Highly efficient, patient- and eco-friendly method, fluid sensor system and computer program product for determining at least one additional property of a sample fluid and thereby reducing waste of consumables and / or sample fluids

Abstract

The invention relates to a method (100) of determining a property of a sample fluid in an IVD analyzer (10) comprising the following steps: introducing (110a) a first fluid (1) into a fluidic system (35) of the IVD analyzer (10), wherein the fluidic system (35) comprises a channel (4) with a resilient seal element configured to change a cross section of the channel (4) in response to a change in a local pressure state; introducing (110b) a sample fluid (2), which is spatially separated from the first fluid (1) into the fluidic system (35); contacting (120) a conductivity sensor unit (5) in the channel (4) with the first fluid (1); detecting (130) a set of conductivity parameter values of the first fluid (1) during a conductivity detection time span (cdts) using the conductivity sensor unit (5) wherein the conductivity parameter values are dependent from the cross section of the channel; and automatically determining (150) the property of the sample fluid (2) based on the detected set of conductivity parameter values of the first fluid. The invention may be considered as being highly efficient, eco-friendly and adding remarkable value to an already existing IVD fluid sensor system. Importantly, patients benefit from additional parameters that may be provided by the IVD system. As the invention allows adding value and increasing the functionality to an already existing IVD system without the need for adding further elements, it may be considered as being very eco-friendly in the sense of a green invention.

Description

[0001] Highly efficient, patient- and eco-friendly method, fluid sensor system and computer program product for determining at least one additional property of a sample fluid and thereby reducing waste of consumables and / or sample fluids

[0002] Field of the Invention

[0003] The invention relates to methods, a fluid sensor system and a computer program product for determining a property in a sample fluid, such as a blood sample in the field of In Vitro Diagnostics (IVD). The invention may be considered as being highly efficient, eco-friendly and adding remarkable value to an already existing IVD fluid sensor system. As the invention allows adding value and increasing the functionality to an already existing IVD system without the need for adding further elements, it may be considered as being very eco-friendly in the sense of a green invention. Importantly, patients benefit from additional parameters that may be provided by the IVD system.

[0004] Background of the Invention

[0005] In medicine, doctor’s diagnosis and patient treatment often relies on the measurement of patient sample parameters carried out by IVD analyzers. It is important that the analyzers are efficient and perform smoothly and correctly by providing precise and reliable measurements with as little downtime as possible. Thus, it is a general requirement for IVD analyzers to implement workflows that ensure analytical performance.

[0006] US 2023 / 304953 Al describes for example a sensor assembly for an IVD analyzer, the sensor comprising two opposite substrates with at least one fluidic conduit for receiving a sample. The electrodes of different types of electrochemical sensors are arranged on the two opposite substrates facing the at least one fluidic conduit for coming in contact with the sample and determining sample parameters.

[0007] US 2022 / 196632 Al describes a sensor device, a method of operating the sensor device and an IVD analyzer for receiving the sensor device for determining chemical and / or physical characteristics of a fluid. The sensor device comprises at least two fluidic conduits for repeatedly receiving fluids, each fluidic conduit comprising at least one sensory element arranged such as to come in contact with a fluid in the respective fluidic conduit.

[0008] US 2020 / 200731 Al describes an apparatus for measuring blood clotting time which includes a blood clot detection instrument and a cuvette for use with the blood clot detection instrument. The cuvette includes a blood sample receptor-inlet; a channel arrangement including at least one test channel for performing a blood clotting time measurement, a sampling channel having at least one surface portion that is hydrophilic, communicating with the blood sample receptor-inlet and the at least one test channel, and a waste channel having at least one surface portion that is hydrophilic, communicating with the sampling channel.

[0009] US 6 022 747 A describes a blood clot detector which includes a pressure transducer on an aspiration line to provide output voltage data to a microprocessor corresponding to the vacuum level during aspiration and a microprocessor which integrates the vacuum readings over time during the aspiration cycle to provide a pressure integral for each test sample aspiration.

[0010] Problematic sample fluids which block a fluidic system / channel system of an IVD analyzer after being introduced are however a source of errors, cause downtime of the instrument and reduce precision and efficiency. Problematic sample fluids may for example comprise clots, aggregates, and / or foreign particles of contaminations and / or human tissue cells in the range between tens of pm to several mm. As an example, blood samples may contain blood clots which fall into this range and therefore such blood samples are problematic for the IVD analyzer such as a Blood Gas- Electrolytes (BGE) analyzer. If a problematic sample fluid is introduced into the fluidic system, it may then be guided deep into the channel of a fluidic system and removal of this sample fluid may become difficult by means of reversing the flow via reversing the pump direction, if it is identified in a late stage. The channel of the fluidic system may then be completely blocked and the flow of fluids through the channel might become impossible.

[0011] If a problematic sample fluid is identified, typically the operating direction of the pump is reversed to discharge the sample fluid. The direction of the pump operation is then supposed to reverse the flow of the problematic sample fluid and discharge it from the channel system. For example, the pump previously operates in a direction in which the sample fluid is aspirated by applying an underpressure. When reversing the operating direction, an overpressure is generated to discharge the problematic sample fluid. This step may be followed by a washing procedure of the channel system. In general, the generation of an overpressure may cause damage to the channel system or other elements and therefore, it is preferred to identify problematic sample fluids, at a very early stage. Specifically, it would be important to identify problematic sample fluids shortly after being introduced into the channel system and / or even before the sample fluid enters the channel system of a cartridge, i.e. when the sample fluid is absorbed in a capillary or in a tube connected to the channel system of a cartridge, specifically before the sample fluid reaches time out measurement points. Thus, the problematic sample fluid can be easily discharged by generating a “mild overpressure”, i.e. a pressure at a shorter duration and / or lower magnitude of the overpressure as compared to pressure values required when the clot travels deep into the channel system. Therefore, the risk of damaging the fluidic channel system can be reduced. Further, it can be avoided that particles can contaminate the system and get permanently stuck in the fluidic channel without the ability to clean the fluidic channel system and wash out the particles. It may therefore be avoided that the particles remain absorbed on the sensors which would compromise their performance even after successful wash out of the majority of the particles.

[0012] In addition to the above-described difficulties, a partial pressure of a certain gas in the sample fluid may drop in response to a dropping underpressure. This can very likely result in a degassing of the sample fluid, which falsifies a measurement result in a blood gas analysis.

[0013] If such a problematic sample fluid enters a channel system, the volume flow rate may drop and / or the underpressure that is generated by the pump may drop below the expected underpressure for unproblematic sample fluids. However, there are also cases in which sample fluids do not contain clots, aggregates and / or other particles but still cause the flow rate and / or the underpressure to drop below the value expected for unproblematic sample fluids - such sample fluids may be unproblematic for the instrument but highly viscous. Typically, highly viscous sample fluids are not very likely to block the channel system and may therefore enter and pass the channel system.

[0014] Thus, a highly viscous sample fluid (also referred to “viscous state”) may enter and pass the channel system without the risk of causing damages and without the risk of measuring falsified blood gas values while a problematic sample fluid should be discharged to avoid damage and contamination. Hence, a distinction between these two categories and / or a determination of the viscosity is preferable. In general, it is preferable to provide an efficient and quick determination of the viscosity.

[0015] As indicated in Fig. 1, a sample fluid is usually identified as being problematic, if the sample fluid does not reach one of the timeout measurement spots / sample sensors 25 after a predetermined timeout period, which is longer than a period required by an unproblematic sample fluid to reach one of the sample sensors 25. Typically, the pump is stopped when a timeout is detected, i.e. when the sample fluid does not reach the timeout measurement spots after the predetermined timeout period. A sample fluid with clots, particularly with big clots is hence prevented from reaching the cartridge. However, it is likely that clots are transported further into the fluidic channel system and when the flow rate is reduced due to a sample fluid, which blocks the fluidic channel system, the underpressure increases. The increasing underpressure moves clots further into the system and renders the removal of a problematic sample fluid by reversing the flow direction even more difficult. Furthermore, microbubbles may leak into the system at the connection points due to the underpressure created in the fluidic channel system (called “channel system”), when it is blocked by a sample fluid with clots. Such microbubbles may cause additional problems later on if they cannot be removed, such as changed and falsified blood gas values, crystallization, etc.

[0016] Typically, it is also not easy to distinguish between a problematic and a highly viscous sample fluid. To overcome this problem, the predetermined timeout period may be set to a shorter value. In expense of a better protection of the channel system, the loss of unproblematic sample fluids (possibly having a high viscosity) might be high as they are discharged by mistake and therefore the so-called “lost-sample-rate” and hence the error rate increases with a reduced predetermined timeout period. In other words, the predetermined timeout setting for the sample fluid to be detected is a balance between the lost sample rate, for which no result is obtained and an error- driven consumable change, in which the channel system cannot always be protected from being blocked. It should hence be decided either to aspirate the sample fluid further into the channel system at an increased risk of aspirating a clot, which could block the channel system and which leads to an "error-driven consumable exchange", or to set a very strict time limit, which might then lead to a high lost-sample rate. The timeout setting hence underlies a trade-off between the degree of protection of the channel system vs. a lost-sample-rate.

[0017] Summary of the Invention

[0018] It is therefore desirable to provide methods and devices, which address the above-mentioned technical challenges, specifically to provide a quick and early identification of the property of the sample fluid. It is also desirable to increase the chance for successfully removing a problematic sample fluid without losing unproblematic sample volumes. Moreover, it is desirable to provide a versatile fluid sensor system of an IVD analyzer.

[0019] The challenges are at least partially overcome by the method, the fluid sensor system and the computer program product according to the independent claims and / or according to at least one of the embodiments described herein or being covered by one of the dependent claims.

[0020] The invention is based on the idea, that one or more sensors, which already exist(s) in a fluidic channel system of an IVD analyzer and which is / are primarily meant to be used to directly measure one or more parameters in a sample fluid, is / are alienated. In addition to their original function, the already existing sensors in a cartridge may hence be used to measure specific parameters which are indicative of a state / characteristic / property in the sample fluid. The measurement results are not directly obtained from the sample fluid itself, but from a predecessor fluid, which is called “first fluid”. The first fluid may be a standby solution and / or a conductive aqueous solution like a buffer, which is introduced into the channel system before the sample fluid is introduced. The fist fluid is isolated from the sample fluid by a gas bubble like an air bubble. In some cases, a gas bubble (which behaves fluidic) may be considered a first fluid (or a third fluid if the first fluid is a liquid).

[0021] Therefore, the determination of whether a sample fluid must be considered problematic and / or the determination of the viscosity of the sample fluid can be performed by probing the first fluid (being a liquid and / or a gas). The said determination is hence performed indirectly at a position deep within the channel system where the sensor(s) is / are positioned while the problematic sample fluid is still near the entrance of the fluidic channel system. In other words, the sensors can already determine whether a sample fluid may be considered problematic without physically contacting the sample fluid itself and / or without directly measuring parameters from the sample fluid.

[0022] The herein described methods, fluid sensor system and computer program product according to at least one embodiment, may have at least one of the following advantages and / or technical effects:

[0023] A quick and early determination / identification of a state of a sample fluid, i.e. the property of the sample fluid is provided. The property of the sample fluid may correspond to the physical nature / state of the sample fluid in terms of viscosity and / or presence / absence of aggregates, clots and / or particles. It may particularly be determined whether or not a sample fluid is

[0024] • problematic, in that it contains clots, aggregates and / or particles;

[0025] • unproblematic but highly viscous (also referred to “viscous state”); or

[0026] • unproblematic and no clots and / or not highly viscous.

[0027] The property of the sample fluid may alternatively or in addition correspond to specific viscosity values and / or ranges of viscosity values, the presence or absence of clots, aggregates and / or particles. The properties of the sample fluid may specifically be classified in “problematic sample”, “unproblematic but highly viscous” and “unproblematic and not highly viscous”. The property of the sample fluid may alternatively or in addition comprise and / or correspond to a certain degree of coagulation. Coagulation is an important property and / or parameter in combination with other cardiac parameters such as NT-proBNP and Troponin T.

[0028] Further, the chance for successfully removing a problematic sample fluid can be increased. The required overpressure loads, i.e. the overpressure duration and magnitude on the fluidic channel system during the removal of a problematic sample fluid, can be reduced. Underpressure loads, i.e. the underpressure duration and magnitude on the fluidic channel system in a situation when the problematic sample fluid moves further into the fluidic channel system, can be reduced. The risk of microbubble intake at connection points and / or degassing of the sample fluid due to abnormal underpressure loads can be reduced and therefore falsified gas values can be reduced or even avoided. The downtime of the instrument may be reduced and / or the lifetime of the consumable having the fluidic channel system, such as the cartridge, may be increased. Further, the number of required elements in the channel system may be reduced as no further pressure sensors are required. A distinction between a problematic and an unproblematic but highly viscous sample fluid can be made. The methods do not underlie a trade-off between the degree of protection of the channel system vs. a lost-sample-rate. Therefore, the methods provide a high degree in sensitivity and efficiency.

[0029] Moreover, the methods allow adding functions to an IVD analyzer, which may for example correspond to a blood gas analyzer, without adding further elements and / or changing the structure of the IVD analyzer. Such an additional function may correspond to the indication of diseases and / or life threatening emergencies caused by blood clots and / or abnormal blood viscosities, specifically high blood viscosities. As an example, a blood gas analyzer, conventionally used to determine parameters related to blood gas, electrolytes, metabolites and / or hematologic parameters, may therefore in addition indicate thromboembolic events, myocardial infarction, and / or ischemia that result in multiple organ failure.

[0030] According to an aspect, which may be considered the first aspect of the present disclosure, a method of determining a property of a sample fluid in an IVD analyzer comprises the following steps: at least once generating at least one change in a local pressure state inside a fluidic system of the IVD analyzer, during the step of the at least once generating of the at least one change in the local pressure state, performing the steps: introducing a first fluid into the fluidic system driven by the at least one change in the local pressure state, wherein the fluidic system comprises a channel with a resilient seal element configured to change a cross section of the channel in response to the at least one change in the local pressure state; introducing a sample fluid into the fluidic system driven by the at least one change in the local pressure state, wherein the sample fluid is spatially separated from the first fluid; driving by the at least one change in the local pressure state the first fluid into a position of a conductivity sensor unit in the channel and contacting the conductivity sensor unit in the channel with the first fluid; detecting a set of conductivity parameter values of the first fluid during a conductivity detection time span using the conductivity sensor unit, wherein the conductivity parameter values are dependent from the cross section of the channel (specifically starting the detecting shortly before or together with starting one of the at least once generating at least one change in a local pressure state, i.e. shortly before or together with (re)starting the pump); and the method further comprising, automatically determining the property of the sample fluid based on the detected set of conductivity parameter values of the first fluid, wherein the property of the sample comprises: a problematic state, in which the sample fluid comprises at least one of clots, particles of human tissue, aggregates and contaminations; or a viscous state, in which the sample fluid has a viscosity and / or lies in, below or above a predetermined viscosity range in which the sample fluid has a viscosity higher than 6mPas; or a normal state, in which the sample fluid does not comprise clots, particles of human tissue, aggregates and contaminations and has a viscosity lower than 6mPas, specifically between 2mPas and 6mPas.

[0031] The step of “at least once generating at least one change in a local pressure state inside a fluidic system of the IVD analyzer” may refer to pumping and generating a pressure change in the fluid system, i.e. an overpressure or more preferred an underpressure. The step may refer to a constant pump action (constant means without interruption for a certain / predetermined period of time).

[0032] The step of “at least once generating at least one change in a local pressure state inside a fluidic system of the IVD analyzer” may alternatively refer to multiple times of starting and stopping a pump action and / or to a pulsed pump action and / or to an interrupted pump action. Some pumps may be configured to perform, for example, in a pulsed manner. It may also be the case that a pump is started and stopped / paused and started again to generate / create an underpressure, wherein the underpressure is not necessarily the same each time and may vary.

[0033] The step of “at least once generating at least one change in a local pressure state inside a fluidic system of the IVD analyzer” may alternatively refer to the creation / generation of an underpressure only once while thereby introducing the first fluid and the sample fluid. The measurement (i.e. the step of detecting a set of conductivity parameter values of the first fluid during a conductivity detection time span using the conductivity sensor unit) may then be started shortly before the creation of the underpressure or at the same time. This may correspond to the case when the conductivity detection time span and / or the gas detection time span overlaps at least partially with an introduction time span, in which the step of introducing the sample fluid into the fluidic system is performed, preferably wherein the conductivity detection time span and / or the gas detection time span starts before or at the same time with the introduction time span. This is however explicitly not a prerequisite for the method according to the first aspect, as the introduction time span may alternatively correspond to a time when the first fluid and / or the sample fluid are drawn into the fluidic system and the pump may then be stopped and started again together with or shortly after the start of the measurement (i.e. the step of detecting a set of conductivity parameter values of the first fluid during a conductivity detection time span using the conductivity sensor unit). For determining the property of the sample fluid, it is only required to initiate the movement of the sample fluid inside the fluidic system, ideally before entering the cartridge. Therefore, in a specific case, The step of “at least once generating at least one change in a local pressure state inside a fluidic system of the IVD analyzer” may correspond to the suction of the first fluid into the fluidic system when pumping for the first time, then the pump may be paused and then the suction of the sample fluid into the fluidic system may be initiated when pumping for the second time and starting the measurement shortly before the second generation of the underpressure or at the same time. In general, regardless of a constant, a pulsed and / or an interrupted pump action, the pump action may be performed, for example, by using a suction pump (such as a vacuum pump and / or a peristaltic pump).

