HK1225593B - Method for producing an analytical magazine - Google Patents

Description

Method for producing analysis box

This application is a divisional application of the prior application filed by the applicant on February 12, 2010, which entered the Chinese national phase on August 19, 2011, and has Chinese application number 201080008521.1 (international application number: PCT/EP2010/000864).

Field of the Invention

The present invention relates to a method for producing an analytical chamber designed to receive a plurality of analytical aids. The present invention also relates to an analytical chamber. Such analytical chambers are used, in particular, in medical diagnostics for the qualitative or quantitative detection of one or more analytes in body fluids. For example, the analytes may be metabolites, such as blood glucose.

Background Art

In the field of diagnostics, it is often necessary to obtain body fluid samples, in particular blood samples or interstitial fluid samples, in order to be able to detect their contents, in particular specific analytes. Examples of such analytes are blood glucose, coagulation parameters, triglycerides, lactate, etc. Based on the detected concentration, for example, a corresponding treatment can then be decided.

In these diagnostic methods, one or more analytical aids are typically used to obtain and/or analyze a body fluid sample. These analytical aids may include, for example, a lancet, i.e., an element designed to create an opening in the subject's skin through which the body fluid can be removed. An example of such a lancet is described in WO 01/36010 A1.

Furthermore, the analytical aid may include one or more test elements comprising test chemicals designed to alter a specific detectable property in response to the analyte to be detected. For example, the analyte may comprise an electrochemically detectable property or a variation thereof and/or an optically detectable property. For such test chemicals, reference is also made to the prior art, for example, J. Hönes et al., Diabetes Technology & Therapeutics, Vol. 10, Appendix 1, 2008, pp. 10-26.

In addition, integrated test elements are also known, which are used for the purpose of producing body fluid samples and for transporting samples and (optionally) even for the purpose of qualitatively and/or quantitatively analyzing the samples. An example of such an analytical aid is a so-called microsampler, in which a puncture or incision is made by a lancet to collect and transport the sample to one or more test fields containing the test chemical. The test field can be arranged separately from the lancet, but can also be an integral part of the lancet itself. Systems of this type (described, for example, in US 2004/0193202A1, US 2008/0249435A1 or WO03/009759A1) are particularly user-friendly due to their high degree of integration.

However, one technical challenge in providing analytical systems and analytical aids is to provide them in large quantities under suitable conditions. Therefore, they usually have to be provided in such a way that the analytical aids are stored under sterile conditions, for example by means of corresponding seals. However, at the same time, the seals must not impair the quality of the analytical aids and must not make them difficult to use. For this purpose, the analytical aids are usually provided in corresponding boxes (magazines) (hereinafter also referred to as analytical boxes). For such systems (i.e., the purpose of which is to perform, for example, fully automatic capillary blood analysis without the need for intervention by the test subject), multiple lancets and multiple test elements (e.g., each containing one or more test chemicals) can be present in, for example, a box of this type.

A variety of different analytical boxes are known from the prior art. In principle, independent of the type of analytical aid, a distinction can be made between three main types of boxes, namely round boxes (e.g. in the form of drums and/or trays), linear boxes (e.g. in the form of stacking boxes, Z-boxes, etc.) and belt boxes, in which the analytical aids are arranged on a belt or on some other form of at least partially flexible carrier. These types of boxes can in principle also be used or modified in the context of the invention described below. In the prior art, round boxes are described, for example, in US 2006/0008389, US 2007/0292314, US 2006/0184064, US 2003/0212347 or US 2002/0087056. Linear boxes are described, for example, in US 6036924 or US 2003/0191415. Belt boxes are described, for example, in US 2002/0188224, US 2008/0103415, EP 1360935 A1 or DE 19819407 A1.

Analytical kits, in particular those with integrated analytical aids (having both lancet and test element functions), often have drawbacks in ensuring freedom from contamination and sterility. For example, one difficulty is that each set of lancet and test element must be kept separate from the other sets, since at least the lancet must remain sterile until it is immediately used.

However, these requirements, in turn, increase the cost of producing the analysis box. Due to the different properties of the lancet and the test element, their origin histories are extremely different. As a result, these elements of the system are usually provided in different forms for the assembly of the entire analysis box. These requirements mean that in practice, the analysis box usually has to be filled individually. Thus, for example, the lancet and the test element must be inserted individually into the analysis box and/or into a single chamber of the analysis box, which usually requires high equipment costs. In this regard, an exception is a system consisting solely of a tape-based system, in which the individual elements can first be applied individually to a carrier tape and wound onto the carrier tape before being filled into the box. In any case, however, the individual analytical aids must be applied piece by piece, which requires considerable production costs.

Summary of the Invention

Therefore, one object of the present invention is to provide a method and an apparatus which at least substantially avoid the disadvantages of the known methods and apparatuses. In particular, the proposed method aims to enable the production of an analytical box in which the equipment costs and thus the overall costs of producing the analytical box can be significantly reduced without thereby impairing the quality of the analytical box and/or the analytical aid.

This object is achieved by a method and apparatus comprising the features of the independent claims. Advantageous developments of the invention, which can be realized individually or in combination, are presented in the dependent claims. A method for producing an analytical box and an analytical box are provided, wherein the analytical box can be produced specifically using the production method of the present invention. Therefore, with respect to possible developments of the analytical box and various aspects of the analytical box, reference can be made to the description of the method, and vice versa.

The analysis box is designed to accommodate multiple analytical aids in multiple chambers. Therefore, an analysis box should be understood to mean a device that can be handled as a unit, which may, for example, have a common housing, and which can generally be used in medical technology. In this context, analysis should generally be understood to mean the possibility of qualitatively and/or quantitatively detecting at least one analyte and/or measuring at least one other detectable property. In this regard, reference may be made, for example, to the above description. In particular, analysis can therefore be understood to mean a diagnostic property, i.e., a property for determining at least one property of the body and/or a component of the body of a test subject. The analysis box can therefore be used in an analysis system, which thus becomes the analysis system of the present invention. By way of example, such a system can be a measuring device that can qualitatively and/or quantitatively detect at least one analyte, such as at least one metabolite, in a test subject's body fluids. By way of example, these systems can be blood glucose measuring devices.

In the context of the present invention, an analytical aid is generally understood to mean an aid that can be used in a supportive manner in the context of the above-mentioned analytical functions. In particular, the analytical aid can be a medical and/or diagnostic aid, in particular an aid designed for the qualitative and/or quantitative detection of at least one analyte, for example one or more of the above-mentioned analytes, in a body fluid (e.g. blood, interstitial fluid, urine or similar body fluid) of a test subject. In particular, the analytical aid can be configured as a disposable aid (single-use), i.e., intended for single use. The analytical aid can therefore comprise, for example, at least one lancet, i.e., an element designed to produce at least one opening in the skin of a test subject (e.g., the earlobe, finger pad or forearm of the test subject). By way of example, the lancet can comprise one or more puncturing elements having a needle tip and/or a pointed end. Alternatively or in addition, other sharp-edged elements, such as blades, sharp-edged tips, etc., can also be used. The lancet can, for example, be produced from a rod-type starting material, for example in the form of a needle-type lancet. However, the use of one or more lancets produced from plate-type material, in particular sheet metal, is particularly preferred in the context of the present invention. This will be explained in more detail below.

As an alternative to or in addition to the lancet, the analytical aid can also each contain one or more test elements. These test elements have at least one test chemical that is designed to change at least one measurable property in the presence of at least one analyte to be detected. The test chemical (which is designed to indicate the presence or its purpose includes identifying the absence of at least one analyte by itself or by interaction with the analyte and/or another auxiliary material) can be configured in different ways. In this regard, reference can also be made to, for example, the paper by J. Hönes et al. mentioned above. In addition, reference can be made to, for example, WO 2007/012494A1, which describes specific moisture-stable test chemicals. In the context of the present invention, the test chemicals mentioned in these documents can also be used alone or in combination. In particular, in the case of detecting a specific reaction with at least one analyte, a highly specific test chemical can be used. The at least one measurable property (the measurement of which enables the qualitative or quantitative detection of at least one analyte) can include, for example, at least one electrochemical property and/or at least one optical property. By way of example, as will be explained in more detail below, the test chemical may be embodied in the form of one or more test fields.

Furthermore, the analytical aids can also be configured in such a way that they are configured as a combined test element. Thus, for example, a combined test element can be used comprising at least one lancet and at least one test chemical, wherein the test chemical can be designed to change at least one measurable property in the presence of at least one analyte to be detected. For example, the test element can be directly integrated into the lancet. Thus, for example, the test chemical can collect at the end of the lancet and/or cover part of the lancet. However, alternatively or in addition, the lancet and test element can also be formed separately, for example, with at least one lancet and at least one test element per chamber of the analytical chamber. These parts of the analytical aid can also be separately operable, so that, for example, the lancet can be operated by a system actuator to perform a puncture and/or collection activity, while the test element remains unchanged, for example, in the chamber. Thus, for example, the system can be designed to perform the puncture and/or collection activities by means of at least one lancet and/or a capillary element optionally contained in the lancet, such that bodily fluid can be collected directly by the lancet during the puncture and/or sampling activities. In this case, a puncture can first be made in the skin of the subject, the bodily fluid collected, and the latter can then be transferred to the test element, for example, during the backward movement of the lancet, back into the chamber. Other configurations are also possible.

As an alternative to or in addition to the lancet and/or test element, the analytical aid may include further elements for analytical purposes. Thus, for example, it may include a transfer element and/or a collecting element that serves the purpose of collecting and/or transferring body fluids. For example, such a transfer element and/or collecting element may be used to collect blood and/or interstitial fluid from the skin of a test subject and/or a part of the test subject's body and/or a part on the test subject's skin and/or to transfer it to a test element, in particular to one or more test fields. Such transfer can, for example, be performed by a transport movement, using one or more transport elements that are configured in a movable manner and can collect and transfer a certain amount of body fluid sample. Alternatively or in addition, other transfer elements and/or collecting elements may be provided, such as capillaries and/or elements with capillary action. For example, closed capillaries or capillary channels, in particular capillary gaps, may be included in this case. An analytical aid that combines at least one lancet function and at least one capillary function is hereinafter also referred to as a microsampler.

As mentioned above, it is particularly preferred that the analytical aids are received in the chambers in such a way that exactly one analytical aid is received in each chamber. If the analytical aids themselves each contain a plurality of analytical sub-assistants, such as, for example, at least one lancet and at least one test element, then, for example, at least one test element and/or at least one lancet can be provided for a single, shared test (e.g., a single body fluid collection and/or body fluid analysis) to be received in a common chamber. This embodiment (in which each chamber receives an analytical aid, for example, at least one sub-assistant in the form of a test element and/or at least one sub-assistant in the form of a lancet) can be implemented, for example, in the case of a disc-shaped case or in the case of another embodiment (e.g., a stick-shaped case). As an alternative to the embodiment in which each analytical aid is received in a separate chamber, an embodiment in which a plurality of analytical aids of the same or different types are received in one chamber is also possible. An example of such a configuration is a belt-type box in which a good winding with a plurality of unused analytical aids is received in a first chamber and a poor winding with a plurality of used analytical aids is received in a second chamber. Other configurations are also possible.

In this context, a chamber is generally understood to mean an element having at least one at least partially enclosed cavity in which the analytical aid can be received. In this context, the cavity may also include one or more openings, as will be explained in more detail below. The chamber may also include one or more subchambers and one or more chamber walls that contribute to the interior space of the chamber.

The method for producing the analytical box comprises the following method steps. The method steps are preferably, but not necessarily, performed in the order presented. Other orders are also possible in principle. In addition, the method may include additional method steps not described. In addition, individual or multiple method steps may be repeated and/or performed in parallel and/or in an overlapping manner.

In a first method step, at least one first component of the analytical box is provided. The first component may comprise, for example, a housing component of the analytical box. For example, the component may be configured so that it is at least partially rigid. The provision method may be manual and/or automated. In this case, the first component has a plurality of sockets. For example, each of the aforementioned chambers may be provided with at least one socket, the at least one socket being assigned to the respective chamber. The sockets may comprise, for example, recesses, grooves, slots, paths, walls, projections, or similar elements that are capable of at least partially securing the analytical aid and/or parts of the analytical aid and/or preventing changes in the position and/or orientation of the analytical aid within predetermined limits. The sockets may also be a component of a subsequent chamber, for example, in the form of a subchamber, such as an upwardly open subchamber, or a chamber that is closed at a subsequent processing stage, in particular by means of another component, such as a cover. For example, the sockets may comprise recesses that subsequently form part of the chamber wall.

