HK40014414A - Method and device for determining a concentration of an analyte in a bodily fluid - Google Patents

Description

Method and device for determining the concentration of an analyte in a body fluid

Technical Field

The present application is a patent No.: 201480065071.8, title of the invention: a divisional application of a method and apparatus for determining the concentration of an analyte in a bodily fluid. The invention discloses a method, an analysis device and an analysis system for determining the concentration of at least one analyte in a body fluid. The methods, systems and uses according to the invention may in particular be used for determining the concentration of glucose in one or more body fluids, such as in whole blood. However, additionally or alternatively, one or more other types of analytes and/or one or other types of bodily fluids may be used. The invention may be applied in the field of diabetes care, both in home monitoring and in hospital applications. Alternatively or additionally, other uses are possible.

Background

A large number of apparatus methods for determining the concentration of one or more analytes in a body fluid are known in the art. Without limiting the scope of the invention, in the following, reference is made mainly to the determination of glucose as an exemplary and preferred analyte.

The determination of The concentration of one or more analytes in a body fluid may in particular be performed by using photometric measurements.A sample of a body fluid may be applied to a test carrier which is illuminated by light to perform photometric measurements.typically, reflection measurements are performed in order to determine The amount of light which is reflected, scattered or re-emitted elastically or inelastically by The test carrier.the test carrier is typically based on The use of at least one test chemical, i.e. The use of one or more chemical compounds or chemical mixtures which are adapted to perform a detectable reaction, which leads to a detectable change of The test carrier, in particular an optical change such as a color change.the test chemical is also commonly referred to as test substance, test chemical, test reagent or detector substance.

By using one or more test chemicals, a detection reaction can be initiated, the course of which depends on the concentration of the analyte to be determined. Typically, as may also be the case in the present invention, the test chemical is adapted to perform at least one detection reaction when the analyte is present in the body fluid, wherein the extent and/or extent of the detection reaction, such as the kinetics of the detection reaction, depends on the concentration of the analyte. In the case of photometric measurements, the test carrier can be irradiated with light, wherein the light can be diffusely reflected from the test carrier and detected by the analysis device. For example, when the detection reaction is complete, the concentration of the analyte in the sample can be determined by measuring the reflectance of the test carrier. Additionally or alternatively, the progress of the detection reaction may be monitored by measuring the temporal change in reflectance. Thus, in photometric measurements, the test chemical may preferably be adapted to change at least one reflective property, preferably a color, due to a detection reaction.

The measurement and analysis of the emitted light typically imposes some technical challenges. On the one hand, these measurements typically involve small currents and/or voltages. However, the measurement of such small currents or voltages is challenging, as disturbances, such as those due to low frequency voltages, may occur. On the other hand, optical disturbances may occur due to ambient light. Thus, in order to determine the concentration of an analyte in a sample using photometric measurements, analytical devices and methods are needed to reduce the cause of these perturbations.

In EP 0632262B 1, a method for detecting and evaluating analog photometric signals in a test carrier analysis device is proposed. The test fields of the test carriers are irradiated by light sources clocked in the light and dark phases. The light and dark phases form an irregular sequence having a frequency spectrum with a large number of different frequencies. The light is reflected and detected by the measurement receiver and its measured value is passed to the measurement integration and digitization circuit for evaluation, where the irregular signal is filtered out.

In EP 1912058B 1, a system for measuring and evaluating optical signals for detecting analytes in an analysis liquid is described. The system includes a test carrier and a light source for illuminating an optical evaluation zone of the test carrier. Furthermore, the system comprises two signal sources adapted for generating two control signals, which are mixed by the mixer unit to generate the light control signal for the light source. The light sensor receives the re-emitted light and converts it into a measurement signal. In addition, the system includes: two frequency selective amplifiers, each receiving one of the measurement signal and the control signal; and an evaluation unit to which the output signal of the frequency selective amplifier is fed. In the evaluation unit, these output signals are compared and from the comparison result information about the disturbance of the external light on the measurement is determined. In case of a determination of interference of a measurement above a certain threshold, the measurement is identified as erroneous. The measurement was rejected and no glucose concentration value was emitted.

In addition, in many cases, the test carrier must be oriented within the device for determining the concentration of one or more analytes so that the device can perform the determination of the concentration. In US 2003/169426 a1, a test meter is described which is capable of determining the orientation of a test member therein. The test member has a first major surface and an opposing second major surface. Each major surface includes an orientation indicator zone that differs by at least one optical property (e.g., reflectivity). The test meter has a test zone for receiving a test member and including an optical orientation sensor. The optical orientation sensor generates an orientation signal indicative of an optical property of the orientation indicator zone.

In US 5526120 a, test strips and devices each having an asymmetry are proposed. The asymmetry combines to permit insertion of the test strip into the device when it is properly aligned, but prevents the test strip from being fully inserted with its wrong side up. The device detects whether the strip has been fully inserted.

Despite the advantages implied by these devices and methods known in the art, a number of technical challenges still remain. Thus, as an example, many devices and methods known in the art are not suitable for identifying disturbances prior to or while measuring. As an example, these disturbances may originate from internal disturbances, such as noise within electronic components of the device and/or fluctuations of one or more light sources. In addition, external disturbances, such as those caused by ambient light, must be taken into account. These disturbances can lead to significant errors and distortions of the measurement results. However, typical methods and apparatus known in the art only allow for error detection at the end of each measurement. For example, in paragraph [0047] of EP 1912058B 1, an analysis result is disclosed which is compared to raw data which has been determined from the output signal of the frequency selective amplifier, rather than directly from the raw data. Thus, in case the measurement is rejected, the entire test carrier wetted by the sample is rejected and a new sample has to be applied on the new test carrier, thereby implying that a new sample has to be taken from the patient or user. Thus, in general, the known methods and devices typically imply the following drawbacks: the test carrier is wasted and the user or patient will have to generate a sample of body fluid repeatedly, at least to some extent, in order to obtain a reliable measurement. In addition, in particular in view of the increasing use of modern light sources, such as energy saving lamps, LEDs, etc., and in view of the increasing trend of analytical devices towards miniaturization, the perturbation of photometric measurements may increase. Thus, there is a strong need for methods and devices adapted to at least partly avoid waste of test carriers and frequent generation of samples by still providing fast and reliable measurement results.

In addition, EP 1912058B 1 discloses that the first signal source generates a first control signal having a fundamental frequency and the second signal source generates a second control signal having a frequency that is a multiple of the fundamental frequency. The strengths of the first control signal and the second control signal are different from each other. However, the use of control signals having different strengths may enhance the likelihood of false detections in the case of low measurement signals due to false identification of the low measurement signals and no detected disturbance. Thus, even if a valid measurement signal is measured, the valid measurement signal may be falsely identified as a disturbance rather than a valid measurement signal.

It is therefore an object of the present invention to provide a method and a device for determining the concentration of an analyte in a body fluid, which overcome the above mentioned drawbacks and challenges of the known devices and methods. Preferably, a method and a device should be disclosed which are capable of reliably determining the concentration of an analyte in a body fluid even in the presence of a perturbation.

Disclosure of Invention

This problem is solved by a method, an analysis device and an analysis system for determining the concentration of at least one analyte in a body fluid having the features of the independent claims. Specific embodiments are set forth in the dependent claims, which may be implemented individually or in any arbitrary combination.

As used hereinafter, the terms "having," "including," or "containing," or any grammatical variations thereof, are used in a non-exclusive manner. Thus, these terms may refer to the following two cases: where no additional features are present in the entities described in this context, other than those introduced by these terms; and where one or more additional features are present. As an example, the expressions "a has B", "a includes B" and "a includes B" may refer to the following two cases: a case where other elements than B do not exist in a (i.e., a case where B is solely and exclusively constituted); and where one or more additional elements (such as element C, elements C and D, or even additional elements) are present in entity a in addition to B.

In a first aspect of the invention, a method for determining a concentration of at least one analyte in a body fluid is disclosed.

The body fluid may generally be or may be selected from any type of body fluid, preferably from the group consisting of: blood, preferably whole blood; tissue fluid; (ii) urine; saliva. Alternatively or additionally, other types of bodily fluids may be used. Alternatively or additionally, it is also possible to use additionally treated body fluids, such as plasma or serum.

The analyte may generally be a substance or compound or a combination of substances or compounds that may be present in the body fluid. The analyte may be a substance that is part of the metabolism of a human or animal life or may be involved in the metabolism. In particular, the analyte may be a metabolite. Preferably, the analyte is selected from the group consisting of: glucose, lactic acid, triglycerides, ketones, ethanol, total cholesterol, HDL cholesterol, LDL cholesterol, urea, uric acid, creatinine, GOT, GPT, GGT, ammonia. Additionally or alternatively, there are other clinical chemistry parameters or analytes, such as alkaline phosphatase (ALP), Creatine Kinase (CK), amylase, pancreatic amylase, glutamyl transferase (GGT), Glutamic Oxaloacetic Transaminase (GOT), glutamic-pyruvic transaminase (GPT), bilirubin, hemoglobin, potassium. Additionally or alternatively, the analyte may be a substance or combination of substances involved in intrinsic and/or extrinsic coagulation pathways. In general, the analyte may be any type of clinical parameter of the bodily fluid that may be of interest for clinical purposes, such as any type of clinical parameter that may be determined from whole blood. Without limiting further embodiments of the invention, in the following, reference will be mostly made to the detection of glucose in whole blood.

The method comprises the method steps as given in claim 1 and as listed below. The method steps can be performed in the given order, i.e. in the order a) -b) -c) -d). However, other orders of method steps are possible, such as b) -a) -c) -d). Further, one or more of the method steps may be performed in parallel and/or in a time overlapping manner, such as by performing method steps a) and b) at least partially simultaneously and/or by performing method steps b), c) and d) at least partially simultaneously. In addition, one or more of the method steps may be performed repeatedly. Thus, as an example, method steps b) and/or c) may be performed repeatedly, such as by performing method steps b) and/or c) at least once before method step a) and performing method steps b) and/or c) at least once after performing method step a). In addition, there may be additional method steps not listed.

The method comprises the following steps:

a) applying a sample of a bodily fluid to a test carrier;

b) illuminating the test carrier by using at least one light source;

c) receiving light re-emitted by the test carrier by using at least one detector;

d) the concentration of the analyte is determined by evaluating at least one detector signal generated by the detector.

Wherein the at least one light source is modulated by using at least two modulation frequencies. The detector signal is demodulated using at least two modulation frequencies to generate at least two demodulated detector signals, each demodulated detector signal corresponding to one of the modulation frequencies. The method further comprises error detection based on a comparison of the at least two demodulated detector signals.

As used herein, application of a bodily fluid sample to a test carrier generally refers to the step of contacting the test carrier with the bodily fluid sample in any technically feasible manner. The application may be performed manually or automatically, such as by applying the sample to at least one application location. The sample may be applied to a test chemical of a test carrier, such as a test field comprising at least one test chemical. Additionally or alternatively, the sample may be applied to different application locations, such as an opening of a capillary element adapted to transport the sample to the test chemical by capillary force. The application of the body fluid sample to the test carrier may be performed before, during or after the test carrier is inserted into a receptacle of an analysis device adapted for performing the method. Generally, means and devices for applying samples to test carriers are known to the skilled person.

In general, further method steps may be performed, such as before method steps a) -d), for example before the application of the body fluid sample to the test carrier as set forth in method step a). Additionally, in certain embodiments, additional method steps may even be performed without the use of a test vehicle. Thus, as outlined in further detail below, it may be possible to perform an ambient light error detection step and/or a determination of a dry empty value and/or a location verification step before performing the method steps a) -d). Thus, in case the optional ambient light error detection step should reveal that ambient light does not allow analyte measurement (such as at least at certain modulation frequencies, the ambient light level should be above a tolerance threshold), the measurement can be aborted without subsequently performing the sample application. Similarly, additionally or alternatively, in case the determination of the at least one dry empty value should lead to a conclusion that the test carrier is not available, such as due to aging or deterioration effects, the measurement may be aborted without subsequently performing the sample application. Similarly, additionally or alternatively, in case the position verification step should reveal that the test carrier is misplaced or not properly aligned, the measurement may be aborted without subsequently performing the sample application.

