HK1218778B

HK1218778B - Method / device for generating a corrected value of an analyte concentration in a sample of a body fluid

Info

Publication number: HK1218778B
Application number: HK16106726.0A
Authority: HK
Inventors: Joachim Hoenes; Christian Ringemann; Andreas Weller
Original assignee: F. Hoffmann-La Roche Ag
Priority date: 2013-03-19
Filing date: 2014-03-18
Publication date: 2019-07-05

Description

Method/device for generating a correction value for the concentration of an analyte in a sample of a body fluid

Technical Field

The invention relates to a method for detecting an analyte in a body fluid, comprising the following steps: a) applying a body fluid sample to a test piece, the test piece comprising at least: (i) a test field having at least one test material adapted to change at least one measurable property in the presence of an analyte, (ii) a capillary adapted to direct a sample through the test field in a flow direction, (iii) first and second measurement locations within the test field, wherein the second measurement location is offset from the first measurement location in the flow direction; (b) measuring the measurable property in the at least one first measurement location, thereby generating at least one first measurement value; (c) measuring the measurable property in the at least one second measurement location, thereby generating at least one second measurement value; (d) detecting the analyte by using an evaluation algorithm having at least two input variables, wherein (i) at least one first input variable of the at least two input variables comprises information about a difference between the first measurement value and the second measurement value, and (ii) at least one second input variable of the at least two input variables comprises measurement information about an analyte-induced change of a measurable property of the test material in at least part of the test field. The invention also relates to a test device and a test system adapted for performing the method of the invention, and to the use of a difference of at least two measurement values measured in at least two different positions of a test field of a test piece for generating a correction value for an analyte concentration in a body fluid sample.

Background

In the field of medical diagnostics, it is in many cases necessary to detect one or more analytes in a body fluid sample, such as blood, interstitial fluid, urine, saliva or other types of body fluids. Examples of analytes to be detected are glucose, triglycerides, lactate, cholesterol or other types of analytes typically present in these body fluids. If desired, depending on the concentration and/or presence of the analyte, an appropriate treatment may be selected.

Generally, devices and methods known to those skilled in the art utilize test pieces that include one or more test chemicals that are capable of performing one or more detectable detection reactions, such as optically detectable detection reactions, in the presence of the analyte to be detected. For these test chemicals, reference is made, for example, to j. hoenes et al: the Technology beyond Glucose Meters, Test Strips, Diabetes Technology & Therapeutics, volume 2008, 10, supplemented with 1, S-10 to S-26. Other types of test chemicals are also possible and may be used in the practice of the present invention.

Typically, one or more optically detectable changes in the test chemical are monitored to derive from the changes the concentration of the at least one analyte to be detected. Examples of test fields, test chemicals and methods for monitoring one or more optically detectable changes in a test field are disclosed in EP 0821234a 2. Thus, as an example, relative remissions of the test field may be detected optically as a function of time, i.e. up to a defined end point of the chemical detection reaction. From the change in relative remission, the concentration of the analyte can be derived. A similar measurement of the amount of light reflected from the test field as a function of time, i.e. up to a defined end point of the detection reaction, is disclosed in EP0974303 a 1.

In order to detect at least one change of the optical properties of the test field, various types of detectors are known from the prior art. Thus, various types of light sources for illuminating the test field and various types of detectors are known. In addition to single detectors such as photodiodes, various types of devices are known that use a detector array having a plurality of photosensitive devices. Thus, in US2011/0201909, an arrangement for measuring the concentration of an analyte contained in a sample of bodily fluid is disclosed. The arrangement comprises, inter alia, a light source and a detector array. Similarly, EP 1359409 a2 discloses a device for determining the concentration of an analyte in a physiological sample. The apparatus includes at least one light source and a detector array.

Furthermore, when using detector arrays, methods for detecting errors and artifacts in images obtained by the detector arrays are known from the prior art. Thus, US2011/0201909 discloses a correction algorithm which is particularly capable of correcting flaws present in reaction spots observed by a detector array. Similarly, EP 1359409 a2 discloses an apparatus for determining whether a sufficient amount of sample is present on each of a plurality of different detector areas, wherein light detected only from those areas determined to have sufficient sample is used to determine the concentration of the analyte. In WO 2006/138226A 2, arrangements and algorithms for calculating the concentration of an analyte contained in a sample are disclosed. Wherein the rate of color change of the test chemical is detected and the hematocrit is determined based on the rate of color change. The glucose concentration is corrected using an appropriate correction factor indicative of the hematocrit.

It is known that the measurement of soluble analytes in suspensions additionally comprising at least one particulate compound is hampered by the fact that: the measured value may deviate from the actual concentration depending on the concentration of the particulate compound. For an example of determining blood glucose levels, it has been proposed to use the viscosity of the sample as an alternative measure of the blood cell concentration, i.e. hematocrit (JP 2005/303968). However, the viscosity of a blood sample depends on several other parameters, such as the concentration of fibrinogen and globulin, red blood cells and platelet aggregation, etc., and therefore the corrections derived from direct or indirect viscosity measurements are often affected by these parameters, thus rendering such corrections inaccurate to a certain extent. WO 2003/089658 discloses a biosensor using a single point measurement of the resistance between two electrodes to estimate the level of hematocrit in a sample and to correct the measured value based on the estimated level of hematocrit and a set of predetermined empirical constants.

Problems to be solved

There is thus a need in the art to provide reliable devices and methods for determining the concentration of soluble analytes in a suspension that also includes a particulate compound and to provide a correction for the measured concentration as a function of the concentration of the particulate compound.

Disclosure of Invention

The invention relates to a method for detecting an analyte in a body fluid, comprising the following steps:

a) applying a body fluid sample to a test piece, the test piece comprising at least:

(i) a test field comprising at least one test material adapted to change at least one measurable property in the presence of an analyte,

(ii) a capillary adapted to guide a sample through the test field in a flow direction,

(iii) first and second measurement locations within the test field, wherein the second measurement location is offset from the first measurement location in a flow direction;

b) measuring the measurable property at the at least one first measurement location, thereby generating at least one first measurement value;

c) measuring the measurable property at the at least one second measurement location, thereby generating at least one second measurement value;

d) detecting the analyte by using an evaluation algorithm having at least two input variables, wherein

(i) At least one first input variable of the at least two input variables comprises information about a difference between the first measured value and the second measured value, an

(ii) At least one second input variable of the at least two input variables comprises measurement information about an analyte-induced change of a measurable property of the test material in at least part of the test field.

As used herein, the expressions "having," "including," and "comprising," as well as grammatical variants thereof, are used in a non-exclusive manner. Thus, the expression "a has B" and the expression "a includes B" or "a includes B" may both refer to the fact that a includes one or more additional components and/or elements in addition to B, and to the fact that no other components, elements or elements are present in a other than B.

The method of the invention is preferably an in vitro method. Moreover, it may comprise steps other than those explicitly mentioned above. For example, the further step may for example involve obtaining a sample of the body fluid for step a), or displaying the result on the determination of the output element in step d). Furthermore, one or more of the steps may be performed by an automated device.

The term "analyte" as used herein relates to a compound present in a body fluid. Preferably, the analyte is a small molecule, i.e. the analyte is preferably not a biomacromolecule, more preferably the analyte is an organic molecule, most preferably the analyte is an organic molecule capable of undergoing a redox reaction in the presence of the test chemical according to the invention. Preferably, the analyte is a molecule metabolized by the subject. Even more preferably the analyte is a compound of low molecular weight, more preferably having a molecular weight of less than 1000 u (1000 Da; 1.66X 10)⁻²⁴kg of compounds of molecular mass. More preferably, the analyte is selected from the list consisting of glucose, lactate, cholesterol and triglycerides. Preferably, the analyte is blood glucose and the actual concentration to be determined is at least 10mg/dL, at least 50mg/dL, at least 60 mg/dL, at least 70 mg/dL, at least 80 mg/dL, at least 90 mg/dL, at least 100mg/dL, at least 110 mg/dL, at least 120 mg/dL, at least 130 mg/dL, at least 140 mg/dL or at least 150 mg/dL.

As used herein, the term "bodily fluid" refers to all bodily fluids of a subject known to include or intended to include the analyte of the present invention, including blood, plasma, tears, urine, lymph, cerebrospinal fluid, bile, stool, sweat, and saliva. Preferably, the body fluid comprises at least one particulate component; preferably, the size difference between the particle component and the analyte allows the separation layer to separate the particle component from the analyte. More preferably, the size ratio (average size of the particulate components over the size of the analyte) is at least 10, at least 20, at least 50, at least 100, at least 200, at least 500, at least 1000, at least 2000, at least 5000 or at least 10000, at least 100000 or at least 1000000. Even more preferably, the particulate compound is a cell; most preferably, the particulate compound is a blood cell. Thus, it is preferred that the body fluid is blood and that the concentration of the particular mixture is the volume percentage of blood cells therein, i.e. the hematocrit. The term "sample" is understood by the person skilled in the art, and the term "sample" relates to any sub-portion of a body fluid, preferably removed from a subject prior to applying said sample to a test piece. Samples may be obtained by known techniques, including, for example, venipuncture or arterial puncture, epidermal puncture, and the like.

The term "detection" relates to the quantification of the amount of an analyte present in a sample of a body fluid, i.e. the measurement of the amount or concentration of said analyte, preferably semi-quantitatively or quantitatively. Detecting the amount of analyte can be accomplished in a variety of ways known to those skilled in the art or described in detail herein below. According to the present invention, the detection of the amount of analyte can be achieved by all known means for detecting the amount of said analyte in a sample, provided they are adapted to specifically detect the analyte of the present invention and are compatible with the requirements of the present invention. The term "amount" as used herein includes the absolute amount of an analyte referred to herein, the relative amount or concentration of an analyte referred to herein, and any value or parameter associated therewith. Such values or parameters include intensity signal values for all specific physical or chemical properties obtained by measuring the analyte referred to herein. It should be understood that the values related to the above mentioned quantities or parameters can also be obtained by all standard mathematical operations.

