WO1999059810A2

WO1999059810A2 - Microstructured films

Info

Publication number: WO1999059810A2
Application number: PCT/EP1999/002971
Authority: WO
Inventors: Frank Krause; Heinz Linder; Franz Schmitt; Georg Wiessmeier; Hansjörg Dürr; Karsten Dierksen; Simone Greven; Klaus Heidenreich; Peter Jähn; Jürgen Klein
Original assignee: Bayer Aktiengesellschaft
Priority date: 1998-05-14
Filing date: 1999-05-03
Publication date: 1999-11-25
Also published as: AU4035899A; EP1079928A2; WO1999059810A3; DE19821627A1; JP2002515351A

Abstract

The invention relates to a module consisting of polymer materials and containing chosen microchannel systems, and to a method for producing a module of this type. The inventive model with microchannels consists of a polymer film (2) whose thickness corresponds to the desired channel depth, with recesses (1) in the shape of the desired microchannel structure. An upper (4) and a lower (3) cover layer provide a seal for this microstructured film on both sides. The cover layers are planar on the side facing towards the structured film and form the top and bottom surfaces of the channels. At least one of the two cover layers has at least two entrances (5) to the microchannel system in the microstructured film. The inventive method for producing a module consisting of polymer materials and containing microchannel systems comprises the structuring of one or several films with the microchannels and connecting one film with the two cover layers in order to seal the microchannels.

Description

Microstructured foils

The invention relates to a module made of polymer materials which contains any microchannel systems and a method for producing such a module.

A microchannel is a channel that has dimensions of less than 1 mm in one or two spatial directions (width and depth) (micrometer range). In another spatial direction (length) it has a dimension that corresponds to a multiple of the dimension in the spatial direction with the smallest dimension. Several interconnected microchannels form a microchannel system. A module is a carrier that contains one or more microchannel systems that can be filled and emptied through access and, if necessary, other elements such as Contains membranes.

Modules with micro-channel systems are used in a variety of technical areas. They are used as mixers, heat exchangers, reactors, microsensors in process equipment and as miniaturized analysis systems, e.g. used in molecular diagnostics. The miniaturization of assemblies is advantageous because processes can run very quickly due to the small distances in the microchannel systems. In addition, the large ratio of surface to volume promotes efficient heat exchange and enables targeted, fast temperature control. Due to their small size, a large number of modules with microchannel systems can be used in parallel and lead to a high throughput. In microchannels, the mass transport through the channels can be controlled in a targeted manner by means of electrical voltages which are applied to the channels.

An excess charge of the substances in the channels and / or the endoosmotic effect, which is caused by the migration of surface charges, is used. The economical use of reagents and eluents in microchannel systems is an advantage for applications in the diagnostic area.

Various methods have hitherto been proposed for structuring polymer materials with microchannels, all of which are based on the fact that a Micro structure, which forms the underside and the channel walls, is incorporated as a depth profile. The channel is then closed on the open side by a planar cover layer, which contains the accesses to the underlying micro-channel system.

In the silicone casting process, the desired channel structure made of silicone is created by the

Pouring out a corresponding mold (C.S. Effenhauser et al., 2nd International Symposium on Miniaturized Total Analysis Systems mTAS '96, Analytical Methods and Instrumentation, Basel 1996). Disadvantages here are the complex production of the casting template and the complicated adjustment of the pressure of the planar cover layer to those that have not been sealed into the silicone

Channels. The pressure must be set so that the channels in the silicone are sealed on the one hand and not closed on the other.

In another manufacturing process using micro-injection molding technology, an original matrix is produced in a silicon substrate. Nickel molds are molded from this, in which the acrylic substrates with the microchannels are produced by injection molding (R.M. McCormick et al., Anal. Chem. 1997, 69, 2626-2630). The disadvantage of this method is that two generations of matrices have to be manufactured before the actual structure can be manufactured. This is very complex and severely limits the flexibility in designing the structures

(Ch. Ziegmann, "Injection Molding of Microstructured Components", 19th IKV Colloquium Aachen 1998).

