MXPA99003180A - Process for the production of analiti devices - Google Patents

Abstract

The present invention relates to a process for the production of analytical devices, in particular of test analytical elements with an active capillary zone for examining liquid samples. In the process a carrier layer is prepared, a spacer layer is laminated on the carrier layer, a contour is punched, cut out or stamped through the laminated spacer layer on the carrier layer which determines the shape of the active capillary zone , those parts of the spacer layer that are not required to form the active capillary zone are removed from the carrier layer and a cover layer is applied to the spacer layer, to result in an active capillary zone. The process according to the invention is preferably suitable for the manufacture of analytical devices from tape-shaped material. The invention also relates to analytical devices produced according to the process described above.

Description

PROCESS FOR THE PRODUCTION OF ANALYTICAL DEVICES The invention relates to a process for the production of analytical devices with an active capillary zone, preferably of analytical test elements for examining leguided samples. In particular, the invention relates to a process for the production of analytical devices from tape-shaped material. In addition, the invention relates to analytical devices that have been. produced by the process according to the invention. The so-called carrier-linked tests (test carriers, test elements) are frequently used for the qualitative or quantitative analytical determination of the components of liquid samples, for example bodily fluids such as blood, serum or urine. In these tests the reagents are embedded in corresponding layers of a liquid carrier which is brought into contact with the liquid sample. 'If an objective analyte is present, the reaction of the liquid sample and the reagents leads to a detectable signal, which is usually a REF .: 29845 V color, which can usually be evaluated or with the help of an instrument, for example, by means of reflection photometry. The test elements or test carriers are frequently in the form of test strips which are essentially composed of an elongated support layer made of plastic material, and the detection layers as test zones which are coupled to it. However, they are also known test carriers that are designed as quadratic wafers. Test elements for clinical diagnostics that are evaluated visually or by reflection photometry are frequently constructed, such that the area of application of the sample and the detection zone are arranged one above the other on a vertical axis, so that for example the sample is applied from above on a sample application area and observe from below a color change. This type of construction is problematic. When the test strip loaded with the sample has to be inserted into an instrument, for example a reflection photometer, for measurement, the Potentially infectious sample material may come in contact with the parts of the instrument and may contaminate them. Furthermore, the volumetric dosage can only be achieved with difficulty especially in cases in which the test strips are used by untrained persons, for example in the self-control of blood sugar by diabetics. In addition, conventional test elements often account for relatively large sample volumes due to their construction, in order to make reliable measurements possible. The more volume of sample required, the more painful the collection of the sample may be for the patient whose blood needs to be examined. The goal is therefore to provide test strips, which require as little test material as possible. The use of analytical test elements with active capillary zones is a method of reliably dosing small amounts, typically a few microliters, of sample volume and transporting it within the test element. Such test elements are described in the prior art.

European Patent EP-B 0 138 152 relates to a disposable cuvette which is suitable for collecting sample liquid almost simultaneously within a sample chamber, with the help of a capillary free space and the measurement thereof. Reagents can be provided within the empty space of the capillary. The void space is at least partially limited by a semipermeable membrane. The reagents can, for example, be accommodated in the empty space by coating the walls or by embedding the reagents in a semipermeable membrane. European Patent EP-A-0 287 883 describes a test element which uses a capillary interstitial space between a detection layer and an inert carrier for volumetric dosing. In order to fill the capillary space, the test element is immersed within the sample to be examined, which requires large sample volumes and that is why this type of volumetric dosage is preferably used to examine sample material that is present in excess such as urine.

