Method for characterizing a mass spectrometer having at least one mass spectrometry cell

Abstract

To provide a method of characterizing a mass spectrometry instrument comprising at least one mass analyzing cell.SOLUTION: A method disclosed herein comprises analyzing a sample (110) containing at least one substance having a known molecular weight using a mass spectrometry instrument (100) so as to provide a mass spectrum of the sample (110), determining an outer envelope and an inner envelope of the mass spectrum, calculating a squared difference between the outer envelope and the inner envelope, and determining a deviation of the calculated squared difference from a theoretical mass to charge ratio value of the substance.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] Technical field This disclosure relates to a method for characterizing a mass spectrometer comprising at least one mass spectrometry cell. [Background technology]

[0002] Background technology There is growing interest in the implementation of mass spectrometry. Mass spectrometry (MS) is an analytical technique used to measure the mass-to-charge ratio of ions. The results are presented as a mass spectrum, i.e., a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used in a wide variety of fields and is applied to both pure samples and complex mixtures.

[0003] A mass spectrum is a plot of ion signals as a function of the mass-to-charge ratio. These spectra are used to determine the elemental or isotopic characteristics of a sample, as well as the mass of particles and molecules, and to reveal the chemical identity or structure of molecules and other compounds.

[0004] In a typical MS procedure, a sample, which may be a solid, liquid, or gas, is ionized, for example, by bombarding it with an electron beam. This allows some of the sample's molecules to be broken down into positively charged fragments, or simply positively charged without being broken down into fragments. These ions (fragments) are then separated according to their mass-to-charge ratio, for example, by accelerating them and applying an electric or magnetic field: ions with the same mass-to-charge ratio undergo the same amount of deflection. The ions are detected by a mechanism capable of detecting charged particles, such as an electron multiplier tube. The result is displayed as a spectrum of the signal intensity of the detected ions as a function of the mass-to-charge ratio. Atoms or molecules in the sample can be identified by correlating them with a known mass, for example, the mass of the entire molecule, or by a characteristic fragmentation pattern.

[0005] A mass spectrometer with at least one mass spectrometry cell has numerous different electronic potentials for guiding, filtering, and at least detecting ions. System parameters should harmonize the behavior of the same ions across different systems. Mass calibration parameters correlate the weight of ions and their resolution to the applied voltage. Due to changes in environmental conditions and system contamination over time, mass calibration can be subject to various fluctuations, shifts, and tendencies, which can negatively affect selectivity and sensitivity and, in the worst case, adversely impact patient outcomes. [Overview of the project] [Problems that the invention aims to solve]

[0006] Issues to be resolved Therefore, it is desirable to provide an automated classification system for the state of mass spectrometers, such as normal and abnormal. [Means for solving the problem]

[0007] overview This problem relates to a mass spectrometry system comprising at least one mass spectrometry cell having the features of an independent claim. This is addressed by methods, computer programs, and computer-readable storage media for characterizing analytical instruments. Convenient embodiments, which may be implemented individually or in any combination, are listed in the dependent claims and throughout the specification.

[0008] When used below, the terms "has...", "companies...", or "includes...", or any grammatical variations thereof, are used in a non-exclusive manner. Thus, these terms can refer to both situations where the entity described in this context has no further features other than those introduced by these terms, and situations where one or more further features exist. For example, the expressions "A has B", "A is equipped with B", and "A includes B" can refer to both situations where A has no other elements besides B (i.e., A is exclusively composed of B), and situations where entity A has one or more further elements besides B, such as element C, elements C and D, or other further elements.

[0009] Furthermore, note that the terms "at least one" or "one or more," or similar expressions indicating that a feature or element may appear more than once, are typically used only once when introducing each feature or element. In most cases below, 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 appear more than once.

[0010] Furthermore, when used below, the terms “preferably,” “more preferably,” “especially,” “even more particularly,” “specifically,” “more specifically,” or similar terms, are used with optional features without limiting the possibility of alternatives. Thus, features introduced by these terms are optional features and are not intended to limit the technical scope of the claims in any way. The present invention may be carried out by using alternative features, as will be understood by those skilled in the art. Similarly, features introduced by “in embodiments of the present invention” or similar expressions are intended to be optional features without any limitation with respect to alternative embodiments of the present invention, without any limitation with respect to the technical scope of the present invention, and without any limitation with respect to the possibility of combining such features with other optional or non-optional features of the present invention.

[0011] Furthermore, it should be noted that, as used herein, the terms “first,” “second,” “third,” “fourth,” or similar expressions serve only to distinguish features or structural members. It should be made clear that these terms are not intended to define any particular order of importance or relevance.

[0012] In a first embodiment, a method is proposed for characterizing a mass spectrometer comprising at least one mass spectrometry cell.

[0013] As used herein, the term “mass spectrometer” 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 any particular or special meaning. Specifically, the term may refer to, but is not limited to, a mass spectrometer used in mass spectrometry. Mass spectrometry (MS) is an analytical technique used to measure the mass-to-charge ratio of ions. The results are presented as a mass spectrum, i.e., a plot of intensity as a function of mass-to-charge ratio. Mass spectrometry is used in a multitude of different fields and is applied to pure samples and complex mixtures. A mass spectrum is a plot of ion signals as a function of mass-to-charge ratio. These spectra determine the elemental or isotopic characteristics of a sample, as well as the masses of particles and molecules, and of molecules and other compounds. It is used to reveal the chemical nature or structure of a substance. In a typical MS procedure, a sample, which may be a solid, liquid, or gas, is ionized, for example, by bombarding it with an electron beam. This allows some of the molecules in the sample to be broken down into positively charged fragments, or simply positively charged without being broken down into fragments. These ions (fragments) are then separated according to their mass-to-charge ratio, for example, by accelerating them and applying an electric or magnetic field to them: ions with the same mass-to-charge ratio experience the same amount of deflection. The ions are detected by a mechanism capable of detecting charged particles, such as an electron multiplier tube. The result is displayed as a spectrum of the signal intensity of the detected ions as a function of the mass-to-charge ratio. Atoms or molecules in the sample can be identified by correlating their known mass (e.g., the whole molecule) with the identified mass, or by characteristic fragmentation patterns.

[0014] As used herein, the term "analysis cell" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to a special or particular meaning. Specifically, without limitation, this term may refer to the part involved in mass resolution in a mass spectrometer. Thus, the analysis cell can resolve the mass of a sample or prepare or facilitate mass resolution.

[0015] As used herein, the term "characteristic evaluation" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to a special or particular meaning. Specifically, without limitation, this term may refer to the determination or detection of the state of a mass spectrometry instrument. In a simple application, the determination or detection can clarify a normal state or an abnormal state.