[0034] Ideally, when detecting the set of conductivity parameter values, the sample fluid has not yet entered the cartridge or at least has not been drawn far into the cartridge, to allow prevention of entering (far into) the cartridge if it corresponds to a problematic and / or highly viscous sample.

[0035] The sample fluid may explicitly already be drawn into the fluidic system before the step of detecting the set of conductivity parameter values. The measurement / the detecting of the set of conductivity parameter values should ideally be started shortly before the pump is started to record the conductivity parameters as an indicator for the contraction behavior of the resilient seal element, which again serves as an indicator for the flow behavior of the sample fluid.

[0036] Specifically, the method of determining the property of the sample fluid in the IVD analyzer may comprise the following steps:

[0037] Generating an underpressure at least once inside a fluidic system of the IVD analyzer, for example by using a pump, specifically a suction pump, during the step of generating the underpressure at least once, performing the steps:

[0038] Introducing and / or drawing the first fluid into the fluidic system driven by the generation / creation of the underpressure, wherein the fluidic system comprises the channel with the resilient seal element configured to change the cross section of the channel in response to the underpressure; introducing and / or drawing the sample fluid into the fluidic system driven by the generation / creation of the underpressure, wherein the sample fluid is spatially separated from the first fluid; driving by the generation / creation of the underpressure the first fluid into the position of the conductivity sensor unit in the channel and contacting the conductivity sensor unit in the channel with the first fluid; detecting the set of conductivity parameter values of the first fluid during the conductivity detection time span using the conductivity sensor unit, wherein the conductivity parameter values are dependent from the cross section of the channel; and the method further comprising, automatically determining the property of the sample fluid based on the detected set of conductivity parameter values of the first fluid, wherein the property of the sample fluid comprises: the problematic state, in which the sample fluid comprises at least one of clots, particles of human tissue, aggregates and contaminations; and / or the viscous state, in which the sample fluid has a viscosity and / or lies in, below or above a predetermined viscosity range in which the sample fluid has a viscosity higher than 6mPas; and / or the normal state, in which the sample fluid does not comprise clots, particles of human tissue, aggregates and contaminations and has a viscosity between 2mPas and 6mPas.

[0039] More specifically, the method of determining the property of the sample fluid in the IVD analyzer may comprise the following steps: generating an underpressure inside a fluidic system of the IVD analyzer, for example by using a pump, specifically a suction pump, during or overlapping with the step of generating the underpressure, performing the steps: introducing and / or drawing the first fluid into the fluidic system driven by the generation / creation of the underpressure, wherein the fluidic system comprises the channel with the resilient seal element configured to change the cross section of the channel in response to the underpressure; introducing and / or drawing the sample fluid into the fluidic system driven by the generation / creation of the underpressure, wherein the sample fluid is spatially separated from the first fluid; driving by the generation / creation of the underpressure the first fluid into the position of the conductivity sensor unit in the channel and contacting the conductivity sensor unit in the channel with the first fluid; detecting the set of conductivity parameter values of the first fluid during the conductivity detection time span using the conductivity sensor unit, wherein the conductivity parameter values are dependent from the cross section of the channel, specifically starting the step of detecting before or at the same time with a starting of the step of generating an underpressure; and the method further comprising, automatically determining the property of the sample fluid based on the detected set of conductivity parameter values of the first fluid, wherein the property of the sample fluid comprises: the problematic state, in which the sample fluid comprises at least one of clots, particles of human tissue, aggregates and contaminations; and / or the viscous state, in which the sample fluid has a viscosity and / or lies in, below or above a predetermined viscosity range in which the sample fluid has a viscosity higher than 6mPas; and / or the normal state, in which the sample fluid does not comprise clots, particles of human tissue, aggregates and contaminations and has a viscosity between 2mPas and 6mPas. The method according to the first aspect has the potential to identify all of the three properties of the sample fluid listed above and the sample fluid may be in at least one of or only in one of the three properties.

[0040] In other words, the method of determining a property of a sample fluid in an IVD analyzer is provided and the method comprises, among other steps described above in line with the first aspect, the following steps: introducing a first fluid into a fluidic system of the IVD analyzer, wherein the fluidic system comprises a channel with a resilient seal element configured to change a cross section of the channel in response to a change in a local pressure state; introducing a sample fluid which is spatially separated from the first fluid into the fluidic system; contacting a conductivity sensor unit in the channel with the first fluid; detecting a set of conductivity parameter values of the first fluid during a conductivity detection time span using the conductivity sensor unit wherein the conductivity parameter values are dependent from the cross section of the channel; and automatically determining the property of the sample fluid based on the detected set of conductivity parameter values.

[0041] The method according to the first aspect has the following technical effects and advantages:

[0042] The method allows to reliably, quickly, efficiently and early identify a property of a sample fluid as it probes the first fluid in an early stage, for example shortly after and / or during aspirating the sample fluid.

[0043] The fluidic system, which is also called channel system, may correspond to the system of tubings, channels, pipes and hoses of the IVD analyzer. Specifically, all fluid guiding elements of the fluidic system, but / except for the resilient seal element, may be substantially rigid in shape, i.e. their shapes resist high pressure values and / or external impact. In other words, elements of the fluidic system (except for the resilient seal element) are substantially “stiff’, i.e. they do not change the volume of the fluidic system as a function of pressure - this is only provided by the resilience of the resilient seal element. As a result, pressure variations and / or pressure changes are directly transmitted (to the channel) and not “damped” by a flexible component (except for the resilient seal element). The advantage of a stiff system may further be an accurate sample positioning. In another but less preferable embodiment, not all fluid guiding elements of the fluidic system (excluding the resilient seal element) are substantially rigid in shape. The term “channel” described herein may specifically correspond to the channel of the cartridge, which comprises the resilient seal element. In other words, pressure variations and / or pressure changes may only be reflected during the detection of the set of conductivity parameter values of the first fluid during the conductivity detection time span caused exclusively by the resilience of the resilient seal element - depending on the behavior / temporal evolution of the conductivity parameter values, the property of the sample fluid may then be derived therefrom. The method may correspond to a direct or an indirect automatic determination of the property of the sample fluid based on the detected set of conductivity parameter values. Specifically, a characteristic temporal evolution of the conductivity parameter, i.e. a temporal change in the conductivity parameter (representing the set of conductivity parameter values) caused by the pressure change can indicate the property of the sample fluid. Aspirating a problematic sample fluid may be reflected in a specific (fast) decrease of the conductivity parameter values (such as the admittance) wherein a highly viscous sample fluid may be reflected in a slower decrease because the fluidic resistance causing the pressure drop is proportional to the amount of sample liquid in the fluidic system / length of fluidic path filled by the sample liquid.

[0044] An unproblematic sample fluid that has a “normal” viscosity might be reflected in a low / mild decrease of the conductivity parameter values. From the specific temporal evolution of the conductivity parameter values, the identification of the property of the sample may be automatically performed, for example using a fit function or a neural network. The recording of the conductivity parameter values is started from the moment when only a first fluid is present in the fluidic system (providing a reference for the conductivity parameter values) to a moment when the sample fluid in introduced into the fluidic system. The fluidic system refers to the fluidic pipe / tubing system of an IVD analyzer. To protect the cartridge from the problematic fluid, it is advantageous to recognize a problematic sample fluid before it is introduced into the channel of the cartridge.

[0045] The said direct determination may rely on an analysis of the detected set of conductivity parameter values from which the property of the sample fluid is determined / derived and / or a classification regarding the property of the sample is performed. The said indirect determination may rely on an analysis of the detected set of conductivity parameter values from which another parameter is determined, such as the pressure state in the channel at a certain position or in a certain portion of the channel. From the determined pressure state in the channel the property of the sample fluid may then be determined / derived and / or a classification regarding the property of the sample may be performed.

[0046] Specifically, the direct automatic determination of the property of the sample fluid based on the detected set of conductivity parameter values may be performed by a neural network that is trained to determine, identify and / or classify the property of the sample fluid based on a set of conductivity parameter values.

[0047] The optional indirect determination may hence require the following steps in an embodiment of the above-described method: detecting a set of conductivity parameter values of the first fluid during a conductivity detection time span using the conductivity sensor unit wherein the conductivity parameter values are dependent from the cross section of the channel;

[0048] • determining a temporal evolution of the local pressure state from the detected set of conductivity parameter values; and

[0049] • automatically determining the property of the sample fluid based on the determined temporal evolution of the local pressure state being indirectly based on the detected set of conductivity parameter values.

[0050] The property of a sample fluid, which is problematic, refers to a state and / or situation in which the sample fluid comprises clots, aggregates and / or particles in the size range between approximately 10pm to several mm at which these clots, aggregates and / or particles can block the fluidic system and specifically the channel of the cartridge and / or cuvette. Specifically, particles, clots and / or aggregates in the sample fluid, which range in size between approximately 15-20 pm and approximately 100 pm or more, are likely to cause lower underpressure values in the fluidic system than normal unproblematic sample fluids like blood. Such particles, clots and / or aggregates in the sample fluid can block the entire fluidic system. The step of automatically determining of the property of the sample fluid based on the detected set of conductivity parameter values may hence specifically correspond to an automatic determination, identification and / or classification whether or not the sample fluid is

[0051] • problematic due to clots, aggregates and / or particles which can block the channel and / or fluidic system;

[0052] • unproblematic but highly viscous and therefore causes a drop in pressure; or

[0053] • unproblematic and does not contain clots, aggregates and / or particles and is not highly viscous.

[0054] The channels described herein may specifically contain volumes ranging between several hundreds of ml to pl or even less. The fluid volumes which can be filled in the channel may therefore range between hundreds of ml to pl or even less.

[0055] A conductivity parameter may refer to the admittance, which is measured directly or the conductivity parameter may refer to other parameters which can be measured, such as the resistance or the impedance, and from which the admittance can be derived.

[0056] Often, cartridges which comprise one or more channels have two plates with at least one recessed path that forms the fluidic channel when the plates are connected. The channel usually comprises a resilient seal element. When a sample fluid with a high viscosity and / or a problematic sample fluid is aspirated into the channel, the underpressure resulting from the aspirating pump force may cause the resilient seal element to be slightly sucked into the channel such that the diameter or the cross section of the channel slightly decreases which may cause an additional decrease in the flow, i.e. the volumetric flow rate which typically underlies the Hagen-Poiseuille law. In other words, the resilient seal element is configured to change a cross section of the channel in response to a change in a local pressure state because it is flexible in shape. The resilient seal element may comprise a rubber material, a silicone material and / or another polymer material that is resilient. The term resilient means herein that the material can deform, particularly contract and / or expand when a force is applied and it can return into the original shape when it is in a relaxed state, i.e. when no force is applied. In other words, the resilient seal element may be reversibly deformed and relaxed many times. The resilient seal element may reduce the cross section of the channel when an underpressure is generated as the resilient seal element is sucked into the channel. The resilient seal element may increase the cross section of the channel when an overpressure is generated as the resilient seal element is pushed out of the channel. An underpressure may be a pressure that is below a certain threshold and an overpressure may be a pressure that is above a certain threshold and the threshold may particularly correspond to an atmospheric pressure and / or a local pressure. As an example, the atmospheric pressure may be considered one atmosphere (atm) as a unit of measurement equal to the average air pressure at sea level at a temperature of 15 degrees Celsius (59 degrees Fahrenheit). One atmosphere is then 1,013 millibars. Not being limited to this scenario, values below 1,013 millibars, under these circumstances, may be considered as underpressure values and values above l,013millibars, under these circumstances, may be considered as overpressure values.

[0057] The conductivity sensor unit is typically realized as two or more conductivity sensor spots, i.e. two or more sensors in a cartridge of an IVD analyzer to detect the conductivity of a liquid. The conductivity sensor spots may be apart from each other by approximately 20cm to approximately 0,5 cm, preferably by approximately 10cm to approximately 2cm. Typically a conductivity sensor unit refers to a pair of conductivity sensor spots. A conductivity sensor unit is not necessarily a permanently fixed pair of conductivity spots over time, but the conductivity spots which can be considered as a pair may change: a first and a second conductivity spot may form the conductivity sensor unit in a first moment in time and the second and a third conductivity spot may form the conductivity sensor unit in a second moment in time. A cartridge may provide several pairs of conductivity sensors forming several conductivity sensor units. Typically, in a conventional method such conductivity sensor units are used to determine Het values and / or to determine the position of the sample fluid in the cartridge.

[0058] In its original function, the conductivity sensor unit allows identifying whether a sample fluid such as blood, whether an air bubble or whether another fluid has entered the fluidic system and specifically the cartridge, when a physical contact between the conductivity sensor unit and the fluid is established. In its original function, the conductivity spots serve to control whether the sample fluid has reached them inside the cartridge and whether there is an air bubble inside the cartridge, specifically in between two conductivity spots. According to the first aspect, the function of this conductivity sensor unit is extended / alienated to another function, namely the identification of the property of a sample fluid. In other words, the already existing conductivity sensor unit in the channel of an IVD analyzer (specifically in the cartridge) is now also used to determine characteristics of a sample fluid without even contacting it, but by contacting and probing the first fluid. As already noted, the conductivity sensor unit may comprise a sensor pair (two sensors) or more conductivity sensors, i.e. two, three, four, five, six or more conductivity sensors. Typically, a cartridge already comprises several conductivity spots at different positions in the channel(s) of the cartridge to detect whether a sample fluid has reached a certain position in the cartridge. Therefore, the sensor spots or sensor elements of the conductivity sensor units already serve a different purpose in the conventional cartridge, which is not the identification of a state in the sample fluid. The conductivity parameter is typically measured between two sensor elements being a sensor pair of a conductivity sensor unit or between two sensor spots.

[0059] Before a sample fluid is introduced into a fluidic system (typically a blood sample aspirated in a BGE analyzer), the entire fluidic system or only a part or the channel may initially be filled with a so-called standby solution, which is an aqueous conductive solution. When the sample fluid is inserted for example through a sample input module of the BGE analyzer, it may be separated from the standby solution by a separation gas bubble, specifically an air bubble. The standby solution is then typically pumped towards a waste container while the sample fluid is transported through the fluidic system and / or towards or through the channel of a cartridge.

[0060] Contacting the conductivity sensor unit in the channel with the first fluid means physically contacting the conductivity sensor unit, i.e. contacting at least partially two conductivity sensors or conductivity sensor spots which form a conductivity sensor unit, with the first fluid such that the conductivity parameter of the first fluid can be measured. The conductivity sensor unit is configured to detect a set of conductivity parameter values of the first fluid during a conductivity detection time span wherein the conductivity parameter values are dependent from the cross section of the channel. The set of conductivity parameter values may be recorded continuously during the conductivity detection time span and / or at distinct moments in time during the conductivity detection time span. The set of conductivity parameter values may specifically be recorded to identify a change of the conductivity parameter in the first fluid when the sample fluid is introduced into the fluidic system. As the position in the channel, where the first fluid is located, is openly connected to the position where the sample fluid is located and / or enters the fluidic system, a change in the local pressure will be detectable at the position where the conductivity parameter of the first fluid is detected. For example, in a case in which the sample fluid is aspirated into the fluidic system, the first fluid also moves deeper into the fluidic system, particularly the channel of the cartridge. The underpressure may drop further if the sample solution is highly viscous and / or contains clots, particles and / or aggregates which causes the resilient seal element to be deformed and to reach further into the channel and thereby decrease the cross section of the channel, which is reflected in a change of the conductivity parameter measured in the first fluid inside the channel with the smaller cross section. Therefore, the property of the sample fluid may be indirectly detected, deep within the fluidic system, specifically the channel of a cartridge. Particularly, by probing the first solution, it may be indirectly detected, deep within the fluidic system, whether a sample fluid at the very entrance of the fluidic system is a normal sample fluid, a highly viscous sample fluid and / or a sample fluid that contains clots, particles and / or aggregates.

[0061] From the detected set of conductivity parameter values, the set of conductivity parameter values is obtained. A reduced cross section (area) of the channel of a cartridge leads to a reduced conductivity parameter recording. As the conductivity parameter, which is recorded in a certain time span, can reflect a change in the cross section of the channel of the cartridge and the cross section of the channel again depends on the local pressure state due to the deformation of the resilient seal element, the conductivity parameter recorded in the said time span reflects a property in the sample fluid that affects the temporal evolution of the local pressure state. Therefore, the property of a sample fluid may be identified from the characteristic temporal evolution of the conductivity parameter.

[0062] In general, the term “cross section” corresponds specifically to the area of the cross section of the channel at different local pressure states.

[0063] The method may further comprise the following steps: detecting a set of partial pressure values of gas in the first fluid and / or in a third fluid during a gas detection time span using a gas sensor unit; automatically determining the property of the sample fluid based on the detected set of partial pressure values of gas; and comparing the property of the sample fluid determined from the detected set of partial pressure values of gas and the property of the sample fluid determined from the detected set of conductivity parameter values. This method allows reliably, quickly, efficiently and early determining a state in a sample fluid.

