WO2010025853A1

WO2010025853A1 - Molecularly imprinted polymer (mip) chip sensor, use thereof, and analytical detection method

Info

Publication number: WO2010025853A1
Application number: PCT/EP2009/006128
Authority: WO
Inventors: Ute Steinfeld; Hyeck-Hee Lee; Jung Tae Kim
Original assignee: Kist-Europe Forschungsgesellschaft Mbh
Priority date: 2008-08-25
Filing date: 2009-08-24
Publication date: 2010-03-11
Also published as: DE102008039624A1; DE102008039624B4

Abstract

The invention relates to a chip sensor for detecting at least one analyte in a sample containing at least one microfluidic system having at least one flow channel and at least one cantilever arranged in the flow channel. Nanoparticles containing at least one molecular imprinted polymer, which has specific binding cavities for the at least one analyte, are arranged on the surface of the cantilever at least in some areas.

Description

MOLECULAR CARRIER POLYMER (MIP) CHIP SENSOR, USE AND ANALYTICAL PROOF PROCESS

The invention relates to a chip sensor for detecting at least one analyte in a sample, wherein the sensor is based on a cantilever with molecularly imprinted polymer (MIP) nanoparticles. The invention further relates to a method for detecting at least one analyte in a sample, in which this chip sensor is used. The sensors according to the invention are used for a variety of analytical applications in the fields of medicine, food chemistry and the environment.

For applications in the field of biosensors, the use of micro-fabrication techniques produced cantilevers as a sensor is known from the prior art. A cantilever is pronounced as cantilevered spring beam and chemically treated with a catcher molecule as specific as possible. coated. This sensor is usually brought into contact with the liquid to be analyzed. If molecules of the desired substance are in the liquid, they bind to the capture molecule. On the one hand there is an altered surface tension on the cantilever, so-called stress, on the other hand an increase in the mass of the cantilever. While surface stress results in minimal mechanical deflection of the cantilever, the mass increase typically causes a decrease in the cantilever's natural frequency. Both the minimum deflection and the change in the vibration behavior can be determined as indicators for the analysis.

Thus, a mechanical change in the state or behavior of the cantilever serves for detection. The high sensitivity of cantilevered micromechanical cantilevers is a particular advantage that is difficult or impossible to achieve by conventional methods.

In the field of analysis, molecular imprinted polymers (MIP) are increasingly being used in recent times. Molecular embossing is a process for the preparation of polymers with molecular imprints, so-called template molecules. For this purpose, bonds with functional monomers are formed at certain points of the template used as a template. This complex is then stabilized in the presence of a solvent by copolymerization with suitable crosslinks. Subsequently, the template is washed out of the crosslinked polymer matrix with a suitable solvent or extracted. The remaining cavities (imprints) have a to Template complementary form and corresponding binding sites on. Both effects account for the affinity of the imprint to the template molecule upon renewed contact with it.

From WO 2005/119233 Al a sensor is known which is based on a cantilever whose surface is provided with a MIP coating. The full-surface and permanent coating of the cantilever, however, involves disadvantages in terms of loading capacity on the one hand and reusability on the other hand.

Proceeding from this, it was an object of the present invention to provide a sensor which eliminates the disadvantages known from the prior art and enables the most flexible handling and the possibility of detecting a wide variety of analytes.

This object is achieved by the chip sensor having the features of claim 1 and the method having the features of claim 19. In claim 22 uses according to the invention are listed. The further dependent claims show advantageous developments.

According to the invention, a chip sensor for detecting at least one analyte in a sample is provided which contains at least one microfluidic system with at least one throughflow channel and at least one cantilever arranged in the throughflow channel. At least in certain regions, nanoparticles are arranged on the surface of the cantilever and contain at least one molecularly imprinted polymer which has a specific binding for the at least one analyte. has cavity.

The sensor thus consists of a microfluidic chip system, in whose microfluidic channels one or more cantilevers are arranged. At the

Surface of the cantilever are nanoparticles containing a molecularly imprinted polymer, temporarily or permanently attached.

Compared to the prior art, the chip sensor according to the invention is characterized in that instead of full-surface coatings of the cantilever nanoparticles are bound to the cantilever surface. This brings significant advantages in terms of the loading capacity of the sensor for a variety of analytes. The use of nanoparticles leads to a significantly increased surface area, which drastically increases the number of bond cavities on the surface of the cantilever. Thus, it is possible for the first time with the system according to the invention to also measure samples with a significantly higher concentration of the analyte. Elaborate dilution steps are eliminated.

