Liquid detector for an analysis device

Abstract

The invention relates to a liquid detector (100) for an analysis device (10), wherein the liquid detector (100) has: i) a temperature sensor device (120) for determining a temperature characteristic (132) over time in response to a provided temperature pulse (131); and, ii) an evaluation device (130) for evaluating a liquid characteristic on the basis of the determined temperature characteristic (132).

Description

DESCRIPTION LIQUID DETECTOR FOR AN ANALYSIS DEVICE AREA OF INVENTION

[0001] The present invention relates to a liquid detector for an analytical device (in particular a sample separation device), wherein the liquid detector comprises: a temperature sensor device for determining a temperature characteristic over time in response to a supplied temperature pulse, and an evaluation device for evaluating a liquid characteristic based on the determined temperature characteristic. The invention further relates to an analytical device comprising the liquid detector and a method for detecting a liquid characteristic. TECHNICAL BACKGROUND

[0002] Analytical devices such as sample separation instruments are designed for the analysis of a sample, particularly a fluidic sample, for example, to perform chromatographic separation of the sample. In an HPLC (high-performance liquid chromatography) analytical instrument, for instance, a liquid (mobile phase) is moved through a stationary phase (for example, in a chromatographic column) at a very precisely controlled flow rate (for example, in the range of microliters to milliliters per minute) and at high pressure (typically 20 to 1000 bar and beyond, currently up to 2000 bar), at which the compressibility of the liquid may be noticeable, in order to separate individual fractions of a sample liquid introduced into the mobile phase. After passing through the stationary phase, the separated fractions of the fluidic sample are detected in a detector.Such an HPLC system is known, for example, from EP 0,309,596 B1 of the same applicant, Agilent Technologies, Inc.

[0003] In analytical instruments, such as HPLC systems, fluids, especially liquids, are used, flowing along flow paths within the instrument. However, fluid-related problems (e.g., unwanted fluid leakage and / or spillage) can occur, such as leaks. To detect such a leak, a PTC thermistor is conventionally used, for example. (positive temperature coefficient) sensor used.

[0004] A current flows through the PTC sensor, heating it. As the temperature increases, so does the resistance of the PTC sensor. Under constant ambient conditions (ambient air), the resistance and temperature of the device stabilize on their own (equilibrium is reached). If a liquid flows over the sensor, this changes the ambient conditions and the current through the device, allowing a liquid leak to be detected.

[0005] However, conventional solutions like the PTC sensor can also have disadvantages. For example, an additional ambient temperature sensor is required, and the amount of liquid present to detect a leak is relatively high. The PTC sensor therefore quickly reaches its limits under conditions where the ambient temperature changes rapidly or where the liquid leak could be at a high temperature (e.g., the leakage sensor in the column thermostat is deactivated in many applications to avoid false alarms). REVELATION

[0006] There may be a need to efficiently and reliably detect a liquid characteristic in an analytical device. This problem is solved by means of the independent claims. Further embodiments are shown in the dependent claims.

[0007] According to a first embodiment of the present invention, a liquid detector (or a device for detecting a liquid characteristic) for an analytical device (e.g. a sample separation device, in particular an HPLC) is described, wherein the liquid detector comprises:

[0008] i) a temperature sensor device for determining a temperature characteristic (e.g. a heat capacity, a decay curve, etc.) over time in response to a provided temperature pulse (in particular provided by a temperature pulse device); and

[0009] ii) an evaluation device (e.g. hardware and / or software) for evaluating a fluid characteristic (or fluid property, fluid problems) based on the specific temperature characteristic (especially by evaluating a decay curve).

[0010] According to a second embodiment of the present invention, an analysis device is described which has at least one liquid detector as described above.

[0011] According to a third embodiment of the present invention, a method for detecting a liquid characteristic with respect to an analytical device is described, the method comprising: i) in particular providing a temperature pulse; ii) determining a temperature characteristic over time in response to the provided temperature pulse; and iii) evaluating the liquid characteristic based on the determined temperature characteristic.

[0012] In the context of this document, the term "temperature characteristic" (or temperature pulse response data) refers specifically to a temperature profile that can be measured / observed in response to a temperature pulse. Such a temperature characteristic can be indicative of a time-dependent change in temperature, particularly triggered by the temperature pulse. In one embodiment, the temperature pulse can provide a short-term warm-up phase, while the temperature characteristic represents a subsequent cooling phase (or vice versa). In another exemplary embodiment, the temperature characteristic can be a decay / fall characteristic (e.g., a decay curve). Here, the temperature characteristic can be seen as (re-)establishing an equilibrium.The term "temperature characteristic" can imply that the temperature profile (after the temperature pulse event) is characteristic of the liquid detector environment. For example, the temperature characteristic in an air environment is different from that in a water environment.

