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DE10034570A1 - Process for the production of microarray chips with nucleic acids, proteins or other test substances - Google Patents

Process for the production of microarray chips with nucleic acids, proteins or other test substances

Info

Publication number
DE10034570A1
DE10034570A1 DE2000134570 DE10034570A DE10034570A1 DE 10034570 A1 DE10034570 A1 DE 10034570A1 DE 2000134570 DE2000134570 DE 2000134570 DE 10034570 A DE10034570 A DE 10034570A DE 10034570 A1 DE10034570 A1 DE 10034570A1
Authority
DE
Germany
Prior art keywords
substrate
carrier substance
fibers
strips
chips
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Withdrawn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
DE2000134570
Other languages
German (de)
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
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 Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft filed Critical Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft
Priority to DE2000134570 priority Critical patent/DE10034570A1/en
Priority to PCT/DE2001/002559 priority patent/WO2002005945A1/en
Publication of DE10034570A1 publication Critical patent/DE10034570A1/en
Withdrawn legal-status Critical Current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
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    • B01J2219/00497—Features relating to the solid phase supports
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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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    • B01J2219/00614—Delimitation of the attachment areas
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    • C—CHEMISTRY; METALLURGY
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    • C40B40/04—Libraries containing only organic compounds
    • C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof

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

Abstract

The invention relates to the production of microarray chips for analyzing a large number of individual values, especially DNA or protein microarray chips. According to said method, the substrate (e.g. DNA, protein or other test substances) is homogeneously distributed in a support substance. The support substance, together with the substrate content therein, is transformed into microscopically thin fibers and different fibers are arranged in a bundle. Alternatively, the support substance and the substrate are applied to each other in layers, the combination layer is cut into strips and different strips are combined to form a block. The bundle or block is cut into thin slices crosswise to the longitudinal axis, applied to a solid support and fixed. The support substance is removed and the substrate is immobilized on said support. This method enables microarray chips to be produced with as many substrates as required. The outstanding advantages of the method are as follows: 1. simple production of an almost unlimited number of chips (one bundle/block 10 cm in length produces 1000 slices = chips 100 micrometers thick); 2. very little variation among the chips in a series (the 1000 slices are almost identical in terms of substrate content). The invention hereby provides an efficient and economical means of producing microarray chips for the increasing demand in biomedical research and industry.

Description

Nicht zuletzt mit dem Humanen Genomprojekt, das kurz vor der vollständigen Entschlüsselung der menschlichen Erbinformation steht, findet zur Zeit ein drastischer Umbruch im biomedizinischen Feld statt. In diesem Zusammenhang scheint die sogenannte Mikroarray-Technik als erste technische Neuheit hervorzugehen, die ein Potenzial hat vergleichbar der PCR-Technik in den 80er Jahren (siehe "insight"-Artikel der Nature- Ausgabe vom 15 Juni 2000, Vol. 405, ab Seite 819: Functional genomics).Not least with the Human Genome Project, which is about to be completed Decryption of human genetic information is currently finding a drastic one Upheaval in the biomedical field instead. In this context, the so-called Microarray technology to emerge as the first technical innovation that has potential comparable to the PCR technique in the 80s (see "insight" article by Nature- Edition of June 15, 2000, Vol. 405, from page 819: Functional genomics).

Gegenwärtig wird die Herstellung von sogenannten Mikroarray-Chips für die biomedizinische Forschung vor allem durch zwei Verfahren realisiert: 1. Auf einer Unterlage (Glas oder Membran) werden die Substrate (DNA oder Protein) als Punkte durch mechanisch betriebene feine Metallspitzen aufgetragen; 2. Das Auftragen der Punkte geschieht durch Düsen, die aus den Düsen von Tintenstrahldruckern adaptiert sind.Currently, the production of so-called microarray chips for biomedical Research mainly carried out by two methods: 1. On a base (glass or Membrane), the substrates (DNA or protein) as points by mechanically operated fine metal tips applied; 2. The application of the dots is done through nozzles that come out the nozzles of inkjet printers are adapted.

