DE102024102761A1 - Determining the configuration of a functional element of an analysis device - Google Patents

Abstract

A computer-implemented method is described for determining a configuration of a functional element (1) in an analysis device (10), the method comprising:i) changing an operating state of the analysis device (10), in particular with regard to the functional element (1);ii) Detecting a change in a parameter, in particular with regard to the functional element (1), as a result of the changed operating state; andiii) determining the configuration of the functional element (1) in the analysis device (10) based on the detected change in the parameter.

Description

TECHNICAL BACKGROUND

The present invention relates to a method for determining a configuration of a functional element (e.g. a sample separation device) in an analysis device, the method comprising: changing an operating state of the analysis device, detecting a change in a parameter as a result of the changed operating state, and determining the configuration of the functional element in the analysis device based on the detected change in the parameter. The invention further relates to the analysis device.

Analysis devices are, for example, chromatography devices, in particular sample separation devices, for analyzing a sample, in particular fluidic sample, for example for carrying out a chromatographic separation of the sample.

For example, in a high performance liquid chromatography (HPLC) chromatography machine, a liquid (mobile phase) is flowed 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.

The actual sample separation of the fluidic sample (in the mobile phase) takes place in a sample separation device that contains the stationary phase. Such a sample separation device is usually implemented as a chromatographic column, which can be arranged in a temperature control chamber or a column oven. Due to the arrangement inside the temperature control chamber, the sample separation device can be tempered; in particular, heat exchangers are provided in the temperature control chamber for this purpose. Furthermore, fluid temperature control devices are often used to temper a fluid (in particular the mobile phase; with or without fluidic sample) before the fluid is flowed through the sample separation device. Such a fluid temperature control device is fluidly connected to the inlet of the sample separation device.

If several sample separation devices (e.g. four) are arranged in the temperature control chamber (e.g. next to one another, one behind the other), then all sample separation devices are usually fluidly coupled to a common switching valve. Depending on the switching position of the switching valve, a specific sample separation device can then be coupled into the flow path within the analysis device (e.g. from fluid drive via sample injection and sample separation device to detector).

However, assignment errors can easily occur with regard to the configuration of the sample separation device in the temperature control chamber. First, the question may arise as to which of the four sample separation devices (e.g. 1 to 4) is arranged at which of four positions (e.g. A to D) in the temperature control chamber (compare 2A) . Furthermore, the question may arise as to which of the four sample separation devices is connected to which switching valve position (eg 35-1 to 35-4).

However, the valve positions are not linked to the sample separation devices or the positions of the sample separation devices. Accordingly, the user must make such a link manually, which increases both the operational effort and the susceptibility to errors. In addition, the conventional approach makes remote operation of the analysis device significantly more difficult because a user cannot simply open the temperature control chamber and check the circuitry.

SUMMARY OF THE INVENTION

There may be a need to efficiently and reliably determine the configuration (e.g. interconnection) of a functional element (e.g. sample separation device) in an analysis device.

A method and an analysis device are described below.

• i) Ändern eines Betriebszustandes der Analysevorrichtung (z.B. Ändern der Temperatur, Veranlassen eines Durchströmens mittels eines Fluids), insbesondere bezüglich des Funktionselements (insbesondere besteht ein (in)direkter Bezug zum Funktionselement, z.B. wird dieses erwärmt/abgekühlt, durchströmt);
• ii) Detektieren einer Änderung eines Parameters (z.B. eine Temperatur, ein Druck, etc.), insbesondere bezüglich des Funktionselements, als Folge des geänderten Betriebszustandes (z.B. wird eine geänderte Temperatur in Erwiderung auf ein Erhöhen der Temperatur in der Temperierkammer detektiert); und
• iii) Bestimmen der Konfiguration des Funktionselements (z.B. der Verschaltung einer Probentrennvorrichtung in einer Temperierkammer) in der Analysevorrichtung basierend auf der detektierten Änderung des Parameters (in anderen Worten: wobei die detektierte Änderung des Parameters für die Konfiguration des Funktionselements indikativ ist).

According to a first aspect of the invention, a (computer-implemented) method for determining a configuration of a functional element in an analysis device is described, the method comprising:

• i) changing an operating state of the analysis device (e.g. changing the temperature, causing a fluid to flow through), in particular with regard to the functional element (in particular there is an (in)direct relationship to the functional element, e.g. it is heated/cooled, flows through);
• ii) detecting a change in a parameter (e.g. a temperature, a pressure, etc.), in particular with regard to the functional element, as a result of the changed operating state (e.g. a changed temperature is detected in response to an increase in the temperature in the temperature control chamber); and
• iii) determining the configuration of the functional element (e.g. the interconnection of a sample separation device in a temperature control chamber) in the analysis device based on the detected change in the parameter (in other words: where the detected change in the parameter is indicative of the configuration of the functional element).

According to a second aspect of the invention, a device for data processing is described which has a processor and is set up to carry out the method as described above.

According to a third aspect of the invention, an analysis device for carrying out an analysis method is described, the analysis device having a device for data processing as described above.