[0013] In the context of this document, the term "liquid characteristic" refers specifically to a liquid property or problem that can be evaluated (especially demonstrated) directly or indirectly using the temperature characteristic described above. A liquid characteristic can, for example, be the presence or absence of a certain characteristic. A liquid characteristic can also relate to the differentiation of liquids. Furthermore, a liquid characteristic can refer to whether a liquid detector is surrounded or submerged by liquid.

[0014] In one embodiment, the term "liquid characteristics" can refer in particular to a characterization of the wetting situation of the liquid detector (or temperature sensor device) surface. From this, conclusions can then be drawn by means of evaluation, such as the presence of a leak, condensation, or icing.

[0015] In the context of this document, the term "temperature sensor device" refers specifically to a device capable of measuring / detecting temperature. In particular, the temperature sensor device is capable of measuring temperature changes over time, allowing, for example, the recording of a temperature decay curve following a temperature pulse event. In a simple example, the temperature sensor device is implemented as a temperature sensor, such as a PTC temperature sensor. In a more complex example, the temperature sensor device can be integrated with a temperature pulse device in a space-saving and robust unit.

[0016] In the context of this document, the term "temperature pulse device" refers specifically to a device capable of providing a temperature pulse, particularly to a temperature sensor device. A temperature pulse can, for example, be implemented as a (heating) current pulse that provides a brief warm-up phase. A corresponding device can thus be designed to provide such a current pulse. In one embodiment, the temperature pulse device can be implemented as a heating element. The temperature pulse device can be integrated with the temperature sensor device in a single unit or operated independently.

[0017] In the context of this document, the term "fluid" is understood to mean, in particular, a liquid and / or a gas, optionally having Solid particles. The term "fluid" can also refer to a mobile phase in which a fluidic sample is transported.

[0018] In the context of this document, the term "fluidic sample" refers in particular to a medium, and more specifically a liquid, that contains the matter to be analyzed (for example, a biological sample), such as a protein solution, a pharmaceutical sample, etc.

[0019] In the context of this document, the term "mobile phase" refers specifically to a fluid, and more specifically a liquid, that serves as a carrier medium for transporting the fluidic sample between a fluid drive and a sample separation device. However, the mobile phase can also be used in a fluid conveying device to influence the fluidic sample. For example, the mobile phase can be a solvent (e.g., organic and / or inorganic) or a solvent composition (e.g., water and ethanol).

[0020] In the context of this document, the term "analytical device" can refer in particular to a device capable of and configured to analyze a fluidic sample, in particular to separate it, and further, in particular, to separate it into different fractions. For example, such sample separation can be carried out by means of chromatography or electrophoresis. Preferably, the analytical device can be a liquid chromatography sample separation device.

[0021] According to an exemplary embodiment, the invention can be based on the idea that a liquid characteristic with respect to an analysis device can be detected efficiently and reliably if a temperature sensor device acquires a temperature characteristic in response to a temperature pulse and an evaluation device evaluates the temperature characteristic with respect to the liquid characteristic. Preferably, the temperature pulse can cause an abrupt temperature increase, while the temperature characteristic describes the (significantly slower) subsequent temperature decrease.

[0022] The inventors were surprised to discover that the temperature characteristic (e.g., a decay curve, see Figures 3 to 5) Reliable conclusions can be drawn about whether the liquid detector is located in an air or liquid environment, for example. This measurement, in turn, allows conclusions to be drawn about whether a liquid problem such as a leak exists.

[0023] Furthermore, the inventors have surprisingly discovered that a multitude of other liquid characteristics, such as condensation, icing, or sedimentation / deposits, can be measured and detected based on temperature characteristics. Accordingly, a wide variety of useful applications can arise for an energy-efficient and compact liquid detector.

[0024] In a preferred embodiment, the described liquid detector can operate independently of temperature gradients (e.g., ambient temperature) and additional temperature references (e.g., an ambient temperature sensor). The described liquid detector can be designed to be compact and robust (particularly resistant to contamination and chemicals). This allows it to be positioned in a variety of locations within the analytical device, including, for example, in thermostats (e.g., column ovens) with widely fluctuating temperatures. Compared to conventional sensors, the described liquid detector can be more sensitive and can also detect the presence of small quantities of liquid (leakage). Furthermore, the described liquid detector can detect a wider range of liquid characteristics / problems (e.g., condensation) and differentiate between fluids (e.g., cool air and warm liquid).This means that the described liquid detector can also be independent of the type of liquid.

