Efficient, patient-friendly and environmentally 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 fluid

Abstract

The present invention relates to a method (100) for determining the properties of a sample fluid in an IVD analyzer (10), the method comprising the steps of: introducing (110a) a first fluid (1) into a fluid system (35) of the IVD analyzer (10), wherein the fluid system (35) includes a channel (4) having an elastic sealing element configured to change the cross-section of the channel (4) in response to a change in local pressure state; introducing (110b) a sample fluid (2) spatially separated from the first fluid (1) into the fluid system (35); contacting (120) a conductivity sensor unit (5) in the channel (4) with the first fluid (1); and using the conductivity sensor unit (5) to detect (130) the first fluid (1) during a conductivity detection time span (cdts). A set of conductivity parameter values, wherein the conductivity parameter values ​​depend on the cross-section of the channel; and the properties of the sample fluid (2) are automatically determined (150) based on the detected set of conductivity parameter values ​​of the first fluid. This invention can be considered efficient, environmentally friendly, and adds significant value to existing IVD fluid sensor systems. Importantly, patients benefit from the additional parameters available from the IVD system. Because this invention allows for adding value and functionality to existing IVD systems without adding additional components, it can be considered very environmentally friendly in the sense of a green invention.

Description

Technical Field

[0001] This invention relates to methods, fluid sensor systems, and computer program products for determining the properties of sample fluids, such as blood samples in the field of in vitro diagnostics (IVD). The invention can be considered efficient, environmentally friendly, and adds significant value to existing IVD fluid sensor systems. Because the invention allows for adding value and functionality to existing IVD systems without adding additional components, it can be considered very environmentally friendly in the sense of a green invention. Importantly, patients benefit from the additional parameters that can be provided by the IVD system. Background Technology

[0002] In medicine, doctors' diagnoses and patient treatments often rely on the measurement of patient sample parameters by IVD analyzers. Importantly, the analyzer must be efficient and operate smoothly and correctly, providing accurate and reliable measurements with minimal downtime. Therefore, a general requirement for IVD analyzers is to implement workflows that ensure analytical performance.

[0003] US 2023 / 304953 A1 describes, for example, a sensor assembly for an IVD analyzer, wherein the sensor includes two opposing substrates having at least one fluid conduit for receiving a sample. Different types of electrodes of the electrochemical sensor are arranged on the two opposing substrates, these electrodes facing at least one fluid conduit, for contacting the sample and determining sample parameters.

[0004] US 2022 / 196632 A1 describes a sensor device, a method of operating the sensor device, and an IVD analyzer for receiving the sensor device to determine the chemical and / or physical properties of a fluid. The sensor device includes at least two fluid conduits for repeatedly receiving fluid, each fluid conduit including at least one sensing element arranged such that it is in contact with the fluid in the respective fluid conduit.

[0005] US 2020 / 200731 A1 describes an apparatus for measuring blood clotting time, the apparatus including a blood clot detection instrument and a cuvette for use with the blood clot detection instrument. The cuvette includes: a blood sample receiver-inlet; a channel arrangement including: at least one test channel for measuring blood clotting time; a sampling channel having at least one hydrophilic surface portion communicating with the blood sample receiver-inlet and the at least one test channel; and a waste channel having at least one hydrophilic surface portion communicating with the sampling channel.

[0006] US 6,022,747 A describes a blood clot detector comprising: a pressure sensor on an aspiration line for providing output voltage data corresponding to a vacuum level to a microprocessor during aspiration; and a microprocessor that integrates the vacuum reading over time during an aspiration cycle to provide a pressure integral for each test sample aspiration.

[0007] However, introducing problematic sample fluid into the fluid system / channel system of an IVD analyzer is a source of error, causing instrument downtime and reducing accuracy and efficiency. Problematic sample fluid may, for example, contain clots, aggregates, and / or contaminants and / or foreign particles of human tissue cells in the range of tens of µm to several mm. As an example, blood samples may contain blood clots falling into this range, and therefore such blood samples are problematic for IVD analyzers such as blood gas-electrolyte (BGE) analyzers. If problematic sample fluid is introduced into the fluid system, it may be directed deep into the fluid system's channels, and if this sample fluid is identified at a later stage, removing it by reversing the flow direction of the pump may become difficult. The fluid system channels may subsequently become completely blocked, and fluid flow through the channels may become impossible.

[0008] If a problematic sample fluid is identified, the pump's operating direction is typically reversed to discharge the sample fluid. It is then desirable that the pump's operating direction reverse the flow of the problematic sample fluid and discharge it from the channel system. For example, the pump was previously operated in the direction of drawing sample fluid by applying negative pressure. When the operating direction is reversed, overpressure is generated to discharge the problematic sample fluid. Following this step, a flushing process can be performed on the channel system. Generally, the generation of overpressure can damage the channel system or other components, and therefore, it is preferable to identify the problematic sample fluid at a very early stage. Specifically, it is important that the problematic sample fluid be identified shortly after it is introduced into the channel system and / or even before the sample fluid enters the channel system of the cartridge, i.e., while the sample fluid is being drawn into the capillary or in the tubing connected to the channel system of the cartridge, specifically before the sample fluid reaches the timeout measurement point. Therefore, by generating "mild overpressure," i.e., pressure at a shorter duration and / or lower overpressure amplitude, compared to the pressure value required when the clot penetrates deeper into the channel system, the problematic sample fluid can be easily discharged. This reduces the risk of damaging the fluid channel system. Furthermore, this avoids the possibility of particles contaminating the system and permanently adhering to the fluid channels, making it impossible to clean the fluid channel system and wash out the particles. Therefore, it prevents particles from remaining adsorbed on the sensor, as these particles can still affect sensor performance even after most particles have been successfully washed out.

[0009] In addition to the difficulties described above, the partial pressure of a certain gas in the sample fluid may decrease in response to a decreasing negative pressure. This is likely to cause degassing of the sample fluid, which can distort the measurement results in blood gas analysis.

[0010] If such problematic sample fluids enter the channel system, the volumetric flow rate may decrease and / or the negative pressure generated by the pump may drop below the expected negative pressure for unproblematic sample fluids. However, there are also cases where the sample fluid does not contain clots, aggregates, and / or other particles, but still causes the flow rate and / or negative pressure to drop below the expected values ​​for unproblematic sample fluids. Such sample fluids may be harmless to the instrument but have high viscosity. Typically, highly viscous sample fluids are unlikely to clog the channel system and therefore may enter and pass through it.

[0011] Therefore, highly viscous sample fluids (also known as "viscous states") can enter and pass through the channel system without the risk of damage or distorted blood gas values, while problematic sample fluids should be evacuated to avoid damage and contamination. Thus, the distinction between these two categories and / or the determination of viscosity is preferred. Generally, it is preferable to provide efficient and rapid determination of viscosity.

[0012] As shown in Figure 1, if the sample fluid does not reach either the timeout measurement point or the sample sensor 25 after a predetermined timeout period longer than the time required for unaffected sample fluid to reach one of the sample sensors 25, the sample fluid is typically identified as problematic. Normally, when a timeout is detected—that is, when the sample fluid fails to reach the timeout measurement point after the predetermined timeout period—the pump stops. This prevents sample fluid with clumps (especially large clumps) from reaching the cartridge. However, it is possible that clumps are further fed into the fluid channel system, and the negative pressure increases as the flow rate decreases due to the sample fluid clogging the fluid channel system. The increasing negative pressure causes the clumps to move further into the system and makes it more difficult to remove the problematic sample fluid by reversing the flow direction. Furthermore, when the fluid channel system is blocked by sample fluid with clumps, microbubbles may leak into the system at connection points due to the negative pressure created in the fluid channel system (referred to as the "channel system"). If these microbubbles cannot be removed, they may cause other problems later, such as altered and distorted blood gas values, crystallization, etc.

[0013] Distinguishing between problematic and high-viscosity sample fluids is often difficult. To overcome this, the predetermined timeout period can be set to a shorter value. However, as a trade-off for better protection of the channel system, the loss of unproblematic sample fluids (which may have high viscosity) can be significant because they are incorrectly discharged, and thus the so-called "sample loss rate," and consequently the error rate, increases with a reduced predetermined timeout period. In other words, the predetermined timeout setting for the sample fluid to be tested is a balance between the sample loss rate of not obtaining results and error-driven consumable replacements (where the channel system cannot always be protected from blockage). Therefore, a decision must be made between further aspirating of sample fluid into the channel system with an increased risk of clumping (which could block the channel system and lead to "error-driven consumable replacements"), or setting a very strict time limit, which could result in a high sample loss rate. Thus, the timeout setting forms the basis of the trade-off between the degree of protection of the channel system and the sample loss rate. Summary of the Invention

[0014] Therefore, it is desirable to provide methods and apparatus for addressing the aforementioned technical challenges, specifically by providing rapid and early identification of the properties of sample fluids. It is also desirable to increase the probability of successfully removing problematic sample fluids without losing volume of unproblematic samples. Furthermore, it is desirable to provide a versatile fluid sensor system for IVD analyzers.

[0015] These challenges are at least partially overcome by methods, fluid sensor systems, and computer program products according to at least one embodiment of the embodiments described herein or covered by one of the dependent claims.

[0016] This invention is based on the concept of transforming one or more sensors already present in the fluid channel system of an IVD analyzer and primarily used for the direct measurement of one or more parameters of the sample fluid. Therefore, in addition to their original function, existing sensors in the cartridge can also be used to measure specific parameters indicating the state / characteristics / properties of the sample fluid. The measurement result is not obtained directly from the sample fluid itself, but from a precursor fluid referred to as the "first fluid." The first fluid can be a backup solution and / or a conductive aqueous solution, such as a buffer solution, introduced into the channel system before the sample fluid is introduced. The first fluid is isolated from the sample fluid by gas bubbles (such as air bubbles). In some cases, a gas bubble (which exhibits fluid behavior) can be considered the first fluid (or a third fluid, if the first fluid is a liquid).

[0017] Therefore, the determination of whether a sample fluid must be considered problematic and / or the determination of its viscosity can be made by probing a first fluid (which is a liquid and / or a gas). Thus, the determination is made indirectly at the location of the sensor, deep within the channel system, while the problematic sample fluid remains near the inlet of the fluid channel system. In other words, the sensor can determine whether a sample fluid can be considered problematic without physical contact with the sample fluid itself and / or without directly measuring parameters from the sample fluid.

[0018] The methods, fluid sensor systems, and computer program products described herein according to at least one embodiment may have at least one of the following advantages and / or technical effects:

[0019] Provides rapid and early determination / identification of the state (i.e., properties) of the sample fluid. The properties of the sample fluid can correspond to its physical properties / state in terms of viscosity and / or the presence / absence of aggregates, clumps, and / or particles. Specifically, it can be determined whether the sample fluid...

[0020] There is a problem because it contains clumps, aggregates, and / or particles;

[0021] No problem but high viscosity (also known as "viscous state"); or

[0022] No problems and no clumping and / or low viscosity.

[0023] The characteristics of a sample fluid may alternatively or additionally correspond to specific viscosity values ​​and / or viscosity ranges, and the presence or absence of clots, aggregates, and / or particles. Sample fluid characteristics may be specifically categorized as "problematic sample," "no problem but high viscosity," and "no problem and low viscosity." Sample fluid characteristics may alternatively or additionally include and / or correspond to a certain degree of coagulation. Coagulation is an important characteristic and / or parameter in combination with other cardiac parameters such as NT-proBNP and troponin T.

[0024] Furthermore, the likelihood of successfully removing the problematic sample fluid can be increased. The required overpressure load—the duration and magnitude of overpressure on the fluid channel system during the removal of the problematic sample fluid—can be reduced. The negative pressure load—the duration and magnitude of negative pressure on the fluid channel system if the problematic sample fluid moves further into the system—can be reduced. The risk of microbubble aspiration and / or degassing of the sample fluid at connection points due to abnormal negative pressure loads can be reduced, and thus distorted gas values ​​can be reduced or even avoided. Instrument downtime and / or the lifespan of consumables (such as cartridges) with fluid channel systems can be reduced. Furthermore, the number of components required in the channel system can be reduced because no additional pressure sensor is needed. Problematic sample fluids can be distinguished from non-problematic but high-viscosity sample fluids. These methods do not constitute the basis for a trade-off between the level of protection of the channel system and the sample loss rate. Therefore, the method offers high sensitivity and efficiency.

[0025] Furthermore, the method allows for the addition of functionality to IVD analyzers (which may correspond, for example, to blood gas analyzers) without requiring additional components and / or altering the structure of the IVD analyzer. Such additional functionality can correspond to indications of illness and / or life-threatening emergencies caused by blood clots and / or abnormal blood viscosity (specifically, high blood viscosity). As an example, blood gas analyzers, conventionally used to determine parameters related to blood gases, electrolytes, metabolites, and / or hematological parameters, could therefore additionally indicate thromboembolic events leading to multiple organ failure, myocardial infarction, and / or ischemia.

[0026] According to one aspect which can be considered a first aspect of this disclosure, a method for determining the properties of a sample fluid in an IVD analyzer includes the following steps:

[0027] At least once causing at least one change in the local pressure state within the fluid system of the IVD analyzer, and during the step of causing at least one change in the local pressure state, the following steps are performed:

[0028] A first fluid is introduced into a fluid system driven by at least one change in local pressure state, wherein the fluid system includes a channel with an elastic sealing element configured to change the cross-section of the channel in response to at least one change in local pressure state.

[0029] A sample fluid is introduced into a fluid system driven by at least one change in local pressure state, wherein the sample fluid is spatially separated from a first fluid;

[0030] The first fluid is driven to the position of the conductivity sensor unit in the channel by at least one change in the local pressure state, and the conductivity sensor unit in the channel is brought into contact with the first fluid.

[0031] A set of conductivity parameter values ​​for a first fluid is detected using a conductivity sensor unit during a conductivity detection time span, wherein these conductivity parameter values ​​depend on the cross-section of the channel (specifically, the detection begins shortly before or simultaneously with at least one of at least one changes causing a local pressure state (i.e., shortly before or simultaneously with starting (restarting) the pump)); and

[0032] The method further includes automatically determining the characteristics of the sample fluid based on a detected set of conductivity parameters of the first fluid, wherein the characteristics of the sample include:

[0033] In a problematic state, the sample fluid contains at least one of the following: clots, human tissue particles, aggregates, and contaminants; or

[0034] In a viscous state, the sample fluid has a viscosity and / or is within, below, or above a predetermined viscosity range, whereby the sample fluid has a viscosity higher than 6 mPas within the predetermined viscosity range; or

[0035] Under normal conditions, the sample fluid does not contain clots, human tissue particles, aggregates, or contaminants, and has a viscosity below 6 mPas, specifically between 2 mPas and 6 mPas.

[0036] The step of “causing at least one change in the local pressure state within the fluid system of the IVD analyzer” can refer to pump suction and causing a pressure change in the fluid system, i.e., overpressure or, more preferably, negative pressure. This step can refer to constant pump operation (constant means without interruption for a certain / predetermined period of time).

[0037] The step of “causing at least one change in the local pressure state within the fluid system of the IVD analyzer” can alternatively refer to multiple starts and stops of pump operation and / or pulsed pump operation and / or interrupted pump operation. Some pumps can be configured, for example, to operate in a pulsed manner. It is also possible to start and stop / pause the pump and then start it again to generate / form a negative pressure, where the negative pressure is not necessarily the same each time and may vary.

[0038] The step of “causing at least one change in the local pressure state within the fluid system of the IVD analyzer” can alternatively refer to the formation / generation of a negative pressure only once, simultaneously with the introduction of the first fluid and the sample fluid. Measurements (i.e., the step of detecting a set of conductivity parameter values ​​of the first fluid using a conductivity sensor unit during the conductivity detection time span) can then begin shortly before or simultaneously with the formation of the negative pressure. This can correspond to a situation where the conductivity detection time span and / or the gas detection time span at least partially overlap with the introduction time span in which the step of introducing the sample fluid into the fluid system is performed, preferably wherein the conductivity detection time span and / or the gas detection time span begin before or simultaneously with the introduction time span. However, this is clearly not a prerequisite for the method according to the first aspect, as the introduction time span can alternatively correspond to the time during which the first fluid and / or the sample fluid is drawn into the fluid system, and can then be stopped and restarted either simultaneously 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 using a conductivity sensor unit during the conductivity detection time span). To determine the characteristics of the sample fluid, it is only necessary to initiate the movement of the sample fluid within the fluid system, ideally before it enters the cartridge. Therefore, in a specific case, the step of “causing at least one change in the local pressure state within the fluid system of the IVD analyzer” could correspond to drawing the first fluid into the fluid system during the first pumping, then pausing the pump, and then initiating the drawing of the sample fluid into the fluid system again during the second pumping and shortly before or simultaneously with the second negative pressure generation.

