Methods for correcting a DC current, recorded by an amperometric sensor in contact with a medical fluid, for a time-dependent hct-induced current drift
The method of batch and individual cartridge characterization with impedance and conductivity measurements addresses time-dependent Hct interference in amperometric sensors, enhancing accuracy and sensitivity while extending sensor life and reducing rejects.
Patent Information
- Application Number
- PCT/EP2025/071756
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-07-31
- Filing Date
- 2025-07-29
- Publication Date
- 2026-02-05
AI Technical Summary
Amperometric sensors used in in vitro diagnostics face time-dependent interference from hematocrit (Hct) levels, leading to inaccurate metabolite concentration measurements due to varying Hct effects over time, which current compensation methods fail to address effectively.
A method involving batch and individual cartridge characterization to determine a correction factor for time-dependent Hct-induced current drift, using impedance and conductivity measurements to calibrate Hct and analyte concentrations, allowing precise compensation for Hct interference.
Improves the accuracy and sensitivity of amperometric sensors by effectively correcting for time-dependent Hct-induced drift, extending their usable life and reducing rejected sensors due to non-compliance with quality standards.
Smart Images

Figure EP2025071756_05022026_PF_FP_ABST
Abstract
Description
[0001] Methods for correcting a DC current, recorded by an amperometric sensor in contact with a medical fluid, for a time-dependent Hct-induced current drift Field of the Invention The present invention relates to Methods for correcting a DC current, recorded by an amperometric sensor in contact with a medical fluid, for a time-dependent Hct-induced current drift in the field of in vitro diagnostics (IVD). Background of the Invention Amperometric sensors are commonly used in IVD measuring the concentration of various analytes in biological, specifically medical samples. These sensors are based on the principle of amperometry, which involves measuring the current generated by a redox reaction at an electrode surface. In the field of IVD, amperometric sensors are used for a wide range of applications. Some common uses include glucose monitoring, enzyme-based assays, electrochemical immunoassays, and DNA / RNA analysis. Amperometric sensors are used in glucose monitoring devices such as blood glucose meters. They enable detecting the concentration of glucose in a blood sample, allowing individuals with diabetes to monitor their blood sugar levels. Further, amperometric sensors can be employed in enzyme-based assays to measure the activity of specific enzymes in biological samples. These assays are used for diagnostic purposes, such as assessing liver function or detecting certain diseases. Moreover, amperometric sensors are utilized in electrochemical immunoassays, which are used to detect and quantify specific antibodies or antigens in biological samples. These assays are valuable in diagnosing infectious diseases and monitoring autoimmune disorders. In addition, amperometric sensors can also be employed in DNA or RNA analysis techniques, such as DNA sequencing or genotyping. They can detect the electrochemical signals generated during these processes, providing valuable information about the genetic composition of the sample. Amperometric sensors may comprise blood gas / electrolyte (BGE) metabolite sensors and / or metabolite sensors that are used in BGE cartridges to enable the detection of concentrations of metabolites such as for example glucose, lactate, creatinine and / or other small molecules including amino acids, lipids, peptides, nucleic acids, carbohydrates, vitamins, and / or minerals. The applied and / or analyzed samples usually comprise whole blood or components thereof. Such amperometric sensors often comprise membrane-covered enzyme-containing anodes as working electrodes. Usually, a three-electrode layout comprises a working electrode, a reference electrode and a counter electrode (also denoted “auxiliary electrode”). In these cases, when analyzing blood samples, it is a common problem that such amperometric sensors exhibit an unwanted sensitivity towards Hematocrit (Hct), the red blood cell component of blood. Hct increasingly interferes resulting in a time-dependent measurement bias. Hct levels are measured in terms of percentage volume fraction of whole blood (i.e. the volumetric fraction of erythrocytes in whole blood) and can vary significantly among individuals. Typical values range between 36–53% in healthy individuals and may extend significantly beyond this range due to physiological and medical factors. Whole blood samples with Hct levels above a certain value may reduce the response, such as a current readout (e.g. in a blood glucose measurement), and therefore have a negative bias when compared with laboratory reference methods. Conversely, for Hct values in a lower range, the response may have a positive bias relative to the reference. This phenomenon has been attributed to diffusion due to increased sample viscosity or the action of RBCs to impede plasma diffusion to the sensor reagent zone and to pore blockage in membrane-based devices. (Vanavanan S., et al.; Performance of a new interference-resistant glucose meter. Clin Biochem.2010; 43(1-2):186–92.) In more, detail, when using multiple amperometric sensors, as for example in BGE analyzers, the cover membrane serves to limit the metabolite flux towards the electrode and thus allows for measurement of diffusion-limited current levels which are indicative of the metabolite concentration. The diffusion of the to-be-measured metabolite in whole blood towards and through the top surface of the used cover membrane is reduced by the erythrocytes contained in the whole blood sample, expressed by the Hct. Consequently, the measured current is falsely negative at elevated Hct levels if no compensation of Hct interference is implemented into themeasurement algorithm (see Fig.1). In Fig.1, the measured Glucose concentration as a functionof Hct of analyzed blood samples is shown for a 12 days in-use time (left diagram of Fig. 1)and for a 10 days in-use time (right diagram of Fig. 1). As can be seen from the diagrams, themeasured glucose concentration on the one hand depends on the Hct concentration and on the other hand on the in-use time. The longer the amperometric sensor is in use and the more Hct is present, the lower the Glucose concentration is measured. Typically, the Hct is measured conductimetrically by an electrode pair, allowing for compensation of the Hct impaired metabolite sensor signal based by an a priori correlation between Hct levels and metabolite-induced sensor current levels. However, the described compensation of Hct-induced signal errors is based on the assumption, that the Hct induced effect onto metabolite sensor signal is constant over time. It was found however, that this is notalways the case. Fig. 2 depicts the Hct effect onto the signal at two different points in