[0025] In a preferred embodiment, the described liquid detector can be more reliable and faster than conventional solutions and can be used more flexibly. Costs, especially energy consumption, can also be reduced. EXEMPLARY EXAMPLES OF EXECUTION

[0026] According to one embodiment, the fluid characteristic relates to at least one of the following: leakage, condensation, icing, swirling, overflow, or a fluid type. This allows for frequent Problems with analytical devices can be identified efficiently and reliably.

[0027] In one embodiment, the liquid characteristic, determined from the temperature characteristic, relates in particular to the presence / absence of liquid in the liquid detector environment, specifically at the liquid detector surface. Liquid problems such as overflow or flooding, condensation, or icing can thus be directly detected. Different liquid types can also be distinguished directly or indirectly.

[0028] Furthermore, in one embodiment, fluid characteristics can also be derived from the measured data. For example, a leak can be inferred from the measured fluid characteristics. Condensation could, for instance, also result from a leak if, for example, fluid escapes or evaporates at another location.

[0029] According to one embodiment, the temperature characteristic exhibits a decay characteristic (decay curve) over time in response to the applied temperature pulse. The temporal progression of this decay characteristic can differ significantly in various sensor environments. This is illustrated, for example, in Figures 4A to 4C (air environment) and Figures 5A to 5C (water environment). The decay characteristic of water after the temperature pulse is significantly faster / steeper than that of air. Different liquid types can be distinguished in the same way. Furthermore, the presence of liquid-related issues such as condensation, icing, or sedimentation can also generate different (characteristic) decay curves.

[0030] According to one embodiment, the liquid detector further comprises: a temperature pulse device for providing the temperature pulse. This allows a temperature pulse to be supplied (in particular directly / selectively) to the temperature sensor device. For example, a temperature pulse device can supply an electric heating current for heating. However, it is also possible for the temperature pulse device to supply heat energy directly, for example by means of a heating coil (such as a resistive heating coil). Preferably, the temperature pulse device is controllable in order to supply heat only in a controlled manner. to provide (in particular controlled with regard to the timing and / or quantity of heat provided).

[0031] According to one embodiment, the temperature pulse exhibits either heating or cooling. According to another embodiment, the temperature pulse device includes a heating element or a cooling element. While the temperature pulse is implemented as heating in a preferred example, it can also be implemented as cooling in a further example (the temperature characteristic could then, for example, be a characteristic heating curve).

[0032] According to one embodiment, the evaluation device is configured to evaluate whether the thermal environment, particularly with respect to the temperature sensor device, has changed. Based on the temperature characteristics, it can be evaluated whether the environment has changed (e.g., compared to a previous measurement). A thermal change in the environment can indicate the presence or absence of a liquid or a change in the liquid's characteristics. In particular, the thermal environment of the liquid detector or temperature sensor device surface can be considered.

[0033] According to one embodiment, the evaluation device is configured to check for the presence of at least one of the following and / or to distinguish between at least one of the following: a gas (in particular air), a liquid (in particular water, organic solvent, a leaking liquid), a leak, a condensate, icing, an adhesion / deposition, a wash / overflow, a sedimentation. This can have the advantage that the liquid detector can detect a variety of liquid problems and, accordingly, the operation of the analysis device can become more efficient and reliable.

[0034] In the present context, the term "sedimentation" can refer specifically to the deposition of unwanted material. For example, such a deposition might consist of dust. In another example, sedimentation could be a salt crust that can form through the evaporation of saline solvents.

[0035] For example, a liquid detector can be used to determine the presence of a liquid characteristic; further conclusions can then be drawn from this. On the other hand, the liquid detector can also be used to differentiate between different (environmental) situations or liquid types.

[0036] According to one embodiment, the liquid detector is independent of the ambient temperature, particularly the liquid temperature. In another embodiment, the liquid detector does not require an additional ambient temperature sensor. This saves costs, effort, and space. Furthermore, reliability and / or flexibility can be increased (e.g., in relation to a thermostat).

[0037] According to one embodiment, the liquid detector is a single-sensor system (in particular without an additional ambient temperature sensor). This can enable a compact and robust design.

[0038] According to one embodiment, the liquid characteristic is independent of the hygrostatic environment, in particular humidity. In another embodiment, the liquid characteristic refers to a liquid as such or to a liquid problem associated with such a liquid (leakage, condensation, icing, etc.). In a specific embodiment, the term "liquid characteristic" does not refer to humidity, and the liquid detector is not a humidity sensor.

[0039] In one embodiment, the temperature pulse provides a temporary temperature change. In another embodiment, the temperature pulse provides a positive energy pulse. This can have the advantage that the temperature pulse can be implemented in a simple and efficient manner.

[0040] According to one embodiment, the temperature pulse device is configured to provide a time-limited pulse of electrical energy, in particular (heating) current, especially (directly / selectively) to the temperature sensor device.

