DE10201653A1 - Device for use in biochip base modules, e.g. for studying enzymatic reactions or nucleic acid hybridization, comprises a flat, porous semiconductor carrier with a functionalized polymer on the pore surfaces - Google Patents

Abstract

Device for use in biochip base modules, comprising: (a) a flat semiconductor carrier material (I) having pores extending vertically through the surface of (I) to the overlying surface; (b) a 3-dimensional matrix of polymer(s) (II), having functional groups for binding scavenger molecules (A) for use in biological-chemical reactions or bonding; and optionally (c) (A) bonded to the functional groups of (II), is new. Device for use in biochip base modules, comprising: (a) a flat semiconductor carrier material (I) having (in at least some regions) pores extending vertically through the surface of (I) to the overlying surface; (b) a 3-dimensional matrix of polymer(s) (II), having functional groups, suitable for binding scavenger molecules (A) for use in biological-chemical reactions or bonding, on at least part of the surface of the pores; and optionally (c) (A) bonded to the functional groups of (II), is new. An Independent claim is included for the production of the device, comprising applying (II) to at least part of the surface of the pores of (I) to form a 3-dimensional matrix.

Description

The present invention relates to a device comprising a semiconductor carrier material which has pores, which is from one surface to the opposite Extend surface of the carrier material, and at least a polymer matrix arranged on the pore surfaces a variety of at least one type of functional Groups that are linked to in biochemical (Binding) reactions capable of using catcher molecules are, and a process for their preparation. The The device according to the invention is suitable as a basis for a "BioChip basic module" in procedures for the detection of biochemical (Binding) reactions and especially for Analysis of enzymatic reactions, nucleic acid Hybridizations, protein-protein interactions and other binding reactions in the field of genome, proteome or drug discovery in biology and medicine.

Molecular biology is increasingly used today Use biochips with those in a quick way Knowledge about organisms and tissues can be gained. For the life sciences and medical diagnostics is the Detection of (bio) chemical reactions, d. H. the detection biologically relevant molecules in defined Examination material of outstanding importance. In this The development of so-called BioChips is steadily becoming a framework promoted. Such BioChips are usually around miniaturized hybrid functional elements with biological and technical components, in particular on a surface of a BioChip basic module immobilized biomolecules as specific Serve interaction partners. Often the structure indicates this Functional elements rows and columns. Then one speaks of so-called "micro arrays". Because thousands of biological or biochemical functional elements on a chip can be arranged, these are usually with microtechnical methods.

Coming as biological and biochemical functional elements especially DNA, RNA, PNA, (for nucleic acids and their Chemical derivatives can e.g. B. single strands like Oligonucleotides, triplex structures or combinations thereof), saccharides, peptides, proteins (e.g. Antibodies, antigens, receptors), derivatives of combinatorial chemistry (e.g. organic molecules), Cell components (e.g. organelles), individual cells, multi-cell organisms as well as cell assemblies in question.

The most common variant of biochips are so-called microarrays. These are small tiles ("chips") made of, for example, glass, gold, plastic or silicon. To the Evidence of appropriate biological or biochemical (Binding) reactions are, for example, small amounts of solubilized different capture molecules, e.g. Legs known nucleic acid sequence, in the form of tiny droplets punctiform and matrix-like, so-called dots, on the Fixed surface of the BioChip basic module.

In practice, a few hundred to a few thousand Droplets used per chip. Then one becomes investigating analyte, for example may contain fluorescent-labeled target molecules via this Pumped surface. This generally happens different chemical (binding) reactions between the target molecules contained in the analyte and the fixed ones or immobilized capture molecules. As already mentioned, are used to observe these reactions or bonds Target molecules with dye molecule building blocks, usually Fluorochrome marked. The presence and the intensity of light emitted by the fluorochromes Information about the course of the reaction or bond in the individual droplets on the substrate, so that conclusions can be drawn the presence and / or property of the target molecules and / or capture molecules can be drawn. If the corresponding fluorescence-labeled target molecules of the Analytes with or on the surface of the Implement carrier molecules immobilized or can bind by optical excitation with a laser and Measurement of the corresponding fluorescence signal this reaction or bond can be demonstrated.

