Method for characterization of a mass spectrometry instrument comprising at least one mass spectrometry cell - Patents.com

Abstract

A method is proposed for characterization of a mass spectrometry instrument (100) comprising at least one mass spectrometry cell (102, 104, 106), comprising the steps of analyzing a sample (110) containing at least one substance having a known molecular weight by the mass spectrometry instrument (100) to obtain a mass spectrum (116, 118, 144, 146) of the sample (110), determining an outer envelope and an inner envelope of the mass spectrum (116, 118, 144, 146), calculating the squared difference between the outer envelope and the inner envelope, and determining the deviation of the calculated squared difference from a theoretical mass-to-charge ratio value of the substance.

Description

[Technical field]

[0001] Technical Field The present disclosure relates to a method for characterization of a mass spectrometry instrument comprising at least one mass spectrometry cell. [Background technology]

[0002] Background technology There is growing interest in the practice 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 mass-to-charge ratio. Mass spectrometry is used in many different fields and is applied to pure samples and complex mixtures.

[0003] A mass spectrum is a plot of ion signals as a function of mass-to-charge ratio. These spectra are used to determine the elemental or isotopic signatures of a sample, as well as the masses 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 solid, liquid or gaseous, is ionized, for example by bombardment with an electron beam. This allows some of the molecules of the sample to break into positively charged fragments, or simply become positively charged without breaking them into fragments. These ions (fragments) are then separated according to their mass-to-charge ratio, for example by accelerating them and subjecting them to an electric or magnetic field: ions of 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. The result is displayed as a spectrum of the signal intensity of the detected ions as a function of their mass-to-charge ratio. Atoms or molecules in the sample can be identified by correlating known masses, for example whole molecules, with identified masses, or by characteristic fragmentation patterns.

[0005] Mass spectrometry instruments, which include at least one mass spectrometry cell, have many different electronic potentials for directing, filtering, and at least detecting ions. The parameters of the system should match the behavior of the same ions in different systems. Mass calibration parameters correlate the weight of ions and their resolution to the applied voltage. Due to changing environmental conditions and contamination of the system over time, mass calibrations can undergo various variations, shifts, and trends, which can adversely affect selectivity and sensitivity, and in the worst case, patient outcomes. Summary of the Invention [Problem to be solved by the invention]

[0006] Problems to be solved It is therefore desirable to provide an automated classification of the state of a mass spectrometry instrument, such as normal and abnormal. [Means for solving the problem]

[0007] overview This problem is addressed by a method, a computer program and a computer readable storage medium for characterization of a mass spectrometry instrument comprising at least one mass spectrometry cell having the features of the independent claims. Advantageous embodiments, which may be realized alone or in any combination, are set out in the dependent claims as well as in the entire specification.

[0008] When used below, the terms "having", "comprises" or "includes" or any grammatical variants thereof are used in a non-exclusive manner. These terms may therefore refer both to the situation where, apart from the features introduced by these terms, no further features are present in the entity described in this context, and to the situation where one or more further features are present. As an example, the expressions "A has B", "A comprises B" and "A includes B" may refer both to the situation where no other elements are present in A apart from B (i.e., the situation where A is exclusively composed of B), and to the situation where, apart from B, one or more further elements are present in the entity A, such as element C, elements C and D, or even further elements.

[0009] Furthermore, it should be noted that the terms "at least one" or "one or more" or similar expressions indicating that a feature or element may be present more than once are typically used only once when introducing each feature or element. In the following, in most cases, when referring to each feature or element, the expressions "at least one" or "one or more" will not be repeated, despite the fact that each feature or element may be present more than once.

[0010] Furthermore, when used hereinafter, the terms "preferably", "more preferably", "particularly", "more particularly", "particularly", "more particularly" or similar terms are used with optional features without limiting the possibilities of alternatives. Features introduced by these terms are therefore optional features and are not intended to limit the scope of the claims in any way. The invention may be implemented by using alternative features, as would be understood by a person skilled in the art. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features without any limitations regarding alternative embodiments of the invention, without any limitations regarding the scope of the invention, and without any limitations regarding the possibilities of combining the features introduced in such a way with other optional or non-optional features of the invention.