In a further method step, a plurality of analytical aids of the aforementioned type are provided. If the analytical aids received in each chamber each consist of different analytical sub-auxiliaries, these sub-auxiliaries can be provided in different method steps and/or all or some of the further sub-auxiliaries can also be provided together. The provision method can furthermore be carried out, for example, manually or fully or partially automatically.

However, unlike the prior art, the production method according to the first aspect of the present invention provides for the analytical aids not to be provided one by one and inserted into the box, but rather preferably all at once. In this case, all chambers can be filled with the analytical aids and/or, if the analytical aids themselves consist of multiple sub-auxiliaries, with the sub-auxiliaries simultaneously (which is equivalent). At the very least, multiple chambers, preferably all chambers, should be filled simultaneously with at least one type of analytical aid and/or sub-auxiliary. This can significantly reduce assembly costs.

Therefore, it is proposed that the analytical aids provided (or the sub-aids, in the same sense) are connected to each other by at least one retaining element and are preferably oriented relative to each other. The providing method can therefore be carried out in such a connection, preferably in an oriented form. In this case, a retaining element should generally be understood to mean an element that is suitable for providing a plurality of analytical aids together. Examples of such retaining elements are described in more detail below. In this case, the orientation of the analytical aids relative to each other can be understood to mean, for example, at least substantially fixed absolute positions and/or spatial orientations (e.g., angular orientations) of the analytical aids relative to each other. In this case, slight deviations are also possible, but they can be within a predetermined tolerance range, for example, they can be predetermined, for example, by the tolerances for receiving the analytical aids in the chamber.

In a further method step, the analytical aid, or an equivalent sub-auxiliary in the context of the present invention, is introduced into the receptacle. This introduction method can be performed, for example, by simple insertion, plugging, etc., and can also be performed manually or at least partially automatically. In this case, in a manner corresponding to the provision of multiple analytical aids, the introduction method can be performed at least substantially simultaneously for multiple, or preferably all, chambers, i.e., substantially simultaneously in one method step for all of the analytical aids or sub-auxiliary provided in the preceding step.

In another method step, the analytical auxiliary is then separated from the retaining element. The separation method can preferably be carried out completely or partially after and/or during the method of introducing the sub-auxiliary part into the socket. In this case, separation during the introduction method should be understood to mean separation in one or more method steps, which are necessary for being able to introduce the sub-auxiliary part into the socket. The production of the sub-auxiliary part can be basically finished at this point in time so that they can still be connected at this point in time. Therefore, the separation can be carried out just before and/or during these method steps and/or at the time point when the sub-auxiliary part has been partially introduced into the socket and/or at the time point when the sub-auxiliary part has been completely introduced into the socket. However, optionally or in addition, the complete or partial separation can also be carried out during and/or before the method of being introduced into the socket. In this case, a fixing device can be used, for example, the purpose is to temporarily fix the analytical auxiliary and/or sub-auxiliary part after the separation of the analytical auxiliary and/or sub-auxiliary part and before introducing them into the socket. The separation method can be carried out using conventional separation methods, for example, in a manner in which the analytical aid or sub-adjuvant is connected to a retaining element. For example, a breaking method, a cutting method (in particular a laser cutting method and/or a mechanical cutting method), a punching method, a chemical separation method, or a combination of the aforementioned and/or other separation methods can be used for this separation method, as will be explained in more detail below.

The method has numerous advantages compared to known methods. A major advantage is the considerable saving in production costs. Thus, for example, an analytical box (in which the analytical aids are preferably arranged separately from one another in different chambers) can be produced at extremely low cost. The analytical aids can, for example, be operated completely or partially independently of one another, i.e., the analytical aids can be received independently in the other chambers, unlike analytical aids that are received on a tape, for example. In addition, the costs of filling the individual chambers with analytical aids can be reduced considerably by the method, since the individual chambers no longer need to be filled individually. Thus, groups of chambers and/or all chambers can now be filled simultaneously. These advantages can be achieved without the associated disadvantages regarding quality losses, since the sterilization of the individual chambers can be ensured, for example, by corresponding seals, which are described in more detail below.

The described method can advantageously be developed in various ways. Therefore, the at least one first component of the analytical box is preferably configured as a substantially rigid component, i.e., as a component that does not experience any significant bending and/or other deformation, at least under the effect of its own weight. Therefore, the aforementioned sockets are preferably arranged in a fixed predetermined orientation and/or fixed position relative to one another. Therefore, as described above, the at least one retaining element may also preferably be configured in a substantially rigid manner.

In principle, the analysis box can contain a plurality of chambers arranged relative to each other in any desired manner. Thus, by way of example, rod-shaped boxes, boxes connected in series, Z-shaped boxes, etc. are conceivable. In particular, reference may be made to boxes of the types described above. It is particularly preferred that the analysis box has a disc shape, in particular a circular disc and/or an annular disc form. Thus, the chambers and/or the sockets can be arranged in a disc-shaped analysis box that is essentially oriented radially. By way of example, the analysis box can be configured in the form of a circular disc and/or an annular disc in such a way that a sampling activity can be carried out with the aid of the analysis and/or with at least one analytical aid received in each chamber and/or with at least one sub-aid. A sampling activity can be understood to mean, for example, a puncture activity and/or a collection activity for producing and/or collecting and/or transferring a body fluid sample and/or a part of a body fluid sample. Thus, such a sampling activity can be carried out, for example, in a radial direction. For this purpose, in the case of an annular disk, at least one opening can be provided, for example, within the housing. For example, at least one actuator of the analysis system and/or a portion of the actuator system can be inserted into the at least one opening, thereby enabling coupling to the analytical aids and/or sub-aids in each chamber (e.g., consecutively) and sampling. For coupling, reference can be made, for example, to the aforementioned prior art, such as WO 02/36010 A1. However, other types of coupling are also possible in principle. Exemplary embodiments of disk-shaped and/or annular disk-shaped housings are described in more detail below.

Thus, the at least one retaining element can also be adapted to the construction of the box. Thus, by way of example, in the case of a rod-type box, the retaining element can be configured to provide analytical aids arranged parallel to one another. In the case of a disc-shaped and/or annular analytical box, the retaining element can be configured, for example, to provide analytical aids that are oriented radially with respect to one another. By way of example, as described above, the analytical aids can comprise lancets and/or microsamplers as analytical aids and/or sub-aids, which can be provided, for example, by means of retaining elements that are oriented radially with respect to one another (i.e., in a radial orientation with respect to one another, e.g., arranged equidistantly). This provision method can be carried out, for example, in such a way that the tips of the lancets and/or microsamplers in each case point radially outwards.

In principle, the retaining element can be of quite complex construction and, for example, can comprise multiple sub-elements. Thus, the retaining element can be configured for a variety of filling methods. However, it is particularly preferred for the retaining element to be configured as a disposable retaining element, configured for only one or a limited number of filling methods. Therefore, it is particularly preferred for the retaining element to be configured quite simply, for example, as a one-piece retaining element. In particular, the analytical aid can be made entirely or partially from the base material of the retaining element. For example, this can be a metal base material, from which analytical aids in the form of lancets and/or microsamplers are manufactured in one or more manufacturing steps, thus creating the actual retaining element and the analytical aid or parts thereof. In principle, any desired manufacturing method can be used, such as mechanical and/or chemical methods, such as etching and/or cutting and/or laser methods. The retaining element can, for example, comprise at least one simple disk, i.e., a flat, essentially plate-like element whose side surfaces extend several times its thickness. For example, the disk-shaped element can comprise a simple metal disk. By way of example, the metal disk can be configured as a substantially rectangular and/or circular metal disk, which is particularly preferred when the analytical housing is a circular analytical housing, in particular when the analytical aid is radially oriented. By way of example, the analytical aid can be made entirely or partially of the disk, thus forming the analytical aid, with the remaining disk forming the retaining element or a portion thereof.

The analytical aid can be manufactured integrally with the retaining element. This is particularly preferred when the retaining element is configured as a disposable retaining element. In this case, the analytical aid can be configured completely or partially integrally with the retaining element. If each analytical aid has multiple sub-auxiliaries, one, multiple, or all of the sub-auxiliaries can be configured integrally with the retaining element.

The one-piece construction can be carried out, for example, in such a way that the analytical aid or (this means the same thing) sub-aid can be made from a blank element (Roh-Element) of the retaining element in one or more production steps. The blank element can, for example, further comprise a plate-shaped element, in particular a disk-shaped element such as a metal disk. The method for manufacturing the analytical aid or sub-aid can, for example, be manufactured by known manufacturing steps, in particular etching methods. Therefore, the lancet can also be manufactured specifically from the blank element of the retaining element, for example by means of one or more etching methods. The use of at least one etching method is also advantageous for other analytical aids or sub-aids. However, as an alternative to or in addition to the etching method, other types of production methods can also be used, in particular production methods due to which the analytical aid or sub-aid is manufactured from a blank element, such as cutting methods, stamping methods, etc.

Another very effective form of holding element is a holding element in the form of a strip or comprising strips, which contain a variety of arrangements of analytical aids and/or sub-aids, such as lancets and/or microsamplers. This allows, for example, roll-to-roll processing.

As described above, the method for separating the analytical aid or sub-aid from the retaining element can be carried out using one or more corresponding separation methods. As described above, a disconnection method is particularly preferred. For this disconnection method, as well as other types of separation methods, it is preferred to provide at least one connection between the analytical aid and the retaining element before separating the analytical aid from the retaining element. The connection can be particularly suitable for at least one separation method. By way of example, the connection can include at least one bridge and/or at least one other connecting element, which is preferably also integrally configured with the retaining element and/or the analytical aid. The connection can preferably include at least one desired disconnection point, particularly when using at least one disconnection method. The desired disconnection point can include, for example, a tapered portion and/or a scored portion of the connecting element and/or some other type of reduced material thickness. A targeted reduction in material strength or embrittlement in the area of the desired disconnection point is also possible, for example, by the targeted generation of glass hardness in an otherwise hard elastic steel (e.g., using a laser). Preferably, the connection is configured in such a way that, after the one or more analytical aids have been separated from the retaining element, substantially no undesirable residues (which could subsequently impair the function of the analytical aid) remain on the analytical aid, such as a lancet. The aforementioned tapered portion and/or the desired disconnection position can thus ensure, for example, that a clean disconnection occurs without impairing the sliding of the lancet and/or other analytical aids and/or sub-aids used for sampling activities. In particular, the desired disconnection position can be configured in such a way that it is offset inwards from the edge of the analytical aid, for example, to the middle of the analytical aid. This has the advantage that, optionally when the analytical aid is separated from the retaining element, any remaining disconnection residues do not hinder the sliding of the analytical aid in the chamber.

Generally, it is preferred that the chamber and/or the analytical aid are configured in such a way that the analytical aid is mounted in a manner that allows them to be fully or partially moved for sampling activities. In this case, the movable mounting can be performed for the entire analytical aid or only for one or more sub-assistances of the analytical aid (e.g. one or more lancets), while the test element can be fixedly held in the chamber and/or elsewhere in the analytical box, for example. The movable mounting can be performed, for example, in such a way that the analytical aid (as will be explained in more detail below) is fully or partially fixed while it is stored in the chamber of the box, whereas this fixation is released and/or overcome for sampling activities. As described above, the sampling activity can be performed, for example, by an analytical system that interacts with and/or contains the analytical box, such as a measuring device, which, for example, can have one or more corresponding actuators. These actuators can be designed to interact with the analytical aid in the chamber and/or with the sub-assistances of the analytical aid and to couple them, preferably individually. These actuators (which may also comprise parts of the box itself) may comprise, for example, corresponding coupling elements and/or sampling elements, by means of which the coupling and/or sampling activities can be carried out, such as one or more clamps, hooks, pistons, slides or combinations of said elements and/or other elements. Preferably, the sampling activity and/or the system can be designed in such a way that the sampling activity comprises a movement towards the skin of the test subject, optionally including a puncture activity in the skin of the test subject, followed by a backward movement away from the skin of the test subject. By way of example, the backward movement may comprise a replacement in the box, i.e. a movement during which at least one analytical auxiliary or sub-auxiliary is completely or partially received again in this chamber and/or another chamber of the analytical box. In this way, a completely satisfactory disposal of the analytical auxiliary from a hygienic point of view can be ensured.

As mentioned above, the method may include further method steps. Thus, for example, the analytical box may include further components in addition to the first component. However, it is particularly preferred that, in addition to the analytical aid and the at least one first component, the number of further components is as small as possible, for example, one, two, three, or preferably a maximum of four further components. This ensures that the analytical box can be produced in the simplest manner.

