Method for measuring concentration of specific electrolyte in blood sample

Abstract

The invention relates to a method and a blood measuring strip (100) for measuring a specific electrolyte concentration in a blood sample using a readout device (200), the blood measuring strip (100) having an input region (1) for receiving a blood sample and a measuring region (3) connected to the input region (1), a luminescent indicator dye being arranged in the measuring region (3), the luminous intensity of the luminescent indicator dye is dependent on the specific electrolyte concentration in the blood sample, characterized in that a luminescent reference dye is arranged in the measurement region (3), the luminous intensity and the luminescence decay time of the luminescent reference dye being independent of the specific electrolyte concentration in the blood sample.

Description

[0001] The present invention relates to a method for measuring the concentration of a specific electrolyte, preferably the concentration of potassium, in a blood sample, wherein:

[0002] The provided blood sample is introduced into the input area of the blood measuring strip and at least a portion of the blood sample is guided to the measuring area of the blood measuring strip; wherein

[0003] The blood measuring strip is combined with the readout device, preferably inserted into the readout device; wherein

[0004] The specific electrolyte of the blood sample reacts with the luminescent indicator dye in the measuring area and wherein the indicator dye is excited by light from at least one light source of the readout device, wherein the luminescence intensity of the indicator dye depends on the concentration of the specific electrolyte of the blood sample.

[0005] The present invention also relates to a blood measuring strip for measuring the concentration of a specific electrolyte, preferably the concentration of potassium, in a blood sample using a readout device, wherein the blood measuring strip has an input area for receiving the blood sample and a measuring area connected to the input area, wherein a luminescent indicator dye is arranged in the measuring area, the luminescence intensity of which depends on the concentration of the specific electrolyte of the blood sample.

[0006] The present invention also relates to a system for measuring the concentration of a specific electrolyte, preferably the concentration of potassium, in a blood sample.

[0007] The concentration of the specific electrolyte refers to the concentration of the specific electrolyte. It is thus not the aim to determine the total concentration of all electrolytes in the blood sample, but the concentration of the specific electrolyte. Typical electrolytes commonly found in blood samples include sodium (Na + ), potassium (K + ), calcium (Ca 2+ ), magnesium (Mg 2+ ), lithium (Li + ), chloride (Cl - ), ammonium (NH4 + ), carbonate (HCO3 - ) or iron (Fe 2+ or Fe 3+ ). The specific electrolyte is preferably selected from these.

[0008] The use of the blood measuring strip for the measurement has the great advantage that fast and accurate measurements can be achieved at any location. These measurement operations are simple and can even be performed by the patient himself without the assistance of a professional.

[0009] In this context, blood refers to whole blood, pre-treated blood or even only one component of blood, such as serum or plasma.

[0010] Blood measurement strip systems for various blood parameters, in particular glucose concentration, are known. However, blood measurement strips for measuring specific electrolytes are hardly known.

[0011] WO 2022 / 251736 A1 discloses a blood measurement strip with which the potassium concentration of a blood sample can be determined using a readout device. This is achieved using an optical method which involves ionophores, ion exchangers and chromogenic ionophores. During the chemical reaction, all potassium in the sample is consumed and the color of the test strip is influenced by the amount of potassium ions absorbed. Thus, the potassium concentration is determined by colorimetry. However, this method and strip design have the disadvantage that the color change depends on the absolute amount of potassium in the sample. Therefore, the blood measurement strip must absorb a precisely defined amount of blood sample in order to determine the potassium concentration. Furthermore, this measurement method is highly sensitive to the pH value and requires a pre-treatment of the blood sample. This strong influence of the measurement on the blood sample also makes it difficult to combine this measurement with the determination of other blood parameters in the same blood sample. All of this means that either the measurement result is rather inaccurate or the construction of the measurement strip is complex and costly. In addition, the response measured optically also depends on a number of other factors, such as the temperature or contamination of the blood sample.

[0012] It is therefore an object of the present invention to provide a method for measuring at least the concentration of a specific electrolyte in a blood sample and a corresponding blood measurement strip, which is low-cost but particularly accurate, robust and reliable.

[0013] The present invention solves this problem by the emission reference dye being excited by a light source, wherein the emission intensity and the emission decay time of the reference dye do not depend on the concentration of the specific electrolyte of the blood sample, the light emitted by the indicator dye and the reference dye upon excitation being detected by at least one detector of the readout device, and the concentration of the specific electrolyte of the blood sample being determined based on the phase shift or the decay time of the signal detected by the detector.

[0014] The problem is also solved by the emission reference dye being arranged in the measurement region, the emission intensity and the emission decay time of the reference dye not depending on the concentration of the specific electrolyte of the blood sample.

[0015] The problem is also solved by the system comprising a readout device and a blood measurement strip,

[0016] wherein the blood measurement strip has an input region for receiving a blood sample and a measurement region connected to the input region, wherein an emission indicator dye is arranged in the measurement region, the emission intensity of the emission indicator dye depending on the concentration of the specific electrolyte of the blood sample,

[0017] wherein the luminescence reference dye is arranged in or on the blood measuring strip and / or in or on the readout device, whose luminescence intensity and luminescence decay time do not depend on the specific electrolyte concentration of the blood sample, and

[0018] wherein the readout device has at least one receiving area for receiving the blood measuring strip, at least one light source for exciting the indicator dye and the reference dye, and at least one detector for detecting the light emitted by the indicator dye and the reference dye as a result of the excitation.

[0019] The determination on the basis of the phase shift of the signal detected by the detector means that the phase shift of the detected signal is included in the determination process. Thus, it can be provided that the determination process additionally contains further parameters or signals.

[0020] It is particularly advantageous to provide a measuring system for measuring a specific electrolyte concentration, which comprises a blood measuring strip according to the application and a readout device, wherein it is provided that the readout device has at least one receiving area for receiving the blood measuring strip, at least one light source for exciting the indicator dye and the reference dye of the blood measuring strip, and at least one detector for detecting the light emitted by the indicator dye and the reference dye as a result of the excitation. The receiving area is usually an insertion channel, the cross section of which matches the cross section of the blood measuring strip. If necessary, a fixing device for the blood measuring strip can be arranged in the receiving area, and the receiving area is at least partially formed by such a fixing device.

[0021] The amplitude, i.e. the intensity, of the signal emitted by the indicator dye depends on the specific electrolyte concentration of the blood sample. However, this amplitude can also be influenced by other factors, such as the temperature, the pH value or impurities.

[0022] It can be provided that the light source has at least two light emitting devices, whose emitted light preferably has the same phase, i.e. no phase shift between each other. The light source preferably contains at least one LED. It is particularly preferred to contain at least two LEDs in series. This enables the in-phase of the LEDs. Preferably, at least some of the LEDs are ring LEDs. The light source can also have several sub-units, which can be spatially and / or electrically separated from each other, and each sub-unit has at least one light source, such as an LED.

[0023] A reference dye is a dye whose luminescence intensity and luminescence decay time do not depend on the specific electrolyte concentration of the blood sample. This is essential for the function of the reference dye. It is preferred that the at least one reference dye and the at least one indicator dye have at least partially overlapping excitation and / or emission spectra. Preferably, the reference dye is inert, photostable and / or has a long decay time. Preferably, the decay time of the reference dye exceeds 1 ps, exceeds 5 ps, preferably exceeds 10 ps, particularly preferably exceeds 50 ps, most particularly preferably exceeds 100 ps. Preferably, the decay time of the reference dye is at least 10 times, particularly preferably at least 50 times, most particularly preferably at least 100 times (of the decay time of the indicator dye).

[0024] Preferably, the reference dye comprises at least one metal-ligand complex and / or at least one inorganic phosphor. Metal-ligand complexes generally have a higher brightness, but can need to be immobilized in a gas barrier polymer such as polyacrylonitrile. For example, the reference dye can comprise at least one ruthenium(II) polypyridyl complex and / or the inorganic phosphors YABCO (yttrium aluminum borate activated with chromium(III), Cr-YAB) and / or GABCO (gadolinium aluminum borate activated with chromium(III), Cr-GAB).

[0025] It can be provided that the light source provides light to the measurement region from at least two sides, wherein the two sides are preferably opposite to each other. This can be achieved, inter alia, by multiple sub-units of the light source. Preferably, at least two sub-units are arranged on opposite sides of the blood measurement strip when the blood measurement strip is arranged in the receiving region as intended, preferably when the blood measurement strip is in the measurement position and / or the calibration position. Correspondingly, it can also be provided that at least two sub-units of the light source illuminate the blood measurement strip from two opposite sides. This facilitates a uniform illumination and, in turn, a uniform excitation.

[0026] It can be provided that the indicator dye and / or the reference dye are excited by light from multiple sides, preferably at least two opposite sides and / or in a ring direction.

[0027] Preferably, the receiving region is light-tight with respect to the surrounding environment. This can prevent ambient light, such as sunlight or indoor artificial light sources, from interfering with the measurement.

