Characterizing consumable material in a container of an analytical instrument

Abstract

A computer-implemented method is described for operating an analytical instrument (10) for carrying out an analytical method, wherein the analytical instrument (10) has at least one container (25) for consumables and at least one pressure sensor (110, 120), comprising the method: i) in particular providing a fluidic coupling between the container (25) and the pressure sensor (110, 120); ii) Measuring a current pressure (p1) using the pressure sensor (110, 120); and iii) Determining a fill level of the consumable in the container (25) based on the measured current pressure (p1).

Description

TECHNICAL BACKGROUND

[0001] The present invention relates to a method for operating an analytical device for performing an analytical method, wherein the analytical device has at least one container for consumable material (e.g., a solvent) and a pressure sensor. Based on a measured pressure with respect to the container, a fill level variable with respect to the consumable material in the container can be determined. Furthermore, a method is described for determining a property, in particular the type and / or geometry / shape, of the container based on removed consumable material and a pressure difference. Furthermore, the invention relates to a data processing device configured to carry out the method, and to the analytical device.

[0002] As analytical devices, for example, chromatography devices, in particular sample separation devices, are provided for the analysis of a sample, in particular a fluidic sample, e.g. for carrying out a chromatographic separation of the sample.

[0003] In an HPLC (high-performance liquid chromatography) chromatography device, for example, a liquid (mobile phase) is moved through a so-called 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 a high pressure (typically 20 to 1000 bar and beyond, currently up to 2000 bar), at which the compressibility of the liquid can 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 by the same applicant, Agilent Technologies, Inc.

[0004] One or more solvents are usually used for the mobile phase, into whose flow the sample to be analyzed is then injected. A solvent represents a consumable that is stored in a container (e.g., a bottle, a container, etc.). For example, a first container is filled with a first solvent (e.g., water), while a second container is filled with a second solvent (e.g., methanol). In the case of a chromatography device, such containers are usually arranged in a container holder above the actual chromatography device (see, for example, Fig. 2).

[0005] To perform an efficient and reliable sample analysis, it is necessary to know the fill level of the consumable in the container. Furthermore, it is necessary to use the correct consumable from the correct container.

[0006] Conventionally, this can be achieved (automatically) by placing a weighing device beneath a container. Based on the measured weight and density of the solvent, the volume present in the container can then be determined. Another conventional approach is to introduce air bubbles into the container and then measure the back pressure. To characterize the solvent in the container, additional (and exclusively) sensors are conventionally used.

[0007] US 9250110 B2 uses a pressure sensor upstream of the pumps in the process direction to determine the pressure in a tank. However, to characterize the solvent in the tank, an additional measurement is required to determine how much solvent volume is withdrawn from the tank. SUMMARY OF THE INVENTION

[0008] There may be a need to characterize a container for consumables in the context of an analytical device efficiently, reliably, and cost-effectively.

[0009] In the following, two characterization methods, a data processing device, and an analysis device are described.

[0010] According to a first aspect of the invention, a (computer-implemented) method is described for operating an analytical device (in particular a chromatography device) for carrying out an analytical method, wherein the analytical device has at least one container (e.g. a solvent bottle) for consumables (e.g. solvent) and at least one pressure sensor (which fulfils at least one function in the analytical device, or whose functionality is not limited to determining the fill level), the method comprising: i) in particular providing a fluidic coupling between the container and the pressure sensor; ii) measuring a current pressure (p1) by means of the pressure sensor (relative to the fluidically coupled container); and iii) Determining a fill level variable (e.g. fill level h, fill level volume V) with respect to the consumable in the container based (only) on the measured current pressure (free / independent of determining the withdrawal quantity (volume difference) of the consumable from the container).

[0011] According to a second aspect of the invention, a (computer-implemented) method is described for operating an analytical device for carrying out an analytical method, wherein the analytical device has at least one container for consumables and at least one pressure sensor, the method comprising: i) determining a first pressure (p1) by means of the pressure sensor; ii) removing consumables (thereby obtaining the difference, e.g. dV between a first volume V1 and a second volume V2) from the container; iii) determining a second pressure (p2) by means of the pressure sensor; and iv) determining a property, in particular the type and / or geometry / shape, of the container based on the removed consumable material and the difference (dp) between the first pressure (p1) and the second pressure (p2).

[0012] According to a third aspect of the invention, a data processing device is described, which has at least one processor and is configured to execute at least one of the methods described above. Furthermore, a program product is described which, when executed on one or more processors, is configured to cause them to execute one of the methods described above.

[0013] According to a fourth aspect of the invention, an analysis device is described for carrying out an analysis method, wherein the analysis device has a device for data processing as described above and / or is configured to carry out at least one of the methods described above.

[0014] In the context of this document, the term "container" can refer in particular to a device having a volume into which a consumable material can be accommodated. In principle, the container can be designed, for example, as a container. In a specific example, the container can be designed as a solvent bottle. The container can be fluidically coupled to other components of the analytical device, in particular to a flow path leading to a fluid drive.