The method may specifically include at least one further method step in which at least one second component is applied. The second component may, for example, be a component of the analytical box housing. The second component may, for example, be applied directly or indirectly to at least one first component. Thus, the first component may be configured, for example, as a base component of the housing, as described above, whereas the second component may be configured, for example, as a covering component of the housing, or vice versa. Other extensions are also possible. The second component may be applied to the first component (for example, with the insertion of another component). In this case, the first component and the second component may be connected to each other by one or more connections, for example, force locking and/or form locking and/or material connection. Particularly preferred is a material connection, for example in the form of an adhesive bonded connection and/or a welded connection, in particular by laser welding and/or ultrasonic welding.

During the step of applying at least one second component, in particular applying it to the first component, the described chambers can, for example, be formed or further formed. These chambers can be created, for example, by the aforementioned sockets in the first component forming part of the chamber walls, while components of the second component form other part of the chamber walls. The second component can therefore also include, for example, recesses and/or similar chamber components, which then form part of the chamber. The chambers, which are preferably formed or further formed by applying at least one second component, can still exist after the application of the second component in such a way that they are partially open, for example, having one or more openings, which will also be described in detail below. In particular, during the application of the at least one second component, the sockets of the first component containing the received analytical aids or sub-auxiliaries of analytical aids can be at least substantially closed. In this case, the term "at least substantially closed" should be understood to mean a process in which the spatial boundaries of the chamber are at least substantially defined. As described above, however, in this case, one or more openings remain, in particular in the chamber walls. For example, at least one sampling opening can be provided on a side of the case that is assigned to the test subject when the analysis case or analysis system is used, such as on the outer circumference of a disk-shaped and/or annular case. These sampling openings, for example, can provide at least one such sampling opening per chamber, allowing the analytical aid and/or sub-adjuvant to exit the chamber, for example, to perform the aforementioned sampling activity. Alternatively or in addition to the sampling openings, actuator openings can be provided, such as at least one actuator opening per chamber. These actuator openings can be configured to allow an actuator and/or a portion of an actuator, particularly an actuator of the analysis system, to fully or partially enter the chamber to activate at least one analytical aid for sampling, or to facilitate sampling by the analytical aid or sub-adjuvant. These actuator openings can be provided, for example, on the side opposite the sampling openings, such as on the side of the case facing away from the test subject's skin surface, such as on the inner circumference of an annular disk. However, alternatively or additionally, the actuator openings can also be provided on a side surface of the chamber, depending on the type of coupling of the actuator to the analytical aid.

Alternatively or in addition to the at least one sampling opening and/or the at least one actuator opening, a measurement opening can also be provided. For example, at least one measurement opening can be provided in each chamber. These measurement openings allow, for example, measurements, such as optical and/or electrical measurements, to be performed on an optional test element that is fully or partially received in the chamber. For example, the measurement opening can include a measurement window, which can be configured as an opening or sealed with a transparent material, for example, to enable measurement of changes in optical properties, such as color changes, at one or more test fields.

As an alternative to or in addition to the above-mentioned type of openings, test element openings can also be provided, for example, preferably at least one test element opening per chamber. Through these test element openings, one or more test elements can be introduced completely or partially into the chamber. As described in more detail below, this can be done, for example, in such a way that one or more test element fields are applied to the test element openings from the outside and/or introduced into the test element openings from at least part of the test element, i.e. parts or regions of the test field are allocated to the interior of the chamber. These regions (which are therefore received inside the chamber) can therefore form sub-auxiliaries in the form of test elements which are separated in themselves, which can be allocated to the chambers respectively. This will be described in more detail below.

During the method of applying at least one second component, in particular, an analytical aid in the chamber, in particular an analytical aid in the receptacle of the first component, can be protected at least substantially from unintentional changes of position, in particular against sliding and/or rotation. This can be done, for example, by applying forces and/or stresses to the aid, which can be ensured, for example, by means of a corresponding shaping of the first and/or second component. The forces and/or stresses and/or deformations can bring about, for example, a deflection of a flexible aid, such as a flexible lancet and/or a microsampler, in particular a metal lancet in the form of a flat lancet. This stress and/or force can, for example, be canceled during the sampling activity and/or overcome by a transmission, for example by a transmission that provides a higher force and/or a higher stress.

The method of the present invention may further comprise a method step in which at least one test chemical is applied. The test chemical may be applied, for example, to the first component and/or the second component and/or a third component not yet mentioned, in particular to a carrier. The method for applying the test chemical may, for example, be performed after the method for applying the second component, but may alternatively or additionally be performed in an upstream method step and/or simultaneously. As described above, the test chemical is designed to change at least one measurable property, for example an optically and/or electrically measurable property, in the presence of at least one analyte to be detected. In this regard, reference may be made to the above description for details.

In this case, the method of applying the test chemical is carried out in such a way that, in each case, at least one area of the test chemical is allocated to the inside of the chamber. For example, in each case, one or more areas of the test chemical can be strictly allocated to a chamber in each case. This can be done, for example, as described above, in such a way that each chamber, for example, has at least one test element opening in its chamber wall, to which the test chemical is applied from the outside and/or the test chemical is at least partially introduced into the opening, so that in each case, at least one area is allocated to the interior space of each chamber. In this way, one or more test fields can be formed in each case by the area of the test chemical (which is allocated to a chamber in each case), which can be a component of an analysis auxiliary and which can specifically form one or more sub-auxiliaries of the analysis auxiliary. In this case, the purpose of the test chemical area (which is allocated to the interior space of the chamber) is preferably to be accessible from the inside of the chamber.

The method of applying at least one test chemical can be performed, for example, by means of at least one carrier. Thus, for example, a carrier in the form of one or more disks and/or membranes and/or other components and/or structural elements can be provided, to which the test chemical is applied, and in such a manner that the test chemical is distributed into the chamber. The carrier can then be removed and/or can also remain, in whole or in part, as an integral part of the analytical chamber.

After applying the test chemical, it can optionally be covered, for example, by sealing it in a moisture-tight manner and/or receiving it in an analysis box. In this way, for example, non-moisture-stable test chemicals can also be used. However, when using moisture-stable test chemicals, such covering of the test chemical can also be completely omitted.

An analytical chamber can also be implemented in which a chamber contains an analytical aid, for example, comprising at least one lancet and at least one test element in the form of at least one test field. Thus, for example, during a sampling operation, a body fluid sample can be generated and/or collected by means of at least one lancet and/or a collection element or transfer element and transferred into the chamber. This transfer can occur, for example, by means of a backward movement as part of the sampling operation, as described above, wherein a portion of the sample (which has already been collected, for example, on the lancet and/or collection element and/or transfer element) is transferred into the interior of the chamber. Alternatively or additionally, this collection and/or transfer can also occur, for example, by capillary action of at least one capillary element of the analytical aid, as described above, which in each case transfers the sample into the interior of the currently used chamber. This transfer can be configured in such a way that, during the transfer process, the collected sample is fully or partially transferred to at least one test element, in particular one or more test fields, such as at least one test field produced by the aforementioned method of applying a test chemical. For this purpose, an analysis system using the analysis box may also include one or more actuators designed to support the transfer of a sample from an analysis aid (e.g., a lancet and/or microsampler) to at least one test element, such as a test field. For example, an actuator may be provided that is inserted into the chamber and presses the sample-filled lancet and/or microsampler onto the test field.

A variant of the above-described method or test element box (in which the test chemical is configured such that at least one area of the test chemical is allocated to the interior of a chamber, particularly in the form of one or more test fields per chamber) can be specifically implemented such that the test chemical is applied jointly to multiple, preferably all, chambers. Thus, by way of example, at least one test chemical can be applied in the form of one or more test chemical fields, particularly one or more continuous test chemical fields. In this case, a test chemical field should be understood to mean an area coated with the test chemical, whether entirely or partially, and which may also include multiple non-adjacent sub-areas. This common test chemical field (which is provided jointly for multiple, or preferably all, chambers) can, in principle, take the form of a rectangular field, a circular field, or, in principle, any field shape. This test chemical field can be applied to, for example, the aforementioned carrier, such as a carrier film and/or some other structural element. The carrier can comprise, for example, a plastic, such as a plastic film, and/or a paper material and/or a ceramic material and/or a metal material, or a combination of these and/or other materials. In particular, a continuous and preferably integral carrier can be used in this case.

In particular, the test chemical field (which is particularly preferably used for a circular analysis box) can be configured in a circular or annular manner. Thus, as an example, at least one chemical ring can be provided, which has an annular carrier, preferably a continuous and especially one-piece carrier (e.g. a carrier ring), and at least one test chemical field, preferably a continuous test chemical field, applied thereon. However, as an alternative, test chemical discs and/or test chemical belts of different designs can also be provided, with corresponding design carriers, preferably continuous and/or one-piece carriers, and at least one test chemical field applied thereto. Other configurations are also possible, but they can be adapted to analysis boxes of respective forms. The purpose of the test chemical field is to provide a test chemical area for a plurality of chambers, preferably for all chambers at the same time, in particular for test fields for respective chambers. If each chamber provides a plurality of test fields with different test chemicals, then, as an example, for each type of test chemical, a separate test chemical field may be provided or applied for a plurality of or preferably all chambers. These different types of test chemical fields can be provided on separate carriers or on a shared carrier. Preferably, in the case of multiple test chemical fields and/or test chemical fields of multiple types, a common carrier, in particular an integrated carrier, is provided. In particular, the carrier can also be entirely covered with the test chemical, that is, the test chemical field is not interrupted for each chamber, but is formed integrally for multiple chambers, preferably for all chambers. However, as an alternative, a carrier that is not entirely coated with the test chemical can also be used. However, the carrier itself is preferably configured integrally, for example, as a one-piece carrier ring.

As mentioned above, the method can include further method steps, in particular method steps in which the chambers are completely or partially sealed, either individually, in groups, or all together. To this end, in at least one further method step, at least one seal can be applied to at least one opening of the chamber. If each chamber has multiple openings, such as the openings described above, these can be closed or sealed individually, in groups, or all together. In this case, the seal can also be applied, for example, in such a way that each type of opening is sealed simultaneously for multiple, or preferably all, chambers. In this case, sealing should generally be understood to mean a method of sealing an opening that at least substantially prevents environmental influences (particularly air humidity and/or pathogens) from entering the chamber, at least during the normal use period or storage period of the analytical box. In this way, for example, it can be ensured that the quality of the analytical aid remains constant over a predetermined storage period (e.g., a storage period of several months to several years).

The seal can be provided, for example, by at least one sealing element, preferably configured so as not to impair the respective function or intended use of the at least one opening. For example, the seal can be configured so that at least one sampling opening is opened for sampling by the analytical aid and/or another element of the analytical housing and/or another element of the analytical system, such as by puncturing and/or cutting. Thus, for example, at least one actuator opening can be configured so that it is opened during a sampling operation for actuator movement, such as by the actuator itself and/or another element of the analytical housing and/or another element of the analytical system. If at least one measurement opening is provided, the seal of this measurement opening can be configured, for example, so that it can be used for measurement without being covered. Alternatively or additionally, depending on the type of measurement, the seal can also be configured, for example, so that it can be used for optical measurements. For this purpose, the seal of at least one measurement opening can be configured, for example, to be transparent to detection light and/or excitation light.

At least one optional test element opening can have a specific function. This test element opening can, for example, already be closed and/or sealed during the application method or by the test chemical application method described above. In addition, at least one seal can be applied to the at least one test element opening, for example, to seal a remaining gap.

The seal may comprise one or more sealing elements, which may be suitable for the aforementioned purposes and may also be formed integrally for multiple openings. For example, a corresponding sealing film, such as a thin plastic and/or metal film, may be provided. Such sealing elements are generally known from the prior art.

As described above, in addition to the methods of one or more of the method variants described above, an analytical kit is also proposed. This analytical kit can be produced, for example, according to the methods of one or more of the method variants described above, although other production methods can also be used in principle. This analytical kit includes a plurality of analytical aids received in a chamber. The analytical kit also includes at least one test chemical designed to alter at least one measurable property in the presence of at least one analyte to be detected.

Furthermore, it is proposed to implement the aforementioned aspects by applying the test chemical jointly to multiple chambers, preferably to all chambers, and optionally independently of the aforementioned production method. Thus, the at least one test chemical can be applied to a continuous carrier and form at least one test chemical field within the aforementioned meaning. In particular, the at least one test chemical field and the continuous carrier can form at least one chemical ring and/or at least one test chemical band. Reference is made to the above description in this regard.