[0064] The present embodiment of the method according to the first aspect corresponds to a combination of the measurement of the set of conductivity parameter values by means of the conductivity sensor unit with the additional optional measurement of the set of partial pressure values of gas by means of the gas sensor unit which can be based on an optical and / or an electrochemical method. The combination of the measurement of a conductivity parameter and a partial pressure values of gas in the first fluid allows identifying the state in a sample fluid using two different measurement principles to cross-verify the results and to provide a more precise and / or reliable identification. The optional additional steps may correspond to a direct or an indirect automatic determination of the property of the sample fluid based on the detected set of partial pressure values of gas. The direct determination may rely on an analysis of the detected set of partial pressure values of gas from which the property of the sample fluid is determined / derived and / or a classification regarding the property of the sample is performed. The indirect determination may rely on an analysis of the detected set of partial pressure values of gas from which another parameter is determined, such as the pressure state in the fluidic system at a certain position or in a certain portion of the fluidic system. From the determined pressure state in the fluidic system the property of the sample fluid may be determined / derived and / or a classification regarding the property of the sample may be performed. The optional indirect determination may hence require the following steps in an embodiment of the above-described method:

[0065] • detecting, assuming and / or determining a set of partial pressure values of gas in the first fluid or in a third fluid during a gas detection time span using a gas sensor unit;

[0066] • determining the temporal evolution of the local pressure state from the detected set of partial pressure values of gas;

[0067] • automatically determining the property of the sample fluid based on the temporal evolution of the local pressure state determined from the detected set of partial pressure values of gas; and

[0068] • comparing the property of the sample fluid determined from the detected set of partial pressure values of gas and the property of the sample fluid determined from the detected set of conductivity parameter values.

[0069] If the gas sensor unit is based on an optical principle, the third fluid which can be probed by the gas sensor unit may comprise a gas and / or a liquid. For an optical gas sensor unit, the fluid that should be analyzed does not need to be a conductive fluid, such as a standby or buffer solution. For example, the third fluid may be an air bubble before or behind the first fluid. Alternatively, the third fluid may be a solution such as an aqueous solution.

[0070] In general, the gas sensor unit described herein may comprise or refer to an oxygen sensor unit, which is configured to detect the partial pressure of oxygen in a fluid such as a sample liquid, a buffer solution and / or a gas bubble. An alternative and / or additional gas sensor unit may comprise or refer to a carbon dioxide sensor unit, which is configured to detect the partial pressure of carbon dioxide in a fluid. An alternative and / or additional gas sensor unit may comprise a sensor unit that is configured to measure other gases.

[0071] In general, the gas sensor unit and specifically the oxygen sensor might rely on at least one of the following two effects: 1. When the local pressure increases the sensor indicates a higher partial pressure of gas, specifically oxygen and when the local pressure decreases the sensor indicates a lower partial pressure of gas, specifically oxygen. 2. The gas sensor unit itself might also react sensitive to pressure, for example as a mechanical response. This mechanical response may depend on the polymer matrix the oxygen sensor is embedded in.

[0072] The sample fluid may be first pumped / aspirated into the sensor cartridge, where the conductivity parameters and / or the partial pressure of gas values are measured. For example, pO2 may be measured in the sensor cartridge. Afterwards, the sample fluid may pass the cuvette, where an optical detection may be performed, in addition.

[0073] In the following, an alternative method according to a second aspect is described. In brief, the above described embodiment of the method according to the first aspect being based on the detection of partial pressure values of gas may be used without the measurement of conductivity parameter values. In other words, the method according to the second aspect primarily relies on the measurement of the set of partial pressure values of gas by the optional gas sensor unit to determine a state in a sample fluid in an IVD analyzer. Shared advantages of both aspects are outlined below.

[0074] Preferably, the property of a sample fluid in an IVD analyzer is determined based on the recordings of multiple conductivity sensor units and at least one gas sensor unit, specifically an oxygen sensor unit and / or a carbon dioxide sensor unit, which improves the degree of reliability and can help distinguishing between different events. In this way, it may be distinguished between the passage of an air bubble and a problematic sample fluid. The air bubble also causes a sudden drop in the conductivity, similarly as a problematic sample solution that is aspirated into the fluidic system. Multiple conductivity sensor units may comprise overlapping conductivity spots. For example, a first and a second conductivity spot may constitute a first conductivity sensor unit and a second and a third conductivity spot may constitute a second conductivity sensor unit.

[0075] According to an aspect, which may be considered the second aspect of the present disclosure, a method of determining a property of a sample fluid in an IVD analyzer is provided and the method comprises the following steps: introducing a first fluid into a fluidic system with a channel of the IVD analyzer; introducing a sample fluid which is spatially separated from the first fluid into the fluidic system; detecting a set of partial pressure values of gas in the first fluid during a gas detection time span using a gas sensor unit; and automatically determining the property of the sample fluid based on the detected set of partial pressure values of gas.

[0076] The difference between the method of the first aspect and the method of the second aspect is given in the detected / recorded measurement parameters. While the method according to the first aspect is based on the detection of a set of conductivity parameter values of the first fluid during a conductivity detection time span using the conductivity sensor unit, the method according to the second aspect is based on the detection of a set of partial pressure values of gas in the first fluid during a gas detection time span using a gas sensor unit. The primary measurement principle of the method according to the first aspect is based on the recording of conductivity parameters and relies on the fact that a cross section of the channel is dependent from the local pressure as the resilient seal element is configured to deform and change dependent from the local pressure. A change in the cross section of the channel is reflected in the conductivity parameter values of the conductivity measurement.

[0077] The primary measurement principle of the method according to the second aspect is based on the detection of the gas partial pressure such as an oxygen partial pressure which may comprise an optical and / or an electrochemical detection. While the collected conductivity parameter values are dependent from the cross section of the channel, the collected partial pressure values of gas correspond to a more direct measure of the local pressure state. The method according to the first aspect (conductivity parameter values measured) requires the channel to be at least partially sealed at some of its sides by a resilient seal element configured to change a cross section of the channel in response to a change in a local pressure state which is not required by the method according to the second aspect (partial pressure of gas, such as oxygen measured). However, in a method in which both measurement principles are combined, the same cartridge may be used in which a resilient seal element is used to seal the channel against the outer space. The gas sensor unit may also be positioned inside the channel of the cartridge or near the cartridge.

[0078] The method according to the first aspect and the second aspect may also comprise specifically: introducing the first fluid into the channel of the cartridge of the fluidic system of the IVD analyzer and introducing the sample fluid which is spatially separated from the first fluid into the fluidic system in a position of the fluidic system outside of the channel of the cartridge and contacting the conductivity sensor unit and / or the gas sensor unit located in the channel with the first fluid before and while the sample fluid is transported through the fluidic system but not yet inside and through the channel of the cartridge.

[0079] Similar as already outlined for the first aspect, the method of the second aspect may correspond to a direct or an indirect automatic determination of the property of the sample fluid based on the detected set of partial pressure values of gas. In general, from the specific temporal evolution of the partial pressure values of gas, the identification of the property of the sample may be automatically performed, for example using a fit function or a neural network. Specifically, the direct automatic determination of the property of the sample fluid based on the detected set of partial pressure values of gas may be performed by a neural network that is trained to determine, identify and / or classify the property of the sample fluid based on a set of partial pressure values of gas. The optional indirect determination may hence require the following steps in an embodiment of the above-described method: detecting a set of partial pressure values of gas in the first fluid or in a third fluid during a gas detection time span using a gas sensor unit;

[0080] • determining the temporal evolution of the local pressure state from the detected set of partial pressure values of gas; and

[0081] • automatically determining the property of the sample fluid based on the temporal evolution of the local pressure state determined from the detected set of partial pressure values of gas

[0082] The methods according to the first and the second aspect represent alternative solutions to a particular problem. In other words, the methods according to the two aspects solve the same problem(s) and achieve one or more of the above objects in two alternative ways.

[0083] For detecting a set of partial pressure values of gas in the first fluid, typically the gas sensor unit is physically contacted with the first fluid. The partial pressure values may be detected either inside the liquid or inside the gas separation bubble. Therefore, the method may comprise the step of contacting the gas sensor unit with the first fluid.

[0084] From the reading of the gas sensor unit (for example an optical oxygen sensor spot), which is the partial pressure of the gas, it should be differentiated between the following types of changes:

[0085] 1. an expected change for normally behaving fluids;

[0086] 2. a change in the partial pressure of the gas due to a changing medium (for example a change from first fluid to air separation bubble being detected);

[0087] 3. a change, particularly a pressure drop due to clots in the sample fluid; and

[0088] 4. a change, particularly a pressure drop due to a high viscosity of the sample fluid.

[0089] These changes / transition of the partial pressure gas values are typically characteristic for each case and may therefore be distinguished. In other words, the temporal evolution of the partial pressure gas values inside the channel reveals the situation in the fluidic system, as for example the four situations described above.

[0090] In a specific embodiment, a neural network can be trained to make such a distinction. Alternatively or in addition to the features of the method according to the second aspect, data may be obtained from the conductivity sensor unit to allow making a more reliable distinction as both methods may confirm the obtained results.

[0091] If the gas sensor unit is based on optical principles, the sensor unit should be in optical contact with the first fluid. In some embodiments, an oxygen sensor is applied on a transparent wall. The optical measurement may be performed through this transparent wall. A light emitter and a detector are in optical contact with the said oxygen sensor. The oxygen sensor is in physical contact with the liquid. If the gas sensor unit is based on an electrochemical principle, the first fluid should be a conductive solution and should physically contact the gas sensor unit. If the gas sensor unit corresponds to an oxygen sensor unit, the principle of measurement of oxygen may particularly be based on the effect of dynamic luminescence quenching by molecular oxygen. The partial pressure of gas measured is directly dependent on the local pressure. Therefore, the gas sensor unit can be used as an indirect pressure sensor while being in a medium with a known gas / oxygen concentration, e.g. a standby solution and / or air. The gas concentration, specifically the oxygen concentration of the first fluid is typically known for normal (pressure) conditions (in which no problematic sample fluid is aspirated) and / or for predetermined pressure values (such as an ambient pressure). The change and particularly the specific temporal evolution of the oxygen pressure that is detected when a sample fluid is aspirated serves as an indication for the property of the sample fluid. Alternatively or in addition, the detection of the partial pressure of gas may also comprise optical measurement principles such as oximetry or electrochemical measurement principles. Optical gas sensor units are highly sensitive and react fast to pressure changes. Optical gas sensor units are faster than electrochemical / electrical gas sensors. Additionally a gas sensor unit may be independent on the changing material properties and manufacturing tolerances of the soft material of the resilient seal element.

[0092] As an example for an optical measurement principle, which can be used to detect the partial pressure of oxygen, luminescence quenching may be applied. This principle is based on the excitation of a dye molecule with light. Dependent from oxygen amount, a different light is emitted. There is an oxygen-dependent "phase shift" between the emitted and received wavelengths. In addition, there is an oxygen-dependent "decay time" that can alternatively be used to determine the oxygen content. There are different "dye molecules" that can be used and the correct excitation wavelength must be chosen for the dye molecules.

[0093] Further, the optical sensor layer shows to be "pressure sensitive" (a similar material / element is often used as "pressure sensitive paint"). This means that in an incompressible medium (e.g., water, standby solution), the optical sensor will indicate increasing oxygen content as the pressure increases. For gases, the two effects overlap: The sensor measures a higher oxygen content because the sensor layer is compressed by the pressure. At the same time, the oxygen content also increases because the gas is compressible and thus there are more oxygen molecules per volume at higher pressure.

[0094] From the detected set of partial pressure values of gas the temporal evolution of the local pressure state can be identified / determined for the gas detection time span, i.e. the time span in which the detection of the set of partial pressure values of gas is started and ended. From the characteristic temporal evolution of the partial pressure of gas, the property of the sample fluid can be determined. The property of the sample fluid is then identified based on the temporal evolution of the local pressure state determined and / or derived from the detected set of partial pressure values of gas.

[0095] In the following, advantages, optional features and embodiments of the methods of the first and the second aspects are described. The advantages apply to one or both of the methods of both aspects and any embodiment thereof. When it is referred to the “methods”, one or both of the methods of the first and second aspects are meant. The optional features and / or embodiments described further below may be combined with any of the methods of the first and the second aspects as well as their embodiments as long as they are not contradicting each other in a logical sense. In other words, the methods of all aspects described herein can be combined with the features and embodiments as described further below.

[0096] In general, a measurement of the set of conductivity parameter values and / or partial pressure values of gas may be recorded and / or started before the sample fluid is aspirated to obtain a reference and / or baseline. In that case, the fluidic system, specifically the channel may be filled with a standby solution, a gas or another reference fluid. In other words, the obtained values for the state before the sample fluid is introduced may serve as a reference or a baseline from which the change in the parameter values can be detected when the sample fluid is introduced. When the sample fluid is aspirated, the temporal evolution of the measured values with respect to the reference and / or baseline measured before indicates the property of the sample fluid.

[0097] The above described methods, as well as any of their embodiments allow identifying a viscosity and / or whether a sample is problematic in that clots, aggregates and / or particles are present in a sample shortly after the sample fluid is introduced into the fluidic system and / or before the sample fluid reaches the channel entrance of the cartridge. In other words, the methods allow for an early identification of the state of a sample fluid. Therefore, the methods can increase the chance for successful removal of the problematic sample fluid, as the distance for removing the sample fluid is relatively short. The early clot detection of the methods can therefore reduce overpressure duration and magnitude on the fluidic system during clot removal by reversing the direction of the pump operation (i.e. the removal of the problematic sample fluid). In addition, a contamination with clots, aggregates and / or particles deep within the fluidic system, specifically the channel of the cartridge can be avoided. At the same time, the early identification of a problematic sample fluid (also denoted “clot detection”) allows reducing underpressure loads, i.e. underpressure duration and magnitude, on the system, as it can be avoided, that the problematic sample fluid moves further into the system. Since underpressure loads may be reduced, the early clot detection of the methods can reduce the risk of microbubble intake at connection points in the system. Due to lower underpressure and overpressure loads which may cause falsified data and / or damage to the system and / or some of the consumable, the early clot detection of the methods may reduce the downtime of the instrument and / or allows to provide more reliable and / or precise methods and instrument. As one or more sensors which is / are already present in the IVD analyzer for analyzing the sample fluid are employed for the clot detection, no additional sensors, detectors or other physical elements are required, and data generated from existing sensors can be used. In other words, the already existing physical resources of the IVD analyzer are alienated and therefore efficiently used to identify a problematic sample fluid at an early stage of introduction into the fluidic system of the IVD analyzer.

[0098] In a system of an IVD analyzer, a controller, machine and / or processor or the like may be configured to perform and / or initiate at least a portion of the steps of the methods according to the first and second aspects. The controller, machine and / or processor may be specifically configured to determine the property of the sample fluid based on the detected set of partial pressure values of gas and / or based on the detected set of conductivity parameters.

[0099] Based on the above described advantages, it may be resumed that the methods according to the first and second aspects can make IVD analysis more efficient (i.e. time efficient and / or cost efficient), less error prone, ecofriendly due to extended longevity of the consumables, more precise and / or reliable, and easier to use for a user and therefore more user friendly.

[0100] Introducing, i.e. aspirating or pushing / pressing a sample fluid into the fluidic system is performed after a first fluid was already introduced into the fluidic system, particularly the channel. The first fluid may even be present in the instrument before being operated. In other words, the sample fluid (which may be considered a second fluid) is introduced into the fluidic system at a later stage than the first fluid. In one scenario, the first fluid is a conductive standby solution that is stored in the channel when the system is not in use. In another scenario, the first fluid is a conductive aqueous solution containing ions from a salt and being different from the standby solution and introduced into the fluidic system shortly before the sample fluid is introduced.

[0101] In general, a fluid may be considered a material in a state at which flow is possible and fluidic behavior of the material can be observed. This is typically the case for liquids and gases and therefore, a fluid may comprise liquids and / or gases. The first fluid according to the first aspect should be a liquid, such as a conductive aqueous salt solution, as for example a buffer solution, since the measurement principle according to the first aspect is based on electrochemistry that requires a conductive solution. The first fluid according to the second aspect may be a liquid and / or a gas if the measurement is based on an optical principle. If however, the measurement principle of the second aspect is based on electrochemistry, the first fluid should also be a liquid, preferably a conductive aqueous solution.

[0102] The sample fluid is typically a liquid, such as a blood sample or another body fluid. The sample fluid is spatially separated from the first fluid in the fluidic system. Hence, the space in the fluidic system between the sample fluid and the first fluid is filled with at least a third fluid, which may comprise a liquid and / or a gas. Preferably, the space in the fluidic system between the sample fluid and the first fluid contains an air bubble. In other words, the sample fluid may be spatially separated from the first fluid in the fluidic system by a gas, specifically an air bubble and an air bubble refers to an air filled volume that moves together with the first fluid and the sample fluid through the fluidic system. The air bubble may be considered a third fluid. The first fluid is introduced into the fluidic system before the sample fluid is introduced into the fluidic system.

