Sensor assembly

Abstract

The invention relates to a sensor assembly (1, 1 ', 1' ') for an IVD analyzer, the sensor assembly (1, 1', 1 '') comprising two opposed substrates (10A, 10B, 20A, 20B, 30A, 30B) having at least one fluid conduit (2, 3, 4) for receiving a sample. The invention relates to an electrochemical sensor comprising two opposing substrates (10A, 10B, 20A, 20B, 30A, 30B) on which electrodes of different types of electrochemical sensors are arranged facing at least one fluid conduit (2, 3, 4) for contacting a sample and determining sample parameters, in which a counter electrode (11C, 11D) and a reference electrode (11B, 12B) are formed on one substrate (10A, 10B, 20A, 20B, 30A, 30B) and a working electrode (11A, 12A, 12A ') is formed on the opposing substrate (10A, 10B, 20A, 20B, 30A, 30B). This enables optimal sensor operating conditions with respect to uniform and symmetrical electric field densities and enables the sensor assembly to have a simpler geometry and a smaller size.

Description

[0001] This application is a divisional application of the Chinese patent application with application number 202111572964X (application date: 2021 / 12 / 21, invention name: sensor component). Technical Field

[0002] The present disclosure relates to a sensor assembly for an IVD analyzer, comprising a sensor disposed in a fluid conduit for determining a sample parameter in a sample. Background Art

[0003] In vitro diagnostic (IVD) analyzers (such as blood gas and electrolyte analyzers) can be used in intensive care units, emergency rooms, hospital wards, surgical units, anesthesia, outpatient clinics, medical practices, or during patient transport. These are typically point-of-care environments where a short turnaround time (TAT or STAT) for diagnostic results is required and / or where multiple samples need to be collected continuously from a patient at short intervals.

[0004] In blood gas and electrolyte testing, parameters such as blood gas partial pressures (PO2, PCO2), oxygen saturation (SO2), pH, electrolyte concentrations (e.g., Na + , K + Mg 2+ , Ca 2+ , Li + , Cl - ), bicarbonate value (HCO3 - ), metabolite concentrations (e.g. glucose, lactate, urea, creatinine), values ​​of hemoglobin and hemoglobin derivatives (e.g. tHb, O2Hb, HHb, COHb, MetHb, SulfHb), bilirubin values, and hematocrit. These parameters allow the physician to obtain important information about the patient's cardiac, pulmonary, and renal function.

[0005] Currently, many IVD analyzers are available on the market that allow these parameters to be measured with different degrees of automation. Typically, these parameters are determined by conductivity, electrochemical and / or optical measuring principles. In the latest generation of these IVD analyzers, the sensors required for these measuring principles are combined in a multi-purpose sensor assembly that is inserted into the IVD analyzer. This allows multiple parameters to be determined simultaneously from a single sample in a single measurement. The usual goal is to use the same sensor assembly for as many measurements as possible. However, when necessary, for example, if one or more sensors reach the end of their use time, the sensor assembly can be replaced with a new sensor assembly.

[0006] The measurement is carried out in a measuring chamber arranged inside the sensor assembly. These measuring chambers can be designed as fluid conduits, which are equipped with corresponding conductivity sensors, electrochemical sensors and / or optical sensors. In order to measure, the sample is introduced into the fluid conduit so that it contacts the sensor. After the measurement, the sample is removed from the fluid conduit and replaced with other fluids, such as standby solutions, washing fluids, quality control (QC) samples, subsequent samples, calibration products, etc.

[0007] Measurements are usually performed on whole blood samples, ideally arterial blood samples. However, collecting arterial blood is particularly cumbersome for the patient. In certain patient groups, for example in newborns, capillary blood samples are drawn. This means that only a limited volume of sample material is available. Therefore, in blood gas and electrolyte testing, it is a general trend to arrange as many sensors as possible into the sensor assembly and to minimize the size of the measuring chamber. This enables as many parameters as possible to be obtained from a single sample, thereby relieving the patient of the sample collection burden and enabling the processing of small sample volumes.

[0008] Advances in the field of integrated circuit technology have made it possible to develop smaller and smaller sensors, for example by using thick film or thin film technology, thereby allowing the size of the entire sensor assembly to be minimized. In addition, sensor arrangements and sensor assembly geometries have been improved. For example, US8728288B2 discloses a sensor assembly in which fully functional analyte sensors are placed on opposite walls of a measuring chamber, thereby allowing the use of smaller sample volumes without reducing the number of sensors in the sensor assembly. However, the sensor distribution presented in the disclosure cannot completely exclude possible interference between sensors. In addition, due to the planar arrangement of the sensors and the lateral flow of the generated sensor current, the electrodes forming these sensors may degrade asymmetrically.

[0009] Furthermore, increasing the usage time of the sensor assembly may be advantageous. Replacing the sensor assembly with a new one results in downtime of the IVD analyzer, including the time the new sensor assembly needs to be initialized. Therefore, frequently replacing the sensor assembly presents disadvantages in terms of economic efficiency, usability, sample processing throughput, time to obtain results, and waste production. Summary of the invention

[0010] Against the foregoing background, embodiments of the present disclosure provide certain non-obvious advantages and advances over the prior art.In particular, it is recognized that there is a need for improved sensor assemblies for in vitro diagnostic (IVD) analyzers.

[0011] Although embodiments of the present disclosure are not limited to specific advantages or functions, it should be noted that the present disclosure allows for a sensor assembly that enables rapid, accurate, non-intrusive and reliable determination of multiple parameters from a single sample with a small sample volume without reducing the number of sensors in the assembly and, therefore, the number of possible parameters to be measured from the sample. This is achieved by arranging the electrodes of the electrochemical sensor in a specific manner on two opposing substrates. Another advantage of this arrangement is that optimal sensor operating conditions are achieved, for example, enabling uniform and symmetrical current density and field distribution on the electrode surface.

[0012] Another advantage of the sensor assembly according to the present disclosure is that the manufacture of the sensor assembly with the corresponding arrangement of the electrochemical sensor is simpler and more cost-effective. For example, if a defective electrode is detected during the manufacturing process, only the affected substrate needs to be discarded instead of the entire sensor assembly, thereby increasing the yield and reducing the manufacturing cost. In addition, certain sensor types or certain sensing elements (such as reference electrodes or counter electrodes) have a simpler design than other sensor types or sensing elements (such as working electrodes). It has been shown that it is advantageous when sensors or electrodes with similar structures and similar manufacturing processes are manufactured on the same substrate.

[0013] Another advantage of the sensor assembly according to certain embodiments is that the use time of the sensor assembly can be further extended, thereby reducing the number of times the sensor assembly needs to be replaced, and thus shortening the downtime of the IVD analyzer during the installation and initialization of the sensor assembly. This also improves the usability in terms of ease of use and simplicity.

[0014] Another advantage of a sensor assembly according to certain embodiments is that it enables temperature controlled measurements of a sample.

[0015] In particular, the present disclosure describes a sensor assembly for an IVD analyzer, comprising two opposing substrates, between which at least one fluid conduit for receiving a sample is formed. The sensor assembly also includes a plurality of electrochemical sensors arranged on the two opposing substrates, the plurality of electrochemical sensors facing at least one fluid conduit, for contacting with the sample and measuring sample parameters. The plurality of electrochemical sensors are selected from current sensors, potential sensors, or a combination thereof, wherein the potential sensor comprises a potential working electrode (PWE) and a potential reference electrode (PRE), and wherein the current sensor comprises a current working electrode (AWE) and a current counter reference electrode (ACRE) or AWE and a current reference electrode (ARE) and a current counter electrode (ACE). PRE and / or ACRE and / or ARE and ACE are thus formed on the same substrate of the two substrates, while PWE and / or AWE are formed on a substrate relative to one of the two substrates.

[0016] As used herein, the term "IVD analyzer" refers to an automated or semi-automated analytical device that is configured to examine in vitro samples in order to provide information for screening, diagnosis and treatment monitoring purposes. The IVD analyzer is designed and adapted for medical application fields, parameters to be determined and corresponding laboratory workflows. For example, in a field care testing environment, an IVD analyzer can be changed from a handheld device with low throughput, short turnaround time and a limited number of measurable parameters to a compact desktop instrument with higher throughput and a higher number of measurable parameters. Such IVD analyzers are designed to detect certain types of parameters, such as gases, electrolytes, metabolites, clinical chemistry analytes, immunochemical analytes, coagulation parameters, hematology parameters, etc. According to the parameters of interest, a variety of different analytical methods and different detection techniques can be applied. For example, in the field of blood gas and electrolyte testing, electrochemical measurement principles and / or conductivity measurement principles and / or optical detection methods are used. The IVD analyzer includes a plurality of functional units, each of which is dedicated to a specific task, and cooperates with each other to achieve automated sample processing and analysis. Such functional units can be, for example, filling ports for receiving samples, pumps, valves, analytical measurement units, optical detection units, hemolysis units, sample injection nozzles, reagent storage, temperature regulation units, controllers, etc. One or more functional units can be integrated into larger units or modules to simplify the operation of the IVD analyzer. An example of such a module is a fluid suit, which combines a filling port for receiving samples, an optical detection unit, a fluid system, a pump, a valve, a bag with system fluid, etc., which can be replaced if necessary. Such a replaceable module is also considered to be a part of the IVD analyzer in the present disclosure, even if it is not a permanently installed component.

