Method for calibrating at least one analytical device having a plurality of duplicate hardware components

Abstract

The invention discloses a method for calibrating at least one analytical device (112) having duplicate hardware components. The analytical device (112) comprises a plurality of hardware components (114). The method comprises the following steps: a) providing at least one calibrator sample i having a known target value of the concentration of at least one analyte; b) at least one measurement step, wherein the measurement step comprises performing at least one measurement on the calibrator sample using the analytical device, wherein at least one detector signal s is acquired. ijk , where i=1,…I, I≥2, where i is the number of calibrator samples, j=1,…J, J≥2, where j is the number of hardware components, and k=1,…K ij , K ij ≥1, wherein k refers to the number of repetitions of the measuring step; c) at least one calibration step, wherein the relationship between the detector signal and the concentration of the analyte and / or the detector signal and a theoretical signal value is determined, wherein the calibration step comprises: c.1: providing at least one parameterized function, wherein the parameterized function has a parameter group, wherein the parameter group comprises parameters describing the analyte-specific part of the parameterized function, wherein the parameter group further comprises parameters for adjusting the parameterized function of the hardware component (114); c.2: determining a calibration value by performing a calibration based on the parameterized function; and c.3: determining an analysis function based on an inverse function of the parameterized function and the determined calibration value.

Description

Technical Field

[0001] The invention relates to a method for calibrating at least one analytical device, a device for calibrating at least one analytical device, a computer or a computer network and a computer program. Background Art

[0002] In general, several methods are known for calibrating an analytical device. Specifically, in order to obtain concentration values ​​from an analytical device, the analytical device needs to be calibrated. In particular, a relationship between the raw signal of the analytical device and the concentration needs to be established. To do this, samples with known concentration values, called "calibrators", are measured on the analytical device and a function is fitted to the obtained data.

[0003] Let f be the calibration function:

[0004] f: concentration → signal

[0005] f p (concentration) = signal,

[0006] where p=(p1,p2,…,p n ), n≥l, where n represents the number of parameters in the calibration model, and where p represents the parameters of the calibration function. In general, the more complex the calibration model, the higher the level of calibrators required to establish a complete calibration model. The calibration curves for mass spectrometry are usually based on three to eight calibrator levels. For example, refer to "Liquid Chromatography-Mass Spectrometry Methods"; Approved Guideline, Clinical and Laboratory Standards Institute (CLSI), document C62-A, Vol.34No.162014.

[0007] Typically, new LC-MS instruments may have a hardware setup where some hardware components are duplicated across the instrument. An example is the use of HPLC multiplexing to increase system throughput. Two known calibration schemes are: (1) using a separate calibration function for each HPLC multiplexed stream; or (2) using a single average function for all streams. If individual calibration functions are currently required for specific hardware components (option (1)), the function f is usually matched individually for each component and different estimated parameter values ​​are obtained ( J ≥ 1, where J refers to the number of hardware components).

[0008] Both approaches may have significant disadvantages. If the HPLC multiplexed streams are not completely comparable, the analytical results obtained on the individual streams will always be biased by the average calibration function. On the other hand, dedicated calibration for each individual stream will result in a very high calibration burden and sometimes even be unfeasible.

[0009] Issues to be resolved

[0010] The object of the present invention is therefore to provide a method for calibrating at least one analytical device with duplicate hardware components, a device for calibrating at least one analytical device with duplicate hardware components, a computer or a computer network and a computer program, which avoid the disadvantages of the known methods, devices, computers and computer programs mentioned above. In particular, the method for calibrating at least one analytical device with duplicate hardware components, the device for calibrating at least one analytical device with duplicate hardware components, the computer or a computer network and the computer program should reduce the calibration burden of analytical devices with duplicate hardware components. Summary of the invention

[0011] This problem is solved by a method for calibrating at least one analytical device with duplicate hardware components, a device for calibrating at least one analytical device with duplicate hardware components, a computer or a computer network and a computer program. Preferred embodiments of the invention are disclosed, which can be realized individually or in any arbitrary combination.

[0012] As used below, the terms "having", "including" or "comprising" or any grammatical variations thereof are used in a non-exclusive manner. Thus, these terms may refer to the absence of other features in the entity described in this context in addition to the features introduced by these terms, as well as the presence of one or more other features. As an example, the expressions "A has B", "A contains B" and "A includes B" may refer to the absence of any other elements in A in addition to B (i.e., A consists solely and exclusively of B), as well as the presence of one or more other elements in entity A in addition to B, such as element C, elements C and D, or even other elements.

[0013] In addition, as used below, the terms "preferably", "more preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features without limiting the alternative possibilities. Therefore, the features introduced by these terms are optional features and are not intended to limit the scope in any way. As the skilled person will recognize, the present invention can be implemented by using alternative features. Similarly, the features introduced by "in an embodiment of the present invention" or similar expressions are intended to be optional features, without any limitation on alternative embodiments of the present invention, without any limitation on the scope of the present invention, and without any limitation on the possibility of combining the features introduced in this manner with other optional or non-optional features of the present invention.

[0014] In a first aspect of the invention, a method for calibrating at least one analytical device having duplicate hardware components is disclosed, wherein the analytical device comprises a plurality of hardware components.

[0015] As used herein, the term "analytical device" is a broad term and is given the ordinary and customary meaning to those of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any device configured to perform at least one analytical test. As further used herein, the term "detection" refers to the process of determining the presence and / or amount and / or concentration of at least one analyte in a sample. Thus, detection may be or may include a qualitative detection, which simply determines the presence of at least one analyte or the absence of at least one analyte, and / or may be or may include a quantitative detection, which determines the amount and / or concentration of at least one analyte.

[0016] Specifically, the analytical device can be a device for determining the concentration of an analyte in a sample (such as a liquid). The term "analyte" generally refers to any element, component, or compound that may be present in a sample, and its presence and / or concentration may be a target user, patient, or medical staff, such as a doctor. In particular, the analyte can be or can include any chemical substance or chemical compound that can participate in the metabolism of the user or patient, such as at least one metabolite. The detection of at least one analyte can specifically be a specific-analyte detection. However, other analytes are also feasible.

[0017] As used herein, the term "concentration" is a broad term and is given the ordinary and customary meaning to those of ordinary skill in the art and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, the abundance of a component divided by the total volume of a mixture, such as solutes and / or solvents in a solution. Concentration can be described in terms of different kinds of quantities, such as mass concentration, molar concentration, number concentration, or volume concentration.

[0018] In particular, the analysis device is selected from the group consisting of: a mass spectrometry device, in particular a liquid chromatography mass spectrometry device; an immunoassay analyzer; a photometric device, a blood gas analyzer, a hematology analyzer, a DNA analyzer. However, other kinds of analysis devices may also be feasible.

