Sensor device

Abstract

The present disclosure relates to a sensor device including: a measurement chamber having at least a first wall, the measurement chamber containing a plurality of analyte sensors; wherein the measurement chamber allows a fluid to be analyzed to interact with each of the plurality of analyte sensors when the fluid is contained within the measurement chamber; the measurement chamber having an inlet configured to receive the fluid to be analyzed and an outlet configured to allow the fluid to exit the measurement chamber after interacting with the plurality of analyte sensors; the measurement chamber defining a sample volume for containing the fluid to be analyzed, the sample volume extending between at least the inlet and the outlet; and a heating element configured to heat the fluid contained within the measurement chamber.

Description

Technical Field

[0001] The present invention relates to a sensor device and an analyzer including such a sensor device.

Background Art

[0002] Analyzers for measuring physical parameters of analytes in fluid samples by respective analyte sensors are widely used in various industries such as the food industry, environmental industry, and medical and clinical industries.

[0003] Such analyzers often include a sensor device having a measurement chamber for accommodating a sample to be analyzed. The measurement chamber may have a plurality of analyte sensors distributed throughout the measurement chamber.

[0004] To ensure accurate and precise results, the performance of such a sensor device requires sufficiently accurate temperature control of the sample to be analyzed. For this purpose, known sensor devices include a heating element.

[0005] An example of a sensor device including a heating element is disclosed in International Publication No. WO 2017 / 120464. Generally, it is desirable to keep the manufacturing cost of a sensor device low or even to reduce the manufacturing cost. This is particularly desirable since sensor devices often have a limited lifespan and are provided as replaceable parts.

[0006] Nevertheless, it is important that the sensor device provides accurate, precise and reliable measurement results. Since the operation of many sensors is sensitive to the sample temperature, it is therefore desirable to maintain a uniform temperature throughout the measurement chamber having a plurality of analyte sensors distributed throughout the measurement chamber.

[0007] The accurate and precise operation of an analytical system is particularly important in clinical analysis applications for analyzing the physical parameters of analytes in body fluids such as whole blood. In addition to the requirements for accuracy, precision and reliability, such analytical systems for clinical applications are also subject to additional significant constraints such as short analysis times, i.e., short times from sample application to obtaining measurement results and the ability to provide highly reliable results from very small sample volumes.

[0008] The combination of all these constraints is particularly relevant to blood analyzers. Blood analyzers provide measurements of various parameters for analyzing the blood of mammalian subjects, for example, for establishing and / or monitoring the biological state of the subject. Typically, the mammalian subject is a human patient. In various cases, it is desirable to measure, for example, the partial pressure of blood gases in a whole blood sample of a mammalian subject, the concentration of electrolytes and metabolites in a blood sample, and the hematocrit value of a blood sample. For example, measuring pCO 2 、pO 2 、pH、Na + 、K + 、Ca 2+ 、Cl - 、Mg 2+ 、glucose, lactate, creatinine, urea, as well as the values of hemoglobin and hemoglobin derivatives, are major clinical indicators in the assessment of the state of a medical patient. Currently, many different analyzers exist for performing such measurements.

Prior Art Documents

Patent Documents

[0009]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0010] In each analysis to be performed, it is desirable to provide a relatively small measurement chamber for containing the sample to be analyzed in order to use as little of the patient's blood as possible and to provide a plurality of analyte sensors so that multiple measurement results can be confirmed using the same sample. Performing blood analysis using a small amount of blood sample is important when a relatively large number of samples have to be taken in a relatively short length of time or when the amount of blood is limited, for example, in newborns. For example, a patient in intensive care may require a sampling frequency of 15 to 20 samples per day for blood gas and clinical chemistry measurements, which can lead to potentially significant blood loss during patient evaluation. Further, in order to limit the number of tests that have to be performed, it is desirable to collect as much information as possible at the end of each test. Further, for the same reason, it is important that the measurement results and corresponding analysis results obtained from these measurements are reliable. In a clinical environment, since important clinical decisions may depend on knowledge of the measurement results, it is also important that the time required to analyze an individual sample is as short as possible. Further, if the analyzer can be operated with high throughput, efficient use of the analyzer is promoted.

[0011] Accordingly, it is still desirable to provide an improved sensor device that meets one or more of the above objectives or at least provides a suitable alternative to known sensor devices.

Means for Solving the Problems

[0012] According to a first aspect, what is disclosed herein is the following: - A measurement chamber having at least a first wall, the measurement chamber including a plurality of analyte sensors; wherein the measurement chamber enables the fluid to be analyzed to interact with each of the plurality of analyte sensors when the fluid is contained within the measurement chamber; the measurement chamber having an inlet configured to receive the fluid to be analyzed and an outlet configured to allow the fluid to exit the measurement chamber after interacting with the plurality of analyte sensors; the measurement chamber defining a sample volume for containing the fluid to be analyzed, the sample volume extending at least between the inlet and the outlet; and - A heating element configured to heat the fluid contained within the measurement chamber; A sensor device embodiment, wherein the heating element is configured to provide a greater heating effect in the vicinity of the inlet of the measurement chamber than in the vicinity of the outlet of the measurement chamber.

[0013] The provision of a heating element configured to provide a greater heating effect in the vicinity of the inlet of the measurement chamber than in the vicinity of the outlet of the measurement chamber has been found to provide a more uniform temperature distribution across the plurality of analyte sensors, thereby facilitating accurate and precise measurements for all analyte sensors while maintaining relatively low manufacturing costs and short measurement cycle times. In particular, the sensor device embodiments described herein provide a uniform sample temperature across the entire measurement chamber or at least along the flow path of the sample fluid between the inlet and the outlet. Further, some embodiments of the present invention provide an increased uniformity in the sample temperature per heating element. Thereby, a similar uniformity in the temperature in the measurement chamber can be achieved using a smaller number of heating elements. This in turn reduces the complexity and cost of manufacturing.

[0014] The heating action provided by a part of the heating element can be defined by the heating action provided over the entire measurement cycle, i.e., from when the sample starts to enter the measurement chamber through the inlet until the sample exits the measurement chamber through the outlet. For this purpose, the heating element can be configured to provide a greater heating force, i.e., a greater heating action per unit time, in the vicinity of the inlet of the measurement chamber than in the vicinity of the outlet of the measurement chamber.

[0015] The measurement results of a sensor device that responds to the interaction with a fluid analyte sensor are typically temperature-dependent. Therefore, accurate and reliable measurement results often require the fluid to have a predetermined temperature. For example, for body fluids, the temperature at which the measurement should be performed is typically specified in a range corresponding to body temperature, such as 35°C to 40°C, 36°C to 39°C, 36°C to 38°C, or about 37°C. However, other target temperatures can be used in other embodiments.

[0016] In one embodiment, the sample temperature of the fluid when entering the measurement chamber is lower than the target temperature at which the measurement should be performed. Furthermore, the initial temperature of the fluid sample when inserted into the analyzer can vary. For example, the fluid samples can have different room temperatures when inserted into the analyzer, or they can be cooled. Even in embodiments where the fluid is preheated by the analyzer before entering the measurement chamber, the sample temperature of the fluid when entering the measurement chamber is often still lower than the target temperature.

[0017] The analyte sensors can be arranged at respective positions and can be distributed across the measurement chamber, for example, across the entire measurement chamber or only across a portion of the measurement chamber. In certain embodiments, the temperature of the fluid inside the measurement chamber should be as uniform as possible across the measurement chamber, at least across the portion of the measurement chamber where the analyte sensors are arranged. The inventors understand that a non-uniform distribution of the heating effect results in a more uniform temperature distribution of the fluid across the measurement chamber, particularly along the flow path defined between the inlet and the outlet. In particular, providing a higher heating effect near the inlet than near the outlet helps avoid overheating the sample once the sample approaches the outlet. Providing a non-uniform heating effect enables interaction with a plurality of analyte sensors at a uniform sample temperature while avoiding an extended processing time, for example, by obtaining a thermal equilibrium or extended preheating of the sample and / or the measurement chamber.

[0018] The measurement chamber can have various shapes and sizes, such as cylindrical, box-shaped, etc. The measurement chamber can be an elongated chamber having an inlet end where the inlet is located and an outlet end where the outlet is located. Generally, the sample flows in a direction from the inlet to the outlet, at least while filling and emptying the measurement chamber. The measurement chamber defines a flow path between the inlet and the outlet of the measurement chamber. The flow path has a length defined between the inlet and the outlet. In certain embodiments, the length of the flow path is greater than the dimension(s) of the measurement chamber in one or both other directions across the flow path, i.e., greater than the width and / or height of the measurement chamber. For example, the measurement chamber can have cross-sectional dimensions in the millimeter and / or sub-millimeter range.

[0019] The measurement chamber defines a sample volume that can be defined by one or more walls of the measurement chamber. For example, the measurement chamber can be defined by walls of an ellipsoidal shape. In other examples, the measurement chamber can be a cylindrical chamber where the first wall is a tubular wall. In other aspects, the sensor device includes a second wall of the measurement chamber that is at least on the side opposite the first wall. For example, the first and second walls can be planar or curved walls, and the measurement chamber can be defined between the first and second walls. The flow path between the inlet and the outlet can be linear, curved, serpentine, and / or can have different shapes. The heating element is configured to provide a greater heating effect along a first portion of the flow path, closer to the inlet, and a smaller heating effect along a second portion of the flow path, downstream of the first portion and closer to the outlet. In one aspect, the heating element is configured to provide a heating effect only along the first portion and substantially no heating effect along the second portion of the flow path.

[0020] Generally, the measurement chamber can have a uniform width and / or height along the flow path. Alternatively, the measurement chamber can have a non-uniform width and / or a non-uniform height along the flow path. For example, the measurement chamber can have one or more widening or narrowing around, for example, the analyte sensor.

[0021] Similarly, the analyte sensor can be attached or integrated to one or more of the walls of the measurement chamber. For example, the analyte sensor can include a material deposited on the wall of the measurement chamber by a sensor such as being attached or integrated to the wall.

