MXPA00005416A - Analytic test element with a capillary canal - Google Patents

Abstract

The invention relates to an analytic test element for determining an analyte in a liquid. The element comprises an inert carrier, a detection element and a canal which permits capillary liquid transport. The canal has a test sample feeding opening situated on one end of the canal which permits capillary liquid transport, and has a vent opening on the other end of said canal. The canal is at least partially constructed by the carrier and the detection element and extends at least to the edge of the detection element, said edge being adjacent to the vent opening, in a direction of the capillary transport. A recess is located in an area, said area constructing the canal which permits capillary liquid transport, on the edge of the analytic test element, said edge constructing the test sample feeding opening, such that said edge of the test element is at least partially discontinuous on one side, and the area opposite the recess is open. The invention also relates to the utilization of said analytic test element for determining an analyte in a liquid and to a method for determining an analyte in a liquid test sample with the assistance of said analytic test element.

Description

ELEMENT FOR ANALYTICAL TEST WITH A CAPILLARY CHANNEL DESCRIPTION OF THE INVENTION The invention relates to an element for analytical testing for the determination of an analyte in a liquid containing an inert carrier, a detection element and a channel capable of carrying out liquid capillary transport, which has a sample application opening in an end and a ventilation opening at the other end of the channel, capable of carrying liquid transport by capillarity. The invention also relates to the use of the analytical test element for the determination of an analyte in a liquid, as well as a method for the determination of an analyte in a liquid sample with the aid of said analytical test element. The so-called carrier-linked tests are frequently used for the qualitative or quantitative analytical determination of components of bodily fluids, in particular blood. In these, the reagents are embedded in the corresponding layers of a solid carrier which is contacted with the sample. Nap REF .: 120460 presents an objective analyte, the reaction of the liquid sample and the reagents leads to a detectable signal, in particular a color change that can be evaluated visually or with the help of an instrument, usually by reflex photometry. The test elements or test carriers are frequently in the form of test strips which are essentially composed of an elongated carrier layer made of plastic material and detection layers which are applied to it as test fields. However, the test carriers are also known, which are in the form of small square or rectangular plates. Test elements for clinical diagnostics that are evaluated visually or by reflection photometry, are frequently constructed such that the sample application zone and the detection zones are arranged one above the other on a vertical axis. This mode 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. In addition, the volumetric dosage can only be achieved with difficulty, especially in cases in which the test strips are used by people not trained for example in the self-control of blood sugar by diabetics. In addition, conventional test elements often require relatively large sample volumes due to their construction, in order to make reliable measurements possible. The more volume of sample required, the more painful this may be for the patient whose blood is being examined. It is therefore a general goal to provide test strips that require as little sample material as possible. European Patent EP-B-0, 138, 152 has to do with a disposable cell or tray which is suitable for almost simultaneously collecting the sample liquid in a sample chamber with the help of a capillary space and measurement. Reagents for specific detection reactions can be provided in the inner part of the capillary cavity. The cavity is at less partially bound with a semipermeable membrane. The reagents can, for example, be coupled by coating the walls or by incrustation of the reagents of the semi-permeable membrane in the cavity. European Patent EP-A-0, 287, 883 discloses a test element that uses a capillary intermediate space between the detection layer and an inert carrier for volumetric dosing. The test element is immersed in the sample to be examined to fill the capillary space that requires large sample volumes, which is why this type of volumetric dosage is mainly suitable for the examination of sample material that is present in excess, such as urine. There is no spatial separation between the site of the sample application and the detection. European Patent EP-BO, 034, 049 has to do with a test element in which the sample is applied to a central sample application site, for example an opening in a cover and is conveyed by capillary force to several. detection zones that are spatially separated from the application site of the sample. The central position of the application site of the sample in u? Test item according to European Patent EP-B-0, 034, 049 does not solve the problem of hygiene of the instrument, as described above. The aim of the present invention was to eliminate the disadvantages of the prior art. In particular, it was intended to provide an easy-to-handle test element that can automatically dose volumes and make possible a spatial separation of the detection zone and the application site of the sample, while using minimum sample volumes. In addition, the transportation of the sample from the application of the sample to the detection zone should be so rapid that this does not limit the time required to analyze a sample. Furthermore, a simple construction of the test element must make it possible for the test element to be manufactured at low cost and in a simple manner. This is achieved by the subject matter of the invention, as characterized in the patent claims. The subject of interest of the invention is an analytical test element for the determination of an analyte in a liquid containing an inert carrier, a detection element and a channel capable of carrying out the liquid transport by capillarity, which has a sample application opening at one end and a ventilation opening at the other end of the channel, capable of carrying out the capillary transport of the liquid, characterized in that the channel capable of carrying out the transport of the liquid by capillary action is formed at least partially by the carrier and the detection element, and extends in the direction of transport by capillarity from the sample application opening towards at least the edge of the detection element that is closest to the ventilation opening, and that a notch is located in one of the surfaces forming the channel, capable of carrying liquid transport by capillarity at the edge of the test element, forming the sample application opening, so that one side of the edge of the test element forming the sample application opening is at least partially discontinuous and the sup The area opposite the notch is exposed. Since the channel capable of transporting the liquid by capillary action completely covers the detection element in the direction of capillary transport, this ensures that the inhomogeneous moistening of the detection element with the sample is avoided. In particular, the thickness of the sample liquid layer that is in contact with the detection element is reproducibly predetermined by the height of the capillary active channel over the entire area of the detection element covering the active capillary channel. This makes possible a spatially distributed detection reaction, its essentially uniform. This therefore increases the accuracy and reproducibility of the measurement. Since in the. Preferred case in which the channel has an essentially rectangular cross section, one dimension, for example the height of the channel, is preset by the physical limits of the capillary activity, the volume of the capillary channel can be adjusted by the appropriate selection of the other two dimensions, for example length and width. The capillary height is for example for aqueous liquids of the order of magnitude of 10 to 500 μm, preferably between 20 and 300 μm, and especially and preferably between 50 and 200 μm, since otherwise capillary activity is not observed . Depending on the desired volume, the width can then be several mm, preferably from 1 to 10 mm, more preferably from 1 to 3 mm and the length can be up to several centimeters, preferably from 0.5 to 5 cm and especially and preferably from 1 to 3 cm. The notch or groove in a surface forming the capillary channel at the edge of the test element forming the sample application opening serves to ensure that the sample liquid can enter the capillary channel. This is achieved since the sample drop can be directly contacted with one of the surfaces, whose extension forms the internal surface of the capillary, at the edge of the test element that is broken by the notch that is closest to the application opening of the sample. The adequate selection of the geometry and the dimensions of the notch, ensures that the drop of liquid comes into contact with the active capillary zone, with very high probability, regardless of the exact position of the dosage, and is easily sucked towards the internal part. of the capillary. For example, the size of the exposed surface must be selected such that at least one site of the drop of liquid that is applied to it comes into contact with the active zone. capillary. For example, a dimension of the notch, for example its width, must be selected such that the diameter of the liquid drop is slightly larger than the selected dimension of the notch. A notch width of 1 mm has proven to be adequate for a 3 μl drop. The suction of the sample droplet inside the capillary channel is particular and preferably achieved by the area exposed by the notch which is hydrophilized and which limits directly on an active capillary zone, at least in the direction of the capillary transport channel. 