The term "test piece" as used herein relates to a unit comprising elements as described herein below, i.e. a test piece comprising at least one capillary and at least one test field. Preferably, the test strip is selected from the group consisting of an optical test strip and an electrochemical test strip. The test piece may optionally further comprise at least one piercing piece, such as at least one incision piece, which preferably may be movably mounted relative to the test field in order to perform a piercing action, a sampling action or an incision action, thereby generating an incision in the skin surface. Preferably, the test field is held in a fixed position during the puncturing, sampling or lancing action, wherein the body fluid sample is transferred to the test field, such as by capillary action and/or by pressing the puncturing element or a part thereof onto the test field after the puncturing, sampling or lancing movement. Preferably, the test piece is a test strip, a test strip or a test tray.

As used herein, the term "capillary" relates to any type of element adapted to draw and/or transport liquid by capillary action. The capillary may comprise a closed channel, such as a channel in a hollow needle, and/or an open channel, such as a capillary groove or a capillary slit. The closed channel may be surrounded all around by a tubular capillary wall, while the open channel may provide an open surface along the longitudinal axis of the channel. In all embodiments, however, at least a portion of the circumference of the capillary element is formed by or comprises at least a portion of the test field, and the capillary element is adapted to guide the sample through the test field in the flow direction. Preferably, the capillary tube extends at least 0.5mm, 0.75 mm, 1mm, 1.25 mm, 1.5 mm, 1.75mm, 2mm, 2.5 mm, 3mm, 3.5 mm, 4 mm, 4.5 mm, 5mm or 10 mm in the longitudinal direction. Preferably, the capillary comprises at least one capillary slit extending through at least a portion of the test field. More preferably, the capillary slit is formed by the surface of the test field and a guide surface at a distance above the surface of the test field. Even more preferably, the guide surface is formed by a surface of a cover plate disposed on the test field surface. Preferably, the capillary slits have a width of 30 to 300 μm, more preferably of 40 to 200 μm, even more preferably of 50 to 100 μm, even more preferably of 60 to 80 μm, most preferably of 70 μm. Preferably, the test field is applied to the substrate on the surface of the substrate facing the capillary. More preferably, the substrate comprises at least one detection window, wherein the detectable property is measured through the detection window. Most preferably, the detection window is an opening or a transparent detection window.

The term "test field" relates to a continuous or intermittent amount of test chemical, which is preferably held by at least one carrier, such as by at least one carrier film. Thus, the test chemical may be formed or may be included in one or more films or layers of the test field, and/or the test field may include a layer arrangement having one or more layers, wherein at least one layer includes the test chemical. Thus, the test field may comprise a layer arrangement arranged on the carrier, wherein the body fluid sample may be applied to the layer arrangement from at least one application side, such as from an edge of the test field and/or an application surface of the test field. Preferably, the test field has a multi-layer arrangement comprising at least one detection layer with at least one test material, and further comprising at least one separation layer adapted to separate out at least one particle component contained in the body fluid, wherein the separation layer is located between the detection layer and the capillary. It will be appreciated by those skilled in the art that all layers optionally present between the fluid and the test field are selected so as to at least allow passage of the analyte. Preferably, the volume enclosed between the test layer and the separation layer is at most 1%, at most 2%, at most 3%, at most 4%, at most 5%, at most 6%, at most 7%, at most 8%, at most 9%, at most 10%, at most 15%, at most 20%, at most 25%, at most 30%, at most 35%, at most 40%, at most 45%, at most 50%, at most 75% or at most 95% of the volume surrounded by the capillaries.

The term "test chemical" or "test material" refers to a substance or mixture of substances adapted to change at least one measurable property in the presence of an analyte. Preferably, the test material performs at least one optically or electrochemically detectable detection reaction in the presence of the analyte. More preferably, the detection reaction is a redox reaction. Most preferably, the detection reaction produces redox equivalents and/or electrons as intermediates and/or products. Preferably, the test reaction is at least partially regulated by at least one enzyme, and thus preferably the test material comprises at least one enzyme adapted to perform at least one enzymatic reaction in the presence of the analyte. The detection reaction may preferably imply a color change of the test chemical or at least a part thereof. With respect to test chemicals, various possibilities for designing test chemicals are known in the prior art. Reference may therefore be made to the above-mentioned prior art documents. Specifically, reference may be made to j. hoenes et al: the Technology BehindGlucose Meters, Test Strips, Diabetes Technology & Therapeutics, volume 2008, Vol.10, supplement 1, S-10 to S-26. However, other types of test chemicals are possible. Preferably, the test chemical comprises at least one enzyme, which reacts preferably directly or indirectly with the analyte, preferably with high specificity, wherein, furthermore, one or more optical indicator substances are present in the test chemical, which substances perform at least one optically detectable property change upon reaction of the at least one enzyme with the analyte. Thus, the at least one indicator may comprise one or more dyes that perform a color change reaction indicative of an enzymatic reaction of the at least one enzyme with the analyte. Thus, the at least one enzyme may comprise glucose oxidase and/or glucose dehydrogenase. However, other types of enzymes and/or other types of test chemicals or active components of test chemicals may be used.

Thus, it is also contemplated by the present invention that the test chemical comprises a chemical reagent that reacts with the analyte to produce an electrochemical signal indicative of the presence of the analyte in the sample fluid. A test chemical is selected for the analyte to be evaluated. As is well known in the art, there are numerous chemicals that can be used with each of the various analytes. The selection of appropriate chemicals is therefore well known to those skilled in the art and no further description is required herein to enable one to make and use the invention.

In the case of glucose as the preferred analyte, the active component of the test chemical will typically include an enzyme that utilizes, preferably specifically utilizes, glucose and a redox mediator. More preferably, the enzyme comprises at least one of glucose oxidase and glucose dehydrogenase. The enzyme oxidizes the glucose in the sample and the mediator reacts with the reduced enzyme. The mediator then shuttles the redox equivalents of the analyzer product to the electrode surface by diffusion. Here the mediator is oxidized quantitatively at a defined anodic potential and the resulting current is related to the apparent glucose concentration. There are many reagent systems for glucose detection, and examples include AC excitation, analyte sensors, and biosensor applications, U.S. patent nos. 5,385,846 and 5,997,817, and U.S. patent application serial No. 10/008788 ("Electrochemical biosensorstorest Strip"); cNAD chemicals as described in WO 2007/012494, WO 2009/103540, WO 2011/012269, WO 2011/012270 and WO 2011/012271; and SCV chemicals as described in EP 0354441, EP 0431456, which are hereby incorporated by reference. Glucose chemicals utilize redox mediators to regulate the current between the working electrode and the glucose analyte, which are otherwise less suitable for direct electrochemical reactions at the electrode. The mediator functions as an electron transfer agent that shuttles electrons between the analyte and the electrode. A large number of redox species are known and can be used as redox mediators. In general, it is preferred that the redox mediator is a rapidly reducible and oxidizable molecule. Examples include ferricyanide, nitrosoaniline and its derivatives, and ferrocene and its derivatives.

From the above, it follows that the at least one measurable property may be any property of the test chemical that changes in the presence of the analyte and that can be converted into any kind of physical signal. Preferably, the change in the measurable property and/or the signal that can be generated therefrom is proportional to the concentration of the analyte in the sample. Preferably, as mentioned above, the measurable property is a change in the color of the test chemical and/or a change in the color intensity of the test chemical, i.e. preferably a change in the absorption spectrum and/or a change in the emission spectrum of the test chemical. Thus, in the variation of the measurable property, the optical property is preferably selected from the group consisting of: reflective properties, preferably reflectivity and/or mitigation; transmissive properties, preferably absorption; color; luminescence, preferably fluorescence. Also preferably, the measurable property is the concentration of reduced or oxidized redox mediator as described above, i.e. preferably, the measurable property is the redox state of the mediator comprised in the test chemical.

Methods of converting a measurable property as defined above into a physical signal (which can be read as a measurement) are known in the art and described in, for example, EP 0821234, EP0974303 and US 2005/0023152.

The term "measurement location" as used herein relates to an area within the test field. Preferably, the location extends over at most 1%, at most 5%, at most 10%, at most 20%, at most 30%, at most 35%, at most 50% or at most 75% of the length of the test field, the term "length of the test field" as used in this specification relates to the dimension of the test field in the flow direction of the capillary. Thus, in a test field having a length of 2-2.5 mm, the position preferably extends in the flow direction over at most 0.05mm, at most 0.1 mm, at most 0.15 mm, at most 0.2mm, at most 0.25, at most 0.3mm, at most 0.5mm, at most 1mm, at most 1.5 mm, at most 2mm or at most 5 mm. Also preferably, the position extends over at most 5%, at most 10%, at most 20%, at most 30%, at most 35%, at most 40%, at most 45%, at most 50%, at most 55%, at most 65%, at most 70%, at most 80%, at most 90% or at most 100% of the width of the test field. It will be appreciated by those skilled in the art that the geometry of the location, i.e. the shape, may vary depending on the detection system used.

The term "first measurement location" or "first location" as used herein relates to a first area within a test field. Preferably, the first position is within the first 75%, within the first half, within the first third, within the first quarter, within the first fifth, within the first sixth, within the first seventh, within the first eighth, within the first ninth, within the first tenth or within the first hundredth of the test field length, as determined from the application site of the sample. It will be appreciated by those skilled in the art that a minimum distance from the application site may be necessary to obtain proper detection conditions.