An analytical test element with an active capillary region is also known from European Patent EP-A-0 212 314. In order to manufacture these test elements, it is proposed that an intermediate layer containing a cut corresponding to the active capillary zone , be placed between two layers of plastic. According to the European Patent EP-A-0 212 314 the trimming must already be present in the intermediate layer before assembly. Especially when using flexible intermediate layers such as for example double-sided adhesive tapes, it is difficult to assemble the analytical element since it is difficult and complicated to achieve a reproducible placement of the intermediate layer, which already contains a cut-out. The object of the invention is to eliminate the disadvantages of the prior art. In particular, the aim of the present invention is to provide a process by which analytical devices can be produced inexpensively, reproducibly and accurately. The object of the invention is to provide a process for the production of analytical devices with an active capillary zone in which: (a) a carrier layer is prepared; (b) a spacer layer is laminated on the carrier layer; (c) a contour, which determines the shape of the active capillary zone, is punched, cut or stamped through the laminating layer laminated on the carrier layer; (d) when the parts of the sparring layer are removed from the carrier layer, which are not regulated for the conformation of the active capillary zone; and (e) a coated layer is placed on the spacer layer, so that an active capillary zone is formed, as well as the analytical devices produced accordingly. Analytical devices in the sense of the invention are understood as devices that can automatically collect clear samples with the help of their active capillary zone, for example by means of capillary forces, and can make them available for simultaneous or subsequent analysis. The active capillary zone can be present as a capillary free space or can be generated by the use of porous active capillary materials, such as, for example, fleeces, papers or membranes. The analytical devices may preferably be analytical test elements in which the appropriate detection reactions that allow the determination of the presence or amount of an analyte in the sample, proceed either during or after the collection of the sample liquid. However, the analytical devices in the inventive sense can also be cuvettes or pipettes which only use the sampling of the sample by the capillary zone, and in which the sample is either released again for analysis or in which the sample occurs. analysis without subsequent reactions. Analytical devices can of course be used to store and maintain sample liquids. The presence of an active capillary zone in the analytical devices produced according to the invention makes it possible to automatically collect a defined sample volume if the active capillary zone is manufactured in a precise and sufficiently reproducible manner. The active capillary zone may have any desired shape, provided that the capillary is secured in at least one dimension. The active capillary zone can have, for example, a triangular, rectangular or semicircular base plane, and the slivers of the profiled areas are preferably rounded as a precaution against the risk of remnants of adhesive in the active capillary zone. The active capillary zones are preferred according to the invention with an essentially cuboid geometry, for example with an essentially rectangular base plane. Many materials that are conveniently used to make analytical devices can be used as the carrier layer to produce an analytical device according to the invention, such as test elements, for example metal or plastic sheets, coated papers or cartons, and although less preferred, glass. If the analytical device is used to examine non-polar liquids, an adequate capillarity of the capillary zone of the analytical device produced according to the invention is already achieved by the use of non-polar carrier layers, for example, plastic sheets. In order to achieve adequate capillarity when examining aqueous samples such as for example water samples, or biological tracers such as blood, serum, urine, saliva or sweat, it is advantageous if the carrier material that is used has a hydrophilic surface on it. at least one side facing the active capillary zone. In this context hydrophilic surfaces are surfaces that attract water. Aqueous samples, which also include blood, diffuse perfectly on such surfaces. Such surfaces are characterized among other things, because a drop of water placed on them forms a sharp edge angle or sharp contact angle at the interface (for example, see the details under the title of "Benetzung" on "CD Ropp Chemie Lexikon"). ", version 1.0, 1995). In contrast, an obtuse edge angle is formed at the interface between a drop of water and the surface, on hydrophobic surfaces, for example, water repellent surfaces. The edge angle which is a result of the surface tensions of the test liquid and the surface to be examined is a measure of the hydrophilicity of a surface. Water, for example, has a surface tension of 72 mN / m. If the surface tension value observed is well below this value, for example, more than 20 mN / m below this value, then the wetting is poor and the resulting edge angle is obtuse. Such a surface is termed as hydrophobic. If the surface tension approaches the value that is found for water, then the wetting is good and the edge angle is sharp. In contrast, if the surface tension is the same or higher than the water level of the value found, then the drop runs and there is a total diffusion of the liquid. Then it is no longer possible to measure a bank angle. The surfaces that form a sharp edge angle with water droplets or on which a total diffusion of the water drop is observed, are termed as hydrophilic. The ability of a capillary to aspirate a liquid depends on the umectability of the capillary surface with the liquid. This means, for aqueous samples, that a capillary must be manufactured from a material whose surface tension reaches almost 72 mN / m or exceeds this value. The sufficiently hydrophilic materials for the construction of a capillary that quickly sucks aqueous samples are, for example, glass, metal or ceramic. However, these materials are often not suitable for use in analytical devices such as test carriers, since they have some disadvantages, such as the risk of breaking in the case of glass or ceramics, or the change in surface properties. over time in the case of numerous metals. Therefore, plastic sheets or molded parts are usually used to make