Leakage test

Abstract

To detect a leakage in a fluidic system of an in vitro diagnostic device as early as possible thereby preventing erroneous analytical results and reducing the operational burden on a device operator.SOLUTION: A method comprises activating a pump (14) to provide a fluid from a fluid supply (12) into an electrically conductive probe (11). The probe (11) is positioned such that a tip of the probe (11) is at a predetermined distance from a reference surface (31) of a reference element (30). In the case of a leakage, an electrical signal, a change in an electrical signal, or a change of the electric or magnetic field between the probe (11) and the reference element (30) is detected in a predetermined measuring time period and at least one maintenance action is triggered.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to an automated method for performing a leak test in a fluid system of an in-vitro diagnostic device, and to an automated in-vitro diagnostic device including a controller configured to perform the leak test. [Background technology]

[0002] Automated in vitro diagnostic (IVD) devices rely on precise and accurate pipetting to ensure reliable analytical results. Typically, the fluidic system of an IVD device includes one or more probes, dosing pumps, fluid conduits, valves, and other components that enable the device to aspirate and / or dispense fluids or transfer fluids from one location to another within the device, e.g., from a fluid supply to a probe, where the fluid may be dispensed, e.g., to a reaction vessel. Fluids typically processed by an IVD device or required to ensure proper functioning of the IVD device include liquid samples, reagents, buffers, wash solutions, system fluids, and the like.

[0003] However, it may happen that one or more components of the fluid system leak, for example, due to deterioration, incorrect installation, or manufacturing defects. Leaks can have multiple effects: They can result in imprecise and inaccurate aspiration or dispensing of fluids, reducing the reliability of analytical results. They can also lead to cross-contamination between patient samples, for example, if the leak causes droplets to form and detach at the tip of the probe. In such cases, when the probe is moved from a first sample container to a second sample container, droplets can detach from the probe and cross-contaminate the sample in the second sample container, again resulting in unreliable analytical results. Furthermore, a leaking fluid system can cause contamination of the IVD device itself, for example, by sample materials, reagents, or liquid system fluids. In particular, fluids can fall from the probe tip while the probe is moving within the device, and can also fall from valves or fluid conduits, for example, thereby contaminating the interior of the device. Reaching these locations can be difficult, causing further inconvenience to device operators, as decontamination procedures often need to be performed manually. This further leads to increased downtime of the IVD device, since the IVD device is typically turned off during such decontamination procedures to prevent injury to the device operator.

[0004] Therefore, it is important to detect leaks in fluid systems as early as possible in order to take necessary corrective action in a timely manner, thereby preventing erroneous analytical results and reducing the operational burden on the equipment operator.

[0005] Various approaches have been proposed in the past for automatically checking the integrity of an IVD device's fluid system. One known approach involves providing a pressure sensor in a specific portion of the fluid system, where pressure changes, particularly pressure drops, can be correlated with the presence of a leak. However, adding additional components to an IVD device increases the device's complexity and cost. Another approach, such as International Publication No. 2020066449, discloses a method for detecting anomalies in a fluid conduit by using a level sensor in the fluid supply. However, this method relies on backflow of fluid from the fluid conduit to the fluid supply, resulting in low sensitivity. Depending on the size of the fluid supply, small changes in fluid volume may not be registered, making small leaks unlikely to be detected. Meanwhile, it may take a long time for a sufficient amount of fluid to flow back into the fluid supply for the level sensor to detect a rise in the fluid level. Furthermore, this approach relies on having a level sensor installed in the fluid supply, thereby increasing the device's cost and complexity. Summary of the Invention

[0006] It is against the above background that aspects of the present disclosure provide certain unobvious advantages and advancements over the prior art. In particular, a need has been recognized for improved leak testing in fluid systems of in vitro diagnostic (IVD) devices.

[0007] It is noted that while aspects of the present disclosure are not limited to any particular benefit or functionality, the present disclosure enables an automated method of performing leak testing and triggering at least one maintenance action within the fluidic system of an IVD device to ensure precise and accurate pipetting and ultimately reliable analytical results.

[0008] Another advantage of the method is that it is reliable, offers a wide detection range, and is highly sensitive to leaks, i.e., it allows for the detection of leaks larger than 1 mL / sec to smaller leaks below 10 μL / sec. Furthermore, the method allows for the detection of leaks in a shorter time compared to proposed prior art solutions.

[0009] Another advantage of certain embodiments is that they enable leak detection by utilizing the liquid level detection capabilities of the pipetting device, i.e., without the need to add additional components or functional units and therefore without adding complexity to the device.

[0010] Another advantage of the method according to certain embodiments is that it can indicate to the equipment operator which component of the fluid system is leaking, which helps the equipment operator to identify the leak and take respective measures to correct the fault.

[0011] In particular, the present disclosure relates to an automated method for performing leak testing on a fluid system of an IVD device that includes an electrically conductive probe fluidly connected to a fluid supply via a fluid conduit and electrically interacting with a reference element. The method includes activating a pump to pump fluid from the fluid supply into the probe and then stopping the pump. The method further includes positioning the probe so that a tip of the probe is a predetermined distance from a reference surface of the reference element. Detecting an electrical signal or a change in the electrical signal between the probe and the reference element within a predetermined measurement period determines a leak and triggers at least one maintenance action.

[0012] As used herein, the term "in vitro diagnostic device" or "IVD device" refers to any type of automated analytical device, pre-analytical device, post-analytical device, or combination thereof. Analytical devices are configured to obtain analytical measurements in vitro from a patient sample to provide information about the patient's health status. Analytical measurements can be qualitative and / or quantitative measurements of analytes. They are designed to automatically perform a series of processing steps optimized for each type of analysis, such as coagulation analysis, hematology analysis, clinical chemistry, and immunochemistry, and can include processing steps such as pipetting, incubation, transport, mixing, heating, cooling, measuring, detecting, and washing. Pre-analytical devices are configured to prepare samples or sample containers that hold samples for subsequent processing by the analytical device. This can include processing steps such as loading / unloading liquid containers and / or consumables, decapping, preliminary checks for sample quality, fill level checks, pipetting, aliquoting, centrifugation, labeling, sorting, and incubation. On the other hand, post-analytical devices are configured to process samples after analysis, including, for example, transferring the sample to a storage container, capping, labeling, fixing, preserving / storing, and discarding. An IVD device can operate as a standalone device or in combination with one or more other in vitro diagnostic devices. An IVD device typically comprises multiple functional units, each dedicated to a specific task and coordinating with each other to enable automated sample processing and analysis. Such functional units can be pipetting units, pumps, valves, conveyors, grippers, incubation units, analytical measurement units, temperature regulation units, controllers, etc.

[0013] A "fluidic system" as referred to in this disclosure is an arrangement of operatively connected functional units and / or components within an IVD device that enables or contributes to the handling of fluids, such components including, for example, any one or more of fluid reservoirs, bubble traps and / or degassers, pipetting units, evacuation units, evaporation units, incubation units, fluid conduits, pumps, valves, sensors such as pressure sensors, etc. The particular arrangement will depend on the setup and function of a given IVD device or given functional unit.

[0014] The term "fluid" as used herein is a generic term referring to any type of liquid material processed in an IVD device. It can refer to a liquid to be analyzed, e.g., a sample. A "sample" can be any biological material suspected of containing one or more analytes or having physical or chemical properties, the detection of which can be qualitative and / or quantitative and related to a medical condition. A sample can be derived from any biological source, such as blood, saliva, spit, intraocular lens fluid, cerebrospinal fluid (CSF), sweat, urine, breast milk, ascites, mucus, synovial fluid, peritoneal fluid, pleural fluid, amniotic fluid, tissue, bone marrow, feces, cells, or similar physiological fluids. The term "fluid" can also refer to a liquid necessary to react with or support the analyte in the sample, e.g., a reagent or buffer. It can also refer to a liquid containing a known level of analyte and used to check or verify the operability of an IVD device, e.g., a QC sample, calibrator, or reference solution. According to embodiments of the present disclosure, the term "fluid" can also refer to a liquid used to place or maintain an IVD analytical instrument in an operating mode, such as a cleaning fluid or system fluid. It is common to operate an IVD device using a liquid-based fluid, such as water, as the hydraulic transmission fluid. However, the fluid system may at least partially contain gaseous components, such as air bubbles between the liquid system fluid and the sample, to separate and avoid contamination between the two liquids. Therefore, the term "fluid" can also refer to gaseous components of otherwise liquid fluids, such as ambient air, pressurized air, nitrogen, etc.