The term "second measuring position" or "second position" relates, where appropriate, to a second region within the test field, wherein the second position is offset in the flow direction from the first position. Preferably, the second position is centered in the flow direction at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% of the offset test field length from the first position.

It will be appreciated by the skilled person that the parameters detailed above may be combined independently, for example in a test field of approximately 2mm (longitudinal = flow direction) X1.75 mm (width), the first position may be centered at 0.2mm (10%), extending over 0.3mm (15%) in the flow direction, and having a width of 0.35mm (20%), while the second position may be centered at 1mm (40% offset from the first position), extending over 0.2mm in the flow direction and having a width of 0.7mm (40%). However, preferably the length and width of the first and second locations, and more preferably their geometry, are the same for a given test field.

The term "measurement" as used herein relates to a value of a physical signal generated by a test chemical and determined as detailed above and related to the concentration of an analyte in a sample. Preferably, the measurement is the value that is considered most reliably correlated to the concentration of the analyte in the sample. It will be appreciated that obtaining a measurement value may comprise measuring the measurable property a plurality of times over time, and selecting the measurement value in dependence on the data thus obtained, for example as detailed in EP 0974303. Preferably, the second measurement value is obtained before the first measurement value, or the second measurement value is measured within less than 5s, within less than 1s, within less than 0.9 s, within less than 0.8 s, within less than 0.7 s, within less than 0.6 s, within less than 0.5 s, within less than 0.4 s, within less than 0.3 s, within less than 0.2 s, within less than 0.1 s, or within less than 0.01s after the first measurement value. More preferably, the first and second measurements are taken substantially simultaneously. Most preferably, the first and second measurement values are measured simultaneously, e.g. preferably over a predetermined time span after applying the body fluid sample to the test piece. More preferably, the first and second measured values are measured at points in time at which a measurement curve indicating that the measurable property is a function of time satisfies at least one predetermined condition, preferably at least one threshold condition, and more preferably wherein the slope of the measurement curve is below or above a predetermined threshold. More preferably, the first and second measurements are measured at the following points in time: at points in time at which a measurement curve indicating that a measurable property at a first measurement location is a function of time satisfies at least one predetermined condition, preferably at least one threshold condition, and more preferably wherein the slope of the measurement curve is below or above a predetermined threshold, and a second measurement value is measured at the following points in time: at points in time where a measurement curve indicating that the measurable property at the second measurement location is a function of time meets at least one predetermined condition, preferably at least one threshold condition, and more preferably wherein the slope of the measurement curve is below or above a predetermined threshold. More preferably, the first and second measurements are measured simultaneously at the following points in time: the method may further comprise the step of determining a slope of the measurement curve at a point in time at which the measurement curve indicating that the measurable property at the first measurement location or the second measurement location is a function of time satisfies at least one predetermined condition, preferably at least one threshold condition, and more preferably wherein the slope of the measurement curve is below or above a predetermined threshold. Preferably, the first and second measurements are selected from the group consisting of: optical measurements, preferably mitigation; electrical measurements, preferably current and/or voltage. Preferably, generating at least one of the first test value and the second measurement value implies using at least one detector for generating the measurement value. Preferably, the detector comprises at least one light source for illuminating at least one of the first and second positions and at least one light sensitive element adapted to determine detected light from at least one of the first and second positions. Preferably, the at least one first location and the at least one second location are illuminated by one of: light having the same wavelength, light having different wavelengths. Thus, in a preferred embodiment, the detector comprises at least two separate light sources, e.g. Light Emitting Diodes (LEDs), preferably having the same wavelength: a first light source illuminating a first location and a second light source illuminating a second location. In such a case, it is preferred that the illumination of the first location by the first light source is offset in time as specified above with respect to the illumination of the second location by the second light source. More preferably, the detector comprises at least two separate light sources, e.g. Light Emitting Diodes (LEDs), preferably with different modulation frequencies: a first light source illuminating a first location with a first modulation frequency and a second light source illuminating a second location with a second modulation frequency. In such a case, it is preferred that the illumination of the first location by the first light source is offset in time as specified above with respect to the illumination of the second location by the second light source; more preferably, the illumination of the first location by the first light source is not offset in time with respect to the illumination of the second location by the second light source. It will be appreciated by those skilled in the art that the foregoing applies mutatis mutandis if more than two light sources and/or more than two measurement positions are used.

Preferably, the detecting light is selected from the group consisting of: light reflected by the test field in at least one of the first and second positions, light transmitted by the test field in at least one of the first and second positions, light emitted by the test field in at least one of the first and second positions.

Preferably, the light sensitive element comprises a detector adapted to detect light emitted by the light source and light reflected and/or transmitted by the test field. The photosensitive element may be a photodiode, for example. It will be appreciated by those skilled in the art that in the case where the illumination of the first location by a first light source is temporally offset relative to the illumination of the second location by a second light source as defined above, the detected light may be detected by one light sensitive element, i.e. by the same light sensitive element. It is also understood by the skilled person that in case the first location is illuminated by a first light source having a different modulation frequency compared to a second light source illuminating the second location, the detected light may also be detected by one light sensitive element, i.e. by the same light sensitive element. More preferably, the light sensitive elements comprise at least one-or two-dimensional matrix of light sensitive elements, preferably at least one camera chip, and more preferably at least one CCD chip. It will be appreciated by the person skilled in the art that in case at least one-or two-dimensional light sensitive element matrix is used comprising at least two light sensitive elements arranged in the flow direction, the measurement position according to the invention can be defined by: selecting at least two different light sensitive elements positioned at different locations along the flow direction, and detecting signals generated by the at least two different light sensitive elements. Thus, preferably, the sensor comprises at least one-or two-dimensional matrix of light sensitive elements comprising at least two light sensitive elements arranged in the flow direction.

From the above, it should be understood that the terms "first" and "second" are used only to enable distinction between the two terms, and that with the term "measurement position" it does have only a temporal meaning in case the first position is wetted by the sample before the second position. However, the measurement of the measurable property at the first and second locations is performed at a point in time when the sample has wetted both locations.

As used herein, the term "first input variable" relates to an input variable comprising information about the difference between a first measurement and a second measurement. It should be appreciated that the first variable may be derived from any arithmetic operation that provides or retains the information. Preferably, the first variable is the difference between the first and second measured values, or the difference between the second and first measured values. However, it will be understood by those skilled in the art that the information is also included in the value pairs themselves of the first and second measurements. Preferably, the first input variable comprises information about the gradient of the measured values over at least a part of the test field. More preferably, said gradient of the measured values over at least a part of the test field is a gradient in the direction of flow.

The term "second input variable" relates to measurement information about an analyte-induced change of a test material in at least part of the test field. The value of the second variable is preferably obtained from any location within the test field. It should be understood that the position may be different from both the first position and the second position, i.e. may be a third position. Preferably, the above definitions also apply, wholly or partly, to the third position. Thus, preferably, for example, the third location is centered within the first 99%, 75%, half, third, quarter, fifth, sixth, seventh, eighth, ninth, tenth or hundredth of the test field length, as determined from the application site of the sample. It will be appreciated by those skilled in the art that a minimum distance from the application site may be necessary to obtain proper detection conditions. More preferably, a first measured value is used as the measurement information, a second measured value is used as the measurement information, the average of the first measured value and the second measured value is used as the measurement information, or an analyte-induced change of a measurable property is measured in at least one third measurement location of the test field, thereby generating at least one third measured value, wherein the third measured value is used as the measurement information.

The term "algorithm" is known in the art and involves an arithmetic or computational process. The evaluation algorithm of the present invention determines the concentration of the analyte by applying an arithmetic or graphical representation of the interdependence of the concentration of the analyte in the sample, the concentration of the particulate compound in said sample and the difference between the first and second measurements to the first and second input variables of the present invention. It will be appreciated by those skilled in the art that the evaluation algorithm may be any suitable algorithm, preferably an algorithm using a multi-dimensional calibration surface or a multivariate statistical algorithm, such as a partial least squares regression (PLS regression) algorithm. Preferably, a plurality of evaluation algorithms are obtained for a plurality of values of at least one additional parameter known or expected to affect the first and/or second input variable. More preferably, the additional parameter is an environmental parameter; even more preferably, the additional parameter is temperature, most preferably ambient temperature. It will be appreciated by those skilled in the art that the temperature at the test chemical is the parameter that most profoundly affects the first and/or second parameters. However, it will be appreciated by those skilled in the art that the mass of the test piece and the mass of the sample in a conventional test piece are small enough to have an ambient temperature at the time of measurement. Thus preferably the method comprises the further step of measuring the ambient temperature. However, it is also envisaged that the method comprises the step of measuring the temperature of the sample and/or measuring the temperature of the test chemical at the time the measurement is obtained, and/or that the method comprises the step of adjusting the temperature of the test piece and/or adjusting the temperature of the test chemical and/or the sample.

Preferably, the evaluation algorithm is a one-step algorithm and said first input variable and said second input variable are simultaneously used to derive the concentration of the analyte in said body fluid by using at least one predetermined calibration surface indicating that the concentration of the analyte is a function of said two input variables. Preferably, said representation of said interdependence is thus obtained by measuring first and second measurements for respective analyte concentrations and at respective concentrations of particulate compounds in the sample. In this way, a three-dimensional figure representing the calibration surface is obtained. The person skilled in the art knows how to approximate the calibration surface thus obtained by the formula. Thus, since there are first and second input variables at hand, a person skilled in the art can directly determine a correction value for the analyte concentration, the term "correction value for the analyte concentration" relating to a value of the analyte concentration corrected for a deviation from an actual value of the analyte concentration caused by the presence of a particulate compound at a given concentration.

