EP1490175A2 - Microarray device - Google Patents

Microarray device

Info

Publication number
EP1490175A2
EP1490175A2 EP20020795070 EP02795070A EP1490175A2 EP 1490175 A2 EP1490175 A2 EP 1490175A2 EP 20020795070 EP20020795070 EP 20020795070 EP 02795070 A EP02795070 A EP 02795070A EP 1490175 A2 EP1490175 A2 EP 1490175A2
Authority
EP
European Patent Office
Prior art keywords
zones
membrane
microarray device
porous
microns
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Withdrawn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
EP20020795070
Other languages
German (de)
French (fr)
Inventor
Stefan FISCHER-FRÜHHOLZ
Eric Jallerat
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.)
Sartorius AG
Original Assignee
Sartorius AG
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 to DE10160605 priority Critical
Priority to DE10160605 priority
Priority to DE10206152 priority
Priority to DE2002106152 priority patent/DE10206152A1/en
Priority to DE10224568 priority
Priority to DE2002124568 priority patent/DE10224568A1/en
Application filed by Sartorius AG filed Critical Sartorius AG
Priority to PCT/EP2002/013109 priority patent/WO2003049851A2/en
Publication of EP1490175A2 publication Critical patent/EP1490175A2/en
Application status is Withdrawn legal-status Critical

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D67/00Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0081After-treatment of organic or inorganic membranes
    • B01D67/0083Thermal after-treatment
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis, ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14Ultrafiltration; Microfiltration
    • B01D61/18Apparatus therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D65/00Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
    • B01D65/003Membrane bonding or sealing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D67/00Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0081After-treatment of organic or inorganic membranes
    • B01D67/0086Mechanical after-treatment
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D69/00Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5088Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00Nanotechnology for materials or surface science, e.g. nanocomposites
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D2325/00Details relating to properties of membranes
    • B01D2325/08Patterned membranes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00279Features relating to reactor vessels
    • B01J2219/00306Reactor vessels in a multiple arrangement
    • B01J2219/00313Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315Microtiter plates
    • B01J2219/00317Microwell devices, i.e. having large numbers of wells
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00659Two-dimensional arrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00677Ex-situ synthesis followed by deposition on the substrate
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0819Microarrays; Biochips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406Moving fluids with specific forces or mechanical means specific forces capillary forces
    • CCHEMISTRY; METALLURGY
    • C40COMBINATORIAL TECHNOLOGY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES, IN SILICO LIBRARIES
    • C40B60/00Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Abstract

The invention relates to a microarray device based on a porous material, preferably on a microporous, polymeric membrane having a multitude of porous regions (zones), which are arranged with a high density according to a predetermined pattern and which can be individually controlled, whereby an exchange of material between the porous regions is possible or not possible according to requirements.

Description

Microarray device

The invention relates to a microarray device. More specifically, the invention relates to a microarray device on the basis of a porous material, for example a microporous polymeric membrane, comprising a plurality of arranged in a predetermined pattern in a high density porous or micro-porous areas (zones), which can be controlled individually, wherein is not possible between the porous or micro-porous regions, depending on the requirements a substance exchange or possible.

Microarrays are an excellent tool to test a large number of different molecules against an unknown substance.

