AU2013202929B2 - System for detection of an analyte in a body fluid - Google Patents

Abstract

C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 Abstract A system (110) is proposed for detection of at least one analyte in a body 5 fluid, in particular for detection of blood glucose. The system (110) is designed to generate a sample (130) of the body fluid and to transfer at least some of the sample to at least one test element (128), in particular a test panel (129). The system (110) is designed such that a time period between the generation of the sample (130) and the application to the test element (128) is less than 1 s, 10 preferably less than 500 ms. (Figure 1)

Description

C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 1 SYSTEM FOR DETECTION OF AN ANALYTE IN A BODY FLUID Field of the invention 5 The invention relates to a system for detection of at least one analyte in a body fluid. Such systems are used, for example, as portable detection devices or also in stationary devices, in order in particular to permit qualitative or quantitative determination of one or more analytes in body fluids such as blood or interstitial fluid. The analytes involved in particular are metabolites. The detection of blood 10 glucose is described below in particular, without ruling out other types of analytes. Prior art Numerous systems for detection of analytes in body fluids are known from the 15 prior art. These systems are generally based on first generating a sample of the body fluid, for example by using at least one lancet. Then, using at least one test element, this sample is generally examined qualitatively or quantitatively for the at least one analyte that is to be detected. This can be done optically and/or electrochemically, for example. The test element can, for example, contain one or 20 more test panels, with a test chemical that is specially designed for the detection of the at least one analyte. For example, the test chemical can undergo one or more detectable reactions or changes in the presence of the at least one analyte, which reactions or changes can, for example, be detected physically and/or chemically. 25 Many such systems are known from the prior art. Thus, for example, US 7,252,804 B2 describes a measuring unit for analysis of a body fluid, comprising a measuring appliance based on the use of test strips, and a lancet connected to the measuring appliance. Moreover, systems are also known in which the generation of a sample and the collection of the sample by a test element are combined. For example, EP 1 30 992 283 Al describes a piercing system with lancets for generating a puncture wound, and with sample-collecting devices for collecting a sample of body fluid. Following a piercing movement, a sampling movement is performed, in which the sample is collected. Similarly, EP 1 881 322 Al describes a portable measuring system for analysis of a liquid sample, which system has a moisture-proof housing C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 2 with a housing interior atmosphere. The liquid sample can be applied to the at least one test element within the housing interior atmosphere. In addition to such systems in which a sample is generated and is then transferred 5 to the test element, systems exist in which the generation of the sample and the collection of the sample are integrated. For example, this can be done using suitable needles, which are designed wholly or partially as capillaries for collecting the liquid sample. By means of these capillaries, the liquid sample can be transferred to a test element which, for example, can be integrated into the needle 10 or generally into a lancet device. Such lancet systems are often also referred to as "get and measure" systems. Examples of integrated lancet systems of this kind are described in WO 2005/084546 A2. Irrespective of the system used, it is a general aim of systems for detection of 15 analytes in body fluids to considerably reduce the sample volume of the samples. Such a reduction is desirable for a number of reasons. First, with reduced sample volumes, it is possible to minimize the pain experienced by the patient in connection with the analysis. Moreover, large sample volumes also cause difficulties, for example in terms of an increased danger of contamination of the 20 analysis equipment by the sample itself. A further reason for reducing the sample volumes lies in the aim of producing integrated systems. This integration requires a higher degree of functionality within the same space, such that the space available for a lancet is generally reduced, and therefore also for the sample volume. Moreover, these systems do not generally afford the possibility of actively 25 manipulating the perforated surface of the skin in order to increase the sample volume ("milking"), such that integrated systems in most cases have to operate with smaller sample volumes. However, as has been discovered in the context of the present invention, a 30 difficulty in systems which operate with reduced sample volumes, for example blood volumes of less than 1 [tm, can lie in the influence of evaporation and the associated at least partial drying of the sample. However, drying of the sample, for example by evaporation of water, in turn results in an increased concentration of the substances dissolved in the liquid sample, for example glucose. In such 35 samples, however, the raised concentrations measured are then inaccurate.

