DE102004027364A1 - Porous, locally-transparent, treated substrate used to detect biochemical binding reactions, includes compartments surrounded by walls with metallic modification - Google Patents

Abstract

A porous, locally-transparent, treated substrate used to detect biochemical binding reactions, includes compartments surrounded by walls with metallic modifications, is new. A substrate is flat and macroporous. Surface pores (11) have diameters in the range 500 nm to 100 mu m, which extend continuously between opposite surfaces (10A, 10B). The substrate includes compartments (11A) with pores (11). Pore walls (11C) surrounding a compartment (11A) are locally-modified with a metallic layer. Each compartment is surrounded by an open grid (12) of modified pore walls (11C), which lie parallel to the surfaces (10A, 10B). Each individual grid is completely separated from its neighbors. Pore density is 104> to 108>/cm2>. The substrate is silica, glass or alumina. The rectangular or square grid (12) contains essentially square pores (11). The optically-transparent material is an organic polymer containing dispersed pigments and/or tiny metal spheres. A further variant of the arrangement is presented.

Description

The The present invention relates to porous, partially transparent Substrates that are used as a basis for a "basic BioChip module" in methods of detection biochemical (binding) reactions and in particular for the investigation of enzymatic reactions, nucleic acid hybridizations, protein-protein interactions and other binding reactions in the field of genome, proteome or Drug research in biology and medicine, being in the porous Substrate optical barriers by local, targeted filling of Pores with optically non-transparent material or by appropriate Modification of pore walls be provided with metal.

In Molecular biology is increasingly finding biochips today Use, with which in a fast way knowledge about organisms and tissues are recovered. For the life sciences and medical diagnostics is the detection (bio) chemical reactions, i. the detection of biologically relevant molecules in defined research material of outstanding importance. In this framework, the development of so-called biochips is steadily promoted. Such biochips are usually to miniaturized hybrid functional elements with biological and technical components, in particular on a surface of a BioChip's basic module immobilized biomolecules serving as specific interaction partners serve. Often has the structure of these functional elements rows and columns. you then speaks of so-called "microarrays." Thousands of biological or biochemical functional elements on a chip can be arranged These are usually made with microtechnical methods.

When biological and biochemical functional elements come in particular DNA, RNA, PNA, (for nucleic acids and their chemical derivatives e.g. single strands such as oligonucleotides, triplex structures or combinations thereof saccharides, peptides, proteins (e.g., antibodies, antigens, Receptors), combinatorial chemistry (e.g., organic Molecules), Cell components (e.g., organelles), single cells, multicellular Organisms and cell aggregates in question.

The The most common variant of biochips are the so-called Microarrays. These are little tiles ("Chips") for example Glass, gold, plastic or silicon. To prove such For example, biological or biochemical (binding) reactions small amounts of solubilized different capture molecules, e.g. a known nucleic acid sequence, in the form of the smallest droplets punctiform and matrix-like, so-called dots, on the surface of the BioChip basic module fixed.

In In practice, a few hundred to several thousand droplets per Chip used. Subsequently becomes an analyte to be examined which, for example, fluorescently labeled targets can contain, about this surface pumped. It generally comes to different chemical (Binding) reactions between the target molecules contained in the analyte and the fixed or immobilized capture molecules. As already stated, will be to observe these reactions or bonds, the target molecules with dye molecule building blocks, usually Marked fluorochromes. The presence and intensity of light, which is emitted by the fluorochromes, provides information about the course the reaction or binding in the individual droplets on the substrate, so that conclusions on the presence and / or the property of the target molecules and / or catcher molecules is drawn can be. When the corresponding fluorescence-labeled target molecules of the analyte with or on the surface of the carrier substrate Reactivate immobilized capture molecules or bind, can by optical excitation with a laser and measurement the corresponding fluorescence signal this reaction or binding be detected.

substrates with high, but defined porosity are the basis for such Biochips face several advantages planar substrates. On the greatly enlarged surface can do more Detection reactions take place. This increases the detection sensitivity for biological Assays. By pumping the target molecules dissolved in the analyte through the channels between front and back of the porous one Substrates will be in close spatial contact with the surface of the substrate Substrate brought (<10 microns). On this size scale Diffusion is a very effective transportation process that takes place within a short time Time the distances between the target molecule to be detected and the on the surface bridged immobilized capture molecule. The Speed of the binding reaction can thereby be increased and thus the duration of the detection procedure will be significantly shortened. Porous substrates are thus suitable due to their advantageous fluidic properties very good as a substrate for such DNA and protein microarrays.