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, by the fact that a drop of water placed on them forms an edge or contour angle or contact angle at the interface. In contrast, an obtuse edge angle is formed at the interface between the water drop and the surface on hydrophobic surfaces, for example, water repellents. The edge angle or flange that is a result of the surface tensions of the liquid The test 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 observed surface tension value of the surface is much lower than this value, for example greater than 20 mN / m, 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 the water, then the wetting is good and the edge angle is sharp. In contrast, if the surface tension is the same as or higher than that of the value found for water, then the drop runs and there is a total diffusion of the liquid. It is no longer possible to measure a bank angle. The surfaces that form a sharp edge angle with water droplets or over which a total diffusion of a drop of water is observed, are termed as hydrophilic. The ability of a capillary to suck a liquid depends on the wettability of the canal surface with the liquid. This means, for aqueous samples, that a capillary must be manufactured from a material whose tension surface reach almost 72 mN / m or exceed 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 not suitable for use in test carriers since they have some severe disadvantages such as the risk of breakage in the case of glass or ceramics, or the change in surface properties over time. in the case of numerous metals. Therefore, the sheets or plastic sheets or molded parts are usually used to manufacture the test elements. As a rule the plastics used hardly exceed a surface tension of 45 m? / M. In a relative sense, even with the most hydrophilic plastics such as polymethyl methacrylate (PMMA) or polyamide (PA) it is only possible-if there is a possibility-to build slow suction capillaries. Capillaries made of hydrophobic plastics such as for example polystyrene (PS), polypropylene (PP) or polyethylene (PE) essentially do not suck aqueous samples. In Consequently, it is necessary to equip the plastics used as a construction material for the test elements, with active capillary channels with hydrophilic properties, for example, to hydrophilize them. In a preferred embodiment, of the analytical test element according to the invention at least • one, but preferably two and especially and preferably two opposing surfaces that form the internal surface of the channel capable of performing liquid transport by capillary action, they are hydrophilized. At least the exposed surface opposite the notch is most preferably 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, are themselves hydrophobic or only very slightly hydrophilic, because they are, for example, composed of non-polar plastic materials. 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 the liquids to be examined and thus the volume of sample can be effectively used by the detection layer. The hydrophilization of the surface of the capillary channel makes it possible for a polar sample liquid, preferably aqueous, to easily enter the capillary channel and be rapidly transported there 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 capillary channel is achieved by the use of a hydrophilic material in its manufacture which, however, can not by itself suck the liquid sample or only to a negligible degree. In cases where this is not possible, a hydrophobic or only very slightly hydrophilic surface can be hydrophilized by suitable coating with a stable hydrophilic layer which is inert to the sample material, for example by covalently linking the photoreactive hydrophilic polymers on a surface of plastic, by applying layers that contain wetting agents or by coating of surfaces with nanocomposites by means of sol-gel technology. In addition, it is also possible to achieve increased 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. These layers are either applied directly to the desired components of the test element, for example by means of vacuum metallization of the workpieces with metallic aluminum and subsequently oxidizing the metal, or by the use of metal foils or sheets or metal-coated plastics. for the construction of the 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 metallic layer is subsequently oxidized to form the oxidized form, in which case above all the oxidation in the presence of water vapor or by boiling in water, have proven to be especially suitable methods in addition to the electrochemical, anodic oxidation. The oxide layers formed in this manner are between 0.1 and 500 nm, preferably between .10 and 100 nm in thickness, depending on the method. The larger layer thicknesses of the metal layer as well as the oxide layer can in principle be realized in practice but do not show any additional advantageous effect. In a preferred embodiment, the detection element of the analytical test element according to the present invention contains all the reagents required for the detection reaction of the target analyte in the sample, and optionally auxiliary substances. The detection element may also only contain part of the reagents or auxiliary substances. Such reagents and auxiliary agents are well known to a person skilled in the art or familiar with the technology of analytical test elements or diagnostic test carriers. For analytes that are detected enzymatically, the detection element can for example contain enzymes, enzyme substrates, indicators, buffer salts, inert fillers, etc. The detection element may be composed of one or several layers and optionally contain a carrier inert, preferably on the side of the detection element that is not in contact with the sample. In the particularly preferred case where the detection reaction leads to an observable change in color, which in this context is understood as either a color change, the formation of a color or the disappearance of the color, it must be ensured by suitable measurements that the carrier allows a visual or optical observation of the detection reaction. For this purpose the carrier material of the detection element can itself be transparent, for example a transparent plastic sheet such as a polycarbonate sheet or having a transparent gap on the detection side. In addition to the detection reactions that lead to color changes, other detection principles are also known to a person skilled in the art, which can be realized with the described test elements such as the electrochemical sensors. It is necessary for the detection element, that materials are used that are capable of collecting the liquid that is going to be examined with the constituents contained therein. These are called absorbent materials such as example, fleeces, fabrics, knitted fabrics or porous plastic materials that can be used as layered materials. Suitable materials must also be capable of carrying reagents that are required for the detection of the analyte to be determined. • Preferred materials for the detection element are porous plastic papers or materials such as membranes. Membranes of polyamide, polyvinylidene difluoride, polyethersulfone or polysulfone are especially preferred as porous membrane materials. The reagents for the determination of the analyte to be detected are usually incorporated in the aforementioned materials by impregnation. The so-called open films as described for example in EP-B-0, 016, 387 are especially and preferably suitable for the detection element. For this, solids such as fine organic or inorganic insoluble particles are added to an aqueous dispersion of the film-forming organic plastics and the reagents required for the detection reaction are additionally added. The trainers of suitable films are preferably organic plastics such as polyvinyl esters, polyvinyl acetates, polyacrylic esters, polymethacrylic acid, polyacrylamides, polyamides, polystyrene, mixed polymers such as butadiene and styrene or maleic acid ester and vinyl acetate or other polymers natural and synthetic organics, film formers, as well as mixtures of these in the form of aqueous dispersions. The