[0015] In the context of this document, the term "consumable" can specifically refer to a material that is at least partially consumed when performing an analysis in an analytical device. For example, if the analytical device is designed as a chromatography device, the consumable can be a solvent used to provide the mobile phase.

[0016] In this document, the term “fluidic sample” is understood to mean a medium, more particularly a liquid, which contains the material to be analyzed (e.g. a biological sample), such as a protein solution, a pharmaceutical sample, etc.

[0017] In the context of this application, the term "mobile phase" refers in particular to a fluid, more particularly 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).

[0018] In the context of the present application, the term "analyzer" can refer in particular to a device that is capable and configured to examine a fluid 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 using chromatography or electrophoresis. Preferably, the analyzer can be a liquid chromatography sample separation device.

[0019] In the context of this document, the term "fill level" or "fill level variable" can specifically refer to the amount of consumable material contained in a container. The fill level variable can be specified using various parameters, such as the volume of the consumable material in the container or the fill level height of the consumable material in the container. The fill level height can be determined, for example, using a measured pressure as described below. Based on the determined fill level height and a cross-section of the container, the volume can then be calculated.

[0020] In the context of this document, the term "pressure sensor" can refer in particular to a device suitable for determining or measuring a pressure. A person skilled in the art is familiar with a variety of devices that can fulfill such a purpose. In one example, the pressure sensor can be arranged in a normal pressure path at or upstream of a pumping device. In another example, the pressure sensor can be arranged in a high pressure path, in particular downstream of the pumping device.

[0021] According to an exemplary embodiment, the invention can be based on the idea that a container with respect to consumables in the context of an analytical device can be characterized efficiently, reliably, and cost-effectively by using a pressure sensor that is already part of the analytical device (and fulfills at least one function therein, e.g., pressure measurement with respect to a pump) and does not have to be provided separately. In this way, the described characterizations can be easily implemented in existing analytical devices without the need for additional hardware modifications. Instead, the existing structure can be applied directly to perform an efficient and reliable measurement.

[0022] According to the first aspect of the invention, a fill level variable (in particular fill level height or fill level volume) can thus be determined efficiently and cost-effectively, with only a single pressure measurement being carried out using an existing pressure sensor. This can be a significant improvement over the prior art (see above), in which the amount of consumable material removed from the container must always be additionally taken into account; moreover, multiple pressure measurements are usually carried out conventionally. Here, the inventors have surprisingly discovered that a single pressure measurement can be sufficient to reliably determine a fill level variable with regard to the consumable material in the container.

[0023] According to the second aspect of the invention, a property of the container, in particular the type of container and / or its geometry, can be determined in an efficient and cost-effective manner. This information can be particularly important when checking whether the correct container or the correct consumable is being used. For example, in the field of chromatography, a large number of containers can be used. These are then connected to one or more pumps via corresponding supply lines. With a larger number of supply lines, the overview can quickly be lost, which can result in incorrect measurements or even damage to the analytical device. The inventors surprisingly discovered that such a characterization of a property of the container can be carried out reliably based solely on a pressure difference and a withdrawal quantity (e.g. volume difference). EXEMPLARY IMPLEMENTATION EXAMPLES

[0024] Additional preferred embodiments are described below.

[0025] According to one embodiment, the fill level variable has a fill level height (h). This can be determined / calculated directly from the measured current pressure (p1): h = p1 / (density of the consumable (p) * gravity (g)).

[0026] According to one embodiment, the method comprises: determining a first fill level (h1) based on the measured current pressure (p1), the density of the consumable (p), and the force of gravity (g), in particular using h1 = p1 / p * g. As described above, this first fill level h1 can be determined directly from the measured pressure and known parameters.

[0027] According to one embodiment, the method comprises: taking into account a height difference (h0) between the pressure sensor and the container (or the lower edge / bottom of the container) to obtain the (absolute) fill level (h) from the determined first fill level (h1), in particular using h = h1 - h0. This allows the actual fill level to be determined directly. The height difference h0 is known in advance or can also be determined.

[0028] According to one embodiment, the method comprises: determining the volume (V) of the consumable material in the container as a fill level variable based on the determined fill level height (h) and at least one cross section (A) of the container, in particular by means of V = A * h. Thus, the volume of the consumable material in the container can be determined in a simple manner using known parameters.

[0029] According to one embodiment, the method further comprises: determining, in particular calculating and / or measuring, an initial pressure (p0) with respect to the at least one container, and / or taking the initial pressure (p0) into account when determining the fill level variable. In particular, the initial pressure (p0) is determined based on the density of the consumable (p), the force of gravity (g), and the height difference (h0), further in particular by means of p0 = p * g * h0. The initial pressure (see Fig. 5) can be determined based on known parameters in order to optimize the determination of the fill level size.

[0030] According to one embodiment, the method further comprises: taking into account (see formulas above) the density (p) of the consumable material when determining the fill level variable, in particular determining the density (p) based on the volume (dV) removed from the container and a weighing device, in particular free of the pressure sensor. In one example, the density of the consumable material is previously known. In another example, the density can be determined in another way, e.g., by means of a weighing device. The determination of the density is preferably carried out independently of the pressure sensor.