[0041] According to one embodiment, the temperature sensor The device consists of at least one of the following: a resistance temperature sensor, a positive temperature coefficient sensor, a negative temperature coefficient sensor, a semiconductor temperature sensor, or a digital temperature sensor. This can have the advantage that known and established systems can be implemented directly. In one example, the PTC or NTC is energized and thereby dissipates heat as an ohmic resistor. Due to the change in temperature, the resistance of the PTC or NTC changes, especially when in contact with liquid, so that the temperature can be inferred from this.

[0042] A design as a resistance temperature sensor, positive / negative temperature coefficient sensor, can be particularly advantageous if the temperature sensor device and the temperature pulse device are the same element. However, if the design uses separate physical elements, a different physical measuring principle can also be used as the temperature sensor device, such as that used in electronic temperature sensor devices, e.g., the use of a heating element (such as a resistor) and an electronic (semiconductor) sensor in close proximity.

[0043] According to one embodiment, the temperature pulse device and the temperature sensor device are integrated into a single device (the same physical element) (see, for example, the example in Figure 2). In this example, the temperature pulse device and the temperature sensor device are the same physical element. This can have the advantage of providing a compact and robust liquid detector. Reliability can also be increased.

[0044] In an exemplary embodiment of the same physical element, for example a PTC can be brought to an increased temperature by a heating current pulse and thus simultaneously function as a temperature sensor device and temperature pulse device.

[0045] In another embodiment (of the same physical element), the heating element (temperature pulse device) can be designed in such a way that both the heating and temperature measurement functions can be fulfilled. This is possible, for example, by using a PTC / PT1000 element. When excited with a small current, no self-heating occurs, and temperature measurement is possible. With a higher current, the temperature measurement function remains unchanged (linear relationship between resistance and voltage drop at a given constant current). Additionally, the same element can also be used for heating (through self-heating of the sensor element). In this case, the sensor design can be simpler.

[0046] According to one embodiment, the temperature pulse device and the temperature sensor device are provided separately. This increases design flexibility. If, in one example, the temperature pulse device and the temperature sensor device are implemented separately, other sensors, such as semiconductor temperature sensors or integrated circuits, can also be used for temperature measurement. These can include sensor signal preprocessing and output the temperature measurement signal digitally. In another example, the temperature pulse device can be embedded within the structure of the temperature sensor device.

[0047] According to one embodiment, the liquid detector further comprises a support structure for mounting the temperature pulse device and the temperature sensor device. In one embodiment, the support structure is arranged between the temperature pulse device and the temperature sensor device, in particular such that the devices are arranged opposite each other. In one example, the support structure can be a mounting structure, in particular a mounting surface / mounting plate (e.g., a ceramic plate). In one embodiment, the support structure has a first main surface on which the temperature pulse device is arranged, and a second (opposite) main surface on which the temperature sensor device is arranged. Using these embodiments, a stable and compact liquid detector can be provided.

[0048] In an exemplary embodiment, a resistive element (NTC or PTC) is used both as a heating element and as a sensing element. The temperature is measured by a small current flowing through the resistor. To heat the element, this current is increased. After the pulse, the current returns to the temperature-measuring current. The volume was reduced and the decay curve observed. In this case, no support structure would be necessary.

[0049] According to one embodiment, the temperature pulse device and / or the temperature sensor device and / or the support structure are encased in a protective material, in particular a polymer, especially a resin. This can provide reliable protection, especially in areas of the analytical device subject to mechanical movement or chemical contamination.

[0050] According to one embodiment, the analytical device comprises at least one module containing the liquid detector. According to another embodiment, the analytical device comprises at least one of the following modules: a pump module, a detector module, a sample separation module (or a thermostat module, in particular a column oven module), a sample handling module, a fraction collector module, and a solvent storage module (in particular a solvent cabinet; leaks can frequently occur here). To increase reliability and safety, one or more modules of the analytical device can be equipped with the described liquid detector.

[0051] According to one embodiment, the analytical device further comprises: a leak detection device, in particular a leakage tray (e.g., the solvent bottle tray), for collecting leakage liquid, wherein the liquid detector is associated with the leakage detection device. In particular, one or more liquid detectors can be coupled / connected to the leakage detection device. Leakage liquid can collect in the leakage detection device, thus enabling efficient and reliable leak detection. For example, the collected leakage liquid can wet the surface of the liquid detector and / or surround / surface it. Upon detection of such a liquid characteristic (in the leakage detection device), the presence of a leak can then be inferred.

[0052] According to one embodiment, the analysis device further comprises: a plurality of liquid detectors, wherein the liquid detectors are configured as a detector array, in particular planar (e.g., on the bottom of a leakage tray). This can have the advantage that the location of a Fluid characteristics Z can be used to locate problems (especially leaks). This makes it easier to identify and eliminate them.

