EP1069941A2 - Procede et dispositif pour realiser des series de syntheses et d'analyses - Google Patents

Procede et dispositif pour realiser des series de syntheses et d'analyses

Info

Publication number
EP1069941A2
EP1069941A2 EP99924724A EP99924724A EP1069941A2 EP 1069941 A2 EP1069941 A2 EP 1069941A2 EP 99924724 A EP99924724 A EP 99924724A EP 99924724 A EP99924724 A EP 99924724A EP 1069941 A2 EP1069941 A2 EP 1069941A2
Authority
EP
European Patent Office
Prior art keywords
substrate
starting materials
products
accumulation
different
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Withdrawn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
EP99924724A
Other languages
German (de)
English (en)
Inventor
Hans Koch
Wolfhard Semmler
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.)
Br Deutschland Vertrd Bundesministerium F Wi
Original Assignee
Institut fuer Diagnostikforschung 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
Priority claimed from DE1998117531 external-priority patent/DE19817531A1/de
Application filed by Institut fuer Diagnostikforschung GmbH filed Critical Institut fuer Diagnostikforschung GmbH
Publication of EP1069941A2 publication Critical patent/EP1069941A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
    • 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
    • B41—PRINTING; LINING MACHINES; TYPEWRITERS; STAMPS
    • B41J—TYPEWRITERS; SELECTIVE PRINTING MECHANISMS, i.e. MECHANISMS PRINTING OTHERWISE THAN FROM A FORME; CORRECTION OF TYPOGRAPHICAL ERRORS
    • B41J2/00—Typewriters or selective printing mechanisms characterised by the printing or marking process for which they are designed
    • B41J2/005—Typewriters or selective printing mechanisms characterised by the printing or marking process for which they are designed characterised by bringing liquid or particles selectively into contact with a printing material
    • B41J2/01—Ink jet
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B41—PRINTING; LINING MACHINES; TYPEWRITERS; STAMPS
    • B41J—TYPEWRITERS; SELECTIVE PRINTING MECHANISMS, i.e. MECHANISMS PRINTING OTHERWISE THAN FROM A FORME; CORRECTION OF TYPOGRAPHICAL ERRORS
    • B41J3/00—Typewriters or selective printing or marking mechanisms characterised by the purpose for which they are constructed
    • B41J3/407—Typewriters or selective printing or marking mechanisms characterised by the purpose for which they are constructed for marking on special material
    • 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
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00378—Piezoelectric or ink jet dispensers
    • 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
    • B01J2219/00603—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
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/0061—The surface being organic
    • 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
    • B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
    • 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
    • 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 method for the production of synthesis or analysis series, in which the smallest variable volumes of different starting materials are combined to form a large number of different accumulation products and, if appropriate, examined with regard to certain physical and / or chemical properties, and to an apparatus for carrying out the method.
  • photometers are used for quantitative and qualitative analysis.
  • Samples of biological origin for example blood
  • a Reagent or several reagents mixed which react with the component to be detected in the sample. This reaction causes a specific change in the optical properties of the mixed product, which is detected with the photometer and recorded quantitatively.
  • the invention is therefore based on the object of specifying a method with which a multiplicity of precisely metered substance accumulations from two or more starting materials in different compositions and / or concentrations can be provided and, if appropriate, investigated in a very short time and with little outlay on equipment.
  • the object in a method for the production of synthesis and analysis series according to the
  • the preamble of claim 1 is solved in such a way that the accumulation products according to the inkjet printer principle are formed in a program-controlled manner at predetermined positions on an essentially planar substrate by the finest droplets or jets of the liquid, which can function as an exchangeable printhead and move linearly back and forth Material discharge head stored starting materials are applied to the surface of the substrate according to a specific computer program with regard to their respective dosage and positioning, and the accumulation products are subsequently analyzed in an analysis by a sensor connected to a linearly movable measuring head at the programmed positions, the substrate line by line a direction perpendicular to the linear movement of the material dispensing head or the measuring head is moved.
