EP1478456A1 - Porte echantillon ultraphobe a zones fonctionnelles hydrophiles et/ou oleophiles - Google Patents

Porte echantillon ultraphobe a zones fonctionnelles hydrophiles et/ou oleophiles

Info

Publication number
EP1478456A1
EP1478456A1 EP03742575A EP03742575A EP1478456A1 EP 1478456 A1 EP1478456 A1 EP 1478456A1 EP 03742575 A EP03742575 A EP 03742575A EP 03742575 A EP03742575 A EP 03742575A EP 1478456 A1 EP1478456 A1 EP 1478456A1
Authority
EP
European Patent Office
Prior art keywords
flat structure
structure according
hydrophilic
ultraphobic surface
ultraphobic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP03742575A
Other languages
German (de)
English (en)
Inventor
Joachim Engelking
Karsten Reihs
Eckhard Nordhoff
Martin Müller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Qiagen GmbH
Scienion GmbH
Original Assignee
Sunyx Surface Nanotechnologies GmbH
Scienion GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE10207616A external-priority patent/DE10207616A1/de
Priority claimed from DE2002155276 external-priority patent/DE10255276A1/de
Application filed by Sunyx Surface Nanotechnologies GmbH, Scienion GmbH filed Critical Sunyx Surface Nanotechnologies GmbH
Publication of EP1478456A1 publication Critical patent/EP1478456A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5088—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above confining liquids at a location by surface tension, e.g. virtual wells on plates, wires
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
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    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B01J2219/00317—Microwell devices, i.e. having large numbers of wells
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00614—Delimitation of the attachment areas
    • B01J2219/00617—Delimitation of the attachment areas by chemical means
    • B01J2219/00619—Delimitation of the attachment areas by chemical means using hydrophilic or hydrophobic regions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00623—Immobilisation or binding
    • B01J2219/00626—Covalent
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00632—Introduction of reactive groups to the surface
    • B01J2219/00637—Introduction of reactive groups to the surface by coating it with another layer
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00639—Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00644—Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium the porous medium being present in discrete locations, e.g. gel pads
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    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00677—Ex-situ synthesis followed by deposition on the substrate
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    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00702—Processes involving means for analysing and characterising the products
    • B01J2219/00707—Processes involving means for analysing and characterising the products separated from the reactor apparatus
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    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
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    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
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    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
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    • G01N1/22—Devices for withdrawing samples in the gaseous state

Definitions

  • Ultraphobic sample carrier with functional hydrophilic and / or oleophilic areas Ultraphobic sample carrier with functional hydrophilic and / or oleophilic areas
  • the present invention relates to a flat structure with an ultraphobic surface and with at least one hydrophilic and / or oleophilic region which, in addition to hydrophilicity and / or oleophilicity, has at least one further functionality. Furthermore, the present invention relates to a method for producing the flat structures according to the invention and their use.
  • microtiter plates or sample carriers are known from the prior art which, for example, have a large number of depressions at regular intervals.
  • Sample carriers are known from WO 98/45406 and DE 196 28 928, the surface of which is hydrophobic and the hydrophilic depressions are incorporated into them.
  • a sample carrier with a hydrophobic surface is known from German published patent application DE 197 54 978. Hydrophilic anchor areas are worked into this hydrophobic surface.
  • sample carriers according to the prior art have the disadvantage that the hydrophilic regions can only be produced in a comparatively complex manner, but in particular that series tests with them are only comparatively complex.
  • the object is achieved according to the invention with a flat structure with an ultraphobic surface and with at least one hydrophilic and / or oleophilic region which, in addition to hydrophilicity and / or oleophilicity, has at least one further functionality.
  • a flat structure in the sense of the invention is any shaped body with an arbitrarily designed surface.
  • the fabric is preferably a plate with a flat surface, very particularly preferably a sample carrier, which, however, preferably has no indentations.
  • the fabric according to the invention is a film which has an ultraphobic surface.
  • the surface of the fabric according to the invention is preferably essentially flat; i.e. however, the topography required for an ultraphobic surface does not have any micro-volumes in which liquid can be collected.
  • the fabric has an ultraphobic surface.
  • An ultraphobic surface in the sense of the invention is characterized in that the contact angle of a drop of water and / or oil lying on the surface is more than 150 ° , preferably more than 160 ° and very particularly preferably more than 170 ° and that Roll angle does not exceed 10 ° .