A microarray is generally composed of a small, specific area, which is already divided from the beginning into numerous smaller areas still in the range 1,000 to 100,000 of these areas per cm 2 and can be divided later. This approximately 1 000 to around 100 000 or smaller areas (zones), which are specific points on the 1 cm 2 large microarray can be individually and independently driven from one another or approached. In normal use, this means that a small amount of liquid, which may contain one or more reagents may be deposited or applied on each of these specific points. The reagent or reagents in each of the small amounts of liquid may or may all be different and it should take place under normal circumstances, no material or information exchange from one point to another. Thus, each point can have a bound on its surface specific reagent. A reaction can then be performed on the entire microarray. This reaction can lead to the surfaces of the individual points to different results on these points, and the results thus generated or signals from each point independently of one another are submitted because of the different reagents. The microarrays currently in use are made based on glass or silicon dioxide. For example, such DNA arrays (or biochips) prepared such nucleic acid arrays, that the nucleic acid oligomers, such as DNA oligomers and RNA oligomers, either photochemically (Affymetrix) are positioned on a solid phase matrix or arranged mechanically. The placement in micro quantities on the target takes place for example by means of contact printers, such as type printer or dot matrix printer or an inkjet printer working piezoelectric or in Solenoidtechnik. The target may for example be a glass substrate. Typical currently applied or deposited substances are nucleic acids (such as oligonucleotides, so-called ESTs, ie Expressed Sequence Tags, cDNAs), proteins or peptides, cells or cell fragments, tissue, etc., that nearly all types of biological molecules or cells, but it can other chemicals, eg for test methods for environmental protection, are deposited. Analyzes using microarrays are described in Ross et al. (2000) Nature Genet. 24, 227-235, and Weinstein et al. (1997) Science 275, 343-349 described. In these studies were ESTs (expressed sequence tags), ie short cDNA portions applied to the identification of cDNA libraries or genomic sequence tags for the characterization of complex genes or gene homolog of species other than arrays. The next step is the application of mRNA samples from a cell line or from a cancer cell sample was carried out. Generally mRNA fragments can be compared on a large scale with this method. In addition, many samples can be analyzed simultaneously. In physical deposition or deposition of the target or target molecules on the substrate, it is important that the substances (target molecules or target) are formed as individual dots on the substrate. This is typically accomplished by selecting an appropriate distance between the separated points on the surface. the surface tension and the nature of the deposited or deposited solution are essential for the size of the spot on the surface. If the surface tension of the substrate is low, and hydrophilic, a lot spreads even to solution of 1 nl to a point with a diameter of more than 200 microns in. Therefore, in order to prevent the formation of large dots and a micro-array to obtain a high density, the surface is optimized in such a way, for example by silanization, that it has hydrophobic properties. In particular, oligonucleotides are deposited on silanized glass to produce microarrays with high density. In the below-mentioned FIG. 1, a deposited droplet on a hydrophobic surface is shown by way of example, of a point with a diameter that may be less than 100 microns after drying. In the below-mentioned Fig. 2 is schematically shown that a drop of solution which is deposited onto a hydrophilic surface can result in a dried spot with a diameter of much greater than 200 microns. Upon drying, the sample containing the reagent at the outer edge of the point gathers. This results later when greater amounts of a further substance to be deposited on this point, to a sensitivity problem, as the reagent of the sample is hardly practically only at the edge of the point, but not, or in the middle of the point. Because of this density or concentration problem, it typically selects a silanized glass as a target for nucleic acid microarrays, such as DNA microarrays.

However, it is with conventional microarrays, if at all, very difficult to deposit a higher concentration of a reagent with the aid of the deposited solution droplets so on a point of the microarray that the reagent is uniformly distributed over the entire point and without a between the solution droplets occurs mass transport or converge the droplets at least partially. For this reason, porous membranes are inter alia Although used as the material for the microarray surface, however, it is hereby not possible in practice to provide microarrays having a droplet or spot distance of less than 200 microns, as porous membranes have the property of absorbing liquids, so that does not have a close and areal differentiation could be achieved. As a result, it has been impossible to create a grid pattern designed interface as it is possible, for example, with glass as a substrate to deposit a reagent-containing droplets on a very small surface. Further, the amount of the deposited amount of reagent is very limited so far.

It is therefore an object of the present invention to provide a microarray device, which are arranged a plurality of a predetermined pattern, comprising individually controllable points, the points may receive a very high concentration of a desired substance, and wherein a fabric or information exchange or does not occur between the individual points, if desired, the possibility of exchanges may be provided between individual points.