[0017] The term "sensor" is generally used herein to refer to a detector configured to detect sample parameters by generating a related signal output that can be quantified and digitized. The sensor can be a biosensor, a chemical sensor or a physical sensor, and is typically a part of a functional unit (e.g., an analytical measurement unit) of an IVD analyzer. The sensor can be selective or specific with respect to a sample parameter of interest, or can be configured to detect and quantify a variety of different sample parameters of interest. Depending on the type of sensor, the sensor can include multiple sensing elements. Therefore, the term "sensing element" refers to a part of a sensor (e.g., a working electrode, a reference electrode, a counter electrode), which is combined with one or more other sensing elements to form a fully functional sensor.

[0018] As used herein, the term "sensor assembly" refers to a functional unit including more than one sensor, wherein the sensors may be of the same type, such as based on the same functional principle and / or sensor design, or may be of different types. The sensor assembly is generally designed as a replaceable multi-purpose unit. However, as used herein, the term "sensor assembly" may also refer to a functional unit permanently installed in an IVD analyzer. Typically, hundreds of samples can be measured with a sensor assembly before it reaches the end of its service life. The sensors of the sensor assembly are generally applied to a substrate, wherein the substrate is a planar element capable of carrying the necessary wiring for connecting the sensor to the electrical contact element. These electrical contact elements need to establish an electrical connection with the IVD analyzer. The substrate has two main surface areas, whereby all sensors applied to the substrate are generally applied to the same main surface area. The sensor assembly can be designed to include two substrates, which are arranged relative to each other so that the main surface areas carrying the sensors face each other. The two relative substrates can be arranged in parallel, or they can be arranged at an inclined angle relative to each other (e.g., at an angle between 0° and 1° or at an angle between 0° and 2° or at an angle between 0° and 5°). The substrate can be made of a non-conductive material (e.g., polymer, ceramic, glass) or a conductive material (e.g., metal, such as steel, aluminum, platinum, gold, or metal alloy). In the latter case, an insulating layer, such as a polymer layer or epoxy resin, is applied between the sensor and the conductive substrate. The sensor assembly can be configured so that two opposing substrates are in a permanently fixed position relative to each other. The substrate can also be in contact with a heat-conducting element (e.g., a metal or metal alloy element), or the substrate itself can be heat-conducting, such as a steel substrate. This allows temperature exchange with a temperature regulating unit (e.g., a heating coil or a Peltier element) of an IVD analyzer. The sensor assembly can be designed as a functional unit permanently installed in an IVD analyzer, or it can be designed as a replaceable consumable. It can also include a housing to protect the sensor and wiring from external environmental influences and facilitate gripping. The housing can be made of any non-conductive material to prevent influence on electrochemical measurements.

[0019] The sensor assembly also includes at least one fluid conduit formed between two relative substrates for receiving a sample so that the sample is contacted with an available sensor. The fluid conduit can be constructed as a recessed portion in a substrate or partially in a substrate and partially in a relative substrate, wherein the sensor is arranged on the substrate so that they face the recessed portion so as to contact with the sample introduced. The two relative substrates can be further divided into subunits, wherein each subunit carries at least one sensor or electrode, and wherein at least one fluid conduit is formed as a continuous fluid conduit passing through the subunit. According to one embodiment, at least one fluid conduit is formed in a spacer arranged between the two relative substrates. The spacer is a planar element, which is arranged between the two relative substrates and parallel to the two relative substrates. The height of the spacer is determined based on the required cross-sectional area of ​​the fluid conduit. Typically, the height of the spacer is between 10um and 700um, for example, between 50um and 600um, or between 70um and 500um. In order to prevent the fluid introduced from leaking, the sensor assembly can include a sealing element for sealing the fluid conduit. Depending on the design of the sensor assembly, a sealing element may be positioned between the two opposing substrates or between each substrate and the spacer.The spacer itself may alternatively also act as a sealing element.

[0020] The sensor assembly may include a plurality of physically separated fluid conduits, i.e., each fluid conduit has a separate fluid inlet and fluid outlet, or it may include a plurality of fluid conduits that converge inside the sensor assembly and at least partially share a common fluid path (e.g., a common fluid inlet and / or a common fluid outlet). Although in the latter case, the fluid conduits are fluidically connected, they are referred to as separate fluid conduits in the present disclosure because the common path is generally not critical for obtaining measurement results. In other words, the areas where the sensor is present and the measurements are performed are spatially separated from each other. In addition, despite the presence of a fluid connection, the functions of the fluid conduits may be different. For example, a reference fluid conduit is a fluid conduit intended for reference measurements in a reference solution, rather than a fluid conduit intended for detecting parameters in a biological sample. However, such a fluid conduit and a reference fluid conduit may share a common fluid outlet.

[0021] The term "sample" as used herein is a general term used to represent any type of material processed in an IVD analyzer. The term may refer to, for example, a biological sample, a liquid containing a known level of an analyte and used to confirm the operability of the IVD analyzer (e.g., a quality control (QC) sample or a calibrator or reference solution), or a liquid used to place or maintain the IVD analyzer in an operating mode (e.g., a standby solution / rinsing solution or a wetting solution).

[0022] The term "biological sample" refers to any biological material suspected of containing one or more analytes whose detection-qualitative and / or quantitative may be associated with a physical condition. It can be derived from any biological source, such as physiological fluids, including blood, saliva, sputum, lens fluid, cerebrospinal fluid (CSF), sweat, urine, milk, ascites, mucus, synovial fluid, peritoneal fluid, pleural fluid, amniotic fluid, tissue, bone marrow, feces, cells, etc. The biological sample can be used directly after being obtained from the source or after pretreatment and / or sample preparation workflow to change the characteristics of the biological sample (such as preparing plasma from blood, diluting viscous fluids, lysing, etc.). The processing method may involve filtration, centrifugation, dilution, concentration, inactivation of interfering components, and addition of reagents, for example, so as to enable one or more in vitro diagnostic tests. Therefore, the term "sample" is not necessarily used to represent the original sample, but may also refer to a sample that has been processed (pipetting, dilution, mixing with reagents, enrichment, purification, amplification, etc.).

[0023] "QC sample" refers to a sample material that simulates a biological sample and contains one or more QC substances of known values. Typically, QC samples are provided at one or more levels (e.g., two or three levels corresponding to different concentration ranges of QC substances). QC samples are typically measured in the same manner as biological samples and under the same conditions as biological samples to check that the calibrated sensor is actually within the specification or allowable range. "QC substance" can be an analyte identical to an analyte of interest whose concentration is known, or a substance that reacts to produce an analyte identical to an analyte of interest whose concentration is known (e.g., CO2 is produced by bicarbonate), or it can be any other equivalent substance of known concentration that simulates a sample parameter of interest or can be otherwise related to a parameter of interest, such as a dye that optically behaves similar to hemoglobin or bilirubin.

[0024] A "calibrator" is a calibration solution containing one or more calibration materials for calibration of known values ​​and measured under the same conditions as the biological sample. Typically, when the sensor responds linearly to the analyte concentration, one or two calibrators are used for a single-point calibration or a two-point calibration, respectively. If the calibration curve is nonlinear, three or more calibrators can be used. In particular, the calibrators can also be provided at different levels corresponding to different concentration ranges of the QC material. The calibration material can be the same as the QC material.

[0025] "Reference solution" is a standard solution (such as a calibrator) with a known analyte concentration, which can be used for calibration, and is routinely used to obtain reference measurements, wherein the reference measurement can be performed before and / or during and / or after the biological sample is measured. For example, the reference solution can have a high KCl concentration. The reference electrode of the potential sensor including a membrane having specificity for chloride is contacted with the reference solution. Compared with the signal returned by the working electrode of the potential sensor in direct contact with the sample of interest, the constant KCl concentration allows the reference electrode to return a constant signal. The reference electrode can be placed in a fluid conduit close to the position of the corresponding working electrode, or placed in a dedicated reference fluid conduit. The reference electrode and the reference fluid conduit can be a part of the sensor assembly, whereby the sensor assembly can include a plurality of reference electrodes and / or reference fluid conduits. Alternatively, the reference electrode and the reference fluid conduit can be a part of an IVD analyzer, wherein the reference electrode and the reference fluid conduit are operatively connected to the corresponding working electrode and the fluid conduit of the sensor assembly respectively.

[0026] A "standby solution / rinsing solution" is a solution that is used to rinse the sensor after a sample measurement has been taken and that remains in contact with the sensor until it is replaced by a sample of another type.