[0019] As used herein, the term "mass spectrometry (MS) device" is a broad term and is given a common and customary meaning to those of ordinary skill in the art, and is not limited to a special or customary meaning. The term may specifically refer to, but is not limited to, a mass analyzer configured to detect at least one analyte based on a mass-to-charge ratio. A mass spectrometer may be or may include at least one quadrupole mass spectrometer. An interface coupling an LC device and a MS may include at least one ionization source configured to generate molecular ions and to transfer the molecular ions to a gas phase.

[0020] As used herein, the term "liquid chromatography (LC) device" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customary meaning. The term may specifically refer to, but is not limited to, an analytical module that is configured to separate one or more target analytes of a sample from other components of the sample for use in detecting the one or more analytes using a mass spectrometer. The LC device may include at least one LC column. For example, the LC device may be a single-column LC device or a multi-column LC device having a plurality of LC columns. The LC column may have a stationary phase through which a mobile phase is pumped to separate and / or elute and / or transfer the target analyte.

[0021] As used herein, the term "liquid chromatography mass spectrometry (LC-MS) device" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a combination of liquid chromatography and mass spectrometry. A liquid chromatography mass spectrometry device may be or may include at least one high performance liquid chromatography (HPLC) device or at least one microfluidic liquid chromatography (μLC) device. A liquid chromatography mass spectrometry device may include a liquid chromatography (LC) device and a mass spectrometry (MS) device, wherein the LC device and the MS are coupled via at least one interface.

[0022] The analysis device may be specifically embodied as an analysis system including repeated hardware components, such as multiple repeated hardware components. Specifically, the analysis device may include multiple hardware components. The term "component" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term specifically refers to, but is not limited to, a part of the analysis device, in particular a part of the analysis system. These components are configured to interact with another component, for example, to achieve at least one common function of the system. The components can be processed independently, or they can be coupled, connected or integrated with each other. Generally, the term "hardware" may refer to the physical and / or tangible parts of the analysis device. The term "hardware component" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term specifically refers to, but is not limited to, a part of a physical and / or tangible part of the analysis device. Hardware components may also be referred to as hardware parts. The term "repeated hardware component" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term specifically refers to, but is not limited to, at least two hardware components of the analysis device. For example, the analytical device may be an HPLC spectrometer multiplexing device. The term "multiplexing" may refer to multiple LC systems running simultaneously into a single mass spectrometer. Each LC system may be separate and / or separate from the other LC systems. For example, the analytical device may include multiple simultaneous HPLC separations and a single mass spectrometer. The hardware components may be selected from the group consisting of: a column, specifically a high performance liquid chromatography column; a flow, specifically a high performance liquid chromatography flow; a sample injection device, specifically a high performance liquid chromatography injection device; a pump; a measurement unit; a detector, specifically a mass spectrometer detector. Other components are also feasible.

[0023] The hardware components can be equivalent hardware components. The term "equivalent" can refer to the implementation and / or functional equivalence of two or more devices. Therefore, the first hardware component and the second hardware component of the analytical device can achieve the same function and / or can be the same in their structure and / or construction. Exemplarily, the first hardware component can be a high performance liquid chromatography column, and the second hardware component can also be a high performance liquid chromatography column. Specifically, the calibration sample can pass through some or all of the hardware components, or can be transported via some or all of the hardware components. However, other embodiments may also be feasible.

[0024] As used herein, the term "calibration" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, an operation or operating process for determining the relationship between the original signal of an analyte determined by an analytical device, such as a mass spectrometer, and the concentration of the analyte. Specifically, calibration may be or may include an operation or operating process, wherein under specified conditions, in a first step, a relationship between a value with a measurement uncertainty provided by a measurement standard and a corresponding indication with an associated measurement uncertainty is established, specifically a calibrated instrument or a secondary standard, and in a second step, a relationship is established using this information to obtain a measurement result from the indication. Specifically, the term "calibration" may include determining the concentration of a sample based on the measurement signal of the sample and / or determining the relationship between the function of the measurement signal and the sample concentration. In a known method for calibrating an analytical device having repeated hardware components, such as an HPLC device, a calibration function is matched separately for each hardware component, such as each HPLC multiplexed stream, or a single average function is used for all hardware components, such as all streams. Both schemes may have significant disadvantages. If the HPLC multiplexed streams are not completely comparable, the analytical results obtained with the average calibration function on the individual streams will always be biased. On the other hand, a dedicated calibration for each individual stream would result in a very high calibration burden, which is sometimes even not feasible. The present invention proposes a related calibration procedure. Using this method, the calibration burden of the instrument is lower than with a common single stream calibration. On the other hand, it can be ensured that the calibration function of each stream is adjusted. The simplified present invention proposes an average calibration function with individual adjustment factors for the streams on all streams.

[0025] The method comprises the following steps, which may be performed in a given order as an example. However, it should be noted that different orders are possible. In addition, one or more method steps may be performed once or repeatedly. In addition, two or more method steps may be performed simultaneously or in a timely overlapping manner. The method may include other method steps not listed.

[0026] The method comprises the following steps:

[0027] a) providing at least one calibrator sample i having a known target value for the concentration of at least one analyte;

[0028] b) at least one measurement step, wherein the measurement step comprises performing at least one measurement on the calibrator sample using the analytical device, wherein at least one detector signal s is acquired ijk , where i=1, ...I, where I≥2, where i is the number of detector samples, j=1, ...J, where J≥2, where j is the number of hardware components, and k=1, ...K ij , Kij ≥1, where k is the number of repetitions of the measurement step;

[0029] c) at least one calibration step, wherein a relationship between the detector signal and the concentration of the analyte and / or between the detector signal and a theoretical signal value is determined, wherein the calibration step comprises:

[0030] c.1: providing at least one parameterized function, wherein the parameterized function has a parameter set, wherein the parameter set comprises parameters describing an analyte-specific portion of the parameterized function, wherein the parameter set further comprises parameters for adjustment of the parameterized function with respect to the hardware component;

[0031] c.2: determining a calibration value by performing a calibration based on the parameterized function; and

[0032] c.3: Determining an analysis function based on the inverse function of the parameterized function and the determined calibration value.

[0033] The method may specifically be a computer-implemented method. As used herein, the term "computer-implemented method" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customary meaning. The term may specifically refer to, but is not limited to, a method involving at least one computer and / or at least one computer network. The computer and / or computer network may include at least one processor configured to perform at least one of the method steps of the method according to the present invention. Preferably, each method step is performed by a computer and / or a computer network. The method may be performed completely automatically (particularly, without user interaction). As used herein, the term "automatically" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customary meaning. The term may specifically refer to, but is not limited to, a process performed entirely by means of at least one computer and / or at least one computer network and / or at least one machine, in particular, without the need for manual operation and / or interaction with a user.

[0034] Method steps b) to c) can be performed fully automatically. For example, the method steps can be performed by at least one computer-implementable processing line.