[0039] Generally speaking, regardless of whether the pump is in constant operation, pulse pump operation, or interrupted pump operation, pump operation can be performed, for example, by using a suction pump (such as a vacuum pump and / or a peristaltic pump).

[0040] Ideally, when a set of conductivity parameters is measured, the sample fluid has not yet entered the cartridge or at least has not been drawn deep into the cartridge, to allow for prevention of entry (deep) into the cartridge if it corresponds to a problematic and / or highly viscous sample.

[0041] Before the step of measuring a set of conductivity parameters, the sample fluid can be clearly already drawn into the fluid system. Ideally, the measurement / detection of a set of conductivity parameters should begin shortly before pump startup to record the conductivity parameters as an indicator of the contraction behavior of the resilient sealing element, which in turn serves as an indicator of the flow behavior of the sample fluid.

[0042] Specifically, methods for determining the properties of sample fluids in an IVD analyzer may include the following steps:

[0043] Within the fluid system of the IVD analyzer, a negative pressure is generated at least once, for example by using a pump (specifically a suction pump). During the step of generating the negative pressure at least once, the following steps are performed:

[0044] Driven by the generation / formation of negative pressure, a first fluid is introduced and / or drawn into a fluid system, wherein the fluid system includes a channel with an elastic sealing element configured to change the cross-section of the channel in response to negative pressure.

[0045] The sample fluid is introduced into and / or extracted into the fluid system under the drive of the generation / formation of negative pressure, wherein the sample fluid is spatially separated from the first fluid;

[0046] The first fluid is driven to the position of the conductivity sensor unit in the channel by the generation / formation of negative pressure, and the conductivity sensor unit in the channel is brought into contact with the first fluid.

[0047] A set of conductivity parameter values ​​for a first fluid is detected using a conductivity sensor unit during a conductivity detection time span, wherein the conductivity parameter values ​​depend on the cross-section of the channel; and

[0048] The method further includes automatically determining the characteristics of the sample fluid based on a detected set of conductivity parameters of the first fluid, wherein the characteristics of the sample fluid include:

[0049] In a problematic state, the sample fluid contains at least one of clots, human tissue particles, aggregates, and contaminants; and / or

[0050] A viscous state, wherein the sample fluid has a viscosity and / or is within, below, or above a predetermined viscosity range, wherein the sample fluid has a viscosity higher than 6 mPas within the predetermined viscosity range; and / or

[0051] Under normal conditions, the sample fluid does not contain clots, human tissue particles, aggregates, or contaminants, and has a viscosity between 2 mPas and 6 mPas.

[0052] More specifically, methods for determining the properties of sample fluids in an IVD analyzer may include the following steps:

[0053] Within the fluid system of the IVD analyzer, a negative pressure is generated, for example, by using a pump (specifically a suction pump). During or overlapping with the step of generating the negative pressure, the following steps are performed:

[0054] Driven by the generation / formation of negative pressure, a first fluid is introduced and / or drawn into a fluid system, wherein the fluid system includes a channel with an elastic sealing element configured to change the cross-section of the channel in response to negative pressure.

[0055] The sample fluid is introduced into and / or extracted into the fluid system under the drive of the generation / formation of negative pressure, wherein the sample fluid is spatially separated from the first fluid;

[0056] The first fluid is driven to the position of the conductivity sensor unit in the channel by the generation / formation of negative pressure, and the conductivity sensor unit in the channel is brought into contact with the first fluid.

[0057] A set of conductivity parameter values ​​for a first fluid is detected using a conductivity sensor unit during a conductivity detection time span, wherein the conductivity parameter values ​​depend on the cross-section of the channel, specifically before or simultaneously with the step initiating the generation of negative pressure; and

[0058] The method further includes automatically determining the characteristics of the sample fluid based on a detected set of conductivity parameters of the first fluid, wherein the characteristics of the sample fluid include:

[0059] In a problematic state, the sample fluid contains at least one of clots, human tissue particles, aggregates, and contaminants; and / or

[0060] A viscous state, wherein the sample fluid has a viscosity and / or is within, below, or above a predetermined viscosity range, wherein the sample fluid has a viscosity higher than 6 mPas within the predetermined viscosity range; and / or

[0061] Under normal conditions, the sample fluid does not contain clots, human tissue particles, aggregates, or contaminants, and has a viscosity between 2 mPas and 6 mPas.

[0062] The method according to the first aspect has the potential to identify all three properties of the sample fluid listed above, and the sample fluid may be in at least one of the three properties or only one of the three properties.

[0063] In other words, a method is provided for determining the properties of a sample fluid in an IVD analyzer, and the method includes other steps consistent with the first aspect described above, as well as the following steps: introducing a first fluid into a fluid system of the IVD analyzer, wherein the fluid system includes a channel having an elastic sealing element configured to change the cross-section of the channel in response to a change in local pressure state; introducing a sample fluid spatially separated from the first fluid into the fluid system; contacting a conductivity sensor unit in the channel with the first fluid; detecting a set of conductivity parameter values ​​of the first fluid using the conductivity sensor unit during a conductivity detection time span, wherein the conductivity parameter values ​​depend on the cross-section of the channel; and automatically determining the properties of the sample fluid based on the detected set of conductivity parameter values.

[0064] The method described in the first aspect has the following technical effects and advantages:

[0065] This method allows for reliable, rapid, efficient, and early identification of the characteristics of a sample fluid when it is probing the first fluid at an early stage, such as shortly after and / or during sample fluid aspiration.

[0066] A fluid system, also known as a channel system, can correspond to the system of tubing, channels, pipes, and hoses in an IVD analyzer. Specifically, all fluid guiding elements of the fluid system (except for resilient sealing elements) can be substantially rigid in shape, meaning their shape is resistant to high pressure values ​​and / or external shocks. In other words, the elements of the fluid system (except for resilient sealing elements) are substantially “rigid,” meaning they do not change the volume of the fluid system with pressure, which is provided solely by the elasticity of the resilient sealing elements. Therefore, pressure changes and / or pressure variations are directly transmitted (to the channel) without being “damped” by flexible components (except for the resilient sealing elements). A further advantage of a rigid system can be accurate sample positioning. In another, but less preferred, embodiment, not all fluid guiding elements of the fluid system (excluding resilient sealing elements) are substantially rigid in shape. The term “channel” described herein can specifically correspond to the channel of a cartridge, which includes resilient sealing elements. In other words, pressure changes and / or pressure variations caused entirely by the elasticity of the elastic sealing element can only be reflected during a set of conductivity parameter values ​​of the first fluid over a conductivity detection time span, and the characteristics of the sample fluid can then be derived from the behavior / time evolution of the conductivity parameter values.

[0067] This method can correspond to the direct or indirect automatic determination of the characteristics of a sample fluid based on a set of detected conductivity parameter values. Specifically, the characteristic time evolution of conductivity parameters caused by pressure changes, i.e., the time change of conductivity parameters (representing the set of conductivity parameter values), can indicate the characteristics of the sample fluid. Problematic aspiration of sample fluid can be reflected in a specific (rapid) decrease in conductivity parameter values ​​(such as admittance), while high-viscosity sample fluids can be reflected in a slower decrease, because the fluid resistance causing the pressure drop is proportional to the amount of sample liquid in the fluid system / the length of the fluid path filled by the sample liquid.

[0068] A problem-free sample fluid with "normal" viscosity can be reflected in a low / slight decrease in conductivity parameter values. The specific temporal evolution of conductivity parameter values ​​can be used, for example, automatically to identify sample characteristics using fitting functions or neural networks. The recording of conductivity parameter values ​​begins from the moment when only the first fluid is present in the fluid system (providing a reference for conductivity parameter values) until the moment the sample fluid is introduced into the fluid system. The fluid system refers to the fluid piping / conduit system of the IVD analyzer. To protect the cartridge from problematic fluids, it is advantageous to identify the problematic sample fluid before introducing it into the cartridge's channels.

[0069] The direct determination can rely on the analysis of a set of detected conductivity parameters to determine / derive the characteristics of the sample fluid and / or classify the characteristics of the sample. The indirect determination can rely on the analysis of a set of detected conductivity parameters to determine another parameter, such as the pressure state at a specific location or in a specific portion of the channel. From the determined pressure state in the channel, the characteristics of the sample fluid can then be determined / derived and / or the characteristics of the sample can be classified.

[0070] Specifically, the direct and automatic determination of the characteristics of a sample fluid based on a set of detected conductivity parameters can be achieved through a neural network trained to determine, identify, and / or classify the characteristics of the sample fluid based on a set of conductivity parameters.

[0071] Therefore, in embodiments of the method described above, optional indirect determination may require the following steps:

[0072] A set of conductivity parameter values ​​for a first fluid is detected using a conductivity sensor unit during a conductivity detection time span, wherein the conductivity parameter values ​​depend on the cross-section of the channel;

[0073] The time evolution of the local pressure state was determined from a set of detected conductivity parameters; and

[0074] The characteristics of the sample fluid are automatically determined based on the determined time evolution of the local pressure state (which is indirectly based on a set of detected conductivity parameters).

[0075] Problematic sample fluid characteristics refer to the state and / or condition of clots, aggregates, and / or particles contained in the sample fluid within a size range of approximately 10 µm to several millimeters. Within this size range, these clots, aggregates, and / or particles may obstruct the fluid system (specifically, the channels of cartridges and / or cuvettes). Specifically, compared to normal, problem-free sample fluids (such as blood), particles, clots, and / or aggregates in the sample fluid with sizes ranging from approximately 15 to 20 µm to approximately 100 µm or larger may result in lower negative pressure values ​​in the fluid system. Such particles, clots, and / or aggregates in the sample fluid may block the entire fluid system. Therefore, the step of automatically determining the characteristics of the sample fluid based on a detected set of conductivity parameter values ​​can specifically correspond to the automatic determination, identification, and / or classification of whether the sample fluid is...

[0076] Problems may arise due to clumps, aggregates, and / or particles that could block channels and / or fluid systems;

[0077] No problem, but the viscosity is high and therefore causes a drop in pressure; or

[0078] It has no problems and is free of lumps, aggregates and / or particles, and has low viscosity.

[0079] The channels described herein can specifically contain volumes ranging from hundreds of ml to µl or even smaller. Therefore, the fluid volume that can be filled in the channels can range from hundreds of ml to µl or even smaller.

[0080] Conductivity parameters can refer to directly measurable admittance, or they can refer to other measurable parameters from which admittance can be derived, such as resistance or impedance.

[0081] Typically, a cartridge comprising one or more channels has two plates with at least one recessed path forming a fluid channel when the plates are joined. The channels typically include a resilient sealing element. When a sample fluid with high viscosity and / or a problematic sample fluid is aspirated into the channel, the negative pressure generated by the suction pump force may cause the resilient sealing element to be slightly drawn into the channel, resulting in a slight reduction in the channel's diameter or cross-section. This may lead to an additional reduction in flow rate (i.e., the volumetric flow rate, typically based on the Hagen-Poiseuille law). In other words, the resilient sealing element is configured to change the cross-section of the channel in response to changes in the local pressure state because it is flexible in shape. The resilient sealing element may comprise a rubber material, a silicone material, and / or another elastic polymer material. The term "resilient" herein means that the material can deform, particularly contract and / or expand, when a force is applied, and when it is in a relaxed state, i.e., when no force is applied, it can return to its original shape. In other words, the resilient sealing element can reversibly deform and relax multiple times. When a negative pressure is generated as the resilient sealing element is drawn into the channel, the resilient sealing element can reduce the cross-section of the channel. When overpressure is generated as the resilient sealing element is pushed out of the channel, the resilient sealing element can increase the cross-section of the channel. Negative pressure can be pressure below a certain threshold, and overpressure can be pressure above a certain threshold, and the threshold can specifically correspond to atmospheric pressure and / or local pressure. As an example, atmospheric pressure can be considered as one atmosphere (atm), which is 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 limited to this scenario, values ​​below 1,013 millibars can be considered negative pressure values, and values ​​above 1,013 millibars can be considered overpressure values.

[0082] A conductivity sensor unit is typically implemented as two or more conductivity sensor sites, i.e., two or more sensors in the cartridge of an IVD analyzer, to detect the conductivity of a liquid. The conductivity sensor sites can be spaced approximately 20 cm to approximately 0.5 cm apart, preferably approximately 10 cm to approximately 2 cm apart. Generally, a conductivity sensor unit refers to a pair of conductivity sensor sites. A conductivity sensor unit is not necessarily a pair of conductivity sites that are permanently fixed over time, but what can be considered a pair of conductivity sites may change: the first and second conductivity sites may form a conductivity sensor unit at a first moment, and the second and third conductivity sites may form a conductivity sensor unit at a second moment. A cartridge can provide several pairs of conductivity sensors forming several conductivity sensor units. Typically, in conventional methods, such conductivity sensor units are used to determine the Hct value and / or to determine the position of the sample fluid in the cartridge.

[0083] In its original function, the conductivity sensor unit allows identification of whether a sample fluid (such as blood), air bubbles, or another fluid has entered the fluid system, specifically the cartridge, once physical contact is established between the conductivity sensor unit and the fluid. In its original function, conductivity points are used to control whether sample fluid has reached them inside the cartridge, and whether air bubbles are present inside the cartridge (specifically between two conductivity points). According to the first aspect, the function of this conductivity sensor unit is extended / differentiated to another function: the identification of the characteristics of the sample fluid. In other words, existing conductivity sensor units in the channels of an IVD analyzer (specifically in the cartridge) are now also used to determine the characteristics of the sample fluid, without even contacting it, but rather by contacting and probing the first fluid. As already noted, the conductivity sensor unit may include sensor pairs (two sensors) or more conductivity sensors, i.e., two, three, four, five, six, or more conductivity sensors. Typically, the cartridge already includes several conductivity points located at different positions in the cartridge's channels to detect whether sample fluid has reached a specific location within the cartridge. Therefore, the sensor sites or sensor elements of a conductivity sensor unit already serve different functions in a conventional cartridge, and these different functions are not for identifying the state of the sample fluid. The conductivity parameter is typically measured between the two sensor elements of a sensor pair or between two sensor sites within a conductivity sensor unit.

[0084] Before the sample fluid (typically a blood sample aspirated in a BGE analyzer) is introduced into the fluid system, the entire fluid system, or only a portion or channel thereof, may initially be filled with a so-called backup solution, which is a conductive aqueous solution. When the sample fluid is inserted, for example, through the sample input module of the BGE analyzer, it is separated from the backup solution by separating gas bubbles (specifically air bubbles). The backup solution is then typically pumped toward a waste container while the sample fluid is delivered through the fluid system and / or toward or through channels in the cartridge.

[0085] Contacting the conductivity sensor unit in the channel with the first fluid means bringing the conductivity sensor unit into contact with the first fluid; that is, bringing the two conductivity sensors or conductivity sensor sites forming the conductivity sensor unit into at least partial contact with the first fluid so that the conductivity parameters 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 ​​depend on the cross-section of the channel. This set of conductivity parameter values ​​can be continuously recorded during the conductivity detection time span and / or at different moments during the conductivity detection time span. Specifically, this set of conductivity parameter values ​​can be recorded to identify changes in the conductivity parameters of the first fluid when a sample fluid is introduced into the fluid system. When the location in the channel where the first fluid is located is open to the location where the sample fluid is located and / or enters the fluid system, changes in local pressure will be detectable at the location where the conductivity parameters of the first fluid are detected. For example, when a sample fluid is aspirated into a fluid system, the first fluid also moves deeper into the fluid system (specifically, the cartridge channel). The negative pressure may further decrease if the sample solution has high viscosity and / or contains lumps, particles, and / or aggregates that cause deformation of the resilient sealing element and extend further into the channel, thereby reducing the channel's cross-section. This is reflected in a change in the conductivity parameter measured in the first fluid within the channel, which has a smaller cross-section. Therefore, the characteristics of the sample fluid can be indirectly detected deep within the fluid system (specifically, the cartridge channel). In particular, by probing the first solution, it is possible to indirectly detect deep within the fluid system whether the sample fluid just at the fluid system inlet is a normal sample fluid, a high-viscosity sample fluid, or a sample fluid containing lumps, particles, and / or aggregates.