[0011] Furthermore, it should be noted that, as used herein, the terms "first," "second," "third," "fourth," or similar expressions merely serve to distinguish features or structural members. It is expressly stated that these terms are not intended to define a particular order of importance or relevance.

[0012] In a first aspect, a method for the characterization of a mass spectrometry instrument comprising at least one mass spectrometry cell is proposed.

[0013] As used herein, the term "mass spectrometry instrument" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, a mass analyzer 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 many different fields and applies 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 are used to determine the elemental or isotopic characteristics of a sample, as well as the masses of particles and molecules, and to reveal the chemical identity or structure of molecules and other compounds. In a typical MS procedure, a sample, which may be solid, liquid, or gas, is ionized, for example by bombardment with an electron beam. This allows some of the molecules of the sample to be broken down into positively charged fragments, or simply positively charged without breaking them into fragments. These ions (fragments) are then separated according to their mass-to-charge ratio, for example by accelerating them and subjecting them to electric or magnetic fields: ions of 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. The results are displayed as a spectrum of the signal intensity of the detected ions as a function of mass-to-charge ratio. Atoms or molecules in the sample can be identified by correlating known masses (e.g., whole molecules) with the identified masses, or by characteristic patterns of fragmentation.

[0014] As used herein, the term "analysis cell" is a broad term and should be given its common and ordinary meaning to one of ordinary skill in the art and should not be limited to a specific or special meaning. The term may specifically, but is not limited to, refer to the portion of a mass spectrometer that is involved in mass resolution. Thus, the analysis cell can resolve the mass of a sample or prepare for or facilitate mass resolution.

[0015] As used herein, the term "characterization" is a broad term and should be given its common and ordinary meaning to one of ordinary skill in the art and should not be limited to a specific or special meaning. The term can specifically refer to, but is not limited to, the determination or detection of a condition of a mass spectrometry instrument. In simple applications, the determination or detection can reveal a normal or abnormal condition.

[0016] The method includes the following method steps, which may in particular be performed in a given order. However, other orders are possible. Furthermore, it is possible for two or more method steps to be performed fully or partially simultaneously. Furthermore, one or more, or all, of the method steps may be performed only once or may be performed repeatedly, e.g., repeated one or more times. Furthermore, the method may include further method steps not listed.

[0017] The method comprises the following steps: - analyzing a sample comprising at least one substance having a known molecular weight with 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 of the calculated squared difference from a theoretical mass-to-charge ratio value of the substance; Includes.

[0018] As used herein, the term "analysis" and equivalents are broad terms and should be given their common and ordinary meaning to those of skill in the art and should not be limited to any specific or special meaning. The term may specifically refer to, but is not limited to, analytical techniques for determining the mass-to-charge ratio of ions.

[0019] As used herein, the term "sample" refers to a biological material suspected of containing one or more analytes of interest, the qualitative and / or quantitative detection of which can be correlated to a clinical condition. Samples can be derived from any biological source, such as physiological fluids, including blood, saliva, eye lens fluid, cerebrospinal fluid, sweat, urine, milk, ascites, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissue, cells, and the like. Samples can be pre-treated prior to use, such as preparation of plasma from blood, dilution of viscous fluids, dissolution, and the like, and methods of treatment can 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 can be used after pre-treatment and / or sample preparation workflows to alter the nature of the sample, such as after addition of an internal standard, dilution with another solution, or mixing with a reagent, for example, to enable the performance of one or more in vitro diagnostic tests, enrich (extract / separate / concentrate) the analytes of interest, and / or remove matrix components that may interfere with the detection of the analytes of interest. The term "sample" is often used to refer to a sample prior to sample preparation, while the term "sample after preparation" is used to refer to a sample after sample preparation. In non-specific cases, the term "sample" may broadly refer to either a sample prior to sample preparation or a sample after sample preparation, or both. Examples of analytes of interest are generally vitamin D, drugs of abuse, therapeutic agents, hormones, and metabolites. However, this list is not exhaustive.