According to one aspect of the invention, a (computer-implemented) method is described for determining a configuration of a functional element in an analysis device, the method comprising: first detecting a parameter relating to the functional element; Changing an operating state of the analysis device with respect to the functional element; second detecting a change in the parameter with respect to the functional element (and/or a further functional element) as a result of the changed operating state of a further functional element; in particular comparing the results of the first detection and the second detection; and determining the configuration of the functional element in the analysis device based on the comparing and/or the detected change in the parameter.

In the context of the present document, the term “analysis device” can in particular refer to a device that is able and configured to examine a fluidic sample, in particular to separate it, and further in particular to separate it into different fractions. For example, such sample separation can be carried out using chromatography or electrophoresis. Preferably, the analysis device can be a liquid chromatography sample separation device. The analysis device is in particular configured to carry out an analysis method or a (possibly planned or programmed) sequence of analysis methods or procedures. Furthermore, the term “analysis method” can also be used to represent a sequence, a sequence, a program, an execution list of analysis methods, procedures or regulations, including adjustment, preparation, equilibration (intermediate) steps, etc.

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 document, 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 document, the term “functional element” can in particular refer to an element (or a device, a unit, a fluid line) which fulfills a function in an analysis device, in particular a function which is related to carrying out the analysis lyse stands. In one example, the functional element is associated with a fluid path, for example coupled or can be coupled into a fluid path between the fluid drive and the detector. In one example, the functional element may comprise a sample separation device (eg a chromatographic separation column). In a further example, the functional element can have a fluid temperature control device, preferably the functional element can have a sample separation device which is coupled to a fluid temperature control device. In another example, the functional element may designate a (part of) a flow path(s), for example a channel or a capillary. Furthermore, a functional element can also be, for example, a valve, a damper, a loop, a mixer or a filter.

In the context of the present document, the term “operating state” can in particular refer to a state which occurs during operation of the analysis device and which can be changed (e.g. via a control device). An operating state can be, for example, the temperature in a temperature control chamber of the analysis device. Changing the operating state can then be, for example, increasing or decreasing the temperature. By changing the operating state, a specific parameter with regard to the functional element can then also change. Another operating condition may be the flow of a fluid through a specific path. For example, a solvent (at a specific temperature) can be flowed through a specific sample separation device. Changing the operating state can then be, for example, coupling or uncoupling the sample separation device. This can also change a certain parameter regarding the sample separation device.

In the context of this document, the term “configuration” can in particular refer to a state of organization/architecture/design with regard to the functional element. The configuration can be changeable so that a current state of the configuration can be determined. The configuration can, for example, refer to an interconnection or a specific position (arrangement) of the functional element. If, for example, a plurality of functional elements (such as sample separation devices) are arranged in a temperature control chamber, the exact position can be determined as a configuration. If the functional elements are connected to a common fluid valve, the connection with a specific valve position can be determined as a configuration, for example.

According to an exemplary embodiment, the invention can be based on the idea that the configuration of a functional element in an analysis device can be determined efficiently and reliably if the change in a parameter is observed or recorded by measurement as a result of a change in an operating state (the change being for the configuration is indicative). The configuration of the functional element can be deduced from this in a surprisingly efficient and reliable manner.

Such a method can be carried out, for example, directly via a control device of the analysis device, so that it is no longer necessary to monitor/check the configuration (or interconnection) manually. In one exemplary embodiment, the column oven does not have to be laboriously opened in order to check the connection between a valve and several sample separation devices. In the specific exemplary embodiment of the temperature control chamber with the sample separation devices, it can now be determined without manual interaction which sample separation device in operation is coupled to which valve position at which position.

Accordingly, remote operation of the analysis device can be carried out significantly faster and more robustly. In addition, the operating effort and the susceptibility to errors by a user can be significantly reduced. The method described can be implemented directly into established analysis devices (essentially) without structural changes.

EXEMPLARY EMBODIMENTS

Additional preferred embodiments are described below.

According to one embodiment, determining the configuration includes at least one of the following (with respect to the configuration): verifying (connected correctly?), identifying (which functional element?), mapping, assigning (which functional element is connected/arranged where?) . This allows various aspects of the configuration to be determined directly and reliably.

In one example, it can be verified whether a functional element is arranged in the correct position or coupled to the correct (valve) position. The active (in the flow path of the analysis device coupled in) functional element can be identified (as such). In one example, several functional elements can be observed (e.g. the parameter is detected several times (in succession) with respect to different functional elements), so that each position can be assigned a functional element or vice versa (mapping). In one example, a functional element can be assigned to a specific position in the analysis device and/or a specific switching position based on the detected parameter change.

According to one exemplary embodiment, the configuration has a, in particular fluidic, connection (in particular tubing) of the functional element. According to an exemplary embodiment, the configuration has an interconnection of the functional element with respect to a flow path (for example an interconnection in a specific flow path). According to one exemplary embodiment, the configuration has an interconnection of the functional element with respect to a fluid valve (e.g. to which valve position is the functional element connected). According to one exemplary embodiment, the configuration has a position, in particular within the analysis device, of the functional element (e.g. an arrangement in a temperature control chamber). According to one exemplary embodiment, the configuration has a position of the functional element relative to another functional element (e.g. which functional elements are connected/arranged one behind the other or next to one another; which ones are connected in series or in parallel). Accordingly, a variety of possible configurations can be derived directly from the detected change in the parameter.