Beide Verfahren sind zwar in der Lage, Chips mit bis zu Millionen von individuellen Punkten von ca. 10-100 Mikrometer Durchmesser herzustellen, jedoch die Herstellung ist aufwendig aufgrund des Herstellungsprinzips, dass jeder Punkt auf jedem Chip einzeln aufgebracht werden muss. Dieser Nachteil nimmt proportional mit der Anzahl der Substrate (Punkte pro Chip) und der Anzahl der Chips zu. Ein weiterer, qualitativer Nachteil ist die Variabilität der Punkte von Chip zu Chip sogar in derselben Herstellungsserie. Dies ist einerseits durch die mechanische Limitation der Pinspitzen der Auftragungsroboter, andererseits wieder im Herstellungsverfahren (das Auftragen von individuellen Punkten) begründet und beeinträchtigt die Vergleichbarkeit der Resultate.Both methods are capable of chips with up to millions of individual points about 10-100 microns in diameter, but the production is complex due to the manufacturing principle that each point is applied to each chip individually must become. This disadvantage increases proportionally with the number of substrates (points per Chip) and the number of chips. Another qualitative disadvantage is the variability of the Points from chip to chip even in the same production series. On the one hand, this is due to the mechanical limitation of the pin tips of the application robots, on the other hand again in Manufacturing process (the application of individual points) justified and affects the comparability of the results.

Vor diesem Hintergrund ist die Aufgabe der vorliegenden Erfindung ein neues Verfahren für die Herstellung von Mikroarray-Chips. Die Hauptziele der Erfindung sind eine geringe Variabilität der Chips (Qualitätsverbesserung) und eine höhere Ökonomie der Herstellung vor allem von großen Mengen gleicher Chips.Against this background, the object of the present invention is a new method for the production of microarray chips. The main objectives of the invention are minor Variability of the chips (quality improvement) and a higher economy of manufacture before all of large quantities of the same chips.

Die Aufgabe der Erfindung wird gemäß den Ansprüchen realisiert. The object of the invention is achieved according to the claims.  

Das erfindungsgemäße Verfahren ist dadurch gekennzeichnet, daß
The inventive method is characterized in that

  • - ein Substrat (z. B. DNA, Protein oder chemische Substanz) in einer Trägersubstanz (z. B. Paraffin, Polyacrylamid) homogen aufgelöst wird,- a substrate (e.g. DNA, protein or chemical substance) in a carrier substance (e.g. Paraffin, polyacrylamide) is dissolved homogeneously,
  • - die Trägersubstanz unter Bedingungen, die das enthaltene Substrat nicht zerstören, in festen Aggregatzustand überführt wird,- The carrier under conditions that do not destroy the substrate contained in solid state is transferred,
  • - die Trägersubstanz mit dem Substrat in eine faserförmige Form mit Durchmesser im Mikrometerbereich gegossen, geformt oder geschnitten wird,- The carrier substance with the substrate in a fibrous shape with a diameter in Micrometer range is poured, shaped or cut,
  • - verschiedene faserförmige Trägersubstanzen mit dem jeweiligen Substrat in beliebiger Zusammensetzung zu einem Bündel kombiniert werden,- Different fibrous carrier substances with the respective substrate in any Composition to be combined into a bundle
  • - die einzelnen Fasern durch Trennmaterial voneinander isoliert im Bündel vorliegen,The individual fibers are isolated from one another in the bundle by separating material,
  • - die Kombination von verschiedenen Fasern in definierter Anordnung gebracht werden,The combination of different fibers are brought in a defined arrangement,
  • - alternativ die Trägersubstanz mit dem Substrat in Schichten gegossen, geformt oder geschnitten wird,- Alternatively, the carrier substance with the substrate is cast, shaped or in layers is cut
  • - verschiedene Schichten in Lagen übereinander geschichtet werden und Trennschichten jeweils Schichten mit unterschiedlichen Substraten separieren,- Different layers are layered on top of each other and separating layers separate layers with different substrates,
  • - die Gesamtschicht in Streifen geschnitten wird,- the entire layer is cut into strips,
  • - verschiedene Streifen zu einem Block zusammengesetzt werden, wobei wiederum Trennschichten zwischen Streifen integriert werden,- Different strips are put together to form a block, again Separating layers between strips are integrated,
  • - die verschiedenen Schichten und Streifen in definierter Anordnung hergestellt werden,The various layers and strips are produced in a defined arrangement,
  • - das Trennmaterial bzw. die Trennschicht aus demselben Trägermaterial ohne Substrat besteht,- The separating material or the separating layer made of the same carrier material without a substrate consists,
  • - das Trennmaterial bzw. die Trennschicht aus einem anderen Material besteht, das am Trägermaterial haftet,- The separating material or the separating layer consists of another material that on Carrier material is liable,
  • - die Bündel oder die Blöcke in dünnen Scheiben von wenigen Mikrometern geschnitten werden,- Cut the bundles or blocks in thin slices of a few micrometers become,
  • - die Scheiben auf einer geeigneten festen Unterlage aufgetragen werden,- the panes are applied on a suitable firm surface,
  • - die Trägersubstanz von der Unterlage entfernt wird und dabei das Substrat an der jeweiligen Stelle auf der Unterlage immobilisiert wird,- The carrier substance is removed from the base and the substrate on the is immobilized on the respective location,
  • - alternativ: die Trägersubstranz nicht entfernt, jedoch das Substrat auf die Oberfläche der Scheibe gebracht und mitsamt der Trägersubstanz auf der Unterlage immobilisiert wird.- alternatively: the carrier substance is not removed, but the substrate is on the surface of the Brought disk and immobilized on the base together with the carrier.

