DE102023128759A1 - Measuring device for an analysis device - Google Patents

Abstract

A measuring device (100) for an analysis device (10) is described, the measuring device (100) having:i) a first fluid line (110) set up for flowing a fluid (115) in a main stream; ii) a second fluid line (120), adapted to flow the fluid (115), the second fluid line (120) being connected in parallel to at least a portion of the first fluid line (110); andiii) a sensor device (130) which is coupled to the second fluid line (120) to determine a measured variable relating to the fluid in the second fluid line (120).

Description

TECHNICAL BACKGROUND

The present invention relates to a measuring device for an analysis device, which has a first fluid line and a second fluid line, the second fluid line being connected in parallel to the first fluid line at least along a section thereof. The second fluid line is equipped with a sensor device for determining a measured variable. The invention further relates to the analysis device and a method for determining a measurement variable.

Analysis devices such as sample separation devices are intended for the analysis of a sample, in particular a fluid sample, e.g. B. to carry out a chromatographic separation of the sample.

For example, in an HPLC (high performance liquid chromatography) analyzer, a liquid (mobile phase) is measured at a very precisely controlled flow rate (e.g. 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, moved through a so-called stationary phase (for example in a chromatographic column) to separate individual fractions of a sample liquid introduced into the mobile phase separate. 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 same applicant, Agilent Technologies, Inc.

In the chromatographic pump of an HPLC (as described above), a solvent (or solvent mixture) as a mobile phase can usually be compressed from normal pressure to system pressure, i.e. to pressures in the range 200-2000 bar. This compression also leads to strong heating of the solvent, which in turn counteracts or can influence a measurement (e.g. pressure measurement) regarding the solvent. In other words, when measuring the mobile phase (directly) in the area of the pump, the thermal effects during compression of the mobile phase can significantly influence the measurement.

For example, a pressure sensor that is attached directly to the pump head suffers from induced tensile and shear stresses during use as well as from the heat input of the solvent caused by pressure changes in the solvent. If the pressure sensor is used, for example, in the primary cylinder of a pump, it is exposed to the full pressure cycle up to, for example, 2000 bar. Therefore, traditional pressure sensors can fail at a very early stage due to fatigue or incorrectly measure pressure during and after compression or decompression.

EPIPHANY

There may be a need to efficiently and reliably determine a measurement variable (e.g. a pressure) in the context of an analytical device.

The task is solved using the independent claims. Further embodiments are shown in the dependent claims.

1. i) eine erste Fluidleitung (z.B. ein erster Kanal), eingerichtet zum Strömen eines Fluids in einem Haupt-Strom;
2. ii) eine zweite Fluidleitung, eingerichtet zum Strömen (eines Teils des Fluids des Haupt-Stroms), wobei die zweite Fluidleitung (in zumindest einem Abschnitt) zu zumindest einem Abschnitt der ersten Fluidleitung parallel geschaltet ist (insbesondere als Bypass-Strom); und
3. iii) eine Sensorvorrichtung (z.B. ein Drucksensor), welche mit der zweiten Fluidleitung gekoppelt ist, um eine Messgröße (z.B. einen Fluiddruck) bezüglich des Fluids in der zweiten Fluidleitung zu bestimmen („messtechnisch gekoppelt“).

According to an exemplary embodiment of the present invention, a measuring device (or a measuring setup) for an analysis device (eg an HPLC) is described, the measuring device having:

1. i) a first fluid line (eg a first channel) arranged to flow a fluid in a main stream;
2. ii) a second fluid line, set up to flow (part of the fluid of the main stream), the second fluid line (in at least one section) being connected in parallel to at least a section of the first fluid line (in particular as a bypass flow); and
3. iii) a sensor device (e.g. a pressure sensor) which is coupled to the second fluid line in order to determine a measured variable (e.g. a fluid pressure) with respect to the fluid in the second fluid line (“measurably coupled”).

According to a further exemplary embodiment of the present invention, using a bypass fluid line to reduce the influence of heat generation on a fluid pressure measurement in an analysis device is described (by means of heat decoupling in the bypass path).

According to a further exemplary embodiment of the present invention, an analysis device is described for analyzing a fluidic sample, in particular to be injected into a mobile phase, the analysis device having at least one measuring device as described above.