dispersions can be diffused on a support to form a uniform layer which results in a water resistant film after drying. The dried films have a thickness of 10 μm to 500 μm, preferably 30 to 200 μm. The film can be used together with the support as a carrier, or be applied to another carrier for the detection reaction. Although the reagents required for the detection reaction are usually added to the dispersion used to produce the open films, it may be advantageous to impregnate the film that is formed with reagents, after their manufacture. It is also possible to pre-impregnate the filling materials with the reagents. A person skilled in the art knows which reagents can be used to determine a particular analyte. This does not need to be elucidated in more detail here. In addition, the detection element can be provided with components that allow exclusion of the interfering components of the sample, from the detection reaction and thus act as filters for example for particulate sample components such as blood cells. For example when analyzing blood samples, the red blood pigment hemoglobin that is present in the red blood corpuscles (erythrocytes) can interfere with visual or optical detection methods. It is expedient to separate these interference components, from the sample, for example the whole blood, before the effective detection reaction. This can be accomplished by preparing the sample prior to the application of the sample to the test element such as by centrifugation of the whole blood and subsequently isolating the serum or plasma. It is more convenient and also simpler for an untrained person if the test element itself carries out this separation step by means of an adequate construction. A person skilled in the art knows the means of test strip technology which ensures reliable exclusion of erythrocytes. Examples are the use of semi-permeable membranes or fiberglass fleeces to separate the red blood corpuscles, as are known for example from European Patent EP-BO, 045, 476. It has been proved that it is particularly preferable that the element of test according to the invention use a detection element composed of two layers of film on a transparent sheet. It is important that the first layer lying on the transparent sheet scatters the light considerably less than the second layer superimposed. Such, detection elements are for example known from German Patent Application No. P-196 29 656.0. While the first layer contains a swelling agent such as for example the copolymer of methyl vinyl ether-maleic acid and optionally a filler material that weakly disperses light, the second layer requires a swelling agent and in any case at least a pigment that strongly disperses light, and may also contain non-filler materials porous as well as porous filler materials such as silica gel in small quantities, without becoming permeable for erythrocytes. Since the fillers that weakly disperse light and the pigments that strongly scatter light are essentially responsible for the optical properties of the film layers, the first and second film layers have different fillers and pigments. The first film layer must not contain fillers or fillers having a refractive index that is close to the refractive index of the water, for example silicon dioxide, silicates and aluminum silicates. The average particle size of the particularly preferred filler particles is about 0.06 μm. The second layer should scatter light, very strongly. Ideally, the refractive index of the pigments in the second film layer is at least 2.5. Therefore, 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 found that it is preferable that the channel capable of carrying out the capillary transport is additionally formed by a cover, in addition to the inert carrier and the detection element, which is preferably adjacent to the detection element and, like it, is the side of the channel opposite the carrier. The covering properties such as the material and coating may be similar to or identical to those of the carrier. A section of this replaces the sensing element, preferably on the side of the capillary transport path facing towards the sample application opening. Since it usually contains valuable reagents such as enzymes and due to its often very complex structure is often more expensive to manufacture than the materials that are suitable for the cover, this measure considerably reduces material and production costs. This applies especially to long capillary transport paths which are understood as paths or trajectories of more than 5 mm. Furthermore, this measurement can accelerate the transport of the sample from the opening of the sample application in the test element to the detection site in the sample element. detection in the test elements in which the detection reaction is detected in an area defined exactly spatially in the detection element, for example, in the case of optical detection in an instrument or where it is intended to separate the area of detection. application of the sample and the detection zone, for example for reasons of hygiene of the instrument 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 limits the time to analyze a sample. In addition, such an arrangement achieves a more convenient operation for the user. The cover and the sensing element must be assembled such that both limit one against the other in the final test element, so that the liquid transport is not interrupted in the capillary at its contact site, for example by an unfavorable change of the capillary cross section which is understood to also include an interruption of a continuous boundary surface of the capillary. The dimensions of the detection element and the cover must be mutually equal for this purpose. If it is not possible to assemble the two components properly one close to each other, capillary contact can be achieved by subsequent sealing. It was surprisingly found that for a particularly preferred embodiment of the test carrier according to the invention, a flexible inert sheet can be mounted on the side of the cover facing the channel, capable of carrying out liquid transport by capillary action, which It extends over the full length of the roof, covers the entire width of the capillary channel and is at least partially enclosed between the opposite surfaces of the cover and the detection element, so that the capillary transport of the liquid does not break at the contact site between the detection element and the cover. The material and optionally the hydrophilizing coating of the sheet or sheet can essentially correspond to those described above for the carrier and cover. In this very especially preferred variant, the detection element and the cover are mounted as close to one another as possible. A preferred embodiment of the test element according to the invention can also contain an intermediate layer between the carrier on one side of the capillary channel and the sensing element, and optionally the cover on the opposite side which, like the aforementioned components, is involved in the formation of the active capillary channel. The length of the intermediate layer in the direction of capillary transport corresponds especially preferably to at least the length of the channel. The intermediate layer is expeditiously designed such that it determines the width and optionally the height of the channel capable of performing the active capillary transport. The intermediate layer preferably has a recess, for example a punched hole, which corresponds to the dimensions of width and height of an active capillary channel. The length of the gap is particularly preferably slightly greater than the length of the active capillary channel, so as to create a ventilation opening. In principle, the intermediate layer can be made of the same materials and optionally with the same coatings that constitute the carrier and / or the cover. However, it has proven to be particularly preferable to manufacture the middle layer of a double-sided adhesive tape or strip, since the intermediate layer can then also having the joint or joint function of the carrier and the detection element and optionally the cover. This connection can also be achieved in other forms, for example, by welding, heat sealing, for example with polyethylene, gluing with cold hardening adhesive or hot melt adhesive, or clamps. In addition to the aforementioned advantages of the test element according to the invention, it also has other merits. The spatial separation of the sample application site and the detection of the signal in conjunction with the dosing of the sample volume makes it possible for the sample material to be handled hygienically. Especially in the case of optical detections for example with the aid of a reflection photometer, the contamination of the instrument is largely discarded since the sample can for example be applied to a test element protruding from the instrument, whereby the The amount of sample required to determine the analyte is sucked into the capillary channel and automatically transported without additional measures to the detection zone of the test element located inside the instrument.