[0022] When a heating element is disposed on one or more of the walls of the measurement chamber, rapid, reliable, and reproducible conditioning of the fluid sample to a desired target temperature at which the analytical measurement can be carried out can be achieved. For this purpose, the heating element can be physically attached to or integrated with one or more of the walls of the measurement chamber. By physically attaching at least one heating element to at least one wall of the measurement chamber or by integrating at least one heating element with at least one wall of the measurement chamber, good heat transfer can be achieved between the heating element and the fluid sample inside the measurement chamber so as to ensure rapid and reproducible transfer of heating energy from the heating element to the fluid sample. Although heat loss is inevitable, the physical attachment of the heating element to at least one wall of the measurement chamber or the integration of the heating element with at least one wall of the measurement chamber provides a well-controlled heating mechanism where the heat transferred to the sample is systematically linked to the heat generated by the heating element and further to the power / energy consumed by the heating element. The heating element can be attached to or integrated with the wall in various ways, for example, by printing, bonding, adhesion, etc. The heating element can be disposed on more than one wall, for example, on both the first and second walls, or on at least one of both the first and second walls and any additional walls. Alternatively, the heating element can be disposed on only the first wall.

[0023] Generally, according to a second aspect, what is disclosed herein is the following: - A measurement chamber having at least a first wall and a second wall opposite the first wall, the measurement chamber including a plurality of analyte sensors; wherein the measurement chamber enables the fluid to be analyzed to interact with each of the plurality of analyte sensors when the fluid is contained within the measurement chamber; the measurement chamber having an inlet configured to receive the fluid to be analyzed and an outlet configured to allow the fluid to exit the measurement chamber after interacting with the plurality of analyte sensors; the measurement chamber defining a sample volume for containing the fluid to be analyzed, the sample volume extending at least between the inlet and the outlet; and - A heating element configured to heat the fluid contained within the measurement chamber; is an aspect of a sensor device, wherein the heating element is disposed only on the first wall.

[0024] It has been found that disposing the heating element only on the first wall, particularly only on a single side of the measurement chamber, provides a sufficiently uniform heat distribution while maintaining relatively low manufacturing costs and short measurement cycle times.

[0025] The aspects and combinations thereof disclosed with reference to the first aspect of the present invention can be equally applied to the second aspect of the present invention, and vice versa. In one aspect, the first wall has a first surface facing the second wall and a second surface facing away from the second wall on the opposite side of the first surface; wherein the heating element is disposed on the second surface of the first wall, for example disposed on or integrated with the first wall. Thus, particularly efficient heating of the contents of the measurement chamber is achieved.

[0026] Generally, the heating element can be any suitable element configured to dissipate heat towards the sample fluid in the measurement chamber. The heating element can be part of a heating system. The heating system can include the heating element as well as further components, such as a temperature control circuit and / or a temperature sensor and / or additional electrical circuitry. For example, the additional electrical circuitry can include electrical contacts and connection lines for electrically connecting the heating element to the temperature control circuit. The temperature control circuit can include, for example, a circuit or device for controlling the heating action of the heating element based on temperature measurement results by a temperature sensor. The temperature control circuit can include one or more of the following components: an A / D converter, a duty cycle adjustment circuit, a properly programmed processing unit.

[0027] The heating element can be an electrical heating element, such as a resistive heating element. In one aspect, the heating element includes a heating trace made of a conductive material disposed on the surface of the first wall and extending between a first end point and a second end point. The heating trace can be deposited on the surface of the first wall or can be integrated into the first wall. In one aspect, the measurement chamber has only a single heating trace. Thus, when a voltage is applied between the first end point and the second end point, current flows through the heating trace. The resistivity of the heating trace dissipates heat by the heating trace. Thus, the heat induced by the current dissipated by the heating trace heats the first wall and the contents of the measurement chamber. By controlling the applied voltage, the degree of heating can be controlled. Other examples of heating elements include semiconductor heating elements. For example, the semiconductors can be arranged with a variable distance between each other. Still other examples of heating elements can utilize heating by microwaves, infrared radiation, and / or an air system.

[0028] In some embodiments, the sensor device or the analyzer into which the sensor device is inserted can include a temperature control circuit configured to control the applied voltage. It will be understood that the voltage can be controlled in many ways, such as by increasing / decreasing the voltage, or by applying the voltage in pulses and varying the pulse width and / or pulse density. The various embodiments of the sensor devices described herein provide highly responsive devices that enable immediate and direct temperature control of the fluid in the sample volume. Power can be supplied to the heating element by any suitable means, such as by conducting a DC or AC current through conductive leads or other forms of terminals to the heating element, for example via inductive coupling.

[0029] The heating trace can be arranged in a heating trace layout that extends across the entire surface of the first wall or only across a portion of the surface of the first wall. In some embodiments, the heating trace can extend across at least a portion of one or more additional walls of the measurement chamber. In some embodiments, the heating trace is arranged in a layout having alternating direction portions, such as a meandering layout, a zigzag layout, a serpentine layout, etc. Other examples of layouts include a spiral layout.

[0030] In one aspect, the heating trace layout defines a trace density as the length of the heating trace per unit surface area. In one aspect, the trace density is higher near the inlet than near the outlet, thereby causing a higher heating output near the inlet than near the outlet. In particular, in one aspect, the trace density is higher along the first portion of the measurement chamber between the inlet and the reference position along the flow path than along the second portion of the measurement chamber extending between the reference position and the outlet. Preferably, the reference position can be defined as the position of the temperature sensor. Alternatively, the reference position can be defined as the midpoint between the inlet and the outlet or in another suitable manner. More specifically, in one aspect, the first wall has an inlet wall portion extending from the inlet to the reference position along the flow path and an outlet wall portion extending from the reference position to the outlet, and the trace density calculated for the entire inlet wall portion is higher than the trace density calculated for the entire outlet wall portion, for example at least 1.0 times greater, for example at least 1.1; 1.5; 2.0; 2.5; 3.0; 3.5; 4.0; 4.5; or 5.0 times higher.

[0031] Alternatively, or in addition, in one aspect, the heating trace has an electrical resistivity that varies along the heating trace. For example, the resistivity of the heating trace can vary by varying the cross-sectional area of the heating trace along the length of the heating trace. The cross-sectional area can vary by varying the height / thickness of the heating trace along the length of the heating trace and / or by varying the width of the heating trace. Further alternatively, or in addition, the resistivity of the heating trace can vary by varying the heating trace material along the length of the heating trace, in particular by selecting heating trace materials with different specific resistivities.

[0032] In one aspect, the sensor device includes a first substrate layer, particularly a first planar substrate layer, defining a first wall of the measurement chamber. Additionally, the sensor device can include a second substrate layer, particularly a second planar substrate layer, defining a second wall of the measurement chamber. The first and second substrate layers can be parallel to each other, and the measurement chamber can be disposed between the first and second substrate layers. In particular, in one aspect, the sensor device includes an intermediate layer disposed between the first and second substrate layers, and the intermediate layer houses the measurement chamber. For example, the intermediate layer can define a peripheral wall, and the first and second substrate layers can define an upper wall and a lower wall, respectively. The intermediate layer can be made of a gasket material defining an aperture, and opposite ends of the aperture can be covered by the first and second substrate layers, respectively.

[0033] In particular, in one aspect, each of the inlet and outlet is formed as an orifice extending through the first substrate layer or the second substrate layer. For example, the measurement chamber can be fabricated as a planar sandwich structure of two counter-stacked substrates / plates separated by a spacer having a recess defining a sample volume. The substrates can be made of ceramic or other suitable substrate materials. The substrates can be flexible or rigid and can be configured using, for example, standard PCBs, flex PCBs, PET, PI, ceramic, glass, etc. For example, the substrates can be made of an inert material, such as a dielectric, a pressure-sensitive adhesive, a laminate, etc. The spacer can be made of a polymer material or another suitable material. A heating element, such as a heating trace, can be printed or otherwise deposited on the surface of the first substrate and optionally the second substrate. When the inlet and outlet are formed in one or both of the substrate layers, the spacer can form a closed peripheral wall of the measurement chamber. In an alternative aspect, the inlet and / or outlet can be formed in the spacer.

[0034] In some embodiments, the first substrate layer can have a width greater than the width of the measurement chamber, measured in a direction transverse to the length of the flow path between the inlet and the outlet of the measurement chamber. In particular, the first substrate layer can include a central layer portion and a peripheral layer portion, the central layer portion defining a first wall of the measurement chamber, and the peripheral layer portion being laterally offset from the measurement chamber, i.e., the surface of the peripheral layer portion does not define the extent of the measurement chamber. According to these embodiments, the measurement chamber defines a flow path having a length defined between the inlet and the outlet of the measurement chamber, and the heating trace includes a peripheral trace portion and a central trace portion, the peripheral trace portion being disposed on the surface of the peripheral layer portion and the central trace portion being disposed on the central layer portion. In some embodiments, the peripheral trace portion is substantially uniformly distributed along the length of the flow path between the inlet end and the outlet end. Thus, the peripheral trace portion can provide a substantially uniform base heating effect along the length of the flow path. The central trace portion can be non-uniformly distributed along the length of the flow path, for example, such that the trace density of the central trace portion is higher near the inlet than near the outlet. Thus, the central trace portion provides a higher additional heating effect near the inlet than near the outlet. In particular, in some embodiments, the central trace portion is disposed only in a portion of the measurement chamber proximal to the inlet, for example, only between the inlet end of the chamber where the inlet is located and a reference position along the flow path (defined, for example, as the position of a temperature sensor or as the center of the measurement chamber).

[0035] In some embodiments, the sensor device includes a temperature sensor, such as a thermistor element, which can be disposed in thermal contact with the sample in the measurement chamber. Alternatively, other types of temperature sensors, such as semiconductor temperature sensors or infrared temperature sensors, can be used.

[0036] Accordingly, a sensor device or an analytical device comprising a sensor device can control a heating element in response to the temperature of the measurement chamber as sensed by a temperature sensor. The control can be carried out, for example, by controlling the voltage applied to the heating element in response to a signal from the temperature sensor. Alternatively, a thermistor integrated into the heating element can be used to provide a self-regulating heating element. In one aspect, the temperature sensor is disposed on a first wall, for example, on the surface of the first wall, for example, on the surface facing the sample volume. The temperature sensor can be attached to the surface or embedded in the wall. In one aspect, the temperature sensor is disposed in the central portion of the measurement chamber, for example, such that the distance between the temperature sensor and the inlet is substantially equal to the distance between the temperature sensor and the outlet, for example, such that the difference between these distances is not greater than 50% of the greater of the two distances, for example, not greater than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or 45% of the greater of the two distances. Thereby, a reliable temperature reading representing the temperature of the fluid sample is achieved. In an alternative aspect, the temperature sensor is disposed proximal to the outlet or proximal to the inlet. In one aspect, the temperature sensor is disposed offset by more than 0.5 mm from the closest portion of the heating element, for example, offset by 1.0 mm, 1.5 mm, 2.0 mm, 2.5 mm, 3.0 mm, 3.5 mm, 4.0 mm, 4.5 mm or 5.0 mm from the closest portion of the heating element, in a portion of the first wall not covered by the heating element.