According to an exemplary embodiment, the configuration relates to a fluidic connection between a fluid valve and a sample separation device. As already explained above, the interconnection of the sample separation device and valve position may be necessary for the operation of the analysis device. On the other hand, a complex manual intervention is necessary to check this connection. A reliable automated solution may be particularly desirable here.

According to one exemplary embodiment, changing the operating state of the analysis device involves a change in temperature, for example heating (in particular of a temperature control chamber) or cooling (in particular of a temperature control chamber). In one example, the temperature change of a sample separation device through which a fluid flows can be different than in a sample separation device through which a fluid does not flow. In one embodiment, the temperature change does not have to occur through a temperature change in the furnace, for example switching on a fluid flow causes a temperature change (frictional heat). According to one embodiment, changing the operating state of the analysis device includes providing a fluid flow (in particular by means of a heated or cooled fluid). According to one embodiment, changing the operating state of the analysis device includes heating using a fluid flow or cooling using a fluid flow. In one example, a (tempered) fluid can be specifically flowed through a functional element in order to provide a change in the operating state that can be detected via the parameter.

According to one embodiment, the functional element has a sample separation device (in particular a chromatographic separation column). Such a sample separation device can be essential for an analysis device, so that the configuration or circuitry in the device must be known. According to one embodiment, the functional element has a fluid path. The flow path may extend through one or more units of the analysis device (e.g. from fluid drive to sample injection to sample separation device). The flow path can be viewed as such, or a specific section can be observed, e.g. formed as a fluid line, capillary, conduit, or channel. According to one embodiment, the functional element has a fluid valve (e.g. a switching valve such as a rotary valve or a shear valve). A fluid valve can have a plurality of connection positions, so information about the exact configuration can be very important.

According to one embodiment, the parameter has at least one of the following: a temperature, a pressure, a flow rate, a mass flow, a conductivity, a density, a volume, a weight. This can have the advantage that a large number of relevant parameters of an analysis device can be used directly.

According to one embodiment, the method comprises: using a sensor device that is associated (or coupled) with the functional element and/or a further functional element. Detecting (measuring) can be carried out efficiently using known and established sensors, for example using one of the following: a temperature sensor, a pressure sensor, a Flow sensor, a conductivity sensor, a weighing device, a thermal camera, a sensor for electromagnetic waves, in particular an IR sensor.

According to one exemplary embodiment, the comparison is carried out using absolute measured values or relative measured values. According to one embodiment, the method is non-invasive with respect to the analysis device. According to one exemplary embodiment, (only) existing equipment is used for the method. According to one embodiment, the method is carried out (substantially) freely by a human operator. According to one exemplary embodiment, the method is carried out remotely with respect to the analysis device. According to one exemplary embodiment, the functional element is coupled (fluidically) into a flow path of the analysis device. These aspects can implement the described method particularly efficiently and advantageously.

According to one exemplary embodiment, the analysis device has: a temperature control chamber for receiving and temperature control of the functional element and/or another functional element (or more). The temperature control chamber can have a volume for arranging one or more functional elements at specific positions. Temperature control can be made possible by heating or cooling the temperature control chamber, for example using a heat exchanger.

According to an exemplary embodiment, the functional element has: a sample separation device (in particular which is associated with a first sensor device), and/or a fluid temperature control device, for pre-tempering a fluid upstream of the sample separation device (in particular which is associated with a second sensor device). According to one embodiment, the sample separation device is fluidly coupled to the fluid temperature control device. According to one embodiment, the fluid temperature control device is arranged upstream in the fluid flow direction with respect to the sample separation device.

As described in detail below, the combination of sample separation device and corresponding fluid temperature control device (if fluidly coupled) can enable a particularly efficient determination of the configuration.

In this context, the term “fluid temperature control device” can in particular refer to a device which is suitable for pre-heating a fluid (e.g. a mobile phase; with or without fluidic sample). In one example, the fluid temperature control device can be provided elongated, in particular column-shaped, in order to realize a temperature control path. The temperature change can be provided within the temperature control chamber, for example by means of a heat exchanger. Preferably, an input of the fluid temperature control device can be connected to the input of the sample separation domain, while an output of the fluid temperature control device is coupled to the input of the sample separation device.

According to an exemplary embodiment, the analysis device further has: a sliding element which is coupled to the sample separation device and/or the fluid temperature control device and is set up, when moving, the sample separation device and the fluid temperature control device together into a position with respect to the analysis device, in particular with respect to the Temperature chamber of the analysis device.