  • the roll angle is understood to be the angle of inclination of a basically flat but structured surface against the horizontal, in which a standing water and / or oil drop with a volume of 10 ⁇ l is moved due to the force of gravity when the surface is inclined.
  • ultraphobic surfaces are described, for example, in WO 98/23549, WO 96/04123, WO 96/21523, WO 99/10323, WO 00/39368, WO 00/39239, WO 00/39051, WO 00/38845 and WO 96 / 34697, which are hereby introduced as a reference and are therefore considered part of the disclosure.
  • the fabric has hydrophilic and / or oleophilic areas.
  • Hydrophilic and / or oleophilic areas within the meaning of the invention are areas on which a drop of water or oil can be deposited; i.e. a drop of water or oil, which is brought into contact with the hydrophilic and / or oleophilic area on a pipetting system, remains attached to it and thus detaches from the pipetting system.
  • a drop of water or oil with a volume of 10 ⁇ l on the hydrophilic and / or oleophilic areas preferably has a contact angle ⁇ 120 °, preferably ⁇ 110 °, very particularly preferably ⁇ 90 ° and / or the roll angle of this drop exceeds 10 °.
  • the hydrophilic and / or oleophilic regions have at least one further functionality in addition to the hydrophilicity and / or oleophilicity.
  • a further functionality in the sense of the invention is any other chemical and / or physical property which the material of the hydrophilic and / or oleophilic areas has in addition to water or oil repellency and which can be used industrially.
  • the properties are mentioned here by way of example but not by way of limitation: the regions can have at least one surface which forms a bond with other molecules; that catalyze chemical reactions; which emits at least one substance which, together with other molecules
  • Form a bond that acts as a reagent for samples to be tested; that delivers at least one substance that acts as a reagent for samples to be tested; another optical property (absorption, reflection, transmission,
  • Reflectance, luminescence, scatter than the environment; which emits light when exposed to heat; which has a different thermal conductivity than the environment; which has another acoustic property (e.g. sound absorption, Speed of sound) than the environment; which has a different surface friction than the environment; which have a different absorption behavior (e.g. absorption speed,
  • Equilibrium coverage than the surrounding area; which has another electrical property (e.g. conductivity,
  • Dielectric constant Dielectric constant
  • the environment which has a different magnetic property (e.g. susceptibility) than that
  • Molecules e.g. Splits biomolecules non-specifically or specifically.
  • the hydrophilic and / or oleophilic areas are preferably completely enclosed by an ultraphobic area.
  • This embodiment makes it possible to anchor a drop of liquid, which is metered onto the hydrophilic and / or oleophilic areas, comparatively firmly there.
  • the hydrophilic and / or oleophilic areas are preferably arranged according to a very specific pattern on the ultraphobic surface. In this way, for example, a grid, a so-called array, can be generated, in which the hydrophilic and / or oleophilic areas can then be easily approached, for example, by a machine for series tests.
  • the hydrophilic and / or oleophilic areas can have any shape and size. However, they preferably have an area of 1 ⁇ m 2 - 10 mm 2 . A liquid drop with a diameter of preferably 5 nm - 5 mm can be deposited on such a surface and preferably anchored in such a way that it does not detach itself from the flat structure according to the invention when it hangs downwards.
  • the hydrophilic and / or oleophilic regions are preferably at a minimum distance of> 10 ⁇ m from one another.
  • the hydrophilic and / or oleophilic areas can be incorporated into the fabric according to the invention in any manner known to the person skilled in the art or can be applied to the ultraphobic surface.
  • the hydrophilic and / or oleophilic area is in each case at least one deposit on the ultraphobic surface.
  • This deposit can be liquid or solid. In the case of a liquid deposit, it must preferably be non-volatile or only slightly volatile, at least at room temperature.
  • the deposited substance can be produced, for example, by a corresponding temperature of the ultraphobic surface or by substances which are preferably applied in a droplet form, preferably dissolved and / or suspended, to the ultraphobic surface and in which the solvent or the liquid phase is then evaporated.
  • the ultraphobic surface must be wettable by the solvent or the liquid phase. Details on this can be found in the parallel applications filed with the German Patent and Trademark Office with the internal file numbers Sy 0028 and Sy 0029, which are hereby introduced as a reference and are therefore considered part of the disclosure.