This object is solved by the features characterized in the claims object. The invention is based on the finding that a microarray device to those listed in the task characteristics can thereby be provided that a porous material, for example a microporous polymeric membrane, is treated in such a manner that the pore structure of the porous material at predetermined locations, for example, a predetermined raster pattern is changed from intersecting lines so that no more pores between the non-treated areas (zones) of the porous material exist or if desired, the porosity of the treated, predetermined locations with respect to the non-treated areas to a desired level is decreased.

The porous material may be self-supporting or deposited on a support. It may also be formed on a support by, for example, a polymer casting or- on a plastic film sheet or on an inorganic support such as a glass or ceramic plate coated and then a porous membrane from the casting solution in a known manner, for example with the aid of the evaporation method or the Fällbadverfahrens is prepared. A self-supporting porous material is as an example of an asymmetric polymeric membrane mentioned, which has a pore structure in which pores of a surface extending through the membrane to the other surface, from which reduces the diameter of the pores have a surface to the opposite surface, so that only pores with a substantially smaller diameter or even more, no pores are present on the opposite surface. In the latter case, the microarray device of the present invention can be prepared so that the only up to a certain depth is present in the membrane pore structure is changed at the predetermined positions such that no connecting channels between the non-treated areas exist more or at least the porosity is reduced to the desired level. Here, the nonvoided part of the membrane acts practically as a support for the formed separate porous regions (zones). In a membrane with continuous pores existing on the opposite side pores with a smaller diameter to a desired depth are to be sealed in a suitable manner. The treatment of the porous material to change the pore structure at the predetermined positions can be performed in different ways, eg by the application of fine cut lines, by milling, engraving, punching, by destroying the pore structure by applying embossing or pressure etc. In order to form very fine and exact structures, the application of a laser is particularly suitable. With the aid of a laser beam finest non-porous lines and areas may be generated (in the case of both thermoplastic and non-fusible material) in the porous material by melting (in the case of thermoplastic materials), or burning off. Thereby can be baked in the porous material as a predetermined pattern, that the pore structure is destroyed in the decisions taken by the laser beam areas, wherein a said predetermined pattern corresponding, non-porous, flatter line structure is formed or a structure in which the respective positions not originally porous material is no longer present. So that it can be, for example, in a "non-porous" area is an area from which the original porous material has been completely removed. Such a condition is for example, achieved when a porous material is applied on a support and then the porous material at the predetermined positions complete, that is down to the underlying substrate is removed so that entirely separate regions of porous material on the carrier remain.

Preferably, the porous material for producing the inventive micro-array devices to a microporous material, preferably a microporous membrane based on polymers.

In the present invention, an apparatus is under the term "microarray device" means having per 1 cm 2 surface about 5 to about 1,000,000, preferably from about 20 to about 100 000. porous zones from each other, are separated by non-porous regions or areas of reduced porosity.

Further, a material or a membrane, the term "microporous material" or "microporous membrane" means that the pores and having a mean diameter of about 0.001 to about 100 microns, preferably from about 0.01 having up to about 30 microns.

The separation of the porous or microporous structures offers the possibility of selective activation of porous or microporous portions. Furthermore, microarrays of the invention can also be used as storage locations for sample libraries due to the large surface. Further, the porous structures can be used as a template for microarrays on unstructured membranes.

The invention is described below with reference to the figures and the example in more detail. In the drawings: Fig. 1: deposited drops of a solution on a hydrophobic substrate Fig. 2: deposited drops of a solution on a hydrophilic substrate Fig. 3: Example of a surface of a microarray device of the invention with a stoved, for example, by a laser raster-line structure (top view and side view)

Fig. 4: schematic three-dimensional view of individual, obtained by, for example, burning with a laser columnar points on the surface of the microarray device of the invention FIG. 5: schematic representation of the control of individual points on the surface of the microarray device of the invention with a reagent-containing solution droplets Fig . 6: exemplary dimensions of an obtained for example by burning with a laser of a microporous membrane of which the surface of the microarray device of the invention

FIG. 7: Example of a configuration and arrangement of dots in the

Surface of the microarray device according to the invention Fig. 8: example of the application of a test sample to the points of a microarray device according to the invention.