In the context of the present document, the term “pushing element” can in particular refer to a device which is suitable for coupling at least one further element and then displacing it. In an illustrative example, the sliding element can be designed as a carriage. In a simple example, the sliding element can have a body with a main surface to which the further element is coupled, for example placed. The sliding element can, for example, have two main extension directions and thereby provide two opposing main surfaces. In a more complex example, the sliding element can have special coupling structures, for example a connection element (with a pivoting mechanism) for connecting (in particular screwing on) a sample separation device. Furthermore, the sliding element can also be set up to provide a fluidic coupling to the sample separation device. At least a part of the sample separation device can be placed on (the main surface of) the sliding element (or supported by it). The sliding element can also have a second coupling region in order to couple another element, for example a fluid temperature control device. In further examples, the sliding element can have a variety of advantageous functionalities, for example a holding element, a pressing element, a guide element, a handling element, etc. In a preferred example, the sliding element can be inserted into a temperature control chamber of an analysis device are pushed out, with at least one of the sample separation device and fluid temperature control device being coupled to the sliding element (in particular fluidly connected to it).

According to an exemplary embodiment, the sliding element further comprises: a first main surface which is configured for coupling the sample separation device; and/or a second main surface that is set up for coupling the fluid temperature control device. According to one embodiment, the first main surface is arranged opposite the second main surface. The main surfaces of the sliding element can be referred to, for example, as the top and bottom. In one example, the sliding element is essentially planar, so that two opposing main surfaces are provided. This can have the advantage that the sample separation device and fluid temperature control device can be arranged opposite each other (with the sliding element in between), and can therefore be moved together in a space-saving and stable manner.

According to one exemplary embodiment, the analysis device or the device for data processing is set up to: change the operating state (in particular heating or cooling the temperature control chamber and/or at least partially flowing a fluid through the first functional element); first detecting the parameter (in particular the temperature, e.g. first temperature measurement) with respect to (in particular the fluid temperature control device), the functional element; second detecting the parameter (in particular the temperature, e.g. second temperature measurement) with respect to (in particular a further fluid temperature control device) one of the further functional elements; and comparing the results of the first detection and the second detection, and determining the configuration of the functional element (and/or the further functional element) in the analysis device (based on the comparing).

In an illustrative example, a fluid at normal temperature can flow through the fluid temperature control device of the first functional element, while the fluid does not flow through the further fluid temperature control device. A change in the temperature in the temperature control chamber also changes the temperature of the fluid temperature control devices, and the fluid at normal temperature can affect this temperature change. If, for example, the temperature is increased, the fluid temperature control device of the first element (through which the fluid flows) is heated less than the further fluid temperature control device of the further functional element (which is not flowed through). If, on the other hand, the temperature is reduced, the fluid temperature control device of the first element (through which the fluid flows) is cooled less than the further fluid temperature control device of the further functional element (which is not flowed through).

In a specific embodiment, a thermostat (temperature chamber) heats and sample separation device and fluid temperature control device are heated by the thermostat. Solvent (mobile phase) at ambient temperature flows in and cools the inlet of the fluid temperature control device. The temperature sensor on the fluid temperature control device of the sample separation device used is lower than all other temperature sensors (of unused fluid temperature control devices in the temperature control chamber).

In a specific embodiment, a thermostat (temperature chamber) cools and solvent at ambient temperature flows into the fluid temperature control device and heats the inlet of the fluid temperature control device. The temperature sensor on the fluid temperature control device of the sample separation device used is higher than all other temperature sensors (of the unused fluid temperature control devices in the temperature control chamber).

According to one exemplary embodiment, the analysis device or the device for data processing is set up to: change the operating state (in particular at least partially flowing a fluid through the first functional element; essentially without changing the temperature); first detecting the parameter (in particular the temperature, first temperature measurement) with respect to (in particular the fluid temperature control device), the functional element; second detecting the parameter (in particular the temperature, second temperature measurement) with respect to (in particular the sample separation device), the functional element; and comparing the results of the first detecting and the second detecting, and determining the configuration of the functional element in the analysis device (based on the comparing).

In an illustrative exemplary embodiment, the temperature difference between the fluid temperature control device and the sample separation device is observed; in particular, each of the two units has its own temperature sensor.

In a specific embodiment, the thermostat is operated near or at ambient temperature. All temperature sensors on fluid temperature control devices will be at a similar temperature level. Nevertheless, due to the frictional heating, the temperature delta of the functional elements used (through which fluid flows) is higher, i.e. the delta between the temperature of the fluid temperature control device and the temperature of the corresponding (fluidically directly coupled) sample separation device.

The (absolute) value of the difference between the temperature of the fluid temperature control device and the ambient temperature is: T _{fluid temperature control device} - T _environment .

According to one exemplary embodiment, the difference between the temperature of the sample separation device and the temperature of the fluid temperature control device is: T _{sample separation device} -T _{fluid temperature control device} .

With regard to the functional elements (in the temperature control chamber), the pair of temperature sensors can now be selected for which both differences are largest: 1 T _{fluid temperature control device} - T _environment |
and | T _{sample separation device} - T _{fluid temperature control device} |.

In an example, the difference between the temperature of the sample separator and the ambient temperature is: T _{sample separator} - T _ambient .