[0015] A "fluid supply" as referred to in this disclosure can be any type of container or reservoir designed to hold a particular type of fluid and configured to make the fluid accessible to an IVD device. A fluid supply may also be an external fluid source, i.e., a separate unit that is external to but fluidly connected to the IVD device, such as a water supply in a laboratory. A fluid supply may also be a liquid container, such as a sample container, reagent container, or bulk liquid container, that is installed within the IVD device or temporarily provided to the IVD device.

[0016] A "pump" as referred to in this disclosure is any type of functional unit that allows the movement of a fluid within a confined space (e.g., within a fluid conduit) by, as the case may be, generating negative or positive pressure within that confined space. Depending on the application and the amount of fluid that needs to be moved, different types of pumps can be used, such as piston, plunger, syringe, displacement pumps, or micro-gear wheel pumps. The term "activating a pump" refers to switching a pump from a non-pumping mode to a pumping mode in which the pump pumps a liquid. On the other hand, a non-pumping mode is a mode in which the pump does not pump a liquid. The opposite process, i.e., switching a pump from a pumping mode to a non-pumping mode, is called "stopping" the pump. Pumps are well known in the state of the art and are widely used, especially in the field of IVD devices, so their functional principle will not be described in further detail in this disclosure.

[0017] A "fluid conduit" as referred to in this disclosure is any element having an internal hollow channel through which a fluid can travel, typically an elongated element such as a tube, pipe, duct, etc. A conduit can simultaneously contain gaseous and liquid fluids, e.g., a system fluid and an air gap that prevents aspirated liquid from mixing with the system fluid. Typically, a fluid conduit provides a fluid connection between two or more functional units or components within an IVD device, allowing the transfer of fluid between them, e.g., between a probe and a pump, a fluid supply and a pump, or a pump and a valve. A conduit can be made of any material, e.g., a flexible material such as silicone, or a rigid material such as metal or glass, and ideally has inert properties to the fluid traveling therethrough to prevent interaction with or contamination of the fluid.

[0018] A "probe" as referred to in this disclosure is a functional element configured to perform pipetting operations, i.e., aspirating and / or dispensing fluids. Typically, a probe has an elongated, tubular, and / or tapered shape with at least one opening at or near the tip of the probe that leads to a hollow internal channel. The hollow internal channel travels through the probe and emerges at the opposite end of the probe, where it is fluidly connected to a pump via a fluid conduit. The pump allows for the generation of negative or positive pressure within the channel so that fluid can be aspirated or dispensed through the tip of the probe. For example, the probe can be designed as a needle with a blunt or sharp tip to facilitate piercing the lid of a closed liquid container from which a certain amount of liquid can be aspirated. Furthermore, the probe may be fluidly connected to a fluid supply from its opposite end. According to an embodiment of the present disclosure, the method includes actuating a pump to provide a fluid, such as a buffer, a wash solution, or a system fluid, from a fluid source into the probe. For example, to rinse the internal channels of the probe and thus prevent cross-contamination, a wash solution can be pumped from a wash solution source through a conduit to the probe and into the probe's channels. As long as the pumps are activated, i.e., delivering wash solution from their respective fluid supplies, the fluid conduits between the fluid supplies, the pumps, and the probe are filled with a constant flow of wash solution, and excess wash solution is discarded through the tip of the probe. To terminate the wash process step, the delivery of wash solution is stopped by stopping the respective pumps. The wash solution remaining in the fluid conduits, valves, and probes can then be flushed out by replacing it with another fluid, such as a system fluid supplied by the respective pump from the system fluid supply. The system fluid can then be used as a hydraulic transmission fluid during subsequent pipetting operations. In another aspect of the present invention, the system fluid and wash solution can be the same fluid, such as water or a solution containing one or more compounds, such as a detergent or antiseptic. In that case, a flushing step is not required.The probe may be designed as a multi-use probe that needs to be cleaned periodically to prevent cross-contamination, or as a disposable probe that is exchanged between different pipetting procedures. Typically, the probe is oriented so that the tip of the probe is below the opposite end of the probe. The longitudinal orientation of the probe may be vertical or at an angle to the vertical axis.

[0019] A "valve" as referred to in this disclosure can be any kind of functional unit for directing, regulating or controlling a fluid in a fluid system by opening, closing or partially blocking a flow path. Examples of commonly used valves are solenoid valves, shut-off valves, proportional valves, rotary valves, etc. Such elements are well known and widely used in the state of the art and will not be described in further detail in this disclosure.

[0020] It may occur that one or more components of a fluid system leak. There can be many reasons for leaks, such as deterioration, incorrect installation, manufacturing inaccuracies, or unintentional damage caused by the equipment operator. A leak occurs when fluid unintentionally escapes or enters a fluid system. In this case, the pressure within the fluid system cannot be kept constant or can no longer be controlled, potentially leading to imprecise and inaccurate pipetting or cross-contamination. The term "leak testing" refers to a method or measurement performed to detect leaks in a fluid system. According to embodiments of the present disclosure, leak testing can be performed at specific time intervals, which may be predefined or may depend on a specific trigger event, such as an out-of-specification QC measurement or calibration result.

[0021] As used herein, "electrical conductivity" refers to a material's ability to conduct electric current, which depends on the availability and density of mobile charge carriers. For example, a material may be considered conductive if it exhibits a dielectric constant >20 μS / cm. Materials for certain components of an IVD device can be selected based on their conductive properties so that an electrical signal can be applied to them. For example, when referring to a "conductive probe," the probe may be made at least partially from a conductive material, such as a metallic material like stainless steel, a conductive plastic material, or the like. This allows the probe to be used not only to aspirate and / or dispense fluids, but also to detect contact with the liquid. For example, to minimize the risk of cross-contamination and facilitate probe cleaning, it may be desirable to position the tip of the probe just below the liquid surface, for example, of a liquid sample. Therefore, to ensure reliable probe placement, it is advantageous to detect when the probe reaches the liquid surface. In another example, according to aspects of the present disclosure, the technical principles for detecting contact with the liquid can also be used to detect leaks in a fluid system.

[0022] For leak testing, a conductive probe or portion of the probe acts as an electrode that interacts with the reference electrode of the reference element. The reference element thus comprises a reference electrode and a reference surface. The reference electrode represents the opposite electrode of the probe and is typically made of a conductive material, such as a metal material like stainless steel or a conductive plastic material. The probe and the reference element interact electrically, which can refer to a configuration that allows direct exchange of charge carriers between the probe and the reference element, but can also refer to a configuration that allows application of a potential difference between, for example, a voltage, a current, or an electric or magnetic field. The probe may be the measurement electrode, and the reference electrode of the reference element may be the ground electrode, or vice versa. The reference element may further be positioned within a certain distance and convenient for the probe to reach so that electrical interaction can be established between the probe and the reference element. The reference surface of the reference element may be positioned between the probe and the reference electrode of the reference element. For example, the reference surface may be the surface of the reference electrode facing the probe and therefore have the same properties as the reference electrode in terms of electrical conductivity. In another example, the reference surface may be a coating layer on the reference electrode that is not necessarily conductive. In yet another example, the reference surface may be the surface of a component located near the reference electrode of the reference element, and the component and its surface may or may not have conductive properties. For example, the reference surface may be the surface of a metal or plastic component, or the surface of a liquid in a liquid container placed between the probe and the reference electrode. The reference surface may have a permittivity and / or permeability different from that of the surrounding air between the reference surface and the probe. The reference element may be a separate element explicitly installed in the IVD device to perform leak testing. Alternatively, the reference element may be integrated into another element, such as a liquid container, a liquid container holder, a probe, or a teaching reference element for calibrating moving components in the IVD device. It may have any shape, such as a plate-like, planar, cubic, cylindrical, or spherical shape.According to an embodiment of the present disclosure, the probe is positioned such that the tip of the probe is at a predetermined distance from the reference surface of the reference element, typically between 0.01 mm and 5 mm, e.g., between 0.1 mm and 2 mm, or between 0.5 mm and 1.5 mm. According to an embodiment of the present disclosure, the reference element is an element having a horizontally flat reference surface. For leak testing, the probe is positioned above the reference surface at a predetermined distance so that the reference surface is located below the probe, e.g., vertically below the tip of the probe. This can be achieved by moving the probe to a suitable position above the reference surface of the reference element, by moving the reference surface of the reference element to a suitable position below the probe, or by moving both the probe and the reference surface of the reference element relative to each other. Due to gravity, a droplet formed on the tip of the probe extends toward and possibly contacts the horizontally flat reference surface.