[0103] In a case when the property of the sample fluid is determined by means of both sensor unit types (the conductivity sensor unit and the gas sensor unit), the two different sensors may be positioned close to each other, particularly in the same cartridge. For example, the two different sensors units (the conductivity sensor unit and the gas sensor unit) may be apart from each other by approximately 1cm to approximately 8cm, preferably by approximately 1,5cm to approximately 5cm and even more preferably by approximately 2cm to approximately 3cm. The distance may be measured from one single sensor element of one sensor unit to another sensor element of the other sensor unit. As an alternative, the two different sensors may be positioned in different units and / or cartridges being connected to each other by the fluidic system, which act as communicating tubes and which should allow to substantially measure the same local pressure state at positions, which are further distant from each other as it would be the case when present in the same cartridge. The conductivity sensor spot diameter (diameter of one single conductivity sensor) is in the range of approx. 0,2mm to 2mm, preferably of approx. 0,5mm to 1,5mm and more preferably between approx. 0,8mm and 1,2mm. The sensor spot distance, i.e. the distance between two conductivity sensors, which may form a conductivity sensor unit may range between approx. 1,5mm to 3,5mm, preferably between approx. 1,8mm to 2,8mm and more preferably between approx. 1,9mm and 2,6mm.

[0104] The step of automatically determining of the property of the sample fluid derived from the detected set of partial pressure values of gas and / or from the detected set of conductivity parameter values may be performed by a machine, a processor or a controller. The step of automatically determining of the property of the sample fluid is typically not performed manually. A machine, a processor or a controller can run a program that is configured to recognize specific characteristics in the temporal evolution of the local pressure state, which are indicative for states of the sample fluid, such as aggregates and / or clots or a high viscosity.

[0105] In general, the methods may be performed each time the IVD instrument / analyzer is started and / or in use to analyze a sample fluid. For example, a user may start the operation or otherwise inform the instrument that a sample fluid is to be analyzed and the IVD analyzer may then automatically initiate the method(s) according to any one of the described embodiments. This has the advantage of automatically protecting the instrument and / or consumables from damage by aspirating problematic sample fluids. Alternatively, a user may manually initiate the method(s) according to any one of the described embodiments.

[0106] If the local pressure state is of interest, it may comprise a pressure difference between a measured local pressure in the fluidic system when a sample fluid is introduced in the fluidic system and a local pressure that is measured at the same position when a reference fluid is introduced in the fluidic system. The local pressure state may in some cases also correspond to an absolute pressure value. The local pressure state may also correspond to a difference between a measured local pressure when a sample fluid is introduced in the fluidic system and a threshold value. As the local pressure state may be derived from readings of stationary sensor units, i.e. the conductivity sensor unit and / or the gas sensor unit, the local pressure state may always be obtained from readings of one or more fixed positions by one or more sensor units.

[0107] In general, even though the channel is described in most embodiments as being a portion of a cartridge, the channel may also be a portion of another element of the fluidic system, which is not a cartridge, such as a cuvette or another flow cell.

[0108] The property of the sample fluid comprises at least one of the following:

[0109] • a problematic state, in which the sample fluid comprises at least one of clots, such as blood clots, particles of human tissue, aggregates and contaminations;

[0110] • a viscous state, in which the sample fluid has a certain viscosity, specifically a highly viscous state, in which the sample fluid has a viscosity higher than 6mPas, particularly higher than 8mPas, such as for example 9mPas; or

[0111] • a normal state, in which the sample fluid does not comprise clots, particles of human tissue, aggregates and contaminations and has a viscosity between 2mPas and 6mPas, specifically, the viscosity of a sample fluid in a normal state does not have a viscosity higher than 6mPas. In other words, the viscosity of a sample fluid in a normal state is below approximately 6mPas.

[0112] Typically, water and aqueous solutions may have a viscosity of approximately ImPas. Whole blood typically has a viscosity of approximately 4,5mPas if it unproblematic and not highly viscous.

[0113] These methods may allow identifying a problematic sample fluid, which is likely to block the fluidic system, namely a sample fluid that comprises clots, aggregates, contaminations and / or particles. A distinction between a problematic and an unproblematic but highly viscous sample fluid can be made. Alternatively or in addition, the methods may allow identifying a viscosity of a sample fluid that exceeds a certain threshold or that lies in a certain range above the expected value for unproblematic sample fluids. The methods may allow determining the value or range of values of the viscosity of the sample fluid. Specifically, the methods may allow distinguishing between a problematic sample fluid that is supposed to be discharged and a highly viscous sample fluid. Therefore, an incorrect identification of the property of the sample fluid may be avoided and a highly viscous sample fluid will not be discharged due to a wrong identification. Therefore, the methods are efficient in preventing the blocking of the fluidic system by a problematic sample fluid while at the same time saving an unproblematic sample fluid that has a high viscosity but is not problematic and which might be discharged due to a timeout in conventional methods. The methods do not underlie a trade-off between the degree of protection of the fluidic system vs. a lost-sample-rate. Therefore, the methods provide a high degree in sensitivity and efficiency.

[0114] In addition to the above listed cases, which can be discriminated between, the methods may also identify the case, in which the medium changes in the channel of the cartridge, i.e. the case when for example a first fluid passes the sensor unit(s) and an air bubble then follows and fills the channel. Therefore, it is a further detectable event when the filling of the channel, particularly when the filling changes the phase from gas to liquid or vice versa, as the different fluids pass the fluidic system.

[0115] In general, the method according to the first and / or second aspect may determine the presence or absence of clots, aggregates and / or particles in the sample fluid and / or the viscosity of the sample fluid and / or a range, in which the viscosity of the sample fluid is found. In other words, a method of determining a property of a sample fluid in an IVD analyzer, namely the presence or absence of clots, aggregates and / or particles may comprise the steps of the method(s) of the first and / or second aspect. Further, a method of determining a property of a sample fluid in an IVD analyzer, namely the viscosity of the sample fluid and / or a range, in which the viscosity of the sample fluid lies may comprise the steps of the method(s) of the first and / or second aspect.

[0116] The step of automatically determining of the property of the sample fluid may comprise applying a trained artificial neural network on the detected set of conductivity parameter values in the first fluid and / or the detected set partial pressure values of the gas in the first fluid or in a third fluid to determine the property of the sample fluid. The method may further also comprise training the artificial neural network using a training data set comprising a set of conductivity parameter values in the first fluid and / or a set of partial pressure values of the gas in the first fluid or in the third fluid corresponding to pre-defined properties and / or states of the sample fluid.

[0117] Specifically, for the method that is based on the conductivity measurement, the artificial neural network may be trained on conductivity readings without the need to translate them into pressure values. The change in conductivity is caused by the pressure change, but it is not required to know the pressure values or the temporal evolution of the local pressure state. The step of automatically determining of the property of the sample fluid derived from the detected set of partial pressure values of gas and / or from the detected set of conductivity parameter values may be performed by a controller, a machine and / or a processor, which make use of a trained artificial neural network trained to recognize the characteristics, which are indicative of a problematic sample fluid or of a highly viscous sample fluid. This allows increasing the reliability and / or the precision of the identification of the property of the sample fluid. The trained artificial neural network may already be provided to the controller, machine and / or processor, or it may be required to previously train the artificial neural network. The training may be performed half or fully automated. The training may be started by providing reference fluids having predetermined states such as a predetermined density and size or size distribution of particles in the solution and / or predetermined viscosities. The training may be required for each cartridge or for one representative of a batch of cartridges. In a simplified explanation, the trained artificial neural network learns how the training data, i.e. the temporal evolution of the conductivity parameter values and / or the partial pressure of gas values, is indicative of the predetermined states and may later be applied to an unknown sample fluid to identify the unknown state. Providing a high number of reference fluids having different predetermined properties (particle, clots, viscosities etc.) may increase the quality of the trained artificial neural network and hence the reliability and / or the precision of the identification of the property of the sample fluid when applying the trained artificial neural network. It should be noted that particles, clots, contaminations and aggregates may lead to similar and / or the same characteristic in the recorded set of conductivity parameter values and / or partial pressure of the gas.

[0118] In the case of a highly viscous sample fluid, the underpressure may slowly increase, i.e. the pressure further drops, as the fluidic resistance is proportional to the length of the portion in the fluidic system filled by the sample liquid. The “total» fluidic resistance may refer to the sum of the resistance caused by moving the standby solution, moving the air separation bubble (neglectable) and moving the sample liquid. The resistance caused by each of these elements is proportional to their length inside the fluidic system. A problematic sample fluid may cause the pressure to further drop that shows a different temporal evolution.

[0119] Specifically if a neural network is applied, the determining of the property of the sample fluid may correspond to a categorization into one of the categories: “problematic sample fluid”, “highly viscous sample fluid” and “unproblematic sample fluid (which is not highly viscous)”. Alternatively or in addition, in general, the determining of the property of the sample fluid may correspond to a determining whether, clots, particles and / or aggregates are present in the sample fluid or not. Alternatively or in addition, in general, the determining of the property of the sample fluid may correspond to a determining the viscosity, the range, in which the viscosity is present and / or whether the viscosity exceeds a predetermined value. Instead or in addition of applying a neural network for determining the property of a sample fluid, the recorded data, regardless whether obtained according to the first and / or the second aspect, may be fitted. In that case, the behavior of a sample fluid having a certain property is known and the temporal evolution of the conductivity parameter and / or the partial pressure value of a gas can be described by a function that is indicative of the property of the sample. The function describing the temporal evolution of the parameter (conductivity parameter and / or the partial pressure value of a gas) for a highly viscous sample fluid may be indicative of the degree of viscosity. If the sample fluid contains clots, the temporal evolution may show a substantially different behavior, which allows the differentiation between the properties. The fitting may be performed by a user or automatically by a machine. It is however more preferable to provide automated steps. In view of the reliability of the result, it is also more preferable to apply machine learning principles based on neural networks for determining the property of a sample fluid.

[0120] The method may further comprise automatically triggering of an action in the IVD analyzer based on the determined property of the sample fluid. The action may comprise at least one of the following steps: stopping the step of introducing the first fluid and / or the sample fluid, reversing an operation direction of a pump, discharging the sample fluid, introducing a washing solution and washing the fluidic system and / or the channel at least partially with the washing solution, continuing the step of introducing the first fluid and / or the sample fluid, optically and / or acoustically outputting an alarm. The step of automatically triggering may differentiate between the following cases: a. when the sample fluid is in a problematic state (i.e. when the sample fluid contains clots, aggregates and / or particles), the action comprises at least one of the following steps: o stopping the step of introducing the first fluid and / or the sample fluid, o reversing an operation direction of a pump, o discharging the sample fluid, and / or o introducing a washing solution and washing the fluidic system and / or the channel at least partially with the washing solution b. when the sample fluid is in a highly viscous or in a normal state, the action comprises the following step: o continuing the step of introducing the first fluid and / or the sample fluid, optically and / or acoustically outputting a control signal, such as a control noise and / or a green and / or a red control light. If a problematic sample fluid has been detected when being introduced into the fluidic system, a step of outputting an alarm and / or a step the introducing of the first fluid and / or the sample fluid may be stopped. These steps may be automatically triggered by the processor, machine and / or controller. Therefore, the pump, which generates the pressure (particularly the underpressure) may be stopped. Additionally or alternatively, a reverse operation of the pump may be triggered when a problematic sample fluid is detected, such that an underpressure is for example turned into an overpressure that presses the problematic sample fluid out of the fluidic system where it can be discharged into a discharging container. Further, a step of washing the fluidic system and / or the channel may be triggered to wash away any potential contaminations of aggregates, clots and / or particles in at least a portion of the fluidic system. The washing may be performed using an aqueous solution, such as a buffer, a salt solution or another non-aqueous solvent.

[0121] If a non-problematic but highly viscous sample fluid is detected, the step of introducing the first fluid and / or the sample fluid may be continued and the pump operation is not changed.

[0122] This has the advantage that a fluidic system can be protected from damage caused by problematic sample fluids. At the same time, unproblematic sample fluids with high viscosities may be allowed to enter and pass the fluidic system. Therefore, unproblematic sample fluids are saved for diagnosis and are not required to be retaken from a patient while at the same time the IVD analyzer is efficiently protected from damage or contamination by a problematic sample fluid. Therefore, the operation of the IVD analyzer is not disturbed and performs efficiently avoiding downtimes of the instrument.

[0123] The conductivity detection time span and / or the gas detection time span may overlap at least partially with an introduction time span, in which the step of introducing the sample fluid into the fluidic system is performed, preferably wherein the conductivity detection time span and / or the gas detection time span starts before or at the same time with the introduction time span.

[0124] Preferably, the conductivity detection time span and / or the gas detection time span overlaps a time span, in which the first fluid is introduced, aspirated and / or transported through the fluidic system, specifically the channel of the cartridge. In general and in typical cases, the fluidic system is already filled with the first fluid, i.e. a standby solution. Before the sample fluid is introduced, typically a small amount of air is introduced to guarantee a separation of standby solution and sample fluid. The measurement of the conductivity parameter values and / or the partial pressure values of gas may preferably be started in a state when the fluidic system, particularly the channel of the cartridge is mostly filled by the first fluid and when an analysis of a sample fluid is performed or planned, i.e. when the instrument is started and actively in use to analyze a sample fluid. The obtained values for the state before the sample fluid is introduced may serve as a reference or a baseline, from which the change in the parameter values can be detected when the sample fluid is introduced. If only the conductivity is detected by recording a set of conductivity parameter values of the first fluid (according to the first aspect as a primary measurement principle), the starting point, at which the first conductivity value is detected may be timed before or in the very moment when the pump is started and the sample fluid is introduced into the fluidic system. In other words, the conductivity detection time span may start before or in the very moment when the sample fluid is introduced, particularly aspirated into the fluidic system.

[0125] If only the partial pressure of gas is detected by recording a set of partial pressure values of gas in the first fluid (according to the second aspect as a primary measurement principle), the starting point, at which the first partial pressure value is detected may also be timed before or in the very moment when the pump is started to introduce the sample fluid. In other words, the gas detection time span may start before or in the very moment when the sample fluid is introduced, particularly aspirated into the fluidic system.

[0126] If the methods are combined and the conductivity as well as the partial pressure of gas is detected in the first fluid, the conductivity detection time span and / or the gas detection time span may start before or in the very moment when the sample fluid is introduced. Preferably, the conductivity detection time span and the gas detection time span can start in the same moment. Therefore, the conductivity detection time span and the gas detection time span can both start before or in the moment when the sample fluid is introduced into the fluidic system.

[0127] The moment, when the sample fluid is introduced into the fluidic system may be a moment, in which the pump is started or it may be a moment before the pump was already running and introducing the first fluid into the fluidic system and when the sample fluid enters the fluidic system from an external reservoir. Therefore, the time span before the sample fluid is introduced into the fluidic system may comprise situations, in which the pump is switched on and / or switched off. In one specific example, the time span before the sample fluid is introduced into the fluidic system may comprise the situation, in which the first fluid is introduced into the fluidic system and in which the first fluid is about to contact at least the conductivity sensor unit. At least in the moment, in which the sample fluid is introduced into the fluidic system, the conductivity sensor unit preferably contacts the first fluid, such that the conductivity parameter can be measured.

[0128] The conductivity detection time span and / or the gas detection time span may range between approximately 0,5s to 60s, preferably between approximately 2s to 20s and more preferably between 3 s and 10s. If started earlier, the conductivity detection time span and / or the gas detection time span may start before the said introduction time span (in which the step of introducing the sample fluid into the fluidic system is performed / started) by approximately 10s, preferably by approximately 5s and more preferable by Is. The time to obtain a result may depend on the operational state of the IVD analyzer. For example, if the IVD analyzer is calibrating in the very moment when a sample fluid is supposed to be introduced, the calibration may be finalized or aborted. The fluidic system needs to be washed after the calibration. Hence, the time to obtain a result can vary.

[0129] In all of the above scenarios, the advantage is that a change in the pressure state can be recorded before or at least starting in the moment, in which the sample fluid enters the fluidic system. An early and reliable identification of the property of the sample fluid can be made such that a problematic sample fluid does not enter deep into the fluidic system and can therefore easily be discharged.

[0130] As an alternative, the conductivity detection time span and / or the gas detection time span may start after the moment, in which the sample fluid is introduced. For example, a conductivity is recorded as a primary measurement principle but the property of the sample fluid cannot be identified unambiguously. In that case, at a later stage, the detection of the partial pressure of gas may be started for verification or for a more reliable identification of the property of the sample fluid.

[0131] The step of introducing the first fluid and / or the sample fluid into the fluidic system may comprise aspirating the first fluid and / or the sample fluid.

[0132] A pump, particularly a peristaltic pump may operate in a direction, in which the fluids are aspirated. Alternatively, a pump may be positioned on the other side of the fluidic system and may operate in the opposite direction, in which an overpressure is generated and presses and / or pushes the fluids into the fluidic system, however, it is more preferable to aspirate the fluids into the fluidic system as it reduces the risk of damaging elements of the fluidic system as overpressures can easily damage elements of the fluidic system, such as seal elements, valves and / or sensitive junction elements. In general, there are different advantages in the use of underpressure rather than pushing sample - i.e. typically in BGE analyzers peristaltic pumps are used which allows improving the control over the sample fluid and therefore, it can be made sure that the biological liquid does not get into contact with the instrument (it only stays in the consumable, such as the cartridge and tubings connected to the cartridge). Further, if sample fluids pass through a pump red blood cells may be damaged or destroyed and additionally also blood gas values may change as the soft peristaltic pump tubes tend to be very oxygen permeable - therefore, it is advantageous for the sample fluid to not pass a pump system before passing the sensors for example in the cartridge or in an optional cuvette.