[0086] The set of conductivity parameter values ​​is obtained from the detected set of values. The reduced cross-sectional area (area) of the cartridge channel results in a reduced conductivity parameter recording. Since the conductivity parameters recorded over a certain time span can reflect changes in the cross-sectional area of ​​the cartridge channel, and since the cross-sectional area of ​​the channel further depends on the local pressure state due to the deformation of the elastic sealing element, the conductivity parameters recorded over the time span reflect the characteristics of the sample fluid's influence on the temporal evolution of the local pressure state. Therefore, the characteristics of the sample fluid can be identified from the characteristic temporal evolution of the conductivity parameters.

[0087] Generally speaking, the term "cross-section" specifically corresponds to the area of ​​the cross-section of a channel under different local pressure conditions.

[0088] The method may further include the following steps: using a gas sensor unit to detect a component pressure of a gas in a first fluid and / or a third fluid during a gas detection time span; automatically determining the characteristics of the sample fluid based on the detected component pressure of the gas; and comparing the characteristics of the sample fluid determined from the detected component pressure of the gas with the characteristics of the sample fluid determined from a set of detected conductivity parameters. This method allows for reliable, rapid, efficient, and early determination of the state of the sample fluid.

[0089] This embodiment of the method according to the first aspect corresponds to a combination of measuring a set of conductivity parameter values ​​by means of a conductivity sensor unit and, optionally, measuring a component pressure value of a gas by means of a gas sensor unit that may be based on optical and / or electrochemical methods. The combination of measuring the conductivity parameters of the first fluid and the partial pressure values ​​of the gas in the first fluid allows for the use of two different measurement principles to identify the state of the sample fluid, cross-validating the results and providing a more accurate and / or more reliable identification.

[0090] Optional additional steps may correspond to the direct or indirect automatic determination of the characteristics of the sample fluid based on the detected component pressure values ​​of the gas. Direct determination may rely on the analysis of the detected component pressure values ​​of the gas to determine / derive the characteristics of the sample fluid and / or classify the characteristics of the sample. Indirect determination may rely on the analysis of the detected component pressure values ​​of the gas to determine another parameter, such as the pressure state at a specific location or in a specific part of the fluid system. From the determined pressure state in the fluid system, the characteristics of the sample fluid can be determined / derived and / or the characteristics of the sample can be classified. Therefore, in embodiments of the method described above, optional indirect determination may require the following steps:

[0091] The gas sensor unit is used to detect, assume, and / or determine the component pressure of a gas in a first fluid or a third fluid during the gas detection time span;

[0092] Determine the time evolution of the local pressure state from the detected component pressure values ​​of the gas;

[0093] The characteristics of the sample fluid are automatically determined based on the time evolution of the local pressure state determined from the detected component pressure values ​​of the gas; and

[0094] The characteristics of the sample fluid determined by a component pressure value detected from the gas are compared with the characteristics of the sample fluid determined by a set of conductivity parameters detected from the gas.

[0095] If the gas sensor unit is based on optical principles, the third fluid that can be detected by the gas sensor unit can include gases and / or liquids. For optical gas sensor units, the fluid to be analyzed does not need to be a conductive fluid, such as a buffer or buffer solution. For example, the third fluid can be an air bubble preceding or following the first fluid. Alternatively, the third fluid can be a solution, such as an aqueous solution.

[0096] Generally, the gas sensor units described herein may include or refer to oxygen sensor units configured to detect the partial pressure of oxygen in a fluid, such as a sample liquid, buffer solution, and / or gas bubble. Alternative and / or additional gas sensor units may include or refer to carbon dioxide sensor units configured to detect the partial pressure of carbon dioxide in a fluid. Alternative and / or additional gas sensor units may include sensor units configured to measure other gases.

[0097] Generally, a gas sensor unit, and specifically an oxygen sensor, can rely on at least one of the following two effects: 1. When the local pressure increases, the sensor indicates a higher partial pressure of the gas (specifically oxygen), and when the local pressure decreases, the sensor indicates a lower partial pressure of the gas (specifically oxygen). 2. The gas sensor unit itself is also sensitive to pressure, for example, as a mechanical response. This mechanical response can depend on the polymer matrix in which the oxygen sensor is embedded.

[0098] The sample fluid can first be pumped / drawn into a sensor cartridge, where conductivity parameters and / or partial pressures of the gas can be measured. For example, pO2 can be measured in the sensor cartridge. Subsequently, the sample fluid can pass through a cuvette, where optical detection can also be performed.

[0099] The following describes an alternative method according to the second aspect. In simple terms, the above-described embodiment of the method according to the first aspect, based on the detection of partial pressure values ​​of the gas, can be used without measuring conductivity parameter values. In other words, the method according to the second aspect primarily relies on the measurement of a component pressure value of the gas by an optional gas sensor unit to determine the state of the sample fluid in the IVD analyzer. The common advantages of both aspects are summarized below.

[0100] Preferably, the characteristics of the sample fluid in the IVD analyzer are determined based on records from multiple conductivity sensor units and at least one gas sensor unit (specifically, an oxygen sensor unit and / or a carbon dioxide sensor unit). This improves reliability and helps distinguish between different events. In this way, the passage of air bubbles and problematic sample fluid can be differentiated. Air bubbles also cause a sudden drop in conductivity, similar to a problematic sample solution aspirated into the fluid system. The multiple conductivity sensor units may include overlapping conductivity sites. For example, a first conductivity site and a second conductivity site may constitute a first conductivity sensor unit, and a second conductivity site and a third conductivity site may constitute a second conductivity sensor unit.

[0101] According to what can be considered a second aspect of this disclosure, a method is provided for determining the characteristics of a sample fluid in an IVD analyzer, and the method includes the steps of: introducing a first fluid into a channeled fluid system of the IVD analyzer; introducing a sample fluid, spatially separated from the first fluid, into the fluid system; detecting a component pressure of a gas in the first fluid during a gas detection time span using a gas sensor unit; and automatically determining the characteristics of the sample fluid based on the detected component pressure of the gas.

[0102] The difference between the methods of the first and second aspects lies in the measured parameters detected / recorded. The method of the first aspect is based on the detection of a set of conductivity parameter values ​​of a first fluid during a conductivity detection time span using a conductivity sensor unit, while the method of the second aspect is based on the detection of a component pressure value of a gas in the first fluid during a gas detection time span using a gas sensor unit. The main measurement principle of the method of the first aspect is based on the recording of conductivity parameters and relies on the fact that the cross-section of the channel depends on the local pressure, as the resilient sealing element is configured to deform and change depending on the local pressure. The change in the cross-section of the channel is reflected in the conductivity parameter values ​​measured in the conductivity measurement.

[0103] The primary measurement principle of the method according to the second aspect is based on the detection of gas partial pressures (such as oxygen partial pressure), which may include optical and / or electrochemical detection. While the collected conductivity parameter value depends on the cross-section of the channel, the collected gas partial pressure value corresponds to a more direct measurement of the local pressure state. The method according to the first aspect (the measured conductivity parameter value) requires the channel to be at least partially sealed on some of its sides by a resilient sealing element configured to change the channel cross-section in response to changes in the local pressure state that are not required by the method according to the second aspect (the partial pressure of the gas, such as the measured oxygen). However, in the method combining both measurement principles, the same cartridge can be used, in which the resilient sealing element is used to seal the channel relative to the external space. The gas sensor unit can also be positioned inside or near the channel of the cartridge.

[0104] The method according to the first and second aspects may further specifically include: introducing a first fluid into the channel of the cartridge of the fluid system of the IVD analyzer, and introducing a sample fluid that is spatially separated from the first fluid into the fluid system at a position outside the channel of the cartridge, and contacting the conductivity sensor unit and / or gas sensor unit located in the channel with the first fluid before and simultaneously before the sample fluid is conveyed through the fluid system but before it is inside or through the channel of the cartridge.

[0105] Similar to that already outlined for the first aspect, the method of the second aspect can correspond to the direct or indirect automatic determination of the characteristics of a sample fluid based on the detected partial pressure values ​​of a gas. Generally, the characteristics of the sample can be automatically identified, for example, using a fitting function or a neural network, based on the specific temporal evolution of the gas partial pressure values. Specifically, the direct automatic determination of the characteristics of a sample fluid based on the detected partial pressure values ​​of a gas can be performed using a neural network trained to determine, identify, and / or classify the characteristics of the sample fluid based on the partial pressure values ​​of a gas. Therefore, in embodiments of the method described above, optional indirect determination may require the following steps:

[0106] A gas sensor unit is used to detect the component pressure of a gas in a first fluid or a third fluid during a gas detection time span;

[0107] Determining the time evolution of local pressure state from the detected component pressure values ​​of the gas; and

[0108] The characteristics of the sample fluid are automatically determined based on the time evolution of the local pressure state determined from the detected component pressure values ​​of the gas.

[0109] The methods described in the first and second aspects represent alternative solutions to a specific problem. In other words, the same problem is solved using the methods described in both aspects, achieving one or more of the aforementioned objectives in two alternative ways.

[0110] To detect the partial pressure of a component gas in a first fluid, a gas sensor unit is typically brought into physical contact with the first fluid. The partial pressure can be detected inside the liquid or inside a gas separation bubble. Therefore, the method may include the step of bringing the gas sensor unit into contact with the first fluid.

[0111] The following types of changes should be distinguished from the readings (which are the partial pressures of the gas) from the gas sensor unit (e.g., the optical oxygen sensor site):

[0112] 1. Expected changes in the behavior of fluids that are otherwise normal;

[0113] 2. Changes in the partial pressure of the gas due to a change in the medium (e.g., a change detected from the first fluid to the air separation bubble);

[0114] 3. Changes, particularly pressure drops due to clots in the sample fluid; and

[0115] 4. Changes, especially pressure drops caused by the high viscosity of the sample fluid.

[0116] These changes / transitions in the partial pressure of the gas are typically unique to each case and are therefore distinguishable. In other words, the temporal evolution of the partial pressure of the gas within the channel reveals the situation in the fluid system, such as the four cases described above.

[0117] In a specific embodiment, a neural network can be trained to perform such distinctions. As an alternative or supplement to the features of the method according to the second aspect, data can be obtained from the conductivity sensor unit to allow for more reliable distinctions, since both methods can confirm the obtained results.

[0118] 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, the oxygen sensor is applied to a transparent wall. Optical measurements can be performed through this transparent wall. A light emitter and detector are in optical contact with the oxygen sensor. The oxygen sensor is in physical contact with the liquid. If the gas sensor unit is based on electrochemical principles, the first fluid should be a conductive solution and should be in physical contact with the gas sensor unit. If the gas sensor unit corresponds to the oxygen sensor unit, the principle of oxygen measurement can be based specifically on the effect of dynamic luminescence quenching of molecular oxygen. The partial pressure of the gas being measured depends directly on the local pressure. Therefore, the gas sensor unit can be used as an indirect pressure sensor while located in a medium with a known gas / oxygen concentration (e.g., a backup solution and / or air). The gas concentration (specifically, the oxygen concentration of the first fluid) is generally known for normal (pressure) conditions (where no problematic sample fluid is aspirated) and / or for a predetermined pressure value (such as ambient pressure). Changes in oxygen pressure detected when the sample fluid is aspirated (and particularly, specific time evolution) can serve as an indication of the characteristics of the sample fluid. Alternatively or additionally, the detection of gas partial pressure can also include optical measurement principles, such as quantitative blood oxygenation or electrochemical measurement principles. Optical gas sensor units are highly sensitive and respond rapidly to pressure changes. Optical gas sensor units are faster than electrochemical / electro-gas sensors. Furthermore, gas sensor units can be independent of variations in material properties and manufacturing tolerances of the soft material of the resilient sealing element.

[0119] As an example of an optical measurement principle that can be used to detect the partial pressure of oxygen, luminescence quenching can be applied. This principle is based on the excitation of dye molecules by light. Different light is emitted depending on the amount of oxygen. There is an oxygen-dependent "phase shift" between the emitted and received wavelengths. Furthermore, there is an oxygen-dependent "decay time" that can be used alternatively to determine the oxygen content. Different "dye molecules" are available, and the correct excitation wavelength must be selected for the dye molecules.

[0120] Furthermore, the optical sensor layer behaves as a "pressure-sensitive" layer (similar materials / elements are often used as "pressure-sensitive coatings"). This means that in incompressible media (e.g., water, a spare solution), the optical sensor will indicate an increase in oxygen content as pressure increases. For gases, the two effects overlap: the sensor measures a higher oxygen content because the sensor layer is compressed by pressure. Simultaneously, the oxygen content also increases because the gas is compressible and therefore has more oxygen molecules per volume at higher pressures.

[0121] From the detected partial pressure values ​​of a gas component, the temporal evolution of the local pressure state can be identified / determined over the gas detection time span (i.e., the time span from the start to the end of the detection of the partial pressure values ​​of the gas component). The characteristic temporal evolution of the gas partial pressures can determine the properties of the sample fluid. The properties of the sample fluid are then identified based on the temporal evolution of the local pressure state determined and / or derived from the detected partial pressure values ​​of the gas.

[0122] The advantages, optional features, and embodiments of the methods of the first and second aspects are described below. The advantages apply to one or both methods of these two aspects and any embodiments thereof. When referred to as "method," it means one or both methods of the first and second aspects. The optional features and / or embodiments further described below can be combined with any method of the first and second aspects and its embodiments, provided they do not contradict each other in a logical sense. In other words, the methods of all aspects described herein can be combined with the features and embodiments further described below.

[0123] Generally, a set of conductivity parameter values ​​and / or a component pressure value of a gas can be recorded and / or measured before aspirating the sample fluid to obtain a reference and / or baseline. In this case, the fluid system (specifically the channel) can be filled with a spare solution, gas, or another reference fluid. In other words, the values ​​obtained in the state before the introduction of the sample fluid can serve as a reference or baseline from which changes in parameter values ​​can be detected upon introduction of the sample fluid. When the sample fluid is aspirated, the time evolution of the measured values ​​relative to the previously measured reference and / or baseline indicates the characteristics of the sample fluid.

[0124] The method described above, and any of its embodiments, allows for the identification of whether a sample is problematic due to viscosity and / or the presence of clumps, aggregates, and / or particles in the sample shortly after the sample fluid is introduced into the fluid system and / or before the sample fluid reaches the channel inlet of the cartridge. In other words, the method allows for early identification of the state of the sample fluid. Therefore, the method can increase the likelihood of successfully removing problematic sample fluid because the distance required for removal is relatively short. Thus, by reversing the direction of pump operation (i.e., removing problematic sample fluid), early clumping detection by the method can reduce the duration and magnitude of overpressure on the fluid system during clumping removal. Furthermore, contamination from clumps, aggregates, and / or particles deep within the fluid system (specifically, the cartridge channel) can be avoided. Simultaneously, early identification of problematic sample fluid (also known as “clump detection”) allows for a reduction in negative pressure load on the system, i.e., the duration and magnitude of negative pressure, as further movement of the problematic sample fluid into the system can be prevented. Because negative pressure load can be reduced, early clumping detection by the method can reduce the risk of microbubble aspiration at connection points in the system. Because lower negative pressure and overpressure loads can lead to distorted data and / or damage to the system and / or some consumables, early clot detection of the method can reduce instrument downtime and / or allow for more reliable and / or more accurate methods and instrumentation. Since one or more sensors already present in the IVD analyzer for analyzing sample fluids are used for clot detection, no additional sensors, detectors, or other physical components are required, and data generated from existing sensors can be used. In other words, the existing physical resources of the IVD analyzer are utilized and thus efficiently used to identify problematic sample fluids at an early stage in the fluid system introduced into the IVD analyzer.

[0125] In an IVD analyzer system, controllers, machines, and / or processors can be configured to perform and / or initiate at least a portion of the steps of the methods according to the first and second aspects. Specifically, the controllers, machines, and / or processors can be configured to determine the characteristics of the sample fluid based on a detected component pressure of the gas and / or based on a detected set of conductivity parameters.

[0126] Based on the advantages described above, it can be summarized that the methods according to the first and second aspects can make IVD analysis more efficient (i.e., more time-efficient and / or cost-efficient), less prone to errors, eco-friendly due to the extended lifespan of consumables, more accurate and / or more reliable, and easier and therefore more user-friendly.

[0127] The sample fluid is introduced (i.e., aspirated or pushed / pressed) into the fluid system after the first fluid has already been introduced into the fluid system (specifically the channel). The first fluid may even be present in the instrument before it is operated. In other words, the sample fluid (which can be considered the second fluid) is introduced into the fluid system at a later stage than the first fluid. In one scenario, the first fluid is a conductive reserve solution 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 the salt and different from the reserve solution, introduced into the fluid system shortly before the sample fluid is introduced.

