Method and device for preparing and/or analyzing biochemical reaction carriers

Abstract

The present invention relates to arrays of biochemical and/or biofunctional elements such as nucleic acids (oligonucleotides, for example) or other biomolecules on a carrier surface and methods of producing such arrays using photoactivation of predetermined areas for synthesis using an illumination matrix that is computer-controlled to generate an exposure pattern. This exposure pattern can be adjusted and monitored by computer using a light sensor matrix, for example a CCD matrix, to allow precise, controlled illumination of specific regions and therefore attachment of array building blocks to those specific regions. The methods and compositions of the invention permit spatially resolved photochemical synthesis of polymer probes on a carrier.

1 - 72 . (canceled) 
     
     
         73 . A method for synthesizing polymers, comprising synthesizing a multiplicity of oligomeric building blocks on a carrier in parallel steps, removing said oligomeric building blocks from said carrier and bringing said oligomeric building blocks into contact with each other to synthesize the polymers. 
     
     
         74 . The method of  claim 73 , wherein said polymers are double-stranded nucleic acid polymers of at least 300 bp. 
     
     
         75 . The method of  claim 74 , wherein said polymers are double-stranded nucleic acid polymers of at least 1000 bp. 
     
     
         76 . The method of  claim 74 , wherein said polymers are nucleic acid polymers selected from the group consisting of genes, gene clusters, chromosomes, viral genomes, bacterial genomes and sections thereof. 
     
     
         77 . The method of  claim 74 , wherein said oligomeric building blocks are from 5 to 150 monomeric units in length. 
     
     
         78 . The method of  claim 74 , wherein said oligomeric building blocks are from 5 to 30 monomeric units in length. 
     
     
         79 . The method of  claim 73 , wherein a first portion of said oligomeric nucleic acid building blocks are partially complementary to a second portion of said oligomeric nucleic acid building blocks and wherein, in successive steps, said first and second portions of oligomeric building blocks are removed from the carrier and brought into contact with each other under hybridization conditions. 
     
     
         80 . A method for preparing a carrier coated with biologically or chemically functional materials, which comprises:
 (a) providing a carrier having a surface with at least one predetermined area and which has photoactivatable groups thereon;   (b) activating said photoactivatable groups on said at least one predetermined area of the carrier surface by location-specific exposure of the carrier using an illumination matrix which can be controlled to generate an optionally adjustable exposure pattern;   (c) binding of biologically or chemically functional materials or building blocks for such materials on at least one of the predetermined areas in a location-specific manner;   (d) optionally repeating (b) and (c) on the same predetermined area, at least one different predetermined area or both; and   (e) at least partially removing said biologically or chemically functional materials on said carrier.   
     
     
         81 . The method of  claim 80 , wherein said biologically or chemically functional materials are polymers selected from the group consisting of nucleic acids, nucleic acid analogs and proteins. 
     
     
         82 . The method of  claim 81 , further comprising using said biologically or chemically functional materials as building blocks for further synthesis of polymers. 
     
     
         83 . The method of  claim 82 , wherein said polymers are nucleic acid polymers. 
     
     
         84 . A method for preparing a carrier coated with biologically or chemically functional materials, which comprises:
 (a) providing a carrier having a surface with at least one predetermined area and which has photoactivatable groups thereon;   (b) activating said photoactivatable groups on said at least one predetermined area of the carrier surface by location-specific exposure of the carrier using an illumination matrix which can be controlled to generate an optionally adjustable exposure pattern;   (c) binding of biologically or chemically functional materials that are selected from the group consisting of nucleic acids, nucleic acid analogs, both nucleic acids and nucleic acid analogs and building blocks for such materials, on at least one of the predetermined areas in a location-specific manner;   (d) optionally repeating (b) and (c) on the same predetermined area, at least one different predetermined area or both;   (e) at least partially removing said biologically or chemically functional materials on different areas of said carrier in successive steps; and   (f) using said biologically or chemically functional materials as building blocks for further synthesis of polymers.   
     
     
         85 . The method of  claim 84 , wherein said polymers are nucleic acid polymers. 
     
     
         86 . The method of  claim 80 , comprising generating said exposure pattern using electromagnetic radiation selected from the group consisting of IR, visible, UV, X-ray or any combination thereof. 
     