Furthermore, the test element according to the invention requires considerably less sample material than conventional test elements in a very particularly preferred embodiment. While the latter frequently require more than 12 μl of sample liquid, the minimum sample volume required for the test element according to the invention is considerably reduced to less than 10 μl, preferably less than 5 μl and particularly preferably from 3 to 4 μl of sample. This is achieved by optimizing the flow of the sample exactly to the site of determination, as well as by the thickness of the defined layer of the sample material under the detection zone. Especially in the case where the sample is blood, this can simplify the collection of the sample for the person being examined and above all be associated with less pain. A further subject of interest of the invention is the use of an analytical test element according to the invention, for the determination of an analyte in a liquid. In addition, the invention relates to a method for the determination of an analyte in a sample liquid, in particular a body fluid such as blood, plasma, serum, urine, saliva, sweat, with the aid of an analytical test element according to the invention. In this process, the liquid sample is first contacted with the test element at the edge of the application opening of the sample which is interrupted by the notch. The sample liquid is transported by the capillary forces inside the channel, which is capable of liquid transport by capillarity. In this process, the sample moistens the surface of the detection element that faces the channel and penetrates into the detection element. Optionally, a specific detection reaction of the analyte occurs between the sample and the reagents contained in the detection element, which can be observed visually or optically by means with apparatuses, preferably by means of reflection photometry, thus making it possible to obtain conclusions regarding the presence and optionally the amount of the analyte that is going to be determined. The invention is elucidated in more detail by Figures 1 to 6 and by the following examples.

