Column device

Abstract

To provide a column device for an automatic analyzer and an automatic analyzer comprising a column device.SOLUTION: An automatic analyzer 100 comprises a high performance liquid chromatography (HPLC) module 102. The HPLC module comprises a fixation device 104 configured to automatically fix and release a chromatographic column 106. The column device comprises a column jacket and a capillary. The capillary comprises a predetermined dimensional shape and is arranged inside the column jacket. The column device is configured to be installed at the HPLC module 102 by the fixation device 104.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a column device for an automatic analyzer and an automatic analyzer equipped with the column device. [Background technology]

[0002] The automated analyzer is configured to obtain measurements from a sample. The automated analyzer is operable to reveal parameter values ​​of the sample or its components through various chemical, biological, physical, optical or other technical procedures. The automated analyzer may be operable to measure said parameters of the sample or at least one analyte and return the obtained measurements. The analytical results returned by the analyzer include, but are not limited to, the concentration of the analyte in the sample, a digital (yes or no) result representing the presence of the analyte in the sample (corresponding to a concentration above the detection level), optical parameters, data obtained from DNA or RNA sequencing, mass spectrometry of proteins or metabolites, and various types of physical or chemical parameters. The automated analyzer may comprise units that assist in pipetting, metering and mixing of samples and / or reagents.

[0003] Automated analyzers may include processing and detection systems whose workflow is optimized for a particular type of analysis. Examples of such analyzers are clinical chemistry analyzers, coagulation chemistry analyzers, immunochemistry analyzers, urine analyzers, nucleic acid analyzers, and mass spectrometers that are used to detect the outcome of a chemical or biological reaction or to monitor the progress of a chemical or biological reaction.

[0004] Such automated analyzers make it possible to increase the analytical process and the number of obtainable measurements. For this reason, such automated diagnostic analyzers use several processing stations to simultaneously process several samples prepared in reaction vessels. For example, there are 2 to 8 or even more different processing stations in such automated analyzers to prepare, process and analyze each sample.

[0005] One of the processing stations of the automated analyzer may be a high performance liquid chromatography (HPLC) module coupled to a detection unit. The detection unit may be, for example, UV, chemiluminescence, electrochemiluminescence, mass spectrometry, or other suitable detector. HPLC is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on a pump to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid sorbent. Each component in the sample interacts slightly differently with the sorbent, resulting in separation of the components as the adsorption time in the column material differs for different components, causing them to flow out of the column at different times. Identification and quantification of the separated components is performed by one or more detectors placed downstream of the column.

[0006] In HPLC applications, the HPLC system itself (without the separation column) can be tested for chromatographic performance not due to the column using a dispersion test case for possible instrument-dependent peak broadening, tested to check the system volume from pump to detector and from injector to detector, and also tested for system leaks not due to the column. To do so, an inert analyte that is not retained on any surface in the system is injected and detected. A connecting capillary is introduced to check if the pump can operate within specifications such as the optimum pressure operating range. The back pressure of this capillary compensates for the drop in system back pressure without the column.

[0007] This procedure entails several drawbacks: The user must manually change the configuration of the system by removing columns and installing additional capillaries to bypass the columns. This process requires tools. It is a manual process that is prone to errors. Only an expert can avoid dead volumes in the system. The capillary volumes and backpressures are prone to errors due to manufacturing tolerances and the manual installation process. Analysis of experimental data requires skilled personnel, is time consuming and prone to errors. The user must select (if any) or fabricate the optimal capillary with the appropriate dimensions for each dedicated LC flow path. Summary of the Invention [Problem to be solved by the invention]

[0008] The disclosed embodiments of the column device aim to at least reduce or overcome these drawbacks, and in particular to provide a defined measurement tool that is not dependent on column performance. [Means for solving the problem]

[0009] Embodiments of the disclosed column device and automated analyzer have the features of the independent claims. Advantageous embodiments, which may be realized in either a single aspect or in any combination, are set out in the dependent claims as well as in the entire specification.

[0010] When used below, the terms "have", "comprise" or "include" or any grammatical variants thereof are used in a non-exclusive manner. These terms may therefore refer both to the situation in which the entity described in this context has no further features other than those introduced by these terms, and to the situation in which one or more further features are present. As an example, the expressions "A has B", "A comprises B" and "A includes B" may all refer to the situation in which, apart from B, no other elements are present in A (i.e., A consists solely and exclusively of B), as well as to the situation in which, apart from B, one or more further elements are present in entity A, such as element C, elements C and D, or even further elements.

[0011] Furthermore, it should be noted that the terms "at least one" or "one or more" or similar expressions indicating that a feature or element may be present one or more times are typically used only once when introducing each feature or element. In the following, in most cases, when referring to each feature or element, the expressions "at least one" or "one or more" will not be repeated, despite the fact that each feature or element may be present one or more times.

