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WO2002005945A1 - Procede de production de puces a jeu ordonne des microechantillons comportant des acides nucleiques, des proteines ou autres substrats tests - Google Patents

Procede de production de puces a jeu ordonne des microechantillons comportant des acides nucleiques, des proteines ou autres substrats tests Download PDF

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Publication number
WO2002005945A1
WO2002005945A1 PCT/DE2001/002559 DE0102559W WO0205945A1 WO 2002005945 A1 WO2002005945 A1 WO 2002005945A1 DE 0102559 W DE0102559 W DE 0102559W WO 0205945 A1 WO0205945 A1 WO 0205945A1
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WIPO (PCT)
Prior art keywords
substrate
carrier substance
fibers
strips
chips
Prior art date
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Ceased
Application number
PCT/DE2001/002559
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German (de)
English (en)
Inventor
Kang-Hun Lee
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.)
Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft
Original Assignee
Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft
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Publication of WO2002005945A1 publication Critical patent/WO2002005945A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/36—Embedding or analogous mounting of samples
    • 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
    • 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
    • B01J2219/00457—Dispensing or evacuation of the solid phase support
    • 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
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    • B01J2219/00497—Features relating to the solid phase supports
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    • B01J2219/0052—Essentially linear supports in the shape of elongated tubes
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00608—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • 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
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    • B01J2219/00614—Delimitation of the attachment areas
    • B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
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    • B01J2219/00626—Covalent
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    • B01J2219/0063—Other, e.g. van der Waals forces, hydrogen bonding
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    • B01J2219/00718—Type of compounds synthesised
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    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
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    • C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof

Definitions

  • the human genome project which is about to be fully decoded, is currently undergoing a drastic change in the biomedical field.
  • the so-called microarray technology appears to be the first technical novelty that has the potential to be comparable to PCR technology in the 1980s (see “insighf” article in the Nature edition of June 15, 2000, vol. 405, from page 819: Functional genomics).
  • the production of so-called microarray chips for biomedical research is mainly implemented by two methods: 1.
  • the substrates DNA or protein
  • the dots are applied through nozzles which are adapted from the nozzles of inkjet printers.
  • the object of the present invention is a new method for the production of microarray chips.
  • the main objectives of the invention are a low variability of the chips (quality improvement) and a higher economy in the production, especially of large quantities of the same chips.
  • the object of the invention is achieved according to the claims.
  • the inventive method is characterized in that
  • a substrate e.g. DNA, protein or chemical substance
  • a carrier substance e.g.
  • Paraffin, polyacrylamide Paraffin, polyacrylamide
  • Micrometer range is cast, shaped or cut, various fibrous carrier substances with the respective substrate in any
  • Composition are combined into a bundle, the individual fibers are isolated from each other in the bundle by separating material, the combination of different fibers is brought in a defined arrangement, alternatively the carrier substance with the substrate is poured, shaped or cut in layers, different layers are stacked in layers and separating layers separate layers with different substrates, the entire layer is cut into strips, different strips are put together to form a block, again
  • Separating layers are integrated between strips, the different layers and strips are produced in a defined arrangement, the separating material or the separating layer consists of the same carrier material without a substrate, the separating material or the separating layer consists of a different material, which
  • Carrier material adheres, the bundles or blocks are cut into thin slices of a few micrometers, the slices are applied to a suitable solid surface, the carrier substance is removed from the surface and the substrate is immobilized at the respective location on the surface, alternatively: the carrier substance is not removed, but the substrate on the surface of the
  • the substrate is homogeneously distributed in a carrier substance as the first step.
  • a carrier substance A wide variety of test substances can be used as a substrate, which are available in large numbers, in particular DNA for gene expression analyzes and proteins for proteome analyzes, but also chemical substances, such as those being investigated in the search for new drugs.
  • a wide variety of substances can be used as the carrier substance, which enable a homogeneous mixture of the substrate and do not damage the substrate.
  • the carrier substance can first be shaped, is then converted into a solid state either chemically (by a chemical reaction, for example polyacrylamide gel) or physically (by cooling, for example paraffin).
  • the carrier substance with the substrate contained therein is cast, drawn or cut in the form of microscopic fibers (up to diameters of less than 100 micrometers). Fibers with different substrates are bundled in a defined arrangement. Separating material separates different fibers so that the substrates are isolated from each other. Alternatively, the carrier substance with the substrate is applied to one another in layers (up to thicknesses of less than 100 micrometers) in layers. Here, too, separating layers isolate layers with different substrates from one another. The entire layer is cut into fine strips (up to widths of less than 100 micrometers). Different strips are combined into a block. The separating material or the separating layer either consists of the same carrier material without a substrate or of a different material that can be adhered to the carrier material.
  • the fiber bundle or strip block is cut across the longitudinal axis into thin slices (up to thicknesses of less than 100 microns), placed on a firm surface and fixed.
  • Glass plates, metal plates or other plates which are suitable for immobilizing the substrate covalently or non-covalently are used as supports.
  • the discs are fixed chemically (e.g. by covalently binding the separating material to the chemically pretreated surface) or physically (e.g. by gluing, pressing or burning).
  • the carrier substance is removed and the substrate is immobilized on the support.
  • the carrier substance is left, for this purpose the substrate is brought from the carrier substance to the surface (e.g. by an electric field with a polyacrylamide gel as carrier substance) and is thus fixed.
  • microarray chips with substrates in the order of 10 6 and more can be produced in a series of 1000 to 10 6 pieces.
  • the number and dimensions of the substrate points correspond to the dimension in the case of chips currently being produced by others
  • DNA microchips for example, have already found their way into research institutes and the pharmaceutical industry, and further areas of application are opening up in rapid succession. A potentially even larger market is expected to be in clinical use for screening tests.
  • the previous manufacturing techniques are relatively inefficient, i.e. measured by the financial and time expenditure, the production is low. As a result, demand is already greater than supply, and this will intensify in the coming years, especially after the completion of the human genome project. It is even more important that the conventional chips are very expensive due to the high technical complexity, making the chips financially unaffordable for many applications that would make scientific and medical sense. The process presented here will be able to drastically reduce production costs and thus prices, while at the same time achieving a qualitative improvement in the chips.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne la production de puces à jeu ordonné des microéchantillons destinées à l'analyse d'un grand nombre de valeurs individuelles, notamment de puces à jeu ordonné de microéchantillons de DNS ou de protéine. Selon ce procédé, le substrat (s-B. DNS, protéine ou autres substrats tests) est réparti de façon homogène dans une substance support. On donne à la substance support et au substrat qu'elle renferme, la forme de minces fibres microscopiques et différentes fibres sont bottelées. En variante, la substance support et le substrat sont appliqués l'un sur l'autre en couches, la couche globale étant découpée en bandes et différentes bandes étant réunies pour former un bloc. La liasse ou le bloc est coupé(e) transversalement à l'axe longitudinal en minces bandes qui sont déposées sur un support solide puis fixées. La substance support est retirée et le substrat est immobilisé sur le support. Ce procédé permet la production de puces à jeu ordonné de microéchantillons avec un nombre quelconque de substrats. Les avantages de ce procédé sont: 1. La production facile d'un nombre quasiment illimité de puces (une liasse/un bloc d'une longueur de 10 cm donnent 1000 bandes = puces à 100 micromètres d'épaisseur ; 2. La faible variabilité des puces d'une série (les 1000 bandes sont quasiment identiques en termes de teneur en substrat). On obtient ainsi une production efficace et économique de puces à jeu ordonné de microéchantillons pouvant répondre aux besoins croissants dans le recherche biomédicale et dans l'industrie.
PCT/DE2001/002559 2000-07-14 2001-07-13 Procede de production de puces a jeu ordonne des microechantillons comportant des acides nucleiques, des proteines ou autres substrats tests Ceased WO2002005945A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10034570.0 2000-07-14
DE2000134570 DE10034570A1 (de) 2000-07-14 2000-07-14 Verfahren zur Herstellung von Mikroarray-Chips mit Nukleinsäuren, Proteinen oder anderen Testsubstanzen

Publications (1)

Publication Number Publication Date
WO2002005945A1 true WO2002005945A1 (fr) 2002-01-24

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DE (1) DE10034570A1 (fr)
WO (1) WO2002005945A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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WO2002076608A3 (fr) * 2001-02-28 2003-12-11 Attomol Gmbh Molekulare Diagno Procede pour produire un jeu ordonne d'echantillons pour detecter des constituants dans un echantillon biologique
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WO2002076608A3 (fr) * 2001-02-28 2003-12-11 Attomol Gmbh Molekulare Diagno Procede pour produire un jeu ordonne d'echantillons pour detecter des constituants dans un echantillon biologique
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WO2002082080A3 (fr) * 2001-04-05 2003-09-12 Biotechnolog Forschung Gmbh Procede pour produire plusieurs copies identiques d'un jeu ordonne plan de molecules sondes
WO2007140889A1 (fr) * 2006-06-09 2007-12-13 Euroimmun Medizinische Labordiagnostika Ag Procédé de préparation de macro- et microréseaux parfaits par combinaison de fragments présélectionnés de phases solides revêtues
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US12429486B2 (en) 2013-05-21 2025-09-30 Nx Pharmagen Inc. Use of Tenascin-C as an extracellular marker of tumor-derived microparticles

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