[0016] This method includes the following method steps, which may be performed in a given order, in particular. However, other orders are possible. Further, two or more method steps can be performed completely or partially simultaneously. Further, one or more, or all, of the method steps may be performed repeatedly, for example, repeated once or multiple times, even if only performed once. Further, this method may include additional method steps not enumerated.

[0017] This method comprises the following steps, namely - Analyzing a sample containing at least one substance having a known molecular weight by a mass spectrometry instrument to provide a mass spectrum of the sample; - Determining an outer envelope and an inner envelope of the mass spectrum; - Calculating the squared difference between the outer envelope and the inner envelope; - Determining the deviation from the theoretical mass-to-charge ratio value of the substance for the calculated squared difference and including.

[0018] As used herein, the term “analysis” and its equivalents are broad in meaning and should be given their general and ordinary meaning to those skilled in the art, and should not be limited to any particular or special meaning. Specifically, the term may refer to analytical techniques for determining the mass-to-charge ratio of ions, but is not limited to these.

[0019] As used herein, the term “sample” refers to a biological substance suspected to contain one or more analytes of interest, whose qualitative and / or quantitative detection can be associated with a clinical condition. Samples may be derived from any biological source, including physiological fluids such as blood, saliva, ocular lens fluid, cerebrospinal fluid, sweat, urine, milk, ascites, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissue, cells, etc. Samples may be prepared by preparing plasma from blood, diluting viscous fluids, Samples can be pre-treated prior to use, such as by dissolution, and pre-treatment methods may include filtration, centrifugation, distillation, concentration, inactivation of interfering components, and addition of reagents. Samples can be used directly as obtained from the source in some cases, or they can be used after pre-treatment and / or sample preparation workflows to alter the properties of the sample, such as after adding an internal standard, diluting with another solution, or mixing with reagents, in order to enrich (extract / separate / concentrate) the analyte of interest and / or remove matrix components that may interfere with the detection of the analyte of interest, for example, to enable the performance of one or more in vitro diagnostic tests. The term "sample" is often used to refer to a sample before preparation, while the term "prepared sample" is used to refer to a sample after preparation. In non-specific cases, the term "sample" may broadly refer to either a sample before preparation or a sample after preparation, or both. Examples of analytes of interest are generally vitamin D, addictive drugs, therapeutic agents, hormones, and metabolites. However, this list is not exhaustive.

[0020] When used herein, the term “envelope” is a broad term, and its general and ordinary meaning to those skilled in the art should be given, and not limited to any particular or special meaning. Specifically, the term may, but not limited to, refer to a curve that is tangent to each member of a group of curves at some point, and these points of tangency together form the entire envelope. Classically, a point on the envelope can be thought of as the intersection of two “minimally adjacent” curves, signifying the limit of intersection of adjacent curves. This idea can be generalized to the envelopes of surfaces in space, and can be generalized to higher dimensions. For an envelope to exist, the individual members of a group of curves must be differentiable curves (otherwise the concept of tangency does not apply), and there must be a smooth transition proceeding through the members. However, these conditions are not sufficient, and it is possible that a given group cannot have an envelope. A simple example of this is given by a group of concentric circles with increasing radii. Depending on whether the curve is located above or below the group of curves, it is called the upper envelope or the lower envelope.

[0021] For example, by closely monitoring the system's state during the startup process, automatic classification of the system state (normal / abnormal) is possible using "noise limits." Identifying abnormal states can prevent false patient outcomes. Furthermore, it is possible to check the proper insulation of electrical circuits or the quality of electrical components used. Using correct labeling of states (e.g., position shift, resolution, and envelope) can trigger correct maintenance actions, thus reducing system downtime and maintenance costs. From a manufacturer's perspective, this method is useful for selecting the correct quadrupole rod and can be helpful in the assembly process.

[0022] The squared difference between the outer envelope and the inner envelope is (f o -f i ) 2 It can be calculated as f oThis is the outer envelope, and f i This represents the inner envelope. According to this particular calculation of the squared difference, the difference between the outer and inner envelopes is weighted more heavily than a simple difference formation would suggest. Therefore, any imbalances that may exist between the two sides of a peak can be better explained or illustrated. Furthermore, this calculation facilitates a better distinction between the ion's mass spectrum and the noise in the ion's peripheral region.

[0023] This method may further include determining the deviation of the difference calculated along the mass-to-charge ratio axis of the mass spectrum. Thus, not only is a single point of the signal observed, but a range along the mass-to-charge ratio axis of the mass spectrum is observed, and therefore, more accurate monitoring of the state of the mass spectrometer becomes possible.

[0024] This method may further include determining the deviation of the calculated difference based on the left and right positions of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum. This allows observation of the left and right sides of the peak of the theoretical mass value of the substance in the mass spectrum. This allows observation of any resulting asymmetric signals (which may indicate an improper state of the mass spectrometer).

[0025] Determining the deviation may involve determining the ratio of the peaks at the left and right positions of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum. This allows us to observe the left and right sides of the peak of the theoretical mass value of the substance in the mass spectrum. If the peak is symmetric, the ratio of the signal heights at the left and right positions should be approximately 1. For asymmetric signal peaks, the ratio of the signal heights at the left and right positions will differ significantly from 1, and may be 2, 3, or even greater.

[0026] This method may further include determining that the mass spectrometer is in an inappropriate state if the deviation determined for the calculated difference exceeds a predetermined difference threshold. Thus, a clear determination regarding the state of the mass spectrometer can be made.

[0027] This method may further include performing a wavelet transform on the mass spectrum and determining the deviation of the amplitude of the wavelet-transformed mass spectrum from the theoretical amplitude value of the substance at a predetermined period. This enables a fairly microscopic observation of the mass spectrum and the state of the mass spectrometer.

[0028] When used herein, the term “wavelet transform” and its equivalents are broad terms, and their general and ordinary meanings to those skilled in the art should be given, and not limited to any particular or special meaning. Specifically, the term may refer, but is not limited to, a representation of a square-integrable (real or complex) function by a particular orthonormal series generated by wavelets. This paper provides formal mathematical definitions of orthonormal wavelets and integral wavelet transforms. A wavelet is a wave-like oscillation that starts at zero amplitude, increases, then decreases and returns to zero. This can typically be visualized as a “short-time oscillation,” such as the oscillations recorded by a seismograph or cardiac monitor. Generally, wavelets are intentionally constructed to have specific properties that make them useful with respect to signal processing. The fundamental idea of ​​wavelet transforms is that the transform should allow only a change in time extension, and not in shape. This is influenced by the selection of appropriate basis functions that enable this. The change in time extension is expected to follow the corresponding analytical frequencies of the basis functions. Based on the uncertainty principle of signal processing, a wavelet transform of the mass spectrum can be performed, and the deviation of the amplitude of the wavelet-transformed mass spectrum from the theoretical amplitude value of the substance at a given period can be determined, provided that the calculated difference does not exceed a predetermined difference threshold. Therefore, when a fairly macroscopic observation of the envelope is rather inconspicuous, a more detailed or microscopic observation of the mass spectrum can be performed, making it possible to detect even smaller deviations from the target state of the mass spectrometer.