[0031] According to one embodiment, determining the property comprises determining a cross-section (A) of the container, in particular using A = ρ * g * (dV / dP). On the one hand, the cross-section can be known in advance and the volume can be determined based on the measured fill level (via the pressure). On the other hand, however, the volume (or another unit for determining the withdrawn quantity) can also be measured, and the cross-section can be determined based on the measured pressure difference. Determining the volume difference and the pressure difference can be repeated several times (e.g., 2-3 times) to obtain several cross-sections. These, in turn, result in a shape / type / kind of container.

[0032] According to one embodiment, the method further comprises: determining a third pressure (p3) (this can also be the second pressure (p2)) by means of the pressure sensor; removing further consumable material (dV2) from the container; determining a fourth pressure (p4) (this can also be a third pressure, e.g. if the third pressure (p3) corresponds to the second pressure (p2)) by means of the pressure sensor; and determining a further cross-section (A2) of the container based on the removed further consumable material (dV2) and the difference (dp2) between the third pressure (p3) and the fourth pressure (p4). As already described above, two or more cross-sections A1, A2, etc. can be obtained in this way.

[0033] According to one embodiment, the cross-section (A) and the further cross-section (A2) are different. This allows direct conclusions to be drawn about the properties of the container, e.g., narrower at the bottle neck.

[0034] According to one embodiment, a discontinuous shape, in particular a bottle shape, of the container is determined by means of the cross section (A) and the further cross section (A2).

[0035] According to one embodiment, determining the property of the container comprises comparing the cross-section (A), and in particular the further cross-section (A2), with a cross-section from a database. Such a comparison allows the property to be determined particularly efficiently and reliably. In particular, such a comparison can be automated. In one example, an artificial intelligence (AI) algorithm can support the comparison or improve itself through training data.

[0036] According to one embodiment, the method further comprises: verifying whether the property of the container corresponds to a desired property of the container. For example, it can be checked whether the correct container size or the correct container type is being used. According to one embodiment, the method comprises: informing a user if the property of the container does not correspond to the desired property of the container. Preferably, a warning is issued to the user if the desired container was not determined. This can significantly improve the reliability of the analysis, because incorrect containers or incorrect container positions (and thus potentially also incorrect solvents) can be (automatically) detected.

[0037] According to one embodiment, the fluidic coupling (or fluidic path) comprises a coupling between the container and at least one fluid drive of the analysis device. In this way, for example, a pressure sensor of the fluid drive (which otherwise performs a pressure measurement with respect to the pumping devices) can be directly inserted.

[0038] In an exemplary embodiment, the method can be carried out as follows: i) Calculate by a one-point measurement of the volume (the rest is given geometrically), optionally equation parameters can be determined by two-point measurement, ii) measuring h0, iii) Density of the consumable material is known, optionally determined by two-point measurement, in particular without using the pressure sensor, but by means of scales / drawn-in volume, iv) Calculate initial pressure p0 (with or without measuring), v) Determining the current (static) pressure p1 via a single measurement, vi) Calculate the first level h1 from density, gravity, and p1, vii) the difference h1 - h0 gives the filling level h, viii) multiplied by the base area of ​​the container gives the volume. ix) Cross section A can also be calculated and a conclusion about the geometry (“container recognition”, “mapping of the container”) can be obtained: dp / dV=(ρ*g*dh) / (A*dh) A=ρ*g*(dV / dp) (Container diameter averaged over measured fill level change with pressure sensor).

[0039] According to one embodiment, at least one of the described methods is performed continuously during an analysis. Additionally or alternatively, at least one of the described methods can be used as soon as a new container is used or connected.

[0040] According to one embodiment, the pressure sensor is arranged in a normal pressure path, in particular upstream of a fluid drive in the process direction. This allows an existing pressure sensor to be used directly, essentially without having to intervene in the operation of the analytical device (in particular the fluid drive).

[0041] According to one embodiment, the pressure sensor is associated with the fluid drive, in particular with a pump device of the fluid drive. For example, the pressure sensor can be assigned to a first piston and / or a second piston of a fluid drive and monitor a pump pressure during normal operation.

[0042] According to one embodiment, the pressure sensor is arranged in a high-pressure path, in particular downstream of a fluid drive in the process direction, further in particular wherein the pressure sensor is arranged downstream of a fluid valve, in particular a flushing valve / mixing valve. It was surprisingly discovered that even a pressure sensor arranged significantly downstream of the container can be efficiently used for characterizing (the consumable material) of the container. To make this pressure sensor available for the described method, a special operating mode of the fluid drive can be implemented (see below).

