A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reacto
A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protecting groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.
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1. An ordered method for forming a plurality of different polypeptides or nucleic acids occupying known locations on a substrate by sequential addition of nucleosides, nucleotides or amino acids to said substrate, comprising: (a) providing a substrate having a surface with a localized area occupi
1. An ordered method for forming a plurality of different polypeptides or nucleic acids occupying known locations on a substrate by sequential addition of nucleosides, nucleotides or amino acids to said substrate, comprising: (a) providing a substrate having a surface with a localized area occupied by a protected nucleoside, nucleotide or amino acid; (b) deprotecting the protected nucleoside, nucleotide or amino acid in a fraction of the localized area to produce a deprotected nucleoside, nucleotide or amino acid; (c) reacting the deprotected nucleoside, nucleotide or amino acid with a protected nucleoside, nucleotide or amino acid, whereby the protected nucleoside, nucleotide or amino acid attaches to the deprotected nucleoside, nucleotide or amino acid to produce a protected nucleic acid or polypeptide; and (d) repeating (b) and (c) at least once wherein the fraction in step (b) is a fraction of a fraction in a previous deprotecting step (b) to produce an array of different nucleic acids or polypeptides occupying different fractions at known locations within the localized area. 2. The method of claim 1, wherein the deprotecting step comprises exposing the fraction in step (b) to a protecting group removal agent. 3. The method of claim 1, wherein the deprotecting step comprises exposing said fraction to an energy source. 4. The method of claim 3, wherein the nucleoside, nucleotide or amino acid is protected by a photosensitive protecting group and said energy source includes light. 5. The method of claim 4, wherein the localized area is less than 0.001 cm2. 6. The method of claim 4, wherein the localized area in step (a) is less than 0.01 cm2. 7. An ordered method for forming a plurality of different nucleic acids or polypeptides occupying known locations on a substrate by sequential addition of nucleosides, nucleotides or amino acids to said substrate, comprising: (a) providing a substrate having a surface with a localized area occupied by a protected nucleoside, nucleotide or amino acid; (b) deprotecting the protected nucleoside, nucleotide or amino acid in a fraction of the localized area to produce a deprotected nucleoside, nucleotide or amino acid; (c) immersing the surface of the substrate in a solution comprising a protected nucleoside, nucleotide or amino acid, whereby the protected nucleoside, nucleotide or amino acids attaches to the deprotected nucleoside, nucleotide or amino acid to produce a protected nucleic acid or polypeptide in the fraction of the localized area; and (d) repeating (b) and (c) at least once wherein the fraction in step (b) is a fraction of a fraction in a previous deprotecting step (b) to produce an array of different nucleic acids or polypeptides occupying different fractions at known locations within the localized area. 8. The method of claim 7, wherein the protected nucleoside, nucleotide or amino acid is protected with a photosensitive protecting group, and the deprotecting is performed by exposing the protected compound to light, and the localized area is less than 0.01 cm2. 9. The method of claim 8, wherein the localized area is less than 0.001 cm2.
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