[0128] Generally, a fluid can be considered a material in a state in which flow can occur and the fluid behavior of the material can be observed. This is typically the case for liquids and gases, and therefore, fluids can include liquids and / or gases. According to the first aspect, the first fluid should be a liquid, such as a conductive aqueous salt solution, for example, a buffer solution, because the measurement principle according to the first aspect is based on the electrochemistry requiring a conductive solution. If the measurement is based on optical principles, then according to the second aspect, the first fluid can be a liquid and / or a gas. However, if the measurement principle of the second aspect is based on electrochemistry, then the first fluid should also be a liquid, preferably a conductive aqueous solution.

[0129] The sample fluid is typically a liquid, such as a blood sample or another bodily fluid. The sample fluid is spatially separated from the first fluid in the fluid system. Therefore, the space between the sample fluid and the first fluid in the fluid system is filled with at least a third fluid, which may include a liquid and / or a gas. Preferably, the space between the sample fluid and the first fluid in the fluid system contains air bubbles. In other words, the sample fluid can be spatially separated from the first fluid in the fluid system by a gas (specifically, an air bubble), and an air bubble refers to a volume of air that moves through the fluid system along with the first fluid and the sample fluid. The air bubble can be considered the third fluid. The first fluid is introduced into the fluid system before the sample fluid is introduced.

[0130] When the characteristics of the sample fluid are determined by means of two sensor unit types (conductivity sensor unit and gas sensor unit), the two different sensors can be positioned close to each other, particularly within the same cartridge. For example, the two different sensor units (conductivity sensor unit and gas sensor unit) can be spaced about 1 cm to about 8 cm apart, preferably about 1.5 cm to about 5 cm apart, and even more preferably about 2 cm to about 3 cm apart. The distance from one individual sensor element in one sensor unit to another individual sensor element in the other sensor unit can be measured. Alternatively, the two different sensors can be positioned in different units and / or cartridges connected to each other by a fluid system that acts as a connecting tube and should allow substantially the same local pressure state to be measured at locations further apart from each other, as is the case when they are in the same cartridge. The diameter of the conductivity sensor site (the diameter of a single conductivity sensor) is in the range of about 0.2 mm to 2 mm, preferably about 0.5 mm to 1.5 mm, and more preferably between about 0.8 mm and 1.2 mm. The sensor site distance (i.e. the distance between two conductivity sensors that can form a conductivity sensor unit) can be between about 1.5 mm and 3.5 mm, preferably between about 1.8 mm and 2.8 mm, and more preferably between about 1.9 mm and 2.6 mm.

[0131] The process of automatically determining the characteristics of a sample fluid from a detected component pressure of a gas and / or from a detected set of conductivity parameters can be performed by a machine, processor, or controller. This automated determination of sample fluid characteristics is typically not performed manually. The machine, processor, or controller can run programs configured to identify specific characteristics of the temporal evolution of local pressure states, indicating the state of the sample fluid, such as aggregates and / or clumping or high viscosity.

[0132] Typically, these methods can be initiated each time the IVD instrument / analyzer is started and / or used to analyze a sample fluid. For example, the user can begin operation or otherwise inform the instrument to analyze a sample fluid, and the IVD analyzer can then automatically initiate a method according to any of the described embodiments. This has the advantage of automatically protecting the instrument and / or consumables from damage by aspirating the problematic sample fluid. Alternatively, the user can manually initiate a method according to any of the described embodiments.

[0133] If local pressure status is of interest, it can include the pressure difference between the measured local pressure in the fluid system when the sample fluid is introduced and the local pressure measured at the same location when the reference fluid is introduced. In some cases, local pressure status can also correspond to an absolute pressure value. Local pressure status can also correspond to the difference between the measured local pressure and a threshold when the sample fluid is introduced into the fluid system. Since local pressure status can be derived from readings of stationary sensor units (i.e., conductivity sensor units and / or gas sensor units), it can always be obtained from readings of one or more sensor units at one or more fixed locations.

[0134] Generally, even though the channel is described as part of the cartridge in most embodiments, the channel may be part of the fluid system but not part of another element of the cartridge, such as a cuvette or another flow cell.

[0135] The properties of the sample fluid include at least one of the following:

[0136] A problematic condition in which the sample fluid contains at least one of clots (such as blood clots), human tissue particles, aggregates, and contaminants.

[0137] The viscous state, in which the sample fluid has a certain viscosity, specifically the high-viscosity state, where the sample fluid has a viscosity higher than 6 mPas, particularly higher than 8 mPas, such as, for example, 9 mPas; or

[0138] Under normal conditions, the sample fluid does not contain clots, human tissue particles, aggregates, or contaminants, and has a viscosity between 2 mPas and 6 mPas. Specifically, the viscosity of the sample fluid under normal conditions does not exceed 6 mPas. In other words, the viscosity of the sample fluid under normal conditions is below approximately 6 mPas.

[0139] Water and aqueous solutions typically have a viscosity of about 1 mPas. Whole blood usually has a viscosity of about 4.5 mPas when it is in good condition and its viscosity is not high.

[0140] These methods allow for the identification of problematic sample fluids that may clog fluid systems, i.e., sample fluids containing agglomerates, aggregates, contaminants, and / or particles. Problematic sample fluids can be distinguished from non-problematic but high-viscosity sample fluids. Alternatively or additionally, the methods can allow for the identification of sample fluid viscosities exceeding a certain threshold or falling within a range higher than expected values ​​for non-problematic sample fluids. The methods can allow for the determination of a value or range of viscosity values ​​for the sample fluid. Specifically, the methods can allow for the differentiation between problematic sample fluids intended for discharge and high-viscosity sample fluids. Therefore, incorrect identification of sample fluid characteristics can be avoided, and high-viscosity sample fluids are not discharged due to incorrect identification. Thus, the methods are efficient in preventing problematic sample fluids from clogging fluid systems while conserving non-problematic sample fluids that are high-viscosity but not problematic and might be discharged due to timeouts in conventional methods. These methods do not constitute a basis for a trade-off between the degree of protection of the fluid system and the sample loss rate. Therefore, the methods offer high sensitivity and efficiency.

[0141] In addition to the identifiable scenarios listed above, the method can also identify situations where the medium changes within the cartridge's channels, such as when a first fluid passes through the sensor unit and an air bubble subsequently follows and fills the channels. Therefore, this is a further detectable event during channel filling, particularly when the filling changes the phase from gas to liquid or vice versa, as different fluids pass through the fluid system.

[0142] Generally, the presence or absence of agglomerates, aggregates, and / or particles in a sample fluid, and / or the viscosity of the sample fluid, and / or the measured range of the sample fluid's viscosity, can be determined according to the methods of the first and / or second aspects. In other words, a method for determining the characteristics of a sample fluid in an IVD analyzer (i.e., the presence or absence of agglomerates, aggregates, and / or particles) may include the steps of the methods of the first and / or second aspects. Further, a method for determining the characteristics of a sample fluid in an IVD analyzer (i.e., the viscosity of the sample fluid and / or the range of the sample fluid's viscosity) may include the steps of the methods of the first and / or second aspects.

[0143] The step of automatically determining the properties of a sample fluid may include applying a trained artificial neural network to a set of detected conductivity parameter values ​​of a first fluid and / or a component pressure value of a gas detected in the first fluid or a third fluid to determine the properties of the sample fluid. The method may further include training the artificial neural network using a training dataset comprising a set of conductivity parameter values ​​of the first fluid and / or a component pressure value of a gas detected in the first fluid or a third fluid corresponding to predefined properties and / or states of the sample fluid.

[0144] Specifically, for methods based on conductivity measurements, artificial neural networks can be trained on conductivity readings without converting them into pressure values. Changes in conductivity are caused by changes in pressure, but it is not necessary to know the pressure value or the temporal evolution of the local pressure state.

[0145] The step of automatically determining the characteristics of a sample fluid derived from a detected partial pressure value of a gas and / or from a detected set of conductivity parameters can be performed by a controller, machine, and / or processor utilizing a trained artificial neural network (ANN) trained to identify characteristics indicating a problematic or highly viscous sample fluid. This allows for improved reliability and / or accuracy in identifying the characteristics of the sample fluid. The trained ANN may have already been provided to the controller, machine, and / or processor, or it may need to be pre-trained. Training can be semi-automatic or fully automated. Training can begin by providing a reference fluid with a predetermined state, such as a predetermined density and size or size distribution of particles in a solution and / or a predetermined viscosity. Training may be required for each cartridge or for a representative of a batch of cartridges. In a simplified description, the trained ANN learns how training data (i.e., the temporal evolution of conductivity parameter values ​​and / or gas partial pressure values) indicates a predetermined state and can later be applied to unknown sample fluids to identify unknown states. When applying a trained artificial neural network, providing a large number of reference fluids with different predetermined properties (particles, agglomerates, viscosity, etc.) can improve the quality of the trained artificial neural network and thus improve the reliability and / or accuracy of identifying the properties of the sample fluid. It should be noted that particles, agglomerates, contaminants, and aggregates may cause similar and / or identical characteristics in a recorded set of conductivity parameter values ​​and / or gas partial pressures.

[0146] In the case of high-viscosity sample fluids, negative pressure can increase slowly, meaning the pressure can decrease further, because fluid resistance is proportional to the length of the portion of the fluid system filled with the sample liquid. "Total" fluid resistance can refer to the sum of the resistance caused by moving the backup solution, moving the air separation bubble (negligible), and moving the sample liquid. The resistance caused by each of these components is proportional to their length within the fluid system. Problematic sample fluids may cause the pressure to decrease further, exhibiting different time evolutions.

[0147] Specifically, if a neural network is applied, the determination of the characteristics of a sample fluid can correspond to categorizing it into one of the following categories: "problematic sample fluid," "high-viscosity sample fluid," and "non-problematic sample fluid (with low viscosity)." Alternatively or further, the determination of the characteristics of a sample fluid can generally correspond to determining the presence of agglomerates, particles, and / or aggregates in the sample fluid. Alternatively or further, the determination of the characteristics of a sample fluid can generally correspond to determining the viscosity, the range of viscosity, and / or whether the viscosity exceeds a predetermined value.

[0148] As an alternative or supplement to applying neural networks to determine the properties of sample fluids, recorded data can be fitted, regardless of whether it is obtained based on the first and / or second aspects. In this case, the behavior of sample fluids with specific properties is known, and the time evolution of conductivity parameters and / or gas partial pressures can be described by functions indicating the properties of the sample. Functions describing the time evolution of parameters (conductivity parameters and / or gas partial pressures) for sample fluids with high viscosity can indicate the degree of viscosity. If the sample fluid contains agglomerates, the time evolution can exhibit substantially different behavior, allowing for differentiation of properties. Fitting can be performed by the user or automatically by the machine. However, providing an automated step is preferred. Given the reliability of the results, it is even more preferable to apply neural network-based machine learning principles to determine the properties of the sample fluids.

[0149] The method may further include automatically triggering actions in the IVD analyzer based on determined characteristics of the sample fluid. These actions may include at least one of the following steps: stopping the introduction of the first fluid and / or sample fluid, reversing the pump's operating direction, discharging the sample fluid, introducing a washing solution and at least partially washing the fluid system and / or channels with the washing solution, continuing the introduction of the first fluid and / or sample fluid, and outputting an alarm optically and / or acoustically. The automatically triggered steps may be differentiated based on the following:

[0150] a. When the sample fluid is in a problematic state (i.e., when the sample fluid contains clots, aggregates, and / or particles), this action includes at least one of the following steps:

[0151] Stop the step of introducing the first fluid and / or sample fluid.

[0152] Reverse the pump's operating direction.

[0153] Discharge sample fluid, and / or

[0154] Introduce a washing solution and wash the fluid system and / or channels at least partially with the washing solution.

[0155] b. When the sample fluid is in a high viscosity state or in a normal state, this action includes the following steps:

[0156] Continue with the steps of introducing the first fluid and / or sample fluid, and output control signals optically and / or acoustically, such as control noise and / or green and / or red control lights.

[0157] If a problematic sample fluid is detected upon introduction into the fluid system, the steps of issuing an alarm and / or introducing the first fluid and / or sample fluid can be stopped. These steps can be automatically triggered by a processor, machine, and / or controller. Thus, the pump generating pressure (especially negative pressure) can be stopped. Alternatively, when problematic sample fluid is detected, the pump can be reversed, causing the negative pressure to become an overpressure, for example, which forces the problematic sample fluid out of the fluid system, where it can be discharged into a discharge container. Further, the step of washing the fluid system and / or channels can be triggered to wash away any potential contaminants, aggregates, and / or particles in at least a portion of the fluid system. Washing can be performed using aqueous solutions, such as buffer solutions, salt solutions, or other non-aqueous solvents.

[0158] If a sample fluid with no issues but high viscosity is detected, the steps of introducing the first fluid and / or the sample fluid can proceed without altering the pump operation.

[0159] This offers the following advantages: it protects the fluid system from damage caused by problematic sample fluids. Simultaneously, it allows unproblematic sample fluids, which have high viscosity, to enter and pass through the fluid system. Therefore, unproblematic sample liquids are preserved for diagnostic use without needing to be retrieved from the patient, while effectively protecting the IVD analyzer from damage or contamination caused by problematic sample fluids. Consequently, the operation of the IVD analyzer remains uninterrupted and operates efficiently, avoiding instrument downtime.

[0160] The conductivity detection time span and / or gas detection time span may overlap at least partially with the introduction time span, in which the step of introducing the sample fluid into the fluid system is performed, preferably wherein the conductivity detection time span and / or gas detection time span begins before or simultaneously with the introduction time span.

[0161] Preferably, the conductivity detection time span and / or gas detection time span overlap with the time span of introducing, aspirating, and / or transporting the first fluid through the fluid system (specifically, the cartridge channel). Generally, and typically, the fluid system is already filled with the first fluid, i.e., the backup solution. A small amount of air is usually introduced before the sample fluid is introduced to ensure separation of the backup solution and the sample liquid. Measurements of the conductivity parameter values ​​and / or the partial pressure values ​​of the gas can preferably begin when the fluid system (especially the cartridge channel) is primarily filled with the first fluid, and analysis of the sample fluid is being performed or planned, i.e., the instrument is started and actively used to analyze the sample fluid. The values ​​obtained in the state prior to the introduction of the sample fluid can serve as a reference or baseline from which changes in the parameter values ​​can be detected upon the introduction of the sample fluid.

[0162] If only conductivity is detected by recording a set of conductivity parameter values ​​of the first fluid (according to the first aspect, as the main measurement principle), then the starting point for detecting the first conductivity value can be timed before or exactly at the moment the pump starts and introduces the sample fluid into the fluid system. In other words, the conductivity detection time span can begin before or exactly at the moment the sample fluid is introduced (especially when it is aspirated into the fluid system).

[0163] If only the partial pressure of the gas is detected by recording a component pressure value of the gas in the first fluid (according to the second aspect, as the main measurement principle), then the starting point for detecting the first partial pressure value can also be timed before or exactly at the moment the pump is started to introduce the sample fluid. In other words, the gas detection time span can begin before or exactly at the moment the sample fluid is introduced (especially when it is aspirated into the fluid system).

[0164] If these methods are combined and conductivity and gas partial pressure are detected in the first fluid, the conductivity detection time span and / or gas detection time span can begin before or just at the moment the sample fluid is introduced. Preferably, the conductivity detection time span and the gas detection time span can begin at the same moment. Therefore, both the conductivity detection time span and the gas detection time span can begin before or just at the moment the sample fluid is introduced into the fluid system.

[0165] The moment the sample fluid is introduced into the fluid system can be the moment the pump is started, or it can be the moment the pump is already running and introducing the first fluid into the fluid system, and the moment the sample fluid enters the fluid system from an external reservoir. Therefore, the time span before the sample fluid is introduced into the fluid system can include situations where the pump is on and / or off. In a specific example, the time span before the sample fluid is introduced into the fluid system can include situations where the first fluid is introduced into the fluid system and where the first fluid will contact at least the conductivity sensor unit. At least at the moment the sample fluid is introduced into the fluid system, the conductivity sensor unit preferably contacts the first fluid so that the conductivity parameter can be measured.

[0166] The conductivity detection time span and / or gas detection time span can be between approximately 0.5 s and 60 s, preferably between approximately 2 s and 20 s, and more preferably between 3 s and 10 s. If starting earlier, the conductivity detection time span and / or gas detection time span can begin approximately 10 s, preferably approximately 5 s, and more preferably 1 s before the introduction time span (within which the step of introducing the sample fluid into the fluid system is performed / begins). The time to obtain results can depend on the operating status of the IVD analyzer. For example, if the IVD analyzer is undergoing calibration at the moment when the sample fluid is expected to be introduced, the calibration can be completed or aborted. The fluid system needs to be flushed after calibration. Therefore, the time to obtain results can vary.

