Method for operating a sensor device

Abstract

The present disclosure relates to a method for operating a sensor device for an analyser apparatus configured to analyse parameters of blood samples. The method comprising the steps of: providing the sensor device, the sensor device comprising: a measurement chamber defining an interior volume for receiving a fluid to be analysed, a chamber inlet and a chamber outlet, a reference electrode in fluid communication with the interior volume, and one or more ion-selective analyte sensors; measuring an electric potential of a blood sample in the interior volume using the reference electrode and at least one of the analyte sensors; and filling the interior volume with an idling liquid, the idling liquid comprising an anti-microbial agent, the anti-microbial agent comprising a sulfur-containing compound. The method further comprises a step of providing a sulfur-reactive agent in the interior volume to at least partially bind the sulfur-containing compound of the anti-microbial agent.

Description

[0001] METHOD FOR OPERATING A SENSOR DEVICE

[0002] TECHNICAL FIELD

[0003] The present invention relates to a method for operating a sensor device, wherein the sensor device is for an analyser apparatus configured to analyse parameters of blood samples.

[0004] BACKGROUND

[0005] Blood gas measurements can be used to provide information about respiratory and metabolic status of patients by measuring various parameters, such as concentration of electrolytes, in the blood of the patient.

[0006] Such blood gas measurements are typically performed by providing a blood sample to an analyser apparatus which performs the measurements. At least some measurements are performed in a sensor device comprising sensors and a measurement chamber defining an interior volume. A fluid to be analysed can then be provided to the interior volume, and measurements are performed by means of the sensors.

[0007] The measurement error of some measurements has been found to increase during use and / or over time. Conventionally, this issue has been solved simply by replacing the sensor device.

[0008] However, it would be far more desirable to reduce or eliminate this measurement error, thereby avoiding untimely and excessive replacement of the sensor device and ensuring maximal measurement accuracy throughout the lifetime of the sensor device.

[0009] SUMMARY

[0010] In light of the above, it is desirable to provide a method for operating a sensor device which reduces or eliminates measurement error.

[0011] A first aspect of the present disclosure relates to a method for operating a sensor device, wherein the sensor device is for an analyser apparatus configured to analyse parameters of blood samples, the method comprising the steps of: providing the sensor device, the sensor device comprising : a measurement chamber defining an interior volume for receiving a fluid to be analysed, a chamber inlet and a chamber outlet each respectively providing a respective fluid passage to the interior volume, a reference electrode in fluid communication with the interior volume, and one or more ion-selective analyte sensors, each analyte sensor comprising a sensor electrode and an ion-selective sensor membrane arranged between the interior volume and the sensor electrode; measuring an electric potential of a blood sample in the interior volume of the sensor device using the reference electrode and at least one of the one or more analyte sensors; and filling the interior volume with an idling liquid, the idling liquid comprising an anti-microbial agent, wherein the anti-microbial agent and / or the blood sample comprise a sulfur- containing compound; wherein the method further comprises a step of: providing a sulfur-reactive agent in the interior volume to at least partially bind the sulfur-containing compound .

[0012] Examples according to the present disclosure are directed at reducing or eliminating measurement error of the sensor device which arise during use over time.

[0013] The inventors have discovered that one source of measurement error arises at least partially due to build-up (e.g. precipitation) of sulfur from a sulfur-containing compound, for example in the form of as Ag?S, on the reference electrode. This gradually cause the reference electrode to stop functioning correctly as the relevant compound builds up, due to proper fluid communication with the fluid to be analysed being reduced.

[0014] Further investigation has established that the sulfur-containing compound may originate from anti-microbial rinse fluid and / or blood used in the analyser apparatus. The anti-microbial rinse fluid is provided to the interior volume of the sensor device when the analyser apparatus is not conducting measurements, i.e., when it is idle. Thus, this anti-microbial rinse fluid is also referred to as an idling liquid comprising an anti-microbial agent. The sulfur-containing compound may, for example, be methylisothiazolinone.

[0015] The sulfur-containing compound may originate from blood residues analysed in the analyser apparatus. The presence of blood residues in the interior volume has been found to worsen the problem, at least in some examples. This could be due to enhanced precipitation of sulfur on the reference electrode, and / or due additional reactions of precipitated sulfur with proteins from the blood.

[0016] To reduce or eliminate precipitation of sulfur on the reference electrode, and thereby reduce or eliminate measurement errors of the sensor device related to the reference electrode, the present disclosure provides of a sulfur-reactive agent in the interior volume to, at least partially, bind the sulfur-containing compound of the anti-microbial agent.

[0017] As a result, the sulfur-containing compound of the idling liquid may, at least partially, react with the sulfur-reactive agent instead of contributing to precipitation on the reference electrode of the sensor device.