[0023] Various methods for detecting the presence or change in liquid level based on measuring or changing an electrical signal are known in the art. For example, in a capacitive detection method, two conductive electrodes form a capacitor. The fluid between the two electrodes acts as a dielectric medium, affecting the capacitance formed between the two electrodes. The change in capacitance can be measured by applying an alternating current (AC) voltage and an alternating current (AC current) or a direct current (DC voltage and DC current) between the two electrodes. Another example of a detection method is a resistive or conductive detection method. Similar to the capacitive detection method, a probe and a reference element function as a pair of electrodes. Again, an AC voltage and an AC current or a DC voltage and a DC current are applied. As soon as liquid is present between the electrodes, it forms part of an electrical circuit and causes a current to flow. The electrical resistance or conductivity is measured and compared to a preset value to determine the presence of liquid. Yet another example of detecting the presence of liquid between two electrodes is measuring a change in inductance. The above-mentioned detection methods represent a non-exhaustive selection of possible implementations and can be applied individually or in combination. In either case, the probe contacting the liquid typically results in a detectable change in an electrical signal, which may first have to be amplified by a signal processing unit. The detection methods described above can further be combined with methods aimed at liquid level monitoring based on other technological principles, such as float sensors, infrared sensors, optical level switches, etc.

[0024] The term "electrical signal" as used in this disclosure refers to any type of electrical parameter or measure. It can refer, for example, to voltage, current, electrical resistance, conductivity, capacitance, or impedance over time, or any derivative thereof. It can also refer, for example, to an electric or magnetic field generated between two electrodes, or a combination of both, or the change in the strength of an electric or magnetic field. Thus, the value of an electrical signal can include AC or DC values, peak values, frequency, phase shift angle, duty cycle, electric field strength, magnetic field strength, etc.

[0025] According to aspects of the present disclosure, the electrical signal is measured or monitored over a predetermined measurement period. The predetermined measurement period defines the maximum duration of the electrical signal checking / monitoring step. It typically includes a period of less than 10 minutes, e.g., up to 5 minutes, or up to 1 minute. According to aspects of the present disclosure, if an electrical signal or a change in the electrical signal is detected within the predetermined measurement period, a leak is determined and at least one maintenance action is triggered. In such a case, the measurement period ends either at the time of signal detection or signal change detection or when the electrical signal reaches a predetermined threshold. In other words, the measurement period ends either when an electrical signal or a change in the electrical signal is detected or when the end of the predetermined measurement period is reached, whichever occurs first. As described above, the change in the electrical signal can be any change in capacitance, resistance, voltage, frequency, inductance, current, etc., and is typically measured by a measurement unit, e.g., a capacitance measurement unit. The measurement unit may be configured to detect the electrical signal or a change in the electrical signal and / or to apply a potential difference, thereby acting as, for example, a voltage source or a current source. Thus, the measurement unit may include a voltage source, a current source, an electrical (sensing) circuit, a signal generator, an oscillator, etc.

[0026] According to an embodiment of the automated method, the probe is moved to a position such that the tip of the probe is a predetermined distance from a reference surface of a reference element. A potential difference is applied between the probe and the reference element, and a predetermined measurement period is initiated. The electrical signal measured between the probe and the reference element during the initial phase of the measurement period is referred to as the electrical baseline signal. The electrical baseline signal can have a constant value or a constant slope. In the event of a leak, the pressure in the fluid system can no longer be maintained, resulting in the formation of a droplet of fluid, e.g., system fluid, at the tip of the probe. The rate of droplet formation depends on the severity of the leak. When the droplet reaches a size that causes contact with the reference surface, the droplet causes a change in the electrical signal from the electrical baseline signal across a signal threshold, which is detected and confirms the presence of a leak in the fluid system.

[0027] According to certain aspects of the present disclosure, a "maintenance action" triggered upon detection of an electrical signal or a change in the electrical signal can be a fully automated processing step that can be performed by the IVD device without manual intervention by an operator, such as calibration, purging the fluid system, labeling the analysis results, repeating a leak test, etc. In another example, the maintenance action may be a visual or acoustic or audiovisual presentation to the operator of the IVD device indicating that a manual maintenance action is required, possibly indicating the type of maintenance action required, and possibly instructing the operator on how to perform the maintenance action, including guiding the operator during the performance of the maintenance action. A manual maintenance action may be, for example, replacing a probe, visually checking the fluid system or its components, tightening or replacing valves or fluid conduits, probes, etc., instructions to contact a service technician, etc.

[0028] According to an aspect of the present disclosure, the method includes closing a valve controlling a fluid passage between the pump and the probe during a measurement period. The valve is thereby fluidly connected to the fluid supply and the probe via a fluid conduit and is typically located downstream of the pump. A valve is in a closed state, within the meaning of the present disclosure, when it is switched or positioned so that the fluid passage is blocked, i.e., so that fluid cannot pass through the valve when the valve is properly operating. The valve can be switched to a closed state at the latest at the beginning of the measurement period, after the fluid supplied from the fluid supply to the probe reaches the tip of the probe. As a result, at the start of the measurement period, the fluid system is in a state in which the fluid conduit connecting the fluid supply and the probe and the probe itself are supplied with the respective fluids, and the valve is in a closed state. The valve remains in a closed state throughout the entire measurement period. When the measurement period ends, i.e., when an electrical signal or a change in the electrical signal is detected, or when the predetermined measurement period ends, the valve can be switched to an open state or remain in a closed state.

[0029] According to another aspect of the present disclosure, the method includes activating a pump during a measurement period. The term "during" refers to any point within the measurement period, particularly a predetermined point within the measurement period. For example, the pump can be activated at the beginning of the measurement period, such that the pump remains in pumping mode for the entire measurement period, i.e., until the end of the predetermined measurement period is reached or until an electrical signal or a change in electrical signal is detected between the probe and the reference element, regardless of which event occurs first. In another example, the pump can be activated at a predetermined point within the predetermined measurement period, such as after half of the predetermined measurement period has elapsed, after two-thirds of the predetermined measurement period has elapsed, or after 20 seconds of the predetermined measurement period has elapsed, such that the pump remains in non-pumping mode for part of the measurement period and in pumping mode for another part of the measurement period. In other words, once the predetermined measurement period begins and activated at a given point, if no electrical signal or change in electrical signal is detected between the probe and the reference element that would have ended the measurement period by that point, the pump remains in non-pumping mode. Activating the pump when performing a leak test increases the pressure in the fluid conduits and / or closed valves located downstream of the pump. Potential leaks, particularly valve leaks, may be more easily detected when exposed to higher pressures. The pressure the pump needs to generate depends on the design of the IVD device, particularly the arrangement of different functional units and / or components of the fluid system relative to one another. For example, the fluid supply, valves, and at least some of the fluid conduits may be located vertically lower than the probe. Thus, the pump may need to generate a pressure high enough to counteract gravity or atmospheric pressure. In another example, the fluid supply, valves, and at least some of the fluid conduits may be located vertically above the probe. As a result, the pump may not need to be activated for a leak test, since potential leaks may be determined based on gravity acting on the fluid in the fluid system.For leak testing, the pump can be operated to create a higher pressure than required during regular operation, allowing the leak test to be performed in a shorter time and / or leaks to be detected earlier, i.e., before they affect the reliability of the measurement results.

[0030] According to another aspect of the present disclosure, the method includes switching a valve controlling a fluid passage between the pump and the probe to an open state during a measurement period. Contrary to the closed state described above, the valve is open when it is switched or positioned to allow fluid passage. The term "during a measurement period" as used in this disclosure refers to any point within the measurement period, particularly a predetermined point within the measurement period. This may be, for example, the beginning of the predetermined measurement period, so that the valve is open throughout the entire measurement period. Alternatively, the valve may be switched to the open state at a given point within the predetermined measurement period, such as after one-third of the predetermined measurement period has elapsed, after one-half of the predetermined measurement period has elapsed, or after 20 seconds of the predetermined measurement period has elapsed, such that the valve is closed during part of the measurement period and open during another part of the measurement period.

[0031] The disclosed leak test can provide an indication of the location of a leak in a fluid system. This is achieved by the way functional elements of the fluid system operate during the leak test. For example, if a valve controlling the passage of fluid between a fluid supply and a probe is closed and the pump is stopped for the measurement time, a leak detected by the leak test may be located in the fluid conduit between the valve and the probe. In another example, if the valve is closed and the pump is in a pumping mode for (part of) the measurement period, a leak detected next may be located in the valve. In yet another example, if the valve and pump are positioned vertically above the level of the tip of the probe and the pump is tightly sealed to the ambient environment when in a non-pumping mode, the pump is stopped for the measurement period and the valve is closed for part of the measurement period and open for another part of the measurement period. In this case, a leak detected during part of the measurement period when the valve is closed may indicate a leak in the fluid conduit between the valve and the probe. On the other hand, a leak detected during part of the measurement period when the valve is open may indicate a leak in the fluid conduit between the pump and the valve. Depending on the location of the leak, a respective maintenance action may be triggered.