[0053] According to an exemplary embodiment, a temperature sensor element operates in two modes. In the first mode, it is operated with a very low current, so there is no self-heating of the element, and the actual temperature of the element can be determined by measuring the resulting voltage across it. In the second mode, a higher current is applied, and the element heats up (self-heating). In this mode, it is still possible to measure the actual temperature of the liquid detector and, specifically, the heating curve. By measuring the heating and cooling curves of the sensor element, it can be determined whether the sensor is surrounded by air or a liquid (in case of a leak). The measurement is continuous, and the device alternates between ambient temperature and a temperature slightly above ambient temperature (to avoid thermal stress on the sensor).This involves thermal modulation and therefore suppresses dependencies on the ambient temperature. Due to its design as a temperature sensor, an additional ambient temperature sensor is no longer necessary.

[0054] Within the scope of this application, the term "sample separation device" can be understood to mean, in particular, a device for analyzing a fluidic sample, especially into different fractions. For this purpose, components of the fluidic sample can first be adsorbed on the sample separation device and then desorbed separately (especially fractionally). For example, such a sample separation device can be configured as a chromatographic separation column.

[0055] According to one embodiment, the analytical device is a sample separation device, in particular a chromatography device, especially a liquid chromatography device, a gas chromatography device, an SFC (supercritical liquid chromatography) device or an HPLC (high-performance liquid chromatography) device.

[0056] According to one embodiment, the analysis device is configured as a microfluidic instrument. According to one embodiment, the Analysis device configured as a nanofluidic device.

[0057] According to one embodiment, the sample separation device is designed as a chromatographic separation device, in particular as a chromatography separation column.

[0058] According to one embodiment, the fluid drive is configured to drive the mobile phase and the fluidic sample under high pressure.

[0059] According to one embodiment, the fluid drive is configured to drive the mobile phase and the fluidic sample with a pressure of at least 500 bar, in particular at least 1000 bar, further in particular at least 1200 bar, and further in particular at least 1500 bar.

[0060] According to one embodiment, the analysis device has a detector for detecting the analyzed, in particular separated, fluidic sample.

[0061] According to one embodiment, the analysis device includes a fractionator for fractionating separate fractions of the fluidic sample.

[0062] The analytical instrument can be a microfluidic measuring device, a life science instrument, a liquid chromatograph, a gas chromatograph, an HPLC (high-performance liquid chromatography), an UHPLC system, or an SFC (supercritical liquid chromatography) instrument. However, many other applications are possible.

[0063] According to one embodiment, the sample separation device can be designed as a chromatographic separation device, in particular as a chromatographic column. In chromatographic separation, the chromatographic column can be provided with an adsorption medium. The fluidic sample can be retained on this medium and only subsequently released fractionally in the presence of a specific solvent composition, thus achieving the separation of the sample into its fractions.

[0064] A pumping system for conveying fluid can, for example, be set up to pump the fluid or the mobile phase at high pressure, to For example, to convey pressures of several hundred bar up to 1000 bar and more through the system.

[0065] The analytical device can include a sample injector for introducing the sample into the fluidic separation path. Such a sample injector can have a sample or injection needle, coupled to a needle seat, within a corresponding fluid path, wherein the sample needle can be extended from this needle seat to receive the sample. After reinsertion of the sample needle into the needle seat, the sample can be located in a fluid path that can be switched into the separation path of the system, for example, by switching a valve. In another embodiment of the invention, a sample injector or sampler can be used with a sample needle that operates without a needle seat.

[0066] The analytical device may include a fraction collector for collecting the separated components. Such a fraction collector can, for example, direct the different components of the separated sample into separate liquid containers. Alternatively, the analyzed sample can be directed to a discharge container.

[0067] Preferably, the analytical device can include a detector for detecting the separated components. Such a detector can generate a signal that can be observed and / or recorded, and which is indicative of the presence and quantity of the sample components in the fluid flowing through the system. BRIEF DESCRIPTION OF THE DRAWINGS

[0068] Other objectives and many of the accompanying advantages of exemplary embodiments of the present invention will become readily apparent and more readily understood with reference to the following more detailed description of exemplary embodiments in conjunction with the accompanying drawings. Features that are essentially or functionally the same or similar are designated with the same reference numerals.

[0069] Figure 1 shows an analysis device designed as a sample separation device, according to an exemplary embodiment of the invention.

[0070] Figure 2 shows a liquid detector according to an exemplary embodiment of the invention.

[0071] Figure 3 shows a temperature-time diagram with a temperature pulse followed by a temperature characteristic, according to an exemplary embodiment of the invention.

[0072] Figures 4A to 4C show temperature-time diagrams in the presence of air, according to exemplary embodiments of the invention.