1. i) Strömen eines Fluids in einem Haupt-Strom; und (insbesondere zeitgleich)
2. ii) Strömen des Fluids in einem Bypass-Strom, welcher zu zumindest einem Abschnitt des Haupt-Stroms parallel geschaltet ist; und
3. iii) Bestimmen der Messgröße mittels einer Sensorvorrichtung, welche mit dem Bypass-Strom gekoppelt ist.

According to a further exemplary embodiment of the present invention, a Method described for determining a measured variable, in particular in an analysis device, comprising the method:

1. i) flowing a fluid in a main stream; and (especially at the same time)
2. ii) flowing the fluid in a bypass stream connected in parallel with at least a portion of the main stream; and
3. iii) Determining the measured variable using a sensor device that is coupled to the bypass current.

In the context of this document, the term “fluidic sample” is understood to mean in particular a medium, more particularly a liquid, which contains the matter actually to be analyzed (for example a biological sample), such as a protein solution, a pharmaceutical sample , Etc.

In the context of the present application, the term “mobile phase” is understood to mean in particular a fluid, more particularly a liquid, which serves as a carrier medium for transporting the fluidic sample between a fluid drive and a sample separation device. However, mobile phase can also be used in a fluid delivery device to influence the fluidic sample. For example, the mobile phase may be a solvent (e.g., organic and/or inorganic) or a solvent composition (e.g., water and ethanol).

In the context of the present application, the term “analytical device” can in particular refer to a device that is able and configured to examine a fluidic sample, in particular to separate it, and in particular to separate it into different fractions. For example, such sample separation can be carried out using chromatography or electrophoresis. The analysis device can preferably be a liquid chromatography sample separation device.

In the context of this document, the term “fluid line” can refer in particular to a volume (or a cavity) through which a fluid (e.g. a mobile phase) can flow, so that the fluid can be directed in one direction. In a preferred example, a fluid line can be designed as a channel. Further designs can include a capillary or a conduit. In a specific example, at least part of the fluid line is designed as part of a pump (in particular pump volume). Using a piston, the fluid in the fluid line can then be compressed and directed/pressed in a specific direction. Furthermore, a fluid line can be coupled to a sensor device in terms of measurement technology, so that the sensor device can determine a measured variable relating to the fluid in the fluid line.

In the context of this document, the term “main stream” may refer in particular to a fluid stream (or fluid path) that (essentially) follows the process direction downstream of an analytical device. Such as in 1 shown, a fluid drive (in particular a pump) can draw mobile phase from the solvent container and then transport it further under high pressure. A sample is then injected into this mobile phase and the solvent flows into the sample separation device. The main stream can thus flow, for example, mobile phase from a first pump to a second pump (in the fluid drive) and then via the sample injection to the sample separation device.

In the context of this document, the term “bypass flow” can refer in particular to a fluid flow that runs at least partially parallel to the main flow, in other words, is connected in parallel. The term “parallel” refers in particular to a flow in two or more sections with a common (possibly imaginary) starting point and a common (possibly imaginary) end point, and (in one example) not to a geometric or spatial orientation of the channels. In one example, a portion of the fluid of the main stream may be diverted (in a first fluid line) and then flow parallel to the main stream via the bypass stream (in a second fluid line). The bypass flow can, for example, flow the separated part of the fluid to a sensor device in order to determine a measured variable. The separated part of the fluid can then be combined (or mixed) again with the fluid of the main stream. The bypass flow can thus achieve a decoupling from the main flow, e.g. with regard to temperature and/or pressure conditions. In particular, the term “parallel” is not to be interpreted geometrically, but can mean that part of the fluid flow is diverted from the main flow and later returned again.

In the context of this document, the term “sensor device” can refer in particular to a device which is suitable for determining a measured variable, in particular with regard to a fluid in a (second) fluid line. The term “sensor device” can in particular include the actual sensor (e.g. a strain gauge) as well as additional elements that are associated with the actual sensor, e.g. a membrane on which a strain gauge is arranged.

According to an exemplary embodiment, the invention can be based on the idea that a measured variable (e.g. a pressure) relating to a fluid can be determined efficiently and reliably in the context of an analysis device if a sensor device for determining the measured variable is arranged on a second fluid line, which has a Part of the fluid branches off from a main stream which flows through a first fluid line.

In contrast to conventional solutions, the measurement is not carried out directly on the main stream, but in a second fluid stream connected in parallel (especially bypass stream). The parallel second fluid line can result in a significantly improved decoupling, in particular thermal decoupling, so that, for example, the thermal effects during liquid compression in the high-pressure pump influence a measurement as little as possible.

