Method for sensor calibration

Abstract

Disclosed herein is an in vitro diagnostic (IVD) analyzer (200) comprising at least one sensor (212) located in a flow-through sensor path (211) of a detection unit and requiring at least one oxygenated calibration fluid (221 ', 222') for calibration. The IVD analyzer (200) further comprises: a fluid supply unit (220) comprising at least one deoxygenated calibration fluid (221, 222); a fluid selection valve (230); the IVD analyzer (200) comprises a fluid selector valve (230), and at least one oxygenation conduit (215, 216) having two ends connected as a loop with the fluid selector valve (230), where the oxygenation conduit (215, 216) comprises an oxygen permeable wall, and where the IVD analyzer (200) further comprises a pump (240) and a controller (250), the controller is configured to control the pump (240) and the fluid selection valve (230) to deliver a deoxygenated calibration fluid (221, 222) into the oxygenation conduit (215, 216), wait for a predetermined time required for oxygenation of the deoxygenated calibration fluid (221, 222) via oxygen uptake from ambient air through the conduit wall, and inject the oxygenated calibration fluid (221 ', 222' ') thus obtained into the oxygenation conduit (215, 216). 222 ') into the sensor path (211) for the calibration of the at least one sensor (212). A corresponding automated method of calibrating at least one sensor (212) is also disclosed herein.

Description

Technical Field

[0001] The present invention relates to an automated method for calibrating a sensor located in a flow-through sensor path and requiring at least one oxygenated calibration fluid for calibration, and to a corresponding in vitro diagnostic analyzer. Background Art

[0002] In medicine, doctors' diagnoses and patients' treatments often rely on the measurement of patient sample parameters by in vitro diagnostic analyzers. It is important that the analyzer performs accurately by providing precise and reliable measurements. Therefore, a general requirement for in vitro diagnostic analyzers is to implement a set of procedures that ensure measurement performance. One of these procedures is calibration. In most cases, calibration is performed using standard solutions of known concentrations or parameters. In this way, the measured signal can be correlated with the quantitative result. Depending on the system and other variables that may affect performance, calibration should be performed more or less frequently.

[0003] In blood gas and electrolyte testing, parameters such as blood gas partial pressure (pO 2 ,pCO 2 ), oxygen saturation (SO 2 ), pH, electrolyte concentration (e.g. Na + , K + Mg 2 + , Ca 2 + , Li + , Cl - ), bicarbonate value (HCO 3 - ), metabolite concentrations (e.g., glucose, lactate, urea, creatinine), values ​​of hemoglobin and hemoglobin derivatives (e.g., tHb, O 2 Hb, HHb, COHb, MetHb, SulfHb), bilirubin value and hematocrit.

[0004] Typically, these parameters are determined by conductivity, electrochemical and / or optical measuring principles. Sensors based on these measuring principles and configured to measure such sample parameters can be combined, for example arranged sequentially in one or more flow-through sensor paths. This allows for simultaneous and / or sequential determination of multiple parameters from a single sample in a single test run.

[0005] Some metabolite sensors (such as glucose sensors and lactate sensors) require the presence of oxygen to perform measurements. Therefore, in order to calibrate these sensors, it is necessary to respectively contain lactate and / or glucose and a calibration fluid of known level of oxygen. However, glucose / lactate and oxygen cannot be stored together as ready-to-use calibration fluids because they react with each other, thus changing their corresponding content with storage time. Therefore, glucose / lactic acid calibration fluids are usually stored in the absence of oxygen, so it is necessary to add oxygen just before sensor calibration in a process referred to as pressure measurement. The process generally includes a predetermined amount of deoxygenated calibration solution being drawn into a fluid line made of a material permeable to oxygen from ambient air (such as made of silicone), and waiting for a predetermined time to allow oxygen to diffuse through the wall of the fluid line into the calibration fluid, until the required oxygenation level is reached before the fresh oxygenation (pressure measurement) calibration fluid is drawn into the sensor path, and the sensor is calibrated.

[0006] Since pressure measurement is only one of the steps required to perform a calibration procedure, and different fluids are delivered sequentially through the same fluid line via the same pump, the step of waiting for diffusion to occur may unduly extend the calibration time. Furthermore, since several calibration fluids requiring pressure measurement may be required, such as in order to perform a multi-point calibration, the pressure measurement process may be even more time consuming. Summary of the invention

[0007] In contrast to the above background art, aspects of the present disclosure provide certain non-obvious advantages and advances over the prior art. In particular, disclosed herein is a new automated method for calibrating a sensor located in a flow-through sensor path of a detection unit of an in vitro diagnostic (IVD) analyzer, the sensor involving a reaction with oxygen in a sample to determine a sample parameter and requiring at least one oxygenated calibration fluid having a certain oxygenation level for calibration, the method enabling pressure measurement of a deoxygenated calibration fluid without unnecessarily extending the calibration time and / or by simultaneously implementing parallel steps, by preventing the use of a fluid system and a pump from being blocked while waiting for a pressure measurement.