The cantilever preferably consists essentially of silicon dioxide, wherein at least one piezoelectric layer is preferably arranged at least in regions on the surface.

In a preferred embodiment, the nanoparticles are at least partially coated with the molecularly imprinted polymer.

The nanoparticles are preferably bound chemically, in particular by covalent or ionic bonding to the cantilever surface. It is the same but also possible that a connection by physical sorption or chemosorption occurs. Furthermore, spacers can be used to bind the nanoparticles to the cantilever surface. Particularly preferred is a chemical linkage via the OH groups of the cantilever surface, since the cantilever consists of silicon dioxide and a multiplicity of SiOH groups exist on the surface.

The particle size of the nanoparticles is generally in the range of 10 to 1000 nm.

In the case of nanoparticles which are bound to the cantilever surface in the manner described above, the nanoparticles preferably have a particle size in the range from 10 to 200 nm, preferably from 10 to 100 nm and particularly preferably from 10 to 30 nm , This can then be followed by coating with the molecularly imprinted polymer of the nanoparticles bound on the can-tilever surface. However, it is also possible that the nanoparticles are pre-coated with the molecularly imprinted polymer and subsequently bonded to the cantilever surface. In this case, the nanoparticles preferably have a particle size in the range from 200 to 1000 nm, preferably from 500 to 800 nm.

A particularly preferred variant of the chip sensor according to the invention provides that the cantilever has electromagnetic regions at least in regions. This includes, for example, an electromagnetic layer, which is preferably arranged on the piezoelectric layer. Electromagnetic interaction can then be used to attach nanoparticles which contain a magnetic or magnetizable material to the surface of the nanoparticle Cantilevers take place. The electromagnetic layer thus allows a temporary fixation of the nanoparticles on the cantilever. This leads to a very flexible and versatile system in terms of microfluidic analysis. This allows the MIP nanoparticles to be easily interchanged, providing a sensor system of any specificity. The easy interchangeability of nanoparticles ensures the recycling and reusability of such systems for the first time.

The magnetic or magnetizable materials are preferably iron-containing materials, in particular magnetite, maghemite and / or hematite.

The magnetic or magnetizable nanoparticles which were coated with the molecularly imprinted polymer before being brought into contact with the cantilever have, including the MIP coating, a particle size in the range from 200 to 1000 nm, preferably from 500 to 800 nm.

The molecularly imprinted polymers used according to the invention follow the molecular imprinting technique, which is based on the complex binding of a template, functional monomers and cross-linkers. Upon polymerization, a detection cavity with specific and well-aligned functional groups is formed, which is complementary to the template molecule. These engineered, template-tailored molecular cavities show highly selective molecular recognition. Advantages of such structures for sensors, in addition to the high specificity, the associated low cost, robustness, high stability and ease of use and Storage for a longer period of time.

The molecularly imprinted polymers used according to the invention are preferably selected from the group consisting of poly (meth) acrylic acids, poly (meth) acrylates, polyacrylamides, polyolefins, polydiolefins, polyvinyl compounds, polylactides, polyglycosides, polyphosphazenes, polyorthoesters, polyanhydrides , Polyurethanes, polysiloxanes and copolymers, blends and mixtures thereof and / or selected from the group of natural polymers consisting of starch, cellulose, chitosan and copolymers, blends and mixtures thereof.

Typical functional monomers used (polymerizable moiety that interacts with the print molecule) may be:

Carboxylic acids, such as acrylic acid, methacrylic acid, Triflu- or methacrylic acid, vinyl benzoic acid, itaconic acid, and their amides;

Sulfonic acids, such as acrylamidomethylpropanesulfonic acid;

heteroaromatic or weak bases, such as substituted or unsubstituted vinylpyridines, vinylpyrimidines, vinylpyrazoles, vinylimidazoles, vinyltriazines, vinylpurines, -indoles, -quinolines, -acridines, -phenanthridines, bis (acrylamido) pyridine;

aliphatic or aromatic vinyl derivatives, such as substituted or unsubstituted styrenes, vinylnaphthalenes, vinylnaphthalenecarboxylic acids, vinylnaphthols, vinylanthracenes, vinylanthracenecarboxylic acids, vinylphenanthrenes, vinylphenanthrenecarboxylic acids, and similar fused aromatics, vinylbenzamidine; Acryloylaminobenzamidine, (amidinoalkyl) -styrene, where the alkyl may be methyl, ethyl or propyl, N-acryloyl- (amidinoalkyl) -aniline, vinyl derivatives having chelating groups, such as iminodiacetic acid, ethylenediaminetetraacetic acid, inter alia, for complexing metal ions, silanes as well as mixtures of such monomers. Other functional monomers can also be used.