In one embodiment, the volume/mass contained in the bypass is only a fraction of the main channel. During compression, only a relatively small amount of heat is generated in the bypass channel compared to the main channel. This small amount of heat can be dissipated relatively easily/quickly via the surrounding material and can contribute to the thermal stability of the measuring device or not have a negative influence on it.

With the solution described, a cost-effective and/or easily replaceable sensor device (e.g. pressure sensor) can be attached to a fluid path, which is, for example, exposed to frequent pressure changes with a high magnitude and a minimal number of fluidic contacts. A simple and cost-effective solution for integrating a sensor device (e.g. strain gauge/piezo/optics) (e.g. in a pump head) is described while eliminating the effects of undesirable factors such as heat transfer (solvent convection) on the measuring range. Therefore, for example, the pressure during and after pressure changes is measured correctly despite heat development by the fluid.

This allows a simple, cost-effective and easily replaceable sensor device to be integrated into a functional element with complex geometry and/or challenging conditions, for example a pump head.

EXEMPLARY EMBODIMENTS

According to one embodiment, the second fluid line in the (at least one) section of the first fluid line carries a portion of the fluid as a bypass flow through the second fluid line. This can have the advantage that the main power does not have to be interrupted, diverted or reduced, so that the analyzer can remain in normal operation during the measurement. This means that the measurement can be carried out parallel to the operation (e.g. a chromatographic analysis) without any loss of time. Shown in the picture, only part of the fluid from the main stream is diverted for measurement (under improved measuring conditions compared to the main stream) and then reunited with the main stream. The principle of a bypass path is therefore used to provide better measurement conditions without restricting the main current.

According to an exemplary embodiment, the measured variable has at least one of the following: a pressure, an electrical and/or thermal conductivity, a temperature, a flow velocity, a viscosity, a density. These measured variables can represent important parameters in the operation of an analysis device. Pressure in particular can be of central importance in high-pressure liquid chromatography. Accordingly, it can be particularly advantageous to determine these measured variables as precisely and reliably as possible. The sensor device on the second fluid line can make this possible in particular by allowing undesirable disruptive factors such as heat development in the main flow to be avoided (through decoupling via the bypass path).

According to one embodiment, the sensor device has at least one of the following sensors: pressure sensor, flow sensor, fluid volume sensor, optical sensor, temperature sensor, conductivity sensor. This means that reliable, tried and tested measuring instruments can be implemented directly. A person skilled in the art may be aware of a large number of such sensors, which can then be selected to suit the desired application.

According to one embodiment, the pressure sensor has at least one of the following: strain gauge, piezoresistive sensor, capacitive sensor, inductive sensor, piezoelectric sensor, optical sensor. Strain gauges (DMS) are established tools for pressure measurement that can be used flexibly. In a preferred example, one or more (particularly a plurality) strain gauges can be attached to a membrane (see 3 ), which is brought into contact with the second fluid line. This enables a pressure measurement with respect to the fluid in the second fluid line. An example of a piezoresistive sensor is in 4 shown. Here the second fluid line can also carry the fluid to a membrane flow past while the actual sensor is positioned behind the membrane (in a liquid).

According to one embodiment, the sensor device has a membrane, wherein the membrane is at least partially in contact, in particular physical contact, with the second fluid line. In addition or as an alternative to the membrane, a plate (e.g. steel plate) can be provided, on which, for example, the strain gauges are arranged. This plate can adjoin the second fluid line or be integrated into it.

According to one exemplary embodiment, two bypass fluid lines (see, for example, reference numbers 121 and 122) open into a chamber (see 123). This chamber can be, for example, a circular depression or a very flat cylinder. In this example, the membrane can sit on the front of the pump head, seal it at the edge, and thus form one end of this cylinder. The cylinder itself can then be milled into the material and the two fluid lines then open into this cylinder at the top and bottom and flush the chamber. The contact from the membrane to the measuring chamber can therefore be a round surface, for example.

According to one embodiment, the membrane is coupled to a sensor, in particular a strain gauge, of the sensor device. This allows the pressure properties of the fluid to be directed directly to the membrane and thus to the strain gauges. The membrane can provide a large surface area here, so that a plurality of strain gauges can be provided and the pressure properties can be optimally recorded.