One greater Part of today's analytical methods in drug discovery and clinical diagnostics uses optical methods for detection of binding events between substance to be detected and capture molecules (e.g.

DNA hybridizations Antibody-antigen interactions and protein interactions). The substance to be detected becomes in this case provided with a marker, which is more suitable after excitation with light wavelength fluoresces (fluorescence) or a chemical reaction triggers that in turn generates light (chemiluminescence method). Bind the demonstrable Substance, i. the target molecule, with the immobilized capture molecule on the Surface, this can be done optically, e.g. above Luminescence, be detected. The term "luminescence" here is the spontaneous emission of photons in the ultraviolet to infrared Spectral range called. Excitation mechanisms of luminescence can optical or non-optical nature, for example electrical, chemical, biochemical and / or thermal excitation processes. Consequently In particular, chemical, bio and electroluminescence and fluorescence and phosphorescence under the term "luminescence" within the meaning of this invention.

One Disadvantage of porous, transparent substrates, however, is the crosstalk of the luminescence signals from neighboring spots. That is, signals, that come from a spot, They also radiate into adjacent spot areas and can therefore increase the signal intensities of the falsify neighboring spots.

To overcome this problem so far the surface is scanned and illuminated only parts of the spot and evaluated. However, this requires the use of complex and expensive detection devices. Another possibility is to separate the spots spatially very far. However, this leads to a low mica density, which is then no longer sufficiently high for many applications. Another possibility is to optically separate transparent porous areas from one another by non-transparent barriers. Thus WO03 / 089925 presents a 3D waveguide structure which has locally transparent regions of SiO ₂ , these transparent regions in turn being surrounded by a reflective frame of walls with silicon core, whereby the optical crosstalk of the luminescence light generated in the structure between the compartments can be prevented by the reflective walls of substantially silicon. The device presented in WO03 / 089925 shows an improved absolute signal yield with an improved signal-to-noise ratio in the context of chemiluminescence-based analysis methods based on fluorescence or chemiluminescence. However, the fabrication of the 3D waveguide structure presented in WO03 / 089925 is difficult to control because of the strong thermal stress of the macroporous silicon due to the volume doubling in the transition from silicon to silicon dioxide. In the worst case, this leads to bending and distortion of the structure. For biochips, however, such non-planar substrates are unsuitable. A disadvantage of such substrates is therefore their complicated production.

Of the The present invention is therefore based on the object, a device or a "biochip basic module" for the detection of biochemical Provide reactions and / or bindings under the of fluorescence or chemiluminescence-based analysis methods, a Comparable to the device presented in WO03 / 089925 favorable provide absolute signal yield with a comparable signal-to-noise ratio, so as to be carried out the detection sensitivity of the finished biochip Tests to increase, but whose production is not the mentioned above Problems of the device presented in WO03 / 089925 shows, but relatively inexpensive.

These The object is achieved by the embodiments characterized in the claims solved.

According to the present The invention provides devices characterized are that in a porous one Substrate optical barriers by locally targeted filling of Pores with optically non-transparent material or by modifying or coating of corresponding pore walls with metal, so that luminescence signals (e.g., from fluorescence, chemiluminescence, etc.) not via the crosstalk optical barriers in the substrate into adjacent porous regions can.

According to a first embodiment of the present invention, a device is provided, comprising a flat-shaped macroporous support material ( 10 ), which distributes a plurality of pores over at least one surface area ( 11 ) having a diameter in the range of 500 nm to 100 μm, which extends from a surface ( 10A ) to the opposite surface ( 10B ) of the carrier material, the device comprising two or more compartments ( 11A ), each having two or more pores ( 11 ), whereby such a compartment ( 11A ) surrounding pores are filled with an optically non-transparent material, so that such a compartment ( 11A ) arranged in each case from one to the longitudinal axes of the pores substantially parallel to the surfaces ( 10A . 10B ) open frames ( 12 ) is surrounded by such filled pores.

The macroporous support material or substrate is subject to no restriction, as long as it is made of transparent Material is. Usually is the macroporous support material selected from silica, glass or alumina.

