EP1673161A1 - Procede et dispositif pour effectuer des reactions - Google Patents

Procede et dispositif pour effectuer des reactions

Info

Publication number
EP1673161A1
EP1673161A1 EP04765899A EP04765899A EP1673161A1 EP 1673161 A1 EP1673161 A1 EP 1673161A1 EP 04765899 A EP04765899 A EP 04765899A EP 04765899 A EP04765899 A EP 04765899A EP 1673161 A1 EP1673161 A1 EP 1673161A1
Authority
EP
European Patent Office
Prior art keywords
reaction
synthesis
metering
reagent
reagents
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP04765899A
Other languages
German (de)
English (en)
Inventor
Wolfgang Ehrfeld
Karoly Nagy
Alexander Azzawi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ehrfeld Mikrotechnik BTS GmbH
Original Assignee
Ehrfeld Mikrotechnik BTS GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ehrfeld Mikrotechnik BTS GmbH filed Critical Ehrfeld Mikrotechnik BTS GmbH
Publication of EP1673161A1 publication Critical patent/EP1673161A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1074—Multiple transfer devices arranged in a two-dimensional array
    • 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
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • 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
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B01J2219/00317—Microwell devices, i.e. having large numbers of wells
    • 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
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00324—Reactor vessels in a multiple arrangement the reactor vessels or wells being arranged in plates moving in parallel to each other
    • B01J2219/00328—Movement by linear translation
    • 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
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00331—Details of the reactor vessels
    • B01J2219/00333—Closures attached to the reactor vessels
    • 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
    • B01J2219/00418—Means for dispensing and evacuation of reagents using pressure
    • 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
    • B01J2219/00513—Essentially linear supports
    • B01J2219/00518—Essentially linear supports in the shape of tapes
    • 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
    • B01J2219/00583—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
    • B01J2219/00614—Delimitation of the attachment areas
    • B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
    • 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
    • B01J2219/00623—Immobilisation or binding
    • B01J2219/00626—Covalent
    • 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
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00675—In-situ synthesis on the substrate
    • 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
    • B01J2219/00677—Ex-situ synthesis followed by deposition on the substrate
    • 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
    • B01J2219/00718—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
    • B01J2219/00731—Saccharides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0812—Bands; Tapes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/12—Libraries containing saccharides or polysaccharides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
    • C40B50/14—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
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1037—Using surface tension, e.g. pins or wires
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00009—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with a sample supporting tape, e.g. with absorbent zones
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1002—Reagent dispensers