The micro-array devices according to the invention have a number of zones with a located thereon porous or microporous structure, which are separated from each other by the produced, for example, with the laser line pattern. The zones may thereby have any desired geometric shape, such as square, rectangular, round, oval, triangular, etc., where more than one geometric form on the microarray may be present one. Thereby, it becomes possible to realize any desired arrangement of zones on the microarray, for example, an arrangement as shown in Figs. 7 and 8 of triangular faces 1, 2 and 3 in close proximity to an application as shown in Fig. 8 a test sample permitted to each other in close proximity to nearby peaks of the triangular faces. Normally, the zones are separated by, for example, the laser treatment of the microporous membrane from each other so that no material or the exchange of information (so-called cross talk) occurs between them. It can also be effected by appropriate control of the laser beam, however, that zones are not completely separated, but a limited mass transfer between pores remaining that have not been eliminated by melting or burning-off of the membrane material, can take place.

The formation of the non-porous regions or regions with reduced porosity, the porous zones are separated from each other by means can be done in various ways and is not particularly limited. Rather, it is particularly dependent on the type and dimensions of the desired non-porous regions or areas of reduced porosity and on the type of porous material used.

The non-porous regions or areas of reduced porosity can be generated mechanically, for example by attaching cutting lines, by milling, engraving, stamping, by compression, optionally at elevated temperature, by punching etc.. However, the porous material can be changed also by physical means, for example by melting the material at the predetermined positions, or chemically, for example by etching or by selective chemical reaction, optionally by the addition of substances which can react with the matrix material as, that no pores remain or the porosity is reduced.

In particular for producing fine and complex structures, the application of laser technology has proven to be advantageous.

The micro-array devices according to the invention have a porous or microporous surface by appropriate treatment, for example by a laser treatment in tiny, three-dimensional, porous or microporous

Zones was divided. A microporous membrane z. B. has a very large ratio between inner and outer surface. A typical used in the microfiltration membrane has an inner surface, ie, a surface of the walls of the pores of about 100 to 400 cm 2, based on one square centimeter outer surface of the membrane. This means that a membrane in comparison with a smooth surface (for example, a glass substrate, a plastic film or a silica surface) can bind a multiple of specific reagent on its surface. Thus, much higher concentrations of specific reagents or greater amounts of for example peptide, protein or DNA may be provided per unit surface area of ​​the microarray according to the invention, wherein the reagent is also uniformly distributed over the entire microporous structure, and thus at any point of the zone for reaction Available.

The inventive micro-array devices and such can now be provided that have a number of chemically different surfaces, such as surfaces with ion-exchange groups or functional groups, such as basic and / or acidic groups having a specific adsorption or formation of covalent bonds to a variety of biomolecules allow. Due to the preferably microporous structure of the regions of the microarray devices according to the invention this one substance to be deposited readily absorb without hydrophilic groups to be introduced into the target. It also ensures that no cross-talk occurs between the zones, even if the zones are arranged in high density on the microarray.

Since larger quantities of devices can be deposited on the substance on the microarray according to the invention, the detection is with, for example CCD-camera systems (charged coupled device camera-system) facilitated. Due to the increased concentration of the target substance, which results from the larger amount recordable, to obtain a better signal to noise ratio between the signal and the background and the signal and the noise. By means of a precise control of the laser beam or with a photographic mask any desired pattern can be etched into the membrane, for example a shown in Fig. 3 regular pattern of squares or rectangles. Thus can be realized even the most complicated structures and patterns in one step on the surface of the microarray.