Bei dem erfindungsgemäßen Verfahren wird als erster Schritt das Substrat in einer Trägersubstanz homogen verteilt. Als Substrat können verschiedenste Testsubstanzen verwendet werden, die in großer Anzahl vorliegen, insbesondere DNS für Genexpressionsanalysen und Proteine für Proteomanalysen, aber auch chemische Substanzen, wie sie bei der Suche nach neuen Medikamenten untersucht werden. Als Trägersubstanz können verschiedenste Substanzen verwendet werden, die eine homogene Mischung des Substrats ermöglichen und nicht das Substrat beschädigen. Die Trägersubstanz ist zunächst formbar, wird dann entweder chemisch (durch eine chemische Reaktion, z. B. Polyacrylamidgel) oder physikalisch (durch Abkühlung, z. B. Paraffin) in einen festen Zustand überführt.In the method according to the invention, the substrate is in a first step Carrier substance distributed homogeneously. A wide variety of test substances can be used as the substrate are used, which are present in large numbers, in particular DNS for Gene expression analysis and proteins for proteome analysis, but also chemical substances, as they are examined when looking for new drugs. As a carrier A wide variety of substances can be used, which a homogeneous mixture of Allow substrate and do not damage the substrate. The carrier is first malleable, then becomes either chemical (through a chemical reaction, e.g. Polyacrylamide gel) or physically (by cooling, e.g. paraffin) to a solid state transferred.

Die Trägersubstanz mit dem darin enthaltenen Substrat wird in Form von mikroskopisch dünnen Fasern (bis zu Durchmessern von unter 100 Mikrometer) gegossen, gezogen oder geschnitten. Fasern mit unterschiedlichen Substaten werden in definierter Anordung gebündelt. Trennmaterial separiert verschiedene Fasern, so dass die Substrate voneinander isoliert sind. Alternativ wird die Trägersubstanz mit dem Substrat in dünnen Schichten (bis zu Dicken von unter 100 Mikrometer) in Lagen aufeinander aufgetragen. Auch hier isolieren Trennschichten Lagen mit verschiedenen Substraten voneinander. Die Gesamtschicht wird in feinen Streifen (bis zu Breiten von unter 100 Mikrometer) geschnitten. Verschiedene Streifen werden zu einem Block vereint. Das Trennmaterial bzw. die Trennschicht besteht entweder aus demselben Trägermaterial ohne Substrat oder aus einem anderen Material, das sich an das Trägermaterial haften lässt.The carrier substance with the substrate contained therein is microscopic cast, drawn or thin fibers (up to diameters of less than 100 microns) cut. Fibers with different substrates are in a defined arrangement bundled. Separating material separates different fibers so that the substrates from each other are isolated. Alternatively, the carrier substance with the substrate in thin layers (up to Thicknesses of less than 100 microns) are applied in layers. Insulate here too Separating layers were layers with different substrates from each other. The entire layer is in cut fine strips (up to widths of less than 100 microns). Different stripes are united into one block. The separating material or the separating layer either exists from the same carrier material without a substrate or from a different material that conforms to the Carrier material adheres.