C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 3 Evaporation effects of liquids have in general been widely examined and described in numerous publications in the literature. Most studies refer to free-falling water droplets or applied water droplets, not to liquids generally in depressions, which 5 can behave fundamentally differently than free droplets. The evaporation is influenced, for example, by the air humidity and the convection in the environment of the surface of the liquid. Under normal conditions, typical evaporation rates of droplets of at least approximately 100 nl range from 0.3 to 0.6 nl/s and, under constant environmental conditions, are dictated by the droplet surface area for 10 example. Said studies of the principles of evaporation in many cases lead to complex theoretical predictions of evaporation, which are based on knowledge of a large number of environmental factors and parameters. However, since analysis systems 15 for detection of analytes in body fluids in many cases have to work across a wide temperature range and air humidity range, and independently of special convection conditions, such predictions and analyses are of relatively little help in practice. Influences exerted by drying effects are also known from the field of medical 20 diagnostics. For example, in US 7,252,804 B2, reference is made to the effect of this drying of blood samples in biosensors with piercing aids. Analogously, US 6,878,262 B2 refers to this effect and proposes that capillaries for blood transport be closed in order to avoid evaporation. An analogous procedure is also chosen in US 6,565,738 BI or in US 6,312,888 BI, for example. In order to avoid drying out 25 of samples, particularly by convection, it is also proposed in US 6,325,980 BI that samples with a volume of less than 0.5 1d be covered. Many of the known approaches thus counter the problem of evaporation by covering the capillaries, but in many cases this is almost impossible in practice or 30 is at least difficult to achieve. Particularly in the "get and measure" systems described above, covering of the lancets, which are constructed as disposable systems, can be realized only with considerable technical effort. In many cases, therefore, evaporation from semi-open capillaries has to be considered. However, such systems with a multiplicity of interfaces can be theoretically described only 35 with difficulty. Because of the abovementioned complex environmental conditions, 4 particularly as regards the temperature range and/or air humidity range and the special convection conditions, it is in particular inadequate to incorporate constant correction factors into the calculation of a glucose concentration and/or of another analyte concentration. In practice, it has been shown in particular that theoretical or 5 semi-empiric approaches to correcting the evaporation in many cases lead to unrealistically low evaporation rates and, consequently, to erroneous corrections. Aim of the invention 10 The present invention seeks to make available a system which is used for detection of at least one analyte in a body fluid and which avoids the disadvantages of known systems. In particular, the system should be inexpensive to produce but should still be able to yield improved detection results within a broad spectrum of realistic environmental conditions. 15 Disclosure of the invention A system for detection of an analyte in a body fluid is therefore proposed which has the features of the independent claims. Advantageous refinements of the 20 invention, which can be implemented singly or in combination, are set forth in the dependent claims. The system is used for detection of an analyte in a body fluid. This fluid can, in particular, be blood and/or interstitial fluid, although other types of body fluid can 25 also be examined alternatively or in addition. The at least one analyte, which can be detected qualitatively and/or quantitatively, can in particular be at least one metabolite. This can be blood glucose in particular. Alternatively or in addition, however, it is also possible to detect analytes such as cholesterol, lactate, coagulate, troponin, myoglobin, proBNP, C-reactive protein, CK-MB or the like. It 30 is also possible to detect a combination of several analytes. The proposed system is designed to generate a sample of the body fluid and to transfer it to at least one test element, in particular to a test panel. For the purpose of generating the sample, the system can in particular comprise at least one lancet 35 for puncturing a skin part of a user. The term lancet is to be interpreted broadly and C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 5 in principle includes any desired element that can generate an incision and/or puncture in the skin part. Moreover, the lancet and/or the system can comprise at least one actuator, which is designed to effect a lancet movement of the element for generating the incision and/or puncture for the purpose of generating the sample of 5 the body fluid. The at least one test element can comprise, for example, at least one test panel. In particular, the at least one test element, particularly the at least one test panel, can comprise at least one test chemical which, in the presence of the at least one 10 analyte, changes at least one measurable property, for example a physically and/or chemically measurable property. For example, this can be an electrochemically measurable and/or optically measurable property, for example a color change. For this purpose, the test element, in particular the test chemical, can comprise suitable chemicals and/or chemical mixtures, for example enzymes, auxiliaries or the like, 15 which are known in principle from the prior art and can also be used in the context of the present invention. For example, reference can be made to J. Hdnes et al., Diabetes Technology and Therapeutics, volume 10, supplement 1, 2008, page 10 to page 26. The test elements and/or test chemicals described there can also be used in the context of the present invention. 20 The test element can be integrated into the at least one lancet and/or can also be designed wholly or partially separate from the at least one lancet. If the test element is integrated into the at least one lancet, it is possible to use lancets known, for example, from known "get and measure" systems, for example in accordance 25 with the prior art cited above. For example, one or more test panels can be arranged at the end of a closed or opened capillary or can also wholly or partially cover a capillary gap, such that the sample is transferred through the capillary gap to the test element. 3 0 To ensure the transfer of the sample, all or some of which can be transferred, to the at least one test element, several mechanisms can be provided. Thus, for example, the transfer of the sample from the site of generation to the test element can take place at least partially, or in some sections, via at least one capillary. This can in particular be a capillary that is wholly or partially integrated into a lancet. In 35 particular, this capillary can be designed as a partially opened capillary, that is to C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 6 say as a capillary in the form of an opened slit in the lancet. As has been described above, this can in particular be a lancet with an integrated test element, that is to say what is called as "get and measure" lancet. 5 Generally, however, the expression transfer of the sample of body fluid to the test element is to be interpreted broadly. This expression generally means that the sample and the test element are to be moved relative to each other, that is to say are to be changed in terms of their position and/or orientation and/or extent and/or shape, such that the sample is transferred to the test element. The use of a capillary 10 is one possibility of moving the sample itself to the test element. Alternatively or in addition, however, it is also possible to use mechanisms in which the test element is moved in order to collect the sample. For example, the system can comprise a mechanism in which the sample is initially generated on and/or in a skin part and is then transferred to the test element by a movement of the test 15 element relative to the skin part and/or to the sample. In other words, blood for example can initially be generated in and/or on a skin part, for example of a finger, in order then to be collected from the skin surface directly via a test panel for example. The mechanism can, for example, be designed analogously to the mechanism described in EP 1 992 283 Al or in EP 1 881 322 Al. 20 Proceeding from a basic system of this kind, which can be applied to all aspects of the invention described below, the invention is based on studies of the drying behavior of blood samples. These experiments were carried out in some cases on open samples, but in some cases also on capillaries, for example opened capillaries 25 in needles. The basic result of these studies is that, as has been described above, theoretical or semi-empiric models, which are based on studies of free or applied droplets of test liquids, for example water, cannot be directly transposed to systems for detection of analytes, of the kind that are used in practice. Accordingly, three concepts are proposed, which can also be used in combination and which can be 30 used to avoid the abovementioned problems of measurement inaccuracy caused by evaporation effects in analysis equipment and systems of the type described above. The concepts are based on the same underlying principle, namely that in conventional systems, on account of the many varied environmental conditions such as pressure, humidity, temperature, convection or similar influences in the 35 area of the sample, corrections of the measurement results on the basis of the C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 7 known analytical or semi-empiric models, for example in the context of constant correction factors or correction functions, cannot be applied unless additional measures are taken. 