[0073] Figures 5A to 5C show temperature-time diagrams in the presence of liquid, according to exemplary embodiments of the invention. DETAILED DESCRIPTION OF THE DRAWINGS

[0074] The representation in the drawing is schematic.

[0075] Figure 1 shows the basic structure of an HPLC system as an example of an analytical device 10 designed as a sample separation instrument according to an exemplary embodiment of the invention, as it can be used, for example, for liquid chromatography. A fluid conveying device or fluid drive 20, which is supplied with solvents from a feed device 25, drives a mobile phase through a sample separation device 30 (such as a chromatographic column) which contains a stationary phase. The feed device 25 comprises a first fluid component source for providing a first fluid or a first solvent component A (for example, water) and a second fluid component source for providing another second fluid or a second solvent component B (for example, an organic solvent).An optional degasser 27 can degasse the solvents supplied by the first fluid component source and by the second fluid component source before they are fed to the fluid drive 20. Optionally, the solvents can be mixed at a mixing point.

[0076] A sample delivery unit, which can also be referred to as injector 40, is arranged between the fluid drive 20 and the sample separation device 30 in order to first receive a sample liquid or a fluidic sample from a sample container into a sample receiving volume in an injector path, and subsequently by switching an injection valve of the injector. 40 to introduce into a fluidic separation path between fluid drive 20 and sample separation device 30. The intake of fluidic sample from the sample container can be achieved, in particular, by extending a sample needle from a sample seat and retracting it into the sample container, drawing fluidic sample from the sample container through the sample needle into the sample intake volume by means of a fluid conveying device designed as a metering device, and then retracting the sample needle back into the needle seat.

[0077] The stationary phase of the sample separation unit 30 is designed to separate components of the sample. A detector 50, which may include a flow cell, detects the separated components of the sample. A fractionator 60 can be provided to discharge the separated components of the sample into designated containers. Unneeded liquids can be discharged into a drain or waste line.

[0078] While a fluid path between the fluid drive 20 and the sample separation device 30 is typically under high pressure, the sample fluid is initially introduced at atmospheric pressure into a section separate from the fluid path, namely the sample loop or sample intake volume, of the sample delivery unit or injector 40. The sample fluid is then introduced into the high-pressure separation path. A sample loop (also referred to as a sample intake volume) can be understood as a section of a fluid line designed to receive or temporarily store a predetermined quantity of fluidic sample.Preferably, before the sample liquid, initially at normal pressure, is introduced into the high-pressure separation path, the contents of the sample receiving volume are brought to the system pressure of the HPLC analyzer 10 by means of a metering device in the form of a fluid conveying device. A control unit 70 controls the individual components 20, 25, 30, 40, 50, 60, etc., of the analyzer 10. A liquid detector 100 is arranged at one or more positions of this analyzer 10, as described in detail below.

[0079] Figure 2 shows a liquid detector 100, according to a Exemplary embodiment of the invention. The liquid detector 100 has a temperature pulse device 110 for providing a temperature pulse 131. The temperature pulse 131 is shown schematically in a temperature-time diagram. In this example, the temperature pulse 131 is a time-limited heating current pulse that causes a brief change in temperature (heating).

[0080] The liquid detector 100 has a temperature sensor device 120 configured to determine a temperature characteristic 132 over time in response to the temperature pulse 131 provided by the temperature pulse device 110. The temperature sensor device 120 can be implemented as a temperature sensor, for example, as one of the following: a resistance temperature sensor, a positive temperature coefficient sensor, a negative temperature coefficient sensor, a semiconductor temperature sensor, or a digital temperature sensor. A temperature-time diagram schematically shows the temperature characteristic 132, which follows the temperature pulse 131 and shows a decrease in temperature over time (cooling). This decay curve can be characteristic of the presence of liquid in the vicinity of the liquid detector 100.

[0081] In the illustrated embodiment, the temperature pulse device 110 and the temperature sensor device 120 are integrated into a common device 100. The liquid detector 100 has a support structure 140 for mounting the temperature pulse device 110 and the temperature sensor device 120. The support structure 140 is designed as a mounting plate, so that the temperature pulse device 110 can be mounted on the first (upper) main surface and the temperature sensor device 120 can be arranged on the opposite, second main surface (i.e., opposite each other). In this configuration, the temperature pulse device 110 can directly supply the temperature pulse 131 to the temperature sensor device 120.

[0082] The liquid detector 100 further comprises a protective material 150, e.g. a resin, in which the temperature pulse device 1 10, the support structure 140, and the temperature sensor device 120 are embedded.

[0083] The schematic representation shows that the temperature pulse device 110 and the temperature sensor device 120 are each coupled (via electrical lines) to an evaluation device 130, which is set up to evaluate the temperature characteristic 132.