time afterstart (10 days vs. 20 days), in other words, it shows the measured Glucose concentration as afunction of in-use time (days, d) and Hct of blood samples analyzed. As evident from Fig. 2,the measurement of solutions of constant Glucose concentration, yet variable Hct, have been observed to decrease with increasing Hct in dependence of its in-use time. Permeability of the metabolite through the membrane may vary due to wet-up and adsorption effects. Consequently, the effect of Hct onto overall mass transfer of the metabolite may vary over in- use time. Hence, the Hct effect constantly alters the performance of the amperometric sensor over time and it is not possible to apply a fixed correction factor to precisely compensate for this effect. Nevertheless, the compensation of a Hct interference is performed based on the assumption that the Hct effect onto the current readout of the metabolite sensor is constant over time. Hct is therefore determined by the measurement of the impedance Z between at least two conductivity electrodes, e.g. two blank electrodes, via an established relation between impedance value andHct as shown in Fig. 3 assuming that the Hct effect onto the current readout of the metabolitesensor is constant over time, a constant correction factor ∆^^ = × ∆1 / ^^ is used to determine^^^^^^^^^^. = ^^^^^^^^^^. − ∆^^.Therefore, amperometric sensors, specifically BGE metabolite sensors may deliver results, which require further improvement in accuracy and / or sensitivity increasingly over time even if a correction for the Hct effect is applied. Summary of the Invention It is therefore desirable to provide improved methods and concepts for compensation of Hct- induced interferences, specifically time-dependent Hct-induced interferences in amperometric sensors that are used to detect metabolites and / or measure the concentration of metabolites in whole blood samples. In general, it is also desirable to improve the degree of accuracy and / or sensitivity of amperometric sensors. Moreover, it is desirable to extend the usage time of an amperometric sensor and / or to reduce the number of rejected amperometric sensors after a random sampling of a batch of amperometric sensors, which does not fulfill the pre-set quality standards. At least some of the said problems and / or challenges are overcome by the aspects of this disclosure, specifically by the subject-matter covered by the independent claims and / or by one or more embodiments thereof. Optional and specific embodiments are covered by the dependent claims.According to a first aspect, a first method of correcting a DC current (^^^^^^^^^^^^^^(^^^^^^^^, ^^)),recorded by an amperometric sensor in contact with a medical fluid, for a time-dependent Hct-induced current drift (∆^^(^^^^^^^^, ^^)) comprises:a. Providing a batch of at least two cartridges comprising at least one test cartridge and at leastone sample cartridge, each cartridge comprising: a fluid container system configured to receive a fluid, and, in contact with an interior volume of the fluid container system, at least two conductivity electrodes (K1, K2,…) and the amperometric sensor; Performing a batch characterization by: a1. Recording with the amperometric sensor of the at least one test cartridge, at at least two different points in time (t) over an in-use period (d), the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^, ^^)) ofat least two medical reference fluids with differing determined Hct concentrations (^^^^^^^^)and identical determined analyte concentration (^^^^^^^^^^^^^^^^), the medical reference fluidsbeing filled for the respective recording in the fluid container system, and obtaining a dependence of the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^, ^^)) from the Hct concentration (^^^^^^^^) foreach of the at least two points in time (t); Performing an individual cartridge characterization of the at least one sample cartridge by:b. Hct-calibrating the at least two conductivity electrodes (K1, K2, …) of the sample cartridgefor an Hct-concentration (^^^^^^^^) by recording a conductivity parameter ^^(^^^^^^^^ ) with the atleast two conductivity electrodes (K1, K2, …) for at least two Hct-calibration fluids with differing determined Hct-concentrations (^^^^^^^^) being filled for the respective recording inthe fluid container system, and obtaining an Hct-calibration curve (^^(^^^^^^^^)^^^^. ^^^^^^^^);c. Analyte-calibrating the amperometric sensor of the sample cartridge for the analyteconcentration (^^^^^^^^^^^^^^^^) by recording a current with the amperometricsensor for at least two analyte-calibration fluids with differing analyte-concentrations (^^^^^^^^^^^^^^^^) being filled for the respective recording in the fluid container system, and obtaining an analyte-calibration curve ^^^^^^^^^^^^^^^^);d. Recording the impedance (^^^^^^^^.) with each recording of the current (^^^^^^^^.(^^^^^^^^^^^^^^^^)) duringthe analyte-calibration and determining the respective quotient (^^ = ^^^^^^^^.(^^^^^^^^^^^^^^^^) ∙ ^^^^^^^^)of the impedance (^^^^^^^^.) and the current (^^^^^^^^.(^^^^^^^^^^^^^^^^)) for each of the at least two analyte-calibration fluids and forming the mean value of all determined quotients (^ത^); At a point in time (^^^^^^^^^^) of an actual measurement during the in-use period (d) of the at least one sample cartridge:e. Determining the Hct-concentration (^^^^^^^^) of the medical fluid filled in the fluid containersystem by recording the conductivity parameter ^^(^^^^^^^^ ) with the at least two calibratedconductivity electrodes (K1, K2, …) and by reading the Hct-concentration (^^^^^^^^) from theHct-calibration curve;f. Determining an impedance difference ∆^^ from the dependence of the impedance(^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^, ^^)) from the Hct concentration (^^^^^^^^) determined in the test cartridge bysubtracting from the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^, ^^)) for the point in time (t) thatcorresponds to the point in time (^^^^^^^^^^) of the actual measurement and for the determinedHct-concentration (^^^^^^^^) of the medical fluid the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^, ^^)) for thepoint in time (t) that corresponds to the point in time (^^^^^^^^^^) of the actual measurement andfor the Hct-concentration (^^^^^^^^) which equals 0:∆^^ = (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^ = det. ^^^^^^^^ of med. fluid, ^^ = ^^^^^^^^^^) − (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^ = 0, ^^ =^^^^^^^^^^);g. Determine a correction factor corresponding to the Hct-induced current drift by multiplyingthe impedance difference ∆^^ with the mean value of all determined quotients (^ത^):∆^^(^^^^^^^^, ^^) = ∆^^ ∙ ^ത^ ; andh. Recoding the DC current ^^^^^^^^^^^^^^.