[0035] The term "step" may generally refer to a work step, a process step, or a phase of an operation or procedure. Thus, the term "calibration step" may refer to an operational phase that includes performing a calibration. Further, the term "measurement step" may refer to an operational phase that includes performing a measurement.

[0036] As used herein, the term "sample" is a broad term and is given a common and customary meaning to those of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any sample, such as a biological sample, also referred to as a test sample, a quality control sample. The sample may include one or more target analytes. For example, the sample may be selected from a group consisting of the following items: physiological fluids, including blood, serum, plasma, saliva, lens fluid, cerebrospinal fluid, sweat, urine, emulsion, ascites, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissue, cells, etc. The sample may be used directly when obtained from the corresponding source, or may be pretreated and / or sample preparation workflow. For example, the sample may be pretreated by adding an internal standard and / or by diluting with another solution and / or by mixing with a reagent, etc. For example, in general, the target analyte may be vitamin D, drugs of abuse, therapeutic drugs, hormones, and metabolites.

[0037] The term "calibrator sample", also known as "calibrator" is a broad term and is given the ordinary and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term specifically refers to, but is not limited to, any sample with a known concentration value. The calibrator sample has a known target value. As used herein, the term "known target value" is a broad term and is given the ordinary and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term specifically refers to, but is not limited to, a known value of one or more parameters of the calibrator sample, specifically a known concentration of a substance. The substance can be the same as the target analyte, or it can be an analyte produced by reaction or derivatization, an analyte that is the same as the target analyte, and / or it can be an analyte whose concentration is known, and / or it can be a substance that mimics the target analyte, or a substance that can be associated with a certain target analyte in other ways.

[0038] The invention may comprise providing at least one calibrator sample i having a known target value for the concentration of at least one analyte and an average calibration curve from which a theoretical signal for the at least one calibrator sample is derived. The average calibration curve may be the relationship between the signal of the analytical device and the non-instrument-specific analyte concentration. For example, a plurality of reference analytical devices may be measured and a plurality of calibration curves determined. Based on the calibration curves, an average calibration curve may be calculated.

[0039] The method for calibrating an analytical device comprises at least one measurement step b). Specifically, step b) can be performed on each hardware component. As described above, step b) may include acquiring at least one detector signal. As used herein, the term "detector" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a device configured to detect incoming ions. The detector may be configured to detect charged particles. The detector may be or may include at least one electron multiplier. The detector may be configured to determine at least one mass spectrum of the detected ions. As used herein, the term "mass spectrum" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a two-dimensional representation of signal intensity and charge-to-mass ratio m / z, wherein the signal intensity corresponds to the abundance of each ion. A mass spectrum may be a pixelated image. In order to determine the resulting intensity of a mass spectrum pixel, the signal detected by the detector within a certain m / z range may be integrated. An analyte in a sample may be identified by at least one evaluation device. In particular, the evaluation device may be configured to associate a known mass with an identification mass, or to associate via a characteristic fragmentation pattern. Thus, the term "detector signal" may refer to a signal acquired by a detector. In particular, the detector signal may be referred to as a raw signal. The detector signal of a desired calibration sample may be acquired. Thus, for each or at least some calibration samples, a separate detector signal may be acquired. Further, the detector signal may be acquired and / or measured on a desired hardware component. As described above, the analysis device comprises a plurality of hardware components. The detector signal of a desired hardware component may be acquired. Thus, for each or at least some hardware components, a separate detector signal may be acquired. Further, the specific acquisition of the detector signal of the desired calibration sample and / or the desired hardware component may be performed multiple times, for example, the acquisition of the detector signal may be repeated.

[0040] As mentioned above, the detector signal can be expressed as s ijk denoted by . i refers to the number of the calibrator sample. Specifically, the method for calibrating at least one analytical device can be performed multiple times. Therefore, for each procedure, a new calibrator sample can be used. Specifically, the number of calibrator samples can correspond to the number of procedures. However, other methods may also be feasible. In addition, j refers to the number of hardware components. j may refer to the number of all hardware components of the analytical device, and may also refer to the number of parts of all hardware components of the analytical device. Specifically, j may refer to the number of equivalent hardware components. k refers to the number of repetitions of the measurement step. The measurement step, in particular step b), can be repeated several times. Specifically, step b) can be repeated several times before performing step c).

[0041] In step c.1, a parameterized function is provided. The term "function" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. Specifically, the term may refer to, but is not limited to, a mathematical function. A function may include one or more variables, and optionally one or more parameters. Specifically, a function may assign a value to a function value. Exemplarily, a function may be a linear function or a quadratic function. However, other embodiments may also be feasible. The term "parameter" generally refers to any quantity that affects the output or behavior of a mathematical function, but is considered to be a constant. Therefore, a parameter may be configured to determine the behavior of a mathematical function. In contrast, a variable of a mathematical function may be evaluated as a changing parameter, which generally does not change or changes more slowly. Typically, the term "parameter group" may refer to multiple parameters of a single mathematical function. The term "parameterized function" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any mathematical function with at least one parameter, specifically at least two parameters.

[0042] The parameter groups may include at least two groups. A first group of parameter groups may correspond to parameters describing the analyte-specific portion of the parameterized function. A second group of parameter groups may correspond to parameters adjusting the parameterized function with respect to the hardware component.

[0043] Therefore, the parameters describing the analyte-specific part of the parameterized function and the parameters used to adjust the parameterized function with respect to the hardware component can be represented by different parameters. The total parameter set consisting of the parameters describing the analyte-specific part of the parameterized function and the parameters used to adjust the parameterized function with respect to the hardware component can be represented as

[0044] p=(p1,p2,...p n , h1, h2, ...h r )

[0045] Where n and r are positive integers, and p1, p2, ...p n corresponds to the parameters describing the analyte-specific part of the parameterized function, where h1, h2, ..h r is a vector describing the parameters used to adjust the parameterized function with respect to the hardware component. h1,h2,...h r It can correspond to a parameter vector. Each parameter vector h r =h 1r ,...h Lr There may be L parameter groups, L being a positive integer. The more parameters used, the more accurate the match to the data. Therefore, dividing the parameter group into a first set of parameters describing the analyte-specific part of the parameterized function and a second set of parameters for adjusting the parameterized function may improve the matching results.

[0046] The parameter set includes parameters describing the analyte-specific portion of the parameterized function. As used herein, the term "parameter describing the analyte-specific portion" is a broad term and is given its ordinary and customary meaning to one of ordinary skill in the art, and is not limited to a special or customized meaning. The term specifically may refer to, but is not limited to, parameters that reflect the relationship between the raw signal and the concentration of the analyte, but are not adjustments based on specific hardware settings. For example, if multiple compounds can be analyzed, the parameters for a single compound may be different.