[0018] Thereby, precipitation of sulfur on the reference electrode may be reduced or eliminated. In turn, measurement errors may be reduced or eliminated, and untimely and excessive replacement of the sensor device may be avoided.

[0019] Sensor devices disclosed herein comprise a measurement chamber defining an interior volume for receiving a fluid to be analysed, such as a medical fluid sample, preferably a blood sample, the blood sample consisting of blood or the blood sample comprising blood dissolved in an analysis solution. In other words, the blood sample may be whole blood, diluted blood, or a (diluted) blood component. Yet, the interior volume is also suitable for receiving other fluids, such as the idling liquid being present in the interior volume in between analysis of, e.g., blood samples. A chamber inlet and a chamber outlet each respectively provide a respective fluid passage to the interior volume from an exterior of the sensor device. This exterior of the sensor device can be an analysis apparatus. Medical fluid samples and idling liquid may thereby enter the interior volume via the chamber inlet and exit the interior volume via the chamber outlet.

[0020] These liquids may be provided via the analyser apparatus, for example by means of a pump of the analyser apparatus.

[0021] Further, sensor devices according to the present disclosure comprise a reference electrode and one or more ion-selective analyte sensors. Together, the reference electrode and an ion- selective analyte sensor can measure a difference in electric potential between the reference electrode and the analyte sensor across a fluid to be analysed when the interior volume accommodates a fluid to be analysed, to, e.g., provide an indication of a concentration of an electrolyte in a blood sample. Each ion-selective analyte sensor comprises a sensor electrode and an ion-selective sensor membrane arranged between the interior volume and the sensor electrode. The ion-selective sensor membrane is configured to ensure that only one or more specific types of ions contribute to a measurement of the electric potential when measuring via the sensor electrode upon which the ion-selective sensor membrane is positioned. Thereby, the ion-selective analyte sensors can be selectively directed at measuring specific types of ions. An ion-selective sensor membrane is an ion-selective membrane positioned on an electrode to provide an ion-selective analyte sensor. Various types of ion-selective membranes are available.

[0022] The anti-microbial agent comprises a sulfur-containing compound. Typically, the sulfur- containing compound has a molecular mass of less than 500 g / mol, preferably less than 250 g / mol. In addition to S, the sulfur-containing compound typically comprises carbon and hydrogen atoms and optionally one or more heteroatoms selected from N, O and P. In an alternative aspect, the sulfur-containing compound is molecular sulfur. In a preferred aspect, the sulfur-containing compound is a heterocyclic compound, such as e.g. isothiazoline or a derivative thereof. Isothiazoline derivatives of interest include methylisothiazolinone (MIT), chloromethylisothiazolinone (CMIT), benzisothiazolinone (BIT), octylisothiazolinone (OIT), dichlorooctylisothiazolinone (DCOIT), and butylbenzisothiazolinone (BBIT), of which methylisothiazolinone (MIT) is of most interest.

[0023] The sulfur-reactive agent is able to at least partially bind the sulfur-containing compound. Binding may take place via the formation of bonds (such as covalent bonds) between the sulfur-reactive agent and the sulfur-containing compound. The sulfur-reactive agent may also bind the sulfur-containing compound in other ways, e.g. via ionic interactions (i.e. formation of ion pairs), metal-ligand interactions, or hydrogen bond formation.

[0024] In one aspect, the sulfur-reactive agent comprises a metal. The sulfur-reactive agent may comprise a metal salt, for example a metal chloride, such as e.g. AgCL The metal of the sulfur-reactive agent comprises a metal from groups 3-15, preferably a metal from groups 3- 12, more preferably Ag, Zn, Fe, Cu, Ni, Tl, Pb, Cd, Co, or Hg. An example of a suitable metal from groups 13-15 is Sn.

[0025] The step of filling the interior volume with an idling liquid may also be referred to as a step of providing an idling liquid to the interior volume, or as a step of rinsing the interior volume with an idling liquid. Providing the sulfur-reactive agent

[0026] In examples according to the present disclosure, the sulfur-reactive agent is dissolved in or suspended in the idling liquid.

[0027] In examples according to the present disclosure, the sulfur-reactive agent is dissolved in or suspended in the idling liquid prior to the step of filling the interior volume with the idling liquid.

[0028] Hence, the sulfur-reactive agent may be provided to the interior volume together with the idling liquid. This simplifies the procedure as only a single liquid may have to be supplied for the purpose of rinsing while reducing or eliminating measurement error arising from precipitation of sulfur.

[0029] In examples according to the present disclosure, the step of providing the sulfur-reactive agent is performed subsequently to the step of filling the interior volume with the idling liquid.