In this case, the test chemical field is applied to a continuous carrier. In this case, a continuous carrier is to be understood as meaning a carrier with test chemicals, which are used simultaneously for a plurality of and preferably all chambers. In particular, the carrier can be configured in one piece, for example as a carrier ring. With regard to possible configurations of the carrier, reference can be made, for example, to the description of the method described above. This at least one test chemical field, as described above, can have one or more subfields, including non-adjacent subfields, which in each case provide at least one area of the test chemical field to the chamber, which in each case at least one area of the test chemical field is allocated to the interior space of the chamber. As described above, this at least one area can therefore specifically for each chamber produce at least one test field in each case, which forms a component of the analytical aid received in the chamber and/or a component of a sub-auxiliary of the analytical aid.

The test chemical field can specifically be a component of the analysis box housing, in particular a component of the outer box housing wall. By way of example, as described above, this can be done in such a way that the test chemical field is applied from the outside to an opening of the housing part of the housing, so that the test chemical field is at least partially accessible from the inside of the chamber. By way of example, as described above, the housing can be formed in a substantially rigid manner, that is to say in such a way that, at least under the effect of its own weight, it does not substantially change its shape. The housing can comprise, for example, the components mentioned above, i.e. at least one first component, optionally at least a second component and optionally one or more further components. The housing can comprise, for example, one or more plastics and/or one or more ceramic materials and/or one or more further materials, such as thermoplastic materials, thermosetting plastics, optionally with corresponding fillers or a combination of the aforementioned and/or other materials.

As described above, the methods and/or analytical kits described in one or more of the embodiments offer numerous advantages over known methods and devices. In particular, the analytical kits can be used in so-called microsamplers, i.e., analytical systems in which sample preparation, sampling, and optional sample analysis are performed in a single, integrated system. Preferably, in this case, small sample volumes can be collected, for example, less than 1 μl, particularly less than 500 μl.

This production method can be essentially limited to handling a small number of components. In a first method step, for example, according to a variation of the above-described method, the structure of individual lancets, such as needle elements, can be etched from a metal sheet. This method can produce, for example, a metal disc containing the retaining element and lancets. The individual lancets can be interconnected via this metal disc. The metal sheet can then be placed, for example, in a first component, such as a plastic component of a housing made entirely or partially of plastic, and/or on the latter. During the subsequent isolation of the lancets, the latter are preferably placed directly, one at a time, into the housing's chambers, preferably without the need for individual orientation of the lancets. This method, for example, eliminates the need for handling individual, particularly miniaturized, disposable components during insertion into their respective housing chambers. In a subsequent step, the housing can be completed with additional housing components (e.g., the now isolated lancets held in their respective chambers). Then, as described above, the housing can be covered, for example, with a chemical ring, preferably containing the entire test chemical field. Overall, production costs and expenses can be significantly reduced in this way.

Furthermore, the proposed method can reliably prevent cross-contamination of analytical aids within the chambers. This can be achieved, for example, by one or more of the aforementioned connection methods, whereby multiple housing components, such as a first component and a second component, are connected to one another, in which case, in particular, the individual chambers can be separated from one another. This can be achieved by laser welding, in particular, whereby adjacent chambers are preferably separated from one another by a continuous weld seam.

In particular, the integrated production of analytical aids and retaining elements or sub-aids and retaining elements has numerous advantages. Thus, for example, a specific etching structure can be used for the lancet and/or microsampler, by means of which the lancet can be connected to a retaining element, such as a metal sheet and/or a metal frame. For example, as described above, the etching structure can have a desired disconnection position and/or a tapered portion so that, for example, when a single lancet is removed and/or separated from the retaining element in some other way, there are no remaining detached residues (which would prevent the lancet from sliding in the chamber). In this way, a high degree of operational reliability can be ensured.

As a result of the preferred rigid design of the test element housing and/or the preferred method of introducing the analytical aids together into a plurality, preferably all, of the chambers by means of corresponding retaining elements, advantages can also be achieved, for example, over analytical aids connected using a tape or similar flexible element and the corresponding analytical housing produced. In this case, handling of the tape is not necessary. However, a rigid design is not absolutely necessary, as, for example, the housing and/or the first component and/or the retaining element can also be configured completely or partially in a flexible manner, for example in the form of a membrane, a tape, a chain, etc.

The second aspect of the present invention proposes an analytical box, which, by way of example but not necessarily, is produced according to the method of the present invention described above. Therefore, for the possible construction of the analytical box described below, reference can be made to the above description of the method or the analytical box produced by the method. However, other ways of producing the analytical box are also possible. In particular, the analytical box can also be produced in different ways using a retaining element for introducing the analytical aid. In addition, the analytical box can also be configured in different ways other than continuous test chemicals, that is, for example, with separate test chemicals for each individual chamber. However, a shared continuous test chemical field (in which, in each case, at least one area faces the respective chamber, for example in the form of a test chemical ring) is also particularly preferred in the second aspect of the present invention. In addition, the preferred construction of the first aspect of the present invention described above (in particular the construction proposed in the dependent claims) can also be implemented in the second aspect of the present invention without depending on the other features of the first aspect of the present invention.

The analytical box according to a second aspect of the present invention contains a plurality of analytical aids. The analytical box has at least two chambers in which analytical aids can be received. In this case, the analytical aids are received in at least one chamber. In this case, two basic principles for receiving the analytical aids in the chambers are conceivable. Thus, by way of example, each chamber can receive one analytical aid, in particular an analytical aid comprising at least one sub-auxiliary in the form of a test element with a test chemical. Optionally, at least one additional sub-auxiliary in the form of a lancet and/or microsampler can be provided, preferably in addition to each chamber. In the case of this principle, the analytical aids can be repacked into the same chamber, particularly after use. However, repacking into different chambers is also possible as an option. This first principle is particularly preferred in the case of disc-shaped or rod-shaped boxes. According to another principle, at least one first chamber for unused analytical aids and at least one second chamber for used analytical aids can be provided. In this case, for example, the analytical aid can be removed from the first chamber for use and, after use, transferred to a second chamber, which can be designed so that it is spatially separated from the first chamber. This principle can be used, for example, in a belt-type box, in which, for example, a good winding is provided in the first chamber for receiving unused analytical aids and a poor winding is provided in the second chamber for receiving used analytical aids.

The analytical aid comprises in each case at least one test element having at least one test chemical for detecting at least one analyte in a liquid sample, in particular in a body fluid. In this case, the analytical aid is often also referred to as a "test piece", independently of its function and construction. In this case, therefore, a test piece can generally be understood to mean at least one analytical aid that can be used in a test method. By way of example, a test element or a lancet or a pair comprising a test element and a lancet can be included in this case, preferably in just one test piece installed in just one chamber. The test piece can also comprise a plurality of mutually related sub-auxiliaries. For example. The test piece can, for example, be received in just one chamber. However, in the context of the present invention, no distinction is made here and hereinafter between the language and meaning of a test piece and an analytical aid, including the possibility that a test piece can comprise a plurality of sub-auxiliaries, for example a test element and a lancet in each case.

Conventional analytical boxes and test elements (particularly for glucose testing) typically use test chemicals that are sensitive to air moisture and, if exposed to air for too long, can degrade or even completely lose their functionality. Therefore, for example, conventional test strips must be stored in containers that are impervious to air moisture. These containers are often partially filled with desiccants, i.e., hygroscopic materials such as activated carbon. In the case of integrated systems, analytical boxes and/or analytical aids, such as disposable aids (disposable items), are developed in which the test elements are packaged individually or in groups, and these packaging must also be made moisture-proof. However, this requirement for moisture-proofing significantly limits the choice of possible materials, particularly for the housing. This is due to the fact that, in particular, there are often other requirements that must be met simultaneously. Therefore, in most cases, the materials used must be sterilizable, particularly by means of ionizing radiation. Alternatively or in addition, the materials used generally do not allow for degassing, particularly after or during exposure to radiation as a result of the sterilization process. Once again, alternatively or additionally, the material used must be suitable for the selected production method, for example, for injection molding and/or some other forming method. Once again, alternatively or additionally, the material used should preferably be biocompatible and/or connectable and/or sealable. Further requirements may exist. In this case, the requirement for a moisture barrier is particularly difficult to meet in practice, since most plastics are permeable to moisture, especially in the case of small wall thicknesses, for example, less than 1 mm.

Therefore, according to a second aspect of the present invention, the test chemical is configured in such a manner that it is at least substantially stable against environmental influences, particularly against moisture. The test chemical can be present specifically as a dry chemical, particularly on a test strip. In the context of the present invention, a test chemical that is substantially stable against environmental influences is understood to mean a test chemical that is stable against air moisture and also amenable to sterilization methods, particularly those using ionizing radiation. The term "stable" in this context means that during storage for three weeks at 32°C and 85% relative humidity under normal pressure, the activity, for example, of the test chemical in the analytical aid decreases by less than 50%, preferably by less than 30%, and particularly preferably by less than 20%. In this context, the activity can, in principle, be determined using any desired method known in the art, as the definition provided herein relates solely to the ratio of the decrease in activity measured by this method to the activity measured by this method before storage or immediately after production of the analytical aid. In this context, the activity is specifically related to the enzymatic activity of the dry chemical, particularly in the test strip. By way of example, methods for measuring enzyme activity are known in which the enzyme is extracted from a test chemical or a test strip and the activity is subsequently measured, for example, by UV absorption. In this regard, reference may be made, for example, to H. U. Bergmeyer: Methoden der enzymatischen Analyse [Method of enzyme analysis], Verlag Chemie, 2nd edition 1970, p. 417, or to Banauch et al.: A glucose dehydrogenase for the determination of glucose concentrations in body fluids, Z. Klin. Chem. Klin. Biochem. 1975 Mar;13(3):101-7. By way of example, for this test, a test strip can be produced with a test chemical, the enzymatic activity of the test chemical enzyme can be determined by conventional methods, the test strip can then be stored as described above, and the same method for measuring the enzyme activity can then be repeated. This method is usually carried out using a representative set of test strips or test chemicals. As an alternative to or in addition to stability to environmental influences in the form of air moisture, it may also be preferred that the test chemical has a high stability to environmental influences in the form of radiation (e.g. gamma radiation and/or beta radiation and/or some other type of ionizing radiation) which is commonly used to sterilize analytical aids and/or the entire analytical box.

As an example of such a test chemical (which is stable to environmental influences), reference can be made to the aforementioned WO 2007/012494 A1. The test chemical described therein can also be used in the context of the present invention, either alone or in combination with one or more other test chemicals. Alternatively or in addition, the test chemical can also be formulated in the manner described in the subsequently published European patent application EP 08003054.7 or the subsequently published international patent application PCT/EP2009/001206 (which are from the same company as the applicant of the present patent application).

In some embodiments, the present invention relates to a method for the preparation of a test chemical comprising the steps of: preparing ...

The enzyme stabilized by the method of the present invention may be a specific coenzyme-dependent enzyme. Examples of suitable enzymes are dehydrogenases selected from the group consisting of glucose dehydrogenase (EC 1.1.1.47), lactate dehydrogenase (EC 1.1.1.27, 1.1.1.28), malate dehydrogenase (EC 1.1.1.37), glycerol dehydrogenase (EC 1.1.1.6), alcohol dehydrogenase (EC 1.1.1.1), α-hydroxybutyrate dehydrogenase, sorbitol dehydrogenase or amino acid dehydrogenases, such as L-amino acid dehydrogenase (EC 1.4.1.5). Other suitable enzymes are oxidases, such as glucose oxidase (EC 1.1.3.4) or cholesterol oxidase (EC 1.1.3.6) and aminotransferases, such as aspartate or alanine aminotransferase, 5'-nucleotidase or creatine kinase. The enzyme is preferably glucose dehydrogenase.

It has been confirmed that it is particularly preferred to use the glucose dehydrogenase of sudden change.As used in the context of the application, term " mutant " refers to a kind of genetic modification variant of natural enzyme, although its amino acid whose number is identical, has the aminoacid sequence that changes with respect to wild-type enzyme, that is, at least one amino group is different from wild-type enzyme.The introducing of sudden change can be at specific position or non-specific position, preferably specific position, is carried out by using recombination method known in the art, and at least one amino acid is exchanged in the aminoacid sequence of natural enzyme, specifically is suitable for concrete requirements and conditions.This mutant particularly preferably has the heat or the hydrolytic stability that improves than wild-type enzyme.

The glucose dehydrogenase of this sudden change can comprise amino acid in principle, and it is compared with corresponding wild-type glucose dehydrogenase, and change has occurred on any position of its aminoacid sequence.The glucose dehydrogenase of this sudden change preferably is included in the sudden change on at least one position in 96,170 and 252 positions of the aminoacid sequence of wild-type glucose dehydrogenase, particularly preferably has the mutant of sudden change on position 96 and position 170, and sudden change on position 170 and position 252.It has been confirmed that advantageously the glucose dehydrogenase of sudden change does not comprise the other sudden change except these sudden changes.