[0037] The inventors recognize that such a position enables control of the heating element such that a particularly uniform temperature distribution is achieved. In one aspect, the sensor device includes only a single heating element, such as only a single heating trace and / or only a single temperature sensor. It has been found that even only a single heating element and / or only a single temperature sensor may be sufficient to achieve a uniform temperature distribution while maintaining a low-cost sensor device. In an alternative aspect, the sensor device includes more than one heating element and / or more than one temperature sensor. For example, finer temperature control can be achieved by providing two or more zones within the measurement chamber, each zone having its own heating element and temperature sensor.

[0038] In one aspect, the fluid contained within the measurement chamber can be held stationary within the measurement while the fluid interacts with the analyte sensor, for example by closing the inlet and / or outlet of the sensor device. In other aspects, the fluid can interact with the analyte sensor while the fluid flows along the measurement chamber from the inlet to the outlet, and thus the fluid does not need to be held stationary. According to one aspect, the measurement can be initiated after the filling of the measurement chamber is complete, optionally after a further delay time.

[0039] In one aspect, during operation of the sensor device, the measurement chamber can be filled with the sample fluid so as to allow the fluid to contact or otherwise interact with the analyte sensor and to perform measurements on the fluid sample. In one aspect, some or all of the analyte sensors are non-contact analyte sensors that do not require physical contact between the analyte sensor and the sample fluid.

[0040] According to one aspect, the sensor device is adapted to measure one or more analytes in a fluid sample to determine the corresponding parameters of the analyte, such as pH, electrolyte concentration, metabolite concentration or enzyme concentration. The fluid sample can be a biological sample, such as a body fluid, i.e., a physiological fluid.

[0041] Examples of biological samples can include liquid samples and / or gas samples. Liquid samples can include body fluids. Liquid samples can be selected from the group consisting of blood, diluted whole blood or undiluted whole blood, serum, plasma, saliva, urine, cerebrospinal fluid, pleural fluid, synovial fluid, ascitic fluid, peritoneal fluid, amniotic fluid, milk, dialysate samples, and any quality control materials and calibration solutions used in analyzer equipment for measuring any of these fluids. Gaseous samples can include respiratory gases, exhaled breath, and any quality control and calibration materials used in analyzer equipment for measuring any of these fluids. Thus, in one aspect, the sensor device is configured to analyze parameters of a liquid sample, such as a body fluid. The sample can be pre-treated prior to testing to make it more amenable to testing. The pre-treatment methods can include one or more of the following: mixing, dilution, filtration, concentration, extraction, removal or inactivation of components that can interfere with the results, and / or addition of reagents. Examples of other biological samples include fermentation broth or microbial cultures, wastewater, food products, and the like.

[0042] Examples of parameters regarding analytes that can be determined by at least some aspects of the sensor devices disclosed herein include pO 2 、pCO 2 、pH; electrolytes such as Li + 、Na + 、K + 、Ca 2+ 、Mg 2+ 、Cl - 、HCO 3- or NH 3 (NH 4 + ) concentration; metabolic factors such as glucose, creatinine, urea (BUN), uric acid, lactic acid, pyruvic acid, ascorbic acid, phosphate or protein concentration; enzyme such as lactate dehydrogenase, lipase, amylase, cholinesterase, alkaline phosphatase, acid phosphatase, alanine aminotransferase, aspartate aminotransferase or creatinine kinase concentration.

[0043] Furthermore, according to certain aspects, the sensor device is adapted to measure the partial pressure of a gas, such as pO 2 or pCO 2 in a fluid sample. The sensor device and / or an analyzer including the sensor device can include a measurement system that includes, for example, an electrical circuit, one or more detectors, sensor readout equipment, signal processing circuitry, and the like. During operation, the measurement system can be configured to read a signal from the analyte sensor, process the signal, and determine a measurement result. It will be understood that while some or all of the analyte sensor can share components of at least a portion of the measurement system, other components of the measurement system can be specific to an individual analyte sensor. In this description, the term analyte sensor means any sensor capable of measuring a physical parameter of a sample fluid, such as the presence and / or concentration of a chemical substance present in the sample fluid. It will be understood that the sensor device and / or analyzer can include one or more different types of analyte sensors, such as optical sensors, electrochemical sensors, and / or sensors utilizing other sensing techniques. In certain aspects, it will be understood that the components of the measurement system can be distributed between the sensor device and an analyzer into which the sensor device can be inserted. For example, some or all of the measurement circuitry, excitation source, detector, etc. can be disposed in the analyzer to enable a relatively simple sensor device.

[0044] Each analyte sensor can define its respective sensing region, for example, on a surface facing the inside of the measurement chamber. Each sensing region can be a portion of the surface facing the inside. When the sample fluid interacts with the sensing region, the analyte sensor can be configured to detect the result of the interaction as, for example, an optical signal or an electrical signal. The sensing regions can be disposed at respective positions throughout the measurement chamber.

[0045] The present disclosure relates to different aspects including the above-described sensor device, corresponding apparatus, system, method, and / or product, each of which provides one or more of the benefits and advantages described in relation to one or more of the other aspects, and each of which has one or more aspects corresponding to those described in relation to one or more of the other aspects and / or disclosed in the appended claims.

[0046] According to one aspect, described herein is a sensor device holding mechanism configured to receive an aspect of the sensor device described above or below, in particular an aspect of an analytical device including a container.

[0047] In one aspect, the sensor device includes at least a measurement chamber, for example a housing accommodating a first and a second substrate layer; wherein the housing includes an opening that exposes a part of the surface of one of the walls of the measurement chamber, in particular a wall other than the first wall, for example a part of the second substrate layer, and the exposed part faces in a direction opposite to the sample volume. Thus, in one aspect, the sensor device holding mechanism includes a heat storage element defining a heat exchange member configured to provide heat exchange contact with the exposed part of the wall, for example the second substrate layer, through the opening when the sensor device is received by the sensor device holding mechanism. Thus, more uniform and accurate heating can be achieved.

[0048] In one aspect, the sensor device holding mechanism includes the following: - a conduit configured to provide fluid communication with the inlet of the sensor device when the sensor device is received by the sensor device holding mechanism; and - a heating element configured to preheat the fluid flowing through the conduit towards the inlet of the sensor device.

[0049] Some embodiments of the analytical device can be configured to analyze a liquid sample. For this purpose, some embodiments of the analytical device preferably include a liquid handling system for controlling the flow of liquid in an automated or semi-automated manner, including, for example, one or more valves, conduits, and / or pumping / transfer means for filling and emptying a measurement chamber with the liquid sample.

[0050] Furthermore, according to some embodiments, the fluid sample is a gas, such as a medical gas, such as a physiological gas. Thus, some embodiments of the analytical device can be adapted to analyze the parameters of a medical gas sample. Examples of particularly useful medical gas samples are selected from the group of respiratory gases, exhaled air, etc., as well as any quality control and calibration materials used in analyzer equipment for measuring any of these fluids. Thus, some embodiments of the analytical device can include a gas handling system preferably including one or more valves, conduits, and / or pumping / transfer means for filling and emptying the measurement chamber with the gas sample in an automated manner. In one embodiment, the analytical device includes fluid handling means suitable for both liquids and gases.

[0051] The analytical device and / or the sensor device can include a temperature control circuit configured to receive a signal from a temperature sensor of the sensor device and to control a heating element in response to the received signal from the temperature sensor, for example, to minimize the difference between the received signal from the temperature sensor and a target value. The temperature control circuit can be embodied by a control unit configured to control the operation of the analyzer, such as the operation of an analyte sensor and / or a sample handling system.

[0052] In one embodiment, the sensor device can be a disposable and / or single-use device that can be used as a stand-alone device or in combination with the analytical device.

[0053] Preferred embodiments of the present invention are described in more detail in connection with the accompanying drawings, where:

Brief Description of the Drawings

[0054]

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Modes for Carrying Out the Invention

[0055] Figure 1 schematically shows an example of an apparatus 1 for the analysis of biological liquid samples, such as body fluids. The apparatus 1 is configured, in one aspect, for the analysis of biological fluid samples, such as medical gas samples and / or body fluids. The apparatus 1 has a sensor device 60, a liquid handling system 20, and a processing unit 8.

[0056] The sensor device 60 includes a measurement chamber 2, which is equipped with one or more analyte sensors that can be read out via contact pins. For this purpose, the sensor device includes contact pins 3(a - i) for establishing electrical contact with the sensor electrodes and a reference electrode 5. In the example of Figure 1, the sensor device 60 is a replaceable sensor cassette, which can be inserted into the enclosure 40 of the analyzer and can be removed from the analyzer again at the end of its operating life. In the embodiment of Figure 1, the sensor device is pO 2 includes a measurement system 4.

[0057] The liquid handling system 20 is adapted to supply a liquid sample through an inlet 6 of the measurement chamber to the sample volume of the measurement chamber 2 and to remove the liquid sample through an outlet 7 of the measurement chamber 2.

[0058] The sensor device 60 has a heating element 32 arranged in good thermal contact with the measurement chamber. In particular, the heating element is arranged on the surface of a substrate 30 that forms the upper wall of the measurement chamber 2. An example of the measurement chamber will be described in more detail below with reference to Figure 2. The sensor device 60 further has a temperature sensor 31 (here a thermistor), which is arranged on the inner surface of the measurement chamber 2 approximately midway between the inlet 6 and the outlet 7. The temperature sensor 31 is for measuring the temperature of the liquid sample inside the measurement chamber and for providing the measurement result to the processing unit 8.

[0059] The processing unit 8 is configured to control the operation of the sensor device 60 and the liquid handling system. In particular, the processing unit 8 controls the operation of the heating element 32 in response to the temperature reading from the temperature sensor 31 so as to match the sample temperature with the target temperature at which the measurement is to be carried out. In an alternative embodiment, it will be understood that the temperature control can be carried out by another temperature control device that can be separate from the processing unit 8.

[0060] The processing unit 8 is further adapted to receive flow data from the liquid handling system 20 and / or measurement data from the analyte sensor of the sensor device 60. The processing unit 8 includes programmed instructions for performing appropriate signal and data processing tasks including data acquisition, process control, etc.