The optically non-transparent material with which the compartment border or the frame ( 12 ) forming pores ( 11 ) are also subject to no restriction, as long as this material is optically non-transparent. As a rule, this material is chosen according to the biological and technical requirements.

Usually, the optically non-transparent material is selected from an organic polymer in which pigments and / or metal beads or metal flakes are dispersed. As an organic polymer, poly (meth) acrylates, polysiloxanes, polyurethanes, polyadducts of bisphenol A and epichlorohydrin, polyolefins such as vinyl chloride copolymers, polyepoxide resins, urea, melamine and phenolic resins can be exemplified here. By way of example here Vinnol ^® -Lackharze Wacker Chemie, Burghausen, can be given. The choice of colors is not limited, as long as the essential requirements such as opacity, processability with common printing processes, no intrinsic fluorescence, biocompatibility and inert surface as possible to avoid non-specific bonds are observed. Thus, both organic and anoganic pigments can be used. Examples of such pigments include Pigment Black 7, Pigment Blue 15.3, Pigment Green 7 and Pigment Red 122. However, it is also possible to provide inorganic pigments such as copper oxides, iron oxides, chromium oxides and mixtures thereof, etc. As metal spheres or platelets, for example, silver, gold spheres or aluminum flakes can be dispersed in such an organic polymer.

Nearly all structuring methods, such as micro-printing, lift-off, stamping, lithography, plasma printing, screen printing, can be used to 12 ) or the superstructure that encloses or demarcates the compartments. Although, by filling the pores according to the invention with optically non-transparent material, there is sometimes no complete optical separation, since light can propagate in the transparent webs and thus a small part of the light can pass from one compartment to the other. However, the proportion is very low, since the masking, optically non-transparent material can be optically denser than the porous support material used and thus light from the webs is refracted and absorbed in the optically non-transparent material used.

The device according to the invention has locally regions or compartments which have two or more pores. These regions are in turn surrounded by a box-like superstructure, which is created by the pores filled with optically non-transparent material which directly adjoin the two or more pores or compartments. This will add one to the surfaces ( 10A . 10B ) open frame or box or cylinder whose cylinder axis is parallel to the pores formed.

According to the present invention, each individual frame is preferably ( 12 ) within the entirety of all frames spatially isolated from the surrounding frame (s). The individual frames, which are produced by pores filled with optically non-transparent material, thus do not hang together or touch each other, but are completely separated from one another. The regions or compartments, which are usually formed by pores with pore walls of glass, Al ₂ O ₃ or SiO ₂ , in particular SiO ₂ , are thus transparent to wavelengths, especially in the visible range. The device according to the invention thus has locally transparent regions, these transparent regions in turn being surrounded by a reflective frame of pores filled with optically non-transparent material. In other words, there are locally completely transparent regions or compartments, in particular glass, Al ₂ O ₃ or SiO ₂ , which are filled with optically non-transparent material-filled pores, which in the device according to the invention virtually surrounds these compartments in a box-like manner Form secondary structure, are separated from each other.

The frame or box formed from pores filled with optically non-transparent material ( 12 ) eliminates stray light and optical crosstalk between the regions or compartments that have two or more pores ( 11 ) with pore walls ( 11B ) of transparent material, in particular glass, Al ₂ O ₃ or SiO ₂ . This is a significant advantage over porous substrates that are completely transparent.

According to a second embodiment of the present invention, a device is provided, comprising a flat macroporous support material ( 10 ), which distributes a plurality of pores over at least one surface area ( 11 ) having a diameter in the range of 500 nm to 100 μm, which extends from a surface ( 10A ) to the opposite surface ( 10B ) of the carrier material extend continuously, wherein the device has two or more compartments ( 11A ), each having two or more pores ( 11 ), wherein the pore walls ( 11C ) of such a compartment ( 11A ) surrounding pores are locally modified with a metal layer, so that such a compartment ( 11A ) arranged in each case from one to the longitudinal axes of the pores substantially parallel to the surfaces ( 10A . 10B ) open frames ( 12 ) from such modified pore walls ( 11C ) is surrounded.

In turn, the device according to the invention has locally regions or compartments which have two or more pores. These regions are in turn surrounded by a box-like or frame-like superstructure, which is surrounded by the pores or pore walls ( 11C ) directly to the two or more pores ( 11 ) or compartments ( 11A ). This, in turn, leads to the surfaces ( 10A . 10B ) open frame or box or cylinder ( 12 ), whose cylinder axis is parallel to the pores formed.