Das Faserbündel bzw. der Streifenblock wird quer zur Längsachse in dünne Scheiben (bis zu Dicken von unter 100 Mikrometer) geschnitten, auf eine feste Unterlage gebracht und fixiert. Als Unterlagen werden Glasplatten, Metallplatten oder sonstige Platten verwendet, die geeignet sind, das Substrat kovalent oder nicht-kovalent zu immobilisieren. Die Fixation der Scheiben erfolgt chemisch (z. B. durch kovalente Bindung des Trennmaterial an die chemisch vorbehandelte Unterlage) oder physikalisch (z. B. durch Kleben, Pressen oder Aufbrennen). Während oder nach der Fixierung wird die Trägersubstanz entfernt und das Substrat auf der Unterlage immobilisiert. Alternativ wird die Trägersubstanz belassen, dafür das Substrat aus der Trägersubstanz an die Oberfläche gebracht (z. B. durch ein elektrisches Feld bei einem Polyacrylamidgel als Trägersubstanz) und so fixiert.The fiber bundle or strip block is cut into thin slices across the longitudinal axis (up to Thicknesses of less than 100 micrometers), placed on a firm surface and fixed. Glass plates, metal plates or other plates are used as documents are suitable for immobilizing the substrate covalently or non-covalently. The fixation of the Disks are made chemically (e.g. by covalently binding the separating material to the chemical pretreated underlay) or physically (e.g. by gluing, pressing or baking). During or after the fixation, the carrier substance is removed and the substrate on the Immobilized underlay. Alternatively, the carrier substance is left, but the substrate is made out brought to the surface of the carrier substance (e.g. by an electric field at a Polyacrylamide gel as a carrier substance) and thus fixed.

Auf diese Weise können Mikroarray-Chips mit Substraten in der Größenordnung von 106 und mehr in einer Serie von 1000 bis 106 Stückzahlen hergestellt werden. Beispielsweise ist ein Chip mit 104 Substrat-Punkten von 100 Mikrometer Durchmesser und einer Trennschichtdicke von ebenfalls 100 Mikrometer (100 × 2 × 100 Mikrometer)2 = 2 × 2 cm2 = 4 cm2 groß, und bei einer Scheibendicke von 100 Mikrometer gehen aus einem Block von 10 cm Länge 1000 Scheiben, also Chips, hervor. Anzahl und Abmessungen der Substrat-Punkte entsprechen der Dimension bei zur Zeit hergestellten Chips durch andere Herstellungsverfahren.In this way, microarray chips with substrates in the order of 10 6 and more can be produced in a series of 1000 to 10 6 pieces. For example, a chip with 10 4 substrate points of 100 micrometers in diameter and a separating layer thickness of also 100 micrometers (100 × 2 × 100 micrometers) is 2 = 2 × 2 cm 2 = 4 cm 2 in size, and go with a wafer thickness of 100 micrometers from a block of 10 cm length 1000 slices, i.e. chips. The number and dimensions of the substrate points correspond to the dimension in the case of chips currently produced by other production processes.

Die herausragenden Vorteile dieser Methode sind:
The outstanding advantages of this method are:

  • 1. Die ökonomische und schnelle Herstellung von einem Vielfachen der Chipmengen, die nach den bisher üblichen Herstellungsverfahren in einer Serie produziert werden. Beispielsweise ergibt ein Faserbündel von 10 cm Länge 1000 Chips. Diese Zahl erreicht bei den Streifenblöcken eine Million Chips, da bei einer Schichtabmessung von 10 cm × 10 cm parallel 1000 Blöcke verarbeitet werden.1. The economical and rapid production of a multiple of the chip quantities that are produced in a series according to the previously usual manufacturing processes. For example, a fiber bundle of 10 cm in length gives 1000 chips. This number reaches one million chips for the strip blocks, since 1000 blocks are processed in parallel with a layer size of 10 cm × 10 cm.
  • 2. Die geringe Variabilität der Chips einer Serie. Dadurch, dass alle Substrate in dem Faserbündel oder Streifenblock in der Längsachse absolut homogen sind und die einzelnen Substrat-Punkte alle die gleiche Größe haben, hängt die Variabilität unter den Chips einer Serie lediglich von der Präzision des Schneidevorgangs ab. Anders als die individuelle Punkt- Auftragung bei der konventionellen Technik der Mikroarray-Chipherstellung, erfolgt der Schnitt in einem Zug durch den gesamten Block, so dass die Variabilität der individuellen Substrat-Punkte prinzipiell geringer ist.2. The low variability of the chips in a series. Because all substrates in the Fiber bundles or block of strips in the longitudinal axis are absolutely homogeneous and the individual Substrate dots are all the same size, the variability among the chips depends on one Series only depends on the precision of the cutting process. Unlike the individual point Application in the conventional technology of microarray chip production, the Cut in one go through the entire block, allowing the variability of the individual In principle, substrate points is lower.