[0061] For example, the processing unit can be configured to determine the initial temperature of the liquid sample entering the measurement chamber 2 based on, for example, flow data from the liquid handling system 20 and / or sample heating data based on the signal from the temperature sensor 31.

[0062] To perform the measurement, the user can provide a liquid sample to the input port of the device 1, which can be brought to two positions 12a / b in the example of FIG. 1. However, other embodiments may have different types of input ports. The liquid sample is transferred through the inlet 6 to the measurement chamber 2. Any preheating of the blood sample is ensured by an optional preheater 38. The preheater can be a tube located upstream from the sensor device. The preheater can be heated electrically or by heat transferred directly through contact from a heat storage body, such as the sensor device holder, to the preheater. When the sample enters the measurement chamber, the sample is heated to a desired target temperature by the heating element 32. The liquid sample contacts or otherwise interacts with each analyte sensor. The analyte sensors are arranged in one aspect to provide substantially simultaneous measurements of analyte parameters in a liquid sample, such as a whole blood sample. Preferably, the sample volume required to obtain accurate and reliable analytical data is as small as possible. Detailed examples of sensor assembly designs particularly suitable for simultaneously measuring multiple different parameters in a body fluid, especially whole blood, and their use in a blood analyzer can be found, for example, in European Patent No. 2 147 307 B1 or in U.S. Patent No. 8,728,288 B2.

[0063] For example, one type of analyte sensor includes an electrochemical sensor. The electrochemical sensor can include one or more analyte electrodes and a reference electrode. The electrochemical sensor can include one or more membranes. The electrochemical sensor can include one or more electrically responsive components configured to provide an electrical response when in contact with a fluid in a measurement chamber containing an analyte to which the electrically responsive components respond.

[0064] Other examples of analyte sensors include optical sensor 4 having a sensor layer that can interact with a sample fluid contained in a measurement chamber. The sensor layer is sensitive to the amount of analyte present in the fluid sample provided in the measurement chamber. The optical sensor further includes equipment for optical readout of the response of the sensor layer to the presence of the analyte. The readout equipment typically includes a device for providing a stimulus to the sensor layer. The readout equipment can further include a detector and / or optical elements, such as lenses and / or optical waveguide components, for collecting the radiation emitted from the sensor layer in response to the stimulus and for further transferring the collected luminescent radiation to a detector of the optical sensor. The stimulus is typically a radiation source, such as a laser or a light-emitting diode (LED), arranged and configured to provide optical probe radiation to the sensor layer.

[0065] The optical sensor can further include any components for optically selecting and / or analyzing the radiation collected from the sensor layer, such as an optical filter and / or an optical amplifier, before the light is received by the detector. The detector converts the detected luminescent radiation into a corresponding signal. Thus, the optical sensor is configured to provide a signal representative of the amount of analyte to which it is sensitized.

[0066] Signals from the optical sensor and / or the electrochemical sensor, and / or from other analyte sensors of the analyzer, are provided to a processing unit 8 of the sample analyzer for analog and / or digital signal processing. The processing unit can store the measurement data in a storage device of the analyzer, display the measurement data on a display of the analyzer, and / or provide the measurement data to an output of the analyzer, such as a communication interface.

[0067] It will be appreciated that the plurality of analyte sensors can share some or all of the reading device and can include respective sensor layers that define respective sensing regions. Further, it will be appreciated that at least some of the components of the reading device can be disposed within the analyzer. For this purpose, the sensor device can include a suitable interface, such as an electrical and / or optical interface, to enable the reading device of the analyzer to cooperate with the sensing layer of the sensor device.

[0068] In one aspect, one or more sensing regions are provided by the sensor layers of the respective analyte sensors. Each sensor layer can define a sensor surface that forms a front interface towards the measurement chamber. During measurement, the front interface can be in contact with the fluid sample. Optical and / or other probing can be performed from the back side of the sensor layer, i.e., from the side facing away from the sample fluid. For this purpose, the sensor layer can be transparent or translucent. The stimulus can typically be provided in the form of excitation light directed towards the sensor layer from the back side so as to generate an excited fraction of the fluorophore in the sensor layer. The excited fluorophore molecules relax under emission of light and return to the ground state, which can also be observed from the back side. Thus, the optical sensor further includes a device for detecting and recording the light emitted from the fluorophore and thus observing the response of the sensor layer to the applied stimulus.

[0069] Measurements are performed using the analyte sensors according to pre-programmed instructions loaded into the processing unit 8 and / or based on user input. The analyte sensors generate a quantitative signal representing the physical parameter regarding the respective analyte and provide the signal to the processing unit 8. The processing unit 8 is adapted to receive and process the signal from the analyte sensors and present the processed signal as an output to the user and / or for subsequent / further data analysis. After the measurement, the liquid sample is discharged and the measurement chamber 2 is prepared for the next measurement.

[0070] The embodiment of the device 1 shown in FIG. 1 is particularly adapted for the measurement of blood parameters and further includes any oxygen measurement device 9 downstream of the measurement chamber 2. Thus, the implementation of measurement, calibration tasks and quality control procedures typically includes loading, unloading, rinsing, cleaning and reloading of different liquids, which can be carried out using the infrastructure of the liquid handling system 20. The handling of liquids can be controlled in an automated manner by the processing unit 8 according to pre-programmed instructions and / or user input. The liquid handling system 20 includes several reservoirs 21 pre-filled with process liquids (designated herein as RINSE / CAL1, CAL2, QC1, QC2, QC3, METCAL, GAS) for rinsing / washing-off, calibration and quality control tasks. The process liquids (RINSE / CAL1, CAL2, QC1, QC2, QC3, METCAL, GAS) have a known composition. The exact composition of a given batch can be stored in a chip 25 that can be attached to the cassette containing the reservoir 21, where the chip 25 can be read by the processing unit 8. The process liquid (RINSE / CAL1, CAL2, QC1, QC2, QC3, METCAL, GAS) for a given process step can be selected by the fluid selector valve 22 and transferred through the supply line 12c through the inlet 6 to the measurement chamber 2. The exact filling of the measurement chamber 2 can be monitored and verified by observing the propagation of the liquid interface through the system by visual inspection or according to known procedures, by liquid sensors 10a, 10b, 10c arranged upstream and downstream of the measurement chamber, for example at the inlet 6 (liquid sensor 10a), at the outlet 7 (liquid sensor 10b), and immediately after the oxygen measurement device 9 (liquid sensor 10c). The flow of fluid through the device 1 is driven by a pump 23, here a peristaltic hose pump arranged downstream of the measurement chamber 2 and the oxygenation measurement device 9 and connected thereto via the fluid line 13. The discharged fluid is finally transported through the fluid line 14 to the waste reservoir 24.

[0071] The analysis device 1 includes a storage device 40 for accommodating the sensor device 60. The wall of the storage device 40 forms a housing having walls and holding mechanisms for holding the sensor device, providing a suitable interface for fluid transfer to and from the sensor device, communicating sensor signals and / or data from the sensor device, and providing operating power to the heating element. The wall of the storage device can be held at a fixed temperature so as to provide a thermal shield and to maintain the immediate environment of the sensor device at a constant temperature.

[0072] FIG. 2 schematically shows a more detailed view of an example of a sensor device for use, for example, in the analyzer of FIG. 1. The sensor device, generally designated 60, includes a housing 61 that houses the various components of the sensor device. The housing can be made of plastic or another suitable material.

[0073] The sensor device has a measurement chamber 2 that defines a sample volume 21. In this example, the measurement chamber is formed as a sandwich structure including substrate layers 30 and 33 and a gasket layer 34. However, it will be understood that other designed measurement chambers are equally possible.

[0074] The measurement chamber includes a first substrate 30 and a second substrate 33 that define the upper and lower walls of the measurement chamber 2. The measurement chamber further includes an intermediate layer 34 made of a gasket material, such as a polymeric material. The intermediate layer, which can also be referred to as a spacer, is disposed sandwiched between the first and second substrate layers. The intermediate layer defines the side walls of the measurement chamber 2. The intermediate layer can define recesses, through-holes or similar voids. It is understood that the terms upper wall, lower wall and side wall as used herein are merely intended to enable easy distinction of the various walls of the measurement chamber; one of ordinary skill in the art will understand that the walls can be oriented in different directions in space depending on the physical orientation of the measurement chamber in the sensor device, i.e., the upper wall need not be above the lower wall etc. The first and second substrates can be ceramic substrates, or they can be made from another suitable material.

[0075] The measurement chamber has an inlet 6 at the inlet end 216 of the sample volume and an outlet 7 at the outlet end 217 of the measurement chamber opposite the inlet end. The inlet and outlet can be disposed all the way at the outermost ends of their respective ends of the measurement chamber, as illustrated in FIG. 2. Alternatively, the measurement chamber can extend further beyond only between the inlet and outlet, i.e., the inlet and / or outlet can be offset from the end walls. In the example of FIG. 2, the inlet 6 and outlet 7 are formed as through-holes in the second substrate 33. However, alternative arrangements of the inlet and / or outlet are possible. For example, one or both of the inlet and outlet can be formed as through-holes passing through the first substrate layer or even through the side walls of the intermediate layer. The inlet 6 is in fluid communication with an inlet port 611 of a housing 61. The inlet port enables the sensor device to be connected to a corresponding supply port 56 of a liquid handling system 20 of an analyzer. Similarly, the outlet 7 is in fluid communication with an outlet port 71 of the housing 61. The outlet port enables the sensor device to be connected to a corresponding return port 57 of the liquid handling system 20 of the analyzer.

[0076] The measurement chamber 2 has analyte sensors 39 for detecting respective analytes. In the example of FIG. 2, the analyte sensors are disposed at respective positions on the inner surface of the measurement chamber facing the sample volume 21. In particular, in the example of FIG. 2, some of the analyte sensors are disposed on the inner surface of the first substrate layer 30 and some of the analyte sensors are disposed on the inner surface of the second substrate layer 33. The analyte sensors 39 can be read out electrically, optically, and / or in another suitable manner apparent to those skilled in the art when faced with the present disclosure. It will be understood that the number and type of analyte sensors can vary. Although the measurement chamber of FIG. 2 has analyte sensors on both substrate layers, those skilled in the art will understand that in some embodiments all of the analyte sensors can be disposed on the same substrate layer. Further, some or even all of the analyte sensors can be otherwise disposed at respective positions across the measurement chamber.

