WO1999060156A2 - Procede et dispositif pour produire par photolithographie des puces d'adn, d'acide nucleique peptidique et de proteine - Google Patents

Procede et dispositif pour produire par photolithographie des puces d'adn, d'acide nucleique peptidique et de proteine Download PDF

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Publication number
WO1999060156A2
WO1999060156A2 PCT/DE1999/001524 DE9901524W WO9960156A2 WO 1999060156 A2 WO1999060156 A2 WO 1999060156A2 DE 9901524 W DE9901524 W DE 9901524W WO 9960156 A2 WO9960156 A2 WO 9960156A2
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WO
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Prior art keywords
dna
mask
pna
production
photolithographic
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PCT/DE1999/001524
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German (de)
English (en)
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WO1999060156A3 (fr
Inventor
Arno Svend Heuermann
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Epigenomics Gmbh
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Application filed by Epigenomics Gmbh filed Critical Epigenomics Gmbh
Priority to AU48968/99A priority Critical patent/AU4896899A/en
Publication of WO1999060156A2 publication Critical patent/WO1999060156A2/fr
Publication of WO1999060156A3 publication Critical patent/WO1999060156A3/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • G—PHYSICS
    • G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
    • G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
    • G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
    • G—PHYSICS
    • G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
    • G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
    • G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
    • G03F7/20—Exposure; Apparatus therefor
    • G03F7/2002—Exposure; Apparatus therefor with visible light or UV light, through an original having an opaque pattern on a transparent support, e.g. film printing, projection printing; by reflection of visible or UV light from an original such as a printed image
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00427—Means for dispensing and evacuation of reagents using masks
    • B01J2219/00432—Photolithographic masks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00427—Means for dispensing and evacuation of reagents using masks
    • B01J2219/00434—Liquid crystal masks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B01J2219/00529—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/0059—Sequential processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00608—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00686—Automatic
    • B01J2219/00689—Automatic using computers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00709—Type of synthesis
    • B01J2219/00711—Light-directed synthesis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00725—Peptides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00729—Peptide nucleic acids [PNA]
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