As used herein, the term test carrier generally refers to a test element adapted for determining the concentration of at least one analyte in a bodily fluid. In particular, the test carrier may be an optical test carrier adapted for optically determining the concentration of the analyte. The test carrier may generally have any technically feasible format. The test carrier may include one or more test chemicals, which may be in direct or indirect contact with the bodily fluid. For potential embodiments of at least one test chemical, reference may be made to the disclosure of potential test chemicals given above or in further detail below. In particular, the test carrier may comprise one or more test fields having one or more continuous or discontinuous detection layers comprising at least one test chemical. Additionally, one or more additional layers may be present, such as one or more reflective layers with one or more colored pigments, such as white pigments, and/or one or more separation layers adapted for separation from one or more components of the body fluid, such as one or more cellular components. Other embodiments are possible. The test carrier may generally have any form or format, such as one or more of the test carrier formats known in the art. As an example, the test carrier may be selected from the group consisting of: test strips, test tapes, test discs, and integrated test carriers having at least one test chemical and at least one lancet element.

The test carrier may include at least one substrate and at least one test chemical applied directly or indirectly to the substrate. The test chemical may be adapted to perform at least one detection reaction in the presence of at least one analyte to be detected and to change at least one optically detectable property as a result of the detection reaction. For potential embodiments of the test chemical, reference may be made to the above-cited prior art documents and/or other embodiments presented in further detail below. In particular, the test chemical may comprise one or more enzymes adapted to perform an enzymatic reaction in the presence of the analyte to be detected. Additionally, the test chemical may include one or more of the following: a colorant or dye; an intermediary; a coenzyme. Other embodiments are possible. The test chemical may be adapted such that the kinetics of the monitoring reaction can be followed by monitoring at least one optically detectable property, such as one or more of color, re-emission, reflection, fluorescence, phosphorescence. Thus, as an example, the test carrier may be adapted such that at least part of the test chemical is accessible for the at least one optical measurement, such as through an opening of the substrate, through a window in the substrate, and/or directly by inspecting the test field.

As used herein, a substrate may generally be any formed element that may serve as a carrier for additional elements. As an example, the form of the substrate may be selected from the group consisting of: strips, bands and discs. Various embodiments are generally possible.

The substrate may comprise a single layer arrangement or may comprise a multi-layer arrangement. Thus, the substrate may comprise one or more of: paper material, plastic material, preferably foil, metal and ceramic material. In addition, combinations of materials are possible. The substrate may comprise a multi-layer arrangement, such as by using lamination. Additionally, the substrate may include one or more fluidic structures. For this purpose, two or more substrates may be provided, wherein a channel is provided between the substrates, such as by separating the substrates with one or more spacers. Alternatively or additionally, one or more fluidic structures on the surface of the substrate may be provided, such as by using one or more open capillary channels (such as one or more capillary slits). Various embodiments are possible and generally known in the art.

As outlined above, the test carrier may comprise at least one test field applied directly or indirectly to the substrate, such as to a surface of the substrate and/or integrated into the substrate, wherein the test field comprises at least one test chemical. Wherein one single test field with at least one test chemical may be applied and/or a plurality of test fields with the same test chemical and/or different types of test chemicals may be used.

The test carrier may comprise at least one application site to which a body fluid sample may be applied. Thus, the at least one application site may be a site where the body fluid sample is applicable to the test carrier. In general, a test carrier may comprise a plurality of application locations.

As outlined above, the at least one test chemical preferably forms and/or is part of the at least one test field. The test field may comprise a single layer arrangement comprising only one detection layer containing the test chemical. Alternatively, the test field may have a multi-layer arrangement of at least two layers, wherein at least one detection layer comprising at least one test chemical may be combined with one or more additional layers, such as with one or more diffusion layers and/or one or more separation layers and/or one or more pigment layers for providing an optical background (such as a white background) for improving the optical measurement. Multilayer arrangements of this type are known in the art. Thus, as an example, the test field may comprise at least one detection layer, and additionally at least one separation layer (e.g. for separating blood cells) and/or an optical layer comprising one or more pigments, such as one or more inorganic pigments, such as one or more metal oxides, preferably titanium dioxide.

For details of potential Test chemicals that may also be used within The present invention, reference may be made to J. Hoenes et al, The Technology Behind Glucose Meters: Test Strips, Diabetes Technology & Therapeutics, Vol. 10, Supplement 1, 2008, S-10 to S-26. In addition, reference may be made to WO 2010/094426A 1 and WO 2010/094427A 1. Additionally or alternatively, test substances as disclosed in WO 2007/012494 a1, WO 2009/103540 a1, WO 2011/012269 a2, WO 2011/012270 a1 or WO 2011/012271 a2, which are also referred to as cdna test substances, may be cited. In addition, reference may be made to EP 0354441 a2, EP 0431456 a1, EP 0302287 a2 to EP 0547710 a2 or to EP 1593434 a 2. Test substances as disclosed in all these documents may also be used within the present invention. Other types of test elements and/or test substances are possible and may be used within the present invention.

As used in method step b), the light source may generally be or may comprise one or more arbitrary light sources adapted to illuminate the test carrier. As used herein, "light" generally refers to electromagnetic waves in one or more of the visible, ultraviolet, and infrared spectral ranges. Herein, the visible spectral range generally refers to the spectral range of 380 nm to 780 nm. The infrared spectral range generally refers to the spectral range of 780 nm to 1 mm, preferably 780 nm to 3.0 μm. The ultraviolet spectral range generally refers to the spectral range of 1 nm to 380 nm, preferably 50 nm to 380 nm and more preferably 200 nm to 380 nm. Most preferably, the light source is adapted to emit light in the visible spectral range.

For example, the light source may be a pulsed light source, such as a light source selected from the group of: a Light Emitting Diode (LED); a laser, preferably a laser diode; an incandescent light source; a bulb. In addition or alternatively, several light sources may be used, for example at least two light sources with different emission wavelengths and/or with different spectral properties.

As used herein, the term re-emitted light as used in method step c) generally refers to light reflected by the test carrier, in particular by the test chemical and more particularly by at least one test field comprising the test chemical. The reflection may occur in a diffuse manner. In general, the reflection may be fully or partially elastic and/or inelastic. In some embodiments, method step c) is performed such that the angle of incidence of the illumination in method step b) is different from the angle of inspection in method step c), such that direct reflection of light is at least partially excluded. The re-emission measurement as used in method steps b) and c) may be performed by illuminating the test carrier and/or parts thereof and by detecting reflected and/or scattered light from the test carrier. By performing this measurement, a color change in the test chemical on the test carrier can be detected, which may occur due to the progress of the detection reaction. As a result of the measurement in method step c), a re-emission signal, such as a relative re-emission, may be generated, as will be outlined in further detail below and as is generally known in the art of optical detection.

The re-emitted light, or a portion thereof, may be received by at least one detector. The detector may be any detector configured to receive light and convert the light into one or more electrical or electronic signals. The detector may comprise at least one light sensitive element for detecting light propagating from the test carrier to the detector. The detector may generate one or more output detector signals, in particular at least one electronic signal, which may be further evaluated. The detector signal may generally be or may comprise an analog signal and/or a digital signal. In particular, the detector signal may comprise a current signal and/or a voltage signal. The at least one detector signal may be a single detector signal or may comprise a plurality of detector signals, such as by providing a continuous detector signal comprising continuously generated detector signals and/or detector signals generated at predetermined points in time and/or at a given detection frequency. The at least one detector signal can be used directly or indirectly in method step b). Thus, the detector signal may be directly processed in order to determine the concentration of the analyte. Additionally or alternatively, one or more processing steps may be applied to the detector signals in order to convert the detector signals as provided by the detectors (also referred to as raw detector signals or primary detector signals) into one or more secondary detector signals, such as by applying one or more of filtering and/or averaging processes. In the following, when referring to detector signals, both the option of using one or more primary detector signals and the option of using one or more secondary detector signals will be implied.

Generally, in certain embodiments, the detector may include at least one photosensitive element selected from the group consisting of: a photodiode; a photomultiplier tube; imaging detectors, in particular camera chips, such as CMOS and/or CCD chips. Other light sensitive elements are possible.

In method step d), the concentration of the analyte is determined by evaluating at least one detector signal generated by the detector. As will be outlined in further detail below, in certain embodiments the evaluation may be performed automatically, in particular by using at least one evaluation algorithm, by using at least one data processing device adapted for automatically performing the evaluation algorithm, such as by using at least one software program.

The at least one light source is modulated by using at least two modulation frequencies. As used herein, the modulation of light may specifically be or may imply a periodic change of at least one parameter of the light, such as at least one parameter selected from the group consisting of amplitude, frequency and phase. As further used herein, the modulation frequency of the modulation is the frequency of the periodic change of the at least one parameter. Thus, mathematically, the modulation may be a multiplication of the parameter to be modulated with a periodic function, such as one or more of the following functions:

a·exp[-i2πf t + φ],

a·sin[-2πf t + φ],

a·cos[-2πf t + φ],

where a denotes the amplitude of the modulation, where f denotes the frequency of the modulation, and where phi denotes the phase of the modulation. Additionally or alternatively, the parameter to be modulated may be multiplied by a periodic delta function and/or may be multiplied by a periodic pulse function, such as a rectangular function. Other types of modulation are possible.

Modulation with at least two modulation frequencies, such as f1 and f2, generally refers to doubling of the multiplication referred to above, i.e. repetitive modulation with two or more modulation frequencies.

The number of possible detection channels and/or frequencies operating in parallel may be limited by processing power, such as the installed processing power, and/or by the energy required for mathematical calculations and processing. For battery-driven analytical devices, such as, for example, battery-driven hand-held meters, three frequencies per light source may be used. However, embodiments with more frequencies are possible, such as an analysis device for connection to an external energy source.

As further used herein, demodulation generally refers to the inverse process as compared to modulation. Thus, as an example, demodulation may imply multiplication or mixing of a modulated function with a periodic function having a particular frequency (which is also referred to as a modulation frequency). In addition, demodulation may imply filtering or suppression of the high frequency components after multiplication and/or mixing is performed in order to obtain the low frequency components. For the first process, an electronic mixer or multiplier may be used, whereby the signal to be modulated is multiplied with at least one demodulation frequency, and for the latter process a low-pass filter may be used. Thus, in general, demodulation may imply a shift or change of the signal from the original frequency of the optical signal to a frequency that is evaluable and analyzable for error detection. The at least one light source may be modulated and/or demodulated by using two or more modulation frequencies.

The modulation frequency may originate from a light source, which may generate two or more control signals having two or more different frequencies, which may be used as modulation frequencies for modulation and/or demodulation. As an example, the same signal source may be used for generating modulation frequencies for both modulation and demodulation. In general, the modulation frequency used for modulation may be the same as the modulation frequency of demodulation. In general, the signal source may be a signal generator, for example, generating a signal selected from the group of: a sinusoidal signal; a rectangular signal; a trapezoidal signal; the delta signal is preferably a periodic delta signal. In an alternative mixer unit, one control signal for controlling the pulsed light source may be generated by mixing the two control signals. The test carrier can be illuminated by the modulated optical signal.

The control signals may have equal strength. As used herein, the term "intensity" refers to the intensity level and/or amplitude level of a signal. The strength of the control signal may be equal to the strength of the detector signal. Thus, in case of a low detector signal, the probability of false detections may be reduced.