[0020] As used herein, the term "envelope" is a broad term and should be given its general and ordinary meaning to those skilled in the art, and should not be limited to a special or special meaning. The term may specifically, but is not limited to, refer to a curve that touches each member of a family of curves at some point, and these tangent points together form the entire envelope. Classically, a point on an envelope can be thought of as the intersection of two "near-minimum" curves, meaning the limit of intersection of the adjacent curves. This idea can be generalized to the envelope of a surface in space, and can also be generalized to higher dimensions. To have an envelope, it is necessary that the individual members of the family of curves are differentiable curves (otherwise the concept of tangency does not apply) and there must be a smooth transition going through the members. However, these conditions are not sufficient and it is possible that a given family cannot have an envelope. A simple example of this is given by a family of concentric circles of increasing radius. Depending on whether the curve lies above or below the family of curves, the curve is called the upper or lower envelope.

[0021] By closely monitoring the condition, for example during the start-up process, an automatic classification of the system condition (normal / abnormal) is possible using a "noise limit". Identification of the abnormal condition can prevent false patient results. Furthermore, a check for proper insulation of the electrical circuits or the quality of the used electrical components is possible. Using correct labeling of the conditions (e.g., shifts in position, resolution, and envelope) the correct maintenance actions can be triggered, thus reducing system downtime and maintenance costs. From the manufacturer's point of view, this method can be useful for selecting the correct quadrupole rods and aid in the assembly process.

[0022] The squared difference between the outer and inner envelopes is (f o -f i ) 2 It can be calculated as f ois the outer envelope and f i is the inner envelope. According to this particular calculation of the squared difference, the difference between the outer and inner envelopes is weighted more than a simple difference formation. Thus, any imbalance that may exist between the two sides of a peak can be better explained or illustrated. Furthermore, this calculation facilitates better discrimination between the mass spectrum of an ion and the noise in the surrounding area of ​​the ion.

[0023] The method may further include determining a deviation of the calculated differences along the mass to charge ratio axis of the mass spectrum, such that rather than just a single point of the signal being observed, a range along the mass to charge ratio axis of the mass spectrum is observed, thus allowing more accurate monitoring of the condition of the mass spectrometry instrument.

[0024] The method may further include determining the deviation of the calculated difference based on the position to the left and right of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum, thereby observing the left and right of the theoretical mass value peak of the substance in the mass spectrum, thereby observing possible asymmetric signals (which give a hint of an improper state of the mass spectrometry instrument).

[0025] Determining the deviation may include determining a ratio of a peak at a position to the left of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum to a peak at a position to the right of the theoretical mass value of the substance, whereby the left and right sides of the peak of the theoretical mass value of the substance in the mass spectrum are observed. If the peak is symmetrical, the ratio of the signal heights at the left and right positions should be approximately 1. For asymmetrical signal peaks, the ratio of the signal heights at the left and right positions may be significantly different from 1, and may be 2 or 3 or even greater.

[0026] The method may further comprise determining that the condition of the mass spectrometry instrument is inadequate if the determined deviation in the calculated difference exceeds a predefined difference threshold, such that a definitive decision can be made regarding the condition of the mass spectrometry instrument.

[0027] The method may further include performing a wavelet transform of the mass spectrum and determining the deviation of the amplitude of the wavelet transformed mass spectrum from a theoretical amplitude value for the material at a given period, thereby allowing a fairly microscopic view of the mass spectrum and the state of the mass spectrometry instrument.