  • the solid deposit can also be a thin film of a solid substance.
  • the deposit can be an adsorbate, the layer thickness of which is only a fraction of a monomolecular layer or up to several molecular layers.
  • the deposits can, for example, with the corresponding solvents can be detached from the ultraphobic surface so that the ultraphobic surface can be reused.
  • the hydrophilic and / or oleophilic region preferably has the additional functionality of a MALDI matrix; i.e. the hydrophilic and / or oleophilic area is also a MALDI matrix for carrying out the so-called MALDI mass spectrometry, which is described, for example, in Nordhoff et, al. "MALDI-MS as a new method for the analysis of nucleic acid (DNA and RNA) with molecular masses up to 150,000 Dalton, Application of modern mass spectrometric methods to plant science research, Oxford University press, (1996) pp. 86-101 is. This publication is hereby introduced for reference and is therefore considered part of the disclosure.
  • Preferred MALDI matrices are 3-hydroxypicolinic acid, ⁇ -cyano-4-hydroxycinnamic acid, 2.5 dihydroxybenzoic acid, sinapic acid, 2, 4, 6 trihydroxyacetophenone nitrobenzyl alcohol, nicotinic acid, ferulic acid, caffeic acid, 2-aminobenzoic acid, picolinic acid, 3-aminobenzoic acid 3,4-trihydroxyacetophenone, 6-aza-2-thiothymidine, urea, succinic acid, adipic acid, malonic acid or a mixture thereof.
  • MALDI matrices are, for example, dissolved in acetonitrile and preferably applied as drops of liquid to the ultraphobic surface and then the solvent is evaporated there, so that the MALDI matrix is present as a preferably crystalline structure on the ultraphobic surface and thus the hydrophilic and / or oleophilic areas to which the samples to be analyzed can be dosed.
  • the flat structure which is particularly preferably a sample carrier, preferably has a multiplicity of locations, each with a MALDI matrix, each of which is completely enclosed by the ultraphobic surface.
  • a sample carrier can have the same matrix or different martices at all of these locations.
  • the samples to be analyzed which do not wet the ultraphobic surface, are generally metered as a liquid onto the preferably crystalline MALDI matrices and preferably at least partially dissolve them. As the solvent evaporates again, the MALDI matrix crystallizes again and the sample molecules to be analyzed are built into or bind to the MALDI matrix to the surface of the MALDI matrix. The samples prepared in this way can then be analyzed with an appropriate mass spectrometer.
  • This preferred embodiment of the present invention has the advantage that sample carriers can be made available on which the MALDI matrix or several MALDI matrices are already present at defined positions.
  • the user only has to apply the samples to be analyzed to the respective MALDI matrices, so that the analysis is considerably simplified for him. He does not have to manufacture and store the MALDI matrices and does not have to have any devices with which the MALDI matrices can be applied to the sample carriers and dried.
  • the MALDI matrix which according to the invention also represents the hydrophilic and / or oleophilic area of the fabric, acts as an anchor for the sample liquid which does not wet the ultraphobic surface and therefore does not come into contact with it, so that the sample does not come into contact with substances the ultraphobic surface can be contaminated.
  • This is of particular importance in MALDI mass spectrometry because the sample liquid is evaporated and the existing impurities are thereby concentrated. Mass spectra of high quality can therefore be determined reproducibly with the flat structures according to the invention.
  • the ultraphobic surfaces can be cleaned and reused after each application.
  • the hydrophilic and / or oleophilic regions also have the functionality of an affinity matrix; ie the hydrophilic and / or oleophilic areas are also affinity matrices.
  • An affinity matrix in the sense of the invention binds only certain molecules of a mixture of molecules. The binding can be reversible or irreversible. The bound molecules can be separated from the mixture by washing, for example, and then analyzed.
  • the selectively bound molecules are preferably biomolecules and / or biological material, in particular DNA, RNA, nucleic acids, nucleic acid analogs, Spiegelmers, aptamers, ribozymes, polypeptides, peptides and / or proteins.
  • the affinity matrix which simultaneously represents the hydrophilic and / or oleophilic region, is preferably in crystalline form.