With regard to the functional elements (in the temperature chamber), you can now select the pair of temperature sensors for which both differences are the largest: $$\left|{\text{T}}_{\text{Fluid temperature control device}}-{\text{T}}_{\text{Vicinity}}\right|\text{and}\left|{\text{T}}_{\text{Sample separation device}}-{\text{T}}_{\text{Vicinity}}\right|.$$

According to an exemplary embodiment, the analysis device further comprises: a tag which is associated with the sample separation device (and/or the fluid temperature control device), in particular coupled to the sample separation device, in particular wherein the tag has at least one of an NFC tag and an RFID tag , a Bluetooth tag (a BLE beacon). Using such a tag, a sample separation device can be characterized/assigned. For example, it can be checked whether the correct sample separation device was inserted in the correct position.

According to an exemplary embodiment, the analysis device further comprises: a tag reader, which is associated with the sample separation device (or the analysis device), in particular wherein the tag reader has at least one of an NFC tag reader, an RFID tag reader, a Bluetooth (a BLE beacon) reader.

Column tags (e.g. RFID tags or tags with electrical contacts) are typically attached to the column with a wire and coupled to a tag reader located outside the column oven. Due to inaccuracy, e.g. in the positioning of the column, the tag can lead to errors due to incorrect assignment (especially when placing multiple columns next to each other). For example, a tag with a plastic part is clicked onto a column or column position. However, this can affect the thermal performance of the column oven and the tag must be manually moved and aligned to the correct position of the corresponding tag reader antenna within the analyzer. In summary, it is a challenge in the prior art to provide an efficient coupling between tag and tag reader in an analysis device.

However, in conjunction with the sliding element, this need can be solved in an elegant and reliable manner. A tag on the sample separation device is automatically attached to the sliding element in the correct position. When inserted into the analysis device, the tag is automatically brought into the correct position and orientation together with the sample separation device. The tag can thus be automatically aligned with the tag reader and (essentially) no manual interaction is required. The following advantages can arise: the assignment within the analysis device is clear. No feedthrough interface for column tag wires is required (no holes in the column oven thermal insulation). The small size and low thermal mass of the tag have a negligible impact on the thermal behavior of the column. The thermal performance of the column oven is not affected by large parts (here the tags or antennas) on the surface of the sample separation device or antennas near the column body (no shields for thermal radiation and no blockage of airflow).

In addition to these advantages, it may be possible to detect whether the sample separation device is installed in the correct liquid flow direction (automatic detection of orientation when a tag is installed). In addition, it may be possible to attach a temperature sensor directly to the body of the sample separation device (or to the sliding element) in order to improve the temperature reference point for temperature control of the temperature chamber.

The tag applications described (in conjunction with the sliding element) can offer various advantages compared to the prior art, as the tag can be mounted directly on/on the sample separation device and is compatible with most available sample separation devices. The tag reader can be installed in the temperature chamber, which can prevent misalignment of the position (and a docking port). In addition, the correct orientation of the sample separation device can be monitored in this way. A simple structure with low cost can be realized. This allows (automatic) identification and monitoring of the sample separation device and/or fluid temperature control device (with low complexity).

In one embodiment, a tag reader position can have the same numbering as a valve position, so that the tag reader position can be linked to the valve position.

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 for driving the mobile phase and the fluidic sample is configured with a pressure of at least 200 bar, in particular at least 500 bar, in particular at least 1000 bar, more particularly at least 1200 bar, more particularly at least 1500 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 analysis device can be a microfluidic measuring device, a life science device, a liquid chromatography device, a gas chromatography device, an HPLC (High Performance Liquid Chromatogra phy), 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 take up 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 analysis device 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.

According to an exemplary embodiment, a sampling space is delimited by a housing in which the sample handling arrangement or sample movement device is arranged.

In one exemplary embodiment, the possible configurations can be referred to as “parallel” or “serial”, whereby the serial connection can be created by switching a valve but can also be canceled again. As an alternative to the sample separation devices, purification or enrichment columns (in addition) could also be used, e.g. connected upstream or downstream of a sample separation device/separation column.

In one embodiment, two or more separate valves may be used, e.g. one for the inputs/high pressure connections to the sample separators and one for the outputs/low pressure connections.

According to an exemplary embodiment, an implementation of a valve port-to-column mapping is implemented (foregoing temperature sensors on the column in order to save costs/effort). In one example, the sample separation device (column) and fluid temperature control device (pre-heater) are connected/coupled to one another via a holder. In one example, the sample separation device can be identified via an (RFID) tag and the absolute position in the temperature control chamber can also be clearly determined by the antenna construction.

According to an exemplary embodiment, the indirect measurement of the heat/cold output of the fluid temperature control device can be carried out by measuring the temperature of the coupled heat exchanger of the temperature control chamber. This makes it possible to determine which fluid temperature control device is currently flowing through.

According to an exemplary embodiment, in the case of the ambient temperature, a short/temporary heating or cooling process would be necessary in order to initially determine the assignment once (a One-time initial determination at the beginning may be sufficient (after starting the drive for the mobile phase)).

According to an exemplary embodiment, since the sample separation device and fluid separation device are mechanically coupled, verification can automatically result that the correct sample separation device is being used (assignment of valve port to sample separation device).