[0027] "Wetting solution" is a solution used to initialize new, unwetted sensors. This process is usually performed when a new sensor or a new set of sensors is put into use, for example after insertion into an IVD analyzer. This is a necessary process to ensure that each sensor works reliably. The sensor is thereby in contact with the wetting solution for a predetermined time. No sample measurements are performed during the wetting process.

[0028] A "cleaning solution" is a solution used to rinse and clean the fluid system and sensor after measuring a sample. To enhance the effectiveness of the cleaning solution in removing traces of previous sample material or debris, etc., it may contain certain additives, such as detergents, sodium hypochlorite, biocides, etc.

[0029] The above-mentioned types of solutions may have different compositions, or they may have the same composition, partially or completely. Therefore, their naming reflects their function. For example, a wetting solution may have the same composition as a standby solution, but it is used for different purposes and in a different way.

[0030] The term "parameter" is used herein as a general term for indicating the composition of a sample or the physical or chemical properties of a sample, which can be measured and analyzed by a suitable method. For example, the term "parameter" can refer to an analyte, which is any substance or compound (e.g., chemical elements such as ions, or molecules such as peptides, proteins, RNA, DNA, fatty acids, carbohydrates, etc.) in a sample that an analytical method or test attempts to detect. Parameters can also refer to the physical or chemical properties of a sample, such as color, temperature, turbidity, viscosity, acidity, alkalinity, etc. Generally speaking, information about the presence, absence, concentration and / or properties of a sample parameter can give an indication of the patient's health state, and can therefore be used to derive a diagnostic result, or the information can be used to determine and adjust a treatment plan. In addition, known analyte levels can be used in, for example, QC samples or calibrators to confirm that the IVD analyzer is still operating within a specification or allowable range. Examples of parameters of interest in the context of this disclosure are gas partial pressures (such as PO2 and PCO2), oxygen saturation (SO2), blood electrolytes (such as sodium (Na + ), potassium (K + ), magnesium (Mg 2 + ), calcium (Ca 2+ ), Lithium + ), chloride (Cl - ), pH-related protons (H + ), bicarbonate value (HCO3 - )) and metabolites (such as glucose, lactate, urea, creatinine). Other parameters of interest are hemoglobin, hemoglobin derivatives such as deoxyhemoglobin, oxyhemoglobin, carboxyhemoglobin, methemoglobin, sulfhemoglobin, and bilirubin. An example of a physical parameter of interest is the hematocrit level.

[0031] In order to perform analytical measurements based on electrochemical measurement principles, such as in blood gas and electrolyte tests, one or more electrochemical sensors need to be contacted with the sample. Therefore, the term "electrochemical sensor" includes any type of sensor that converts a (bio) chemical reaction into an electrical signal. Depending on the parameter to be measured, different measurement principles can be applied. For example, electrolytes or ions can be determined by the potentiometric principle. A potentiometric sensor measures the potential or voltage between two electrodes in a solution. Therefore, a potentiometric sensor generally includes at least a working electrode (also referred to as a measuring electrode) and a reference electrode. In the present disclosure, the term "potential working electrode" (PWE) is used to describe the working electrode in a potentiometric sensor. Similarly, the term "potential reference electrode" (PRE) refers to the reference electrode of a potentiometric sensor. A membrane sensitive to a specific electrolyte or ion is arranged between the sample and the working electrode. The membrane generally has a complex composition, which includes, for example, a polymer, a plasticizer, an ion carrier, and a lipophilic salt. An ion carrier is a class of compounds that reversibly binds ions to increase the permeability of the membrane to specific ions of interest and is selected according to the parameter to be measured by the sensor. The ions of interest are able to pass through the membrane, thereby generating a potential change that is detected by the working electrode. On the other hand, the reference electrode is in direct contact with the reference solution, which itself is in contact with the sample (liquid junction), so no sample-induced potential change is established. In this way, the reference sensor returns a constant signal that is independent of the ion concentration in the sample. The voltage difference between the reference electrode and the working electrode is then used to calculate the concentration of the ion of interest in the solution. In fact, the voltage difference between these electrodes is proportional to the logarithm of the concentration of the ion of interest. Since these types of sensors are ion-selective, they are also called ion-selective electrodes. They are able to measure many parameters, such as potassium (K + ), sodium (Na + ), calcium (Ca 2+ ), chloride (Cl - ), magnesium (Mg 2+ ), Lithium + ) etc., and / or the chemical properties of the sample can be determined, for example, by measuring the pH value of the sample. However, the potentiometric principle not only allows the measurement of electrolytes or ions, but is also used to measure blood gas levels, such as PCO2 (using a Severinghaus type sensor), and / or metabolites, such as urea, ammonium. In addition to the working electrode and the reference electrode, the potentiometric sensor may also include a correction electrode for correcting potential background noise or interference. In addition, the potentiometric sensor may include an electrode supplemented with a specific enzyme, i.e., the enzyme is applied to the electrolyte layer or electrolyte fluid between the membrane and the electrode. For example, the Severinghaus type sensor includes carbonic anhydrase, which catalyzes the hydration of carbon dioxide to bicarbonate in the presence of water.

[0032] Another electrochemical measurement principle is the current measurement principle. The current sensor measures the current flow between two electrodes, thereby generating current through oxidation / reduction reaction. Therefore, the current sensor usually includes at least a working electrode (also referred to as a measuring electrode) and a counter electrode. In this dual electrode arrangement, the counter electrode also acts as a reference electrode to serve as a reference when measuring and stabilizing the potential of the working electrode. Therefore, the term "current working electrode" (AWE) is used to describe the working electrode of the current sensor, and the term "current counter reference electrode" (ACRE) is used to describe the electrode that serves as both a counter electrode and a reference electrode in the current sensor. However, the reference electrode can also be implemented as an independent electrode except the working electrode and the counter electrode. Therefore, in the present disclosure, the electrodes of this arrangement will be referred to as "current working electrode" (AWE), "current counter electrode" (ACE) and "current reference electrode" (ARE).

[0033] In the field of IVD, different types of amperometric sensors are used. For example, sensors for measuring oxygen partial pressure (PO2) can work according to the Clark measurement principle, in which oxygen diffuses through a membrane to a working electrode that maintains a constant negative voltage relative to a counter-reference electrode. Oxygen is reduced at the working electrode, thereby inducing a current between the working electrode and the counter-reference electrode. The current can be measured, and the current is proportional to the oxygen contained in the sample. Other types of amperometric sensors include enzyme-linked electrodes, in which enzymes accelerate certain desired reactions. For example, certain glucose sensors based on glucose oxidase catalyze the conversion of glucose into hydrogen peroxide and gluconic acid in the presence of water and oxygen. The working electrode is maintained at a constant voltage relative to the reference electrode, which oxidizes hydrogen peroxide, decomposing it into hydrogen ions, oxygen and electrons. This causes a current that can be measured, and the current is proportional to the glucose concentration in the sample. Due to the application of enzymes, these sensors are also referred to as biosensors. In addition to measuring PO2 and glucose, amperometric sensors can also be used to measure other metabolites, such as lactate, creatinine, creatine, etc.

[0034] By forming the reference electrode and the counter electrode (PRE and / or ACRE and / or ARE and ACE) on the same substrate and forming the working electrode (PWE and / or AWE) on the opposite substrate, a simpler and space-saving geometry of the sensor assembly is achieved. In addition, in contrast to the asymmetric curved electric field seen in the sensor arrangement of the prior art, the arrangement enables the current to flow directly across the entire electrode surface and the electric field to be symmetrically and evenly distributed during measurement. Asymmetric electric fields and uneven current densities may lead to uneven losses of the electrode surface, thereby producing areas of different impedances on the electrode, which may have a negative impact on measurement accuracy and reliability. In addition, the proposed arrangement simplifies the manufacturing process because higher manufacturing tolerances can be accepted. For example, in a lateral sensor arrangement, the working electrode and the counter electrode of the current-type sensor are typically formed adjacent to each other. However, slight misalignment of the electrodes may have a significant adverse effect on the performance of the sensor and therefore need to be prevented. In contrast, the electrodes forming the sensor on two opposing substrates allow for a certain misalignment without reducing the performance of the sensor.