[0008] In particular, the method comprises controlling a pump and a fluid selection valve by a controller, comprising delivering a deoxygenated calibration fluid from a fluid supply unit into an oxygenation conduit having two ends connected in a loop with the fluid selection valve, the oxygenation conduit comprising an oxygen permeable wall, the fluid selection valve comprising one or more fluid input holes for selecting at least one fluid at a time, and a common outlet hole fluidically connected or fluidically connectable to a sensor path via a fluid line. The method further comprises waiting for a predetermined time required for oxygenation of the deoxygenated calibration fluid via oxygen uptake from ambient air through the conduit wall until a desired oxygenation level is obtained, thereby obtaining an oxygenated calibration fluid, delivering the oxygenated calibration fluid thus obtained into the sensor path and calibrating at least one sensor.

[0009] Also disclosed herein is an in vitro diagnostic analyzer configured to perform the automated method and present the same advantages.

[0010] As used herein, the term "in vitro diagnostic analyzer" or "IVD analyzer" refers to an automated or semi-automated analytical device that is configured to examine in vitro samples to provide information for screening, diagnosis or treatment monitoring purposes. The IVD analyzer is designed and configured according to the medical application field, the parameters to be determined and the corresponding laboratory workflow. For example, in a field care testing environment, the IVD analyzer can be changed from a handheld device with low throughput, short turnaround time and a limited number of measurable parameters to a compact desktop instrument with higher throughput and a higher number of measurable parameters. Such IVD analyzers are designed to detect certain types of parameters, such as gases, electrolytes, metabolites, clinical chemistry analytes, immunochemical analytes, coagulation parameters, hematology parameters, etc. According to the parameters of interest, a variety of different analytical methods and different detection techniques can be applied. For example, in the field of blood gas and electrolyte testing, electrochemical measurement principles and / or conductivity measurement principles and / or optical detection methods are used. The IVD analyzer generally includes a plurality of functional units, each of which is dedicated to a specific task and cooperates with each other to achieve automated sample processing and analysis. Such functional units may include, for example, a sample input interface for receiving a sample, a fluid system, an analytical measurement unit or a detection unit, a fluid supply unit, etc. One or more functional units may be integrated into a larger unit or module in order to simplify the operation of the IVD analyzer.

[0011] In particular, the in vitro diagnostic (IVD) analyzer of the present disclosure includes at least one sensor located in a flow-through sensor path of a detection unit, the at least one sensor involving a reaction with oxygen in a sample to determine a sample parameter and requiring at least one oxygenated calibration fluid having a certain oxygenation level for calibration. The IVD analyzer further includes: a fluid supply unit, the fluid supply unit containing at least one deoxygenated calibration fluid; a fluid selection valve, the fluid selection valve including one or more fluid input holes for selecting at least one fluid at a time, and a common outlet hole connected to or fluidically connectable to the sensor path via a fluid pipeline. The IVD analyzer further includes at least one oxygenation conduit, the at least one oxygenation conduit having two ends each connected to the fluid selection valve to form a loop, the oxygenation conduit including an oxygen permeable wall. The IVD analyzer further comprises a pump and a controller configured to control the pump and the fluid selection valve to deliver the at least one deoxygenated calibration fluid from the fluid supply unit into the oxygenation conduit, wait a predetermined time required for oxygenation of the deoxygenated calibration fluid via oxygen uptake from ambient air through the conduit wall until a desired oxygenation level is obtained, and deliver the oxygenated calibration fluid thus obtained into the sensor path for calibration of the at least one sensor.

[0012] According to the present disclosure, a "detection unit" is an analytical measurement unit of an IVD analyzer including at least one flow-through sensor path. A "flow-through sensor path" is a fluid conduit that may include one or more sensors, and a sample flowing through the sensor path contacts the one or more sensors, such as arranged sequentially along the path, such as sensors for each different parameter / analyte to be detected, and may be embodied in a replaceable box-like structure including a plurality of sensors, and the plurality of sensors may be distributed on a plurality of sensor paths. Alternatively, the IVD analyzer may include a plurality of detection units, each of which has a sensor path including a sensor specifically for one parameter / analyte, and may also be replaceable or non-replaceable. Therefore, the sample may flow into one or more sensing paths, and different parameters / analytes may be determined by the corresponding sensors. The detection unit may also optionally include a flow-through optical measurement unit. The flow-through sensor path may be an integrated part of the fluid system of the IVD analyzer or part of an independent component, such as, for example, a sensor box that is fluidically connected to the fluid system of the IVD analyzer in the following manner: at least one fluid line is fluidically connected to at least one sensor path.

[0013] The term "sensor" is generally used herein to represent a detector configured to detect sample parameters by generating a correlated signal output that can be quantified and digitized. The sensor can be, for example, a biosensor, a chemical sensor or a physical sensor, and is typically a part of a functional unit (e.g., an analytical measurement unit or a detection unit) of an IVD analyzer. The sensor can be selective or specific with respect to a target sample parameter, or can be configured to detect and quantify a variety of different target sample parameters. Depending on the type of sensor, the sensor can include multiple sensing elements. Therefore, the term "sensing element" refers to a part of a sensor (e.g., a working electrode, a reference electrode, a counter electrode), which is combined with one or more other sensing elements to form a fully functional sensor.