Furthermore, the manufacture of microstructures by laser ablation of polymeric or ceramic substrates e.g. proposed with an excimer laser

(U.S. Patent 5,500,071). However, laser ablation is not suitable for large quantities because of the large amount of time it takes.

Photolithography and wet-chemical etching processes are known from semiconductor technology for the production of microstructures. But you will only be on

Silicon, quartz, glass (S.C. Terry et al., IEEE Trans. Electron. Devices, ED-26, 1979,

1880; A. Manz et al, J. Chromatogr. 593, 1992, 253-258) and other semiconductor materials applied. Because of the large adsorption on their surface, these materials are at least unsuitable for biological applications. In addition, this type of manufacture of microstructures is too complex for the mass production of single-use modules.

Microstructured stack structures are preferably produced from metallic materials as highly efficient heat exchangers. The structures are either machined or formed using chemical etching processes (US Pat. No. 4,516,632). The individual microchannels are not used as individual process units, but as integral parts of a macroscopic module. The

Microchannels primarily serve to enlarge the surface (B. Sunden et al. Adv. Eng. Heat Transf., Proc. Balt. Heat Transf. Conf., 1995).

The requirements for a module with microchannels are varied and vary depending on the area of application. The general rule is that the channels in the modules should be 10-100 μm deep and 10 μm to 5 mm wide. They can be of any length.

The channels must continue to be connected to sample, reagent and buffer reservoirs in order to fill and empty them.

The channel structures must be able to be sealed and they must ensure efficient heat supply and heat dissipation. Efficient heat dissipation is particularly necessary to dissipate the Joule heat that arises when electrical voltages are applied to the microchannels and electrical currents flow.

For many applications, it is desirable to insert separation membranes into the channel system of the module, for example to carry out a size selection of molecules. For some applications, such as capillary electrophoresis, the channel structures must be electrically insulated so that electrolytic current transport can take place in the channels.

For many applications, especially in the analytical-diagnostic area, the

Microchannels be accessible for optical detection.

For use as a processing apparatus, a micro sensor or micro-analysis system ^• in medical / biological environment good biocompatibility is desired. Biocompatibility means that, for example due to the corresponding surface properties, no proteins accumulate in the channels.

With a view to wide use, the microstructured modules should be able to be produced in large numbers at low cost and should be easy to dispose of.

The module with microchannels according to the invention consists of a polymer film, the thickness of which corresponds to the desired channel depth with cutouts in the form of the desired microchannel structure. An upper and a lower cover layer seal this microstructured film on both sides. The cover layers are planar on the side facing the structured film and form the top and bottom of the channels. At least one of the two cover layers has at least two accesses to at least one microchannel in the microstructured film.

In addition to this simplest structure with a micro-structured film between the two cover layers, the modules can also contain a plurality of micro-structured films stacked one above the other between the two cover layers. The microchannels are then in different planes and have overlap areas seen perpendicular to the film plane. These allow the transition from one level to the next. In this way, arbitrarily linked, three-dimensional channel structures can be built. Crystalline or semi-crystalline plastics are suitable as the polymer material for the films. Transparent plastics such as polycarbonate or polymethyl methacrylate are particularly suitable. Films can also be used which have a strong absorption in certain optical or infrared wavelength ranges. A module can contain foils made of different materials.

Each film can be made up of different layers. The individual layers can perform various functions, such as adhesive function or sealing functions through elastic deformability. Individual layers can also have different absorption spectra. In a film e.g. a non-absorbent core can be framed by absorbent cover layers.

The surface properties of the channels with regard to adsorption or surface potential can be specifically adapted to an application by coating the cover layers forming the channel walls or the films. Possible

Coatings are polyacrylamide, polyvinyl alcohol, oligomeric alkylamines, nonionic detergents such as polyoxyethylene ether and polymeric sugars such as hydroxypropylmethyl cellulose or methyl cellulose.