  • the basic idea of the invention lies in the use of an inkjet printer connected to a computer for producing a large number of synthetic products or mixtures of substances or reaction products which differ in their material and quantitative composition for a subsequent investigation with regard to certain properties or effects, the presence of active substances, etc .. That is, the known active principles of an inkjet printer trained for color printing are used, which in the program-controlled spraying of different substances and quantities of substance onto a base by controlled opening and closing of the respective nozzles of the material dispensing head connected to storage containers or electrostatic or magnetic deflection of the unwanted material beams exist to synthesize products or accumulation products for a subsequent analysis on a surface to produce formed substrate.
  • the material dispensing head can be made in one piece with several storage containers for different, separately controlled Nozzle channels can be formed, or a plurality of material dispensing heads, each with a storage container, can be provided in a depot, in which case the corresponding material dispensing head is activated in accordance with the material to be dispensed.
  • the material discharge head and the measuring head are arranged separately from each other. However, it is also conceivable to train both as one unit. ⁇ ⁇
  • the invention is used in the production of extensive synthesis series and analysis series, for example ELISA test with microtiter plates, in the creation of tests with combinatorial libraries or DNA chips, in cell differentiation, in the execution of tests in the field of dry chemistry and in vitro diagnostics or used in the photometric analysis of reaction kinetics.
  • both the individual material components and the substrate have a specific, coordinated surface tension in order to prevent the substances or the substance mixture from running on the substrate.
  • the substrate consists of a flexible material, such as paper or plastic film, or of a rigid base, for example made of glass, plastic or the like.
  • the substrate has a large number in a suitable manner, for example, lithographically produced depressions in the starting materials for the produced synthesis product or - that are then injected under investigation analysis product from the various reservoirs of the material dispensing head.
  • the accumulation products are generated in a protective gas atmosphere, in a vacuum or under a certain temperature and / or pressure regime.
  • the starting materials can also be heated themselves, if necessary, to bring them into a flowable state which can be easily discharged from the storage containers (material chambers) of the material dispensing head.
  • the substrate is prepared with certain substances in order to trigger an optical reaction for the analysis, for example.
  • a serum sample is to be examined for the presence of certain components, such as albumin, cholesterol, glucose and others.
  • certain components such as albumin, cholesterol, glucose and others.
  • the albumin present in a serum with bromocresol green should be detected.
  • the material chambers assigned to the print head acting as the material output head of a color jet printer ⁇ from each of which separate nozzle channels lead to the material output head, with the serum and with different reagents which, when mixed with the serum, are capable of mixing a specific enzyme into a certain color reaction with the serum to prove the serum, filled.
  • the material delivery head which can be moved back and forth on a rail, is connected to a computer. His movements too predetermined
  • the substrate used here is a transparent plastic film that, like in a printing process with an inkjet printer, is moved perpendicular to the direction of movement of the material dispensing head after a line on the substrate has been filled with the mixtures of sample and reagents.
  • the individual mixtures on the substrate which are now illuminated by a light source, are run over by the measuring head under program control, whereby a attached to this sensor Measures the color and intensity of the light emanating from the illuminated mixture.
  • the measurement results are forwarded to the computer and analyzed by it.
  • the application of the mixtures and their scanning of the sensor is carried out while measuring the air pressure, the air humidity and temperature, or under ⁇ ⁇ predefined external conditions, so that the examination is also reproducible. It is also conceivable that with the sequential supply of several samples to the sample chamber and with the use of intermediate washing processes, different serum samples are applied to the substrate film.
  • the method according to the invention is used to produce synthetic products from different amino acids.
  • a quartz plate with a large number of depressions formed by lithographic etching is used as the substrate.
  • the individual wells are controlled one after the other by the material dispensing head with its material chambers receiving the various starting substances, in order to use them in accordance with the ink jet printing process in the specified sequence and dosage