[0014] According to certain aspects, the detection unit comprises pO 2 Sensor, pCO 2 Sensors, pH sensors, for determining electrolyte values ​​(such as Na + , K + , Ca 2 + and Cl - One or more ion selective electrode (ISE) sensors for determining parameters such as lactate and glucose, one or more metabolite sensors for determining parameters such as lactate and glucose. The sensors may be, for example, based on the amperometric principle, the potentiometric principle or the conductometric principle, respectively.

[0015] For example, pO 2 The sensor usually operates according to the Clarke measurement principle. This means that oxygen diffuses through the membrane to the gold multifilament system which has a negative potential within the sensor. Oxygen is reduced here, resulting in a current that is proportional to the oxygen contained in the sample. This current is measured amperometrically.

[0016] pCO 2 The sensor is usually a Severinghouse type sensor. This means that the CO 2 Diffusion through a membrane similar to an oxygen sensor. In this sensor, CO 2 The concentration changes and causes a change in the pH value of the internal buffer system, which is measured potentiometrically.

[0017] pH sensors usually include a pH sensitive membrane. Depending on the pH value of the test sample, an electric potential is generated in the boundary layer between the membrane and the sample. This potential can be measured potentiometrically by a reference sensor.

[0018] Na + , K + , Ca 2+ and Cl -ISE sensors usually work according to the potentiometric measurement principle. They differ only by different membrane materials that are sensitive to the respective electrolyte.

[0019] Glucose sensors typically use glucose oxidase, which oxidizes glucose to gluconolactone using oxygen available in the sample. The H formed in this process 2 O 2 Measured amperometrically at a manganese dioxide / carbon electrode.

[0020] Lactate sensors typically use lactate oxidase, which oxidizes lactate to pyruvate using oxygen available in the sample. The H formed in this process 2 O 2 The determination is amperometrically in a manner similar to that of a glucose sensor.

[0021] According to one embodiment, at least one sensor is a metabolite sensor including at least one of a glucose sensor and a lactate sensor, or any other biosensor involving reaction with oxygen.

[0022] A "fluid line" is a portion of a larger fluid system that may include one or more hollow conduits (such as pipes, channels, chambers, or combinations thereof), which includes one or more portions adapted to pass fluids in at least a fluid-tight manner, and may have any shape and size, but is typically optimized to minimize internal volume and dead volume. The portions may be flexible, rigid, or elastic, or a combination thereof. One or more fluid lines may be at least partially connected or connectable to each other, for example via fluid connections and / or valves.

[0023] The term "fluid selection valve" refers to a flow regulating device for controlling, redirecting, limiting or stopping flow, and specifically refers to a switch valve or a rotary valve, i.e., a porous valve capable of selecting a fluid connection. This is usually achieved by moving one or more valve conduits to switch the communication between different elements. The elements can be fluidically connected through another conduit (e.g., a pipe, a tube, a capillary, a microfluidic channel, etc.). For example, the valve can be integrated into a manifold, which includes a channel and a corresponding input hole for each fluid reservoir, wherein when the valve is switched (e.g., by rotating), a fluid connection is established between one fluid reservoir at a time and a common outlet hole of a fluid line connected or connectable to a flow-through sensor path. Alternatively, the manifold may include an input hole for each fluid reservoir, all of which lead to a common fluid input hole of a common channel and a fluid selection valve, in which case a separate on / off valve may be arranged corresponding to each fluid reservoir or fluid input hole to allow a selected fluid from a selected fluid reservoir to flow into the common channel and flow to the fluid selection valve. The valve may comprise further input ports for other fluids, for example for ambient air and / or for a sample.

[0024] The IVD analyzer also includes at least one pump (e.g., a peristaltic pump, a syringe pump, a diaphragm pump or any other suitable pump) to convey a sample from a sample container, other fluids from a fluid supply unit or ambient air through at least one fluid line and through a detection unit. In particular, the pump is used to deliver a deoxygenated calibration fluid from the fluid supply unit to an oxygenation pipeline via a fluid selection valve, and to deliver the obtained oxygenated calibration fluid from the oxygenation pipeline to a sensor path. The pump is typically located downstream of the detection unit, but it can be located at any other position and can be connected to the fluid system via other elements (such as valves and switches). In addition, the pumping direction can be reversible.

[0025] As used herein, a "fluid supply unit" is a module or component of an IVD analyzer that includes one or more fluid reservoirs and may also include one or more waste containers in which the fluid that circulates through the fluid system may be disposed of at the end of the process. The term "fluid" may refer to a gas or a liquid or a mixture thereof. The fluid may be, for example, a sample, a reagent, a reference fluid (such as a quality control fluid or a calibration fluid), a cleaning fluid, a wetting fluid, air, or other gases.