It is possible to proceed so here is that initially the predetermined pattern with the laser is fired into the microporous membrane, and then the substance (s) is deposited on the individual zones or deposited or to be. but it can also work in reverse order, or the burning of the pattern and the deposition of the substances take place simultaneously or in parallel operation.

The inventive micro-array devices microporous zones can be realized, the liquid sample can record in the nanoliter to microliter range, said microporous zones with a base in the micrometer range, for example a square base of 80 microns page length can be produced. The distance between the zones may in this case be even lower, for example 40 microns. When using, for example, microporous membranes having a thickness ranging from 10 microns to 500 microns, corresponding thicknesses of the zones can be obtained after the laser treatment, the surface area should naturally result in reasonable proportion to the thickness of the zones. Thus, in the microporous membranes have a minimum side length of the zones is accepted by about one-third of the membrane thickness. In a square base of 80 microns side length of the zone has a thickness of 140 microns readily be realized for example, as shown in Fig. 6. Unless the microarray device of the invention comprises a support, the thickness of the overall device, consisting of the porous or micro-porous material and the support, in the range of 100 microns to 4 mm, preferably from 200 microns to 3 mm, and more preferably 300 microns to 2 mm. As porous or microporous membranes which can be used for the preparation of the microarray device of the present invention, in principle all polymers, porous or microporous membranes in question, for example, membranes based on polyamides (such as nylon), polyvinylidene fluoride (PVDF), polyethersulfones (PES), polysulfones (PS), polycarbonates, polypropylene (PP), cellulose acetate, cellulose nitrate, regenerated cellulose with chemically modified surface, etc., or mixtures thereof, said membranes are preferably based on cellulose acetate, cellulose nitrate or regenerated cellulose having chemically modified surfaces.

As examples of the above chemically modified membranes regenierte cellulose membranes may be mentioned, in the specific functional groups such as aldehyde, epoxy, sulfonic acid, carboxylic acid, quaternary ammonium and / or Diethylammoniumgruppen be introduced. Because of the functional groups and the ionic charges introduced peptides, proteins or nucleic acids, including DNA, reversibly or covalently (eg, aldehyde and epoxy-modified membranes) are bound. By a further pre-activation also selective partial reactive groups can be produced by, for example, a regenerated cellulose membrane after patterning by oxidative agents (eg I 2) is oxidized to the corresponding aldehyde.

The microarray devices of the invention may for example be prepared as follows.

A prefabricated microporous membrane is used either as such or laminated on an inorganic or organic carrier. The organic supports all polymeric films can be used in principle. Preferably the carrier is formed as a plate, in particular made of PVC. Thereafter, the predetermined desired pattern of lines or areas in the microporous membrane is baked, for example, with a laser. The intensity of the laser beam can be adjusted so that the laser beam, the microporous structure of the membrane completely destroyed to those adopted by the laser beam points, whereby only hydrophobic blackened webs remain down to the molecular level, which prevent any liquid transport between the resulting zones. However, the intensity of the laser beam and / or the irradiation time can be adjusted such that the microporous structure of the membrane is only up to a certain depth destroyed, so that a compound of the zones formed is still maintained in a predetermined, limited fashion for a material transport.

The invention is further illustrated by the following example.

example

A microporous membrane (nitrocellulose, pore size 0.2 micron) with a thickness of about 140 microns is laminated to a carrier film (PVC). Subsequently, using a laser (Nd YAG), a predetermined pattern (array) of square dots having a side length of 80 microns so stoved that arise lines having a width of 40 microns between dots. The microarray device obtained has about 6900 from each other completely separate square microporous points (subzones) on a floor area of about 6400 microns respectively 2 and a thickness of about 140 microns.