[0029] This method may further include determining that the state of the mass spectrometer is inappropriate if the deviation determined for the amplitude exceeds a predetermined amplitude threshold. Therefore, a clear determination regarding the state of the mass spectrometer can be made.

[0030] In a second embodiment, a method is proposed for characterizing a mass spectrometer comprising at least one mass spectrometry cell.

[0031] This method includes the following method steps, which may be performed in a given order. However, However, other orders are also possible. Furthermore, it is possible to perform two or more method steps completely or partially simultaneously. Moreover, one or more or all of the method steps may be performed only once, or repeatedly, for example, once or multiple times. Furthermore, this method may include further method steps that are not listed.

[0032] This method involves the following steps, namely -A step of analyzing a sample containing at least one substance with a known molecular weight using a mass spectrometer to obtain a mass spectrum of the sample, - The step of performing a wavelet transform on the mass spectrum, - A step of determining the deviation of the amplitude of the mass spectrum after wavelet transform from the theoretical amplitude value of the material at a predetermined period. Includes.

[0033] In this regard, it should be clearly stated that the method of the second embodiment may be combined with the method of the first embodiment. In particular, the method of the second embodiment may be performed after the method of the first embodiment, for example, when it is not necessary to determine the deviation of the calculated squared difference from the theoretical mass-to-charge ratio of the substance in the method of the first embodiment. Therefore, the method of the second embodiment allows for a more detailed observation of the state of the mass spectrometer.

[0034] This method may further include generating a heatmap of the mass spectrum after wavelet transform and determining the amplitude deviation at a given period in the heatmap. Such a heatmap allows observation of highly affected regions in the mass spectrum after wavelet transform.

[0035] As used herein, the term “heatmap” 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 any particular or special meaning. Specifically, the term may refer, but is not limited to, a data visualization technique that shows the magnitude of a phenomenon as color in two dimensions. The change in color may be by hue or intensity and give the reader a clear visual cue about how the phenomenon is clustered or changes in space. There are two fundamentally different categories of heatmaps: cluster heatmaps and spatial heatmaps. In cluster heatmaps, magnitudes are laid out in a matrix of fixed-cell sizes, where the rows and columns of the matrix are discrete phenomena and categories, and the sorting of rows and columns is intentional and somewhat arbitrary for the purpose of proposing clusters or depicting clusters as discovered by statistical analysis. The cell size is arbitrary but large enough to be clearly visible. In contrast, the position of magnitude in a spatial heatmap is constrained by the position of magnitude in that space, the concept of cells does not exist, and the phenomenon is considered to change continuously.

[0036] When wavelets are used, a heatmap is also known as a scalogram. In a scalogram, the results of the wavelet transform are visualized as a three-dimensional graph. The first spatial dimension is the defined range of the signal, which is the mass-to-charge ratio m / z on the x-axis as used herein. The second spatial dimension is the frequency or period of the signal on the y-axis. The third spatial dimension represents the amplitude of a specific period at a particular position within the defined range, i.e., m / z, i.e., the wavelet power. The latter is represented not in a spatial way, but in a colored way, specifically gray for lower amplitudes and white for higher amplitudes.

[0037] As used herein, the term “period” is a broad term and should be given its general and ordinary meaning to those skilled in the art, and not a specific or special meaning. The meaning should not be limited. Specifically, this term can refer to periodic signal portions located within the frequency range and definition range of a signal, though not limited to these. Therefore, it can indicate potential frequency variations within a frequency range, and significant frequencies can be clearly associated with specific portions within the definition range.

[0038] This method may further include determining the amplitude deviation at a predetermined period according to the wavelet power.

[0039] As used herein, the term “wavelet power” 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 any particular or special meaning. Specifically, the term may refer to, but is not limited to, the amplitude of a particular period associated with a particular position within the defined range of the mass spectrum after the wavelet transform. Thus, the amount of a particular periodic signal portion may be visualized in comparison to all other periodic signal portions. Thus, relative descriptions are possible that allow for the derivation of the amount of a particular frequency in the signal.

[0040] This method may further include determining that the state of the mass spectrometer is inappropriate if the deviation determined for the amplitude exceeds a predetermined amplitude threshold. Therefore, a clear determination regarding the state of the mass spectrometer can be made.

[0041] The mass spectrometry cell may be a quadrupole. Therefore, the mass spectrometer may be a so-called quadrupole mass spectrometer. Consequently, the sample can be analyzed with high resolution.

[0042] As used herein, the term “quadrupole mass spectrometer” 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 any particular or special meaning. Specifically, the term may refer to, but is not limited to, one type of mass spectrometer used in mass spectrometry. A quadrupole mass spectrometer (QMS) is also known as a transmission quadrupole mass spectrometer, quadrupole mass filter, or quadrupole mass spectrometer. As the name suggests, it consists of four cylindrical rods set parallel to each other. In a quadrupole mass spectrometer, the quadrupole is the mass spectrometer and is a component of the instrument that plays a role in selecting sample ions based on their mass-to-charge ratio (m / z). The ions are separated in the quadrupole based on the stability of their orbits in the oscillating electric field applied to the rods. The quadrupole consists of four parallel metal rods. Each opposing pair of rods is electrically connected to each other, and a radio frequency (RF) voltage with a DC offset voltage is applied between one pair of rods and the other pair of rods. Ions flow down the quadrupole between the rods. At a given voltage ratio, only ions with a specific mass-to-charge ratio reach the detector, while other ions become orbitally unstable and collide with the rods. This allows for the selection of ions with a specific m / z value, or allows the operator to scan a range of m / z values ​​by continuously varying the applied voltage. Mathematically, this can be modeled with the help of Mathieu's differential equations. Ideally, the rods are hyperbolic, but cylindrical rods with a specific ratio of rod diameter to spacing are easier to manufacture and provide a sufficient approximation of a hyperbola. Small variations in the ratio have a significant impact on the resolution and peak shape. Different manufacturers choose slightly different ratios to fine-tune the operating characteristics in the context of expected application requirements.

[0043] The mass spectrometer may have two or more mass spectrometry cells, and this method may be performed on each mass spectrometry cell.

