Support bound probes and methods of analysis using the same

Abstract

The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

What is claimed is:  
     
         1 . A binary method for combinatorial synthesis of more than 10 3  molecules in a total area of less than 1 cm 2  on a single support, comprising: 
 a) providing a single support structure having reaction regions, the number of reaction regions being greater than 10 3 /cm 2 ;    b) directing energy at a selected first set of localized areas to activate the first set of areas for synthesis of a molecule, thereby creating a first set of activated areas;    c) contacting a monomer of the molecule with an area inclusive of the first set of activated areas of the support;    d) coupling the monomer to the first set of activated areas of the support;    e) directing energy at a selected second set of localized areas which are the same as or different from, in whole or in part, the first set of localized areas to activate the second set of areas for synthesis of a molecule, thereby creating a second set of activated areas;    f) contacting a monomer of the molecule with an area inclusive of the second set of activated areas of the support;    g) coupling the monomer to the second set of activated areas of the support; and    h) repeating steps (e), (f) and (g) until the molecules are synthesized.    
     
     
         2 . The method of  claim 1 , wherein there are more than 10 4  molecules in a total area of less than 1 cm 2  on a single support.  
     
     
         3 . The method of  claim 2 , wherein there are more than 10 5  molecules in a total area of less than 1 cm 2  on a single support.  
     
     
         4 . The method of  claim 1 , wherein the method does not include the physical separation of liquids.  
     
     
         5 . The method of  claim 1 , wherein the support has a surface which can be composed of the same or different material as the support and the support or the surface comprises polymers, plastics, resins, polysaccharide, silicon, silicon based materials, carbon, metals, inorganic glasses, glasses, membranes, particles, strands, precipitates, gels, sheets, tubing, spheres, containers, capillaries, pads, slices, films, plates or slides.  
     
     
         6 . The method of  claim 1 , wherein the molecules are selected from the group consisting of nucleic acids, polypeptides, carbohydrates, alpha-, beta-, and omega-amino acids, polyurethanes, polyesters, polycarbonates, polyureas, polyamides, polyethyleneimines, polyarylene sulfides, polysiloxanes, polyimides, polyacetates, and mixed polymers.  
     
     
         7 . The method of  claim 1 , wherein the monomers of the molecules comprise a photosensitive protecting group.  
     
     
         8 . A method of synthesizing polymers, comprising: 
 providing a support;    iteratively, inactivating selected regions of the support in regions where activation is not desired;    iteratively, independently activating selected regions of the support; and    contacting the activated regions with a monomer under coupling conditions;    wherein monomers are covalently attached to the support in the activated regions on the support to form the polymers.    
     
     
         9 . The method of  claim 8 , wherein more than 10 4  polymers are synthesized on the support.  
     
     
         10 . The method of  claim 9 , wherein more than 10 5  polymers are synthesized on the support.  
     
     
         11 . The method of  claim 8 , wherein the method does not include the physical separation of liquids.  
     
     
         12 . The method of  claim 8 , wherein the support has a surface which can be composed of the same or different material as the support and the support or the surface comprises polymers, plastics, resins, polysaccharide, silicon, silicon based materials, carbon, metals, inorganic glasses, glasses, membranes, particles, strands, precipitates, gels, sheets, tubing, spheres, containers, capillaries, pads, slices, films, plates or slides.  
     
     
         13 . The method of  claim 8 , wherein the polymers are selected from the group consisting of nucleic acids, polypeptides, carbohydrates, alpha-, beta-, and omega-amino acids, polyurethanes, polyesters, polycarbonates, polyureas, polyamides, polyethyleneimines, polyarylene sulfides, polysiloxanes, polyimides, polyacetates, and mixed polymers.  
     
     
         14 . The method of  claim 8 , wherein the monomers comprise a photosensitive protecting group.  
     
     
         15 . A method of using combinatorial chemistry methods to synthesize polymers in n x  steps, comprising: 
 providing a set of monomers having n members;    iteratively, coupling the monomers to a support to achieve length x in n x  steps by selectively activating areas of the support and coupling monomers to activated areas of the support, wherein the support is protected from coupling in unwanted areas by protecting groups that are removed during the activation step.    
     
     
         16 . The method of  claim 15 , wherein more than 10 4  polymers are synthesized on the support.  
     
     
         17 . The method of  claim 16 , wherein more than 10 5  polymers are synthesized on the support.  
     
     
         18 . The method of  claim 15 , wherein the method does not include the physical separation of liquids.  
     
     
         19 . The method of  claim 15 , wherein the support has a surface which can be composed of the same or different material as the support and the support or the surface comprises polymers, plastics, resins, polysaccharide, silicon, silicon based materials, carbon, metals, inorganic glasses, glasses, membranes, particles, strands, precipitates, gels, sheets, tubing, spheres, containers, capillaries, pads, slices, films, plates or slides.  
     
     
         20 . The method of  claim 15 , wherein the polymers are selected from the group consisting of nucleic acids, polypeptides, carbohydrates, alpha-, beta-, and omega-amino acids, polyurethanes, polyesters, polycarbonates, polyureas, polyamides, polyethyleneimines, polyarylene sulfides, polysiloxanes, polyimides, polyacetates, and mixed polymers.  
     
     
         21 . The method of  claim 15 , wherein the protecting groups are photosensitive protecting groups.