[0028] It is preferred to provide that the time profile of the signal, in particular the time profile of the phase shift, is taken into account in the determination of the specific electrolyte concentration. In particular when thicker indicator and / or reference dye layers are used, it takes a certain time until the blood, and thus the electrolytes, reach the indicator dye and interact with it. Here, the phase angle converges within a time window towards a stable value, which is determined by the specific electrolyte concentration of the blood sample. From the curve of the phase angle as a function of the measurement time, the steady state can be inferred, so that the specific electrolyte concentration can be determined with higher reproducibility and robustness. Accordingly, it is advantageous if the evaluation unit is designed to take the time profile of the signal, in particular the time profile of the phase shift, into account in the determination of the specific electrolyte concentration.

[0029] In this regard, it is advantageous if the blood measuring strip has a layer comprising the indicator substance, and the thickness of this layer is at most 20 pm, preferably 20 pm, particularly preferably at most 30 pm and / or at least 5 pm, particularly preferably at least 10 pm.

[0030] It can also be provided that the time profile of the signal intensity, the luminescence decay time, the signal rise kinetics, the spectral shift of the signal, etc. are taken into account in the determination of the specific electrolyte concentration.

[0031] Furthermore, it can be provided that the light source excites the reference dye and / or the indicator dye with at least two signals of different frequencies, and the light emitted by the indicator dye and the reference dye as a result of the excitation by the at least two signals is detected by at least one detector of the readout device; and the specific electrolyte concentration of the blood sample is determined on the basis of the at least two detected signals. Preferably, the excitation with these signals takes place sequentially, as does the detection.

[0032] This utilizes the following fact: the signal phase shift of a kind of dyestuff (particularly reference dye) may depend on the frequency of excitation signal, while the signal phase shift of another kind of dyestuff (particularly indicator dye) then does not depend on this frequency or is less affected by it.Under higher excitation frequency, a kind of dyestuff causes phase shift to increase because of its longer half-life, and this can produce substantially uniform output signal.Can determine the signal composition and / or mixing ratio of reference dye and indicator dye separately from the signal obtained thus, thereby improve assessment accuracy.Preferably provide that the cycle duration of at least one signal is less than twice of (a kind of dyestuff, particularly reference dyestuff) half-life, preferably less than its half-life, and / or the cycle duration of at least one signal is greater than twice of (a kind of dyestuff, particularly reference dyestuff) half-life, preferably greater than its three times. In this regard, it is also advantageous if the light source is designed to excite the reference dye and / or the indicator dye with at least two signals of different frequencies, and / or the at least one detector of the readout device is designed to detect light emitted by the indicator dye and the reference dye as a result of the excitation by the at least two signals, and / or the computing unit is designed to determine the concentration of a specific electrolyte in the blood sample based on the at least two detected signals. Preferably, the excitation with these signals is performed sequentially, and the detection thereof is also performed sequentially.

[0033] Furthermore, it can be provided that at least one reference light signal is generated (preferably by at least one light source and / or at least one reference light source), that the at least one reference light signal is detected by at least one detector, and that the determination of the specific electrolyte concentration of the blood sample incorporates the reference light signal detected by the detector. Accordingly, it can also be provided that the readout device has at least one reference light source, which is designed to transmit at least one reference light signal to the at least one detector. In this way, the state and / or changes (e.g., aging) of the detector can be detected and incorporated into the determination of the specific electrolyte concentration. In particular, this enables adjustments to the measurement electronics to improve or standardize the measurement accuracy of the electronics. Preferably, at least one parameter (such as the phase, spectrum, and / or intensity of the at least one reference light signal) is known and / or specified.

[0034] Furthermore, it can be provided that at least one parameter of the detected reference light signal is stored in at least one electronic memory and / or at least one parameter of at least one detected reference light signal is compared with at least one parameter of at least one reference light signal stored in the electronic memory.

[0035] It can also be provided that the reference light signal is guided onto the blood measuring strip or through the blood measuring strip before reaching the detector. This additionally enables properties or states of the blood measuring strip to be detected and also included in the determination process.

[0036] Preferably, the generation and detection of the reference light signal takes place before or after the excitation of the reference dye and the indicator dye and the detection of the resulting signal.

[0037] In the measurement region, the indicator dye can be present mixed with the reference dye. However, it can also be provided that the indicator dye and the reference dye are at least partially spatially separated. For example, one half of the measurement region can comprise the indicator dye and the other half can comprise the reference dye. It is important, however, that the indicator dye and the reference dye are arranged in such a way that the sum of the light signals of both dyes can be measured.

[0038] In particular, it can be provided that the indicator dye and the reference dye are at least partially spatially separated and, preferably, the indicator dye is arranged in a first layer of the blood measurement strip, preferably a first film, particularly preferably a first side of the first film, and the reference dye is arranged in a second layer of the blood measurement strip, preferably a second film and / or a second side of the first film. The dyes can be applied to the respective films and / or be contained therein. It can also be provided that the first layer and the second layer have at least one mixing region in which they mix with one another.

[0039] It can be provided that the indicator dye and the reference dye at least partially overlap when projected onto the plane of the blood measurement strip. The plane of the blood measurement strip refers to the plane along which the blood measurement strip mainly extends. Usually, the blood measurement strip is designed in a flat and elongated shape, thereby defining the plane.

[0040] It is preferably provided that the reference dye is excited by the light source in the measurement region. In this regard, it is advantageous if the system has at least one blood measurement strip according to the application.

[0041] It can be advantageous if the reference dye is located in the measurement region of the blood measurement strip.

[0042] It can also be provided that the reference dye is arranged in another part of the blood measurement strip and / or that the reference dye is arranged in or on the readout device.

[0043] It can be provided that, in at least a part of the measurement region, preferably in the entire measurement region, the indicator dye and the reference dye are mixed with one another and / or present in the same layer and / or the same polymer matrix. This makes it particularly easy to achieve a constant mixing ratio. By "mixed with one another" is meant that the two dyes are mixed together. The dyes do not have to be in the same state of aggregation.

[0044] It is particularly advantageous if the indicator dye is arranged in a first layer, preferably a first membrane, of the blood measuring strip and the reference dye is arranged in a second layer, preferably a second membrane, of the blood measuring strip. Correspondingly, the measuring region can have two or more different sections which are partially or completely separated from one another. The first layer and the second layer are at least partially part of the measuring region. This makes it easier to achieve a uniform, reproducible mixing ratio. Preferably, the first layer and the second layer are separated by at least one separating layer, wherein the separating layer is preferably a carrier layer, such as a carrier membrane or a carrier plate. This facilitates the construction. In this case, the first layer and the second layer, and particularly preferably also the separating layer, most preferably all layers between the first layer and the second layer, are preferably transparent to the excitation light and / or the signal of the light source. This enables detection from only one side, the separating layer side.

[0045] Preferably, the indicator dye is arranged in a first polymer matrix and the reference dye is arranged in a second polymer matrix. The first and the second polymer matrix are preferably spatially separated from one another. The first and the second polymer matrix can comprise the same material or different materials.

[0046] The first layer can comprise a polymer matrix and / or the second layer can comprise a polymer matrix, wherein preferably the first layer and the second layer each comprise a polymer matrix.

[0047] By using a reference dye in combination with an indicator dye, such as a dye sensitive to a specific electrolyte, such as a potassium-sensitive dye, it is possible to measure the concentration of a specific electrolyte using a dual-lifetime reference method. This enables precise measurements which are largely insensitive to contamination and other parameter variations in the blood sample.

[0048] The light emitted by the reference indicator has a decay time or a phase shift relative to the excitation signal, which decay time or phase shift is independent of the analyte. By jointly evaluating the sum signal from the light emission of the indicator dye and the reference dye, the amplitude change of the indicator dye which is related to the electrolyte concentration is converted into a robust decay time or phase change. Thus, the specific electrolyte concentration is not calculated purely on the basis of the amplitude of the light emission response of the indicator dye, but rather the specific electrolyte concentration is determined using a reference value from the decay or phase behavior of the measured total signal.

[0049] By taking into account the decay time or the phase shift of the measurement signal relative to the light used for excitation, it is possible to robustly determine the specific electrolyte concentration.

[0050] Amplitude changes, such as those caused by contamination, have the same effect on both indicators and thus cancel each other out. This makes the measurement independent of disturbing factors and enables a simple and robust measurement using a blood measuring strip.

[0051] Correspondingly, it is particularly advantageous if the readout device has a computing unit which is designed to evaluate the signals detected by the detector and to determine the specific electrolyte concentration on the basis of the decay time or the phase shift.

[0052] A further particular advantage of the application is that the readout device can also be constructed simply and cost-effectively. All that is required is one or more light sources which can provide the light of the wavelength required to excite the indicator and reference dyes, and one or more detectors which can detect the light of the respective wavelength emitted by the dyes by luminescence. In the simplest case, this can be achieved by a single light source and a single detector, or alternatively by two or more light sources and detectors.