[0044] For example, the mass spectrometer may be a so-called triple quadrupole mass spectrometer (TQMS). As used herein, the term "triple quadrupole mass spectrometer" is a broad term, and its general and ordinary meaning to those skilled in the art should be given. The term should not be limited to a specific or special sense. Specifically, it may refer to a tandem mass spectrometer consisting of two quadrupole mass spectrometers in series, with a (non-mass-resolving) radio frequency (RF)-only quadrupole between them that functions as a cell for collision-induced dissociation. This configuration is often abbreviated as QqQ, and here as Q1q2Q3. Essentially, a triple quadrupole mass spectrometer operates on the same principle as a single quadrupole mass spectrometer. Each of the two mass filters (Q1 and Q3) contains four parallel cylindrical metal rods. While both Q1 and Q3 are controlled by direct current (dc) and radio frequency (rf) potentials, the collision cell q receives only an RF potential. The RF potential associated with the collision cell (q) allows the passage of all selected ions. In some instruments, the standard quadrupole collision cell is replaced with a hexupole or octupole collision cell for improved efficiency.

[0045] Unlike traditional MS techniques, MS / MS techniques allow for continuous mass spectrometry across different regions of the instrument. TQMS follows a tandem arrangement in space, as ionization, primary mass selection, collision-induced dissociation (CID), mass spectrometry of fragments generated in CID, and detection occur in separate segments of the instrument. Sector instruments tend to outperform TQMS in mass resolution and mass range. However, triple quadrupoles have the advantages of being less expensive, easier to operate, and highly efficient. Furthermore, when operating in a selected reaction monitoring mode, TQMS offers superior detection sensitivity and quantification. Triple quadrupoles enable the study of low-energy, small-molecule reactions, which is useful when small molecules are being analyzed.

[0046] This method may be performed at predetermined points in time. In particular, these points in time may include at least the startup of the mass spectrometer. Therefore, the state can be checked at regular intervals.

[0047] This method may further include being implemented as a predictive maintenance measure. Therefore, any defective component of the mass spectrometer can be replaced before the entire mass spectrometer becomes defective.

[0048] This method may be computerized. As used herein, the term “computerized implementation” is a broad term, and its general and ordinary meaning to those skilled in the art should be given, and not limited to any particular or special meaning. Specifically, the term may refer to a process that is fully or partially implemented by using data processing means, such as data processing means comprising at least one processing unit of focus electronics and control systems, but not limited to these. Thus, the term “computer” can generally refer to an apparatus, or combination or network of apparatuses having at least one data processing means, such as at least one processing unit. The computer may further comprise one or more further components, such as at least one of data storage devices, electronic interfaces, or human-machine interfaces.

[0049] In a further embodiment, a computer program comprising instructions is proposed, which, when the program is executed by a mass spectrometer comprising at least one mass spectrometer cell, causes the mass spectrometer to perform the method according to any one of the prior claims of the Method.

[0050] In a further embodiment, a computer-readable storage medium containing instructions is proposed, which, when a program is executed by a mass spectrometer having at least one mass spectrometer cell, causes the mass spectrometer to perform the method according to any one of the prior claims of the Method.

[0051] As used herein, the term “moving average” 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 any particular or special meaning. Specifically, the term can refer to a calculation for analyzing data points by creating a set of averages of different subsets of an entire dataset, though not limited to these. Also known as a moving average (MM) or rolling average, it is a type of finite impulse response filter. Variations include simple, cumulative, or weighted forms. Given a set of numbers and a fixed subset size, the first element of the moving average is obtained by taking the average of the first fixed subset of the set of numbers. The subset is then modified by a “forward shift,” i.e., by excluding the first number from the set of numbers and including the next number in the subset. Moving averages are commonly used in time series data to smooth short-term fluctuations and highlight long-term trends or cycles. The threshold between short-term and long-term depends on the application, and the parameters of the moving average are set accordingly. For example, it is often used in the technical analysis of financial data such as stock prices, returns, or transaction volumes. It is also used in economics to examine GDP, employment, or other macroeconomic time series. Mathematically, since the moving average is a type of convolution, it can be thought of as an example of a low-pass filter used in signal processing. When used with non-time series data, the moving average removes high-frequency components regardless of time, but typically implies some kind of ordering. Simply put, it can be thought of as data smoothing.

[0052] Further disclosures and proposals herein include computer-executable instructions for performing a method according to the present invention in one or more embodiments included herein when the program is executed on a computer or computer network. Specifically, the computer program may be stored on a computer-readable data carrier and / or computer-readable storage medium.

[0053] As used herein, the terms “computer-readable data carrier” and “computer-readable storage medium” may specifically refer to non-temporary data storage means such as hardware storage media storing computer executable instructions. Specifically, the computer-readable data carrier or storage medium may be, or may comprise, a storage medium such as random access memory (RAM) and / or read-only memory (ROM).

[0054] Therefore, specifically, one, two or more, or all of the method steps a) to d) described above may be performed using a computer or computer network, preferably using a computer program.

[0055] Further disclosures and proposals herein include computer program products having program code means for performing methods according to one or more embodiments included herein when the program is executed on a computer or computer network. Specifically, the program code means may be stored in a computer-readable data carrier and / or computer-readable storage medium.

[0056] For example, data carriers storing data structures that, after being loaded into a computer or computer network, can perform methods according to one or more embodiments disclosed herein are further disclosed and proposed herein, such as the working memory or main memory of a computer or computer network.

[0057] When this program is run on a computer or computer network, Computer program products, in which program code means are stored on a machine-readable carrier, are further disclosed and proposed herein for carrying out methods according to one or more embodiments of those disclosed herein. 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 paper format, or on a computer-readable data carrier and / or computer-readable storage medium. Specifically, a computer program product may be delivered over a data network.

[0058] Finally, modulated data signals containing instructions readable to a computer system or computer network for performing a method according to one or more embodiments disclosed herein are disclosed and proposed herein.

[0059] With regard to computer implementations of the present invention, one or more or all of the method steps of a method according to one or more embodiments disclosed herein may be performed by using a computer or computer network. Therefore, generally, any method step involving data provision and / or manipulation may be performed by using a computer or computer network. Generally, these method steps may include any method step except for method steps that require manual work, such as in certain embodiments that typically involve sample provision and / or actual measurement.

[0060] Specifically, in this specification, - A computer or computer network comprising at least one processor, the processor configured to perform a method according to one of the embodiments described herein, - A computer-loadable data structure configured to perform a method according to one of the embodiments described herein when running on a computer, - A computer program configured to perform a method according to one of the embodiments described herein when running on a computer, - A computer program comprising programming means for performing a method according to one of the embodiments described herein when running on a computer or computer network, - A computer program comprising a programming means according to a prior embodiment, wherein the programming means is a computer program stored in a computer-readable storage medium. - A storage medium that stores a data structure, and is configured to perform a method according to one of the embodiments described herein after being loaded into the main memory and / or working memory of a computer or computer network, and - A computer program product having program code means that can be stored on or stored on a storage medium, wherein when the program code means is executed on a computer or computer network, the method according to one of the embodiments described herein is performed. Further information will be disclosed.