The at least one light source may comprise at least one first light source modulated by at least two modulation frequencies and at least one second light source modulated by at least two modulation frequencies different from the at least two modulation frequencies used for modulating the first light source. Thus, in this embodiment, it may be possible to illuminate the tracking carrier by two light sources. This may be advantageous, since illumination of two different positions on the tracking carrier indicative of a determination of two measurement values may be possible.

In general, when more than one light source is used, it may be possible to illuminate one, two or more different locations. Thus, the at least one first light source may be adapted to illuminate at least one first position and the at least one second light source may be adapted to illuminate at least one second position, wherein the at least one first position and the at least one second position may be completely or partially identical or may be completely or partially different, such as partially separated and/or overlapping. For example, these different locations may be located on the same test carrier and/or may be located on different trace carriers. Thus, it may be possible to illuminate two or more locations on two or more different test carriers and thus determine two or more measurements of the two or more different test carriers with the same apparatus. Different test carriers may have different configurations, such as different geometries and/or different photometric properties.

The detector signal is demodulated with at least two modulation frequencies to generate at least two demodulated detector signals, each demodulated detector signal corresponding to one of the modulation frequencies.

The process of demodulation may be understood as extracting the demodulated optical signal from the detector signal. In the above-mentioned embodiments, wherein two light sources each modulated by two modulation frequencies may be used, at least two demodulated detector signals may be generated for the modulation frequency used to modulate the first light source and at least two demodulated detector signals may be generated for the modulation frequency used to modulate the second light source.

Demodulation may include independently multiplying the detector signal with the modulation frequency and filtering the result by using a low pass filter. A low-pass filter may be understood as an electronic component configured to pass signals having a frequency lower than a cut-off frequency and to attenuate or suppress signals having a higher frequency.

The demodulation may further comprise filtering the detector signal by using at least one band pass filter before multiplying the detector signal with the modulation frequency. A band pass filter is an electronic device configured to allow frequencies within a certain predetermined range to pass and reject other frequencies outside the range. The band pass filter may be adjustable. Thus, it may be possible to adjust the pass band to the frequency used in the measurement.

The method comprises error detection based on a comparison of at least two demodulated detector signals. False detection may be understood as identifying disturbances, in particular disturbances due to one or more ambient lights, disturbances of one or more light sources, and disturbances of one or more electronic components. Other perturbations are possible. As used herein, error detection based on a comparison of at least two demodulated detector signals generally refers to the fact that: error detection takes into account the comparison by any suitable means, such as by implementing one result of the comparison as an error detection algorithm as a variable and/or as a parameter. Thus, as an example, as will be outlined in further detail below, the error detection may imply comparing one or more variables to at least one threshold, wherein the one or more variables may imply at least one result of the comparison.

In addition, false detection may provide the possibility to determine a reliable measurement value of a photometric measurement and/or to reject the measurement in the presence of ambient light. The error detection may be an online error detection performed permanently or repeatedly. The error detection may be repeated once or several times during the photometric measurement.

The error detection is based on a comparison of at least two demodulated detector signals. Generally, as used herein, a comparison of at least two demodulated detector signals refers to an algorithm adapted to generate a comparison result that depends on the magnitude of each demodulated detector signal and/or on a difference forming two normalized demodulated detector signals. Thus, as an example, the comparison may imply forming a difference between the at least two demodulated detector signals and/or may imply forming a quotient of the at least two demodulated detector signals. In case the demodulated detector signals each comprise a sequence of single values, the comparison may imply comparing the current or present value of the series. As an example, the comparison may comprise at least one algorithm selected from the group consisting of: a comparison of at least one demodulated detector signal with at least one other demodulated detector signal; a comparison of the at least one demodulated detector signal with at least one average of the demodulated detector signal; comparison of the at least one demodulated detector signal with at least one threshold. Thus, in general, the demodulated detector signals may be directly compared to each other or may be compared to at least one representative value representing, for example, normal conditions and/or an entity representing the demodulated detector signals.

Generally, as outlined above, the error detection may imply at least one threshold comparison. Thus, as an example, one or more of the demodulated detector signal and/or the difference between at least two demodulated detector signals and/or the quotient of two or more detector signals may be directly or indirectly compared to one or more thresholds.

The error detection may include detecting an erroneous demodulated detector signal. The demodulated detector signal may be identified as erroneous if at least two of the generated demodulated detector signals show a difference greater than a predetermined tolerance. In an embodiment, more than two modulation frequencies may be used, e.g. three. Thus, if the difference from the other two demodulated detector signals is greater than a predetermined tolerance while the two other demodulated detector signals show similar values, one of the three demodulated detector signals can be identified as erroneous. In the event that the differences of all demodulated detector signals are greater than a predetermined tolerance, the entire set of demodulated signals can be detected as erroneous.

The comparison of the at least two demodulated detector signals may comprise comparing at least a first one of the demodulated detector signals with at least a second one of the demodulated detector signals and determining that the first one of the demodulated detector signals is erroneous, preferably deviating by a margin of 0-2%, more preferably by a margin of 0-1%, if the deviation of the first one of the demodulated detector signals from the second one of the demodulated detector signals is larger than a predetermined margin.

In addition, the error detection may include rejecting demodulated detector signals identified as erroneous demodulated detector signals, and may imply using only non-erroneous demodulated detector signals for determining the concentration of the at least one analyte in the body fluid. Rejecting one of the demodulated detector signals for determining a concentration of at least one analyte in the bodily fluid if the demodulated detector signal is detected as erroneous. If the entire set of demodulated detector signals is detected as erroneous, the measurement is repeated with the new set of frequencies. In the latter case, a change in the set of frequencies may result in a certain settling time of the measurement device (e.g. a band pass filter). The demodulated detector signals may each be a sequence of measured values, wherein rejecting erroneous demodulated detector signals may comprise a rejection algorithm selected from the group consisting of: rejecting current measurements determined to be erroneous; the entire sequence of measured values is rejected in case at least one measured value is determined to be erroneous. In case all demodulated detector signals are determined to be erroneous, the method may be aborted. Additionally, each demodulated detector signal may comprise a sequence of individual measurements, wherein error detection may be based on a comparison of the individual measurements. A single measurement may be understood as raw, non-evaluated and/or non-analyzed data. For example, a single measurement is issued by the detector every 20 ms (preferably every 10 ms).

Additionally or alternatively, the above-mentioned error detection may comprise detecting an erroneous demodulated detector signal. Error detection may include determining a degree of defectiveness for the demodulated detector signal determined to be erroneous. Thus, it is possible that at least one erroneous demodulated detector signal may be used for determining the concentration of the analyte, taking into account the degree of defectiveness.

The method may be performed repeatedly, wherein in case an erroneous demodulated detector signal is found for a particular modulation frequency in one repetition of the method, said modulation frequency may not be used in a subsequent repetition of the method. In general, in case an erroneous demodulated detector signal is found for a particular modulation frequency, another frequency not used so far may be changed. However, then a settling time will occur.

In the above-mentioned embodiments, in which two or more light sources each modulated by at least two modulation frequencies may be used, error detection may be performed for both the demodulated detector signal of the modulation frequency used to modulate the first light source and the demodulated detector signal of the modulation frequency used to modulate the second light source. Thus, for example, by using only light of non-erroneous light sources, reliable measurements of the concentration of the analyte may be possible even if one or more demodulated detector signals are detected as erroneous in one set of demodulation frequencies modulating the modulation frequencies of a light source selected from the group of first and second light sources, and if an erroneous demodulated detector signal has not been detected in another set of demodulation frequencies modulating the modulation frequencies of another light source selected from the group of first and second light sources.

The error detection may be performed at least once before applying the sample of the body fluid to the test carrier. As outlined above, the method may comprise further steps, which may in particular be performed fully or partially before performing the method steps a) -d), for example before applying the sample of the body fluid to the test carrier as proposed in method step a), and/or may be performed at least once independently of method step a).

Thus, the method may further comprise determining at least one dry empty value by evaluating at least one detector signal generated by the detector before applying the sample of body fluid to the test carrier. It is well known to the skilled person to perform a re-emission measurement of the test carrier before applying a sample of the body fluid (so-called dry empty value). The error detection may be performed at least once during the determination of the dry empty value. The dry empty value may be compared to a reference value to determine the usability of the test carrier. In case the usability of the test carrier may be limited due to imperfections, e.g. aging imperfections due to environmental influences such as humidity, light or temperature, it may be possible to reject the test carrier and/or to adjust the measurement values, e.g. one or more of the determined concentration of the analyte and the at least one detector signal, before applying the sample of the body fluid to the test carrier.

Additionally or alternatively, the method may further comprise at least one location verification step, wherein the location verification step may comprise the method steps of:

i) inserting the test carrier into an analytical device;

ii) illuminating the test carrier by at least one light source;

iii) receiving light re-emitted by the test carrier by using at least one detector;

iv) determining at least one position of the test carrier within the analytical device by evaluating at least one detector signal generated by the detector, wherein the position comprises at least one of a position and/or an orientation of the test carrier.

The method steps may be performed in a given order, i.e. in the order i) -ii) -iii) -iv). However, other orders of method steps are possible, such as ii) -i) -iii) -iv). Thus, as an example, the test carrier may be or may comprise a strip-shaped test carrier or test strip, which may be inserted into a receptacle of an analysis device before the test carrier is illuminated by the at least one light source. Additionally or alternatively, a test carrier such as a test strip and/or test strip may include one or more of the following: at least one marking, at least one coating and/or at least one other information item. The at least one information item may comprise at least one visually detectable information item, which may be detected by the at least one analysis device. The at least one item of information may comprise at least one item of information about the proper use of the test carrier, such as at least one calibration information, and/or may comprise at least one other item of information, such as a positioning mark or a fiducial mark. The analysis device may be adapted for reading the at least one information item, such as during insertion of the test carrier into and/or within the analysis device. The analyzing device may further be adapted for evaluating the at least one information item and/or for controlling the at least one process in dependence of the at least one information item. Thus, the analysis device may be adapted for controlling the positioning of the test carrier and/or detecting whether the test carrier is correctly positioned. As an example, the analysis device may be adapted for illuminating the test strip and detecting at least one marker on the test strip and/or detecting at least one test field on the test strip, for controlling the positioning of the test strip and/or for detecting whether the test strip is correctly positioned. The control of the positioning of the test strip may be performed by controlling a suitable feeding mechanism of the analysis device, such as by controlling a motor for positioning the test strip. Thus, in particular in the latter case, the irradiation of the test carrier may take place before or during the insertion of the test carrier into the analysis device, such as for the purpose of monitoring the insertion process itself, such as a positioning process.

Further, one or more method steps may be performed in parallel and/or in a time overlapping manner, such as by performing method steps i) and ii) at least partially simultaneously and/or by performing method steps ii), iii) and iv) at least partially simultaneously. In addition, one or more method steps may be repeatedly performed. Thus, as an example, method steps ii) and/or iii) may be performed repeatedly. In addition, there may be additional method steps not listed.

The test carrier can be inserted into a receptacle of an analysis device. The test carrier and/or the analysis device and/or the light source and/or the detector may in particular be identical to the corresponding devices used in method steps a) -d). However, additionally or alternatively, at least one additional light source and/or at least one additional detector is dedicated to the location verification step. For the description of possible embodiments and definitions of these devices, reference may be made to the above-mentioned devices used in methods a) -d) and to the above-mentioned analysis device according to the invention. In general, other configurations of these devices may be possible.