(^^^^^^^^, ^^) with the amperometric sensor and correct for thetime-dependent Hct-induced current drift ∆^^(^^^^^^, ^^) by determining the corrected current(^^^^^^^^^^): The method according to the first aspect effectively and precisely compensates for Hct-induced interferences, specifically time-dependent Hct-induced interferences in amperometric sensors that are used to detect metabolites and / or measure the concentration of metabolites in whole blood samples. It allows improving the degree of accuracy and / or sensitivity of amperometric sensors. Moreover, the usage time of an amperometric sensor can be extended as strong Hct effects over a long in-use time can be compensated. Further, the number of rejected goods can be reduced after a random sampling of a batch of amperometric sensors, which would usually without proper compensation not fulfill the pre-set quality standards. The method according to the first aspect relies on a characterization of a batch of cartridges that comprise at least one amperometric sensor. In other words, one or more cartridges is characterized representing an example for the entity of the batch of cartridges. This is possible as the production circumstances for the entity of the batch are similar or even the same. In terms of the first aspect, the test cartridge of the batch of cartridges may be understood as a cartridge that is used for performing the batch characterization of the method according to the first aspect and may be disposed afterwards. The sample cartridge may in general be understood herein as the cartridge of interest that is supposed to be used for the testing of a patient’s blood, for example.According to a second aspect, a second method of correcting a DC current (^^^^^^^^^^^^^^(^^^^^^^^, ^^)),recorded by an amperometric sensor in contact with a medical fluid, for a time-dependent Hct-induced current drift (∆^^(^^^^^^^^, ^^)) comprises:a. Providing at least one sample cartridge comprising:a fluid container system configured to receive a fluid, and, in contact with an interior volume of the fluid container system, at least two conductivity electrodes (K1, K2,…) and the amperometric sensor;b. Hct-calibrating the at least two conductivity electrodes (K1, K2, …) of the sample cartridgefor an Hct-concentration (^^^^^^^^) by recording a conductivity parameter ^^(^^^^^^^^ ) with the atleast two conductivity electrodes (K1, K2, …) for at least two Hct-calibration fluids with differing determined Hct-concentrations (^^^^^^^^) being filled for the respective recording inthe fluid container system, and obtaining an Hct-calibration curve (^^(^^^^^^^^)^^^^. ^^^^^^^^);c. Analyte-calibrating the amperometric sensor of the sample cartridge for the analyteconcentration (^^^^^^^^^^^^^^^^) by recording a current with the amperometricsensor for at least two analyte-calibration fluids with differing analyte-concentrations (^^^^^^^^^^^^^^^^) being filled for the respective recording in the fluid container system, and obtaining an analyte-calibration curve ^^^^^^^^^^^^^^^^);d. Recording the impedance (^^^^^^^^.) with each recording of the current (^^^^^^^^.(^^^^^^^^^^^^^^^^)) duringthe analyte-calibration and determining the respective quotient (^^ = ^^^^^^^^.(^^^^^^^^^^^^^^^^) ∙ ^^^^^^^^)of the impedance (^^^^^^^^.) and the current (^^^^^^^^.(^^^^^^^^^^^^^^^^)) for each of the at least two analyte-calibration fluids and forming the mean value of all determined quotients (^ത^); At a point in time (^^^^^^^^^^) of an actual measurement during the in-use period (d) of the at least one sample cartridge:e. Determining the Hct-concentration (^^^^^^^^) of the medical fluid filled in the fluid containersystem by recording the conductivity parameter ^^(^^^^^^^^ ) with the at least two calibratedconductivity electrodes (K1, K2, …) and by reading the Hct-concentration (^^^^^^^^) from theHct-calibration curve;f. Recording the impedance (^^^^^^^^^^^^^^(^^^^^^^^, ^^)) of the medical fluid having the determinedHct-concentration (^^^^^^^^) and determining an impedance difference ∆^^ by subtracting fromthe recorded impedance (^^^^^^^^^^^^^^(^^^^^^^^, ^^)) of the medical fluid the impedance being derivedfrom the recorded impedances (^^^^^^^^.) during the analyte-calibration corresponding to thesame analyte concentration of the medical fluid, the point in time (^^^^^^^^^^) of the actual measurement, and the Hct-concentration (^^^^^^^^) which equals 0: ^^^^^^^^^^);g. Determine a correction factor corresponding to the Hct-induced current drift by multiplyingthe impedance difference ∆^^ with the mean value of all determined quotients (^ത^):∆^^(^^^^^^^^, ^^) = ∆^^ ∙ ^ത^ ; andh. Recoding the DC current ^^^^^^^^^^^^^^.(^^^^^^^^, ^^) with the amperometric sensor and correct for thetime-dependent Hct-induced current drift ∆^^(^^^^^^, ^^) by determining the corrected current(^^^^^^^^^^): The method according to the second aspect effectively and precisely compensates for Hct- induced interferences, specifically time-dependent Hct-induced interferences in amperometric sensors that are used to detect metabolites and / or measure the concentration of metabolites in whole blood samples. It allows improving the degree of accuracy and / or sensitivity of amperometric sensors. Moreover, the usage time of an amperometric sensor can be extended as strong Hct effects over a long in-use time can be compensated. Further, the number of rejected goods can be reduced after a random sampling of a batch of amperometric sensors, which would usually without proper compensation not fulfill the pre-set quality standards. The method according to the second aspect relies on a characterization of each individual cartridge that comprises at least one amperometric sensor. In other words, each cartridge, specifically each cartridge of a batch, is characterized individually. The method according to aspect 1 and the method according to aspect 2 may represent alternative methods. Applying to the entire disclosure, a “cartridge” may correspond to a cartridge for blood gas / electrolyte detection (BG / E or BGE cartridge). The cartridge may be considered a disposable device used in blood gas analyzers to measure various parameters in a patient's blood sample. The cartridge may therefore be disposed after several uses and / or after several hours and / or days of use. These cartridges may enable rapid and accurate analysis of blood gases (such as oxygen and carbon dioxide), electrolytes (such as sodium, potassium, and chloride), and other related parameters. The cartridge typically contains electrodes and sensors that interact with the blood sample to measure the concentrations of different analytes. It may also include reagents and / or solutions for the chemical reactions involved in the measurement process. The cartridge may be inserted into a blood gas analyzer, where it interfaces with the instrument's measurement system. The blood sample (typically whole blood or components thereof) may be introduced into the cartridge through a port or opening, and the analytes may be measured using various detection methods, such as potentiometry, amperometry, and / or ion- selective electrodes. The results may then be displayed on the analyzer's screen or transmitted to a connected computer system for interpretation and analysis. Cartridges for blood gas / electrolyte detection may be designed for single-use or usage of only a predetermined number of times for a single sample to ensure accuracy