5 A first concept of the present invention is to limit the time taken for the above described transfer of the sample of body fluid to the test element. It was discovered that, with typical and preferred sample volumes in the range below 1 1d, the time between generation of the sample and application to the test element should be less than 1 s, preferably less than 800 ms, particularly less than 500 ms. In typical 10 setups and with typical sample volumes and typical test geometries, such transfer times of less than 1 s lead to still tolerable discrepancies resulting from evaporation effects, for example discrepancies of the measured results of less than 20%, preferably of less than 5%. Therefore, according to a first aspect of the present invention, the system can be configured such that a time between generation of the 15 sample and application to the test element is less than 1 s, preferably less than 500 ms. Transfer times of less than 200 ms or even of less than 100 ms are particularly preferred. Here, and in the text below, the transfer time is generally understood as the time between the moment an element effecting the sample transfer makes first contact with a primary sample (for example body fluid in and/or on the skin of a 20 test subject) to the moment when the sample first makes contact with the at least one test element, in particular the at least one test chemical. A primary sample is understood here as the sample in and/or on the skin of a test subject. The transfer time can also be divided into several time segments, for example a collection time, for the actual pickup of the sample by the transfer element (for example the 25 capillary), and the time for the actual transfer to the test element, which could also be designated as the transport time. The collection time and the transport time can also overlap since, for example, a collecting procedure does not necessarily need to have been concluded during the actual transfer. 30 This condition for the transfer time can be guaranteed in the system in different ways, depending on the nature of the transfer. For example, one of the above described types of transfer can be guaranteed in the system. For example, a capillary can be used, in particular a capillary integrated into a lancet. The capillary can be closed or also at least partially opened, for example designed as an at least C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 8 partially open channel with in principle any desired cross section, for example a rectangular, round or triangular cross section. In particular, in order to ensure preferably the above-described transfer times in 5 systems of this kind with a capillary, particularly an opened capillary, generally and without limitation to the other above-described features, it is preferred if the length of the capillary is not more than 8 mm (length < 8 mm or < 8 mm), preferably not more than 6 mm (length < 6 mm or < 6 mm) and particularly preferably not more than 4 mm (length < 4 mm or < 4 mm). As capillaries, for 10 example, it is possible to use gaps with a gap width of 20 micrometers to 500 micrometers, preferably between 50 micrometers and 200 micrometers, and particularly preferably of 100 micrometers. Said preferred conditions apply in particular to systems of the type described above, but also generally to other systems which are used for detection of at least one analyte in a body fluid and 15 which are designed to generate a sample of the body fluid and to transfer at least some of it to at least one test element and in which at least one capillary is provided for the transfer of the sample. It has been shown that a filling speed of a capillary can be dependent on the 20 capillary length and/or capillary geometry. In particular, the filling speed of the capillary, that is to say of the capillary section relevant to the measurement, can decrease exponentially as a function of the capillary length. However, in order to ensure a short filling time, a particularly preferred capillary geometry has a ratio of the fillable capillary length to the capillary diameter that is less than 100, 25 preferably less than 30, in particular less than 20, and particularly preferably 15 or less. Alternatively to the capillary diameter, other dimensions characterizing the width of the capillary cross section can also be used, for example, in the case of an opened capillary, particularly a semi-open capillary, instead of the diameter also the length of the bottom surface plus twice the height of the capillary walls. 30 In order to accelerate the transfer, that is to say in order to shorten the transfer time, the at least one capillary, regardless of whether it is designed as a closed capillary or as an at least partially opened capillary, can further comprise at least one hydrophilization. This can involve one or more hydrophilic coatings, for 35 example. Coatings with detergents can be used for example. In particular, one or C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 9 more of the following materials can be used for the hydrophilization: heparin; polyacrylic acid or polyacrylic acid derivatives; chondroitin sulfate; dioctyl sodium sulfosuccinate (DSS); polysorbate; nonionic surfactants. In this context, reference can be made, for example, to the European patent application with the application 5 number EP 07 114 414.1, or alternatively to EP 1 887 355 Al. Alternatively or in addition, however, hydrophilizing surface treatments can be carried out, for example hydrophilizing plasma treatments, for example oxygen plasma treatments or the like. In this way, the transfer of the sample can be additionally accelerated, for example since the collection time is shorter. The transfer time, which is the 10 time between the generation of the sample on a skin part and the transfer to the test element, or to a test panel of the test element, can be composed of several segments for example. Thus, part of the transfer time can consist of a collection time and/or filling time of the capillary, followed by, for example, a transport time to the test element until the latter is brought into contact with the blood. In this way, for 15 example, it is possible to achieve the transfer times described above. In systems which use other transfer concepts as an alternative or addition to the use of a capillary, the stated transfer times can also be achieved. Thus, for example, the system described above can be designed to generate the sample on a skin surface, 20 with the system being further designed to then move the test element relative to the skin surface in such a way that the test element picks up all or some of the sample. This can be done, for example, by means of the mechanism described above. The sample pickup can be configured, for example by suitable design of the mechanism, in such a way that this sample pickup takes place within a time of less 25 than 1 s, in particular of less than 500 ms, particularly preferably of less than 200 ms or even 100 ms. By using the stated transfer times, which lie within the stated preferred time frames, it is possible to minimize the evaporation effects and their influence on the 30 measurement accuracy, such that the measurement accuracy lies within tolerances that are conventionally predefined in blood glucose meters for example, in the range of tolerance of 20% for example. In blood glucose meters, tolerances of 20% are typically predefined at concentrations of over 100 mg/dl, whereas tolerances of 20 mg/dl are predefined below 100 mg/dl. The data are in each case based on 95% 35 of the values lying within the tolerance interval.