With respect to this second embodiment of the present invention, preferably each individual frame ( 12 ) within the entirety of all frames spatially isolated from the surrounding frame (s). The individual frames which are produced by the pores modified with a metal layer thus do not hang or touch each other but are completely separated from one another. The areas or compartments, which are usually through pores with pore walls ( 11B ) of glass, Al ₂ O ₃ or SiO ₂ , in particular SiO ₂ , are thus transparent to wavelengths, especially in the visible range. The device according to the invention thus has locally transparent regions, these transparent regions in turn being formed by a reflective frame (FIG. 12 ) made of pores modified with a metal layer ( 11C ) are surrounded. In other words, locally completely transparent regions or compartments ( 11A ) in particular glass, Al ₂ O ₃ or SiO ₂ , which are separated from each other by the modified with a metal layer pores, which in the device according to the invention virtually a these compartments completely surrounding, box-like secondary structure.

The frame or box formed from the pores modified with a metal layer ( 12 ) eliminates stray light and optical crosstalk between the regions or compartments ( 11B ), the two or more pores ( 11 ) with pore walls ( 11B ) of transparent material, in particular glass, Al ₂ O ₃ or SiO ₂ .

The porous transparent substrates with a thickness between 200 microns and 1 mm and pore diameter between 1 micron and 50 μm are locally masked with metal or metal ions around the compartments train. The metal layer can thus be based on elementary Metal or a metal compound, in particular its chalcogenides, insofar as they are in the carrier material diffuse and change the optical properties. These are these materials on a metal basis usually first in corresponding lacquer resins, e.g.

Vinnol ^® -Lackharze Wacker Chemie, Burghausen, dispersed. The metals or their chalcogenides such as oxides and sulfides (eg FeS, FeO, Fe ₃ O ₄ , CuO, Cr ₂ O ₃ , Pb ₃ O ₄ , TiO ₂ , etc.) can also be used in the form of their commercially available enamel paints be used. It is also possible to provide black solder (copper-iron oxide mixture) and silver yellow (when burning in silver nitrate, a colloidal, elemental silver forms a yellow color). It is also possible to use metallic nanoparticles of, for example, copper, silver or gold. Subsequently, with the aid of an annealing process or baking process, parts of the metal or metal compound present on the surface are driven into the pore walls of the carrier material in order to specifically change the optical properties in the pore walls or webs. The penetration depth of the metal into the material of the pore walls of the support material is controlled by temperature and time. The pores with the metal layer on the walls and their optically modified ridges or pore walls then form a compartment. Light that is broken into the lands by a compartment may be largely absorbed or reflected by the modified lands.

in the Within the scope of the present invention, the compartment frames the above two embodiments an aspect ratio from about 1: 1: 100 to 1: 1: 1 (height × width × depth) exhibit.

In the devices according to the invention, at least one surface region of the macroporous support material ( 10 ) distributes a plurality of usually periodically arranged pores extending from a surface ( 10A ) to the opposite surface ( 10B ) of the substrate extend. In the context of the present invention, on the areal macroporous support material ( 10 ) partially blind holes, ie only after one of the surface sides ( 10A . 10B ) open pores are provided.

The macroporous support material used preferably has a pore diameter of 1 μm to 100 μm, more preferably 1 to 20 μm. The thickness of the macroporous support material is usually 100 to 1,000 .mu.m, preferably 250 to 450 .mu.m. The distance from the center of the pore to the center of the pore (pitch), ie, two adjacent or adjacent pores, is usually 1 to 100 μm, preferably 2 to 12 μm. The pore density is usually in the range of 10 ⁴ to 10 ⁸ / cm ² .

The pores ( 11 ) may be in hexagonal or square arrangement. Furthermore, the pores ( 11 ) may be designed in the inventive devices, for example, substantially round or elliptical. In a preferred embodiment of the present invention, the pores ( 11 ) is formed substantially square. The frame formed of pores filled with optically non-transparent material ( 12 ) may then be in substantially square or rectangular shape.

As described above, according to the present invention, as described above, a so-called hybrid structure device composed of contiguous compartments and non-contiguous compartments is also included. In this regard, the entirety of the German patent application DE 10 2004 018846.7 Reference, the disclosure of which should be part of the present application.