[0167] In all the above cases, the advantage is that changes in pressure can be recorded before the sample fluid enters the fluid system, or at least from the moment the sample fluid enters the fluid system. Early and reliable identification of the sample fluid's characteristics is possible, preventing problematic sample fluid from entering the fluid system and allowing for easy evacuation.

[0168] Alternatively, the conductivity detection time span and / or gas detection time span can begin after the moment the sample fluid is introduced. For example, conductivity may be recorded as the primary measurement principle, but the properties of the sample fluid cannot be definitively identified. In this case, at a later stage, the detection of the partial pressure of the gas can begin to verify or more reliably identify the properties of the sample fluid.

[0169] The step of introducing the first fluid and / or sample fluid into the fluid system may include aspirating the first fluid and / or sample fluid.

[0170] Pumps (especially peristaltic pumps) can operate in the direction in which the fluid is drawn. Alternatively, the pump can be positioned on the opposite side of the fluid system and can operate in the opposite direction, where an overpressure is generated that forces and / or pushes the fluid into the fluid system. However, it is more preferable to draw the fluid into the fluid system, as this reduces the risk of damaging components of the fluid system, such as seals, valves, and / or sensitive engagement elements, which can be easily damaged by overpressure. Generally, there are different advantages to using negative pressure instead of pushing the sample in, i.e., peristaltic pumps are commonly used in BGE analyzers. This allows for improved control of the sample fluid and, therefore, ensures that the biological fluid does not come into contact with the instrument (it remains only in consumables, such as cartridges and the tubing connected to them). Furthermore, if the sample fluid passes through the pump, red blood cells may be damaged or destroyed, and additionally, blood gas values ​​may be altered, as soft peristaltic pump tubing tends to be very oxygen-permeable. Therefore, it is advantageous that the sample fluid, for example, in the cartridge or optional cuvette, does not pass through the pump system before passing through the sensor.

[0171] The process of detecting the partial pressure of a gas can be based on optical measurement principles. Alternatively, the process can be based on electrochemical principles; however, optical principles generally allow for faster and more reliable detection. Electrochemical sensors can be used to detect the partial pressure of gases when they are not too slow.

[0172] The step of detecting a component pressure of gas in a first fluid can be to detect a component pressure of gas in a gas bubble (i.e., a gas-filled chamber, such as an air bubble) and / or a liquid-filled chamber, such as a solution (e.g., a spare solution).

[0173] As further mentioned above, optically based gas sensor units can detect the partial pressure of gas in gas-filled or liquid-filled chambers, making optical methods versatile and applicable to any type of fluid containing gas and / or liquid. Furthermore, the optical methods used to detect gas partial pressure are fast, accurate, reliable, and efficient.

[0174] Generally, parameters indicating the characteristics of the sample fluid can also be detected, such as the partial pressure of oxygen within the sample fluid itself. However, determining the characteristics of the sample fluid is more difficult in this case because the oxygen content (partial pressure of oxygen) in the sample fluid entering the fluid system is unknown, and the oxygen sensor will need some time to converge to the oxygen value. However, when the sample is inserted, the oxygen sensor will also (usually) have already converged to the partial pressure of oxygen in the standby solution. When the oxygen sensor is already in contact with the sample fluid, the superposition of the two effects (convergence to the sample value) and (pressure change caused by clots) makes detecting clots even more difficult.

[0175] Furthermore, if the temporal evolution of local pressure states is detected, this can include determining the pressure drop during sample fluid aspiration. When sample fluid is aspirated into a fluid system, pressure may drop if the sample fluid is highly viscous and / or if it contains particles, clumps, and / or aggregates. In other words, the force of the negative pressure generated by the pump becomes stronger when the sample fluid, under extreme conditions, reduces its flow rate and / or clogs the fluid system. The temporal evolution of such pressure drops during sample fluid aspiration indicates whether the sample fluid is viscous and / or contains particles, clumps, and / or aggregates. As further described above, artificial intelligence can be trained to recognize such characteristic evolutions of pressure drops to more reliably identify whether the sample fluid is highly viscous and / or contains particles, clumps, and / or aggregates.

[0176] The method according to the first and / or second aspects may include the step of calibrating the fluid system, particularly with respect to viscosity detection (when the characteristics of the sample fluid to be determined correspond to viscosity). For example, the fluid system can be calibrated for pressure measurement using the fluid system in accordance with a normal sensor calibration process, which is efficient. The viscosity of the fluid can be varied to achieve the purpose of calibrating the fluid system for pressure and / or viscosity measurement. As a first step, the actual pump rate (viscosity depends on temperature) must be measured using a known liquid with a known viscosity at a known temperature. Fluid can be pumped through the fluid system, and the actual volumetric flow rate related to the pump rate can be determined using two sensor points (which may correspond to timeout points). After determining the pump rate, different fluids of known viscosity can be pumped through the fluid system at different known velocities / pump rates, especially through the SIM needle. With known viscosity and known velocity, the resulting pressure difference can be calculated as described in more detail below.

[0177] If a sample fluid with high viscosity (exceeding a predetermined threshold) enters the fluid system, it can be allowed to pass through the cartridge for further parameter detection. In this case, the pump is further operated to aspirate the sample fluid. Additionally, an alert can be triggered indicating a problematic health condition of the patient associated with the sample fluid. In response to the alert, a physician can be notified, and actions can be initiated immediately to protect the patient's life. The IVD analyzer can automatically trigger the determination of parameters such as hematocrit (Hct) and potassium (K). +The determination of specific markers (such as troponin T (TnT)), NT-proBNP, D-dimer, cTnT, etc.) is performed, specifically in cases of high viscosity, but also in cases where clots and / or strong clotting are observed (when the observed property includes clotting). These observations can indicate cardiac problems. Such determinations can be performed by the IVD analyzer itself or by another entity specifically designed to determine the target parameters. The measured parameters can then confirm or specify the patient's indicated health condition. Furthermore, Hct measurements can indicate and / or specify whether the viscosity of the blood sample stems from a high Hct value, which can, for example, indicate dehydration.

[0178] According to another aspect of this disclosure, which can be considered a third aspect, a fluid sensor system for determining the state of a sample fluid in an IVD analyzer is provided, wherein the sensor system includes: a cartridge having a channel connectable to a pump for inducing a change in local pressure state to drive fluid through the channel of the cartridge, specifically wherein the cartridge has a channel configured to guide fluid through the cartridge; a conductivity sensor unit inside a sleeve configured to detect conductivity parameters of a first fluid and a sample fluid; and / or a gas sensor unit configured to detect partial pressures of gases in the first fluid and the sample fluid; and a controller configured to cause the IVD analyzer to perform steps according to the method of the first aspect and / or the second aspect or any embodiment thereof.

[0179] Fluid sensor systems share the same advantages as their corresponding methods or embodiments. A fluid sensor system for performing the method according to the first aspect includes a conductivity sensor unit. A fluid sensor system for performing the method according to the second aspect includes a gas sensor unit. The fluid sensor system may specifically include two sensor types, namely a conductivity sensor unit and a gas sensor unit, such that the fluid sensor system can perform both the method according to the first aspect and the method according to the second aspect.

[0180] The conductivity sensor unit is positioned inside a cartridge with channels in the fluid system. The gas sensor unit can also be positioned inside the cartridge, but it can also be positioned outside the cartridge in a fluid system that is fluidly connected to the channels of the cartridge.

[0181] The controller can 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. Specifically, the controller can be configured to perform some of the method steps itself, such as mathematical operations, and / or steps to determine the time evolution of a local pressure state from a detected set of conductivity parameter values ​​and / or partial pressure values ​​of the gas, and / or steps to automatically determine the characteristics of the sample fluid based on the determined time evolution of the local pressure state. The controller can specifically trigger actions directly or indirectly when a particular state is identified in the sample fluid. For example, when a problematic sample fluid is identified, the controller can trigger effluent and / or rinsing steps, as further described above.

[0182] The cartridge further includes: a first plate having a first surface including a channel; a second plate having a second surface including a channel; and a resilient sealing element connecting the first plate and the second plate and at least partially sealing the channel, wherein the resilient sealing element is configured to deform in response to a change in local pressure state and thereby change the cross-section of the channel.

[0183] The fluid sensor system may further include a pump, specifically configured to generate negative pressure to drive fluid through a channel in the cartridge, specifically to draw and / or suck fluid into the fluid channel and into the cartridge.

[0184] This type of cartridge may already exist in IVD analyzers, and therefore no additional components are needed, particularly no additional channels (systems) and / or sensor housing units, for identifying whether the sample fluid is problem-free (expected / normal sample fluid), problem-free but with high viscosity, and / or must be considered a problem sample fluid. The resilient sealing element is sensitive to the temporal evolution of local pressure (especially negative pressure) because it deforms and changes the cross-sectional area of ​​the channel when the local pressure changes. A conductivity sensor unit can detect this change in the channel's cross-sectional area. Therefore, the structural features of existing cartridges can be utilized, and their transformation in a highly efficient manner can be achieved to identify the state of the sample fluid.

[0185] The first fluid may include a backup solution. The backup solution may be a conductive aqueous solution containing salt ions, such as a buffer solution or any other type of salt solution. When the instrument is not in operation, the backup solution can be stored in the fluid system, particularly in the cartridge channels, to prevent components such as the reference electrode from drying out. When the sample fluid is introduced into the fluid system, the sensor remains in contact with the backup solution, and therefore, the introduction of the first fluid may have occurred long before the introduction of the sample fluid. In other words, minutes, hours, or even days before the sample fluid is introduced for analysis, the first fluid may have already filled the fluid system, particularly the cartridge channels. Therefore, using the backup solution to determine the state of the sample fluid is convenient and efficient for the user.

[0186] Sample fluids can include bodily fluids, such as blood samples and / or tears. In BGE analyzers, blood is typically used as the sample fluid for analysis.

[0187] A computer program product, which can be considered a fourth aspect, is provided having instructions stored thereon that cause the machine of an IVD analyzer to initiate and / or perform the steps of the methods described herein (i.e., the methods of any aspect or any of the described embodiments).

[0188] Computer program products and their corresponding methods or embodiments have the same advantages.

[0189] According to another aspect of this disclosure, which can be considered a fifth aspect, a method is provided for determining the local pressure state in a fluid system (specifically, a cartridge channel) of an IVD analyzer, and the method includes the steps of: introducing a first fluid into a channel of the IVD analyzer, wherein the channel includes a resilient sealing element configured to change the 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 ​​depend on the cross-section of the channel; and determining the local pressure state from the detected one or more conductivity parameter values.

[0190] According to the fifth aspect of this disclosure, it is advantageous to determine the local pressure state in a channel (particularly a fluid channel or channel system) by utilizing the (side) effect of the resilient sealing element being configured to change the cross-section of the channel in response to changes in the local pressure state.

[0191] The conductivity sensor units already present in many cartridges used in IVD analyzers are used to detect one or more conductivity parameter values. Therefore, this method is highly efficient in identifying local pressure conditions, such as overpressure conditions in the channel system and / or any components, the channel system, and / or the instrument that could potentially damage the cartridge. This method also allows for the detection of whether a local pressure condition corresponds to atmospheric pressure, and in particular whether the local pressure condition cannot be changed by altering pump settings, which would be the case when the pump is defective and unable to generate pressure, especially when there is negative pressure, or when there is a leak in the channel system. The method according to the fifth aspect may require calibration, where the correspondence of conductivity parameter values ​​for multiple local pressure conditions is identified.

[0192] The local pressure state, particularly changes in the local pressure state, is derived from one or more conductivity parameter values. This can be performed by a controller, machine, and / or processor. During the conductivity detection time span (particularly when the first fluid physically contacts the conductivity sensor unit in the channel), one or more conductivity parameter values ​​are detected, measured, and / or recorded in a first fluid. The first fluid is typically a conductive liquid, such as an aqueous solution containing ions. One or more conductivity parameter values ​​may correspond to a set of conductivity parameter values. The method may include the step of determining the temporal evolution of the local pressure state from the detected set of conductivity parameter values. The method may include the steps of automatically identifying and / or deriving indications of the state of an instrument, IVD analyzer, cartridge, pump, and / or fluid system by analyzing the local pressure state, particularly its temporal evolution. For example, a leak in a fluid system can be reflected by the characteristics of the temporal evolution of the local pressure state derived from the detected set of conductivity parameter values. In some cases, the method may allow differentiation between states such as a defective pump and a leak in the fluid system.

[0193] Furthermore, the method may include the step of introducing a second fluid, which may be a sample fluid introduced after the first fluid has been introduced into the fluid system. The second fluid may be spatially separated from the first fluid in the fluid system, particularly through gas bubble separation. The method may then include the step of automatically determining the characteristics of the sample fluid based on a determined time evolution of the local pressure state.

[0194] The method according to the fifth aspect may include one or more of the features mentioned above, and if the feature is compatible with the detection of one or more conductivity parameter values ​​using a conductivity sensor unit, then the feature has corresponding advantages.

[0195] According to one example of this disclosure, a method for determining the local pressure state in a channel of an IVD analyzer is provided, and the method includes the steps of: introducing a first fluid into the channel of the IVD analyzer; introducing a sample fluid spatially separated from the first fluid into the channel; detecting a component pressure value of a gas in the first fluid during a gas detection time span using a gas sensor unit; and determining the local pressure state from the detected component pressure value of the gas. Furthermore, the method according to this example may include one or more of the features described above, which have corresponding advantages if they are compatible with the detection of one or more conductivity parameter values ​​using a gas sensor unit.

[0196] Generally, the local pressure value can be determined, for example, by using an optical oxygen sensor unit to determine the actual partial pressure in air. Therefore, by utilizing the semi-filled channel of the cartridge, the oxygen sensor unit in air, and the conductivity sensor unit in a spare solution, the conductivity sensor unit can be calibrated to indirectly measure the local pressure value.

[0197] Generally, additional sensors and / or sensor units (cameras, ultrasound, electric fields) can be provided in the instrument, at the fluid system, and / or within it. These additional sensors and / or sensor units can be used to measure the conditions of the fluid system, such as the shape of the fluid in the peristaltic pump tubing or the fluid within the fluid system and / or the channels filled with conductive fluid inside the soft peristaltic pump tubing. The flexible tubing that can be used in the fluid system can also respond to pressure changes in the fluid system and thus reveal information about the characteristics of the sample fluid. This allows for the detection of indications of clots to confirm results obtained by the methods according to the first and / or second aspects, without placing the sensor directly in a periodically set consumable.

[0198] The most important advantage of this invention is that the intended characteristics of the sample fluid can specifically relate to the state of blood coagulation, aggregation, and / or the viscosity of the blood sample. Existing facilities for fluid sensor systems can be used efficiently without the need for additional sensors, avoiding additional materials and system complexity, thus making the IVD system very environmentally friendly and operationally efficient. Since the fluid sensor system is protected from the passage of coagulated and therefore problematic samples and potential blockages that could render the fluid sensor system unusable, it can be disposed of without disposal. This further improves the environmental friendliness of the fluid sensor system and reduces downtime and potential maintenance required for IVD devices. Furthermore, high-viscosity sample fluids can be identified and differentiated relative to coagulated blood samples, allowing disposal of only coagulated blood samples and not high-viscosity samples. This allows the avoidance of having to obtain additional blood samples from the patient, and therefore the invention is also very patient-friendly, as his / her sample is used efficiently by the IVD system. Furthermore, the invention adds value to the functionality of the IVD system by determining additional parameters that can not only protect the fluid sensor system from damage but also indicate the patient's health status. Therefore, this invention is efficient, patient-friendly, and environmentally friendly, and adds significant value to existing IVD devices. Detailed Implementation

[0199] In the following description, some exemplary embodiments will be described in detail, wherein the invention should not be construed as being limited to the described exemplary embodiments. The following examples and drawings are provided to aid in understanding the invention, and the true scope of the invention is set forth in the appended claims. Individual features described in particular embodiments may be combined arbitrarily, as long as they are not mutually exclusive. Furthermore, the different features provided together in the exemplary embodiments should not be considered as limiting the invention.

[0200] Those skilled in the art will understand that the elements in the accompanying drawings are shown for simplicity and clarity and are not necessarily drawn to scale. For example, the dimensions of some elements may be enlarged relative to other elements, while other elements may have been omitted or represented by reduced quantities to enhance clarity and improve understanding of aspects of this disclosure.