Die Anwendungsgebiete sind bereits jetzt als immens einzuschätzen, eine genaue Abschätzung des gesamten potenziellen Anwendungsgebiets ist kaum möglich. Angespornt durch das Humane Genomprojekt haben beispielsweise DNS-Mikrochips bereits massiven Einzug in Forschungsinstitute und in die pharmazeutische Industrie erhalten, und weitere Anwendungsbereiche eröffnen sich in rasanter Folge. Ein möglicherweise noch größerer Markt ist voraussichtlich in der klinischen Anwendung für Screening-Untersuchungen.The areas of application can already be assessed as immense, an exact one It is hardly possible to estimate the entire potential area of application. inspired through the Human Genome Project, for example, DNA microchips already have massive ones Getting into research institutes and the pharmaceutical industry, and more Areas of application open up in rapid succession. A possibly bigger one Market is expected to be in clinical use for screening exams.

Die bisherigen Herstellungtechniken sind relativ ineffizient, d. h. gemessen an dem finanziellen und zeitlichen Aufwand ist die Produktion gering. Dadurch ist bereits jetzt die Nachfrage größer als das Angebot, und dies wird sich in den kommenden Jahren verschärfen, vor allem nach der Fertigstellung des Humanen Genomprojekts. Wichtiger noch ist, dass aufgrund des hohen technischen Aufwandes die konventionellen Chips sehr teuer sind und damit die Chips für viele Anwendungen, die wissenschaftlich und medizinisch sinnvoll wären, finanziell unerschwinglich machen. Das hier vorgestellte Verfahren wird die Produktionskosten und damit die Preise drastisch senken können und gleichzeitig eine qualitative Verbesserung der Chips erreichen.The previous manufacturing techniques are relatively inefficient, i. H. measured by that Production is low in financial and time expenditure. This is already the Demand greater than supply, and this will intensify in the coming years, especially after the completion of the human genome project. More importantly, that due to the high technical effort, the conventional chips are very expensive and thus the chips for many applications that make scientific and medical sense would be financially prohibitive. The procedure presented here is the Production costs and thus the prices can drastically reduce and at the same time one achieve qualitative improvement of the chips.

Claims (31)