Mutations at positions 96, 170, and 252 can, in principle, include any amino acid exchange that stabilizes the wild-type enzyme, for example, by increasing thermal or hydrolytic stability. The mutation at position 96 preferably involves an amino acid exchange from glutamic acid to glycine, while at position 170, an amino acid exchange from glutamic acid to arginine or lysine, with glutamic acid to lysine being particularly preferred. The mutation at position 252 preferably involves an amino acid exchange from lysine to leucine.

The mutant glucose dehydrogenase can be obtained by mutation of a wild-type glucose dehydrogenase of any biological origin, where the term "biological origin" in the context of the present invention includes both prokaryotes, such as bacteria, and eukaryotes, such as mammals and other animals. The wild-type glucose dehydrogenase is preferably derived from bacteria, particularly preferably from Bacillus megaterium, Bacillus subtilis or Bacillus thuringiensis, in particular from Bacillus subtilis.

In a particularly preferred embodiment of the present invention, the mutated glucose dehydrogenase is a glucose dehydrogenase obtained from a mutation of a wild-type glucose dehydrogenase derived from Bacillus subtilis, and has the amino acid sequence described in SEQ ID No.: 1 (GlucDH_E96G_E170K) or the amino acid sequence described in SEQ ID No.: 2 (GlucDH_E170K_K252L).

Stable coenzyme is preferably such coenzyme, it has been chemically modified compared with natural coenzyme, and it has stability (for example hydrolytic stability) higher than natural coenzyme.Stable coenzyme is preferably stable for the hydrolysis under test conditions.Compared with natural coenzyme, this stable coenzyme can have the binding constant that reduces for enzyme, for example reduced 2 times (reduced to 1/2) or more times of binding constant.

Preferred examples of stable coenzymes are stable derivatives of nicotinamide adenine dinucleotide (NAD/NADH) or nicotinamide adenine dinucleotide phosphate (NADP/NADPH), or truncated NAD derivatives, e.g. without the AMP moiety or with non-nucleoside groups, e.g. hydrophobic groups. Also preferred stable coenzymes in the context of the present invention are compounds of formula (I):

.

Preferred stable derivatives of NAD/NADH and NADP/NADPH are described in the aforementioned references, the disclosures of which are hereby incorporated by reference. Particularly preferred stabilized coenzymes are described in WO 2007/012494 and US 11/460366, the disclosures of which are hereby expressly incorporated by reference. The stabilized coenzymes are particularly preferably compounds selected from the group consisting of the general formula (II):

in

A = adenine or its analogs,

T = O, S, independently in each case

U = independently in each case OH, SH, BH ₃ ^- , BCNH ₂ ^- ,

V = independently in each case OH or a phosphate group, or two groups forming a cyclic phosphate group;

W = COOR, CON(R) ₂ , COR, CSN(R) ₂ , wherein R = independently in each case H or C ₁ -C ₂ -alkyl,

X ¹ , X ² = independently in each case O, CH ₂ , CHCH ₃ , C(CH ₃ ) ₂ , NH, NCH ₃ ,

Y = NH, S, O, _CH2 ,

Z = a linear or cyclic organic radical, provided that Z and the pyridine residue are not linked by a glycosidic bond, or a salt or, where appropriate, a reduced form thereof.

Z in the compounds of formula (II) is preferably a linear group having 4 to 6 C atoms, preferably 4 C atoms, of which 1 or 2 C atoms are optionally substituted by one or more heteroatoms selected from O, S and N, or a group comprising a cyclic group having 5 or 6 C atoms and which optionally contains heteroatoms selected from O, S and N and optionally one or more substituents, and a group CR ⁴ ₂ , where CR ⁴ ₂ is a bond to the cyclic group and to X ² , and R ⁴ = is independently in each case H, F, Cl, CH ₃ .

Z is particularly preferably a saturated or unsaturated carbocyclic or heterocyclic 5-membered ring, in particular a compound of the general formula (III):

Here, a single bond or a double bond may be present between R ^5' and R ^5" , and

R ⁴ = independently in each case H, F, Cl, CH ₃ ,

^R5 = ^CR42 _,

Here R ^5′ = O, S, NH, NC ₁ -C ₂ -alkyl, CR ⁴ ₂ , CHOH, CHOCH ₃ , and

If there is a single bond between R ^5' and R ^5" , then R ^5" = CR ⁴ ₂ , CHOH, CHOCH ₃ , and

If there is a double bond between R ^5′ and R ^5″ , then here R ^5′ = R ^5″ = CR ⁴ , and

R ⁶ , R ^6′ = independently in each case CH or CCH ₃ .

In a preferred embodiment, the compounds of the invention comprise adenine or an adenine analog, such as, for example, _C8- and _N6 -substituted adenine, a deaza variant, such as a 7-deaza, an aza variant, such as an 8-aza, or a combination, such as a 7-deaza or 8-aza, or a carbocyclic analog, such as metopromycin, which in the case of the 7-deaza variant may be substituted at position 7 with halogen, _C1 - _C6 -alkynyl, -alkenyl or -alkyl.

In another preferred embodiment, the compound comprises an adenosine analog that replaces ribose, including, for example, 2-methoxydeoxyribose, 2'-fluorodeoxyribose, hexitol, altritol or polycyclic analogs such as bicyclo-, LNA- and tricyclo-sugars.

In particular, the (di)phosphate oxygen in the compound of formula (II) may be iso-substituted, such as ^, for example, O- ^replaced by ^S- or _BH3- , O replaced by NH, _NCH3 or _CH2 , and =O replaced by =S.

In the compound of formula (II) of the present invention, W is preferably CONH ₂ or COCH ₃ .

In the group of formula (III), R ⁵ is preferably CH ₂ . R ^5′ is further preferably selected from CH ₂ , CHOH and NH. In a particularly preferred embodiment, R ^5′ and R ^5″ are each CHOH. In yet another preferred embodiment, R ^5′ is NH and R ^5″ is CH ₂ .

In the most preferred embodiment, the stable coenzyme is carbaNAD.

Preferred test chemicals are particularly formulated in such a way that they contain a long-term stable enzyme. This means that the enzyme stabilized with the stable coenzyme is stored, for example as dry matter, for a period of at least two weeks, preferably at least four weeks and particularly preferably at least eight weeks, and in this case the enzyme activity preferably decreases by less than 50%, particularly preferably by less than 30% and most preferably by less than 20% relative to the initial value of the enzyme activity.

The test chemical can further be configured for storage of the enzyme stabilized with the stable coenzyme at elevated temperature, for example at a temperature of at least 20° C., preferably at least 25° C., and particularly preferably at least 30° C. In this case, the enzyme activity is preferably reduced by less than 50%, particularly preferably by less than 30% and most preferably by less than 20% relative to its initial value.

The stabilization according to the invention allows the enzyme stabilized with the stabilized coenzyme to be stored for the aforementioned long periods of time even without a desiccant and/or at the aforementioned high temperatures. The stabilized enzyme can also be stored at high relative humidity, for example at a relative humidity of at least 50%, in which case the enzyme activity decreases by preferably less than 50%, particularly preferably by less than 30%, and most preferably by less than 20% relative to the initial value.

The storage of enzymes stabilized with a stable coenzyme can be carried out as a dry substance on the one hand, or in a liquid phase on the other hand. The storage of the stabilized enzyme is preferably stored on or in a test element suitable for measuring the analyte. In this case, the enzyme stabilized with a stable coenzyme is a component of a preferred test chemical, which may optionally also include other components such as salts, buffers, etc. In this case, the test chemical is preferably free of a modifier.

The enzyme stabilized with the stable coenzyme can generally be used to detect an analyte, for example a parameter in a body fluid such as blood, serum, plasma or urine, or in a sewage sample or food.

The analyte that can be detected is any biological or chemical substance, which can be detected by redox reaction, such as the substrate material of a coenzyme-dependent enzyme or the material of a coenzyme-dependent enzyme itself. Preferred examples of analytes are glucose, lactic acid, malic acid, glycerol, alcohol, cholesterol, triglyceride, ascorbic acid, cysteine, glutathione, peptide, urea, ammonium, salicylic acid, pyruvic acid, 5'-nucleotidase, creatine kinase (CK), lactate dehydrogenase (LDH), carbon dioxide, etc. The analyte is preferably glucose. In this regard, it is particularly preferred to detect glucose by means of glucose dehydrogenase (GlucDH).

In principle, the change in the stable coenzyme by reacting with the analyte can be detected in any manner. In principle, all methods known in the prior art for detecting enzyme reactions can be used. However, the change in the coenzyme is preferably detected by optical methods. Optical detection methods include, for example, absorption measurement, fluorescence, circular dichroism (CD), optical rotation dispersion (ORD), refractive index detection, etc.

A preferred optical detection method in the context of the present application is photometry. However, the photometric measurement of the changes in the coenzyme as a result of the reaction with the analyte requires the additional presence of at least one modulator, which increases the reactivity of the reduced coenzyme and allows electron transfer to a suitable optical indicator or optical indicator system.

Suitable modulators for the purposes of the present invention are nitrosoanilines, such as [(4-nitrosophenyl)imino]dimethanol hydrochloride, quinones, such as phenanthroline quinones, phenanthroline quinones or benzo[h]quinoline quinones, phenazines, such as 1-(3-carboxypropoxy)-5-ethylphenazinium trifluoromethanesulfonate, and/or diaphorase (EC 1.6.99.2). Preferred examples of phenanthroline quinones include 1,10-phenanthroline-5,6-quinones, 1,7-phenanthroline-5,6-quinones, 4,7-phenanthroline-5,6-quinones, and N-alkylated and N,N'-dialkylated salts thereof. In the case of N-alkylated and N,N'-dialkylated salts, the counterion is preferably a halide, trifluoromethanesulfonate or other anion that increases solubility.

As an optical indicator or optical indicator system, any of the following substances can be used, which are reducible and, by reduction tests, show detectable changes in their optical properties, such as color, fluorescence, reflectivity, transmittance, polarization, and/or refractive index. The presence or amount of the analyte in the sample can be measured with the naked eye or/and by a detection device using a photometric method suitable for use by a person skilled in the art. Heteropoly acids and particularly 2,18-phosphomolybdic acid are preferably used as optical indicators and are reduced to the corresponding heteropoly blue.

The change in the coenzyme is particularly preferably detected by measuring fluorescence. Fluorescence measurements are highly sensitive and enable the detection of even low concentrations of analyte in miniaturized systems.

A kind of optional possibility still uses suitable test element, for example, such as electrochemical test strips, to detect the change in the coenzyme electrochemistry.Preconditioning for this is to use suitable conditioning agent again, and it can be converted into reduced form by the transfer of electrons by the coenzyme of reduction.This analyte is measured by measuring electric current, and described electric current is required for the conditioning agent of this reduction again, and it is relevant with the analyte concentration in the sample.The example of conditioning agent that can be used for electrochemical measurement specifically includes the aforementioned conditioning agent for photometric measurement.

Liquid test pieces can be used to detect the analyte, in which case the reactant is, for example, in the form of a solution or suspension in water or a non-aqueous liquid, or as a powder or lyophilizate. However, dry test pieces can also be used, in which case the reactant is applied to a carrier, such as a test strip. The carrier can include, for example, a test strip that includes an absorbent and/or a swellable material (which is moistened with the sample liquid under investigation).

A particularly preferred test format involves the use of the enzyme glucose dehydrogenase with a stable NAD derivative for the detection of glucose, in which case a derivative of the reduced coenzyme NADH is formed. NADH is detected optically, for example, by photometry or fluorescence measurement after UV excitation. A particularly preferred test system is described in US 2005/0214891, which is incorporated herein by reference.

In particular, the stable test chemical can be configured to comprise an enzyme stabilized with a stable coenzyme, wherein the stabilized enzyme exhibits an enzyme activity that is reduced by less than 50%, preferably less than 30% and most preferably less than 20% compared to the initial value when stored for preferably at least two weeks, particularly preferably at least four weeks and most preferably at least eight weeks at a temperature of preferably at least 20°C, particularly preferably at least 25°C and most preferably at least 30°C (optionally with high air humidity and without desiccant).

Alternatively or in addition, other types of stable test chemicals may be used, such as those described in WO 2007/012494 A1. In principle, the test chemical may be contained in the test element in any manner. The test chemical and/or the test element may be suitable for dry or liquid testing. For example, the test chemical may be applied to a carrier material suitable for this purpose, such as a plastic and/or ceramic material and/or a paper material.