[0061] In summary, without ruling out the possibility of further embodiments, the following embodiments can be envisioned.

[0062] Embodiment 1: A method for characterizing a mass spectrometer comprising at least one mass spectrometry cell, - Analyzing a sample containing at least one substance having a known molecular weight using a mass spectrometry instrument to obtain a mass spectrum of the sample, - Determining an outer envelope and an inner envelope of the mass spectrum, - Calculating the squared difference between the outer envelope and the inner envelope, - Determining, for the calculated squared difference, the deviation from the theoretical mass-to-charge ratio value of the substance A method comprising:

[0063] Embodiment 2: The squared difference between the outer envelope and the inner envelope is calculated as (f o - f i ), 2 where f o is the outer envelope and f i is the inner envelope, the method according to the preceding claim.

[0064] Embodiment 3: The method according to any one of the preceding claims, further comprising determining the deviation of the calculated difference along the mass-to-charge ratio axis of the mass spectrum.

[0065] Embodiment 4: The method according to the preceding claims, further comprising determining the deviation of the calculated difference based on the positions on the left and right sides of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum.

[0066] Embodiment 5: Determining the deviation comprises determining the ratio of the peak at the position on the left side and the peak at the position on the right side of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum, the method according to the preceding claim.

[0067] Embodiment 6: The method according to any one of the preceding claims, further comprising determining that the state of the mass spectrometry instrument is inappropriate when the determined deviation of the calculated difference exceeds a predetermined threshold difference.

[0068] Embodiment 7: The method according to the prior claim, further comprising performing a wavelet transform on a mass spectrum and determining the deviation of the amplitude of the wavelet-transformed mass spectrum from the theoretical amplitude value of the substance at a predetermined period.

[0069] Embodiment 8: A method according to a prior claim, wherein a wavelet transform of the mass spectrum is performed, and the deviation of the amplitude of the wavelet-transformed mass spectrum from the theoretical amplitude value of the material at a predetermined period is performed if the calculated difference does not exceed a predetermined difference threshold.

[0070] Embodiment 9: The method according to the prior claims, further comprising determining that the state of the mass spectrometer is inappropriate when the determined amplitude deviation exceeds a predetermined amplitude threshold.

[0071] Embodiment 10: A method for characterizing a mass spectrometer comprising at least one mass spectrometry cell, -Analyze a sample containing at least one substance with a known molecular weight using a mass spectrometer to obtain the mass spectrum of the sample, - Performing a wavelet transform on the mass spectrum, - Determining the deviation of the amplitude of the mass spectrum after wavelet transform from the theoretical amplitude value of the material at a given period. A method that includes this.

[0072] Embodiment 11: The method according to the prior claims, further comprising generating a heatmap of the mass spectrum after wavelet transform and determining the amplitude deviation at a predetermined period in the heatmap.

[0073] Embodiment 12: Determining the amplitude deviation at a predetermined period based on wavelet power. A method according to any one of the two prior claims, further comprising doing.

[0074] Embodiment 13: A method according to any one of the prior claims, further comprising determining that the state of a mass spectrometer is inappropriate when the determined amplitude deviation exceeds a predetermined amplitude threshold.

[0075] Embodiment 14: A mass spectrometer comprising two or more mass spectrometer cells, wherein the method is performed for each of the prior claims, according to any one of the prior claims.

[0076] Embodiment 15: The method according to the prior claims, wherein the mass spectrometry cell is a quadrupole.

[0077] Embodiment 16: A method according to any one of the prior claims, which is performed at a predetermined time.

[0078] Embodiment 17: The method according to the prior claims, wherein the time interval includes at least the startup of the mass spectrometer.

[0079] Embodiment 18: A method according to any one of the prior claims, further comprising performing the method as a predictive maintenance measure.

[0080] Embodiment 19: A method according to any one of the claims of the prior art, which is computer-implemented.

[0081] Embodiment 20: A computer program comprising instructions, wherein the instructions cause the mass spectrometer to perform a method according to any one of the prior claims relating to the method when the program is executed by the mass spectrometer comprising at least one mass spectrometer cell.

[0082] Embodiment 21: A computer-readable storage medium including instructions, wherein the instructions cause the mass spectrometer to perform a method according to any one of the prior claims relating to the method when the program is executed by the mass spectrometer having at least one mass spectrometer cell. [Brief explanation of the drawing]

[0083] Further optional features and embodiments are disclosed in more detail in subsequent descriptions of embodiments, preferably in conjunction with dependent claims. Each optional feature may be implemented independently or in any feasible combination, as will be understood by those skilled in the art. The scope of the present invention is not limited by preferred embodiments. Embodiments are schematically shown in the figures, where the same reference numerals in these figures refer to the same or functionally equivalent elements. In the figure,

[0084] [Figure 1] This shows a schematic diagram of a mass spectrometer. [Figure 2] A flowchart of the method for characterizing a mass spectrometer according to the first embodiment is shown. [Figure 3A] An example of the first mass spectrum from the first analysis cell is shown. [Figure 3B] The second example mass spectrum of the third analysis cell is shown. [Figure 4A] An example of the first mass spectrum from the first analysis cell is shown. [Figure 4B] The second example mass spectrum of the third analysis cell is shown. [Figure 5A] An illustrative diagram of the squared difference calculated according to the mass-to-charge ratio of the first analysis cell is shown. [Figure 5B] An illustrative diagram of the squared difference calculated according to the mass-to-charge ratio of the third analysis cell is shown. [Figure 6] A flowchart of a method for characterizing a mass spectrometer according to a second embodiment is shown. [Figure 7A] The third example mass spectrum of the first analysis cell is shown. [Figure 7B] An example of the fourth mass spectrum from the third analysis cell is shown. [Figure 8A] The first heatmap shows an example of the first analysis cell. [Figure 8B]The second heatmap shows an example of the third analysis cell. [Figure 9A] The first wavelet transform diagram illustrates the first analysis cell. [Figure 9B] The second wavelet transform diagram illustrates the third analysis cell. [Figure 10A] An illustrative first wavelet amplitude diagram of the first analysis cell is shown. [Figure 10B] An exemplary second wavelet amplitude diagram of the third analysis cell is shown. [Modes for carrying out the invention]