It should be understood that the same results may be obtained by generating a series of calibration curves instead of a calibration surface. For example, a series of graphs may be generated, wherein in each graph the signal intensity is related to the respective concentration of the analyte measured at a given concentration of the particulate compound, which signal intensity is equivalent to a certain intensity difference between the first and second measurement location. The best estimate of the concentration of the analyte can then be determined by selecting the curve closest to the measured intensity difference.

It should be appreciated that the above algorithm may also be performed as a two-step algorithm, wherein the algorithm comprises two separate steps: in a first step of the algorithm, an estimate of the concentration is derived from the second input variable by using at least one predetermined first calibration curve indicating that an uncorrected concentration of an analyte is a function of the second input variable, and in a second step of the algorithm, the estimate of the concentration is corrected by applying at least one correction algorithm to the estimate, the correction algorithm providing a correction to the estimate by using the first input variable. Preferably, the first calibration curve is an arithmetic or graphical representation of the interdependence of the analyte concentration in the sample and the second variable of the invention at a fixed concentration of the particulate compound. Preferably, said representation of said interdependence is thus obtained by obtaining the second variable for the various analyte concentrations at a fixed concentration of the particulate compound, preferably at a fixed concentration of the particulate compound corresponding to an average concentration of the particulate compound present in many subjects. The estimate thus obtained is then corrected by applying a correction algorithm using the first and second variables.

Advantageously, in the experiments on which the invention is based it was found that the presence of a particulate component in the sample causes a deviation of the measured value from the actual concentration of the analyte along the test piece in the flow direction. Moreover, it was found that the deviation (deviation) increases with increasing concentration of the particulate compound and increasing distance from the application site. As a result, the gradient along the test piece can be used to correct the measured value for shifts caused by particulate compounds; furthermore, an optimal estimate of the actual concentration of the analyte without correction for the offset is obtained by taking measurements close to the application site. In particular, in the experiments on which the invention is based, it was found that, depending on the hematocrit of the blood sample, a concentration gradient occurs along the test strip which allows to correct the measured value of the hematocrit.

The definitions made above apply, mutatis mutandis, to the following:

in a further embodiment, the invention relates to a method for detecting an analyte in a body fluid, the method having the steps of:

a) applying a body fluid sample (122) to a test piece (120), the test piece (120) comprising at least: ()

(i) A test field (128) having at least one test material (130) adapted to change at least one measurable property in the presence of an analyte,

(ii) a capillary (126) adapted to guide the sample (122) in a flow direction (146) through the test field (128),

(iii) at least one single measurement location (158) within the test field (128);

b) measuring a measurable property in the single measurement location (158), thereby generating at least one measurement value;

c) detecting the analyte by using an evaluation algorithm having the measurable property as an input variable,

wherein the single measurement location is located within the first third of the test field (128) as determined by the application site.

As used herein, the term "single measurement location" or "single location" relates to a measurement location as defined above that is located within the first third of the test field (128) as defined in terms of the application site. Preferably, the single measurement location is centered within the first quarter, the first fifth, the first sixth, the first seventh, the first eighth, the first ninth, the first tenth or the first hundredth of the test field length, as determined from the application site of the sample. Those skilled in the art will appreciate that a minimum distance from the application site may be necessary to obtain proper detection.

In a further embodiment, the invention relates to a test device for detecting an analyte in a body fluid, wherein the device comprises:

a) at least one test piece receptacle for receiving at least one test piece having

(i) At least one test field having at least one test material adapted to change at least one measurable property in the presence of an analyte, and

(ii) having a capillary adapted to guide a sample through the test field in a flow direction,

b) wherein the receptacle is adapted to position the test piece in at least one application position in which a sample of a body fluid can be applied to the test piece,

c) wherein the device further comprises at least one detector for measuring the detectable property, wherein the detector is adapted to

(i) Measuring said measurable property in at least one first location of said test field, thereby generating at least one first measurement value,

(ii) measuring the measurable property in at least one second position of the test field, thereby generating at least one second measurement value, wherein the second position is offset from the first position in the flow direction,

d) wherein the test device further comprises at least one evaluation unit adapted to determine the concentration of the analyte by using an evaluation algorithm with at least two input variables,

(i) wherein at least one first input variable of the at least two input variables comprises information about a difference between the first measured value and the second measured value, an

(ii) Wherein at least one second input variable of the at least two input variables comprises measurement information about an analyte-induced change of the test material in at least part of the test field.

Preferably, the test device is adapted to measure analyte-induced changes of the measurable property in at least two measurement positions as defined herein above. Preferably, the test device is adapted to measure the analyte-induced change of the measurable property in at least one third position of the test field, thereby generating at least one third measurement value. It is however more preferred to measure the measurable property in two locations. Preferably, the test device further comprises at least one sensor for determining an environmental parameter. Preferably, the test device further comprises at least one temperature sensor for determining the ambient temperature. It is also preferred that the test device is a handheld test device.

The term "test piece receptacle" is known to the person skilled in the art and relates to an element of the device which is shaped to accommodate at least one test piece according to the invention, to provide one or more connectors and/or detectors suitable for detecting an analyte in a body fluid, and which is adapted to position the test piece in at least one application position in which a body fluid sample can be applied to the test piece. The particular embodiment of the test piece receptacle will preferably depend on the type of test piece and the test chemistry used herein.

The term "detector" is also known to the person skilled in the art. As described above, the skilled person knows how to use different test chemicals and how to use appropriate detectors for the respective test chemicals. Thus preferably, the detector is adapted to measure a measurable property of the test chemical as described herein above. Preferably, the detector comprises at least one light source for illuminating at least one of the first and second positions and at least one light sensitive element adapted to determine detected light from at least one of the first and second positions.

As used herein, the term "evaluation unit" relates to a unit of the device that applies at least one algorithm according to the invention to the first and second input variables as defined herein above. Thus, the evaluation unit is adapted to determine the concentration of the analyte by using an evaluation algorithm having at least two input variables. Preferably, the evaluation unit is further adapted to select the measured values as described herein above, to select an algorithm according to the environmental parameters, and/or to store the reference values and/or the reference curves and/or the reference areas. More specifically, the evaluation unit is adapted to perform all calculations and evaluations needed for printing out the concentration value of the analyte in the bodily fluid sample. Most preferably, the evaluation unit is adapted to receive the one or more detector signals and to detect and print the blood glucose level of a blood sample in a test piece inserted in the test piece receptacle. Preferably, the evaluation unit comprises at least one data processing device, preferably at least one microprocessor.

In a further embodiment, the invention relates to a test device (112) for detecting an analyte in a body fluid, wherein the test device (112) comprises:

a) at least one receptacle (118) for receiving at least one test piece (120), the test piece (120) having

(i) At least one test field (128), the at least one test field (128) having at least one test material (130) adapted to change at least one measurable property in the presence of an analyte and

(ii) at least one capillary (126) adapted to guide the sample (122) through the test field (128) in a flow direction (146),

b) wherein the receptacle (118) is adapted to position the test piece (120) in at least one application position in which a sample (122) of a body fluid can be applied to the test piece (120),

c) wherein the apparatus further comprises at least one detector (132) for measuring the measurable property, wherein the detector (132) is adapted to measure the measurable property in at least one single location (158) of the test field (128), thereby generating at least one measurement value,

d) wherein the test device (112) further comprises at least one evaluation unit (138) adapted to determine the concentration of the analyte by using an evaluation algorithm having at least the variable value as an input variable,

wherein the detector is adapted to measure the measurable property within the first third of the test field.

In another embodiment, the invention relates to a test system for detecting an analyte in a body fluid, comprising at least one test device according to one of the preceding claims referring to a test device and at least one test piece, wherein the test piece has at least one test field with at least one test material adapted to change at least one measurable property in the presence of an analyte and a capillary element adapted to guide the sample through the test field in a flow direction.

In a further embodiment, the invention relates to the use of a difference of at least two measured values measured in at least two different positions of a test field of a test piece for generating a correction value for an analyte concentration in a body fluid sample, wherein the body fluid sample is guided through the test field by a capillary in a flow direction, wherein the at least two different positions are offset in the flow direction.

The invention also discloses and proposes a computer program comprising computer-executable instructions for performing the method according to the invention in one or more embodiments disclosed herein, when the program is executed on a computer or a computer network. Here, one, more than one, or all of the method steps may be performed and/or supported using a computer. In particular, the computer program may be stored on a computer-readable data carrier.

The invention also discloses and proposes a computer program product comprising computer code means for performing a method according to the invention in one or more embodiments disclosed herein, when the program is executed on a computer or a computer network. In particular, the computer code means may be stored on a computer readable data carrier.

Furthermore, the present invention discloses and proposes a data carrier having a data structure stored thereon, which data carrier, after being loaded into a computer or computer network (such as in a working memory or in a main memory of a computer or computer network), can perform a method according to one or more embodiments disclosed herein.

The invention also discloses and proposes a computer program product comprising computer code means stored on a machine-readable carrier, for performing a method according to one or more embodiments disclosed herein, when the program is executed on a computer or a computer network. As used herein, a computer program product relates to a program that is a tradable product. The product is typically present in any format, such as a paper format, or on a computer-readable data carrier. In particular, the computer program product may be distributed over a data network.

Finally, the present invention proposes and discloses a modular data signal containing instructions readable by a computer system or a computer network for performing the method of one or more embodiments disclosed herein.

Preferably, with respect to the computer-implemented aspects of the invention, one or more, or even all, of the method steps of the method according to one or more embodiments disclosed herein may be performed by using a computer or a computer network. Thus, any of the method steps, which typically include data provision and/or manipulation, may be performed by using a computer or a network of computers. In general these method steps may comprise any of the method steps, typically in addition to those requiring manual work, such as providing a sample and/or a specific aspect to perform the actual measurement.