analytical devices. As a rule, the plastics used hardly exceed a surface tension of approximately 45 nM / m. Even with the more hydrophilic plastics, in a relative sense, such as polymethyl methacrylate (PMMA), or polyamide (PA), it is only possible (if possible) to build capillaries that aspire very slowly. The capillaries made of hydrophobic plastics such as for example polystyrene (PS), polypropylene (PP) or polyethylene (PE), essentially do not aspirate aqueous samples. Consequently, it is necessary to provide the plastics used as a construction material for analytical devices, with an active capillary zone, such as, for example, test elements with a capillary free space, with hydrophilic properties for example to hydrophilize them. In a preferred embodiment of the analytical devices produced according to the invention at least one, but preferably two and especially preferably two opposite surfaces forming the internal surface of the channel capable of transporting the capillary liquid, are hydrophilized. If more than one surface is hydrophilized, then the surfaces can be either made hydrophilic using the same or different methods. Hydrophilization is particularly necessary when the materials forming the active capillary channel, in particular the carrier layer, are themselves hydrophobic or only very slightly hydrophilic because they are, for example, non-polar plastic compounds. Non-polar plastics such as for example polystyrene (PS), polyethylene (PE), polyethylene terephthalate (PET) or polyvinyl chloride (PVC), are advantageous as carrier materials because they do not absorb and are not attacked by the aqueous liquids that are going to be examined. The hydrophilization of the surface of the capillary zone makes it possible for a sample liquid, polar, preferably aqueous, to easily enter the active capillary zone. If the analytical device is a test element, the aqueous sample is additionally quickly transported to the detection element or to the site of the detection element where the detection takes place. Ideally, the hydrophilization of the surface of the active capillary zone is achieved by the use of a hydrophilic material in its manufacture, which, however, can not by itself absorb the sample liguid or only to a negligible degree. In cases where this is not possible, a hydrophobic or only a very slightly hydrophilic surface can be hydrophilized by a suitable coating with a stable hydrophilic layer which is inert towards the sample material, for example by the covalent bond of photoreactive hydrophilic polymers, on a plastic surface, by applying layers containing wetting agents, or by coating the surfaces with nanocomposites by means of this sol-gel technology. In addition, it is also possible to increase the hydrophilicity by thermal, physical or chemical treatment of the surface. Hydrophilization is very special and preferably achieved by the use of thin layers of oxidized aluminum, as described in German Patent Application No. P19753848.7. These layers are either applied directly to the desired components of the test element, for example by vacuum coating the workpieces with metallic aluminum and subsequently oxidizing the metal, or by the use of metal foils or metal-coated plastics, for the construction of test carriers which also have to be oxidized to achieve the desired hydrophilicity. In this case, the thicknesses of the metal layer from 1 to 500 nm are suitable. The metal layer is subsequently oxidized to form the oxidized form in which case all oxidation in the presence of water vapor or by boiling water have proven to be especially suitable methods in addition to anodic electrochemical oxidation. The oxide layers formed in this way are between 0.1 and 500 'nm, preferably between 10 and 100 nm in thickness, depending on the method. The thicknesses of the largest layer of the metal layer, as well as of the oxide layer can in principle be achieved in practice, but do not show any additional advantageous effect. The capillary zone of the analytical device produced according to the invention is formed from the carrier layer, a sparrow layer and a cover layer. The purpose of the spacer zone is preferably to define the dimension, which results in the capillarity of the zone. The thickness of the spacer layer is preferably used to define this dimension. However, it is also possible to cut or punch a piece of appropriate width from the spacer layer, resulting in an area of an active capillary dimension. At least one dimension of the area is defined by the physical limits of capillary activity. In the case of aqueous limits, this dimension is of the order of magnitude of 10 to 500 μm, preferably between 20 and 300 μm, and more preferably between 50 and 200 μm, since otherwise capillary activity would not be observed. Although the spacer layer can in principle be fabricated from all materials that are inert towards the sample liquid to be analyzed, double-sided adhesive tape has proven to be preferable, since this simply solves the problem of coupling the spacer layer on the carrier layer on the one hand, and on the cover layer on the other part. This avoids time consuming and costly processes of bonding or adhesiveness in the manufacture of the analytical device. However, if this advantage is not used, the analytical device can also be produced according to the invention using additional joining processes, for example by welding, heat sealing for example with polyethylene, gluing with adhesives with cold hardening or adhesive hot melt, or by clamping the carrier layer to a spacer layer, or the spacer layer to the cover layer. In this context, the spacer layer can in principle be manufactured from materials that are also suitable for the carrier layer. Since the spacer layer in conjunction with the carrier layer and the cover layer determines the geometry of the active capillary region, an outline is introduced into the spacer layer in the process according to the invention, after the spacer layer has been mounted on the carrier layer, which allows those portions of the spacer layer that are not required to form the geometry of the active capillary region, to be removed again from the carrier layer. An example is that part of the spacer layer which forms the capillary region of the analytical device, after decoupling from the carrier layer. The contour can in principle be introduced by the spacer layer using all methods that make possible a clean separation of the parts of the spacer layer that remain on the carrier layer from those parts that have to be removed from the carrier layer. Examples are punching, trimming or embossing, of