[0028] As used herein, the term "wavelet transform" and its equivalents are broad terms and should be given their common and ordinary meaning to those skilled in the art, and should not be limited to any special or special meaning. The term may specifically, but not be limited to, the representation of a square-integrable (real or complex-valued) function by a particular orthonormal series generated by a wavelet. This paper provides formal mathematical definitions of orthonormal wavelets and integral wavelet transforms. A wavelet is a wave-like oscillation whose amplitude starts at zero, increases, and then decreases back to zero. This can typically be visualized as a "short-time oscillation" such as the oscillations recorded by a seismograph or a heart monitor. In general, wavelets are purposefully created to have certain properties that make them useful for signal processing. The basic idea of ​​the wavelet transform is that the transform should only allow for changes in time dilation, not shape. This is affected by choosing appropriate basis functions that allow this. The changes in time dilation are expected to follow the corresponding analytical frequencies of the basis functions. Based on the uncertainty principle of signal processing, performing a wavelet transform of 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 given period may be performed if the determined deviation of the calculated difference does not exceed a given difference threshold. Thus, if a fairly macroscopic observation of the envelope is rather unremarkable, a closer or more microscopic observation of the mass spectrum can be performed, making it possible to detect even smaller deviations from the target state of the mass spectrometry instrument.

[0029] The method may further comprise determining that the condition of the mass spectrometry instrument is inadequate if the determined deviation in amplitude exceeds a predefined amplitude threshold, such that a definitive decision can be made regarding the condition of the mass spectrometry instrument.

[0030] In a second aspect, a method for the characterization of a mass spectrometry instrument comprising at least one mass spectrometry cell is proposed.

[0031] The method includes the following method steps, which may in particular be performed in a given order. However, other orders are possible. Furthermore, it is possible for two or more method steps to be performed fully or partially simultaneously. Furthermore, one or more, or all, of the method steps may be performed only once or may be performed repeatedly, e.g., repeated one or more times. Furthermore, the method may include further method steps not listed.

[0032] The method comprises the following steps: - analyzing a sample comprising at least one substance having a known molecular weight with a mass spectrometry instrument to provide a mass spectrum of the sample; - performing a wavelet transform of the mass spectrum; - determining the deviation of the amplitude of the mass spectrum after the wavelet transformation from the theoretical amplitude value of the substance at a given period; Includes.

[0033] In this respect, it is expressly stated that the method of the second aspect may be combined with the method of the first aspect. In particular, the method of the second aspect may be carried out after the method of the first aspect, for example, in the case where in the method of the first aspect no deviation from the theoretical mass-to-charge ratio value of the substance of the calculated squared difference has to be determined. The method of the second aspect therefore allows a closer observation of the state of the mass spectrometer.

[0034] The method may further comprise generating a heat map of the wavelet transformed mass spectrum and determining the amplitude deviation at predetermined periods in the heat map, such a heat map allowing for observing highly affected regions of the wavelet transformed mass spectrum.

[0035] As used herein, the term "heatmap" is a broad term and should be given its common and ordinary meaning to those skilled in the art, and should not be limited to a special or special meaning. The term may specifically, but is not limited to, refer to a data visualization technique that shows the magnitude of a phenomenon as color in two dimensions. The color variations may be by hue or intensity, giving the reader a clear visual cue as to how the phenomena are clustered or vary in space. There are two fundamentally different categories of heatmaps: cluster heatmaps and spatial heatmaps. In cluster heatmaps, the magnitudes are laid out in a matrix of fixed cell size, the rows and columns of the matrix are discrete phenomena and categories, and the sorting of the rows and columns is deliberate and somewhat arbitrary, with the goal of proposing clusters or depicting clusters as discovered by statistical analysis. The size of the cells is arbitrary, but large enough to be clearly visible. In contrast, the location of the magnitudes in a spatial heatmap is constrained by the location of the magnitudes in the space, there is no concept of cells, and the phenomena are considered to vary continuously.