[0012] Furthermore, when used below, the terms "preferably", "more preferably", "particularly", "more particularly", "particularly", "more particularly" or similar terms are used in conjunction with any feature without limiting the possibility of substitution. Thus, the features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. The present invention may be implemented by using alternative features, as understood by those skilled in the art. Similarly, features introduced by the phrase "in an embodiment of the invention" or similar phrases are intended to be optional features and do not entail any limitations with respect to alternative embodiments of the invention, any limitations with respect to the scope of the invention, and any limitations with respect to the possibility of combining the features introduced in such a way with other optional or non-optional features of the invention.

[0013] According to a first aspect of the present disclosure, a column device for an automated analyzer is disclosed. The automated analyzer includes a high performance liquid chromatography (HPLC) module. The HPLC module includes a fixing device configured to automatically fix and release a chromatography column. The column device includes a column jacket and a capillary tube. The capillary tube has a predetermined geometry and is disposed or located within the column jacket. The column device is configured to be installed in the HPLC module by the fixing device.

[0014] Thus, a defined measurement tool is provided. It consists of a dummy column mimic with a capillary tube built in rather than a column. It is configured to be used similarly to the chromatographic columns used in automatic analyzers. In particular, the fixing device is an automatic device, not a manual device, and therefore simple and tool-free. Any field service engineer or even a user can easily install the column device to allow the system to perform self-checks automatically. Since the pump can be run in a specified pressure range without a column, it is possible to perform automatic self-checks that include analysis of the data and a determination of the reliability of the chromatographic performance not due to the column, checks of the system volume from the pump to the detector and from the injector to the detector, as well as pump characteristics such as the accuracy and precision of the mixing, using a dispersion test case for possible instrument-dependent peak broadening.

[0015] The term "automated analyzer" as used herein is a broad term and should be given its common and ordinary meaning to one of skill in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, any device or device component operable to perform one or more processing / workflow steps on one or more chemical and / or biological samples. Thus, the term "processing step" refers to a processing step that is physically performed, such as centrifugation, splitting, sample analysis, etc. The term "analyzer" also encompasses pre-analytical sample work cells, post-analytical sample work cells, and analytical work cells. Examples of automated analyzers are, but are not limited to, clinical chemistry analyzers, coagulation chemistry analyzers, immunochemistry analyzers, urine analyzers, and nucleic acid analyzers that are used to detect the results of or monitor the progress of chemical or biological reactions. One of the processing stations of an automated analyzer is an HPLC module.

[0016] The term "High Performance Liquid Chromatography (HPLC) module" as used herein is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, an instrument, equipment, or device configured to separate, identify, and quantify each component in a mixture. The term is used synonymously with the term "HPLC instrument." It relies on a pump to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid sorbent. Each component in the sample interacts slightly differently with the sorbent, resulting in different flow rates for the different components, resulting in the separation of the components as they exit the column. HPLC can be used for manufacturing purposes (e.g., in pharmaceutical and biological product manufacturing processes), legal purposes (e.g., detection of performance enhancing drugs in urine), research purposes (e.g., separating components of complex biological samples or similar synthetic chemicals from each other), and medical purposes (e.g., detection of vitamin D levels in serum). Chromatography can be described as a mass transfer process involving adsorption. HPLC relies on pumps to pass pressurized liquid and sample mixtures through columns filled with sorbents, resulting in separation of the sample components. The sorbents, the active components of the columns, are typically granular materials made of solid particles (e.g., silica, polymers, etc.) with sizes ranging from 2 to 50 μm. Components of the sample mixture are separated from each other due to their differing degrees of interaction with the sorbent particles. The pressurized liquid is typically a mixture of solvents (e.g., water, acetonitrile, and / or methanol) and is called the "mobile phase". Its composition and temperature play a major role in the separation process by influencing the interactions that occur between the sample components and the sorbent. These interactions are physical in nature, such as hydrophobic (dispersive), dipole-dipole, and ionic, and are most often combinations. HPLC is distinguished from conventional ("low pressure") liquid chromatography because of its significantly higher operating pressures (50-350 bar), whereas conventional liquid chromatography typically relies on gravity to pass the mobile phase through the column.Due to the small amount of sample separated in analytical HPLC, typical column dimensions are 2.1-4.6 mm in diameter and 30-250 mm in length. HPLC columns are also fabricated with smaller sorbent particles (average particle size 2-50 μm). This gives HPLC superior resolution (ability to distinguish compounds) when separating mixtures, and thus HPLC has become a common chromatographic technique. An overview of an HPLC module or HPLC instrument typically includes a degasser, a sampler, a pump, and a detector. The sampler brings the sample mixture into a mobile phase stream that carries the sample mixture into the column. The pump delivers the desired flow and composition of the mobile phase through the column. The detector generates a signal proportional to the amount of sample component coming out of the column, thus allowing quantitative analysis of the sample components. A digital microprocessor and user software controls the HPLC module and provides data analysis. Some types of mechanical pumps in the HPLC module can mix multiple solvents together in time-varying ratios to create a composition gradient in the mobile phase. A variety of detectors are commonly used, such as UV / Vis, photodiode array (PDA), or mass spectrometry based detectors. Most HPLC instruments further have a column oven that allows adjustment of the temperature at which the separation takes place.