[0053] A further advantage of this method is that the luminescent indicator dye generally binds reversibly to the electrolyte, preferably potassium. This creates an equilibrium between the electrolyte bound to the indicator dye and the free electrolyte or the free indicator dye. The luminescence response of the indicator dye therefore does not depend on the absolute number of free electrolyte ions in the blood sample provided, but on the specific electrolyte concentration, which is also to be determined. The amount of blood sample actually in contact with the indicator dye is therefore not important, provided that there is a sufficient minimum amount for the measurement. This minimum amount is, however, very small, in the range of a few microlitres, for example 5-15 microlitres.

[0054] In addition, precise measurements can be achieved without prior treatment of the blood sample.

[0055] A further advantage is that the indicator dye is not consumed due to the reversible binding to the electrolyte ions. The blood measurement strip can therefore be cleaned and reused. This enables particularly resource-saving use, which is particularly important in professional settings such as hospitals, laboratories or doctors' offices. Such blood measurement strips are also easily sterilisable, which facilitates simple production and reuse.

[0056] In addition, further parameters such as pH value, glucose or sodium can be easily determined in such a blood measurement strip. The additional or further parameters can also include: electrolyte parameters (Na + , K + , Ca 2+ , Mg 2+ , Li+, Cl-, pH value, NH4 + , HCO3 - ), degree of haemolysis, haemoglobin, lipids, blood gases (such as pO2, pCO2), coagulation parameters and / or metabolites (such as lactate, creatinine, urea and / or ketone bodies). Since the blood sample does not have to be changed for the measurement of the specific electrolyte concentration, these measurements can even be carried out in the same measurement range.

[0057] It may also be provided that the blood measuring strip has at least one further measuring area, which is preferably used to measure at least one other parameter (see the list of examples in the previous paragraph), and that the at least one measuring area is connected to the input area. In this regard, it may be provided that at least a portion of the blood sample is guided from the input area to the at least one further measuring area of ​​the blood measuring strip, preferably for measuring the at least one other parameter.

[0058] The input area of ​​the further measuring area is preferably identical to the input area of ​​the measuring area, but it can also be provided that the input area of ​​the further measuring area is another input area different from the input area of ​​the measuring area.

[0059] Preferably, at least one additional luminescent indicator dye is arranged in the additional measurement region, the luminescence of which depends on at least one other parameter of the blood sample. Preferably, at least one additional luminescent reference dye is arranged in the additional measurement region, wherein the luminescence intensity and luminescence decay time of the reference dye do not depend on the specific electrolyte concentration of the blood sample. The additional reference dye may include a reference dye or be identical to the reference dye. In this regard, it can also be provided that the light emitted by the additional indicator dye and the reference dye upon excitation is detected by at least one detector of the readout device; and the additional parameter of the blood sample is determined based on a phase shift of the signal detected by the detector.

[0060] Alternatively, it may also be provided that another detection method is used for at least one parameter.

[0061] The measurement region and at least one further measurement region can be connected in parallel and / or in series with the input region. Series connection means that at least one measurement region is connected to the input region via at least one other measurement region, i.e., blood from the input region must first flow through one measurement region before reaching the other measurement region.

[0062] It can be provided that the measuring region and the at least one further measuring region are arranged on different sides of the blood measuring strip.

[0063] It is also possible that the measuring region and the at least one further measuring region are arranged in different layers of the blood measuring strip.

[0064] The measurement area refers to the spatial region where the indicator dye and reference dye are arranged.

[0065] Preferably, the light source excites the indicator dye and the reference dye with a time- varying light signal, i.e. an oscillating signal, such as a sinusoidal light signal or a pulsed light signal. In this way, an equivalent oscillating light signal of both dyes is received as a response signal by the detector and can be measured continuously and repeatedly, or, in the case of a pulsed light signal, a certain time window of the light pulses or the afterglow after the light source is switched off can be measured. Accordingly, it can be provided that the light source is designed to generate an oscillating or pulsed light signal.

[0066] It is not necessary to introduce the entire blood sample into the measurement region. It can be provided that only a certain volume portion is introduced into the measurement region. It can also be provided that only a certain component is introduced into the measurement region, for example only the plasma.

[0067] The above-mentioned method steps do not necessarily have to be carried out in the order specified. It can be provided that the method steps can be carried out in a different order and / or that steps can overlap and / or be carried out simultaneously.

[0068] The control of the light source and / or the detector and / or the evaluation of the measurement results and the determination of the concentration of the specific electrolyte can be carried out by a computing unit of the readout device.

[0069] A luminescent dye is a substance which, after being excited by light of a certain wavelength, can emit light of another certain wavelength, possibly by interaction with another substance, as is the case between the indicator dye and the electrolyte ions, or can change the wavelength of the emitted light depending on the interaction with this other substance. In this context, fluorescence and delayed phosphorescence can occur.

[0070] It is preferably provided that the indicator dye reacts to the excitation by fluorescence and / or the reference dye reacts to the excitation by phosphorescence. In this way, a response of the indicator dye without phase shift and a response of the reference dye with phase shift to the excitation signal can be achieved.

[0071] In order to obtain as clear a signal as possible and to avoid distortions, it can be provided that at least the red blood cells in the blood sample, preferably all cellular components in the blood sample, are prevented from entering the measurement region, which is preferably achieved by passing the blood sample through a separation membrane before it enters the measurement region. Since usually only the extracellular electrolyte concentration is relevant, this filtration is harmless to the measurement, for example the determination of the potassium concentration, since the intracellular potassium concentration is significantly higher. Accordingly, the above also applies if it is provided that the blood measurement strip has a separation membrane between the input region and the measurement region to prevent at least the red blood cells in the blood sample, preferably all cellular components in the blood sample, from entering the measurement region.

[0072] It is preferred to provide that the measuring region is connected with at least one detection region, wherein the measuring region is arranged along the flow connection between the input region and the detection region. In the detection region, at least one property of the blood sample can preferably be evaluated optically. For example, it can be determined whether there is enough blood sample introduced into the blood measuring strip to carry out an accurate measurement. Preferably, the blood measuring strip is transparent at least on one side of the detection region. In this regard, it is also advantageous to evaluate at least one property of the blood sample by optical evaluation of the detection region in fluid connection with the measuring region.

[0073] It is particularly advantageous to provide that the blood measuring strip has at least one separation membrane between the measuring region and the detection region to prevent at least red blood cells, preferably all cellular components of the blood sample. This enables a determination of a property or state of the blood sample, for example its degree of hemolysis, in the detection region.

[0074] The volume of the required blood samples is very small. Therefore, they are usually taken by puncturing, such as a finger prick. This can result in some cells being damaged or destroyed, with their intracellular electrolytes entering the liquid component of the blood sample. Since the potassium concentration inside the cells is significantly higher than in the extracellular space, this can distort the measurement result. Therefore, it is particularly advantageous to determine the degree of hemolysis in the blood sample, preferably optically and / or preferably by measuring the free hemoglobin in the plasma, and to take the determined degree of hemolysis into account when determining the electrolyte concentrations, in particular the potassium concentration. Accordingly, it can be provided that the readout device is designed to determine the degree of hemolysis in the blood sample. For example, this can determine the amount of red blood cells and / or free hemoglobin in the plasma by colorimetry and, based on this amount, infer the amount of electrolytes released from the hemolyzed cells and incorporate it into the determination process of the specific electrolyte concentration. This incorporation can include, for example, changing the electrolyte value depending on the determined degree of hemolysis and / or determining the quality of a specific electrolyte measurement depending on the degree of hemolysis. For example, it can be provided that a specific electrolyte measurement is evaluated as valid or invalid depending on the determined degree of hemolysis. For example, if the degree of hemolysis is on one side of a predetermined threshold, in particular above a predetermined threshold, the specific electrolyte measurement can be evaluated as invalid; if the degree of hemolysis is on the other side of the predetermined threshold, in particular below a predetermined threshold, it is evaluated as valid.

[0075] It can be provided that the light source provides light to the measurement region from one side and the detector detects the light emitted due to excitation from the opposite side or the same side. This can be achieved by arranging at least a portion of the receiving region between the light source and the detector. In other words, either a transmissive light method can be employed (the dye is excited from one side and its luminescence is detected from the opposite side) or a reflective light method can be employed (the emitted light is detected from the same side as the dye is excited). If the transmissive light principle is employed, it must be ensured that light of the relevant wavelength can reach the dye from both sides and from the dye to the detector. This can be achieved, for example, by arranging the dye between transparent holding layers. If the back light principle is employed, it is only necessary to ensure that light of the relevant wavelength can reach the dye from the side facing the detector and the light source and from the dye to the detector. Accordingly, it can also be provided that the measurement region is located between the light source and the detector when the blood measurement strip is positioned as intended in the receiving region or that the light source and the detector are located on the same side of the blood measurement strip when the blood measurement strip is positioned as intended in the receiving region.