[0085] Detailed description of the embodiment Figure 1 shows a schematic diagram of the mass spectrometer 100. The mass spectrometer 100 comprises at least one mass spectrometry cell 102. In this exemplary embodiment, the mass spectrometer 100 is a triple quadrupole mass spectrometer comprising three analysis cells 102, 104, and 106. Thus, each of the analysis cells 102, 104, and 106 is a quadrupole. In particular, the mass spectrometer 100 comprises a first analysis cell 102, a second analysis cell 104, and a third analysis cell 106, which are arranged to form a tandem mass spectrometer consisting of two quadrupole mass filters 102, 106 in series, with a (non-mass-resolving) radio frequency (RF) only quadrupole located between them, which functions as a cell 104 for collision-induced dissociation. The mass spectrometer 100 further comprises an ionization source 108, such as an electrospray ionization (ESI) source or an atmospheric pressure chemical ionization (APCI) source, located adjacent to the first analysis cell 102, to which the sample 110 may be input. The mass spectrometer 100 further comprises a particle multiplication unit 112 located adjacent to the third analysis cell 106 and configured to produce an output signal 114. In this configuration, the sample 110 is ionized in the ionization source. The first analysis cell 102 performs mass-charge selection (m / z selection) of the sample ions. The second analysis cell 104 cleaves the sample ions. The third analysis cell 106 performs mass-charge selection (m / z selection) of the cleaved sample ions. The basic operating principle of such a mass spectrometer is known to those skilled in the art from the prior art described above, for example, so a further explanation of the operating principle is omitted. Some conventional mass spectrometers have a fairly low resolution of 20 points / Da. The determination of the maximum signal intensity (accuracy of mass calibration) and the full width at half maximum of the maximum signal intensity (separation efficiency to adjacent ions) can be performed very easily. However, signal shifts or other changes are not accurate enough to monitor. In this embodiment, the mass spectrometer 100 has a higher resolution, limited to 0.0076 Da, which enables data evaluation with higher accuracy of 1000 points / Da.

[0086] Figure 2 shows a flowchart of a method for characterizing a mass spectrometer 100 comprising at least one mass spectrometry cell 102 according to a first embodiment of the present disclosure. The method of the present disclosure begins with step S10, in which a sample 110 containing at least one substance having a known molecular weight is analyzed by the mass spectrometer 100 to obtain a mass spectrum of the sample 110. The method then proceeds to step S12, in which the outer envelope and inner envelope of the mass spectrum are determined. The method then proceeds to step S14, in which the squared difference between the outer envelope and the inner envelope is calculated. The method then proceeds to step S16, in which the calculated squared difference is determined from the theoretical mass-to-charge ratio of the substance. The method then proceeds from the theoretical mass-to-charge ratio of the substance determined from the calculated difference. The process proceeds to step S18, which determines whether the deviation exceeds a predetermined difference threshold. If the deviation determined for the calculated difference exceeds the predetermined difference threshold, the method proceeds to step S20, which determines that the state of the mass spectrometer is inappropriate. Conversely, if the deviation determined for the calculated difference does not exceed the predetermined difference threshold, the method proceeds to step S22, which determines that the state of the mass spectrometer is appropriate. This method may be performed for each of the mass spectrometer cells 102, 104, and 106.

[0087] This method and any modifications made as needed will be described in more detail below.

[0088] Figure 3A shows an exemplary first mass spectrum 116 of a first analysis cell 102 for testosterone and its internal standard analyzed by the mass spectrometer 100 of this embodiment. Figure 3B shows an exemplary second mass spectrum 118 of a third analysis cell 106 for testosterone and its internal standard analyzed by the mass spectrometer 100 of this embodiment. In Figures 3A and 3B, the mass-to-charge ratio (m / z ratio) is given as x-axis 120. The signal intensity (in %) is given as y-axis 122. Graph 124 shows the signal intensity corresponding to the mass-to-charge ratio. As can be seen from Figure 3A, a less pronounced front shoulder 126 can be observed, and multiple maxima 128 exist in the higher region. Therefore, higher resolution and data evaluation with more data points can result in better calibration efficiency. As can be seen from Figure 3B, differences in quadrupoles can be observed; for example, the upward flank 130 on the left is noisier than the downward flank 132 on the right. Therefore, the method described herein is based on the finding that it is possible to characterize the fingerprint of a quadrupole based on the behavior of its mass spectrum, including monitoring system-specific or long-term effects.

[0089] Figure 4A shows an exemplary first mass spectrum 116 of a first analysis cell 102 for testosterone and its internal standard analyzed by the mass spectrometer 100 of this embodiment. Figure 4B shows an exemplary second mass spectrum 118 of a third analysis cell 106 for testosterone and its internal standard analyzed by the mass spectrometer 100 of this embodiment. Hereafter, only the differences from Figures 3A and 3B will be described, and similar features will be indicated by the same reference numerals. As shown in Figures 4A and 4B, the method according to this disclosure shows the outer envelope f of the mass spectra 116, 118. o and inner envelope f i The step further includes determining the signal intensity of the mass spectra 116, 118 and the outer envelope f. o , and inner envelope f i This shows the outer envelope f. o and inner envelope fi The difference between these results in a left-hand relative spectrum that can further characterize the quadrupole state. Variations in environmental conditions such as humidity, temperature, and pressure, or contamination of the matrix provided by sample 110, can be visualized by this characterization of the "macroscopic" fingerprint. As can be seen from the comparison between Figure 4A and Figure 4B, the envelope f of the first mass spectrum 116 of the first analysis cell 102 o and f i This is the outer envelope f o This exhibits higher symmetry than the second mass spectrum 118 of the third analysis cell 106, which shows a bulge 134 on the left side.

[0090] The method described herein involves the outer envelope f o and inner envelope f i The step further includes calculating the squared difference between the outer envelope and the inner envelope. The squared difference between the outer envelope and the inner envelope is (f o -f i ) 2 It is calculated as f o This is the outer envelope, and f i This is the inner envelope.

[0091] Figure 5A shows an example of the squared difference calculated in this way according to the mass-to-charge ratio (m / z ratio) of the first analysis cell 102. Figure 5B shows an example of the squared difference calculated in this way according to the mass-to-charge ratio (m / z ratio) of the third analysis cell 106. Below, only the differences from Figures 3A and 3B are described, and similar features are indicated by the same reference numerals. In Figures 5A and 5B, the mass-to-charge ratio (m / z ratio) is given as x-axis 120. The calculated outer envelope f o and inner envelope f i The squared difference between and is given as y-axis 122. Graph 136 shows the squared difference calculated according to the mass-to-charge ratio (m / z ratio) to the left of the theoretical value. Graph 138 shows the squared difference calculated according to the mass-to-charge ratio (m / z ratio) to the right of the theoretical value. As can be seen from the comparison between Figure 5A and Figure 5B, the envelope fo ,f i The squared difference between them is much larger with respect to the third analysis cell 106.