Definitions

  • the invention relates to a method and a device for carrying out, in particular, chemical reactions with reagent amounts in the picomole to micromole range, such as those e.g. can be used for the synthesis of various oligonucleotides.
  • the device for carrying out chemical reactions comprises a reaction slider in which a plurality of through openings serving as reaction chambers are formed. Furthermore, the device comprises a selector slider which is arranged on the upper surface of the reaction slider and which has at least one continuous control opening, the selector slider being displaceable with respect to the reaction slider such that its control opening is in alignment with one of the reaction chambers of the reaction slider, so that a continuous connection for supplying the reaction chambers with a predetermined reagent is created.
  • a chemical slider is arranged below the reaction slider and is designed with passages for supplying chemicals to the individual reaction chambers of the reaction slider.
  • the chemicals can be fed to the chemical slider premixed via a valve arrangement.
  • a device is provided for applying a force to the slider, this device being designed such that the force acts in the region of the axis of rotation.
  • microtiter plates for the synthesis of oligonucleotides is described in Ji-Yen Cheng et al., "High throughput parallel synthesis of oligonucleotides with 1536 Channel Synthesizer", Nucleic Acids Research, 2002, Vol. 30, No. 18, e93 different oligonucleotides are simultaneously synthesized in the individual wells of the microtiter plate.
  • BESTATIGUNGSKOPIE In the devices for the synthesis of oligonucleotides known from the prior art, the individual solutions and reagents are pumped from the storage bottles via a sufficient number of controllable valves into a reaction chamber containing a solid phase.
  • the synthetic scales currently used for carrying out oligonucleotide syntheses are above 20 nmol.
  • a parallelization of the valve technology used in the state-of-the-art synthesis machines can only be carried out to a small degree due to the space requirement and the increasing dead volume with increasing complexity.
  • reaction chamber usually only one reaction chamber is attached to the end of a fluid distribution path.
  • the individual reaction steps require a predetermined reaction time which cannot be shortened. During this time, the complex dosing unit waits until the next process step can be started.
  • Amounts in the lower nanomole range of an oligonucleotide sample are sufficient for many applications. This means that the synthesizers currently used are oversized with a synthesis scale of more than 20 nmol.
  • the object of the present invention is to provide a device for carrying out reactions on a synthesis scale of less than 20 nmol, in which the syntheses can be carried out continuously and in parallel.
  • the solution according to the invention consists in a device for carrying out, in particular, chemical reactions with reagent amounts in the picomole to micromole range, in which the reagents are metered via metering stations to reaction sites which move along a reaction path, with at least one metering station and one removal point being arranged in this way are that the time in which the reaction sites move on the reaction path corresponds at least to the reaction time required for a reaction step.
  • the metering stations are designed such that they each comprise a belt on which the reagent is metered in sections at metering positions, at least one hole in the belt at each metering position, the cross section of which is dimensioned such that the reagent is due to its surface tension does not flow through the at least one hole without the action of an additional force.
  • the belt is then transported to the reaction sites to be filled. There the reagent is transported through the holes in the belt to the reaction sites.
  • the reagents are preferably transported from the conveyor belt to the reaction sites by applying an overpressure.
  • the tape used to meter the reagents is preferably a single-use polymer film. In addition to a reusable belt, it is also possible to use a reusable endless belt.
  • movable plates can be used, on which the metering positions are arranged, the plates actually being arranged in a band-like manner by means of flexible connections, or else being freely displaceable relative to one another and thus being able to take over the function of a band.
  • sheets are understood to mean that the type or design (thickness) of the material used leads to greater dimensional stability.
  • the individual plates are preferably "washable and reusable.
  • the band is to be made from a material that is chemically stable against the reagents used.
  • the band is designed such that it can be wetted by the reagent at the dosing positions and the reagent repels at all other locations. This can e.g. by different coatings on the surface.
  • the band is provided with depressions at the metering positions.
  • the depressions can be introduced into the band during its manufacture or, in particular when a single-use band is used, preferably after it has been removed from a supply roll within the device.
  • the wells can be covered with the reagents after filling in order to protect the reagents from damaging external influences.
  • the covering can be done, for example, by applying a film.
  • the reaction sites are arranged on individual synthesis grids.
  • a synthesis grid is understood to mean the support of the reaction sites on which they are arranged in a predetermined manner, preferably in rows and columns.
  • the reaction sites are preferably introduced as depressions in the synthesis grid.
  • Suitable synthesis grids are, for example, microtiter plates as are generally known to the person skilled in the art and are commercially available (for example from Brand GmbH, Becton-Dickinson and many others). Such microtiter plates comprise, for example, 6, 12, 24, 48, 96, 356 or 1536 wells.
  • reaction sites can also be flat or can be introduced as flat depressions in the synthesis grids.