[0076] It is particularly advantageous if, in addition to the specific electrolyte concentration, at least one other blood parameter of the blood sample is determined, preferably using at least one other indicator dye. In this way, a plurality of parameters of the blood can be determined using a single measurement strip. It can be provided that the measurement of the other parameter is temporally or spatially offset from the measurement of the specific electrolyte concentration. For example, it can be provided that the measurement of the other parameter takes place in another measurement region, which can be separate or adjacent to the measurement region of the specific electrolyte concentration. Accordingly, it can be provided that at least one further measurement region is connected to the transport channel for measuring the further parameter. The above applies equally if the blood measurement strip has at least one other dye for measuring at least one other blood parameter of the blood sample, wherein the other dye is preferably arranged spatially separate from the indicator dye. An additional light source and / or detector can also be provided, which is set up to measure the further blood parameter.

[0077] The one or more additional blood parameters are preferably selected from the following examples: temperature, pH value, sodium value, potassium value, calcium value, magnesium value, cholesterol value (such as total cholesterol, low-density lipoprotein or high-density lipoprotein), iron value, number of platelets, red blood cells and / or white blood cells, and / or clotting time. The additional or other parameters can also include: electrolyte parameters (Na + , K + , Ca 2+ , Mg 2+ , Li + , Cl - , pH value, NH4 + , HCO3 - ), degree of hemolysis, hemoglobin, lipids, blood gases (such as pO2, pCO2), clotting parameters and / or metabolites (such as lactate, creatinine, urea and / or ketone bodies).

[0078] The measurement of further parameters can be similar to the measurement of the specific electrolyte concentration, using luminescent dyes. Alternatively, other measurement methods can also be used, such as other photochemical methods, spectroscopic methods or electrochemical methods.

[0079] In addition to the specific electrolyte concentration, it can also be advantageous to determine the temperature of the blood sample, preferably using a temperature-sensitive dye, and preferably in a temperature measurement region which is different from the measurement region. Since the temperature can have a strong influence on the measurement of the specific electrolyte concentration, at least a partial compensation of this influence is possible by measuring the temperature of the blood sample. Such a temperature-sensitive dye can be the reference dye or another dye. In the former case, it can be provided that a further reference measurement is provided. Correspondingly, it can be provided that the blood measurement strip has at least one temperature-sensitive dye for determining the temperature. Alternative temperature measurement methods can be, for example, the measurement of the infrared radiation of the blood sample or the provision of an infrared measurement device in the readout device to determine the temperature.

[0080] It can also be provided that the readout device at least partially controls the temperature of the blood measurement strip. Correspondingly, the readout device can also have a temperature control device for the blood measurement strip. In this way, a specific temperature can be set and its influence on the measurement reduced. Preferably, the temperature control is at least partially carried out by at least one Peltier element, in particular a Peltier element of the readout device. In this regard, it is advantageous if the temperature control device comprises at least one Peltier element. This has the particular advantage that the temperature can also be measured, in particular at high ambient temperatures.

[0081] It can be provided that the blood sample in the measurement region penetrates into a polymer matrix, preferably a hydrogel, in which the indicator dye is arranged and preferably also the reference dye. Correspondingly, it can also be provided that a polymer matrix, preferably a hydrogel, is arranged at least in the measurement region, in which the indicator dye and the reference dye are arranged. This enables a stable storage of the dyes in the blood measurement strip, since the polymer matrix can fix the dyes. At the same time, it can absorb the blood sample, thus bringing it into contact with the dyes. Hydrogels are particularly suitable for this purpose, since they have a hydrophilic nature. A further advantage of the polymer matrix is that it can precisely adjust the ratio between the dyes. It is possible to first prepare the polymer matrix and then add precisely metered amounts of the indicator dye and the reference dye. Alternatively, at least one of the indicator dye or the reference dye can be added to the polymer matrix base, from which the polymer matrix is then prepared.

[0082] The polymer matrix preferably comprises at least one reflecting substance, such as titanium oxide, preferably titanium dioxide. This makes the detectability of the luminescence signal better. Correspondingly, it can also be provided that the signal of the dye is reflected by at least one reflecting substance, such as titanium oxide in the polymer matrix.

[0083] It is particularly advantageous if the indicator dye and preferably the reference dye, preferably together with the polymer matrix, is applied to the carrier surface of the blood measuring strip prior to the application of the blood sample by a continuous or discontinuous coating process, preferably by a dispensing process and / or a piezoelectric jetting process and / or by a doctor blade and / or a screen printing and / or a rotary screen printing and / or an aerosol jet printing and / or an ultrasonic spray coating. This enables a low-cost production of a large number of blood measuring strips while allowing an accurate adjustment of the dye concentration and achieving a high degree of measuring accuracy and reproducibility. The same applies if the polymer matrix is to be arranged on a transparent outer film of the blood measuring strip and is preferably printed by a continuous printing process such as a dispensing process and / or a piezoelectric jetting and / or applied by a doctor blade and / or a screen printing and / or a rotary screen printing and / or an aerosol jet printing.

[0084] It is particularly advantageous if the blood sample is guided from the input region via the transport channel to the measuring region and air downstream of the measuring region is discharged, preferably along the transport channel, through at least one air outlet opening. This enables a spatial separation between the input region and the measuring region and better protection of the measuring region from external influences or contamination. The same applies if the blood measuring strip is designed to have a transport channel for transporting the blood sample, the input region and the measuring region are arranged along the transport channel and the air outlet opening is preferably provided along the transport channel for air discharge and particularly preferably the measuring region is arranged along the transport channel between the input region and the air outlet opening. The air outlet opening ensures that the blood sample can flow along the channel unhindered and that no excessive pressure builds up in the channel. This is because the channel is preferably substantially closed to prevent contamination or handling.

[0085] It can be provided that a transport material is arranged in the transport channel. It is preferably designed to accelerate the flow of blood from the input region to the measuring region. Preferably, the material of the transport material comprises at least one porous membrane material or a fibrous material, particularly preferably paper or cellulose.

[0086] It is particularly advantageous if at least one calibration measurement is carried out, preferably before the light emitted by the indicator dye and the reference dye as a result of excitation is detected, in which:

[0087] a. at least one luminescent calibration dye is excited by light emitted by at least one light source (201) of the readout device (200); and

[0088] b. the light emitted by the calibration dye upon excitation is detected by at least one detector (202) of the readout device (200); and

[0089] c. the specific electrolyte concentration is determined based on the detected signal of the calibration dye.

[0090] Alternatively or additionally, at least one calibration measurement can also be performed after and / or during the detection of the light emitted by the indicator dye and the reference dye upon excitation. Such a calibration measurement can improve the accuracy of the measurement. The calibration performed in this way can be, for example, a calibration, alignment or tuning, in which the measurement signals of the reference dye and the indicator dye are set, preferably relative to the signal of the calibration dye. In this way, in addition to or as an alternative to the absolute parameters of the signals of the reference dye and the indicator dye, relative parameters relative to the signal of the calibration dye can also be taken into account in the determination of the specific electrolyte concentration. "Based on the detected signal" means that the detected signal is taken into account in the determination. For example, for the signal of the calibration measurement, a signal change of the reference dye and the indicator dye (for example caused by aging) can be determined and the signal corrected accordingly.

[0091] It can be provided that the calibration dye is part of the readout device. This makes it possible for the calibration measurement to be performed independently of the blood measurement strip and without the need for a prior arrangement of the calibration dye. In this regard, it can be provided that the at least one calibration measurement comprises the performance of steps a) and b) using the calibration dye as part of the readout device.

[0092] "Part of the readout device" means that the calibration dye cannot be removed or replaced by the user during normal operation. For example, the calibration dye can be arranged in a coating of the readout device.

[0093] It is particularly advantageous if the at least one calibration measurement comprises the introduction of the calibration dye into the readout device before or during step a).

[0094] It can be provided that a calibration solution containing the calibration dye is introduced into the readout device, for example by means of dropwise addition or pipetting.

[0095] It can also be provided that a calibration test strip containing a calibration measurement region in which the calibration dye is arranged is combined with the readout device. A calibration test strip separate from the blood measurement strip allows the same calibration test strip to be used for multiple measurements. It can be provided that the calibration test strip is inserted into a receiving region of the readout device into which the blood measurement strip is also inserted. It can also be provided that the calibration test strip is inserted into a calibration container of the readout device. This makes it possible for the measurement of the blood measurement strip to be performed independently of the calibration test strip.

[0096] In particular, if it is provided that a calibration dye is inserted into the readout device before or during step a), it is advantageous to use the same calibration dye for the calibration measurement until a predetermined interval is reached. This allows the calibration dye to be used multiple times. The interval can comprise a number of measurements of the blood measuring strip and / or a period of time. For example, it can be provided that the calibration dye is used until a set of test strips or a batch of blood measuring strips is used up. The period of time prevents the calibration dye from being used for too long, which can lead to measurement errors associated with aging.