According to one embodiment, the first fluid line is associated with a pump. According to one embodiment, the first fluid line is associated with a pumping of mobile phase, in particular a high-pressure pump. A pump (especially a high-pressure pump) can be particularly challenging for pressure measurement. At the same time, it can also be particularly important to carry out precise pressure measurement for the reliable operation of a (high-pressure) pump. In one example, the first fluid line can be at least partially integrated within the pump and/or connected directly to it (e.g. inlet/outlet channel of the pump volume/pump cylinder).

According to an exemplary embodiment, the first fluid line is associated with a sample treatment (sampler), in particular a dosing pump. A fluidic sample can be sucked into a sample needle using a pump, for example. A particularly precise pump (e.g. the dosing pump) may be necessary for this. The first fluid line can be designed as part of such a pump or can be coupled directly to it (e.g. inlet/outlet channel of the pump volume/pump cylinder). Fluidic sample can thus be transported further from the sample needle by means of the first fluid line in the main flow, for example to the fluid drive (high-pressure pump). The second fluid line (bypass) can then decouple fluid from the main stream (in particular fluidic sample) from disadvantageous measurement conditions in the main stream.

According to one embodiment, the first fluid line is associated with a precompression, in particular a compression pump. In this example, pre-compaction of the sample and/or the solvent (the mobile phase) can be carried out. This compression can be carried out upstream of the high-pressure pump, particularly in the process direction. For example, the (pre-)compression pump can be provided upstream of the fluid drive. Here too, the second fluid line (bypass) can then decouple fluid from the main stream (in particular fluidic sample) from disadvantageous measurement conditions in the main stream.

According to one exemplary embodiment, at least a first main section of the first fluid line is at least partially designed as part of the pump, in particular as a pump chamber, pump head, or pump cylinder. The fluid (in particular the mobile phase) can be introduced into the pump volume (e.g. a first pump device of two pump devices connected in series or parallel) through an inlet and flow through this to an outlet. A pumping element such as a piston can then be pushed into the pump volume to create the pressure and continue to flow the fluid (under high pressure).

According to one exemplary embodiment, a pump pressure (in particular high pressure) can cause undesirable heat development (for precise measurement). The bypass flow can provide (at least partial) thermal decoupling with respect to the heat or cold development of the fluid due to the compression or decompression of the fluid in the first fluid line, in particular by means of the pump.

According to one embodiment, the bypass flow provides thermal decoupling/minimization of heat generation. As also described above, the second fluid line or the bypass flow can provide an advantageous decoupling through the parallel connection in order to improve the measurement conditions.

According to one exemplary embodiment, the measuring device is configured to bring the fluid to high pressure, in particular by means of the pump, in particular to a pressure in the range of 200 to 2000 bar.

According to one embodiment, the second fluid line has: a first bypass section that flows the fluid from the main stream to the sensor device. According to one embodiment, the second fluid line has: a second bypass section that flows the fluid from the sensor device back to the main flow. According to an exemplary embodiment, the second fluid line further has: a measuring section (measuring chamber) which flows the fluid at least partially along the sensor device, in particular on or in a membrane of the sensor device. According to an exemplary embodiment, the second fluid line further has: a measuring section in which the fluid can act on the sensor device, in particular is guided past or in a membrane of the sensor device. Using this structure, a particularly efficient bypass current can be provided, which is limited to the most necessary functional parts. However, the bypass current can also contain additional sections or be routed in a different way.

According to one embodiment, the first bypass section (input line) is attached to the lower/upper end of the measuring section (or measuring space) and the second bypass section (output line) is attached to the lower/upper end of the measuring section. This can prevent potential floating of solvent in the measuring section and/or enable efficient flushing.

According to one embodiment, the diameter of the first fluid line (at least in sections) is different (in particular larger) than the diameter of the second fluid line. According to one embodiment, the diameter of the first bypass section is (at least partially) the same or different (larger or smaller) to the diameter of the second bypass section. In a specific example, at least two lines/bores have different diameters to enable a preferred direction of flow and/or to control the fluid resistance of the line. This can, for example, set a splitting or division of the flow rates for the main stream and the bypass stream. In this way, for example, the rate at which the volume in the measuring chamber is exchanged can be controlled, e.g. one exchange per cycle or only one exchange per several cycles (e.g. five).