[0047] The term "parameters for adjusting parameterized functions about hardware components" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, parameters that reflect adjustments based on a specific hardware setup. The parameters for adjusting parameterized functions about hardware components relate to the effects on the detector signal caused by a single hardware component of the analytical device. In order to determine these parameters, calibrator samples can be measured on each single hardware component, where information about which hardware component the signal comes from can also be input into the matching process. Since all hardware components can be considered together in the matching process, fewer measurements with the calibrator may be required to obtain reliable calibration curves for all hardware components compared to known methods in which each hardware component is considered separately. In addition, the signals of different hardware components can be quality checked, which is not possible when each hardware component is calibrated separately.

[0048] As described above, step c.2 comprises determining calibration values ​​by calibration based on a parameterized function. This step c.2 may specifically comprise determining parameter values ​​of a parameter set. Further, in particular, matching of the detector signals may be performed.

[0049] The term "value" as further used herein may refer to a parameter value of a mathematical function. The term "calibrated value" as further used herein may refer to a parameter value of any calibration function. In particular, a calibration value may refer to a parameter value in a parameter set of a parameterized function. The term "calibrating based on a parameterized function" may refer to calibrating by using a parameterized function. In particular, a matching may be performed, for example, a mathematical function of a series of data points, in particular a mathematical function of a detector signal, may be constructed. Thus, a parameter value of a mathematical function may be obtained. In particular, a calibration value may be expressed as

[0050] In step c.3., the calibration step further comprises determining an analysis function based on the inverse function of the parameterized function and the determined calibration value. Via the analysis function, the concentration can be determined from the detector signal. The term "analysis function" may generally refer to any function that is configured to determine a parameter of a sample, such as a concentration, from a measured detector signal. Thus, the analysis function may describe the relationship between a parameter of the sample, such as a concentration, and the measured detector signal. Based on the calibration function, the analysis function may be determined. Specifically, the analysis function may be formed by an inverse function of the calibration function.

[0051] A parameterized function with defined calibration values ​​can be expressed as a calibration function or a signal-concentration function. The calibration function is defined as

[0052] f p (Concentration) = detector signal.

[0053] The calibration function may be specifically a linear function. The calibration function may include one or both of a hardware component specific intercept and a hardware component specific slope.

[0054] Exemplarily, the calibration function is expressed as

[0055] S ijk =μ+a j +b·C i +ε ijk

[0056] where ε ijk Corresponding to the random region, the region is normally distributed with a mean of 0 and a variance of S ijk Corresponding to the detector signal, C i The target value corresponding to the i-th calibrator sample, where i = 1, ... I, I ≥ 2, where i is the number of calibrator samples, j = 1, ... J, J ≥ 2, where j is the number of hardware components, and k = 1, ... K ij , K ij ≥1, where k is the number of repetitions of the measurement step.

[0057] Further, illustratively, the calibration function is expressed as

[0058] S ijk =μ+b j ·C i +ε ijk

[0059] where ε ijk Corresponding to the random region, the region is normally distributed with a mean of 0 and a variance of S ijk Corresponding to the detector signal, C iThe target value corresponding to the i-th calibrator sample, where i = 1, ... I, I ≥ 2, where i is the number of calibrator samples, j = 1, ... J, J ≥ 2, where j is the number of hardware components, and k = 1, ... K ij , K ij ≥1, where k is the number of repetitions of the measurement step.

[0060] Further, illustratively, the calibration function is expressed as

[0061] S ijk =μ+a j +b j ·C i +ε ijk

[0062] where ε ijk Corresponding to the random region, the region is normally distributed with a mean of 0 and a variance of S ijk Corresponding to the detector signal, C i The target value corresponding to the i-th calibrator sample, where i = 1, ... I, I ≥ 2, where i is the number of calibrator samples, j = 1, ... J, J ≥ 2, where j is the number of hardware components, and k = 1, ... K ij , K ij ≥1, where k is the number of repetitions of the measurement step.

[0063] Further, illustratively, the calibration function is expressed as

[0064] S ijk =(p1+p2·C i )·h j +ε ijk

[0065] Where S ijk Corresponding to the detector signal, C i The target value corresponding to the i-th calibrator sample, where i = 1, ... I, I ≥ 2, where i is the number of calibrator samples, j = 1, ... J, J ≥ 2, where j is the number of hardware components, and k = 1, ... K ij , K ij ≥ 1, where k is the number of repetitions of the measurement step. p1, p2, describe the analyte-specific calibration parameters, h1, …, h J Describes the hardware part specific adjustment factor. ε ijk Corresponding to the random region, the region is normally distributed with a mean of 0 and a variance of

[0066] The method according to the invention can be combined with a comprehensive calibration and recalibration method of the analytical device.

[0067] For example, step c) may correspond to a comprehensive calibration of the analytical device. A comprehensive calibration may include determining the relationship between the detector signal and the analyte concentration. A comprehensive calibration may be performed, for example, during initial setup of the analytical device. A comprehensive calibration may be performed repeatedly.

[0068] Furthermore, for example, step c) may correspond to a recalibration of the analysis device. In this case, only the signal adjustment function of the analysis device is determined. The signal adjustment function is defined as

[0069] g p (Theoretical signal) = detector signal.

[0070] Thus, in a calibration step, the relationship between the detector signal and the theoretical signal may be additionally or alternatively determined. Generally, the terms "theoretical signal value" and "theoretical signal" may refer to a signal determined via one or more different analytical devices, such as a reference analytical device, via performing one or more measurements and via determining an average signal value based on the one or more measurements. For example, the calibration process may comprise at least two steps, a first step and a second step. The first step may comprise determining the relationship between the signal of the analytical device and the non-instrument-specific concentration of the analyte. Exemplarily, for this purpose, three reference analytical devices are measured and three different calibration curves are determined. Based on the three different calibration curves, an average calibration curve may be calculated. The second step may comprise an adjustment of the analytical device to be calibrated. Thus, the detector signal is adjusted with respect to the theoretical signal. Thus, the parameterized function may be a signal adjustment function. Exemplarily, the signal-adjustment-function is represented as

[0071] S ijk =(p1+p2·Stheor i )·h j +ε ijk ,

[0072] Where S ijk Corresponding to the detector signal, Stheor i Theoretical signal corresponding to the i-th calibrator sample, where i = 1, ... I, I ≥ 2, where i is the number of calibrator samples, j = 1, ... J, J ≥ 2, where j is the number of hardware components, and k = 1, ... K ij , K ij ≥1, where k is the number of repetitions of the measurement step. p1, p2, describe the analyte-specific calibration parameters, h1, ..., h J Describes the hardware part specific adjustment factor. ε ijk Corresponding to the random region, the region is normally distributed with a mean of 0 and a variance of

[0073] As described above, in step c), the relationship between the detector signal and the analyte concentration and / or the detector signal and the theoretical signal value is determined. During commissioning of the analytical device, a comprehensive calibration may be performed. At a subsequent time point, in particular during use of the analytical device, a recalibration may be performed. Optionally, a comprehensive calibration may be performed at a subsequent time point, such as during use of the analytical device.