The depth of the channels corresponds to the film thickness or its multiple if several films of the same structure are stacked on top of one another. Deeper channels allow higher throughput. The microstructured films have a thickness of 10 to 1000 μm, preferably 10 to 100 μm. Film thicknesses of 25 to 75 μm are particularly suitable.

The length of the channels in the microstructured film is preferably 1 mm to 100 mm, particularly preferably 5 to 50 mm. The channel width can at most correspond to the width of the film minus a sealing edge. It is preferably 1 μm to 5 mm and can be constant or vary over the channel length.

The channels can assume any orientation to one another and to limit the film. In addition to channels with a rectangular basic shape, channels with curved sides can be realized. By stacking appropriately structured foils, vertical channels in which the cutouts lie one above the other or diagonal channels in which the cutouts are offset one above the other can also be produced.

The upper and lower cover layers serve to seal the channel structure of the film in between. The cover layers can be formed by foils with a thickness of 50 to 500 μm or by plates with a thickness greater than 500 μm. At least one of the cover layers has at least two accesses to at least one microchannel. Corresponding openings are present in one or both cover layers. The cover layers can be transparent.

Sample, reagent and / or buffer vessels are attached to the outside of at least one cover layer above the accesses to the microchannels below. The channels are filled via the sample, reagent and buffer vessels. Pressure differences or electrical potentials can also be generated via the sample, reagent and buffer vessels in order to effect mass transport in the channels. The sample, reagent and buffer vessels can also be incorporated into the outer surface of the plates as a macro structure when using planar plates.

Membranes can be installed in the module. A membrane that works according to the size exclusion principle (ultrafiltration membrane) is often suitable for the separation of macromolecules, particles, bacteria, cells or viruses. The range of membranes ranges from a molecular weight of 3000 daltons for small proteins or nucleotides, to size exclusion ranges in the lower nm range for large nucleic acids and viruses, to 0.45 μm for cells. The membranes are microstructured polymers, preferably polyether sulfone (PES), polyester, fleece-based acrylic polymer, polytetrafluoroethylene (PTFE), polysulfone, polypropylene (PP), glass fiber, nylon or polycarbonate. In addition, ion exchange membranes and adsorption phases can be used. The choice of Membrane depends on the type of molecule desired and is micro-structure independent.

The membranes can be inserted between a cover layer and a microstructured film and / or between two films. They can also be attached to the outside of the cover layers between the cover layer and the sample, reagent or buffer vessel.

The membranes can be introduced into the module as an additional layer. If the membrane covers the entire surface, its membrane properties only function in the areas through which it flows. However, it can also have membrane properties only at the overlap areas of the channels.

Membranes can also be in the form of pieces which only cover the channel area through which flow occurs at the overlap areas of the channel structures between two foils or in the

Transitional area between the entrances of the cover layer and the underlying channels. Another possibility is that the membranes are located directly in the accesses to the microchannels in the cover layer.

The supply or removal of heat on the module can take place via the cover layers by contact, air or liquid cooling of the cover layers. A particularly intensive heat exchange can be achieved using a film that has many parallel microchannels through which a liquid or gas flow can be conducted for heat exchange.

A method for producing a module from polymer materials with a microchannel system comprises structuring one or more films with the microchannels and connecting the one film with the two cover layers or connecting several stacked films with one another and with the two cover layers so that the microchannels are sealed. The foils can be coated before processing or before assembling the module. Membranes can also be inserted into the module.

The foils can be microstructured by etching, laser ablation or punching.

However, a cutting method according to the invention is advantageous.

The film to be structured is fixed on a dimensionally stable and elastic base.

For cutting, the cutting tool and the holding unit of the film to be cut can be moved against each other in all three spatial directions. In a particularly advantageous embodiment of the cutting process, the film is fastened on a rotatable roller in a pretensioned state.

Depending on the manufacturing process and the tension structure of the material, elastic films are pretensioned parallel to the cutting line or across the cutting line in order to optimize the cutting process. The degree of preload depends on the modulus of elasticity of the film to be cut.