One of the main problems with this method is that small amount of catcher molecules in the individual dots or spots of planar chips are included. This allows the optical signals, in particular from Fluorescence markers go out, which are used to evaluate the (Binding) reactions are available, be very weak, with the result that the array is limited when the Target molecules in the analyte and / or the immobilized Catcher molecules deliver false negative signals. Hence the test to be carried out is often not sensitive enough.

Especially when using silicon biochips in It connects with fluorescent marker groups in addition often to optical attenuation and Fluorescence quenching phenomena (so-called quenching). This Effect occurs especially when the optically marked biomolecules are spatially very close to the Silicon surface or in the case of the so-called porous Silicon chips are bound to the pore walls.

A magnification approach known in the art the amount of capture molecules in the spots is that on the surface of the chip a polymer, for example a epoxy-functional polysiloxane or polyethylene becomes. The polymer has a three-dimensional matrix numerous binding sites for the capture molecules. Therefore the capture molecules are not in a thin monomolecular layer on the chip surface, but instead are in a multi-layer, three-dimensional network bound to the surface of the chip. By doing this may have a higher concentration of binding sites for the Accumulation of the capture molecules per surface unit of the chip can be achieved.

A further procedure is known in the prior art, which is that the chip has the smallest voids or pores or channels or capillaries, which differ from one Surface of the chip to the opposite surface extend, is provided (so-called porous chip or Engl. "flow-through chip", FTC). The fact that on the surfaces the pores the immobilizer molecules are immobilized on is the effective density of capture molecules per surface unit increased compared to conventional chips. At this Procedure, it is also possible to use the analyte solution, for example a hybridization solution through the pores pump, causing biochemical reactions or bonds, e.g. B. the hybridization of nucleic acids, nothing more diffusion-limited, but due to a optimal mixing of the target molecules are accelerated.

In particular when detecting those to be evaluated Binding events using fluorescence-labeled molecules in combination with a silicon-based FTC however, the problem of one already mentioned above Reduction of the evaluable signal due to Fluorescence quenching phenomena. This signal reduction can only partially by increasing the effective Surface are compensated, which is why with the known FTCs usually more expensive and less user-friendly Marking substances, for example Chemiluminescent groups can be used.

The present invention is therefore based on the object a device or a "BioChip basic module" for verification to provide biochemical reactions and / or bonds, at which the local concentration of capture molecules per unit area of the chip compared to the state of the Technology should be increased further, so as to increase the sensitivity of to increase with the biochip tests to be carried out, whereby it in particular, the above should be made possible Advantages of fluorescent labeling even with porous ones To use silicon chips.

This task is accomplished by the in the claims characterized embodiments solved.

In particular, a device is provided comprising a flat semiconductor carrier material or Substrate with at least partially arranged pores, which is essentially vertical from a surface of the Backing material to the opposite surface of the Extend support material throughout, on the Surface of the pores, at least in regions, a first one three-dimensional matrix is arranged, which from at least one polymer with a variety of functional groups is built, the functional Binding groups in biochemical Catcher molecules usable reactions / bonds are. The expression "binding of in biochemical Reactions / bonds usable capture molecules "means that the capture molecules are covalent to the functional groups or ionic or via electrostatic / adsorptive Interactions, like coordinative bonds, Trapping, etc., may be bound. Covalent bonds are particularly preferred. The term "Large number of functional groups" preferably means on average 0.1 to 10 functional groups per recurring unit in the polymer, are particularly preferred 0.5 to 2 functional groups on average. The pores or (discrete) channels of the semiconductor carrier material for example a diameter of approximately 500 nm to approximately 100 μm, in particular from 5 µm to 10 µm.

