METHOD AND DEVICE FOR PREPARING AND/OR ANALYZING BIOCHEMICAL REACTION CARRIERS

• US 20080214412A1
• Filed: 01/09/2008
• Published: 09/04/2008
• Est. Priority Date: 08/28/1998
• Status: Abandoned Application

• Current Assignee: Cord F. Stahler, Fritz Stahler, Hans Lindner, Manfred Muller, Peer F. Stahler
• Original Assignee: Cord F. Stahler, Fritz Stahler, Hans Lindner, Manfred Muller, Peer F. Stahler
• Inventors: Muller, Manfred, Lindner, Hans, Stahler, Cord F., Stahler, Peer F., Stahler, Fritz
• Application Number:
  US11/971,805
• Publication Number:
  US 20080214412A1
• Time in Patent Office: Days
• US Class Current: 506/30
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00436 Maskless processes
• CPC Class Codes: B01J 2219/00439 using micromirror arrays
• CPC Class Codes: B01J 2219/00441 using lasers
• CPC Class Codes: B01J 2219/00448 using microlens arrays
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00603 Making arrays on substantially continuous surfaces
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 : by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 : by coating it with another layer
• CPC Class Codes: B01J 2219/00648 : by the use of solid beads
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 : In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00704 : integrated with the reactor apparatus
• CPC Class Codes: B01J 2219/00711 : Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01L 2300/0654 : Lenses; Optical fibres
• CPC Class Codes: B01L 2300/069 : Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 : comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12N 15/10 : Processes for the isolation, preparation or purification of DNA or RNA chemical preparation of DNA or RNA C07H21/00; preparation of non-structural polynucleotides from microorganisms or with enzymes C12P19/34
• CPC Class Codes: C12P 19/34 : Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/6454 : using an integrated detector array
• CPC Class Codes: G01N 33/551 : the carrier being inorganic
• CPC Class Codes: G03F 7/70216 : Mask projection systems
• CPC Class Codes: Y10S 435/97 : Test strip or test slide
• CPC Class Codes: Y10S 435/973 : Simultaneous determination of more than one analyte

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.

Claims

1-72. -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.

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 μ

m² to 1 cm².

99. The method of claim 98, wherein said predetermined area comprises from 100 μ

m² to 1 mm².

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.

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.