Figure 1 shows a particularly preferred embodiment of the test element according to the invention. A schematic top view of the test element according to the invention is shown in Figure IA, in Figures IB to 1F showing each cross-sectional views along the lines A-A ', B-B', CC, D-D ', and EE' respectively. Figure 2 shows another particularly preferred embodiment of the test element according to the invention. A schematic top view of the test element according to the invention is shown in Figure 2A. Figures 2B to 2F each show cross-sectional views along the lines A-A ', B-B', C-C, D-D ', and E-E' respectively. Figure 3 also shows a particularly preferred embodiment of the test carrier according to the invention. A top view of the test element is shown in Figure 3A. Figures 3B to 3F each show transverse views along the axes A-A ', B-B', C-C, D-D ', and E-E' respectively. Figure 4 also shows another particularly preferred embodiment of the test carrier of according to the invention. A schematic top view of the test element is shown in Figure 4A. Figures 4A to 4D each show cross-sectional views along the lines C-C, D-D ', and E-E' respectively. Figure 5 shows a particularly preferred embodiment of the test element according to the invention. A schematic top view of the test element according to the invention is shown in Figure 5A. Figures 5B to 5G each show cross-sectional views along lines A-A '(5B), B-B' (5C), C-C (5D and 5G), D-D '(5E), and E-E' (5F) respectively. Figure 6 shows an enlargement in perspective of the details of the area of application of the sample of the test carrier, according to the invention. The numbers in the Figures denote: 1. carrier 2. detection element 3. capillary channel 4. sample application opening 5. notch for sample application 6. ventilation opening cover sheet free space cover 9. intermediate layer 10 support sheet Various views (Figures IA to 1F) of a particularly preferred embodiment of the test element according to the invention are shown schematically in Figure 1. It is intended that the views shown give a three-dimensional impression of the test element according to the invention . The test element is composed of a carrier (1) which is shaped such that the area that is covered by the detection element (2) forms a capillary channel (3) together with this detection element. For example, a depression can be stamped or machined in the carrier. In the embodiment shown, a notch (5) is provided in the carrier (1) on the sample application opening (4) of the test element which makes it possible for the drop of liquid to be directly contacted with the capillary zone active (3) when the sample is applied. A ventilation opening (6) is located on the side of the capillary channel (3) which is opposite the opening (4) of application of the sample, which allows the air to escape when the capillary channel is filled with the sample liquid. The capillary zone (3) extends from the sample application opening (4) towards the opposite end of the detection element (2) and thus ensures a homogeneous distribution of the sample on the detection element (2). The opening (4) for application of the sample and the ventilation opening (6) limit the active capillary region (3) in the direction of capillary transport. When the test element shown is used, the opening (4) for application of the sample, of the test element, is brought, for example, in contact with a drop of blood located on the tip of a finger. In this process the drop of blood comes into contact with the exposed surface which is optionally hydrophilized and simultaneously with the capillary channel (3) through the notch (5) in the carrier (1). The capillary channel is filled by itself with sample until it is filled from the opening (4) for application of the sample to the ventilation opening (6). After this, the test carrier is removed from the finger of the patient, which ensures that only the sample that is present in the capillary channel (3) is available for the detection element (3). A particularly preferred additional embodiment is shown in Figure 2 as an alternative to the test element shown in Figure 1. The partial views in Figures 2A to 2F are intended to also give a spatial impression of the test element according to the invention. The test element shown contains a channel (3) capable of carrying out the liquid transport by capillary action, which is formed by an inert carrier (1), the detection element (2) and a cover (7). The cover (7) and the detection element (2) are mounted end to end in such a way that the capillary channel (3) extends without interruption from the sample application opening (4) towards the ventilation opening ( 6). The test element shown also contains a notch (5) which facilitates the penetration of the sample liquid into the capillary channel. Figure 3 shows schematically, based on the various views (Figure 3A to 3F) how the use of a sheet or cover sheet (8) of free space can reliably prevent the area active capillary (3) is broken at the contact site between the sensing element (2) and the cover (7) The sheet or sheet (8) of free space cover can also be provided with a hydrophilic surface on the side facing the capillary channel (3), which facilitates the capillary transport of a drop of liquid from the sample application opening (4) to the ventilation opening (6).

