Immobilizing molecules on a solid support

Abstract

A method for selectively orienting molecules on a surface of a solid support. The method includes: (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.

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 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         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 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 on the solid support.