[0030] In examples according to the present disclosure, the sulfur-reactive agent is dissolved in or suspended in an auxiliary fluid separate from the idling liquid, wherein the method comprises a step of filling the interior volume with the auxiliary fluid to thereby provide the sulfurreactive agent in the interior volume to at least partially bind the sulfur-containing compound of the anti-microbial agent.

[0031] In examples according to the present disclosure, the step of filling the interior volume with the auxiliary fluid is performed subsequent to the step of filling the interior volume with the idling liquid.

[0032] Thus, the sulfur-reactive agent may also be provided via a separate auxiliary fluid in addition or as an alternative to providing the sulfur-reactive agent via the idling liquid. Having a separate idling liquid and auxiliary fluid ensures that quantities and timings can be chosen more liberally.

[0033] In examples according to the present disclosure, the step of filling the interior volume with the idling liquid is performed separately from the step of measuring an electric potential.

[0034] In other words, the idling liquid is separate from the blood sample in which the electric potential is measured. In examples according to the present disclosure, the step of filling the interior volume with the idling liquid is performed when the analyser apparatus is idle from performing a measurement on a blood sample.

[0035] In examples according to the present disclosure, the step of filling the interior volume with the auxiliary fluid is performed when the analyser apparatus is idle from performing a measurement on a blood sample.

[0036] Thus, the sulfur-reactive agent may be provided as a process separate from providing and measuring electric potential of a blood sample.

[0037] Other specifics

[0038] In examples according to the present disclosure, the sulfur-containing compound comprises isothiazolinone, or a derivative thereof, such as methylisothiazolinone. The sulfur-containing compound may comprise sulfur-containing impurities from the production of isothiazolinone. The sulfur-containing compound may also be a component of blood.

[0039] The provision of a sulfur-reactive agent at least appears to be efficient to bind a sulfur- containing compound in the form of methylisothiazolinone.

[0040] In examples according to the present disclosure, the sulfur-reactive agent comprises a metal, for example a metal from groups 3-15, preferably a metal from groups 3-12, more preferably Ag, Zn, Fe, Cu, Ni, Tl, Pb, Cd, Co, or Hg.

[0041] Generally, metals and metal salts are promising as they exhibit at least some reactivity with a sulfur-containing compound, and are thereby suitable as a sulfur- reactive agent.

[0042] Hereunder, metals from groups 3-15, and in particular from groups 3-12 of the periodic table of elements are suitable. An example of a preferable metal from groups 13-15 is Sn.

[0043] Reference electrode

[0044] In examples according to the present disclosure, the reference electrode comprises a reference electrode liquid and a diffusion-tight diaphragm arranged between the interior volume and the reference electrode liquid, the diffusion-tight diaphragm having a through- going orifice covered by a reference electrode membrane permitting diffusion of ions therethrough. In examples according to the present disclosure, the reference electrode liquid comprises Ag ions, preferably Ag and Cl ions.

[0045] Chemical reaction

[0046] In examples according to the present disclosure, the sulfur-reactive agent at least partially binds the sulfur-containing compound by means of a chemical reaction between at least the sulfur-containing compound and the sulfur-reactive agent.

[0047] In examples according to the present disclosure, the sulfur-reactive agent at least partially binds the sulfur-containing compound by means of a chemical reaction between at least the sulfur-containing compound, the sulfur-reactive agent, and blood residues from the blood sample.

[0048] In examples according to the present disclosure, the anti-microbial agent prevents microbial growth in the measurement chamber by means of the sulfur-containing compound.

[0049] A liquid comprising sulfur-reactive agent

[0050] A second aspect of the present disclosure relates to an idling liquid for an analyser apparatus configured to analyse parameters of blood samples, the idling liquid comprising an antimicrobial agent, the anti-microbial agent comprising a sulfur-containing compound, the idling liquid further comprising a sulfur-reactive agent.

[0051] An idling liquid according to the second aspect of the present disclosure may generally provide the same or similar effects and advantages as provided by the method according to the first aspect of the present disclosure. Accordingly, an idling liquid according to the second aspect may reduce or eliminate precipitation of sulfur on the reference electrode, and in turn, measurement errors may be reduced or eliminated and excessive replacement of the sensor device may be avoided.

[0052] In examples according to the present disclosure, the sulfur-reactive agent is able to bind said sulfur-containing compound by means of a chemical reaction between at least the sulfur- containing compound, the sulfur-reactive agent and blood residue from a blood sample.

[0053] In examples according to the present disclosure, the sulfur-containing compound comprises isothiazolinone or a derivative thereof, such as methylisothiazolinone. In examples according to the present disclosure, the sulfur-reactive agent comprises a metal, for example a metal from groups 3-15, preferably a metal from group 3-12, more preferably Ag, Zn, Fe, Cu, Ni, Tl, Pb, Cd, Co, or Hg.