[0133] The step of detecting of the set of partial pressure values of gas may be based on an optical measurement principle. In addition or alternatively, the step of detecting of the set of partial pressure values of gas may be based on electrochemical principles, however optical principles typically allow a faster and reliable detection. Electrochemical sensors may be used to detect partial pressure values of gas if they are not too slow. The step of detecting the set of partial pressure values of gas in the first fluid may be a detecting of the set of partial pressure values of gas in gas bubble, i.e. a gas-filled room, such as an air bubble and / or in a liquid filled room, such as a solution like a standby solution.

[0134] As already mentioned further above, a gas sensor unit that is based on an optical principle may detect the partial pressure values of gas in a gas-filled room or in a liquid-filled room, which makes the optical method versatile and suitable to any kind of fluids containing gas and / or liquids. Further, optical methods for detecting partial pressure values of gas are fast, precise, reliable and efficient.

[0135] In general, it is also possible to detect the parameter values being indicative of the property of the sample fluid, such as a set of partial pressure values of oxygen, inside the sample fluid itself. In that case, it is however more difficult to determine the property of the sample fluid, as the oxygen value (partial pressure values of oxygen) in the sample fluid, that enters the fluidic system, is unknown and the oxygen sensor will need some time to converge to the oxygen value. It may however also be likely that the oxygen sensor will (usually) have already converged to the partial pressure values of oxygen in the standby solution, when a sample is inserted. The superposition of the two effects (convergence to sample value) and (pressure change due to clot) make it more difficult to detect a clot while the oxygen sensor is already in contact with the sample fluid.

[0136] Moreover, if the temporal evolution of the local pressure state is detected this may comprise determining a pressure drop when aspirating the sample fluid. When a sample fluid is aspirated into the fluidic system, the pressure might drop if the sample fluid is highly viscous and / or if the sample fluid contains particles, clots and / or aggregates. In other words, the underpressure or the force of the underpressure generated by the pump becomes stronger as the sample fluid reduces the flow rate and / or blocks the fluidic system in extreme cases. The temporal evolution of such a pressure drop, when aspirating the sample fluid, is indicative of whether a sample fluid is viscous and / or contains particles, clots and / or aggregates. As described further above, an artificial intelligence may be trained to recognize such a characteristic evolution of a pressure drop to more reliably identify whether a sample fluid is highly viscous and / or if the sample fluid contains particles, clots and / or aggregates.

[0137] The method according to the first and / or second aspect may comprise a step of calibrating the fluidic system, particularly with respect to the detection of viscosities (when the property of the sample fluid that is to be determined corresponds to the viscosity). The fluidic system may for example be calibrated for pressure measurements, by using the fluidic system for normal sensor calibration processes, which is highly efficient. The viscosity of fluids can be varied to serve the purpose of calibrating the fluidic system for pressure and / or viscosity measurements. As a first step, the actual pump speed has to be measured using a known liquid with a known viscosity at a known temperature (viscosity is temperature dependent). The fluid may be aspirated through the fluidic system and the two sensor points (which may correspond to the timeout points) may be used to determine the actual volumetric flow rate related to the pump rate. After the pump rate is determined, different fluids of known viscosity can be aspirated through the fluidic system at different known velocities / pump rates, especially through the SIM needle. With a known viscosity and a known velocity, the resulting pressure difference can be calculated as described in more detail further below.

[0138] If a sample fluid that is detected to have a high viscosity (exceeding a predetermined threshold) enters the fluidic system, it may be allowed to pass the cartridge for the detection of further parameters. In that case, the pump is further operated to aspirate this sample fluid. In addition, an alert may be triggered, which indicates a problematic heath condition of the patient associated with the sample fluid. In response to the alert, a medical doctor may be informed and (immediate) actions to safe the patient’s life may be initiated. The IVD analyzer may (automatically) trigger the determination of parameters, such as the determination of hematocrit (Het), Potassium (K+), specific markers such as Troponin T (TnT), NT-proBNP, D-Dimer, cTnT and the like, specifically in a case, when the viscosity is high but also in cases when clots and / or strong coagulation is observed (when the observed property comprises coagulation). These observations may indicate cardiac problems. Such a determination may either be performed by the IVD analyzer itself or by another entity, which is specialized in the determination of the parameter of interest. The measured parameter might then confirm or specify the indicated health condition of the patient. Further, the Het measurement may indicate and / or specify whether or not the viscosity of a blood sample arises from a high Het value, which may for example indicate a dehydration.

[0139] According to a further aspect of the present disclosure, which may be considered a third aspect, a fluid sensor system for determining a state in a sample fluid in an IVD analyzer is provided, wherein the sensor system comprises: a cartridge with a channel being connectable to a pump for creating a change in a local pressure state to drive a fluid through the channel of the cartridge specifically wherein the cartridge with the channel being configured to guide the fluid through the cartridge; a conductivity sensor unit inside the cartridge configured to detect a conductivity parameter of a first fluid and a sample fluid; and / or a gas sensor unit configured to detect a partial pressure of gas in the first fluid and the sample fluid; and a controller configured to cause the IVD analyzer to perform the steps of the method according to the first and / or the second aspect or any embodiment thereof.

[0140] The fluid sensor system has the same advantages as the corresponding methods or embodiments thereof. The fluid sensor system that is used to perform the method according to the first aspect, comprises the conductivity sensor unit. The fluid sensor system that is used to perform the method according to the second aspect, comprises the gas sensor unit. The fluid sensor system may particularly comprise both sensor types, namely the conductivity sensor unit and the gas sensor unit such that the fluid sensor system may perform the method according to the first aspect and the method according to the second aspect.

[0141] The conductivity sensor unit is positioned inside the cartridge having a channel of the fluidic system. The gas sensor unit may also be positioned inside the cartridge but it may also be positioned outside the cartridge in the fluidic system that is in fluidic connection with the channel of the cartridge.

[0142] The controller may also be considered a machine and / or a processor. The controller is configured to cause the IVD analyzer to perform the method steps described herein. Particularly, the controller may be configured to perform some of the method steps by itself such as mathematical operations and / or performing the steps of determining a temporal evolution of the local pressure state from the detected set of conductivity parameter values and / or partial pressure values of gas and / or the step of automatically determining of the property of the sample fluid based on the determined temporal evolution of the local pressure state. The controller may particularly trigger directly or indirectly an action when a certain state is identified in the sample fluid. For example, the controller may trigger a discharge step and / or a washing step, as described further above, when a problematic sample fluid is identified.

[0143] The cartridge further comprises: a first plate that comprises a first surface of the channel; a second plate that comprises a second surface of the channel; a resilient seal element, which connects the first plate with the second plate and seals the channel at least partially, wherein the resilient seal element is configured to deform and thereby change a cross section of the channel in response to a change in a local pressure state.

[0144] The fluid sensor system may further comprise the pump, specifically wherein the pump is configured to generate an underpressure to drive the fluid through the channel of the cartridge, specifically to draw and / or suck the fluid into the fluidic channel and into the cartridge.

[0145] This type of cartridge may already be present in IVD analyzer and therefore, no additional element, particularly no additional channel (system) and / or sensor containing unit is required to perform the identification of whether a sample fluid is unproblematic (expected / normal sample fluid), unproblematic but highly viscous and / or must be considered as being a problematic sample fluid. The resilient seal element is sensitive to a temporal evolution of the local pressure, particularly an underpressure, as it deforms upon a change in the local pressure and changes the area of the cross section of the channel. The conductivity sensor unit can detect this change in cross section of the channel. The structural features of the already existing cartridge may therefore be employed, i.e. alienated in an efficient way to identify a state in a sample fluid.

[0146] The first fluid may comprise a standby solution. The standby solution may comprise a conductive aqueous solution having ions of a salt, such as a buffer solution or any other type of salt solution. The standby solution may be stored in the fluidic system, particularly the channel of the cartridge, when the instrument is not operated, such that elements, like reference electrodes do not dry out. When a sample fluid is introduced into the fluidic system, the sensors may still be in contact with the standby solution and therefore, the step of introducing the first fluid may already be performed long before the sample fluid is introduced. In other words, the first fluid may already be filled into the fluidic system, particularly the channel of the cartridge, minutes, hours or even days before the sample fluid is introduced to be analyzed. Therefore, it is convenient and efficient for a user to use the standby solution to determine a state in the sample fluid.

[0147] The sample fluid may comprise a body fluid such as a blood sample and / or lacrimal fluid. In BGE analyzers, typically blood is analyzed as a sample fluid.

[0148] A computer program product, which may be considered a fourth aspect, is provided having instructions stored thereon, which cause a machine of an IVD analyzer to initiate and / or perform the steps of the methods described herein, i.e. the method of any of the aspects or any one of the described embodiments.

[0149] The computer program product has the same advantages as the corresponding methods or embodiments thereof.

[0150] According to a further aspect of the present disclosure, which may be considered a fifth aspect, a method of determining a local pressure state in a fluidic system, specifically a channel of a cartridge, in an IVD analyzer is provided and the method comprises the following steps: introducing a first fluid into the channel of the IVD analyzer, wherein the channel comprises a resilient seal element configured to change a cross section of the channel in response to a change in the local pressure state; contacting a conductivity sensor unit in the channel with the first fluid; detecting one or more conductivity parameter values of the first fluid using the conductivity sensor unit wherein the conductivity parameter values are dependent from the cross section of the channel; determining the local pressure state from the detected one or more conductivity parameter values.

[0151] According to the fifth aspect of the present disclosure, it is an advantage to make use of the (side) effect that a resilient seal element is configured to change a cross section of the channel in response to a change in the local pressure state for determining a local pressure state in a channel, particularly in a fluidic channel or channel system.

[0152] A conductivity sensor unit, which already exists in many cartridges used in IVD analyzers is used to detect one or more conductivity parameter values. Therefore, the method is very efficient in identifying a local pressure state, such as an overpressure state that might have the potential to damage the channel system and / or any element of the cartridge, the channel system and / or the instrument. The method may also allow detecting whether the local pressure state corresponds to the atmospheric pressure and particularly whether the local pressure state cannot be changed by changing a pump setting, which would be the case, when the pump is defect and cannot generate a pressure, particularly and underpressure or when the channel system has a leak. The method according to the fifth aspect may require a calibration, in which the correspondence of the conductivity parameter values for a number of local pressure states is identified.

[0153] From the one or more conductivity parameter values, a local pressure state, particularly a change in the local pressure state, is derived, which can be performed by a controller, a machine and / or a processor. The one or more conductivity parameter values are detected, measured and / or recorded in the first fluid during a conductivity detection time span, particularly when the first fluid physically contacts the conductivity sensor unit in the channel. The first fluid is usually a conductive liquid, such as an ion containing aqueous solution. The one or more conductivity parameter values may correspond to a set of conductivity parameter values. The method may comprise a step of determining a temporal evolution of the local pressure state from the detected set of conductivity parameter values. The method may comprise a step of automatically identifying and / or deriving an indication of a state of the instrument, the IVD analyzer, the cartridge, the pump and / or the fluidic system by analyzing the local pressure state, particularly the temporal evolution of the local pressure state. For example, a leak in the fluidic system may be reflected by a characteristic in the temporal evolution of the local pressure state derived from the detected set of conductivity parameter values. In some cases, the method may allow distinguishing between states such as a defect pump and a leak in the fluidic system.

[0154] Further, the method may comprise the step of introducing a second fluid, which may be a sample fluid after the first fluid was already introduced into the fluidic system. The second fluid may be spatially separated from the first fluid in the fluidic system, particularly by a gas bubble. The method may then comprise a step of automatically determining of the property of the sample fluid based on the determined temporal evolution of the local pressure state.

[0155] The method according to the fifth aspect may comprise one or more of the above features having the corresponding advantages if the features are compatible with the detection of the one or more conductivity parameter values using the conductivity sensor unit.

[0156] According to an example of the present disclosure, a method of determining a local pressure state in a channel in an IVD analyzer is provided and the method comprises the following steps: introducing a first fluid into a channel of the IVD analyzer; introducing a sample fluid, which is spatially separated from the first fluid into the channel; detecting a set of partial pressure values of gas in the first fluid during a gas detection time span using a gas sensor unit; determining from the detected set of partial pressure values of gas the local pressure state. Also, the method according to this example may comprise one or more of the above features having the corresponding advantages if the features are compatible with the detection of the one or more conductivity parameter values using the gas sensor unit.

[0157] In general, concerning the determination of the local pressure value, using an optical oxygen sensor unit, the actual partial pressure value may be determined, e.g. in air. Therefore, with a half-filled channel of the cartridge, the oxygen sensor unit in air and with the conductivity sensor unit in standby solution, the conductivity sensor unit could be calibrated to indirectly measure the local pressure value.

[0158] In general, an additional sensor and / or sensor unit (camera, ultrasound, electric field) may be provided in the instrument, at and / or in the fluidic system, which may be used to measure the condition of the fluidic system, such as the peristaltic pump tube or the fluid in the fluidic system and / or the shape of the channel filled with the conductive fluid inside the soft peristaltic pump tube. A soft tubing, which may be used in the fluidic system may also responds to pressure changes in the fluidic system and may therefore also reveal information on the property of the sample fluid. This may allow detecting indications of clots to confirm the result obtained by the method according to the first and / or second aspect without placing a sensor directly in the consumable that is regularly disposed.

[0159] Resuming the most important advantages of the present invention: The property of interest in the sample fluid may specifically relate to a state of blood clotting, aggregation and / or the viscosity of the blood sample. The already existing facilities of a fluid sensor system may be efficiently used without the requirement of additional sensors, which avoids additional material and system complexity making the IVD system very eco-friendly and efficient to operate. As the fluid sensor system may be protected from the passage and the potential blockage by a clotted and therefore problematic sample, which could otherwise render the fluid sensor system useless, the fluid sensor system may be saved from being disposed. This further improves the degree-of eco-friendliness of the fluid sensor system and reduces downtime of the IVD apparatus and potentially required maintenance. Moreover, the a highly viscous sample fluid may be identified and differentiated from a clotted blood sample, such that only a clotted blood sample is disposed and not a highly viscous blood sample. This allows avoiding that a further blood sample must be taken from a patient and therefore the invention is also very patient-friendly as his / her sample is efficiently used by the IVD system. Further, the invention adds value to the functionality of an IVD system as additional parameters can be determined, which may not only be used to protect the fluid sensor system from damage but also to indicate a health condition of a patient. Therefore, the invention is highly efficient, patient- and eco-friendly and adds remarkable value to an already existing IVD- apparatus.

[0160] Detailed Description of the Invention In the following, some example embodiments will be described in detail, wherein the invention should not be understood to be limited to the example embodiments described. The following examples and figures are provided to aid the understanding of the present invention, the true scope of which is set forth in the appended claims. Single features being described in a particular embodiment may be arbitrarily combined, given that they are not excluding each other. In addition, different features, which are provided together in the example embodiments are not to be considered restrictive to the invention.

[0161] Skilled artisans appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements whereas other elements may have been left out or represented in a reduced number in order to enhance clarity and improve understanding of the aspects of the present disclosure.

[0162] The same reference numerals are used among different embodiments and examples for the same or similar elements or elements that have similar or the same effects.

[0163] Description of the Figures

[0164] Fig- 1 is a schematic drawing of a typical fluidic system;

[0165] Fig. 2a and Fig. 2b are schematic drawings of a fluidic system at different stages of aspiration according to an embodiment;

[0166] Fig. 3a is a schematic drawing of a channel cross section under ambient pressure conditions according to an embodiment;

[0167] Fig. 3b and Fig. 3c are photographic illustrations of a channel cross section under ambient pressure conditions and under underpressure conditions according to an embodiment;

[0168] Fig. 4a is a flow chart of a method of determining a state in a sample fluid in an IVD analyzer using a conductivity sensor unit according to an embodiment;

[0169] Fig. 4b is a flow chart of a method of determining a local pressure state in an IVD analyzer using a conductivity sensor unit according to an embodiment;

[0170] Fig- 5 is a flow chart of the method of determining a state in a sample fluid in an IVD analyzer using a conductivity sensor unit according to a further embodiment;

[0171] Fig- 6 is a flow chart of the method of determining a state in a sample fluid in an IVD analyzer using a conductivity sensor unit and a gas sensor unit according to another embodiment;

[0172] Fig. 7 is a flow chart of a method of determining a state in a sample fluid in an IVD analyzer using a gas sensor unit according to an embodiment; Fig. 8a and Fig. 8b are schematic time tables for the detection time spans with respect to the introduction time span according to embodiments of the application;

[0173] Fig- 9 is a photographic illustration with added scheme and annotations of a cartridge that may be used in an IVD analyzer such as the fluidic system according to Fig. 1;

[0174] Fig. 10 is a recording of the conductivity parameter of a first fluid when the fluidic path is blocked;

[0175] Fig. 11 is a photographic illustration with added scheme and annotations of the cartridge of Fig. 9 to illustrate the sample positioning with respect to a conductivity sensor unit and a gas sensor unit; and

[0176] Fig. 12 is a photographic illustration with added scheme and annotations of the cartridge of Fig. 9 to illustrate the sample positioning with respect to a conductivity sensor unit and a gas sensor unit if a problematic sample fluid blocks the channel.