[0084] Figure 3 shows a temperature-time diagram with a temperature pulse. 131 followed by a temperature characteristic 132, according to an exemplary embodiment of the invention. The X-axis shows the time profile (in seconds), while the Y-axis shows the temperature (in °C). Starting from the normal temperature To, the temperature pulse 131 causes an abrupt rise in temperature to Tmax. After the temperature pulse 131, the temperature falls in a decay curve 132, which can be considered a temperature characteristic (warm-up phase / curve and cooling phase / curve).

[0085] Figures 4A to 4C show temperature-time diagrams in the presence of (dry) air, according to exemplary embodiments of the invention. Figure 4A shows a time profile (in seconds) with four temperature pulses 131 (intensity is shown) or four corresponding temperature characteristics. Figure 132 (in °C), while Figures 4B and 4C show a section of the temperature characteristic. Figure 4B shows the beginning and maximum of the temperature pulse 131, and Figure 4C shows the beginning and halfway point of the temperature characteristic 132. This example demonstrates that an air environment can be clearly derived from the decay curve 132. In many embodiments, it can be considered the normal state that the liquid detector 100 is surrounded by air. The temperature pulse 131 can be used periodically or only in phases.

[0086] Figures 5A to 5C show temperature-time diagrams in the presence of liquid, according to exemplary embodiments of the invention. Figure 5A shows a time course with four temperature pulses 131 and four corresponding temperature characteristics 132, while Figures 5B and 5C show a section of the time course. Figure 5B shows the beginning and maximum of the temperature pulse 131, and Figure 5C shows the beginning and halfway point of the temperature characteristic 132. These points can be directly compared with those in Figures 4B and 4C. This example shows that a liquid environment (e.g., water) can be clearly deduced from the decay curve 132. From this example, it can now be concluded that the liquid detector 100 is surrounded by liquid or already submerged. The reason for this could be, for example, a leak.

[0087] For these examples in Figures 4 and 5, the following values ​​can be determined (at a temperature of 24°C): Air: dT (Kelvin): 0.331 ; dTmax (seconds): 1.6; dTso (seconds): 8.1 . Water: dT : 0.234; dTmax: 1.3; dTso: 1.9.

[0088] In other words, the main difference between an air environment and a liquid environment is the decay time dT from the maximum of the measured temperature dTmax to halfway (time dTso), in which the temperature falls from the temperature peak Tmax to the value temperature peak - dT*0.5. The time deviation here is a factor of 4.26.

[0089] Reference sign 10 Analysis device 20 Fluid drive 25 Feeding device 27 degassers 30 Sample separation device 40 injectors 50 Detector 60 fractionators 70 Control unit 100 liquid detectors 110 Temperature Pulse Device 120 Temperature Sensor Device 130 Evaluation device 131 Temperature Pulse 132 Temperature characteristic 140 support structure 150 protective materials

Claims

AMENDED CLAIMS received by the International Bureau on 05 February 2026 (05.02.2026) 1. A liquid detector (100) for an analysis device (10), wherein the liquid detector (100) comprises: a temperature pulse device (110) for providing a temperature pulse (131); a temperature sensor device (120) for determining a temperature characteristic (132) over time in response to the provided temperature pulse (131); and an evaluation device (130) for evaluating a liquid characteristic based on the determined temperature characteristic (132); wherein the temperature pulse device (110) is configured to provide the temperature pulse (131) directly to the temperature sensor device (120).

2. The liquid detector (100) according to claim 1, wherein the temperature sensor device (120) is configured to determine the temperature characteristic (132) of the temperature sensor device (120) over time in response to the provided temperature pulse (131).

3. The liquid detector (100) according to claim 1 or 2, wherein the liquid characteristic relates to at least one of the following: a leakage, a condensation, an icing, a swirl, a flood, a liquid type.

4. The liquid detector (100) according to one of the preceding claims, wherein the temperature characteristic (132) has: a decay characteristic over time in response to the provided temperature pulse (131 ).

5. The liquid detector (100) according to any one of the preceding claims, wherein the temperature pulse (131) comprises: heating or cooling; and / or wherein the temperature pulse device (110) comprises: a heating element or a cooling element.

6. The liquid detector (100) according to one of the preceding Claims, wherein the evaluation device (130) is configured to evaluate whether the thermal environment, in particular with respect to the temperature sensor device (120), has changed.

7. The liquid detector (100) according to one of the preceding Claims, wherein the evaluation device (130) is configured to test the Presence of and / or differences between at least one of the following: a gas, in particular air, a liquid, in particular a leakage liquid, a leak, a condensate, an icing, an adhesion / deposition, a bathing / washing, a sedimentation.