C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 10 Alternatively or in addition to the concept of accelerating the transfer time, a concept is further proposed in which the sample volume is deliberately influenced. As has been explained above, sample volumes of generally less than 1 1d are aimed 5 for in modern blood glucose meters. Surprisingly, in the context of the tests described in detail below, in which it was established that the evaporation is considerably greater than would be assumed from the literature, it was nonetheless discovered that this minimizing of the sample volumes can lead to serious problems if there is no lower limit to the sample volumes. It was discovered in 10 particular that sample volumes of 10 nl or less have such considerable evaporation effects that, in most cases, the measurement inaccuracy caused by the evaporation exceeds the range that can be tolerated at least for blood glucose meters. Therefore, according to a further aspect of the present invention, a system of the 15 kind described above is proposed in which the volume of the sample is less than 500 nl, particularly less than 400 nl, less than 300 nl, less than 200 nl or even less than 100 nl, but still greater than 10 nl. The sample volume is preferably at least 12 nl. 20 In the context of the present invention, the sample volume generally designates the volume of sample that is originally picked up by the system, that is to say before evaporation effects have set in. Preferably all of this sample volume is transferred to the test element, although some of it can remain in other parts of the system, for example in a capillary. Therefore, the term sample volume is to be distinguished 25 from the total volume of the sample that is generated, for example blood on and/or in a finger pad, an ear lobe, or a skin part in the arm area. Of this total volume of the sample, only the sample volume is picked up by the system. The sample volume can preferably be detected by the system, as is explained in detail below. In the context of the present invention, the sample volume thus detected is also 30 designated as the actual sample volume. The sample volume can therefore lie in particular in a range of between 10 nl and 500 nl (that is to say 10 nl < sample volume < 500 nl), preferably in the ranges of 10 nl < sample volume < 400 nl, 10 nl < sample volume < 300 nl, 10 nl < sample 35 volume < 200 nl, and particularly preferably in the range of 10 nl < sample volume C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 11 < 100 ni or even in the range of 10 ni < sample volume < 50 nl. The lower limit of the range is preferably slightly more than 10 nl, preferably at least 12 nl. As has been indicated above, the sample can once again be transferred to the test 5 element by one or more of the stated methods, for example. Particular mention may be made again to the transfer by means of at least one capillary, in particular by means of at least one at least partially opened capillary. Particular mention may be made again to a capillary integrated in a lancet, in particular an at least partially opened capillary. Once again, the lancet can be designed as a lancet with an 10 integrated test element, that is to say as a "get and measure" lancet or, using the equivalent term below, as a microsampler. Alternatively or in addition, however, the system can once again also be designed with a mechanism in which the sample is first generated on a skin part and is then transferred to the test element by a movement of the test element relative to the skin part and/or to the sample. 15 Regarding the possible configurations, reference can be made to the above description which, as has been indicated, is applicable to all of said concepts according to the invention. Since the sample volume, as has been indicated above, plays an important role in 20 the described evaporation effects, a control of the sample volume is proposed according to the invention. This can be ensured, for example, by virtue of the fact that the system is designed to detect an actual sample volume of the sample collected by the system and/or of the sample transferred to the test element. As has been indicated above, the sample volume is to be differentiated from the generated 25 sample volume, for example the volume of a droplet of blood on a skin surface. The actual sample volume therefore represents an actual measured value of the sample collected by the system and/or of the sample transferred to the test element. The detection of the analyte can then take place, for example, taking into account 30 the actual sample volume. For example, one or more correction factors and/or other corrections, for example correction functions, can be used in order that measured values, which are generated as a result of the detection, are corrected accordingly to the actual sample volume. In this way, it is possible to at least partially compensate for evaporation effects dependent on sample volume, and for 35 associated changes in concentration of the at least one analyte. In this way, it is C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 12 possible, for example, to at least partially compensate for and/or correct increases in concentration of the sample resulting from evaporation effects. The actual sample volume can be detected in different ways, it being possible in 5 principle to use any desired physical and/or chemical measuring methods for example. This detection can, for example, involve an optical detection. Thus, for example, a spatial extent of the sample can be detected optically, in particular a spatial extent on the test element and/or in a capillary. This can be done, for example, by detecting differences in contrast between the sample and the 10 surrounding materials, which differences in contrast can also be specifically improved by suitable coloring of the system and/or of the system components coming into contact with the sample. For the optical detection, at least one optical sensor for example can be provided, for example an imaging sensor, for example a semiconductor sensor, and, if appropriate, suitable image processing. In this way, 15 for example, the size of a spot of sample on a test panel can be detected, as a result of which conclusions can in turn be reached regarding, for example, the actual sample volume that was transferred to the test element. Similar measurement principles are known from US 6,847,451 B2, for example, in which, when using a detector array, only those fields of the array are used that have areas of a test panel 20 sufficiently covered with sample. In contrast to this, it is possible for example, in the context of the present invention, to use similar techniques to reach quantitative conclusions regarding the actual sample volume. Alternatively or in addition, other optical measurement principles can also be used, for example diffraction measurements, transmission measurements, absorption measurements, reflection 25 measurements, fluorescent light measurements or combinations of said and/or other optical measurements, from which conclusions regarding the actual sample volume can be drawn. For example, in a capillary and/or at another representative location of the system, it is possible to carry out absorption measurements and/or transmission measurements and/or reflection measurements from which the 30 product of the concentration of a sample-specific substance, for example hemoglobin, and of a filling state variable, for example a filling height of a capillary, can be determined. From this, the actual sample volume can in turn be determined absolutely and/or relatively. For example, the capillary, in particular an inner surface of the capillary, can also be wholly or partially roughened, for 35 example by an etching process. This roughening can, for example, increase a C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 13 reflectance of the surface. In this way, for example, an optical contrast enhancement can be achieved, particularly in metal capillaries. The reflectance can be specifically influenced by roughening, in order to make it possible or easier, for example by absorption measurements and/or transmission measurements and/or 5 reflection measurements, to measure a filling level and/or a volume filling in the capillary. Alternatively or in addition to an optical detection, however, other types of detections and/or sensors can also be used, for example electric sensors and/or capacitive sensors. The concept of detecting the actual sample volume can be transposed to all of the above-described transfer concepts and/or to other types of 10 transfer concepts. The sample volume that is collected by the system and/or transferred to the test element can be adjusted in various ways. For example, the geometries of a lancet and/or of a capillary and/or of the test element can play a role here. Thus, for 15 example, the collected sample volume can be influenced by adjusting a capillary geometry. On the other hand, the collected sample volume can be influenced, for example, by the design of a lancet tip and/or by a puncture depth of the lancet, since, for example, generation of a larger amount of sample can lead to an increased amount of collected sample. 20 Particularly in connection with the detection of the actual sample volume, but also in other system configurations, the system can in particular be designed to actively control and/or regulate the sample volume. This can be done in particular by adjusting a puncture depth of a lancet. Regulation can be provided in connection 25 with the detection of the actual sample volume. Thus, for example, the system can be designed to detect the sample volume actually collected. Thereafter, the sample volume can be regulated, for example iteratively and/or continuously in a control process, for example by the puncture depth of a lancet and/or the duration of a puncturing procedure being influenced. This can take place in the context of a 30 single puncturing process or also in the context of multiple puncturing. In this way, the preferred sample volume described above can be ensured in particular. A third concept, which can once again also be applied in combination with one or both of the concepts described above, and which is likewise based on a knowledge 35 of evaporation effects, is one in which the environmental conditions are C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 14 specifically taken into account and/or controlled. This idea is based on the underlying concept that, in real systems for detection of analytes, the environmental conditions can vary considerably. In particular, as has been described above, this can be the result of different geometries, air humidities, 5 pressures, temperatures, air movements (for example convection) or similar influences. In order to be better able to detect the influence of these parameters, which in particular can have an influence on the evaporation, it is proposed, in the context of 10 the third concept, that a humidity, for example an absolute and/or relative air humidity, be detected during generation of the sample and/or during transfer of the sample to the test element. The detection of the analyte can then be carried out taking this humidity into account. For example, the humidity can be detected at one or more locations inside and/or outside the system, for example using one or more 15 suitable humidity sensors. For example, the humidity can be determined at the site of generation of the sample and/or at one or more locations in the area of the sample transfer and/or at the site of the at least one test element, particularly at the site of the at least one test panel. 20 The system can preferably be designed in such a way that the influence of variations in environmental parameters, for example air humidity, pressures, temperatures, air movements (for example convection) or similar parameters, is at least substantially eliminated, such that variations can be reduced, which in turn makes it easier to take account of the influence of these parameters, particularly of 25 the humidity, in the detection of the at least one analyte. Accordingly, the system can be further designed such that the generation of the sample and the transfer to the test element are carried out within a substantially closed housing. A substantially closed housing is to be understood here as a housing that is airtight and/or moisture-proof, so as to close off an interior of the housing from an 30 environment of the system. In this connection, reference can be made to EP 1 881 322 Al, for example, and to the possible ways, set out in said document, of closing off a housing. The housing should be closed off in such a way that, at least during typical measuring times of not more than 5 to 10 s, for example, the environmental conditions, for example in respect of the abovementioned parameters, in the 35 interior of the housing are practically unchanged, with the result that changes in C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 15 these parameters have only a negligible influence on the evaporation rate or the change in the evaporation rate. For example, variations of not more than 5% in the evaporation rate can be tolerated. 5 The housing can be designed, for example, in one piece or in several pieces and can, for example, comprise a metal housing and/or a plastic housing. The housing can in particular comprise one or more openings, preferably at least one closable opening. This opening should be designed such that a skin part, in particular a skin part of a finger, can be placed wholly or partially in the opening, wherein the skin 10 part then at least partially closes, preferably completely closes, the opening. This closing of the opening by the skin part can be maintained throughout the measurement procedure, such that the above-described screening of the interior of the housing from the environment is achieved. The interior of the housing can preferably be kept as small as possible in order to keep the conditions therein as 15 constant as possible, for example smaller than 100 ml, in particular smaller than 50 ml, and particularly preferably smaller than 10 ml. Alternatively or in addition, the opening too can be kept very small, for example smaller than 100 mm2, in particular smaller than 50 mm 2 , preferably smaller than 20 mm 2 , 10 mm 2 or less. The sample can then be generated in the skin part placed in the opening. Moreover, 20 as has been described above, the transfer of the sample to the test element also takes place inside the interior of the housing. This transfer can once again be effected, for example, by means of the above-described concepts. Thus, for example, at least one capillary can again be used, in particular a capillary at least partially integrated in a lancet. In particular, a lancet with an integrated test 25 element can once again be used. Alternatively or in addition, however, a method can also be used in which the sample is first generated on the skin part, and at least some of the sample is then transferred to the test element by a movement of the test element relative to the skin part and/or to the sample. A mechanism can once again be provided for this purpose. Combinations of the stated transfer concepts and/or 30 of other transfer concepts are also possible. If at least one opening is provided, the latter can be closed, for example, by means of a closure mechanism while the system is not being used for measurement. For example, the opening can be closed by means of at least a slide, a flap, a flexible 35 sealing lip or similar, such that the opening can be opened in order to carry out a C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 16 measurement. Alternatively, however, it is also possible to provide openings which remain opened during a rest phase in which no measurement is being carried out. It is only during the measurement, when the opening is closed by the skin part, that preferably substantially constant environmental conditions are ensured inside the 5 interior of the housing. As has been indicated above, it is proposed that a humidity be detected, in particular inside the housing, during the generation of the sample and/or the transfer of the sample to the test element. For this purpose, one or more humidity 10 sensors can be provided which are able to detect an absolute and/or relative air humidity of the atmosphere at one or more of the abovementioned locations, for example in the interior of the housing. The system can then in particular be designed to detect the analyte taking into account the at least one humidity. For example, if several humidities are measured, they can be taken into account 15 individually or in combination, for example in the form of mean values. The humidity actually present, in particular the air humidity, which is subject to relatively small and negligible variations as a result of the described preferred encapsulation of the housing, can be taken into account using a known influence of the air humidity on an evaporation rate. Thus, for example, correction factors 20 and/or correction functions and/or other types of corrections can be used in which, taking into account the geometries actually present in the system for example, evaporation effects at the actual air humidity and the associated increase in concentration of the sample are corrected. The corrections can be based, for example, on analytical, semi-empiric or empiric knowledge of the evaporation. 25 In contrast to known systems and/or theoretical approaches, a correction in the proposed system according to the third concept of the invention can be realized in a simple way. This is because at least some of the unknown influences which, in conventional systems, prevent the correction or at least make the correction 30 difficult, are known in the proposed system and preferably also substantially eliminated. By means of the encapsulation by the optional housing, for example, a convection and/or a change in the convection conditions during the measurement is substantially avoided. Variations in the air humidity can also be eliminated.