According to an exemplary embodiment, the first fluid line has: a second main section, which flows the fluid from the first main section, in particular the pump chamber, to a further process, in particular an analysis process. According to one embodiment, the second main section is fluidly coupled to the second bypass section. This means that the diverted fluid can be fed back into the main stream after the measurement, thereby avoiding the area that is problematic in terms of measurement (here the pump).

According to one exemplary embodiment, the first fluid line and/or the second fluid line is at least partially designed as one of the following: channel, capillary, conduit, pump chamber, membrane (with fluid flowing through them at least partially. This means that lines established in the area of analysis devices can be implemented directly or existing lines can be redirected/repurposed. The diameters of the first/second fluid lines (channels) can differ from one another; this can be used, for example, to create a preferred direction of flow in order to flush the measuring volume with new eluent.

According to one embodiment, a flow capacity and/or a volume of the bypass stream is lower than in the main stream. In order not to impair the main stream (so that the operation of the analysis device is not disturbed at best), only a part of the volume of the fluid in the main stream is diverted, so that ultimately (significantly) more fluid remains in the main stream than is diverted off . For example, the volume of fluid in the main stream can be at least 25%, in particular at least 50%, more particularly at least 100%, larger than in the bypass stream.

According to one embodiment, a flow resistance of the bypass stream is greater than a flow capacity of the main stream. This may allow a smaller volume to flow through the bypass stream. For example, if fresh solvent (colder/warmer than the measuring device) flows past the sensor, this could change the temperature of the measuring chamber/membrane and disrupt the measurement. Excessive flushing should therefore be avoided in the bypass.

According to an exemplary embodiment, the method further comprises: compressing the fluid of the main stream and/or the bypass stream, in particular by means of a pump, and thereby generating heat generation. According to one embodiment, the method includes: minimizing heat generation in the bypass flow, thereby providing thermal decoupling. The amount of heat generated is preferred Heat kept to a minimum in the bypass channel in which the volume is kept to a minimum. Small volume generally produces little heat and can be quickly dissipated through the adjacent material, which can improve measurements.

According to an exemplary embodiment, the method comprises: separating (diverting) part of the fluid from the main stream into the bypass stream, passing the sensor device of the fluid in the bypass stream (so that the measured variable can be determined), and (thereafter) Combining (mixing) the fluid in the bypass stream with the fluid in the main stream.

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.

In the context of the present application, the term “sample separation device” can be understood in particular to mean a device for analyzing a fluidic sample, in particular into different fractions. For this purpose, components of the fluidic 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.

According to one embodiment, the analysis device 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.

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.

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

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

According to one embodiment, the fluid drive is configured for driving the mobile phase and the fluidic sample with a pressure of at least 500 bar, in particular at least 1000 bar, more in particular at least 1200 bar, more in particular at least 1500 bar, more in particular at least 2000 bar.

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

According to one embodiment, the analysis device has a fractionator for fractionating separate fractions of the fluidic sample.

The analytical device can be a microfluidic measuring device, 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 liquid chromatography) device. However, many other applications are possible.

According to one exemplary embodiment, the sample separation device can be designed as a chromatographic separation device, in particular as a chromatography separation column. In the case of a chromatographic separation, the chromatographic separation column can be provided with an adsorption medium. The fluidic sample can be stopped at this and only then be detached fractionally again in the presence of a specific solvent composition, thereby accomplishing the separation of the sample into its fractions.

A pump system for conveying fluid can, for example, be set up to convey the fluid or the mobile phase through the system at a high pressure, for example a few 100 bar up to 1000 bar and more.

The analysis device can have a sample injector for introducing the sample into the fluidic separation path. Such a sample injector can have a sample or injection needle that can be coupled to a needle seat in a corresponding liquid path, whereby the sample needle can be moved out of this needle seat in order to to take a sample. After reinserting the sample needle into the needle seat, the sample can be 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 is operated without a needle seat.

The analyzer may have a fraction collector for collecting the separated components. Such a fraction collector can, for example, lead the various components of the separated sample into different liquid containers. The analyzed sample can also be fed to a drain container.

Preferably, the analysis device can have a detector for detecting the separated components. Such a detector can produce a signal that can be observed and/or recorded and which is indicative of the presence and amount of the sample components in the fluid flowing through the system.