[0035] According to certain embodiments, the sensor assembly includes at least one conductivity sensor, which includes a pair of electrodes for measuring the conductivity of the sample, wherein these electrodes are formed on relative substrates. Conductivity sensors are generally not as complex as the above-mentioned potential type sensors or current type sensors. For example, they generally do not include ion selective membranes. Conductivity sensors generally include electrodes of the same structure and are used to measure the ability of a solution to conduct current. The current increases in proportion to the number of ions (or charged particles) dissolved in the solution, their charge and their mobility. Conductivity sensors can be used, for example, to detect the presence or absence of a sample or other fluid in a fluid conduit, for determining parameters (such as the hematocrit level in a sample), for detecting bubbles or clots in a sample, or for calibration purposes. In the sensor assembly of the prior art, the electrodes of the conductivity sensor are generally arranged at the beginning and end of the fluid conduit, and another sensor is placed between these two ends to measure the conductivity of the sample introduced along the fluid conduit. However, the disadvantage of this arrangement is that the conductivity measurement may interfere with the sensor working between the conductivity electrodes, and vice versa. In addition, potential ion concentration gradients or inhomogeneities due to trapped bubbles within the sample may lead to undesired deviations and erroneous hematocrit values. Placing the conductivity electrodes opposite to each other allows for accurate measurement of conductivity. When placed adjacent to, for example, a glucose sensor, it may enable accurate determination of the hematocrit near the glucose measurement location. Abnormal hematocrit levels may interfere with blood glucose measurements and are therefore an important indicator for interpreting glucose measurement results.

[0036] According to one embodiment, at least one substrate is at least partially transparent so that optical detection can be performed. As used herein, the term "optical detection" generally refers to any photometric or spectral measurement method suitable for optical detection of sample parameters (e.g., transmittance of light through a sample or emissivity of light emitted from an irradiated sample). Typical optical detection methods are, for example, photometry, fluorescence spectroscopy, turbidimetry, fluorescence polarization, etc. The sample can be analyzed as is or after dilution with another solution or after mixing with a reagent. Optical detection methods can be used to detect the results of a chemical reaction or a biological reaction, or to monitor the progress of a chemical reaction or a biological reaction. In order to perform an optical detection method on a sample introduced into a fluid conduit of a sensor assembly, at least one of the two opposing substrates is partially transparent. It can be made entirely of a transparent or translucent material (e.g., polypropylene, acrylic acid, polycarbonate, glass, etc.), or it can include a transparent area or a recessed portion (optical measurement window). For example, a metal substrate can have one or more recessed portions in this region of the fluid conduit. This allows a light source installed in an IVD analyzer to illuminate a sample in the fluid conduit. The photoreceptor detects light transmitted or emitted from the sample, thereby converting electromagnetic energy into an electrical signal. Examples of photoreceptors are photodiodes, including avalanche photodiodes, phototransistors, photoconductivity detectors, linear sensor arrays, CCD detectors, CMOS photodetectors (including CMOS array detectors), photomultiplier tubes, photomultiplier tube arrays, etc. The combination of a light source and a photoreceptor is also considered a sensor in the sense of the present application.

[0037] According to certain embodiments, at least one substrate is heat-conductive, or at least one heat-conductive element is arranged adjacent to at least one of the substrates, so as to adjust the operating temperature in the fluid conduit. As used herein, "operating temperature" refers to the temperature or temperature range that provides optimal conditions for sample measurement of the parameter of interest inside the fluid conduit. For example, when measuring PO2, the operating temperature is set to about 37 ° C. Other sensor types may require other operating temperatures. In view of this, a controlled heat transfer to or from the fluid conduit can be established. The operating temperature can be indirectly adjusted via an IVD analyzer, which is equipped with (for example, by a heating coil, a Peltier element, a radiator, etc.) a unit required to transfer heat to the sensor assembly or remove heat from the sensor assembly. The sensor assembly is installed in the IVD analyzer so that the temperature regulating unit of the IVD analyzer is in direct contact with the heat-conductive substrate or heat-conductive element of the sensor assembly. The heat-conductive element can be permanently attached to at least one substrate, or can be integrated into the housing of the sensor assembly. The surface of the heat-conductive element can cover multiple substrates, can cover the entire main surface area of ​​a single substrate, or can partially cover a single substrate, such as being confined to a specific area of ​​the fluid conduit. If different areas in the fluid conduit require different operating temperatures, or if multiple fluid conduits that require separate temperature control are available, the substrate can be provided with multiple thermally conductive elements. The thermally conductive element can be, for example, a metal element or a metal alloy element, or any other suitable material. Alternatively, the thermally conductive element can be designed to actively regulate temperature, for example, if it is a Peltier element. In this case, the IVD analyzer can actuate the thermally conductive element by providing power via corresponding electrical contacts on the sensor assembly.

[0038] According to one embodiment, the PWE and PRE of the potential type sensor are formed on opposite substrates so that they are arranged opposite to each other, and / or the AWE and ACRE or AWE and ACE of the current type sensor are formed on opposite substrates so that they are arranged opposite to each other. For example, the working electrode of the glucose sensor (current type sensor) can be formed on a first substrate, and the counter electrode of the glucose sensor can be formed on a second substrate, wherein these substrates are arranged so that the two electrodes are positioned opposite to each other, that is, as close to each other as possible. The height of the fluid conduit extending between the two substrates thus determines the distance from the working electrode to the counter electrode.

[0039] According to another embodiment, at least one PWE is arranged in a first fluid conduit, and at least one PRE is arranged in a reference fluid conduit different from the first fluid conduit. In order to obtain a more stable potential at the reference electrode of the potentiometric sensor, the reference electrode is usually exposed to a reference solution with a known ion concentration, such as a high concentration KCl solution, rather than performing a reference measurement with, for example, a biological sample. Therefore, the reference electrode is positioned in a separate reference fluid conduit that enables a reference solution to be provided to the reference electrode when the working electrode contacts the sample of interest. Therefore, multiple working electrodes of different potentiometric sensors can share the same reference electrode, or each working electrode can correspond to a separate reference electrode. As an alternative to arranging the reference fluid conduit in the IVD analyzer, it can also be integrated into the sensor assembly. If necessary, the sensor assembly can include multiple reference fluid conduits.

[0040] According to one embodiment, PRE and ARE are the same electrode. Thus, the reference electrode may be arranged in the same fluid conduit as PWE and AWE, or it may be arranged in a separate reference fluid conduit inside or outside the sensor assembly. In any case, the reference electrode is operatively connected to either the potentiometric working electrode or the amperometric working electrode.

[0041] According to one embodiment, the sensor assembly also includes a plurality of fluid conduits and a plurality of sensors in each fluid conduit, wherein the plurality of sensors in each fluid conduit are respectively the same. The additional fluid conduit can serve as a substitute for the first fluid conduit. Therefore, each fluid conduit is equipped with the same set of sensors. In the first stage, measurements are performed only in the first fluid conduit, that is, the sample of interest is introduced into the first fluid conduit for measurement, and all other available fluid conduits are blocked. Only when it has been detected that the sensors in the first fluid conduit do not meet the specifications or these sensors have reached the end of their use time, can the replacement fluid conduit be used. Once such an event occurs, the first fluid conduit is blocked and prevented from being used for additional measurements, and the second fluid conduit is enabled to measure the sample. When the sensor in the expected first fluid conduit does not meet the specifications or reaches the end of its use time, the wetting process of the replacement fluid conduit can be initiated when the first fluid conduit is still in use. Sensor aging or degradation can be detected by monitoring the signal output or signal behavior (such as signal slope or signal drift) generated by the sensor during sample measurement, and comparing the signal output with a reference signal and / or a reference range. Once the signal output reaches a predetermined threshold, it is considered that the sensor is approaching the end of its use time. Aging or degradation can be further detected in the context of the calibration process. The wetting process includes providing a wetting solution to the replacement fluid conduit to enable the corresponding sensor, thereby ensuring a seamless transition from the first fluid conduit to the replacement fluid conduit. This concept can be extended to even more fluid conduits. A switchable valve can be used to guide the sample into an appropriate fluid conduit. Such a valve can be installed in an IVD analyzer, or can be integrated into a sensor assembly. In one example, the entry fluid conduit can be adjusted by controlling a physical obstacle installed in the fluid conduit, such as a gas bag or a liquid bag, a movable flap, a gate-like structure, etc. These physical obstacles can be controlled by establishing a mechanical connection with a counterpart in the IVD analyzer, or can be controlled by a conductive or magnetic mechanism, or can be controlled by any other suitable mechanism. Providing an alternative fluid conduit allows the sensor assembly to have a longer use time.

[0042] According to another embodiment, at least one AWE and at least one ACRE or at least one ACE and ARE are arranged in a second fluid conduit different from the first fluid conduit and different from the reference fluid conduit. These sensors are distributed between multiple fluid conduits based on their measurement principles and / or based on their frequency of use. For example, a potential sensor is arranged in the first fluid conduit, and an electric current sensor is arranged in the second fluid conduit. It may be advantageous to classify measurable parameters into "groups" based on their frequency of use in a clinical environment. For example, doctors more often require the determination of blood gas parameters and electrolytes. However, it may not be often required to measure metabolites (such as glucose or lactate). Therefore, it may be advantageous to physically separate sensors measuring different groups of parameters in the sensor assembly. Preventing sensors from being in unnecessary contact with sample materials prevents unnecessary degradation and thus prolongs their use time. In addition, separation prevents any potential measurement interference between sensors of different measurement types.

