Chemical amplification for the synthesis of patterned arrays

Abstract

Radiation-activated catalysts (RACs), autocatalytic reactions, and protective groups are employed to achieve a. highly sensitive, high resolution, radiation directed combinatorial synthesis of pattern arrays of diverse polymers. When irradiated, RACs produce catalysts that can react with enhancers, such as those involved in autocatalytic reactions. The autocatalytic reactions produce at least one product that removes protecting groups from synthesis intermediates. This invention has a wide variety of applications and is particularly useful for the solid phase combinatorial synthesis of polymers.

1 - 16 . (canceled)  
     
     
         17 . A method for synthesizing polymers of diverse sequences comprising the steps of 
 a) forming a surface comprising 
 i) a photosensitive compound or group, said photosensitive compound or group producing a catalyst when irradiated, and  
 ii) an autocatalytic compound or group, said autocatalytic compound or group generating a protecting group removing product when said autocatalytic compound is activated by said catalyst;  
   b) irradiating at least a part of said surface to remove said protecting group;    c) contacting the surface with a first monomer;    d) irradiating at least another part of said surface to remove said protecting group; and    e) contacting the surface with a second monomer.    
     
     
         18 . The method recited in  claim 17  wherein said photosensitive compound is a PAC.  
     
     
         19 . The method recited in  claim 17  wherein said autocatalytic compound is a masked acid.  
     
     
         20 . The method recited in  claim 17  wherein said synthesis intermediate is a linker molecule.  
     
     
         21 . The method recited in  claim 17  wherein said synthesis intermediate is a nucleotide.  
     
     
         22 . The method re cited in  claim 17  wherein said synthesis intermediate is a [[an]] polynucleotide.  
     
     
         23 . The method recited in  claim 17  wherein said synthesis intermediate is an amino acid.  
     
     
         24 . The method recited in  claim 17  wherein said synthesis intermediate is a polypeptide.  
     
     
         25 . The method recited in  claim 17  wherein said removable protecting group is an acid removable group.  
     
     
         26 . The method recited in  claim 17  wherein said photosensitive compound is a toluenesulfonic acid.  
     
     
         27 . The method recited in  claim 17  wherein said autocatalytic compound is a pentafluorobenoic acid.  
     
     
         28 . The method recited in  claim 17  wherein said acid removable protecting group is 5′ demethoxytrityl.  
     
     
         29 - 40 . (canceled)  
     
     
         41 . A method for hybridizing nucleic acid comprising the steps of: 
 a) forming a surface comprising 
 i) a photosensitive compound or group, said photosensitive  
 ii) compound or group producing a catalyst when irradiated, and  
 ii) an autocatalytic compound or group, said autocatalytic compound or group generating a protecting group removing product when said autocatalytic compound is activated by said catalyst;  
   b) irradiating at least a part of said surface to remove said protecting group;    c) contacting the surface with a first monomer;    d) irradiating at least another part of said surface to remove said protecting group;    e) contacting the surface with a second monomer;    f) repeating steps a to e to synthesize polynucleotide arrays of desired length; and    g) hybridizing a target nucleic acid to said polynucleotide arrays.    
     
     
         42 . The method recited in  claim 41  wherein said synthesis intermediate is a linker molecule.  
     
     
         43 . The method recited in  claim 41  wherein said synthesis intermediate is a nucleotide.  
     
     
         44 . The method recited in  claim 41  wherein said synthesis intermediate is a [[an]] polynucleotide.  
     
     
         45 . The method recited in  claim 41  wherein said removable protecting group is an acid removable group.  
     
     
         46 . The method recited in  claim 41  wherein said photosensitive compound is a toluenesulfonic acid.  
     
     
         47 . The method recited in  claim 41  wherein said autocatalytic compound is apentafluorobenzoic acid.  
     
     
         48 . The method recited in  claim 41  wherein said acid removable protecting group is 5′ dimethoxytrityl.  
     
     
         49 . A method for synthesizing a polymer array on a substrate comprising the steps of: 
 a) providing a surface of the substrate having one or more synthesis intermediates bound thereon and a catalyst system, the synthesis intermediates having a reactive group protected from reaction by a protective group;    b) irradiating the surface of the substrate with radiation of certain wavelength;    c) initiating a catalytic reaction to remove the protective group from the synthesis intermediates to produce unprotected reactive groups;    d) reacting a subsequently added synthesis intermediate with the unprotected reactive group, the subsequently added synthesis intermediate having a reactive group protected from reaction by a protective group;    e) repeating steps b) through d), or not, until a desired polymer sequence is obtained.    
     
     
         50 - 51 . (canceled)