and prevent cross-contamination between samples. Cartridges for blood gas / electrolyte detection may be designed for usage of a predetermined number of times of different samples with a cleaning procedure between the measurement of each sample to prevent cross-contamination between samples. BG / E analysis and diagnostics is an important method in clinical settings, such as hospitals, to monitor and assess a patient's acid-base balance, oxygenation status, and / or electrolyte levels and a BGE cartridge having the hardware and / or electronics in contact with the sample is essential to a BGE analyzer. Applying to the entire disclosure, an “amperometric sensor” may correspond to a type of electrochemical sensor that is configured to measure the concentration of a specific / predetermined analyte based on a current (response) generated from an electrochemical reaction. It operates by detecting changes in current flow resulting from a redox reaction between the analyte of interest and the sensing electrode. The basic setup of an amperometric sensor generally includes a working electrode, a reference electrode, and / or a counter electrode. The working electrode may be made of a conductive material coated with a catalyst or enzyme specific to the target analyte. The reference electrode may provide a stable and known potential, while the counter electrode may complete the electrical circuit. When the analyte of interest comes into contact with the working electrode, an oxidation or reduction reaction may occur. This leads to the transfer of electrons and the generation of a current proportional to the analyte concentration. The current is measured and converted into a quantitative measurement of the analyte concentration. Amperometric sensors are commonly used in various fields, including environmental monitoring, biomedical applications, and industrial processes. They offer advantages such as high sensitivity, fast response times, and the ability to measure a wide range of analytes. Specific designs and configurations of amperometric sensors may vary depending on the intended application and the analyte being measured. Different sensing materials and techniques may be employed to optimize sensitivity and selectivity. Hematrocrit (Hct), also known as packed cell volume (PCV), is a measure of the volume percentage of red blood cells (RBCs) in whole blood – for simplicity it is referred herein in this context to the term “Hct concentration”. It represents the proportion of blood that is made up of red blood cells compared to the total volume of blood. Hct is measured herein to determine the Hct interference that alters the measurement of another parameter. In other contexts, Hct typically represents an important parameter in assessing the composition and function of blood. It is typically expressed as a percentage. For example, a Hct value of 45% means that 45% of the total blood volume is occupied by red blood cells. Hct levels can vary depending on factors such as age, sex, altitude, and certain medical conditions. Higher Hct values may indicate conditions such as dehydration, polycythemia (an abnormal increase in the number of red blood cells), or certain lung or heart diseases. Conversely, lower Hct values can be indicative of conditions like anemia, blood loss, or bone marrow disorders. Not applying to this disclosure, Hct is often measured through a laboratory test called a complete blood count (CBC). In this test, a blood sample is taken, and the Hct level is determined by separating the red blood cells from the plasma and measuring the volume of the packed red blood cells. In general, a fluid may be understood as a substance that can flow and take the shape of its container. It includes both liquids and gases and in some cases solids if having the form of a powder or granule. Unlike other solids than powders and granules, fluids do not have a fixed shape or volume. They can be easily deformed under the influence of external forces, such as pressure or temperature changes. Examples of fluids include water, air, oil, and gas. In the present case, fluids are mainly considered medical fluids, which are liquids at most and specifically blood. Applying to the entire disclosure, the step of recording one or more parameters and / or measurement data refers to the process of capturing and preferably documenting the numerical values obtained from one or more measurements. It may involve systematically documenting the results of experiments, observations, or tests in a reliable and organized manner. The amperometric sensor may comprise at least a working electrode and a counter electrode and / or a reference electrode. The amperometric sensor may therefore comprise and / or correspond to a two-electrode system or a three-electrode system. A two-electrode system (only comprising a working electrode and a counter electrode) and a three-electrode system (a working electrode, a counter electrode and a reference electrode) are configurations commonly used in electrochemical measurements and experiments. In a two- electrode system, there are two electrodes involved: a working electrode and a counter electrode. The working electrode is the electrode where the electrochemical reaction of interest takes place. The counter electrode is responsible for carrying the current to and from the working electrode to maintain charge balance in the system. This system is simpler and more straightforward, but it has limitations in terms of potential control and potential drift due to the absence of a separate reference electrode. In contrast, a three-electrode system includes an additional electrode known as the reference electrode. The reference electrode provides a stable and known potential against which the potential of the working electrode can be measured. This configuration allows for precise control of the working electrode potential and eliminates potential drift issues. The counter electrode in a three-electrode system still serves the same purpose as in a two-electrode system. The three-electrode system is typically used in various electrochemical techniques, such as cyclic voltammetry, chronoamperometry, and impedance spectroscopy, where precise potential control and accurate measurements are required. The present methods may be performed based on a two-electrode system or a three-electrode system. The amperometric sensor may correspond to a blood gas / electrolyte (BGE) metabolite sensor. Specifically, the amperometric sensor may be one sensor comprised by a BGE cartridge. Therefore, when improving the quality, sensitivity, precision, life span and / or value of the amperometric sensor, the quality, sensitivity, precision, life span and / or value of the BGE cartridge is also improved. Further, if an amperometric sensor of a BGE cartridge is found to be low-performing, the BGE cartridge or even an entire batch of cartridges might be required to be disposed even though the other components are intact and working properly. Therefore, waste is reduced and / or the life span and / or potential in-use time of a BGE cartridge is