The device according to the invention is suitable as a basis for a "basic biochip module" in detection procedures biochemical reactions and / or bonds and for this especially for the investigation of enzymatic reactions, Nucleic acid (e.g. DNA) hybridizations, protein-protein Interactions, protein-ligand interactions and other connection reactions in the field of genome, proteome or drug research in biology and medicine and for Detection of low molecular weight substances via enzymatic Reactions.

The provision of the substrate or carrier material The device according to the invention can be used in the prior art known methods. The carrier material is preferably a porous semiconductor carrier material is selected made of silicon, silicon oxide and silicon with at least one or several (different) layers selected from Silicon oxide, silicon nitride, germanium and gallium arsenide. A porous silicon chip is particularly preferred. In a preferred embodiment can in particular the pores of a porous silicon chip additionally one or more Have layers of silicon oxide and / or silicon nitride, which, for example, by means of CVD on the pore surface can be applied. The thickness of the substrate is, for example, in the range from 400 µm to 700 µm, preferably about 500 microns.

The polymer used according to the invention is, for example from the group consisting of polysiloxanes, acrylamides and Derivatives thereof such as isopropylacrylamide, (meth) acrylates and Derivatives thereof, polyvinyl pyridines, polyimines, PMMA-PEGs, Alkoxysilanes such as 3-glycidyloxypropyltrimethoxysilane, Tetraethoxylsilane (TEOS), tetramethoxysilane (TMOS), Polyethers, hydrogels such as polysaccharides, and polyethylene as well as possible copolymers thereof. such Polymers are e.g. B. also partially in EP-A-0 562 370, EP-A-0 562 373 and DE-A-198 53 815. The polymer can also as a dendrimer, that is, as a tree-shaped Structure. Furthermore, it is possible to three-dimensional matrix as a gel or as a foam provide. Examples include TMOS, TEOS and hydrogels.

According to a preferred embodiment, the polymer is in the three-dimensional matrix uses a copolymer which at least from a first type of monomer, which at least has a functional group which is suitable for binding with in biochemical reactions / bonds can be used Catcher molecules, and from a second Monomer type is built up, which as a scaffold monomer for the Copolymer serves and unspecific bonds essentially prevented. Such copolymers are described, for example, in DE-A-198 53 815 described.

A major advantage of the device according to the invention is the extraordinarily high density of the binding sites per Surface unit of the carrier material for if necessary binding capture molecules, which on the one hand on the Provision of the three-dimensional polymer matrix with one Variety of binding sites for capture molecules and others on the through the cavities or channels or pores or capillaries in the carrier material or substrate strong enlarged surface. So the surprising synergistic effect of the two above Contributions to sensitivity improvement, especially with Fluorescence markers performed biochemical tests achieved is the accessibility of the entire structure for the test liquid to be applied in such a test and the target molecules of vitally important. Therefore, the carrier material is included Pores including the three-dimensional arranged therein trained polymer matrix at least for liquids and target molecules dissolved therein are permeable.

According to a preferred embodiment to ensure this property of the device according to the invention, the at least one polymer matrix is present in such a way that half the diameter of the pores of the carrier material is larger than the thickness of the polymer matrix (cf. also FIG. 1 (a)). In another embodiment, the polymer matrix is present in the pores of the carrier material over the entire pore cross section (cf. also FIG. 1 (b)).

In this regard, polymer matrices are particularly suitable increased porosity, for example a foam structure, exhibit. With denser materials, such as gels, which is a flow of liquids with target molecules or complicate washing liquids, it is also possible to Permeation processes by electrokinetic processes, such as for example electrophoresis. This is it is possible to create charged molecules by applying a electric field also through relatively dense media, especially gels to move.

The type of functional groups present in the polymer is not particularly limited as long as they are capable of binding with capture molecules that can be used in biological-chemical reactions and / or bonds. Examples of functional groups for a preferably covalent bond are -COOH, -SH, -epoxy, -NH ₂ , -NR ₄ + where R is in each case independently of one another H or a C _1-4 -alkyl radical, -Glycidyl and -Cl.