[0032] According to certain aspects of the present disclosure, at least one maintenance action is selected from a set of possible conduit maintenance actions. The conduit maintenance action can refer to a corresponding automatic maintenance step, such as calibration, purging the fluid system, repeating a leak test, etc. Additionally or alternatively, the conduit maintenance action can refer to a corresponding manual maintenance action. Thus, an instruction can be presented to an operator of the IVD device containing information that a fluid conduit is leaking and manual maintenance is required. The manual maintenance step can be any or a combination of locating and confirming the leak, replacing the affected conduit, realigning or tightening the conduit, manually initiating a repeat leak test, contacting a service technician to resolve the problem, etc.

[0033] According to certain aspects of the present disclosure, at least one maintenance action is selected from a set of possible conduit and / or valve maintenance actions. The valve maintenance action may refer to a corresponding automatic maintenance step, such as calibration, purging the fluid system, switching the valve, resetting the valve, resetting the IVD device, repeating a leak test, etc. Additionally or alternatively, the valve maintenance action may refer to a corresponding manual maintenance action. Corresponding instructions may be presented to an operator of the IVD device, including information that the valve is leaking and manual maintenance is required. The manual maintenance step may be any one or a combination of locating and verifying the leak, replacing the valve, replacing a valve component, readjusting or tightening the valve, manually initiating a repeat leak test, contacting a service technician to resolve the issue, etc. Referring to the example above, if the valve is closed for the measurement period and the pump is in a non-pumping mode for part of the measurement period and a pumping mode for another part of the measurement period, a leak detected while the pump is in the non-pumping mode indicates a leak in the fluid conduit. The corresponding conduit maintenance action is triggered. On the other hand, a leak detected while the pump is in pumping mode indicates a leak in the valve, and a corresponding valve maintenance operation is triggered. It may happen that a leak is detected at the time of operating the pump or switching the valve from a closed state to an open state, or shortly thereafter. In this case, it may be uncertain to indicate the location of the leak. Therefore, both a conduit maintenance operation and a valve maintenance operation may be triggered.

[0034] According to certain aspects of the present disclosure, at least one maintenance action is determined based on the time to detection, where the time to detection is the time measured from the start of a predetermined measurement period until an electrical signal or a change in the electrical signal is detected. Thus, the predetermined measurement period includes the time to detection. Based on the length of the time to detection, certain characteristics of the leak can be estimated. For example, the length of the time to detection can be correlated with the size of the leak, i.e., the shorter the time to detection, the larger the leak. One or more thresholds can be determined to determine the appropriate maintenance action. For example, if the time to detection ends before a first threshold, the leak is deemed substantial or at high risk for producing unreliable analytical results and thus requiring urgent maintenance action. The corresponding automatic maintenance action to correct the defect may be automatic notification to a service technician, prevention of further analytical measurements, etc. The corresponding manual maintenance action may be replacing the affected conduit, reconditioning the conduit, replacing the valve, replacing valve components, reconditioning or tightening the valve, etc. In another example, if the detection period ends between the first and second thresholds, the leak can be considered a medium or low risk for producing unreliable analytical results and therefore requiring periodic maintenance actions, which can be calibration, purging the fluid system, switching valves, resetting valves, resetting the IVD device, calibrating the pump, repeating the leak test, etc.

[0035] According to certain aspects of the present disclosure, triggering at least one maintenance action includes generating an alert indicating the at least one maintenance action. An alert can refer to any type of visual, acoustic, or audiovisual presentation to an operator of an IVD device that indicates that at least one automatic maintenance action is about to be performed and / or that a manual maintenance action is required, possibly indicating the location of a leak, requesting the operator to confirm the proposed maintenance action, or providing instructions on how to perform the manual maintenance action. An alert can be a light signal, such as a light of a specific wavelength or a flashing light. An alert can also be an acoustic signal, such as a siren, to attract the operator's attention. An alert can also be visual information displayed to the operator on a display, possibly including more detailed instructions on how to perform the manual maintenance action to resolve the leak. An alert can also refer to any combination of the above-mentioned examples. Regardless of the technical method underlying the alert, it can be configured to convey information about the type of maintenance action, as well as indicate that a maintenance action has been triggered. For example, a specific wavelength can correspond to a specific maintenance action, or a specific acoustic pattern can correspond to a specific maintenance action.

[0036] The present disclosure further relates to an IVD device comprising a fluid system and a controller, the fluid system comprising a fluid supply, a pump, and a conductive probe fluidly connected to the fluid supply via a fluid conduit and electrically interacting with a reference element, the controller being configured to control the IVD device to perform a leak test of the fluid system according to the automated method described above.

[0037] The term "controller," as used in this disclosure, refers to a programmable logic controller or processor that executes a computer-readable program with instructions for performing actions according to an operational plan. The term can refer to a central processing unit, a microprocessor, a microcontroller, a reduced instruction set computer (RISC), an application-specific integrated circuit (ASIC), a logic circuit, and any other circuit or processor capable of performing the functions / methods described herein. Regardless of the type of processor, the controller is configured to perform one or more of the methods described herein. The controller may be integrated into the IVD device, a unit, subunit, or module of the IVD device, or a separate logical entity that communicates with the IVD device or its units, subunits, or modules via a direct connection, wired or wireless, or indirectly via a wired or wireless communication network, such as the Internet or a wide area network, such as a healthcare provider's local area network or intranet, via a network interface device. In some embodiments, the controller can be integrated with a data management unit implemented on a computing device such as, for example, a desktop computer, laptop, smartphone, tablet, PDA, etc., or can consist of a server computer and / or be distributed / shared across / among multiple IVD devices. Furthermore, the system can include remote devices, remote servers, and cloud-based elements, or remote PC / server or cloud-based systems, communicating wired or wirelessly (e.g., infrared, cellular, Bluetooth). The processor may also be configurable to control the IVD device such that workflows and workflow steps are performed by the IVD device.

[0038] According to aspects of the present disclosure, the fluid system further comprises a valve controlling a fluid passage between the pump and the probe.

[0039] According to an embodiment of the present disclosure, a conductive probe is configured to detect liquid level by determining contact with a liquid surface using any one or a combination of measurement principles, including capacitance, resistance, conductivity, and inductive measurement principles. Liquid level detection is typically performed on a liquid in a liquid container. The liquid container may be, for example, a sample container, a QC vial, a calibration vial, a reagent container, etc. When a probe is moved, typically vertically downward, into a liquid container for aspiration or dispensing, it is important to detect when the probe touches the liquid surface in the liquid container to minimize the risk of cross-contamination or to prevent damage to the probe, for example, by hitting the bottom of the liquid container. Two examples of methods for detecting the presence of liquid based on measuring electrical signals have already been described above. These methods are well established and known in the prior art and will not be described in further detail.

[0040] According to embodiments of the present disclosure, the probe is horizontally translatable and / or rotatable relative to a reference element or liquid, and vertically translatable. Typically, in an IVD device, aspiration of liquid occurs at a specific location within the device, but dispensing of the liquid occurs at a location different from the aspiration location. For example, an aliquot of a liquid sample needs to be aspirated from a sample container and transferred and dispensed into a reagent container located at a different location from the sample container, e.g., for incubation or transfer to an analysis module. Furthermore, washing of the probe may occur at a dedicated location within the device, e.g., a wash location. The probe, which is typically part of a pipetting unit, is usually configured to be movable so that different operational steps can be performed at different locations within the IVD device. The probe can move between positions in a translational motion in the horizontal direction, i.e., the Cartesian x- and / or y-directions. Alternatively, it may move horizontally in a rotational motion. Typically, the probe is configured to move in vertical translation, i.e., in the Cartesian z-direction, to lower the probe into a sample container, reagent container, wash station, or taught reference point, for example, when calibrating pipetting head movement.