Such hydrophilization in the area of the notch (5) in the carrier (1) is particularly advantageous, since it accelerates the penetration of the sample material into the capillary channel. In contrast to the particularly preferred embodiments of the test carrier according to the invention shown in Figures 1 to 3, the geometry of the capillary channel (3) in the test element shown in Figure 4, which is also a particular embodiment preferred of the subject matter of the invention, is not determined by the shape of the carrier (1), but rather mainly by an intermediate layer (9). Figures 4A to 4D are in turn intended to give a three-dimensional impression of the construction of the test carrier. The intermediate layer (9) can be made of a double-sided adhesive tape. which, apart from determining the geometry of the capillary channel, also serves to join the other components that are involved in the formation of the active capillary zone (3), for example the carrier (1), the cover (7) and the element of detection (2). The cover (7) and the detection element (2) in the shown test element are again mounted so closely end to end that the capillary channel (3) extends without interruption of the notch (5) in the opening (4) of application of the sample towards the ventilation opening (6). The test element shown in the various views in Figures 5A to 5F is a very particularly preferred embodiment of the subject matter of the invention. It combines all the components and thus other advantages of the test elements shown in Figures 1 to 4. An intermediate layer (9) is mounted on a carrier (1) in the form of a double-sided adhesive tape. . In the area of the capillary channel (3) the intermediate layer (9) has a gap that determines the length and width of the channel (3). Its height is given by the thickness of the intermediate layer (9).