The location verification step may be performed before performing the method steps a) -d). The position verification step may comprise determining the position and/or orientation of the test carrier, including determining the likelihood of the position or location of the portion of the test carrier within the analysis device, such as the position or location of at least one test field of the test carrier. As outlined above, the method steps i) -iv) may be performed at least once before applying the sample of the bodily fluid to the test carrier, such as before performing a combination of the method steps a) -d). In this embodiment, the method steps i) -iv) may be performed at least once before applying the sample of the bodily fluid to the test carrier in order to determine at least one position of the test carrier within the analysis device. The test carrier and/or the test field of the carrier may comprise markings, for example colour markings and/or for example further arbitrary markings with a known re-emission. As used herein, a "position" may be a location and/or orientation of a test carrier or a portion thereof, such as a location and/or orientation of at least one test field of the test carrier, and/or an indicia of the test carrier within an analysis device (e.g., within a receptacle of the analysis device). The re-emission of light of the test carrier, for example of the test strip, the test disc and the integrated test carrier and/or the test field of the carrier, can depend on its position within the analysis device. Proper alignment within the analysis device may be required for reliable measurements.

After performing method steps i) -iv), the determined measurement values, e.g. one or more of the at least one detector signal and the determined concentration of the analyte, may be compared with reference values. In the case of proper alignment of the test carrier, the determined measurement value may correspond to the reference value within specified limits (such as within one or more thresholds).

The determination of the position may be performed once before applying the sample of the body fluid to the test carrier and/or during the photometric measurement. Thus, in case the test carrier is not properly aligned with the analysis device, it may be possible to abort the measurement at any desired time, e.g. before applying the sample to the test carrier, and/or to adjust the measurement values, e.g. one or more of the at least one detector signal and the determined concentration of the analyte. In case it is determined that the test carrier is not properly aligned within the analysis device, the alignment may be performed by a user and/or automatically. Additionally, where at least one or more of the modulation frequencies may be susceptible, the evaluation for analyte concentration may not take into account that the susceptible modulation frequency and/or set of frequencies may be altered. In addition, the error detection may be performed at least once during the determination of the position of the test carrier.

In some embodiments, the ambient light error detection step may be performed without using a test carrier. Herein, the method may further comprise at least one ambient light error detection step, wherein the ambient light error detection step may comprise the method steps of:

I. receiving ambient light by using at least one detector;

evaluating at least one detector signal generated by a detector;

performing ambient light error detection by comparing at least one detector signal generated by the detector with the modulation frequency.

The method steps may be performed in a given order, i.e. in the order i. However, other orders of method steps are feasible, such as ii. Further, one or more of the method steps may be performed in parallel and/or in a time overlapping manner, such as by performing method steps i.and ii. In addition, one or more of the method steps may be performed repeatedly. In addition, there may be additional method steps not listed.

In other embodiments, the ambient light detection may be performed after insertion of the test carrier into the analysis device. Herein, the method may further comprise at least one ambient light error detection step, wherein the ambient light error detection step may comprise the method steps of:

I. inserting the test carrier into an analytical device;

illuminating the test carrier by at least one light source;

receiving ambient light by using at least one detector;

evaluating at least one detector signal generated by the detector;

v. performing ambient light error detection by comparing at least one detector signal generated by the detector with the modulation frequency.

The method steps may be performed in a given order, i.e. in the order of i. However, other orders of method steps are feasible, such as ii. Further, one or more of the method steps may be performed in parallel and/or in a time overlapping manner, such as by performing method steps i.and ii. at least partially simultaneously and/or by performing method steps ii. In addition, one or more of the method steps may be performed repeatedly. Thus, as an example, method steps ii. In addition, there may be additional method steps not listed.

In some embodiments, the first ambient light error detection step may be performed prior to inserting the test carrier into the analysis device, and the second ambient light error detection step may be performed after inserting the test carrier into the analysis device.

In all of these embodiments, the ambient light error detection step may be based on a comparison of the at least one detector signal with the modulation frequency. As used herein, when referring to a modulation frequency in the context of ambient light error detection and comparison of at least one detector signal to the modulation frequency, the modulation frequency may specifically be or may comprise a frequency component of the detector signal at the respective modulation frequency. Thus, a complete or partial frequency analysis of the at least one detector signal may be performed, thereby deriving frequency components of the detector signal and in particular frequency components of the detector signal at the modulation frequency. Thus, as used herein, the expression "comparing at least one detector signal generated by a detector with a modulation frequency" may generally refer to the fact that: the above-mentioned frequency components may be evaluated in order to determine whether at least one condition is satisfied. Thus, as will be outlined in further detail below, the frequency components may be compared to one or more thresholds and/or to one or more tolerance ranges and/or to one or more conditions.

The ambient light error detection step may be performed before performing the method steps a) -d), e.g. before applying the sample of the body fluid to the test carrier. Thus, in general, method steps i. -iii. can be performed without inserting the test carrier into the analysis device (such as by emptying the receptacle of the analysis device). In particular, ambient light error detection may be performed without a test carrier, such as without a test strip and/or without a test strip. Alternatively, the test carrier may be inserted into the analysis device, such as into at least one receptacle of the analysis device, and the ambient light error detection step may comprise at least one step of inserting the test carrier into the analysis device. Thus, ambient light false detection may optionally occur in real-world environments, where the test carrier is inserted into the analysis device.

Ambient light error detection may be performed without using the light source of the analyzing device, such as by detecting only ambient light. Alternatively, ambient light error detection may be performed with the additional use of at least one light source. Thus, without inserting the test carrier into the analysis device, the at least one light source may illuminate at least one empty receptacle of the analysis device and/or may illuminate at least one point or zone within the analysis device, which is typically occupied by the test carrier and/or a part thereof (such as a test field of the test carrier). Thus, in general, ambient light false detection may also imply illumination, such as by illumination of the analysis device and/or parts thereof with at least one light source. Thus, the at least one detector signal generated by the detector may comprise at least one portion due to ambient light and at least one portion due to light generated by the at least one light source of the analysis device.

In case at least one test carrier is inserted into the analysis device for the purpose of and/or during ambient light error detection, the process itself may also imply applying a sample of the body fluid to the test carrier. In the latter case, the ambient light error detection may in particular be performed before applying the sample of the body fluid to the test carrier, for example before detecting the at least one detector signal for the purpose of ambient light error detection and/or before switching on the light source and/or after switching on the light source. Other options are possible.

The performance of ambient light error detection by comparing the at least one detector signal generated by the detector with the modulation frequency may also imply a comparison, such as a mathematical comparison, of the frequency components of the at least one detector signal at the modulation frequency with one or more thresholds and/or conditions and/or tolerance ranges. For this purpose, the frequency components of the at least one detector signal may each be compared to one or more thresholds and/or conditions and/or tolerance ranges, either alone or in combination, as raw values or after performing one or more pre-processing steps (such as filtering or normalization). As an example, two or more of the frequency components of at least one detector signal are combined as the original signal or after performing one or more pre-processing steps, using for example a quotient and/or a difference between two or more of the frequency components, and the result of this mathematical operation may be compared to one or more thresholds and/or conditions and/or tolerance ranges. Ambient light false detection may depend on the comparison. Thus, by way of example, in the event that one or more threshold values are exceeded and/or in the event that the results of the discovery are outside of one or more tolerance ranges and/or in the event that one or more error conditions are found to be met, errors due to ambient light may be detected and, optionally, one or more appropriate actions may be taken, such as providing an alarm and/or preventing further measurements, preferably automatically. Additionally or alternatively, in case at least one detector signal, one or more of a plurality of detector signals, or at least one signal component of at least one detector signal is found to be erroneous, a corresponding erroneous measurement signal or measurement signal component or a corresponding modulation frequency may be excluded from the method for determining the concentration of at least one analyte in a body fluid, such as due to a disturbance of ambient light. Thus, as an example, ambient light error detection may determine whether one or more of the at least two modulation frequencies falsify the demodulated detector signal for the respective at least one modulation frequency and may exclude the respective at least one modulation frequency from the determination of the analyte concentration, which may be denoted as "false modulation frequency". Thus, as an example, the wrong modulation frequency may be replaced by another modulation frequency for determining the analyte concentration. Additionally or alternatively, at least one demodulated detector signal for the wrong modulation frequency (which may also be referred to as "wrong demodulated detector signal") may be excluded from further evaluation and/or may be used with a lower weighting factor than other demodulated detector signals. The demodulated detector signal may be used to determine an average value of the analyte concentration, such as a weighted average, in particular a moving average or a weighted moving average. Averaging may occur before, during, or after determination of the analyte concentration. Thus, the determination of the analyte concentration may be performed based on one, more than one or all of the demodulated detector signals, such as by independently determining the analyte concentration using a common correlation between the demodulated detector signals as an input variable and the analyte concentration as an output variable and/or by independently using the demodulated detector signals as input variables, and then such as by determining a mean or average or a weighted average combining the independent results. Wherein in case the one or more demodulated detector signals are determined to be erroneous demodulated detector signals during ambient light error detection, the one or more erroneous demodulated detector signals may be excluded from the determination of the analyte concentration and/or may be used with a lower weight, such as by using a lower weighting factor in a weighted average as compared to non-erroneous demodulated detector signals.

The test carrier may be inserted into a receptacle of an analytical device. The test carrier and/or the analytical device and/or the light source and/or the detector may be identical to the devices used in method steps a) -d). However, additionally or alternatively, at least one additional light source and/or at least one additional detector is dedicated to the ambient light error detection step. For a description of possible embodiments and definitions of these devices, reference may be made to the above-mentioned devices used in methods a) -d) and to the above-mentioned analysis device according to the invention. In general, other configurations of these devices may be possible.

The expression "ambient light" may be understood as light emitted by any light source present during the execution of the proposed method, such as sunlight, light of an artificial light source. The ambient light error detection step may be performed, such as before performing method steps a) -d), in order to determine the contribution of one or more possible modulation frequencies within the ambient light.

The detector may receive ambient light and may generate at least one detector signal. At least one detector signal generated by the detector may be evaluated with respect to contributions of one or more possible modulation frequencies within the ambient light. The evaluation may comprise comparing the at least one detector signal with at least one modulation frequency and/or a set of modulation frequencies, which may be used for modulating the light source. In case the ambient light shows a contribution of at least one modulation frequency that may be used for modulating the light source, the evaluation for the analyte concentration may not take the at least one modulation frequency into account and/or the set of frequencies may be changed.

As outlined above, method step d) implies that the concentration of the analyte is determined by evaluating at least one detector signal generated by the detector. As used herein, the evaluation of the at least one detector signal generally refers to any algorithm for deriving the concentration of the analyte from the at least one detector signal. The algorithm may be or may include an analysis algorithm, such as an evaluation function. Additionally or alternatively, any other type of algorithm may be used, such as a look-up table or any other algorithm adapted to assign a specific value of the detector signal to the concentration of the analyte. These algorithms are generally known to the skilled person. As an example, the end point values of a measurement curve comprising a sequence of detector signals may be used as characteristic values, and the analyte concentration may be derived therefrom. Thus, as an example, algorithms as disclosed in EP 0821234 and US 2002/0146835 a1 may be used, wherein the measurement curve is directly or indirectly compared to one or more threshold values. Thus, as an example, EP 0821234B 1 discloses a method in which the slope of the measurement curve is determined by deriving difference values for the colors and comparing these difference values with a predetermined threshold value. Thus, the end point of the detection reaction can be determined. Similarly, in US 2002/0146835 a1, endpoints are determined by calculating an intermediate analyte level of the test element at predetermined intervals and calculating a ratio corresponding to the (n) th measurement to the (n-5) th measurement. When two successive ratios are less than or equal to a predetermined value, the endpoint is considered reached and the final analyte level can be determined.