[0017] The principle of operation is as follows: The sample mixture to be separated and analyzed is introduced in discrete small volumes (typically a few microliters) into a stream of mobile phase that permeates through the column. The components of the sample migrate through the column at different rates that are a function of their specific physical interactions with the adsorbent (also called the stationary phase). The rate of each component depends on its chemical nature, the nature of the stationary phase (column), and the composition of the mobile phase. The time at which a particular analyte elutes (comes out of the column) is called its retention time. The retention time measured under specific conditions is the identifying characteristic of a given analyte. Many different types of columns are available, packed with adsorbents of different particle sizes and surface properties ("surface chemistry"). The use of smaller particle size packing materials requires the use of higher operating pressures ("back pressure") and typically improves chromatographic resolution (the degree of separation of peaks between successive analytes coming out of the column). Adsorbent particles may be hydrophobic or polar in nature. Common mobile phases used include any miscible combination of water and various organic solvents (acetonitrile and methanol being the most common). Some HPLC techniques use anhydrous mobile phases (see normal phase chromatography below). The aqueous component of the mobile phase may contain acids (e.g., formic acid, phosphoric acid, or trifluoroacetic acid) or salts to aid in the separation of the sample components. The composition of the mobile phase may be kept constant ("isocratic elution mode") or may vary ("gradient elution mode") during the chromatographic analysis. Isocratic elution is typically useful for the separation of sample components with very different affinities for the stationary phase. In gradient elution, the composition of the mobile phase typically changes from low to high elution strength. The elution strength of the mobile phase is reflected by the retention time of the analytes, with high elution strength resulting in fast elution (=shorter retention time). A typical gradient profile in reversed-phase chromatography might begin with 5% acetonitrile (in water or aqueous buffer) and progress linearly to 95% acetonitrile over 5-25 min. A period during which the composition of the mobile phase is constant may also be part of any gradient profile.For example, the composition of the mobile phase may be kept at 5% acetonitrile for 1-3 minutes and then changed linearly to 95% acetonitrile. The composition selected for the mobile phase (also called the eluent) depends on the strength of the interactions (e.g., hydrophobic interactions in reversed-phase HPLC) between the various sample components ("analytes") and the stationary phase. Depending on their affinity for the stationary and mobile phases, the analytes are partitioned between the two during a partitioning process that occurs in the column. This partitioning process is similar to that occurring during liquid-liquid extraction, but is continuous rather than stepwise. In this example, using a water / acetonitrile gradient, the more hydrophobic components elute (come out of the column) later as the mobile phase becomes more concentrated in acetonitrile (i.e., the mobile phase of higher elution strength). The choice of mobile phase components, additives (such as salts or acids), and gradient conditions depend on the nature of the column and sample components. Often, a series of trials is performed with the sample to find an HPLC method that results in a suitable separation.

[0018] The term "chromatography column" as used herein is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but not be limited to, refer to a tubular device used with an HPLC module. Inside this tubular device, a material called the stationary phase is fixed. Chromatography columns are used to separate the components of a mixture. The mixture is dissolved in a fluid called the mobile phase, which carries the mixture through the column. Different components of the mixture have different affinities for the stationary phase. Different molecules will remain on the stationary phase longer or for a shorter period of time depending on their interactions with the surface sites of the stationary phase. Thus, they move at different apparent velocities in the moving fluid and their separation occurs. Separation is based on differential partitioning between the mobile phase and the stationary phase. Small differences in the partition coefficients of compounds result in differential retention in the stationary phase and thus affect the separation. While small scale columns range from 0.5 cm internal diameter and pressure resistance up to 130 MPa, large scale industrial columns reach diameters up to 2 m and operate at much lower pressures (less than 1 MPa). Although it is preferable to observe the packed bed of the column, large scale columns are manufactured from steel due to its superior elasticity.

[0019] The term "fixing device" as used herein is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but not exclusively, refer to any device configured to releasably fix a chromatography column to a target position in an HPLC module. The term may more specifically refer to a device that fixes a chromatography column to a target position in an HPLC module automatically, i.e., without manual support, with the aid of a motor, actuator, or any other servo device.

[0020] The term "column jacket" as used herein is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, a cover or enclosure for the core or interior of a column apparatus. The column jacket may be made of a solid material. The solid material may be an elastic or rigid material. The column jacket may have insulating properties.

[0021] The term "capillary" as used herein is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, a tubular device having a fairly small inner diameter. Its length is usually significantly greater than the inner diameter, such as 5, 10, 20, or more times.

[0022] The term "geometry" as used herein is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, the size or geometric geometry of a capillary. In chromatography, geometry is used to define a capillary because devices of the same volume but different geometry can result in significant changes in separation behavior. Thus, geometry includes, among other things, the length, inner diameter, internal volume, orientation, expansion, and cross-sectional shape of the capillary.

[0023] The predetermined dimensions may include an internal volume and / or a back pressure. Thus, the dimensions of the column device can be appropriately adjusted so that its behavior is known and predictable. In particular, the capillary may be a so-called restrictive capillary that provides a predetermined back pressure, but may also define an internal volume for the analyte or mobile phase flowing therethrough.

[0024] The column device may have the same external dimensions as a chromatography column that can be used in an HPLC module, and therefore the column device may be easily integrated into the HPLC module.