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Abstract

L'invention concerne un procédé pour produire une pluralité de différents produits d'accumulation de très faibles volumes à partir de différents produits de départ et avec des dosages variés des constituants individuels ainsi bien pour la synthèse que pour l'analyse des produits mélangés afin de déterminer leurs propriétés physiques et chimiques. Selon ce procédé, les produits d'accumulation sont appliqués en des positions prédéterminées d'un substrat plan, de façon commandée par programme, selon le principe de l'imprimante à jet d'encre. De minuscules gouttes des matériaux de départ coulants, stockés dans différents compartiments à matériaux associés à une tête de distribution de matériau, sont injectées, sur la base d'un programme informatique, dans des dosages déterminés, en des positions prédéterminées sur le substrat ou dans des évidements correspondants pratiqués dans ledit substrat, et éventuellement analysées au moyen d'un détecteur associé à une tête de mesure. Ce procédé permet, avec des appareils simples et peu nombreux, de façon très brève et avec des besoins réduits en matériaux, de préparer des produits d'accumulation dosés de manière précise, servant à réaliser des séries de synthèses et d'analyses.
EP99924724A 1998-04-09 1999-03-25 Procede et dispositif pour realiser des series de syntheses et d'analyses Withdrawn EP1069941A2 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE1998117531 DE19817531A1 (de) 1998-04-09 1998-04-09 Verfahren und Vorrichtung zur Anfertigung von Synthese- oder Analysereihen
DE19817531 1998-04-09
US9091998P 1998-06-29 1998-06-29
US90919P 1998-06-29
PCT/DE1999/000957 WO1999052625A2 (fr) 1998-04-09 1999-03-25 Procede et dispositif pour realiser des series de syntheses et d'analyses

Publications (1)

Publication Number Publication Date
EP1069941A2 true EP1069941A2 (fr) 2001-01-24

Family

ID=26045628

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99924724A Withdrawn EP1069941A2 (fr) 1998-04-09 1999-03-25 Procede et dispositif pour realiser des series de syntheses et d'analyses

Country Status (2)

Country Link
EP (1) EP1069941A2 (fr)
WO (1) WO1999052625A2 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1140977B1 (fr) * 1998-12-14 2005-03-09 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Procedes et dispositifs permettant d'appliquer des substances sur un substrat, notamment de monomeres pour la synthese combinatoire de bibliotheques de molecules
DE10102152C1 (de) * 2001-01-18 2002-06-20 Roland Zengerle Vorrichtung und Verfahren zum Dosieren kleiner Flüssigkeitsmengen
DE10117064A1 (de) * 2001-04-05 2003-02-06 Morphochem Ag Vorrichtung zum automatischen Dispensieren mikroskopischer Volumina von Fluiden

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5288644A (en) * 1990-04-04 1994-02-22 The Rockefeller University Instrument and method for the sequencing of genome
US5508200A (en) * 1992-10-19 1996-04-16 Tiffany; Thomas Method and apparatus for conducting multiple chemical assays
EP0904542B1 (fr) * 1996-03-01 2005-06-29 Beckman Coulter, Inc. Systeme d'essais multiples simultanes de fixation de ligands
JP2000512744A (ja) * 1996-05-16 2000-09-26 アフィメトリックス，インコーポレイテッド 標識材料を検出するシステムおよび方法
US5958342A (en) * 1996-05-17 1999-09-28 Incyte Pharmaceuticals, Inc. Jet droplet device
CA2257287A1 (fr) * 1996-05-30 1997-12-04 D. Lansing Taylor Procedes et appareil a groupement miniaturise de cellules pour le criblage sur la base de cellules

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9952625A3 *

Also Published As

Publication number Publication date
WO1999052625A2 (fr) 1999-10-21
WO1999052625A3 (fr) 2000-01-06

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