When using test chemicals that are at least essentially stable to environmental influences (as in the manner provided by the second aspect of the present invention), the housing and/or greater selectivity of the material can be produced by means of better and more sophisticated connection technology. Therefore, the second aspect of the present invention proposes to configure the analysis box in such a way that the latter has a housing with at least two parts (for example, two half boxes). In this case, the two parts do not need to be configured in equal parts. The housing, in particular the at least two parts together, can form at least two chambers. It is particularly preferred that the at least two parts are connected to each other by a method that does not use an adhesive. In particular, a material connection method that does not use an adhesive is appropriate here. Because of the high accuracy and the low degree of contamination caused, it is particularly preferred to use at least one laser welding method. Therefore, the second aspect of the present invention proposes to rely on a laser welding method to connect at least two parts to each other.

Using the laser welding method, uniform weld seams with small width and high precision can be obtained, the method being simultaneously well thermally controllable and localizable and also being able to be carried out virtually without any contamination.

Particularly when using laser welding methods, as also proposed by the present invention, it is advantageous for a first of the at least two components to have a different transparency than a second of the at least two components. For example, the first of the at least two components can be configured so that it is almost completely transparent, and the second of the at least two components can be configured so that it absorbs within the wavelength range used for the laser welding method. In this case, the at least two components can preferably consist of the same base material but each have a different absorption for light in the visible and/or infrared and/or ultraviolet spectral ranges. For example, the at least two components can have different absorption in the spectral range of 500-1200 nm, particularly in the spectral range of 700-1100 nm or 700-1000 nm, which is the spectral range within which conventional lasers used for laser welding, such as semiconductor lasers and/or Nd:YAG lasers, emit. To achieve different transparencies or absorptivity of at least two components, the base materials of the components (which can also be identical for both components) can be of different colors, for example by mixing the base material of one component (e.g., polycarbonate, PC) with a dye to reduce the transparency. By way of example, the two components can have a transparency difference of at least 5%, preferably at least 20%, and particularly preferably at least 50% for the laser radiation used in the wavelength range mentioned. In this context, transparency is understood to mean the degree of transparency.

If welding is used to connect the at least two components, the weld seam can have, for example, a maximum of 0.5 mm, in particular a maximum of 0.3 mm, and particularly preferably a maximum of 0.2 mm. As will be explained below, this significantly contributes to increasing the packaging density. It is particularly advantageous if the test chemical is at least substantially stable to environmental influences, since moisture transfer from one chamber to the other is largely irrelevant in this case.

In general, a variety of materials can be used for the housing, particularly for at least two of its components, such as the two half-boxes. In particular, thermoplastic materials can be used. A particular advantage of using test chemicals that are at least largely stable to environmental influences is that these plastics do not have to meet specific requirements for moisture-tightness. Therefore, the selection and design of the plastic can be based on other criteria, such as its processing capabilities in a specific forming method (e.g., injection molding). Cost-effective materials are also considered. By way of example, one or more of the following plastics can be used: PC (polycarbonate); ABS (acrylonitrile butadiene styrene); COC (cyclic olefin copolymer); PMMA (polymethyl methacrylate); PS (polystyrene); and PET (polyethylene terephthalate). These materials offer advantages in terms of processing properties and/or cost, but if vapor-tightness requirements must also be met, their use can generally be difficult.

PC has, for example, high resistance to ionizing radiation and high transparency over a wide spectrum. It is a cost-effective material that can be mass-produced, but it has a relatively high permeability to water vapor. However, because this permeability is generally irrelevant in the context of the present invention, especially when using stable test chemicals, and because the processing properties of this material are particularly good in practice, this material is particularly preferred in the context of the present invention.

ABS is very easy to process and can be injection molded very well, so it is also advantageous to use this material. This material also has very good transparency over a wide spectrum and is low in cost.

COC is recognized to have high transparency over a wide spectral range from the ultraviolet to the infrared and provides a good vapor barrier, but is relatively expensive and only moderately stable to ionizing radiation.

PMMA has little or no intrinsic fluorescence in the UV range and also has good transparency across the entire optical spectrum. Its high vapor permeability is acceptable in the context of the present invention, particularly when using stable test chemicals, and it is a cost-effective material. Therefore, this material can also be advantageously used in the context of the present invention.

PS is easy to process, particularly by injection molding. It has good transparency over a wide spectrum of light. Furthermore, it is a cost-effective, mass-produced plastic. Therefore, in summary, this material can also be successfully used in the context of the present invention.

With this expanded range of materials (which are no longer limited by vapor-impermeability requirements), it is possible, in principle, to connect preferably at least two components of the analytical housing by laser welding, instead of conventional ultrasonic welding and/or adhesive bonding methods (which leave opaque materials). Identical materials can be welded very simply, for example, by laser welding, such as PC to PC and/or COC to COC, etc., particularly if one component is light-absorbing for the laser wavelength (e.g., by appropriate coloring and/or doping) and the other component is configured to be transparent or more transparent. While opaque components can, in principle, also be irradiated in such a way that welding can be used, the weld seam is generally rougher and requires more space. Compared to components with high transparency and smooth surfaces, very narrow weld seams can be achieved, such as those with a width of 0.3 mm as mentioned above. These small weld seams allow the analytical housing to be manufactured very compactly, for example, with the preferred packaging density mentioned above. Furthermore, laser welding avoids the formation of dust that typically occurs with other welding methods, such as ultrasonic welding. Such dust formation can manifest itself in an unfavorable manner, in particular in the case of analytical aids or sub-aids in the form of test elements, since the test chemicals of the test elements can be contaminated by dust and other contaminants arising during the welding process. Alternatively or in addition, if a lancet and/or a microsampler is used as an analytical aid or analytical sub-aid, dust is also formed in a very unfavorable manner, since, for example, the hydrophilicity of the lancet and/or microsampler can be influenced by dust. This can be avoided by using a laser welding method. In addition, no vibrations occur, which could lead to resonances in the structure or components of the analytical box. In addition, no additional materials, such as adhesives, are required, which could, for example, contaminate the interior of the chamber and/or the analytical aid and thereby, for example, jeopardize the hydrophilicity of the lancet or microsampler.

Furthermore, in particular by using laser welding and/or preferably plastics, a new method for closing and/or sealing the analytical box, for example for sealing the final analytical box, becomes possible. Previously, analytical boxes have often been heat-sealed using films that can be bonded using hot-melt adhesives. However, the hot-melt adhesives used in these cases can, in certain circumstances, affect the analytical aids. Thus, for example, the vapors of the hot-melt adhesive can affect the lancet and/or microsampler, for example by reducing their hydrophilicity. However, by virtue of the proposed invention, in particular by using the laser welding method and/or the aforementioned materials, it is possible, as an alternative or in addition, to use, for example, a metal film, such as an aluminum film, for sealing the analytical box, or one or more plastic films, which, for example, can be welded by means of a laser, instead of being bonded with an adhesive.

Overall, this newly gained freedom in material selection thus provides the basis for a considerably more compact system. This is not only because the analytical box can be configured with a relatively smaller installation space and/or a relatively greater packaging density. It can also significantly simplify its production and/or handling and make its manufacture more cost-effective.

The analytical box generally has (especially in the second aspect of the present invention) preferably one or more of the following properties: total volume not greater than 10 cm ³ ; outer diameter not greater than 5 cm; inner diameter 0.5 cm-2 cm; thickness not greater than 1 cm; number of analytical aids 10-100; volume 3 cm ³ -30 cm ³ ; packaging density of analytical aids greater than 5/cm ³ .

It is particularly preferred that the outer volume of the analysis box (i.e., not taking into account the volume of the holes or other openings of the analysis box) does not exceed 5 cm ³ , preferably does not exceed 3 cm ³ and particularly preferably does not exceed 2 cm ^3. By way of example, the outer volume can be 1.94 cm ^3. It is particularly preferred that the empty volume of the analysis box (i.e., the total volume of the openings optionally present in the analysis box) does not exceed 0.8 cm ³ , preferably does not exceed 0.5 cm ³ and particularly preferably does not exceed 0.4 cm ^3. By way of example, the empty volume can be 0.39 cm ^3. The opening can be, for example, the inner opening of a disk-shaped analysis box, into which a drive can be inserted, for example. The empty volume is not intended to refer to the interior space in the housing, such as a chamber. In this context, the net volume is generally understood to mean the outer volume minus the empty volume. Thus, in the case of a disk-shaped box, the volume result essentially results from the diameter and height of the disk, and in the case of an annular disk-shaped box, the net volume result relates to the net volume of the corresponding disk minus the volume of the central cutout. Therefore, it is preferred that the net volume of the analysis box (ie outer volume minus void volume) does not exceed 5 cm ³ , particularly preferably does not exceed 3 cm ³ , and in particular does not exceed 2 cm ³ . By way of example, the net volume may be 1.55 cm ³ .

In the context of the present invention, packaging density is generally understood to mean the number of analytical aids per net volume of the analytical box. However, as described above, each analytical aid can contain a plurality of sub-adjuvants that can interact with each other, for example as test pieces in each case. Preferably, each analytical aid contains a test element with at least one test chemical as a sub-adjuvant. In addition, each analytical aid can also contain at least one lancet as a further sub-adjuvant, which is used for sampling to produce a body fluid sample, which is then applied to the relevant test element. However, if an analytical aid contains a plurality of analytical sub-adjuvants, then for the purpose of calculating the packaging density, the analytical sub-adjuvants belonging to the same whole are still counted as one analytical aid, for example, a test element and an associated lancet are counted as a common analytical aid. As an example, in each case, exactly one analytical aid with at least one test element and optionally at least one lancet can be received in the respective chamber. However, as described above, other configurations are also possible.

Therefore, the analysis box can be configured as an annular disk, for example, with an outer diameter of less than 100 mm, for example 50 mm, and the cut inner diameter of the annular disk is less than 50 mm, for example 22.5 mm. The thickness of the analysis box can be, for example, less than 5.0 mm, for example a thickness of 3.1 mm. The analysis box can preferably contain more than 20 analysis aids, for example at least 50 analysis aids and even 100 analysis aids or more. As an example, 50 such analysis aids can be provided, each of which has a test element and optionally each additionally has a lancet, where in each case the test element and the associated lancet are counted as one analysis aid, also referred to as a "test piece". As an example, in each case one analysis aid of this type can be received in the respective chamber. Thus, the packing density can be, for example, at least 50 analytical aids/5 cm ³ = 1 analytical aid/0.1 cm ³ , preferably at least 50 analytical aids/3 cm ³ = 1 analytical aid/0.06 cm ³ , and particularly preferably at least 50 analytical aids/2 cm ³ = 1 analytical aid/0.04 cm ³ . By way of example, the packing density can be 50 analytical aids/1.55 cm ³ = 1 analytical aid/0.031 cm ³ . However, different configurations of the analytical box as a disk are also possible, for example with one or more of the above-mentioned geometries. A configuration as a belt-type box is also possible, in which case, for example, one chamber of the belt-type box contains a good winding with unused analytical aids, and another chamber of the belt-type box contains a poor winding, on which used analytical aids can be received.

High packing density can also be achieved specifically in the following way, that is, the analytical aids are installed very densely adjacent to each other, without having to seal and separate them. In this regard, the use of stable test chemicals occurs in a particularly advantageous manner. Therefore, as an example, an analytical box can be used that has a shell with a wall thickness of at most 1.2 mm. In this case, the wall thickness should be understood to mean the thickness of the shell between the chamber containing the analytical aids and the surroundings or adjacent chambers, in particular the thinnest position of the shell. It is particularly preferred that the wall thickness is not greater than 1.0 mm, and in particular not greater than 0.8 mm. As an example, the wall thickness can be selected to be 0.3 mm-0.8 mm.

Once again as an alternative or in addition, the analysis box can for example dispense with the use of a desiccant such as activated carbon. Therefore, it is particularly preferred that the analysis box is configured without a desiccant. This also saves structural space.

If such stable test chemicals are used, it is generally possible to completely dispense with the moisture-tight design of the individual chambers. The analytical chamber can therefore typically include multiple analytical aids housed in at least two chambers. In this case, each of the analytical aids can include at least one test element containing at least one test chemical for detecting at least one analyte in a liquid sample, particularly a body fluid, wherein the test chemical is configured to be at least substantially stable to environmental influences (particularly moisture). In this case, typically in the second aspect of the present invention, but also in the first aspect described above, the chambers can be configured so that they are separated from one another in such a way that moisture can be exchanged between the chambers (e.g., between adjacent chambers). For example, the chambers can have walls with gaps or other openings provided in or on the sides thereof, preferably with an opening width of no more than 20 μm, particularly no more than 10 μm. These opening widths allow for the exchange of air moisture between the chambers, but generally prevent the passage of coarser contaminants or microorganisms.