  • the synthesis grid is preferably wettable by the reagent at the reaction sites and repels the reagent at all other sites.
  • a band section provided with the reagent is brought over the reaction sites in the synthesis grid in such a way that the metering positions on the band section match the positions of the reaction sites.
  • the synthesis grid is preferably moved up to the contact with the belt section and closed pressure-tight from above with a lid. By applying an overpressure above the band section, the reagent located at the individual dosing positions is then emptied to the reaction sites below. After the band section has been emptied to the reaction sites, the synthesis grid and the belt are transported further so that a further synthesis grid can be filled.
  • reagents can also be dosed at one dosing position. This is particularly advantageous if reagents are to be mixed before they are added to the reaction site. Reagents can also be incubated at the metering positions of the tape before they are metered to the reaction sites. In addition to the mixing and incubation of reagents at the metering positions of the tape, other preparation steps known to the person skilled in the art are also possible before metering the reagents into the reaction sites.
  • Another advantage of using a tape for metering the reagents is that separate feed lines and metering nozzles can be provided for each reagent. On this eliminates the use of a very large number of valves susceptible to faults and the problem that cross-contamination can occur due to the use of a single supply line for several reagents. It is also advantageous that the dosing unit can be used immediately to fill further synthesis grids by further transporting the synthesis grid after filling. Waiting times until the next process step, which can result, for example, from waiting for the necessary reaction times to expire, can thus be used for metering reagents into further synthesis grids.
  • the synthesis grids are arranged on a conveyor belt along a reaction path along which several dosing stations can be located.
  • a separate dosing station is preferably provided for each reaction step in which a reagent has to be added.
  • the distance between the dosing stations is preferably selected so that the transport time of the synthesis grid from one dosing station to the next corresponds to the required reaction time for a reaction step.
  • the conveyor belt itself is designed as a synthesis grid, so that the reaction sites are arranged directly on the conveyor belt.
  • the reagents are preferably metered in sections to the reaction sites on the conveyor belt.
  • the reagents can also be metered to the reaction sites of the synthesis grid by means of a dispenser unit.
  • the dispenser unit is preferably designed in such a way that reaction sites of the synthesis grid located in one row or column or several rows and columns can be filled simultaneously.
  • at the positions of each reaction location to be filled in the dispenser unit Dispensing nozzles arranged.
  • An individual metering nozzle with its own feed line is preferably provided for each reagent to be metered.
  • the device for carrying out the chemical reactions is encapsulated in a manner that is impervious to light and / or gas.
  • the device encapsulated in this way can, for example, prevent damage to the reaction products or reagents, e.g. be purged by an inert gas.
  • the reaction path is preferably designed in such a way that the synthesis grid with the reaction sites return to the beginning of the reaction path after the last process step has been completed. With the reaction path closed in this way, the synthesis grid can be removed after the synthesis of the reagents of the first process step after completion of the synthesis. A new synthesis grid can then be positioned at the position at which the synthesis grid was removed.
  • At least one hole is formed at each reaction site, the cross-sectional area of which is selected such that the liquid located at the reaction site can only flow through the hole due to its surface tension by applying an additional force.
  • the reaction product is withdrawn from the reaction site.
  • it is e.g. through a hole at the reaction site enables the rinsing solution, which is introduced in the rinsing processes required for oligonucleotide synthesis, to be withdrawn again from the reaction site.
  • rinsing stations are preferably arranged in front of the metering stations.
  • the reagents are metered at metering stations at reaction sites which move along a reaction route, with at least one metering station and one removal point being arranged such that the time which is move the reaction sites on the reaction route, which corresponds to the required reaction time for the reaction. If a film is used to dose the reagents to the reaction sites, the reagents can be prepared for the reaction before the addition to the reaction sites. This includes, for example, mixing several reagents or incubating.
  • the device or the method are used to carry out, in particular, chemical reactions for the parallel synthesis of different oligonucleotides. Further preferred reactions in which these can be used are the parallel synthesis of peptides or of oligosaccharides.
  • FIG. 1 shows a reaction path for oligonucleotide synthesis
  • FIG. 2 shows a dosing station with a belt for dosing the reagents in a perspective view
  • FIG. 3 shows a dosing station with a belt for dosing the reagents in a sectional view
  • Figure 4 is a top view of a dispensing unit with dispenser unit.
  • FIG. 1 A reaction path for oligonucleotide synthesis is shown in FIG.
  • synthesis frames 1 are transported along a reaction path 2.
  • reaction sites for example depressions in a microtiter plate, are formed on the synthesis grid 1.
  • the synthesis grid 1 is fed to reaction zone 2 at the feed point marked with arrow 4.
  • the position of the task and removal of the synthesis grid 1 depends on the synthesis variant. For example, in a so-called trityl-off synthesis, the drop point is at the position marked with the arrow 4.1.