increased. The amperometric sensor may comprise at least one of: a glucose sensor, a lactate sensor, a creatinine sensor, hydrogen peroxide sensor, and / or sensors for other enzymes and / or biomolecules. The working electrode may comprise a membrane and at least one enzyme, such as glucose oxidase (GOD), lactase oxidase (LOD), Creatine kinase (CK), cholesterol oxidase, Glucose Dehydrogenase (GDH), Lactate Dehydrogenase (LDH), and / or other enzymes and / or biomolecules. The amperometric sensor may correspond to a glucose sensor for which GOD is embedded in latex and therefore weakly immobilized. The amperometric sensor may correspond to a lactase sensor for which LOD is embedded in latex and therefore weakly immobilized. The cover membrane may comprise PVC. GOD and / or LOD may be adhesively bound in solution on the working electrode of the glucose sensor and / or the lactase sensor and immobilized on this by covering with hydrophilic polyurethane (HPU) membrane. The medical fluid may correspond to a bodily fluid, specifically a blood sample, a component and / or derivative thereof. The batch of at least two cartridges may comprise 50 or more cartridges, specifically 80 or more cartridges and more specifically 100 or more cartridges. The fluid container system may comprise a fluid channel and / or a fluid channel system and specifically a microfluid channel. When testing very small volumes of a sample, such as capillary blood samples, it is advantageous to provide microfluid channels through which the sample volume can be actively or passively transported and be brought into contact with one or more sensors. The in-use period may correspond to about 2 to 100 days, specifically to about 10 to 50 days and more specifically to 20 to 40 days. These are typical in-use periods for cartridges. It is to be understood that the present invention is not limited to the particular embodiments and examples described herein as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Detailed Description of the Invention In the following, some embodiments will be described in detail, wherein the invention should not be understood to be limited to the embodiments described. The following embodiments and figures are provided to aid the understanding of the present invention, the true scope of which is set forth in the appended claims. Single features being described in a particular embodiment may be arbitrarily combined, given that they are not excluding each other. In addition, different features which are provided together in the example embodiments are not to be considered restrictive to the invention. Skilled artisans appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements whereas other elements may have been left out and / or represented in a reduced number in order to enhance clarity and improve understanding of the aspects of the present disclosure. The same reference numerals are used among different embodiments and examples for the same or similar elements or elements that have similar or the same effects. Description of the Figures Fig. 1 shows to diagrams for the measured Glucose concentration as a function of Hct of analyzed blood samples for a 12 days in-use time (left) and for a 10 days in-use time (right); Fig.2 is a diagram showing the Hct effect onto the signal after two different in-use-times (10 days vs.20 days); Fig.3 is a diagram showing how the impedance depends on the Hct concentration (1 / (1-h)) (h corresponds to the Hct concentration, i.e. the Hct percentage volume fraction of whole blood); Fig.4a is a scheme of a cartridge with an amperometric sensor comprising a working electrode, according to an embodiment;Fig. 4b is a scheme of the working electrode of Fig. 4a along the cut line A-A’, according toan embodiment; Fig.5 is a flow diagram of a method of correcting a DC current, according to an embodiment; Fig. 6 is scheme illustrating the method of correcting a DC current, according to theembodiment of Fig. 5;Fig. 7 is a flow diagram of a method of correcting a DC current, according to another embodiment; Fig.8 is a diagram showing the total impedance measured between two conductivity electrodes (e.g. gold blank electrodes) as a function of in-use time and Hct of blood samples analyzed; and Fig. 9 is a diagram showing the total impedance measured with an amperometric sensor to determine the compensation.Fig. 1, 2 and 3 were already discussed in view of the prior art in the above background section.Fig.4a is a scheme of a cartridge 12 as it may be used for example in a blood gas / electrolyte analyzer for example. It may comprise a plastic material. The cartridge 12 has an amperometric sensor 14 comprising a working electrode WE, a reference electrode RE and a counter electrode CE, according to an embodiment. The cartridge 12 further has a fluid container system 13, i.e. a container system for transporting a fluid form an entrance EN to an exit port EX. More specifically a fluid channel 15 and / or a fluid channel system through which a fluid can pass at least partially. Further, the cartridge has conductivity electrodes K1and K2between which a conductivity can be measured when both of them are contacted via a fluid that passes by or is just present in their location of the fluid channel 15. The conductivity electrodes K1and K2may comprise blank gold electrodes, i.e. electrodes which are directly in contact with a fluid when it passes the position of the conductivity electrodes K1 and K2 in the fluid channel 15.Fig. 4b is a scheme of the working electrode WE of Fig. 4a along the cut line A-A’, accordingto an embodiment. The working electrode WE is positioned inside the fluid channel 15, having side walls 21, a bottom wall and a top wall, such that the working electrode WE may contacted with the fluid that passes the position of the working electrode WE. The working electrode WE comprises a core electrode piece, which corresponds to an anode 20 and / or cathode 20 depending on the type of electrochemical reaction, and which is positioned on a substrate 17. Further, the working electrode WE, specifically the anode / cathode 20 may be electrically connected with a controller and / or a potentiostat and / or an electrochemical analyzer via a conductor and / or circuit path 18. Moreover, the working electrode WE, specifically the anode / cathode 20 is embedded in an isolating layer 19 and covered by a cover membrane 16 (or just denoted “membrane”) which acts as a diffusion barrier. The membrane 16 comprises an enzyme, such as for example glucose oxidase (GOD), lactase oxidase (LOD), Creatine kinase (CK), cholesterol oxidase, Glucose Dehydrogenase (GDH), Lactate Dehydrogenase (LDH), and / or other enzymes and / or biomolecules. Fig. 5 is a flow diagram of a method 100 of correcting a DC current, according to anembodiment. The method 100 may be performed using a cartridge 12 as shown in Fig. 4ahaving a working electrode WE as shown in Fig. 4b. Fig. 6 is scheme illustrating the method100 of correcting a DC current, according to the embodiment of Fig.5. The cartridges 12 shownin Fig. 6 may correspond to or may at least be