal ion is selected from the group consisting of zinc, copper, cobalt, nickel, sodium, potassium, magnesium, calcium and lithium.

25. The biosensor of claim 21 wherein the tag is a peptide chain containing one or more chelate forming amino acids independently selected from the group consisting of cysteine, lysine, histidine, and arginine.

26. The biosensor of claim 25 wherein the tag is a peptide containing three to six histidine residues.

27. The biosensor claim 21 wherein the solid support is a noble metal selected from the group consisting of silver, gold, platinum and palladium.

28. The biosensor of claim 21 wherein the linker molecule includes a spacer between the head and tail groups.

29. The biosensor of claim 28 wherein the spacer is a carbon-based chain between the head and tail groups.

30. The biosensor of claim 29 wherein the carbon-based chain is two to fifteen atoms in length.

31. The biosensor of claim 30 wherein the carbon-based chain is two to six atoms in length.

32. The biosensor of claim 21 wherein the head group is sulphur, oxygen or selenium.

33. The biosensor of claim 21 wherein the molecule is a peptide or a protein.

34. The biosensor of claim 33 wherein the tag in the tagged molecule is covalently bound to the protein at a position on the protein that is separated from the active site or recognition region of the protein.

35. A method for selectively orienting and immobilizing molecules on a solid support having a gold surface, the method comprising:

treating the gold surface with a mercaptopropionic acid to form a mercaptopropionic acid self-assembled monolayer;

treating the mercaptopropionic acid self-assembled monolayer with a tetradentate derivative of 1,4,7-triazacyclononane to form a macrocycle modified mercaptopropionic self-assembled monolayer;

treating the macrocycle modified mercaptopropionic self-assembled monolayer with a metal desirous of octahedral coordination to form a metallo macrocycle modified mercaptopropionic self-assembled monolayer; and

treating the metallo macrocycle modified mercaptopropionic self-assembled monolayer with a solution containing a 6*his tagged molecule to form a highly orientated monolayer of immobilized molecules.