  • the feed point is preferably arranged before the addition of the reagents for the first reaction step and the removal point preferably after the end of the last reaction step required for the synthesis.
  • the reaction sites 3 of the synthesis grid 1 preferably contain a carrier material.
  • a nucleic acid or an oligonucleotide is connected to the carrier material with a covalent or non-covalent bond.
  • they are protected, for example, by monomethoxitrityl or dimethoxitrityl.
  • 5 acid is metered in at a first metering station. Even when producing different oligonucleotides at the individual reaction sites 3 of the synthesis grid 1, this step is the same for all oligonucleotide syntheses at the individual reaction sites 3.
  • the synthesis grid 1 is transported along the reaction path 2 in the transport direction indicated by the arrow 6. However, the transport is preferably carried out step by step from one intermediate position 7 to the next.
  • the time that the synthesis grid 1 remains at the intermediate positions 7 corresponds to the maximum time required for metering in the reagents or for rinsing.
  • the number of intermediate positions 7 between the first dosing station 5 and a first rinsing station 8 results from the time required for the detritylation.
  • a rinsing solution is added in order to wash out excess reagents. After a short exposure time, the rinsing solution together with the excess reagents is removed from reaction site 3.
  • at least one hole is preferably made at the reaction site. The cross section of the at least one hole is to be selected so that the liquid located at the reaction site 3 can only flow through the hole due to its surface tension by applying an additional force.
  • a vacuum is applied to the underside of the synthesis grid 1. As a result, the rinsing solution together with the liquid constituents contained therein, which are located at reaction site 3, are removed through the hole at reaction site 3.
  • the synthesis grid 1 is transported to a second dosing station 9.
  • phosphoramidites are added, which are coupled to the nucleotides contained at the reaction sites 3.
  • the nucleotide to be coupled must be activated. The activation is preferably carried out with tetrazole or a tetrazole derivative.
  • the nucleotide to be coupled and the tetrazole can already be dosed together on the tape, so that the activation already done on the tape.
  • the activated nucleotide derivative is then preferably metered through a hole at the metering position in the band to the reaction site 3.
  • the synthesis grids 1 are transported to a second rinsing station 10.
  • the synthesis grid 1 is transported step by step from one intermediate position 7 to the next.
  • the number of intermediate positions 7 between the second dosing station 9 and the second rinsing station 10 is selected such that the transport duration of the synthesis grid 1 corresponds to the reaction time required for the synthesis.
  • the second rinsing station 10 analogous to the first rinsing station 8, excess reagents are rinsed from the reaction site 3 of the synthesis grid 1.
  • the second rinsing station 10 is followed by a third metering station 11, at which a reagent for capping unreacted 5'-OH groups is metered in.
  • the synthesis grid is transported to a third rinsing station 12 via intermediate positions 7, the number of which in turn depends on the duration of the reaction.
  • the third rinsing station 12 is followed by a fourth dosing station 13, at which a suitable reagent for the oxidation of the phosphorus is added.
  • the synthesis grid 1 is transported to a fourth rinsing station via several intermediate positions 7, the number of which in turn depends on the reaction time.
  • unreacted reagents and reaction by-products are removed from the reaction site 3 analogously to the rinsing stations 8, 10, 12 by adding a suitable rinsing solution.
  • the fourth rinsing station 14 is followed by a grid exchange position 15, from which the synthesis grid 1 can be removed from the reaction zone 2 after the oligonucleotide synthesis has been completed.
  • a new synthesis grid 1 from a supply 17 is placed at the grid exchange position 15 as soon as a synthesis grid 1 has been removed.
  • the processes carried out at the first dosing station 5, the third dosing station 11 and the fourth dosing station 13 are the same for all syntheses, regardless of the oligonucleotides to be synthesized. For this reason can be metered directly to the reaction sites 3 at these metering stations 5, 11, 13, for example with metering nozzles arranged above the reaction sites 3. This makes it possible to dispense with a complex control which ensures that the correct reagent is metered into each reaction site 3.
  • the dosing stations 5, 9, 11, 13 can also be followed by parking positions to which the synthesis grids 1 are transported. After the reaction time required for the individual reaction step, the synthesis grids 1 are then removed from the park position and transported to the next rinsing station 8, 10, 12, 14 and from there to the next metering station 5, 9, 11, 13.
  • the device is also suitable for carrying out any other chemical reaction in which only small amounts of reaction products are produced.
  • the device is particularly suitable for simultaneously synthesizing a large number of different products, which are each produced under the same conditions. These include, for example, peptide synthesis or oligosaccharide synthesis.
  • reaction sites 3 When carrying out chemical reactions in which no rinsing precursors are required, it is not necessary to provide the reaction sites 3 with at least one hole. Since in this case the reaction products are only removed when the synthesis grid 1 has been removed from the reaction zone 2, a removal can then also take place directly from the reaction site 3 via the feed openings of the reaction sites 3 in depressions or chambers in the synthesis grid 1 or in the case of flat reaction sites 3.
  • FIG. 2 shows a dosing station with a belt for dosing the reagents in a perspective view.