BRIEF DESCRIPTION OF THE FIGURES

• 1 zeigt eine Analysevorrichtung konfiguriert als Chromatografiegerät, gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 2A zeigt eine Temperierkammer einer Analysevorrichtung mit vier Probentrennvorrichtungen und 2B zeigt eine zugehörige Verschaltung, gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 3 zeigt eine Schiebeelement Anordnung mit einer Probentrennvorrichtung und einer Fluid-Temperiervorrichtung, gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 4 zeigt eine Schiebeelement Anordnung mit einem Tag, gemäß einem exemplarischen Ausführungsbeispiel der Erfindung.
• 5 zeigt eine Temperierkammer einer Analysevorrichtung mit vier Probentrennvorrichtungen und vier Fluid-Temperiervorrichtungen, 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.
• 2A shows a temperature control chamber of an analysis device with four sample separation devices and 2 B shows an associated circuit, according to an exemplary embodiment of the invention.
• 3 shows a sliding element arrangement with a sample separation device and a fluid temperature control device, according to an exemplary embodiment of the invention.
• 4 shows a sliding element arrangement with a tag, according to an exemplary embodiment of the invention.
• 5 shows a temperature control chamber of an analysis device with four sample separation devices and four fluid temperature control devices, 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 or chromatography device, according to an exemplary embodiment of the invention, as can be used for liquid chromatography, for example. A fluid conveyor or fluid drive 20, supplied with solvents from a feeder 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.

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. 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 (sampler), is arranged between the fluid drive 20 and the sample separation device 30 in order to first receive a sample liquid or a fluidic sample from a sample container into a sample receiving volume in an injector path, and subsequently by switching an injection valve of the injector 40 into a fluidic separation path between the fluid drive 20 and the sample separation device 30. 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. The sample separation device 30 can be in a temperature control chamber 120 (or a column oven). be arranged. The fluid path from the fluid drive 20 is coupled to an input of the temperature control chamber 120, while an output of the temperature control chamber 120 is coupled to a detector 50.

The 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 under normal pressure is first introduced into an area separate 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 HPLC by means of a metering device in the form of the fluid conveying device. A control device or a control system 70 controls the individual components or elements 20, 25, 30, 40, 50, 60, etc., of the analysis device 10. Each of these components can have a separate housing, or two or more components can be in the same Housing be arranged.

2A shows a temperature control chamber 120 of an analysis device 10 with four sample separation devices 1 to 4, according to an exemplary embodiment of the invention. The sample separation devices 1 to 4 are designed as chromatographic separation columns and each is arranged at a specific position A to D in the temperature control chamber 120. In addition, each sample separation device 1 to 4 is fluidly coupled at its column inlet to a valve position 35-1 to 35-4 of a fluid valve 35.

2 B schematically illustrates the complexity of the connection between the positions or the configuration of a functional element (e.g. column 1). Each valve position 35-1 to 35-4 is assigned to a column inlet 1 to 4, with each column 1 to 4 in turn being assigned to a specific spatial position A to D in the temperature control chamber 120. It can be seen that such an interconnection (particularly in remote operation) is complex and error-prone, so that an automated solution such as the method described is particularly desirable. This can also apply if two or more valves are connected.

3 shows a temperature control chamber 120 with a sliding element arrangement 100, according to an exemplary embodiment of the invention. A sliding element 150 has a first coupling area (top) on a first main surface (top) for coupling the sample separation device 30. The sample separation device 30 is coupled or connected to the first coupling area in order to provide the sliding element arrangement 100. The sliding element 150 is set up to bring the sample separation device 30 into a position relative to a temperature control chamber 160 of the analysis device 10 when it is moved. In particular, the sample separation device 30 should be inserted (or pushed out) into the temperature control chamber 120 by means of the sliding element 150 in order to enable efficient and user-friendly insertion and connection of the sample separation device 30.

The sliding element 150 further has a second coupling region on a second main surface (underside) for coupling a fluid temperature control device 110. The second main surface is arranged opposite and parallel to the first main surface.

The coupling between sample separation device 30 and sliding element 150 via a connecting element 130 is mechanical here. The fluidic coupling (with the fluid drive 20) takes place via a fluid connector 31 (separation path input fluid path). This connection runs at least partially through the connection element 130.

The sliding element 150 is further designed to bring the sample separation device 30 and the fluid temperature control device 110 together into the desired position with respect to the temperature control chamber 120 of the analysis device 10 when moving. The fluid temperature control device 110 has a fluid inlet that can be coupled, for example, to the flow path of the fluid drive 20. Downstream, the fluid Temperature control device 110 has a fluid outlet, which is fluidly connected to the input of sample separation device 30 via fluid connector 31. A fluid temperature control path therefore runs through the fluid temperature control device 110, in which the fluid can be pre-tempered.

In 3 The separation path output 32 of the sample separation device 30 is also shown. The sample separation device 30 is significantly longer than the sliding element 150 (and the fluid temperature control device 110). Nevertheless, the sample separation device 30 can be stably coupled and moved, and the length of the sample separation device 30 can be very flexible.