[0041] According to an embodiment of the present disclosure, the valve is positioned at a vertical level lower than the level of the tip of the probe at the leak determination position. Typically, IVD laboratory space is limited, which places certain constraints on the size of IVD devices. Therefore, IVD devices are designed to have as small a footprint as possible. Often, consumables or reagents are inserted or stored at the bottom of the device, while sample handling and analysis operations are performed at a higher level of the device, typically at the operator's working height. Therefore, certain fluids, such as system fluids or cleaning solutions, may need to be transferred from the bottom of the device to a higher level, which can be achieved by a pump. As a result, IVD devices can be designed so that the valve controlling the fluid passage between the fluid supply and the probe is located at a lower level than the probe, particularly at a vertical level lower than the tip of the probe at the leak determination position. In such situations, the leak test can include keeping the pump stationary for the measurement period, so that any determined leak can be traced with high certainty to a leak in a fluid conduit that is at least partially at a vertical level higher than the level of the probe's tip. To determine whether the valve is leaking, the leak test may include operating the pump during a measurement period. The probe may be vertically translatable, and the leak test position may be determined accordingly, i.e., such that when the probe is placed at the leak test position, the valve is at a vertically lower level than the tip of the probe. However, outside the leak test position, the tip of the probe may be lowered to a level vertically below the valve.

[0042] According to aspects of the present disclosure, the device further includes an alert function configured to indicate the leak determination and at least one maintenance action. As described above, an alert can refer to any type of visual, acoustic, or audiovisual presentation to an operator of the IVD device that indicates that at least one automatic maintenance action is about to be performed and / or that a manual maintenance action is required, possibly indicating the location of the leak, or requesting the operator to confirm the proposed maintenance action, or providing instructions on how to perform the manual maintenance action. Thus, the alert function can be, for example, any type of light source for emitting a light of a specific wavelength or a flashing light signal. The alert function can also be a functional unit that emits an acoustic signal to attract the operator's attention, such as a speaker or siren. The alert function can also be visual information displayed to the operator on the display of the IVD device, possibly including more detailed instructions on how a manual maintenance action needs to be performed to resolve the leak. As those skilled in the art will recognize, an alert can also refer to any combination of the above examples.

[0043] According to aspects of the present disclosure, a controller is configured to initiate a method for performing a leak test on a fluid system at predetermined time intervals, in response to a trigger event, or in response to operator input. The leak test can be performed at predetermined time intervals, e.g., daily, weekly, or monthly, during routine operation, as part of a sample measurement procedure, upon instrument initialization, etc. It may also be performed in conjunction with other instrument maintenance operations, such as QC measurements or calibrations, that are typically performed at regular time intervals. It may also be performed in response to a trigger event, e.g., an out-of-specification QC measurement or calibration result. Alternatively, the controller can initiate a leak test based on manual input by an operator of the IVD device. For example, the operator can request a leak test on the user interface of the IVD device. [Brief explanation of the drawings]

[0044] [Figure 1] 1 shows a schematic diagram of an in vitro diagnostic (IVD) device including a fluidic system and a controller according to an embodiment of the present disclosure. [Figure 2] 2 shows a modification of the IVD device of FIG. 1 according to a further aspect of the present disclosure. [Figure 3] 3 shows yet another variation of the IVD device of FIGS. 1 and 2 according to a further aspect of the present disclosure. [Figure 4] 1 illustrates a flow diagram of a method for performing a leak test according to an aspect of the present disclosure. [Figure 5] 10 shows a flow diagram of a method for performing a leak test according to a further aspect of the present disclosure. [Figure 6] 10 shows a flow diagram of a method for performing a leak test according to a further aspect of the present disclosure. [Figure 7] 10 shows a flow diagram of a method for performing a leak test according to a further aspect of the present disclosure. [Figure 8a] 1 shows a diagram illustrating the evolution of an electrical signal over time during a leak test. [Figure 8b] 1 shows a diagram illustrating the evolution of an electrical signal over time during a leak test. DETAILED DESCRIPTION OF THE INVENTION

[0045] Those skilled in the art will appreciate that the elements in the figures are illustrative for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of aspects of the present disclosure. Also, parts that do not contribute to the teaching of the present disclosure have been omitted.

[0046] 1 illustrates schematically an example of an in-vitro diagnostic device (IVD device) 100 comprising a fluidic system 10 and a controller 90. The fluidic system 10 comprises an electrically conductive probe 11 fluidly connected to a fluid supply 12 via a fluid conduit 18. The fluidic system 10 further comprises a pump 14 configured, upon operation, to pump fluid, e.g., a system fluid, from the fluid supply 12 to the probe 11.

[0047] Probe 11 is configured to perform pipetting operations, i.e., aspirating and / or dispensing fluid. To achieve greater flexibility, fluid system 10 of the present example further includes a syringe pump 20 for aspirating and / or dispensing fluid, e.g., a sample from a sample container (not shown), through probe 11. Alternatively, pump 14 can be used to aspirate and / or dispense a sample through probe 11. However, syringe pump 20 typically allows for more precise dosing than pump 14, which is used to move bulk fluids.

[0048] According to another aspect of the present invention, the probe 11 is horizontally translatable and / or rotatable relative to the reference element 30 or the liquid, and vertically translatable. Referring to FIG. 1 , the probe 11 is attached to a pipetting head 40, which can be operated to translate or rotate in a horizontal plane, i.e., in the x and / or y directions. The pipetting head 40 can further be configured to translate vertically, i.e., along the z axis, for example, to move the probe 11 into a sample container or to position the tip of the probe 11 at a predetermined distance from the reference surface 31 of the reference element 30. Alternatively, the probe 11 can be movably attached to the pipetting head 40 so that it can be operated to translate vertically relative to the pipetting head 40. The IVD device 100 can include multiple probes 11, at least some of which can be configured to perform the same operation, such as aspirating and dispensing a sample or aspirating and dispensing a reagent. In such a configuration, multiple probes 11 can be attached to the same pipetting head 40, which allows for parallelization and thereby increases throughput. The plurality of probes 11 may be movably attached to the pipetting head 40 so that they can move individually relative to the pipetting head 40, for example vertically.

[0049] Continuing to refer to FIG. 1 , when performing a leak test, the probe 11 is positioned so that its tip is a predetermined distance from the reference surface 31 of the reference element 30. This is achieved by controlling the pipetting head 40 and / or the probe 11 and / or the reference element 30 to move relative to each other accordingly. The leak test is based on the detection of liquid between the probe 11 and the reference surface 31. In the event of a leak, the pressure within the fluid system 10 cannot be maintained, causing the fluid within the fluid system 10 to flow vertically from a higher level to a lower level. As a result, a droplet of system fluid forms at the tip of the probe 11 and extends toward the reference surface 31 due to gravity.

[0050] In the example shown in Figure 1, the potential presence of a liquid is detected capacitively. The probe 11 and the reference element 30 are operably connected electrically, in the sense that a potential difference can be applied between them. The probe 11 may be a measurement electrode, and the reference element 30 may comprise a ground electrode, or vice versa. The probe 11 and the reference element 30 are electrically connected to a measurement unit 32, which is configured to apply, for example, a DC or AC voltage between the probe 11 and the reference element 30.

[0051] According to an embodiment of the present disclosure, the probe 11 is configured to detect the liquid level by determining contact with the liquid surface in, for example, a liquid container (not shown) by any one or combination of measurement principles including capacitance, resistance, conductivity, or inductive measurement principles. The technical principles implemented in the device 100 for detecting the liquid level in a liquid container can be the same as the technical principles used to perform a leak test according to the present disclosure.

[0052] 2 shows a schematic representation of another example of an IVD device 100' according to a further aspect of the present disclosure. The device 100' comprises a fluidic system 10', a controller 90, and an alarm function 50. The fluidic system 10' comprises an electrically conductive probe 11 fluidly connected to a fluid supply 12 via fluid conduits 18, 19. The fluidic system 10' further comprises a pump 14 configured, upon operation, to pump fluid, e.g., system fluid, from the fluid supply 12 to the probe 11.

[0053] According to an embodiment of the present disclosure, the fluidic system 10′ further includes a valve 16 that controls a fluid passage between the fluid supply 12 and the probe 11. The valve is thereby positioned downstream of the pump 14, i.e., between the pump 14 and the probe 11. The probe 11 is configured to perform pipetting operations, i.e., aspirating and / or dispensing fluid. Similar to the example shown in FIG. 1 , the fluidic system 10′ of this example includes a syringe pump 20 for aspirating and / or dispensing fluid, e.g., a sample from a sample container (not shown), via the probe 11. During aspirating of a sample from a sample container by operating the syringe pump 20, the valve 16 is normally closed, thereby preventing passage of fluid from one portion of the fluid conduit 19 through the valve 16 to another portion of the fluid conduit 18. The probe 11 is further attached to a pipetting head 40, which is translatably and / or rotationally movable in a horizontal plane and translatable in a vertical direction.