[0043] According to one embodiment, the method comprises: fluidically coupling the container to the fluid drive (e.g., pumping / drawing in consumables), opening at least one (check) valve of the fluid drive, stopping at least one pumping device of the fluid drive, in particular at least one piston, and then measuring the pressure (p1, p2) using the pressure sensor. In particular, the fluid drive is operated (stopped) such that the system pressure approaches (is reduced) or is 0. In the case of a binary pump (see figures), in which a first pumping device and a second pumping device are connected in series or in parallel, two (check) valves and two pumping devices can be controlled accordingly. In addition to binary pumps, ternary, quaternary, etc. pumps can also be used.

[0044] A check valve or a rotary valve can be used as a valve.

[0045] According to one embodiment, the method further comprises: drawing in consumable material from the container by means of the pumping device (in particular the first pumping device) of the fluid drive, in particular before opening the at least one (check) valve.

[0046] According to an exemplary embodiment, the method can be carried out as follows: i) the container with consumables is fluidically coupled to the fluid drive (see e.g. Fig. 3 and Fig. 4), ii) cleaning the flow path (solvent path) by degassing and / or purging, iii) the first piston of the first pumping device draws in solvent (in-take) and the first check valve is opened, iv) the second piston of the second pumping device is moved and the second check valve is opened, the retraction of the second piston being greater than the retraction of the first piston, v) both pistons (essentially) stop their movement, vi) optional: if a rotary valve is used as a fluid valve, it can switch to the waste position; the system pressure is minimized so that the check valves are in a half-open / half-closed state, vii) the static pressure p1 of the vessel can now be measured.

[0047] According to an exemplary embodiment, opening (unblock) of the valves can be carried out as follows (see also Fig. 4): i) the container with the consumable is fluidically coupled to the fluid drive, ii) the flow path (solvent path) is cleaned by degassing, and the pump is flushed, iii) a first piston of the first pumping device draws in solvent and the first check valve is opened, iv) the piston movement is stopped, v) the fill level can be determined using a pressure sensor of the piston, and vi) the procedure can be repeated to further monitor the fill level during operation of the analysis dish.

[0048] According to one embodiment, the container can be isolated / decoupled from the static pressure of at least one other container by means of a separation valve. This can increase measurement accuracy. For example, gradient-forming valves (MCGV, 4CGV) or solvent selection valves can be used.

[0049] According to one embodiment, the method further comprises cleaning the fluidic coupling (or the flow path) between the container and the fluid drive, in particular by means of at least one of degassing, rinsing, and priming. This measure can also further increase the measurement accuracy.

[0050] According to one embodiment, the transport device comprises a robot arm or cantilever arm. Such an arm is known per se and enables efficient and reliable movement / transportation, e.g., within a sample chamber. A sample handling device (gripper) can be used as the transport device.

[0051] According to one embodiment, the analysis device is designed as a sample separation device. According to one embodiment, the analysis device has a fluid drive for driving a mobile phase and a fluidic sample injected into the mobile phase. According to one embodiment, the analysis device has a sample separation device for separating the fluidic sample injected into the mobile phase. According to one embodiment, the analysis device is configured to analyze at least one physical, chemical, and / or biological parameter of the fluidic sample. According to one embodiment, the analysis device is configured as a sample separation device for separating the fluidic sample.

[0052] In the context of the present application, the term "sample separation device" can be understood in particular as a device for analyzing a fluid sample, in particular into different fractions. For this purpose, components of the fluid sample can first be adsorbed on the sample separation device and then desorbed separately (in particular fractionally). For example, such a sample separation device can be designed as a chromatographic separation column.

[0053] According to one embodiment, the analytical device is a chromatography device, in particular a liquid chromatography device, a gas chromatography device, an SFC (supercritical fluid chromatography) device or an HPLC (high performance liquid chromatography) device.

[0054] According to one embodiment, the analysis device is configured as a microfluidic device. According to one embodiment, the analysis device is configured as a nanofluidic device.

[0055] According to one embodiment, the sample separation device is designed as a chromatographic separation device, in particular as a chromatography separation column.

[0056] According to one embodiment, the fluid drive is configured to drive the mobile phase and the fluidic sample under high pressure.

[0057] 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 of at least 1000 bar, further in particular of at least 1200 bar, further in particular of at least 1500 bar.

[0058] According to one embodiment, the analysis device has a detector for detecting the analyzed, in particular separated, fluidic sample.

[0059] According to one embodiment, the analysis device comprises a fractionator for fractionating separate fractions of the fluidic sample.

[0060] The analytical device can be a microfluidic instrument, a life science device, a liquid chromatography device, a gas chromatography device, an HPLC (high-performance liquid chromatography), a UHPLC system, or an SFC (supercritical fluid chromatography) device. However, many other applications are possible.

[0061] According to one embodiment, the sample separation device can be designed as a chromatographic separation device, in particular as a chromatography separation column. In a chromatographic separation, the chromatography separation column can be provided with an adsorption medium. The fluid sample can be retained on this adsorption medium and only subsequently detached fractionally in the presence of a specific solvent composition, thus achieving the separation of the sample into its fractions.

[0062] A pumping system for conveying fluid can, for example, be designed to convey the fluid or mobile phase through the system at a high pressure, for example a few hundred bars up to 1000 bars and more.