which punching or trimming is preferred according to the invention. It has been found to be particularly advantageous for a clean separation of the parts of the spacer layer that remain on the carrier layer from the parts that have to be removed from the carrier layer, if the contour is trimmed through the spacer layer , and thus cuts lightly within the carrier layer, taking care that the cutout in the carrier layer is not deep enough to make it inadequate. This can be reliably avoided by properly accurate cutting tools. For the preferred embodiment of the analytical device in which the spacer layer is formed from a double-sided adhesive tape, it has been found to be advantageous to laminate the spacer layer on the carrier layer immediately prior to punching, cutting or stamping , of the contour of the active capillary zone and eliminating those parts of the spacer layer that are not required to form the active capillary zone, immediately after the punching, trimming or stamping of the contour of the active capillary zone. When the parts are removed this avoids problems such as for example, that adhesive residues remain in the active capillary zone or the union of the spaced zone parts separated by punching, trimming or stamping. Furthermore, it was surprisingly found that the edges of the cut-out area in the spacer layer are particularly smooth compared to the use of pre-punched adhesive tapes, and thus are favorable for capillarity. With the preferred use of the double-sided adhesive tape as the spacer layer it is necessary, after removing the parts of the adhesive tape that are not required and before the application of the cover layer, to remove the cover sheet (inner lining). ) of the adhesive tape that is generally present to make it possible to join the cover layer. All the materials which are also suitable for the carrier layer are suitable as the cover layer for the active capillary zone of the analytical device produced according to the invention. Accordingly, the analytical device can be essentially composed of identical materials for the carrier layer, the spacer layer and the cover layer, but any combinations of materials are also possible. For the preferred case in which the analytical device is used for an optical examination of the sample material, it is advantageous if at least the carrier layer or the cover layer or both are completely or partially manufactured from a transparent material, preferably a transparent plastic . For the preferred case that the process according to the invention is used to produce an analytical test element, a one-piece layer is used as the carrier layer, while the cover layer may be composed of one or several parts . The cover layer can be completely or partially composed of an analytical detection film as described for example in German Patent Application No. P 196 29 656.0. This detection film is composed of two layers of film on a transparent sheet and the film as a whole contains all the reagents and auxiliary substances that are required for an analytical detection reaction with the sample liquid. Such reagents and their auxiliary substances are known to a person skilled in the art in numerous variants for numerous analytes, for example from German Patent Application No. P 196 29 656.0. The reagents and auxiliary substances contained in the detection film preferably lead to a qualitative or quantitative signal which can be detected visually or optically by means of an apparatus when the target analyte is present in the liquid sample to be examined. An important feature of the detection film that is preferred here for the preferred embodiment of an analytical test element is that the first layer lying on the transparent film or sheet scatters the light considerably less than the second overlapped layer. While the first layer contains a swelling agent such as the methyl vinyl ether-maleic acid copolymer and optionally a filler that weakly disperses light, the second layer requires a swelling agent and in any case at least one pigment which strongly disperses the light, and may also contain in addition non-porous fillers and porous fillers such as silica gel in small amounts without becoming permeable for particulate components of the sample, such as erythrocytes. Since fillers that weakly disperse light and pigments that strongly scatter light are responsible for the optical properties of film layers, the first and second film layers contain different fillers and pigments. The first film layer must not contain fillers or fillers whose refractive index is close to the refractive index of the water, for example silicon dioxide, silicates and aluminum silicates. The particularly preferred average particle size of the filler particles is about 0.06 μm. The second layer must advantageously be very strongly light scattering. The refractive index of the pigments in the second film layer is ideally at least 2.5. Of course, titanium dioxide is preferably used. Particles with an average diameter of about 0.2 to 0.8 μm have proven to be particularly advantageous. Furthermore, it has been proved that it is preferable that, when a detection film is used, the cover layer is additionally formed by an additional film or film cover, which preferably lies next to the detection film and, as this is on the side of the carrier layer that is opposite the capillary zone. The film or film cover replaces the detection element on part of the capillary zone. Since the detection element usually contains valuable reagents such as enzymes and, due to its often complex structure, is much more expensive to manufacture than a simple cover sheet, this measure considerably reduces material and production costs. This applies particularly to the case of long capillary zones which are understood as zones of more than 5 mm in length. In addition, in the test elements in which the detection reaction is detected in the detection film in an exactly defined spatial region, for example in the case of optical detection in an instrument, and in which it is desirable to separate the area of application of the sample and the detection zone, for example, for reasons of hygiene of the instrument, this measure makes possible an accelerated transport of the sample from the opening of application of the sample in the test element to the detection site in the detection element, so that the transport of the sample in the capillary channel from the area of application of the sample to the detection area is so rapid that no time limitation is imposed on the analysis of a sample. In addition such arrangement makes the use for the user more convenient.