C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 17 Moreover, the system can also be designed to at least temporarily interrupt the detection of the analyte when a predefined minimum humidity is not attained. Thus, for example, the measurement can be discontinued and/or a warning can be generated. For example, one or more humidity thresholds can be predefined, which 5 are compared with the actual measured value of the air humidity. For example, it is possible to establish in this way that an evaporation resulting from too low an air humidity would in fact be too great, and the associated influence of the detection of the analyte would exceed a tolerance range. In this case, for example, a warning can be output to a user to repeat the measurement at a later time and/or under 10 different environmental conditions. Alternatively or in addition, a user can also be prompted, for example, to blow or puff through an opening into the interior of the housing, in order to use the respiratory air to deliberately increase a humidity in the interior of the housing and/or at other locations. 15 The system can also be designed to detect at least one further parameter, particularly inside the housing, during the generation of the sample and/or during the transfer of the sample to the test element. In particular, this can be a parameter that has an influence on the evaporation or the evaporation rate of the sample and/or of constituents of the sample. For example, a pressure and/or a temperature 20 can be detected, for example a pressure in the interior of the housing and/or a temperature of a test element and/or of the lancet and/or an air temperature, in particular inside the housing. This at least one further parameter can likewise preferably be taken into account in the detection of the analyte in the sample, for example by suitable corrections, analogously to the above-described correction in 25 knowledge of the air humidity. The proposed system, which for example can be designed wholly or partially as a portable measuring appliance and/or as a stationary appliance, has many advantages over known systems. Thus, by means of the concepts described above, 30 effects of evaporation can be influenced in a specific way (for example by detection and/or control of the sample volume) and/or at least controlled to such an extent that variations in these influences as a result of a change in environmental conditions and/or in sampling conditions can be at least substantially eliminated. For example, by means of the above-described detection of the actual volume of 35 the sample, an evaporation rate can be assumed, for example at the same time 18 taking account of a measured humidity in the interior of a housing. In this way, for example, a correction of the measurement can be made which, for example, takes into account the contribution of the evaporated sample. Such a correction can in particular be carried out in a technically simple way if, as has been described above, the complete procedure takes place in the interior of a housing that provides a screening of the kind described. For example, a puncturing procedure and a transfer of blood to the test element can take place entirely within the system, that is to say in the housing interior, such that a constant air humidity can be assumed during the course of the measurement. According to one aspect, the present invention provides a system for detection of at least one analyte in a body fluid, wherein the system is designed to generate a sample of the body fluid and to transfer the sample to at least one test element, the system being designed to effect the generation of the sample and the transfer to the test element within a substantially closed housing, the system also being designed to detect an actual sample volume of the sample picked up by the system and/or of the sample transferred to the test element, the system also being designed to detect humidity within the housing during the generation of the sample and/or during the transfer of the sample to the test element, and wherein the system is further designed to detect the analyte taking into account the humidity, and wherein the system is further designed to detect the analyte taking into account the actual sample volume, and wherein evaporation effects, dependent on sample volume, and resulting changes in concentration are at least partially compensated, and wherein the system has at least one 2 opening smaller than 100mm , wherein a skin part can be placed wholly or partially in the opening, wherein the skin part at least partially closes the opening, and wherein the sample is generated in the skin part placed in the opening. Brief description of the figures Further details and features of the invention will become clear from the following description of preferred illustrative embodiments, particularly in conjunction with the dependent claims. The respective features can be embodied singly, or several of them in combination with one another. The invention is not limited to the illustrative embodiments. The illustrative embodiments are shown schematically in the figures. Identical reference numbers in the 18A individual figures designate elements which are identical or whose functions are identical or which correspond to one another in terms of their functions. Figure 1 shows a schematic illustrative embodiment of a system according to the invention; Figure 2 shows a relationship, known from the literature, between an evaporation rate and an opening surface area of a liquid; Figure 3 shows a measurement of a relative deviation of a measured glucose concentration from the mean value as a function of the duration of the time interval between sample collection and sample application; Figure 4 shows typical filling times of differently coated capillaries; Figure 5 shows extrapolated data of an evaporation time as a function of the relative air humidity in percent; and C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 19 Figures 6A and 6B show surface images of metal capillaries without roughening and with roughening. 5 Figure 1 shows a highly schematic depiction of an illustrative embodiment of a system 110 according to the invention for detection of at least one analyte in a body fluid. In the illustrative embodiment shown, the system 110 comprises a substantially moisture-proof housing 112, which has a substantially closed design. The housing 112 comprises an interior 114 which, in the illustrative embodiment 10 shown, is temporarily accessible through an opening 116 in the housing 112 for a measurement. The opening 116 can be designed such that it can be closed, for example, by means of a slide (not shown in Figure 1), wherein a patient or some other user can, in order to perform a measurement, open the slide using one finger 118. 15 A lancet 120 is arranged in the interior 114 and is designed in such a way that, when the finger 118 is placed onto the opening 116, with the finger 118 wholly or at least partially closing the opening 116, the lancet 120 punctures a skin part 122 in the area of a pad of the finger 118. An actuator 124, for example, can incite the 20 lancet 120 to perform a puncturing movement. In the illustrative embodiment shown, the system 110 further comprises a transfer device 126 and at least one test element 128 for detection of the analyte in a sample 130 generated on the skin part 122 by the lancet 120, in the present case a 25 droplet of blood or interstitial fluid. In the illustrative embodiment, the transfer device 126 is designed as a capillary 132, which can be formed, for example, as a gap in the lancet 120. By means of this capillary 132, the sample 130 is transferred wholly or partially to the test element 128, which in this case can be designed, for example, in one piece with the lancet 120. The lancet 120 can therefore be 30 designed, for example, as what is called a microsampler or "get and measure" lancet. The test element 128 can, for example, comprise a test panel 129, which is arranged at the end of the capillary 132. Moreover, a measuring device 134 can be 35 provided, which is coupled, for example electrically and/or optically, to the test C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 20 element 128, in order to detect the at least one analyte in the sample 130 after transfer to the test element 128. It will be noted that the manner indicated in Figure 1 for transferring the sample 5 130 to the test element 128 or the test panel 129 is just one of several transfer possibilities, which can also be realized in combination. For example, as has been described above, and as is known from EP 1 992 283 Al or EP 1 881 322 Al for example, a sample 130 can also be initially generated on the skin part 122 by means of the lancet 120, after which this sample is retrieved, for example by a 10 suitable movement of the test element 128, from the skin part 122 and is transferred to the test element 128. The system 110 can further comprise a control 136. This control 136 can, for example, be wholly or partially identical to the measuring device 134, but it can 15 also be designed separately from the latter and connected thereto, as is shown in Figure 1. The control can further be connected to the actuator 124 and can regulate the latter, for example. The control 136 can also, for example, comprise one or more data processing devices, which are able to control the entire measurement sequence of the system 110 and/or can evaluate the measurement of the at least 20 one analyte. Alternatively or in addition, other electronic evaluation devices can also be provided in the control 136. The control 136 can also be provided, for example, with one or more input and output means, for example operating elements, display elements or the like, in order to allow a user to influence the system control 110 and/or in order to output information to the user. For the design 25 of such input and output means, reference may be made, for example, to conventional blood glucose meters. The control 136 can also comprise, for example, one or more memories, for example volatile and/or nonvolatile memories, which can also be equipped, if appropriate, with a database system for storing measured values. The control 136 can be designed, for example, using 30 program technology in order to execute the above-described methods in one or more of the described variants, that is to say, for example, taking evaporation effects into account and/or correcting such effects in the evaluation of the detection of the at least one analyte.