1. Verfahren zur Herstellung von Mikroarray-Chips, dadurch gekennzeichnet, dass
ein Substrat mit einer Trägersubstanz homogen vermischt wird,
die Trägersubstanz mit dem Substrat in eine Form gebracht wird,
verschiedene Substrat-Trägersubstanz-Gemische zu einem Bündel zusammensetzt werden,
anschließend das Bündel in dünne Scheiben geschnitten wird,
die Scheiben auf eine geeignete feste Unterlage gebracht werden und
schließlich die Trägersubstanz entfernt und dabei das Substrat auf der Unterlage immobilisiert wird.1. A method for producing microarray chips, characterized in that
a substrate is homogeneously mixed with a carrier substance,
the carrier substance is brought into a shape with the substrate,
different substrate-carrier substance mixtures are put together to form a bundle,
then the bundle is cut into thin slices,
the panes are placed on a suitable firm surface and
finally the carrier substance is removed and the substrate is immobilized on the base. 2. Verfahren nach Anspruch 1, gekennzeichnet durch ein biologisches oder chemisches Testmaterial als Substrat.2. The method according to claim 1, characterized by a biological or chemical Test material as a substrate. 3. Verfahren nach Anspruch 1 und 2, gekennzeichnet durch Nukleotidsequenzen als Substrat.3. The method according to claim 1 and 2, characterized by nucleotide sequences as Substrate. 4. Verfahren nach Anspruch 1 und 2, gekennzeichnet durch Peptidsequenzen als Substrat.4. The method according to claim 1 and 2, characterized by peptide sequences as a substrate. 5. Verfahren nach Anspruch 1, gekennzeichnet durch ein Material als Trägersubstanz, das von einem formbaren Zustand in einen festen Aggregatzustand versetzt werden kann, ohne das Substrat zu beschädigen.5. The method according to claim 1, characterized by a material as a carrier substance can be brought from a malleable state to a solid physical state, without damaging the substrate. 6. Verfahren nach Anspruch 1 und 5, gekennzeichnet durch Paraffin als Trägersubstanz.6. The method according to claim 1 and 5, characterized by paraffin as a carrier. 7. Verfahren nach Anspruch 1 und 5, gekennzeichnet durch Polyacrylamid als Trägersubstanz.7. The method according to claim 1 and 5, characterized by polyacrylamide as Carrier. 8. Methode zur Verarbeitung und Bündelung von Substrat-Trägersubstanz-Gemischen nach Anspruch 1, dadurch gekennzeichnet, dass
das Substrat-Trägersubstanz-Gemisch in Form von Fasern gezogen oder gegossen wird und
eine gewünschte Anzahl von Fasern mit unterschiedlichen Substraten zu einem geordneten Bündel zusammengesetzt werden.8. Method for processing and bundling substrate-carrier substance mixtures according to claim 1, characterized in that
the substrate-carrier substance mixture is drawn or cast in the form of fibers and
a desired number of fibers with different substrates can be assembled into an ordered bundle. 9. Methode nach Anspruch 8, dadurch gekennzeichnet, dass Fasern von beliebigem Durchmesser, insbesondere auch von Durchmessern unter 100 Mikrometer, hergestellt werden. 9. The method according to claim 8, characterized in that fibers of any Diameter, in particular also of diameters less than 100 microns become.   10. Methode nach Anspruch 8, gekennzeichnet durch eine sonstige Anordnung der Fasern mit verschiedenen Substraten, die geignet ist, um die Fasern im Querschnitt eindeutig zu identifizieren.10. The method according to claim 8, characterized by another arrangement of the fibers with various substrates, which is suitable to clearly define the fibers in cross section identify. 11. Methode nach Anspruch 8, dadurch gekennzeichnet, dass Fasern von beliebigem Querschnitt, insbesondere auch von quadratischem Querschnitt, hergestellt werden.11. The method according to claim 8, characterized in that fibers of any Cross section, in particular also of square cross section, are produced. 12. Methode nach Anspruch 8, dadurch gekennzeichnet, dass Fasern mit verschiedenen Substraten in einem konzentrischen Raster (Abb. 1a) geordnet werden.12. The method according to claim 8, characterized in that fibers with different substrates are arranged in a concentric grid ( Fig. 1a). 13. Methode nach Anspruch 8, dadurch gekennzeichnet, dass Fasern mit verschiedenen Substraten in einem rechteckigen Raster (Abb. 1b) geordnet werden.13. The method according to claim 8, characterized in that fibers with different substrates are arranged in a rectangular grid ( Fig. 1b). 14. Methode zur Verarbeitung und Bündelung von Substrat-Trägersubstanz-Gemischen nach Anspruch 1, dadurch gekennzeichnet, dass
das Substrat-Trägersubstanz-Gemisch in Form von Schichten gebracht wird,
beliebig viele Schichten mit unterschiedlichen Substraten aufeinander geschichtet werden,
die Schichten in Streifen geschnitten werden und
schließlich die Streifen zu einem Bündel zusammengesetzt werden.14. Method for processing and bundling substrate-carrier substance mixtures according to claim 1, characterized in that
the substrate-carrier substance mixture is brought in the form of layers,
any number of layers with different substrates can be stacked on top of each other,