In this example, a first temperature sensor 111 is additionally attached to the fluid temperature control device 110, while a second temperature sensor 131 is attached to the sample separation device 30.

4 shows a sliding element arrangement 100 with a tag 180, according to an exemplary embodiment of the invention. Due to the defined position of the sample separation device 30 on the sliding element 100, a fixed length L (or offset) can be maintained. In other words, the position of the tag 180 on the sample separation device 30 can be precisely determined. Electrical contacts 182 (e.g. contact pins) can electrically connect the tag 180 to the sliding element 150 (via contact areas 181.

In a specific example, a tag/EEPROM 180 is placed on a label/flexboard that is insulated from and wrapped around the column 30 and includes plated metallic contact pads (preferably gold) surrounding the cylindrical surface of the column 30. The label could be constructed as an adhesive label/sticker that can be wrapped around the column 30. Flexboards or similar processes as with RFID tag labels can be used to produce the conductive layers. The sliding element 150 here has spring-loaded contact pins 182, which have a defined offset to the column entry point 104 and a connection to the electrical contact surfaces 181 on the column 30 produce.

In one example, tag 180 is a component that only requires two connection pins to simplify the connection effort (e.g. one-wire EEPROM). To address the risk of corrosion (solvent fumes), two gold contacts can be used for each contact surface and the surfaces can be designed to be rough and free of surface contaminants.

The pins 182 and also the sliding element 150 can be inexpensive and can be replaced regularly. Such a construction makes it possible, for example, to write or cut a barcode or a readable serial number into the metallic surface using a laser (ablation of surface material; engraving, laser engraving) (or to add a normal sticker with this information). A self-destruction of tag 180 when removed from column 30 can be implemented. The same tag 180 can be used for columns of different types, e.g. with different diameters/lengths.

The sliding element 150 means that no manual alignment of the tag 180 is required. With appropriate design, the column orientation can be recorded with low thermal load. No complex antenna-based systems are required for this, so that no regulatory problems arise, e.g. with RFID. Optionally, a temperature sensor can be added to the column 30 or to the sliding element 150.

5 shows a temperature control chamber 120 of an analysis device 10 with four sample separation devices 1 to 4 and four fluid temperature control devices 110-1 to 110-4, according to an exemplary embodiment of the invention. This embodiment is similar to that of 2 , wherein additionally each sample separation device 30 is fluidically coupled to a corresponding fluid temperature control device 110.

The functional element 1 has a sample separation device 30 which is coupled to a temperature sensor 131. In addition, the first functional element 1 in this example has a fluid temperature control device 110-1 for pre-temperature control of a fluid upstream of the sample separation device 30. The fluid temperature control device 110-1 is also coupled to a temperature sensor 111. Furthermore, the sample separation device 30 is fluidly coupled to the fluid temperature control device 110 and the fluid temperature control device 110 is arranged upstream in the fluid flow direction with respect to the sample separation device 30 net. Such an arrangement can be made, for example, by means of the for 3 and 4 Sliding element arrangements 100 described can be realized.

The other functional elements 2 to 4 are constructed in the same way as the functional element 1, i.e. in each case a sample separation device 2 to 4 is coupled to a corresponding fluid temperature control device 110-2 to 110-4. The sample separation devices 1 to 4 are each via the fluid temperature control devices 110-1 to 110-4 (eg as in the 3 and 4 shown) coupled to the switching valve 35. The configuration, for example, of the first of the functional elements 1 can now be determined, for example, as follows:

The operating state is changed by heating or cooling the temperature control chamber 120 and flowing a fluid through the first functional element 1. The temperatures (as parameters) relating to the fluid temperature control devices 110-1 to 110-4 of the functional elements 1 to 4 are determined by means of corresponding temperature sensors 111, 131.

The results are compared to determine which temperature measurement of the fluid temperature control devices 110-1 to 110-4 has the largest difference (temperature delta) compared to the others. The connection of the functional element 1 can be determined/verified accordingly.

Reference symbols

1

functional element

2-4

Another functional element

10

Analysis device

20

Fluid propulsion

25

Feeding device

27

Degasser

30

Sample separation device

31

inlet

32

outlet

35

Fluid valve

40

injector

50

detector

60

fractionator

70

Control device

100

Sliding element arrangement

110

Fluid temperature control device

111

First temperature sensor

120

Temperature chamber, column oven

130

Connection element

131

Second temperature sensor

150

Sliding element

180

Day

181

Electrical contact area

182

Contact pin

S

Sliding direction

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 (19)