[0074] The method may further include performing at least one measurement on a sample having at least one analyte of unknown concentration. By using the analysis function, the concentration of the sample can be determined based on the measurement signal of the sample. The measurement signal can be a detector signal. Specifically, the measurement signal can correspond to the detector signal obtained in step b) of the method for calibrating at least one analytical device. However, the measurement signal may also correspond to a detector signal obtained in a separate measurement step. The additional sample may correspond to a calibration sample used in step a) of the method for calibrating at least one analytical device. However, the additional sample also corresponds to a sample different from the calibration sample used in step a) of the method for calibrating at least one analytical device.

[0075] In another aspect of the present invention, a device for calibrating at least one analytical device having duplicate hardware components is disclosed. The device includes an analytical device composed of a plurality of hardware components. The analytical device is configured to perform at least one measurement on a calibrator sample i having a known target value of at least one analyte concentration. The analytical device is configured to acquire at least one detector signal s ijk , where i = 1, ... I, I ≥ 2, where i is the number of calibrator samples, j = 1, ... J, J ≥ 2, where j is the number of hardware components, and k = 1, ... K ij , K ij ≥1, where k is the number of repetitions of the measurement step.

[0076] In addition, the device includes at least one evaluation device. The evaluation device is configured to perform at least one calibration step, wherein the relationship between the detector signal and the concentration of the analyte and / or the detector signal and the theoretical signal value is determined. Further, the evaluation device is configured to provide at least one parameterized function, wherein the parameterized function has a parameter set. The parameter set includes parameters describing the analyte-specific part of the parameterized function. The parameter set further includes parameters for adjusting the parameterized function with respect to the hardware component. The evaluation device is further configured to determine a calibration value by calibrating based on the parameterized function. The evaluation device is further configured to determine an analysis function based on an inverse function of the parameterized function and the determined calibration value.

[0077] The device may be configured to perform the method for calibrating at least one analytical device as described above or in further detail below.

[0078] The term "evaluation device" generally refers to any device suitable for performing the method steps as described above, preferably by using at least one data processing device, and more preferably by using at least one processor and / or at least one application specific integrated circuit. Thus, as an example, the at least one evaluation device may include at least one data processing device having software code stored thereon, the software code comprising a plurality of computer commands. The evaluation device may provide one or more hardware elements for performing one or more specified operations, and / or may provide one or more processors with software running thereon for performing one or more method steps.

[0079] In another aspect, a computer program is disclosed. The computer program is suitable for performing steps b) to c) of the method for calibrating at least one analytical device as described above or in further detail below when the program is executed on a computer or a computer network, in particular on a processor. The computer program may comprise computer executable instructions for performing the method for calibrating at least one analytical device, in particular for performing steps b) to c).

[0080] Therefore, in general, a computer program is disclosed and proposed herein, which includes computer executable instructions for executing the method according to the present invention in one or more embodiments attached herein when the program is executed on a computer or a computer network. Specifically, the computer program can be stored on a computer readable data carrier. Therefore, specifically, one, more than one or even all method steps as indicated above can be performed by using a computer or a computer network, preferably by using a computer program. Specifically, the computer can be fully or partially integrated into a mass spectrometer, and the computer program can be specifically embodied as software. However, alternatively, at least a portion of the computer can also be located outside the mass spectrometer.

[0081] In another aspect, a computer program is disclosed, comprising program means for executing steps b) to c) of the method for calibrating at least one analytical device as described above or in further detail below when the computer program is executed on a computer or a computer network. Specifically, the program means can be stored on a computer-readable storage medium.

[0082] In another aspect, a computer program product with program code means is disclosed. The program code means can be stored or stored on a storage medium, and when the program code means is executed on a computer or a computer network, it is used to perform the steps b) to c) of the method for calibrating at least one analytical device described above or described in further detail below. Specifically, the program code tool can be stored on a computer-readable data carrier. As used herein, a computer program product refers to a program as a tradable product. The product can generally exist in any format (such as a paper format) or on a computer-readable data carrier. Specifically, the computer program product can be distributed on a data network.

[0083] In another aspect, a computer or computer network comprising at least one processor is disclosed. The processor is adapted to perform steps b) to c) of the method for calibrating at least one analytical device as described above or in further detail below.

[0084] In another aspect, a computer loadable data structure is disclosed, which, when executed on a computer, is adapted to perform steps b) to c) of the method for calibrating at least one analytical device as described above or in further detail below.

[0085] In another aspect, a storage medium is disclosed, wherein a data structure is stored on the storage medium, and wherein the data structure, after being loaded into a main memory and / or a working memory of a computer or a computer network, is suitable for performing steps b) to c) of the method for calibrating at least one analytical device as described above or in further detail below. In particular, the storage medium may refer to a data carrier. The data structure may be loaded into a computer or a computer network, for example into a working memory or a main memory of the computer or a computer network, and the method may be performed.

[0086] The method for calibrating at least one analytical device, the device for calibrating at least one analytical device, the computer or computer network and the computer program according to the invention offer numerous advantages over known methods, devices, computers and computer programs.

[0087] With the proposed method, the calibration burden of the analytical device may be lower than with common single stream calibration methods. Further, adjustment of the calibration function for each stream may be ensured. The simplified proposed method may be viewed as an average calibration function over all streams with stream-individual adjustment factors.

[0088] In order to be able to match the parameterized functions, calibrator samples can be measured on each individual hardware component and information on which hardware component the signal comes from can also enter into the matching process. Since all hardware components can be considered together in the matching process, fewer calibrator measurements may be required to obtain reliable calibration curves for all hardware components compared to common prior art approaches, where each hardware component is considered individually. Furthermore, quality control checks can be performed on the signals of the different hardware components, which is usually not possible if each hardware component is calibrated individually.

[0089] The method according to the invention can be applied to any multiplexing system item, such as detector units or reagent containers, and can also be generally applied to most analytical techniques.