[0054] An example of a suitable metal from groups 13-15 is Sn. Generally, metals may be present in the idling liquid in a concentration of up to 100 pM. When the metal is Cu or Ag the metal concentration in the idling liquid could be in the range 0.1-10 pM.

[0055] The following examples are provided where the sulfur reactive agent is found a total concentration of 1 pM, calculated using Visual MINTEQ.

[0056] Use of liquid A third aspect of the present disclosure relates to use of an idling liquid according to the first aspect of the present disclosure to at least partially bind a sulfur-containing compound in an analyser apparatus configured to analyse parameters of blood samples.

[0057] Use according to the third aspect of the present disclosure may generally provide the same or similar effects and advantages as provided by the method according to the first aspect of the present disclosure. Accordingly, use according to the third aspect may reduce or eliminate precipitation of sulfur on the reference electrode, and in turn, measurement errors may be reduced or eliminated and excessive replacement of the sensor device may be avoided.

[0058] Analyser apparatus

[0059] A fourth aspect of the present disclosure relates to an analyser apparatus configured to analyse parameters of blood samples, the analyser apparatus comprising : a sensor device, the sensor device comprising : a measurement chamber defining an interior volume for receiving a fluid to be analysed, a chamber inlet and a chamber outlet each respectively providing a respective fluid passage to the interior volume from an exterior of the sensor device, a reference electrode in fluid communication with the interior volume, and one or more ion-selective analyte sensors, each separate analyte sensor of the one or more analyte sensors comprising a sensor electrode and an ion-selective sensor membrane arranged between the interior volume and the sensor electrode; and a processing unit configured to measure a difference in electrical potential between the reference electrode and the separate analyte sensor across the fluid to be analysed when the fluid to be analysed is present in the interior volume for each of the analyte sensors; wherein the analyser apparatus further comprises: an idling liquid according to the second aspect, or an auxiliary fluid comprising a sulfur-reactive agent; wherein the idling liquid or auxiliary fluid fills the interior volume or wherein the analyser apparatus is configured to supply the idling liquid or auxiliary fluid to the interior volume. An analyser apparatus according to the third aspect of the present disclosure may generally provide the same or similar effects and advantages as provided by the method according to the first aspect of the present disclosure. Accordingly, use according to the third aspect may reduce or eliminate precipitation of sulfur on the reference electrode, and in turn, measurement errors may be reduced or eliminated and excessive replacement of the sensor device may be avoided.

[0060] The analyser may be configured to supply the idling liquid to the interior volume by means of a pump. The idling liquid may be stored in a process liquid reservoir of the analyser apparatus. The analyser apparatus may further comprise a fluid selector arrangement configured to fluidly connect the process liquid reservoir storing the idling liquid to the interior volume.

[0061] Alternatively, the idling liquid may be provided from a source external from the analyser apparatus.

[0062] BRIEF DESCRIPTION OF THE DRAWINGS

[0063] Embodiments of the invention will now be further described by reference to the accompanying drawings, in which:

[0064] Fig. 1 illustrates a sensor device for an analyser apparatus,

[0065] Fig. 2 illustrates an exemplary reference electrode of a sensor device,

[0066] Fig. 3 illustrates an analyser apparatus according to the present disclosure,

[0067] Fig. 4 illustrates a flow chart of method steps according to the present disclosure, and

[0068] Fig. 5 illustrates experimental data indicative of performance of a reference electrode under different conditions.

[0069] Fig. 6 shows a comparison of a precipitate formed on the aperture of the reference electrode, with or without sulfur reactive agent. DETAILED DESCRIPTION

[0070] It should be understood that the detailed description and specific examples, while indicating embodiments of the disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure will become apparent to those skilled in the art from this detailed description.

[0071] Fig. 1 illustrates a sensor device 60 for an analyser apparatus. The analyser apparatus is configured to analyser parameters of blood samples by using the sensor device 60.

[0072] The sensor device 60 comprises a measurement chamber 2 defining an interior volume 82 for receiving a fluid to be analysed. A chamber inlet 6 and a chamber outlet 7 each provide a fluid passage to this interior volume 82 from an exterior of the sensor device.

[0073] Prior to insertion of the sensor device 60 into an analyser apparatus, the interior volume will typically be filled with a gas such as atmospheric air or an inert gas. When in use, a fluid to be analysed, such as a blood sample, can be provided via the chamber inlet 6 from the exterior of the sensor device 60, for example via an analyser apparatus. The fluid to be analysed can leave the interior volume 82 via the chamber outlet 7. Further, the sensor device 60 may also receive other liquids during use, for example an idling liquid, in between measurements.