In addition, several evaluation algorithms using one or more fitting algorithms are known in the prior art, wherein a measurement curve comprising detector signals is analyzed by using one or more fitting functions. Thus, in WO 2011/061257 a1, a method and a device for analyzing a body fluid are disclosed, wherein a photometric measurement curve is measured. The transmission behavior of the optical transmission system is controlled by detecting the measured values at two different measurement wavelengths. In addition, a fitting function is generated for the two measurement curves, and the deviation of the measurement values is determined by extrapolating the fitting curve. In US 2008/0087819 a1, a method for analyzing a fluid sample is disclosed, wherein two different wavelengths are used again for deriving two measurement curves. By performing a suitable fitting algorithm with two different types of time constants, the measurement curve is fitted by using an exponential rise followed by an exponential fall.

In WO 01/25760 a1, a time independent algorithm for determining the appropriate time for measurement of the reaction between the sample fluid and the reagent on the analyte strip is disclosed. Wherein the measurement profile of the properties of the substrate to which the sample fluid is applied is measured both before and after application of the sample fluid. Subsequently, a transformation of the measurement curve to a function which is independent in time or at most linearly different in time is made. The second derivative of the transformed function is then analyzed to determine when the second derivative falls below a predetermined threshold. At this point in time, the transformed function will yield the analyte concentration in the sample fluid. In EP 1413883 a1, a method of reducing the analysis time of an endpoint-type reaction profile is disclosed. For this purpose, a detection reaction is initiated, whereby at least three measurements of the level or value of an observable associated with the detection reaction are obtained at three different points in time. Subsequently, endpoint values for the observables are estimated from the measurements by using a suitable fitting function. In WO 2006/138226 a2, algorithms and arrangements for calculating the concentration of an analyte contained in a sample are disclosed. Wherein the rate of color change of the test chemical is detected and the hematocrit is derived from the rate of color change. An appropriate correction factor indicative of hematocrit is used to correct the glucose concentration.

These algorithms and/or any other evaluation algorithm known to the skilled person may be used to perform method step d), wherein in certain embodiments only the non-erroneous detector signals are used in method step d) in order to determine the analyte concentration.

Step d) of the method may also be performed by using a data processing device and/or a computer. For example, the error detection may be performed by using a data processing device and/or a computer, in particular a comparison of the demodulated detector signals.

Furthermore, it may be possible to store information of error detections for certain frequencies and/or reoccurrence error detections for certain frequencies. Thus, the method may imply storing information about previous error detections in at least one data storage for use in future measurements. As an example, information regarding one or more modulation frequencies known to be erroneous and/or known to be non-erroneous may be stored in the at least one data store. Thus, it may be possible to start the measurement at a frequency that is not susceptible or erroneous. The method may be performed such that one or more modulation frequencies known to be non-erroneous are chosen, such as from previous measurements, either automatically or by manual adjustment by a user. Thus, the analysis device performing the method may be adapted to provide two or more modulation frequencies to a user and/or may be adapted to automatically choose at least two or more reliable modulation frequencies known to be non-erroneous, such as from previous measurements, without requiring user input.

In certain embodiments, the method may further comprise one or more or even all of the following method steps, which may in embodiments be performed before performing method step a), i.e. before applying the sample of body fluid to the test carrier:

i. inserting the test carrier into an analytical device;

initiating error detection;

obtaining a dry empty value.

As outlined above in relation to method steps a) to d), these method steps i. -iii can be performed in the given order and/or in any other feasible order, as will be apparent to the skilled person. In addition, one or more or even all of these additional method steps may be combined with one or more of the method steps a) to d).

For further details of the analysis device, reference may be made to the disclosure of the second aspect of the invention as given below.

The method according to the invention allows error detection to be performed at substantially any reasonable time of photometric measurement, as will be apparent to the skilled person. In addition, it may be possible to avoid erroneous or inaccurate measurements caused by disturbances of ambient light by changing from the used, susceptible frequency to a less susceptible frequency. This is achieved on the one hand by comparing the demodulated detector signal at a very early stage of the measurement (e.g. during the determination of the dry null) instead of comparing the estimated value of the concentration of the analyte. In addition, this is achieved by using more than one set of modulation frequencies. Thus, it is possible to change the set frequency in case of false detection. Generally, the amount of frequency change is not limited. However, the settling time of the measuring device used may have to be taken into account.

Furthermore, false detection at very early stages of the described measurement provides the following possibilities: the robustness of the determined concentration value of the analyte is protected by detecting the perturbation before applying the sample of the bodily fluid to the test carrier. Preselection of the set of frequencies may be possible by performing one or more frequency changes and/or one or more error detections before applying the sample of body fluid to the test carrier. Thus, the set of frequencies with the lowest susceptibility may be preselected.

For example, the method may be performed with two modulation frequencies 1,488 kHz and 1,587 kHz. If the demodulated detector signal generated during the determination of the dry null for the set of frequencies shows a fault above a certain threshold, the pair may be detected as erroneous and may be rejected. In this case, the frequency set may be changed to another frequency set, for example, 1,302 kHz and 1,389 kHz. If the set of frequencies again shows flaws above a certain threshold, the pair may be detected as erroneous and may also be rejected. Again, the second set of frequencies may be changed to another set of frequencies, such as 1,645 kHz and 1,754 kHz. In case the third set of frequencies is not detected as erroneous, the sample is applied to the carrier and a measurement of the concentration of the analyte will be started.

In addition to or alternatively to the comparison of the demodulated detector signal to one threshold, two or more thresholds may be established. The at least one threshold may be or may comprise at least one predetermined threshold and/or may be or may comprise at least one adjustable threshold, which may be manually and/or automatically adjustable. E.g. a narrow threshold, e.g. 0.5% deviation of the demodulated detector signal, and a wider threshold, e.g. 1-2% deviation of the demodulated detector signal. In case the deviation of the demodulated detector signal lies within a narrow threshold range, an alarm may be generated to show the user that the measurement is not reliable. Alternatively, if the deviation of the demodulated detector signal lies within a wide threshold range, a suspension of measurements or a change of the susceptible frequency may be performed.

In another embodiment, more than two frequencies may be used for modulating the light source. For example, three, four or more frequencies may be used for modulating the light source, e.g. f_i, f_ii, f_iii... In this embodiment, three demodulated detector signals for three modulation frequencies may be generated and compared. Thus, if only one frequency is susceptible, it may be possible to use only the non-erroneous demodulated detector signalTo assess the analyte concentration. The resulting detector signal may be determined as an average of the non-erroneous demodulated detector signals. For example, if the frequency f_iIs susceptible to and f_iiAnd f_iiiIs not susceptible, it may be possible to consider only the frequency f_iiAnd f_iiiFor the assessment of analyte concentration. As an example, the method may only be aborted if all three demodulated detector signals show different values. Thus, it may be possible to determine the concentration of the analyte even if a false detection for one frequency does not change the entire set of frequencies.

For example, in one embodiment, two light emitting diodes may be used as light sources. Three frequencies, e.g. f, may be utilized_1a = 977 Hz, f_1b= 1465 Hz and f_1c= 1953 Hz to modulate the signal of one light source. Three other frequencies, e.g. f, may be utilized_2a = 1172 Hz, f_2b= 1563 Hz and f_2c= 2344 Hz to modulate the signals of the other light sources. During error detection, in a first step, f can be compared_1aAnd f_1bThe demodulated detector signal of (a). In a second step, these demodulated detector signals can be combined with f_1cThe demodulated detector signals of (a). The average detector output signal may be evaluated from equal values only, where equal indicates equality within a certain threshold. At least two values may be required for the evaluation of the average detector output signal. If the difference of all demodulated detector signals is greater than a predefined threshold, an error value may be generated and a change to a frequency other than the vulnerable frequency may be performed. The equality method may be applied to the frequency of the second light source. The two determined averages may be further evaluated to determine the concentration of the analyte. At this later stage of the measurement, it may further be possible to compare the two determined concentrations of the analyte. If the two measurements are not equal, an alarm and/or error value may be raised.

In another aspect of the invention, an analytical device for determining a concentration of at least one analyte in a bodily fluid is disclosed, comprising at least one receptacle for receiving at least one test carrier. As used herein, an analysis device generally refers to a device adapted to perform at least one analysis in order to determine the concentration of one or more analytes in a body fluid. The analysis device may be a handheld device or may be a fixed or portable device.

At least one sample of a body fluid may be applied to the test carrier. To achieve this, the analysis device may be adapted such that a sample of the body fluid may be applied to the test carrier before the test carrier is inserted into the receptacle and/or in a state in which the test carrier is inserted into the receptacle. In the first case, the receptacle may be designed such that a test carrier with a sample applied thereto may be inserted into the receptacle. In the latter case, the container may be designed such that at least one portion of the test carrier with at least one application position is user-accessible in order to allow application of the sample.

The analysis device may be adapted to perform the method according to the method described in the first aspect of the invention. For the description of possible embodiments and definitions, reference may be made to the above-mentioned method according to the invention.

As used herein, a receptacle may be any formed device configured to allow insertion of a test carrier. The container may also be adapted to enable application of a sample of the bodily fluid to the test carrier. The container may generally comprise at least one means for holding the test carrier in at least one predetermined position. Thus, as an example, the container may comprise one or more of a socket, a guide structure, a holder, a chamber. Other types of containers are possible. The container may be adapted to hold the test carrier in place during photometric measurements. The receptacle may include at least one opening, such as one or more of a socket opening, a rectangular opening, a circular opening, adapted to insert the test carrier into the receptacle.

The analysis device further comprises at least one light source adapted for illuminating the test carrier and at least one detector adapted for receiving light re-emitted by the test carrier. For potential embodiments of the light source, reference may be made to the definitions and embodiments given above or in further detail below.

The analysis device further comprises at least one evaluation unit adapted for determining the concentration of the analyte by evaluating at least one detector signal generated by the detector. As used herein, an evaluation unit generally refers to a device or a system of multiple devices configured to evaluate at least one detector signal generated by a detector. For example, the evaluation unit may comprise a data processing device and/or a computer. Thus, as an example, the microprocessor may be integrated in the evaluation unit. Alternatively or additionally, the external data processing device may be included into an analysis device such as one or more personal computers, one or more computer networks, or one or more other types of data processing devices.

The analyzing device further comprises at least one modulation device adapted for modulating the light source by using at least two modulation frequencies. As used herein, a modulation device generally refers to at least one device configured to perform modulation as defined above. Thus, the modulation device may generally be adapted to periodically modulate the light emitted by the at least one light source and/or at least one parameter of the at least one light source.

The signal source may be adapted to generate one or more control signals having at least two modulation frequencies. In particular, the modulation device is adapted to modulate the light source by using at least three modulation frequencies.

The analysis device further comprises at least one demodulation device adapted for demodulating the detector signal with at least two modulation frequencies in order to generate at least two demodulated detector signals, each demodulated detector signal corresponding to one modulation frequency. As used herein, a demodulation apparatus generally refers to an apparatus configured to perform a demodulation process as defined above. Thus, the demodulation device may be adapted to demodulate a signal modulated by at least two modulation frequencies. The demodulation apparatus may be adapted such that the demodulation comprises independently multiplying the detector signal with one or more modulation frequencies and filtering the result by using one or more low pass filters. Furthermore, the demodulation device may be adapted such that the demodulation comprises filtering the detector signal by using at least one band pass filter before multiplying the detector signal with the modulation frequency. In certain embodiments, the band pass filter is manually and/or automatically adjustable.

The demodulation apparatus may comprise at least one lock-in amplifier. For example, the lock-in amplifier may be or may include a single phase lock-in amplifier. A single-phase lock-in amplifier may include a single lock-in structure using one reference signal. In an embodiment, the lock-in amplifier may be a digital bi-phase lock-in amplifier, such as to be phase independent. The digital bi-phase lock-in amplifier may include a double lock-in structure. The double-lock structure may include two single-lock structures that each include a reference signal. The reference signal may have the same modulation frequency used to modulate the light source and/or the reference signal may be modulated with the same modulation frequency. One reference signal of the double-lock configuration may be offset, for example the reference signal may be offset by 90 °. The output signal of the bi-phase lock-in amplifier may depend on the square root of the sum of the squared individual signals. As used herein, the term "lock-in amplifier" may be used as a synonym for a bi-phase lock-in amplifier.