[0201] The same reference numerals are used for the same or similar elements or elements having similar or the same effect in different embodiments and examples. Attached Figure Description

[0202] Figure 1 is a schematic diagram of a typical fluid system;

[0203] Figures 2a and 2b are schematic diagrams of a fluid system at different suction stages according to one embodiment;

[0204] Figure 3a is a schematic diagram of a channel cross-section under ambient pressure conditions according to one embodiment;

[0205] Figures 3b and 3c are photographic illustrations of the channel cross-section under ambient pressure and negative pressure conditions according to one embodiment;

[0206] Figure 4a is a flowchart of a method for determining the state of a sample fluid in an IVD analyzer using a conductivity sensor unit according to one embodiment;

[0207] Figure 4b is a flowchart of a method for determining the local pressure state in an IVD analyzer using a conductivity sensor unit according to one embodiment;

[0208] Figure 5 is a flowchart of a method for determining the state of a sample fluid in an IVD analyzer using a conductivity sensor unit according to another embodiment;

[0209] Figure 6 is a flowchart of a method for determining the state of a sample fluid in an IVD analyzer using a conductivity sensor unit and a gas sensor unit according to another embodiment;

[0210] Figure 7 is a flowchart of a method for determining the state of a sample fluid in an IVD analyzer using a gas sensor unit according to one embodiment;

[0211] Figures 8a and 8b are schematic timelines of the detection time span relative to the introduction time span according to embodiments of this application;

[0212] Figure 9 is a photographic illustration with additional schemes and annotations of cartridges (such as the fluid system according to Figure 1) that can be used in IVD analyzers;

[0213] Figure 10 shows a record of the conductivity parameters of the first fluid when the fluid path is blocked;

[0214] Figure 11 is a photographic illustration of the cartridge of Figure 9 with additional scheme and annotations, showing the sample positioning relative to the conductivity sensor unit and the gas sensor unit; and

[0215] Figure 12 is a photographic illustration of the cartridge of Figure 9 with additional scheme and annotations, to show the sample positioning relative to the conductivity sensor unit and the gas sensor unit in the case of a problematic sample with fluid blocked channels.

[0216] Figure 1 is a schematic diagram of the fluid system 35 of the IVD analyzer 10, and is described in detail below.

[0217] A first fluid path 28 passes through the cartridge 30. This path corresponds to a flow sensor path including channel 4, in which multiple sensors 5 and 6 are positioned. A second fluid path 29 corresponds to a flow optical path, which includes a cuvette 14 arranged between the light source 36 and the photodetector 37, thereby forming an optical detection unit 13 (such as a blood oxygen quantification module) for optically measuring biological samples introduced into the cuvette 14 via the second fluid path 29.

[0218] The IVD analyzer 10 further includes a pump 11 (such as a peristaltic pump) located downstream of the fluid system 35 and a fluid supply unit 17 comprising multiple fluids in a fluid supply container 18, as well as a waste container 32 in which the fluid circulating through the fluid system 35 can be disposed of by the action of the pump 11. The IVD analyzer 10 further includes a fluid selection valve 24 (or rotary valve) for selecting between fluids and / or air 16 from different fluid supply containers 18.

[0219] The IVD analyzer 10 further includes a sample input interface / sample input module (SIM) 21, which includes a sample input port 31 having an external input port side 34 configured for insertion into a sample container 12, which provides sample fluid, and an internal input port side 19 for introducing the sample fluid into a fluid system 35. The discharge position of SIM 21 is a position where SIM 21 is rotated toward the interior of a consumable such as a discharge container 23, at which it ejects the problematic sample fluid outside an area predetermined to capture clots. Once clots are detected via a timeout procedure, pump 11 is reversed to discharge the clots. Furthermore, if the IVD analyzer 10 is used according to the invention and clots are detected, pump 11 can be reversed to discharge the clots. More specifically, in the case of clot detection, SIM 21 is rotated toward the discharge container 23 and pump 11 is reversed.

[0220] In this example, sample container 12 is a capillary sample container. Sample input interface 21 further includes aspiration needle 27, which has an upstream end and a downstream end. The downstream end of aspiration needle 27 is fluidly connected to fluid system 35 via fluid line 22, while the upstream end is configured to alternately connect to inner input port side 19 to aspirate sample 2 from sample container 12 inserted into outer input port side 34 and to fluid supply unit port 38, which is fluidly connected to the common outlet port 39 of fluid selector valve 24 via a separate conduit. However, fluid line 22 may also be directly connected to outlet port 39 of fluid selector valve 24, and the sample may be introduced via, for example, a different fluid line separately connected to fluid selector valve 24.

[0221] If the sample fluid does not reach one of the sample sensors 25 after a predetermined timeout period, the problematic sample fluid is routinely detected / identified in the fluid system 35. The timeout for sample sensor aspiration can be set, for example, to 12 seconds in syringe operation mode and 20 seconds in capillary operation mode. The longer timeout in capillary operation mode is because manual QC is sometimes performed using a capillary adapter, and aspiration takes longer. During pumping, a negative pressure is generated in the channel 4 of the cartridge 30 as fluid is directed toward the waste container 32. The channel 4 of the cartridge 30 is simplified in this figure; typically, a cartridge includes several channels 4 that are fluidly connected to each other and form a cartridge channel system. In other words, a cartridge that can be used to implement the present invention may include a cartridge channel system comprising channels 4. In this conventional clot detection method, clots may be transported deep into the fluid system 35, and when the flow rate decreases due to the problematic sample fluid clogging the fluid system 35, the negative pressure drops below the typical expected value. Such negative pressure causes the clots to move further into the fluid system 35 and makes it more difficult to remove the problematic sample fluid by reversing the flow direction.

[0222] Furthermore, when fluid system 35 is blocked by the problematic sample fluid, microbubbles may leak into the system at connection points due to the negative pressure created within the fluid system. If such microbubbles cannot be removed, they may cause additional problems later, such as altered and distorted blood gas values, crystallization, etc. The further the problematic sample fluid is transported into fluid system 35, the higher the stress generated by overpressure on the fluid channel system during the clot removal procedure, and the lower the probability of successful removal of the problematic sample fluid. If the problematic sample fluid cannot be removed, consumables, such as cartridges, must be replaced.

[0223] At least the hardware components of the fluid system 35 of Figure 1 can be used to implement the present invention, namely one or more of the embodiments described below. The controller 40 and / or software used by the controller 40 of the fluid system 35 of Figure 1 need to be configured to initiate, trigger, and / or perform at least some steps of the method of the present invention. At least some of the cartridge sensor conductivity sites K1 to K5 (as shown in Figure 9) of the cartridge 30 according to one embodiment can be used as conductivity sensor units in the fluid system 35 of Figure 1. When a negative pressure is detected in the cartridge 30, the channel 4 of the cartridge 30 contracts as the resilient sealing element (i.e., the 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 Figure 3c). The reduction in the area of ​​the reduced cross-section constitutes the admittance between the conductivity sites of the conductivity sensor unit 5 (which is considered a possible conductivity parameter).

[0224] As indicated above, the fluid properties of blood can vary drastically from patient to patient, and therefore data must be carefully evaluated to distinguish between clotted sample fluids and high-viscosity sample fluids. High-viscosity sample fluids may move more slowly and result in lower pressure compared to low-viscosity samples. In the case of high-viscosity sample fluids, flow resistance is proportional to the amount of sample in the system, so flow resistance increases slowly, and negative pressure “builds up,” i.e., decreases further. In the case of clots, flow resistance rises more abruptly, which allows for the differentiation of problematic sample fluids with clots from high-viscosity samples.

[0225] Sample fluid can be aspirated via the sample input module needle 27, as shown in Figure 1. In one embodiment, the diameter of the sample input module needle 27 can be 0.6 mm. Particles larger than this diameter cannot enter the channel system. In one embodiment, the tubing and / or channel system can have elements with a diameter of approximately 0.75 mm. Generally, the diameter of the sample input module needle 27 can range from approximately 0.3 mm to approximately 10 mm, and the tubing and / or channel 4 of the cartridge can range from approximately 0.1 mm to approximately 12 mm. Some channels that can be connected to the channel system or can be constituted by a fluid system can even be in the µm range, and thus represent microchannels.

[0226] As shown in Figure 1, the optional cuvette 14 for optical measurements may have a minimum distance between the two walls and / or a diameter of approximately 0.1 mm, and therefore, particles, clots, and aggregates larger than approximately 100 µm in size can cause problems. The minimum distance between the two walls and / or the diameter of the cuvette is typically in the range of approximately 0.05 mm to approximately 0.5 mm. Generally, the size of discoid human red blood cells is typically in the range of approximately 7.5 μm to approximately 8.7 μm in diameter and in the range of approximately 1.7 μm to approximately 2.2 μm in thickness. These are the largest objects that can be expected in normal, problem-free sample fluids (such as blood). Therefore, particles, clots, and / or aggregates in sample fluids with sizes ranging from approximately 15 to 20 µm to approximately 100 µm or larger may result in lower negative pressure values ​​in the fluid system 35 compared to normal, problem-free sample fluids. Such particles, clots, and / or aggregates in the sample fluid may clog the entire fluid system 35.

[0227] Figures 2a and 2b are partial schematic diagrams of the fluid system 35 in two different aspiration phases of an IVD analyzer 10 according to one embodiment. In these schematic diagrams, the sensor system 20 and cartridge 30 of the IVD analyzer 10 are scaled to size; these dimensions do not represent their actual dimensions relative to the size of the IVD analyzer 10. The dimensions were chosen to better illustrate the details of the sensor system 20 and cartridge 30 of the IVD analyzer 10. The fluid system 35 is shown in a simplified manner to outline the concept of the embodiment.

[0228] Channel 4 is part of fluid system 35 and is contained in cartridge 30. Peristaltic pump 11 draws first fluid 1, sample fluid 2 and other fluids 3a, 3b (referred to as third fluids), such as gas bubbles, through channel 4. Gas bubble 3a may be, for example, an air bubble used to separate first fluid 1 from sample fluid 2.

[0229] Generally speaking, even though channel 4 is described herein as part of cartridge 30, channel 4 may also be part of fluid system 35 that is not part of another element of cartridge 30 (such as a cuvette or another flow cell, such as some other microfluidic cell).

[0230] In this embodiment, the cartridge 30 includes a conductivity sensor unit 5 with two conductivity sensor sites 5a and 5b, and a gas sensor unit 6 positioned in the channel 4 to detect the fluid passing through the sensors 5 and 6. The sensors 5 and 6 are connected to a controller 40. The controller 40 can control the sensor units 5 and 6 and / or process the data collected using the sensor units 5 and 6. The conductivity sensor unit 5 is based on an electrochemical measurement principle, and the gas sensor unit 6 can be based on an optical measurement principle or an electrochemical measurement principle. In this example, only two sensor units 5 and 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 typically located in the cartridge can be used to determine the characteristics of the sample fluid 2 derived from the time evolution of the collected data / values.

[0231] The IVD analyzer 10 may also exclude the gas sensor unit 6, or the cartridge 30 may also exclude the gas sensor unit 6. In the latter case, the gas sensor unit 6 may be located outside the cartridge 30 in another unit. In particular, when the IVD analyzer does not include the gas sensor unit 6, the local pressure state and / or characteristics of the sample fluid 2 can be determined or identified solely by means of the conductivity sensor unit 5. However, even if the gas sensor unit 6 is provided in the IVD analyzer 10, the characteristics of the sample fluid can be determined or identified solely by means of the conductivity sensor unit 5. Alternatively, the IVD analyzer may also exclude or utilize the conductivity sensor unit 5. Then, the characteristics of the sample fluid 2 can be determined or identified solely by means of the gas sensor unit 6.

[0232] Figures 3a, 3b, and 3c show the cross-sectional area (area) of channel 4 in the cartridge 30, as illustrated in the schematic diagrams of Figures 2a and 2b. In Figure 3a, a schematic diagram of the channel cross-section is shown under relaxed conditions, such as when virtually no negative or overpressure is applied to channel 4. In Figure 3b, a photograph of the actual cross-section of channel 4 is shown under relaxed conditions. In Figure 3c, a photograph of the cross-section of the same channel 4 is shown under conditions where pressure is reduced and negative pressure is applied to channel 4.

[0233] In the embodiments shown in Figures 3a, 3b, and 3c, the cartridge channel 4 is formed by a first plate 7, which can be considered an upper plate, and a second plate 8, which can be considered a lower plate, and one or more resilient sealing elements 9. More specifically, the first plate 7 includes a first surface 7a, i.e., the upper surface of the channel 4, and the second plate 8 includes a second surface 8a, i.e., the lower surface of the channel 4. The resilient sealing elements 9 include segments of the surfaces of the channel 4, i.e., the side surfaces of the channel 4.

[0234] When the pressure decreases, for example, by creating a negative pressure and applying it to channel 4, a portion of the resilient sealing element 9 is drawn into the internal volume of channel 4, as can be seen when comparing the areas indicated by white circles in Figures 3b and 3c. Therefore, the cross-section of channel 4 decreases when a negative pressure is applied, as indicated in Figure 3c, compared to the cross-section of channel 4 in the relaxed state as shown in Figure 3b. Conductivity parameters (such as admittance) measured in channel 4 are sensitive to this change in cross-section and can therefore be used as a probe for the local pressure state and / or characteristics of a sample.

[0235] Combination Figure 3a Referring to Figures 3c, 2a, and 2b, the concept of a method according to one embodiment can be described in more detail below, wherein the conductivity sensor unit 5 is used to determine the properties and / or state of the sample fluid and / or the local pressure state.

[0236] In Figure 2a, the fluid system 35 is in a state in which, for example, a first fluid 1 (a spare solution) has been filled into the channel 4 of the cartridge 30, and the sample fluid 2 has been drawn into the fluid system 35, but not yet into the channel 4 of the cartridge 30. Specifically, the majority of the fluid system 35 may be filled with the first fluid 1. In other words, in the state shown in Figure 2a, the first fluid 1 has been drawn into the channel 4 of the cartridge 30, i.e., behind the channel inlet 4a (or the inlet port of the cartridge 30), while the sample fluid 2 has not yet passed through the channel inlet 4a of the cartridge 30. In this exemplary state, the first fluid 1 has not yet come into contact with any of the sensors 5, 6, and in particular, the first fluid 1 has not yet come into contact with the conductivity sensor unit 5, which consists of the two conductivity sites 5a, 5b shown in Figures 2a and 2b. The first fluid 1 and the sample fluid 2 are separated by an air bubble 3a. Sample fluid 2 can be followed by another air bubble 3c. Air bubbles 3a and 3b can each be considered as a third fluid.

[0237] In the scenario shown in Figure 2a, when sensors 5 and 6 are brought into contact with the first fluid 1, a set of conductivity parameter values ​​of the first fluid 1 (specifically a liquid) and / or a component pressure value of the gas in the first fluid 1 (specifically a liquid and / or a gas bubble) can be recorded. In other words, the fluid system 35 is in a state where the first fluid 1 is in contact with the two conductivity sensor sites 5a and 5b of the conductivity sensor unit 5 and the gas sensor unit 6, while the sample fluid 2 has not yet reached the channel 4 of the cartridge 30, specifically the channel inlet 4a. If the controller 40, which receives and processes this data, identifies or determines the temporal evolution of these values, indicating that the sample fluid 2 is problematic due to the presence of clumps or other particles, it can initiate or trigger the inverted rotation of the peristaltic pump 11 to eject the problematic sample fluid 2. If the controller 40 identifies that the behavior of the sample fluid 2 is as expected and without problems, the sample fluid 2 can pass through the channel 4 of the cartridge 30, as shown in Figure 2b.

[0238] In Figure 2b, the first fluid 1 is pumped across the outlet port 4b of cartridge 30 toward the discharge container. The separation bubble 3a and the blood sample (sample fluid 2) have already entered the channel 4 of cartridge 30 after passing through the inlet port 4a. After identifying sample fluid 2 as not being problematic (i.e., free of any clots or particles / aggregates), it is allowed to enter channel 4. Therefore, the original functions of the sensor units 5, 6 in channel 4 of cartridge 30 can be used to analyze sample fluid 2. Specifically, the target blood gas parameters can be determined under this configuration. If sample fluid 2 would be identified as problematic in the state shown in Figure 2a, the pump 11 and the flow of fluid are reversed to discharge the problematic sample 2 from the fluid system 35.

[0239] It should also be noted that the conductivity changes when air bubble 3a reaches sensor sites 5a and 5b. In this case, the conductivity typically drops sharply, and is therefore very specific to this event.