  • an affinity matrix examples include chemical groups known to those skilled in the art from solid-phase chromatography, such as, for example: anion exchange chromatography: -NH 2 , - (CH 2 ) 4-NH 2 or - (CH 2 ) 6 -NH 2 or cation exchange chromatography: -C 6 H 4 -SO 3 H or reverse phase chromatography: - (CH 2 ) 3-CH 3 , - (CH 2 ) 7-CH3, - (CH 2 ) ⁇ 7 -CH 3 .
  • the affinity matrix is very particularly preferably also a MALDI matrix.
  • Such substances are, for example, ⁇ -cyano-4-hydroxycinnamic acid, 2, 4, 6-trihydroxyacetophenone, caffeic acid, sinapic acid or a mixture thereof.
  • the affinity matrices are dissolved, for example, in acetone, acetone / acidic water mixture, acetonitrile, ethanol, isopropanol or a mixture thereof and are preferably applied as drops of liquid to the ultraphobic surface and then the solvent is evaporated off there, so that the affinity matrices are preferably crystalline
  • the structure is punctually present on the ultraphobic surface and thus represents the hydrophilic and / or oleophilic areas to which the samples to be separated and then analyzed can be dosed.
  • a biomolecule in the sense of the present invention is any molecule that is produced by any virus or single or multicellular organism in the course of the life cycle.
  • Biomolecules contain at least one oxygen, nitrogen, sulfur, and / or phosphorus atom.
  • Examples of biomolecules are: Spielgelmere, aptamers, ribozymes, peptides, polypeptides, proteins, antibodies, nucleic acids, nucleic acid analogues, DNA, double-stranded DNA, RNA, double-stranded RNA DNA, vitamins, carbohydrates, hormones, glycopeptides, glycoproteins, lipids, fatty acids and cholesterol.
  • Biomaterial in the sense of the inventions contains at least one biomolecule. However, this can also involve large amounts of the same or different biomolecules. These can exist side by side unorganized or build functional units due to interactions. Examples of this are protein complexes, genomes, cell nuclei, ribosomes, cells, cell assemblies, tissues or complete organisms.
  • This preferred embodiment of the present invention has the advantage that sample carriers can be made available on which an affinity matrix or several affinity matrices is already present at defined positions. Different affinity matrices on a sample carrier have the advantage that different molecules can be selectively bound to the respective affinity matrices. The user only has to apply the sample liquid to be separated to the respective affinity matrices, so that the separation of individual connections is considerably simplified for him.
  • the affinity matrix which according to the invention also represents the hydrophilic and / or oleophilic area of the fabric, acts as an anchor for the sample liquid which does not wet the ultraphobic surface and therefore does not come into contact with it, so that the affinity matrix bound molecules cannot be contaminated by substances on the ultraphobic surface.
  • the molecules selectively bound to the affinity matrix are preferably biomolecules and / or biological materials, very particularly preferably nucleic acids, nucleic acid analogs, Spiegelmers, aptamers, ribozymes, polypeptides, peptides and / or proteins. The bound molecules can then be analyzed or are available for further reactions. The ultraphobic surfaces can be cleaned and reused after each application.
  • the hydrophilic and / or oleophilic region is at least one substrate to which at least one molecule, preferably a biomolecule and / or biological material, can be bound reversibly or irreversibly, covalently.
  • substrates are polyacrylamide, polyethylene glycol, polyvinyl alcohol, agarose, nylon, nitrocellulose and / or methyl cellulose.
  • the substrate preferably has a three-dimensional, preferably porous structure, the pore size of which is preferably 1-100 nm, particularly preferably 1-20 nm and very particularly preferably 1-10 nm.
  • Other examples of such substrates are inorganic compounds. Any substances can be bound to these substrates.
  • biomolecule chips can also be referred to as biomolecule arrays, on which preferably several different biomolecules and / or biological materials, but preferably of the same genus, are immobilized.
  • biomolecule chips are also an object of the present invention.
  • Preferred biomolecules are DNA, RNA, peptides and / or proteins. These biomolecules can be used, for example, to produce so-called DNA or protein chips, on which many different DNA or protein molecules are bound in the form of a defined grid. The molecules immobilized on these chips are then incubated with a sample solution.
  • the hydrophilic and / or oleophilic region is a biomolecule or biological material, which is preferably applied to the ultraphobic surface in a dissolved and / or suspended manner and in which the solvent or the liquid phase is then evaporated.
  • the solvent or liquid phase must wet the ultraphobic surface.
  • biomolecules or immobilized biological materials immobilized in this way are then available, for example, for further biochemical or biological experiments.