Specifically, the invention also discloses:

a computer or computer network comprising at least one processor, wherein the processor is adapted to perform a method according to one of the embodiments described in the present specification,

a computer-loadable data structure adapted to perform a method according to one of the embodiments described in the present specification when the data structure is being executed on a computer,

a computer program, wherein the computer program is adapted to perform a method according to one of the embodiments described in the present specification, when the program is being executed on a computer,

a computer program comprising program means for performing a method according to one of the embodiments described in the present description, when the computer program is executed on a computer or a computer network,

-a computer program comprising program means according to the preceding claim, wherein the program means are stored on a computer readable storage medium,

-a storage medium, wherein a data structure is stored on the storage medium and wherein the data structure is adapted to perform a method according to one of the embodiments described in the present specification after having been loaded into a main storage and/or a working storage of a computer or a computer network, and

a computer program product with program code means, which program code means can be stored on or in the storage medium for performing a method according to one of the embodiments described in the present specification, if the program code means is executed on a computer or a network of computers.

Summarizing the findings of the present invention, the following examples are preferred:

example 1: a method for detecting an analyte in a bodily fluid, the method having the steps of:

(i) a test field having at least one test material adapted to change at least one measurable property in the presence of an analyte,

Example 2: the method of the preceding embodiment, wherein the measurement information about the analyte-induced change in the measurable property of the test material in at least part of the test field is generated by one or more of the following processes:

-said first measurement value is used as said measurement information;

-said second measurement value is used as said measurement information;

-an average of the first and second measurement values is used as the measurement information;

-measuring an analyte-induced change of a measurable property at least one third measurement location of the test field, thereby generating at least one third measurement value, wherein the third measurement value is used as the measurement information.

Example 3: the method according to one of the preceding embodiments, wherein the measurement information used in step d) (ii) is a measurement value generated at a test position located within the first 75% of the test field in the flow direction, preferably within the first half of the test field, more preferably within the first third of the test field, and most preferably within the first quarter of the test field.

Example 4: the method according to one of the preceding embodiments, wherein method steps b) and c) are performed as follows:

-a predetermined time span after applying the body fluid sample to the test piece; or

-at a point in time at which a measurement curve indicating that the measurable property is a function of time satisfies at least one predetermined condition, preferably at least one threshold condition, and more preferably wherein the slope of the measurement curve is below or above a predetermined threshold.

Example 5: the method according to one of the preceding embodiments, wherein,

-the evaluation algorithm comprises a one-step evaluation algorithm, and

-the first input variable and the second input variable are simultaneously used for deriving the concentration of the analyte in the body fluid by using at least one predetermined calibration curve, the predetermined calibration curve indicating that the concentration of the analyte is a function of the two input variables.

Example 6: the method according to one of the preceding embodiments, wherein,

the evaluation algorithm comprises at least two separate steps,

-in a first step of the algorithm, an estimate of the concentration is derived from the second input variable by using at least one predetermined first calibration curve indicating an uncorrected concentration of the analyte as a function of the second input variable, and

-in a second step of the algorithm, the estimated value of the concentration is corrected by applying at least one correction algorithm to the estimated value, the correction algorithm providing a correction to the estimated value by using the first input variable.

Example 7: the method according to the preceding embodiment, wherein,

-the sample of the body fluid is blood,

-in a first step of the algorithm, generating an estimate of the blood glucose concentration, an

-in a second step of the algorithm, providing a correction for the estimated value of the actual hematocrit of the blood, thereby generating information about the glucose concentration in the blood without determining the actual hematocrit of the blood.

Example 8: method according to one of the preceding embodiments, wherein, in method step d), the at least one first input variable comprises information about a gradient of measured values over at least a part of the test field.

Example 9: the method of the preceding embodiment, wherein the gradient is a gradient in the direction of flow.

Example 10: method according to one of the preceding embodiments, wherein in method step d) the evaluation algorithm is selected from a set of evaluation algorithms, wherein the selection is made in dependence on at least one environmental parameter.

Example 11: the method according to the preceding embodiment, wherein the environmental parameter is an environmental temperature, wherein the set of evaluation algorithms comprises a plurality of evaluation algorithms for different environmental temperatures.

Example 12: the method according to the preceding embodiment, wherein the method further comprises at least one method step of measuring the ambient temperature.

Example 13: the method according to one of the preceding embodiments, wherein the test material comprises at least one enzyme adapted to perform at least one enzymatic reaction in the presence of an analyte.

Example 14: the method of the preceding embodiment, wherein the enzyme comprises at least one of glucose oxidase and glucose dehydrogenase.

Example 15: the method according to one of the preceding embodiments, wherein the first and second measurements are selected from the group consisting of: optical measurements, preferably mitigation; electrical measurements, preferably current and/or voltage.

Example 16: the method of any preceding embodiment, wherein the test strip is selected from an optical test strip and an electrochemical test strip.

Example 17: the method according to one of the preceding embodiments, wherein the test material is adapted to change at least one optical property in the presence of the analyte.

Example 18: the method of the preceding embodiment, wherein the optical property is selected from the group consisting of: reflective properties, preferably reflectivity and/or mitigation; transmissive properties, preferably absorption; color; luminescence, preferably fluorescence.

Example 19: the method according to one of the two preceding embodiments, wherein at least one of the method steps b) and c) implicitly uses at least one detector for generating the measurement values.

Example 20: the method according to the preceding embodiment, wherein the detector comprises at least one light source for illuminating at least one of the first and second positions and at least one light sensitive element adapted to determine detected light from at least one of the first and second positions.

Example 21: the method of the preceding embodiment, wherein the detecting light is selected from the group consisting of: light reflected by the test field in at least one of the first and second positions, light transmitted by the test field in at least one of the first and second positions, light emitted by the test field in at least one of the first and second positions.

Example 22: the method according to one of the two preceding embodiments, wherein the light sensitive elements comprise at least one-or two-dimensional matrix of light sensitive elements, preferably at least one camera chip, and more preferably at least one CCD chip.

Example 23: the method according to one of the six preceding embodiments, wherein in method steps b) and c) the at least one first location and the at least one second location are illuminated by one of the following: light having the same wavelength, light having different wavelengths.

Example 24: the method according to one of the seven preceding embodiments, wherein in method steps b) and c) the at least one first location and the at least one second location are illuminated with modulated light having different modulation frequencies.

Example 25: the method according to one of the preceding embodiments, wherein the body fluid is selected from the group consisting of blood, plasma, urine and saliva.

Example 26: the method according to one of the preceding embodiments, wherein the analyte is preferably a compound having a molecular mass of less than 1000 u (1000 Da; 1.66X 10-24 kg), and more preferably selected from the group consisting of: glucose, lactate, cholesterol, triglycerides.

Example 27: the method of any of the preceding embodiments, wherein the test piece is a test strip.

Example 28: the method according to one of the preceding embodiments, wherein the test field has a multi-layer arrangement comprising at least one detection layer with at least one test material, and further comprising at least one separation layer adapted to separate out at least one particle component contained in the body fluid, wherein the separation layer is located between the detection layer and the capillary.

Example 29: the method according to one of the preceding embodiments, wherein the capillary element comprises at least one capillary slit extending through at least a portion of the test field.

Example 30: the method according to the preceding embodiment, wherein the capillary slit is formed by the surface of the test field and a guiding surface at a distance above the surface of the test field.

Example 31: the method of the preceding embodiment, wherein the guide surface is formed by a surface of a cover plate disposed over a test field surface.

Example 32: the method according to one of the three preceding embodiments, wherein the capillary slit has a width of 30 to 300 μm, preferably of 40 to 200 μm, more preferably of 50 to 100 μm, even more preferably of 60 to 80 μm, most preferably of 70 μm.

Example 33: method according to one of the preceding embodiments, wherein a test field is applied to a substrate on a surface of the substrate facing the capillary, wherein the substrate comprises at least one detection window, wherein in method steps b) and c) the measurable property is measured through the detection window.

Example 34: a test device for detecting an analyte in a bodily fluid, wherein the device comprises:

(i) At least one test field having at least one test material adapted to change at least one measurable property in the presence of an analyte and

Example 35: the test device according to the preceding embodiment, wherein the test device is adapted to perform the method according to one of the preceding method embodiments.

Example 36: the test device according to one of the preceding embodiments relating to a test device, wherein the at least one first input variable comprises information about a gradient of a measured value over at least a part of the test field.

Example 37: the test apparatus according to the preceding embodiment, wherein the gradient is a gradient in a flow direction.

Example 38: the test device according to one of the preceding embodiments relating to a test device, wherein,

-the test device is adapted to measure an analyte-induced change of the measurable property in at least one third position of the test field, thereby generating at least one third measurement value,

-said third measurement value is used as said measurement information,

-the test field extends in a flow direction, and wherein,

-the third position is located within the first 75% or half of the test field in the flow direction, preferably within the first third of the test field, and more preferably within the first quarter of the test field.

Example 39: test device according to one of the preceding embodiments relating to a test device, wherein the evaluation unit comprises at least one data processing device, preferably at least one microprocessor.

Example 40: the test device according to one of the preceding embodiments relating to a test device, wherein the test device is a handheld test device.

Example 41: the test device according to one of the preceding embodiments relating to a test device, wherein the test device further comprises at least one temperature sensor for determining an ambient temperature.

Example 42: the test device according to one of the preceding embodiments relating to a test device, wherein the first and second measurement values are selected from the group consisting of: optical measurements, preferably mitigation; electrical measurements, preferably current and/or voltage.