A further advantageous embodiment of the device according to the invention is obtained if two or more three-dimensionally designed matrices are arranged one above the other in layers on the surface of the pores of the carrier material (cf. also FIG. 1 (c)). The functional groups in the first polymer matrix can differ from those in a second polymer matrix or the other polymer matrices, so that different capture molecules can be coupled in the polymer matrices. Such a layered arrangement of several polymer matrices, at least in the pores of the carrier material, makes it possible, for example, in the case of enzymes as capture molecules, to start a chemical reaction in an underlying polymer matrix by a reaction product from the outermost polymer matrix or to generate a fluorophore different from a first dye ,

In general, the polymer matrix does not require any additional ones Aid for training sufficient liability or Anchoring to the surface of the semiconductor substrate. To further improve the adhesion to the surface of the Semiconductor carrier material can, however, in the prior art well-known adhesion promoters, such as silanes, between the Polymer matrix and the surface of the semiconductor Carrier material may be arranged.

The present invention further relates to "BioChip basic module" based on the above described device, in which the three-dimensional matrix building up at least one polymer via the functional groups capture molecules, selected from the group consisting of, for example, nucleic acids, Proteins, enzymes, peptides and low molecular weight organic ligands, covalent, ionic or via electrostatic interactions are bound. Especially preferred capture molecules are oligonucleotides.

This basic BioChip module according to the invention is advantageously used in tests in which the Target molecules at least one label, for example one Dye, a luminescent group or a radioactive Group. Especially when analyzing Hybridizations with oligonucleotides is preferred optical evaluation made in which the target molecules with a luminescent group, especially one fluorescent group, are marked.

The BioChip basic module according to the invention enables surprisingly the use of common fluorescent Groups for the evaluation of (binding) reactions under Use of preferably porous silicon chips (FTC). A major advantage of the used according to the invention Polymer matrix exists in that the capture molecules not arranged directly on the surface as a carrier material are and thus a quenching after binding of fluorescence-labeled target molecules essentially is prevented.

As fluorescent groups or fluorochromes can be used in such diagnostic methods, for. B. hybridization tests, usual fluorescent groups are used, such as. B. hydroxycoumarin, aminocoumarin, methoxycoumarin, cascade blue, lucifer yellow, NBD, R-phycoerythrin (PE), PE-Cy5 conjugates, PE-Cy7 conjugates, Red 613 , fluorescein, BODIPY-FL, Cy3, TRITC, X-rhodamine, Lissamin Rhodamin B, PERCP, Texas Red, Cy5, Cy7, Allophycocyanin (APC), TruRed, APC-Cy7 conjugates, Hoechst 33342, DAPI, Hoechst 33258, SYTOX Blue, Chromomycin A3, Mithramycin, YOYO- 1 , SYTOX Green, SYTOX Orange , Ethidium bromide, 7-AAD, acridine orange, TOTO-1, TO-PRO-1, thiazole orange, propidium iodide (PI), TOTO-3, TOPRO-3, LDS 751 , Indo-1, Fluo-3, DCFH, DHR , SNARF, Y66F, Y66H, EBFP, wild type, GFPuv, ECFP, Y66W, S65A, S65C, S65L, S65T, EGFP, EYFP, DsRed, monochlobimane, calcein and fluorescent naphthalene-1,4,5,8-tetracarboxylic acid bisimides.

Another object of the present invention relates a method of making one as above Described device according to the invention, comprising the Step of applying at least one above defined polymer at least in some areas on the Surface of the pores defined above Carrier material with the formation of a three-dimensional Matrix.

