Very large scale immobilized polymer synthesis

Abstract

A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

1 - 104 . (canceled)  
     
     
         105 . A method for forming a polymer array, the method comprising: providing a substrate suitable for synthesizing polymer sequences; forming an array, each one of a plurality of locations of the array having at least one strand end; forming photosensitive protection on the strand ends; selectively scanning and modulating at least one energy beam to expose a pattern on the photosensitive protection; removing a protective group from selected strand ends based on the exposed pattern; and adding a predetermined one or more polymeric subunits to the deprotected strand ends.  
     
     
         106 . The method according to  claim 105 , wherein the forming photosensitive protection includes depositing a layer of photoresist to cover the strand ends.  
     
     
         107 . The method according to  claim 105 , wherein the one or more energy beams includes light from an ultra-violet laser.  
     
     
         108 . The method according to  claim 105 , wherein the polymer sequences are DNA sequences.  
     
     
         109 . The method according to  claim 105 , wherein the substrate includes a plurality of wells formed on a major surface of the substrate.  
     
     
         110 . The method according to  claim 105 , wherein the selectively scanning and modulating includes simultaneously scanning two or more beams of light from ultraviolet lasers.  
     
     
         111 . A system for forming a polymer array on a substrate, the system comprising: an energy-beam source that produces an energy beam; a scanner configured to move the energy beam in a scanned pattern on the substrate; a computer operatively coupled to the scanner to control the scanned pattern of energy according to a sequence definition for each of a plurality of desired polymer sequences being synthesized; a reagent source configured to add one of a plurality of monomers at each end location of each of a plurality of strands formed on the substrate; and apparatus to provide photosensitive protection that controls an order of monomers based on the scanned pattern of light.  
     
     
         112 . The system according to  claim 111 , wherein the apparatus to provide photosensitive protection includes apparatus that deposits a layer of photoresist to cover the strand ends.  
     
     
         113 . The system according to  claim 111 , wherein the energy-beam source includes an ultra-violet laser.  
     
     
         114 . The system according to  claim 111 , wherein the polymer sequences are DNA sequences.  
     
     
         115 . The system according to  claim 111 , wherein the substrate includes a plurality of wells formed on a major surface of the substrate.  
     
     
         116 . The system according to  claim 111 , wherein the energy-beam source produces two or more beams of light from ultraviolet lasers.  
     
     
         117 . The system according to  claim 111 , further comprising a modulator, operatively coupled to be controlled by the computer, that modulates an intensity of the light.  
     
     
         118 . A system for forming a polymer array on a substrate, the system comprising: means for scanning a pattern of energy on the substrate according to a sequence definition for each of a plurality of desired polymer sequences being synthesized on the substrate; a reagent source configured to add one of a plurality of monomers at each end location of each of a plurality of strands formed on the substrate; and means for providing photosensitive protection that controls an order of monomers based on the scanned pattern of light.  
     
     
         119 . The system according to  claim 118 , wherein the apparatus to provide photosensitive protection includes apparatus that deposits a layer of photoresist to cover the strand ends.  
     
     
         120 . The system according to  claim 118 , wherein the means for scanning includes an ultra-violet laser.  
     
     
         121 . The system according to  claim 118 , wherein the polymer sequences are DNA sequences.  
     
     
         122 . The system according to  claim 118 , wherein the means for scanning includes two or more beams of light from ultraviolet lasers.  
     
     
         123 . The system according to  claim 118 , wherein the means for scanning includes a modulator for modulating an intensity of the light.  
     
     
         124 . A system for forming a polymer microarray on a substrate, the system comprising: a first ultraviolet laser; a first scanner configured to move light from the first ultraviolet laser in a scanned pattern on the substrate; a computer operatively coupled to the first scanner to control the scanned pattern of light according to a sequence definition for each of a plurality of desired polymer sequences being synthesized; a reagent source configured to add one of a plurality of monomers at each end location of each of a plurality of strands formed on the substrate; and apparatus to provide photoresist layer that is patterned by the scanned light pattern to controls an order of monomers based on the computer-controlled scanned pattern of light.  
     
     
         125 . The system according to  claim 124 , wherein the polymer sequences are DNA sequences.  
     
     
         126 . The system according to  claim 124 , wherein the substrate includes a plurality of wells formed on a major surface of the substrate.  
     
     
         127 . The system according to  claim 124 , further comprising: a second ultraviolet laser; and a second scanner configured to move light from the second ultraviolet laser in a scanned pattern on the substrate, wherein the computer is operatively coupled to the second scanner to control the scanned pattern of light according to a sequence definition for each of a plurality of desired polymer sequences being synthesized.