[0063] The analytical device may include a sample injector for introducing the sample into the fluidic separation path. Such a sample injector may include a sample or injection needle that can be coupled to a needle seat in a corresponding fluid path, wherein the sample needle can be retracted from this needle seat to collect the sample. After reinserting the sample needle into the needle seat, the sample may 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 with a sample needle that is operated without a needle seat can be used.

[0064] The analyzer may include a fraction collector for collecting the separated components. Such a fraction collector can, for example, direct the various components of the separated sample into different liquid containers. The analyzed sample can also be directed to a waste container.

[0065] Preferably, the analyzer may include a detector for detecting the separated components. Such a detector may generate a signal that can be observed and / or recorded and is indicative of the presence and quantity of the sample components in the fluid flowing through the system.

[0066] According to an exemplary embodiment, a sampling space is defined by a housing in which the sample handling arrangement or sample movement device is arranged. SHORT DESCRIPTION OF THE CHARACTERS

[0067] Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and better understood by reference to the following more detailed description of embodiments taken in conjunction with the accompanying drawings. Features that are substantially or functionally the same or similar are designated by the same reference numerals. Fig. 1 shows an analytical device as a chromatography device, according to an exemplary embodiment of the invention. Fig. 2 shows an implementation of the chromatography device with containers for consumables, according to an exemplary embodiment of the invention. Fig. 3 shows a detailed view of the chromatography device according to an exemplary embodiment of the invention. Fig. 4 shows a further detailed view of the chromatography device according to an exemplary embodiment of the invention. Fig. 5 shows a pressure curve over time, according to an exemplary embodiment of the invention. Fig. 6 schematically shows an arrangement of the container and the pressure sensors, according to an exemplary embodiment of the invention. The Fig. 7A and Fig. 7B each show a container holding device according to an exemplary embodiment of the invention. Fig. 8 shows a detailed view of the frame of the container holding device, according to an exemplary embodiment of the invention. Fig. 9 shows a cross section through the container holding device according to an exemplary embodiment of the invention. DETAILED DESCRIPTION OF THE FIGURES

[0068] The representation in the drawing is schematic.

[0069] Fig. Figure 1 shows the basic structure of an HPLC system as an example of an analytical device 10 designed as a sample separation device or chromatography device according to an exemplary embodiment of the invention, as can be used, for example, for liquid chromatography. A fluid conveying device or fluid drive 20, which is supplied with solvents from a supply device 25 (or consumables from a container), drives a mobile phase through a sample separation device 30 (such as a chromatographic column) containing a stationary phase.

[0070] The solvents are a consumable material which is stored in one or more containers 25. The supply device usually comprises a first fluid component source (e.g. first container) for providing a first fluid or a first solvent component A (e.g. water) and a second fluid component source (e.g. second container) for providing another second fluid or a second solvent component B (e.g. an organic solvent).

[0071] An optional degasser 27 can degas the solvents provided by the first fluid component source and by the second fluid component source before they are fed to the fluid drive 20. A sample application unit, which can also be referred to as an injector 40, is arranged between the fluid drive 20 and the sample separation device 30 in order to first collect a sample liquid or a fluidic sample from a sample container 130 into a sample receiving volume in an injector path, and subsequently introduce it into a fluidic separation path between the fluid drive 20 and the sample separation device 30 by switching an injection valve of the injector 40.The collection of fluidic sample from the sample container can be carried out in particular by moving a sample needle out of a sample seat and into the sample container 130, by means of a fluid conveying device designed as a dosing device, fluidic sample is sucked from the sample container 130 through the sample needle into the sample receiving volume, and the sample needle is then moved back into the needle seat.

[0072] The stationary phase of sample separation device 30 is designed to separate sample components. A detector 50, which may comprise a flow cell, detects separated sample components. A fractionation device or fractionator 60 may be provided to discharge separated sample components into designated containers. Liquids no longer required can be discharged into a waste container or waste line.

[0073] While a fluid path between the fluid drive 20 and the sample separation device 30 is typically under high pressure, the sample fluid is first introduced under normal pressure into a region separated from the fluid path, namely the sample loop or sample receiving volume, of the sample application 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 receiving volume, can be understood as a section of a fluid line designed to receive or temporarily store a predetermined amount of fluid sample.Preferably, before the sample liquid in the sample receiving volume, initially at atmospheric pressure, is added to the high-pressure separation path, the contents of the sample receiving volume are brought to the system pressure of the HPLC-designed analyzer 10 by means of a dosing device in the form of a fluid delivery device. A control device 70 controls the individual components 20, 25, 30, 40, 50, 60, etc., of the analyzer 10.