[0177] Fig- 1 is a schematic drawing of a fluidic system 35 of an IVD analyzer 10 and is described in more detail as follows.

[0178] A first fluidic path 28 goes through a cartridge 30. This path corresponds to a flow-through sensor path comprising a channel 4, in which a plurality of sensors 5, 6 are positioned. A second fluidic path 29 corresponds to a flow-through optical path comprising a cuvette 14 arranged between a light source 36 and a photodetector 37, thereby forming an optical detection unit 13 such as an oximetry module for an optical measurement of a biological sample brought into the cuvette 14 via the second fluidic path 29.

[0179] The IVD analyzer 10 further comprises a pump 11, such as a peristaltic pump, located downstream of the of the fluidic system 35, and a fluid-supply unit 17 comprising a plurality of fluids in the fluid supply containers 18, and a waste container 32 where fluids circulated through the fluidic system 35 may be disposed of, by the action of the pump 11. The IVD analyzer 10 further comprises a fluid-selection valve 24 (or rotary valve) for selecting between fluids from different fluid supply containers 18 and / or air 16.

[0180] The IVD analyzer 10 further comprises a sample input interface / sample input module (SIM) 21, comprising a sample input port 31, which has an outer input-port side 34 configured for pluggingin an open end of a sample container 12, which provides a sample fluid and an inner input-port side 19 for introducing the sample fluid into the fluidic system 35. The discharge position of the SIM 21 is a position where the SIM 21 is turned towards the inside of a consumable like a discharge container 23, where it spits out a problematic sample fluid to a zone, which is predetermined to capture clots. Once a clot is detected by the timeout procedure, the pump 11 is reversed with the objective to discharge the clot. Also, if the IVD analyzer 10 is used in terms of the present invention and a clot is detected, the pump 11 can be reversed with the objective to discharge the clot. In more detail, in case of a detected clot, the SIM 21 is turned towards the discharge container 23 and the pump 11 is reversed.

[0181] The sample container 12 is in this example a capillary-like sample container. The sample input interface 21 further comprises an aspiration needle 27 comprising an upstream end and a downstream end. The downstream end of the aspiration needle 27 is fluidically connected to the fluidic system 35 via a fluidic line 22, whereas the upstream end is configured to alternately couple to the inner input-port side 19 in order to aspirate a sample 2 from the sample container 12 plugged in the outer input-port side 34 and to a fluid-supply unit port 38 fluidically connected to a common outlet port 39 of the fluid-selection valve 24 via a further conduit. The fluidic line 22 may however also be directly connected to the outlet port 39 of the fluid-selection valve 24, whereas samples may be introduced via a different fluidic line separately connected to the fluid- selection valve 24, for example.

[0182] A problematic sample fluid is conventionally detected / identified in this fluidic system 35 if the sample fluid does not reach one of the sample sensors 25 after a predetermined timeout period. The timeout for the sample sensor aspiration may for example be set to 12 sec in a syringe operation mode and 20 sec in a capillary operation mode. In the capillary operation mode, the timeout is longer as sometimes manual QC is measured with a capillary adapter and moreover it takes longer to aspirate. While pumping, underpressure is generated in the channel 4 of the cartridge 30 when fluids are guided towards the waste container 32. The channel 4 of the cartridge 30 is simplified in this drawing - often, cartridges comprises several channels 4, which may be in fluidic connection to each other and form a cartridge channel system. In other words, a cartridge, which may be used to realize the present invention, may comprise a cartridge channel system, which comprises the channel 4. In this conventional way of clot detection, clots may be transported far into the fluidic system 35 and when the flow rate is reduced due to a problematic sample fluid, which blocks the fluidic system 35, the underpressure drops below typical expected values. Such an underpressure moves clots further into the fluidic system 35 and renders the removal of a problematic sample fluid by reversing the flow direction more difficult.

[0183] Furthermore, microbubbles may leak into the system at the connection points due to the underpressure created in the fluidic system 35, when it is blocked by a problematic sample fluid. Such microbubbles may cause additional problems later on if they cannot be removed, such as changed and falsified blood gas values, crystallization, etc. The further the problematic sample fluid is transported into the fluidic system 35, the higher the stress becomes due to overpressure on the fluidic channel system during the clot removal procedure and the lower the chances are of successfully removing the problematic sample fluid. If the problematic sample fluid cannot be removed, the consumable, such as the cartridge, must be replaced. At least the hardware components of the fluidic system 35 of Fig. 1 can be used to realize the present invention, i.e. one or more of the below described embodiments of the present invention. A controller 40 and / or a software used by the controller 40 of the fluidic system 35 of Fig. 1 need(s) to be configured to initiate, trigger and / or perform at least some of the steps of the methods of the invention. At least some of the cartridge sensor conductivity spots K1-K5 (as shown in Fig. 9) of the cartridge 30 according to one embodiment may be used in the fluidic system 35 of Fig. 1 as conductivity sensor unit(s). When an underpressure is identified in the cartridge 30, the channel 4 of the cartridge 30 contracts as the resilient seal element, i.e. a soft sealing material, moves slightly into the channel 4 of the cartridge 30. This changes the cross section (i.e. the area of the cross section) of the channel 4 (as shown in Fig. 3c). The reduced area of the cross section reduces the admittance (which is considered one possible conductivity parameter) between the conductivity spots, which constitute a conductivity sensor unit 5.

[0184] As already indicated above, the fluidic properties of blood may vary strongly depending on the patient and therefore data has to be evaluated carefully to distinguish between a clotted and a highly viscous sample fluid. A highly viscous sample fluid might move slowly and lead to lower pressure than a low viscosity sample. In the case of a highly viscous sample fluid, the flow resistance is proportional to the amount of the sample in the system, therefore the flow resistance is slowly increasing and the underpressure “builds up”, i.e. drops further. In case of a clot, the flow resistance rises more abruptly, which allows differentiating between a problematic sample fluid having clots vs. highly viscous sample.

[0185] The sample fluid may be aspirated via a sample input module needle 27 as shown in Fig. 1. The diameter of the sample input module needle 27 may be 0,6mm in one embodiment. Particles, which are larger than this diameter, may not enter the channel system. The tubing and / or the channel system may have elements with a diameter of approximately 0,75mm in one embodiment. In general, the diameter of the sample input module needle 27 may range between approximately 0,3 mm and approximately 10mm and the tubing and / or the channel 4 of the cartridge may range between approximately 0,1mm and approximately 12mm. Some channels, which can be connected to the channel system or which can be comprised by the fluidic system may even be in the pm range and therefore represent a microchannel.

[0186] An optional cuvette 14 for an optical measurement as shown in Fig. 1, may have a smallest distance between two walls and / or a diameter of approximately 0,1mm and therefore, particles, clots and aggregates, which are larger in size than approximately 100 pm would cause problems. The smallest distance between two walls and / or a diameter of the cuvette may range in general between approximately 0,05mm and approximately 0,5 mm.

[0187] In general, the size of the discocyte shaped human red blood cells typically ranges between approximately 7,5 pm and approximately 8,7 pm in diameter and approximately 1,7 pm and approximately 2,2 pm in thickness. In a normal unproblematic sample fluid like blood, these are the largest objects, which may be expected. Therefore, particles, clots and / or aggregates in the sample fluid, which range in size between approximately 15-20 pm and approximately 100 pm or more, are likely to cause lower underpressure values in the fluidic system 35 than normal unproblematic sample fluids. Such particles, clots and / or aggregates in the sample fluid can block the entire fluidic system 35.

[0188] Fig. 2a and Fig. 2b are schematic drawings of a portion of a fluidic system 35 in an IVD analyzer 10 at two different stages of aspiration according to an embodiment. The sensor system 20 and the cartridge 30 of the IVD analyzer 10 are scaled in this schematic drawing at dimensions, which do not represent the realistic dimensions with respect to the dimension of the IVD analyzer 10. The dimensions are selected to better illustrate the details of the sensor system 20 and the cartridge 30 of the IVD analyzer 10. The fluidic system 35 is illustrated in a simplified scheme to outline the concept of the embodiment.

[0189] The channel 4 is part of the fluidic system 35 and is contained in the cartridge 30. The peristaltic pump 11 aspirates the first fluid 1, the sample fluid 2 and other fluids 3a, 3b (called third fluid(s)), like gas bubbles through the channel 4. A gas bubble 3a may for example be an air bubble to separate the first fluid 1 from the sample fluid 2.

[0190] In general, even though the channel 4 is described herein as being a portion of the cartridge 30, the channel 4 may also be a portion of another element of the fluidic system 35, which is not a cartridge 30, such as a cuvette or another flow cell, for example some other micro fluidic cell.

[0191] In the present embodiment, the cartridge 30 comprises a conductivity sensor unit 5 having two conductivity sensor spots 5a, 5b and a gas sensor unit 6 positioned in the channel 4 to probe the fluids, which pass by the sensors 5, 6. The sensors 5, 6 are connected to a controller 40. The controller 40 may control the sensor units 5, 6 and / or process the data, which are collected using the sensor units 5, 6. The conductivity sensor unit 5 is based on electrochemical measurement principles and the gas sensor unit 6 can be based on optical measurement principles or on electrochemical measurement principles. In the present example, only two sensor units 5, 6 are shown, however, typically more than two sensor units or sensors are provided in the cartridge 30. Therefore, one, two or more of the sensors or sensor units, which are typically provided in a cartridge may be used to determine the property of a sample fluid 2 derived from the temporal evolution of the collected data / values.

[0192] It may also be that the IVD analyzer 10 does not comprise a gas sensor unit 6 or the cartridge 30 does not comprise a gas sensor unit 6. In the latter case, a gas sensor unit 6 may be positioned outside the cartridge 30 in another unit. Particularly in the case, when the IVD analyzer does not comprise a gas sensor unit 6, the local pressure state and / or the property of the sample fluid 2 may be determined or identified by means of the conductivity sensor unit 5 alone. However, even if a gas sensor unit 6 is provided in the IVD analyzer 10, the property of the sample fluid may be determined or identified by means of the conductivity sensor unit 5 alone. Alternatively, it may also be that the IVD analyzer does not comprise or make use of a conductivity sensor unit 5. Then, the property of the sample fluid 2 may be determined or identified by means of the gas sensor unit 6 alone.

[0193] Fig. 3a, Fig. 3b and Fig. 3c illustrate the channel cross section (area) of a channel 4 as it may be present in a cannel 4 of a cartridge 30 that is illustrated in the schematic drawings of Fig. 2a and Fig. 2b. In Fig. 3a a schematic drawing of the channel cross section is shown under relaxed conditions, for example under ambient conditions, in which substantially no underpressure or overpressure is applied to the channel 4. In Fig. 3b, a photograph of a real cross section of a channel 4 is illustrated under relaxed conditions. In Fig. 3c, a photograph of the cross section of the same channel 4 is illustrated under conditions, in which the pressure is reduced and an underpressure is applied to the channel 4.

[0194] In the embodiments illustrated in Fig. 3a, Fig. 3b and Fig. 3c, the channel 4 of a cartridge is formed by a first plate 7, which may be considered an upper plate, and a second plate 8, which may be considered a lower plate, as well as a resilient seal element 9 or several resilient seal elements 9. In more detail, the first plate 7 comprises a first surface 7a, namely an upper surface of the channel 4 and the second plate 8 comprises a second surface 8a, namely a lower surface of the channel 4. The resilient seal element(s) 9 comprise(s) a small section of the surface of the channel 4, namely a side surface of the channel 4.

[0195] When the pressure drops, for example an underpressure is generated and applied to the channel 4, a portion of the resilient seal element(s) 9 is sucked into the inner volume of the channel 4, which can be seen when comparing the regions indicated by the white circles in Fig. 3b and Fig. 3c. As a result, the cross section of the channel 4 is reduced when an underpressure is applied as indicated in Fig. 3c in comparison with the cross section of the channel 4 under a relaxed condition as indicated in Fig. 3b. The conductivity parameter, such as the admittance, which is measured in the channel 4, is sensitive to this change in cross section and can therefore serve as a probe for the local pressure state and / or the property of the sample.

[0196] Together with Fig. 3a-3c and Fig. 2a and Fig. 2b, the concept of the method according to an embodiment, for which the conductivity sensor unit 5 is used to determine a property and / or state in the sample fluid and / or a local pressure state, may be described in more detail, as follows.

[0197] In Fig. 2a, the fluidic system 35 is in a state, in which the first fluid 1, which may for example be a standby solution is already filled in the channel 4 of the cartridge 30 and the sample fluid 2 is already aspirated in the fluidic system 35 but not yet inside the channel 4 of the cartridge 30. Specifically, a large portion of the fluidic system 35 may be filled with the first fluid 1. In other words, in the state illustrated in Fig. 2a, the first fluid 1 is already aspirated into the channel 4 of the cartridge 30, namely behind the channel entrance 4a (or entrance port of the cartridge 30) while the sample fluid 2 has not yet passed the channel entrance 4a of the cartridge 30. In this exemplary state, the first fluid 1 is not yet in contact with any of the sensors 5, 6, particularly the first fluid 1 is not yet in contact with the conductivity sensor unit 5, which consists of two conductivity spots 5 a, 5b shown in Fig. 2a and 2b. The first fluid 1 and the sample fluid 2 are separated by an air bubble 3a. The sample fluid 2 may be followed by another air bubble 3c. The air bubbles 3a, 3b may each be considered a third fluid.

[0198] In the situation shown in Fig. 2a, the set of conductivity parameter values in the first fluid 1 (specifically a liquid) and / or the set of partial pressure values of gas in the first fluid 1 (specifically a liquid and / or a gas bubble) may be recorded, as the sensors 5, 6 are contacted with the first fluid 1. In other words, the fluidic system 35 is in a state, in which the first fluid 1 contacts both conductivity sensor spots 5a, 5b of the conductivity sensor unit 5 and the gas sensor unit 6 while the sample fluid 2 is has not reached the channel 4 of the cartridge 30, specifically the channel entrance 4a, yet. If the controller 40, which receives and processes these data identifies or determines a temporal evolution in these values, which indicate that the sample fluid 2 is problematic as it contains clots or other particles, it may initiate or trigger the reverse rotation of the peristaltic pump 11 to spit out the problematic sample fluid 2. If the controller 40 identifies that the sample fluid 2 behaves as expected and unproblematic, the sample fluid 2 may pass the channel 4 of the cartridge 30, which is shown in Fig. 2b.

[0199] In Fig. 2b, the first fluid 1 is pumped across the exit port 4b of the cartridge 30 towards a discharge container. The separation bubble 3a and the blood sample (sample fluid 2) have entered the channel 4 of the cartridge 30 after passing the entrance port 4a of the cartridge 30. The sample fluid 2 was allowed to enter the channel 4 after it was identified as not being a problematic sample fluid 2, i.e. not containing any clots or particles / aggregates. The sample fluid 2 may therefore be analyzed using the original functions of the sensor units 5, 6 in the channel 4 of the cartridge 30. Specifically, the blood gas parameters of interest may be determined in this configuration. If the sample fluid 2 would have been identified as being problematic in the state of Fig. 2a, the pump 11 and the flow of the fluids would have been reversed to discharge the problematic sample 2 from the fluidic system 35.

[0200] It is also noted that the conductivity changes when the air bubble 3a arrives at the sensor spots 5a, 5b. In that case, the conductivity typically drops sharply and is therefore very specific for this event.

[0201] In the following, the method according to several embodiments is further described together with the flow charts of Fig. 4a to Fig. 7 and the time tables of Fig. 8a and Fig. 8b. Fig. 4a is a flow chart of a method 100 of determining a property of a sample fluid 2 in an IVD analyzer 10 using a conductivity sensor unit 5 according to an embodiment. Fig. 4b is a flow chart of a method 300 of determining a local pressure state in an IVD analyzer 10 using a conductivity sensor unit 5 according to an embodiment. Fig. 5 is a flow chart of the method 100 of determining a property of a sample fluid 2 in an IVD analyzer 10 using a conductivity sensor unit 5 according to a further embodiment. Fig. 6 is a flow chart of the method 100 of determining a property of a sample fluid in an IVD analyzer using a conductivity sensor unit 5 and a gas sensor unit 6 according to another embodiment. Fig. 7 is a flow chart of a method 200 of determining a property of a sample fluid 2 in an IVD analyzer 10 using a gas sensor unit 6 according to an embodiment. The methods 100, 200, 300 according to one or more of the embodiments may be compatible with the above described fluidic system(s) 35 and therefore, the methods 100, 200, 300 described in view of Fig. 4a to Fig. 7 may be combined with the fluidic systems 35 described in Fig. 1 to Fig. 3a-c.