For the production of a biochip with respect to both embodiments, as described above, then, for example, the attachment or binding of linker molecules to the pore surfaces can take place. Such linker molecules are not specifically limited as long as they are capable of covalently bonding to, for example, the OH groups present on the surface of a porous glass, SiO ₂ or Al ₂ O ₃ support material and further having a functional group capable of covalent bonding with as probes in biochemical reactions usable catcher molecules is capable. Such linker molecules are usually based on a silicon-organic compound. Such bifunctional organosilicon compounds may be, for example, alkoxysilane compounds having one or more terminal functional groups selected from epoxy, glycidyl, chloro, mercapto or amino. Preferably, the alkoxysilane compound is a glycidoxyalkylalkoxysilane such as 3-glycidoxypropyltrimethoxysilane, a mercaptoalkylalkoxysilane such as γ-mercaptopropyltrimethoxysilane, or an aminoalkylalkoxysilane such as N-β- (aminoethyl) γ-aminopropyltrimethoxysilane. The length of the spacer as a spacer between the functional group, such as epoxy or glycidoxy, which binds with the capture molecule or the probe, and the Trialkoxysilangruppe acting alkylene is subject to no restriction. Such spacers may also be polyethylene glycol radicals.

For the final production of a biochip then the binding or coupling of capture molecules such as oligonucleotides or DNA molecules to the support material via the linker molecules according to the conventional methods, for example by treating the porous support material using epoxysilanes as linker molecules by subsequent reaction of the terminal epoxide groups with terminal primary amino groups or thiol groups of oligonucleotides or DNA molecules which function in corresponding analysis methods as immobilized or fixed capture molecules for the target molecules present in the analyte to be investigated. In this case, for example, the oligonucleotides which can be used as catcher molecules can be synthesized using the synthesis strategy as described in Tet. Let. 22, 1981, pages 1859-1862. The oligonucleotides can be derivatized during the preparation process either at the 5 or the 3-terminal position with terminal amino groups. Another way of attaching such capture molecules to the interior wall surfaces of the pores can be accomplished by first exposing the substrate to a source of chlorine such as Cl ₂ , SOCl ₂ , COCl ₂ or (COCl) ₂ , optionally using a free radical initiator such as peroxides, azo compounds or Bu ₃ SnH, and then with a corresponding nucleophilic compound, in particular with oligonucleotides or DNA molecules having terminal primary amino groups or thiol groups or other corresponding functional groups are reacted (see WO 00/33976).

• – Bereitstellen einer erfindungsgemäßen Vorrichtung bzw. BioChips;
• – Einleiten einer Synthesesubstanz in zumindest eine der Poren des Trägermaterials;
• – Einkoppeln von Licht in die Pore zum optischen Anregen zumindest der Synthesesubstanz.

The devices according to the invention are also particularly suitable for the localized, light-controlled synthesis of molecules on the pore walls. Another object of the present invention thus relates to a method for controlling chemical or biochemical reactions or syntheses the steps:

• Providing a device according to the invention or biochips;
• Introducing a synthetic substance into at least one of the pores of the carrier material;
• - Coupling of light into the pore for the optical excitation of at least the synthesis substance.

For planar substrates, the process of light-directed synthesis is, for example, in EP 0 619 321 and EP 0 476 014 described. With regard to the structure and the light-controlled synthesis process, reference is made in its entirety to the disclosure content of these publications, so that these documents are to Offenba content of the present application. Due to the efficient propagation of the light into the pores, photochemical reactions can be driven or controlled on the pore walls. In particular, complex sequential light-controlled chemical reactions can be carried out on the pore boundary surfaces in this way.

Optical crosstalk between the individual pores or areas / compartments is through the reflective walls prevented from pores filled with optically non-transparent material. In order to becomes a major problem in planar synthesis in light-directed synthesis Substrates solved.

The The present invention will be described below with reference to FIGS Figures described by way of example. It shows:

1 an exemplary device according to the invention of macroporous carrier material ( 10 in which pores are completely filled with optically non-transparent material to form a frame as described above ( 12 ) are filled. The filled pores form the frame ( 12 ), which in turn is a compartment ( 11A ) encloses. The pore walls ( 11B ), ie the webs between the pores ( 11 ), within the Compartment ( 11A ) are transparent. 1 (A) shows the supervision and 1 (B) the side view of a section of such a device. While the 1 (A) and 1 (B) show an embodiment with square pores, is in 1 (C) schematically shows the top view of an embodiment with hexagonal pores.