In one embodiment, the advantage of the proposed sensor system is that a miniature adhesive element (DMS) can be attached to a smooth plate (steel membrane), making the sensor easily replaceable and inexpensive, and its integration into a complex geometry such as a Pump head easier. A further advantage in a particular embodiment is that the plate with the sensor can be attached to the pump head using a flow divider construction. The main stream is directed into the pump head, while the side stream (bypass) flows through the measuring cell. This way, adding the sensor does not create a blind hole in the pump head. In addition, the large amount of heat generated in the compression stage of the liquid in the piston chamber is thermally separated from the measuring cell and has no influence on the measurement.

BRIEF DESCRIPTION OF THE FIGURES

• 1 zeigt ein Analysegerät konfiguriert als Chromatografiegerät, gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• Die 2A und 2B zeigen eine Messvorrichtung in dem Analysegerät, gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 3 zeigt eine Sensorvorrichtung mit Dehnungsmesstreifen, gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 4 zeigt einen piezo-resistiven Sensor als Sensorvorrichtung, gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 5 zeigt die Messvorrichtung direkt an einer Pumpvorrichtung des Analysegeräts, gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.

Other objects and many of the attendant advantages of embodiments of the present invention will become readily apparent and better understood by reference to the following more detailed description of embodiments taken in conjunction with the accompanying drawings. Features that are essentially or functionally the same or similar are given the same reference numerals.

• 1 shows an analysis device configured as a chromatography device, according to an exemplary embodiment of the invention.
• The 2A and 2 B show a measuring device in the analysis device, according to an exemplary embodiment of the invention.
• 3 shows a sensor device with strain gauges, according to an exemplary embodiment of the invention.
• 4 shows a piezo-resistive sensor as a sensor device, according to an exemplary embodiment of the invention.
• 5 shows the measuring device directly on a pump device of the analysis device, according to an exemplary embodiment of the invention.

DETAILED DESCRIPTION OF THE FIGURES

The representation in the drawing is schematic.

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

The solvents are here 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 (for example an organic solvent).

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 supplied 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 initially transfer a sample liquid or a fluid sample from a sample container into a sample holder lumen in an injector path, and subsequently introduced into a fluidic separation path between fluid drive 20 and sample separation device 30 by switching an injection valve of the injector 40. The collection of fluidic sample from the sample container can be done in particular by moving a sample needle out of a sample seat and moving it into the sample container, sucking fluidic sample from the sample container through the sample needle into the sample receiving volume by means of a fluid delivery device designed as a dosing device, and the sample needle then moved back into the needle seat.

The stationary phase of the sample separation device 30 is intended to separate components of the sample. A detector 50, which may include a flow cell, detects separated components of the sample. A fractionation device or fractionator 60 may be provided to dispense separated components of the sample into designated containers. Liquids that are no longer needed can be dispensed into a drain container or waste line.

While a liquid path between the fluid drive 20 and the sample separation device 30 is typically under high pressure, the sample liquid is first introduced under normal pressure into an area separated from the liquid path, namely the sample loop or the sample receiving volume, of the sample application unit or the injector 40. The sample liquid is then introduced into the high-pressure separation path. A sample loop as a sample receiving volume (also referred to as a sample loop) can be understood as a section of a fluid line that is designed to receive or temporarily store a predetermined amount of fluidic sample. Preferably, before the sample liquid, which is initially under normal pressure, is switched on in the sample receiving volume into the high-pressure separation path, the contents of the sample receiving volume are brought to the system pressure of the analysis device 10 designed as an HPLC by means of a metering device in the form of the fluid delivery device. A control device 70 controls the individual components 20, 25, 30, 40, 50, 60, etc., of the analysis device 10.

A measuring device 100 is shown schematically, which can be implemented, for example, in or on the fluid drive 20. Detailed exemplary embodiments are for the 2 until 5 described below.

The 2A and 2 B show a measuring device 100 in the analysis device 10, according to an exemplary embodiment of the invention. 2 B shows in comparison to 2A a slightly different perspective. The measuring device 100 has a first fluid line 110, which is set up to flow a fluid 115 in a main stream. As already in 1 indicated, the measuring device 100 in this example is implemented in a fluid drive 20 or a pump device of the analysis device 10. A first main section 111 of the first fluid line 110 is designed as a pump chamber (or cylinder) of the pump device, wherein a piston of the pump, not shown, can be moved in the pump chamber (see 5 ). The first fluid line 110 also has a second main section 112, which flows the fluid 115 from the first main section (the pump chamber 111) to a further process 180, in particular in the process direction of the sample separation device 30. The further process 180 can also be a further pump device (eg another pump room), for example if the fluid drive 20 is implemented as a binary pump, with two pump devices connected in series or in parallel.

