Replicable probe array

Abstract

A system for producing substantially identical specific binding ligand (e.g., nucleic acid) probe arrays, for instance, by preparing and replicating an original master array and/or by providing a reusable assay array that is capable of being regenerated. In one embodiment the system includes the preparation and use of a) a master array surface having address sequences immobilized in the form of a patterned, and optionally random, array, b) a multi-ligand conjugate having a binding domain complementary to an address sequence, a binding domain complementary to a target sequence, and a third ligand for use in forming (e.g., by binding or polymerization) the conjugates into or onto the surface of assay array, which can be used with or upon disassociation of the address and its complementary sequences.

What is claimed is:  
     
         1 . A system for replicating a specific binding ligand probe array, the system comprising: 
 a) a master array comprising a support surface having a plurality of address ligands immobilized thereon in the form of a patterned array;    b) a plurality of multi-ligand conjugates, each multi-ligand conjugate comprising a core having attached thereto: (i) at least one molecule of a first ligand binding domain, comprising a ligand selected to bind in a specific manner with a particular address ligand of the master array, (ii) at least one molecule of a second ligand binding domain, comprising a ligand selected to bind in a specific manner with a target ligand, and (iii) at least one molecule of a third ligand, selected from the group consisting of binding ligands and polymerizable groups; and    c) an assay array support comprising a support surface for the replicate array.    
     
     
         2 . A system according to  claim 1  wherein the address ligands, and the first and second binding ligands each, independently, comprise a nucleic acid.  
     
     
         3 . A system according to  claim 2  wherein the nucleic acids each comprise a synthetic oligonucleotide.  
     
     
         4 . A system according to  claim 1  further comprising a linking agent, the linking agent providing attachment of the address ligand with the master array support surface.  
     
     
         5 . A system according to  claim 4  wherein the linking agent comprises a micro-bead.  
     
     
         6 . A system according to  claim 1  wherein the first ligand binding domain, second ligand binding domain and third ligand are independently attached to the core of the multi-ligand conjugate.  
     
     
         7 . A system according to  claim 1  wherein the binding ligands comprise biotin derivatives.  
     
     
         8 . A system according to  claim 1  wherein the polymerizable groups are selected from the group consisting of acrylic and vinyl groups.  
     
     
         9 . A system according to  claim 1  wherein the assay array support is coated with attachment sites for the third ligand.  
     
     
         10 . A system according to  claim 9  wherein the third ligand comprises a binding ligand, and the attachment sites comprise molecules of a binding partner specific for the third ligand.  
     
     
         11 . A method for replicating a specific binding ligand probe array, the method comprising: 
 a) providing a master array comprising a support surface having a plurality of address ligands immobilized thereon;    b) providing a plurality of multi-ligand conjugates, each multi-ligand conjugate comprising a core having attached thereto: (i) at least one molecule of a first ligand binding domain, comprising a ligand selected to bind in a specific manner with a particular address ligand of the master array, (ii) at least one molecule of a second ligand binding domain, comprising a ligand selected to bind in a specific manner with a target ligand, and (iii) at least one molecule of a third ligand, selected from the group consisting of binding ligands and polymerizable groups;    c) attaching the multi-ligand conjugates to the master array by allowing the first ligand binding domains to bind in a specific manner with complementary address ligands;    d) providing an assay array support comprising a support surface for the replicate array;    e) bringing the assay array support into sufficient proximity with the master array, under conditions suitable to permit the attached multi-ligand conjugates to attach to the assay array support; and    f) disassociating the bound complementary address ligand and first ligand binding domain under conditions suitable to permit the assay array support to be recovered and used.    
     
     
         12 . A method according to  claim 11 , wherein the third ligand comprises a polymerizable group, wherein the polymerizable groups can be reacted to form a polymer film.  
     
     
         13 . A method according to  claim 11  wherein the address ligands, and the first and second binding ligands each, independently, comprise a nucleic acid.  
     
     
         14 . A method according to  claim 13  wherein the nucleic acids each comprise a synthetic oligonucleotide.  
     
     
         15 . A method according to  claim 11  further comprising a linking agent, the linking agent providing attachment of the address ligand with the master array support surface.  
     
     
         16 . A method according to  claim 15  wherein the linking agent comprises a micro-bead.  
     
     
         17 . A method according to  claim 11  wherein the first ligand binding domain, second ligand binding domain and third ligand are independently attached to the core of the multi-ligand conjugate.  
     
     
         18 . A method according to  claim 11  wherein the binding ligands comprise biotin derivatives.  
     
     
         19 . A method according to  claim 11  wherein the polymerizable groups are selected from the group consisting of acrylic and vinyl groups.  
     
     
         20 . A method according to  claim 11  wherein the assay array support is coated with attachment sites for the third ligand.  
     
     
         21 . A method according to  claim 20  wherein the third ligand comprises a binding ligand, and the attachment sites comprise molecules of a binding partner specific for the third ligand.  
     
     
         22 . A system for preparing a replicable array, in the form of a reusable array, the system comprising: 
 a) a master array comprising a plurality of optical fibers, each optical fiber having a support surface located at the distal end of the fiber; and    b) a plurality of oligonucleotide binding domains, each oligonucleotide binding domain comprising an oligonucleotide sequence selected to bind in a specific manner with a target ligand.