[0077] The measurement chamber includes an electrical heating element 32 disposed on the outer surface of the first substrate layer 30, i.e., facing away from the sample and the measurement chamber 21. In an alternative embodiment, the measurement chamber can include one or more heating elements at alternative or additional positions, e.g., on the second substrate layer, on the inner surface of the first or second substrate layer, i.e., facing the sample and the measurement chamber 21, embedded within the first substrate layer, etc. The electrical heating element has the form of a resistive heating trace disposed on or integrated with the surface of the first substrate in a suitable heating trace layout. Different examples of heating trace layouts will be described in connection with FIGS. 5A - D below. The heating element receives power via endpoints 301 and an electrical interface 36. The measurement chamber of this example includes only a single heating trace disposed only on the first substrate layer.

[0078] The measurement chamber further includes a thermistor 31 or another suitable temperature sensor. In the example of FIG. 2, the thermistor is disposed on the inner surface of the first substrate layer 30, approximately midway between the inlet 6 and the outlet 7. In other embodiments, the temperature sensor can be disposed at different locations, such as on a second substrate and / or offset from the center.

[0079] The measurement chamber can optionally include additional components, such as an electrical circuit 35 and / or components related to an analyte sensor, which can be disposed on the outer surface of the first substrate and / or at different locations of the sensor device 60. The electrical circuit 35 can provide electrical contacts between the electrical interface 36 of the sensor device and various electrical components, such as the analyte sensor and / or the thermistor 31. The electrical interface 36 provides an electrical connection to the processing unit 8 via a corresponding interface 58. It will be understood that in certain embodiments, power and / or signals can be communicated between the sensor device and other components of the analyzer in a non-contact manner, such as by electromagnetic induction.

[0080] The sensor device 60 is an exchangeable sensor device that can be inserted into the analyzer. For this purpose, as schematically shown in FIG. 2, the analyzer can include a sensor device holding mechanism 45 in the form of, for example, a recess, an adapter, a container, etc. The sensor device holding mechanism 45 can be part of the storage device, as described in connection with FIG. 1. The sensor device holding mechanism 45 provides a supply port 56 and a return port 57 for providing a fluid connection between the inlet 6 and the outlet 7 of the measurement chamber via the respective inlet and outlet ports 611 and 71 of the sensor device. The analyzer further provides an electrical interface 58 for connecting the heating element 32 and the thermistor 31 to the corresponding electrical interface 36 of the sensor device via the processing unit 8 of the analyzer. The interfaces 36 and 58 can also serve to transmit the sensor signal from the analyte sensor of the sensor device in response to the liquid sample interacting with the analyte sensor 39 in the measurement chamber. The interface 58 can be arranged, for example, in the holding mechanism or at a different suitable location, such as on the lid part or other part of the storage device for accommodating the sensor device. When the electrical interface is arranged on the side of the sensor device opposite to the side where the inlet and outlet are arranged, the risk of potential liquid leakage affecting the electrical interface is reduced.

[0081] The sensor device holding mechanism 45 can further serve to maintain a constant temperature in the measurement chamber 2. For this purpose, the sensor device holding mechanism includes a heat transfer block 41 of such a shape and size as to extend through a corresponding opening in the housing of the sensor device so that the heat transfer block 41 is brought into direct contact with the second substrate layer 33 when the sensor device is inserted into or otherwise connected to the sensor device holding mechanism 45. Thus, the sensor device holding mechanism 45 conducts heat directly to the measurement chamber. As described above, the sensor device holding mechanism can further include a thermal lid (not explicitly shown), which can be a part or a storage device that can house the sensor device inside a storage device that can prevent the sensor device from contributing to the thermal environment around the sensor device and heat from being drawn away from the sensor device. The sensor device holding mechanism 45 can further include a heater and optionally a temperature sensor, such as a thermistor. The provision of the heat transfer block 41 in contact with the second substrate layer can be particularly useful in embodiments where the measurement chamber includes only heating elements in the first substrate.

[0082] FIG. 3 schematically shows a top view of an example of the second substrate layer of the measurement chamber of FIG. 2, for example. The second substrate layer 33 includes through holes that define an inlet 6 and an outlet 7, respectively. FIG. 4 schematically shows a top view of an example of the intermediate layer of the measurement chamber of FIG. 2, for example. The intermediate layer 34 includes a gasket material, such as a polymer material, that defines the sidewalls of the sample volume 21. The intermediate layer forms a spacer that separates the first and second substrate layers.

[0083] FIGS. 5A-5D schematically show top views of the outer surfaces of examples of the first substrate layer of the measurement chamber of FIG. 2, for example, as seen from the side facing the opposite direction of the measurement volume. The first substrate layer 30 has a temperature sensor, such as a thermistor, disposed on its inner surface that is centrally located with respect to the assembled measurement chamber. The position of the temperature sensor is indicated by the square 31 in FIGS. 5A - 5D. In particular, the temperature sensor is arranged such that its distance from the inlet end is approximately equal to its distance from the outlet end. The temperature sensor is also arranged such that it is substantially equally distant from the sides of the measurement chamber.

[0084] The first substrate layer 30 further includes a single resistive heating element 32 formed as a heating trace that extends between endpoints 301A and 301B. The heating trace extends in a serpentine / trace layout across the outer surface of the first substrate layer. The heating trace can be disposed on the surface, for example, printed, or can also be integrated into the substrate layer.

[0085] In FIGS. 5A - 5D, the range of the sample volume defined by the intermediate layer when the first substrate is assembled with the intermediate layer is indicated by the dashed line 21. The sample volume is an elongated volume that extends between an inlet end disposed adjacent to the inlet of the measurement chamber and an outlet end disposed adjacent to the outlet of the assembled measurement chamber when the first substrate layer is assembled with other components to form the measurement chamber. The positions of the inlet and outlet are indicated by the circles 6 and 7, respectively, in FIGS. 5A - 5D.

[0086] The examples in FIGS. 5A - 5D have their heating traces arranged in different trace layouts. In all examples, the trace layout includes a peripheral portion 303 that extends along the longitudinal sides of the measurement chamber 21 across the entire length between the inlet 6 and the outlet 7. The peripheral portion 303 of the trace layout is disposed outside the footprint of the measurement chamber, i.e., offset laterally from the measurement chamber.

[0087] The trace layout also includes a central portion 304 disposed inside the installation area of the measurement chamber 21. In the examples of FIGS. 5A to 5D, the central portion 304 of the trace layout extends to different extents along the length of the measurement chamber, particularly along the flow path between the inlet 6 and the outlet 7.

[0088] In the example of FIG. 5A, the central portion of the trace layout covers only about half of the length of the measurement chamber, particularly only the half close to the inlet 6, while there is no heating trace on the other half of the wall of the measurement chamber close to the outlet 7. In the example of FIG. 5A, the heating trace 32 extends beyond the position of the temperature sensor 31, that is, the portion of the inner surface of the first substrate near the temperature sensor 31 is covered by the heating trace. In one aspect, the entire length of the heating trace has a resistivity per unit length that is uniform, that is, the heating effect per unit length of the heating trace is substantially uniform along the length of the heating trace, that is, the heating effect of the heating element is higher in the region of the substrate layer having a high heating trace density (measured as the length of the heating trace per unit surface area) than in the region having a low heating trace density. Therefore, the heating element 32 of the substrate layer in FIG. 5A provides a higher heating effect in the half of the measurement chamber close to the inlet 6 and a lower heating effect in the half of the measurement chamber close to the outlet 7.

[0089] In an alternative aspect, the resistivity per unit length of the heating trace can vary along its length. For example, the heating trace can be provided with different resistivities per unit length within the region indicated by the dotted line 305, for example, by changing the trace material and / or the cross-sectional area of the heating trace.

[0090] The trace layout shown in FIG. 5B is the same as that in FIG. 5A, except that the central portion 304 of the trace layout covers less than half of the length of the sample volume, particularly less than half of the length of the flow path between the inlet and the outlet. In particular, the position of the temperature sensor 31 is not covered by the heating trace.

[0091] In the trace layout shown in FIG. 5C, the central portion of the trace layout covers most of the length of the measurement chamber, particularly most of the length of the flow path between the inlet and the outlet. However, in the half of the installation area of the measurement chamber closest to the inlet 6, the trace density is higher than that in the half closest to the outlet 7.

[0092] Therefore, in all examples of FIGS. 5A to 5C, the lateral central portion of the trace layout has a higher trace density in the half of the installation area of the measurement chamber closest to the inlet 6 than in the half closest to the outlet 7.

[0093] FIG. 5D shows an example of a trace layout in which the heating trace extends substantially uniformly over the entire length of the measurement chamber, particularly along the entire length of the flow path between the inlet 6 and the outlet 7. This example was used as a reference in the following comparative tests.

[0094] FIG. 6 schematically shows another example of a measurement chamber. The measurement chamber 2 in FIG. 6 is similar to the measurement chamber described in relation to FIG. 2 in that it is formed as a layered structure including a first substrate layer 30, an intermediate layer 34, and a second substrate layer 33 (all as described in relation to FIG. 2). The first substrate element 34 includes a heating element 32 formed as a heating trace extending between the inlet end 216 and the outlet end 217 of the measurement chamber. The heating trace is arranged in a meandering / serpentine layout such that the trace density is higher in the vicinity of the inlet end 216 than in the vicinity of the outlet end 217.

Example

[0095] Sensor devices having measurement chambers with resistive heating elements having different heating trace layouts were compared. The sensor devices were of the type described in relation to FIGS. 2 to 5. Four different examples of the measurement chamber were manufactured. The examples were identical except for the heating trace layout on the first substrate layer: - Example A had a first substrate layer as shown in Figure 5A with a uniform resistivity of the heating trace.

[0096] - Example B had a first substrate layer as shown in Figure 5B with a uniform resistivity of the heating trace. - Example C had a first substrate layer as shown in Figure 5C with a uniform resistivity of the heating trace.

[0097] - Example D had a first substrate layer as shown in Figure 5A but had a non-uniform resistivity of the heating trace. In particular, the cross-sectional area of the heating trace, and thus its resistivity, within the region indicated by line 305 was different from that of the remainder of the heating trace. Alternatively, or in addition, the resistivity can be varied by providing different material compositions to different parts of the heating trace.