  • the reagents which are metered to the reaction sites 3 are prepared on a belt 18.
  • the tape 18 is removed from a film supply 19, which is preferably designed as a roll, on which the tape 18 is wound.
  • indentations 20 are first embossed in sections in the band 18. This can be done, for example, by deep drawing.
  • the hole is dimensioned in such a way that the liquid in the recess 20 can only flow through the hole due to its surface tension by applying an additional force.
  • the belt With the help of rollers 21, the belt is moved in the conveying direction indicated by arrow 22.
  • the depressions 20 produced at the embossing position 23 are conveyed to a metering position 24, at which the reagent to be metered to the reaction sites 3 is metered into the depressions 20.
  • the belt section 37 with the wells 20 filled with reagent is transported over a synthesis grid 1. It should be ensured that the depressions 20 in the film are congruent with the reaction sites 3 of the synthesis grid 1.
  • the synthesis grid 1 is moved from below against the band section 37 and at the same time a cover 25 is placed on from above. By applying an overpressure to the lid 25, the reagent contained in the depressions 20 is emptied to the reaction sites 3 of the synthesis grid 1.
  • Synthesis grid 1 is preferably arranged such that the next synthesis grid 1 is pushed directly under the belt 18 when the synthesis grid 1 is transported. At the same time, a new band section 37 with reagent-containing recesses 20 is placed over the
  • a band 18 which has already been embossed can also be used.
  • the dosing positions can be covered in a further embodiment after dosing. This can be done, for example, by welding or gluing a film.
  • Figure 3 shows a metering station with a belt for metering the reagents in a sectional view.
  • the belt 18 is transported by means of rollers 21 in the conveying direction indicated by the arrow 22.
  • depressions 20 are embossed, at the bottom of which there is at least one hole 26.
  • the hole 26 is preferably dimensioned such that the liquid in the recess 20 can only flow through the hole 26 due to its surface tension by applying an additional force.
  • the reagent required for the reaction is metered into the depressions 20 with the aid of metering nozzles 27.
  • the reagent drops emitted by the metering nozzles 27 are identified by the reference symbol 28.
  • one or more different reagents can be metered into the individual wells 20.
  • a separate metering nozzle 27 is provided for each reagent. This prevents cross-contamination from occurring in the dosing nozzles 27.
  • the wells 20 filled with the reagent are transported to the synthesis grid 1 shown schematically here.
  • the synthesis grid 1 is pressed against the band section 37 in the direction indicated by the arrow 29.
  • a cover 25 is placed on the band section 37 from above.
  • the cover 25 is preferably designed such that a pressure-tight connection is established between the synthesis grid 1, the band section 37 and the cover 25.
  • a pressure surge is generated above the band section 37.
  • the pressure surge is identified here by the arrow with reference number 30. Due to the overpressure above the depressions 20 in the band section 37, the reagents located in the depressions 20 are emptied through the holes 26 to the reaction sites 3 of the synthesis grid 1.
  • the lid 25 is opened, the synthesis grid 1 is moved further, a new synthesis grid 1 being simultaneously transported under the belt 18 for filling.
  • the emptied belt 18 is moved further in the conveying direction 22, with wells 20 filled with reagent being transported simultaneously via the new synthesis grid 1.
  • band 18 is used only once. This means that the band 18 is disposed of after the depressions 20 have been emptied. This ensures that dosing is absolutely contamination-free.
  • an endless belt can also be used for metering.
  • the band 18 has to be cleaned after emptying the depressions 20 in order to remove residues. After cleaning, the band 18 can then be used again for metering the reagents.
  • the belt 18 can comprise individual movable plates, each corresponding to a belt section 37 and on which the metering positions are arranged.
  • Figure 4 shows a dosing point with a dispenser unit in plan view.
  • the metering nozzles 21 for metering the reagents onto the belt 18 are arranged in a dispenser unit 31.
  • the dispenser unit comprises a piezo dispenser array 32 and a control unit 33.
  • nozzle units 34 are arranged next to one another in the piezo dispenser array 32 such that a number of metering positions on the belt 18 are simultaneously filled can be.
  • Each nozzle unit 34 preferably comprises a plurality of metering nozzles 27, one metering nozzle 27 being provided for each reagent to be metered.
  • the dispenser unit 31 makes it possible to dose different reagents simultaneously to different dosing positions in the row which is being filled.
  • the dosing positions filled with different reagents are identified by the reference symbol 38.
  • the dosing nozzles 27 are controlled with the aid of the control unit 33.
  • Electronic connections 35 are provided on the control unit 33, with which the control unit 33 e.g. can be connected to an external data processing system.
  • the dosing nozzles 27 are supplied with the reagents required for the reaction via fluid connections 36.
  • the dispenser unit shown in FIG. 4 is also suitable for metering the reagents directly to the reaction sites 3 of the synthesis grid 1. In this case, however, only one can be used
  • Reagent are metered in, a mixture of several reagents before metering to reaction sites 3 or incubation of the reagents prior to addition to reaction sites 3 is not possible.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nanotechnology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Composite Materials (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Materials Engineering (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • Clinical Laboratory Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