[0025] The capillary may have an inner diameter of 1 μm to 1000 μm, and therefore has an inner diameter that exhibits good flow characteristics for self-checking of the HPLC module.

[0026] The capillary tube may have a length of 10 mm to 50 mm, and therefore has a length that exhibits good flow characteristics for self-checking of the HPLC module.

[0027] The column device according to any one of the preceding claims, further comprising at least one guide element configured for inserting the column device into the fixation device. For example, the guide element may enable the insertion of the column device by hard-coding a supported insertion in the fixation device. Thus, the column device may be accurately inserted into the fixation device such that the final or insertion position of the column device is fixed without variation.

[0028] The term "guiding element" as used herein is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, any device or element configured to allow a column device to be moved to a target position within or on a fixture. The guiding element may comprise a rail or groove, or the like.

[0029] A guide element may be located on the outer surface of the column jacket, which facilitates the insertion of the column device.

[0030] The column device may further comprise an RFID tag, which contains information about the column type, the manufacturing lot, and optionally the reference value and / or correction factor of the capillary. Thus, an automated analyzer may automatically receive the technical data about the column device by reading the RFID tag with an RFID reader.

[0031] The RFID tag may be configured to automatically, preferably fully automatically, trigger or enable the diagnostic process of the HPLC module. Thus, as soon as the column device is inserted into the fixture and the information from the RFID tag is read, the diagnostic process of the HPLC module may be started without requiring extensive preparation by the user. For example, the diagnostic process may be started automatically after the column device is inserted into the fixture and the information from the RFID tag is read, or may be started by a confirmation command from the user.

[0032] The column device may further comprise a human readable label containing information regarding the capillary tube, allowing a user to easily identify technical data regarding the column device.

[0033] In a second aspect, an automated analyzer is disclosed. The automated analyzer comprises a high performance liquid chromatography (HPLC) module. The HPLC module comprises a fixing device configured to automatically fix and release a chromatography column, and a column device according to any one of the preceding or following embodiments. The automated analyzer is configured to perform a diagnostic process of the HPLC module with the column device fixed by the fixing device.

[0034] The pump may be configured to provide a flow of inert analyte and inject it through a capillary. Such inert analyte is not retained on any surface in the system and is detectable. The capillary is introduced to check that the pump can function within its specifications. The back pressure of this capillary compensates for the drop in system back pressure without the chromatography column. In particular, the flow may be adjusted by the amount of inert analyte injected, which may depend on the time the inert analyte is injected.

[0035] The term "inert analyte" as used herein is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, any analyte that is not retained by any surface within the HPLC module and is detectable by a detector of the HPLC module. In other words, an inert analyte is not adsorbed or attached to any surface within the HPLC module and is detectable by a detector of the HPLC module.

[0036] The automated analyzer may be configured to perform the diagnostic process fully automatically when triggered by the column device, and thus may perform a self-check of the HPLC module without the need for any process steps performed by the user.

[0037] The term "diagnostic process" as used herein is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but not exclusively, refer to the identification of the nature and cause of a particular phenomenon. In the field of the present disclosure, it is typically used to determine the cause, alleviation, and solution of a symptom. The term may more specifically refer to any process configured to check the operating characteristics or condition of an HPLC module.

[0038] The column device may be equipped with an RFID tag, and the automatic analyzer may further be equipped with an RFID reader and may be configured to execute a diagnostic process of the HPLC module when it identifies the RFID tag. Thus, as soon as the column device is inserted into the fixed device and the information from the RFID tag is read, the diagnostic process of the HPLC module may be started without requiring extensive preparation by the user. For example, the diagnostic process may be started automatically after the column device is inserted into the fixed device and the information from the RFID tag is read, or may be started by a confirmation command from the user.

[0039] The type of diagnostic process may depend on the information stored in the RFID tag, and thus, depending on the information stored in the RFID tag, different diagnostic processes may be initiated and different diagnostic results may be revealed.

[0040] The automated analyzer may further comprise a display device configured to display information to a user according to the information stored in the RFID tag. Thus, the user may also read the information stored in the RFID tag. This may also assist the operator by providing information about the equipment and guidance on required actions such as maintenance.

[0041] The automated analyzer may be configured to trigger predefined operations of the HPLC module, in particular to free up the HPLC module for routine operations, to trigger maintenance of the HPLC module, and to trigger predictive maintenance of the HPLC module, thus providing a user-friendly automated process for checking the HPLC module.

[0042] The automated analyzer may be configured to automatically evaluate the diagnostic data obtained from the diagnostic process, thus automatically providing information to a user regarding the status of the HPLC module.

[0043] The diagnostic data may include information regarding at least one item selected from the group consisting of pressure, chromatographic behavior, peak dispersion, flow-through time, flow rate, contamination source, carryover or artifact peaks on a chromatographic column, HPLC module delay, HPLC module injector performance, HPLC module pump performance, HPLC module detector module performance, baseline noise, and drift, and may thus provide a variety of interesting information.

[0044] The fixture may be a tool-free device, such as a click-in device, and is therefore easy to operate and less prone to errors due to variability in the installation process of the column device.