The cutting tool can be fixed or arranged as a rotating circular knife. The circular knife exerts a cutting rolling movement, whereby the film is fixed under the knife and is not deformed. This is advantageous for plastic films with a low modulus of elasticity. A fixed cutting tool is advantageous for cutting exact contours from one material.

A channel can advantageously be cut along its edges with two knives arranged in parallel, the distance between the knives corresponding to the channel width. This procedure provides exact cut surfaces and should be selected in particular if the required channel widths are less than 500 μm or if the cut is not made at a 90 ° angle to the film surface, so that the channel cross section of deviates from the rectangular shape. The parallel cut stabilizes the film to be cut and prevents the film from moving.

Many parallel channels and also the parallel outer boundaries of the foils can be cut at the same time by a large number of parallel knives. The multiple parallel cuts enable rapid structuring of foils with a large number of channels.

If the cover layers are solid plates, they can be produced by injection molding or with other common manufacturing processes for structures made of polymer materials. Sample and buffer vessels can be made in one piece with the cover plate.

The microstructured foils can be connected to one another and to the cover layers to form a module by printing, gluing or welding.

A tight connection by pressure can only be achieved with solid panels as cover layers. The pressure is exerted on the two cover plates from the outside. They are pressed against each other and on the foils in between. This seals the channels of the microstructured foils.

Cover plates show microscopic bumps on the surfaces, which are embossed in the intervening foils and can lead to leakage currents. The use of particularly elastic films such as films made of thermoplastic polyurethane (TPU) or films coated with an adhesive-like leveling compound can prevent the leaks. The elastic film and the leveling compound adapt to the unevenness of the surface and seal it.

The strength of the pressure on the film in between depends on the elastic properties of the film material used. A pressure of 5 to 50%, a particularly advantageous 5 to 25% of the pre-tensioning of the film is favorable O 99/59810. \ Q. PCT / EP99 / 02971

Film thickness causes. The preload is measured by changing the length of the film compared to the untensioned state.

The pressure on the cover plates of the module is maintained by detachable or non-detachable connections. Detachable connections are screws, clips or clamping elements. Inseparable connections are made by riveting or welding the two cover plates on their outer edges. When welding, the one or more foils are passively fixed between the cover plates.

The foils and cover layers can be tightly connected to one another by gluing. The adhesive can be self-curing, thermosetting or photo-curing.

Unreleasable connections are particularly advantageous, which are created by welding the foils and cover layers directly at the edges of the channels. The

There is no problem of leaks due to unevenness in the cover plates. The cover layers do not have to be dimensionally stable. They can also be slides.

There are various methods for welding the foils to one another and to the cover layer.

In hot stamping, the desired area is melted by one-sided heating with direct contact.

In contrast to hot stamping, heating element welding involves thermal contact on both sides.

Infrared beam welding can be carried out on one side or on both sides. For this, at least one of the foils must have an infrared-absorbing layer.

In laser welding, at least one of the foils must have a layer that absorbs the laser light. In radiographic welding, the entire sorbent layer melted. With butt welding, only the surface is melted. Butt welding can be carried out on one side or on both sides.

In ultrasonic welding, the energy density required for welding is generated by ultrasonic waves. In the case of total module thicknesses of up to 1 mm, the use of energy directors can be dispensed with using conventional ultrasonic welding devices, since the amount of energy per material volume is sufficient even without a measure for bundling the energy.

With high-frequency welding, an alternating electric field of high frequency is radiated. Part of the energy of the alternating electrical field is converted into heat in the plastic. The module made of polymer materials is welded when the dielectric loss factor tan δ of the polymer is greater than 0.01, that is to say a sufficiently high proportion of the energy in the field is drawn off and converted into heat.

Laser and infrared welding have proven to be particularly advantageous.

By using a microstructured film that absorbs all or in individual layers and transparent cover layers, the film can be selectively melted and permanently connected to the cover layers.