The analytical box in one or more of the above-mentioned configurations can also advantageously be constructed in different ways. In particular, as described above, the analytical accessories can each include a test element and a lancet with a test chemical (in particular a test chemical that is stable to environmental influences). These sub-auxiliaries can be stored together in one and the same chamber, for example a pair containing a lancet and a test element in each case in one chamber, or a plurality of such pairs in a common chamber. The use of a test chemical (which is stable to environmental influences, in particular air moisture and/or beta radiation) can eliminate the basic requirement for separate packaging of the lancet and the test element. In addition, the need to seal the test chemical in a water vapor-proof packaging and/or to insert a desiccant into the chamber and/or the analytical box can also be eliminated. As a result, new concepts become possible, particularly for analytical boxes with a combination of a lancet and a test element. The lancet and the test element do not have to be stored separately from each other. In addition, as will be explained in even more detail below, other materials are also possible for the box components, since it is no longer necessary to meet the requirements of radiation stability and vapor impermeability at the same time.

Since the analytical aid, in particular the barrier between the lancet and the test element, can be dispensed with, a relatively more compact arrangement of the lancet element and the test element can be achieved, for example, in the same chamber of the analytical box. The lancet tip can be located in the vicinity of the test chemical when stored in the chamber and, for example, is also suitable as a location for transferring the sample to the test chemical after it has been obtained. As a result, the mechanism for activating the analytical aid can be designed relatively simply compared to conventional analytical boxes, since, for example, an additional movement for the purpose of overcoming a second barrier (e.g., a barrier between the lancet and the test element) can be dispensed with and since the lancet does not have to be moved to a different position. In contrast to previous concepts in which the lancet and the test chemical were packaged separately, the test chemical also does not require any necessary movement in order to remove it from its packaging. In this case, it is usually only necessary to park the lancet on a corresponding actuator and move it.

Therefore, in another aspect of the present invention, another method for producing an analytical box is provided. This analytical box can specifically be an analytical box according to one or more of the aforementioned extensions and/or an analytical box that can be produced according to a method having one or more of the aforementioned extensions. However, in principle, other extensions are also possible.

The analysis box is designed to accommodate multiple analytical aids in multiple chambers. Each analytical aid contains at least one test chemical. In particular, this can be a test chemical that, as described above, is at least substantially stable against environmental influences. The test chemical can, for example, be a component of a test element that is preferably completely housed in a housing (e.g., a chamber). In the method of the present invention, multiple analytical aids are introduced into at least one chamber. For example, each chamber can contain exactly one analytical aid, or multiple analytical aids can be introduced into a single chamber. The analysis box also has a housing having at least two components. Before or after the method of introducing the analytical aids into the at least one chamber, the at least two components are connected to each other by laser welding. Each analytical aid can also contain at least one lancet. These lancets preferably have at least one capillary channel for collecting body fluids, which are then transferred to the test element via the lancet. Advantageously, the capillary channel (e.g., needle element), in particular the capillary structure, of the lancet is coated, preferably hydrophilically, to enhance the transfer of body fluids. The analytical box can also be sterilized using ionizing radiation, in particular after the laser welding process has been performed. With regard to the advantages of the method proposed in one or more of the aforementioned embodiments, reference is primarily made to the above description. In particular, the laser welding process has the effect of enabling high packaging densities and preventing the analytical aids (in particular the lancets) from becoming contaminated or significantly contaminated during the production process, for example by dust that could potentially deposit on the hydrophilic coating of the lancets.

BRIEF DESCRIPTION OF THE DRAWINGS

Further details and features of the present invention will become apparent from the following description of preferred exemplary embodiments, in particular in conjunction with the accompanying drawings. In this case, the respective features can be realized by themselves or in multiple combinations with one another. The present invention is not limited to this exemplary embodiment. This exemplary embodiment is schematically shown in the accompanying drawings. In this case, the same reference numerals in the various figures indicate identical or functionally identical elements, or elements that correspond to one another in terms of their function.

Specifically:

1A and 1B show different perspective views of the first component of the analysis box;

2A and 2B show a plurality of analytical aids provided in the form of lancets;

FIG3 shows the first component of FIG1A and FIG1B after the lancet according to FIG2A and FIG2B has been inserted;

FIG4 shows a perspective view of the second component of the analysis box;

FIG5 shows a perspective view of the analysis box after application of the second component according to FIG4 ;

FIG6 shows an exemplary diagram of a sealing member for sealing the opening of the analysis box; and

7A and 7B show different perspective views of the final analysis box.

DETAILED DESCRIPTION

A possible embodiment of the method for producing an analytical box 110 according to the present invention, as well as a working example of such an analytical box 110, will be described below with reference to Figures 1A-7B. The final analytical box 110 is shown in Figures 7A and 7B. In this case, the analytical box 110 constitutes a working example of the first aspect of the present invention described above, in which multiple analytical aids are simultaneously introduced into the housing during production. However, the analytical box 110 can also be used as a working example of the second aspect of the present invention described above, in which a laser welding method is used as the joining method.

In the first method step shown in Figures 1A and 1B, a first component 112 of an analysis box 110 is provided. In this case, Figure 1A shows a view of the first component 112 from below, i.e., a perspective view obliquely from the side of the first component 112 facing away from the interior of the analysis box 110, while Figure 1B also shows a perspective view obliquely from above, i.e., from the side associated with the interior of the analysis box 110 in the assembled state of the analysis box 110.

As can be seen from the figure, the first component 112, and the analysis box 110 as a whole, is configured in the form of an annular disk with an outer circumference 114 and a circular inner opening 116. An analysis system (not shown) using the analysis box 110 can, for example, fully or partially receive the analysis box 110 and be fully or partially inserted into the inner opening 116. Thus, for example, a gear and/or the center of the analysis system can be fully or partially inserted into the toothing of the inner opening 116. The analysis system can, for example, include a corresponding transport device that interacts with a transport element 118 on the analysis box 110 (see, for example, FIG. 5 below) to, for example, further transport the analysis box 110, such as by moving it forward. Reference can be made to the prior art in this regard. The transport element can, for example, include corresponding grooves, teeth, hooks, pegs, projections, recesses, etc. The transport element 118 is shown, for example, in FIG. 5 , which is described in more detail below, where, for example, it is configured as a peg. Furthermore, the analysis box 110 optionally includes recesses 119 in FIG1A . These recesses 119 can, for example, be used for positioning in an assembly device, for example, in the example shown, on the outside of the recesses 119. In the example shown, the inner recesses 119 are used to lower the gate during production using a forming method, such as an injection molding method.

As shown in Figures 1A and 1B, the first component 112 can be configured, for example, as an annular disk and can be manufactured entirely or partially from a plastic material. The first component 112 has a plurality of sockets 120, which form components of a chamber 122 of the analytical box 110 in the assembled state. These sockets 120 and chamber 122 can be seen in Figure 1B. As can be seen from this figure, in the working embodiment shown, the sockets 120 are arranged radially and have corresponding recesses in the first component 112. The sockets 120 are preferably just wide enough so that the puncture and collection elements, described in more detail below, serving as analytical aids and/or sub-aids, can fit snugly into them. Thus, by way of example, the outer dimensions of the socket 120 can correspond to those of the analytical aids, plus an optional amount of play (e.g., several hundred millimeters in one or more dimensions, in the form of clearance, e.g., to ensure movement of the puncture and collection elements or analytical aids).

On the opposite side, i.e., on the side facing away from the socket 120, the first component 112 has an annular groove 124 in the illustrated working embodiment. In the illustrated working embodiment, an opening 126 is provided in each of the annular grooves 124. In each case, one opening 126 is provided in each chamber 122 in the illustrated working embodiment. In the illustrated working embodiment, the openings 126 are configured as elongated, radially extending slits. In the illustrated working embodiment, the openings 126 subsequently serve as test element openings 128 or test field windows, respectively, which define a test field accessible from the chamber 122. This will be explained in more detail below.

In addition to the test element opening 128, the chamber 122 has another opening 126 in the illustrated working embodiment. These openings 126 are partially formed in the first component 112, but can also be received in the other components of the analysis box 110 in whole or in part. Therefore, the socket 120, in the illustrated working embodiment, as shown in Figure 1B, specifically has an opening 126 on the outer circumferential side 114, which subsequently serves as a sampling opening 130. Through these sampling openings 130, the analysis auxiliary can be completely or partially walked out for sampling activities. In addition, the socket 120 has an opening 126 on the side assigned to the inner opening 116, which serves as a driver opening 132 in the subsequent operation of the analysis box 110, and enables a driver (not shown) to enter the chamber 122 interior, such as currently being in the chamber 122 of the analysis box 110 on the application position.

In a further method step, as shown in Figures 2A and 2B, a plurality of analytical aids 134 are provided. In the illustrated case, these are lancets 136 in the form of microsamplers, which can each form an analytical aid 134 or a sub-agent of these analytical aids 134. In this case, Figure 2A shows an overall perspective view of the provided lancet 136, while Figure 2B also shows a detailed view. In the illustrated working embodiment, the lancet 136 is configured as a microsampler and has a tapered, outwardly facing lancet end 138 with a lancet tip and a lancet body 140 that widens in each case. At the end opposite the lancet tip, the lancet 136 can include one or more coupling elements 141 for coupling to an actuator, such as a small ring, a guide hole, etc. Each lancet 136 has a capillary channel 137, such as a capillary gap, which is indicated by dashed lines in Figure 2B and is used to collect a blood sample. The lancet 136 can be made of a metal disk 142, for example etched into a flat lancet, which can be seen in Figure 2 A. The metal disk 142 can have, for example, a single radial lancet arrangement or a plurality of lancet arrangements, which can be applied sequentially to different box housings as an example.

The metal disc 142 and/or parts of the metal disc 142 act as a retaining element 144, by means of which the lancets 136 are interconnected. The retaining element 144 can comprise, for example, an etching grid, which is etched from the metal disc 142. The lancet 136 can be connected to the retaining element 144 via a connecting element 146, which can be a component of the retaining element 144 or which can also directly form the retaining element 144, for example by means of the lancets 136 being directly interconnected via a taper or the like. The connecting element 146 can, for example, act as a tapered portion 147 in the lancet body 140 (which can be seen in FIG. 2B ). The connecting element can in particular comprise a desired disconnection position, which makes it easier for the lancet 136 to disconnect from the composite shown in FIG. 2A and 2B . The tapered portion 147 ensures that the disconnection debris moves inward from the edge of the lancet body 140, so that these disconnection debris do not hinder the movement of the lancet 136 in the chamber 122.

In the scenario presented in Figures 2A and 2B, the lancet 136 is radially positioned against the retaining element 144, so that the lancet 136 is oriented in a manner corresponding to the socket 120 of Figure 1B. Subsequently, the analytical aid 134 or the lancet 136, connected to each other in this manner, is optionally separated from the retaining element 144, for example by disconnecting it, and placed in the socket 120 of the first component 112, and separated from the retaining element 144, for example by disconnecting it. This disconnection process can be performed before and/or after the process of placing it in the socket 120. The result of these process steps is shown in Figure 3. The diagram here is similar to Figure 1B, so reference can be made primarily to that diagram.

The method for placing the analytical aid 134 or the lancet 136 into the socket 120 can be carried out, for example, by means of a holding element 144, which is clamped by means of a suction unit, a clamp or a similar device and is positioned accordingly. This method can be carried out automatically or manually. The metal disk 142 and/or the holding element 144 can contain further positioning aids for this purpose, such as the positioning opening 145 shown in Figure 2A. The analytical aid 134 or the connecting element 146 can be separated, for example, by mechanical stamping, applying pressure or similar separation methods, such as the above-mentioned disconnection method. In this case, the individual lancets 136 can be fixed, for example, to an isolation tool, such as a magnetic tool and/or by means of a vacuum fixation or a similar fixing device, in particular until the lancets 136 are located in their respective chambers 122.

This figure shows that one purpose of the socket 120 is to at least partially secure the analytical aid 134 in its spatial orientation after separation from the retaining element 144. The socket 120 can therefore be configured so that it does not need to include a recess, as shown, and thus the recess can also be replaced, for example, with other elements and/or configured to have a desired small depth. However, the embodiment shown is preferred due to its good securing properties. The depth of the socket 120 is preferably designed to be at least equal to the depth of the lancet 136 or the analytical aid 134.