[0026] The sample typically enters the fluid system via a sample input interface that is different from the fluid supply unit, which is another module or component of the in vitro diagnostic analyzer, which is typically arranged at a position that is conveniently accessible to the operator and is configured to transfer the sample from the sample container presented by the operator to the in vitro diagnostic analyzer. The sample input interface can, for example, include a sample input hole, which includes an outer input port side and an inner input port side, the outer input port side being configured for coupling, attachment, connection, placement, introduction or insertion of a sample container (e.g., capillary type or syringe type), the inner input hole side being coupled to or for coupling to one end of a sample input conduit, which is, for example, fluidically connected or connectable to a detection unit / sensor path at the other end directly or via a fluid selection valve. According to one embodiment, the sample input conduit is the same fluid line leading from the fluid selection valve to the sensor path, and is configured to be alternately connected to the inner input hole side and to the fluid selection valve with the same end, for example, directly connected to the outlet hole of the fluid selection valve, or connected to another hole connected to the outlet hole of the fluid selection valve via another conduit, so as to alternately aspirate the sample from the sample input hole and aspirate the fluid other than the sample through the fluid selection valve, while the other end is connected to the detection unit / sensor path. According to one embodiment, if also used as a sample input conduit, the fluid line can be at least partially embodied as a rigid aspiration needle, which is configured to be connected to the inner input hole side of the sample input hole and to the outlet hole of the fluid selection valve or an extension thereof. According to one embodiment, ambient air can also be directly aspirated into the fluid line via the sample input hole or aspirated via a dedicated air hole of the fluid selection valve.

[0027] "Calibration fluid" is a reference or standard solution usually provided in a fluid supply unit, which contains known values ​​of one or more calibration substances for calibration, and which is measured under the same conditions as the biological sample. The calibration substance can be an analyte that is potentially present in the biological sample and detected by a specific sensor, but its concentration is known, or an analyte that is the same as the analyte of interest is produced by a reaction, and its concentration is known, or it can be any other equivalent substance of known concentration, which simulates the sample parameter of interest or can be associated with a certain parameter of interest in other ways, for example, a dye that optically behaves similar to the analyte of interest. Typically, when the sensor responds linearly to the analyte concentration, one or two calibration fluids are used for single-point calibration or two-point calibration, respectively. If the calibration curve is nonlinear, three or more calibration fluids can be used. In particular, the calibration fluid can be provided at different levels corresponding to different concentration ranges of the calibration substance.

[0028] In particular, according to the present disclosure, at least one deoxygenated calibration fluid is provided in the fluid supply unit. The term "deoxygenated" means that the oxygen level is zero or sufficiently low so that the content of any other calibration substance in the calibration fluid does not change significantly over storage time due to reaction with the oxygen contained therein. In other words, the level of oxygen or oxygen partial pressure in the calibration fluid is such that the shelf life of the calibration fluid is not affected by its oxygen level. Deoxygenation can be obtained at the time of manufacture by, for example, degassing the solvent used for the calibration fluid or replacing the oxygen with another inert gas, and is typically obtained by performing the manufacturing process in a deoxygenated environment so that oxygen uptake from the air is prevented before the calibration fluid is sealed in a liquid and gas sealed fluid reservoir. In order to keep the oxygenation level at a low level or close to zero during storage, a chemical deoxygenator can be used in the deoxygenated calibration fluid, for example in order to interact with and neutralize any oxygen that eventually penetrates into the fluid reservoir during storage, but its reaction kinetics are slow enough so that it does not interfere with the oxygenation process in the fluid pipeline.

[0029] Oxygenation of the deoxygenated calibration fluid takes place in an oxygenation conduit, in exactly the amount required and just before use for calibration. In particular, an "oxygenation conduit" is a fluid conduit which, unlike the rest of the fluid system, is both liquid-tight and gas-tight in order to avoid influencing sample parameters during transport, is only liquid-tight and is therefore permeable at least to oxygen from the ambient air. Thus, the oxygenation conduit comprises an oxygen-permeable wall, i.e. made of a material permeable to oxygen, such as silicone.

[0030] According to one embodiment, the IVD analyzer includes oxygenation tubing for each different deoxygenated calibration fluid to be oxygenated.

[0031] According to one embodiment, the method thus comprises conveying different deoxygenated calibration fluids to be oxygenated into respective oxygenation conduits.

[0032] The term "oxygenation" with respect to the calibration fluid refers to the oxygenation level or oxygen partial pressure obtained after delivering the deoxygenated calibration fluid into the oxygenation tubing and waiting for a predetermined time for the uptake of oxygen from the ambient air through the wall of the oxygenation tubing. The predetermined time is the time required to obtain a near saturation or equilibrium level corresponding to the desired oxygenation level or oxygen partial pressure that is most suitable and / or sufficient for calibrating at least one sensor, since extending this waiting time will hardly further increase the oxygenation level and the process will be unnecessarily prolonged. The oxygen partial pressure in the oxygenated calibration fluid obtained is typically about 80-90% of the oxygen partial pressure in ambient air, i.e. about 110-170 mmHg, depending on, for example, the altitude.