similar to the cartridge 12 shown in Fig. 4a.The Method 100 is used for correcting a DC current (^^^^^^^^^^^^^^(^^^^^^^^, ^^)), recorded by anamperometric sensor 14 that is in contact with a medical fluid inside a fluid channel 15 of asample cartridge 12b, for a time-dependent Hct-induced current drift (∆^^(^^^^^^^^, ^^)). The method100 comprises the following steps:a. Providing 101 a batch 11 of cartridges 12 (here 5 shown, can be more such as fifty or more)comprising at least one test cartridge 12a and at least one sample cartridge 12b. The test cartridge 12a and the sample cartridge 12b are substantially identical. Each cartridge 12 comprises a fluid container system 13, such as a fluid channel 15 configured to receive and / or guide and / or transport a fluid, and at least two conductivity electrodes (here two shown: K1, K2) and the amperometric sensor 14 (three electrode system here) being configured and / or positioned in the fluid channel system 15 to be in contact with an interior volume I of the fluid container system 13 and in contact with the medical sample fluid when being filled / introduced into the fluid container system 13. Performing 102 a batch characterization (based on a characterization of the test cartridge 12 a) by: a1. Picking a cartridge 12 that should be used as the test cartridge 12a and recording 102a with the amperometric sensor 14 of the test cartridge 12a, at at least two different points in time tover an in-use period d, the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^, ^^)) of at least two medicalreference fluids with differing determined Hct concentrations (^^^^^^^^) and identicaldetermined analyte concentration (^^^^^^^^^^^^^^^^), the medical reference fluids being filled for therespective recording in the fluid container system 13, and obtaining a dependence of the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^, ^^)) from the Hct concentration (^^^^^^^^) for each of the at leasttwo points in time t; After performing and completing 102 the batch characterization, the test cartridge 12a is preferably disposed or at least not used any more for the characterization of a real sample. Picking a cartridge 12 remained in the batch 11 (other than the test cartridge 12a) that should be used as the sample cartridge 12b for characterizing a real sample, such as blood sample that corresponds to the fluid that is introduced into the fluid channel 15. The sample cartridge 12b may therefore be placed in an in vitro diagnostic analyzer / system (IVD system) as indicated in Fig.6. Performing 103 an individual cartridge characterization (i.e. a characterization of the sample cartridge 12b) of the at least one sample cartridge 12b by:b. Hct-calibrating 103a the at least two conductivity electrodes (K1, K2, …) of the samplecartridge 12b for an Hct-concentration (^^^^^^^^) by recording a conductivity parameter ^^(^^^^^^^^) with the at least two conductivity electrodes (K1, K2, …) for at least two Hct- calibration fluids with differing determined Hct-concentrations (^^^^^^^^) being filled for therespective recording in the fluid container system 13 (i.e. the fluid channel 15 here), and obtaining an Hct-calibration curve (^^(^^^^^^^^)^^^^. ^^^^^^^^);c. Analyte-calibrating 103b the amperometric sensor 14 of the sample cartridge for the analyteconcentration (^^^^^^^^^^^^^^^^) by recording a current with the amperometricsensor 14 for at least two analyte-calibration fluids with differing analyte-concentrations (^^^^^^^^^^^^^^^^) being filled for the respective recording in the fluid container system 13, and obtaining an analyte-calibration curve ^^^^^^^^^^^^^^^^);d. Recording 103c the impedance (^^^^^^^^.) with each recording of the current (^^^^^^^^.(^^^^^^^^^^^^^^^^))during the analyte-calibration and determining the respective quotient (^^ = ^^^^^^^^.(^^^^^^^^^^^^^^^^) ∙^^^^^^^^) of the impedance (^^^^^^^^.) and the current (^^^^^^^^.(^^^^^^^^^^^^^^^^)) for each of the at least twoanalyte-calibration fluids and forming the mean value of all determined quotients (^ത^); At a point in time (^^^^^^^^^^) of an actual measurement (to characterize the blood sample) during the in-use period d of the at least one sample cartridge 12b:e. Determining 103d the Hct-concentration (^^^^^^^^) of the medical fluid filled in the fluidcontainer system 13 by recording the conductivity parameter ^^(^^^^^^^^ ) with the at least twocalibrated conductivity electrodes (K1, K2, …) and by reading the Hct-concentration (^^^^^^^^)from the Hct-calibration curve;f. Determining 103e an impedance difference ∆^^ from the dependence of the impedance(^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^, ^^)) from the Hct concentration (^^^^^^^^) determined in the test cartridge 12bby subtracting from the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^, ^^)) for the point in time t thatcorresponds to the point in time (^^^^^^^^^^) of the actual measurement and for the determinedHct-concentration (^^^^^^^^) of the medical fluid the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^, ^^)) for thepoint in time t that corresponds to the point in time (^^^^^^^^^^) of the actual measurement andfor the Hct-concentration (^^^^^^^^) which equals 0:∆^^ = (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^ = det. ^^^^^^^^ of med. fluid, ^^ = ^^^^^^^^^^) − (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^ = 0, ^^ =^^^^^^^^^^);g. Determine 103f a correction factor corresponding to the Hct-induced current drift bymultiplying the impedance difference ∆^^ with the mean value of all determined quotients(^ത^): ∆^^(^^^^^^^^, ^^) = ∆^^ ∙ ^ത^ ; andh. Recoding 103g the DC current ^^^^^^^^^^^^^^.(^^^^^^^^, ^^) with the amperometric sensor 14 and correctfor the time-dependent Hct-induced current drift ∆^^(^^^^^^, ^^) by determining the correctedcurrent (^^^^^^^^^^): Fig.7 is a flow diagram of an alternative method 200 of correcting a DC current, thus accordingto another embodiment. The method 200 of correcting the DC current (^^^^^^^^^^^^^^(^^^^^^^^, ^^)),recorded by an amperometric sensor 14 in contact with a medical fluid, for a time-dependentHct-induced current drift (∆^^(^^^^^^^^, ^^)) comprises:a. Providing 201 at least one sample cartridge 12b comprising:a fluid container system 13 configured to receive a fluid, and, in contact with an interior volume of the fluid container system 13, at least two conductivity electrodes (K1, K2,…) and the amperometric sensor 14;b. Hct-calibrating 202 the at least two conductivity electrodes (K1, K2, …) of the samplecartridge for an Hct-concentration (^^^^^^^^) by recording a conductivity parameter ^^(^^^^^^^^ )with the at least two conductivity electrodes (K1, K2, …) for at least two Hct-calibration fluids with differing determined Hct-concentrations (^^^^^^^^) being filled for the respectiverecording in the fluid container system 13, and obtaining an Hct-calibration curve (^^(^^^^^^^^)^^^^. ^^^^^^^^);c. Analyte-calibrating 203 the amperometric sensor 14 of the sample cartridge 12b for theanalyte concentration (^^^^^^^^^^^^^^^^) by recording a current with theamperometric sensor 14 for at least two analyte-calibration fluids with differing analyte- concentrations (^^^^^^^^^^^^^^^^) being filled for the respective recording in the fluid container system 13, and obtaining an analyte-calibration curve (^^^^^^^^.