As cross-linker (unit with two or more linkages with the functional monomers) can serve:

Isomers of divinylbenzene;

Bis (acryloyl) alkanes, ethane, propane and butane being suitable as alkanes;

Systems based on acrylic acid or methacrylic acid, e.g. Ethylene glycol dimethacrylate (EDMA) and trimethylolpropane trimethacrylate (TRIM);

tri- and tetrafunctional acrylate cross-linkers, e.g. Pentaerythritol triacrylate (PETRA) and pentaerythritol tetraacrylate (PETEA) as well as

Cross-linkers containing functional groups, such as acrylamide units, which are linked to the amide nitrogens by means of aliphatic (methylene-inter alia), aromatic (phenylene-ua) or heteroaromatic (pyridinyl-ua) spacers. Other cross-linkers can also be used, for example, UV crosslinkers or even stable UV crosslinkers. As porogens (solvents that serve as solvents for the polymerization reaction and induce porosity into the imprinted polymer), different dielectric constant solvents may be used, including parameters such as different swelling properties of the polymer, different morphologies of the polymer having different structures and pore diameters / porosity or affect different binding strengths of noncovalent interactions, in particular aliphatic or alicyclic hydrocarbons such as hexane, heptane or cyclohexane;

aromatic hydrocarbons, such as toluene;

halogenated hydrocarbons, such as chloroform, dichloromethane or 1, 2-dichloroethane;

short-chain alcohols, such as methanol, ethanol, propanol;

Ether, acetonitrile, tetrahydrofuran, ethyl acetate, acetone, dimethylformamide, dioxane, dimethyl sulfoxide;

also in mixtures with each other and with water.

The addition of a porogen in the preparation of the molecularly imprinted polymers has the effect that the resulting nanoparticles have macropores with a pore size in the range of 10 to 50 nm.

The polymerization can be initiated in various ways. In addition to thermal initiation, this also includes the addition of initiators (radical initiators) for radical polymerization. 2, 2'-azobis-isobutyronitrile (AIBN), 2,2'-azobis (2,4-dimethyl-valeronitrile) (ADVN) and others can be used as initiators, and the use of UV light is also possible.

The molecularly imprinted polymers used according to the invention preferably have binding cavities for biomolecules, in particular bacteria, viruses, proteins, peptides, antigens, antibodies, vitamins, prions, tumor markers, DNA sequences, DNA sequences, RNA sequences, cells and specific DNAs On cell surfaces. Likewise, the polymers binding cavities for pollutants, pharmaceuticals and personal care products (PPCP) endocrine disrupting chemicals (EDC), herbicides, pesticides, nitrates, phosphates, chlorinated hydrocarbons (Lindane, PCB) and organic phosphorus compounds. It is likewise possible that the polymers have bonding cavities for a plurality of the abovementioned groups.

The specific binding cavities are preferably generated by the incorporation of specific epitopes, receptors or parts thereof. These are then removed again from the polymer matrix, z. B. by the use of hydrolytic enzymes or by thermal or chemical decomposition. It is also possible that the specific binding cavities are produced by the incorporation of specific proteins, polysaccharides, fats and / or nucleic acids and then removed with hydrolysis by lysosomal enzymes.

The invention likewise provides a method for detecting at least one analyte in a sample Use of the chip sensor described above provided. The method has the following steps:

a sample containing the at least one analyte and present in liquid or gaseous form is introduced into the throughflow channel,

the sample is brought into contact with the cantilever, whereby a binding to the cantilever surface takes place through interaction between the at least one analyte and the binding cavities,

the mass increase of the cantilever caused by the binding of the at least one analyte is determined by means of a measurement of the vibration behavior,

a release of the analyte bound to the cantilever surface occurs and

- The sample is removed from the at least one desorbed analyte from the flow channel.

