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WO1999039205A1 - Procede de fabrication de corps d'essai pour la detection specifique de reactants individuels de complexes de substances recepteurs-substances ligands - Google Patents

Procede de fabrication de corps d'essai pour la detection specifique de reactants individuels de complexes de substances recepteurs-substances ligands Download PDF

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Publication number
WO1999039205A1
WO1999039205A1 PCT/DE1999/000184 DE9900184W WO9939205A1 WO 1999039205 A1 WO1999039205 A1 WO 1999039205A1 DE 9900184 W DE9900184 W DE 9900184W WO 9939205 A1 WO9939205 A1 WO 9939205A1
Authority
WO
WIPO (PCT)
Prior art keywords
reactants
substance
detection
immobilized
layer
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.)
Ceased
Application number
PCT/DE1999/000184
Other languages
German (de)
English (en)
Inventor
Rainer Fislage
Wladimir Teterin
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of WO1999039205A1 publication Critical patent/WO1999039205A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
    • C12Q1/6837—Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe 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
    • 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
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/5436—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals with ligand physically entrapped within the solid phase
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • 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
    • B01J2219/00596—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
    • B01J2219/00673—Slice arrays

Definitions

  • the invention relates to a method for producing test bodies (stacked layer chips (SL chips)) for the specific detection of individual reactants of receptor substance-ligand substance complexes according to the preamble of patent claim 1.
  • SL chips stacked layer chips
  • the invention is used in the field of medical diagnostics, food monitoring, environmental analysis, molecular biological analysis, and in the development of pharmaceutical preparations.
  • membrane-based methods such as Southern blots [1], Northern blots [2], Western blots [3,4], dot blots [5,6] or Slot blots or other flat test pieces [10], some of which are referred to as DNA microchips.
  • the latter have a large number of ordered immobilized reactants in the smallest areas, which allow the sequence-specific detection of nucleic acids.
  • the corresponding test specimens are built up on suitable documents.
  • oligonucleotides are synthesized by suitable methods in situ at fixed positions on areal substrates [7] or using physical methods such as e.g. modified inkjet printers [8] applied. Methods for the synthesis of various immobilized peptides on a surface and a subsequent analysis process on this surface are also known [9].
  • REPLACEMENT SHEET / (RULE 26) The orderly immobilization of a large number of nucleic acids, proteins or other bindable substances is currently only possible at high costs and with considerable expenditure on equipment. The invention seeks to remedy this.
  • the invention specified in the claims is based on the problem of creating a simple and inexpensive method for the orderly immobilization of various bindable substances in a very small space.
  • Essential to the invention is the use of a macroscopic arrangement for producing three-dimensional microscopic structures.
  • the immobilizable reactants are each bound to a suitable matrix material and arranged in layers on top of one another.
  • the smallest distance between two immobilized reactants is only determined by the technically achievable minimum layer thickness.
  • the areal expansion of the substance-binding area is not limiting, so that the devices described can be produced in a wide variety of shapes and with variable external dimensions.
  • Binding substances are detected using suitable detection systems after a binding reaction against immobilized reactants on the cut surfaces of the three-dimensional object.
  • the cuts are to be made in such a way that the relevant layers of the three-dimensional arrangement are exposed and accessible to the mixture of substances. Physical or chemical methods can be used to expose the layers.
  • substances to be analyzed can bind not only to the cut surface itself, but also to the surfaces that point into the depth of the three-dimensional object.
  • a particular advantage of the invention is the possibility of immobilizing reactants with different basic chemical structures by varying the test body matrix while maintaining the test body geometry.
  • FIG. 1 shows a structural diagram of the SL chip from the example.
  • the numbers in the drawing have the following meaning:
  • Nylon membranes were either loaded with alkaline denatured DNA from phage lambda or with likewise alkaline denatured genomic DNA from chicken erythrocytes and fixed by UV light. The individual membranes each had an area size of 1 cm x 2 cm. The use of nylon membranes is only one possibility for matrix immobilization of DNA. In general, all immobilization methods can be used which are suitable for the construction of objects according to claim 1 -2 and which allow substances to be bound and detected by suitable detection systems on their cut surfaces.
  • the membranes were glued to one another with contact adhesive according to the manufacturer's instructions, so that a membrane object with the dimensions 2 cm ⁇ 1 cm and a total thickness of 2 mm resulted.
  • the contact adhesive is not absolutely necessary according to the invention.
  • the membrane layers can also be physically fixed.
  • the distinction between matrix and adhesive can also be omitted. In general, all methods can be used which are suitable for the construction of objects according to patent claims 1-2 and which permit the binding and detection of substances on their cut surfaces by means of suitable detection systems.
  • the detection and detection methods are not limited to those described here. Suitable and specific methods must be selected depending on the substance bound.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'analyse de mélanges complexes de substances peut être considérablement accélérée par des séries d'essais effectués à l'aide de réactants immobilisés, liant spécifiquement les composants individuels du mélange de substances. A cet effet, les réactants sont liés à un matériau matriciel approprié et disposés en couches de manière à obtenir un objet tridimensionnel. Des coupes appropriées à travers un tel objet peuvent être utilisées pour la détection de ligands liés de façon spécifique sur les surfaces de section ainsi formées. Le nombre de réactants devant être utilisés pour la détection est limité par l'épaisseur de couche de la matrice d'immobilisation utilisée, le pouvoir séparateur, dans l'espace, de l'appareil de mesure utilisé pour la détection, ainsi que par la sensibilité du système de détection.
PCT/DE1999/000184 1998-01-28 1999-01-26 Procede de fabrication de corps d'essai pour la detection specifique de reactants individuels de complexes de substances recepteurs-substances ligands Ceased WO1999039205A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19803077.0980128 1998-01-28
DE1998103077 DE19803077C1 (de) 1998-01-28 1998-01-28 Verfahren zur Herstellung von Testkörpern zum spezifischen Nachweis einzelner Reaktanden von Rezeptorsubstanz-Ligandensubstanz Komplexen

Publications (1)

Publication Number Publication Date
WO1999039205A1 true WO1999039205A1 (fr) 1999-08-05

Family

ID=7855810

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1999/000184 Ceased WO1999039205A1 (fr) 1998-01-28 1999-01-26 Procede de fabrication de corps d'essai pour la detection specifique de reactants individuels de complexes de substances recepteurs-substances ligands

Country Status (2)

Country Link
DE (1) DE19803077C1 (fr)
WO (1) WO1999039205A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996017246A1 (fr) * 1994-11-30 1996-06-06 Pharmacia Biotech Ab Surfaces multifonctionnelles
DE19612356A1 (de) * 1996-03-28 1997-10-02 Knoell Hans Forschung Ev Optischer Nachweis von Hybridisierungs-Signalen
WO1997046313A1 (fr) * 1996-06-07 1997-12-11 Eos Biotechnology, Inc. Nouveaux reseaux d'oligonucleotides lineaires immobilises

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996017246A1 (fr) * 1994-11-30 1996-06-06 Pharmacia Biotech Ab Surfaces multifonctionnelles
DE19612356A1 (de) * 1996-03-28 1997-10-02 Knoell Hans Forschung Ev Optischer Nachweis von Hybridisierungs-Signalen
WO1997046313A1 (fr) * 1996-06-07 1997-12-11 Eos Biotechnology, Inc. Nouveaux reseaux d'oligonucleotides lineaires immobilises

Also Published As

Publication number Publication date
DE19803077C1 (de) 1999-04-22

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