[0074] Fig. 2 shows an implementation of the chromatography device 10 with the containers 25 for consumables, according to an exemplary embodiment of the invention. In this example, the components of the chromatography device 10 are stacked vertically on top of one another. A container holding device is provided at the top, for example a tray, in which a plurality of the containers 25 can be arranged (or placed). Each of the containers 25 is filled with the consumable, which in the present example is a solvent (e.g., water, methanol, acetonitrile, etc.). The containers 25 are each coupled to the fluid drive 20 by means of supply lines 26, such that the consumable can be introduced from the respective container 25 through the corresponding supply line 26 via the fluid drive 20 into the analytical path (to sample separation device 30) of the analytical device 10.

[0075] As already mentioned for Fig. 1 described above, the chromatography device 10 further comprises the units detector 50, sample injection (autosampler) 40 and sample separation device 30, which are stacked vertically in this implementation.

[0076] Fig. 3 shows a detailed view of the chromatography device 10 according to an exemplary embodiment of the invention. In this example, the supply devices have four containers 25, which contain the solvents A1, B1, A2, and B2 as respective consumables. Here, the two left-hand containers A1, B1 are coupled to a first fluid drive 20, 130, while the right-hand containers A2, B2 are coupled to a second fluid drive 140. Both fluid drives 130, 140 are fluidically coupled to a common fluid valve 150 (here a purge valve). The fluid valve 150 can be coupled to a waste 151 and / or to the analytical domain (sample separation device 30). Furthermore, a mixing device (e.g., a Jet Weaver Mixer) can be coupled to the fluid valve 150.

[0077] The first fluid drive 130 has a first pumping device 131 and, downstream in the process direction, a second pumping device 132. A first check valve 135 is arranged upstream of the first pumping device 131 in the process direction, and a second check valve 136 is arranged between the first pumping device 131 and the second pumping device 132. Similarly, the second fluid drive 140 has a further first pumping device 141 and a further second pumping device 142. A further first check valve 145 is arranged upstream of the further first pumping device 141 in the process direction, and a further second check valve 146 is arranged between the further first pumping device 131 and the further second pumping device 132.

[0078] A first pressure sensor 110 is arranged on the supply line 26 between the container 25 and the first fluid drive 20, 130. Additionally or alternatively, the first pressure sensor 110 is arranged, for example, on the first pump device 131 or associated with it. The same applies to the second fluid drive 140 and corresponding sensors. The first pressure sensor 110 is thus arranged in a normal pressure path and is fluidically coupled to the container 25.

[0079] A second pressure sensor 120 is arranged downstream of the fluid drive 20, 130 and the fluid valve 150 in the process direction. This second pressure sensor 120 can be used for both the first fluid drive path and the second fluid drive path. The second pressure sensor 120 is thus arranged in a high-pressure path downstream of the fluid drives 130, 140 or pump devices 131, 132, 141, 142. A fluidic coupling to the container 25 via at least one of the fluid drive paths is possible.

[0080] The implementation of the chromatography device 10 in this example further comprises: a first (inline) filter 138 and a second (inline) filter 138. By means of a separation valve 29, a container 25 to be examined can be isolated from the static pressure of at least one other container.

[0081] Fig. 4 shows a further detailed view of the chromatography device 10 according to an exemplary embodiment of the invention. The left side illustrates the above-described first fluid drive 130, which comprises, in the process direction, a first check valve 135, a first pumping device 131, a second check valve 136, and a second pumping device 132. The right side illustrates the above-described second fluid drive 140, which comprises, in the process direction, a further first check valve 145, a further first pumping device 141, a further second check valve 146, and a further second pumping device 142. A first solvent A is provided to the first fluid drive 130, while a second solvent B is provided to the second fluid drive 140.

[0082] Both fluid drives 130, 140 are coupled downstream in the process direction to a common mixing chamber 160. This is followed in the process direction by a damper 161, a mixer 162, and the fluid valve 150. Furthermore, it is schematically shown that the first pressure sensor 110 is arranged in a normal pressure path upstream of the fluid drive 130 (additionally or alternatively to the second fluid drive 140), while the second pressure sensor 120 is arranged in a high pressure path downstream of the fluid valve 150.

[0083] Fig. 5 shows a pressure curve over time, according to an exemplary embodiment of the invention. While the Y-axis indicates the static pressure, the X-axis indicates time. When carrying out an embodiment of the described method, the system pressure is first reduced (ideally to 0). As a result, the static pressure initially drops to a first level. The static pressure now measured depends on two factors: i) the height h0 of the container with respect to the pressure sensor (usually fixed) and ii) the fill level (or fill height h) of the consumable material in the container (variable). Accordingly, the existing fill level can be determined based on one or more pressure measurements. This method eliminates the previous need to also measure the removed volume of consumable material.

[0084] Fig. 6 schematically shows an arrangement of the container 25 and the pressure sensors 110, 120 according to an exemplary embodiment of the invention. H0 schematically represents the height difference between the lower edge (the bottom) of the container 25 and the pressure sensor 110, 120 used (here 106.5 mm). H denotes the fill level (as fill level variable) of the consumable in container 25 (here 51.4764 mm). The sum of the height difference h0 and the fill level h is the height h1 determined during a pressure measurement (here 157.9764 mm), so that h is determined using: h1-h0.