The cover sheet and the detection film should be assembled such that they limit the final test element with each other so that the transport of the liquid is not interrupted in the capillary at the contact point of the cover sheet and the detection film, for example by an unfavorable change in the capillary cross section, which is also understood to include an interruption of a continuous boundary surface or boundary of the capillary. For this purpose, the dimensions of the detection film and the cover sheet must be matched appropriately. If it is not possible to assemble the two components sufficiently together, an interruption of the active capillary zone can be avoided by the subsequent sealing. Surprisingly, it has been found that for a particularly preferred embodiment of the test element produced according to the invention, a flexible inert sheet can be additionally mounted on the side of the cover sheet facing the channel, capable of carrying out the capillary transport of the liguid, which extends over the entire length of the cover, covers the capillary zone over its entire length, and is at least partially enclosed between the opposite edge surfaces of the cover sheet and the detection film, so that the capillary transport of the liquid does not break at the contact site of the detection film and the cover sheet. The material and optionally the hydrophilizing coating of the sheet may correspond essentially to that already described above for the carrier layer and the cover layer. In this especially preferred variant, the detection film and the cover sheet are also mounted as closely as possible. The process according to the invention is preferably used to produce analytical devices in large numbers so that the process can be substantially automated. For this purpose, the materials for the analytical devices such as the carrier layer, the spacer layer and the cover layer are provided in the form of a tape material similar to a roll of film. The contour that determines the shape of the active capillary zone is preferably cut through the spacer layer, which is laminated on the carrier layer, by the use of a rotary cutting tool, which preferably contains a cutter roller and a cylinder of back pressure. This advantageously results in a continuous cut in or through the spacer layer, which has a precise and reproducible relative position on the continuous tape, and consequently on the analytical devices manufactured according to the invention. In this particularly preferred process according to the invention, the analytical devices, for example the analytical test elements, are separated after assembly of the cover layer by cutting or punching, for example, separated from the previous tape form as essentially rectangular strips, preferably narrow. Therefore, the production according to the invention can be carried out in an operation at a high production speed (0.1 m / min up to approximately 50 m / min.). The advantages of the invention can be summarized as follows: • Extensive automation of the production process is possible, and therefore the production costs for the individual analytical devices remain low.