On the side of the capillary channel (3) which is opposite the carrier (1), a cover (7) adjacent to the detection element (3) is located. A sheet or cover sheet (8) of free space is provided to ensure capillary continuity. This can be hydrophilized to make possible a rapid transport of the sample from the opening (4) for application of the sample to the ventilation opening (6), which marks the opposite end of the capillary channel. An additional advantage of the hydrophilization is that a drop of sample liquid can be applied directly to a hydrophilic surface in the area of the notch (5) that is surrounded on several sides of boundary or boundary by the active capillary zone (3). This leads to a rapid penetration of the liquid droplet inside the test element. Figure 5G shows how the intermediate layer (9) can be covered by a sheet or protective sheet (10), in order to cover the exposed areas of the adhesive tape. However, in this case the ventilation opening (6) must not be covered. Finally an enlarged detail of a perspective view of the application area of the sample, of a particularly preferred embodiment of the test element according to the invention, is shown in Figure 6. The notch (5) in the-carrier (1) facilitates the penetration of a sample liquid from the opening (4). ) of application of the sample to the active capillary zone (3) which in the present case is formed by the carrier (1), the intermediate layer (9) and the cover (7). In addition to the shape shown, the notch may also have any other desired shape, which serves the purpose according to the invention.

Example 1 Fabrication of the test analytical element according to the invention A double-sided adhesive tape with a thickness of 100 μm is glued on a sheet of 350 μm thick polyethylene terephthalate (Melinex®, ICI, Frankfurt am Main, Germany) covered with an aluminum layer of 30 nm thickness , which was completely oxidized with water vapor. The sheet has a length of 25 mm and is 5 mm wide. A hollow in the form of a central notch of 1 mm wide of 2 mm in length is located on one of the short sides. The adhesive tape has a punched hole 2 mm wide and more than 15 mm long that defines the dimensions of the capillary channel. The length of the punched hole is selected to be slightly larger than the desired length of the active capillary channel, which is determined by its cover in order to ensure ventilation of the channel during filling with the sample liquid. A detection film 3 mm long and 5 mm wide is glued on the side of the adhesive tape that provides ventilation at a distance of 1 mm from the end of the punched hole. 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 layer 12 mm long and 5 mm wide is glued on the region of the adhesive tape which is still open between the notch-shaped recess and the detection film, so that the cover layer and the Detection film limit one with the other. The cover layer is composed of a sheet of polyethylene terephthalate 150 μm thick provided on one side with adhesive on which is glued a sheet of 6 μm thick polyethylene terephthalate (both from: Hostaphan®, Hoechst, Frankfurt am Main, Germany) coated with an oxidized aluminum layer 30 nm thick, on the side facing the capillary channel. In this case the thinner sheet extends approximately 500 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 protruding end of the thinner sheet is placed between the detection element and the thicker sheet of the cover layer. In order to cover areas of the adhesive sheet that are still exposed, they are covered with a Melinex® sheet of 175 μm thickness, however without 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.

Example 2 Measurement of blood glucose concentration with the help of the test element of example 1 A drop of the sample liquid is placed on the sample application site of the test element of Example 1. The capillary of the sample element • Test is automatically filled with the sample in about 2 seconds. If the glucose is present in the sample, a development of color in the detection film is visible after a few seconds. The end point of the reaction is reached after approximately 30 to 35 seconds. The color obtained can be correlated with the glucose concentration of the sample and either evaluated visually or by reflection photometry.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (14)

RE IVINDICAC IONS Having described the invention as above, the content of the following claims is claimed as property:

1. An analytical test element for the determination of an analyte in a liquid containing an inert carrier, a detection element and a channel capable of carrying out liquid transport by capillary action, which has a sample application opening at one end and a ventilation opening at the other end of the channel, capable of carrying out the liquid transport by capillarity, characterized in that the channel capable of carrying out the liquid transport by capillarity is formed at least partially by the carrier and the detection element and extends in the direction of capillary transport from the sample application opening towards at least the edge of the detection element that is closest to the ventilation opening and wherein a notch is located on one of the surfaces forming the channel capable of carry out liquid transport by capillarity, at the edge of the element of test that forms the application opening of the sample, so that one side of the edge of the test element forming the sample application opening is at least partially discontinuous and the surface opposite the notch is exposed.