[0085] As already mentioned for the Fig. 3 and Fig. As described in Figure 4, the container 25 is coupled to the fluid drive 20, 130. This involves a fluidic coupling to the normal path pressure sensor 110 (upstream of the fluid drive) and / or the high-pressure path pressure sensor 120 (downstream of the fluid drive), so that the pressure measurement can be performed.

[0086] The diagram also shows a pressure curve in relation to the volume (fill level) of the consumable in the container 25: the higher the pressure, the higher the fill level. The lowest possible pressure is the initial pressure p0 = density of the consumable * gravity * height difference h0. The higher the pressure, the higher the fill level h (see Fig. 5) and thus the volume (V = cross-section of the container A * filling level h).

[0087] The Fig. 7A and Fig. 7B each show a container holding device 200 according to an exemplary embodiment of the invention. Fig. 7A is a side view showing the containers 25 in the container holding device 200, which has a frame 201 at the top. Fig. Figure 7B shows a top view of this container holding device 200. A fill level measurement is performed by measuring the weight of the solvent bottle, with the weighing device (weight sensor) located at the edge of the solvent tray (container holding device 200) (not below the containers). The weighing device 220 is further associated with a coupling device 210, with which the container holding device 200 can be suspended.

[0088] The system weighs (in this example) up to 6 solvent bottles (containers 25) individually and monitors their weight loss during liquid extraction by the fluid drives (LC pumps). It reduces the risk of empty solvents for the user and increases the reliability of the system and its operations. Additionally, monitoring the container fill level enables other intelligent functions, such as predicting how long the available solvent quantity will last or warning the user before a measurement. Additional holders (various sizes, e.g., 1-15 L, 2-2.5 L) can be provided for the containers 25.

[0089] Fig. Figure 8 shows a detailed view of the frame 201 of the container holding device 200, according to an exemplary embodiment of the invention. A status indicator (e.g., LED) can be used in the frame 201.

[0090] Fig.Figure 9 shows a cross-section through the container holding device 200 according to an exemplary embodiment of the invention. This can have an eccentric design (e.g., a drainage opening in the center) that allows the solvent bottle to be kept away from electronic components. The holder has a contact point 230 to support the eccentric design. This allows the separation of vertical and horizontal forces from a mechanical perspective. This directs all vertical forces (i.e., the gravitational forces) to the contact / coupling point on the load cell 220. A potential disadvantage of this design can be the friction of the contact point 230. The friction could be reduced, for example, by using low-friction materials or pulleys.

[0091] The coupling device 210 (holder) sits at the coupling point 230 on the load cell 220. The cone-in-cone design allows for easy guidance to improve usability and user experience and reduce potential failure modes. A snap-in function provides the user with haptic and audible feedback when the holders are correctly positioned.

[0092] It should be noted that the term "comprising" does not exclude other elements, and "a" does not exclude a plurality. Elements described in connection with different embodiments may also be combined. It should also be noted that reference numerals in the claims should not be construed as limiting the scope of the claims. Reference symbol 10 Analysis device, chromatography device 20 Fluid drive 25 containers for consumables 26 Supply line 27 degassers 28 Weighing device 29 Selection valve 30 Sample separation device 40 Injector 41 Mixing device 50 detector 60 fractionators 70 Control device 110 Pressure sensor normal pressure 120 Pressure sensor high pressure 130 First fluid drive 131 First pumping device 132 Second pumping device 135 First check valve 136 Second check valve 138 filters 140 Second fluid drive 141 Further first pumping device 142 Additional second pumping device 145 Additional first check valve 146 Additional second check valve 148 Additional filter 150 Fluid valve, flush valve 151 Waste 160 mixing chamber 161 dampers 162 mixers 200 container holding device 201 frames 210 coupling device 220 Weighing device, load cell 230 contact point QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions. Cited patent literature

[0000] EP 0,309,596 B1

[0003] US 9250110 B2

[0007]