C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 21 The system according to Figure 1 further comprises a plurality of sensors. Thus, for example, an optical sensor 138 can be provided, which can detect an actual sample volume of a received sample 130 and which, for example, can be connected to the control 136 in order to transmit to the control 136 information concerning 5 this actual sample volume. The optical sensor 138 can, for example, determine a filling level and/or a filling volume of the capillary 132, for example by means of a reflection measurement and/or by means of other optical measurement methods. The capillary 132 can, for example, be specially designed for this purpose, in particular in order to facilitate a reflection measurement. The capillary 132 can, for 10 example, be provided with a roughened surface in order to facilitate a reflection measurement. This is illustrated by way of example in Figures 6A and 6B, which show surface images of metal surfaces. For example, the capillary 132 can be made of a metallic material, for example a metal sheet, for example steel. Figure 6A shows an image of an untreated metal surface, whereas Figure 6B shows an image 15 of a metal surface that has been roughened by means of an etching process. For example, one capillary channel of the capillaries 132 can be wholly or partially roughened in this way, in particular in order to be able to specifically set one of the capillary channels. If information concerning the actual sample volume is obtained, for example by means of the sensor 138, the control 136 can be designed in 20 particular to take account of this information when evaluating the measurement of the at least one analyte. The system 110 can further comprise at least one humidity sensor 140, which can likewise be connected to the control 136 and which can measure humidity in the 25 interior 114. The control 136 can in turn be designed to take this information on humidity into account when evaluating the measurement. One or more further sensors 142 for the measurement of further parameters can also be provided in the interior 114 and/or outside of the interior 114. For example, as is indicated in Figure 1, one or more sensors can be provided for a pressure, a temperature or 30 similar parameters. These sensors 142 can also be connected to the control 136, such that the evaluation of the measurement can be carried out taking into account the additional parameters. To examine the problem of evaporation, which can have an influence on the 35 detection of the at least one analyte in the sample 130, various studies known from C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 22 the literature were assessed. Thus, when collecting blood by aspiration, for example through an open microcapillary, a partial evaporation of the blood serum can be expected even before the latter reaches the test element 128, for example the test panel 129. It will be noted that, instead of an individual test panel 129, other 5 types of test elements 128 can also be used, for example test strips, test tapes, test disks or the like, for example test elements used in the prior art. However, the tests described below relate mainly to microcapillaries, although they can easily be transposed to other types of systems. 10 The described evaporation generally leads inevitably to an increase in the concentration of all the dissolved analytes. This generally causes a measurement error, which is already caused by the sample collection on the transport path. However, by knowing the rate of evaporation that is to be expected, the error to be expected can at least be calculated. A problem here is, however, that the 15 functionality is intended to be ensured over as wide as possible a range of temperature and function of the system 110. Therefore, a global correction, for example of 5%, is not sufficient, because the evaporation effects can vary considerably. If the aspiration of the sample 130 or the transfer always proceeds sufficiently quickly, for example being completed within 1 s, at least the time 20 factor would not have to be taken into consideration as a variable parameter. The evaporation, that is to say the conversion of liquid particles to the vapor phase below the boiling point, is a diffusion-limited process which has been described in different ways in the literature. The driving force of the evaporation is the 25 concentration gradient of the vapor pressure, for example of the water vapor pressure, between the surface of the sample 130 and distant environment. The gradient becomes steeper as the ambient air becomes drier and therefore more receptive. In air at rest, this gradient as a result of the evaporation forms gradually. 30 By contrast, in moving air, the gradient has no opportunity to develop geometrically formed. Therefore, with a draft, that is to say moving air, the concentration gradient over the liquid is maintained at its maximum, whereas, with standing air, it decreases as a result of the increasing rise in the air humidity over the liquid. Looking at the same circumstances in another way, the diffusion 35 boundary becomes increasingly smaller and, therefore, the gradient steeper.