[0045] The diagnostic process may be a computer-implemented method, for example, an automated analyzer may be equipped with an input device such as a keyboard that allows a user to enter an initiation or confirmation command to initiate a diagnosis performed under the control of the automated analyzer computer.

[0046] A computer program is further disclosed and proposed, which includes computer executable instructions for performing the operating method according to the present disclosure in one or more of the embodiments contained herein when the program is executed on a computer or a computer network. In particular, the computer program may be stored on a computer readable data carrier and / or a computer readable storage medium.

[0047] As used herein, the terms "computer-readable data carrier" and "computer-readable storage medium" may specifically refer to non-transitory data storage means such as hardware storage media that store computer-executable instructions. A computer-readable data carrier or storage medium may specifically be or include a storage medium such as a random access memory (RAM) and / or a read-only memory (ROM).

[0048] Thus, in particular, one, more than one or all of the method steps as described above may be carried out using a computer or a computer network, preferably using a computer program.

[0049] Further disclosed and proposed herein is a computer program product having program code means for carrying out the method according to the invention in one or more of the embodiments contained herein when the program is executed on a computer or a computer network. In particular, the program code means may be stored on a computer readable data carrier and / or a computer readable storage medium.

[0050] Further disclosed and proposed herein is a data carrier having stored thereon a data structure capable of performing the methods according to one or more of the embodiments disclosed herein after being loaded into a computer or computer network, such as into a working or main memory of the computer or computer network.

[0051] Further disclosed and proposed herein is a computer program product having program code means stored on a machine-readable carrier for carrying out the method according to one or more of the embodiments disclosed herein when the program is executed on a computer or computer network. As used herein, a computer program product refers to a program as a tradeable product. The product may generally be present in any format, such as a paper format, or may be present on a computer-readable data carrier and / or a computer-readable storage medium. In particular, the computer program product may be distributed via a data network.

[0052] Finally, disclosed and proposed herein is a modulated data signal that includes instructions readable by a computer system or computer network for carrying out a method according to one or more of the embodiments disclosed herein.

[0053] With respect to computer-implemented aspects of the present invention, one or more or all of the method steps of the method according to one or more of the embodiments disclosed herein can be performed by using a computer or a computer network.Thus, in general, any of the method steps including providing and / or manipulating data can be performed by using a computer or a computer network.In general, these method steps can include any method steps, except for those that typically require manual operations, such as providing samples and / or certain aspects of performing actual measurements.

[0054] Specifically, the following is further disclosed herein: - A computer or computer network comprising at least one processor, the processor being configured to execute a method according to one of the embodiments described herein. - a computer-loadable data structure configured, when executed on a computer, to carry out a method according to one of the embodiments described in this specification. - a computer program adapted to carry out the method according to one of the embodiments described herein when said computer program is run on a computer. A computer program comprising program means for carrying out the method according to one of the embodiments described herein when the computer program is run on a computer or on a computer network. A computer program comprising the program means according to the preceding embodiment stored on a computer readable storage medium. - a storage medium storing a data structure, the data structure being configured to perform a method according to one of the embodiments described herein after being loaded into a main memory and / or a working memory of a computer or a computer network. A computer program product comprising program code means storable or stored on a storage medium, which program code means, when executed on a computer or a computer network, performs a method according to one of the embodiments described herein.

[0055] In summary, without excluding further possible embodiments, the following embodiments can be envisaged:

[0056] Embodiment 1: A column apparatus for an automated analyzer, the automated analyzer comprising a high performance liquid chromatography (HPLC) module, the HPLC module comprising a fixing device configured to automatically fix and release a chromatography column, the column apparatus comprising a column jacket and a capillary tube, the capillary tube having a predetermined dimension and disposed within the column jacket, the column apparatus configured to be installed in the HPLC module by the fixing device.

[0057] Embodiment 2: The column device of embodiment 1, wherein the predetermined dimensions include an internal volume and / or a back pressure.

[0058] Embodiment 3: The column device according to embodiment 1 or 2, wherein the column device has the same external dimensions as a chromatography column that can be used with the HPLC module.

[0059] Embodiment 4: The column device according to any one of embodiments 1 to 3, wherein the capillary has an inner diameter of 1 μm to 1000 μm.

[0060] Embodiment 5: The column device according to any one of embodiments 1 to 4, wherein the capillary has a length of 10 mm to 50 mm.

[0061] Embodiment 6: A column device according to any one of embodiments 1 to 5, further comprising at least one guiding element configured for inserting the column device into the fixation device.

[0062] Embodiment 7: The column apparatus of embodiment 6, wherein the guide element is disposed on the outer surface of the column jacket.

[0063] Embodiment 8: A column device according to any one of embodiments 1 to 7, further comprising an RFID tag, said RFID tag including information regarding the type of column, the manufacturing lot, and optionally a reference value and / or a correction factor for said capillary.

[0064] Embodiment 9: A column device according to embodiment 8, wherein the RFID tag is configured to automatically, preferably fully automatically, trigger or enable a diagnostic process of the HPLC module.