[0090] In summary and without excluding further possible embodiments, the following embodiments may be envisaged:

[0091] Embodiment 1: A method for calibrating at least one analytical device having duplicate hardware components, wherein the analytical device comprises a plurality of hardware components, wherein the method comprises the following steps:

[0092] a) providing at least one calibrator sample i having a known target value for the concentration of at least one analyte;

[0093] b) at least one measurement step, wherein the measurement step comprises performing at least one measurement on the calibrator sample using the analytical device, wherein at least one detector signal s is acquired ijk , where i=1, ...I, where I≥2, where i is the number of detector samples, j=1, ...J, where J≥2, where j is the number of hardware components, and k=1, ...K ij , K ij ≥1, where k is the number of repetitions of the measurement step;

[0094] c) at least one calibration step, wherein a relationship between the detector signal and the concentration of the analyte and / or between the detector signal and a theoretical signal value is determined, wherein the calibration step comprises:

[0095] c.1: providing at least one parameterized function, wherein the parameterized function has a parameter set, wherein the parameter set comprises parameters describing an analyte-specific portion of the parameterized function, wherein the parameter set further comprises parameters for tuning the parameterized function to the hardware component;

[0096] c.2: determining a calibration value by performing a calibration based on the parameterized function; and

[0097] c.3: Determining an analysis function based on the inverse function of the parameterized function and the determined calibration value.

[0098] Example 2: A method according to the previous embodiment, wherein the parameter set is composed of p=(p1, p2, ... p n , h1, h2, ...h r ), where n and r are positive integers, and p1, p2, ...p n corresponds to the parameters describing the analyte-specific part of the parameterized function, where h, h2, ... h r refers to a vector describing the parameters used to tune the parameterized function to the hardware component, wherein the calibration values ​​are given by express.

[0099] Example 3: A method according to any of the preceding embodiments, wherein the relationship between the detector signal and the theoretical signal value is determined, wherein the parameterized function is a signal conditioning function.

[0100] Example 4: A method according to the preceding embodiment, wherein the signal adjustment function is defined as g p (Theoretical signal) = detector signal.

[0101] Example 5: The method according to any of the preceding embodiments, wherein a relationship between the detector signal and the concentration of the analyte is determined, wherein the parameterized function is a signal-concentration-function.

[0102] Example 6: A method according to the preceding embodiment, wherein the signal-concentration-function is defined as f p (Concentration) = detector signal.

[0103] Embodiment 7: The method according to any of the two preceding embodiments, wherein the signal-concentration-function is a linear function.

[0104] Example 8: The method according to the preceding embodiment, wherein the signal-concentration function comprises one or both of a hardware-part specific intercept and a hardware-part specific slope.

[0105] Embodiment 9: The method according to any of the three preceding embodiments, wherein the signal-concentration-function is a linear function with at least one hardware part-specific adjustment coefficient.

[0106] Embodiment 10: The method according to any one of the preceding embodiments, wherein the analytical device is a device for determining the concentration of an analyte in a liquid.

[0107] Embodiment 11: The method according to any one of the preceding embodiments, wherein the analysis device is selected from the group consisting of: a mass spectrometry device, in particular a liquid chromatography-mass spectrometry device; an immunoassay analyzer; a photometric device, a blood gas analyzer, a hematology analyzer, a DNA analyzer.

[0108] Embodiment 12: A method according to any one of the preceding embodiments, wherein the hardware components are equivalent hardware components.

[0109] Example 13: A method according to any one of the preceding embodiments, wherein the hardware component is selected from the group consisting of: a column, specifically a high performance liquid chromatography column; a flow, specifically a high performance liquid chromatography flow; a sample injection device, specifically a high performance liquid chromatography injection device; a pump; a measuring unit; a detector, specifically a mass spectrometer detector.

[0110] Embodiment 14: The method according to any one of the preceding embodiments, wherein the calibrator sample is run through or transported via some or all of the hardware components.

[0111] Example 15: A method according to any one of the preceding implementations, wherein step b) is performed on each hardware component.

[0112] Embodiment 16: An apparatus for calibrating at least one analytical device having duplicate hardware components, comprising:

[0113] at least one analytical device comprising a plurality of hardware components, wherein the analytical device is configured to perform at least one measurement on a calibrator sample i having a known target value for the concentration of at least one analyte, wherein the analytical device is configured to acquire at least one detector signal s ijk , where i=1, ... I, I ≥ 2, where i refers to the number of the calibrator samples, j=1, ... J, J ≥ 2, where j refers to the number of the hardware components, and k=1, ... K ij , K ij ≥1, where k is the number of repetitions of the measurement step; and

[0114] ·At least one evaluation device, wherein the evaluation device is configured to perform at least one calibration step, wherein a relationship between the detector signal and the concentration of the analyte and / or between the detector signal and a theoretical signal value is determined, wherein the evaluation device is configured to provide at least one parameterized function, wherein the parameterized function has a parameter group, wherein the parameter group includes parameters describing the analyte-specific part of the parameterized function, wherein the parameter group further includes parameters for adjustment of the parameterized function with respect to the hardware component; wherein the evaluation device is further configured to determine a calibration value by calibrating based on the parameterized function, wherein the evaluation device is further configured to determine an analysis function based on an inverse function of the parameterized function and the determined calibration value.

[0115] Embodiment 17: The device according to the preceding embodiment, wherein the apparatus is configured to perform the method for calibrating at least one analytical device as mentioned in any one of the preceding embodiments.

[0116] Embodiment 18: A computer or a computer network comprising at least one processor, wherein the processor is adapted to perform steps b) to c) of the method for calibrating at least one analytical device according to any one of the preceding embodiments relating to the method for calibrating at least one analytical device.

[0117] Embodiment 19: A computer-loadable data structure, which, when being executed on a computer, is suitable for performing steps b) to c) of the method for calibrating at least one analytical device according to any one of the preceding embodiments.

[0118] Embodiment 20: A computer program, wherein the computer program is adapted to perform steps b) to c) of the method for calibrating at least one analytical device according to any one of the preceding embodiments relating to the method for calibrating at least one analytical device when the program is executed on a computer.

[0119] Example 21: A computer program comprising program means for executing steps b) to c) of the method for calibrating at least one analytical device according to any of the preceding embodiments, the method being a method for calibrating at least one analytical device when the computer program is executed on a computer or a computer network.

[0120] Embodiment 22: A computer program comprises program means according to the aforementioned embodiments, wherein these program means are stored on a computer-readable storage medium.

[0121] Example 23: A storage medium, wherein a data structure is stored on the storage medium and wherein the data structure is suitable for performing steps b) to c) of a method for calibrating at least one analytical device according to any of the preceding embodiments, the embodiment referring to a method for calibrating at least one analytical device after being loaded into the main memory and / or working memory of a computer or a computer network.

[0122] Embodiment 24: A computer program product having a program code device, wherein the program code device can be stored or stored on a storage medium, and is used to execute steps b) to c) of the method for calibrating at least one analytical device according to any of the preceding embodiments when the program code device is executed on a computer or a computer network, referring to a method for calibrating at least one analytical device. BRIEF DESCRIPTION OF THE DRAWINGS

[0123] Further optional features and embodiments will be disclosed in more detail in the subsequent description of the embodiments. Wherein, as will be appreciated by those skilled in the art, each optional feature can be implemented in an isolated manner and in any arbitrarily feasible combination. The scope of the present invention is not limited by the preferred embodiments. Embodiments are schematically depicted in the accompanying drawings. Wherein, the same reference numerals in these figures refer to the same or functionally comparable elements.