C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 23 Consequently, in the system 110 according to the invention in Figure 1, any air movement is avoided by provision of the closed housing 112, such that both the generation of the sample 130 and also the transfer and measurement thereof by the test element 128 take place in the interior 114. In this way, the influence exerted on 5 the evaporation rate by fluctuations caused by movements of the air is at least kept constant to the extent that, in contrast to conventional systems, it can likewise be kept constant. In this way, it is possible to avoid theoretical or semi-empiric approaches to correcting the influence of convection on the evaporation rate. 10 The evaporation is influenced not just by the interfering movement of air, or convection, but by a large number of parameters. Parameters within the context of the present invention are understood as all the possible influences that can have an effect on the evaporation. These can include environmental parameters, for example the air pressure, the air temperature, the air humidity, the temperature of 15 parts of the system 110, a concentration of analytes in the sample 130 (which can exert an influence, for example, through an increase in vapor pressure) or other parameters or combinations of said and/or other parameters. In addition, system inherent parameters are in particular the surface properties of individual parts of the system 110, for example of the capillary 132, the geometries of individual parts 20 of the system 110, for example again of the capillary 132, or of other component parts. Figure 2 shows a relationship, known from the literature, between an evaporation rate R, given in nl/s, and an opening surface area A, given in mm 2, in a pyramid 25 shaped, etched depression in silicon. The measurement shown is taken from Mayer et al., 1997, Sens. Actuators A, 60, 202-207. The measurements were carried out here with a sample volume of ca. 8 nl. The situation of these measurements is at least approximately comparable to the evaporation from semi-open capillaries, for example the capillary 132. The measurements in Fig. 2 were carried out in water, 30 at a temperature of 22 0 C and a relative air humidity of ca. 50%. The measurement in Figure 2 shows that the evaporation rate is at least approximately proportional to the surface area A. The uppermost value in Figure 2 is from microcontainers with a surface of 0.64 mm2, which comes nearest to the 2 35 surface area of open channels in flat lancets, namely ca. 1 mum . From said C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 24 publication by Mayer et al., it is possible to extrapolate, for flat lancets with a 2 surface area of 1 mm , evaporation rates of ca. 0.5 nl/s. Therefore, 100 nl of water would be evaporated in ca. 200 s. 5 With the volume of ca. 90 to 140 nl used in the literature reference from Mayer et al., this would correspond to an initial evaporation, and therefore change in concentration, of ca. 0.2 to 0.3%, that is to say a value that is very low compared to the established measurement accuracy, for example of blood glucose meters. It could therefore be expected from these literature references that the problem of 10 evaporation is irrelevant in microcapillaries. In order to verify these predictions from the literature, we carried out our own experiments on evaporation from a capillary 132. These results are shown in Table 1. 15 Droplet Capillary Volume Water Blood Water Blood 150 nl 0.6 [tg/s 0.5 [tg/s - 50 nl 0.5 g/s - 1.0 g/s 1.0 g/s Table 1: Measurement results of actual evaporation rates Evaporation rates in [tg/s are shown here for water and for blood. As regards the droplet, the application volume of blood was 500 nl, whereas the application 20 volume in the capillary was 250 nl. The rates, however, were each determined at the values specified in the first column. Measurement results with an initial droplet volume of 150 nl and 50 nl are shown, which results were achieved both on 2 droplets and also inside an opened capillary with a surface area of ca. 1 mm2 25 Surprisingly, these results show that the evaporation is much greater than was to be expected from the abovementioned literature. 1 jag corresponds to approximately 1 nl of water. The measurements were carried out at 22'C and at a slightly lower air humidity than in the literature (45%). The slightly reduced air humidity, however, cannot be held responsible for the very great difference from the expected values, 30 since, as tests have shown, the relative air humidity in this range, at a change of ca. 5%, can only influence the evaporation rate by a maximum of 20 to 30%. This is C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 25 clear, for example, from the graph in Figure 5, in which the evaporation time T in minutes for a water droplet with 0.5 mm diameter is plotted as a function of the relative air humidity H in %. This graph is also taken from Mayer et al., 1997, Sens. Actuators A, 60, 202-207. 5 In the measurements shown in Table 1, the convection was minimized by using an encapsulated balance. It is true that, in the measurement series shown in Table 1, a capillary with an untypical length of 8 mm was used, such that the surface area increases to ca. 1 mm2 and, therefore, the evaporation rate, in extrapolation of 10 Figure 2, increases to 0.6 nl/s. It could also be argued that an applied droplet of the same volume (80 nl) has a surface area of 0.7 mm , since only a half of the droplet comes into contact with the environment. However, neither approach can in any way explain the discrepancy between the literature-based expectation (ca. 0.6 nl/s) and the measured values in Table 1, which are at evaporation rates of 1.0 nl/s. 15 According to the invention, it is therefore proposed that the influence of the evaporation on the measurement results of the analyte determination, which influence is difficult to predict and to control, be minimized by various measures and/or be kept constant and therefore correctable and/or that this influence be eliminated by suitable control measures or corrective measures. 20 One measure lies in the above-described encapsulation of the system 110 by the housing 112, preferably a housing 112 designed independently of the lancet 120 and/or of the actuator 124, as a result of which the evaporation by convection is minimized. 25 Another measure is to keep the time between the generation of the sample and the application of the sample to the test element 128 very short, preferably less than 1 s. 30 Thus, Figure 3 shows relative measured deviations of a glucose concentration from a mean value of the measurement series (cglu-cref)/cref as a function of the time t in seconds of the interval between generation of the sample and application of the sample to the test element 128, that is to say as a function of the transfer time. The tests were carried out by bringing a capillary 132 into contact with a sample 130 35 and then bringing the filled capillary manually into contact with a test element 128 C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 26 in the form of a test strip. The test setup was in this case not encapsulated. The influence on the measured glucose concentration was thus examined. The measurement series shown in Figure 3 clearly illustrates a systematic change 5 in the measured glucose value with the duration of the interval between pickup of the sample and application of the sample to the test strip. It can be seen in particular that there are significant deviations from an initial value even within 1 s. This shows that said interval between the generation of the sample and the test by the test element 128 should preferably be shorter than 1 s if costly encapsulation of 10 the capillary 132 is to be avoided. Various possible ways of influencing this transfer time between the generation of the sample 130 and the contact with the test element 128 have already been discussed above. Figure 4 shows an example of a possible way of influencing said 15 transfer time, namely by influencing the surface properties of the capillary 132. A filling time t of a capillary in seconds is plotted here as part of the above-described collection time, for a capillary with a width of 120 micrometers, a depth of 80 micrometers and a length of 8 mm, as a function of a distance d in mm traveled by water within the capillary 132. Measurements were carried out on capillaries 20 whose surfaces had been treated in various ways. In principle, for hydrophilic surface treatment, a large number of suitable methods and/or coatings or materials can be used that are also known to a person skilled in the art from other areas of technology, for example coatings with detergents. The surface treatment in Figure 4 involves hydrophilization, for example by means of a suitable hydrophilic 25 surface coating. In Figure 4, the curves with the closed triangle symbols designate measurements on capillaries 132 with a hydrophilic coating, whereas the curves with the open circle symbols designate measurements on capillaries 132 without a suitable coating. 30 It will also be noted from the measurements in Figure 4 that the length of the capillary 132 may also have an effect on the filling speed. Thus, for example, it will be seen from the curves with the closed triangle symbols that the partial filling time between 0 mm and 4 mm differs considerably from the partial filling time of the section between 4 mm and 8 mm. Accordingly, in systems 110 that detect at 35 least one analyte in a body fluid and that use at least one capillary 132 for a sample C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 27 transfer, short capillaries 132 are generally preferred, irrespective of the design of the rest of the system. Using the above-described, preferred relationship between fillable capillary length 5 and capillary diameter, we obtain, for an open capillary 132 with a width of 120 micrometers and a depth of 80 micrometers, a capillary diameter, within the meaning of the above definition, of 2 x 0.08 mm + 0.120 mm = 0.280 mm. For capillary lengths of 8 mm, this therefore gives a ratio of length to diameter of 29, for capillary lengths of 6 mm a ratio of 21, and for capillary lengths of 4 mm a 10 ratio of 14. Therefore, in the context of the present invention, and with the stated capillary dimensions, capillaries 132 are preferred that have a length of not more than or even less than 8 mm, in particular not more than or even less than 6 mm, and particularly preferably not more than or even less than 4 mm. 15 Conversely, it is possible, from these measurements of a distance d traveled within a capillary 132, and from the above-described evaporation rates, to draw conclusions concerning a minimum sample volume that has to be collected by the system 110 in order to keep the effects of evaporation on the measurement results tolerable. 20 It is thus possible to conclude, for example from the measurement results shown in Figures 3 and 4 and in Table 1, that more than 10 nl, preferably at least 12 nl, of sample volume must be present if, at an evaporation rate of 2 nl/s and a typical capillary filling time of 100 ms and a transfer time of 200 ms, the error contributed 25 by evaporation is to be less than the 5% that is typically still tolerable. In addition, as has been explained with reference to Figure 1, it is helpful if parameters that influence the evaporation and that may vary can be specifically measured by sensors and taken into consideration in the evaluation of the 30 measurement. Thus, for example, an actual sample volume can be detected by the optical sensor 138. For example, the size of a spot of sample 130 transferred onto a test panel 129 can be detected in this way. The measurement can then be corrected to this actual sample volume, and an expected relative change in concentration caused by evaporation can thus be calculated and corrected. For example, this C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 28 calculated value can be used to correct the measured value of the glucose concentration. Other parameters can also be used additionally or alternatively for these 5 corrections. For example, for such correction, a knowledge of the temperature, for example measured by means of the sensor 142 and/or of the air humidity, for example measured by means of the sensor 140, can additionally be included in the calculated value used for the correction. The humidity sensor 140 can, for example, comprise a commercially available hygrometer, which can be configured to save 10 space and can be implemented inexpensively into the system 110. Another proposal for reducing the influence of evaporation on the measurement of the analyte concentration, and one that can be implemented into a given system 110 according to the present invention in addition to or as an alternative to the 15 possibilities described above, can involve changing the geometry of the capillaries 132. For example, an aspect ratio of these capillaries can be changed, that is to say a ratio between the width of the opening and the depth of the capillary gap. For example, the capillary can be made deeper instead of wider, that is to say have a depth of 120 [m and a width of only 80 [m instead of a depth of 80 [m and a 20 width of 120 [m. In this way, with a constant volume, the surface area and therefore the evaporation rate are reduced. The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as, an 25 acknowledgement or admission or any form of suggestion that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates. Throughout this specification and the claims which follow, unless the context 30 requires otherwise, the word "comprise", and variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