[0202] Fig. 4a refers to a method 100 of determining the property of the sample fluid 2 in the IVD analyzer 10 by primarily using the conductivity sensor unit 5. The method 100 comprises the following steps: a. introducing 110a the first fluid 1 into the fluidic system 35 of the IVD analyzer 10, specifically into a channel 4 of the fluidic system 35, wherein the fluidic system 35 comprises the channel 4 and the channel 4 may be part of a cartridge and comprises the resilient seal element 9 and is at least partially sealed by the resilient seal element 9 configured to change the cross section of the channel in response to the change in a local pressure state when a sample fluid 2 is aspirated b. introducing 110b the sample fluid 2, which is spatially separated from the first fluid 1 into the fluidic system 35 c. physically contacting 120 the conductivity sensor unit 5, i.e. physically contacting 120 at least two conductivity sensor spots 5 a, 5b of the conductivity sensor unit 5 in the channel 4 with the first fluid 1 d. detecting 130 and / or recording the set of conductivity parameter values, such as the admittance of the first fluid 1 during the conductivity detection time span cdts (as indicated in Fig. 8a and Fig. 8b) using the conductivity sensor unit 5 wherein the conductivity parameter values are dependent from the cross section of the channel and e. automatically determining 150 of the property of the sample fluid 2 based on the detected set of conductivity parameter values of the first fluid, which is dependent from the pressure. Above described steps a. 110a and b. 110b of the method 100 may respectively correspond to an aspiration of the first fluid 1 and / or the sample fluid 2. Step e. 150 is automatically performed by a controller, a processor and / or a machine. Steps a., b. c. and d. (110a, 110b, 120, 130) may be performed at the same time. At least some of these steps 110a, 110b, 120, 130 may overlap each other. Step a. 110a and step b. 110b are typically not started at the same time, as the first fluid 1 is introduced before the sample fluid 2 and then both fluids 1 and 2 are introduced together further into the fluidic system 35, at the same time. At least some of these steps may also follow each other instead of overlapping each other. The possibility that all of the steps a. to d. (110a, 110b, 120, 130) may be performed at the same time is indicated in Fig. 4a by the boxes corresponding to the steps being arranged next to each other. Step e. 150 may follow the steps a. to d. (110a, 110b, 120, 130), which is indicated by the arrows in Fig. 4a. Step e. may partially overlap one or all of the steps a. to d. (110a, 110b, 120, 130). This also applies to the other flow charts.

[0203] Fig. 4b refers to an alternative method 300, namely a method of determining the local pressure state in the channel 4 in the IVD analyzer 10 wherein the method 300 comprises the following steps: a. introducing 310 the first fluid into the fluidic system 35 of the IVD analyzer 10, specifically into a channel 4 of the fluidic system 35, wherein the channel 4 comprises the resilient seal element 9 configured to change the cross section of the channel in response to the change in the local pressure b. contacting 320 the conductivity sensor unit 5 in the channel 4 with the first fluid 1 c. detecting 330 one or more conductivity parameter values of the first fluid 1 using the conductivity sensor unit 5 wherein the conductivity parameter values are dependent from the cross section of the channel 4 d. determining 340 the local pressure state from the detected one or more conductivity parameter values.

[0204] The method 300 outlined in Fig. 4b deviates from the method 100 outlined in Fig. 4a as the pressure state in the channel 4 is determined instead of the property of the sample fluid 2. Method 300 may however also be comprised by method 100 and therefore, most advantages that apply to the corresponding steps of method 100 also apply to the method 300. Further, the method 300 may be combined with features of the embodiments of method 100. In method 300 the local pressure state is determined wherein the conductivity parameter is used as a probe to determine a local pressure state for example in a cartridge 30, while in method 100, the state of a sample fluid is derived from a time evolution of a local pressure state that is obtained from a set of conductivity parameter values of a first fluid. It may be required that the relation between the conductivity and the pressure state is determined in a calibration for each channel or for a representative one of a batch of channels and / or cartridges.

[0205] Fig- 5 refers to the method 100 of Fig. 4a having additional optional steps. The step of automatically determining 150 comprises in the method of Fig. 5 an optional step of applying 155 a trained artificial neural network on the determined temporal evolution of the local pressure state to determine the property of the sample fluid. In that case, the method 100 may further also comprise an optional step of training 105 the artificial neural network using a training data set comprising (the temporal evolution of) the conductivity parameter values corresponding to predefined states of the sample fluid 2. The training 105 is typically performed before the actual measurement is initiated, being started with one or all of the steps 110a, 110b, 120 and 130.

[0206] For example, the (main) training might performed by the producer or retailer of the consumable (like the cartridge) and the trained neural network might then be provided to the customer. Additional partial training of the neural network could be done on the customer side during the startup phase to fine-tune it for the individual cartridge. Ideally, this could be done without additional workflows - but rather based on observing values during standard workflows that would have to be performed during the startup phase anyway.

[0207] Alternatively or in addition, the method 100 may comprise a step of automatically triggering 160 of an action in the IVD analyzer 10 based on the determined property of the sample fluid 2. The action may comprise at least one of the following steps 165: when a problematic sample fluid 2, that contains clots for example, is identified:

[0208] • stopping the step of introducing 110a, 110b the first fluid 1 and / or the sample fluid 2

[0209] • reversing an operation direction of a pump

[0210] • discharging the sample fluid 2

[0211] • introducing a washing solution and washing the channel at least partially with the washing solution

[0212] • optically and / or acoustically outputting an alarm when a sample fluid 2 is identified, that is not problematic:

[0213] • continuing the step of introducing 110a, 110b the first fluid 1 and / or the sample fluid 2

[0214] • optically and / or acoustically outputting a control signal, such as a green light or a noise that confirms that the sample fluid 2 is not problematic. Fig. 6 refers to the method 100 of Fig. 4a having additional optional steps. The method of Fig. 6 having some or all of the optional steps may be combined with some or all of the steps outlined in Fig- 5. The method 100 of Fig. 6 comprises some or all of the following optional steps:

[0215] • detecting 230 a set of partial pressure values of gas in the first fluid 1 or in a third fluid 3a, 3b (e.g. air bubble) during a gas detection time span odts (as shown in Fig. 8a and Fig. 8b) using a gas sensor unit 6, specifically detecting 230 a set of partial pressure values of oxygen in the first fluid 1 or in a third fluid 3a, 3b (e.g. air bubble) during an oxygen detection time span odts (as shown in Fig. 8a and Fig. 8b) using an oxygen sensor unit 6

[0216] • automatically determining 250 the property of the sample fluid 2 based on the temporal evolution of the partial pressure values of gas and

[0217] • optionally comparing 260 the property of the sample fluid 2 determined from the detected set of partial pressure values of gas and the property of the sample fluid 2 determined from the detected set of conductivity parameter values.

[0218] If it can be identified based on the detected set of partial pressure values of gas that the sample fluid is problematic, the detected set of conductivity parameter values may also be used to derive the property of the sample fluid 2 to confirm the result. If the result cannot be confirmed, an action may be triggered. For example, a further measurement of conductivity parameter values and / or partial pressure of gas may be performed. Alternatively or in addition, the step of introducing 110a, 110b the first fluid 1 and / or the sample fluid 2 may be stopped by stopping the pump 11 and / or an alarm may be initiated to inform a user of a potential problem.

[0219] Fig. 7 refers to a method 200 of determining the property in a sample fluid 2 in the IVD analyzer 10 by primarily using the gas sensor unit 6. The method 200 comprises the following steps: a. introducing 210a the first fluid 1 into the fluidic system 36, specifically the channel 4 of a cartridge of the fluidic system 36 in an IVD analyzer 10 b. introducing 210b the sample fluid 2, which is spatially separated from the first fluid 1 into the fluidic system 36 c. detecting 230 the set of partial pressure values of gas in the first fluid 1 during the gas detection time span odts using the gas sensor unit 6, specifically detecting 230 the set of partial pressure values of oxygen in the first fluid 1 during the gas / oxygen detection time span odts using the oxygen sensor unit 6 d. automatically determining 250 the property of the sample fluid 2 based on the temporal evolution of the detected set of partial pressure values of gas. The method 200 of Fig. 7 may also comprise the optional steps 105, 155 related to the training of and the processing performed by the neural network as described together with Fig. 5. Alternatively or in addition, the steps 160, 165 may be comprised by the method 200 as described already together with Fig. 5.

[0220] Fig. 8a and Fig. 8b are schematic time tables for the detection time spans cdts, odts with respect to the introduction time span its according to embodiments of the application. The conductivity detection time span cdts and / or the gas detection time span odts may start before the introduction time span its, when the sample fluid 2 is introduced into the fluidic system 35, particularly when it is aspirated into the fluidic system 35, as indicated by Fig. 8a. The conductivity detection time span cdts and / or the gas detection time span odts may even start before or at the same time when the sample fluid 2 is introduced into the fluidic system 35 of the IVD analyzer. Therefore, the detection time span cdts and / or odts may start when the sample fluid 2 is still in a vial before it enters the fluidic system 35 of the IVD analyzer 10. The conductivity detection time span cdts and / or the gas detection time span odts may particularly start before the pump 11 is started.

[0221] The conductivity detection time span cdts and / or the gas detection time span odts may start together with the introduction time span its, when the sample fluid 2 is introduced into the fluidic system 35, as indicated by Fig. 8b. The conductivity detection time span cdts and / or the gas detection time span odts may particularly start in the moment when the pump 11 is started.

[0222] Fig- 9 is a photographic illustration with added scheme and annotations of a cartridge 30 that may be used in an IVD analyzer 10, specifically in a fluidic system 35 such as the one shown Fig. 1 and / or the IVD analyzer 10, which is schematically illustrated in Fig. 2a and Fig. 2b. In Fig. 9, ellipses and lines in the added scheme indicate positions, where blood gases (dashed line), electrolytes (solid lines), and metabolites (dashed and dotted line) are detected by the according sensors. Further, conductivity spots K1-K6 (indicated by arrows) are shown. One or more of the conductivity spots KI -K6 may be used to detect the conductivity parameter values in the method(s) of one or more of the embodiments, in which a conductivity sensor unit 5 is used. The conductivity spots KI and K2 (5a, 5b) may constitute a first conductivity sensor unit 5. In a later stage possibly, the conductivity spots K2 and K3 (5a, 5b) may constitute a second conductivity sensor unit 5.

[0223] One or more of the sensors, which are used to measure the blood gases may be used to detect the partial pressure of gas in the method(s) of one or more of the embodiments, in which a gas sensor unit 6 is used. Specifically, the oxygen sensor units 6 may be used to detect the partial pressure of oxygen in an air bubble or a liquid.

[0224] Fig. 10 is a recording of the conductivity parameter of the first fluid 1 taken by the conductivity sensor unit 5 as an example for a conductivity measurement. The conductivity parameter corresponds to the admittance in this recording and is plotted in pS against the time in s. Figure 10 was recorded in a similar setting as described together with Fig. 1 with a rotary valve. The pump 11 is started (indicated by the arrow and the letter “a”) and in response the channel 4 contracts and the admittance drops dramatically - the pump 11 is stopped (indicated by the arrow and the letter “b”) and the channel 4 extends and the admittance increases to a baseline value of 85,2 pS. The pump 11 is started three times in the presented recording. The short rise in admittance before the drop is due to a switch in the rotary valve, which was performed in this measurement. The conductivity parameter values were detected in the sensor cartridge 30 (Cobas bl23). When the pump 11 is started (indicated by “a”), an underpressure is generated and the resilient seal element 9 moves inwards into the channel 4, reducing the area of the channel cross section. A strong decrease in admittance can be observed in this case.

[0225] Alternatively or in addition, a gas sensor unit 6, which corresponds to an optical gas sensor unit spot in the cartridge 30 shown in Fig. 9 may be used to determine the partial pressure of a gas such as oxygen (02) and / or carbon dioxide (CO2) in the channel 4 and particularly the property of the sample fluid 2. The sensor cartridge 30 shown in Fig. 9 features an optical oxygen sensor unit spot, which measures the partial pressure of oxygen in air and in liquids. The principle of measurement is based on the effect of dynamic luminescence quenching by molecular oxygen. The partial pressure of gas measured is directly dependent on the local pressure. Therefore, the oxygen sensor unit 6 can be used as an indirect pressure sensor while being in a medium with a known oxygen concentration, e.g. a standby solution and / or air.

[0226] Optical gas sensor units are highly sensitive and react fast to pressure changes. Additionally, a gas sensor unit may be less dependent on the changing material properties and manufacturing tolerances of the soft material of the resilient seal element. Conductivity parameter measurements may complement the measurements of the partial pressure of gas very well. It may however be that the response of the resilient seal element is regarded, which makes the detection somewhat slower.

[0227] Fig. 11 is a photographic illustration with an added scheme and annotations of the cartridge 30 of Fig. 9 to illustrate the sample positioning with respect to the conductivity sensor units 5 and the gas sensor units 6 and Fig. 12 b) is a corresponding photographic illustration in which a problematic sample fluid 2 blocks the channel 4. The cartridge 30 shown in Figs. 9, 11 and 12 have both sensor types, conductivity sensor units 5 and gas sensor units 6 and therefore, the property of the sample fluids may be determined by means of one or more of both of the detector types. Further, the cartridge 4 comprises a main channel 4 for introducing a first fluid 1 and a sample fluid 2 and a reference channel 33 for introducing a reference solution.

[0228] The measurement principle according to an embodiment will be described with respect to Fig. 11 and Fig. 12 in further detail. Both sensors types (conductivity and gas, i.e. oxygen here) are used together to provide reliable data to determine whether there is a clot or not. Using both sensor types may also prevent errors induced by changes, which occur when a first fluid 1 passes the sensors 5, 6 followed by an air bubble (or any other third fluid) being followed by the sample fluid 2.

[0229] For example, such changes may occur when a standby solution (first fluid 1) is followed by a gas separation bubble (third fluid 3a), which separates the space between the standby solution (first fluid 1) and the blood sample (sample fluid). For example, when the standby solution is pumped towards the exit port 4b of the cartridge 30, a separation bubble and a blood sample may enter the cartridge 30.

[0230] Two conductivity sensor spots (e.g. K1K2, K2K3, K3K4, and K4K5), which are used to measure the conductivity parameter between them, may be considered as being one conductivity sensor unit 5.

[0231] In Fig. 11 a), the main channel 4 is filled with a standby solution (first fluid 1) and the reference channel is filled with a reference solution and the following determinations are made by means of the sensors:

[0232] - K1K2 (constituting a first conductivity sensor unit): “normal” standby conductivity

[0233] - K2K3 (constituting a second conductivity sensor unit): “normal” standby conductivity

[0234] - K3K4 (constituting a third conductivity sensor unit): “normal” standby conductivity

[0235] - K4K5 (constituting a fourth conductivity sensor unit): “normal” standby / ref conductivity (reference conductivity refers to the conductivity of the reference solution, see also Fig. 9)

[0236] - 02 (oxygen sensor unit 6): Standby oxygen level.

[0237] In Fig. 11 b), the main channel 4 is filled with a standby solution (as first fluid 1), an air bubble (as third fluid 3a) and blood (as sample fluid 2) and the reference channel is filled with a reference solution and the following determinations are made by means of the sensors:

[0238] - K1K2 (constituting a first conductivity sensor unit): very low conductivity (air bubble)

[0239] - K2K3 (constituting a second conductivity sensor unit): “normal” standby conductivity

[0240] - K3K4 (constituting a third conductivity sensor unit): “normal” standby conductivity

[0241] - K4K5 (constituting a fourth conductivity sensor unit): “normal” standby / ref conductivity

[0242] - 02 (oxygen sensor unit 6): Standby oxygen level.

[0243] When the separation bubble reaches the conductivity spot KI, the conductivity between KI and K2 drops sharply, but not to zero as there is still conductivity from the liquid film (Fig. 11 b)). The conductivity between the other pairs of conductivity spots remains on the “normal” standby solution level of the conductivity parameter.

[0244] In Fig. 11 c), the main channel 4 is filled with a standby solution (as first fluid 1), an air bubble (as third fluid 3a) and blood (as sample fluid 2), wherein the fluids are transported further across the channel 4 compared to Fig. 11 b). The reference channel is filled with a reference solution and the following determinations are made by means of the sensors:

[0245] - K1K2 (constituting a first conductivity sensor unit): very low conductivity (air bubble)

[0246] - K2K3 (constituting a second conductivity sensor unit): very low conductivity (air bubble)

[0247] - K3K4 (constituting a third conductivity sensor unit): “normal” standby conductivity

[0248] - K4K5 (constituting a fourth conductivity sensor unit): “normal” standby / ref conductivity

[0249] - 02 (oxygen sensor unit 6): lower oxygen level (blood).

[0250] When the air separation bubble moves further along the channel 4, covering conductivity spot K2, the conductivity also drops for the sensor pair K2K3. When the air separation bubble between the standby solution and the sample fluid enters the cartridge 30, the positions of the sensors K4, K5 of the sensor pair K4K5 (Main channel 4 -Reference channel 33) may be considered the optimal positions to evaluate the conductivity with the objective of clot detection, because K4 is the last spot to be covered by the air bubble. When measuring conductivity changes for one of the conductivity spot pairs after the other, it may be derived therefrom that these are caused by a separation air bubble. For a normal measurement workflow, i.e. when the sample fluid 2 is not problematic, the gas sensor unit 6 will first detect the standby solution oxygen level, then air and then blood oxygen level.