൫^^^^^^^^^^^^^^^^൯^^^^. ^^^^^^^^^^^^^^^^);d. Recording 204 the impedance (^^^^^^^^.) with each recording of the current (^^^^^^^^.(^^^^^^^^^^^^^^^^))during the analyte-calibration and determining the respective quotient (^^ = ^^^^^^^^.(^^^^^^^^^^^^^^^^) ∙^^^^^^^^) of the impedance (^^^^^^^^.) and the current (^^^^^^^^.(^^^^^^^^^^^^^^^^)) for each of the at least twoanalyte-calibration fluids and forming the mean value of all determined quotients (^ത^); At a point in time (^^^^^^^^^^) of an actual measurement during the in-use period (d) of the at least one sample cartridge:e. Determining 205 the Hct-concentration (^^^^^^^^) of the medical fluid filled in the fluidcontainer system 13 by recording the conductivity parameter ^^(^^^^^^^^ ) with the at least twocalibrated conductivity electrodes (K1, K2, …) and by reading the Hct-concentration (^^^^^^^^)from the Hct-calibration curve;f. Recording 206 the impedance (^^^^^^^^^^^^^^(^^^^^^^^, ^^)) of the medical fluid having the determinedHct-concentration (^^^^^^^^) and determining an impedance difference ∆^^ by subtracting fromthe recorded impedance (^^^^^^^^^^^^^^(^^^^^^^^, ^^)) of the medical fluid the impedance being derivedfrom the recorded impedances (^^^^^^^^.) during the analyte-calibration corresponding to thesame analyte concentration of the medical fluid, the point in time (^^^^^^^^^^) of the actual measurement, and the Hct-concentration (^^^^^^^^) which equals 0: ^^ℎ^^ ^^^^^^. ^^^^^^^^^^, ^^ = ^^^^^^^^^^) − (^^^^^^^^(^^^^^^^^ = 0, ^^ =^^^^^^^^^^);g. Determine 207 a correction factor corresponding to the Hct-induced current drift bymultiplying the impedance difference ∆^^ with the mean value of all determined quotients(^ത^): ∆^^(^^^^^^^^, ^^) = ∆^^ ∙ ^ത^ ; andh. Recoding 208 the DC current ^^^^^^^^^^^^^^.(^^^^^^^^, ^^) with the amperometric sensor 14 and correctfor the time-dependent Hct-induced current drift ∆^^(^^^^^^, ^^) by determining the correctedcurrent (^^^^^^^^^^): The above described methods 100, 200 may be phrased in other words: Impedance-based methods are used to correct the in-use time-dependent Hct-induced current decrease of an amperometric BG / E metabolite sensor 14. It represents an approach for correction of a time inconstant Hct effect onto the read-out of an amperometric metabolite sensor 14: A total impedance Z value is measured between the working electrode WE and the counterelectrode CE of the respective metabolite sensor 14 at several in-use days (see Fig.3 as exampleof the relation between Hct and measured impedance Z). A relationship between totalImpedance Z and Hct is established, as depicted in Fig. 3. This diagram shows the totalimpedance measured between working WE and counter electrode CE of a glucose sensor as a function of in-use time (days, d) and Hct of blood samples analyzed (h=Hct [%] / 100); Glucosesensor; f= 10kHz; ^VRMS: 30 mV; Polarisation voltage: 350 mV).A DC current I is afterwards measured at the working electrode WE of the metabolite sensor 14. Using two blank electrodes (conductivity electrodes K1, K2) which show time-constantdependence of impedance on Hct, the Hct is determined (see Fig. 8 as an example). Fig. 8 is adiagram showing the total impedance Z measured between two conductivity electrodes K1, K2(e.g. gold blank electrodes) as a function of in-use time d and Hct of blood samples analyzed(h=Hct [%] / 100; f= 10kHz; ^VRMS: 30 mV).The difference ^Z = Zmeasured – Zreference, Hct for a given in-use time and h (Hct / 100) (see Fig. 3for exemplary relationship). The current correction ^I (Icorr. = Imeas. - ^I) is determined to correctfor the Hct effect: ^I = ^x ^I / Z whereby ^Z = f(^Hct) (see Fig. 3). Hct is determined by the measurement of the impedance Z between the two blank electrodes (amperometric sensor) via an established relation between impedance value Z and Hct (asshown in Fig. 9). Fig. 9 is a diagram showing the total impedance measured with anamperometric sensor to determine the compensation. Assuming that the Hct effect onto thecurrent readout of the metabolite sensor is constant over time, a constant correction factor ^I =^x ^1 / Z is used to determine Icorr. = Imeas. - ^I. Further, Z (Hct-Zstdby) vs. 1-1 / h (h=Hct / 100) ismeasured as the Calibration curve and Hct is determined from Z. This allows compensating I vs. Hct. In this way, the time-dependent Hct sensitivity of a glucose sensor due to the variable permeability of the cover membrane may be corrected.
[0002] Reference list 11 Batch of cartridges12 Cartridge12a Test cartridge12b Sample cartridge13 Fluid container system14 Amperometric sensor15 Fluid channel16 Membrane17 Substrate18 Conductor / Circuit path19 Isolating layer20 Anode / Cathode21 Side walls of the fluid channel100 Method of correcting a DC current200 Method of correcting a DC currentWE Working electrodeCE Counter / Auxiliary electrodeEN Entrance portEX Exit portK1, K2 Conductivity electrodes RE Reference electrode
Claims
Patent claims1. Method (100) of correcting a DC current (^^^^^^^^^^^^^^ ^^)), recorded by an amperometricsensor (14) in contact with a medical fluid, for a time-dependent Hct-induced current drift (∆^^(^^^^^^^^, ^^)), the method comprising:a. Providing (101) a batch (11) of at least two cartridges (12) comprising at least one testcartridge (12a) and at least one sample cartridge (12b), each cartridge (12) comprising: a fluid container system (13) configured to receive a fluid, and, in contact with an interior volume (I) of the fluid container system (13), at least two conductivity electrodes (K1, K2,…) and the amperometric sensor (14); Performing (102) a batch characterization by: a1. Recording (102a) with the amperometric sensor (14) of the at least one test cartridge (12a), at at least two different points in time (t) over an in-use period (d), the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^, ^^)) of at least two medical reference fluids with differing determined Hctconcentrations (^^^^^^^^) and identical determined analyte concentration (^^^^^^^^^^^^^^^^), themedical reference fluids being filled for the respective recording in the fluid container system (13), and obtaining a dependence of the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^, ^^)) from theHct concentration (^^^^^^^^) for each of the at least two points in time (t);Performing (103) an individual cartridge characterization of the at least one sample cartridge by:b. Hct-calibrating (103a) the at least two conductivity electrodes (K1, K2, …) of the samplecartridge for an Hct-concentration (^^^^^^^^) by recording a conductivity parameter ^^(^^^^^^^^ )with the at least two conductivity electrodes (K1, K2, …) for at least two Hct-calibration fluids with differing determined Hct-concentrations (^^^^^^^^) being filled for the respectiverecording in the fluid container system (13), and obtaining an Hct-calibration curve (^^(^^^^^^^^)^^^^. ^^^^^^^^);c. Analyte-calibrating (103b) the amperometric sensor (14) of the sample cartridge for theanalyte concentration (^^^^^^^^^^^^^^^^) by recording a currentwith theamperometric sensor (14) for at least two analyte-calibration fluids with differing analyte- concentrations (^^^^^^^^^^^^^^^^) being filled for the respective recording in the fluid container system (13), and obtaining an analyte-calibration curve^^^^^^^^^^^^^^^^);d. Recording (103c) the impedance (^^^^^^^^.) with each recording of the current(^^^^^^^^.