2 an exemplary device according to the invention of macroporous carrier material ( 10 ), in which pore walls ( 11C ) forming a framework as described above ( 12 ) are modified, for example by applying a metal layer so that they are no longer transparent. The thus modified pores form the framework ( 12 ), which in turn is a compartment ( 11A ) encloses. The pore walls ( 11B ), ie the webs between the pores ( 11 ), within the Compartment ( 11A ) are transparent. 1 (A) and 1 (B) show upfront and 1 (C) the side view of a section of such a device. While the 1 (A) . 1 (B) and 1 (C) show an embodiment with square pores, is in 1 (D) schematically shows the top view of an embodiment with hexagonal pores.

10

macroporous carrier material

10A, 10B

Substrate surfaces

11

pore

11A

compartment

11B

Pore walls or Footbridges within a compartment

11C

modified pore walls

12

frame

Claims (16)

Device comprising a flat macroporous support material ( 10 ), which distributes a plurality of pores over at least one surface area ( 11 ) having a diameter in the range of 500 nm to 100 μm, which extends from a surface ( 10A ) to the opposite surface ( 10B ) of the carrier material, the device comprising two or more compartments ( 11A ), each having two or more pores ( 11 ), whereby such a compartment ( 11A ) surrounding pores are filled with a non-transparent material, so that such a compartment ( 11A ) arranged in each case from one to the longitudinal axes of the pores substantially parallel to the surfaces ( 10A . 10B ) open frames ( 12 ) is surrounded by such filled pores. Apparatus according to claim 1, wherein each individual frame ( 12 ) is completely spatially isolated from the surrounding frames within the totality of all frames. Apparatus according to claim 1 or 2, wherein the pore density is in the range of 10 ⁴ to 10 ⁸ / cm ² . Apparatus according to claim 1, 2 or 3, wherein said support material is selected from silica, glass or alumina. Device according to one of claims 1 to 4, wherein the pores ( 11 ) are formed substantially square and the frame ( 12 ) in substantially square or rectangular shape. Device according to one of claims 1 to 5, wherein the optical transparent material of an organic polymer in which Pigments and / or metal spheres are dispersed is. Device according to one of the preceding claims, wherein on at least one of the pores ( 11 ) are at least partially covalent capture molecules selected from the group consisting of DNA, proteins and ligands bound. The device according to claim 7, wherein the capture molecules are oligonucleotide probes which are bound via terminal amino or thiol groups to linker molecules which in turn are attached to the pores via covalent and / or ionic groups ( 11 ) are bound. Device comprising a flat macroporous support material ( 10 ), which distributes a plurality of pores over at least one surface area ( 11 ) having a diameter in the range of 500 nm to 100 μm, which extends from a surface ( 10A ) to the opposite surface ( 10B ) of the carrier material, the device comprising two or more compartments ( 11A ), each having two or more pores ( 11 ), wherein the pore walls ( 11C ) of such a compartment ( 11A ) surrounding pores are locally modified with a metal layer, so that such a compartment ( 11A ) arranged in each case from one to the longitudinal axes of the pores substantially parallel to the surfaces ( 10A . 10B ) open frames ( 12 ) from such modified pore walls ( 11C ) is surrounded. Apparatus according to claim 9, wherein each individual frame ( 12 ) is completely spatially isolated from the surrounding frames within the totality of all frames. Apparatus according to claim 9 or 10, wherein the pore density is in the range of 10 ⁴ to 10 ⁸ / cm ² . Apparatus according to claim 9, 10 or 11, wherein the support material is selected from silica, glass or alumina. Device according to one of claims 9 to 12, wherein the pores ( 11 ) are formed substantially square and the frame ( 12 ) in substantially square or rectangular shape. Device according to one of claims 9 to 13, wherein the metal layer based on elemental metal or a metal compound thereof in particular their chalcogenides. Device according to one of claims 9 to 14, wherein on at least one of the pores ( 11 ) are at least partially covalent capture molecules selected from the group consisting of DNA, proteins and ligands bound. The device according to claim 15, wherein the capture molecules are oligonucleotide probes which are bound via terminal amino or thiol groups to linker molecules, which in turn are attached to the pores via covalent and / or ionic groups ( 11 ) are bound.