[0043] According to another embodiment, the sensor assembly includes a potential sensor and / or an amperometric sensor having different sensitivities to degradation when in contact with a sample or other fluid, wherein the potential sensor and / or the amperometric sensor having a higher degradation sensitivity is arranged along a first fluid conduit, and the potential sensor and / or the amperometric sensor having a lower degradation sensitivity is arranged along a fluid conduit different from the first fluid conduit. It is known that the sensor degrades over time. If the calibrated sensor repeatedly does not meet the specification or the allowable range and cannot be restored to the specification by calibration, the sensor is no longer reliable and needs to be replaced. In other words, the sensor has reached the end of its service time. The degradation rate is highly dependent on the structure of the sensor, for example, it depends on the type of ion carrier applied to the ion selective electrode. When determining the expected service time of the sensor, this naturally occurring degradation can be predicted and taken into account. However, there are other factors that affect the degradation rate in an unpredictable manner and may degrade the sensor at a faster rate than the predicted rate, for example, if the sensor has a high sensitivity to a certain compound in a liquid (e.g., a reagent or a cleaning solution). In the present disclosure, such sensors are referred to as having "higher degradation sensitivity" compared to sensors that are not affected by the liquid or are minimally affected by it (referred to herein as having "lower degradation sensitivity"). For example, an enzyme-linked sensor may be more sensitive to a cleaning solution. Certain components of the cleaning solution (e.g., sodium hypochlorite) may interfere with the enzyme and thereby denature the enzyme, thereby gradually deteriorating the function of the sensor in an unpredictable manner. The service life of the sensor may become much shorter than expected, thereby also shortening the service life of the entire sensor assembly. However, for sensors with different structures, such as those for measuring sodium (Na +) sensors, the same cleaning solution may be ineffective or have a negligible effect. In order to increase the service life of the sensor assembly, it may be advantageous to prevent the sensor with higher degradation sensitivity from contacting the interfering liquid. Therefore, it may be advantageous to arrange them in a separate fluid conduit that is different from the fluid conduit that accommodates the sensor with lower degradation sensitivity. Valves and / or separate fluid paths can be implemented to prevent the interfering liquid from contacting the sensor with higher degradation sensitivity while allowing the liquid to be supplied to the sensor with lower degradation sensitivity. Alternatively, the sensor with higher degradation sensitivity can be formed exactly the same in both fluid conduits. If the first sensor in the first fluid conduit reaches the end of its service life, the second fluid conduit can be used to perform sample measurements.

[0044] According to one embodiment, each fluid conduit in the multiple fluid conduits has a separate fluid inlet and a separate fluid outlet. According to another embodiment, at least two fluid conduits have at least one common fluid inlet and / or at least one common fluid outlet. A fluid connection must be established between the sensor assembly and the IVD analyzer so as to enable the sample to be transferred to and from the fluid conduit of the sensor assembly. Therefore, the IVD analyzer is equipped with a pair of components tightly connected to the available fluid inlet and fluid outlet of the sensor assembly. In the case of a sensor assembly with multiple fluid conduits, each fluid conduit can have a separate fluid inlet and a separate fluid outlet. Alternatively, these fluid conduits can converge inside the sensor assembly to share a common fluid inlet and / or a common fluid outlet.

[0045] According to one embodiment, the sensor assembly includes at least one switchable valve for directing a sample into any one of the fluid conduits. The switchable valve is operatively connected to the IVD analyzer. Thus, a controller of the IVD analyzer can control the switchable valve to direct an available sample into a selected fluid conduit.

[0046] According to one embodiment, the potentiometric sensor is a sodium or potassium or calcium or chloride or pH or carbon dioxide or urea or ammonium or lithium or magnesium sensor and the amperometric sensor is a glucose or lactate or creatinine or creatine or oxygen sensor. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 is a schematic three-dimensional exploded view of a sensor assembly according to one embodiment, the sensor assembly comprising two opposing substrates;

[0048] Figure 2Ais a schematic three-dimensional exploded view of a sensor assembly according to another embodiment, the sensor assembly including two opposing substrates with a spacer between the two substrates;

[0049] Figure 2B Schematically shows Figure 2A A lateral cross-sectional view of a sensor assembly;

[0050] Figure 3 is a schematic three-dimensional exploded view of a sensor assembly according to further embodiments, the sensor assembly comprising two opposing substrates and a valve for directing fluid into either of the fluid conduits.

[0051] It will be appreciated by the skilled person that the elements in the drawings are shown for simplicity and clarity and are not necessarily drawn to scale. For example, the size of some elements in the drawings may be enlarged relative to other elements to help enhance understanding of the embodiments of the present disclosure. DETAILED DESCRIPTION

[0052] Figure 1 An example of a sensor assembly 1 is schematically shown in a three-dimensional exploded view. The sensor assembly includes two opposing substrates 10A, 10B. One of the two opposing substrates 10B includes a recessed portion forming a fluid conduit 2, 4 (indicated by a dotted line). Alternatively, the opposing substrates 10A, 10B may include complementary recessed portions that, when assembled, form the fluid conduits 2, 4 (not shown). A sealing element may be positioned between the two opposing substrates 10A, 10B for sealing the fluid conduits 2, 4 and preventing leakage (not shown). The sealing element may be a polymer having appropriate properties with respect to viscosity and elasticity (e.g., an elastomer such as a thermoplastic elastomer, rubber, silicone, latex, etc.). The first substrate 10A is a steel substrate, while the opposing substrate 10B is a transparent polymer substrate. Electrodes 11A, 12A, 13A are formed on the steel substrate 10A. An insulating layer (not shown) exists between the electrodes 11A, 12A, 13A and the steel substrate 10A. Alternatively, both substrates may be made of a non-conductive material (eg, a polymer, ceramic, glass material), or both substrates may be made of a conductive material (eg, a metal or a metal alloy).

[0053] When the sensor assembly 1 is positioned in an in vitro diagnostic (IVD) analyzer, the heat-conductive steel substrate 10A is operatively connected to a temperature regulating unit (e.g., a heating coil, a Peltier element, a heat sink) of the IVD analyzer (not shown). The IVD analyzer controls the temperature regulating unit according to a predetermined protocol to transfer heat to or from the fluid conduits 2, 4 via the heat-conductive substrate 10A. Thus, the operating temperature in the fluid conduits 2, 4 can be adjusted.

[0054] A plurality of sensors are arranged on two opposing substrates 10A, 10B, facing the fluid conduits 2, 4. Figure 1 In the depicted embodiment, the sensor assembly 1 includes an amperometric sensor, a potentiometric sensor, and a conductivity sensor. The amperometric sensor includes an amperometric working electrode (AWE) 11A, an amperometric counter electrode (ACE) 11C, and an amperometric reference electrode (ARE) 11B. The amperometric sensor is used to detect a variety of sample parameters, such as PO2, glucose, or lactate. Figure 1 The potentiometric sensor in the embodiment includes a potentiometric working electrode (PWE) 12A and a potentiometric reference electrode (PRE) 12B. The potentiometric sensor is used to detect such substances as PCO2, pH, Na + , Ca 2+ , K + and Cl - And other parameters. Figure 1 The conductivity sensor in comprises two electrodes 13A, 13B, and is used to measure the ability of the sample to conduct current. This can be used to determine, for example, the hematocrit level in the sample. The order in which the electrodes 11A, 11B, 12A, 12B, 13A, 13B are arranged on two opposite substrates 10A, 10B can be based on different factors. For example, electrodes that may interfere with each other can be arranged to be as far away from each other as possible. In particular, some materials used to form the sensing element may leach between adjacent sensing elements, thereby causing interference. For example, the release of Ag ions from the Ag / AgCl electrode may have an adverse effect on the stability of the enzyme fixed on the working electrode of the current-type sensor. In another example, the leaching of the enzyme from the working electrode of the current-type sensor may have an adverse effect on the function of other current-type working electrodes (for example, the bovine serum albumin working electrode may be contaminated by the lactate oxidase and / or glucose oxidase leached from the lactate working electrode or the glucose working electrode, respectively). In another example, the leaching of plasticizers and / or ion carriers from the ion-selective electrode membrane may have an adverse effect on the function of the adjacently arranged potential-type sensor. Sensors based on the same measuring principle or operating in the same temperature range can be combined. Figure 1 In the illustrated embodiment, the ARE 11B, ACE 11C and PRE 12B are formed on the same substrate 10B, while the AWE 11A and PWE 12A are formed on the opposite substrate 10A. Therefore, when the two opposite substrates 10A, 10B are assembled, the ACE 11C is positioned opposite to its corresponding AWE 11A. With respect to the conductivity sensor, the first electrode 13A is formed on the first substrate 10A, and the second electrode 13B is formed on the opposite substrate 10B.