Example 43: the test device according to one of the preceding embodiments relating to a test device, wherein the test piece is selected from an optical test piece and an electrochemical test piece.

Example 44: the test device according to one of the preceding embodiments relating to a test device, wherein the detector comprises:

at least one light source for illuminating at least one of the first and second positions, an

At least one photosensor configured to measure detected light from at least one of the first location and the second location.

Example 45: the test apparatus of the previous embodiment, wherein the detection light is selected from the group consisting of: light reflected by the test field in at least one of the first and second positions, light transmitted by the test field in at least one of the first and second positions, light emitted by the test field in at least one of the first and second positions.

Example 46: the test device according to one of the two preceding embodiments, wherein the light sensitive elements comprise at least one-or two-dimensional matrix of light sensitive elements, preferably at least one camera chip, and more preferably at least one CCD chip.

Example 47: the test device according to one of the preceding embodiments relating to a test device, wherein the detector is configured to illuminate the at least one first location and the at least one second location by one of: light having the same wavelength, light having different wavelengths.

Example 48: a test system for detecting an analyte in a bodily fluid, the test system comprising:

a) at least one test device according to one of the preceding embodiments relating to a test device, and

b) at least one test strip, wherein the test strip has at least one test field having at least one test material adapted to change at least one measurable property in the presence of an analyte and a capillary element adapted to direct the sample through the test field in a flow direction.

Example 49: the test apparatus according to the preceding embodiment, wherein the test piece is selected from the group consisting of: test strip, test tray.

Example 50: the test system according to one of the preceding embodiments directed to a test system, wherein the test material comprises at least one enzyme adapted to perform at least one enzymatic reaction in the presence of an analyte.

Example 51: the test device of the previous embodiment, wherein the enzyme comprises at least one of glucose oxidase and glucose dehydrogenase.

Example 52: the test system according to one of the preceding embodiments relating to a test system, wherein the test material is adapted to change at least one optical property in the presence of the analyte.

Example 53: the test apparatus according to the previous embodiment, wherein the optical property is selected from the group consisting of: reflective properties, preferably reflectivity and/or mitigation; transmissive properties, preferably absorption; color; luminescence, preferably fluorescence.

Example 54: the test system according to one of the preceding embodiments relating to a test system, wherein the body fluid is selected from the group consisting of: blood, plasma, urine and saliva.

Example 55: the test system according to one of the preceding embodiments directed to a test system, wherein the analyte is a compound having a molecular mass of less than 1000 u (1000 Da; 1.66X 10-24 kg), more preferably selected from the group consisting of: glucose, lactate, cholesterol, triglycerides.

Example 56: the test system according to one of the preceding embodiments directed to a test system, wherein the test piece is a test strip.

Example 57: the test system according to one of the preceding embodiments relating to a test system, wherein the test field has a multi-layer arrangement comprising at least one detection layer with at least one test material, and further comprising at least one separation layer adapted to separate out at least one particle component contained in the body fluid, wherein the separation layer is located between the detection layer and the capillary.

Example 58: the test system according to one of the preceding embodiments directed to a test system, wherein the capillary element comprises at least one capillary slit extending through at least a portion of the test field.

Example 59: the test system according to one of the preceding embodiments relating to a test system, wherein the capillary slit is formed by a surface of the test field and a guiding surface at a distance above the surface of the test field.

Example 60: the test apparatus of the previous embodiment, wherein the guide surface is formed by a surface of a cover plate disposed above the test field surface.

Example 61: the testing system according to one of the three preceding embodiments, wherein the capillary slit has a width of 30 to 300 μm, preferably a width of 40 to 200 μm, more preferably a width of 50 to 100 μm, even more preferably a width of 60 to 80 μm, most preferably a width of 70 μm.

Example 62: the test system according to one of the preceding embodiments relating to a test system, wherein a test field is applied to a substrate on a surface of the substrate facing the capillary, wherein the substrate comprises at least one detection window, wherein the test device is adapted to measure the measurable property through the detection window.

Example 63: the test system according to one of the preceding embodiments related to a test system, wherein the capillary element comprises at least one application opening, wherein the capillary element is adapted to conduct the body fluid from the application opening towards the test field.

Example 64: the test device according to the previous embodiment, wherein the capillary element is adapted to guide the body fluid by capillary force.

Example 65: the test system according to one of the two preceding embodiments, wherein the application opening is located on the front side of the test piece.

Example 66: use of the difference of at least two measured values measured in at least two different positions of a test field of a test piece for generating a correction value for the analyte concentration in a body fluid sample, wherein the body fluid sample is guided through the test field by a capillary in a flow direction, wherein the at least two different positions are offset in the flow direction.

Example 67: use according to the preceding embodiment, wherein the correction value is dependent on the concentration of a particulate component, preferably hematocrit, in the body fluid.

All references cited in this specification are hereby incorporated by reference in their entirety as well as the disclosure specifically mentioned in this specification. The following examples will merely illustrate the invention. They should not be construed as limiting the scope of the invention in any way.

Drawings

In the subsequent description of preferred embodiments, further optional features and embodiments of the invention will be disclosed in more detail, preferably in conjunction with the dependent claims. Wherein the respective optional features may be implemented in isolation and in any arbitrary feasible combination, as will be appreciated by a person skilled in the art. The scope of the invention is not limited by the preferred embodiments. Embodiments are schematically depicted in the figures. In which like reference numerals refer to identical or functionally comparable elements throughout the separate views.

In the figure:

FIG. 1 shows a cross-sectional view of an exemplary embodiment of a test apparatus and test system according to the present invention;

FIG. 2 shows a schematic cross-sectional view of a test piece for use in the test system according to FIG. 1;

3A-D illustrate different embodiments of detector arrangements for measuring mitigation values in at least two different locations of a test field;

FIG. 4 shows a schematic diagram of an image of a test field taken by a camera, where two different regions of the image are selected to generate mitigation values at least two different locations of the test field;

FIG. 5 illustrates an exemplary embodiment of subdividing a test field into different locations along a flow path of a sample; left: an embodiment of a test piece; and (3) right: subdividing the test piece into ten measurement positions of equal size; the direction of flow 146 along the test field is indicated.

FIG. 6 shows the measured relative signal intensity (I) along the test field for various Hematocrit (HK) values at a glucose concentration of 200mg/ml_rel). The% value in the index of the abscissa relates to the percentage of the total length of the test field spanned by the respective measurement position in the flow direction.

Fig. 7 shows the measurable intensity difference (Δ I) between sub-window 10 and sub-window 2 as shown in fig. 5 as a function of glucose concentration at two different hematocrit values.

Fig. 8 shows the dependence of the deviation of the glucose concentration determined from the correction curve from the actual glucose concentration (mean deviation mb, vertical axis) on the position of the measurement location of the sample and on the Hematocrit (HCT) of the sample. The sub-window closer to the beginning of the test field shows a smaller hematocrit dependence. A calibration curve was obtained at a hematocrit of 42%.

Fig. 9 shows the dependence of the actual glucose concentration (c) in the blood sample on the linearization relief (R) measured at the measurement location sub-window 8, and the relief difference (Δ R) between the two measurement location sub-windows 10 and 8 using SCV chemicals. By determining the parameters at several glucose concentrations and several hematocrit values, a code surface is obtained instead of a code curve. To obtain linearization mitigation, the mitigation was first linearized at 42% hematocrit using a standard curve.

Fig. 10 shows the dependence of the actual glucose concentration in the blood sample on the linearization relief (R) measured at the measurement location sub-window 8, and the difference (Δ R) between the two measurement location sub-windows 10 and 8 using the nad chemistry. By determining the parameters at several glucose concentrations and several hematocrit values, a code surface is obtained instead of a code curve. Linearization mitigation is achieved as described in fig. 9.

Fig. 11 shows the average deviation of the determined glucose concentration from the actual glucose concentration (average deviation, mb, vertical axis) in samples with various Hematocrit (HCT) values (horizontal axis) determined by the calibration curve (black bars) or by the calibration area (white bars) shown in fig. 10. The buffering difference is calculated from the values measured in the sub-windows 8 and 10.

Fig. 12 shows the average deviation of the determined glucose concentration from the actual glucose concentration (average deviation, mb, vertical axis) in samples with various hematocrit values (HCT, horizontal axis) determined by the calibration curve (black bars) or by the calibration area (white bars) shown in fig. 10. The buffering difference is calculated from the values measured in the sub-windows 4 and 10.

Fig. 13 shows the average deviation of the determined glucose concentration from the actual glucose concentration (average deviation, mb, vertical axis) in samples with various hematocrit values (HCT, horizontal axis) determined by the calibration curve (black bars) or by the calibration area (white bars) shown in fig. 10. The mitigation difference is calculated from the values measured in sub-windows 2 and 4.

Fig. 14 shows the average deviation of the determined glucose concentration from the actual glucose concentration (average deviation, mb, vertical axis) in samples with various hematocrit values (HCT, horizontal axis) determined by the calibration curve (black bars) or by the calibration area (white bars) shown in fig. 9. The mitigation difference is calculated from the values measured in the sub-windows 2 and 9.

Fig. 15 shows the dependence of the actual glucose concentration in the blood sample on the linearization relief (R) measured at the measurement location sub-window 2, and the difference (Δ R) between these two measurement location sub-windows 9 and 2 using the nad chemistry. By determining the parameters at several glucose concentrations and several hematocrit values, a code surface is obtained instead of a code curve.