[0097] It can be provided that, in order to perform the at least one calibration measurement, the calibration dye is arranged in a calibration measurement region of the blood measuring strip. This allows calibration and actual measurement to be performed with only one test strip. In this regard, it is advantageous if the blood measuring strip has at least one calibration measurement region in which at least one luminescent calibration dye is arranged, and the calibration measurement region is preferably connected to the input region.

[0098] It can be provided that, before or during the performance of step a), at least a portion of the blood sample is guided into the at least one calibration measurement region, preferably a calibration measurement region of the blood measuring strip. It can be provided that the luminescence intensity and / or the decay time of the calibration dye is dependent on at least one parameter of the blood sample, such as the pH value, the temperature or the presence or concentration of at least one substance. This allows the measurement result to be better interpreted.

[0099] The connection to the input region can be direct, for example via a channel connecting the input region and the calibration measurement region. It can also be indirect, for example via a connection between the calibration measurement region and the measurement region, or via a channel connecting the measurement region and the input region.

[0100] It is particularly preferred to provide that the blood measuring strip:

[0101] - is combined with the readout device (200) in a calibration position, and the at least one calibration measurement is performed at the calibration position;

[0102] - is combined with the readout device (200) in a measurement position, and at the measurement position:

[0103] • the indicator dye is excited by light emitted by at least one light source (201) of the readout device (200), wherein the luminescence intensity of the indicator dye is dependent on the specific electrolyte concentration of the blood sample;

[0104] • the luminescent reference dye is excited by the light source (201), wherein the luminescence intensity and the luminescence decay time of the reference dye are independent of the specific electrolyte concentration of the blood sample; and

[0105] • the light emitted by the indicator dye and the reference dye as a result of the excitation is detected by at least one detector (202) of the readout device (200); and

[0106] wherein the calibration position and the measurement position are different positions. Position here refers to the spatial arrangement of the readout device relative to the blood measuring strip. Preferably, the blood measuring strip is arranged in the same receiving area of the readout device in both the calibration position and the measurement position. This makes it possible for the independent calibration not to interfere with the actual measurement and vice versa. It can be provided that the blood measuring strip and the readout device are first combined together in the calibration position or first combined together in the measurement position. In this regard, it is advantageous if the calibration dye comprises a reference dye and / or a zero indicator dye. If the calibration dye comprises a reference dye, the calibration measurement can comprise exciting the reference dye according to the application, detecting the light emitted by the indicator dye and the reference dye as a result of the excitation, and determining the specific electrolyte concentration of the blood sample based on the phase shift of the signal detected by the detector according to the independent method claim.

[0107] By using a reference dye, at least one property of the reference dye (e.g. the aging of the reference dye) can be detected and taken into account in the determination of the specific electrolyte concentration. A zero indicator dye is an alternative to an electrolyte-dependent indicator dye. It can be used for calibration. It provides an amplitude at zero phase, i.e. due to a very short light emission decay time (typically in the nanosecond range) which is practically no measurable phase shift due to the time resolution of the measurement system and the excitation frequency used, and which is also electrolyte-independent.

[0108] In particular, if the calibration dye comprises a reference dye, it can be provided that one region of the blood measuring strip represents both the calibration region or a part of the calibration region and the measurement region or a part of the measurement region. In this case, one region can serve both purposes.

[0109] It can be provided that the calibration measurement and the actual measurement are carried out simultaneously. In this regard, it can be useful if the readout device has at least one further light source for exciting the calibration dye and / or at least one further detector for detecting the light emitted by the calibration dye as a result of the excitation. In this regard, it is particularly advantageous if the readout device has at least one calibration recording area for recording the calibration measurement strip. The calibration measurement can be carried out dry or wet.

[0110] It can also be provided that in at least one calibration measurement at least one reference dye and / or at least one indicator dye of the measurement region is used, which is also used for detecting the light emitted by the indicator dye and the reference dye as a result of excitation, and that this calibration measurement is preferably carried out before at least one portion of the blood sample is introduced into the measurement region. The calibration measurement can comprise a measurement of the decay time, the intensity and / or the phase shift. In particular, if this calibration measurement is carried out before at least one portion of the blood sample is introduced, the reference dye and the indicator dye in the measurement region can be measured in the dry state. This makes it possible to detect fluctuations in the production of the test strip, inter-stripl differences in a batch and / or the ageing of the test strip and to take this into account in the calculation.

[0111] According to the application, it is also possible to provide a measuring strip set for measuring the concentration of a specific electrolyte of a blood sample using a readout device, wherein the set comprises at least one blood measuring strip according to the application and the set comprises at least one calibration measuring strip, which has at least one calibration measurement region, in which at least one luminescent calibration dye is arranged, and which is preferably connected to an input region of the calibration measuring strip. In addition to the blood measuring strip according to the application, the set can comprise further measuring strips, in particular blood measuring strips, for example for measuring other blood parameters. Such a set makes it possible, in particular, to take into account the ageing of the blood measuring strip in the determination of the concentration of the specific electrolyte by means of the calibration measuring strip. Since such a set is usually stored and transported together, this means that the measuring strips are essentially exposed to the same environmental influences. The system according to the application can comprise such a set.

[0112] It is advantageous to provide a hydrophilic transport material, preferably in the form of a hydrophilic membrane, in the transport channel and preferably also in the measurement region. This improves the transport of the blood sample along the channel. The blood measuring strip preferably has a carrier plate. This serves to impart the necessary mechanical strength to the blood measuring strip. The carrier plate can have openings or recesses, for example air outlet holes and / or openings as part of or constituting the input region.

[0113] If a transmission light method is used, it can be provided that the carrier plate is at least in a portion of the measurement region transparent or even the entire carrier plate is transparent to allow the light from the light source or the luminescence signal from the dye to pass through. If a back-lighting method is used, it is advantageous if the carrier plate is at least on the side facing the dye essentially monochromatic, preferably black, in order to prevent as far as possible interfering light signals.

[0114] Preferably, at least a portion of the input region, at least a portion of the measurement region and / or at least a portion of the transport channel is formed by at least one hydrophilic film. This improves the flow of the sample. Preferably, it is a plastic film, particularly preferably comprising polyvinyl chloride (PVC), polyethylene terephthalate (PET) and / or polymethyl methacrylate (PMMA) and / or polycarbonate (PC). Preferably, the hydrophilic film has at least one hydrophilic coating and / or a hydrophilic surface treatment. The hydrophilic coating and / or the hydrophilically modified surface is particularly preferably directed towards at least a portion of the measurement region and / or the transport channel. Such a surface treatment can include at least one treatment with an acid (e.g. trichloroacetic acid) or a base, a plasma treatment and / or a corona treatment.

[0115] It is preferably provided that the input region spans the entire width of the blood measurement strip. This makes the input region particularly large, thereby facilitating the application of the sample.

[0116] Preferably, the width of the input region narrows at least partially in the direction towards the measurement region. This improves the flow of the sample to the measurement region.

[0117] It is preferably provided that the carrier plate and / or the cover film is at least partially interrupted along the entire width of the blood measurement strip in the region of the input region. This increases the flexibility of the measurement strip.

[0118] Preferably, the at least one indicator dye is selected from the group consisting of coumarin dyes, carbocyanine dyes, benzofuran dyes and / or BODIPY (boron difluoride dipyrromethene) dyes.

[0119] Preferably, a dye having the following structure is used as indicator dye:

[0120]

[0121] The blood measurement strip preferably comprises an injection-molded part and / or a pre-structured film, which is preferably thin. Preferably, at least a portion of the input region, the transport channel, the detection region, the air outlet hole and / or the measurement region is arranged in the injection-molded part and / or the film.

[0122] Preferably, at least a portion of the blood measurement strip is manufactured or processed by injection molding, deep drawing, thermoforming, hot stamping, extrusion coating and / or UV stamping.