The method of separating the analytical aids 134 can be carried out before, during, or after the method of inserting the analytical aids 134 into the receptacle 120. Thus, for example, a separation method can be carried out after the insertion method and/or already when the analytical aids 134 are still connected to one another by means of the holding element 144 and are positioned in a suspended manner above the first component 112. In particular, the separation method can be carried out simultaneously for all analytical aids 134 or a plurality of analytical aids 134, i.e., for example, all lancets 136 can be disconnected from the holding element 144 or the etching grid at once so that they can fall into the underlying receptacle 120.

In another method step, the socket 120 can be closed with the analytical aid 134 received therein. This can, in principle, be accomplished by applying any desired second component 148, which can also be configured as a membrane, for example. However, in an optional embodiment shown in FIG4 , the second component 148 is configured, for example, as an annular disk serving as the upper portion. This annular disk ( FIG4 shows an oblique view from below of the second component 148 (i.e., viewed from the chamber 122)) can also be produced, for example, from plastic and is preferably configured to be substantially rigid.

The second component 148 can include a plurality of elements corresponding to the socket 120. In the working embodiment shown, the second component 148 includes a plurality of recesses 150 corresponding to the socket 120 and also arranged radially. By way of example, as shown in FIG4 , the recesses 150 can further include openings 126 on the outer circumferential surface 114 and/or on the side assigned to the inner opening 116. The openings 126 can then form an integral part of the sampling opening 130 and/or the actuator opening 132.

Furthermore, the second part 148 comprises a plurality of ribs 152, which are likewise arranged in a manner corresponding to the socket 120. These ribs (optionally also together with the curved bottom of the socket 120 of the first part 112) can impart elastic bending to analytical aids 134, such as lancets 136 or samplers, and thus protect them from falling out.

FIG5 shows the analytical box 110 or a partially completed portion of the analytical box 110 after the second component 148 has been applied to the first component 112 as shown in FIG3 . This view is shown from an oblique perspective from above, looking toward the second component 148. The second component 148 and the first component 112 can be connected to each other, for example, by welding, such as laser welding. For this purpose, for example, one of the components 112, 148 can be configured so that it is transparent to laser radiation, while the other of the components 112, 148 can be configured so that it absorbs laser radiation. In particular, the two components 112, 148 can be made of materials with different absorption properties. Using one or more of the aforementioned plastics is particularly preferred. In this case, the same base material, such as the same plastic, can be used for both components 112, 148, but their absorption properties can differ, for example, by the addition of additives such as dyes. In this way, in particular in the wavelength range of 500 nm - 1200 nm, in particular 700 nm - 1100 nm, differences in the absorbance of components 112, 148 and/or the constituent parts of said components 112, 148 can be produced, for example differences in absorbance of at least 20%, preferably at least 50% or even at least 80% or more.

As can be seen from the figure, the second component 148 can, for example, have a transfer element 118 on its top side, which cannot be seen in FIG. 4 . This is only difficult to discern in FIG. In FIG. 5 , it is clearly visible that the second component 148 has additional openings 126 in the form of a plurality of transfer openings 154. These transfer openings 154 can be arranged, for example, in such a way that each chamber 122 has one such transfer opening 154. Thus, the transfer openings 154 (which are shown as circular transfer openings 154 in the working embodiment shown) are arranged in a circular pattern on the top side of the housing 156 of the test element chamber 110, which is formed by the first component 112 and the second component 148. However, other configurations are also possible in principle.

The transfer opening 154 in the second part 148 is then used to transfer the sample from the lancet 136 to the test field 170 during use of the analysis box 110, for example, in an analysis system, which is described in more detail below. Thus, for example, an actuator (e.g., a piston) can be introduced into the chamber 122, for example, in the application position of the analysis system, through the transfer opening 154 and press the lancet 136 (or microsampler) with the sample onto the test field 170, thus transferring the sample from the lancet 136 to the test field 170. The transfer opening 154 can thus also serve as the actuator opening 132 and is also shown accordingly in the figure.

In a further method step, a test chemical 158 is then applied to the underside of the housing 156. This is shown in FIG7B . The test chemical 158 can be configured, for example, as a test chemical field 160, in particular as a continuous test chemical field 160, preferably in the form of an annular test chemical field 160. The test chemical 158 is preferably configured in such a way that it is at least substantially stable to environmental influences, in particular to air humidity. This stability is also advantageous with respect to conventional ionizing radiation used for sterilization. Reference is made to the above description for possible configurations of the test chemical 158.

The test chemical 158 can be applied to, for example, a carrier 164, such as the same annular carrier 164, which is preferably configured as a continuous carrier 164 for all chambers 122, preferably as an integrated carrier 164. In this working embodiment, the carrier 164 and the test chemical field 160 together form a continuous chemical ring 162. As an example, the carrier 164 can be configured in the form of a self-adhesive film or a non-adhesive film and/or a plastic carrier. Other carrier materials are also possible in principle. In the working embodiment shown, the carrier 164 with the test chemical 158 (which is arranged on the top side of the carrier 164 in the figure shown in FIG7B) is introduced into the annular groove 124 on the rear side of the first component 112. The test element opening 128 is preferably completely sealed by the test chemical 158 and the carrier 164, so that the carrier 164 and/or the test chemical 158 can also serve as a seal 166 for the test element opening 128 at the same time. However, as an alternative or in addition, another seal 166 can also be provided. The latter can be applied, for example, to the rear side of the carrier 164 after the carrier 164 has been applied into the annular groove 124 , for example by means of an adhesive bonding method and/or a lamination method.

The carrier 164 and/or the test chemical field 160 are preferably completely covered with the test chemical 158. In the region in which the test chemical field 160 covers the test element opening 128, a region 168 of the test chemical field 160 respectively forms a test field 170 which is associated with the interior of the chamber 122 and thus also forms a component of the analytical aid 134 or a sub-aid.

The test chemical 158 is then located directly below the lancet 136 in the chamber 122, and each chamber 122 is separated from the following chamber 122. Only the sampling opening 130, the actuator opening 132 and the transfer opening 154 remain open. If the sampling activity is then carried out by means of the lancet 136, the body fluid (especially blood) can be collected through the capillary channel 137, for example by means of the capillary effect and/or the surface effect of the lancet 136. As a result of the lancet 136 moving back into the chamber 122, the body fluid is then brought into the vicinity of the test chemical 158, so that the sample can be transferred from the lancet 136 into the test chemical 158 or into the corresponding test field 170 of the chamber 122 currently being used.

In order to protect the anti-environmental influence of currently unused chamber 122, particularly the influence of moisture, other opening 126 can be sealed in such method step, and this method step is before the method step of Fig. 7, sometimes simultaneously or afterwards carries out.Therefore, as an example, Fig. 6 has represented sealing 166, and as an example, this sealing can be used for simultaneously or continuously sealing measurement opening 154 and/or actuator opening 132 and/or sampling opening 130.Described sealing can comprise for example wafer, and this wafer comprises the element of thin aluminum foil or similar foil type.Seal 166 (it can also be formed with multi-part form) can rely on for example deep drawing method to carry out.Seal 166 can for example be connected to shell 156 by bonding and/or lamination in form-locking mode and/or material condensation mode and/or force-locking mode.

In FIG7A , the analysis box 110 is shown in a sealed configuration. As described above, the analysis box can be placed, for example, in an analysis system, wherein the analysis box 110 can be rotated about a rotation axis, for example, by means of a corresponding transport mechanism, to move each chamber 122 to at least one application position, for example, for sampling. Furthermore, additional positions, such as measurement positions, can be provided, where changes in the color and/or other properties of the test field 170 can be measured, for example, via the measurement opening 154.

In the application position, on the inner circumference associated with the inner opening 116, a driver (e.g., a driver comprising at least one driver piston) can enter, e.g., penetrate, into the chamber 122 located in the application position, in which case (e.g., simultaneously and/or beforehand) the seal 166 of the driver opening 132 of the chamber 122 located in the application position can be opened, e.g., punctured. A sampler in the form of a lancet 136 can then be released during activation through the seal 166, e.g., a membrane on the outer circumferential surface 114.

The measurement of the change in the properties of the test field 170 can be performed, for example, from outside the analysis chamber 110, for example, through the carrier 164 of the test chemical 158. For this purpose, the carrier 164 can be configured, for example, such that it is completely or partially transparent, so that, for example, in FIG. 7B , the color change can be measured from below the test element chamber 110.

Reference Signs List

110 Analysis Box

112 First Part

114 outer circumference

116 inner opening

118 Transmission Elements

119 Notch

120 socket

122 Chamber

124 annular groove

126 Opening

128 Test element opening

130 Sampling opening

132 Transmission opening

134 Analysis Aids

136 Lancet

137 Capillary channel

138 Lancet Tip

140 lancet body

141 Coupling element

142 Metal Plate

144 holding element

145 Positioning opening

146 Connecting elements

147 tapered section

148 Second Part

150 Depression

152 ribs

154 Transfer Opening

156 housing

158 test chemicals

160 Testing Chemical Field

162 Chemical Environment

164 carrier

166 Seal

168 Area allocated to chamber

170 test site.

Claims (14)

1. An analytical chamber (110) comprising a plurality of analytical accessories (134), wherein the analytical chamber (110) has at least two chambers (122), the analytical accessories (134) being received into said chambers, wherein the analytical accessories (134) are received into at least one chamber (122), wherein each analytical accessory (134) comprises at least one test element (170) having at least one test chemical (158) for detecting at least one analyte in a liquid sample, wherein the test chemical (158) is at least substantially stable with respect to environmental impact, wherein the analytical chamber (110) has at least two components (112, 148) The outer shell (156) of the at least two components (112, 148) is connected to each other by laser welding, wherein the first and second of the at least two components (112, 148) have different transparency, wherein at least one of the first components (112) of the at least two components (112, 148) is configured as a substantially rigid component, wherein “substantially rigid” means that the component does not undergo any significant bending and/or other deformation under its own weight, and wherein adjacent chambers are separated from each other by a continuous welded joint having a maximum width of 0.3 mm. 2. The analytical chamber (110) of claim 1, wherein the liquid sample is a body fluid. 3. The analytical chamber (110) of claim 1 or 2, wherein the analytical chamber (110) has a housing (156) with at least two components (112, 148), wherein the housing (156) comprises a material selected from the following: polycarbonate; acrylonitrile-butadiene-styrene; cyclic olefin copolymer; polymethyl methacrylate; polystyrene; polyethylene terephthalate. 4. The analysis box (110) of claim 2, wherein the analysis accessory (134) further comprises at least one lancet (136) having at least one capillary channel (137) for receiving body fluid and guiding the body fluid to the test element (170) via the lancet (136). 5. The analytical chamber (110) of claim 4, wherein the capillary channel (137) of the needle element is coated to improve the transport of bodily fluids. 6. The analytical chamber (110) of claim 4, wherein the capillary channel (137) of the needle element is hydrophilically coated to improve the transport of bodily fluids. 7. The analytical chamber (110) of claim 1 or 2, wherein the at least two components comprise the same base material, but in each case have different absorption for light in the visible and/or infrared and/or ultraviolet spectral ranges. 8. The analysis chamber (110) of claim 1 or 2, wherein the two components have a transparency difference of at least 5% with respect to the laser radiation used. 9. The analysis chamber (110) of claim 1 or 2, wherein the two components have a transparency difference of at least 20% with respect to the laser radiation used. 10. The analysis chamber (110) of claim 1 or 2, wherein the two components have a transparency difference of at least 50% with respect to the laser radiation used. 11. The analytical chamber (110) of claim 1 or 2, wherein a field of test chemicals is applied to a continuous carrier, wherein the carrier simultaneously carries test chemicals for multiple chambers. 12. The analytical chamber (110) of claim 11, wherein the carrier simultaneously carries test chemicals for all chambers. 13. A method of producing the analytical box (110) of any one of claims 1-12 relating to the analytical box (110), wherein the analytical box (110) is designed to receive a plurality of analytical accessories (134) in a plurality of chambers (122), wherein each of the analytical accessories (134) has a test chemical (158), wherein the plurality of analytical accessories (134) are introduced into at least one chamber (122), wherein the analytical box (110) has at least two components (112, 1... 48) housing (156), wherein the first and second of the at least two components (112, 148) have different transparency, wherein the at least two components (112, 148) are connected to each other by laser welding before or after the analytical accessory (134) is introduced into the chamber (122), and wherein adjacent chambers are separated from each other by continuous weld seams having a maximum width of 0.3 mm. 14. The method of claim 13, wherein each of the analytical accessories (134) further comprises at least one lancet (136), wherein the analytical chamber (110) is sterilized by ionizing radiation after the laser welding method is performed.