[0054] As in the previous example, the probe 11 is positioned such that the tip of the probe 11 is a predetermined distance from the reference surface 31 of the reference element 30 when performing a leak test. A droplet 33, e.g., a droplet of system fluid, formed on the tip of the probe 11 and contacting the reference surface 31 induces a change in capacitance, indicating a leak in the fluid system 10′. This change in capacitance is detected by the measurement unit 32. In response to the determination of a leak, at least one maintenance action is triggered. The maintenance action can include generating an alert indicating the at least one maintenance action.

[0055] The IVD device 100' includes a warning function 50 configured to indicate a leak determination and at least one maintenance action according to an embodiment of the present invention. The warning function 50 may refer to any type of visual, acoustic, or audiovisual presentation to an operator of the IVD device 100'. In this example, the warning function 50 may refer to displaying a warning in visual form on a display integrated into the IVD device 100' in response to determining a leak in the fluid system 10'. The displayed information may indicate that a leak has been determined and which maintenance action has been triggered. It may further display detailed instructions on how to perform manual maintenance actions to resolve the leak, or may indicate the location of the leak, etc. The warning function 50 is controlled by the controller 90.

[0056] According to an embodiment of the present disclosure, the valve 16 is positioned at a vertically lower level than the level of the tip of the probe 11 at the leak determination position. The IVD device 100′ in the example of FIG. 2 is designed so that the fluid supply 12, containing, for example, a system fluid or a cleaning solution, is positioned at the bottom of the device 100′. This requires pumping fluid to a higher level within the device 100, for example, to the probe 11. Positioning the valve 16 at a vertically lower level than the level of the tip of the probe 11 allows for better localization of potential leaks. For example, if a leak test is performed with the pump 14 deactivated and the valve 16 closed and a leak is detected, the leak must have occurred in a portion of the fluid conduit 19 between the valve 16 and the probe 11 that is at least partially at a vertically higher level than the level of the tip of the probe 11. To determine whether the valve 16 is leaking, the leak test can include operating the pump 14 during a measurement period.

[0057] FIG. 3 shows a schematic diagram of another example of an IVD device 100″ according to another embodiment of the present invention. The IVD device 100″ comprises a fluidic system 10″, a controller 90, and an alarm function 50. The fluidic system 10″ comprises a plurality of conductive probes 11A, 11B, 11C fluidly connected to a first fluid supply 12 via first fluid conduits 18A, 18B, 18C, 19A, 19B, 19C and to a second fluid supply 22 via a second fluid conduit 28. The fluidic system 10″ further comprises a first pump 14 configured to move fluid from the first fluid supply 12 to the probes 11A, 11B, 11C upon activation, and a second pump 24 configured to move fluid from the second fluid supply 22 to the probes 11A, 11B, 11C upon activation.

[0058] According to an embodiment of the present invention, fluidic system 10″ includes a first set of valves 16A, 16B, and 16C that control fluid passage in first fluid conduits 18A, 18B, 18C, 19A, 19B, and 19C, respectively, between fluid supply 12 and probes 11A, 11B, and 11C. Valves 16A, 16B, and 16C are thereby located downstream of pump 14, i.e., between pump 14 and probes 11A, 11B, and 11C, respectively. Similar to the example shown in FIGS. 1 and 2, fluidic system 10″ in this example includes respective syringe pumps 20A, 20B, and 20C for aspirating and / or dispensing fluid through probes 11A, 11B, and 11C, e.g., for aspirating sample from a sample container (not shown). During aspirating or dispensing by operating syringe pump 20, each valve 16A, 16B, 16C is normally in a closed state, thereby preventing fluid from passing from one portion of fluid conduit 19A, 19B, 19C through each valve 16A, 16B, 16C to another portion of fluid conduit 18A, 18B, 18C, respectively.

[0059] The fluid system 10'' further includes a second set of valves 26A, 26B, 26C configured to switch between the first fluid conduits 18A, 18B, 18C, 19A, 19B, 19C and the second fluid conduit 28 to control the passage of fluid from the first fluid supply 12 or the second fluid supply 22 to the probes 11A, 11B, 11C. For example, the second fluid supply 22 may contain a cleaning solution for cleaning the probes 11A, 11B, 11C. During the cleaning procedure, the probes 11A, 11B, 11C are typically moved to a cleaning position (not shown). A second pump 24 is actuated to supply the cleaning solution from the second fluid supply 22 to the probes 11A, 11B, 11C via the second fluid conduit 28. The second set of valves 26A, 26B, 26C are switched to an open state with respect to the second fluid conduit 28 and to a closed state with respect to the first fluid conduits 18A, 18B, 18C, 19A, 19B, 19C, allowing cleaning fluid to pass through the probes 11A, 11B, 11C. In a second step of the cleaning procedure, the probes 11A, 11B, 11C may be flushed with another fluid, e.g., system fluid, supplied from the first fluid supply 12. Accordingly, the second pump 24 is stopped to stop the supply of cleaning fluid, and the second set of valves 26A, 26B, 26C are switched to an open state with respect to the first fluid conduits 18A, 18B, 18C, 19A, 19B, 19C and to a closed state with respect to the second fluid conduit 28. The first set of valves 16A, 16B, 16C are switched to an open state. The first pump 14 is actuated to pump system fluid from the first fluid supply 12 to the probes 11A, 11B, 11C. In another example, the second set of valves 26A, 26B, 26C may be switched to a closed state for both the first fluid conduits 18A, 18B, 18C, 19A, 19B, 19C and the second fluid conduit 28.

[0060] Similar to the examples of FIGS. 1 and 2, probes 11A, 11B, and 11C are mounted to a pipetting head 40′, which can be operated to translate or rotate in a horizontal plane, i.e., in the x and / or y directions. The pipetting head 40′ may further be configured to translate vertically, i.e., along the z axis. Probes 11A, 11B, and 11C can be movably mounted to the pipetting head 40′ so that they can be individually manipulated to translate vertically relative to the pipetting head 40′, for example, to individually move any of probes 11A, 11B, and 11C into a sample container or to individually position the tip of any of probes 11A, 11B, and 11C at a predetermined distance from the reference surface 31 of the reference element 30. Mounting multiple probes on the same pipetting head 40′ enables parallelization, thereby increasing throughput.

[0061] In the example shown in FIG. 3 , a leak test can be performed using each of the probes 11A, 11B, and 11C individually. When performing a leak test, each probe 11B is positioned so that its tip is a predetermined distance from the reference surface 31 of the reference element 30. The probes 11A, 11B, and 11C and the reference element 30 are electrically connected to a measurement unit 32 configured to apply a potential difference, such as a DC or AC voltage, between the respective probe 11B and the reference element 30. The measurement unit 32 is further configured to detect an electrical signal or a change in the electrical signal. To perform a leak test on a portion of the fluid system 10″ including the first fluid conduits 18B and 19B and the valve 16B fluidly connected to the probe 11B, the respective second valves 26B are switched to an open state with respect to the first fluid conduits 18B and 19B and to a closed state with respect to the second fluid conduit 28. If an electrical signal or change in the electrical signal is detected between probe 11B and reference element 30 by measurement unit 32 within a predetermined measurement time, it is determined that a leak has occurred somewhere in probe 11B or fluid conduit 19B between valve 16B and probe 11B, or in valve 16B or fluid conduit 18B between pump 14 and valve 16B, depending on whether valve 16B is closed or open and whether pump 14 was activated or deactivated during the measurement time. At least one corresponding maintenance action is triggered. The leak test may then be repeated in a similar manner for any other portion of fluid system 10″, including, for example, fluid conduits 18A, 18C, 19A, 19C and valves 16A, 16C fluidly connected to probes 11A, 11C. Alternatively, IVD device 100″ can include multiple reference elements 30 to enable parallel leak testing using multiple or all probes 11A, 11B, 11C simultaneously. Similarly, a leak test may be performed on the portion of fluid system 10'' that includes second fluid conduit 28. Accordingly, each valve of second set of valves 26A, 26B, 26C is switched to an open state with respect to second fluid conduit 28 and to a closed state with respect to first fluid conduits 18A, 18B, 18C, 19A, 19B, 19C.