• The position and size of the active capillary zone on the analytical device are accurately and reproducibly maintained; its position relative to other functional components of the analytical device can be easily adjusted, and is reproducible. • The active capillary zone has exact and cleanly defined limits, with the spacer layer that makes it possible for the capillary properties to be adjusted in a precise manner. The invention is further elucidated by the following examples and figures.

Figure 1 shows schematically a part of the automatic manufacture of an analytical device according to a preferred embodiment of the process according to the invention.

Figure 2 shows schematically six stages (A to F) of the manufacture of an analytical device according to a preferred embodiment of the process according to the invention.

Figure 3 shows an exploded schematic diagram of a preferred embodiment of an analytical device which can be produced by the process according to the invention.

The numbers in the figures denote: 1 the carrier layer 2 the spacer layer (spacer) 3 the cutting roller 4 the counter-pressure cylinder 5 the rest of the spacer layer that has to be pulled from the carrier layer 6 the take-up roller 7 the remnant of the spacer layer remaining on the carrier layer 8 the active capillary zone 9 the gap in the carrier layer 10 the detection film 11 the cover sheet 12 the protective sheet Part of an automatic production plant for the analytical devices and in Particular for the analytical test elements is shown schematically in Figure 1, which operates according to a particularly pure variant of the process according to the invention. In figure 1, a carrier layer 1 on which a spacer layer 2 has already been laminated in the form of a double-sided adhesive tape in an immediately preceding production step, is made possible as a tape material on the left side, and it is automatically transported to the right. In this process, the composite laminate of the carrier layer 1 and the spacer layer 2 passes through a rotary cutting tool containing a cutter roller 3 and a counterpressure cylinder 4, which introduce a contour in the shape of a meander essentially rectangular through the spacer layer 2, using the cutter roll 3 which determines the geometry of the active capillary region of the final test analytical element. Immediately after the passage of the cutting tool containing a cutting roller 3 and a back pressure cylinder 4, the remainder 5 of the spacer layer 2 to be removed, is pulled from the carrier layer 1. The take-up roller 6, the which is passed from side to side in this process, ensures that the part 5 of the spacer layer 2 to be pulled, is pulled cleanly and free of debris in the direction of the cut capillary geometry, without the remaining 5 gue tear during the retreat. The very narrow remains 5 of the spacer layer 2 can be reproducibly and reliably removed in this manner. The remainder 7 of the spacer layer 2 which remains on the carrier layer, essentially determines the geometry of the active capillary zone 8, which is formed by the subsequent coverage of the spacer layer 2 with a cover sheet not shown in this. figure, during which the intermediate lining of the adhesive tape is removed immediately before mounting the cover sheet. The individual test elements which each have an active capillary zone 8 are obtained at the end of the manufacturing process from the continuous tape generated in this way, composed of the carrier layer 1, the spacer layer 2 and a cover sheet , by cutting or punching. Six manufacturing steps (A to F) of the analytical test element, which can be produced according to a preferred embodiment of the invention, are shown schematically in Figure 2. In stage A a carrier layer 1 is prepared in the which is punctured by a slit 9 which in the final analytical test element can serve, among other things as an orientation aid for the application of the sample and to facilitate the taking of the sample inside the capillary (stage B). Stage C shows the carrier layer 1 on which, after the insertion of the slit 9, a spacer layer 2 has been applied in the form of a double-sided adhesive tape. In this case, the outline of the capillary zone 8 has already been cut through the spacer layer 2, the unwanted remains of the spacer layer 2 have been removed. and the cover sheet (inner lining) has been pulled out of the adhesive tape. Subsequently (step D) an analytical detection film 10 is laminated on the appropriate site of the spacer layer 2 which remains on the carrier layer 1. The previously uncovered, remaining area of the active capillary zone 8 is covered by a coated sheet to result in an active, continuous capillary zone, which includes the cover sheet 11, as well as the detection film 10 (step E). For manufacturing reasons the remaining exposed areas of the adhesive tape are subsequently provided with a protective foil 12 which is directed to prevent unwanted adhesion of the analytical test elements, manufactured according to the invention (step F). Hence, a small clearance usually of a few millimeters in size usually remains in this process between the protective sheet 12 and the detection film 10. which allows air to escape from the active capillary zone when it is filled with the sample liquid. For the same reason the zone 8 is not completely covered by the cover sheet 11 and the detection element 10 is not completely covered on the side facing the protective sheet. 12. The test analytical element of Figure 2 produced according to the invention is again shown schematically in Figure 3 in an exploded diagram. A spacer cap 2 defining the contour and height (corresponding to the thickness of the spacer layer) of the active capillary channel is located on the carrier layer 1 into which a slit 9 has been inserted. A cover sheet 11, a film of detection 10 as well as a protective sheet 12 are in turn placed on it. The cover sheet 11 and the detection film 10 are mounted so closely together that the active capillary zone 'extends from the free edge of the cover sheet 11 lying on the slit 9, to the opposite free edge of the film. of detection 10. The cut-out area in the spacer layer 10 is made slightly longer than the cover sheet 11 and the detection element 10, together, so that usually one remains. uncovered free space a few millimeters in width, from which the air can escape, when the active capillary zone is filled with the sample liquid. This free space also remains uncovered by the protective sheet 12 so that its function remains ensured.