[0033] The difference between the deoxygenated and oxygenated calibration fluids according to the present disclosure is only given by the different oxygenation levels, respectively.

[0034] As used herein, the term "controller" may include any physical or virtual processing device, and in particular a programmable logic controller running a computer readable program provided with instructions to perform operations according to an operation plan, and in particular according to the method of calibrating a sensor disclosed herein. The controller may include a processor, a controller, a central processing unit (CPU), a microprocessor, a microcontroller, a reduced instruction set circuit (RISC), an application specific integrated circuit (ASIC), a logic circuit, or any other circuit or processor configured to perform one or more of the functions / methods described herein. In particular, the controller is configured to control a pump and a fluid selection valve to deliver a deoxygenated calibration fluid from a fluid supply unit into an oxygenation conduit, wait for a predetermined time required for oxygenation of the deoxygenated calibration fluid via oxygen uptake from ambient air through the conduit wall, and deliver the oxygenated calibration fluid thus obtained into the sensor path for calibration of at least one sensor.

[0035] According to one embodiment, the controller is further configured to control the pump and the fluid selection valve to deliver any other fluid from the fluid supply unit into the sensor path while the at least one oxygenation conduit is fluidly isolated and the deoxygenated calibration fluid is being oxygenated.

[0036] According to one embodiment, the method therefore comprises controlling the pump and the fluid selection valve to deliver any other fluid from the fluid supply unit into the sensor path while the at least one oxygenation conduit is fluidically isolated and the deoxygenated calibration fluid is being oxygenated.

[0037] According to one embodiment, the controller is further configured to control the pump and the fluid selection valve to deliver oxygenated calibration fluid from the oxygenation tubing into the sensor path while simultaneously introducing fresh deoxygenated fluid into the oxygenation tubing for oxygenation.

[0038] According to one embodiment, the method thus includes controlling the pump and the fluid selection valve to deliver oxygenated calibration fluid from the oxygenation conduit into the sensor path while simultaneously introducing fresh deoxygenated fluid into the oxygenation conduit for oxygenation.

[0039] Other and further objects, features and advantages will appear from the following description of exemplary aspects and accompanying drawings, which serve to explain the principles in more detail. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1A An in vitro diagnostic analyzer comprising a flow-through sensor path and a first step of an automated method of calibrating a sensor located in the flow-through sensor path is schematically shown.

[0041] Figure 1B Schematically shows Figure 1AThe second step is the same in vitro diagnostic analyzer and the same automated method.

[0042] Figure 1C Schematically shows Figure 1A-1B The same in vitro diagnostic analyzer and the third step of the same automated method.

[0043] Figure 1D Schematically shows Figures 1A-1C The fourth step is the same in vitro diagnostic analyzer and the same automated method.

[0044] Figure 1E Schematically shows Figures 1A-1D The fifth step is the same in vitro diagnostic analyzer and the same automated method.

[0045] Figure 2 Schematically shows Figures 1A-1E The same in vitro diagnostic analyzer and the steps of delivering the sample for analysis after sensor calibration.

[0046] Figure 3 Schematically shows Figures 1A to 1E The same in vitro diagnostic analyzer and Figure 1E Variations of the steps shown.

[0047] Figure 4 In more detail, Figure 1A A cross-sectional portion of the fluid selection valve integrated into the manifold and oxygenation tubing during the steps shown.

[0048] Figure 5 Shown in Figure 3 During the steps shown Figure 4 Similar details.

[0049] Figure 6 Similar to Figure 4 , but with Figure 1D The steps shown are relevant.

[0050] Figure 7 The progressive oxygenation levels achieved with different predetermined times of oxygen uptake in the oxygenation conduit are shown.

[0051] The skilled person will appreciate that the elements in the figures are shown for simplicity and clarity, and are not necessarily drawn to scale. For example, the sizes of some elements in the figures may be exaggerated relative to other elements, while other elements may have been omitted or represented in reduced quantities in order to enhance clarity and improve understanding of aspects of the present disclosure. DETAILED DESCRIPTION

[0052] Figures 1A to 1ESchematically illustrated together are examples of an in vitro diagnostic analyzer 200 including a flow-through sensor path 211 according to the present disclosure and an automated method for calibrating a sensor 212 located in the flow-through sensor path 211. In particular, the in vitro diagnostic analyzer 200 includes a detection unit 210, the detection unit including the flow-through sensor path 211, the flow-through sensor path 211 including at least one sensor 212, the at least one sensor involving a reaction with oxygen in a sample to determine a sample parameter and requiring at least one oxygenated calibration fluid with a certain oxygenation level for calibration. According to one embodiment, at least one sensor 212 is a metabolite sensor including at least one of a glucose sensor and a lactate sensor.