[0062] FIG. 4 shows a flow diagram of an automated method A for performing a leak test in a fluid system of an IVD device according to an embodiment of the present disclosure, the IVD device including a controller 90 configured to control the device to perform a leak test according to method A. In particular, the method includes activating a pump 401 to supply fluid from a fluid supply into a probe. The pump is thereby operated in a pumping mode long enough to ensure that the fluid conduits and probes being leak tested are fully supplied with the respective fluid. Excess fluid supplied from the fluid supply may be discarded through the tip of the probe, typically to a fluid waste unit of the IVD device. Once the fluid conduits and probes are filled with fluid, the method includes stopping the pump 402 to stop further fluid supply. For example, referring to FIG. 1 , the pump 14 is activated and operated in a pumping mode until the fluid conduits 18 and probe 11 are filled with fluid from the fluid supply 12. Once the probe 11 is filled with fluid, the pump 14 is stopped, stopping further fluid supply.

[0063] Continuing with reference to FIG. 4, the probe is positioned (403) so that its tip is a predetermined distance from the reference surface of the reference element. Positioning the probe may include controlling the movement of the pipetting head and / or the respective probe. For example, with reference to FIG. 1, the pipetting head 40 is controlled to move in the x and y directions to position the probe 11 above the reference surface 30. The probe 11 is then controlled to move in a vertical downward movement relative to the pipetting head 40 until its tip reaches the predetermined distance from the reference surface 31.

[0064] Continuing with reference to FIG. 4 , the method includes monitoring and possibly detecting (405) whether an electrical signal or a change in the electrical signal between the probe and the reference surface occurs during a predetermined measurement period 404. The predetermined measurement period 404 is a period defining the maximum duration of the monitoring / detection step 405. The start of the measurement period 404 may coincide with the time when the tip of the probe reaches a predetermined distance from the reference surface. Detecting an electrical signal or a change in the electrical signal within the measurement period 404 indicates that the fluid system is leaking. As a result, as soon as an electrical signal or a change in the electrical signal is detected, the measurement period 404 is stopped and at least one maintenance action is triggered (406). If the predetermined measurement period 404 ends without detecting an electrical signal or a change in the electrical signal between the probe and the reference surface in step 405, the fluid system is considered not to be leaking and no maintenance action is required (407).

[0065] FIG. 5 shows a flow diagram of an automated method B for performing a leak test in a fluid system of an IVD device according to a further embodiment. The IVD device includes a controller 90 configured to control the device to perform a leak test according to method B. The first three method steps 501, 502, and 503 are similar to the first three method steps 401, 402, and 403 of method A shown in FIG. 4 and will not be further described here. Method B further includes closing (504) a valve controlling a fluid path between the fluid supply and the probe before starting a measurement period 505 or at the latest when the measurement period 505 starts. When the valve is in a closed state, the valve is switched or positioned so that the fluid path is obstructed. Similar to method A, method B includes monitoring, and possibly detecting, whether an electrical signal or a change in the electrical signal between the probe and a reference surface occurs during a predetermined measurement period 505 (506, 509). With respect to Method A, Method B further includes operating (508) the pump until a predetermined time within the predetermined measurement period 505, e.g., after half of the predetermined measurement period 505 has elapsed or after two-thirds of the predetermined measurement period 505 has elapsed, when no electrical signal or change in electrical signal is detected (506) between the probe and the reference surface, which would have ended the measurement period 505. If an electrical signal or change in electrical signal is detected in the monitoring / detection step 506 before the predetermined time for operating the pump (508) is reached, this indicates that the fluid system is leaking. At the detection time, the valve can be ruled out as leaking based on the valve being closed and the pump being stopped. Therefore, a leak has occurred in the fluid conduit between the valve and the probe. As a result, as soon as an electrical signal or change in electrical signal is detected, the measurement period 505 is stopped and at least one conduit maintenance action is triggered (507).

[0066] Activating the pump (508) when performing a leak test results in a pressure increase in the fluid conduit and / or on a closed valve located downstream of the pump. Thus, detection of an electrical signal or a change in the electrical signal in the monitoring / detection step 509 after the pump is activated (508) indicates a highly likely valve leak. In response, a valve maintenance action is triggered (510). Activating the pump (508) during the measurement period 505 may be implemented in devices where the fluid supply and / or valve and / or part of the fluid conduit are located at a vertically lower level than the tip of the probe, requiring the fluid to move against gravity.

[0067] Method B further includes generating an alert 511 in response to the determined leak, the alert indicating the at least one triggered maintenance action, for example, by displaying an alert on a display of the IVD device, possibly with further information regarding the type of maintenance action triggered and / or the expected location of the leak, etc. If the predetermined measurement period 505 expires without detecting an electrical signal or change in the electrical signal between the probe and the reference surface, the fluid system is deemed not to be leaking and no maintenance action is required 512.

[0068] Applying method B to the example shown in FIG. 2 involves activating pump 14 to supply fluid from fluid supply 12 into probe 11. Once fluid conduits 18, 19 and probe 11 are filled with their respective fluids (indicated by the wavy lines in probe 11), the method then involves stopping pump 14 to prevent further fluid supply. Probe 11 is then positioned so that its tip is a predetermined distance from reference surface 31 of reference element 30, e.g., by controlling the movement of pipetting head 40 and / or each probe 11. Valve 16 is closed before or at the start of a measurement period. A leak in fluid system 10' results in the ejection of fluid 33 from the tip of probe 11. When a droplet of fluid 33 contacts reference surface 31, an electrical signal or a change in the electrical signal is detected. If detection occurs during the phase of the measurement period when pump 14 is stopped, a leak is likely occurring in the portion of fluid conduit 19 between valve 16 and probe 11, and at least one corresponding conduit maintenance operation is triggered. If the detection occurs after the pump 14 has been activated, a leak has likely occurred in the valve 16 and at least one corresponding valve maintenance action is triggered.

[0069] FIG. 6 shows a flow diagram of an automated method C for performing a leak test in a fluid system of an IVD device according to a further embodiment. The IVD device includes a controller 90 configured to control the device to perform a leak test according to method C. A leak test according to method C can be implemented in a device in which a valve and a portion of a fluid conduit are located vertically above the tip of a probe. Method C differs from method B in that it includes a method step 608 in which a valve is opened at a predetermined time within a predetermined measurement period 605, e.g., after half of the predetermined measurement period 605 has elapsed or after two-thirds of the predetermined measurement period 605 has elapsed, unless an electrical signal or a change in an electrical signal between the probe and a reference surface that would terminate the measurement period 605 has been detected (606) by that time. If an electrical signal or a change in an electrical signal is detected in monitoring / detection step 606 before the predetermined time for opening the valve (608) is reached, this indicates that the fluid system is leaking. At the time of detection, the valve was in a closed state and the pump was stopped, which may indicate a leak in the fluid conduit or valve between the valve and the probe. The measurement period 605 is stopped upon detecting an electrical signal or a change in the electrical signal, and at least one conduit maintenance action and / or valve maintenance action is triggered (607). If an electrical signal or a change in the electrical signal is detected in the monitoring / detection step 609 after the valve is opened (608), this is an indication that the fluid system is leaking upstream of the valve, i.e., in the fluid conduit between the pump and the valve. Because no leak was detected while the valve was closed (606), a leak in the valve or the fluid conduit between the valve and the probe can be ruled out. The measurement period 605 is stopped upon detecting an electrical signal or a change in the electrical signal, and at least one conduit maintenance action is triggered (610). All other method steps are similar to the corresponding method steps of Method B shown in FIG. 5 and will not be described in further detail here.

[0070] FIG. 7 shows a flow diagram of an automated method D for performing a leak test in a fluid system of an IVD device according to a further embodiment. The IVD device includes a controller 90 configured to control the device to perform a leak test according to method D. As with methods A, B, and C described above, the leak test according to method D further includes a method step 706 in which at least one maintenance action is determined based on a time to detection. The time to detection begins at the beginning of a predetermined measurement period and continues until detection of an electrical signal or a change in the electrical signal. Based on the length of the time to detection, certain characteristics of the leak can be estimated. For example, the length of the time to detection can be correlated with the size of the leak; i.e., the shorter the time to detection, the larger the leak. All other method steps are similar to the corresponding method steps of the previously described methods, such as method A shown in FIG. 4, and therefore will not be described in further detail here. As those skilled in the art will recognize, the method step of determining at least one maintenance action based on the time to detection can be combined with determining a maintenance action based on the location of the leak, as described in methods A, B, and C described above.