[0251] In Fig. 11 c), the main channel 4 is filled with blood (as sample fluid 2) and the standby solution (as first fluid 1) and the air bubble (as third fluid 3 a) are transported out of the channel 4. The reference channel is filled with a reference solution and the following determinations are made by means of the sensors:

[0252] - K1K2 (constituting a first conductivity sensor unit): “HCT dependent” blood conductivity

[0253] - K2K3 (constituting a second conductivity sensor unit): “HCT dependent” blood conductivity

[0254] - K3K4 (constituting a third conductivity sensor unit): “HCT dependent” blood conductivity

[0255] - K4K5 (constituting a fourth conductivity sensor unit): “HCT dependent” blood / ref conductivity

[0256] 02 (oxygen sensor unit 6): lower oxygen level (blood). In view of the above, blood generally has a lower oxygen level. However, for patients under artificial aspiration with pure oxygen, the oxygen level can also be higher than the air or standby oxygen level.

[0257] Fig. 12 a) corresponds to Fig. 11 a), however in a situation when it may be determined that the blood sample is problematic and must not enter the channel 4 of the cartridge 30. This determination might be performed conventionally by a timeout measurement or according to one of the above-described embodiments based on the measurement of the conductivity parameter values and / or the partial pressure of gas. In Fig. 12 b), a problematic sample fluid 2, namely a blood sample with clots blocks the flow through the channel 4. The blood has not reached the channel 4 yet but the fluids cannot further flow as the pressure cannot further transport these fluids through the channel 4 and the entire fluidic system 35. This situation should be efficiently avoided by the present invention.

[0258] If there is a clot in the sample fluid, which blocks the flow as shown in Fig. 12 b), the standby solution will remain in the cartridge 30 and the pressure will decrease. This pressure drop is immediate and directly visible in the sensor values. Unlike in the previous example of Fig. 11, the pressure drop acts on all conductivity sensor pairs simultaneously and is therefore distinguishable from the effects of a separation bubble. Evaluating data from the conductivity spots and from the gas sensor unit spot at the same time increases the reliability of the method.

[0259] In case of a clot in the sample fluid 2, the gas sensor unit 6 will detect a drop in partial pressure of gas. Depending on the altitude above sea level of the instrument and on the flow resistance of the blood sample, the pressure in the separation bubble 3a and therefore also the partial pressure of gas / oxygen in the separation bubble varies. It can be lower than the partial pressure of gas / oxygen in the standby solution and can therefore also lead to a drop in the reading of the gas / oxygen sensor unit 6.

[0260] As an example for this scenario, in Fig. 12 b), the main channel 4 is filled with a standby solution (first fluid 1) and the reference channel is filled with a reference solution and the following determinations are made by means of the sensors:

[0261] - K1K2 (constituting a first conductivity sensor unit): low conductivity (lower pressure)

[0262] - K2K3 (constituting a second conductivity sensor unit): low conductivity (lower pressure)

[0263] - K3K4 (constituting a third conductivity sensor unit): low conductivity (lower pressure)

[0264] - K4K5 (constituting a fourth conductivity sensor unit): low conductivity (lower pressure)

[0265] - 02 (oxygen sensor unit 6): lower partial pressure of oxygen (lower pressure) Referring again to Fig. 1, the principle of determining the viscosity and / or a range, in which the viscosity lies is described according to one embodiment. In addition or alternatively to the determination of whether clots are present or absent in a sample fluid, the method(s) according to the first and / or second embodiment(s) may be used to determine the viscosity of the sample fluid. The viscosity of a blood sample may serve as an indicator for a disease and therefore has a clinical relevance. For example, the Hyperviscosity syndrome (HVS), which relates to very high blood viscosities, corresponds to an oncological emergency, and timely treatment can prevent lifethreatening complications such as thromboembolic events, myocardial infarction, and catastrophic ischemia that result in multiple organ failure. Therefore, an IVD analyzer, which may for example comprise a blood gas analyzer, may provide the additional function of indicating diseases and / or emergencies caused by high blood viscosities. This combination is specifically advantageous as the BGE point of care analyzer is often situated in emergency rooms and / or intensive care units - places where critical patients will appear first and who will profit from a faster and / or integrated analysis of such a critical situation.

[0266] The detection of blood clots (which completely block the flow in the fluidic system of a BGE analyzer) is indicated by a sharp decrease of the pressure in the fluidic system when aspirating a sample with clots into the fluidic system. In the following, a possibility to determine the viscosity of sample fluids such as whole blood samples in a point of care BGE analyzer is described. No additional measurement steps (in addition to the method according to the first and / or second aspect) and / or instruments and no changes in the system are required.

[0267] The fluidic system 35 can be calibrated for pressure measurements, while using the fluidic system 35 for normal sensor calibration processes. The fluidic system 35 is configured to transport / guide different reagents of known and / or different viscosities, for example, the viscosity of reagents can be modified deliberately to serve the purpose of calibrating the fluidic system 35 for pressure and / or viscosity measurements. The (metal) needle 27 of the Sample Input module (SIM) 21 has very tight tolerances in terms of the dimensions, whereas other parts of the fluidic system have larger tolerances in this respect. Therefore, the needle 27 of the SIM 21 is best suited for measuring the viscosity.

[0268] As a first step, the actual pump speed has to be measured using a known liquid, as for example a standby solution with a known viscosity at a known temperature (viscosity is temperature dependent). The Standby solution is aspirated through the fluidic system 35 and the two sensor points 25 may be used to determine the actual volumetric flow rate.

[0269] The flow rate may vary due to at least one of the following parameters and / or scenarios:

[0270] • the viscosity of the pumped liquid a counterpressure • variations in the peristaltic pump tube (material batch to batch variations, diameter batch to batch variations, wear of the peristaltic pump tube, environmental temperature)

[0271] • spatial tolerances between pump head and FTP consumable (the pump head may be situated inside the instrument and the peristaltic pump tube may be in the FTP, a consumable and separate component)

[0272] • Variations in the springs of the peristaltic pump head

[0273] • Fluidic resistance (diameters of channels in the consumable, undercuts, etc. . .)

[0274] The accuracy of the measurement of the actual pump speed suffers from at least one of the following:

[0275] • Inaccuracy of viscosity (temperature, batch dependent)

[0276] • Volume between sample sensors (tube diameter tolerances)

[0277] • Variation in distance between sample sensors

[0278] After the pump rate is determined, different fluids, specifically liquids of known viscosity can be aspirated through the fluidic system 35 at different known velocities, especially through the SIM needle 27 with tight diameter tolerances. With a known viscosity and a known velocity, the resulting pressure difference can be calculated using the following formulas:

[0279] (Formula 1) wherein for laminar flows in a circular tube, the Hagen-Poiseuille-law applies and

[0280] (Formula 2)

[0281] Wherein Re corresponds to the Reynolds number.

[0282] The reaction of the conductivity sensor units 5 and / or the gas sensor units 6 in the fluidic system 35 to the predetermined underpressure can be measured to calibrate the fluidic system 35 for measuring pressure values. The data needed for calibration can be collected using the “normal” calibration workflows of the system, without the need of additional workflows - in this case, the system would over time improve its ability to measure (partial) pressure values and thereby the sample viscosities. Alternatively, at the very beginning, a set of additional workflows could be performed to calibrate the fluidic system 35 for viscosity measurements before the first sample measurement.

[0283] When aspirating a whole blood sample, the sample enters the fluidic system 35 through the SIM needle 27 with very repeatable diameter tolerances (because it is made of steel). When pumping a sample fluid into the fluidic system 35, the fluidic resistance increases with the known distance into the fluidic system 35 and the unknown viscosity of the sample fluid 2. The fluidic resistance will cause underpressure, which can be measured by the calibrated system. With the measured temporal underpressure evolution, the viscosity of the sample can be estimated using the above formulas and / or using machine learning to account for uncertainities / complex geometries.

[0284] Modifications and variations of the disclosed aspects are also certainly 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 otherwise than as specifically devised in the above examples.

[0285] Particularly, it is to be understood that at least some of the drawings or parts are only schematic and provided as way of example only. Also the relationship between elements may be other than the one shown, whereas parts not relevant for the purpose of this disclosure have been omitted.

[0286] Also, reference throughout the preceding specification to "one aspect", "an aspect", "one example" or "an example", “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the aspect or example or embodiment is included in at least one aspect, example or embodiment. Thus, appearances of the phrases "in one aspect", "in one aspect", "one example" or "an example", “one embodiment” or “an embodiment”, in various places throughout this specification are not necessarily all referring to the same aspect or example or embodiment.

[0287] 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 or embodiments.

[0288] Reference list

[0289] 1 first fluid

[0290] 2 sample fluid

[0291] 3a third fluid, particularly gas / air bubble

[0292] 3b third fluid, particularly gas / air bubble

[0293] 3c third fluid, particularly gas / air bubble

[0294] 4 channel

[0295] 4a entrance port of the cartridge / channel entrance

[0296] 4b exit port of the cartridge

[0297] 5 conductivity sensor unit

[0298] 6 gas sensor unit

[0299] 7 first plate

[0300] 7a first surface of the channel

[0301] 8 second plate

[0302] 8a second surface of the channel

[0303] 9 resilient seal element

[0304] 10 In Vitro diagnostic (IVD) analyzer

[0305] 11 (peristaltic) pump

[0306] 12 sample container / vial

[0307] 13 optical detection unit, oxymetry module

[0308] 14 cuvette

[0309] 16 air

[0310] 17 fluid supply unit fluids provided from fluid containers inner input-port side sample sensor (system) sample input interface / module (SIM) fluidic line discharge container rotary valve / fluid-selection valve timeout measurement points / sensor points aspriarion needle first fluidic path second fluidic path cartridge sample input port waste reference channel outer input-port side fluidic system light source photodetector fluid- supply unit port common outlet port controller method of determining a state in a sample fluid in an IVD analyzer using a conductivity sensor unit training an artificial neural network a introducing a first fluid b introducing a second fluid contacting a conductivity sensor unit in the channel with the first fluid detecting a set of conductivity parameter values of the first fluid automatically determining the property of the sample fluid applying a trained artificial neural network on the determined temporal evolution of the local pressure state to determine the property of the sample fluid automatically triggering of an action triggered action method of determining a state in a sample fluid in an IVD analyzer using a gas sensor unit a introducing a first fluid b introducing a second fluid detecting a set of partial pressure values of gas in the first fluid automatically determining the property of the sample fluid method of determining a local pressure state in a channel in an IVD analyzer introducing a first fluid into the channel of the IVD analyzer contacting a conductivity sensor unit in the channel with the first fluid detecting one or more conductivity parameter values of the first fluid determining the local pressure state from the detected one or more conductivity parameter values cdts conductivity detection time span odts gas detection time span specifically oxygen detection time span without limitation its introduction time span

[0311] K1-K5 cartridge sensor conductivity spots

Claims

Patent Claims1. A method (100) of determining a property of a sample fluid in an IVD analyzer (10) comprising the following steps: at least once generating at least one change in a local pressure state inside a fluidic system (35) of the IVD analyzer (10), during the step of the at least once generating of the at least one change in the local pressure state, performing the steps: introducing (110a) a first fluid (1) into the fluidic system (35) driven by the at least one change in the local pressure state, wherein the fluidic system (35) comprises a channel (4) with a resilient seal element configured to change a cross section of the channel (4) in response to the change in the local pressure state; introducing (110b) a sample fluid (2) into the fluidic system (35) driven by the at least one change in the local pressure state, wherein the sample fluid (2) is spatially separated from the first fluid (1); driving by the at least one change in the local pressure state the first fluid (1) into a position of a conductivity sensor unit (5) in the channel (4) and contacting (120) the conductivity sensor unit (5) in the channel (4) with the first fluid (1); detecting (130) a set of conductivity parameter values of the first fluid (1) during a conductivity detection time span (cdts) using the conductivity sensor unit (5) wherein the conductivity parameter values are dependent from the cross section of the channel; and the method further comprising: automatically determining (150) the property of the sample fluid (2) based on the detected set of conductivity parameter values of the first fluid, wherein the property of the sample fluid (2) comprises: a problematic state, in which the sample fluid (2) comprises at least one of clots, particles of human tissue, aggregates and contaminations; or a viscous state, in which the sample fluid has a viscosity and / or lies in, below or above a predetermined viscosity range in which the sample fluid has a viscosity higher than 6mPas; or a normal state, in which the sample fluid does not comprise clots, particles of human tissue, aggregates and contaminations and has a viscosity lower than 6mPas.

2. The method (100) of claim 1, further comprising the steps:detecting (230) a set of partial pressure values of gas in the first fluid (1) or in a third fluid (3a, 3b) during a gas detection time span (odts) using a gas sensor unit (6); automatically determining (250) the property of the sample fluid (2) based on the detected set of partial pressure values of gas; comparing (260) the property of the sample fluid (2) determined from the detected set of partial pressure values of gas and the property of the sample fluid (2) determined from the detected set of conductivity parameter values and identifying whether or not the compared states of the sample fluid (2) are identical or similar.

3. A method (200) of determining a property of a sample fluid in an IVD analyzer (10) comprising the following steps: introducing (210a) a first fluid (1) into a fluidic system (35) with a channel (4) of the IVD analyzer (10); introducing (210b) a sample fluid (2), which is spatially separated from the first fluid (1) into the fluidic system (35); detecting (230) a set of partial pressure values of gas in the first fluid (1) during a gas detection time span (odts) using a gas sensor unit (6); and automatically determining (250) the property of the sample fluid (2) based on the detected set of partial pressure values of gas.

4. The method (100; 200) of any one of the preceding claims, wherein the step of automatically determining (150; 250) comprises applying (155) a trained artificial neural network on the detected set of conductivity parameter values of the first fluid (1) and / or the detected set of partial pressure values of gas in the first fluid (1) or in a third fluid (3 a, 3b) to determine the property of the sample fluid; and preferably, wherein the method (100; 200) further comprises: training (105) the artificial neural network using a training data set comprising a set of conductivity parameter values of the first fluid (1) and / or a set of partial pressure values of gas in the first fluid (1) or in the third fluid (3a, 3b) corresponding to pre-defined properties of the sample fluid (2).

5. The method (100; 200) of any one of the preceding claims, further comprising automatically triggering (160) an action in the IVD analyzer (10) based on the determined property of the sample fluid (2), preferably wherein, when the sample fluid (2) is in the problematic state, the action comprises at least one of the following steps (165):optically and / or acoustically outputting an alarm; stopping the step of introducing (110a, 110b) the first fluid (1) and / or the sample fluid (2); reversing an operation direction of a pump; discharging the sample fluid (2); introducing a washing solution and washing the channel at least partially with the washing solution; or wherein, when the sample fluid (2) is in the viscous or in the normal state, the action comprises the following step (165): continuing the step of introducing (110a, 110b) the first fluid (1) and / or the sample fluid (2), optically and / or acoustically outputting control signal.

6. The method (100; 200) of any one of the preceding claims, wherein the conductivity detection time span (cdts) and / or the gas detection time span (odts) overlaps at least partially with an introduction time span (its), in which the step of introducing (110) the sample fluid (2) into the fluidic system (35) is performed, preferably wherein the conductivity detection time span (cdts) and / or the gas detection time span (odts) starts before or at the same time with the introduction time span (its).

7. The method (100; 200) of any one of the preceding claims, wherein the introducing (110a, 110b) of the first fluid (1) and / or the sample fluid (2) into the fluidic system (35) comprises aspirating the first fluid (1) and / or the sample fluid (2).

8. The method (100; 200) of any one of the claims 2 to 7, wherein the detecting (230) of the set of partial pressure values of gas is based on an optical measurement principle.

9. The method (100; 200) of any one of the claims 2 to 8, wherein the detecting (230) of the set of partial pressure values of gas in the first fluid (1) is a detecting of the set of partial pressure values of gas in an air bubble or in a standby solution.

10. A fluid sensor system (20) for determining a state in a sample fluid in an IVD analyzer (10), the sensor system (20) comprises: a cartridge (30) with a channel (4) being connectable to a pump for creating a change in a local pressure state to drive a fluid (1, 2, 3 a, 3b) through the channel (4) of the cartridge (30); a conductivity sensor unit (5) inside the cartridge (30) configured to detect a conductivity parameter of a first fluid (1) and a sample fluid (2); and / ora gas sensor unit (6) configured to detect a partial pressure of gas in the first fluid (1) and the sample fluid (2); and a controller (40) configured to cause the IVD analyzer (10) to perform the steps of the method (100; 200) of any one of the preceding claims, wherein the cartridge (30) comprises: a first plate (7) that comprises a first surface (7a) of the channel (4); a second plate (8) that comprises a second surface (8a) of the channel (4); and a resilient seal element, which connects the first plate with the second plate and seals the channel at least partially, wherein the resilient seal element is configured to deform and thereby change a cross section of the channel in response to a change in a local pressure state.

11. The fluid sensor system (20) of claim 10, further comprising the pump, specifically wherein the pump is configured to generate an underpressure to drive the fluid (1, 2, 3a, 3 b) through the channel (4) of the cartridge (30).

12. The fluid sensor system of claim 10 or 11, wherein the first fluid (1) comprises a standby solution and / or wherein the sample fluid (2) comprises a body fluid preferably including blood.

13. A computer program product having instructions stored thereon, which cause a machine and / or controller of an IVD analyzer to initiate and / or perform the steps of the methods according to any one of claims 1 to 9.

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