A computer-implemented method for determining a configuration of a functional element (1) in an analysis device (10), the method comprising: Changing an operating state of the analysis device (10), in particular with regard to the functional element (1); Detecting a change in a parameter, in particular with regard to the functional element (1), as a result of the changed operating state; and Determining the configuration of the functional element (1) in the analysis device (10) based on the detected change in the parameter. The procedure according to Claim 1 , wherein determining the configuration comprises at least one of the following with respect to the configuration: verifying, identifying, mapping, assigning. The procedure according to Claim 1 or 2 , wherein the configuration has at least one of the following: an, in particular fluid, interconnection of the functional element (1), an interconnection of the functional element (1) with respect to a flow path, an interconnection of the functional element (1) with respect to a fluid valve (35), a position, in particular within the analysis device (10), of the functional element (1), a position of the functional element (1) relative to a further functional element (2, 3, 4). The method according to any one of the preceding claims, wherein the configuration relates to a fluidic connection between a fluid valve (35) and a sample separation device (30). The method according to any one of the preceding claims, wherein changing the operating state of the analysis device (10) comprises at least one of the following: heating, in particular of a temperature control chamber (120), cooling, in particular of the temperature control chamber (120), providing a fluid flow, in particular by means of a heated or cooled fluid, heating by means of a fluid flow, cooling by means of a fluid flow. The method according to one of the preceding claims, wherein the functional element (1) has at least one of the following: a sample separation device (30), in particular a chromatographic separation column; a fluid path, in particular at least one of a capillary, a conduit, a channel, a fluid line; a fluid valve (35), in particular a rotary valve or a shear valve. The method according to any one of the preceding claims, wherein the parameter relates to at least one of the following: a temperature, a pressure, a flow rate, a mass flow, a conductivity, a density, a volume, a weight. The method according to any one of the preceding claims, further comprising: Using a sensor device (111, 131) that is associated with the functional element (1) and/or the further functional element (2, 3, 4), in particular at least one of a temperature sensor, a pressure sensor, a flow sensor, a conductivity sensor, a weighing device, a thermal camera, a sensor for electromagnetic waves, in particular an IR sensor. The method according to one of the preceding claims, further comprising at least one of the following features: wherein the comparison is carried out based on absolute measured values or relative measured values; wherein the method is non-invasive with respect to the analysis device (10); using existing equipment for the process; wherein the method is performed substantially freely by a human operator; wherein the method is carried out remotely with respect to the analysis device (10); wherein the functional element (1) is coupled into a fluid path. A device for data processing that has a processor and the method is set up according to any of the Claims 1 until 9 to carry out. An analysis device (10) for carrying out an analysis method, the analysis device (10) being a device for data processing according to Claim 10 having. The analysis device (10) according to Claim 11 , comprising: a temperature control chamber (120) for receiving and/or temperature control of the functional element (1) and/or the further functional element (2, 3, 4). The analysis device (10) according to Claim 11 or 12 , wherein the functional element (1) has: a sample separation device (30), in particular which is associated with a first sensor device (131); a fluid temperature control device (110), for pre-temperature control of a fluid upstream of the sample separation device (30), in particular which is associated with a second sensor device (111), wherein the sample separation device (30) is fluidically coupled to the fluid temperature control device (110). is, and wherein the fluid temperature control device (110) is arranged upstream in the fluid flow direction with respect to the sample separation device (30). The analysis device (10) according to one of Claims 11 until 13 , further comprising: a sliding element (150), which is coupled to the sample separation device (30) and / or the fluid temperature control device (110), and is set up when the sample separation device (30) and the fluid temperature control device (110) are moved. together into a position with respect to the analysis device (10), in particular with respect to the temperature control chamber (120) of the analysis device (10). The analysis device (10) according to Claim 14 , wherein the sliding element (150) further comprises: a first major surface adapted to couple the sample separation device (30); and/or a second main surface that is set up for coupling the fluid temperature control device (110); and/or wherein the first main surface is arranged opposite the second main surface. The analysis device (10) according to one of Claims 11 until 15 , wherein the device for data processing is set up to: change the operating state, in particular heating or cooling the temperature control chamber (120) and / or flow through the first functional element (1) at least partially with a fluid, first detecting the parameter, in particular the temperature, with respect to, in particular the fluid temperature control device (110), the functional element (1), second detecting the parameter, in particular the temperature, with respect to, in particular a further fluid temperature control device, the further functional element (2, 3, 4), comparing the results of the first detection and second detecting and determining the configuration of the functional element (1) in the analysis device (10) based on the comparing. The analysis device (10) according to one of Claims 11 until 16 , wherein the data processing device is set up to: change the operating state, in particular flow through the first functional element (1) at least partially with a fluid, first detect the parameter, in particular the temperature, with respect to, in particular the fluid temperature control device (110), the functional element ( 1), second detecting the parameter, in particular the temperature, with respect to, in particular, the sample separation device (30), the functional element (1), comparing the results of the first detection and the second detection, and determining the configuration of the functional element (1) in the analysis device (10) based on comparing. The analysis device (10) according to one of the Claims 13 until 17 , further comprising: a tag (180) which is associated with the sample separation device (30), in particular with the sample separation device direction (30), in particular wherein the tag has at least one of an NFC tag, an RFID tag, a Bluetooth tag; and/or a tag reader which is associated with the analysis device (10), in particular the sliding element (150), in particular wherein the tag reader has at least one of an NFC tag reader, an RFID tag reader, a Bluetooth tag -Reader; in particular, wherein the tag (180) and the tag reader are arranged so that they can communicate with one another. The analysis device (10) according to one of the Claims 11 until 18 , 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.