[0240] In the following description, methods according to several embodiments are further described together with the flowcharts of Figures 4a to 7 and the timelines of Figures 8a and 8b. Figure 4a is a flowchart of a method 100 for determining the characteristics of a sample fluid 2 in an IVD analyzer 10 using a conductivity sensor unit 5 according to one embodiment. Figure 4b is a flowchart of a method 300 for determining the local pressure state in an IVD analyzer 10 using a conductivity sensor unit 5 according to one embodiment. Figure 5 is a flowchart of a method 100 for determining the characteristics of a sample fluid 2 in an IVD analyzer 10 using a conductivity sensor unit 5 according to another embodiment. Figure 6 is a flowchart of a method 100 for determining the characteristics of a sample fluid in an IVD analyzer using a conductivity sensor unit 5 and a gas sensor unit 6 according to another embodiment. Figure 7 is a flowchart of a method 200 for determining the characteristics of a sample fluid 2 in an IVD analyzer 10 using a gas sensor unit 6 according to one embodiment. Methods 100, 200, 300 according to one or more of these embodiments are compatible with the fluid system 35 described above, and therefore, methods 100, 200, 300 according to Figures 4a to 7 can be combined with the fluid system 35 described in Figures 1 to 3a to 3c.

[0241] Figure 4a illustrates a method 100 for determining the characteristics of the sample fluid 2 in the IVD analyzer 10 primarily through the use of the conductivity sensor unit 5. Method 100 includes the following steps:

[0242] a. The first fluid 1 is introduced into the fluid system 35 of the IVD analyzer 10, specifically into the channel 4 of the fluid system 35, wherein the fluid system 35 includes the channel 4, and the channel 4 may be part of a cartridge and includes an elastic sealing element 9 and is at least partially sealed by the elastic sealing element 9, which is configured to change the cross-section of the channel in response to changes in the local pressure state when the sample fluid 2 is aspirated.

[0243] b. Introduce the sample fluid 2, which is spatially separated from the first fluid 1, into the fluid system 35 via 110b.

[0244] c. Make the conductivity sensor unit 5 physically contact the first fluid 1 120, that is, make at least two conductivity sensor sites 5a and 5b of the conductivity sensor unit 5 in channel 4 physically contact the first fluid 120.

[0245] d. Using conductivity sensor unit 5, a set of conductivity parameter values, such as admittance, of the first fluid 1 are detected and / or recorded during the conductivity detection time span cdts (as indicated in Figures 8a and 8b), wherein the conductivity parameter values ​​depend on the cross-section of the channel, and

[0246] e. The characteristics of sample fluid 2 are automatically determined based on a set of detected conductivity parameters of the first fluid, which are dependent on pressure.

[0247] Steps a. 110a and b. 110b described above in method 100 may correspond to the aspiration of the first fluid 1 and / or sample fluid 2, respectively. Step e. 150 is performed automatically by a controller, processor, and / or machine. Steps a., b., c., and d. (110a, 110b, 120, 130) may be performed simultaneously. At least some of these steps 110a, 110b, 120, and 130 may overlap with each other. Steps a. 110a and b. 110b are not typically started simultaneously because the first fluid 1 is introduced before the sample fluid 2, and subsequently both fluids 1 and 2 are further introduced into the fluid system 35 simultaneously. At least some of these steps may also follow each other rather than overlap. The possibility that all steps a. through d. (110a, 110b, 120, 130) can be performed simultaneously is indicated in Figure 4a by boxes corresponding to steps arranged adjacent to each other. Step e. 150 can follow steps a. through d. (110a, 110b, 120, 130), as indicated by the arrows in Figure 4a. Step e. can partially overlap with one or all of steps a. through d. (110a, 110b, 120, 130). This also applies to other flowcharts.

[0248] Figure 4b illustrates alternative method 300, which is a method for determining the local pressure state in channel 4 of the IVD analyzer 10, wherein method 300 includes the following steps:

[0249] a. A first fluid is introduced into the fluid system 35 of the IVD analyzer 10, specifically into a channel 4 of the fluid system 35, wherein the channel 4 includes an elastic sealing element 9 configured to change the cross-section of the channel in response to changes in local pressure.

[0250] b. Make the conductivity sensor unit 5 in channel 4 contact the first fluid 1 320

[0251] c. Using conductivity sensor unit 5 to detect one or more conductivity parameter values ​​of the first fluid 1 at 330°, wherein the conductivity parameter values ​​depend on the cross-section of channel 4.

[0252] d. Determine the 340 local pressure state from one or more detected conductivity parameter values.

[0253] When determining the pressure state in channel 4 rather than the properties of sample fluid 2, method 300 outlined in FIG4b deviates from method 100 outlined in FIG4a. However, method 300 can also be included by method 100, and therefore most of the advantages applicable to the corresponding steps of method 100 also apply to method 300. Further, method 300 can be combined with features of embodiments of method 100. In method 300, a local pressure state is determined, wherein a conductivity parameter is used as a probe to determine, for example, the local pressure state in cartridge 30, while in method 100, the state of the sample fluid is derived from the time evolution of the local pressure state from a set of conductivity parameter values ​​obtained from a first fluid. It may be necessary to determine the relationship between conductivity and pressure state in calibration for each channel or for a representative of a batch of channels and / or cartridges.

[0254] Figure 5 illustrates method 100 of Figure 4a with additional optional steps. In the method of Figure 5, the automatic determination step 150 includes the optional step of applying a trained artificial neural network 155 to the determined time evolution of the local pressure state to determine the properties of the sample fluid. In this case, method 100 may further include the optional step of training the artificial neural network 105 using a training dataset that includes the time evolution of conductivity parameter values ​​corresponding to a predefined state of the sample fluid 2. Training 105 is typically performed before initiating actual measurements, starting with one or all of steps 110a, 110b, 120, and 130.

[0255] For example, (primary) training can be performed by the manufacturer or retailer of consumables (such as cartridges), and the trained neural network can then be provided to the customer. In the initial phase, additional training of the neural network can be performed on the customer side to fine-tune it for individual cartridges. Ideally, this can be done without additional workflows, based on observations during a standard workflow that must be performed in the initial phase anyway.

[0256] Alternatively or additionally, method 100 may include the step of automatically triggering an action in the IVD analyzer 10 based on the determined characteristics of the sample fluid 2. This action may include at least one of the following steps 165:

[0257] When a problematic sample fluid 2 is identified (which contains, for example, clumps):

[0258] Stop the steps of introducing the first fluid 1 and / or sample fluid 2 into 110a and 110b.

[0259] Reverse the operating direction of the pump

[0260] Discharge sample fluid 2

[0261] Introduce a washing solution and wash the channel at least partially with the washing solution.

[0262] When sample fluid 2 is identified as having no problems, an alarm is output optically and / or acoustically:

[0263] Continue with the steps of introducing the first fluid 1 and / or sample fluid 2 into 110a and 110b.

[0264] Optically and / or acoustically output control signals, such as a green light or noise, to confirm that there are no problems with the sample fluid 2.

[0265] Figure 6 refers to method 100 of Figure 4a with additional optional steps. The method of Figure 6, having some or all of the optional steps, can be combined with some or all of the steps outlined in Figure 5. Method 100 of Figure 6 includes some or all of the following optional steps:

[0266] Gas sensor unit 6 is used to detect a component pressure of gas in the first fluid 1 or the third fluids 3a and 3b (e.g., air bubbles) during the gas detection time span odts (as shown in Figures 8a and 8b). Specifically, oxygen sensor unit 6 is used to detect a component pressure of oxygen in the first fluid 1 or the third fluids 3a and 3b (e.g., air bubbles) during the oxygen detection time span odts (as shown in Figures 8a and 8b).

[0267] The characteristics of sample fluid 2 (250 μg / mL) are automatically determined based on the time evolution of gas partial pressure values.

[0268] Optionally, compare the characteristics of sample fluid 260 determined from a component pressure value detected from the gas and the characteristics of sample fluid 2 determined from a set of detected conductivity parameters.

[0269] If a problem with the sample fluid can be identified based on the detected partial pressure values ​​of a component of the gas, then the detected set of conductivity parameters can also be used to determine the characteristics of sample fluid 2 to confirm the result. If the result cannot be confirmed, actions can be triggered. For example, further measurements of the conductivity parameters and / or the partial pressures of the gas can be performed. Alternatively or additionally, the steps of introducing the first fluid 1 and / or sample fluid 2 into 110a, 110b can be stopped by stopping pump 11, and / or an alarm can be triggered to inform the user of a potential problem.

[0270] Figure 7 illustrates a method 200 for determining the characteristics of the sample fluid 2 in the IVD analyzer 10 primarily through the use of the gas sensor unit 6. Method 200 includes the following steps:

[0271] a. Introduce the first fluid 1 into the fluid system 36 via 210a, specifically into the channel 4 of the cartridge in the fluid system 36 of the IVD analyzer 10.

[0272] b. Introduce the sample fluid 2, which is spatially separated from the first fluid 1, into the fluid system 36 via 210b.

[0273] c. Using the gas sensor unit 6, detect the component pressure of a gas in the first fluid 1 (230°C) during the gas detection time span (odts). Specifically, using the oxygen sensor unit 6, detect the component pressure of oxygen in the first fluid 1 (230°C) during the gas / oxygen detection time span (odts).

[0274] d. The characteristics of sample fluid 250 are automatically determined based on the time evolution of the detected component pressure values ​​of the gas.

[0275] The method 200 of Figure 7 may also include optional steps 105, 155 related to the training of the neural network and the processing performed by the neural network, as described together with Figure 5. Alternatively or additionally, steps 160, 165 may be included by method 200, as already described together with Figure 5.

[0276] Figures 8a and 8b are schematic timelines of detection time spans cdts and odts relative to introduction time spans its, according to embodiments of this application. The conductivity detection time spans cdts and / or gas detection time spans odts can begin before the introduction time spans its, when sample fluid 2 is introduced into fluid system 35 (particularly when it is aspirated into fluid system 35), as indicated in Figure 8a. The conductivity detection time spans cdts and / or gas detection time spans odts can even begin before or simultaneously with the introduction of sample fluid 2 into the fluid system 35 of the IVD analyzer. Therefore, the detection time spans cdts and / or odts can begin while sample fluid 2 is still in the vial before it enters the fluid system 35 of the IVD analyzer 10. The conductivity detection time span (cdts) and / or the gas detection time span (odts) can specifically begin before pump 11 is started.

[0277] The conductivity detection time span (cdts) and / or the gas detection time span (odts) can begin simultaneously with the introduction time span (its) when sample fluid 2 is introduced into fluid system 35, as indicated in Figure 8b. Specifically, the conductivity detection time span (cdts) and / or the gas detection time span (odts) can begin at the moment pump 11 is started.

[0278] Figure 9 is a photographic illustration with additional schemes and annotations of a cartridge 30 that can be used in an IVD analyzer 10, specifically in a fluid system 35 (such as the fluid system shown in Figure 1) and / or an IVD analyzer 10 (which is schematically shown in Figures 2a and 2b). In Figure 9, the ellipses and lines in the additional scheme indicate the locations where blood gases (dashed lines), electrolytes (solid lines), and metabolites (dashed and dashed lines) are detected by the corresponding sensors. Further, conductivity sites K1 to K6 are shown (indicated by arrows). One or more of conductivity sites K1 to K6 can be used to detect conductivity parameter values ​​in one or more embodiments of the method in which conductivity sensor unit 5 is used. Conductivity sites K1 and K2 (5a, 5b) can constitute a first conductivity sensor unit 5. In a possible later stage, conductivity sites K2 and K3 (5a, 5b) can constitute a second conductivity sensor unit 5.

[0279] One or more sensors used to measure blood gases can be used to detect the partial pressure of a gas in one or more embodiments of the method in which the gas sensor unit 6 is used. Specifically, the oxygen sensor unit 6 can be used to detect the partial pressure of oxygen in an air bubble or liquid.

[0280] Figure 10 is a record of the conductivity parameters of the first fluid 1, measured by the conductivity sensor unit 5 as an example of conductivity measurement. The conductivity parameters correspond to the admittance in this record and are plotted in µS against time in s. Figure 10 is recorded in a similar setting, as described with Figure 1 with a rotary valve. Pump 11 is started (indicated by the arrow and letter "a"), and in response, channel 4 contracts, and the admittance drops significantly; pump 11 is stopped (indicated by the arrow and letter "b"), and channel 4 extends, and the admittance increases to a baseline value of 85.2 µS. In the presented record, pump 11 is started three times. The brief rise in admittance before the drop is due to a switching in the rotary valve, which is performed in this measurement. The conductivity parameter values ​​are detected in sensor cartridge 30 (Cobas b123). When pump 11 starts (indicated by "a"), a negative pressure is generated, and the resilient sealing element 9 moves inward into channel 4, reducing the cross-sectional area of ​​the channel. In this situation, a significant decrease in admittance can be observed.

[0281] Alternatively or additionally, the gas sensor unit 6, corresponding to the optical gas sensor unit site in the cartridge 30 shown in Figure 9, can be used to determine the partial pressure of gases (such as oxygen (O2) and / or carbon dioxide (CO2)) in channel 4, and in particular the characteristics of sample fluid 2. The sensor cartridge 30 shown in Figure 9 is characterized by an optical oxygen sensor unit site that measures the partial pressure of oxygen in air and liquids. The measurement principle is based on the effect of dynamic luminescence quenching of molecular oxygen. The measured partial pressure of the gas depends directly on the local pressure. Therefore, the oxygen sensor unit 6 can be used as an indirect pressure sensor while located in a medium with a known oxygen concentration (e.g., a spare solution and / or air).

[0282] The optical gas sensor unit is highly sensitive and responds rapidly to pressure changes. Furthermore, the gas sensor unit is less dependent on variations in the material properties and manufacturing tolerances of the soft material of the resilient sealing element. Measurement of the electrical conductivity parameter can well complement the measurement of the gas partial pressure. However, the response of the resilient sealing element can be considered, which makes detection slightly slower.

[0283] Figure 11 is a photographic illustration of the cartridge 30 of Figure 9 with additional scheme and annotations to show the sample positioning relative to the conductivity sensor unit 5 and the gas sensor unit 6, and Figure 12b) is a corresponding photographic illustration in which the problematic sample fluid 2 is blocking the channel 4. Figure 9 , 11 The cartridge 30 shown in Figure 12 has two sensor types, a conductivity sensor unit 5 and a gas sensor unit 6, and therefore, the characteristics of the sample fluid can be determined by means of one or more of the two detector types. Further, the cartridge 4 includes a main channel 4 for introducing the first fluid 1 and the sample fluid 2, and a reference channel 33 for introducing the reference solution.

[0284] The measurement principle according to one embodiment will be described in further detail with respect to Figures 11 and 12. Two sensor types (conductivity and gas, i.e., oxygen in this case) are used together to provide reliable data to determine the presence of agglomerates. Using two sensor types also prevents errors caused by changes that occur when the first fluid 1 (followed by the sample fluid 2) passes through sensors 5 and 6, and then through an air bubble (or any other third fluid).

[0285] For example, such a change may occur when a gas separation bubble (third fluid 3a) follows the backup solution (first fluid 1), which separates the space between the backup solution (first fluid 1) and the blood sample (sample fluid). For example, when the backup solution is pumped toward the outlet port 4b of the cartridge 30, the separation bubble and the blood sample can enter the cartridge 30.

[0286] Two conductivity sensor sites (e.g., K1K2, K2K3, K3K4, and K4K5) used to measure the conductivity parameters between them can be considered as a conductivity sensor unit 5.

[0287] In Figure 11a), the main channel 4 is filled with a spare solution (first fluid 1), and the reference channel is filled with a reference solution, and the following determinations are made by means of a sensor:

[0288] -K1K2 (constituting the first conductivity sensor unit): "Normal" standby conductivity

[0289] -K2K3 (constituting the second conductivity sensor unit): "Normal" standby conductivity

[0290] -K3K4 (constituting the third conductivity sensor unit): "Normal" standby conductivity

[0291] -K4K5 (constituting the fourth conductivity sensor unit): "Normal" standby / reference conductivity (reference conductivity refers to the conductivity of the reference solution, see Figure 9).

[0292] -O2 (Oxygen sensor unit 6): Backup oxygen level.

[0293] In Figure 11b), the main channel 4 is filled with a spare solution (as the first fluid 1), an air bubble (as the third fluid 3a), and blood (as the sample fluid 2), and the reference channel is filled with a reference solution. The following determinations are made using a sensor:

[0294] -K1K2 (consisting of the first conductivity sensor unit): extremely low conductivity (air bubble)

[0295] -K2K3 (constituting the second conductivity sensor unit): "Normal" standby conductivity

[0296] -K3K4 (constituting the third conductivity sensor unit): "Normal" standby conductivity

[0297] -K4K5 (constituting the fourth conductivity sensor unit): "Normal" standby / reference conductivity

[0298] -O2 (Oxygen sensor unit 6): Backup oxygen level.