The method according to the invention is based on passing a sample in liquid or gaseous form over the chip sensor. If the desired analytes are present in the sample, they bind in the corresponding specific cavities and the mass on the cantilever surface increases. This mass increase changes the vibration behavior of the cantilever. The measurement can here preferably be based on the amplitude, the frequency and / or the phase of

Oscillation, ie its intensity and temporal behavior. In this way, the detection of analytes takes place in real time and without changing or marking them in any way. As a result, an undesired influence by the marker molecules and thus a falsification the investigated interaction avoided. This is in contrast to classical sensors in which, for example, fluorescent markers are used to identify the substances to be investigated.

The release of the analyte bound in the binding cavities preferably takes place by chemical or thermal desorption, pH-dependent, by lysosomal hydrolysis and / or magnetic interaction.

In the latter case, the magnetic or magnetizable nanoparticles are again completely removed from the cantilever surface. This has the great advantage that in a very simple way, the cantilever surface can be coated with new nanoparticles that are specific for other analytes.

The chip sensors according to the invention are used for any analytical questions. For example, the sensors can be used in the following areas:

• medicine, both for diagnostic and therapeutic purposes,

• Food chemistry, especially for quality control of food and monitoring of processes in the food industry,

• environment, in particular for the treatment, purification and / or quality improvement of liquids, in particular of waste water such as industrial wastewater, process wastewater from the chemical or pharmaceutical industry or paper and pulp industrial effluents, hospital effluents, animal excretions, including in connection with microbial treatment, and food chemistry,

• Laboratory analysis in research and screening,

• detection of biological weapons,

• DNA or RNA detection, sequence selectivity, detection of specific ds DNA sequences, ss DNA sequences or RNA sequences.

The chip sensor according to the invention finds application for the detection of biomolecules, especially bacteria, viruses, proteins, peptides, antigens, antibodies, vitamins, prions, tumor markers, ds DNA sequences, ss DNA sequences, RNA sequences, cells and specific cell surfaces and Pollutants, pharmaceutical substances and personal care products, endocrine disruptors, herbicides, pesticides, nitrates, phosphates, chlorinated hydrocarbons (lindane, PCB) and organic phosphorus compounds in liquid samples, in particular water or blood, or gaseous samples, in particular in the air.

The subject according to the invention is intended to be explained in more detail with reference to the following figures, without restricting it to the specific embodiments shown here.

Fig. 1 shows the structure of a Can- tilevers invention.

2 shows a first variant of a chip sensor according to the invention. 3 shows a second variant of a chip sensor according to the invention.

4 shows the functional principle of the measuring method and of the cantilever sensor in conjunction with paramagnetic nanoparticles.

Fig. 5 shows a micro-cantilever sensor unit and the overall view of the microfluidic platform for multiple detection and simultaneous sample preparation.

FIG. 1 shows a cantilever 1 according to the invention, which is provided on one of its surfaces with a piezoelectric layer 2. An electromagnetic layer is arranged on the piezoelectric layer, by means of which an electromagnetic interaction with the magnetic or magnetizable nanoparticles 4 is made possible. The electromagnetic layer 3 can be omitted here, if another binding of the nanoparticles takes place on the cantilever, z. As a chemical bond or a connection by physisorption or Chemisorpti- on.

FIG. 2 shows a first variant of a chip sensor system according to the invention. This consists of a microfluidic system with a through-flow channel 5, at the inlet opening of which the sample containing the analyte to be detected is introduced. In the flow channel a plurality of inventive cantilevers 6, 6 'and 6' 'are arranged, which come into contact with the sample, thereby causing an interaction between the analyte and the

Bonding cavities of the molecularly imprinted polymer the cantilever surface thus comes to the specific connection. In this case, an increase in the mass of the cantilever is then detected, which can be detected by measuring the vibration behavior, for example the amplitude, the frequency and / or the phase of the vibration.

FIG. 3 shows a second variant of a chip sensor according to the invention. In this case, the throughflow channel 5 has bifurcations, so that the sample is introduced via a first inlet opening, and further reagents can be added via a second inlet opening, so that a chemical reaction takes place in the throughflow channel. Again, analogous to FIG. 2, a plurality of cantilevers 6, 6 'and 6 "are arranged again.

For better clarity, FIG. 4 schematically illustrates the functional principle of the measuring method and the cantilever sensor in connection with paramagnetic nanoparticles.