The fluid 115 in this example is a mobile phase which essentially contains solvents, for example water, methanol, or acetonitrile. The mobile phase is pumped towards the analytical domain (e.g. sample separation device 30) by means of the fluid drive 20, with the fluid 115 being brought to high pressure by means of the pump. Due to the high pressure (e.g. 1000 bar) and the compression of the fluid 115 by means of the pump, heat is generated in the fluid 115. However, this heat development can significantly (negatively) influence the determination of a measurement variable relating to the fluid 115, for example a pressure measurement.

For this reason, a bypass stream 120 is provided, which provides thermal decoupling with regard to heat development. For this purpose, a second fluid line 120 is provided, which is set up to flow the fluid 115, the second fluid line 120 being connected in parallel to at least a section of the first fluid line 110. This provides a bypass flow to the main flow, which enables heat decoupling of the fluid 115 to be measured.

For this purpose, the measuring device 100 has a sensor device 130, which is coupled to the second fluid line 120 in order to determine a measured variable relating to the fluid in the second fluid line 120. In the example shown, the measured variable is a fluid pressure and the sensor device 130 is accordingly designed as a pressure sensor. The sensor device 130 has a membrane 135, which is arranged transversely to the flow direction of the fluid 115 in the second fluid line 120. The membrane 135 is at least partially in physics physical contact, with the second fluid line 120, so that the fluid 115 flows along the membrane 135 (“measuring chamber”), in particular a large surface area is provided for the measurement. The membrane 135 is coupled to the actual sensor 131, which in this example is arranged in the center of the membrane 135. The sensor 131 is designed as a strain gauge (DMS). A holding device 170 can press the membrane 135 (or sensor device 130) against the second fluid line 120 (for example, be screwed in).

The second fluid line 120 is constructed from the following three sections: a first bypass section 121 flows the fluid 115 out of the main stream 110 (separating) and towards the sensor device 130. A measuring section 123, the fluid 115 flows along the sensor device 130 as already described. A second bypass section 122 (mixing channel) finally flows the fluid 115 from the sensor device 130 back to the main flow 110. The second main section 112 of the first fluid line 110 is fluidically coupled to the second bypass section 122 of the second fluid line 120, so that the part of the fluid 115 that was passed through the bypass stream is guided back into the main stream after the measurement at the sensor device 130.

3 shows a detailed view of the pressure sensor of the sensor device 130, according to an exemplary embodiment of the invention. This has the membrane 135 (here on a stainless steel plate), on the surface of which a plurality of strain gauges 131 are arranged.

4 shows a known piezo-resistive sensor as a sensor device 130, according to an exemplary embodiment of the invention. A membrane 135 is provided within a housing 132, which separates a channel bore (top) from a liquid 134 (eg oil) (bottom). An active layer 133 is attached to the actual (physical) sensor 131. The second fluid line 120 can be coupled to this sensor device 130 via the channel bore.

5 shows the measuring device 100 arranged/implemented on a pump device of the analysis device 10, according to an exemplary embodiment of the invention. The structure is the same as that of 2A and 2 B comparable. However, it is shown that a first section 111 of the first fluid line 110 is designed as a pump chamber/pump volume of a pump device. A pump piston 160 is pressed into the pump volume and thereby significantly increases the pressure of the fluid 115 in the pump volume. Together with the pressure (P), the temperature (T) also increases (which is undesirable for the measurement).

Reference symbols

10

Analyzer

20

Fluid drive, high pressure pump

25

Feeding device

27

Degasser

30

Sample separation device

40

injector

50

detector

60

fractionator

70

Control device

100

Measuring device

110

First fluid line, main stream

111

First main section, pump room

112

Second main section, forwarding

120

Second fluid line, bypass flow

121

First bypass section, supply line

122

Second bypass section, derivation

123

Measuring section

130

Sensor device

131

Sensor, strain gauge

132

Sensor housing

133

Active layer

134

oil

135

membrane

160

pump, piston

170

Holding device

180

Further process

QUOTES INCLUDED IN THE DESCRIPTION

This list of documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The 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

• EP 0309596 B1 [0003]

Claims (20)