[0299] When the separating bubble reaches conductivity point K1, the conductivity between K1 and K2 drops sharply, but not to zero, because the conductivity from the liquid membrane still exists (Figure 11b). The conductivity between other pairs of conductivity points remains at the “normal” standby solution level of conductivity parameters.

[0300] In Figure 11c), the main channel 4 is filled with a spare solution (as first fluid 1), an air bubble (as third fluid 3a), and blood (as sample fluid 2), wherein, compared to Figure 11b), the fluids are further transported across channel 4. The reference channel is filled with a reference solution, and the following determinations are made using a sensor:

[0301] -K1K2 (consisting of the first conductivity sensor unit): extremely low conductivity (air bubble)

[0302] -K2K3 (constituting the second conductivity sensor unit): extremely low conductivity (air bubble)

[0303] -K3K4 (constituting the third conductivity sensor unit): "Normal" standby conductivity

[0304] -K4K5 (constituting the fourth conductivity sensor unit): "Normal" standby / reference conductivity

[0305] -O2 (Oxygen sensor unit 6): Lower oxygen level (blood).

[0306] As the air separation bubble moves further along channel 4 and covers conductivity point K2, the conductivity also decreases for sensor pair K2K3. When the air separation bubble between the backup solution and the sample fluid enters cartridge 30, the positions of sensors K4 and K5 (from main channel 4 to reference channel 33) in sensor pair K4K5 can be considered the optimal positions for assessing conductivity with clot detection as the target, since K4 is the last point covered by the air bubble. When measuring conductivity changes for one conductivity point in a conductivity point pair after another conductivity point, it can be deduced that these changes are caused by the separation of the air bubble. For a normal measurement workflow, i.e., when there are no issues with sample fluid 2, gas sensor unit 6 will first detect the oxygen level of the backup solution, then the air, and subsequently the blood oxygen level.

[0307] In Figure 11c), the main channel 4 is filled with blood (as sample fluid 2), and a backup solution (as first fluid 1) and an air bubble (as third fluid 3a) are delivered out of channel 4. The reference channel is filled with a reference solution, and the following determinations are made using a sensor:

[0308] -K1K2 (constituting the first conductivity sensor unit): "HCT-dependent" blood conductivity

[0309] -K2K3 (constituting the second conductivity sensor unit): "HCT-dependent" blood conductivity

[0310] -K3K4 (constituting the third conductivity sensor unit): "HCT-dependent" blood conductivity

[0311] -K4K5 (constituting the fourth conductivity sensor unit): "HCT-dependent" blood / reference conductivity

[0312] -O2 (Oxygen sensor unit 6): Lower oxygen level (blood).

[0313] Given the above, blood typically has a low oxygen level. However, for patients undergoing artificial oxygen aspiration, the oxygen level may be higher than that of air or a spare oxygen supply.

[0314] Figure 12 a) corresponds to Figure 11 a), but in a case where it can be determined that the blood sample is problematic and must not enter channel 4 of cartridge 30. This determination can be made conventionally by timeout measurement, or according to one of the embodiments described above based on measurements of conductivity parameter values ​​and / or partial pressures of the gas. In Figure 12 b), the problematic sample fluid 2, i.e., the blood sample with clots, is blocking the flow through channel 4. The blood has not yet reached channel 4, but the fluid cannot flow further because the pressure is insufficient to further deliver these fluids through channel 4 and the entire fluid system 35. The present invention should efficiently avoid this situation.

[0315] If flow-blocking clumps are present in the sample fluid, as shown in Figure 12b), the spare solution will remain in cartridge 30, and the pressure will decrease. This pressure drop is instantaneous and directly visible on the sensor values. Unlike the previous example in Figure 11, the pressure drop acts simultaneously on all conductivity sensor pairs and is therefore distinguishable from the effect of the separation bubble. Simultaneously evaluating data from conductivity sites and gas sensor unit sites improves the reliability of this method.

[0316] In the event of clots in sample fluid 2, gas sensor unit 6 will detect a decrease in the partial pressure of the gas. Depending on the instrument's altitude and the flow resistance of the blood sample, the pressure in the separation bubble 3a changes, and therefore the partial pressure of gas / oxygen in the separation bubble also changes. It may be lower than the partial pressure of gas / oxygen in the backup solution, and thus may also cause a decrease in the reading of gas / oxygen sensor unit 6.

[0317] As an example of this scenario, in Figure 12 b), the main channel 4 is filled with a spare solution (first fluid 1), and the reference channel is filled with a reference solution, and the following determination is made by means of a sensor:

[0318] -K1K2 (consisting of the first conductivity sensor unit): low conductivity (lower pressure)

[0319] -K2K3 (constituting the second conductivity sensor unit): low conductivity (lower pressure)

[0320] -K3K4 (consisting of the third conductivity sensor unit): low conductivity (lower pressure)

[0321] -K4K5 (consisting of the fourth conductivity sensor unit): low conductivity (lower pressure)

[0322] -O2 (Oxygen sensor unit 6): Lower partial pressure (lower pressure) of oxygen.

[0323] Referring again to Figure 1, the principle of determining viscosity and / or the range of viscosity is described according to one embodiment. As a supplement to or alternative to determining the presence of clots in a sample fluid, the viscosity of the sample fluid can be determined using the methods according to the first and / or second embodiments. The viscosity of a blood sample can serve as an indicator of disease and is therefore clinically relevant. For example, hyperviscosity syndrome (HVS) associated with extremely high blood viscosity corresponds to a cancer emergency, and timely treatment can prevent life-threatening complications such as thromboembolic events, myocardial infarction, and catastrophic ischemia leading to multiple organ failure. Therefore, an IVD analyzer, including, for example, a blood gas analyzer, can provide the additional functionality of indicating disease and / or emergency conditions caused by high blood viscosity. This combination is particularly advantageous because BGE point-of-care analyzers are typically located in the emergency room and / or intensive care unit—locations where critically ill patients will first appear and will benefit from faster and / or comprehensive analysis of such critical conditions.

[0324] The detection of blood clots (which completely obstruct flow in the fluid system of a BGE analyzer) is indicated by a sharp drop in pressure within the fluid system when a sample with a clot is aspirated into it. The possibility of determining the viscosity of sample fluids (such as whole blood samples) in a point-of-care BGE analyzer is described below. No additional measurement steps (other than those according to the methods of the first and / or second aspects) and / or instrumentation are required, nor are any changes to the system necessary.

[0325] The fluid system 35 can be calibrated for pressure measurements while simultaneously being used in normal sensor calibration procedures. The fluid system 35 is configured to deliver / guide different reagents of known and / or varying viscosities; for example, the viscosity of the reagents can be intentionally modified for the purpose of calibrating the fluid system 35 for pressure and / or viscosity measurements. The (metal) needle 27 of the sample input module (SIM) 21 has very tight dimensional tolerances, while other components of the fluid system have even larger tolerances in this regard. Therefore, the needle 27 of the SIM 21 is best suited for viscosity measurements.

[0326] As a first step, the actual pumping speed (viscosity depends on temperature) must be measured using a known liquid with a known viscosity (e.g., a backup solution) at a known temperature. The backup solution is pumped through fluid system 35, and two sensor points 25 can be used to determine the actual volumetric flow rate.

[0327] The flow rate may vary due to at least one of the following parameters and / or circumstances:

[0328] Viscosity of the pumped liquid

[0329] back pressure

[0330] Variations in peristaltic pump tubing (batch-to-batch material changes, batch-to-batch diameter changes, peristaltic pump tubing wear, ambient temperature)

[0331] Spatial tolerance between the pump head and the FTP consumable (the pump head can be located inside the instrument, and the peristaltic pump tubing can be in the FTP (a consumable and separate component)).

[0332] Changes in the spring of the peristaltic pump head

[0333] Fluid resistance (diameter, undercut, etc. of channels in consumables)

[0334] The accuracy of actual pump speed measurements is affected by at least one of the following:

[0335] Viscosity inaccuracies (temperature, batch dependence)

[0336] Volume (tube diameter tolerance) between sample sensors

[0337] Changes in distance between sample sensors

[0338] After determining the pump rate, different fluids, specifically liquids of known viscosity, can be pumped through the fluid system 35 at different known velocities, particularly through the SIM needle 27 with tight diameter tolerances. Given the known viscosity and known velocity, the resulting pressure difference can be calculated using the following formula:

[0339] (Equation 1)

[0340]

[0341] For laminar flow in a circular tube, the Hagen-Poiseuille law applies, and

[0342] (Equation 2)

[0343]

[0344] Where Re corresponds to the Reynolds number.

[0345] The response of the conductivity sensor unit 5 and / or the gas sensor unit 6 in the fluid system 35 to a predetermined negative pressure can be measured to calibrate the fluid system 35 for measuring pressure values. The data required for calibration can be collected using the system's "normal" calibration workflow without additional workflows, in which case the system will improve its ability to measure pressure (partial pressure) values ​​over time, and thus improve sample viscosity. Alternatively, initially, an additional set of workflows can be performed to calibrate the fluid system 35 for viscosity measurements prior to the first sample measurement.

[0346] When aspirating whole blood samples, the sample enters the fluid system 35 through a highly repeatable SIM needle 27 (as it is made of steel). As the sample fluid is pumped into the fluid system 35, fluid resistance increases with the known distance into the fluid system 35 and the unknown viscosity of the sample fluid 2. This fluid resistance results in a negative pressure, which can be measured using a calibrated system. Utilizing the measured time-varying negative pressure, the viscosity of the sample can be estimated using the above equation and / or machine learning to account for uncertainties / complex geometries.

[0347] Based on the above description, modifications and variations to the disclosed aspects are of course possible. Therefore, it should be understood that, within the scope of the appended claims, the invention can be practiced in ways different from the specific designs described in the above examples.

[0348] In particular, it should be understood that at least some of the accompanying drawings or parts are merely schematic and provided as examples only. Furthermore, the relationships between elements may differ from those shown, and portions irrelevant to the purpose of this disclosure have been omitted.

[0349] Furthermore, throughout this specification, references to "an aspect," "an aspect," "an example," or "an embodiment" or "an embodiment" refer to a specific feature, structure, or characteristic described in connection with that aspect, example, or embodiment being included in at least one aspect, example, or embodiment. Therefore, the phrases "in an aspect," "in a aspect," "an example," or "an embodiment" appearing throughout this specification do not necessarily refer to the same aspect, example, or embodiment.

[0350] Furthermore, specific features, structures, or characteristics may be combined in any suitable combination and / or sub-combination in one or more aspects, examples, or embodiments.

[0351] List of reference numerals

[0352]

Claims

1. A method (100) for determining the properties of a sample fluid in an IVD analyzer (10), the method comprising the following steps: At least once causing at least one change in the local pressure state within the fluid system (35) of the IVD analyzer (10), and during the step of causing at least one change in the local pressure state, the following steps are performed: A first fluid (1) is introduced (110a) into the fluid system (35) by being driven by at least one change in the local pressure state, wherein the fluid system (35) includes a channel (4) having an elastic sealing element configured to change the cross-section of the channel (4) in response to the change in the local pressure state. The sample fluid (2) is introduced (110b) into the fluid system (35) by means of at least one change in the local pressure state, wherein the sample fluid (2) is spatially separated from the first fluid (1); The first fluid (1) is driven to the position of the conductivity sensor unit (5) in the channel (4) by at least one change in the local pressure state, and the conductivity sensor unit (5) in the channel (4) is brought into contact (120) with the first fluid (1); The conductivity sensor unit (5) is used to detect (130) a set of conductivity parameter values ​​of the first fluid (1) during a conductivity detection time span (cdts), wherein the conductivity parameter values ​​depend on the cross-section of the channel; and The method further includes: automatically determining (150) the characteristics of the sample fluid (2) based on a detected set of conductivity parameter values ​​of the first fluid, wherein the characteristics of the sample fluid (2) include: In a problematic state, the sample fluid (2) contains at least one of clots, human tissue particles, aggregates, and contaminants; or In a viscous state, the sample fluid has a viscosity and / or is within, below, or above a predetermined viscosity range, whereby the sample fluid has a viscosity higher than 6 mPas within the predetermined viscosity range; or In the normal state, the sample fluid does not contain clots, human tissue particles, aggregates, and contaminants, and has a viscosity of less than 6 mPas.

2. The method (100) according to claim 1, further comprising the following steps: The gas sensor unit (6) is used to detect (230) a component pressure of the gas in the first fluid (1) or the third fluid (3a, 3b) during the gas detection time span (odts); The characteristics of the sample fluid (2) are automatically determined (250) based on the detected component pressure of the gas; The characteristics of the sample fluid (2) determined from a detected component pressure value of the gas are compared (260) with the characteristics of the sample fluid (2) determined from a detected set of conductivity parameter values, and it is identified whether the compared states of the sample fluid (2) are the same or similar.

3. A method (200) for determining the properties of a sample fluid in an IVD analyzer (10), the method comprising the following steps: The first fluid (1) is introduced (210a) into the fluid system (35) with channel (4) of the IVD analyzer (10); The sample fluid (2), which is spatially separated from the first fluid (1), is introduced (210b) into the fluid system (35); The gas sensor unit (6) is used to detect (230) the component pressure values ​​of the gas in the first fluid (1) during the gas detection time span (odts); as well as The properties of the sample fluid (2) are automatically determined (250) based on the detected component pressure of the gas.

4. The method (100; 200) according to any one of the preceding claims, wherein the step of automatically determining (150; 250) comprises applying (155) a trained artificial neural network to a set of detected conductivity parameter values ​​of the first fluid (1) and / or a set of detected component pressure values ​​of the gas in the first fluid (1) or the third fluid (3a, 3b) to determine the properties of the sample fluid; and preferably, wherein the method (100; 200) further comprises: The artificial neural network is trained (105) using a training dataset, which includes a set of conductivity parameter values ​​of the first fluid (1) corresponding to predefined characteristics of the sample fluid (2) and / or a component pressure value of the gas in the first fluid (1) or the third fluid (3a, 3b).

5. The method (100; 200) according to any one of the preceding claims, further comprising automatically triggering (160) an action in the IVD analyzer (10) based on determined characteristics of the sample fluid (2), preferably When the sample fluid (2) is in the problematic state, the action includes at least one of the following steps (165): Optically and / or acoustically output alarm; The step of stopping the introduction (110a, 110b) of the first fluid (1) and / or the sample fluid (2); Reverse the pump's operating direction; Discharge the sample fluid (2); Introduce a washing solution and wash the channel at least partially with the washing solution; or When the sample fluid (2) is in the viscous state or in the normal state, the action includes the following steps (165): Continue with the steps of introducing (110a, 110b) the first fluid (1) and / or the sample fluid (2), and output control signals optically and / or acoustically.

6. The method (100; 200) according to any one of the preceding claims, wherein the conductivity detection time span (cdts) and / or the gas detection time span (odts) overlap at least partially with the introduction time span (its) of the step of introducing the sample fluid (2) (110) into the fluid system (35) therein, preferably wherein the conductivity detection time span (cdts) and / or the gas detection time span (odts) begin before or simultaneously with the introduction time span (its).

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

8. The method (100; 200) according to any one of claims 2 to 7, wherein the detection (230) of the pressure value of said component of the gas is based on an optical measurement principle.

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

10. A fluid sensor system (20) for determining the state of a sample fluid in an IVD analyzer (10), the sensor system (20) comprising: A cartridge (30) having a channel (4) that can be connected to a pump for causing a change in local pressure state to drive fluid (1, 2, 3a, 3b) through the channel (4) of the cartridge (30); A conductivity sensor unit (5), located inside the cartridge (30), is configured to detect the conductivity parameters of the first fluid (1) and the sample fluid (2); and / or A gas sensor unit (6) is configured to detect the partial pressure of the gas in the first fluid (1) and the sample fluid (2); as well as A controller (40) configured to cause the IVD analyzer (10) to perform the steps of the method (100; 200) according to any one of the preceding claims. The cartridge (30) mentioned above includes: A first plate (7) comprising a first surface (7a) of the channel (4); The second plate (8) includes the second surface (8a) of the channel (4); and An elastic sealing element connects the first plate to the second plate and at least partially seals the channel, wherein the elastic sealing element is configured to deform in response to changes in local pressure conditions and thereby change the cross-section of the channel.

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

12. The fluid sensor system according to claim 10 or 11, wherein the first fluid (1) comprises a backup solution, and / or wherein the sample fluid (2) comprises bodily fluid, preferably blood.

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

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