     
         87 . The method of  claim 80 , comprising exposing said carrier to radiation that is selected from the group consisting of pulsating, coherent, monochromatic, parallel radiation and any combination thereof, and wherein said radiation optionally is focused in different planes. 
     
     
         88 . The method of  claim 80 , wherein said carrier has more than one predetermined area. 
     
     
         89 . The method of  claim 88 , wherein more than one different predetermined areas are exposed parallel. 
     
     
         90 . The method of  claim 80 , wherein said illumination matrix is a reflection matrix, wherein said reflection matrix optionally has a mirror arrangement deformable in a controlled way. 
     
     
         91 . The method of  claim 90 , wherein said reflection matrix is selected from a light modulator with viscoelastic control layers and a light modulator with micromechanical mirror arrays. 
     
     
         92 . The method of  claim 80 , wherein said illumination matrix is a matrix arrangement that comprises light sources or individually controllable areas of one light source. 
     
     
         93 . The method of  claim 92 , wherein said illumination matrix is prepared on a chip. 
     
     
         94 . The method of  claim 92 , wherein said illumination matrix is selected from the group consisting of a laser array, a diode array and both a laser array and a diode array. 
     
     
         95 . The method of  claim 80 , wherein said carrier is optically transparent. 
     
     
         96 . The method of  claim 80 , wherein said carrier has a surface consisting of semiconducting materials. 
     
     
         97 . The method of  claim 96 , wherein said semiconducting materials are selected from the group consisting of silicon, germanium aresenide, gallium arsenide, glass, quartz glass, plastics and a combination thereof. 
     
     
         98 . The method of  claim 80 , wherein said predetermined area comprises from 1 μm 2  to 1 cm 2 . 
     
     
         99 . The method of  claim 98 , wherein said predetermined area comprises from 100 μm 2  to 1 mm 2 . 
     
     
         100 . The method of  claim 80 , wherein said predetermined area is surrounded by nonactivated or/and nonactivatable areas. 
     
     
         101 . The method of  claim 100 , wherein said illumination matrix inherently generates an exposure pattern that illuminates said predetermined areas. 
     
     
         102 . The method of  claim 80 , wherein said biologically or chemically functional materials are selected from the group consisting of biological substances and materials that react with biological substances. 
     
     
         103 . The method of  claim 80 , wherein said biologically or chemically functional materials are selected from the group consisting of nucleic acids, nucleotides, oligonucleotides, nucleic acid analogs, PNA, peptides, proteins, amino acids, saccharides, cells, subcellular preparations, cell organelles, cell membranes, viral particles, cell aggregates, allergens, pathogens, pharmacological active substances and diagnostic reagents. 
     
     
         104 . The method of  claim 80 , comprising synthesizing said biologically or chemically functional materials on the carrier in two or more stages from monomeric or/and oligomeric building blocks. 
     
     
         105 . The method of  claim 80 , comprising generating on the carrier a substance library comprising a multiplicity of different biologically or chemically functional materials. 
     
     
         106 . The method of  claim 80 , wherein activating said photoactivatable groups comprises cleaving a protective group off the carrier itself or off materials or building blocks thereof which are bound on said carrier. 
     
     
         107 . The method of  claim 80 , wherein said exposure of the carrier by said illumination matrix takes place at a rate of from 1/10000 to 1000 light patterns per second. 
     
     
         108 . The method of  claim 80 , wherein said exposure of the carrier by said illumination matrix takes place at a rate of from 1/10 to 100 light patterns per second. 
     
     
         109 . The method of  claim 80 , further comprising monitoring said exposure of the carrier, and optionally controlling said exposure of the carrier, using a sensor matrix. 
     
     
         110 . The method of  claim 109 , wherein said sensor matrix is a CCD matrix. 
     
     
         111 . The method of  claim 110 , wherein said illumination matrix, carrier and sensor matrix form a transmitted-light arrangement. 
     
     
         112 . The method of  claim 110 , wherein said illumination matrix, carrier and sensor matrix form a reflected-light arrangement. 
     
     
         113 . The method of  claim 110 , further comprising precalibrating said carrier using said illumination matrix and said sensor matrix.