Numerous systems for detection of analytes in body fluids are known from the 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 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.
Many such systems are known from the prior art. Thus, for example, U.S. Pat. No. 7,252,804 B2, the disclosure of which is incorporated by reference herein in its entirety, 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 1 992 283 A1, the disclosure of which is incorporated by reference herein in its entirety, 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 A1, the disclosure of which is incorporated by reference herein in its entirety, describes a portable measuring system for analysis of a liquid sample, which system has a moisture-proof housing with a housing interior space. The liquid sample can be applied to the at least one test element within the housing interior space.
In addition to such systems in which a sample is generated and is then transferred 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 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, the disclosure of which is incorporated by reference herein in its entirety.
Irrespective of the system used, it is a general aim of systems for detection of analytes in body fluids to considerably reduce the 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 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 manipulating the perforated surface of the skin (“milking”) in order to increase the sample volume, 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 difficulty in systems which operate with reduced sample volumes, for example blood volumes of less than 1 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 samples, however, the raised concentrations measured are then inaccurate.
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 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 0.6nl/s and, under constant environmental conditions, are dictated by the droplet surface area for 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 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 diagnostics. For example, in U.S. Pat. No. 7,252,804 B2, reference is made to the effect of this drying of blood samples in biosensors with piercing aids. Similarly, U.S. Pat. No. 6,878,262 B2, the disclosure of which is incorporated by reference herein in its entirety, refers to this effect and proposes that capillaries for blood transport be closed in order to avoid evaporation. An analogous procedure is also chosen, for example, in U.S. Pat. No. 6,565,738 B1 or in U.S. Pat. No. 6,312,888 B1, the disclosures of which are incorporated by reference herein in their entireties. In order to avoid drying out of samples, particularly by convection, it is also proposed in U.S. Pat. No. 6,325,980 B1, the disclosure of which is incorporated by reference herein in its entirety, that samples with a volume of less than 0.5 μl 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 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 with difficulty. Because of the abovementioned complex environmental conditions, 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 semi-empiric approaches to correcting the evaporation in many cases lead to unrealistically low evaporation rates and, consequently, to erroneous corrections.
Thus, an object of the present invention is 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. 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.
USPTO Backgrounds
USPTO Backgrounds