[0055] Once a sample (e.g. a biological sample, a calibrator, a quality control (QC) sample, a reference solution) is introduced into the fluid conduits 2, 4 via the respective fluid inlets 5, 7, it comes into contact with the electrodes 11A, 11B, 11C, 12A, 12B, 13A, 13B and a measurement can be performed. Figure 1 In the depicted embodiment, fluid conduit 4 is a reference fluid conduit and is designated for receiving a reference solution for making a reference measurement. Reference fluid conduit 4 has a separate fluid inlet 7 through which a reference solution is delivered to sensor assembly 1 from a reservoir in an IVD analyzer (not shown). Reference electrodes PRE 12B and ARE 11B are formed along reference fluid conduit 4. First fluid conduit 2 and reference fluid conduit 4 converge and lead to a common fluid outlet 8 through which fluid is transferred out of sensor assembly 1 and returned to the fluid system of the IVD analyzer, in which case the fluid may be wasted (not shown). Fluid inlets 5, 7 and fluid outlet 8 are arranged in a manner similar to those of FIG. 1 . Figure 1 10B is depicted as a hole. However, in order to establish a fluid connection with a corresponding counterpart in an IVD analyzer, the fluid inlet 5, 7 and the fluid outlet 8 can protrude from the substrate, for example in a tubular shape, thereby forming a male part of a mating connector pair. The counterpart in the IVD analyzer can be designed as a receptacle for the protruding tubular shape. These tubular protrusions can be formed by the substrate 10B, or can be formed by a housing (not shown) surrounding the sensor assembly 1.

[0056] The electrical contact element 14 is used to establish an electrical connection between the sensor of the sensor assembly 1 and the IVD analyzer. Figure 1 In the embodiment shown, the electrodes 11A, 12A, 13A formed on the first substrate 10A are connected to the corresponding electrical contact elements 14 via conductive paths (e.g., silver, silver chloride, platinum or carbon paths) printed on the substrate 10A. On the second substrate 10B, the electrodes 11B, 11C, 12B, 13B are connected to the corresponding electrical contact elements 14 via through holes through the substrate 10B, whereby the through holes are filled with conductive material. Thus, the electrodes 11B, 11C, 12B, 13B and the electrical contact elements 14 are formed on opposite major surface areas of the second substrate 10B. Alternatively, the electrical contact elements 14 may be formed on the same major surface area as the electrodes 11B, 11C, 12B, 13B and connected via conductive paths printed on the substrates.

[0057] When assembled during manufacturing, the two opposing substrates 10A, 10B are permanently attached to each other. This can be achieved, for example, with an adhesive or by welding, or with a mechanical fastening method (such as a snap lock mechanism, screws, bolts, etc.). The sensor assembly 1 also includes a housing (not shown), which is usually made of a non-conductive material (such as a polymer) to protect the sensor and wiring from the external environment and facilitate gripping. The sensor assembly 1 including its housing is replaceably inserted into a corresponding receiving unit of an IVD analyzer (not shown), and then the analytical measurement is performed therein.

[0058] Figure 2A Another example of a sensor assembly 1' according to another embodiment of the present disclosure is schematically shown. The sensor assembly includes two opposing substrates 20A, 20B. A spacer 20C is arranged between the two opposing substrates 20A, 20B, wherein the spacer 20C includes a recessed portion forming a fluid conduit 2, 3, 4, one of which is a reference fluid conduit 4. The spacer 20C is made of an inert non-conductive material (e.g., a polymer, ceramic, or glass material). In addition, the spacer can have appropriate properties with respect to viscosity and elasticity to ensure sufficient sealing of the fluid conduits 2, 3, 4. Alternatively, a sealing element can be arranged between the first substrate 20A of the two substrates and the spacer 20C and between the second substrate 20B of the two substrates and the spacer 20C for sealing the fluid conduits 2, 3, 4 and preventing leakage (not shown). The first substrate 20A is a steel substrate and the second substrate 20B is a transparent polymer substrate. The steel substrate 20A enables the operating temperature in the fluid conduits 2, 3, 4 to be adjusted. Therefore, it is arranged to be operatively connected to a temperature regulation unit (not shown) of an IVD analyzer. The transparent polymer substrate 20B can enable optical detection of sample parameters of interest. An optical detection unit (including, for example, a light source and a photoreceptor) can be installed in an IVD analyzer (not shown). Once the sensor assembly 1 'is positioned in the IVD analyzer, the optical detection unit is aligned with one or more of the fluid conduits 2, 3, 4. Figure 2AIn the illustrated embodiment, it is assumed that a light source (not shown) is positioned above the second substrate 20B, whereby the light emitted by the light source is directed through the sample in the first fluid conduit 2, and the transmitted light is detected by a photoreceptor (not shown) positioned below the first substrate 20A. Therefore, the first substrate 20A includes a hole 15 that allows the transmitted light to reach the photoreceptor. The hole 15 is a recessed portion formed in the first substrate 20A and filled with a transparent material (e.g., a polymer or glass). Alternatively, both the light source and the photoreceptor can be positioned on the same side of the sensor assembly 1 ', for example, above the second substrate 20B. In one example, an optical detection method for determining the oxygen level in a sample can be based on fluorescence quenching. Therefore, a fluorescence signal that is inversely proportional to the oxygen level in the sample is detected by the photoreceptor and converted into an electrical signal. The samples may have to be pre-treated, for example, they may have to be mixed with a reagent before measurement.

[0059] A plurality of sensors are arranged on two opposing substrates 20A, 20B to face the fluid conduits 2, 3, 4 formed in the spacer 20C. In this case, the sensors are grouped based on their sensitivity to degradation caused by the system fluid. Sensors with higher degradation sensitivity are arranged along the first fluid conduit 2. Figure 2A In the embodiment shown, this refers to sensors measuring, for example, pH, glucose or lactate. Therefore, the corresponding working electrodes AWE 11A and PWE 12A and the counter electrode ACE 11C are formed along the first fluid conduit 2. Therefore, the counter electrode ACE 11C is formed on the first substrate 20A, while the working electrodes AWE 11A and PWE 12A are formed on the opposite substrate 20B. The sensor with lower degradation sensitivity is arranged along a fluid conduit 3 different from the first fluid conduit 2. This refers to sensors measuring, for example, Na + , Ca 2+ , K + and Cl - The corresponding working electrode PWE 12A' is formed on the opposite substrate 20B. All reference electrodes ARE 11B and PRE 12B are formed on the first substrate 20A along the reference fluid conduit 4, whereby a single current-type reference electrode ARE 11B is operatively connected to a plurality of current-type working electrodes AWE 11A and a current-type counter electrode ACE 11C, and a single potential-type reference electrode PRE 12B is operatively connected to a plurality of potential-type working electrodes PWE 12A, 12A'. Figure 2AIn the embodiment of the present invention, the sensor assembly 1' comprises two pairs of conductivity sensors 13A, 13A', 13B, 13B'. Two electrodes 13A, 13A' are formed on a first substrate 20A, and two electrodes 13B, 13B' are formed on a second substrate 20B. A pair of conductivity electrodes 13A', 13B' are formed on two opposing substrates 20A, 20B so that they are positioned directly opposite each other in the first fluid conduit 2. They can be used to determine the hematocrit of a sample that is close to or adjacent to the glucose sensor. Other conductivity electrodes 13A, 13B are formed in the reference fluid conduit 4 and the second fluid conduit 3, respectively, and can be used to detect whether a sample is present in the corresponding fluid conduits. Figure 2A The electrical contact elements 14 in FIG. 1 are connected to the sensor via conductive paths printed onto the substrates 20A, 20B and represent electrical contact points between the sensor assembly 1 ′ and the IVD analyzer.

[0060] like Figure 2A The illustrated sensor assembly 1' includes separate fluid inlets 5, 6, 7 for each of a plurality of fluid conduits 2, 3, 4, one of which is a reference fluid conduit 4 and is designated for receiving a reference solution for reference measurement. The plurality of fluid conduits 2, 3, 4 converge and lead to a common fluid outlet 8, through which the fluid is transported out of the sensor assembly 1' and returned to the fluid system of the IVD analyzer, in which case the fluid may be wasted (not shown). The fluid inlets 5, 6, 7 and the fluid outlet 8 are formed in the second substrate 20B and are respectively incorporated into the fluid conduits 2, 3, 4 in the spacer 20C. Alternatively, the fluid inlets 5, 6, 7 and the fluid outlet 8 may be formed in the first substrate 20A and may be respectively incorporated into the fluid conduits 2, 3, 4 from there, or they may be formed in the spacer 20C. As Figure 2A As depicted, the fluid connection between the sensor assembly 1 'and the IVD analyzer is parallel to the flow direction of the fluid conduit, which reduces the risk of bubble formation at the interface and ensures reliable flushing or cleaning. However, the fluid connection between the sensor assembly 1 'and the IVD analyzer can be established at any angle between 0° and 90°.