The analysis device further comprises at least one error detection device adapted for performing error detection based on a comparison of the at least two demodulated detector signals. An error detection device is a device or system of devices configured to perform the error detection described above. The error detection device may comprise a data processing device and/or a computer. The error detection device may be fully or partially part of the evaluation device and/or may be fully or partially embodied as a separate device. In addition, the error detection device may be adapted to perform error detection as online error detection, which may be performed permanently or repeatedly. As used herein, online error detection generally refers to error detection performed during a measurement protocol of a photometric measurement, such as during determination of an analyte concentration.

For details of potential embodiments of error detection, reference may be made to the disclosure of the method as given above and/or as given in further detail below. The error detection device may be adapted such that the comparison of the at least two demodulated detector signals comprises at least one algorithm selected from the group consisting of: a comparison of at least one demodulated detector signal with at least one other demodulated detector signal; a comparison of the at least one demodulated detector signal with at least one average of the demodulated detector signal; comparison of the at least one demodulated detector signal with at least one threshold. For example, the error detection device may be adapted such that the comparison of the at least two demodulated detector signals comprises comparing at least a first one of the demodulated detector signals with at least a second one of the demodulated detector signals, and determining that the first demodulated detector signal is erroneous if the first demodulated detector signal deviates from the second demodulated detector signal by more than a predetermined tolerance, preferably by a tolerance of 0-2%, more preferably by a tolerance of 0-1%.

In general, the error detection device may be adapted such that the error detection comprises detecting the erroneous demodulated detector signal. In certain embodiments, the error detection device may be adapted such that the error detection further comprises rejecting erroneous demodulated detector signals and using only non-erroneous demodulated detector signals for determining the concentration of the at least one analyte in the body fluid. As used within this disclosure, rejecting refers generally to the process of preventing further use of demodulated detector signals that are identified as erroneous. The rejection may be an automatic rejection that automatically prevents the use of the wrong demodulated detector signal. Alternatively or additionally, the rejection may be a semi-automatic and/or manual rejection, such as by providing an alert to the user indicating that a particular modulation frequency or demodulated detector signal is erroneous.

In particular, the demodulation device may be adapted such that the demodulated detector signals each comprise a sequence of measurement values, wherein rejecting erroneous demodulated detector signals may comprise a rejection algorithm selected from the group consisting of: rejecting current measurements determined to be erroneous; the entire sequence of measurement values is rejected in case it is determined that at least one measurement value is erroneous. The analysis device may be adapted such that determining the concentration of the analyte is aborted in case all demodulated detector signals are determined to be erroneous. Furthermore, the analysis device may be adapted such that in case the determination of the concentration of the analyte is aborted, an output indicating the abort is issued.

Additionally or alternatively, the error detection device may be adapted such that the error detection comprises determining a degree of defect for the demodulated detector signal determined to be erroneous. The evaluation unit may be adapted such that the at least one erroneous demodulated detector signal is used for determining the concentration of the analyte, wherein the degree of defect is taken into account.

In a certain embodiment, the at least one light source may comprise at least one first light source modulated by at least two modulation frequencies and at least one second light source modulated by at least two modulation frequencies different from the at least two modulation frequencies used to modulate the first light source. For each light source, at least two signals each having a modulation frequency may be generated by the signal source. In the mixer unit, one control signal for the control is generated by mixing two signals for each light source, in particular summing the two signals. Each of the two light sources may be controlled by one of the generated control signals and may illuminate the test carrier. The re-emitted light may be detected by a detector. In this embodiment, the demodulation device may be adapted such that at least two demodulated detector signals are generated for a modulation frequency used for modulating the first light source and wherein at least two demodulated detector signals are generated for a modulation frequency used for modulating the second light source. Thus, the error detection device may be adapted such that error detection is performed for both the demodulated detector signal of the modulation frequency used for modulating the first light source and the demodulated detector signal of the modulation frequency used for modulating the second light source.

In another embodiment, the demodulation device may be adapted such that each demodulated detector signal comprises a sequence of signal measurements, wherein the error detection device may be adapted such that the error detection is based on a comparison of the individual measurements. The advantage of comparing individual measurement data is that the comparison takes place at an early stage of the measurement and that these measurement data can be quickly available, since no evaluation steps (such as calculations and/or integrations) are determined.

The error detection device may be adapted such that the error detection is performed at least once before applying the sample of the body fluid to the test carrier. The analysis device may be adapted to determine at least one dry empty value by evaluating at least one detector signal generated by the detector before applying the sample of the body fluid to the test carrier. The error detection device may be adapted such that the error detection is performed at least once during the determination of the dry empty value. Thus, error detection may be performed before determining the concentration of the analyte in the body fluid. Thus, it may be possible to abort the measurement before applying the sample to the test carrier, so that the inserted test carrier is still usable and not rejected.

In another aspect of the invention, an analytical system for determining at least one analyte in a body fluid is disclosed, comprising an analytical device as described above. Thus, in general, as used herein, an analytical system refers to a combination of at least one analytical device and at least one test carrier as independent entities, which may be handled independently or may be handled in combination and which may cooperate in order to determine a concentration of at least one analyte in at least one bodily fluid. For the description of possible embodiments and definitions, reference may be made to the above-mentioned method and the above-mentioned analysis device according to the invention.

The analysis system comprises at least one test carrier. The test carrier may be selected from the group consisting of: test strips, test tapes, test discs, and integrated test carriers having at least one test chemical and at least one lancet element.

As used herein, a lancet element can be any element configured to drill and/or lance into a user's skin to generate at least one sample of a body fluid. The lancet element can include one or more of a rounded tip, a sharp tip, a flat tip, a needle tip, and an edge. The lancet element may comprise further elements, such as elements configured to sample and/or transport a sample of a body fluid, in particular a capillary tube.

The test carrier may comprise at least one substrate and at least one test chemical applied to the substrate, wherein the test chemical may be adapted to perform at least one detection reaction in the presence of the analyte to be detected and to change at least one optically detectable property as a result of the detection. The optically detectable property may be any optical property that changes as a result of the detection reaction, and its measurement may thus provide at least one item of information about the progress, extent or state of the detection reaction. In certain embodiments, the at least one optically detectable information is selected from the group consisting of: the chemicals are tested for color, reflective properties such as re-emission, and fluorescence. Other embodiments are possible.

As described in detail above, the light source may use at least two frequencies. The described device and/or system allows reliable measurement results even in case of disturbances. The described devices and/or systems are operable even in the event that an error frequency is used and/or detected.

The invention also discloses and proposes a computer program comprising computer-executable instructions for performing the method according to the invention and/or parts thereof, when the program is executed on a processor residing within an analysis device, on a computer or on a computer network, in one or more embodiments attached herein. In particular, the computer program may be stored on a computer readable data carrier, for example on a ROM (such as a flash ROM), such as a ROM (such as a flash ROM) of a computer readable data carrier and/or a test carrier. Thus, in particular, one, more than one or even all of the method steps a) -d) as indicated above may be performed by using a processor residing within the analysis device, computer or computer network, preferably by using a computer program. In particular, one or more of determining the concentration of the analyte, demodulation of the at least one detector signal and error detection as disclosed in method step d) may be performed by using a processor residing within the analysis device, computer or computer network.

The invention also discloses and proposes a computer program product having program code means for performing the method according to the invention and/or parts thereof when the program is executed on a processor residing in an analysis device, on a computer or on a computer network, in one or more embodiments enclosed herein. In particular, the program code means may be stored on a computer readable data carrier.

Furthermore, the present invention discloses and proposes a data carrier having stored thereon a data structure which, after being loaded into a data storage residing within an analysis device, a computer or a computer network, such as into a working memory or a main memory of a computer or a computer network, may carry out a method and/or parts thereof according to one or more embodiments disclosed herein.

The invention also proposes and discloses a computer program product with program code means stored on a machine-readable carrier, in order to perform a method according to one or more embodiments disclosed herein and/or parts thereof, when the program is executed on a processor residing within an analysis device, on a computer or on a computer network. As used herein, a computer program product refers to a program that is a merchantable product. The product may generally be present in any format, such as in a paper format or on a computer readable data carrier. In particular, the computer program product may be distributed over a data network.

Finally, the present invention proposes and discloses a modulated data signal containing instructions readable by a processor residing within an analysis device, a computer system or a computer network for performing a method and/or parts thereof according to one or more embodiments disclosed herein.

Preferably, with reference to the computer-implemented aspects of the invention, one or more of the method steps, or even all of the method steps of the method according to one or more embodiments disclosed herein, may be performed by using a processor residing within the analysis device, computer or computer network. Thus, in general, any method steps including the provision and/or manipulation of data may be performed by using a processor residing within the analysis device, computer or computer network. Generally, these method steps may include any of the method steps, typically excluding method steps that require manual work, such as providing a sample and/or performing some aspect of the actual measurement.

Specifically, the invention also discloses:

an analysis device, a computer or a computer network comprising at least one processor, wherein the processor is adapted to perform a method according to one embodiment described in the present description and/or parts thereof,

a computer-loadable data structure adapted to perform a method according to one embodiment described in the present description and/or parts thereof, while the data structure is being executed on a computer,

a computer program, wherein the computer program is adapted to perform a method according to one embodiment described in the present description and/or parts thereof, while the program is executed on a processor residing on a computer or within an analysis device,

a computer program comprising program means for performing a method according to one embodiment described in the present description and/or parts thereof, while the computer program is executed on a processor residing within the analysis device, on a computer or on a computer network,

-a storage medium, wherein the data structure is stored on the storage medium, and wherein the data structure is adapted to perform a method according to one embodiment described in the present description and/or parts thereof after having been loaded into a main and/or working storage of an analysis device, a computer or a computer network, and

a computer program product having program code means, wherein the program code means may be stored or stored on a storage medium for performing a method according to one embodiment described in the present description and/or parts thereof, if the program code means is executed on an analysis device, a computer or a computer network.

Summarizing the findings of the present invention, reference is made in particular to the following examples:

example 1: a method for determining a concentration of at least one analyte in a bodily fluid, the method comprising:

a) applying a sample of a bodily fluid to a test carrier;

b) illuminating the test carrier by using at least one light source;

c) receiving light re-emitted by the test carrier by using at least one detector;

d) determining a concentration of the analyte by evaluating at least one detector signal generated by the detector;

wherein the at least one light source is modulated by using at least two modulation frequencies, wherein the detector signal is demodulated with the at least two modulation frequencies in order to generate at least two demodulated detector signals, each demodulated detector signal corresponding to one modulation frequency,

wherein the method comprises error detection based on a comparison of at least two demodulated detector signals.

Example 2: the method according to the aforementioned embodiment, wherein the error detection is an online error detection performed permanently or repeatedly.

Example 3: the method according to any of the preceding embodiments, wherein the at least one light source is modulated by using at least three modulation frequencies.

Example 4: the method according to any of the preceding embodiments, wherein the comparison of the at least two demodulated detector signals comprises at least one algorithm selected from the group consisting of: a comparison of at least one demodulated detector signal with at least one other demodulated detector signal; a comparison of the at least one demodulated detector signal with at least one average of the demodulated detector signal; comparison of the at least one demodulated detector signal with at least one threshold.

Example 5: the method according to any of the preceding embodiments, wherein the comparing of the at least two demodulated detector signals comprises comparing at least a first one of the demodulated detector signals with at least a second one of the demodulated detector signals and determining that the first demodulated detector signal is erroneous if the first demodulated detector signal deviates from the second demodulated detector signal by more than a predetermined margin, preferably by a margin of 0-2%, more preferably by a margin of 0-1%.

Example 6: the method according to any of the preceding embodiments, wherein the error detection comprises detecting an erroneous demodulated detector signal.