Claims

[1] A computer-implemented method for operating an analytical device (10) for performing an analytical method, wherein the analytical device (10) has at least one container (25) for consumables and at least one pressure sensor (110, 120), the method comprising: Measuring a current pressure (p1) by means of the pressure sensor (110, 120); and Determining a fill level variable with respect to the consumable material in the container (25) based on the measured current pressure (p1). [2] The method according to claim 1, comprising at least one of the following features: wherein the fill level variable has a fill level height (h); Determining a first fill level (h1) based on the measured current pressure (p1), the density of the consumable (p), and the force of gravity (g), in particular by means of h1 = p1 / p * g; Taking into account a height difference (h0) between the pressure sensor (110, 120) and the container (25) to obtain the fill level (h) from the determined first fill level (h1), in particular by means of h = h1 - h0; Determining the volume (V) of the consumable material in the container as a fill level variable based on the determined fill level height (h) and at least one cross section (A) of the container (25). [3] The method according to claim 1 or 2, further comprising: Determining, in particular calculating and / or measuring, an initial pressure (p0) with respect to the at least one container (25); and Taking the initial pressure (p0) into account when determining the fill level variable; in particular, wherein the initial pressure (p0) is determined based on the density of the consumable (p), the force of gravity (g), and the height difference (h0), further in particular by means of p0 = p * g * h0. [4] The method according to any one of the preceding claims, further comprising: Taking into account the density (p) of the consumable material when determining the fill level variable, in particular determining the density (p) based on the volume (dV) removed from the container (25) and a weighing device (26), in particular free from the pressure sensor (110, 120). [5] A computer-implemented method for operating an analytical device (10) for carrying out an analytical method, wherein the analytical device (10) has at least one container (25) for consumables and at least one pressure sensor (110, 120), the method comprising: Determining a first pressure (p1) by means of the pressure sensor (110, 120); Removing consumables (dV) from the container (25); Determining a second pressure (p2) by means of the pressure sensor (110, 120); and Determining a property, in particular the type and / or geometry, of the container (25) based on the removed consumable material (dV) and the difference (dp) between the first pressure (p1) and the second pressure (p2). [6] The method according to claim 5, wherein determining the property comprises determining a cross-section (A) of the container (25), in particular by means of A = ρ * g * (dV / dp). [7] The method according to claim 5 or 6, further comprising: Determining a third pressure (p3) by means of the pressure sensor (110, 120); Removing additional consumables (dV2) from the container (25); Determining a fourth pressure (p4) by means of the pressure sensor (110, 120); and Determining a further cross-section (A2) of the container (25) based on the further consumable material removed (dV2) and the difference (dp2) between the third pressure (p3) and the fourth pressure (p4). [8] The method according to claim 6 or 7, comprising at least one of the following features: wherein the cross-section (A) and the further cross-section (A2) are different; wherein a discontinuous shape, in particular a bottle shape, of the container (25) is determined by means of the cross section (A) and the further cross section (A2); wherein determining the property of the container (25) comprises: Comparing the cross-section (A), and in particular the further cross-section (A2), with a cross-section from a database. [9] The method according to any one of claims 5 to 8, further comprising: Verifying whether the property of the container (25) corresponds to a desired property of the container (25), in particular informing a user if the property of the container (25) does not correspond to the desired property of the container (25). [10] The method according to one of the preceding claims, wherein the fluidic coupling comprises a coupling between the container (25) and at least one fluid drive (20) of the analysis device (10). [11] The method according to one of the preceding claims, wherein the pressure sensor (110) is arranged in a normal pressure path, in particular upstream of a fluid drive (20) in the process direction. [12] The method according to claim 11, wherein the pressure sensor (110) is associated with the fluid drive (20), in particular a pumping device (131, 132) of the fluid drive (20). [13] The method according to any one of the preceding claims, wherein the pressure sensor (120) is arranged in a high-pressure path, in particular downstream of a fluid drive (20) in the process direction, further in particular wherein the pressure sensor (120) is arranged downstream of a fluid valve (150), in particular a flushing valve. [14] The method according to any one of claims 10 to 13, comprising: fluidic coupling of the container (25) to the fluid drive (20); Opening at least one valve (135) of the fluid drive (20); Stopping at least one pumping device (131) of the fluid drive (20), in particular at least one piston; and thereafter Carrying out the measurement of the pressure (p1, p2) by means of the pressure sensor (110, 120). [15] The method according to claim 14, further comprising: Drawing in consumable material from the container (25) by means of the pumping device (131, 132) of the fluid drive (20), in particular before opening the at least one valve (135). [16] The method according to any one of the preceding claims, wherein the container (25) is isolated from the static pressure of at least one further container by means of a separation valve (29). [17] The method according to any one of the preceding claims, further comprising: Cleaning the fluidic coupling between container (25) and fluid drive (20), in particular by means of at least one of degassing, rinsing, priming. [18] A data processing device comprising at least one processor and arranged to carry out the method according to any one of claims 1 to 17. [19] An analysis device (10) for performing an analysis method, wherein the analysis device (10) comprises a data processing device according to claim 18. [20] The analysis device (10) according to claim 19, further comprising at least one of the following features: the analysis device (10) is designed as a sample separation device; the analysis device (10) has a fluid drive (20) for driving a mobile phase and a fluidic sample injected into the mobile phase; the analysis device (10) has a sample separation device (30) for separating the fluidic sample injected into the mobile phase; the analysis device (10) is configured to analyze at least one physical, chemical and / or biological parameter of the fluidic sample; the analysis device (10) is configured as a sample separation device for separating the fluidic sample; the analysis device (10) is a chromatography device, in particular a liquid chromatography device, a gas chromatography device, an SFC (supercritical fluid chromatography) device or an HPLC (high performance liquid chromatography) device; the analysis device (10) is configured as a microfluidic device; the analysis device (10) is configured as a nanofluidic device; the sample separation device (30) is designed as a chromatographic separation device, in particular as a chromatography 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 with a pressure of at least 500 bar, in particular of at least 1000 bar, further in particular of at least 1200 bar; the analysis 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.

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