[0053] The IVD analyzer 200 further includes a fluid supply unit 220, which includes at least one deoxygenated calibration fluid 221, 222 and other fluids 223; a fluid selection valve 230 for selecting at least one fluid 221, 222, 223 at a time; and a fluid pipeline 213 included between the valve 230 and the sensor path 211. The IVD analyzer 200 further includes a sample input interface 100, which includes a sample input hole 10, and the sample input port includes an outer input port side 11 and an inner input port side 12 configured to be inserted into the open end of the sample container 1. In this example, the sample container 1 is a capillary sample container. The sample input interface 100 further includes an aspiration needle 30, which includes an upstream end 31 and a downstream end 32. The downstream end 32 of the aspiration needle 30 is fluidically connected to the sensor path 211 via a fluid line 213, while the upstream end 31 is configured to be alternately connected to the inner input hole side 12 so as to aspirate a sample from the sample container 1 inserted into the outer input hole side 11 and to be connected to the fluid supply unit hole 40 which is fluidically connected to the common outlet hole 231 of the fluid selection valve 230 via another conduit 214. However, the fluid line 213 can be directly connected to the outlet port 231 of the fluid selection valve 230, and the sample can be introduced via, for example, a different fluid line separately connected to the fluid selection valve 230. The fluid selection valve also includes an air hole 232. In this example, the IVD analyzer 200 further includes two oxygenation conduits 215, 216 each having two ends connected to the fluid selection valve 230 as a loop, the oxygenation conduits including oxygen permeable walls.

[0054] The IVD analyzer 200 further includes a pump 240, such as a peristaltic pump, located downstream of the sensor path 211 and a waste container 224 located in the fluid supply unit 220, in which the fluid circulating through the fluid line 213 and the sensor path 211 can be disposed.

[0055] The IVD analyzer 200 further includes a controller 250 configured to automatically perform any of the method steps disclosed herein.

[0056] In particular, Figure 1A Schematically showing the location of fluids represented by bold lines, this is the first step of an automated method for calibrating at least one sensor 212 located in a flow-through sensor path 211 of a detection unit 210 of an in vitro diagnostic (IVD) analyzer 200, the at least one sensor involving a reaction with oxygen in a sample to determine a sample parameter and requiring at least one oxygenated calibration fluid having a certain oxygenation level for calibration. The method includes controlling a pump 240 and a fluid selection valve 230 by a controller 250, including delivering a first deoxygenated calibration fluid 221 from a fluid supply unit 220 into a first oxygenated conduit 215.

[0057] like Figure 1B As shown, the method proceeds by waiting for a predetermined time required for oxygenation of the deoxygenated calibration fluid 221 via oxygen uptake from ambient air through the wall of the oxygenation conduit 215 until a desired oxygenation level is obtained, thereby obtaining a first oxygenated calibration fluid. The method further includes delivering a second deoxygenated calibration fluid 222 to be oxygenated into a second corresponding oxygenation conduit 216 while the first oxygenation conduit 215 is fluidically isolated and the first deoxygenated calibration fluid 221 is being oxygenated.

[0058] like Figure 1C As shown, the method further includes controlling the pump 240 and the fluid selection valve 230 to deliver any other fluid 223 from the fluid supply unit 220 into the sensor path 211 while the oxygenation conduits 215, 216 are fluidly isolated and the calibration fluid is being oxygenated.

[0059] like Figure 1D and Figure 1E As shown, the method further includes delivering the obtained first oxygenated calibration fluid 221' from the oxygenation conduit 215 into the sensor path 211 and calibrating the at least one sensor 212, while the second deoxygenated calibration fluid 222 continues the oxygenation step. Once the oxygenation step for the second deoxygenated calibration fluid 222 is completed, the method further includes delivering the second obtained second oxygenated calibration fluid 222' from the second oxygenation conduit 216 into the sensor path 211 and calibrating the at least one sensor 212 (not shown).

[0060] Figure 2 Schematically shows Figures 1A to 1E The same in vitro diagnostic analyzer 200 and the following steps: the sample 2 is transferred from the sample container 1 inserted into the outer input hole side 11 of the sample input hole 10, and the upstream end 31 of the aspiration needle 30 is connected to the inner input hole side 12 of the sample input hole 10 for use in Figures 1A to 1EThe sample 2 is analyzed by the sensor 212 after calibration by the method. After calibration and before delivering the sample, an intermediate cleaning step (not shown) using another fluid may be performed. In this case, the controller 250 is also configured to control the aspiration needle 30 to be alternately connected to the inner input hole side 12 to aspirate the sample from the sample container 1 inserted into the outer input hole side 11 and to the fluid supply unit hole 40 for performing other steps. The steps of delivering the sample and analyzing the sample can also be performed while the calibration fluid is in the oxygenation pipeline and the oxygenation step is in progress.

[0061] Overall, Figures 1A to 1E The method enables pressure measurement of deoxygenated calibration fluids without unnecessarily extending calibration time and / or enables parallel steps to be performed simultaneously by preventing use of the fluid system and pumps from being blocked while waiting for oxygenation.