The paramagnetic MIP nanoparticles are injected into the microcantileversensor 30 (A) with a magnetic field applied (B). The nanoparticles arrange themselves on the surface of the cantilever 30. By washing the sensor unit, non-immobilized particles are removed (C). Subsequently, a sample containing the target molecules is injected into the system. The target molecules are bound and detected by the nanoparticles (D, E). After detection, the magnetic field is deactivated and the system washed to remove all nanoparticles (F). The uncoated cantilever can now be used for the next test. By using of other MIPs that have been imprinted with other target molecules, different target molecules can be detected with the same cantilever.

Advantages:

• Multiple detection of target molecules

• Continuous monitoring of a target molecule

• Easy and fast preparation of the sensor surface • Excellent thermal and mechanical stability of the detection element

• Low costs

• Reusable sensor unit

Advantages over other techniques:

• High measuring sensitivity (in the ppt range)

• Fast and simultaneous on-line screening of different target molecules

• Selective detection • No disturbing matrix effects due to haze

• Only small amounts of sample required

FIG. 5 shows a further application of the chip sensor according to the invention in a microfluidic platform. In this case, a sample chip 10 is arranged in a supporting frame 15 via a connecting bridge 11 with a detector chip 12. In the example chip of FIG. 5, a storage container 19 is integrated in the sample chip 10 and the sample chip also has accesses for the samples 16. In the detector chip 12 is a

Mikrocantileversensorfeld 17 arranged with a waste chamber 20, and a particle reservoir 18. Der The advantage now is that the separate sample chips 10 and detector chips 11 can be easily connected to each other via the connecting bridge 11. Another advantage of such a system is that the sample flows over the surface of the cantilever sensor in the micro-cantilever field 17 and there is no direct reaction with the surface. Therefore, the system can be cleaned after each detection and reused with new nanoparticles. By simply modifying the fluidic channels, an application for continuous online detection of environment-relevant substances is also possible.

Claims

claims

1. A chip sensor for detecting at least one analyte in a sample containing at least one microfluidic system with at least one throughflow channel and at least one cantilever arranged in the throughflow channel, wherein nanoparticles comprising at least one molecularly embossed polymer, which for the at least one analyst has specific binding cavities arranged.

2. Chip sensor according to claim 1, characterized in that the cantilever consists essentially of silicon dioxide.

3. Chip sensor according to one of the preceding claims, characterized in that at least one piezoelectric layer is arranged at least partially on the surface of the cantilever.

4. Chip sensor according to one of the preceding claims, characterized in that the surface of the nanoparticles is at least partially coated with the molecularly imprinted polymer.

5. Chip sensor according to one of the preceding claims, characterized in that the nanoparticles are bound chemically, by covalent or ionic bonding, physisorption or chemosorption and / or a spacer to the surface of the cantilever.

6. The chip sensor according to claim 5, characterized in that the nanoparticles are bound to the SiOH groups of the cantilever surface to this.

7. Chip sensor according to one of claims 5 or 6, characterized in that the nanoparticles have a particle size of 10 to 200 nm, preferably from 10 to 100 nm and more preferably from 10 to 30 nm.

8. Chip sensor according to one of claims 1 to 4, characterized in that the cantilever at least partially electromagnetic regions, in particular an applied on the piezoelectric layer has electromagnetic layer, which by electromagnetic interaction binding of nanoparticles containing a magnetic or magnetizable material, on the surface of the cantilever.

9. Chip sensor according to claim 7, characterized in that on the surface of the cantilever at least partially nanoparous particles containing a magnetic or magnetizable material are reversibly bound.

10. Chip sensor according to claim 8 or 9, characterized in that the magnetic or magnetizable material is an iron-containing material, in particular magnetite, maghemite and / or hematite.

11. Chip sensor according to one of claims 8 to 10, characterized in that the nanoparticles have a particle size of 200 to 1000 nm, in particular 500 to 800 nm.

12. Chip sensor according to one of the preceding claims, characterized in that the molecularly imprinted polymer is selected from the group consisting of poly (meth) acrylic acids, poly (meth) - acrylates, polyacrylamides, polyolefins, polydiolefins, polyvinyl compounds, polylactides , Polyglycosides, polyphosphazenes, polythioesters, polyanhydrides, polyurethanes, polysiloxanes and copolymers, blends and mixtures thereof and / or selected from the group of natural polymers consisting of starch, cellulose, chitosan and copolymers, blends and mixtures thereof.