[0061] Figure 2B It is shown that the Figure 2ASchematic diagram of a cross section of a sensor assembly 1'. The sensor assembly 1' is shown in an assembled form, that is, the substrates 20A, 20B and the spacer 20C are connected to each other. The AWE 11A and ACE 11C of the current type sensor are formed on two opposite substrates 20B and 20A, respectively, so that they are arranged opposite to each other in the first fluid conduit 2, which enables a uniform and symmetrical current density and field distribution on the electrode surface during measurement. In addition, the PWE 12A' and PRE 12B of the potential type sensor are formed on two opposite substrates 20B and 20A, respectively, wherein the PWE 12A' faces the second fluid conduit 3 and the PRE 12B faces the reference fluid conduit 4. A contact element 14 connected to an electrode (e.g., AWE 11A) formed on the substrate 20B is also shown.

[0062] Figure 3 Yet another example of a sensor assembly 1″ according to another embodiment of the present disclosure is schematically shown in a three-dimensional exploded view. The sensor assembly 1″ includes two opposing substrates 30A, 30B. A spacer 30C is arranged between the two opposing substrates 30A, 30B, wherein the spacer 30C includes a recessed portion forming the fluid conduits 2, 3 and the reference fluid conduit 4. Both opposing substrates 30A, 30B are polymer substrates, whereby the second substrate 30B is made of a transparent polymer to enable optical detection of sample parameters of interest. The sensor assembly 1″ also includes thermally conductive elements 40A, 40B, which are arranged adjacent to the first substrate 30A and are made of a thermally conductive material (e.g., a metal or a metal alloy). The sensor assembly 1″ may include a single thermally conductive element, or it may include a plurality of thermally conductive elements 40A, 40B. In the latter case, the plurality of thermally conductive elements 40A, 40B may be made of the same thermally conductive material, or may be made of different materials having different properties with respect to thermal conductivity. When the sensor assembly 1" is positioned in an IVD analyzer, the thermally conductive elements 40A, 40B are operatively connected to a separate temperature regulating unit (not shown) of the IVD analyzer. This enables heat to be supplied to or extracted from the fluid conduits 2, 3 and the reference fluid conduit 4 of the sensor assembly 1" independently via the thermally conductive elements 40A, 40B. Figure 3 The arrangement shown allows the operating temperature in the first fluid conduit 2 and the reference fluid conduit 4 to be adjusted by supplying or extracting heat via the first heat-conducting element 40A. The operating temperature in the second fluid conduit 3 can be adjusted separately by supplying or extracting heat via the second heat-conducting element 40B. A heat-insulating layer may be implemented between the two heat-conducting elements 40A, 40B to prevent temperature exchange between them (not shown).

[0063] Two opposing substrates 30A, 30B include a plurality of sensors facing the fluid conduits 2, 3 and the reference fluid conduit 4 formed in the spacer 30C. In this case, they are allocated to different fluid conduits according to their frequency of use in a clinical environment, that is, the potential-type working electrode PWE 12A of the potential-type sensor is arranged along the first fluid conduit 2, and the current-type working electrode AWE 11A and the current-type counter-reference electrode ACRE 11D are arranged along the second fluid conduit 3 different from the first fluid conduit 2 and the reference fluid conduit 4. The potential-type reference electrode PRE 12B is formed along the reference fluid conduit 4. The PWE 12A and AWE 11A are thus formed on the first substrate 30A, while the PRE 12B and ACRE 11D are formed on the opposing substrate 30B. A single PRE 12B is operatively connected to a plurality of PWE 12A, thereby forming a sensor for measuring, for example, pH, Na + , Ca 2+ , K + and Cl - The plurality of AWEs 11A and ACREs 11D form a plurality of current sensors for measuring, for example, glucose or lactate. The sensor assembly 1 further comprises two pairs of conductivity sensors 13A, 13B. The two electrodes 13A are formed on a first substrate 30A and are operatively connected to the two electrodes 13B formed on an opposite substrate 30B. An electrical connection between the sensor assembly 1″ and the IVD analyzer is established via the electrical contact element 14. According to another embodiment not shown in the present disclosure, the same set of sensors can be formed in both the first fluid conduit 2 and the second fluid conduit 3. Sample measurements can be performed in the first fluid conduit 2 until, for example, the first sensor in the first fluid conduit 2 does not meet specifications or reaches the end of its service life. When the first sensor in the first fluid conduit 2 is expected to not meet specifications or reach the end of its service life, a wetting process of the second fluid conduit 3 can be initiated while the first fluid conduit 2 is still in use. The wetting process includes providing a wetting solution to the second fluid conduit 3 to enable the corresponding electrodes 11A, 11D. After the wetting process is completed, the sample inflow can then be directed into the second fluid conduit 3 while blocking the inflow from entering the first fluid conduit 2. Sample measurements can then be performed in the second fluid conduit 3 until, for example, the first sensor in the second fluid conduit 3 reaches the end of its service life. Until then, the sensor assembly 1″ must be replaced by the operator, thereby increasing the service life of the sensor assembly 1″.

[0064] like Figure 3The illustrated sensor assembly 1" includes two separate fluid inlets 5, 7 formed in the second substrate 30B. The first fluid inlet 7 leads to a reference fluid conduit 4 formed in the spacer 30C. The second fluid inlet 5 is a common fluid inlet for the first fluid conduit 2 and the second fluid conduit 3. The first fluid conduit 2, the second fluid conduit 3 and the reference fluid conduit 4 converge and lead to a common fluid outlet 8, through which the fluid is transported out of the sensor assembly 1" and returned to the fluid system of the IVD analyzer, in which case the fluid may be wasted (not shown). In order to direct the sample into the first fluid conduit 2 or the second fluid conduit 3 or into both fluid conduits 2, 3 at the same time, the sensor assembly 1" includes a switchable valve 9, which is Figure 3 It is shown as a rotatable valve. However, it can also be implemented as a flap or gate-like element, etc., or as a magnetically actuated element. Figure 3 In the depicted embodiment, the valve 9 extends from the first substrate 30A through the spacer 30C to the opposite substrate 30B (indicated by the dashed line), where it provides a mechanical or sensing contact point for a counterpart in the IVD analyzer. When the sensor assembly 1 "is positioned in the IVD analyzer, the valve 9 is operatively connected to a corresponding counterpart in the IVD analyzer (not shown), which enables the valve 9 to be switched to a desired position. For example, in Figure 3 In the embodiment of the present invention, the valve is switched to a position that enables the sample to be transferred into the second fluid conduit 3, while blocking the sample from entering the first fluid conduit 2. Depending on the position of the valve 9, the sample can be directed only into the first fluid conduit 2, or into both fluid conduits 2, 3 at the same time.

[0065] In the foregoing description, the device and method according to various embodiments are described in detail. The device and method can be embodied in many different forms, and should not be construed as being limited to the embodiments set forth and illustrated herein. Therefore, it should be understood that the device and method are not limited to the specific embodiments disclosed, and modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are used herein, these terms are only used in a general and descriptive sense, rather than for the purpose of limitation. Unless otherwise defined, all scientific and technological terms used herein have the same meaning as commonly understood by those skilled in the art to which the present disclosure belongs. Although any methods and materials similar or equivalent to those methods and materials described herein can be used in the practice or testing of the method, preferred methods and materials are described herein.

[0066] In addition, referring to a certain element by the indefinite article "a" or "a kind" does not exclude the possibility of the presence of more than one element, unless the context clearly requires that there is and there is only one element. Therefore, the indefinite article "a" or "a kind" usually means "at least one / kind". Similarly, the terms "have", "comprise" or "include" or any arbitrary grammatical variation thereof are used in a non-exclusive manner. Therefore, these terms can refer to the situation in which, in addition to the features introduced by these terms, there are no other features in the entity described in the context, and can also refer to the situation in which there are one or more other features. For example, expressions such as "A has B", "A contains B" and "A includes B" can refer to the situation in which, in addition to B, there are no other elements in A (i.e., A is only and exclusively composed of B), and can also refer to the situation in which, in addition to B, there are one or more other elements (such as element C, element C and element D, or even other elements) in A.

[0067] In addition, references throughout this specification to "one embodiment" or "an example" mean that a particular feature, structure, or characteristic described in conjunction with the embodiment or example is included in at least one embodiment. Therefore, the phrases "in one embodiment" or "an example" appearing in various places throughout this specification do not necessarily all refer to the same embodiment or example.

[0068] Furthermore, the particular features, structures or characteristics may be combined in any suitable combinations and / or subcombinations in one or more embodiments or examples.