[0065] Embodiment 10: A column device according to any one of embodiments 1 to 9, further comprising a human-readable label containing information relating to said capillary tube.

[0066] Embodiment 11: An automated analyzer comprising a high performance liquid chromatography (HPLC) module having a fixing device configured to automatically fix and release a chromatography column, and a column device described in any one of embodiments 1 to 10, wherein the automated analyzer is configured to perform a diagnostic process of the HPLC module with the column device fixed by the fixing device.

[0067] Embodiment 12: The automated analyzer of embodiment 11, wherein the automated analyzer is configured to provide and inject a flow of an inert analyte through the capillary tube.

[0068] Embodiment 13: The automated analyzer of embodiment 11 or 12, wherein the automated analyzer is configured to perform the diagnostic process fully automatically when triggered by the column device.

[0069] Embodiment 14: The automated analyzer of embodiment 13, wherein the column device is equipped with an RFID tag, and the automated analyzer further comprises an RFID reader and is configured to execute the diagnostic process of the HPLC module upon identifying the RFID tag.

[0070] Embodiment 15: The automated analyzer of embodiment 14, wherein the type of diagnostic process is dependent on the information stored in the RFID tag.

[0071] Embodiment 16: An automated analyzer according to any one of embodiments 13 to 15, further comprising a display device configured to display information to a user according to the information stored in the RFID tag.

[0072] Embodiment 17: The automated analyzer of any one of embodiments 11 to 16, wherein the automated analyzer is configured to trigger a predetermined operation of the HPLC module, in particular to release the HPLC module for routine operations, to trigger maintenance of the HPLC module, and to trigger predictive maintenance of the HPLC module.

[0073] Embodiment 18: An automated analyzer according to any one of embodiments 11 to 17, wherein the automated analyzer is configured to automatically evaluate diagnostic data obtained from the diagnostic process.

[0074] Embodiment 19: The automated analyzer of embodiment 18, wherein the diagnostic data includes information regarding at least one item selected from the group consisting of pressure, chromatographic behavior, peak dispersion, flow-through time, flow rate, source of contamination, carryover or artifact peaks on the chromatographic column, HPLC module delay, performance of the injector of the HPLC module, performance of the pump of the HPLC module, performance of the detector module of the HPLC module, baseline noise, and drift.

[0075] Embodiment 20: The automated analyzer according to any one of embodiments 11 to 19, wherein the fixing device is a tool-free device. [Brief description of the drawings]

[0076] Further optional features and embodiments are disclosed in more detail in the following description of the embodiments, preferably in conjunction with the dependent claims. Here, each optional feature may be realized in an independent manner or in any possible combination, as understood by a person skilled in the art. The scope of the present invention is not limited by the preferred embodiments. The embodiments are illustrated diagrammatically in the drawings, where the same reference numbers in these figures refer to the same or functionally equivalent elements.

[0077] [Figure 1] 1 shows a schematic diagram of an automated analyzer according to an embodiment of the present disclosure. [Diagram 2] 1 shows a cross-sectional view of a chromatography column. [Diagram 3] 1 shows a cross-sectional view of a column apparatus. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0078] 1 shows a schematic diagram of an automated analyzer 100 according to an embodiment of the present disclosure. The automated analyzer 100 includes a high performance liquid chromatography (HPLC) module 102. The HPLC module includes a locking device 104 configured to automatically lock and release a chromatography column 106. For example, the locking device 104 may include a gripping device or a pair of flanges that can move toward and away from each other to releasably lock the chromatography column 106. The locking device 104 may be a tool-free device, such as a click-in device.

[0079] The automated analyzer 100 further comprises a computer 108 including a processing unit configured to control the operation of the automated analyzer 100 and its components. For example, the securing and releasing operations of the securing device 104 may be under the control of the computer 108. The securing device 104 may be operated by an input device of the computer 108, such as a keyboard or a graphical interface, or the securing device 104 may be operated by a separate device that allows a user to input commands, such as one or more buttons. The automated analyzer 100 further comprises an RFID reader 110. The RFID reader 110 is positioned adjacent or in close proximity to the securing device 104. This allows the RFID reader 110 to read RFID tags in its vicinity.

[0080] The automated analyzer 100 further includes a display device 112 .

[0081] FIG. 2 shows a cross-sectional view of a chromatography column 106 that can be used with the automated analyzer 100. The cross-section is taken along the length of the chromatography column 106. The chromatography column 106 has a circular cross-section. The chromatography column 106 is filled with a sorbent 114 that provides separation of sample components of a sample flowing through the chromatography column 106. The sorbent 114, which is the active component of the chromatography column 106, is typically a granular material made of solid particles (e.g., silica, polymers, etc.) with sizes between 2 and 50 μm. The components of the sample mixture are separated from each other due to different degrees of interaction with the sorbent particles. The pressurized liquid is typically a mixture of solvents (e.g., water, acetonitrile, and / or methanol) and is called the mobile phase. As described above, the chromatography column 106 may be installed in the HPLC module 102 by a fixing device 104.