8. The liquid detector (100) according to one of the preceding Claims, comprising at least one of the following features: wherein the liquid detector (100) is independent of the ambient temperature, in particular of the liquid temperature; wherein the liquid detector (100) is free of an additional ambient temperature sensor; wherein the liquid detector (100) is a single-sensor system; wherein the liquid characteristic is free of the hygrostatic environment, in particular the humidity.

9. The liquid detector (100) according to any one of the preceding claims, wherein the temperature pulse (131) provides a temporary temperature change; and / or wherein the temperature pulse (131) provides a positive energy pulse.

10. The liquid detector (100) according to one of the preceding claims, wherein the temperature pulse device (110) is configured to provide a time-limited pulse of electrical energy, in particular current, in particular to the temperature sensor device (120).

11. The liquid detector (100) according to one of the preceding Claims, wherein the temperature sensor device (120) comprises at least one of the following: a resistance temperature sensor, a positive Temperature coefficient sensor, a negative temperature coefficient sensor, a semiconductor temperature sensor, a digital temperature sensor.

12. The liquid detector (100) according to one of the preceding claims, wherein the temperature pulse device (110) and the temperature sensor device (120) are installed in a common device and / or wherein the temperature pulse device (110) and the temperature sensor device (120) are the same physical element; or wherein the temperature pulse device (110) and the temperature sensor device (120) are provided separately from each other.

13. The liquid detector (100) according to one of the preceding claims, further comprising: a support structure (140) for mounting the temperature pulse device (110) and the temperature sensor device (120), in particular opposite each other.

14. The liquid detector (100) according to claim 13, wherein the temperature pulse device (110) and the temperature sensor device (120) are embedded in a protective material (150), in particular a polymer, in particular resin.

15. An analysis device (10) comprising at least one liquid detector (100) according to any one of the preceding claims.

16. The analytical device (10) of claim 15, further comprising at least one of the following features: the analytical device (10) is configured as a sample separation device; the analytical device (10) has a fluid drive (20) for driving a mobile phase and a fluidic sample injected into the mobile phase; the analytical device (10) has a sample separation device (30) for separating the fluidic sample injected into the mobile phase; the analytical device (10) is configured for analyzing at least one physical, chemical and / or biological parameter of the fluidic sample; the analytical device (10) is configured as a sample separation device for separating the fluidic sample; the analytical device (10) is a chromatography device, in particular a liquid chromatography device, a gas chromatography device, an SFC (supercritical liquid chromatography) device or an HPLC (high-performance liquid chromatography) device;The analytical device (10) is configured as a microfluidic device; the analytical device (10) is configured as a nanofluidic device; the sample separation device (30) is designed as a chromatographic separation device, in particular as a chromatographic separation column; the fluid drive (20) is configured to drive the mobile phase and the fluidic sample under high pressure; the fluid drive (20) is configured to drive the mobile phase and the fluidic sample at a pressure of at least 500 bar, in particular at least 1000 bar, and further in particular at least 1200 bar; the analytical device (10) has a detector (50) for detecting the; analyzed, in particular separated, fluidic sample; the analysis device (10) has a fractionator (60) for fractionating separate fractions of the fluidic sample.

17. The analytical device (10) according to one of the preceding claims 15 or 16, wherein the analytical device (10) comprises at least one module comprising the liquid detector (100), in particular wherein the analytical device (10) comprises at least one of the following modules: a pump module (20), a detector module (50), a sample separation module (30), in particular a thermostat module, a sample handling module (40), a fraction collector module (60), a solvent storage module (25).

18. The analysis device (10) according to any one of the preceding claims 15 to 17, further comprising: a leakage device, in particular a leakage tray, for collecting leakage liquid, wherein the liquid detector (100) is associated with the leakage device.

19. The analysis device (10) according to one of the preceding claims 15 to 18, further comprising: a plurality of the liquid detectors (100), wherein the liquid detectors (100) are configured as a detector array, in particular planar.

20. A method for detecting a liquid characteristic with respect to an analytical device (10), comprising the method: Providing a temperature pulse (131) from a temperature pulse device (110) directly to a temperature sensor device (120); Determining a temperature characteristic (132) over time in response to the provided temperature pulse (131); and Evaluating the liquid characteristics based on the determined temperature characteristics (132). DECLARATION MENTIONED IN ARTICLE 19 (1) Amended claims 1 to 20 are filed, which are based on the original claims 1 to 20. Independent claims 1 and 20 have been amended. A new claim 2 has been inserted. The amendments are supported by the description (see paragraphs [0022, 0032, 0040, 0041, 0081]) and claims 4 and 10. Claims 3 and 4 are based on the original claims 2 and 3. An obvious typographical error in claim 7 has been corrected.

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