Detailed Description

In FIG. 1, a cross-sectional view of an embodiment of a test equipment 112 and a test system 114 according to the present invention is depicted. The test device 112 is preferably embodied as a handheld device. The testing device 112 preferably includes a housing 116, which may have a width of less than 1000cm³Preferably less than 500 cm³For people to carry. The test equipment 112 includes a receptacle 118 for receiving a test piece 120, the test piece 120 also forming part of the test system 114 in addition to the test equipment 112. The receptacle is adapted to position the test element 120 at least one application location (such as an application opening 124 of a capillary element 126) where a body fluid sample 122 can be applied to the test element 120, as will be explained in more detail below. The test piece 120 comprises at least one test field 128 with at least one test material 130, the test material 130 being adapted to change at least one measurable property in the presence of an analyte (such as glucose) to be detected by the test system 114.

The test device 112 further comprises a detector 132, which detector 132 in this particular embodiment comprises at least one light source 134 for illuminating the test field 128 and at least one light sensitive element 136, which light sensitive element 136 is adapted to measure detected light emitted and/or transmitted and/or reflected from the test field 128.

The test device 112 further comprises at least one evaluation unit 138 adapted to determine the concentration of the analyte by using an evaluation algorithm disclosed above or disclosed in more detail below. The evaluation unit 138 may preferably be or comprise at least one processing device, such as at least one computer and/or at least one application specific integrated circuit. As an example, the evaluation unit 138 may comprise a microcomputer. Furthermore, the evaluation unit 138 may comprise one or more further elements, such as at least one data storage device and/or other components.

The evaluation unit 138 is connected unidirectionally or bidirectionally to the detector 132, such as to receive measured values from the detector 132. Furthermore, the evaluation unit 138 may be adapted to control the overall functionality of the test device 112, such as for controlling the measurement process performed by the detector 132.

The test equipment 112 may also include one or more human machine interfaces such as at least one display 140 and/or at least one control element 142 such as at least one button. The elements 140, 142 may also be connected to an evaluation unit 138.

The test device 112 may also include one or more additional sensors for detecting one or more environmental parameters, such as one or more temperature sensors 145 adapted for determining an ambient temperature. As outlined above, these one or more environmental parameters may be used by the evaluation unit 138 to select an appropriate algorithm.

The test equipment 112 may also include at least one electronic interface 144 for uni-directional and/or bi-directional exchange of data and/or commands with one or more external devices, such as wireless and/or wire-based interfaces.

In fig. 2, a cross-sectional view of an exemplary embodiment of a test piece 120 is depicted. In this exemplary embodiment, the test piece 120 is designed as a test strip. However, other types of test pieces 120 may additionally or alternatively be used, such as test strips and/or test discs.

As outlined above, the test piece 120 includes at least one test field 128 and at least one capillary 126. Capillary 126 is adapted to direct bulk liquid sample 122 across test field 128 in flow direction 146. Thus, capillary 126 can draw sample 122 through test field 128 by capillary force. To increase capillary force, the test piece 120 may also include one or more vents 128.

Test field 128 includes at least one detection layer 150, detection layer 150 including at least one test material 130. The test field 128 may also include one or more additional layers, such as at least one separation layer 152 covering the detection layer 150 on the side facing the capillary 126. The separation layer 152 may comprise one or more pigments, preferably inorganic pigments, such as inorganic oxides, which may provide a broad optical background for optical measurements. Furthermore, the separation layer 152 may be adapted for separating at least one particulate component contained in the body fluid.

The test piece 120 comprises at least one detection window in the substrate 156 through which changes in optical properties in the test field 128 can be detected by using the detector 132. It should be noted that in the embodiment depicted in fig. 2, an optical test piece 120 is depicted, wherein the test material 130 is adapted to change at least one optical property in the presence of an analyte to be detected. Additionally or alternatively, other types of test pieces 120 may be used, such as electrochemical test pieces 120, in which at least one test material 130 is adapted to change at least one electrochemical property in the presence of an analyte to be detected. In the latter case, the test field 128 may comprise one or more electrodes adapted to provide suitable voltage signals and/or current signals that may be used to generate suitable measurements.

In fig. 3A to 3D, four different potential arrangements of the detector 132 of the test equipment 112 according to fig. 1 are depicted. According to the invention, the detector is adapted for measuring at least one optical property of the test field 128, such as at least one mitigation characteristic, in at least two different positions of the test field 128. In fig. 3A to 3D, the first position is symbolically designated by reference numeral 158, and the second position is symbolically designated by reference numeral 160. The positions 158,160 are offset in the direction of the flow direction 146, wherein the flow direction 146 is also symbolically depicted in fig. 3C.

In order to measure the optical properties of the test field 128 in the first 158 and second 160 positions, various techniques are possible. Thus, such an arrangement is depicted in fig. 3A: the detector 132 comprises a first light source 162 and a second light source 164, wherein the first light source 162 illuminates the first location 158 and wherein the second light source 164 is adapted to illuminate the second location 160. The first and second light sources 162, 164 may include, by way of example, one or more light emitting devices, such as one or more light emitting diodes. Other types of light sources are possible. The first light source 162 and the second light source 164 may be adapted to illuminate the first location and the second location, respectively, with light having the same wavelength and/or light having different wavelengths. Thus, the optical properties of the light emitted by the first and second light sources 162, 164 may be the same or may be different. Further, optionally, the first light source 162 and the second light source 164 may emit light at the same time, or may emit light at different points in time, such as by using an intermittent timing schedule.

The detection detector 132 may further comprise a first photosensitive element adapted to detect light emitted by the first light source 162 and reflected and/or transmitted by the test field 128 in the first position 158; and at least one second light sensitive element 168 adapted to detect light emitted by the second light source 164 and reflected and/or transmitted by the test field 128 in the second position 160. It should be noted that preferably the light sensitive elements 166, 168 are adapted to receive the light scattered in the first 158 and second 160 positions, respectively, such as by measuring mitigation values in these positions 158, 160. Additionally or alternatively, other measurement settings are possible. Thus, the transmitted light and/or the light sources 162, 164 may be adapted to stimulate emission of light, such as fluorescence and/or phosphorescence, in the test field 128.

In fig. 3B, a modification of the arrangement of fig. 3A is depicted, wherein only one light source 134 is used to illuminate at least one first location 158 and at least one second location 160. Still, the first photosensor 166 and the second photosensor 168 are used to detect light from the first location 158 and the second location 160, respectively. As shown in fig. 3A, the photosensitive elements 166, 168 may be or may include any type of photosensitive element, such as a photodiode. Additionally or alternatively, a camera may be used, as will be explained in more detail below. Other embodiments are possible.

In fig. 3C, a further modification of the arrangement shown in fig. 3A is described. In this arrangement, only one light source 134 and only one light sensitive element 136 are used to detect light from the first location 158 and the second location 160. Various measurement arrangements for achieving this are possible. Thus, an optical switch may be provided to subsequently illuminate the first position 158 and the second position 160 at different points in time by using the same light source 134. Thereby, by using an intermittent timing scheme, light detected by the light sensitive element 136 at a specific point in time can be distributed to one of the first position 158 and the second position 160. Additionally or alternatively, the photosensitive element 136 may be adapted to spatially resolve the detected light so as to spatially distinguish between light from the first location 158 and light from the second location 160. Thus, as outlined above and as outlined in more detail below, the light sensitive element 16 may be or may comprise a camera and/or a camera chip, such as a CCD chip.

In fig. 3D, a further modification of the arrangement shown in fig. 3A is depicted. In this arrangement, two light sources 134 and only one photosensor 136 are used to detect light from the first location 158 and the second location 160. Various measurement arrangements for achieving this are possible. The light source may then be triggered to illuminate the first location 158 and the second location 160 at different points in time. Thereby, by using an intermittent timing scheme, light detected by the light sensitive element 136 at a specific point in time can be distributed to one of the first position 158 and the second position 160. Additionally or alternatively, the photosensitive element 136 may be adapted to spatially resolve the detected light so as to spatially distinguish between light from the first location 158 and light from the second location 160. Thus, as outlined above and as outlined in more detail below, the light sensitive element 136 may be or may comprise a camera and/or a camera chip, such as a CCD chip.

The embodiment of fig. 3C or 3D is schematically depicted in fig. 4. In this embodiment, an image 170 of the test field 128 captured at a specific point in time is shown, wherein again reference numeral 146 schematically shows the direction of flow of the liquid 122 in the image 170. In the image 170, a first region 172 is marked, which corresponds to the image pixels representing the first location 158, and a second region 174 is marked, which may contain the pixels of the image 170 corresponding to the second location 160.

In fig. 5, different ways of subdividing the test field 128 are shown. In which the image 170 of the test field 128 is subdivided into ten different regions, numbered from 1 to 10 in figure 5. Any of the regions 1 through 10 in fig. 5 may be selected as the first location 158 and/or the first region 172. Further, combinations of regions may be used for first location 158 and/or first region 172. Similarly, any of the regions 1 to 10 or combinations of the regions 1 to 10 of fig. 5 may be selected as the second location 160 and/or the second region 174 as long as the second region is offset from the first region in the flow direction 146.

In the following, several measurements will be shown for illustrating the optical measurements taken at the first 158 and second 160 locations, and the difference between these measurements may be used to correct the analyte concentration for the bulk hematocrit. Wherein different types of test materials 130 are used. In general, with respect to test materials 130 that may be used in the present invention, reference may be made to the prior art documents listed above. Further, reference may be made to j. hoenes et al: the Technology BehindGlucose Meters, Test Strips, Diabetes Technology & Therapeutics, volume 2008, Vol.10, supplement 1, S-10 to S-26. Additionally or alternatively, other types of test materials 130 may be used. Thus, in the following, reference will be made to the following types of test materials:

first, a test material also known as "SCV chemical" was used. Such SCV test chemicals are disclosed in, for example, EP 0354441a2, and may comprise a PQQ-dependent deoxyenzyme and a direct electron acceptor, which may be an aromatic nitroso compound or an oxime-like compound. Further, one or more indicators, such as one or more dyes, may be present. Thus, as an example, a heteropoly blue indicator as disclosed in EP 0431456a1 may be used.