[0082] 3 illustrates a cross-sectional view of a column apparatus 116. As described in further detail below, the column apparatus 116 is configured for use with an HPLC module 102 of an analytical analyzer 100. The column apparatus 116 includes a column jacket 118 and a capillary tube 120 disposed within the column jacket 118. The capillary tube 120 includes an inner diameter 122 between 1 μm and 1000 μm. The capillary tube 120 includes a length 124 between 10 mm and 50 mm. The capillary tube 120 includes predetermined dimensions. The predetermined dimensions include an internal volume and / or a back pressure.

[0083] The column device 116 is configured to be installed in the HPLC module 102 by the fixing device 104. To this end, the column device 116 has the same external dimensions as a chromatography column 106 that can be used with the HPLC module 102, such as the chromatography column 106 shown in FIG. 2. To facilitate the installation of the column device 116 in the HPLC module 102, the column device 116 further comprises at least one guiding element 126 configured to insert the column device 116 into the fixing device 104. The guiding element 126 is arranged on an outer surface 128 of the column jacket 118.

[0084] The column device 116 further comprises an RFID tag 130. The RFID tag 130 contains information about the type of column, the manufacturing lot, and optionally reference values ​​and / or correction factors for the capillary tube 120. The RFID tag 130 is configured to automatically, preferably fully automatically, trigger or enable a diagnostic process of the HPLC module 102. The RFID tag 130 may be provided on the outer surface 128 of the column jacket 118 so that the RFID tag 130 and the information stored therein can be read by the RFID reader 110 of the automated analyzer 100. The column device 116 may optionally further comprise a human-readable label 132 containing information about the capillary tube 120, such as the dimensions and shape of the capillary tube 120.

[0085] The automated analyzer 100 is configured to execute the diagnostic process of the HPLC module 102 with the column device 116 fixed by the fixing device 104. In other words, the automated analyzer 100 is configured to execute the diagnostic process of the HPLC module 102 when the column device 116 is inserted into the fixing device 104. The automated analyzer 100 is configured to execute the diagnostic process fully automatically when triggered by the column device 116. The automated analyzer 100 is configured to execute the diagnostic process of the HPLC module 102 when the RFID reader 110 identifies the RFID tag 130. The type of diagnostic process is dependent on the information stored in the RFID tag 130. In particular, the automated analyzer 100 is configured to provide and inject a flow of inert test substance through the capillary tube 120. The automated analyzer 100 is further configured to automatically evaluate diagnostic data obtained from the diagnostic process. The diagnostic data includes information regarding at least one item selected from the group consisting of pressure, chromatographic behavior, peak dispersion, flow-through time, flow rate, contamination sources, carryover or artifact peaks on the chromatographic column, HPLC module delay, performance of the injector of the HPLC module 102, performance of the pump of the HPLC module 102, performance of the detector module of the HPLC module 102, baseline noise, and drift. Evaluation of the diagnostic data may be performed by the computer 100 with corresponding software and / or evaluation algorithms.

[0086] The display device 112 is configured to display information to a user according to the information stored on the RFID tag 130. Additionally, the automated analyzer 100 is configured to trigger predetermined actions of the HPLC module 102, such as releasing the HPLC module 102 for routine operations, triggering maintenance of the HPLC module 102, triggering predictive maintenance of the HPLC module 102, etc.

[0087] An example of an automated analyzer 100 and a column device 116 are described in more detail below. It should be noted that the following description is merely an example and does not represent a limitation of the embodiments described herein. The system additional column volume of each of the automated analyzer 100 and the HPLC module 102 may be in the range of 15-30 μL. A column device 116 using a capillary tube 120 having a length 124 of 50 mm and an inner diameter 122 of 100 μm with an inner diameter accuracy of ±10% given by the design of the system has a volume of 0.39 ±0.09 μL and is therefore considered suitable. The volume variation can be easily measured during manufacturing and stored in the RFID tag 130 as a correction factor. This process is believed to facilitate measurements with higher accuracy, if necessary. When the pump operates at the optimal operating pressure, a capillary tube 120 having a length 124 of 50 mm and an inner diameter 122 of 0.04 mm is believed to apply a back pressure of approximately 94 bar. In total, the system or HPLC module 102 is believed to operate between 150-200 bar to promote optimal results. The optimal dimensions of the capillary tube 120 result from standardized components and precisely known liquid chromatography flow paths.

[0088] An example of the operation of the automated analyzer 100 and the column device 116 is described in more detail below. In normal operating conditions, the chromatography column 106 resides in the HPLC module 102 and is held in place by the retaining device 104. When it is intended to check the HPLC module 102, for example for necessary maintenance or routine checks, the user operates the retaining device 104 to release the chromatography column 106. For example, the user enters a command in the computer 108 or presses a button on the retaining device 104. The retaining device 104 opens and the user can remove the chromatography column 106 from the retaining device 104.