[0098] Furthermore, a reference measurement chamber (current situation) was manufactured that was identical to Examples A - D except that the first and second substrate layers had heating traces that were distributed substantially uniformly as shown in Figure 5D with respect to the first substrate.

[0099] All measurement chambers were equipped with four identical analyte sensors (“K sensors”) for measuring potassium. The K sensors were chosen because they have a high temperature dependence. By placing the same type of sensor at different positions across the measurement chamber, the differences in the measurement results indicate temperature differences in the sample liquid across the measurement chamber. The measurements were carried out using a reference liquid with a predetermined potassium concentration.

[0100] All tests were carried out using an ABL-90 analyzer from Radiometer Medical ApS (Denmark). The analyzer was equipped with a special software version that could read all analyte sensors as K sensors.

[0101] The heater resistance was measured before being set in the analyzer for all measurement chambers. All K sensors were calibrated such that their temperature sensitivity coefficients were known. Several scenarios were tested as described in Table 1 below.

[0102] - The analyzer was placed in a standard test institution at room temperature (about 25 °C) or in a temperature-controlled room (set to different temperatures, i.e., 15 °C or 32 °C). - All samples analyzed were samples of the rinsing solution and were placed in an ice water bath (for samples at 0 °C) or in a room at a controlled temperature.

[0103] - Measurements were taken frequently (suction was performed as soon as the ABL90 was ready - maximum 2 minutes between each start - 10 measurements in a row).

[0104]

Table 1

[0105] Figures 7 - 12 show the average of the temperatures measured by the K sensors for each sensor position and each heating trace layout under different environmental conditions. In Figures 7 - 12, the sensor positions are labeled "K", "Na", "pH", and "Ca" respectively (reflecting the type of sensor normally placed at each position in the measurement chamber). The heating trace layouts are labeled "TEMP_A" (Example A), "TEMP_B" (Example B), "TEMP_C" (Example C), "TEMP_D" (Example D), and "TEMP_REF" (Reference) respectively.

[0106]

Table 2

[0107] Based on the above experimental data, even when compared to existing relatively complex measurement chamber designs having heating traces on both the first and second walls of the measurement chamber, all Examples A - D having only heating elements disposed on the first wall provide acceptable results, but heating trace layout B appears to be preferred for the following reasons: - The performance results are comparable to existing relatively complex measurement chamber designs having heater lanes on both the first and second walls of the chamber.

[0108] - The temperature uniformity across the measurement chamber is favorable compared to other tested examples (i.e., Examples A, C, and D). The present invention has been described with reference to specific embodiments, but various modifications will be apparent to those skilled in the art without departing from the spirit and scope of the invention as outlined in the claims appended hereto.

[0109] In particular, some embodiments have been described mainly with reference to a particular type of measurement chamber. However, it will be understood that other embodiments of the sensor device can include other types of measurement chambers. Accordingly, various embodiments of the heating element or system of heating elements described herein configured to heat the fluid contained within the measurement chamber (where the heating element is configured to provide a greater heating effect near the inlet of the measurement chamber than near the outlet of the measurement chamber) can be included in various different types of sensor devices, particularly sensor devices having different types of measurement chambers.

[0110] Generally, in one aspect, the heating element described herein includes the following: a) a first electronic wiring substrate having first and second surfaces and at least one analyte sensor formed on the first surface thereof (the at least one analyte sensor is connected by one or more electrical contacts), b) a second electronic wiring substrate having first and second surfaces and at least one analyte sensor formed on the first surface portion thereof (the at least one analyte sensor is connected by one or more electrical contacts), and c) a spacer having a through-going recess with first and second openings; and is included in a sensor device, where the first substrate, the second substrate, and the spacer are arranged in a layered structure, where the first surface of the first substrate closes the first opening of the spacer and the first surface of the second substrate closes the second opening of the spacer, thereby forming a measurement chamber, and at least one analyte sensor from each of the substrates faces the measurement chamber. Such a sensor device is described in International Publication No. WO 2008 / 131767 (Radiometer Medical ApS). In a further aspect thereof, the volume of the measurement chamber is less than 1 ml, for example less than 0.5 ml, for example less than 200 microliters, for example less than 100 microliters, for example less than 50 microliters, for example less than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters.In a further aspect, the volume of the measurement chamber is from 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters. Thus, in one aspect, the amount used for determination, i.e., the amount contained within the measurement chamber, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as from 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters. The recess in the spacer and the measurement chamber provided by the first surfaces of the first and second substrates preferably provide a volume of about 25 to 45 microliters, more preferably a volume of about 30 to 40 microliters. Such a volume requires a very small amount of sample for measurement by the analyte sensor in the measurement chamber. Preferably, the dimensions of the spacer are within the following ranges: length 20 to 60 mm, width 5 to 20 mm and thickness 0.2 to 0.6 mm.The recess in the spacer can have dimensions within the following ranges: length 10 to 50 mm, width 1 to 5 mm, and depth 0.2 to 0.6 mm. The dimensions of the first and second substrates and the spacer, and thus the dimensions of the sensor device, can be adapted according to the intended use. However, in a preferred embodiment, the first substrate has dimensions within the following ranges: length of about 20 to 60 mm, width of about 5 to 20 mm, and thickness of about 0.3 to 0.8 mm. The width and / or length of the second substrate can be somewhat larger than the width and / or length of the first substrate. This is due to the fact that in some preferred embodiments, it is preferred that the first surface of the second substrate protrudes beyond the edges of the spacer and the first substrate in the sensor device. The second substrate preferably has dimensions within the following ranges: length of about 20 to 60 mm, width of about 5 to 40 mm, and thickness of 0.3 to 0.8 mm. The length and width of the second substrate can provide an extension beyond the edges of the first substrate and the spacer in the range of about 4 to 20 mm.

[0111] In another aspect, the heating element described herein is included in a sensor device that includes: a base, an upper portion spaced above the base, and a housing having an outer wall extending from the base to the upper portion; an inlet in the housing sized to receive a sample of fluid; a plurality of compartments disposed around the fluid inlet and substantially isolated from each other, each compartment having a port at the fluid inlet for receiving a portion of the sample of fluid received by the fluid inlet; and at least one sensor in each compartment, where the at least one sensor is reactive to the fluid when the fluid contacts the at least one sensor, and where the sensor device is configured to selectively direct a sample of fluid received from the fluid inlet by one or more of the plurality of compartments into contact with the at least one sensor. Such sensor devices are described in International Publication No. WO 2018 / 112017. In a further aspect, the amount used for determination in each compartment, i.e., the amount contained within the compartment, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters.

[0112] In another aspect, the heating element described herein is included in a sensor device that includes: a first outer sheath, a first membrane core within the first outer sheath, and a first micro-sensor having a first conductive element at least partially encapsulated by and in contact with the first membrane core, where the first conductive element detects a first electrical response signal when the first membrane core comes into contact with a fluid; and a second micro-sensor adjacent to the outer surface of the first micro-sensor, the second micro-sensor having a second outer sheath, a second membrane core within the second outer sheath, and a second conductive element at least partially encapsulated by and in contact with the second membrane core, where the second conductive element detects a second electrical response signal when the second membrane core comes into contact with a fluid. Such a sensor device is described in International Publication No. WO 2018 / 112012. In a further aspect, the amount used for determination, i.e., the amount contained within the measurement chamber, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters.

[0113] In another aspect, the heating element described herein is included in a microcapillary sensor device that includes: a sensor body elongated along a longitudinal axis, the sensor body having a first end, a second end spaced from the first end along the longitudinal axis, an outer surface and an inner surface, where the inner surface defines a hollow capillary extending from the first end toward the second end along the longitudinal axis; a sensing element extending through the sensor body from the outer surface to the hollow capillary; and a conductive element in contact with the sensing element; where the conductive element detects a response signal generated by a reaction between the sensing element and a fluid when the fluid flows through the hollow capillary and contacts the sensing element. Such a sensor device is described in International Publication No. WO 2018 / 112008. In a further aspect, the amount used for determination, i.e., the amount contained within the measurement chamber, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as from 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters.

[0114] In another aspect, the heating element described herein is included in a sensor device that includes: a first planar substrate having a first planar surface; a second planar substrate having a second planar surface; a first sensing region and a second sensing region, the first sensing region and the second sensing region being disposed between the first planar surface and the second planar surface, both the first sensing region and the second sensing region including a chemical and / or reagent electrically connected to a first electrode and a second electrode, respectively; a first planar intermediate spacer layer having a flow path, wherein the first sensing region is opposite the second sensing region and the flow path is disposed between the first sensing region and the second sensing region; and a first heating element disposed between the first planar surface and the second planar surface. Such a sensor device is described in International Publication No. WO 2017 / 120464. In a further aspect, the amount used for determination, i.e., the amount contained within the measurement chamber, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters.

[0115] In another aspect, the heating element described herein is included in a sensor device that includes: a first planar intermediate isolation layer having at least a first sensing region; a second planar intermediate isolation layer having at least a second sensing region; a third planar intermediate isolation layer having a flow path 14, where the first sensing region is opposite the second sensing region and the flow path is disposed between the first and second sensing regions; a first planar conductive layer disposed adjacent to a first intermediate isolation layer opposite the third planar intermediate isolation layer; a first planar substrate disposed adjacent to the first planar conductive layer opposite the first intermediate isolation layer; a second planar substrate disposed adjacent to the second planar intermediate isolation layer opposite the third planar intermediate isolation layer, the second planar substrate having a first conductive via that is in electrical contact with at least the second sensing region; and a second planar conductive layer disposed in contact with the second planar substrate opposite the second planar intermediate isolation layer, the second planar conductive layer being in electrical contact with the first conductive via, where each of the first planar intermediate isolation layer, the second planar intermediate isolation layer, the third planar intermediate isolation layer, the first planar conductive layer, the first planar substrate, the second planar substrate, and the second planar conductive layer has two planar surfaces separated by a thickness, each of the two planar surfaces of each has an approximately equal planar area, and where the planar area of the first conductive layer is larger than the planar area of each of the first planar intermediate isolation layer, the second planar intermediate isolation layer, the third planar intermediate isolation layer, the second planar substrate, and the second planar conductive layer. Such a sensor device is described in International Publication No. WO 2017 / 019609.In a further aspect, the amount used for the determination, i.e., the amount contained within the measurement chamber, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as from 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters.