As a second type of test material 130, also referred to as "cnd chemical", test materials as disclosed in WO 2007/012494a1, WO 2009/103540a1, WO 2011/012269 a2, WO 2011/012270 a1 and WO 2011/012271 a2 are disclosed. Thus, in WO 2007/012494A1, derivatives of cNAD are disclosed. In WO 2009/103540a1, stabilized enzyme/coenzyme complexes are disclosed. In WO 2011/012269 a2, WO 2011/012270 a1 and WO 2011/012271 a2, the synthesis of cdna and cdna/derivatives and intermediates/leads is disclosed.

At 10 blood glucose concentrations: 0mg/dl, 25mg/dl, 50mg/dl, 75mg/dl, 100mg/dl, 150mg/dl, 250mg/dl, 350mg/dl, 450mg/dl, 550mg/dl and 5 hematocrit values for each blood glucose concentration: measurements were performed at 20%,30%, 42%, 50%, 60%; the measurement was repeated 10 times using a test field having a length of 2.07mm and a width of 1.76mm in the flow direction.

The measurements represented in FIGS. 6-9, 11-13, and 15 were performed using cNAD-chemistry; the measurements represented in figures 10 and 14 were performed using SCV chemicals.

List of reference numerals

112 test equipment

114 test system

116 casing

118 receiver

120 test piece

122 sample

124 coating port

126 capillary member

128 test field

130 test material

132 detector

134 light source

136 light sensitive element

138 evaluation unit

140 display

142 control element

144 interface

145 temperature sensor

146 direction of flow

148 air vent

150 detection layer

152 separating layer

154 detection Window

156 substrate

158 first position

160 second position

162 first light source

164 second light source

166 first photosensitive element

168 second photosensitive element

170 image

172 first region

174 second region

Claims

1. A method for detecting an analyte in a blood sample, said analyte being a low molecular weight organic molecule, the method having the steps of:

a) applying a sample (122) of a blood sample to a test piece (120), the test piece (120) comprising at least:

(ii) a capillary (126) adapted to guide the sample (122) through the test field (128) in a flow direction (146),

(iii) first and second measurement locations (158, 160) within the test field (128), wherein the second measurement location (160) is offset from the first measurement location (158) in the flow direction (146);

b) measuring the measurable property at the at least one first measurement location (158), thereby generating at least one first measurement value;

c) measuring the measurable property at the at least one second measurement location (160), thereby generating at least one second measurement value;

(i) At least one first input variable of the at least two input variables comprises information about a difference between a first measured value and a second measured value, an

(ii) At least one second input variable of the at least two input variables comprises measurement information about an analyte-induced change of a measurable property of the test material (130) in at least part of the test field (128),

wherein the test material (130) performs at least one optically or electrochemically detectable detection reaction in the presence of the analyte,

wherein the detection reaction is a redox reaction.

2. The method of the preceding claim, wherein the measurement information about the analyte-induced change of the measurable property of the test material (130) in at least part of the test field (128) is generated by one or more of the following processes:

-said first measurement value is used as said measurement information;

-said second measurement value is used as said measurement information;

-measuring an analyte-induced change of a measurable property at least one third measurement location of said test field (128), thereby generating at least one third measurement value, wherein the third measurement value is used as said measurement information.

3. The method according to one of the preceding claims, wherein the measurement information used in step d) (ii) is a measurement value generated in the flow direction (146) at a measurement position located within the first half of the test field (128).

4. Method according to one of claims 1 to 2, wherein method steps b) and c) are performed at one of the following:

-a predetermined time span after applying a sample (122) of a blood sample to the test piece (120); and

-at points in time at which a measurement curve indicating that the measurable property is a function of time satisfies at least one predetermined condition.

5. The method of claim 4, wherein the at least one predetermined condition is at least one threshold condition.

6. The method of claim 4, wherein the slope of the measurement curve is below or above a predetermined threshold.

7. The method according to one of claims 1 to 2,

-the evaluation algorithm comprises a one-step evaluation algorithm, and

-the first input variable and the second input variable are simultaneously used for deriving the concentration of the analyte in the blood sample by using at least one predetermined calibration curve indicating that the concentration of the analyte is a function of both input variables.

8. The method according to one of claims 1 to 2,

the evaluation algorithm comprises at least two separate steps,

-in a first step of the algorithm, an estimate of the concentration of said analyte in said blood sample is derived from a second input variable by using at least one predetermined first calibration curve indicating that the uncorrected concentration of the analyte is a function of said second input variable, and

9. The method of claim 8, wherein,

-in a first step of the algorithm, generating an estimate of the glucose concentration, an

10. The method of claim 1, wherein the analyte is a low molecular weight organic molecule having a molecular mass of less than 1000 Da.

11. The method of claim 1, wherein the test material comprises at least one enzyme adapted to perform at least one enzymatic reaction in the presence of an analyte.

12. A method for detecting an analyte in a blood sample, said analyte being a low molecular weight organic molecule, the method having the steps of:

(iii) a single measurement location (158) within the test field (128);

wherein the single measurement location is located within the first third of the test field (128) determined according to the application site, and

wherein the detection reaction is a redox reaction.

13. Test device (112) for detecting an analyte in a blood sample, the analyte being an organic molecule of low molecular weight, wherein the test device (112) comprises

(i) At least one test field (128), the at least one test field (128) having at least one test material (130) adapted to change at least one measurable property in the presence of an analyte, and

b) wherein the receptacle (118) is adapted to position the test piece (120) in at least one application position in which a sample (122) of a blood sample can be applied to the test piece (120),

c) wherein the apparatus further comprises at least one detector (132) for measuring the measurable property, wherein the detector (132) is adapted to

(i) Measuring the measurable property in at least one first location (158) of the test field (128), thereby generating at least one first measurement value,

(ii) measuring the measurable property in at least one second position (160) of the test field (128), thereby generating at least one second measurement value, wherein the second position (160) is offset from the first position (158) in the flow direction (146),

d) wherein the test device (112) further comprises at least one evaluation unit (138) adapted to determine the concentration of the analyte by using an evaluation algorithm having at least two input variables,

(i) wherein at least one first input variable of the at least two input variables comprises information about a difference between a first measured value and a second measured value, an

(ii) Wherein at least one second input variable of the at least two input variables comprises measurement information about an analyte-induced change of the test material (130) in at least part of the test field (128),

wherein the detection reaction is a redox reaction.

14. The test device (112) according to claim 13, wherein the test device (112) is adapted to perform the method according to one of the preceding method claims.

15. The test device (112) according to one of claims 13 to 14, wherein the at least one first input variable comprises information about a gradient of measured values over at least a part of the test field (128).

16. The test device (112) of one of claims 13 to 14,

-the test device (112) is adapted to measure an analyte-induced change of the measurable property in at least one third position of the test field (128), thereby generating at least one third measurement value,

-a third measurement value is used as the measurement information,

-the test field (128) extends in the flow direction (146), and wherein,

-the third position is located within the first 99% of the test field (128) in the flow direction (146).

17. The test device (112) of claim 16, wherein the third location is within a first third of the test field (128).

18. The test device (112) of claim 16, wherein the third location is within a first quarter of the test field (128).

19. The test device (112) according to one of claims 13 to 14, wherein the test device (112) further comprises at least one temperature sensor (145) for determining an ambient temperature.

20. A test device (112) for detecting an analyte in a blood sample, the analyte being an organic molecule of low molecular weight, wherein the test device (112) comprises

(iii) At least one test field (128), the at least one test field (128) having at least one test material (130) adapted to change at least one measurable property in the presence of an analyte, and

(iv) at least one capillary (126) adapted to guide the sample (122) through the test field (128) in a flow direction (146),

c) wherein the apparatus further comprises at least one detector (132) for measuring the measurable property, wherein the detector (132) is adapted to measure the measurable property in a single measurement location (158) of the test field (128), thereby generating at least one measurement value,

d) wherein the test device (112) further comprises at least one evaluation unit (138) adapted to determine the concentration of the analyte using an evaluation algorithm with the at least one measurement value as an input variable,

wherein the detector is adapted to measure the measurable property within the first third of the test field, an

wherein the detection reaction is a redox reaction.

21. A test system (114) for detecting an analyte in a blood sample, the analyte being a low molecular weight organic molecule, the test system comprising:

a) at least one test device (112) according to one of the preceding claims relating to a test device (112), and

b) at least one test piece (120), wherein the test piece (120) has at least one test field (128), the at least one test field (128) has at least one test material (130) and a capillary element (126), the at least one test material (130) being adapted to change at least one measurable property in the presence of an analyte, the capillary element (126) being adapted to guide the sample (122) through the test field (128) in a flow direction (146), and wherein the test material (130) performs at least one optically or electrochemically detectable detection reaction in the presence of an analyte,

wherein the detection reaction is a redox reaction.

22. Use of a difference of at least two measurements measured in at least two different positions (158, 160) of a test field (128) of a test piece (120) for generating a correction value for an analyte concentration in a blood sample (122), the test field (128) having at least one test material (130) adapted to change at least one measurable property in the presence of an analyte, the analyte being an organic molecule of low molecular weight, wherein the blood sample comprises at least one particle component, wherein the blood sample (122) is guided through the test field (128) by a capillary element (126) in a flow direction (146), wherein the at least two different positions (158, 160) are shifted in the flow direction (146), and

wherein the detection reaction is a redox reaction.