[0123] The application is explained in more detail below with reference to non-limiting examples, in which:

[0124] Figure 1 A first embodiment of a blood measurement strip according to the application is shown in a top view;

[0125] Figure 2 An embodiment from Figure 1 is shown in an exploded view;

[0126] Figure 3 A second embodiment of a blood measuring strip according to the application is shown;

[0127] Figure 4 An embodiment in Figure 3 is shown in an exploded view;

[0128] Figure 5 A third embodiment of a blood measuring strip according to the application is shown in a top view;

[0129] Figure 6 An embodiment in Figure 5 is shown in an exploded view;

[0130] Figure 7 A fourth embodiment of a blood measuring strip according to the application is shown in a top view;

[0131] Figure 8 An embodiment in Figure 7 is shown in an exploded view;

[0132] Figure 9 A fifth embodiment of a blood measuring strip according to the application is shown in a top view;

[0133] Figure 10 An embodiment in Figure 9 is shown in an exploded view;

[0134] Figure 11 A sixth embodiment of a blood measuring strip according to the application is shown in a top view;

[0135] Figure 12 An embodiment in Figure 11 is shown in an exploded view;

[0136] Figure 13 A seventh embodiment of a blood measuring strip according to the application is shown in a top view;

[0137] Figure 14 An embodiment in Figure 13 is shown in an exploded view;

[0138] Figure 15 An eighth embodiment of a blood measuring strip according to the application is shown in a top view;

[0139] Figure 16 An embodiment in Figure 15 is shown in an exploded view;

[0140] Figure 17 A first embodiment of a system according to the application is shown in a schematic cross-section;

[0141] Figure 18A second embodiment of a system according to the application is shown in a schematic cross-section;

[0142] Figure 19 A third embodiment of a system according to the application is shown in a schematic cross-section;

[0143] Figure 20 A fourth embodiment of a system according to the application is shown in a schematic cross-section;

[0144] Figure 21 A fifth embodiment of a system according to the application is shown in a schematic cross-section;

[0145] Figure 22 A sixth embodiment of a system according to the application is shown in a schematic cross-section;

[0146] Figure 23 A ninth embodiment of a blood measuring strip according to the application is shown in an exploded view;

[0147] Figure 24 The ninth embodiment is shown in a top view.

[0148] As Figure 1 and Figure 2 The blood measuring strip embodiment shown as such, as is typical for such blood measuring strips, is essentially strip-shaped and flat. It has a narrow opening on one wide side, forming an input area 1. This input area is connected to a first part of a transport channel 2a, which leads to a measuring area 3 of greater width. Downstream of the measuring area, a further part of the transport channel 2b leads to a slightly narrower widened area 4, which is connected to an air outlet hole 5 in a carrier plate 6. When blood is dispensed within the blood measuring strip along the transport channel 2a, 2b, air can be discharged from the transport channel 2b.

[0149] In the embodiment shown, only one measuring area is provided. It is also possible to provide a plurality of measuring areas, which can be arranged one after the other along the flow direction of the channel or side by side. One measuring area can be used for an indicator dye, i.e. for measuring a specific electrolyte concentration, and another measuring area can be used for measuring at least one other blood parameter. This also applies to the other embodiments.

[0150] The blood measuring strip preferably has a layered structure, as shown in the embodiments of the figures, comprising at least one carrier plate or carrier film, at least one cover film and at least one reaction layer arranged between the carrier plate and the cover film, which reaction layer comprises an indicator dye and a reference dye. The cover film can serve only to seal off the outer area or, like the carrier plate, have rigidity and thus act as a support.

[0151] The carrier plate 6 is made of black plastic and has the necessary rigidity to ensure that the blood measuring strip can be handled correctly and inserted into a reading device. Alternatively, the carrier plate 6 can also be designed as a carrier film.

[0152] The carrier plate or carrier film 6 has a substantially flat surface facing the other layers of the blood measuring strip. The carrier plate 6 is connected to the spacer layer 9 by means of a double-sided adhesive tape 7, which is preferably designed as a film. Its outer dimensions and shape are adapted to those of the carrier plate 6. However, it has a recess in its interior, which defines the shape and dimensions of the above-mentioned areas and channels 1-4. The double-sided adhesive tape 7 can also be replaced by any other adhesive layer, for example by a liquid adhesive applied to the carrier layer. Preferably, and as shown in the example, the double-sided adhesive tape 7 also fixes the film 8 relative to the carrier plate 6.

[0153] In other words, the spacer layer 9 is provided, the inner contour of which defines the width of at least a portion of the transport channels 2a, 2b and the measuring area 3. This can also be useful in other embodiments.

[0154] The spacer layer 9 forms the side walls of the areas 1-4.

[0155] In the range of the input area 1, the first portion 2a of the transport channel up to the end of the measuring area 3 remote from the input area 1, the hydrophilic film 8 extends between the spacer layer 9 and the double-sided adhesive tape 7. The film 8 forms the upper wall of the input area 1, the first portion 2a of the transport channel and the measuring area 3. It improves the flow of the blood sample. The film 8 extends beyond the boundary walls of the transport channel 2 and the other areas 1, 3, but this does not matter. Because the walls of the spacer layer 9, which form the areas 1-4, prevent the blood from spreading outside these walls. The film 8 is preferably water-impermeable.

[0156] Furthermore, a cover film 11 is provided, which closes the side of the spacer layer 9 opposite the carrier plate 6, thereby forming the bottom wall of the areas 1-4. At the height of the measuring area, the reaction layer 10 is arranged on the cover film 11, which is designed as a hydrogel, in which the indicator dye and the reference dye are immobilized. The inner side of the cover film 11 is thus used as a carrier surface.

[0157] It can be provided that the reaction layer 10 extends beyond the boundary walls of the transport channel 2, as shown in the example. Alternatively, it can be provided that the reaction layer 10 is arranged completely within the boundary walls of the transport channel 2.

[0158] Figures 3-4 A second embodiment is shown, which is very similar to the first embodiment. Therefore, only the most significant differences will be discussed here; the above explanations apply here where applicable.

[0159] In this embodiment, the input area 1 is arranged on the carrier plate 6, preferably circular. The double-sided adhesive tape 7 is also correspondingly provided with a corresponding recess. The separation membrane 12 is arranged between the carrier plate 6 and the hydrophilic membrane 8, which prevents red blood cells from entering the transport channel 2a. This is particularly advantageous when the degree of hemolysis in a blood sample is to be measured on the basis of the hemoglobin content, since only free hemoglobin causes the blood sample to turn red.

[0160] Below the input area 1, the transport channel 2a is circular in order to accommodate particularly large quantities of blood sample.

[0161] Figures 5-16 The embodiments shown each have two areas 3a, 3b, which are spaced apart from one another but are connected to one another by the transport channels 2a, 2c. In the embodiment shown in Figures 5-12 In the embodiment shown, the areas 3a, 3b are connected to the input area 1 in series one after the other, whereas in the embodiment shown in Figures 13-16 In the embodiment shown, they are connected to the input area 1 in parallel via the respective transport channels 2a, 2c and each have an outlet aperture 5a, 5b arranged at the widened area 4a, 4b accordingly. The widened areas 4a, 4b are in fluid connection with the areas 3a, 3b by means of the guide channels 2b, 2d.

[0162] Figure 6 , 7 The embodiments shown in Figures 12 and 13 and 14 have two reaction layers 10a, 10b, which are arranged on the same plane and side by side. The areas 3a and 3b are both part of the measurement area 3. One reaction layer 10a is arranged at least partially as part of the first area 3a and the other reaction layer 10b is arranged at least partially as part of the second area 3b. Both reaction layers 10a, 10b have a polymer matrix, in the polymer matrix of the first area 3a an indicator dye is arranged and in the polymer matrix of the second area 3b a reference dye is arranged. These dyes are thus separated from one another.

[0163] Figure 6 , 7 These embodiments shown in Figures 12 and 13 and 14 can also be used to measure two parameters. To this end, the reference dye and the indicator dye would be arranged in one area 3a, 3b and at least one dye for determining another parameter would be arranged in the other area 3a, 3b, for example.

[0164] In the embodiment shown in Figures 7-10, 15 and 16 shown in the embodiment, reference dye and indicator dye are present in different layers, but these layers are arranged at different heights.Every layer has a reaction layer 10a, 10b, and each reaction layer all has polymer matrix, and corresponding dye is fixed in this polymer matrix.The reaction layer 10a that is fixed with reference dye overlaps with the reaction layer 10b that is fixed with indicator dye.Therefore, only be arranged with reference dye in a regional 3a, and not only be arranged with reference dye but also be arranged with indicator dye in another regional 3b.This makes regional 3a can serve as calibration area by using reference dye as calibration dye.Regional 3b serves as measurement area.

[0165] exist Figure 9 and 10 In the embodiment shown, the width of the reaction layers 10a, 10b corresponds substantially to the width of the blood measuring strip. Figure 15 and 16 In the embodiment shown, the width of the reactive layer 10b corresponds substantially to the width of the blood measuring strip. Figure 7 and 8 In the embodiment shown, the width of the reaction layers 10a, 10b is smaller than the width of the blood measuring strip.

[0166] exist Figure 11 and 12 In the illustrated embodiment, two cover films 11a and 11b are arranged one above the other. A reaction layer 10b containing an indicator dye is arranged on cover film 11b, which is positioned between cover film 11a and spacer layer 9. A reaction layer 10a containing a reference dye is also arranged on cover film 11a. Therefore, the reference dye does not come into contact with blood. Both cover films 11a and 11b are transparent.

[0167] Figure 17 A system according to the present invention is shown, which includes a blood measuring strip 100 and a reader 200. For example, a blood measuring strip 100 as in the previous figures can be used. Blood measuring strip 100 is shown with an input area 1 on its edge. Blood has been introduced into blood measuring strip 100 via input area 1 and has penetrated into measurement area 3. Furthermore, blood measuring strip 100 has been inserted into a slotted receiving area 204 of reader 200.