  • biomolecule chips can also be made available as biomolecule arrays, on which preferably several different biomolecules, but preferably of the same genus, are immobilized.
  • the biomolecule chips are also a subject of present invention.
  • biomolecules are DNA, RNA, peptides and / or proteins. These biomolecules can be used, for example, to produce so-called DNA or protein chips, on which many different DNA or protein molecules are bound in the form of a defined grid. The biomolecules immobilized on these chips are then incubated with a sample solution. In the case of DNA-DNA, DNA-RNA or RNA-RNA interactions, this process is also referred to as hybridization. If proteins are immobilized, protein-protein, protein-DNA, protein-RNA interactions or the interaction of the immobilized proteins with pharmacological active substances are of particular interest.
  • both the immobilization of the biomolecules and their further use take place on an ultraphobic surface, so that contamination of the biomolecules with substances which are stored on the ultraphobic surface is almost impossible and background signals are significantly reduced in the analysis.
  • the biomolecules adhere directly to the ultraphobic surface without any further substance, so that the production of these flat structures is particularly simple and inexpensive.
  • the ultraphobic surfaces can be cleaned and reused after each application.
  • the flat structures according to the invention are suitable for the analysis of any liquid, as are known, for example, from active ingredient research or in biotechnology.
  • the fabric according to the invention is particularly suitable for expression, mass spectrometric and / or optical analysis of biomolecules and / or biological materials, in particular nucleic acids, nucleic acid analogs, Spiegelmers, aptamers, ribozymes, polypeptides, proteins and / or peptides. These uses are also the subject of the present invention.
  • hydrophilic and / or oleophilic region can also be a peptide nucleic acid which is hybridized with DNA single strands.
  • Another object of the present invention is a method for producing the fabric according to the invention, in which a functional substance, which is dissolved and / or suspended in a solvent which wets the ultraphobic surface, is preferably metered dropwise onto the ultraphobic surface and the liquid Phase or the solvent is then evaporated.
  • the method according to the invention is simple and inexpensive to carry out.
  • the functional substance which simultaneously represents hydrophilic and / or oleophilic areas, can be removed again after each use and the ultraphobic surface can be reused.
  • the ultraphobic surface Preferably, several different substances are dosed onto the ultraphobic surface, so that so-called arrays can be produced.
  • the functional substances are preferably MALDI matrices, affinity matrices, biomolecules, in particular DNAs, proteins and / or binding molecules.
  • the method according to the invention can accordingly be used to produce DNA or protein chips.
  • the ultraphobic surface is designed as a disposable article.
  • a multilayer sheet with a first layer with an ultraphobic surface and a carrier layer is particularly suitable for this embodiment, the first layer being reversibly applied to the carrier layer and the maximum local deviation of the flat structure from the flatness is 100 ⁇ m, particularly preferably ⁇ 20 ⁇ m.
  • This flat structure has the advantage that the first layer with the ultraphobic surface can be detached from the carrier layer after one or more uses and can be replaced by a new first layer, so that it is impossible for this first layer to have been contaminated by previous previous experiments is.
  • the first layer with the ultraphobic surface is particularly cheap to produce as a disposable item.
  • the flatness defined according to the invention ensures that the flat structure can be used in all common mass spectrometric and / or optical analysis devices.
  • the first layer is glued to the carrier layer.
  • the preferred sheet can be used in a variety of ways, but is preferably suitable for mass spectroscopic and / or optical analyzes.
  • a roll-polished AIMg3 sheet with an area of 26 ⁇ 76 mm 2 and a thickness of 0.15 mm was then degreased at room temperature with chloroform (pa) for 20 seconds (s) in aqueous NaOH (5 g / l) at 50 ° C.
  • the mixture was then pre-pickled in H 3 PO 4 (100 g / l) for 20 s, in distilled water for 30 s.
  • the sheet treated in this way was coated with an approximately 40 nm thick gold layer by sputtering in a high vacuum. Finally, the sample was coated for 24 hours by immersion in a solution of the thiol CF 3 - (CF 2 ) 7- (CH 2 ) 2 -SH in benzotrifluoride (pa, 1 g / l) at room temperature in a closed vessel with a monolayer, then rinsed with benzotrifluoride (pa) and dried.
  • the surface has a static contact angle of 178 ° C for water. If the surface inclines by ⁇ 2 ° C, a water droplet with a volume of 10 ⁇ l rolls off.