[0074] The sensor device 60 further comprises a reference electrode 5 and selective sensors 39a-c. These are configured to measure a difference in electrical potential across a fluid to be analysed present in the interior volume 82. Each sensor 39a-c comprises a respective sensor electrode 42a-c and a respective selective membrane 43a-c arranged between the interior volume and the respective sensor electrode.

[0075] The sensor device 60 of the present example comprises three ion-selective analyte sensors 39a-c. Of these, a first analyte sensor 39a comprises a first sensor electrode 42a and a first ion-selective sensor membrane 43a arranged between the interior volume 82 and the first sensor electrode 42a, a second analyte sensor 39b comprises a second sensor electrode 42b and a second ion-selective sensor membrane 43b arranged between the interior volume 82 and the second sensor electrode 42b, and a third analyte sensor 39c comprises a third sensor electrode 42c and a third ion-selective sensor membrane 43c arranged between the interior volume 82 and the third sensor electrode 42c. Each of the ion-selective sensor membranes 43a-43c are configured to allow voltage measurement of a specific ion in a liquid medium, i.e., a specific electrolyte, for example Li+, Na+' K+' Ca2+, Mg2+, Cl’, HCO3’, NH4+, or a combination thereof.

[0076] Such measurements may be performed by measuring a difference in electrical potential between the reference electrode 5 and a specific ion-selective analyte sensor 39a-c. Thereby, an indication of an electrolyte ion concentration may be obtained.

[0077] In typical examples according to the present disclosure, measurements can be performed when the sensor device 60 is inserted into an analyser apparatus, which then performs the measurement via electrical communication with the reference electrode 5 and one or more of the sensor electrodes 42a-c. The analyser apparatus may for example have a processing unit configured to conduct the measurement. However, in alternative examples, the measurement may also be performed by means of a processing unit in the sensor device 60. For example, a sensor device may comprise a measurement system configured to read out and / or gather signals between the reference electrode 5 and one or more of the analyte sensors 39a-c.

[0078] In between measurements, an idling liquid, for example an anti-bacterial rinse fluid comprising methylisothiazolinone, i.e., a sulfur compound, can be provided to the interior volume 82. This methylisothiazolinone may cause precipitation of sulfur in the form of Ag?S on the reference electrode 5.

[0079] However, according to examples of the present disclosure, a sulfur-reactive agent is provided to the interior volume. As an example, the sulfur-reactive agent is Ag ions. As a result, the sulfur-containing compounds of the anti-microbial rinse fluid (such as methylisothiazolinone) or their derivatives, will tend to react with this sulfur-reactive agent instead of precipitating onto the reference electrode.

[0080] The illustrated sensor device 60 is suitable for insertion / engagement with an analyser apparatus. The sensor device 60 may thereby comprise an electrical device interface (not shown) for electrical communication with an electrical apparatus interface. In such examples, the reference electrode and the one or more analyte electrodes are electrically connected to the electrical device interface.

[0081] Additionally, the sensor device may optionally comprise other elements and corresponding interfaces for connecting these elements to an analyser apparatus. For example, the sensor device may comprise other sensor types, such as optical sensors, chemical sensors, and / or sensors utilizing other sensing technologies. Further, a sensor device may comprise heating element configured to be controlled by an analyser apparatus. Fig. 2 illustrates an exemplary reference electrode 5 of a sensor device. The illustration is provided as a cross-sectional view.

[0082] In some sensor devices according to the present disclosure, the reference electrode 5 comprises a reference electrode liquid 51 and a diffusion-tight diaphragm 52 arranged between the interior volume 82 of the sensor device and the reference electrode liquid as illustrated in Fig. 2. The diffusion-tight diaphragm 52 has a through-orifice 53 covered by a reference electrode membrane 55 permitting diffusion of ions therethrough. In this particular example, the reference electrode membrane 55 comprises two sub-membranes: a porous polycarbonate membrane and a cellophane membrane. The diffusion-tight diaphragm is formed of a polyester material. The reference electrode liquid is a saturated AgCI solution.

[0083] The reference electrode 5 further comprises a reference electrode pin 54 in contact with the reference electrode liquid 51 for electrical contact when measuring the electric potential in a fluid to be analysed.

[0084] When no sulfur-reactive agent is used, sulfur may tend to precipitate onto the through-going orifice 53.

[0085] Fig. 3 illustrates an analyser apparatus 1 according to the present disclosure.

[0086] The analyser apparatus 1 comprises an enclosure 40 configured to receive a sensor device 60, such as the sensor device illustrated in Fig. 1. The enclosure 40 is further configured to affix the sensor device within the analyser apparatus 1 and enable various communications between the sensor device 60 and other components of the analyser apparatus 1, such as the processing unit 8 and the liquid handling system 20.