[0071] 8a and 8b show diagrams illustrating the change in an electrical signal over time during a leak test. According to the automated method for performing a leak test of the present disclosure, the method includes determining a leak upon detecting an electrical signal or change in the electrical signal between a probe and a reference element. The diagram in FIG. 8a illustrates the change in such an electrical signal, i.e., capacitance, in picofarads (pF) over time in seconds (sec), which may be measured by a measurement unit. The time span included in the diagram on the x-axis may correspond to a predetermined measurement period or a segment of a predetermined measurement period. Time point 0 represents the start of the predetermined measurement period and thus coincides with the start of the leak test. At this point, fluid is supplied to the probe and the corresponding fluid conduit connecting the probe to the fluid supply. The probe is further positioned so that the tip of the probe is at a predetermined distance from the reference surface of the reference element. When the leak test is initiated, the measurement unit is controlled to apply a potential, e.g., a DC or AC voltage, between the probe and the reference element to the probe and / or the reference element. Depending on the detection method, the baseline electrical signal may be measured during a leak test at stage 801, when a leak is not determined. For example, the diagram in FIG. 8a shows a baseline capacitance measurement of approximately 30 pF, which may be attributed to noise. In the case of a leak in the fluid system, pressure within the fluid system cannot be maintained, resulting in fluid being expelled at the tip of the probe. When the fluid contacts the reference surface, the electrical signal changes accordingly, thereby confirming the presence of a leak in the fluid system. In the example of FIG. 8a, a change 802 in the electrical signal is detected after approximately 0.3 seconds, and the capacitance increases from approximately 30 pF to approximately 440 pF. The capacitance is affected by the fluid now present between the probe and the reference surface, where air was previously present. A leak may be determined regardless of the magnitude of the signal change. The detected change in the electrical signal triggers at least one maintenance action. According to aspects of the present disclosure, the at least one maintenance action is determined based on a time to detection, which is the time measured from the start of a predetermined measurement period to the detection or change in the electrical signal.8a, the time to detection corresponds to the period between time 0 and the detection of the change in the electrical signal 802. Based on the length of the time to detection, the magnitude of the leak can be assumed.

[0072] The diagram in FIG. 8b illustrates the change in resistance in kiloohms (kOhms) over time, measured between the probe and the reference element during a leak test, in seconds (sec). Time point 0 again indicates the beginning of the predetermined measurement period, thus coinciding with the start of the leak test. According to embodiments of the present disclosure, a signal threshold 812 can be determined. As shown in FIG. 8b, a baseline signal 811 is measured during the early stages of the leak test above the signal threshold 812. When the electrical signal falls below the signal threshold 812, this is considered a "change in the electrical signal" and a leak is determined. On the other hand, if the measured electrical signal remains above the signal threshold 812 for the entire duration of the predetermined measurement period, despite certain signal variance, the fluid system is deemed not to be leaking. In the example of FIG. 8b, the baseline signal 811 is recorded at approximately 530 kOhms. A leak is detected approximately 0.18 seconds after the signal falls below the signal threshold 812, e.g., at 200 kOhms. Those skilled in the art will recognize that the signal threshold 812 can be determined based on the detection method implemented. Conversely to the example above, the baseline signal may be determined to be below the signal threshold 812. A leak is determined only if the electrical signal rises above the signal threshold 812. Alternatively, rather than determining an absolute value for the signal threshold 812, the signal threshold 812 may be determined relative to the baseline signal 811. For example, the signal threshold 812 may be considered exceeded if a capacitance difference of greater than 100 pF (>100 pF) is measured from the baseline measurement 811, or if a resistance difference of greater than 100 kOhm (>100 kOhm) is measured from the baseline measurement 811.

[0073] The foregoing specification describes in detail various aspects of the apparatus and methods. The apparatus and methods can be embodied in many different forms and should not be construed as limited to the aspects described and illustrated herein. It is therefore to be understood that the apparatus and methods are not to be limited to the particular aspects disclosed, and that modifications and other aspects are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present methods, the preferred methods and materials are described herein.

[0074] Furthermore, reference to an element by the indefinite article "a" or "an" does not exclude the possibility that a plurality of elements is present, unless the context clearly requires that one and only one element is present. Thus, the indefinite article "a" or "an" normally means "at least one." Similarly, the terms "have," "comprise," or "include," or any grammatical variations thereof, are used in a non-exclusive manner. Thus, these terms may refer both to a situation in which, in addition to the feature introduced by these terms, no further features are present in the entity described in this context, and to a situation in which one or more additional features are present. For example, the expressions "A has B," "A comprises B," and "A includes B" can all refer to a situation in which no other elements are present in A besides B (i.e., a situation in which A consists solely and exclusively of B), or to a situation in which, in addition to B, one or more further elements are present in A, such as element C, elements C and D, or additional elements.

[0075] Also, throughout the specification, references to "one embodiment," "embodiment," "one example," or "example" mean that the particular feature, structure, or characteristic described in connection with that embodiment or example is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment," "in an embodiment," "one example," or "example" in various places throughout this specification are not necessarily all referring to the same embodiment or example.

[0076] Furthermore, the particular features, structures or characteristics may be combined in any suitable combinations and / or subcombinations in one or more embodiments or examples.

Claims

1. 1. An automated method for performing leak testing of a fluid system (10, 10', 10'') of an in-vitro diagnostic device (100, 100', 100'') comprising a conductive probe (11, 11A, 11B, 11C) fluidly connected to a fluid supply (12, 22) via a fluid conduit (18, 18A, 18B, 18C, 19, 19A, 19B, 19C, 28) and electrically interacting with a reference element (30), comprising: activating a pump (14, 24) to supply fluid from the fluid supply (12, 22) into the probe (11, 11A, 11B, 11C); stopping the pump (14, 24); Positioning the probes (11, 11A, 11B, 11C) so that the tips of the probes (11, 11A, 11B, 11C) are at a predetermined distance from a reference surface (31) of the reference element (30); detecting an electrical signal or a change in the electrical signal between the probe (11, 11A, 11B, 11C) and the reference element (30) within a predetermined measurement period to determine a leak and trigger at least one maintenance action; A method comprising:

2. 2. The method of claim 1, further comprising closing a valve (16, 16A, 16B, 16C, 26A, 26B, 26C) controlling the passage of fluid between the pump (14, 24) and the probe (11, 11A, 11B, 11C) during the measurement period.

3. 2. The method of claim 1, further comprising switching valves (16, 16A, 16B, 16C, 26A, 26B, 26C) that control the passage of fluid between the pump (14, 24) and the probe (11, 11A, 11B, 11C) to an open state during the measurement period.

4. The method of claim 1 , wherein the at least one maintenance action is selected from a set of possible conduit maintenance actions.

5. 2. The method of claim 1, further comprising operating the pump (14, 24) during the measurement period.

6. The method of claim 5 , wherein the at least one maintenance action is selected from a set of possible conduit maintenance actions and / or valve maintenance actions.

7. 2. The method of claim 1, wherein the at least one maintenance action is determined based on a time to detection, the time to detection being the time measured from the start of the predetermined measurement period until the electrical signal or a change in the electrical signal is detected.

8. The method of claim 1 , wherein triggering the at least one maintenance action comprises generating an alert indicating the at least one maintenance action.

9. An in vitro diagnostic device (100, 100', 100''), comprising: A fluid system (10, 10', 10'') comprising: a fluid supply (12, 22); a pump (14, 24); a conductive probe (11, 11A, 11B, 11C) fluidly connected to said fluid supply (12, 22) via a fluid conduit (18, 18A, 18B, 18C, 19, 19A, 19B, 19C, 28) and electrically interacting with a reference element (30); a fluid system (10, 10', 10'') comprising: a controller (90) configured to control the apparatus (100) to perform a leak test on the fluid system (10, 10', 10'') according to the method of claim 1; An in-vitro diagnostic device (100, 100', 100'').

10. 10. The apparatus of claim 9, wherein the fluid system further comprises a valve controlling a fluid passage between the pump and the probe.

11. 10. The device according to claim 9, wherein the conductive probe (11, 11A, 11B, 11C) is configured to detect the liquid level by determining contact with the liquid surface by any one or combination of measurement principles including capacitance, resistance, conductivity, and inductive measurement principles.

12. 10. The device according to claim 9, wherein the probe (11, 11A, 11B, 11C) is horizontally translatable and / or rotatable relative to the reference element (30) or liquid and vertically translatable.

13. 11. The device according to claim 10, wherein the valve (16, 16A, 16B, 16C, 26A, 26B, 26C) is disposed at a level vertically lower than the level of the tip of the probe (11, 11A, 11B, 11C) at the leak detection position.

14. 10. The apparatus of claim 9, further comprising an alarm function (50) configured to indicate a leak determination and the at least one maintenance action.

15. 15. Apparatus according to any one of claims 9 to 14, wherein the controller is configured to initiate the method of claim 1 at predetermined time intervals, or in response to a trigger event, or in response to operator input.

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