13. Chip sensor according to one of the preceding claims, characterized in that the molecularly embossed polymer of at least one monomer selected from the group consisting of (meth) acrylic acids, p-vinylbenzoic acid, itaconic acid, 4-ethylstyrene, styrene, 4-vinylpyridine, 2-vinylpyridine, 1-vinylimidazole, 2-acrylamido-2-methyl 1-propanesulfonic acid, (meth) acrylamide, trans-3- (3-pyridyl) -acrylic acid 2,5-distyrylpyrazine, diethyl-p-phenylenediacrylate and mixtures thereof.

14. Chip sensor according to one of the preceding claims, characterized in that the molecularly imprinted polymer by means of a crosslinking agent selected from the group consisting of divinylbenzene crosslinker, (meth) acrylic acid crosslinker, tri- and tetrafunctional crosslinkers, acrylamide crosslinkers and mixtures thereof, in particular N, N '-1, 4-phenylenediacrylamine, N, N'-methylenediacrylamide, ethylene glycol dimethacrylate,

3, 5-bis (acrylolamido) benzoic acid, divinylbenzene, N, O-bisacryloylphenylalaniol, 1,3-diisoprenylbenzene, tetramethylenedimethacrylate, 1,4-diacryloylpiperazine, 2,6-biacryloylamidopyridine, dimethylformamide, trimethylpropane trimethacrylate,

Pentaerythritol tetraacrylate and mixtures thereof.

15. Chip sensor according to one of the preceding claims, characterized in that the molecularly imprinted polymer has macropores with a size in the range of 10 to 50 nm, which is based on the addition of porogens, in particular selected from the group consisting of polyvinyl acetate, water. alcohols, especially methanol and ethanol, acetonitrile, dimethylsulfoxide and mixtures thereof, are due to the production of the polymer.

16. Chip sensor according to one of the preceding claims, characterized in that the molecularly imprinted polymer binding cavities for biomolecules, insbesondre bacteria, viruses, proteins, peptides, antigens, antibodies, vitamins, prions,

Cells and specific cell surfaces and pollutants, pharmaceuticals and personal care products, endocrine disruptors, tumor markers, herbicides and pesticides.

17. A chip sensor according to any one of the preceding claims, characterized in that the specific binding cavities have been generated by the incorporation of specific binding cavities by the incorporation of specific epitopes, receptors or parts thereof and subsequently removed again from the polymer matrix, e.g. through the use of hydrolytic enzymes, thermal or chemical decomposition.

18. Chip sensor according to one of the preceding claims, characterized in that the specific binding cavities were generated by incorporation of specific proteins, polysaccharides, fats and / or nucleic acids and were removed with subsequent hydrolysis by lysosomal enzymes.

19. Method for detecting at least one analyte in a sample using a chip sensor according to one of the preceding claims, in which a sample containing the at least one analyte and present in liquid or gaseous form is introduced into the throughflow channel,

the sample is brought into contact with the cantilever, whereby a binding to the cantilever surface takes place by interaction between the at least one analyte and the binding cavities,

a release of the analyte bound to the cantilever surface takes place and the sample with the at least one desorbed analyte is removed from the flow channel.

20. The method according to claim 19, characterized in that the measurement of

Vibration behavior based on the amplitude, the frequency and / or the phase of the vibration takes place.

21. The method according to claim 19 or 20, characterized in that the release is effected by chemical or thermal desorption, pH-dependent, by lysosomal hydrolysis and / or by magnetic interaction.

22. Use of the chip sensor according to one of claims 1 to 18 for analysis in the areas

• Medicine, both for diagnostic and therapeutic purposes, • Food chemistry, especially for quality control of food and monitoring of processes in the food industry,

• Environment, in particular for the treatment, cleaning and / or quality improvement of

Liquids, in particular of waste water, such as industrial wastewater, process effluents from the chemical or pharmaceutical industry or the paper and pulp industry, municipal wastewaters, hospital wastewater, animal excrement, including in connection with microbial treatment processes, and food chemistry,

• Laboratory analysis in research and screening,

• detection of biological weapons,

23. Use according to claim 22 for the detection of biomolecules, in particular bacteria, viruses, proteins, peptides, antigens, antibodies, vitamins, prions, tumor markers, ds DNA sequences, ss DNA sequences, RNA sequences, cells and specific cell surfaces and pollutants , phar- medicines and personal care products, endocrine disruptors, herbicides, pesticides, nitrates, phosphates, chlorinated hydrocarbons (lindane, PCB) and organic phosphorus compounds in liquid samples, in particular water or blood, or gaseous samples, in particular in the air.