Claims

claims
1. microarray device comprising zones of a porous material, which are arranged in a predetermined pattern, the zones being separated by non-porous regions or areas of reduced porosity.
2. The microarray device of claim 1, wherein the areas of porous material are coated on a support.
3. The microarray device of claim 2, wherein the support is a plastic film, a plastic film or a plastic plate.
4. microarray device according to any one of claims 1 to 3, wherein the zones are formed from a microporous material.
5. microarray device according to one or more of claims 1 to 4, wherein the zones are formed from a membrane.
6. The microarray device of claim 5, wherein the membrane is a microporous membrane.
7. microarray device according to 6, wherein the microporous membrane is a microporous polymer membrane.
8. The microarray device of claim 7, wherein the membrane on the basis of polyamides, polyvinylidene fluoride, polyether sulfones, polysulfones,
Polycarbonates, polypropylene, cellulose acetate, cellulose nitrate or regenerated cellulose having chemically modified surface is formed, or mixtures thereof.
9. microarray device according to one or more of claims 1 to
8, wherein the porous regions have a side length in the range of about 40 microns to about 100 microns.
10. microarray device according to one or more of claims 1 to
9, wherein the porous regions have a spacing of about 20 microns to about 60 microns of each other.
11. microarray device according to one or more of claims 1 to
10, wherein said porous zones are separated by non-porous regions.
12. microarray device according to one or more of claims 1 to 11, wherein the microarray device has a thickness of about 10 microns to about 500 microns.
13. microarray device according to one or more of claims 2 to 12, wherein the carrier is formed as a plate, preferably of PVC.
14. A process for the preparation of a microarray device, comprising the steps of:
Providing a porous material, and - forming zones in the porous material, which are separated by non-porous regions or areas of reduced porosity.
15. The method of claim 14, wherein the porous material before or after forming the zones by non-porous regions, or
Regions are separated from each other with reduced porosity, is applied to a carrier.
16. The method of claim 15, wherein the support is a plastic film, a plastic film or a plastic plate.
17. The method according to any one of claims 14 to 16, wherein forming the separate zones is carried out with a laser.
18. The method according to one or more of claims 14 to 17, wherein the porous material is a microporous material.
19. The method according to one or more of claims 14 to 18, wherein the porous material is a membrane.
20. The method according to one or more of claims 14 to 19, wherein the membrane is a microporous membrane.
21. The method of claim 20, wherein the microporous membrane is a microporous polymer membrane.
22. The method of claim 21, wherein the microporous polymer membrane was produced by coating a polymeric casting solution onto a support and forming the membrane from the casting solution in the evaporation method or quenching method.
23. The method of claim 22, wherein the microporous membrane on the basis of polyamides, polyvinylidene fluoride, polyether sulfones, polysulfones, polycarbonates, polypropylene, cellulose acetate, cellulose nitrate or regenerated cellulose having chemically modified surface was formed, or mixtures thereof.
24. The method according to one or more of claims 14 to 23, wherein the zones are formed in the porous material so that they have a side length in the range from about 40 microns to about 100 microns.
25. The method according to one or more of claims 14 to 24, wherein the non-porous regions or areas of reduced porosity are formed such that the zones are separated from each other in the porous material, that the distance is in the range of about 20 microns to about 60 microns.
26. The method according to one or more of claims 14 to 25, wherein the formation of the zones is carried out in the porous material such that the zones are separated by non-porous regions from each other completely.
EP20020795070 2001-12-10 2002-11-22 Microarray device Withdrawn EP1490175A2 (en)

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DE10160605 2001-12-10
DE10160605 2001-12-10
DE10206152 2002-02-14
DE2002106152 DE10206152A1 (en) 2001-12-10 2002-02-14 A micro-array, for testing a large number of molecules, has porous zones formed by a membrane in a given screen pattern, with points separated from each other to prevent cross contamination
DE2002124568 DE10224568A1 (en) 2001-12-10 2002-06-03 Microarray device
DE10224568 2002-06-03
PCT/EP2002/013109 WO2003049851A2 (en) 2001-12-10 2002-11-22 Microarray device

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WO2003049851A2 (en) 2003-06-19
DE20218984U1 (en) 2003-05-08

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