[0168] The light source 201 emits light having at least the wavelength that excites the indicator dye and the reference dye from one side of the blood measuring strip 100, preferably from the side of the cover film 11, onto the measuring region 1. The indicator dye and the reference dye thus excited emit corresponding light signals by fluorescence or phosphorescence, which are measured by the detector 202. The computing unit 203 is connected to the light source 201 and the detector 202 and controls these two components, receives the measurement data from the detector 202 and calculates the specific electrolyte concentration of the blood sample from the phase shift of the detection sum signal of the indicator dye and the reference dye and the light source excitation signal.

[0169] Figure 18 A modified embodiment is shown, in which two sub-units of the light source 201 are provided, which excite the blood measuring strip 1 from the same side. The detector 202 is arranged between these sub-units. Figure 17

[0170] Figure 19 Another modified embodiment is shown, in which a transmission light method is used. The light source 201 is arranged on the side of the blood measuring strip 1 opposite the detector 202.

[0171] Figure 20 Another modified embodiment is shown, in which two different measuring regions 3 are provided. One for measuring potassium and the other for measuring another parameter, for example sodium. Correspondingly, two light sources 201, detectors 202 and computing units 203 are also provided. In alternative embodiments, one of the measuring regions 3 can be designed as a detection region 14, and a corresponding light source 31 and detector 202 can be provided to optically determine whether a blood sample has flowed to the detection region 14 and / or to determine another property of the blood sample, such as its degree of hemolysis. This makes it possible to conclude that a sufficient blood sample has been introduced into the blood measuring strip 1 and / or to conclude something about other essential properties of the blood sample, such as the degree of hemolysis.

[0172] In such embodiments, it is also possible to perform the calibration measurement using one light source and one detector, for example when using the blood measuring strip shown in Figures 5-12 .

[0173] It can also be provided that the elements are used twice, in particular the same computing unit 203 is used for both determinations.

[0174] In the embodiment shown in Figure 21 , Figure 17 ​The illustrated embodiment is extended by a reference light source 205. The reference light source emits a reference light signal directly to the detector 202 without first interacting with the blood measuring strip 1. For this purpose, it is arranged on the same side of the receiving area 204 as the detector. Once the phase, intensity, spectrum and other parameters of the reference light signal are known, contamination, aging or other changes of the detector 202 can be detected by comparing the detected signal with the known reference light signal and taken into account in the determination of the specific electrolyte concentration.

[0175] In Figure 22 The illustrated embodiment is extended by a reference light source 205. The reference light source emits a reference light signal directly to the detector 202 without first interacting with the blood measuring strip 1. For this purpose, it is arranged on the same side of the receiving area 204 as the detector. Once the phase, intensity, spectrum and other parameters of the reference light signal are known, contamination, aging or other changes of the detector 202 can be detected by comparing the detected signal with the known reference light signal and taken into account in the determination of the specific electrolyte concentration. Figure 17 The illustrated embodiment is likewise extended by a reference light source 205. Here, the reference light source 205 is arranged on the opposite side of the receiving area 204 from the detector 202. The reference light signal thus passes through the blood measuring strip before being received by the detector. This additionally enables detection of, for example, contamination of the blood measuring strip.

[0176] Figure 23 And 24 A ninth embodiment of a blood measuring strip is disclosed. It has an input area 1 which spans the entire width of the blood measuring strip. The carrier plate 6 is interrupted in the area of the input area 1. It is preferably designed in two pieces. This increases the flexibility in the area of the input area 1.

[0177] The input area 1 narrows toward the measuring area 3. The spacer layer 9 of the blood measuring strip has walls which are inclined to one another.

[0178] The cover film 11 extends over the entire length of the blood measuring strip.

[0179] A part of the input area 1, the transport channel 2a and the measuring area 3 are formed by the film 8.

[0180] The film 8 and the carrier plate 6 have outlet openings 5 to allow air to escape through them.

[0181] The reaction layer of this ninth embodiment preferably contains only indicator dye. The reference dye is preferably located in the readout device.

[0182] The carrier plate 6 has a recess 1 in the area of the input area which is bounded by the carrier plate 6 on the sides. This facilitates the drop application of the sample.

[0183] As Figure 23 The film 8 can also have a recess 1 in the area of the input area which is bounded by the film 8 on the sides, as illustrated. This further facilitates the drop application of the sample.

[0184] Another preferred embodiment can be designed similarly to Figure 23 And 24 but completely without a carrier plate 6 by designing the film 8 to be sufficiently stable to completely assume the function of the carrier plate 6.

[0185] If the carrier plate 6 and / or membrane 8 are not transparent, a detection area 14 may be arranged along the transport channel 2b. This detection area 14 may comprise a recess and / or a transparent window area in the carrier plate 6 and / or membrane 8. The detection area 14 may be used to check whether the measurement area 3 is completely filled with the blood sample and / or to determine another property of the blood sample (such as its degree of hemolysis). This check for complete filling and / or determination of other properties of the blood sample may be performed visually or, preferably, by optical detection in the device.

[0186] The detection area 14 can be arranged within the range of the conveying channel 2b, between the measuring area 3 and the air outlet opening 5, in such a way that it is possible to ensure and / or check that the blood measuring strip is filled with a specific volume of blood sample and / or a specific minimum volume of blood sample.

[0187] In order to ensure and / or check that the test strip has been filled with a specific volume of blood sample, the filling in the transport channel 2b caused and / or driven by capillary forces can be stopped immediately after the detection area 14. This can be achieved by providing a change in the channel geometry (e.g., a sudden increase in the channel height or channel width) and / or a change in the wettability of at least one channel wall, which acts as a capillary valve.

[0188] Likewise, the air outlet hole 5 itself can also function as such a capillary valve.

Claims

1. A method for measuring the concentration of a specific electrolyte in a blood sample, preferably the concentration of potassium, wherein: A provided blood sample is introduced into an input area (1) of a blood measuring strip (100), and at least a portion of the blood sample is directed to a measuring area (3) of the blood measuring strip (100); The blood measurement strip (100) is combined with a reading device (200); wherein the electrolyte in the blood sample reacts with a luminescent indicator dye in the measurement region (3), and wherein the indicator dye is excited by light from at least one light source (201) of the readout device (200), wherein the luminescence intensity of the indicator dye depends on the electrolyte concentration of the blood sample; Its characteristics are: A luminescent reference dye is excited by the light source (201), wherein the luminescence intensity and luminescence decay time of the reference dye do not depend on the electrolyte concentration of the blood sample; and Light emitted by the indicator dye and the reference dye upon excitation is detected by at least one detector (202) of the readout device (200); and wherein The specific electrolyte concentration of the blood sample is determined based on a phase shift and / or decay time of a signal detected by the detector (202).

2. The method according to claim 1, wherein The reference dye is excited by the light source in the measurement region (3).

3. The method according to claim 1 or 2, wherein: The indicator dye responds to excitation by fluorescence and / or the reference dye responds to excitation by phosphorescence.

4. The method according to any one of claims 1 to 3, characterized in that At least red blood cells in the blood sample, preferably all cellular components in the blood sample, are prevented from entering the measuring region (3), preferably by causing the blood sample to pass through a separation membrane (12) before entering the measuring region (3).

5. The method according to any one of claims 1 to 4, characterized in that The degree of hemolysis in the blood sample is determined, preferably optically and / or preferably by measuring free hemoglobin in the plasma, and the determined degree of hemolysis is taken into account when determining the specific electrolyte concentration.

6. The method according to any one of claims 1 to 5, characterized in that The light source (201) provides light to the measurement region (3) from one side, and the detector (202) detects light emitted by the excitation from the opposite side or the same side.

7. The method according to any one of claims 1 to 6, characterized in that In addition to the specific electrolyte concentration, at least one other blood parameter of the blood sample is determined, preferably using at least one other indicator dye.

8. The method according to any one of claims 1 to 7, characterized in that In addition to the specific electrolyte concentration, the temperature of the blood sample is determined, preferably using a temperature sensitive dye, and wherein the temperature determination is preferably performed in a temperature measurement region different from the measurement region (3).

9. The method according to any one of claims 1 to 8, characterized in that The blood sample in the measurement region penetrates into a polymer matrix, which is preferably a hydrogel, wherein the indicator dye and preferably also the reference dye are arranged in the polymer matrix.

10. The method according to claim 9, wherein Prior to applying the blood sample, the indicator dye and preferably also the reference dye, preferably together with the polymer matrix, are applied to the carrier surface of the blood measuring strip (100) by a continuous or discontinuous coating process, preferably by a dispensing process and / or a piezoelectric jet process and / or by a doctor blade and / or screen printing and / or rotary screen printing and / or aerosol jet printing and / or ultrasonic spraying.