[0087] In the present illustration, reference numerals have been omitted from most elements of the sensor device to avoid obscuring the figure with unnecessary details. However, for the sake of understanding the functionality of the analyser apparatus 1, the elements of the sensor device 60 may be assumed to be the same as those described in relation to Fig. 1.

[0088] The analyser apparatus comprises a processing unit 8 in communication with the sensor device 60.

[0089] This processing unit 8 is configured to process measurements of a fluid to be analysed in the sensor device 60, such as measurements of electrical potential in the fluid to be analysed using the reference electrode and ion-selective analyte sensors of the sensor device 60. The processing unit 8 may comprise or communicate with a voltmeter for measuring electrical potential(s) between the reference electrode and one or more sensor electrodes.

[0090] The processing unit 8 may further be configured to control the liquid handling system 20, to perform analysis of measurements, to serve results from measurements and / or results from analysis of measurements to a user or an external device, to control other various components of the analyser apparatus 1, or any combination thereof. Other components of the analyser apparatus 1 may for example be valves, sensors (in or external to the sensor device 60), a temperature regulation unit, or some combination thereof.

[0091] The analyser apparatus 1 comprises a liquid handling system 20. The liquid handling system 20 comprises a pump 23 fluidly connected to the chamber outlet of the sensor device 60. The liquid handling system 20 further comprises a fluid selector arrangement 22 fluidly connected to the pump 23 and to the chamber inlet of the sensor device 60. The fluid selector arrangement 22, the sensor device 60, and the pump thereby form a fluid liquid circuit path through which the pump 23 may pump liquid.

[0092] The liquid handling system further comprises process liquid reservoirs 21 and a waste reservoir 24 fluidly connected to the fluid selector arrangement 22. The process liquid reservoirs 21 may comprise various individual reservoirs of process liquids, such as the idling liquid, and liquids with known compositions for calibration and quality control purposes. The waste reservoir 24 is intended to receive fluid after it has been passed through the sensor device. The fluid selector arrangement 22 is configured to select a fluid from the process liquid reservoirs 21 based on a given process step. The fluid selector arrangement 22 may for example do so via controlling valves based on signal from the processing unit 8. Thereby, a relevant fluid can be transferred from the process liquid reservoirs 21 via the fluid selector arrangement 22 to the sensor device 60 using the pump 23, which also further transfers fluid into the waste reservoir 24.

[0093] The analyser apparatus 1 also comprises two feed lines 12a-b, through which a user may provide a liquid sample. The connection from the inlet of the sensor device 60 to the fluid selector arrangement 22 further constitutes a third feed line 12c. Thereby, three feed lines 12a-c are available for supplying a fluid to the sensor device 60.

[0094] In accordance with the present disclosure, a sulfur-reactive agent may be provided to the interior volume of the sensor device 60. This sulfur-reactive agent can for example be suspended in or dissolved in the idling liquid in a reservoir of the process liquid reservoirs 21 and thereby be provided to the interior volume together with the idling liquid. Optionally, the sulfur-reactive agent may alternatively be suspended in or dissolved in an auxiliary fluid stored in an auxiliary fluid reservoir 25 in fluid communication with the fluid selector arrangement 22. Thereby, the sulfur-reactive agent may be provided to the interior volume by means of the auxiliary fluid, separate from the idling liquid. Alternatively, the sulfurreactive agent may be provided from a source external from the apparatus 1, for example by means of a feed line 12a-12b, for example from a user of the analyser apparatus 1. The external source may for example provide an idling liquid or an auxiliary fluid comprising the sulfur-reactive agent.

[0095] Fig. 4 illustrates a flow chart of method steps S1-S4 according to the present disclosure. The method is a method for operating a sensor device, such as a sensor device for an analyser apparatus configured to analyse parameters of blood samples.

[0096] In a first step SI of the method, the sensor device is provided. The sensor device comprises a measurement chamber defining an interior volume for receiving a fluid to be analysed, a chamber inlet and a chamber outlet each respectively providing a respective fluid passage to the interior volume, a reference electrode in fluid communication with the interior volume, and one or more ion-selective analyte sensors, each analyte sensor comprising a sensor electrode and an ion-selective sensor membrane arranged between the interior volume and the sensor electrode. The sensor device may be inserted into an analyser apparatus, for example such that the sensor device can facilitate measurements in blood samples.

[0097] In another step S2 of the method, an electric potential of a blood sample in the interior volume of the sensor device is measured using the reference electrode and at least one of the one or more analyte sensors. The measurement may be controlled by a processing unit of the analyser apparatus configured to measure electric potential to determine an indication of a concentration of an electrolyte in the blood sample in the sensor device.