  • the invention relates to a process for the preparation of oligonucleotides photolithogra ⁇ phical on two-dimensional matrices for the production of so-called DNA, PNA or protein chips, and an apparatus for performing the method.
  • DNA chips Surfaces on which a large number of different DNA molecules are fixed or synthesized in the smallest area are referred to as DNA chips. From any point on such a chip, it is generally known which DNA is on it. An important class of these chips is characterized in that short sequences, so-called oligonucleotides, are synthesized in situ on the chip surface. This considerably limits the number of chemical reaction steps that would otherwise be required to synthesize huge numbers of different sequences.
  • DNA chips can be made in several ways. The simplest but most expensive and most complex is the application of previously synthesized molecules using pipetting systems. Such methods are unlikely to be competitive in the future.
  • nucleotide building systems which carry two types of protective groups.
  • such protective groups which protect the functionalities of the bases
  • a different type of protective group which only allows chain extension by a single building block.
  • the removal of this last protecting group is essential for the m situ synthesis.
  • Protective groups must be split off quantitatively at extremely many points of a matrix without causing such a split-off at the other points. Chemical methods quickly reach the limit of the resolution of the pipetting systems. The individual drops that are applied are too large and overlap from a certain density.
  • Points will be drawn. Two ways are feasible to achieve a high resolution and thus occupancy density on such surfaces.
  • each individual point of a surface is individually controlled with a light beam - for example a laser - and so the protective groups of the nucleotide chains are only deprotected at the illuminated points.
  • the necessary irradiation time is so long that these methods are still too time-consuming.
  • DNA is also destroyed by laser bombardment.
  • the possibly tens of thousands of points have to be addressed one after the other. Even complex ones were possible for example mirror mechanisms which control many points at the same time. Such devices are currently not available.
  • the second and most common method today is to install masks between the chip surface and a light source.
  • the light from the light source is only let through at the points to the chip surface where deprotection is to take place. Therefore, virtually any number of reactions can be carried out in parallel.
  • four different masks must be positioned sequentially over the surface in order to extend all oligonucleotides by one nucleotide.
  • 120 masks have to be produced and successively positioned extremely precisely above the surface.
  • the proposed method according to the invention is intended to enable the future to be able to dispense with the establishment of own factories for the production of DNA and PNA chips.
  • the method is said to make the most complex step of chip division, the production and positioning of the masks superfluous.
  • the object of the present invention is to provide a method which overcomes the disadvantages of the prior art.
  • the object is achieved by a process for the photolithographic production of oligonucleotides on two-dimensional matrices for the production of so-called DNA, PNA or protein chips, in which a dynamically controllable liquid crystal mask is used as the photolithographic mask.
  • a device for the photolithography production of oligonucleotides on two-dimensional matrices for the production of so-called DNA, PNA or protein chips is made available, in which a dynamically controllable liquid crystal mask is arranged between the chip and the light source as the photolithographic mask.
  • the method according to the invention achieves the task in a completely new way by combining commercially available components. Compared to modern methods, the synthesis of DNA and PNA chips is therefore cheaper by several orders of magnitude. The monopoly of a few large factories can thus be broken and the manufacture of inexpensive DNA chips made accessible to the general public.
  • the basic concept of the method is the fact known per se that liquid crystal matrices can be used as dynamically controllable photolithographic masks (Bertsch et al., J Photochem. & Photobiol. 107, 275-281 (1997)). However, this technique has never been used or discussed in the field of synthesis of biochemical polymers on surfaces.
  • the method according to the invention eliminates the need to produce a large number of different photolithographic masks.
  • the liquid crystal lattice according to the invention can be driven at every point of the matrix by vapor-deposited transistors.
  • the resolution of the chips to be produced is therefore only dependent on the number of individually controllable cells of the liquid crystal. Instead of a physical arrangement of holes in an opaque surface, each mask is achieved by the purely electronic control of the individual cells.
  • the resolution of the mask - limited by the minimum size of the individual cells - can be increased practically infinitely by using a larger liquid crystal matrix than the final chip.
  • the light that falls through this large dynamic mask can then be telescoped onto the surface through optical lenses.
  • This technology can also prevent the otherwise fading effect of the liquid crystals: less light falls on the liquid crystals per area than is required behind them for deprotection on the chip surface.
  • the control of the liquid crystal is simply changed by the computer in the method according to the invention.
  • Deprotection lies in the synthesis of chemical steps for which no light energy is necessary. This also takes place within the device according to the method, without the movement of the chip or the mask being necessary. Due to the rigid arrangement and extremely precise positioning of the chip, mask and light source, mechanical problems such as the repositioning that is often necessary according to the prior art are avoided.
  • a device according to the method can therefore be designed mechanically in a very simple manner.
  • a device is characterized in that chip blanks are produced which either have chemically activatable surfaces (to which any nucleotide building block can be coupled) or are already covered with protected, photochemically removable molecules.
  • Such molecules can, for example, directly represent individual nucleotides or PNA building blocks which have been applied uniformly to the surface during production.
  • An essential property of these blanks is their packaging. These are manufactured in a clean, pollution-free manner and packaged in such a way that they can be inserted into the device in a manner that enables any contact with an unfiltered “normal” laboratory environment.
  • such a packaging can be sealed with a penetrable film
  • a blank packaged in this way can be inserted into the device by means of a seal, the actual blank being pressed out of the packaging, the film being pierced and then latching into the actual device (FIG. 1), which is the exact and immovable positioning of the blank during all further steps. Furthermore, contamination is excluded.
  • the blank comes to lie below the liquid crystal matrix.
  • the blank thus forms the bottom, the lower electrode plate of the liquid crystal matrix the ceiling of a very small cavity, which is also sealed on the sides. Chemical solutions are introduced into this cavity via several feed lines and this can also be air or gas dried.
  • the ceiling of the cavity can also be directly one of the components of the liquid crystal display due to a surface other than egg. For example, this can consist of a last part of the optics, which focus the light transmitted through the various cells of the liquid crystal.
  • the liquid crystal matrix itself consists in a manner known per se of liquid crystals, which are enclosed between two planar layers of a material which is transparent to the wavelengths essential for deprotection. Wavelengths that cannot specifically contribute to photo-deprotection are absorbed by these layers or other parts of the optics. Particularly short-wave ultraviolet light is absorbed by these layers. This destroys DNA.
  • One layer of material also acts as an electrode. Cables are placed on the other layer in such a way that the entire matrix is defined by cells that can be electrically controlled individually and divided into a narrow grid of points. Electrical excitation leads to an alignment of the liquid crystals only at the defined points. Light is then absorbed there. On the other hand, it is also possible that only the excited points become transparent to light of a certain wavelength.
  • the liquid crystal matrix can have exactly the size of the underlying chip surface. Then light with a relatively parallel beam path must be radiated onto the matrix by a simple light source. However, the liquid crystal matrix can also be of any size than the irradiated surface. In this case, an optical system must be introduced between the matrix and the chip, which bundles the translucent light.
  • the advantages of such an arrangement are that the energy acting on the matrix per area becomes lower than on the chip surface. This avoids the problematic effect which reduces the absorption capacity of the liquid crystals in the event of permanent irradiation.
  • the number of individual points on the chip surface can be increased practically as desired (FIG. 2).
  • a device designed according to the method according to the invention can operate independently by entering one or more sequences which are to be tested by hybridizing a target DNA with the chip.
  • the data processing can independently calculate the oligonucleotides to be synthesized from the sequences entered and calculate the sequence of the masks required for their synthesis. Coordinated with the various chemical reaction steps, these are then implemented fully automatically during the synthesis by the pattern of the voltages applied to the matrix in the individual deprotection steps.
  • a detector for example a CCD camera
  • this can then send signals to the register and evaluate individual points on the chip surface.
  • FIG. 1 shows a schematic illustration of a device according to the invention in the form of a work station
  • Fig. 2 is a schematic representation of a detailed view of the exposure device according to the invention.
  • the DNA or PNA chip 4 is inserted in the processing station 9 and supplied with the chemicals necessary for the reaction from the reagent storage 11.
  • the actual exposure station consists of the light source 1 and the LCD mask 2.
  • the other components shown, namely the polarizer 3, the focusing 7 and the barrier 8 serve to optically process the light. All functions are controlled by means of the computer 10, in particular the LCD mask 2 is controlled accordingly.
  • FIG. 2 shows a detailed view of a further embodiment of the device according to the invention.
  • the LCD mask 2 is again shown.
  • the chip 4 is arranged below the LCD mask 2.
  • the other optical elements namely a diffuser 5, a polarization 3 and a lens 6 are shown.