  • a sample carrier with a surface according to Example 1 is used.
  • Various aliquots of MALDI matrices e.g. 3-hydroxypicolinic acid, sinapic acid and ⁇ -cyano-4-hydroxycinnamic acid, were dissolved in acetone, acetonitrile or a mixture of water and one of the organic solvents mentioned, using a piezo dispensing station on the unpurified, ultraphobic surface of this sample holder the solvent content should be at least 50% by volume. After the solvent has evaporated rapidly, all of the matrices tested are deposited in the form of small crystals as hydrophilic areas on the ultraphobic surface and adhere to them so firmly that they could not be removed with a wipe or compressed air.
  • the locations covered with matrices each had a diameter of 200-1000 ⁇ m.
  • the matrices are hydrophilic in the sense of the invention; ie they have two functionalities.
  • 0.5-2.0 ⁇ l of different samples, which had biomolecules, were metered into the locations occupied by matrices.
  • the samples contained, for example, peptides or proteins dissolved in 0.1% TFA water or oligonucleotides dissolved in water, the biomolecule content in each case being 0.1-1 pmol per ⁇ l.
  • the samples were applied to the matrices with a hand pipette and evaporated at room temperature and then analyzed in a MALDI-TOF mass spectrometer MTP Autoflex from Bruker Daltonik GmbH, 28359 Bremen in linear or reflector mode. In all cases, high quality reproducible mass spectra were recorded, although the ultraphobic surface was not cleaned before the respective application. This is particularly important for the analysis of nucleic acids that are falsified by the slightest contamination, for example by Na or K salts on the sample carriers.
  • FIG. 1 shows the flat structure 101 that consists of a first layer 201 with an ultraphobic surface 301 and a carrier layer 401.
  • the first layer 201 is fixed on the carrier layer by means of an adhesive layer 501.
  • the adhesive layer 501 need not necessarily be present.
  • the adhesive layer 501 consists of an electrically conductive material, so that there is an electrical contact between the first layer 201 and the carrier material.

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Abstract

L'invention concerne une structure plane à surface ultraphobe et au moins une zone hydrophile et/ou oléophile, cette dernière présentant, en plus de l'hydrophilie et/ou de l'oléophilie, une fonctionnalité supplémentaire. L'invention concerne également un procédé de production de ladite structure plane ainsi que son utilisation.
EP03742575A 2002-02-22 2003-02-24 Porte echantillon ultraphobe a zones fonctionnelles hydrophiles et/ou oleophiles Withdrawn EP1478456A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE10207616 2002-02-22
DE10207616A DE10207616A1 (de) 2002-02-22 2002-02-22 Ultraphober Probenträger mit funktionalen hydrophilen und/oder oleophilen Bereichen
DE2002155276 DE10255276A1 (de) 2002-11-26 2002-11-26 Flächengebilde mit einer ultraphoben Oberfläche als Einmalartikel
DE10255276 2002-11-26
PCT/EP2003/001860 WO2003070364A1 (fr) 2002-02-22 2003-02-24 Porte echantillon ultraphobe a zones fonctionnelles hydrophiles et/ou oleophiles

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DE10340429A1 (de) * 2003-09-02 2005-04-07 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Hydrophober Gegenstand mit Raster hydrophiler Bereiche, dessen Herstellung und Verwendung
EP2087504A2 (fr) * 2006-11-23 2009-08-12 Philips Intellectual Property & Standards GmbH Dispositif pour la separation et l'analyse maldi par desorption / ionisation par impact laser assistee par matrice d'un analyte dans un echantillon
DE102008059506A1 (de) 2008-11-28 2010-06-10 Qiagen Gmbh Trägerplatte zum Einsatz als Träger einer Zellsuspension bei der Elektroporation und Verfahren zur Elektroporation mit einer derartigen Trägerplatte
DE102015003440A1 (de) * 2015-03-16 2016-09-22 Friedrich-Schiller-Universität Jena Verfahren zur MALDI-MSI Analytik von Objekten, insbesondere biologischen Gewebeproben, und Target zur Analytik sowie dessen Herstellung
CN109917060B (zh) * 2019-02-28 2022-02-01 云南中烟工业有限责任公司 一种利用示踪剂-顶空气相色谱法测定纸张疏油度的方法

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