[0062] Figure 3 Schematically shows Figures 1A to 1E The same in vitro diagnostic analyzer and Figure 1E A variation of the steps shown. A variation of the method includes controlling the pump 240 and the fluid selection valve 230 to deliver oxygenated calibration fluid 221 ′ from the oxygenation conduit 215 to the sensor path 211 while simultaneously introducing fresh deoxygenated fluid 221 into the oxygenation conduit 215 for oxygenation.

[0063] Figure 4 A perspective cross-sectional view of various portions of an embodiment including a fluid selection valve 230 integrated into a manifold 260, an oxygenation conduit 215 connected in a loop with the manifold 260, and a fluid reservoir 225 in which an on / off valve 226 is also connected to the manifold 260 is shown in more detail. In particular, the manifold 260 includes a channel 261 and a corresponding input aperture 262, 263 for each fluid reservoir 225 (only one fluid reservoir is shown for simplicity). The input apertures 262, 263 both lead to the same and common channel 261 and the common fluid input aperture 233 of the fluid selection valve 230. Each fluid reservoir 225 includes a separate on / off valve 226 through which the fluid reservoir 225 is connected to the corresponding input aperture 262 of the manifold 260 so as to allow a selected fluid 221 from a selected fluid reservoir 225 to flow into the common channel 261 and the fluid selection valve 230. Figure 4 The arrows schematically show Figure 1AThe same steps shown include delivering the deoxygenated calibration fluid 221 from the fluid reservoir 225 to the oxygenation conduit 215 (for simplicity, only one oxygenation conduit is shown). In particular, the fluid selection valve 230 is in a switching position, which is obtained by the rotation of the actuating member 234, which enables the calibration fluid to flow into the fluid selection valve 230 via the fluid input hole 233 and flow through the oxygenation conduit 215 via the fluid selection valve 230, and flow out again via the fluid selection valve 230 through the outlet hole 231. The on / off valve 226 is in an open state, while all other on / off valves (not shown) of other fluid reservoirs (not shown) are in a closed state.

[0064] Figure 5 Shown are front views and partial cross-sectional views, with details and components similar to Figure 4 In particular, Figure 5 Also shown is a second fluid reservoir 227 containing a fluid 223, in this example a fluid different from the calibration fluid, connected to an input hole 263 of the manifold 260 via an on / off valve 228. The on / off valve 228 is in an open state, while the on / off valve 226 and all other on / off valves (not shown) of other fluid reservoirs (not shown) are in a closed state. The fluid selection valve 230 is in a switching position obtained by rotation of the actuating member 234, which enables a different fluid 223 to flow into the fluid selection valve 230 via the manifold channel 261 and the fluid input hole 233 and flow via the fluid selection valve 230 to the sensor path ( Figure 5 The outlet hole 231 (not shown) is fluidly isolated from the oxygenation conduit 215 in which the calibration fluid is being oxygenated. The oxygenation conduit 215 is made of a material that is permeable to oxygen from the ambient air, such as silicone. Figure 5 The arrows also schematically show that Figure 1C , any other fluid 223 is delivered from the fluid supply unit into the sensor path while the oxygenation tubing 215 is fluidically isolated and the deoxygenated calibration fluid is being oxygenated.

[0065] Figure 6 and Figure 4 Almost the same, but also schematically shown by arrows Figure 3 The same steps as shown include delivering oxygenated calibration fluid 221' from oxygenation conduit 215 through outlet port 231 to the sensor path ( Figure 6 In the process (not shown), fresh deoxygenated fluid 221 is simultaneously introduced into the oxygenation pipeline 215 for oxygenation.

[0066] Continue to refer Figures 4 to 6, a controller (not shown) is configured to control the on / off valves 226, 228 in addition to the fluid selection valve 230 and the pump 240 so as to select the fluid at a time.

[0067] Figure 7 The oxygen partial pressure pO is measured at different time points. 2 (in mmHg), for example by repeating the process with progressively longer wait times and measuring the corresponding pO of the partially oxygenated calibration fluid in the sensor path 2 , a graph of the progressive oxygenation level of a calibration fluid achieved over time in an oxygenation pipeline as used in the above example. It can be seen that in order to obtain an adequate level of oxygenation, i.e. typically about 80% to 90% of the partial pressure of oxygen in ambient air, i.e. about 110 mmHg to 170 mmHg, depending on e.g. its altitude, it may be necessary to wait several minutes, beyond the time shown in the graph. Although not explicitly shown in the above example, it is clear that several other steps may be performed during this time, as the fluid system and pump remain available during this time.

[0068] Modifications and variations of the disclosed aspects are of course possible in light of the above description. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced in a manner other than that specifically designed in the above examples.

[0069] In particular, it should be understood that at least some of the drawings or parts are only schematic and are provided only as examples. In addition, the relationship between the elements may be different from the relationship shown, and parts that are not related to the purpose of the present disclosure have been omitted.

[0070] In addition, references to "an example" or "an example" throughout this specification refer to a particular feature, structure, or characteristic described in conjunction with that aspect or example being included in at least one aspect. Therefore, the phrases "an example" or "an example" appearing in different places in this specification do not necessarily refer to the same example.