C:\NRPortbl\DCC\KMH\5047988_1.DOC - 8/4/13 29 List of reference signs 110 system for detection of an analyte in a body fluid 5 112 housing 114 interior 116 opening 118 finger 120 lancet 10 122 skin part 124 actuator 126 transfer device 128 test element 129 test panel 15 130 sample 132 capillary 134 measuring device 136 control 138 optical sensor 20 140 humidity sensor 142 sensors for further parameters

Claims (11)

1. A system for detection of at least one analyte in a body fluid, wherein the system is designed to generate a sample of the body fluid and to transfer the sample to at least one test element, the system being designed to effect the generation of the sample and the transfer to the test element within a substantially closed housing, the system also being designed to detect an actual sample volume of the sample picked up by the system and/or of the sample transferred to the test element, the system also being designed to detect humidity within the housing during the generation of the sample and/or during the transfer of the sample to the test element, and wherein the system is further designed to detect the analyte taking into account the humidity, and wherein the system is further designed to detect the analyte taking into account the actual sample volume, and wherein evaporation effects, dependent on sample volume, and resulting changes in concentration are at least partially compensated, and 2 wherein the system has at least one opening smaller than 100mm , wherein a skin part can be placed wholly or partially in the opening, wherein the skin part at least partially closes the opening, and wherein the sample is generated in the skin part placed in the opening.

2. The system as claimed in claim 1, wherein the at least one test element is a test panel.

3. The system as claimed in any one of the preceding claims, wherein the at least one opening is a closable opening.

4. The system as claimed in any one of the preceding claims, wherein the skin part is a skin part of a finger. 31

5. The system as claimed in any one of the preceding claims, wherein the system is further designed to at least temporarily interrupt the detection of the analyte and/or generate a warning when a predefined minimum humidity is undershot.

6. The system as claimed in any one of the preceding claims, wherein the system is further designed to detect at least one further parameter during the generation of the sample and/or during the transfer of the sample to the test element.

7. The system as claimed in claim 6, wherein the system is designed to detect the at least one further parameter within the housing.

8. The system as claimed in claim 6 or 7, wherein the system is further designed to take the at least one further parameter into account in the detection of the analyte in the sample.

9. The system as claimed in any one of the preceding claims, wherein the sample volume is less than 1pl.

10. The system as claimed in claim 9, wherein the sample volume is in a range between lOnl and 500nl.

11. A system for the detection of at least one analyte in a body fluid, substantially as herein described with reference to the accompanying figures.