L'invention concerne un dispositif servant à effectuer des réactions au moyen de quantités de réactifs comprises entre 0,5 et 10 nmol, les réactifs étant dosés par l'intermédiaire de stations de dosage (5, 9, 11, 13) situées sur des sites de réaction (3) qui se déplacent le long d'un parcours de réaction (2). Au moins une station de dosage (5, 9, 11, 13) et une zone de prélèvement (16) sont disposées de sorte que le laps de temps, pendant lequel les sites de réaction (3) se déplacent sur le parcours de réaction (2), correspond au moins au temps de réaction requis pour une étape de réaction. Au moins une des stations de dosage comprend une bande (18) sur laquelle le réactif est en partie dosé au niveau d'emplacements de dosage, un orifice (26) se trouvant dans la bande (18) au niveau de chaque emplacement de dosage.
EP04765899A 2003-10-08 2004-10-08 Procede et dispositif pour effectuer des reactions Withdrawn EP1673161A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2003147311 DE10347311A1 (de) 2003-10-08 2003-10-08 Verfahren und Vorrichtung zur Durchführung von Reaktionen
PCT/EP2004/011291 WO2005035110A1 (fr) 2003-10-08 2004-10-08 Procede et dispositif pour effectuer des reactions

Publications (1)

Publication Number Publication Date
EP1673161A1 true EP1673161A1 (fr) 2006-06-28

Family

ID=34428320

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04765899A Withdrawn EP1673161A1 (fr) 2003-10-08 2004-10-08 Procede et dispositif pour effectuer des reactions

Country Status (3)

Country Link
EP (1) EP1673161A1 (fr)
DE (1) DE10347311A1 (fr)
WO (1) WO2005035110A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1694428A4 (fr) * 2003-12-15 2010-10-06 Life Technologies Corp Synthese automatisee d'oligomeres
US8685750B2 (en) 2008-04-28 2014-04-01 Douglas Scientific, Llc. High throughput screening employing combination of dispensing well plate device and array tape
WO2014144221A2 (fr) 2013-03-15 2014-09-18 Douglas Scientific Courroie réutilisable avec matrice de puits
KR20220042053A (ko) * 2019-04-10 2022-04-04 니토 덴코 아베시아 인크. 생물 중합체의 순차 합성을 위한 방법 및 장치
WO2024163644A1 (fr) * 2023-02-01 2024-08-08 Arrowhead Pharmaceuticals, Inc. Processus de fabrication de réacteur à courroie pour la synthèse d'oligomères