[0124] In the attached figure:

[0125] Figure 1 shows an exemplary embodiment of an apparatus for calibrating at least one analytical device; and

[0126] FIG. 2A to FIG. 2D Shows various experimental results. DETAILED DESCRIPTION

[0127] Figure 1 A device 110 for calibrating at least one analyzing device 112 is shown. In particular, the analyzing device 112 may be selected from the group consisting of: a mass spectrometry device, in particular a liquid chromatography mass spectrometry device; an immunoassay analyzer; a photometric device, a blood gas analyzer, a hematology analyzer, a DNA analyzer. However, other kinds of analyzing devices may also be feasible.

[0128] The analysis device 112 includes multiple hardware components 114. The analysis device 112 may be specifically embodied as an analysis system including repeated hardware components 114, such as multiple repeated hardware components 114. The hardware components 114 may be processed independently or may be coupled, connected or integrated with each other.

[0129] Exemplarily, the analysis device 112 can be a mass spectrometer 116. For example, the analysis device 112 can be an HPLC multiplexing device. The analysis device 112 can be or can include multiple LC systems that are simultaneously run into a single mass spectrometer. Each LC system can be separate and / or separated from other LC systems. For example, the analysis device 112 can include multiple simultaneous HPLC separations and a single mass spectrometer. The hardware component 114 can be selected from the group consisting of: a column, specifically a high performance liquid chromatography column; a flow, specifically a high performance liquid chromatography flow; a sample injection device, specifically a high performance liquid chromatography injection device; a pump; a measurement unit; a detector, specifically a mass spectrometer detector. Other components are also feasible.

[0130] exist Figure 1, exemplarily shown, the analysis device 112 includes a first hardware component 118 and a second hardware component 120. Exemplarily, the first hardware component 118 and the second hardware component 120 may be a column 122. Further, the analysis device 112 may include an additional hardware component 124. The further hardware component 124 may be different from the hardware component 118 and the second hardware component 120. Exemplarily, the additional hardware component 124 may be a mass spectrometer detector 126.

[0131] The analysis device 112 is configured to perform at least one measurement on a calibrator sample i having a known target value of at least one analyte concentration. The analysis device 112 is further configured to acquire at least one detector signal s ijk , where i = 1, ... I, I ≥ 2, where i is the number of calibrator samples, j = 1, ... J, J ≥ 2, where j is the number of hardware components, and k = 1, ... K ij , K ij ≥1, where k is the number of repetitions of the measurement step.

[0132] Further, the apparatus 110 comprises at least one evaluation device 128. The evaluation device 128 is configured to perform at least one calibration step, wherein a relationship between a detector signal and a concentration of an analyte and / or a detector signal and a theoretical signal value is determined. Further, the evaluation device 128 is configured to provide at least one parameterized function, wherein the parameterized function has a parameter set. The parameter set comprises parameters describing an analyte-specific portion of the parameterized function. The parameter set further comprises parameters for adjusting the parameterized function with respect to a hardware component. The evaluation device 128 is further configured to determine a calibration value by calibrating based on the parameterized function. The evaluation device 128 is further configured to determine an analysis function based on an inverse function of the parameterized function and the determined calibration value.

[0133] Figures 2A to 2D Indicates various experimental results. Figure 2AIn Figure 1, the detector signals, specifically the area ratios, are shown for three different samples, denoted CA005, CA006, and CA007, which were acquired on an instrument with two HPLC pumps and two different HPLC columns. The two pumps and columns can be switched together, so that there are a total of four different HPLC streams on the instrument. From left to right, the first data point of each sample graph is the detector signal measured on stream 1, which corresponds to the C1 column and pump P1; the second data point is the detector signal measured on stream 2, which corresponds to the C1 column and pump P2; the third data point is the detector signal measured on stream 3, which corresponds to the C2 column and pump P1; and the fourth data point is the detector signal measured on stream 4, which corresponds to the C2 column and pump P2. It can be seen that the detector signals on streams 2 and 4 are higher than the detector signals acquired on streams 1 and 3.

[0134] Figure 2B The results of the variance-component analysis based on the detector signal are shown. The variance-component analysis was performed to analyze the main sources of variation coming from differences in hardware components and related to the repeatability of the system for multiple samples CA001 to CA007 over a range of concentrations, i.e., error components. The larger the number of samples, the higher the concentrations. Figure 2B In Figure 1, the percentage of each component in the total variability is shown. It can be seen that a variable component pump exists, i.e. there is a significant variation in the detector signal between the two different pumps, and therefore also between the four HPLC streams.

[0135] Figure 2C The coefficient of variation CV% representing the different sources of variation can be seen that for all samples there is a large contribution to the CV due to the variability of the detector signal between the two pumps, which is also a part of the HPLC flow. With the calibration method according to the invention it is possible to minimize the flow differences in the concentrations read out.

[0136] Figure 2D The total percentages of CA005, CA006 and CA007 samples (left column) and the coefficient of variation CV (right column) are shown.

[0137] - Individual flow calibrations were performed ( Figure 2D “Fully calibrated” in

[0138] - Calibration without flow specific parameters was performed ( Figure 2D “System Calibration” in

[0139] - Calibration without flow specific slope was performed ( Figure 2D denoted as “slope calibration” in

[0140] - Flow specific coefficient calibration was performed ( Figure 2D denoted as “coefficient calibration” in ),

[0141] Among them, the latter two methods are methods according to the present invention. For the model with stream-specific slope calibration, a linear function is matched with a common intercept between streams and different slopes. For the model with stream-specific slope calibration, a linear function is matched with a common intercept between streams and different slopes. For the model with stream-specific coefficient calibration, a linear function is matched with a common intercept and slope between streams, and a stream-specific multiplicative adjustment coefficient.

[0142] It can be seen that both methods according to the present invention are effective and can provide results as good as or even better than single stream calibration and can minimize the differences in concentration values ​​between streams. By these two methods, the pump-to-pump variability of concentration values ​​can be minimized.

[0143] Reference numerals list

[0144] 110 Devices

[0145] 112 Analysis device

[0146] 114 Hardware Components

[0147] 116 Mass Spectrometry Device

[0148] 118 First Hardware Component

[0149] 120 Second Hardware Component

[0150] 122 columns

[0151] 124 Additional Hardware Components

[0152] 126 Mass Spectrometer Detector

[0153] 128 Evaluation device.