[0036] With wavelets, the heat map is also known as a scalogram. In a scalogram, the result of the wavelet transform is 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 particular period associated with a particular position in the defined range, i.e. m / z, i.e. the wavelet power. The latter is represented not in a spatial manner but in a colored manner, in particular with grey for lower amplitudes and white for higher amplitudes.

[0037] As used herein, the term "periodic" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term can specifically refer to, but is not limited to, a periodic signal portion located in a frequency range and definition range of a signal. Thus, it can indicate potential variations in frequency in a frequency range and can clearly associate prominent frequencies with specific portions of the definition range.

[0038] The method may further comprise determining the deviation in amplitude at a given period as a function of 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 a special or special meaning. The term may specifically, but not exclusively, refer to the amplitude of a particular period associated with a particular position within a defined range of a mass spectrum after a wavelet transform. Thus, the amount of a particular periodic signal portion may be visualized when compared to all other periodic signal portions. Thus, a relative description is possible that allows the amount of a particular frequency in a signal to be derived.

[0040] The method may further comprise determining that the condition of the mass spectrometry instrument is inadequate if the determined deviation in amplitude exceeds a predefined amplitude threshold, such that a definitive decision can be made regarding the condition of the mass spectrometry instrument.

[0041] The mass analysis cell may be a quadrupole, and therefore the mass analysis instrument may be a so-called quadrupole mass analyzer, so that the sample can be analyzed with high resolution.

[0042] As used herein, the term "quadrupole mass analyzer" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, a type of mass analyzer used in mass spectrometry. A quadrupole mass analyzer (QMS) is also known as a transmission quadrupole mass analyzer, a quadrupole mass filter, or a quadrupole mass. 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 analyzer and is the component of the instrument responsible for selecting sample ions based on their mass-to-charge ratio (m / z). Ions are separated in the quadrupole based on the stability of their trajectories in an oscillating electric field applied to the rods. The quadrupole consists of four parallel metal rods. Each pair of opposing 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 of a particular mass-to-charge ratio reach the detector, others become unstable in their trajectories and collide with the rods. This allows the selection of ions with a particular m / z, 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 the Mathieu differential equation. Ideally, the rods are hyperbolic, but cylindrical rods with a particular ratio of rod diameter to spacing provide an easy to manufacture and sufficient approximation of the hyperbola. Small variations in the ratio have a large effect on the resolution and peak shape. Different manufacturers choose slightly different ratios to fine-tune the operating characteristics in the context of the expected application requirements.

[0043] The mass spectrometry instrument may comprise two or more mass spectrometry cells and the method may be performed for each mass spectrometry cell.

[0044] For example, the mass spectrometry instrument may be a so-called triple quadrupole mass spectrometer (TQMS). As used herein, the term "triple quadrupole mass spectrometer" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, a tandem mass spectrometer consisting of two quadrupole mass analyzers in series with a (non-mass resolving) radio frequency (RF) only quadrupole between them that serves as a cell for collision induced dissociation. This configuration is often abbreviated as QqQ, and is abbreviated here as Q1q2Q3. In essence, a triple quadrupole mass spectrometer operates on the same principle as a single quadrupole mass analyzer. Each of the two mass filters (Q1 and Q3) contains four parallel cylindrical metal rods. Both Q1 and Q3 are controlled by direct current (dc) and radio frequency (rf) potentials, while the collision cell q is only subjected to RF potentials. The RF potential associated with the collision cell (q) allows the passage of all selected ions. In some instruments, the normal quadrupole collision cell has been replaced with a hexapole or octapole collision cell, which improves efficiency.