Several foils stacked on top of one another are also connected to one another in this way. The microchannel structures are not absorbent, so that the energy can be radiated in over a large area and the contour of the channels does not have to be followed exactly. By using differently absorbent foils and successive melting, even complex layer structures can be created

Channel structures are built.

The surfaces of the films that contribute to the formation of a channel structure and also the channel-side surfaces of the cover layer can be coated before cutting or before assembly in order to change surface properties such as biocompatibility and surface potential. Membranes are fixed together with the connection of the foils and cover layers by pressing, gluing or welding. If individual membrane pieces are introduced in the area of an access to a channel between a cover layer and a film or between two films, the membrane must face the direction in which the channel continues with the cover layer or with the film that does not support the channel ^• * 0-ζt ",) can be connected.

The modules according to the invention with microchannels are distinguished on the one hand by the construction from simple standard materials (polymer films). The used

Polymer materials such as polycarbonate or polymethyl methacrylate can be used for a large number of applications because they combine the properties of inertness, biocompatibility, electrical insulation and transparency.

On the other hand, the manufacturing process for the modules according to the invention is simple and flexible. In comparison to the known silicone casting processes and micro injection molding processes, no original molds are produced, which then only result in one embodiment of the microchannel structure. Instead, the foils can be simply structured using the known methods of etching, laser ablation, punching or particularly advantageously using the cutting method according to the invention. At the

Cutting is done with simple cutting tools such as Razors cut any structure.

The connection of the foils to the module, in particular by means of the proposed laser and infrared welding processes, can also be carried out quickly and easily.

The modules according to the invention are therefore suitable for automated mass production and can also be produced inexpensively because of the inexpensive materials. Polymer materials are also easy to dispose of. It is therefore worthwhile to manufacture them as single-use modules for single use. Single-use modules have the advantage, particularly in the medical field, that they do not carry germs and contaminants can come, and their use therefore allows more precise analyzes and increases the safety of staff and patients.

The heat exchange is even more efficient than with conventional systems with microchannels due to the thin walls of the foils.

A module of polymeric materials containing any microchannel system is suitable for many types of applications for microchannel structures. Examples of applications are the chemical laboratory, polymerase chain reaction (PCR), immunodiagnostics, virus analysis and DNA analysis on the chip, implants, dosing devices and analysis with miniaturized total analysis systems or with micro-preparative sample preparation modules for DNA extraction.

The substances in the microchannels can be detected using optical methods. Absorption and fluorescence methods can be used. Because of its high sensitivity, laser-induced fluorescence detection is often used.

Figures and examples

Show it

Fig. 1 layer structure of a module with a microstructured film. Fig. 2 layer structure of a module with several microstructured films.

Fig. 3 Introduction of separation membranes in the layer structure.

Fig. 4 layer structure of a module with vessels on a cover layer.

Fig. 5 arrangement for cutting the films.

Fig. 6 module that is connected by pressure. Fig. 7 Manual cutting apparatus for microstructuring polymer films.

Fig. 8 photocopy of the laser-welded layer structure of a module.

Fig. 9 electrophoretic transport in a microchannel structure.

1 shows a film 2 with a microchannel structure 1. The thickness of the film 2 corresponds to the channel depth. The film 2 is enclosed by the lower cover layer 3 and the upper cover layer 4. The cover layers form the upper and lower channel walls. The cover layer 4 has the accesses 5 to the microchannel structure 1 in the film 2.

2 there are two differently microstructured foils 2a and 2b with the microstructures la and lb between the cover layers 3 and 4. When the foils are stacked, an overlap 11 of the two microchannels la and lb is formed. The accesses 5b 'and 5b to the microchannel 1b in the lower film 2b are in the film 2a and the cover layer 4. The accesses 5a to the microchannel la in the upper film 2a are in the cover layer 4.