(^^^^^^^^^^^^^^^^)) during the analyte-calibration and determining the respective quotient (^^ = ^^^^^^^^.(^^^^^^^^^^^^^^^^) ∙ ^^^^^^^^) of the impedance (^^^^^^^^.) and the current (^^^^^^^^.(^^^^^^^^^^^^^^^^)) foreach of the at least two analyte-calibration fluids and forming the mean value of all determined quotients (^ത^); At a point in time (^^^^^^^^^^) of an actual measurement during the in-use period (d) of the at least one sample cartridge:e. Determining (103d) the Hct-concentration (^^^^^^^^) of the medical fluid filled in the fluidcontainer system (13) by recording the conductivity parameter ^^(^^^^^^^^ ) with the at leasttwo calibrated conductivity electrodes (K1, K2, …) and by reading the Hct-concentration (^^^^^^^^) from the Hct-calibration curve;f. Determining (103e) an impedance difference ∆^^ from the dependence of the impedance(^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^, ^^)) from the Hct concentration (^^^^^^^^) determined in the test cartridge bysubtracting from the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^, ^^)) for the point in time (t) thatcorresponds to the point in time (^^^^^^^^^^) of the actual measurement and for the determinedHct-concentration (^^^^^^^^) of the medical fluid the impedance (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^, ^^)) for thepoint in time (t) that corresponds to the point in time (^^^^^^^^^^) of the actual measurementand for the Hct-concentration (^^^^^^^^) which equals 0:∆^^ = (^^^^^^^^^^ ^^^^^^^^^^.(^^^^^^^^ = det.med. fluid,^^^^^^^^^^);g. Determine (103f) a correction factor corresponding to the Hct-induced current drift bymultiplying the impedance difference ∆^^ with the mean value of all determined quotients(^ത^): ∆^^(^^^^^^^^, ^^) = ∆^^ ∙ ^ത^ ; andh. Recoding (103g) the DC current ^^^^^^^^^^^^^^.(^^^^^^^^, ^^) with the amperometric sensor (14) andcorrect for the time-dependent Hct-induced current drift ∆^^(^^^^^^, ^^) by determining thecorrected current (^^^^^^^^^^):
2. Method (200) of correcting a DC current (^^^^^^^^^^^^^^(^^^^^^^^, ^^)), recorded by an amperometricsensor (14) in contact with a medical fluid, for a time-dependent Hct-induced current drift (∆^^(^^^^^^^^, ^^)), the method comprising:a. Providing (201) at least one sample cartridge (12b) comprising:a fluid container system (13) configured to receive a fluid, and,in contact with an interior volume of the fluid container system (13), at least two conductivity electrodes (K1, K2,…) and the amperometric sensor (14);b. Hct-calibrating (202) the at least two conductivity electrodes (K1, K2, …) of the samplecartridge for an Hct-concentration (^^^^^^^^) by recording a conductivity parameter ^^(^^^^^^^^ )with the at least two conductivity electrodes (K1, K2, …) for at least two Hct-calibration fluids with differing determined Hct-concentrations (^^^^^^^^) being filled for the respectiverecording in the fluid container system (13), and obtaining an Hct-calibration curve (^^(^^^^^^^^)^^^^. ^^^^^^^^);c. Analyte-calibrating (203) the amperometric sensor (14) of the sample cartridge for theanalyte concentration (^^^^^^^^^^^^^^^^) by recording a currentwith theamperometric sensor (14) for at least two analyte-calibration fluids with differing analyte- concentrations (^^^^^^^^^^^^^^^^) being filled for the respective recording in the fluid container system (13), and obtaining an analyte-calibration curve^^^^^^^^^^^^^^^^);d. Recording (204) the impedance (^^^^^^^^.) with each recording of the current (^^^^^^^^.during the analyte-calibration and determining the respective quotient (^^ =^^^^^^^^.(^^^^^^^^^^^^^^^^) ∙ ^^^^^^^^) of the impedance (^^^^^^^^.) and the currentfor each ofthe at least two analyte-calibration fluids and forming the mean value of all determined quotients (^ത^); At a point in time (^^^^^^^^^^) of an actual measurement during the in-use period (d) of the at least one sample cartridge:e. Determining (205) the Hct-concentration (^^^^^^^^) of the medical fluid filled in the fluidcontainer system (13) by recording the conductivity parameter ^^(^^^^^^^^ ) with the at leasttwo calibrated conductivity electrodes (K1, K2, …) and by reading the Hct-concentration (^^^^^^^^) from the Hct-calibration curve;f. Recording (206) the impedance (^^^^^^^^^^^^^^(^^^^^^^^, ^^)) of the medical fluid having thedetermined Hct-concentration (^^^^^^^^) and determining an impedance difference ∆^^ bysubtracting from the recorded impedance (^^^^^^^^^^^^^^(^^^^^^^^, ^^)) of the medical fluid theimpedance being derived from the recorded impedances (^^^^^^^^.) during the analyte-calibration corresponding to the same analyte concentration of the medical fluid, the point in time (^^^^^^^^^^) of the actual measurement, and the Hct-concentration (^^^^^^^^) which equals0:^^^^^^^^^^);g. Determine (207) a correction factor corresponding to the Hct-induced current drift bymultiplying the impedance difference ∆^^ with the mean value of all determined quotients(^ത^): ∆^^(^^^^^^^^, ^^) = ∆^^ ∙ ^ത^ ; andh. Recoding (208) the DC current ^^^^^^^^^^^^^^.(^^^^^^^^, ^^) with the amperometric sensor (14) andcorrect for the time-dependent Hct-induced current drift ∆^^(^^^^^^, ^^) by determining thecorrected current (^^^^^^^^^^):
3. The method (100, 200) of claim 1 or 2, wherein the amperometric sensor (14)comprises at least a working electrode (WE) and a counter electrode (CE) and specifically a reference electrode (RE).
4. The method (100, 200) of claim 3,wherein the amperometric sensor (14) corresponds to a blood gas / electrolyte metabolite sensor; and / or wherein the amperometric sensor (14) comprises at least one of: a glucose sensor, a lactate sensor, a creatinine sensor; and / or wherein the working electrode (WE) comprises a membrane (16) and at least one enzyme.
5. The method (100, 200) of any one of the preceding claims, wherein the medical fluidcorresponds to bodily fluid, specifically a blood sample and / or derivative thereof.
6. The method (100) of claim 1, wherein the batch (11) of at least two cartridges (12)comprises 50 or more cartridges (12), specifically 80 or more cartridges (12) and more specifically 100 or more cartridges (12).
7. The method (100, 200) of any one of the preceding claims, wherein the fluid containersystem (13) comprises a fluid channel (15) and / or a fluid channel system and specifically amicrofluid channel.
8. The method (100, 200) of any one of the preceding claims, wherein the in-use period(d) corresponds to about 2 to 100 days, specifically to about 10 to 50 days and more specifically to 20 to 40 days.
Citation Information
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