[0092] The method according to this disclosure further includes the step of determining the deviation of the calculated squared difference from the theoretical mass-to-charge ratio value of the substance. The deviation of the calculated difference is determined along the mass-to-charge ratio axis of the mass spectrum. In particular, the deviation of the calculated difference is determined based on the left and right positions of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum. Determining the deviation includes determining the ratio of the peak at the left position to the peak at the right position of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum. The ratio of the peak heights of the calculated squared difference is approximately equal to 1 for the left and right sides in the case of symmetry, as shown by line 140 in Figure 5A. In the case of asymmetricity, this is not the case, and the difference in height can be determined as shown by line 142 in Figure 5B. Thus, if the deviation determined for the calculated difference does not exceed a predetermined difference threshold, as shown, for example, by approximately the same peak height in Figure 5A, the state of the mass spectrometer 100 is determined to be appropriate. Conversely, if the deviation determined for the calculated difference exceeds a predetermined difference threshold, as shown by the different peak heights in Figure 5B, for example, the state of the mass spectrometer 100 is determined to be inappropriate.

[0093] Figure 6 shows a flowchart of a method for characterizing a mass spectrometer 100 comprising at least one mass spectrometry cell 102 according to a second embodiment of the present disclosure. It should be explicitly stated that the method of the second embodiment may be combined with the method of the first embodiment, for example, if the calculated difference does not exceed a predetermined difference threshold. Needless to say, the method of the second embodiment may be carried out independently of the method of the first embodiment. The method of the present disclosure begins with step S30, in which a sample 110 containing at least one substance having a known molecular weight is analyzed by the mass spectrometer 100 to obtain a mass spectrum of the sample 110. The method then proceeds to step S32, in which a wavelet transform of the mass spectrum is performed. The method then proceeds to step S34, in which a deviation of the amplitude of the wavelet-transformed mass spectrum from the theoretical amplitude value of the substance at a predetermined period is determined. The method then proceeds to step S36, in which a deviation of the amplitude of the wavelet-transformed mass spectrum from the theoretical amplitude value of the substance at a predetermined period is determined to exceed a predetermined amplitude threshold. If the deviation of the amplitude of the mass spectrum after wavelet transform from the theoretical amplitude value of the substance at a predetermined period determined to exceed a predetermined amplitude threshold, the method proceeds to step S38, in which it is determined that the mass spectrometer is in an inappropriate state. Conversely, if the deviation of the amplitude of the mass spectrum after wavelet transform from the theoretical amplitude value of the substance at a predetermined period determined to exceed a predetermined amplitude threshold, the method proceeds to step S40, in which it is determined that the mass spectrometer is in an appropriate state. This method may be performed for each of the mass spectrometer cells 102, 104, and 106.

[0094] This method and any modifications made as needed will be described in more detail below.

[0095] Figure 7A shows an exemplary third mass spectrum 144 of the first analysis cell 102 for testosterone analyzed by the mass spectrometer 100 of this embodiment. Figure 7B shows an exemplary fourth mass spectrum 146 of the third analysis cell 106 for testosterone analyzed by the mass spectrometer 100 of this embodiment. In Figures 7A and 7B, the mass-to-charge ratio (m / z ratio) is given as x-axis 120. Signal intensity and signal intensity The moving average is given as y-axis 122. Graph 148, shown at the top of Figures 7A and 7B, shows the signal intensity according to the mass-to-charge ratio. Graph 150, shown at the bottom of Figures 7A and 7B, shows the moving average of the signal intensity according to the mass-to-charge ratio.

[0096] The method of the second embodiment is based, in particular, on the discovery that an alternative method for characterizing the mass spectrum is to "microscopically" examine the wavelet transform of the signal. At the noise frequency, it can be expected that the amplitude of the fourth mass spectrum 146 of the third analysis cell 106 will be larger than that of the third mass spectrum 144 of the first analysis cell 102.

[0097] This method further includes generating a heatmap of the mass spectrum after wavelet transform and determining the amplitude deviation at a predetermined period in the heatmap. In particular, the amplitude deviation at a predetermined period is determined according to the wavelet power.

[0098] Figure 8A shows an exemplary first heatmap 152 of a first analysis cell 102 for testosterone analyzed by the mass spectrometer 100 of this embodiment. Figure 8B shows an exemplary second heatmap 154 ​​of a third analysis cell 106 for testosterone analyzed by the mass spectrometer 100 of this embodiment. In Figures 8A and 8B, the mass-to-charge ratio (m / z ratio) is given as x-axis 120. The period (mz) is given as y-axis 156 on the left. The wavelet power level is shown as y-axis 158 on the right, with high wavelet power levels shown in white and low wavelet power levels or even lower wavelet power levels shown in gray or black for simplification. The region with the largest amplitude in a given period may be observed in the second heatmap 154 ​​of the third analysis cell 106, as indicated by circle 160 in the second heatmap 154 ​​of the third analysis cell 106.

[0099] Figure 9A shows an exemplary first wavelet transform figure 162 of a first analysis cell 102 for testosterone analyzed by the mass spectrometer 100 of this embodiment. Figure 9B shows an exemplary second wavelet transform figure 164 of a third analysis cell 106 for testosterone analyzed by the mass spectrometer 100 of this embodiment. In Figures 9A and 9B, the mean wavelet power is given as x-axis 120, and the period (mz) is given as y-axis 122. Graph 166 shown in Figure 9A shows the third mass spectrum 144 after wavelet transform of the first analysis cell 102. Graph 168 shown in Figure 9B shows the fourth mass spectrum 146 after wavelet transform of the third analysis cell 106. As shown by graph 166, there are no significant signals of less than one period in the first wavelet transform figure 162 of the first analysis cell 102. As shown by circle 170, a larger amplitude can be observed only for the third analysis cell 106, as a prominent signal of 0.02 periods / 5 kHz, at a predetermined period marked in this manner.

[0100] Figure 10A shows an exemplary first wavelet amplitude figure 172 of a first analysis cell 102 for testosterone analyzed by the mass spectrometer 100 of this embodiment. Figure 10B shows an exemplary second wavelet amplitude figure 174 of a third analysis cell 106 for testosterone analyzed by the mass spectrometer 100 of this embodiment. In Figures 10A and 10B, the mass-to-charge ratio m / z is given as x-axis 120. The wavelet amplitude is given as y-axis 122. Graph 176 shown in Figure 10A shows the wavelet amplitude of the third mass spectrum 144 of the first analysis cell 102 in proportion to the mass-to-charge ratio m / z. Graph 178 shown in Figure 10B shows the wavelet amplitude of the fourth mass spectrum 146 of the third analysis cell 106 in proportion to the mass-to-charge ratio m / z. As shown by Graph 176, the wavelet amplitude does not show a significant signal at 0.02 period / 5kHz. As shown by circle 180, the signal is the mass spectral pea Because it is at the highest point at position K, a large wavelet amplitude exists at approximately 0.02 periods / 5kHz.