Example 7: the method according to the preceding embodiment, wherein the error detection further comprises rejecting erroneous demodulated detector signals and using only non-erroneous demodulated detector signals to determine the concentration of the at least one analyte in the body fluid.

Example 8: the method according to the preceding embodiment, wherein the demodulated detector signals are each a sequence of measured values, wherein rejecting erroneous demodulated detector signals comprises a rejection algorithm selected from the group consisting of: rejecting current measurements determined to be erroneous; the entire sequence of measurement values is rejected in case it is determined that at least one measurement value is erroneous.

Example 9: the method according to any of the preceding three embodiments, wherein the method is aborted in case all demodulated detector signals are determined to be erroneous.

Example 10: the method according to any of the preceding four embodiments, wherein the error detection comprises determining a degree of defectiveness for the demodulated detector signal determined to be erroneous.

Example 11: the method according to the preceding embodiment, wherein the at least one erroneous demodulated detector signal is used for determining the concentration of the analyte, wherein the degree of defectiveness is taken into account.

Example 12: the method according to any one of the preceding six embodiments, wherein the method is performed repeatedly, wherein in case an erroneous demodulated detector signal is found for a particular modulation frequency in one repetition of the method, said modulation frequency is not used in a subsequent repetition of the method.

Example 13: the method according to any of the preceding embodiments, wherein the at least one light source comprises at least one first light source modulated by at least two modulation frequencies and at least one second light source modulated by at least two modulation frequencies different from the at least two modulation frequencies used for modulating the first light source.

Example 14: the method according to the aforementioned embodiment, wherein the at least two demodulated detector signals are generated for a modulation frequency used for modulating the first light source, and wherein the at least two demodulated detector signals are generated for a modulation frequency used for modulating the second light source.

Example 15: the method according to the aforementioned embodiment, wherein the error detection is performed for both the demodulated detector signal modulating the modulation frequency used by the first light source and the demodulated detector signal modulating the modulation frequency used by the second light source.

Example 16: the method according to any one of the preceding embodiments, wherein each demodulated detector signal comprises a sequence of individual measurement values, wherein the error detection is based on a comparison of the individual measurement values.

Example 17: the method according to any one of the preceding embodiments, wherein the error detection is performed at least once before applying the sample of the body fluid to the test carrier.

Example 18: the method according to the preceding embodiment, wherein the method further comprises determining at least one dry empty value by evaluating at least one detector signal generated by the detector before applying the sample of the bodily fluid to the test carrier.

Example 19: the method according to the preceding embodiment, wherein the error detection is performed at least once during the determination of the dry empty value.

Example 20: the method according to any of the preceding embodiments, wherein the method further comprises at least one location verification step, wherein the location verification step comprises the method steps of:

i) inserting the test carrier into an analytical device;

ii) illuminating the test carrier by at least one light source;

iii) receiving light re-emitted by the test carrier by using at least one detector;

iv) determining at least one position of the test carrier within the analytical device by evaluating at least one detector signal generated by the detector, wherein the position comprises at least one of a position and/or an orientation of the test carrier.

Example 21: the method according to any of the preceding embodiments, wherein the method further comprises at least one ambient light error detection step, wherein the ambient light error detection step comprises the method steps of:

I. receiving light re-emitted from the test carrier by using at least one detector;

evaluating at least one detector signal generated by a detector;

performing ambient light error detection by comparing at least one detector signal generated by the detector with the modulation frequency.

Example 22: the method according to any of the preceding embodiments, wherein the method further comprises at least one ambient light error detection step, wherein the ambient light error detection step comprises the method steps of:

I. inserting the test carrier into an analytical device;

illuminating the test carrier by at least one light source;

receiving ambient light by using at least one detector;

evaluating at least one detector signal generated by the detector;

v. performing ambient light error detection by comparing at least one detector signal generated by the detector with the modulation frequency.

Example 23: the method according to any of the preceding embodiments, wherein demodulating comprises independently multiplying the detector signal with the modulation frequency and filtering the result by using a low pass filter.

Example 24: the method according to the preceding embodiment, wherein the demodulating comprises filtering the detector signal by using at least one band pass filter before multiplying the detector signal with the modulation frequency.

Example 25: the method according to the preceding embodiment, wherein the band pass filter is adjustable.

Example 26: the method according to any one of the preceding embodiments, wherein the test carrier is selected from the group consisting of: test strips, test tapes, test discs, and integrated test carriers having at least one test chemical and at least one lancet element.

Example 27: the method according to any one of the preceding embodiments, wherein the test carrier comprises at least one substrate and at least one test chemical applied to the substrate, wherein the test chemical is adapted to perform at least one detection reaction in the presence of the analyte to be detected and to change at least one optically detectable property as a result of the detection reaction.

Example 28: the method according to any of the preceding embodiments, wherein step d) is performed by using a data processing device and/or a computer.

Example 29: the method according to any of the preceding embodiments, wherein the error detection is performed by using a data processing device and/or a computer.

Example 30: the method according to one of the preceding embodiments, wherein the method further comprises at least one of the following method steps, such as before performing method step a):

i. inserting the test carrier into an analytical device;

initiating error detection;

obtaining a dry empty value.

Example 31: an analysis device for determining a concentration of at least one analyte in a body fluid, the analysis device comprising at least one receptacle for receiving at least one test carrier to which at least one sample of the body fluid is applicable, the analysis device further comprising at least one light source adapted for illuminating the test carrier, the analysis device further comprising at least one detector adapted for receiving light re-emitted by the test carrier, the analysis device further comprising at least one evaluation unit adapted for determining the concentration of the analyte by evaluating at least one detector signal generated by the detector, the analysis device further comprising at least one modulation device adapted for modulating the light source by using at least two modulation frequencies, the analysis device further comprising at least one demodulation device adapted for demodulating the detector signal with at least two modulation frequencies in order to generate at least two demodulated detector signals, each demodulated detector signal corresponding to a modulation frequency, the analysis device further comprising at least one error detection device adapted for performing error detection based on a comparison of at least two demodulated detector signals.

Example 32: the analysis device according to the previous embodiment, wherein the analysis device is adapted to perform the method according to any of the previous method embodiments.

Example 33: the analysis device according to any of the preceding embodiments of the reference device, wherein the evaluation unit comprises a data processing device and/or a computer.

Example 34: the analysis device according to any of the preceding embodiments with reference to the device, wherein the error detection device comprises a data processing device and/or a computer.

Example 35: the analysis device according to any of the preceding embodiments with reference to the device, wherein the modulation device comprises at least one signal source.

Example 36: the analysis device according to the aforementioned embodiment, wherein the signal source is adapted to generate a control signal having at least two modulation frequencies.

Example 37: the analysis device according to any of the preceding embodiments with reference to the device, wherein the error detection device is adapted to perform the error detection as an online error detection, which is performed permanently or repeatedly.

Example 38: the analysis device according to any of the preceding embodiments with reference to the device, wherein the modulation device is adapted to modulate the light source by using at least three modulation frequencies.

Example 39: the analysis device according to any of the preceding embodiments of the reference device, wherein the error detection device is adapted such that the comparison of the at least two demodulated detector signals comprises at least one algorithm selected from the group consisting of: a comparison of at least one demodulated detector signal with at least one other demodulated detector signal; a comparison of the at least one demodulated detector signal with at least one average of the demodulated detector signal; comparison of the at least one demodulated detector signal with at least one threshold.

Example 40: the analysis device according to any of the preceding embodiments of the reference device, wherein the error detection device is adapted such that the comparison of the at least two demodulated detector signals comprises comparing at least a first one of the demodulated detector signals with at least a second one of the demodulated detector signals and determining that the first demodulated detector signal is erroneous if the first demodulated detector signal deviates from the second demodulated detector signal by more than a predetermined margin, preferably by a margin of 0-2%, more preferably by a margin of 0-1%.

Example 41: the analysis device according to any of the preceding embodiments with reference to the device, wherein the error detection device is adapted such that the error detection comprises detecting an erroneous demodulated detector signal.

Example 42: the analysis device according to the previous embodiment, wherein the error detection device is adapted such that the error detection further comprises rejecting erroneous demodulated detector signals and using only non-erroneous demodulated detector signals for determining the concentration of the at least one analyte in the body fluid.

Example 43: the analysis device according to the preceding embodiment, wherein the demodulation device is adapted such that the demodulated detector signals are each a sequence of measured values, wherein rejecting erroneous demodulated detector signals comprises a rejection algorithm selected from the group consisting of: rejecting current measurements determined to be erroneous; the entire sequence of measurement values is rejected in case it is determined that at least one measurement value is erroneous.

Example 44: the analysis device according to any of the preceding three embodiments, wherein the analysis device is adapted such that determining the concentration of the analyte is aborted if all demodulated detector signals are determined to be erroneous.

Example 45: the analysis device according to any of the preceding four embodiments, wherein the error detection device is adapted such that the error detection comprises determining a degree of defect for the demodulated detector signal determined to be erroneous.

Example 46: the analysis device according to the preceding embodiment, wherein the evaluation unit is adapted such that the at least one erroneous demodulated detector signal is used for determining the concentration of the analyte, wherein the degree of defect is taken into account.

Example 47: the analysis device according to any of the preceding embodiments with reference to the device, wherein the at least one light source comprises at least one first light source modulated by at least two modulation frequencies and at least one second light source modulated by at least two modulation frequencies different from the at least two modulation frequencies used for modulating the first light source.

Example 48: the analysis device according to the aforementioned embodiment, wherein the demodulation device is adapted such that at least two demodulated detector signals are generated for a modulation frequency used for modulating the first light source, and wherein at least two demodulated detector signals are generated for a modulation frequency used for modulating the second light source.

Example 49: the analyzing device according to the aforementioned embodiment, wherein the error detection device is adapted such that the error detection is performed for both the demodulated detector signal for the modulation frequency used for modulating the first light source and for the demodulated detector signal for the modulation frequency used for modulating the second light source.

Example 50: the analysis device according to any one of the preceding embodiments of the reference device, wherein the demodulation device is adapted such that each demodulated detector signal comprises a sequence of individual measurement values, wherein the error detection device is adapted such that the error detection is based on a comparison of the individual measurement values.

Example 51: the analysis device according to any of the preceding embodiments of the reference device, wherein the error detection device is adapted such that the error detection is performed at least once before applying the sample of the body fluid to the test carrier.

Example 52: the analysis device according to the previous embodiment, wherein the analysis device is adapted to determine the at least one dry empty value by evaluating at least one detector signal generated by the detector before applying the sample of the body fluid to the test carrier.

Example 53: the analyzing device according to the previous embodiment, wherein the error detecting device is adapted such that the error detection is performed at least once during the determination of the dry empty value.

Example 54: the analysis device according to any of the preceding embodiments with reference to the device, wherein the demodulation device is adapted such that the demodulation comprises independently multiplying the detector signal with the modulation frequency and filtering the result by using a low-pass filter.

Example 55: the analysis device according to the preceding embodiment, wherein the demodulation device is adapted such that the demodulation comprises filtering the detector signal by using at least one band pass filter before multiplying the detector signal with the modulation frequency.

Example 56: the analysis device according to the previous embodiment, wherein the band-pass filter is adjustable.

Example 57: an analysis system for determining the concentration of at least one analyte in a body fluid, the analysis system comprising an analysis device according to any of the preceding device embodiments, the analysis system further comprising at least one test carrier.

Example 58: the assay system according to the preceding embodiment, wherein the test carrier is selected from the group consisting of: test strips, test tapes, test discs, and integrated test carriers having at least one test chemical and at least one lancet element.

Example 59: the assay system according to any one of the two preceding embodiments, wherein the test carrier comprises at least one substrate and at least one test chemical applied to the substrate, wherein the test chemical is adapted to perform at least one detection reaction in the presence of the analyte to be detected and to change at least one optically detectable property as a result of the detection reaction.