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  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nanotechnology (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • Materials Engineering (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Composite Materials (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Liquid Crystal (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un procédé pour produire par photolithographie des puces d'oligonucléotides sur des matrices bidimensionnelles pour la production de puces d'ADN, d'acide nucléique peptidique et de protéine. L'invention est caractérisée en ce que l'on utilise comme masque photolithographique un masque à cristaux liquides pouvant être commandé de façon dynamique. L'invention concerne également un dispositif pour mettre en oeuvre ledit procédé.
PCT/DE1999/001524 1998-05-18 1999-05-17 Procede et dispositif pour produire par photolithographie des puces d'adn, d'acide nucleique peptidique et de proteine WO1999060156A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU48968/99A AU4896899A (en) 1998-05-18 1999-05-17 Method and device for photolithographic production of dna, pna and protein chips

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE1998123454 DE19823454A1 (de) 1998-05-18 1998-05-18 Verfahren zur photolithographischen Herstellung von DNA, PNA und Protein Chips
DE19823454.6 1998-05-18

Publications (2)

Publication Number Publication Date
WO1999060156A2 true WO1999060156A2 (fr) 1999-11-25
WO1999060156A3 WO1999060156A3 (fr) 2000-02-17

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AU (1) AU4896899A (fr)
DE (1) DE19823454A1 (fr)
WO (1) WO1999060156A2 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000013017A2 (fr) * 1998-08-28 2000-03-09 Febit Ferrarius Biotechnology Gmbh Procede et dispositif de fabrication et/ou d'analyse de supports de reaction biochimiques
US6539102B1 (en) 2000-09-01 2003-03-25 Large Scale Proteomics Reference database
US6980674B2 (en) 2000-09-01 2005-12-27 Large Scale Proteomics Corp. Reference database
US7115738B2 (en) 2000-03-14 2006-10-03 Active Motif Hydroxyproline/phosphono oligonucleotide analogues, methods of synthesis and methods of use
US7470540B2 (en) 2000-10-17 2008-12-30 Febit Ag Method and device for the integrated synthesis and analysis of analytes on a support
EP2159290A1 (fr) 2008-08-27 2010-03-03 Samsung Electronics Co., Ltd. Procédé de production de micro-réseau doté d'une sonde d'acide nucléique à double brin immobilisé incluant une région à double brin et une région à simple brin

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19922941A1 (de) * 1999-05-14 2000-11-30 Epigenomics Gmbh Vorrichtung und Verfahren zur photolithographischen Belichtung von biologischen Stoffen
US6713309B1 (en) 1999-07-30 2004-03-30 Large Scale Proteomics Corporation Microarrays and their manufacture
US6653151B2 (en) 1999-07-30 2003-11-25 Large Scale Proteomics Corporation Dry deposition of materials for microarrays using matrix displacement
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