11. The method according to any one of claims 1 to 10, characterized in that The blood sample is guided from the input region (1) via a transport channel (2a, 2b) to the measuring region (3), and air downstream of the measuring region (3) is preferably discharged along the transport channel (2a, 2b) through at least one air outlet opening.

12. The method according to any one of claims 1 to 11, characterized in that Preferably, before the light emitted by the indicator dye and the reference dye upon excitation is detected, at least one calibration measurement is performed, wherein a. at least one luminescent calibration dye is excited by light from at least one light source (201) of the readout device (200); and wherein b. The light emitted by the calibration dye due to excitation is detected by at least one detector (202) of the reading device (200); and wherein c. The specific electrolyte concentration is determined based on the detected signal of the calibration dye.

13. The method according to claim 12, wherein: At least one calibration measurement comprises: before or during step a), the calibration dye is introduced into the readout device, and / or preferably, a calibration solution containing the calibration dye is introduced into the readout device, for example by dripping or pipetting, and / or preferably, a calibration measurement strip comprising at least one calibration measurement area in which the calibration dye is arranged is combined with the readout device (200).

14. The method according to claim 12 or 13, wherein: In order to perform at least one calibration measurement, a calibration dye is arranged in at least one calibration measurement area of ​​the blood measuring strip.

15. The method according to claim 12 or 13, wherein: Before step a) is performed, at least a portion of the blood sample is directed into at least one calibration measurement area.

16. The method according to claim 15, wherein: - the blood measuring strip is combined with the reading device (200) in a calibration position, and wherein at least one calibration measurement is performed in the calibration position; - the blood measuring strip is combined with the reading device (200) in a measuring position, and at the measuring position: o the indicator dye is excited by light from the at least one light source (201) of the readout device (200), wherein the luminescence intensity of the indicator dye depends on a specific electrolyte concentration of the blood sample; o the luminescent reference dye is excited by the light source (201), wherein the luminescence intensity and luminescence decay time of the reference dye do not depend on the specific electrolyte concentration of the blood sample; and o Light emitted by the indicator dye and the reference dye due to excitation is detected by at least one detector (202) of the readout device (200); The calibration position and the measurement position are different positions.

17. The method according to any one of claims 12 to 16, characterized in that The calibration dye includes the reference dye and / or the zero indicator dye.

18. The method according to any one of claims 12 to 17, characterized in that In at least one calibration measurement, at least one reference dye and / or at least one indicator dye of the measuring area is used, which is also used to detect the light emitted by the indicator dye and the reference dye due to excitation, and this calibration measurement is preferably performed before at least a portion of the blood sample is introduced into the measuring area.

19. The method according to any one of claims 1 to 17, characterized in that At least one property of the blood sample is evaluated by optically evaluating a detection region in fluid communication with the measurement region.

20. A blood measuring strip (100) for measuring the concentration of a specific electrolyte in a blood sample using a readout device (200), the specific electrolyte concentration preferably being a potassium concentration, wherein the blood measuring strip (100) has an input area (1) for receiving the blood sample and a measurement area (3) connected to the input area (1), wherein a luminescent indicator dye is arranged in the measurement area (3), the luminescence intensity of the luminescent indicator dye being dependent on the specific electrolyte concentration of the blood sample, characterized in that A luminescent reference dye is arranged in the measurement region (3), the luminescence intensity and luminescence decay time of the luminescent reference dye being independent of the specific electrolyte concentration of the blood sample.

21. The blood measuring strip (100) according to claim 18, characterized in that The blood measuring strip (100) has a separation membrane (12) between the input area (1) and the measuring area (3) to block at least red blood cells of the blood sample, preferably all cellular components in the blood sample.

22. The blood measuring strip (100) according to claim 18 or 19, characterized in that The measuring region (3) is connected to at least one detection region (14), wherein the measuring region (3) is arranged along the flow connection between the input region (1) and the detection region (14).

23. The blood measuring strip (100) according to claim 21, characterized in that The blood measuring strip (100) has at least one separation membrane between the measuring area (3) and the detection area (14) to block at least red blood cells in the blood sample, preferably all cellular components in the blood sample.

24. The blood measuring strip (100) according to claim 18 or 19, characterized in that The blood measuring strip (100) has a transport channel (2a, 2b) for transporting the blood sample, the input area (1) and the measuring area (3) are arranged along the transport channel, and preferably an air outlet hole (5) is provided along the transport channel (2a, 2b) for air discharge, and particularly preferably the measuring area (3) is arranged along the transport channel (2a, 2b) between the input area (1) and the air outlet hole (5).

25. The blood measuring strip (100) according to claim 20, characterized in that A hydrophilic transport material is arranged in the transport channel (2a, 2b) and preferably also in the measurement region (3), preferably in the form of a hydrophilic membrane (8).

26. The blood measuring strip (100) according to any one of claims 18 to 21, characterized in that A polymer matrix, preferably a hydrogel, is arranged at least in the measurement region (3), the indicator dye and the reference dye being arranged in the polymer matrix.

27. The blood measuring strip (100) according to claim 22, characterized in that The polymer matrix is ​​arranged on the transparent outer film (11) of the blood measuring strip (100) and is preferably printed by a continuous printing process such as a dispensing process and / or piezoelectric jetting, and / or applied by doctor blade and / or screen printing and / or rotary screen printing and / or aerosol jet printing.

28. The blood measuring strip (100) according to any one of claims 18 to 23, characterized in that The blood measuring strip (100) has at least one further dye for measuring at least one further blood parameter of the blood sample, wherein the further dye is preferably arranged spatially separated from the indicator dye.

29. The blood measuring strip (100) according to any one of claims 18 to 24, characterized in that The indicator dye and the reference dye are at least partially spatially separated, and preferably the indicator dye is arranged in the first layer, preferably the first film, particularly preferably the first side of the first film of the blood measuring strip, while the reference dye is arranged in the second layer, preferably the second film and / or the second side of the first film of the blood measuring strip.

30. The blood measuring strip (100) according to any one of claims 18 to 26, characterized in that The blood measuring strip has at least one calibration measurement area in which at least one luminescent calibration dye is arranged, and wherein the calibration measurement area is preferably connected to the input area.

31. The blood measuring strip (100) according to any one of claims 18 to 27, characterized in that The calibration dye includes the reference dye and / or the zero indicator dye.

32. A measuring strip kit for measuring the concentration of a specific electrolyte in a blood sample using a readout device, the specific electrolyte concentration being preferably the potassium concentration, wherein the kit comprises at least one blood measuring strip (100) according to any one of claims 18 to 27, characterized in that The set contains at least one calibration measurement strip having at least one calibration measurement area in which at least one luminescent calibration dye is arranged and which is preferably connected to an input area of ​​the calibration measurement strip.

33. A system for measuring the concentration of a specific electrolyte in a blood sample, preferably the concentration of potassium, wherein the system comprises a readout device (200) and a blood measuring strip (100), The blood measurement strip (100) has an input area (1) for receiving the blood sample and a measurement area (3) connected to the input area (1), wherein a luminescent indicator dye is arranged in the measurement area (3), and the luminescence intensity of the luminescent indicator dye depends on the specific electrolyte concentration of the blood sample, wherein a luminescent reference dye (3) is arranged in or on the blood measuring strip (100) and / or in or on the reading device (200), and its luminescence intensity and luminescence decay time do not depend on the specific electrolyte concentration of the blood sample, and The reading device (200) comprises at least one receiving area (204) for receiving the blood measuring strip (100), at least one light source (201) for exciting the indicator dye and the reference dye (3), and at least one detector (202) for detecting light emitted by the indicator dye and the reference dye due to the excitation.

34. The system of claim 29, wherein: The system comprises at least one blood measuring strip (100) according to any one of claims 11 to 17.

35. The system according to claim 29 or 30, wherein: The system comprises the kit of claim 28.

36. The system according to any one of claims 29 to 31, wherein The reference dye is arranged in the measurement area (3) of the blood measurement strip (100).

37. The system according to any one of claims 29 to 33, wherein: The readout device (200) has a calculation unit (203) which is designed to evaluate the signal detected by the detector (202) and to determine the specific electrolyte concentration based on the decay time and / or phase shift of the luminescence signal.

38. The system according to any one of claims 29 to 33, wherein: When the blood measuring strip (100) is arranged in the receiving area (204) as intended, the measuring area (3) is arranged between the light source (201) and the detector (202), or when the blood measuring strip (100) is arranged in the receiving area (204) as intended, the light source (201) and the detector (202) are arranged on the same side of the blood measuring strip (100).

39. The system according to any one of claims 29 to 34, wherein: The readout device (200) has at least one further light source for exciting the calibration dye and / or at least one further detector for detecting light emitted by the calibration dye as a result of the excitation.

40. The system of any one of claims 29 to 34, wherein: The reading device (200) comprises at least one further light source and / or at least one further detector for detecting filling of the test strip with the blood sample and / or determining the degree of hemolysis of the sample.

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