Drawings

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

In the drawings:

fig. 1 shows a schematic view of an exemplary embodiment of the proposed analysis system comprising an exemplary embodiment of the proposed analysis apparatus and a test carrier; and

fig. 2 shows an exemplary embodiment of the signals of the detector.

Detailed Description

In fig. 1, a schematic diagram of an analysis system 110 for determining a concentration of at least one analyte in a body fluid 112 is depicted. The analysis system 110 includes an analysis device 114. In addition, the analysis system 110 includes a test carrier 116, which in this exemplary embodiment may be embodied as a test strip. The test carrier 116 may include at least one substrate 118 and at least one test chemical 120, which may be applied to the substrate 118 and/or integrated into the substrate 118. The test chemical 120 is adapted to change at least one optically detectable property as a result of the detection reaction. The analysis device 114 comprises a receptacle 122 into which the test carrier 116 can be inserted.

The analyzing device 114 may comprise at least one, preferably two or more modulating devices 124. Each modulation device 124 may include at least one signal source 125. Each signal source 125 may generate a different set of control signals, such as three or more control signals, having different modulation frequencies, such as three or more different modulation frequencies.

In the embodiment depicted in fig. 1, the three modulation frequencies of the three control signals of the first modulation device 124 are represented by f_1a, f_1bAnd f_1cAnd the three modulation frequencies of the three control signals of the second modulation device 124 are denoted by f_2a, f_2bAnd f_2cAnd (4) showing.

For further reference, devices and processes involving a first set of frequencies may be referred to as a first channel, while devices, frequencies and processes involving a second set of frequencies may be referred to as a second channel. The analysis device may also include two or more mixer units 126. For potential details of the mixer unit 126 reference may be made to EP 1912058B 1. The control signal generated by the first channel may be passed into a mixer unit 126a and the control signal of the second channel may be passed into another mixer unit 126 b. In both channels, the control signal may be generated by mixing the three control signals in the mixer unit 126.

The analyzing device 114 comprises at least one light source 127. The light source 127 includes a first light source 128 and a second light source 130 as depicted in fig. 1. The first light source 128 may be controlled by a control signal of a first channel, and the second light source 130 may be controlled by a control signal of a second channel. Test carrier 116 is illuminated by light originating from first light source 128 and second light source 130. The test carrier 116 re-emits light that is detected by the detector 132. The detector 132 may convert the optical signal into an electronic signal, which is also referred to as detector signal in the following and is symbolically referred to with reference numeral 133 in fig. 1. The detector signal 133 is modulated by six modulation frequencies in this embodiment.

The analysis device 114 further comprises at least one demodulation device 134. The demodulation device 134 is adapted to demodulate the signal of the detector 132. As shown in fig. 1, the demodulation device 134 may include three multiplication devices 136 and three low pass filters 138 for each of the two channels. In each multiplication device 136, the detector signal may be multiplied or mixed with a modulation frequency, wherein each modulation frequency is used only once. In each low pass filter 138, the result of the previous multiplication may be filtered. Thus, at the output port of the respective low pass filter 138, a demodulated detector signal may be provided, symbolically represented in fig. 1 by reference numeral 139. In an alternative naming process, each of the outputs providing demodulated detector signals 139 may form a channel of demodulation device 134.

As depicted in fig. 1, the combination of one multiplication device 136 and one low pass filter 138 may be implemented as a lock-in amplifier 140. The demodulation device 134 may further include a band pass filter 142 configured to filter the detector signal before passing the detector signal to the lock-in amplifier 140.

The analysis device 114 further comprises (e.g. for each of the two channels) an error detection device 144 configured to perform error detection. The error detection device 144 may be adapted to perform a comparison procedure, which is symbolically indicated in fig. 1 by reference numeral 146. During the comparison procedure 146, the demodulated detector signal 139, which is indicated as val (f), may be compared_{1a, b, c}) And val (f)_{2a, b, c}). E.g., in the first channel, at the demodulated detector signal val (f)_1a), val (f_1b) And val (f)_1c) May reject demodulated detections of respective susceptible frequencies from further evaluation in case one of the demodulated detector signals differs from the other demodulated detector signals by more than a certain threshold valueThe detector signal. As long as the two demodulated detector signals are equal, at least within a predetermined or adjustable tolerance, an average value can be calculated from these demodulated detector signals for further evaluation. If all demodulated detector signals differ from each other by more than a predetermined or adjustable threshold, an error value may be issued and/or photometric measurements may be restarted with a new set of frequencies. The comparison process 146 may be performed using a data processing device and/or a computer.

Error detection may be performed as online error detection. Thus, error detection may be performed repeatedly or permanently during photometric measurements. Additionally, error detection may be performed prior to applying the sample of bodily fluid 112 to the test carrier 116, for example, during a determination of a dry empty value.

Furthermore, the analysis device 114 of fig. 1 comprises an evaluation unit 148 adapted for determining the concentration of the analyte by evaluating the input of the error detection device 144 of each of the two channels. In the evaluation unit 148, the concentrations of the analytes determined in the two channels may be compared and an error value may be issued if the determined values differ from each other by more than a certain threshold value. For details of the evaluation unit 148 reference may be made to the disclosure given above and/or to the prior art documents as cited above.

In fig. 2, an exemplary embodiment of the signal 133 of the detector 132 is depicted. The dependence of the frequency f Hz on the attenuation a dB is depicted. The signal 133 may include six modulation frequencies 150 and 160. The signal 133 may be determined by the detector 132 before demodulation by the demodulation device 136 and before the measurement result is determined by the evaluation unit 148. The signal 133 may not include disturbances. The six modulation frequencies 150-160 used may have equal strength. Further, the signal-to-noise ratio, SNR, of the signal 133 is shown. The SNR may be large enough to distinguish each modulation frequency 150 and 160 from the noise of the detector 132.

List of reference numerals

110 analysis system

112 body fluid

114 analysis device

116 test carrier

118 substrate

120 test chemical

122 container

124 modulation device

125 signal source

126 mixer unit

127 light source

128 first light source

130 second light source

132 detector

133 detector signal

134 demodulation apparatus

136 multiplication device

138 low pass filter

139 demodulated detector signal

140 lock-in amplifier

142 band-pass filter

144 error detection apparatus

146 comparison procedure

148 evaluation unit

150 modulation frequency

152 modulation frequency

154 modulation frequency

156 modulation frequency

158 modulation frequency

160 modulation frequency.

Claims (18)

1. A method for determining a concentration of at least one analyte in a bodily fluid (112), the method comprising:

a) applying a sample of a bodily fluid (112) to a test carrier (116);

b) illuminating the test carrier (116) by using at least one light source (127) comprising at least one first light source modulated by at least two modulation frequencies and at least one second light source modulated by at least two modulation frequencies different from the at least two modulation frequencies used for modulating the first light source;

c) receiving light re-emitted by the test carrier (116) by using at least one detector (132);

d) determining a concentration of the analyte by evaluating at least one detector signal generated by a detector (132);

wherein the at least one light source (127) is modulated by using at least two different modulation frequencies, wherein the detector signal is demodulated with the at least two modulation frequencies in order to generate at least two demodulated detector signals, each demodulated detector signal corresponding to one modulation frequency,

wherein the method comprises error detection based on a comparison of at least two demodulated detector signals.

2. The method according to claim 1, wherein the error detection is an online error detection performed permanently or repeatedly.

3. The method according to claim 1 or 2, wherein the at least one light source (127) is modulated by using at least three modulation frequencies.

4. A method according to claim 1 or 2, wherein the error detection comprises detecting an erroneous demodulated detector signal.

5. The method according to claim 4, wherein the error detection further comprises rejecting erroneous demodulated detector signals and using only non-erroneous demodulated detector signals for determining the concentration of the at least one analyte in the body fluid (112).

6. The method of claim 5, wherein at least one erroneous demodulated detector signal is used to determine the concentration of the analyte, wherein the degree of defectiveness is taken into account.

7. The method according to claim 1 or 2, wherein the at least one light source (127) comprises at least one first light source (128) modulated by at least two modulation frequencies and at least one second light source (130) modulated by at least two modulation frequencies different from the at least two modulation frequencies used for modulating the first light source.

8. The method of claim 7, wherein the at least two demodulated detector signals are generated for a modulation frequency used to modulate the first light source (128), and wherein the at least two demodulated detector signals are generated for a modulation frequency used to modulate the second light source (130).

9. The method of claim 8, wherein the error detection is performed for both a demodulated detector signal of a modulation frequency used to modulate the first light source (128) and a demodulated detector signal of a modulation frequency used to modulate the second light source (130).

10. Method according to claim 1 or 2, wherein the error detection is performed at least once before applying the sample of the body fluid (112) to the test carrier (116).

11. The method according to claim 10, wherein the method further comprises determining at least one dry empty value by evaluating at least one detector signal generated by the detector (132) before applying the sample of the body fluid (112) to the test carrier (116).

12. A method according to claim 1 or 2, wherein the method further comprises at least one location verification step, wherein the location verification step comprises the method steps of:

i) inserting the test carrier (116) into an analysis device (114);

ii) irradiating the test carrier (116) by at least one light source (127);

iii) receiving light re-emitted by the test carrier (116) by using at least one detector (132);

iv) determining at least one position of the test carrier (116) within the analytical device (114) by evaluating at least one detector signal (133) generated by the detector (132), wherein the position comprises at least one of a position or an orientation of the test carrier (116).

13. A method according to claim 1 or 2, wherein the method further comprises at least one ambient light error detection step, wherein the ambient light error detection step comprises the method steps of:

I. receiving ambient light by using at least one detector (132);

evaluating at least one detector signal generated by a detector (132);

performing ambient light error detection by comparing at least one detector signal generated by the detector (132) with the modulation frequency.

14. A method according to claim 1 or 2, wherein demodulating comprises independently multiplying the detector signal with the modulation frequency and filtering the result by using a low pass filter (138).

15. The method of claim 14, wherein demodulating comprises filtering the detector signal by using at least one band pass filter (142) before multiplying the detector signal by the modulation frequency.

16. The method according to claim 1 or 2, wherein the method further comprises at least one of the following method steps:

-inserting the test carrier (116) into the analysis device (114);

-initiating an error detection;

-obtaining a dry empty value.

17. An analytical device (114) for determining a concentration of at least one analyte in a body fluid (112), the analytical device (114) comprising at least one receptacle (122) for receiving at least one test carrier (116), wherein at least one sample of the body fluid (112) is applicable to the test carrier (116), the analytical device (114) further comprising at least one light source (127) adapted for illuminating the test carrier (116), the at least one light source comprising at least one first light source modulated by at least two modulation frequencies and at least one second light source modulated by at least two modulation frequencies different from the at least two modulation frequencies used for modulating the first light source, the analytical device (114) further comprising at least one detector (132) adapted for receiving light re-emitted by the test carrier (116), the analytical device (114) further comprising at least one detector signal adapted for determining the analyte by evaluating at least one detector signal generated by the detector (132) At least one evaluation unit (148) of the concentration of (b),

the analyzing device (114) further comprises at least one modulating device (124) adapted for modulating the light source (127) by using at least two different modulation frequencies, the analyzing device (114) further comprises at least one demodulating device (134) adapted for demodulating the detector signal with the at least two modulation frequencies in order to generate at least two demodulated detector signals, each demodulated detector signal corresponding to one modulation frequency,

the analyzing device (114) further comprises at least one error detection device adapted for performing error detection based on a comparison of the at least two demodulated detector signals.

18. An analysis system (110) for determining a concentration of at least one analyte in a body fluid (112), the analysis system (110) comprising an analysis device (114) according to claim 17, the analysis system (110) further comprising at least one test carrier (116).