the layers are cut into strips and
finally the strips are put together into a bundle. 15. Methode nach Anspruch 14, gekennzeichnet durch eine beliebige Dicke der Schichten, insbesondere auch Dicken von unter 100 Mikrometer.15. The method according to claim 14, characterized by any thickness of the layers, especially thicknesses of less than 100 microns. 16. Methode nach Anspruch 14, dadurch gekennzeichnet, dass zwei übereinander liegende Schichten durch eine Trennschicht separiert sind (Abb. 2a).16. The method according to claim 14, characterized in that two layers lying one above the other are separated by a separating layer ( Fig. 2a). 17. Methode nach Anspruch 14, dadurch gekennzeichnet, dass die zusammengesetzten Schichten mit beliebig vielen Lagen in Streifen (Abb. 2b) geschnitten werden.17. The method according to claim 14, characterized in that the composite layers with any number of layers are cut into strips ( Fig. 2b). 18. Methode nach Anspruch 14, dadurch gekennzeichnet, dass geschnittenen Streifen eine beliebige Breite haben, insbesondere Breiten von unter 100 Mikrometer.18. The method according to claim 14, characterized in that cut strips a have any width, in particular widths of less than 100 micrometers. 19. Methode nach Anspruch 14, dadurch gekennzeichnet, dass geschnittenen Streifen mit anderen Streifen an den Schnittstellen zusammengesetzt werden (Abb. 2c).19. The method according to claim 14, characterized in that cut strips are assembled with other strips at the interfaces ( Fig. 2c). 20. Methode nach Anspruch 14, dadurch gekennzeichnet, dass zusammengesetzten Streifen durch eine Trennschicht separiert sind (Abb. 2c).20. The method according to claim 14, characterized in that composite strips are separated by a separating layer ( Fig. 2c). 21. Methode zur Herstellung von Mikroarray-Chips aus Bündeln nach Anspruch 1, dadurch gekennzeichnet, dass
das Bündel quer zur Längsachse in Scheiben geschnitten wird,
die Scheiben auf eine geeignete feste Unterlage gebracht werden,
die Trägersubstanz entfernt und das Substrat auf der Unterlage immobilisiert wird. 21. Method for producing microarray chips from bundles according to claim 1, characterized in that
the bundle is cut into slices transversely to the longitudinal axis,
the panes are placed on a suitable firm surface,
the carrier substance is removed and the substrate is immobilized on the support. 22. Methode nach Anspruch 21, gekennzeichnet durch Scheiben beliebiger Dicke, insbesondere von Dicken unter 100 Mikrometer.22. The method according to claim 21, characterized by panes of any thickness, especially thicknesses below 100 microns. 23. Methode nach Anspruch 21, gekennzeichnet durch ein festes Material als Unterlage, das die Haftung des Substrates gewährleistet.23. The method according to claim 21, characterized by a solid material as a base, the guarantees the adhesion of the substrate. 24. Methode nach Anspruch 21, gekennzeichnet durch unbehandeltes Glas als Material der festen Unterlage.24. The method according to claim 21, characterized by untreated glass as the material of firm base. 25. Methode nach Anspruch 21, gekennzeichnet durch behandeltes Glas als Material der festen Unterlage.25. The method according to claim 21, characterized by treated glass as the material of firm base. 26. Methode nach Anspruch 21, dadurch gekennzeichnet, dass die Trägersubstanz chemisch herausgelöst wird.26. The method according to claim 21, characterized in that the carrier substance is chemical is extracted. 27. Methode nach Anspruch 21, dadurch gekennzeichnet, dass die Trägersubstanz physikalisch herausgelöst wird, z. B. Verdampfung durch Wärme-Einwirkung.27. The method according to claim 21, characterized in that the carrier substance is physically released, e.g. B. Evaporation by exposure to heat. 28. Methode nach Anspruch 21, dadurch gekennzeichnet, dass die Trägersubstanz biologisch herausgelöst wird, z. B. Verdauung durch Enzyme.28. The method according to claim 21, characterized in that the carrier substance is biological is extracted, e.g. B. Digestion by enzymes. 29. Methode nach Anspruch 21, dadurch gekennzeichnet, dass das Substrat nicht-kovalent auf der Unterlage immobilisiert wird.29. The method according to claim 21, characterized in that the substrate is non-covalent the document is immobilized. 30. Methode nach Anspruch 21, dadurch gekennzeichnet, dass das Substrat kovalent an der Unterlage gebunden wird.30. The method according to claim 21, characterized in that the substrate is covalently attached to the Document is bound. 31. Methode nach Anspruch 21, dadurch gekennzeichnet, daß
das Trägermaterial nicht entfernt wird,
das Substrat an die Oberfläche der Scheibe gebracht wird,
das oberflächliche Substrat mit dem darunter liegenden Trägermatrial an der Unterlage fixiert wird.31. The method according to claim 21, characterized in that
the carrier material is not removed,
the substrate is brought to the surface of the disk,
the superficial substrate with the underlying carrier material is fixed to the base.
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