Various possibilities for introducing the membranes 6a, 6b and 6c into the layer structure are shown in FIG. 3. The membrane 6b is located above the access 5 above the cover layer 4. The membrane 6a is located between the film 2 and the cover layer 4 in the area of an access 5 to the microchannels 1 the film 2. The membrane 6c forms the passage in the covering layer 4 to the microchannels 1 in the film 2.

4 shows a module consisting of a film 2 with microchannels 1 and the covering layers 3 and 4. On the covering layer 4 above the accesses 5 there are

Sample, reagent and buffer tubes 7.

Fig. 5 shows an arrangement for cutting the films. The film 9 to be structured is located under the cutting knife 8 on the cutting table 10. The film 9 to be structured is preloaded by a force 81.

6 shows a module in which the structured film 13 is fixed between two dimensionally stable cover plates 14 and 15. The pressure by which the microchannels in the film are sealed off by the cover plates is exerted by the screw 12 and / or the rivet 16. A plurality of foils could also be stacked one above the other between the cover plates 14 and 15.

7a shows a cutting apparatus for microstructuring polymer films. FIG. 7b shows a microstructured film as can be produced with a cutting apparatus according to FIG. 7a. The cutting apparatus consists of a rotatable roller 18 for receiving the film, a handwheel with latching positions 19, a pair of cutting knives 20 for cutting the lateral boundary of the microstructure film. The two pairs of cutting blades 21 are used for cutting the longitudinal channels a and b of the microstructure. The punching knife receptacle 22 can hold various punching knives for punching the transverse channel c, for punching the structure borders e and for punching the film borders f.

The guide 23 is used to execute the position bores designated by g.

Figure 8 is a photocopy of a module. In a 100 μm thick, black pigmented

Film 2 made of polycarbonate was cut with the manual cutting apparatus from FIG. 7 microchannels 1, 3 and 4. The structured film was between two O 99/59810 _ ig _ PCT / EP99 / 02971

transparent foils made of polycarbonate of 400 μm thickness and extensively welded around the channel structure with the transparent foils by an infrared laser (dark area). The permanently connected module has intact channel structures.

FIG. 9 a shows how the electrophoretic transport of fluorescence-labeled DNA takes place in the laser-welded layer module from FIG. 8. 9b shows the fluorescence signal at a wavelength of 520 nm, as it is detected in the thin channel on the detector 24. Under the influence of the voltage 25a, the DNA is transported electrokinetically into the wide channel (Fig. 9a- (a)). Then the

Voltage 25b is applied between the wide and narrow channels and the DNA is conducted with the current into the transverse channel (Fig. 9a- (b)). There it moves under the influence of the voltage 25c past the narrow channel electrokinetically past the detector 24 (FIG. 9a (c)). In Fig. 9b, a detector signal only appears in the phase shown in Fig. 9a (c).

example 1

To produce a micro-structured film with a manual cutting apparatus from FIG. 7, a suitable piece of 100 μm thick film is first fixed on the rotatable roller 18 by means of adhesive tape. By folding in the two pairs of cutting knives 21 and turning the handwheel 19, the longitudinal cuts for microchannel a with a width of 2 mm with the corresponding knife spacing of 2 mm and for microchannel b with 100 μm width with the corresponding knife spacing of

Cut 100 μm into the film. The cutting length is limited to 55 mm by two locking positions of the handwheel. By folding in the two cutting knives 20 and turning the handwheel i9, the longitudinal limits of the film are cut with a distance of 20 mm. The cut limitation after 91 mm is also done by two locking positions of the handwheel. The cross-sections are punched after inserting the respective punching knives into the punching knife receptacle 22 by folding the punching knives onto the roller 18 and the film located thereon. In this way, the transverse channel c, the upper and lower limits of the microchannels d and e and the upper and lower limits of the film f are punched. There is a locking position of the handwheel for each punching position. In the same way, the adjustment bores g are produced by means of a punch 23 and two locking positions of the handwheel. The microstructured film thus produced with defined external dimensions contains a narrow channel b of 100 μm in width and 55 mm in length, a wide channel a of 2 mm in width and 55 mm in length and a narrow transverse channel c of 100 μm in width and 4 mm in length. The outer dimensions of the film are 20 mm wide and 91 mm long.