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2353856A1 (fr) * 1976-06-02 1977-12-30 Chateau Guy Ruban destine a servir de support a une reaction par exemple chimique ou biochimique, et procede d'analyse le mettant en oeuvre
US5310674A (en) * 1982-05-10 1994-05-10 Bar-Ilan University Apertured cell carrier
US5763263A (en) * 1995-11-27 1998-06-09 Dehlinger; Peter J. Method and apparatus for producing position addressable combinatorial libraries
US5985214A (en) * 1997-05-16 1999-11-16 Aurora Biosciences Corporation Systems and methods for rapidly identifying useful chemicals in liquid samples
WO2000066269A1 (fr) * 1999-05-03 2000-11-09 Ljl Biosystems, Inc. Systeme integre de traitement d'echantillons
DE59906395D1 (de) * 1998-12-30 2003-08-28 Mwg Biotech Ag Vorrichtung zur durchführung von chemischen reaktionen
US6432719B1 (en) * 1999-02-16 2002-08-13 Pe Corporation (Ny) Matrix storage and dispensing system
US6245297B1 (en) * 1999-04-16 2001-06-12 Pe Corporation (Ny) Apparatus and method for transferring small volumes of substances
WO2001077640A2 (fr) * 2000-04-05 2001-10-18 Alexion Pharmaceuticals, Inc. Procedes et dispositifs de stockage et de distribution de liquides
US6841663B2 (en) * 2001-10-18 2005-01-11 Agilent Technologies, Inc. Chemical arrays

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005035110A1 *

Also Published As

Publication number Publication date
WO2005035110A1 (fr) 2005-04-21
DE10347311A1 (de) 2005-05-12

Similar Documents

Publication Publication Date Title
EP1171232B1 (fr) Dispositif de manipulation de fluide a conversion de format
DE69804653T2 (de) Verfahren und vorrichtung zur herstellung von matrixen von proben
DE19950809B4 (de) Verfahren und Vorrichtung für eine Flüssigkeitsübertragung
DE69909511T2 (de) Vorrichtung zum abgeben von flüssigkeit und abgabemethoden
DE60111310T2 (de) Verfahren, Vorrichtung und Rechnerprogramm zur Herstellung eines Arrays chemischer Vebindungen
DE60018392T2 (de) Verfahren und vorichtung zum abgaben von tröpfchen auf einem substrat
DE19827754C1 (de) Einrichtung für eine nahezu gleichzeitige Synthese einer Vielzahl von Proben
DE69927975T2 (de) Fläschchen und Mehrgefäß rotierende Synthesevorrichtung
EP0629144B1 (fr) Dispositif pour realiser des reactions chimiques de maniere simultanee ou sequentielle
EP1313551B1 (fr) Dispositif et procede pour deposer sans contact des microgouttelettes sur un substrat
DE60131735T2 (de) Vorrichtung zur abgabe von genau kontrollierten kleinen flüssigkeitsmengen
EP0885395B1 (fr) Systeme de test pour substances chimiques ou melanges de substances
EP1070963B1 (fr) Bac de rinçage
EP1610129B1 (fr) Procédé et dispositif de préparation de substrates avec affinité pour un analyte
WO2020108942A1 (fr) Procédé et système d'épandage de quantités dosées d'une matière multigrain au moyen d'une machine agricole ainsi que machine de distribution
WO2001017669A1 (fr) Dispositif et procede pour deposer une pluralite de microgouttelettes sur un substrat
EP1673161A1 (fr) Procede et dispositif pour effectuer des reactions
DE69805156T2 (de) Verfahren und Vorrichtung zur Behandlung von Musterplatten
WO2001062388A2 (fr) Distributeur doseur
WO2002057015A2 (fr) Dispositif et procede de dosage de petites quantites de liquide
DE60116326T2 (de) Hochparallele herstellung von mikroarrays mittels tintenstrahldruckkopf
EP0925828B1 (fr) Dispositif pour effectuer des réactions chimiques sequentielles
DE19823876B4 (de) Mit unterschiedlichen Verbindungen beladenes Bauteil (Biochip) sowie Verfahren zu dessen Herstellung
EP1173275B1 (fr) Procede et dispositif pour la production en parallele d'oligonucleotides
EP0969919A1 (fr) Procede et dispositif de synthese automatique de macromolecules

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20060508

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PL PT RO SE SI SK TR

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

17Q First examination report despatched

Effective date: 20090922

18W Application withdrawn

Effective date: 20090926