A measuring device (100) for an analysis device (10), the measuring device (100) having: a first fluid line (110) adapted to flow a fluid (115) in a main stream; a second fluid line (120) adapted to flow the fluid (115), the second fluid line (120) being connected in parallel to at least a portion of the first fluid line (110); and a sensor device (130) which is coupled to the second fluid line (120) to determine a measured variable relating to the fluid in the second fluid line (120). The measuring device (100) according to Claim 1 , wherein the second fluid line (120) in the section of the first fluid line (110) leads a part of the fluid (115) as a bypass flow through the second fluid line (120) past the section of the first fluid line (110). The measuring device (100) according to Claim 1 or 2 , wherein the measured variable has at least one of the following: a pressure, an electrical and / or thermal conductivity, a temperature, a flow rate, a viscosity, a density. The measuring device (100) according to one of Claims 1 until 3 , wherein the sensor device (130) has at least one of the following sensors (131): pressure sensor, flow sensor, fluid volume sensor, optical sensor, temperature sensor, conductivity sensor, in particular wherein the pressure sensor (131) has at least one of has the following: strain gauges, piezoresistive sensor, capacitive sensor, inductive sensor, piezoelectric sensor, optical sensor. The measuring device (100) according to one of the preceding claims, wherein the sensor device (130) comprises a membrane (135); wherein the membrane (135) is at least partially in contact, in particular physical contact, with the second fluid line (120), in particular wherein the membrane (135) is coupled to a sensor (131), in particular a strain gauge, of the sensor device (130). The measuring device (100) according to one of the preceding claims, wherein the first fluid line (110) is associated with a pump (160), in particular in one of the following areas: - pumping mobile phase (20), in particular a high-pressure pump, - a sample treatment, in particular a dosing pump, - a pre-compression, in particular a compression pump. The measuring device (100) according to Claim 6 , wherein at least a first main section (111) of the first fluid line (110) is at least partially designed as part of the pump (160), in particular as a pump chamber, pump head, or pump cylinder. The measuring device (100) according to Claim 6 or 7 , wherein the bypass stream (120) provides thermal decoupling with regard to heat development. The measuring device (100) according to one of the preceding claims is configured to bring the fluid (115), in particular by means of the pump (160), to high pressure, in particular to a pressure in the range 200 to 2000 bar. The measuring device (100) according to one of the preceding Claims 2 until 9 , wherein the second fluid line (120) comprises: a first bypass section (121) which flows the fluid (115) from the main stream (110) to the sensor device (130); and/or a second bypass section (122) which flows the fluid (115) from the sensor device (130) back to the main stream (110); and/or a measuring section (123) in which the fluid (115) can act on the sensor device (130), in particular being guided past or in a membrane (135) of the sensor device (130). The measuring device (100) according to one of the preceding claims, wherein the first fluid line (110) comprises: a second main section (112), which flows the fluid (115) from the first main section (111), in particular the pump chamber, to a further process (180), in particular an analysis process. The measuring device (100) according to Claim 10 and Claim 11 , wherein the second main section (112) is fluidly coupled to the second bypass section (122). The measuring device (100) according to one of the preceding claims, wherein the first fluid line (110) and/or the second fluid line (120) is at least partially designed as one of the following: channel, capillary, conduit, pump chamber, membrane; and/or wherein a flow capacity and/or a volume of the bypass stream is lower than in the main stream. An analysis device (10) for analyzing a fluidic sample, in particular to be injected into a mobile phase, wherein the analysis device (10) has at least one measuring device (100) according to one of the preceding claims. The analyzer (10) after Claim 14 , 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 liquid 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 at least 1000 bar, more particularly 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. Using a bypass fluid line (120) to reduce the influence of heat generation on a fluid pressure measurement in an analysis device (10). A method for determining a measurement variable, in particular in an analysis device (10), the method comprising: flowing a fluid (115) in a main stream (110); and at the same time flowing the fluid (115) in a bypass stream (120) which is connected in parallel to at least a portion of the main stream (110); and Determining the measured variable using a sensor device (130) which is coupled to the bypass current (120). The procedure according to Claim 17 , further comprising: minimizing heat development in the bypass stream (120), thereby providing thermal decoupling. The procedure according to Claim 17 or 18 , further comprising: separating a portion of the fluid (115) from the main stream (110) into the bypass stream (120); and passing the sensor device (130) of the fluid (115) in the bypass stream (120). The procedure according to Claim 19 , further comprising: combining the fluid (115) in the bypass stream (120) with the fluid (115) in the main stream (110).

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