[0069] In summary, the present invention includes but is not limited to the following items:

[0070] 1. A sensor assembly (1, 1', 1") for an IVD analyzer, comprising:

[0071] - two opposing substrates (10A, 10B, 20A, 20B, 30A, 30B) between which at least one fluid conduit (2, 3, 4) for receiving a sample is formed;

[0072] - a plurality of electrochemical sensors arranged on the two opposing substrates (10A, 10B, 20A, 20B, 30A, 30B), the plurality of electrochemical sensors facing the at least one fluid conduit (2, 3, 4), for contacting the sample and determining sample parameters, the plurality of electrochemical sensors being selected from amperometric sensors, potentiometric sensors or a combination thereof;

[0073] - wherein the potentiometric sensor comprises a potentiometric working electrode (PWE) (12A, 12A') and a potentiometric reference electrode (PRE) (12B);

[0074] - wherein the amperometric sensor comprises an amperometric working electrode (AWE) (11A) and an amperometric counter reference electrode (ACRE) (11D) or an AWE (11A) and an amperometric reference electrode (ARE) (11B) and an amperometric counter electrode (ACE) (11C);

[0075] - wherein the PRE (12B) and / or the ACRE (11D) and / or the ARE (11B) and the ACE (11C) are formed on the same substrate of the two substrates (10A, 10B, 20A, 20B, 30A, 30B), and wherein the PWE (12A, 12A') and / or the AWE (11A) are formed on an opposite one of the two substrates (10A, 10B, 20A, 20B, 30A, 30B).

[0076] 2. A sensor assembly (1, 1', 1") according to item 1, wherein the at least one fluid conduit (2, 3, 4) is formed in a spacer (20C, 30C) arranged between the two opposing substrates (10A, 10B, 20A, 20B, 30A, 30B).

[0077] 3. A sensor assembly (1, 1', 1") according to any one of items 1 or 2, which also includes at least one conductivity sensor, wherein the conductivity sensor includes a pair of electrodes (13A, 13A', 13B, 13B') for measuring the conductivity of the sample, wherein the electrodes (13A, 13A', 13B, 13B') are formed on relative substrates (10A, 10B, 20A, 20B, 30A, 30B).

[0078] 4. The sensor assembly (1, 1', 1") according to any of the preceding items, wherein at least one substrate (10A, 10B, 20A, 20B, 30A, 30B) is at least partially transparent to enable optical detection.

[0079] 5. A sensor assembly (1, 1', 1") according to any of the preceding items, wherein at least one substrate (10A, 10B, 20A, 20B, 30A, 30B) is thermally conductive, or wherein at least one thermally conductive element (40A, 40B) is arranged adjacent to at least one of the substrates (10A, 10B, 20A, 20B, 30A, 30B) so as to regulate the operating temperature in the fluid conduit (2, 3, 4).

[0080] 6. A sensor assembly (1, 1', 1") according to any one of the preceding items, wherein the PWE (12A, 12A') and the PRE (12B) of a potential-type sensor are formed on the relative substrates (10A, 10B, 20A, 20B, 30A, 30B) so that they are arranged opposite to each other, and / or wherein the AWE (11A) and the ACRE (11D) or the AWE (11A) and the ACE (11C) of an amperometric sensor are formed on the relative substrates (10A, 10B, 20A, 20B, 30A, 30B) so that they are arranged opposite to each other.

[0081] 7. A sensor assembly (1, 1', 1") according to any one of items 1 to 5, wherein at least one of the PWEs (12A, 12A') is arranged in a first fluid conduit (2), and at least one of the PREs (12B) is arranged in a reference fluid conduit (4) different from the first fluid conduit (2).

[0082] 8. The sensor assembly (1, 1', 1") according to any of the preceding items, wherein the PRE (12B) and the ARE (11B) are the same electrode.

[0083] 9. A sensor assembly (1, 1', 1") according to any one of the preceding items, comprising a plurality of fluid conduits (2, 3) and a plurality of sensors in each fluid conduit, wherein the plurality of sensors in each fluid conduit are respectively identical.

[0084] 10. A sensor assembly (1, 1', 1") according to any one of items 1 to 8, wherein at least one of the AWE (11A) and at least one of the ACRE (11D) or at least one of the ACE (11C) and the ARE (11B) are arranged in a second fluid conduit (3) which is different from the first fluid conduit (2) and different from the reference fluid conduit (4).

[0085] 11. A sensor assembly (1, 1', 1") according to any one of items 1 to 8, comprising a potential-type sensor and / or an amperometric sensor having different sensitivities to degradation occurring through a system fluid, wherein the potential-type sensor and / or the amperometric sensor having a higher degradation sensitivity is arranged along a first fluid conduit (2), and the potential-type sensor and / or the amperometric sensor having a lower degradation sensitivity is arranged along a fluid conduit (3) different from the first fluid conduit (2).

[0086] 12. A sensor assembly (1, 1', 1") according to any one of items 9 to 11, wherein each of the plurality of fluid conduits (2, 3, 4) has a separate fluid inlet (5, 6, 7) and a separate fluid outlet (8).

[0087] 13. A sensor assembly (1, 1', 1") according to any one of items 9 to 11, wherein at least two fluid conduits (2, 3, 4) have at least one common fluid inlet (5, 6, 7) and / or at least one common fluid outlet (8).

[0088] 14. The sensor assembly (1, 1', 1") according to item 13, comprising at least one switchable valve (9) for directing the sample into any one of the fluid conduits (2, 3, 4).

[0089] 15. A sensor assembly (1, 1', 1") according to any of the preceding items, wherein the potentiometric sensor is a sodium or potassium or calcium or chloride or pH or carbon dioxide or urea or ammonium or lithium or magnesium sensor, and the amperometric sensor is a glucose or lactate or creatinine or creatine or oxygen sensor.

Claims

1. A sensor assembly (1, 1', 1") for an IVD analyzer, comprising: - two opposing substrates (10A, 10B, 20A, 20B, 30A, 30B) between which at least one fluid conduit (2, 3, 4) for receiving a sample is formed; - a plurality of electrochemical sensors arranged on the two opposing substrates (10A, 10B, 20A, 20B, 30A, 30B), the plurality of electrochemical sensors facing the at least one fluid conduit (2, 3, 4), for contacting the sample and measuring sample parameters, the plurality of electrochemical sensors comprising amperometric sensors and potentiometric sensors; - wherein the potentiometric sensor comprises a potentiometric working electrode (PWE) (12A, 12A') and a potentiometric reference electrode (PRE) (12B); - wherein the amperometric sensor comprises an amperometric working electrode (AWE) (11A) and an amperometric counter reference electrode (ACRE) (11D) or an AWE (11A) and an amperometric reference electrode (ARE) (11B) and an amperometric counter electrode (ACE) (11C); - wherein the PRE (12B) and / or the ACRE (11D) and / or the ARE (11B) and the ACE (11C) are formed on the same substrate of the two substrates (10A, 10B, 20A, 20B, 30A, 30B), and wherein the PWE (12A, 12A') and / or the AWE (11A) are formed on an opposite one of the two substrates (10A, 10B, 20A, 20B, 30A, 30B); At least one of the substrates (10A, 10B, 20A, 20B, 30A, 30B) is thermally conductive, or at least one thermally conductive element (40A, 40B) is arranged adjacent to at least one of the substrates (10A, 10B, 20A, 20B, 30A, 30B) so as to adjust the operating temperature in the fluid conduit (2, 3, 4).

2. The sensor assembly (1, 1', 1") according to claim 1, wherein the at least one fluid conduit (2, 3, 4) is formed in a spacer (20C, 30C) arranged between the two opposing substrates (10A, 10B, 20A, 20B, 30A, 30B).

3. The sensor assembly (1, 1', 1") according to any one of claims 1 or 2, further comprising at least one conductivity sensor, the conductivity sensor comprising a pair of electrodes (13A, 13A', 13B, 13B') for measuring the conductivity of the sample, wherein the electrodes (13A, 13A', 13B, 13B') are formed on opposite substrates (10A, 10B, 20A, 20B, 30A, 30B).

4. The sensor assembly (1, 1', 1") according to any of the preceding claims, wherein at least one substrate (10A, 10B, 20A, 20B, 30A, 30B) is at least partially transparent to enable optical detection.

5. A sensor assembly (1, 1', 1") according to any one of the preceding claims, wherein the PWE (12A, 12A') and the PRE (12B) of a potential-type sensor are formed on the relative substrates (10A, 10B, 20A, 20B, 30A, 30B) so that they are arranged opposite to each other, and / or wherein the AWE (11A) and the ACRE (11D) or the AWE (11A) and the ACE (11C) of an amperometric sensor are formed on the relative substrates (10A, 10B, 20A, 20B, 30A, 30B) so that they are arranged opposite to each other.

6. The sensor assembly (1, 1', 1") according to any one of claims 1 to 4, wherein at least one of the PWEs (12A, 12A') is arranged in a first fluid conduit (2), and at least one of the PREs (12B) is arranged in a reference fluid conduit (4) different from the first fluid conduit (2).

7. The sensor assembly (1, 1', 1") according to any one of the preceding claims, wherein the PRE (12B) and the ARE (11B) are the same electrode.

8. A sensor assembly (1, 1', 1") according to any of the preceding claims, wherein the potentiometric sensor is a sodium or potassium or calcium or chloride or pH or carbon dioxide or urea or ammonium or lithium or magnesium sensor, and the amperometric sensor is a glucose or lactate or creatinine or creatine or oxygen sensor.

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