The result of the cutting process is shown in the photocopy for a black polycarbonate film as a photocopy in FIG. 8.

Example 2

A module with an elastic, micro-structured film made of thermoplastic polyurethane (TPU) of 75 μm thickness and a sealing by contact pressure was produced.

The microchannel structure was produced in accordance with Example 1. The elastic

Foil was placed between two polycarbonate sheets and fixed with 19 screws. The machined plates were each 6 mm thick and the upper plate contained 4 holes that each ended at the channel ends in the microstructured film. Small buffer reservoirs were located above these holes. By tightening the screws firmly, the elastic TPU film was pressed together so that it appeared transparent. Tris / borate buffer, which was 0.1 molar and had a pH of 8.5, was filled into the buffer reservoirs and the entire module was deaerated in vacuo. Electrodes were inserted into the buffer reservoirs. The entire module was cooled to 10 ° C using contact cooling with thermostatted metal surfaces. A voltage of 700 V was first applied across the wide channel across the electrodes and a current of 350 μA was measured. When a voltage of 1 kV was applied, a current of O 99/59810 _ _{J g} _ PCT / EP99 / 02971

25 μA measured. The ratio of the measured currents corresponds to the ratio of the channel cross sections of narrow and wide channels. This shows that the electrical line runs exclusively through the buffer-filled channels and the module is otherwise electrically insulating.

Example 3

A module with a black pigmented infrared absorbing microstructured polycarbonate film of 100 μm thickness was produced. The module was sealed by laser welding.

The microchannel structure was produced in the polycarbonate film essentially in accordance with Example 1. The only difference to the method from Example 1 was that the narrow channel was cut with a width of 200 μm. The microstructured film was between two more transparent

Laying foils of 400 μm in thickness, one of the foils having 4 round holes each at positions which correspond to the ends of the long channels in the microstructured foil. The holes that can be assigned to the narrow channel have a diameter of 400 μm, the holes corresponding to the wide channel have a diameter of 3 mm. The films were pressed together on a solid surface with a glass plate and scanned over a large area around the microstructure with an Nd: YAG laser beam with an effective power of 8 W. The laser beam had a diameter of 2.2 mm at the location of the foils and the scanning speed was 18 mm / s. The irradiated areas can be seen in FIG. 8 by the more intense black. Although only one side was irradiated, the three foils are permanently and firmly fused. As a result of the melting process, the narrow channel narrowed from 200 μm to 120 μm. Example 4

The module from Example 3 was glued with the side on which the hole-carrying film is located to a machined polycarbonate plate using fast-curing adhesive. The plate has four buffer vessels with holes of 2 mm in diameter, which are located above the holes in the cover film of the module. Tris / borate buffer, which was 0.1 molar, contained 0.1% methyl cellulose and had a pH of 8.5, was introduced into the buffer reservoirs and the entire module was deaerated in vacuo. Electrodes were inserted into the buffer reservoirs. The entire module was cooled to 10 ° C using contact cooling with thermostatted metal surfaces. A voltage of 1 kV was first applied across the electrodes along the wide channel and a current of 270 μA was measured. A voltage of 1 kV was also applied along the narrow channel and a current of 25 μA was measured. This shows that the electrical line runs exclusively through the buffer-filled channels and the module is otherwise electrically insulating.