• 1. Ein fertig synthetisiertes Polymer wird in einem entsprechenden Lösungsmittel aufgelöst. Diese Lösung kann durch Tauchen, Spotten oder Pumpen in die Poren des Substrates gebracht werden. Die Schichtdicke wird über die Viskosität (ähnlich wie beim Aufschleudervorgang) eingestellt. Ein Haftvermittler an den Porenwänden, z. B. eine dünne Silanschicht, kann eine kovalente Bindung des Polymer an die Porenwände unterstützen. Während oder nach dem Aufbringen kann ein Teil der Lösung über ein Vakuum abgepumpt oder mit Druck aus den Poren entfernt werden. Das Lösungsmittel aus dem verbleibenden Film verdampft danach von alleine oder durch Spülen mittels Stickstoff oder durch Erhitzen. Erst dann wird das Polymer funktionalisiert, so dass eine Anbindung von Biomolekülen möglich ist.
• 2. Eine nicht oder nur teilweise polymerisierte Lösung wird in die Poren gebracht (Tauchen, Spotten oder Pumpen) und erst in den Poren die Lösung fertig synthetisiert. Dies ist z. B. bei photovernetzbaren Polymeren möglich oder bei Polymeren, die durch Radikalstarter polymerisieren. Das Polymer wird anschliessend funktionalisiert oder die Monomere enthalten schon vorher die funktionelle Gruppe. Im Falle der Siloxane kann z. B. eine Aktivierung der Oberfläche die Polymerisation der Monomerenlösung (Tetramethoxysilan, Trimethoxymethylsilan, Dimethoxydimethylsilan in einem bestimmten Mischungsverhältnis, um große Poren zu erzeugen) auslösen. So wächst eine Polymerschicht an den Wänden der Poren auf.
• 3. Ferner kann in die Monomerenlösung ein makromolekulares Porogen eingebracht werden. Das können flüssige (z. B. Polyalkylenglykol, Polypropylenglykol) oder feste (z. B. Natriumchlorid, Natriumhydrogencarbonat) Porogene sein. Nach dem Abscheiden des Polymerfilms wird thermisch aufgeschäumt (z. B. Pyrolyse von polymeren Porogenen), oder es entstehen Gase (z. B. im Falle von Ammoniumbicarbonat Ammoniak und CO₂), oder das polymere oder feste Porogen wird gelöst (z. B. wasserlösliche Polyvinylmethylether). Dadurch entsteht eine definierte Porosität und eine Oberflächenvergrößerung. Anschließend wird chemisch funktionalisiert.

Three methods for coating the porous substrates or semiconductor carrier materials are listed below by way of example.

• 1. A completely synthesized polymer is dissolved in an appropriate solvent. This solution can be brought into the pores of the substrate by dipping, spotting or pumping. The layer thickness is set via the viscosity (similar to the spin coating process). An adhesion promoter on the pore walls, e.g. B. a thin silane layer, can support a covalent bond of the polymer to the pore walls. During or after application, part of the solution can be pumped off under a vacuum or removed from the pores with pressure. The solvent from the remaining film then evaporates by itself or by flushing with nitrogen or by heating. Only then is the polymer functionalized so that biomolecules can be bound.
• 2. A solution that is not or only partially polymerized is brought into the pores (dipping, spotting or pumping) and the solution is only synthesized in the pores. This is e.g. B. possible with photocrosslinkable polymers or with polymers that polymerize by radical initiators. The polymer is then functionalized or the monomers contain the functional group beforehand. In the case of siloxanes, e.g. B. activation of the surface trigger the polymerization of the monomer solution (tetramethoxysilane, trimethoxymethylsilane, dimethoxydimethylsilane in a certain mixing ratio to produce large pores). A polymer layer grows on the walls of the pores.
• 3. A macromolecular porogen can also be introduced into the monomer solution. These can be liquid (e.g. polyalkylene glycol, polypropylene glycol) or solid (e.g. sodium chloride, sodium bicarbonate) porogens. After the polymer film has been deposited, thermal foaming is carried out (e.g. pyrolysis of polymeric porogens), or gases are formed (e.g. in the case of ammonium bicarbonate, ammonia and CO ₂ ), or the polymeric or solid porogen is dissolved (e.g. water-soluble polyvinyl methyl ether). This creates a defined porosity and an increase in surface area. It is then functionalized chemically.