[0045] Unlike traditional MS techniques, MS / MS techniques allow for sequential mass analysis in different regions of the instrument. TQMS follows a tandem-in-space configuration since ionization, primary mass selection, collision-induced dissociation (CID), mass analysis of the fragments generated in CID, and detection occur in separate segments of the instrument. Sector instruments tend to surpass TQMS in mass resolution and mass range. However, triple quadrupoles have the advantage of being cheaper, easier to operate, and extremely efficient. Also, when operating in selected reaction monitoring mode, TQMS has superior detection sensitivity as well as quantification. Triple quadrupoles allow for the study of low-energy small molecule reactions, which is useful when small molecules are being analyzed.

[0046] The method may be performed at predetermined times, in particular those times may include at least the start-up of the mass spectrometry instrument, so that the status can be checked at regular intervals, etc.

[0047] The method may further include performing the method as a predictive maintenance measure, so that any defective components of the mass spectrometry instrument can be replaced before the entire instrument becomes defective.

[0048] The method may be computer-implemented. As used herein, the term "computer-implemented" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to a process that is fully or partially performed by using a data processing means, such as, but not limited to, a data processing means comprising at least one processing unit, in particular of the focus electronics and control system. Thus, the term "computer" may generally refer to a device having at least one data processing means, such as at least one processing unit, or a combination or network of devices. The computer may further comprise one or more further components, such as at least one of a data storage device, an electronic interface, or a human-machine interface.

[0049] In a further aspect, a computer program is proposed comprising instructions which, when the program is executed by a mass spectrometry instrument comprising at least one mass spectrometry cell, cause the mass spectrometry instrument to carry out a method according to any one of the preceding method claims.

[0050] In a further aspect, a computer readable storage medium is proposed comprising instructions, which when the program is executed by a mass spectrometry instrument comprising at least one mass spectrometry cell, causes the mass spectrometry instrument to perform a method according to any one of the preceding claims relating to a method.

[0051] As used herein, the term "moving average" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term can specifically refer to, but is not limited to, a calculation for analyzing data points by creating a series of averages of different subsets of the entire data set. Also called 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 series 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 series of numbers. The subset is then modified by "shifting forward," i.e., by excluding the first number in the series 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, they are often used in technical analysis of financial data such as stock prices, returns, or trading volumes. It is also used in economics to look at gross domestic product, employment, or other macroeconomic time series. Mathematically, a moving average can be thought of as an example of a low-pass filter used in signal processing, since it is a type of convolution. When used on non-time series data, a moving average removes high frequency components without regard to time, although some kind of ordering is typically implied. In simple terms, it can be thought of as smoothing the data.

[0052] Further disclosed and proposed herein is a computer program comprising computer executable instructions for carrying out the method according to the present invention in one or more of the embodiments contained herein when the program is executed on a computer or a computer network. In particular, the computer program may be stored on a computer readable data carrier and / or a computer readable storage medium.

[0053] As used herein, the terms "computer-readable data carrier" and "computer-readable storage medium" may specifically refer to non-transitory data storage means such as a hardware storage medium having computer-executable instructions stored thereon. The computer-readable data carrier or storage medium may specifically be or comprise a storage medium such as a random access memory (RAM) and / or a read-only memory (ROM).

[0054] Thus, in particular, one, more than one or all of the method steps a) to d) as described above may be carried out using a computer or a computer network, preferably using a computer program.

[0055] Further disclosed and proposed herein is a computer program product, which comprises program code means for executing the method according to the invention in one or more of the embodiments contained herein when the program is executed on a computer or a computer network. In particular, the program code means may be stored on a computer readable data carrier and / or a computer readable storage medium.

[0056] Further disclosed and proposed herein is a data carrier storing a data structure which, after being loaded into a computer or computer network, such as a working memory or main memory of a computer or computer network, is capable of performing the methods according to one or more of the embodiments disclosed herein.

[0057] Further disclosed and proposed herein is a computer program product having program code means stored on a machine-readable carrier for executing the method according to one or more of the embodiments disclosed herein when the program is executed on a computer or computer network. As used herein, a computer program product refers to a program as a tradeable product. The product can generally be in any format, such as a paper format, or can be on a computer-readable data carrier and / or a computer-readable storage medium. In particular, the computer program product can be distributed over a data network.