Claims

1. A method for calibrating at least one analytical device (112) having duplicate hardware components, wherein the analytical device (112) comprises a plurality of hardware components (114), wherein the hardware components are physical and / or tangible parts of the analytical device (112), wherein the method comprises the following steps: a) providing at least one calibrator sample i having a known target value for the concentration of at least one analyte; b) at least one measurement step, wherein the measurement step comprises performing at least one measurement on the calibrator sample using the analysis device (112), wherein at least one detector signal s is acquired ijk , where i=1, ... I, where I≥2, where i refers to the number of the calibrator sample, j=1, ... J, where J≥2, where j refers to the number of the hardware component, where k=1, ... K ij , where K ij ≥1, where k is the number of repetitions of the measurement step; c) at least one calibration step, wherein a relationship between said detector signal and said concentration of said analyte is determined, wherein said calibration step comprises: c.1: providing at least one parameterized function, wherein the parameterized function has a parameter set, wherein the parameter set comprises parameters describing an analyte-specific part of the parameterized function, wherein the parameter set further comprises parameters for adjusting the parameterized function of the hardware component (114), wherein in order to determine the parameters for adjusting the parameterized function of the hardware component (114), a calibrator sample is measured on each individual hardware component, wherein information from which hardware component the signal comes is also input into the matching process, and all hardware components are considered together in the matching process; c.2: determining a calibration value by performing a calibration based on the parameterized function; and c.3: Determine an analysis function based on the inverse function of the parameterized function and the determined calibration value.

2. A method for calibrating at least one analytical device (112) having duplicate hardware components, wherein the analytical device (112) comprises a plurality of hardware components (114), wherein the hardware components are physical and / or tangible parts of the analytical device (112), wherein the method comprises the following steps: A) providing at least one calibrator sample i having a known target value for the concentration of at least one analyte and an average calibration curve from which a theoretical signal of the at least one calibrator sample is derived; B) at least one measurement step, wherein the measurement step comprises performing at least one measurement on the calibrator sample using the analysis device (112), wherein at least one detector signal s is acquired ijk , where i=1, ... I, where I≥1, where i refers to the number of the calibrator sample, j=1, ... J, where J≥2, where j refers to the number of the hardware component, where k=1, ... K ij , where K ij ≥1, where k is the number of repetitions of the measurement step; C) at least one calibration step, wherein the relationship between the detector signal and a theoretical signal value is determined, wherein the calibration step comprises: - providing at least one parameterized function, wherein the parameterized function has a parameter set, wherein the parameter set comprises parameters describing an analyte-specific part of the parameterized function, wherein the parameter set further comprises parameters for adjusting the parameterized function of the hardware components (114), wherein in order to determine the parameters for adjusting the parameterized function of the hardware components (114), a calibrator sample is measured on each individual hardware component, wherein information from which hardware component a signal comes is also input into the matching process, and all hardware components are considered together in the matching process; - determining a calibration value by performing a calibration based on said parameterized function; and - determining an analysis function based on the inverse function of said parameterized function and the determined calibration values.

3. The method according to claim 1 or 2, wherein the method further comprises: At least one measurement is performed on a further sample, wherein the concentration of the further sample is determined based on the measurement signal of the further sample by using the analysis function.

4. The method according to claim 1 or 2, wherein the parameter group is composed of p=(p1, p2, ... p n , h1, h2, ...h r ), where n and r are positive integers, and p1, p2, ...p n corresponds to the parameters describing the analyte-specific part of the parameterized function, where h1, h2, ... h r refers to a vector describing the parameters of the parameterized function for adjusting the hardware component (114), wherein the calibration value is given by express.

5. The method according to claim 1 or 2, wherein a relationship between the detector signal and a theoretical signal value is determined, wherein the parameterized function is a signal adjustment function.

6. The method according to claim 1 or 2, wherein a relationship between the detector signal and the concentration of the analyte is determined, wherein the parameterized function is a signal-concentration-function. The method according to claim 6 , wherein the signal-concentration function is a linear function.

8. The method of claim 6, wherein the signal-concentration function comprises one or both of a hardware-part specific intercept, a hardware-part specific slope.

9. The method according to claim 6, wherein the signal-concentration function is a linear function with hardware-part-specific adjustment factors.

10. The method according to claim 1 or 2, wherein the analysis device (112) is selected from the group consisting of: a mass spectrometry device (116), specifically a liquid chromatography-mass spectrometry device; an immunoassay analyzer; a photometric device, a blood gas analyzer, a hematology analyzer, a DNA analyzer.

11. The method of claim 1 or 2, wherein the hardware components (114) are equivalent hardware components.

12. The method according to claim 1 or 2, wherein the hardware component (114) is selected from the group consisting of: a column (122), specifically a high performance liquid chromatography column; a flow, specifically a high performance liquid chromatography flow; a sample injection device, specifically a high performance liquid chromatography injection device; a pump; a measuring unit; a detector, specifically a mass spectrometer detector (126).

13. The method of claim 1 or 2, wherein the calibrator sample is run through or transported via some or all of the hardware components (114).

14. An apparatus (110) for calibrating at least one analytical device (112) having duplicate hardware components, wherein the hardware components are physical and / or tangible parts of the analytical device (112), the apparatus (110) comprising: at least one analytical device (112) comprising a plurality of hardware components (114), wherein the analytical device (112) is configured to perform at least one measurement on a calibrator sample i having a known target value for the concentration of at least one analyte, wherein the analytical device (112) is configured to acquire at least one detector signal s ijk , where i=1, ... I, where I≥2, where i refers to the number of the calibrator sample, j=1, ... J, where J≥2, where j refers to the number of the hardware component, where k=1, ... K ij , where K ij ≥1, where k is the number of repetitions of the measurement step; and at least one evaluation device (128), wherein the evaluation device (128) is configured to perform at least one calibration step, wherein a relationship between the detector signal and the concentration of the analyte and / or between the detector signal and a theoretical signal value is determined, wherein the evaluation device (128) is configured to provide at least one parameterized function, wherein the parameterized function has a parameter set, wherein the parameter set comprises parameters describing an analyte-specific part of the parameterized function, wherein the parameter set further comprises parameters for adjusting the parameterized function of the hardware components (114), wherein in order to determine the parameters for adjusting the parameterized function of the hardware components (114), a calibrator sample is measured on each individual hardware component, wherein information from which hardware component a signal comes is also input into the matching process and all hardware components are considered together in the matching process; The evaluation device (128) is further configured to determine a calibration value by performing a calibration based on the parameterized function, wherein the evaluation device (128) is further configured to determine an analysis function based on an inverse function of the parameterized function and the determined calibration value.

15. A computer or a computer network comprising at least one processor, wherein the processor is adapted to perform steps b) to c) and / or B) to C) of the method for calibrating at least one analytical device (112) according to any one of the preceding claims relating to a method for calibrating at least one analytical device (112).

16. A computer program, wherein the computer program is suitable for performing steps b) to c) and / or B) to C) of the method for calibrating at least one analytical device (112) according to any of the preceding claims relating to a method for calibrating at least one analytical device (112) when the program is executed on a computer.

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