According to a preferred embodiment of the invention The process is carried out according to the step of Application and coupling of suitable carrier molecules at least one other polymer matrix on top of the first Polymer matrix applied. The functional Groups in the first polymer matrix, of which in the further Polymer matrix or the polymer matrices may be different. This enables different target or other molecules in the different polymer layers or -matrices to tie.

Furthermore, it is preferred to use the polymer matrices in this way to apply that half the diameter of the pores of the Carrier material larger than the thickness of the polymer matrix (ces) is, and / or the polymer matrix (ces) for liquids and target molecules dissolved therein are permeable. By at least one of these measures ensures that at performing a biochemical test using of a BioChip basic module produced in this way target molecules present in the analysis liquid as Analyte (s) optimally reach the binding sites.

As stated above, this is one Polymer constructing the matrix according to the invention is not special limited. However, it is preferred that the above defined step comprises polymerizing a polymer. Such polymers and their production and application on common chip surfaces are state of the art generally described or defined above and exemplified.

A particularly preferred embodiment of the invention Procedure results if defined in the above Step a copolymer of at least one first type of monomer, which has at least one functional group which for Bond, preferably covalent bond with in biological chemical reactions and / or bonds can be used Catcher molecules, and from a second Is copolymerized type of monomer, which as a framework monomer serves for the copolymer. As stated above such copolymers, for example in the prior art described. In this variant of the invention Procedures are first in the step defined above Capture molecules, for example nucleic acids, proteins or low molecular weight organic ligands to which monomers from first type on the functional group covalent, ionic or bound by electrostatic interactions and then these monomers with the skeletal monomers, d. H. the Second type monomers copolymerized. Thus the Installation of the capture molecules in the polymer matrix and that Applying the same, d. H. for example on the Substrate surface and the pore surfaces of the Carrier material, in one step. This approach is particularly economical, because so far in general with the Production of biochips first the surfaces for Coupling of the capture molecules are treated accordingly and then the application of the capture molecules in Form of the dots takes place. The fact that in the above mentioned, preferred embodiment of the Manufacturing process the framework structure, d. H. the the Catcher-binding polymer matrix, (which is otherwise separate preparation of the chip to be carried out for coupling) and the capture molecules themselves applied in one step will be a significantly simplified manufacture of a BioChip basic module enables. Furthermore, with this Procedure increases the stability of the capture molecules become. Another advantage is that by choosing the type and amount of capture molecules and the ratio of the monomer type with functional group (s) for Scaffold monomer binds the capture molecules to the Polymer matrix can be controlled much more differentiated.

Of course, it is also possible both in the case the formation of a copolymer as well as in the case of Applying other types of polymer, for example those already polymers defined above, after the application of Polymer layer according to the step defined above Capture molecules, especially those from the group consisting for example of nucleic acids, proteins and low molecular weight organic ligands are selected the polymer layer or the outermost polymer layer over the to bind functional groups, for example, covalently.

The figures show:

Fig. 1 shows schematically three embodiments (a), (b) and (c) of the inventive device, wherein (1) the semiconductor substrate, (2) a pore, and (3) and (4) different polymer matrices.