2. The analytical test element according to claim 1, characterized in that at least one of the surfaces forming the internal surface of the channel capable of carrying out the capillary transport of the liquid is hydrophilized.

3. The analytical test element according to claim 2, characterized in that the exposed surface opposite the notch is hydrophilized.

4. The analytical test element according to any of claims 2 or 3, characterized in that the hydrophilization is achieved by the use of a hydrophilic material or by coating a hydrophilic material with a hydrophilic layer.

5. The analytical test element according to claim 4, characterized in that a layer of oxidized aluminum is used for hydrophilization.

6. The analytical test element according to any of claims 1 to 5, characterized in that the detection element contains all the reagents necessary for the detection reaction of the target analyte in the sample, as well as optional auxiliary substances.

7. The analytical test element according to any of claims 1 to 6, characterized in that the detection element acts as a filter for the particulate components of the sample.

8. The analytical test element according to any of claims 1 to 7, characterized in that the channel capable of carrying out liquid transport by capillary action is at least partially formed by the carrier, an inert cover and the detection element, in wherein the cover and the sensing element are located on the side of the channel that is opposite the carrier, and are arranged adjacent to each other, in such a way that the cover is located on the side facing the application opening of the sample.

9. The analytical test element according to claim 8, characterized in that the detection element and the cover limit one with the other, so that the capillary transport of the liquid is not interrupted at the contact point of the detection element and the cover .

10. The analytical test element according to claim 9, characterized in that a flexible, inert sheet or sheet is mounted on the side of the cover facing the channel capable of carrying out the capillary transport of the liquid extending over the length complete cover, covers the full width of the capillary channel and is at least partially enclosed between the opposite surfaces of the cover and the sensing element, so that the capillary transport of the liquid is not breaks at the contact site between the detection element and the cover.

11. The analytical test element according to any of claims 1 to 10, characterized in that an intermediate layer is present between the carrier and the detection element, and optionally the cover that also participates in the formation of the channel capable of carrying out the transport capillary fluid.

12. The analytical test element according to claim 11, characterized in that the intermediate layer further serves to join the carrier and the detection element and optionally the cover.

13. The use of an analytical test element according to any of claims 1 to 12, for the determination of an analyte in a liquid.

14. A method for the determination of an analyte in a liquid sample, with the help of an analytical test element in accordance with any of claims 1 to 12, characterized in that the liquid sample is brought into contact with the test element at the edge of the sample application opening which is interrupted by the notch, and is transported by the capillary forces within of the channel that is able to carry out the capillary transport of the liquid, in this process the sample moistens the surface of the detection element that faces the channel and penetrates inside it and optionally a specific detection reaction of the analyte occurs with the reagents contained in the detection element that can be observed visually or optically by means of apparatuses, preferably by means of reflection photometry, thus making it possible to obtain conclusions regarding the presence and optionally the quantity of the analyte to be determined. SUMMARY OF THE INVENTION The invention relates to an analytical test element for the determination of an analyte in a liquid containing an inert carrier, a detection element and a channel capable of carrying out the capillary transport of the liquid having an opening for application of the sample in an end and a vent opening at the other end of the channel capable of carrying out the capillary transport of the liquid, wherein the channel capable of carrying out the capillary transport of the liquid is formed at least partially by the carrier and the detection element, and extends in the direction of capillary transport from the sample application opening at least towards the edge of the detection test element that is closest to the ventilation opening, and wherein a notch is located in one of the surfaces forming the channel capable of carrying out the capillary transport of the liquid at the edge of the test element, forming the application opening of the The sample, so that one side of the edge of the test element forming the sample application opening, is at least partially discontinuous and the surface opposite the notch is exposed. This also refers to the use of the analytical test element for the determination of an analyte in a liquid, as well as a method for the determination of an analyte in a liquid sample, with the help of the analytical test element.