[0071] Furthermore, the particular features, structures or characteristics may be combined in any suitable combinations and / or sub-combinations in one or more aspects or examples.

Claims

1. An in vitro diagnostic (IVD) analyzer (200) comprising at least one sensor (212) located in a flow-through sensor path (211) of a detection unit (210), the at least one sensor involving a reaction with oxygen in a sample to determine a sample parameter and requiring at least one oxygenated calibration fluid (221', 222') having a certain oxygenation level for calibration, the IVD analyzer (200) further comprising: include: A fluid supply unit (220) comprising at least one deoxygenated calibration fluid (221, 222), a fluid selection valve (230) comprising one or more fluid input holes for selecting at least one fluid (221, 222, 223) at a time, a common outlet hole (231) fluidically connected or fluidically connectable to the sensor path (211) via a fluid line (214, 213), wherein the IVD analyzer (200) further comprises at least one oxygenation conduit (215, 216) having two ends connected to the fluid selection valve (230) in a loop, wherein the oxygenation conduit (215, 216) comprises an oxygen permeable wall, and wherein the The IVD analyzer (200) further comprises a pump (240) and a controller (250), the controller being configured to control the pump (240) and the fluid selection valve (230) to deliver a deoxygenated calibration fluid (221, 222) from the fluid supply unit (220) into the oxygenation conduit (215, 216), wait for a predetermined time required for oxygenation of the deoxygenated calibration fluid (221, 222) via oxygen uptake from ambient air through the conduit wall until a desired oxygenation level is obtained, and deliver the oxygenated calibration fluid (221', 222') thus obtained into the sensor path (211) for calibration of the at least one sensor (212).

2. The IVD analyzer (200) of claim 1, wherein the at least one sensor (212) is a metabolite sensor comprising at least one of a glucose sensor and a lactate sensor.

3. The IVD analyzer (200) according to claim 1 or 2, comprising an oxygenation conduit (215, 216) for each different deoxygenated calibration fluid (221, 222) to be oxygenated.

4. The IVD analyzer (200) according to any of the preceding claims, wherein the controller is further configured to control the pump (240) and the fluid selection valve (230) to deliver any other fluid (223) from the fluid supply unit (220) into the sensor path (211) while the at least one oxygenation conduit (215, 216) is fluidically isolated and the deoxygenated calibration fluid (221, 222) is being oxygenated.

5. The IVD analyzer (200) according to any one of the preceding claims, wherein the controller (250) is further configured to control the pump (240) and the fluid selection valve (230) to deliver the oxygenated calibration fluid (221') from the oxygenation pipeline (215) to the sensor path (211), while introducing fresh deoxygenated fluid (221) into the oxygenation pipeline (215) for oxygenation.

6. An automated method for calibrating a sensor (212) located in a flow-through sensor path (211) of a detection unit (210) of an in vitro diagnostic (IVD) analyzer (200), the sensor involving a reaction with oxygen in a sample to determine a sample parameter and requiring at least one oxygenated calibration fluid (221', 222') having a certain oxygenation level for calibration, the method comprising controlling a pump (240) and a fluid selection valve (230) by a controller (250), comprising - delivering deoxygenated calibration fluids (221, 222) from a fluid supply unit (220) to an oxygenation conduit (215, 216) having two ends fluidically connected to the fluid selection valve (230) in a loop, the oxygenation conduit (213) comprising an oxygen permeable wall, the fluid selection valve (230) comprising a valve for selecting at least one fluid (221, 222, 223) and via one or more fluid input ports and fluid lines (214, 213) a common outlet opening (231) which is fluidly connected or fluidly connectable to said sensor path (211), - waiting for a predetermined time required for oxygenation of said deoxygenated calibration fluid (221, 222) via oxygen uptake from ambient air through the pipe wall until the desired oxygenation level is obtained, thereby obtaining an oxygenated calibration fluid (221', 222'), - The oxygenated calibration fluid (221', 222') thus obtained is conveyed into the sensor path (211) and calibrates at least one sensor (212).

7. The method of claim 6, wherein the at least one sensor (212) is a metabolite sensor comprising at least one of a glucose sensor and a lactate sensor.

8. The method according to claim 6 or 7, comprising conveying different deoxygenated calibration fluids (221, 222) to be oxygenated into respective oxygenation conduits (215, 216).

9. The method according to any one of claims 6 to 8, further comprising: include: The pump (240) and the fluid selection valve (230) are controlled to deliver any other fluid (223) from the fluid supply unit (220) into the sensor path (211) while at least one oxygenation conduit (215, 216) is fluidically isolated and the deoxygenated calibration fluid (221, 222) is being oxygenated.

10. The method according to any one of claims 6 to 9, further comprising: include: The pump (240) and the fluid selection valve (230) are controlled to deliver the oxygenated calibration fluid (221') from the oxygenation pipeline (215) to the sensor path (211), while introducing fresh deoxygenated fluid (221) into the oxygenation pipeline (215) for oxygenation.

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