Example 1 Production of an analytical test element by the process according to the invention.

A double-sided adhesive tape with a thickness of 100 μm is covered with glue as a spacer layer on a 350 μm thick polyethylene terephthalate sheet (Melinex®, ICI, Frankfurt am Main, Germany). The carrier layer has a length of 25 mm and is 5 mm in width. A central recess in the form of a slit 1 mm wide and 2 mm long is located on one of the short sides of the carrier layer as also described for example in German Patent Application No. P 197 53 850.9. The contour for a cut of 2 mm in width and 16 mm in length that defines the geometry of the capillary channel is introduced through the adhesive tape laminated on the carrier layer, with the help of an appropriately shaped cutting tool, without the layer carrier that is cut so deeply that its rigidity and stability could be compromised. The length of the cut-out has to be selected to be slightly larger than the desired length of the active capillary channel, which is determined by its coverage, in order to ensure ventilation of the channel during filling with the sample liquid. The non-required parts of the adhesive tape are pulled from the carrier layer immediately after the introduction of the contour. An action film 3 mm long and 5 mm wide is covered with glue on the side of the remaining adhesive tape which provides ventilation at a distance of 1 mm from the end of the cut. A film is used as the detection film, as is known from German Patent Application No. P 196 29 656.0. The detection film is specific for the detection of glucose. A cover sheet 12 mm in length and 5 mm in width is glued on the region of the adhesive tape which is still open between the gap in the form of a slit and the detection film, so that the cover layer and the film of detection limit one with the other. The cover sheet is composed of a sheet of polyethylene terephthalate 150 μm thick, provided on one side with adhesive on which is glued on the side facing the capillary channel a sheet of polyethylene terephthalate 6 μm thick ( both from: Hostaphan®, Hoechst, Frankfurt am Main, Germany) coated with an oxidized aluminum layer 30 nm thick. In this case the thinner sheet extends approximately 50 μm beyond the thicker sheet on the side facing the detection film. When the cover layer is mounted on the adhesive tape, care must be taken that the projecting end of the thinner sheet is placed between the detection element and the thicker sheet of the cover sheet. In order to cover the areas of the adhesive tape that are still exposed, they are covered with a Melinex® sheet of 175 μm thickness without, however, covering the functional areas. The test element obtained in this way has a capillary channel of 15 mm in length, 2 mm in width and 0.1 mm in height. The channel can collect 3 μl of sample liquid. An area of 3 mm x 2 mm of the detection film is wetted by the sample.

It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, property is claimed as contained in the following:

Claims (12)

RE I INDICATIONS

1. A process for the production of analytical devices with an active capillary zone, characterized in that: (a) a carrier layer is prepared; (b) a spacer layer is laminated on the carrier layer; (c) a contour, which determines the shape of the active capillary zone, is punched, cut or stamped through the laminated spacer layer on the carrier layer; (d) those parts of the spacer layer are removed from the carrier layer, which are not required for the conformation of the active capillary zone; and (f) a coated layer is placed on the spacer layer, so that an active capillary zone is formed.

2. The process according to claim 1, characterized in that the spacer layer is a double-sided adhesive tape.

3. The process according to claim 1 or 2, characterized in that the cover layer is composed of one or several parts.

4. The process according to any of claims 1 to 3, characterized in that the cover layer is composed at least partially of an analytical detection film.

5. The process according to any of claims 1 to 4, characterized in that the analytical device is an analytical test element.

6. The process according to any of claims 1 to 5, characterized in that the spacer layer is laminated on the carrier layer immediately before punching, trimming or stamping the contour of the active capillary region.

7. The process according to any of claims 1 to 6, characterized in that those parts of the spacer layer that are not required to form the active capillary zone are removed immediately after the punching, trimming or stamping of the area contour. active capillary

8. The process according to any of claims 1 to 7, characterized in that the carrier layer, the spacer layer and the cover layer are provided in the form of tape material.

9. The process according to claim 8, characterized in that the contour is introduced as a continuous cut by a rotary cutting tool.

10. The process according to claim 9, characterized in that the rotary cutting tool contains a cutting roll and a back pressure cylinder.

11. The process according to any of claims 8 to 10, characterized in that the analytical devices are separated by cutting or punching after the application of the cover layer.

12. An analytical device, characterized in that it is obtainable by a process according to any of claims 1 to 11.