Printing molecular library arrays

Abstract

A method and apparatus for selectively applying a print material onto a substrate for the synthesis of an array of oligonucleotides at selected regions of a substrate. The print material includes a barrier material, a monomer sequence, a nucleoside, a deprotection agent, a carrier material, among other materials. The method and apparatus also relies upon standard DMT based chemistry, and a vapor phase deprotection agent such as solid TCA and the like.

What is claimed is:  
     
         1 . A method of forming polymers having diverse monomer sequences on a substrate, said method comprising: 
 providing a substrate comprising a linker molecule layer thereon, said linker molecule layer comprising a linker molecule and a protective group;    applying a barrier layer overlying said linker molecule layer, said applying step forming selected exposed regions of said linker molecule layer; and    exposing said selected exposed regions of said linker molecule layer to a vapor comprising a deprotecting agent.    
     
     
         2 . The method of  claim 1  wherein said deprotection agent is an acidic vapor selected from a group consisting of TCA, DCA, and HCl.  
     
     
         3 . The method of  claim 1  wherein said deprotection agent is at a temperature ranging from about 20° C. to about 50° C.  
     
     
         4 . The method of  claim 1  wherein said applying step is selected from a group consisting of relief press printing, letter press printing, gravure printing, intaglio printing, stencil printing, and lithography.  
     
     
         5 . The method of  claim 1  wherein said barrier layer is selected from a group consisting of a lacquer, an epoxy, an oil, a polyester, and a polyurethane.  
     
     
         6 . The method of  claim 1  wherein said barrier layer is a liquid.  
     
     
         7 . The method of  claim 1  wherein said deprotection agent comprises a carrier gas.  
     
     
         8 . The method of  claim 1  wherein said deprotection agent comprises a water vapor.  
     
     
         9 . A method of deprotecting selected regions of a substrate, said method comprising: 
 providing a substrate comprising a layer of linker molecules thereon, each of said linker molecules having a protective group;    applying a vapor deprotection agent to selected regions of said linker molecule layer.    
     
     
         10 . The method of  claim 9  wherein said deprotection agent is selected from a group consisting of TCA, DCA, and HCl.  
     
     
         11 . The method of  claim 9  wherein said deprotection agent is at a temperature ranging from about 20° C. to about 50° C.  
     
     
         12 . The method of  claim 9  wherein said applying step occurs through forced convention.  
     
     
         13 . The method of  claim 9  wherein said deprotection agent comprises a carrier gas.  
     
     
         14 . The method of  claim 9  wherein said deprotection agent comprises a water vapor.  
     
     
         15 . A method of applying a medium in selected regions of a substrate, said method comprising the steps of: 
 providing a partially completed substrate comprising an array of monomers, said partially completed substrate having a top surface;    selectively applying a medium comprising an element selected from a group consisting of a barrier material, a receptor, a deprotection agent, a monomer group, a carrier material, and an activator to selected regions of said substrate top surface.    
     
     
         16 . The method of  claim 15  wherein said medium is selected from a group consisting of TCA, DCA, HCL, and any other acidic vapor.  
     
     
         17 . The method of  claim 15  wherein said medium is at a temperature ranging from about 20° C. to about 50° C.  
     
     
         18 . The method of  claim 15  wherein said medium is a deprotection agent.  
     
     
         19 . The method of  claim 18  wherein said deprotection agent comprises a carrier gas.  
     
     
         20 . The method of  claim 18  wherein said deprotection agent comprises a water vapor.  
     
     
         21 . The method of  claim 15  wherein said selectively applying step is selected from a group consisting of relief press printing, letter press printing, gravure printing, intaglio printing, and stencil printing.  
     
     
         22 . The method of  claim 15  wherein said selectively applying step occurs through a drop-on-demand printhead.  
     
     
         23 . A method of synthesizing an oligonucleotide comprising the steps of: 
 coupling a first portion of said oligonucleotide to said substrate, said first portion of said oligonucleotide comprising a removable protecting group;    removing said protecting group with a vapor phase deprotection agent to expose a functional group on said first portion of said oligonucleotide; and    covalently bonding a second portion of said oligonucleotide to said first portion of said oligonucleotide.    
     
     
         24 . The method as recited in  claim 23  wherein said surface of said substrate is selectively protected by a mask during said removing step.  
     
     
         25 . The method as recited in  claim 24  further comprising repeating said removing and covalently bonding steps to form an array of oligonucleotides.  
     
     
         26 . The method of  claim 24  wherein said vapor phase deprotection agent is selected from a group consisting of TCA, DCA, and HCl.  
     
     
         27 . The method of  claim 24  wherein said mask is selected from a group consisting of an epoxy, a silicone oil, a metal, a silicon material, a lacquer, a oil, and a polyester.  
     
     
         28 . The method of  claim 24  wherein said mask is held in place by electrostatic force.