Photoelectrochemical Synthesis of High Density Combinatorial Polymer Arrays

Abstract

In a method for creating polymer arrays through photoelectrochemically modulated acid/base/radical generation for combinatorial synthesis, electrochemical synthesis is guided by a spatially modulated light source striking a semiconductor in an electrolyte solution. A substrate having at its surface at least one photoelectrode that is proximate to at least one molecule bearing at least one chemical functional group is provided, along with a reagent-generating chemistry co-localized with the chemical functional group and capable of generating reagents when subjected to a potential above a threshold. An input potential is then applied to the photoelectrode that exceeds the threshold in the presence of light and that does not exceed the threshold in the absence of light, causing the transfer of electrons to or from the substrate, and creating a patterned substrate. The process is repeated until a polymer array of desired size is created.

What is claimed is: 
     
         1 . A method for photoelectrochemical synthesis of a biomolecule array, comprising the steps of:
 (a) providing a semiconductor substrate having at least one light-addressable photoelectrode proximate to the substrate surface;   (b) providing an photoelectrochemical reaction-generating chemistry that is in contact with the semiconductor substrate and is capable of generating reagents when subjected to a potential above a threshold, the photoelectrochemical reaction-generating chemistry comprising an electrolyte solution, matrix, gel, or solid that is suitable for photoelectrochemical reactions at a surface;   (c) applying an input potential to the light-addressable photoelectrode to generate charge carriers in areas of the substrate under illumination and thereby create a patterned substrate, the applied input potential exceeding the threshold in the presence of light and not exceeding the threshold in the absence of light, the input potential being generated by light from a spatially-modulated light source, the light being patterned by a mask, LED, LCD, steered mirror, or digital micromirror array, wherein the charge carriers generate electrochemical reactions via transfer of electrons between the semiconductor substrate and the photoelectrochemical reaction-generating chemistry; and   (d) repeating steps (a) to (c) until a biomolecule array of desired size is synthesized.   
     
     
         2 . The method of  claim 1 , wherein the light-addressable photoelectrode is proximate to at least one molecule bearing at least one chemical functional group, the chemical functional group is protected, and the generated reagents are deprotecting. 
     
     
         3 . The method of  claim 1 , wherein the light-addressable photoelectrode is proximate to at least one molecule bearing at least one chemical functional group, the chemical functional group is unprotected, and the generated reagents are activating. 
     
     
         4 . The method of  claim 2 , wherein the protected chemical functional group is located on a second parallel substrate and the photoelectrochemical reaction-generating chemistry can diffuse towards the protected chemical function group on the second substrate. 
     
     
         5 . The method of  claim 1 , wherein the light-addressable photoelectrode is proximate to at least one molecule bearing at least one chemical functional group and reagents generated by the photoelectrochemical reaction-generating chemistry promote the removal of a protecting group from the chemical functional group by another agent. 
     
     
         6 . The method of  claim 1 , wherein reagents generated by the photoelectrochemical reaction-generating chemistry promote the addition of a monomer. 
     
     
         7 . The method of  claim 2 , wherein reagents generated by the photoelectrochemical reaction-generating chemistry inhibit the removal of a protecting group from the chemical functional group by another agent. 
     
     
         8 . The method of  claim 1 , wherein reagents generated by the photoelectrochemical reaction-generating chemistry inhibit the addition of a monomer. 
     
     
         9 . The method of  claim 1 , in which the photoelectrode is selected from the group consisting of a semiconductor, silicon, an organic photoconductor, titanium dioxide, dye sensitized titanium dioxide, a schottky diode, a layered structure of silicon and another semiconductor, a P-I-N diode, a P-N junction, and a P-N junction having a top layer coated with an inert metal. 
     
     
         10 . The method of  claim 1 , wherein the applied input potential is selected from the group consisting of: the peak potential of the substrate, within +/−0.5V of the peak potential of the substrate, AC, AC and synchronized with the illumination source, pulsed, and pulsed and synchronized with the illumination source. 
     
     
         11 . The method of  claim 1 , wherein the photoelectrode acts as a photoconductor that generates a potential that is approximately linearly proportional to an applied light field and is biased below the threshold. 
     
     
         12 . The method of  claim 1 , wherein the photoelectrode acts as a photoconductor that is biased above the bandgap threshold potential of the substrate so that there exists sufficient energy for the electrons to overcome the bandgap when no light is applied. 
     
     
         13 . The method of  claim 1 , further comprising the step of generating getters for rendering neutral reagents generated by the electrochemical reaction-generating chemistry by oppositely biasing, to the photoelectrode, one or more adjacent photoelectrodes. 
     
     
         14 . The method of  claim 13 , wherein the getters spatially localize the effect of any deprotecting reagents. 
     
     
         15 . The method of  claim 14 , wherein the deprotecting reagents are acids and the getters are bases, the deprotecting reagents are acids and the getters are radicals, the deprotecting reagents are bases and the getters are acids, the deprotecting reagents are radicals and the getters are acids, or the deprotecting reagents are radicals and the getters are radicals. 
     
     
         16 . The method of  claim 1 , wherein the polymer array is a DNA array and the photoelectrochemical reactions comprise phosphoramidite synthesis. 
     
     
         17 . The method of  claim 1 , wherein the synthesis is performed in a fluidic capable of electrochemical synthesis and chemical resistance to solvents, acids, and bases. 
     
     
         18 . The method of  claim 1 , further comprising the step of providing a porous reaction layer disposed on the substrate. 
     
     
         19 . The method of  claim 1 , wherein the light-addressable photoelectrode is proximate to at least one molecule bearing at least one chemical functional group that can be cleaved and the photoelectrochemical reaction-generating chemistry is capable of generating cleaving reagents. 
     
     
         20 . The method of  claim 19 , wherein the cleaving agent selectively promotes the cleavage of a molecule from a surface by another agent. 
     
     
         21 . The method of  claim 19 , wherein the cleaving agent selectively inhibits the cleavage of a molecule from a surface by another agent. 
     
     
         22 . The method of  claim 1 , wherein the photoelectrode is a continuous photoelectrode such that different regions of the photoelectrode may be differentially optically addressed and further comprising the step of differentially optically addressing the continuous photoelectrode to create a spatial pattern of material. 
     
     
         23 . The method of  claim 1 , wherein the spatially-modulated light source is temporally modulated. 
     
     
         24 . The method of  claim 1 , wherein there is a one-dimensional or two-dimensional array of photoelectrodes. 
     
     
         25 . The method of  claim 24 , wherein the photoelectrodes are differentially optically addressed to create a spatial pattern of material. 
     
     
         26 . The method of  claim 2 , further comprising the step of monitoring the generation of deprotecting agents in real-time using a pH-sensitive dye. 
     
     
         27 . The method of  claim 2 , further comprising the step of monitoring the deprotection reactions in real-time using UV absorption spectroscopy. 
     
     
         28 . The method of  claim 2 , further comprising the step of electrochemically monitoring the generation of deprotecting agents using the photoelectrode.