Claims (21)

1. Device comprising a flat one Semiconductor carrier material with at least some areas arranged pores, which are substantially vertical from one surface of the carrier material to the opposite Extend the surface of the carrier material continuously, whereby on the surface of the pores at least in some areas first three-dimensionally formed matrix is arranged, which consists of at least one polymer with a variety of functional groups is built, the functional Binding groups in biochemical Catcher molecules usable reactions / bonds are. 2. The apparatus of claim 1, wherein the semiconductor Carrier material from the group consisting of silicon, Silicon oxide, and silicon with at least one or more Layers selected from silicon oxide, silicon nitride, Germanium and gallium arsenide is selected. 3. Device according to claim 1 or 2, wherein the polymer from the group consisting of polysiloxanes, acrylamides and Derivatives thereof, (meth) acrylates and derivatives thereof, Polyvinyl pyridines, polyimines, PMMA-PEGs, alkoxysilanes, Tetraethoxysilane, tetramethoxysilane, polyethers, hydrogels and polyethylene and copolymers thereof. 4. The device of claim 3, wherein the copolymer at least from a first type of monomer, which at least has a functional group which is suitable for binding with in biochemical reactions / bonds can be used Catcher molecules, and from a second Monomer type is built up, which as a scaffold monomer for the Copolymer is used. 5. Device according to one of the preceding claims, where half the diameter of the pores of the carrier material is greater than the thickness of the polymer matrix and / or the Polymer matrix for liquids and substances dissolved in them is permeable. 6. Device according to one of the preceding claims, wherein the at least first polymer matrix as a gel or as Foam is formed. 7. Device according to one of the preceding claims, wherein the functional groups contained in the polymer are selected from the group consisting of -COOH, -SH, -epoxy, -NH ₂ and -NR ₄ ⁺ , -Glycidyl and -Cl. 8. Device according to one of the preceding claims, wherein at least on the pore surfaces two or more Polymer matrices are arranged layered one above the other. 9. The device according to claim 8, wherein each functional groups in the first polymer matrix of which in the second polymer matrix or the other polymer matrices are different. 10. Device according to one of the preceding claims, being between the substrate surface and the polymer matrix Adhesion promoter is arranged. 11. Device according to one of the preceding claims, where the polymer matrix (ces) via the functional Groups of capture molecules selected from the group consisting of from nucleic acids, proteins, enzymes and low molecular weight organic ligands. 12. A method for producing a device according to a of the preceding claims, comprising the steps of Applying at least one polymer defined above at least in some areas on the surface of the pores carrier material defined above to form a three-dimensional matrix. 13. The method of claim 12, wherein after the step of Applying at least one further polymer matrix to the first polymer matrix is applied. 14. The method of claim 13, wherein each functional groups in the first polymer matrix of which in the further polymer matrix or the others Polymer matrices are different. 15. The method according to any one of claims 12 to 14, wherein the Polymer matrix (ces) is / are applied such that the half the diameter of the pores of the carrier material is greater than the thickness of the polymer matrix (ces), and / or the Polymer matrix (ces) for liquids and dissolved therein Target molecules are permeable. 16. The method according to any one of claims 12 to 15, wherein the Step of applying polymerizing a polymer, selected from the group defined in claim 3. 17. The method of claim 16, wherein the copolymer at least from a first type of monomer, which at least has a functional group which is suitable for binding with in biochemical reactions / bonds can be used Catcher molecules, and from a second Is copolymerized type of monomer, which as a framework monomer serves for the copolymer. 18. The method according to claim 17, wherein in the step of First capture molecules selected from the group, consisting of nucleic acids, proteins, enzymes and low molecular weight organic ligands to which monomers from first type are bound via the functional group and then the monomers that bind the capture molecules to it have to be copolymerized with the skeleton monomers. 19. The method according to any one of claims 12 to 18, which further the step of covalently binding Capture molecules selected from the group consisting of Nucleic acids, proteins, enzymes and low molecular weight organic ligands, to the polymer matrix or the outermost Polymer matrix on the functional groups of the polymer or the polymer comprises. 20. BioChip basic module, comprising the device according to one of claims 1 to 11, wherein the polymer or the polymers Capture molecules on its or its functional groups has or have bound. 21. Use of the BioChip basic module according to claim 20 in methods for the detection of biochemical reactions and / or Binding and especially for the investigation of enzymatic reactions, nucleic acid hybridizations, Protein-protein interactions and protein ligand Interactions.