[0098] In another step S3 of the method, the interior volume is filled with an idling liquid. The idling liquid comprises an anti-microbial agent. The anti-microbial agent comprises a sulfur- containing compound. The idling liquid may be provided to the interior volume when the sensor device or analyser apparatus is idle between measurements of blood samples to disinfect and / or restrict bacterial growth within the sensor device until a new blood sample is provided to the interior volume of the sensor device, for example to measure an electric potential across this blood sample by using an ion-selective analyte sensor and the reference electrode.

[0099] In another step S4 of the method, a sulfur-reactive agent is provided to the interior volume to a least partially bind the sulfur-containing compound of the anti-microbial agent. Thereby, precipitation of sulfur onto the reference electrode may be reduced. Optionally, the sulfur-reactive agent may be provided simultaneously with the idling liquid filling the interior volume, for example by means of the sulfur-reactive agent being suspended in or dissolved in the idling liquid.

[0100] Fig. 5 illustrates experimental data indicative of performance of a reference electrode under different conditions.

[0101] To test the impact of a sulfur-reactive agent, sensor devices were each supplied with a solid element formed by Ag / AgCI placed onto a wall of the measurement chamber in fluid communication with the interior volume to thereby contact a fluid to be analysed, such as a blood sample. Such a solid element may be referred to as a sulfur-reactive element. Even though such a sulfur reactive-element does not constitute a sulfur-reactive agent dissolved in or suspended in an idling liquid or in an auxiliary fluid, it most likely releases ionic Ag into the idling liquid, at least in small concentrations, which helps binding sulfur. Hence, the impact of such a sulfur-reactive element is indicative of the impact of such a sulfur-reactive agent.

[0102] Sensor devices as schematically illustrated in Fig. 1 were used in an analyser apparatus as schematically illustrated in Fig. 3. Five sensor devices with a sulfur-reactive element formed by Ag / AgCI, and five sensor devices without a sulfur-reactive element were tested. Each sensor device was subjected to 1200 samples over 28 days. In between samples, the interior volume was filled with an idling liquid comprising an anti-microbial agent, the anti-microbial agent comprising a sulfur-containing compound in the form of methylisothiazolinone.

[0103] During the measurement period, the reliability of the reference electrode was tested, providing a value in potentiometric units indicative of the functionality of the reference electrode, with a greater value being indicative of reduced functionality. If the value is above 1 potentiometric unit in two consecutive measurements, the sensor device is disposed.

[0104] In Fig. 5, the left-hand panel shows the results from sensor devices without a sulfur- reactive element, and the right-hand panel shows the results from sensor device with a sulfurreactive element. The horizontal axis provides the number of days in which a given sensor device has been in the analyser apparatus. The vertical axis provides the value indicative of the functionality of the reference electrode.

[0105] Each different type of symbol plotted in the panels correspond to specific sensor device and is plotted together with a respective trend line.

[0106] A comparison between the left-hand panel and the right-hand panel evidently exhibits that the functionality of sensor devices, specifically the functionality of the reference electrode, declines significantly during the measurement period for the sensor devices in which a sulfurreactive element is absent. For several of these devices, the value indicative of functionality of the reference electrode rises to 0.8-1.0 after 15 to 28 days, which indicates a reduced functionality. In contrast, for sensor devices comprising a sulfur-reactive element, almost all measurements of the value indicative of the functionality of the reference electrode lie overwhelmingly below 0.8 within the entire measurement period.

[0107] Figure 6 shows a comparison of a precipitate formed on the aperture of a reference electrode with sulfur reactive agent (Cu2 + , image on the left) and without (image on the right) in the idling liquid. There is visibly less precipitate when the sulfur reactive agent is added.

[0108] Accordingly, the provision of a sulfur-reactive element can reduce measurement errors and avoid untimely and excessive replacement of the sensor device. In a similar manner, a sulfur-reactive agent provided to the interior volume may also reduce measurement errors and avoid untimely and excessive replacements.

[0109] Various versions and elements of the invention have been exemplified for the purpose of clarification rather than limitation. Well-known details of methods and systems have been omitted to not obscure the content of the disclosure with redundancy. Various elements and features of the invention and this disclosure may be combined in any way possible within the scope of the claims.

[0110] List of figure references:

[0111] 1 analyser apparatus

[0112] 2 measurement chamber

[0113] 5 reference electrode

[0114] 6 chamber inlet

[0115] 7 chamber outlet

[0116] 8 processing unit

[0117] 12 feed line

[0118] 20 liquid handling system

[0119] 21 process liquid reservoirs

[0120] 22 fluid selector arrangement

[0121] 23 pump

[0122] 24 waste reservoir

[0123] 26 auxiliary fluid reservoir

[0124] 39 ion-selective analyte sensor

[0125] 40 enclosure

[0126] 42 sensor electrode 43 ion-selective sensor membrane

[0127] 51 reference electrode liquid

[0128] 52 diffusion-tight diaphragm

[0129] 53 through-going orifice 54 reference electrode pin

[0130] 55 reference electrode membrane

[0131] 60 sensor device

[0132] 82 interior volume

[0133] S1-S4 method steps

Claims

CLAIMS1. A method for operating a sensor device, wherein the sensor device is for an analyser apparatus configured to analyse parameters of blood samples, the method comprising the steps of: providing the sensor device, the sensor device comprising : a measurement chamber defining an interior volume for receiving a fluid to be analysed, a chamber inlet and a chamber outlet each respectively providing a respective fluid passage to the interior volume, a reference electrode in fluid communication with the interior volume, and one or more ion-selective analyte sensors, each analyte sensor comprising a sensor electrode and an ion-selective sensor membrane arranged between the interior volume and the sensor electrode; measuring an electric potential of a blood sample in the interior volume of the sensor device using the reference electrode and at least one of the one or more analyte sensors; and filling the interior volume with an idling liquid, the idling liquid comprising an anti-microbial agent, wherein the anti-microbial agent and / or the blood sample comprise a sulfur- containing compound; wherein the method further comprises a step of: providing a sulfur-reactive agent in the interior volume to at least partially bind the sulfur-containing compound.

2. The method according to claim 1, wherein the sulfur-reactive agent is dissolved in or suspended in the idling liquid.

3. The method according to any of the preceding claims, wherein the sulfur-reactive agent at least partially binds the sulfur-containing compound by means of a chemical reaction between at least the sulfur-containing compound and the sulfur-reactive agent.

4. The method according to claim 3, wherein the sulfur-reactive agent at least partially binds the sulfur-containing compound by means of a chemical reaction between at least the sulfur- containing compound, the sulfur-reactive agent, and blood residues from the blood sample.

5. The method according to any of the preceding claims, wherein the anti-microbial agent prevents microbial growth in the measurement chamber by means of the sulfur-containing compound.

6. The method according to any of the preceding claims, wherein the sulfur-containing compound comprises isothiazolinone or a derivative thereof, such as methylisothiazolinone.

7. The method according to any of the preceding claims, wherein the step of filling the interior volume with the idling liquid is performed separately from the step of measuring an electric potential.

8. The method according to any of the preceding claims, wherein the step of filling the interior volume with the idling liquid is performed when the analyser apparatus is idle from performing a measurement on a blood sample.

9. The method according to any of the preceding claims, wherein the sulfur-reactive agent comprises a metal, for example a metal from groups 3-15, preferably a metal from groups 3- 12, more preferably Ag, Zn, Fe, Cu, Ni, Tl, Pb, Cd, Co, or Hg.

10. An idling liquid for an analyser apparatus configured to analyse parameters of blood samples, the idling liquid comprising an anti-microbial agent, the anti-microbial agent comprising a sulfur-containing compound, the idling liquid further comprising a sulfurreactive agent.

11. The idling liquid according to claim 10, wherein the sulfur-reactive agent is able to bind said sulfur-containing compound by means of a chemical reaction between at least the sulfur- containing compound, the sulfur-reactive agent and blood residue from a blood sample.

12. The idling liquid according to any one of claims 10-11, wherein the sulfur-containing compound comprises isothiazolinone or a derivative thereof, such as methylisothiazolinone.

13. The idling liquid according to any one of claims 10-12, wherein the sulfur-reactive agent comprises a metal, for example a metal from groups 3-15, preferably a metal from group 3- 12, more preferably Ag, Zn, Fe, Cu, Ni, Tl, Pb, Cd, Co, or Hg.

14. Use of an idling liquid according to any of claims 10-13 to at least partially bind a sulfur- containing compound in an analyser apparatus configured to analyse parameters of blood samples.

15. An analyser apparatus configured to analyse parameters of blood samples, the analyser apparatus comprising : a sensor device, the sensor device comprising : a measurement chamber defining an interior volume for receiving a fluid to be analysed, a chamber inlet and a chamber outlet each respectively providing a respective fluid passage to the interior volume from an exterior of the sensor device, a reference electrode in fluid communication with the interior volume, and one or more ion-selective analyte sensors, each separate analyte sensor of the one or more analyte sensors comprising a sensor electrode and an ion-selective sensor membrane arranged between the interior volume and the sensor electrode; and a processing unit configured to measure a difference in electrical potential between the reference electrode and the separate analyte sensor across the fluid to be analysed when the fluid to be analysed is present in the interior volume for each of the analyte sensors; wherein the analyser apparatus further comprises: an idling liquid according to any one of claims 10-13, or an auxiliary fluid comprising a sulfur-reactive agent; wherein the idling liquid or auxiliary fluid fills the interior volume or wherein the analyser apparatus is configured to supply the idling liquid or auxiliary fluid to the interior volume.

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