The module prepared in this way was tested with the experimental set-up according to FIG. 9. For this purpose, a laser-induced fluorescence detector 24 was additionally positioned above the microstructure. The laser light from an argon-ion laser with a wavelength of 488 nm was irradiated onto the module surface at an angle of 45 ° using a light guide. A second light guide was positioned such that it directed light emitted at an angle of 90 ° to the module surface to the detector 24. DNA that was intercalated with a fluorescence marker that was 10 micromolar was filled into a wide channel buffer reservoir. The DNA was transported along the wide channel by applying a voltage of 700 V (FIG. 9a (a)). After 3 minutes, a voltage of 1 kV was applied for 10 seconds between the wide and narrow channels in order to transport the DNA across the transverse channel (FIG. 9a (b)). After switching the voltage to 1 kV along the narrow channel, the DNA was detected via its fluorescence wavelength at 520 nm. The detection signal can be seen at (c) in FIG. 9b.

Claims

claims

1. Module made of polymer materials with a microchannel system, consisting of one or more superimposed polymer films with recesses in the form of the microchannel structure, the open channels on the top and

The underside of the film or the film stack can be closed off by an upper and a lower cover layer and at least one of the cover layers contains at least two accesses to at least one microchannel.

2. Module according to claim 1, characterized in that the cover layers and / or films are transparent.

3. Module according to claim 1, characterized in that the foils absorb radiation with wavelengths in the optical or infrared range.

4. Module according to one of claims 1, characterized in that films made of polycarbonate or polymethymethacrylate are used.

5. Module according to one of claims 1, characterized in that the films are made up of different layers, at least one of which

Layer adhesive function, absorption function or elastic sealing function.

6. Module according to one of claims 1 to 5, characterized in that the foils and / or the cover plates forming the channel walls are coated on the side facing the channel.

7. Module according to claim 6, characterized in that for coating polyacrylamide, polyvinyl alcohol, oligomeric alkylamines, nonionic detergents such as polyoxyethylene ether or polymeric sugars such as hydroxypropyl methyl cellulose or methyl cellulose are used.

8. Module according to one of claims 1 to 7, characterized in that the

Films have a thickness of 10-1000 μm, preferably 10-100 μm, particularly preferably 25-75 μm.

9. Module according to one of claims 1 to 8, characterized in that

Channel lengths 1 mm to 100 mm, preferably 5 - 50 mm and the channel widths are preferably 1 μm to 5 mm.

10. Module according to one of claims 1 to 9, characterized in that on the side facing away from the channel of one or both cover layers above the accesses to the microchannels are sample, reagent and / or buffer vessels.

11. Module according to one of claims 1 to 10, characterized in that one or more separating membranes are located in the access area to the microchannel between an outer cover layer and a film or between two films in the overlap area of the microchannels or directly in the accesses in the cover layer.

12. A method for producing a module from polymer materials according to claim 1, characterized in that one or more foils are microstructured and the one microstructured foil is connected to the cover layers or several superimposed microstructured foils are connected to one another and to the cover layers, so that the Channels in the or the micro-structured films are sealed.

13. The method according to claim 12, characterized in that the microstructuring of the films is carried out by etching, laser ablation, punching and / or cutting.

14. The method according to claim 13, characterized in that the foils are pretensioned and the individual channels are cut in the longitudinal direction by two knives arranged in parallel, the distance between the knives corresponding to the channel width and the channels being limited in the transverse direction by cutting or punching.

15. The method according to claim 12, characterized in that the films and the cover layers are connected to one another by pressure, gluing or welding.

16. The method according to claim 15, characterized in that solid plates are used as the cover layer, which are connected by screws, clips, clamping elements, rivets or welding and exert pressure on the foils located between the cover layers.

17. The method according to claim 15, characterized in that the foils and the cover layers are joined together by hot stamping, heating element welding, infrared radiation welding, laser welding, ultrasonic welding or high-frequency welding.

18. The method according to claim 17, characterized in that the cover layers are transparent and absorb the one or more microstructured films in the optical or infrared range and the unconnected arrangement with radiation in a wavelength that corresponds to the absorption wavelength of the films, irradiated and is merged into a module.

19. A method for producing a module according to any one of claims 12 to 18, characterized in that the cover layers on the side facing the channel and / or the films are coated before cutting. Method for producing a module according to one of Claims 12 to 19, characterized in that separating membranes are used before the foils and the cover layers are connected.