[0089] The user then inserts the column device 116 into the fixing device 104, which is facilitated by the guiding element 126. To help the user as to whether it is the correct or intended column device 116, the column device 116 is provided with a label 132 containing information about the capillary tube 120, such as the dimensions and shape of the capillary tube 120, which the user can read. Furthermore, the user operates the fixing device 104 to fix the column device 116. For example, the user enters a command in the computer 108 or presses a button on the fixing device 104. The fixing device 104 is closed and the column device 116 is fixed by the fixing device 104. The RFID reader 110 then reads the RFID tag 130 provided on the outer surface 128 of the column device 116. The reading operation of the RFID reader 110 may be automatically triggered by the fixing operation of the fixing device 104. Alternatively, the read operation of the RFID reader 110 must be triggered by the user entering a command at the computer 108 or by pressing a button on the RFID reader 110 .

[0090] The automated analyzer 100 performs the diagnostic process fully automatically when triggered by the column device 116. In particular, as soon as the RFID reader 110 reads the information stored in the RFID tag 130 of the column device 116, the automated analyzer 100 performs the diagnostic process of the HPLC module 102. As mentioned above, the type of diagnostic process is a function of the information stored in the RFID tag 130. In particular, the automated analyzer 100 is configured to bring about and inject a flow of an inert analyte through the capillary tube 120 for diagnostic purposes. After the diagnostic process, the automated analyzer 100 automatically evaluates the diagnostic data obtained from the diagnostic process. The diagnostic data includes information about at least one item selected from the group consisting of pressure, chromatographic behavior, peak dispersion, flow-through time, flow rate, contamination source, carryover or artifact peaks on the chromatographic column, HPLC module delay, performance of the injector of the HPLC module 102, performance of the pump of the HPLC module 102, performance of the detector module of the HPLC module 102, baseline noise, and drift. The evaluation of the diagnostic data is carried out by the computer 100 equipped with corresponding software and / or evaluation algorithms. Alternatively, the evaluation of the diagnostic data may be performed by an external computer in communication with the automated analyzer 100. [Explanation of symbols]

[0091] 100 automatic analyzer 102 HPLC Module 104 Fixation device 106 Chromatography Columns 108 Computer 110 RFID Reader 112 Display device 114 Adsorbents 116 Column Apparatus 118 Column Jacket 120 Capillary 122 Inner diameter 124 Length 126 Guidance elements 128 External surface 130 RFID tags 132 Label

Claims

1. A column apparatus (116) for an automated analyzer (100), comprising: The automated analyzer (100) comprises a high performance liquid chromatography module (102), The high performance liquid chromatography module (102) comprises a fixing device (104) configured to automatically fix and release a chromatography column (106); The column device (116) comprises a column jacket (118) and a capillary tube (120); The capillary tube (120) has a predetermined dimension and is disposed within the column jacket (118); The column device (116), configured to be mounted in the high performance liquid chromatography module (102) by the fixing device (104).

2. The column apparatus (116) of claim 1, wherein the predetermined dimensions include an internal volume and / or a back pressure.

3. 3. The column device (116) of claim 1 or 2, wherein the column device (116) has the same external dimensions as a chromatography column (106) that can be used with the high performance liquid chromatography module (102).

4. The column device (116) of any one of claims 1 to 3, wherein the capillary (120) has an inner diameter (122) of between 1 μm and 1000 μm.

5. The column device (116) of any one of claims 1 to 4, wherein the capillary tube (120) has a length (124) of between 10 mm and 50 mm.

6. The column device (116) of any one of claims 1 to 5, further comprising at least one guide element (126) configured for inserting the column device (116) into the fixation device (104).

7. The column apparatus (116) of claim 6, wherein the guide element (126) is disposed on an outer surface (128) of the column jacket (118).

8. 8. The column device (116) of claim 1, further comprising an RFID tag (130), the RFID tag (130) containing information regarding the column type, manufacturing lot, and optionally reference values ​​and / or correction factors for the capillary tube (120).

9. a high performance liquid chromatography module (102) comprising a fastening device (104) configured to automatically fasten and release a chromatography column (106); An automated analyzer (100) comprising the column device (116) according to any one of claims 1 to 8, an automated analyzer (100) configured to perform a diagnostic process of the high performance liquid chromatography module (102) with the column device (116) fixed by the fixing device (104);

10. 10. The automated analyzer (100) of claim 9, wherein the automated analyzer (100) is configured to provide and inject a flow of an inert analyte through the capillary tube (120).

11. 11. The automated analyzer (100) of claim 9 or 10, wherein the automated analyzer (100) is configured to perform the diagnostic process fully automatically when triggered by the column device (116).

12. The column device (116) includes an RFID tag (130); 12. The automated analyzer (100) of claim 11, further comprising an RFID reader (110) configured to execute the diagnostic process of the high performance liquid chromatography module (102) upon identifying the RFID tag (130).

13. 13. The automated analyzer (100) of claim 12, wherein the type of diagnostic process is dependent on information stored on the RFID tag (130).

14. The automated analyzer (100) of any one of claims 11 to 13, further comprising a display device configured to display information to a user in response to the information stored in the RFID tag (130).

15. The automated analyzer (100) of any one of claims 9 to 14, configured to trigger predetermined operations of the high performance liquid chromatography module (102), in particular to release the high performance liquid chromatography module (102) for routine work, to trigger maintenance of the high performance liquid chromatography module (102), and to trigger predictive maintenance of the high performance liquid chromatography module (102).

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