[0116] In another aspect, the heating element described herein is included in a sensor device that includes: a single substrate having a first surface, the first surface having a first region and a second region separated by a line, the first region being opposite the second region of the first surface of the single substrate; a conductor layer disposed on the single substrate, the conductor layer including a first electrode group printed on the first region and a second electrode group printed on the second region; a dielectric layer disposed on the conductor layer, the dielectric layer including a first region of dielectric material disposed on the first electrode group and a second region of dielectric material disposed on the second electrode group, the first region of dielectric material and the second region of dielectric material each including a respective first reaction well group and second reaction well group formed in the dielectric layer, at least one reaction well being electrically coupled to each electrode and containing a chemical; and a spacer layer adjacent to the first region of dielectric material and the second region of dielectric material, the spacer layer forming a flow path between the first reaction well group and the second reaction well group. Such a sensor device is described in International Publication No. WO 2016 / 106320. In a further aspect, the amount used for determination, i.e., the amount contained within the measurement chamber, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as from 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters.

[0117] In another aspect, the heating element described herein is included in a test coupon that includes: a first planar substrate having a coplanar electrode on a first planar surface and a second planar substrate having a coplanar electrode on a second planar surface, the first planar substrate and the second planar substrate being arranged such that the first surface of the first planar substrate is opposite the second planar surface of the second planar substrate; an intermediate layer disposed between the opposed first surface of the first planar substrate and the second planar surface of the second planar substrate; the first planar surface of the first planar substrate having a first sensing region electrically connected to a first electrical contact; and the second planar surface of the second planar substrate having a second electrical contact electrically connected to the first electrical contact via a conductive element, the conductive element extending between the first surface of the first planar substrate and the second surface of the second planar substrate without passing through the first planar substrate or the second planar substrate. Such test coupons are described in International Publication No. WO 2016 / 011308. In a further aspect, the amount used for determination, i.e., the amount contained within the measurement chamber, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as from 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters.

[0118] In another aspect, the heating element described herein is included in a sensor device that includes: a first planar substrate having a base layer, a conductive layer formed on a first planar surface of the base layer, and a dielectric layer formed on at least one of the first planar surface of the conductive layer or the first planar surface of the base layer, the dielectric layer having a first planar surface disposed slightly away from the first planar surface of the conductive layer, the conductive layer including at least a first electrical contact and a second electrical contact electrically insulated from the first electrical contact, the dielectric layer defining a liquid flow path therethrough, the flow path having two side walls and a bottom surface extending between the two side walls, the two side walls extending between the first planar surface of the base layer and the first planar surface of the dielectric layer, and the dielectric layer further defining a first sensing region and a second sensing region over each of the first electrical contact and the second electrical contact of the conductive layer, the first sensing region and the second sensing region enabling the liquid in the flow path to contact the first electrical contact and the second electrical contact, respectively; and a second planar substrate, the second substrate being adhered to the first substrate, and when adhered to the first substrate, the second substrate defining an upper surface of the liquid flow path, the upper surface of the liquid flow path extending between the two side walls and being disposed slightly away from the bottom surface of the flow path. Such a sensor device is described in International Publication No. WO 2016 / 007716. In a further aspect, the amount used for determination, i.e., the amount contained within the measurement chamber, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 microliters.

[0119] In another aspect, the heating element described herein is included in a sensor device that includes: a substrate having a first surface and a second surface opposite the first surface; at least one analyte sensor located on at least one of the first and second surfaces of the substrate; and at least one electrical contact located on the substrate in electrical communication with a corresponding one of the at least one analyte sensor, wherein the substrate is configured to define a tube having an inner surface and an outer surface, at least a portion of the first surface of the substrate defines the inner surface of the tube, and the at least one analyte sensor is disposed on at least one of the inner and outer surfaces of the tube. Such sensor devices are described in International Publication No. WO 2013 / 163120. In a further aspect, the amount used for determination, i.e., the amount contained within the measurement chamber, is less than 1 ml, such as less than 0.5 ml, such as less than 200 microliters, such as less than 100 microliters, such as less than 50 microliters, such as from 2 to 50 microliters, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 microliters to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 4 9 or 50 microliters. This specification includes the disclosure of the following invention. [Item 1] A sensor device, comprising: - A measurement chamber having at least a first wall, the measurement chamber including a plurality of analyte sensors; wherein the measurement chamber enables a fluid to be analyzed to interact with each of the plurality of analyte sensors when the fluid is contained within the measurement chamber; the measurement chamber has an inlet configured to receive the fluid to be analyzed and an outlet configured to allow the fluid to exit the measurement chamber after interacting with the plurality of analyte sensors; the measurement chamber defines a sample volume for containing the fluid to be analyzed, the sample volume extending at least between the inlet and the outlet; and - A heating element configured to heat the fluid contained within the measurement chamber; A sensor device, wherein the heating element is configured to provide a greater heating effect near the inlet of the measurement chamber than near the outlet of the measurement chamber. [Item 2] The sensor device according to Item 1, including a second wall of the measurement chamber on the opposite side of at least the first wall. [Item 3] The sensor device according to Item 1 or 2, wherein the heating element is disposed only on the first wall. [Item 4] A sensor device, comprising: - A measurement chamber having at least a first wall and a second wall opposite the first wall, the measurement chamber including a plurality of analyte sensors; wherein the measurement chamber enables a fluid to be analyzed to interact with each of the plurality of analyte sensors when the fluid is contained within the measurement chamber; the measurement chamber has an inlet configured to receive the fluid to be analyzed and an outlet configured to allow the fluid to exit the measurement chamber after interacting with the plurality of analyte sensors; the measurement chamber defines a sample volume for containing the fluid to be analyzed, the sample volume extending at least between the inlet and the outlet; and - A heating element configured to heat the fluid in the measurement chamber; A sensor device including the heating element disposed only on the first wall. [Item 5] The sensor device according to any one of Items 2 to 4, wherein the first wall has a first surface facing the second wall and a second surface facing in the opposite direction to the second wall on the side opposite to the first surface, and the heating element is disposed on the second surface of the first wall. [Item 6] The sensor device according to any one of Items 1 to 5, wherein the heating element includes a heating trace made of a conductive material disposed on the surface of the first wall and extending between a first end point and a second end point. [Item 7] The sensor device according to Item 6, wherein the heating trace is disposed in a tortuous layout and / or a meandering layout and / or a spiral layout. [Item 8] The sensor device according to Item 6 or 7, wherein the heating trace is disposed in a heating trace layout, the heating trace layout defines a trace density as the length of the heating trace per unit surface area, and the trace density is higher near the inlet than near the outlet. [Item 9] The sensor device according to Item 8, wherein the measurement chamber defines a flow path between the inlet and the outlet of the measurement chamber, and the trace density is higher along a first portion of the measurement chamber between the inlet and a reference position along the flow path than along a second portion of the measurement chamber extending between the reference position and the outlet. [Item 10] The sensor device according to any one of Items 6 to 9, wherein the heating trace has an electrical resistivity that varies along the heating trace. [Item 11] The sensor device according to any one of Items 1 to 10, including a first substrate layer defining the first wall of the measurement chamber. [Item 12] The sensor device according to Item 11, wherein the first substrate layer includes a central layer portion and a peripheral layer portion, the central layer portion defines a first wall of the measurement chamber, the peripheral layer portion is disposed laterally displaced from the measurement chamber, the measurement chamber defines a flow path defined between the inlet and the outlet of the measurement chamber, and the heating trace includes a peripheral trace portion and a central trace portion, the peripheral trace portion is disposed on the surface of the peripheral layer portion, and the central trace portion is disposed on the central layer portion. [Item 13] The sensor device according to Item 12, wherein the peripheral trace portion is substantially uniformly distributed along the length of the flow path between the inlet and the outlet. [Item 14] The sensor device according to Item 12 or 13, wherein the central trace portion is non-uniformly distributed along the length of the flow path between the inlet and the outlet such that the trace density of the central trace portion is higher near the inlet than near the outlet. [Item 15] The sensor device according to Item 14, wherein the central trace portion is disposed only in a portion of the measurement chamber proximal to the inlet, for example, only between the inlet end and the central portion of the measurement chamber. [Item 16] The sensor device according to any one of Items 11 to 15 when dependent on any one of Items 2 to 5, including a second substrate layer that defines the second wall of the measurement chamber. [Item 17] The sensor device according to Item 16, including an intermediate layer disposed between the first and second substrate layers, the intermediate layer housing the measurement chamber. [Item 18] The sensor device according to Item 16 or 17, wherein each of the inlet and the outlet extends through the first substrate layer or the second substrate layer. [Item 19] The sensor device according to any one of Items 1 to 18, including at least a housing that houses the measurement chamber, the housing including an opening that exposes a part of the surface of at least one wall of the measurement chamber, and the exposed portion facing in a direction opposite to the sample volume. [Item 20] A sensor device according to any one of Items 1 to 19, the sensor device including a temperature sensor, particularly a thermistor element. [Item 21] A sensor device according to Item 20, wherein the temperature sensor is disposed on the surface of the first wall at a position not including a heating trace. [Item 22] A sensor device according to Item 20 or 21, wherein the temperature sensor is disposed in the central portion of the measurement chamber. [Item 23] A sensor device according to any one of Items 1 to 22, the sensor device including only a single heating element. [Item 24] A sensor device according to any one of Items 1 to 23, wherein each of the analyte sensors is as follows: - pO 2 , pCO 2 , pH; - electrolytes such as Li + , Na + 、K + , Ca 2+ , Mg 2+ 、Cl - , HCO 3- or NH 3 (NH 4 +) concentration; - metabolic factors such as glucose, creatinine, urea (BUN), uric acid, lactic acid, pyruvic acid, ascorbic acid, phosphate or protein concentration; and - enzymes such as lactate dehydrogenase, lipase, amylase, choline, esterase, alkaline phosphatase, acid phosphatase, alanine aminotransferase, aspartate, aminotransferase or creatinine kinase concentration; A sensor device configured to sense parameters of one or more analytes selected from the group. [Item 25] A sensor device according to any one of Items 1 to 24, the sensor device being configured to analyze parameters of a liquid sample, such as a body fluid. [Item 26] A sensor device according to any one of Items 1 to 25, wherein the fluid sample is a liquid selected from the group consisting of blood, diluted whole blood or undiluted whole blood, serum, plasma, saliva, urine, cerebrospinal fluid, pleural fluid, synovial fluid, ascitic fluid, peritoneal fluid, amniotic fluid, milk, dialysis fluid sample. [Item 27] A sensor device according to any one of Items 1 to 26, wherein the fluid sample is a medical gas sample selected from the group consisting of respiratory gas or exhaled breath. [Item 28] An analyzer including a sensor device holding mechanism configured to receive a sensor device according to any one of Items 1 to 27. [Item 29] The analyzer according to Item 28, wherein the sensor device holding mechanism is configured to receive the sensor device according to Item 19, and the sensor device holding mechanism is configured such that when the sensor device is received by the sensor device holding mechanism, it extends through the opening to provide heat exchange contact with the exposed portion of the surface. An analyzer including a heat storage element defining a heat exchange member. [Item 30] The analyzer according to Item 28 or 29, wherein the sensor device holding mechanism is as follows: - A conduit configured to provide fluid communication with the inlet of the sensor device when the sensor device is received by the sensor device holding mechanism; and - A heating element configured to preheat the fluid flowing through the conduit toward the inlet of the sensor device. An analyzer including. [Item 31] The analyzer according to any one of Items 28 to 30, wherein the analyzer is adapted to analyze parameters of a medical gas sample.