[0101] Therefore, if the deviation determined for the amplitude does not exceed a predetermined amplitude threshold, as shown by the absence of a peak or amplitude in Figure 9A, for example, the state of the mass spectrometer 100 is determined to be appropriate. Conversely, if the deviation determined for the amplitude exceeds a predetermined amplitude threshold, as shown by the peak or amplitude in Figure 9B, for example, the state of the mass spectrometer 100 is determined to be inappropriate.

[0102] The methods according to each embodiment described herein may use the following exemplary parameters to classify the state of the mass spectrometer 100 as appropriate / normal or inappropriate / abnormal.

[0103] Regarding the resolution in Da, a suitable state can be defined as 0.8 ± 0.1, and an unsuitable state can be defined as < 0.7 and > 0.9. Regarding precision, i.e., the position of the mass axis (in units of Da), a suitable state can be defined as an acceptable shift range of ± 0.1, and an unsuitable state can be defined as a shift > 0.1. Regarding high-precision characterization, i.e., multiple systems with machine learning, a suitable state can be defined as being comparable to other systems and having no shift or environmental changes over time, and an unsuitable state can be defined as the quadrupole not being comparable to other systems and having shift or environmental changes over time. Regarding envelope characterization, a suitable state can be defined as a symmetrical arrangement of the outer and inner envelopes, and an unsuitable state can be defined as an asymmetrical arrangement of the outer and inner envelopes. Regarding wavelets or Fourier transforms, a suitable state can be defined as the absence of characteristic frequencies, and an unsuitable state can be defined as interference between signal and noise frequencies.

[0104] The methods according to each embodiment described herein are performed at predetermined points in time, particularly including at least the startup of the mass spectrometer 100. For example, the method is performed as a predictive maintenance measure. The methods according to each embodiment described herein may be computer-implemented. For example, the method may be performed automatically under the control of a computer or computer system. A Fourier transform may be performed instead of a wavelet transform. [Explanation of symbols]

[0105] List of reference numbers 100 Mass spectrometry equipment 102 First analysis cell 104 Second analysis cell 106 Third analysis cell 108 Ionization source 110 samples 112 Particle multiplication section 114 Signal 116 First mass spectrum of the first analysis cell 118 Second mass spectrum of the third analytical cell 120 x axis 122 y-axis 124 Signal strength according to mass-to-charge ratio 126 Front shoulder 128 Maximum value 130 Left side, uphill flank 132 Right-hand downhill flank 134 Bulge 136 Squared difference calculated according to the mass-to-charge ratio on the left side from the theoretical value 138 Squared difference calculated according to the mass-to-charge ratio on the right side from the theoretical value 140 Ratio of symmetrical peak heights 142 Ratio of asymmetrical peak heights 144 Third mass spectrum of the first analysis cell 146. Fourth mass spectrum of the third analytical cell. 148 Signal strength according to mass-to-charge ratio 150 Moving average of signal intensity according to mass-to-charge ratio 152 Example of the first analysis cell: First heatmap 154 Example of the third analysis cell: Second heatmap 156 Left y-axis 158 Right y-axis 160 Region of maximum amplitude in a predetermined period 162 First wavelet transform diagram of the first analysis cell 164 Second wavelet transform diagram of the third analysis cell 166 Third mass spectrum after wavelet transform of the first analysis cell 168 Fourth mass spectrum after wavelet transform of the third analysis cell 170 Predetermined period 172 First wavelet amplitude diagram of the first analysis cell 174 Second wavelet amplitude diagram of the third analysis cell 176 Wavelet amplitude of the third mass spectrum of the first analysis cell according to the mass-to-charge ratio m / z 178 Wavelet amplitude of the fourth mass spectrum of the third analysis cell 180 Large wavelet amplitude S10 Analyze the sample Determine the outer and inner envelopes of the S12 mass spectrum. S14 Calculate the squared difference between the outer envelope and the inner envelope. S16 Determine the deviation of the calculated squared difference from the theoretical mass-to-charge ratio of the material. S18 Determine whether the deviation of the calculated difference from the theoretical mass-to-charge ratio value of the substance exceeds a predetermined difference threshold. S20 Determine that the mass spectrometer is in an inappropriate state. S22 Determine that the mass spectrometer is in proper condition. S30 Analyze a sample containing at least one substance with a known molecular weight. S32 Perform wavelet transform on the mass spectrum. S34 Determine the deviation of the amplitude of the mass spectrum after wavelet transform from the theoretical amplitude value of the material at a given period. S36 Determine whether the deviation of the amplitude of the mass spectrum after wavelet transform from the theoretical amplitude value of the material at a predetermined period exceeds a predetermined amplitude threshold. S38 Determine that the mass spectrometer is in an inappropriate state. S40 Determine that the mass spectrometer is in proper condition.

Claims

1. A method for characterizing a mass spectrometer (100) comprising at least one mass spectrometry cell (102, 104, 106), - The step of analyzing the sample (110) with the mass spectrometer (100) to obtain the mass spectrum (116, 118, 144, 146) of the sample (110) containing at least one substance having a known molecular weight, - A step of performing a wavelet transform on the mass spectrum (116, 118, 144, 146), - A step of determining the deviation of the amplitude of the mass spectrum (116, 118, 144, 146) after the wavelet transform from the theoretical amplitude value of the substance at a predetermined period (160), Methods that include...

2. The method according to claim 1, further comprising the steps of generating a heatmap (162, 164) of the wavelet transform mass spectra (116, 118, 144, 146), and determining the deviation of the amplitude at a predetermined period (160) in the heatmap (162, 164).

3. The method according to claim 1, further comprising the step of determining the deviation of the amplitude in the predetermined period (160) according to the wavelet power.

4. The method according to any one of claims 1 to 3, further comprising the step of determining that the state of the mass spectrometer (100) is inappropriate if the determined deviation exceeds a predetermined amplitude threshold.

5. The method according to any one of claims 1 to 3, wherein the mass spectrometer (100) comprises two or more mass spectrometer cells (102, 104, 106), and the method is performed for each mass spectrometer cell (102, 104, 106).

6. The method according to any one of claims 1 to 3, wherein the mass spectrometer (100) comprises two or more mass spectrometer cells (102, 104, 106), the mass spectrometer cells are quadrupoles, and the method is performed for each mass spectrometer cell (102, 104, 106).

7. The method according to any one of claims 1 to 3, wherein the method is performed at a predetermined time, the time including at least the start of the mass spectrometer (100).

8. The method according to any one of claims 1 to 3, further comprising the step of performing the method as a predictive maintenance measure.

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