Explanation of Symbols

[0120] 1 Device 2 Measurement Chamber 3 Contact Pin 4 pO 2 Measurement System 6 Inlet 7 Outlet 8 Processing Unit 9 Oxygen Measurement Device 10a Liquid Sensor 10b Liquid Sensor 10c Liquid Sensor 12a Position 12b Position 12c Supply Line 13 Fluid Line 14 Fluid Line 20 Liquid Handling System 21 Reservoir 23 Pump 24 Waste Reservoir 25 Chip 30 Substrate 31 Temperature Sensor 32 Heating Element 33 Substrate Layer 34 Gasket Layer 35 Electrical Circuit 36 Electrical interface 38 Preheater 39 Analyte sensor 40 Storage device 41 Heat transfer block 45 Sensor device holding mechanism 56 Supply port 57 Return port 58 Electrical interface 60 Sensor device 61 Housing 71 Outlet port 216 Inlet end 217 Outlet end 301 End point 303 Peripheral part 304 Central part 305 Dashed line 611 Inlet port

Claims

1. A sensor device, comprising: - A measurement chamber having at least a first wall, the measurement chamber including a plurality of analyte sensors; wherein the measurement chamber enables a fluid to be analyzed to interact with each of the plurality of analyte sensors when the fluid is contained within the measurement chamber; the measurement chamber has an inlet configured to receive the fluid to be analyzed and an outlet configured to allow the fluid to exit the measurement chamber after interacting with the plurality of analyte sensors; the measurement chamber defines a sample volume for containing the fluid to be analyzed, and the sample volume extends at least between the inlet and the outlet ； and - A heating element configured to heat the fluid contained within the measurement chamber; wherein the heating element is configured to provide a greater heating effect near the inlet of the measurement chamber than near the outlet of the measurement chamber, and each of the analyte sensors is configured to sense a parameter of one or more analytes selected from the group consisting of: -pO ２ , pCO ２ , pH; - The concentration of an electrolyte; - The concentration of a metabolic factor; and - The concentration of an enzyme; A sensor device.

2. The sensor device according to claim 1, wherein the electrolyte is selected from the group consisting of Li+, Na+, K+, Ca2+, Mg2+, Cl−, HCO3−, and NH3 (NH4+).

3. The sensor device according to claim 1 or 2, wherein the metabolic factor is selected from the group consisting of glucose, creatinine, urea (BUN), uric acid, lactic acid, pyruvic acid, ascorbic acid, phosphate, and protein.

4. The sensor device according to any one of claims 1 to 3, wherein the enzyme is selected from the group consisting of lactate dehydrogenase, lipase, amylase, choline, esterase, alkaline phosphatase, acid phosphatase, alanine aminotransferase, aspartate aminotransferase, and creatine kinase.

5. A sensor device according to any one of claims 1 to 4, comprising at least a second wall of the measurement chamber on the opposite side of the first wall.

6. The sensor device according to any one of claims 1 to 5, wherein the heating element is disposed only on the first wall. **Claim 7** A sensor device, comprising: - A measurement chamber having at least a first wall and a second wall opposite to the first wall, the measurement chamber including a plurality of analyte sensors; wherein the measurement chamber enables the fluid to be analyzed to interact with each of the plurality of analyte sensors when the fluid is contained within the measurement chamber; the measurement chamber has an inlet configured to receive the fluid to be analyzed and an outlet configured to allow the fluid to exit the measurement chamber after interacting with the plurality of analyte sensors; the measurement chamber defines a sample volume for containing the fluid to be analyzed, the sample volume extending at least between the inlet and the outlet; and - A heating element configured to heat the fluid in the measurement chamber; wherein the heating element is disposed only on the first wall, a) the heating element includes a heating trace made of a conductive material disposed on the surface of the first wall and extending between a first end point and a second end point, the heating trace having a varying electrical resistivity along the heating trace, and / or b) the sensor device includes a first substrate layer defining the first wall of the measurement chamber, the first substrate layer including a central layer portion and a peripheral layer portion, the central layer portion defining the first wall of the measurement chamber, the peripheral layer portion being disposed laterally displaced from the measurement chamber, the measurement chamber defining a flow path defined between the inlet and the outlet of the measurement chamber, and the heating trace including a peripheral trace portion and a central trace portion, the peripheral trace portion being disposed on the surface of the peripheral layer portion, the central trace portion being disposed on the central layer portion. **Claim 8** The sensor device according to any one of claims 5 to 7, wherein the first wall has a first surface facing the second wall and a second surface opposite to the first surface and facing in the opposite direction to the second wall, and the heating element is disposed on the second surface of the first wall. **Claim 9** The sensor device according to any one of claims 1 to 8, wherein the heating element includes a heating trace made of a conductive material disposed on the surface of the first wall and extending between a first end point and a second end point.

10. The sensor device according to claim 9, wherein the heating trace is arranged in a tortuous layout and / or a meandering layout and / or a spiral layout.

11. The sensor device according to claim 9 or 10, wherein the heating trace is arranged in a heating trace layout, the heating trace layout defines a trace density as the length of the heating trace per unit surface area, and the trace density is higher in the vicinity of the inlet than in the vicinity of the outlet.

12. The sensor device according to claim 11, wherein the measurement chamber defines a flow path between the inlet and the outlet of the measurement chamber, and the trace density is higher along a first portion of the measurement chamber between the inlet and a reference position along the flow path than along a second portion of the measurement chamber extending between the reference position and the outlet.

13. The sensor device according to any one of claims 9 to 12, wherein the heating trace has an electrical resistivity that varies along the heating trace.

14. The sensor device according to any one of claims 1 to 13, including a first substrate layer that defines a first wall of the measurement chamber.

15. The sensor device according to claim 14, wherein the first substrate layer includes a central layer portion and a peripheral layer portion, the central layer portion defines the first wall of the measurement chamber, the peripheral layer portion is disposed laterally offset from the measurement chamber, the measurement chamber defines a flow path defined between the inlet and the outlet of the measurement chamber, and the heating trace includes a peripheral trace portion and a central trace portion, the peripheral trace portion is disposed on the surface of the peripheral layer portion, and the central trace portion is disposed on the central layer portion.

16. The sensor device according to claim 15, wherein the peripheral trace portion is substantially uniformly distributed along the length of the flow path between the inlet and the outlet.

17. The sensor device according to claim 15 or 16, wherein the central trace portion is unevenly distributed along the length of the flow path between the inlet and the outlet such that the trace density of the central trace portion is higher near the inlet than near the outlet.

18. The sensor device according to claim 17, wherein the central trace portion is disposed only in a portion of the measurement chamber proximal to the inlet.

19. The sensor device according to any one of claims 14 to 18 when dependent on any one of claims 5 to 8, the sensor device including a second substrate layer defining the second wall of the measurement chamber.

20. The sensor device according to claim 19, including an intermediate layer disposed between the first and second substrate layers, the intermediate layer housing the measurement chamber.

21. The sensor device according to claim 19 or 20, wherein each of the inlet and the outlet extends through the first substrate layer or the second substrate layer.

22. The sensor device according to any one of claims 1 to 21, including at least a housing housing the measurement chamber, the housing including an opening exposing a part of the surface of at least one wall of the measurement chamber, the exposed portion facing in a direction opposite to the sample volume.

23. The sensor device according to any one of claims 1 to 22, including a temperature sensor, particularly a thermistor element.

24. The sensor device according to claim 23, wherein the temperature sensor is disposed on the surface of the first wall at a position not including a heating trace.

25. The sensor device according to claim 23 or 24, wherein the temperature sensor is disposed in a central portion of the measurement chamber.

26. The sensor device according to any one of claims 1 to 25, including only a single heating element.

27. The sensor device according to any one of claims 1 to 26, configured to analyze parameters of a liquid sample.

28. A sensor device according to any one of claims 1 to 27, wherein the fluid is a liquid selected from the group consisting of blood, diluted whole blood or undiluted whole blood, serum, plasma, saliva, urine, cerebrospinal fluid, pleural fluid, synovial fluid, ascitic fluid, peritoneal fluid, amniotic fluid, milk, and dialysis fluid sample.

29. A sensor device according to any one of claims 1 to 28, wherein the fluid is a medical gas sample selected from the group consisting of respiratory gas or exhaled breath.

30. An analyzer comprising a sensor device holding mechanism configured to receive a sensor device according to any one of claims 1 to 29.

31. The analyzer according to claim 30, wherein the sensor device holding mechanism is configured to receive the sensor device according to claim 22, and the sensor device holding mechanism defines a heat exchange member configured to extend through the opening and effect heat exchange contact with the exposed portion of the surface when the sensor device is received by the sensor device holding mechanism, the analyzer comprising a heat storage element.

32. The analyzer according to claim 30 or 31, wherein the sensor device holding mechanism comprises: - a conduit configured to provide fluid communication with the inlet of the sensor device when the sensor device is received by the sensor device holding mechanism; and - a heating element configured to preheat the fluid flowing through the conduit towards the inlet of the sensor device. The analyzer comprising.

33. The analyzer according to any one of claims 30 to 32, wherein the analyzer is adapted to analyze parameters of a medical gas sample.

34. The heating element is configured to provide a greater heating effect in the vicinity of the inlet of the portion of the measurement chamber where the analyte sensor is disposed than in the vicinity of the outlet in the portion of the measurement chamber where the analyte sensor is disposed, the sensor device according to any one of claims 1 to 29.

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