[0058] Finally, a modulated data signal containing instructions readable by a computer system or computer network for carrying out a method according to one or more of the embodiments disclosed herein is disclosed and proposed herein.

[0059] With respect to computer-implemented aspects of the present invention, one or more or all of the method steps of the method according to one or more of the embodiments disclosed herein may be performed by using a computer or a computer network.Thus, in general, any of the method steps including providing and / or manipulating data may be performed by using a computer or a computer network.In general, these method steps may include any method steps, except for those method steps that typically require manual operations, such as providing a sample and / or performing the actual measurement in certain aspects.

[0060] Specifically, in this specification, a computer or computer network comprising at least one processor, the processor being configured to execute a method according to one of the embodiments described herein, - a computer-loadable data structure configured, when executed on a computer, to carry out a method according to one of the embodiments described herein; a computer program configured, when it is run on a computer, to carry out a method according to one of the embodiments described herein, a computer program comprising program means for carrying out a method according to one of the embodiments described herein when said computer program is run on a computer or on a computer network, a computer program comprising program means according to the preceding embodiment, the program means being stored on a computer readable storage medium; a storage medium storing a data structure, the data structure being configured to execute a method according to one of the embodiments described herein after being loaded into a main memory and / or a working memory of a computer or a computer network, and A computer program product comprising program code means storable or stored on a storage medium, the program code means performing the method according to one of the embodiments described herein when executed on a computer or a computer network. is further disclosed.

[0061] In summary, without excluding further embodiments, the following embodiments can be envisaged:

[0062] Embodiment 1: A method for characterization of a mass spectrometry instrument comprising at least one mass spectrometry cell, comprising: - analyzing a sample comprising at least one substance having a known molecular weight with a mass spectrometry instrument to provide a mass spectrum of the sample; - determining the outer and inner envelope of the mass spectrum; - calculating the squared difference between the outer envelope and the inner envelope; - determining the deviation of the calculated squared difference from the theoretical mass-to-charge ratio value of the substance; The method includes:

[0063] Embodiment 2: The squared difference between the outer envelope and the inner envelope is (f o -f i ) 2 It is calculated as f o is the outer envelope and f i is the inner envelope.

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

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

[0066] Embodiment 5: A method according to the preceding claims, wherein determining the deviation comprises determining a ratio of a peak at a position to the left of a theoretical mass value of the substance along a mass-to-charge ratio axis of the mass spectrum to a peak at a position to the right of the theoretical mass value of the substance.

[0067] Embodiment 6: A method according to any one of the preceding claims, further comprising determining that the condition of the mass spectrometry instrument is inadequate if the determined deviation of the calculated difference exceeds a predefined difference threshold.

[0068] Embodiment 7: A method according to the preceding claims, further comprising performing a wavelet transform of the mass spectrum and determining the deviation of the amplitude of the wavelet transformed mass spectrum from a theoretical amplitude value for the substance at a given period.

[0069] Embodiment 8: A method according to the preceding claims, wherein performing a wavelet transform of the mass spectrum and determining the deviation of the amplitude of the wavelet transformed mass spectrum from a theoretical amplitude value of the substance at a predetermined period is performed if the determined deviation of the calculated difference does not exceed a predetermined difference threshold.

[0070] Embodiment 9: The method according to the preceding claims, further comprising determining that the condition of the mass spectrometry instrument is unsuitable if the determined deviation in amplitude exceeds a predefined amplitude threshold.

[0071] Embodiment 10: A method for characterization of a mass spectrometry instrument comprising at least one mass spectrometry cell, comprising: - analyzing a sample comprising at least one substance having a known molecular weight with a mass spectrometry instrument to provide a mass spectrum of the sample; - performing a wavelet transform of the mass spectrum; - determining the deviation of the amplitude of the mass spectrum after the wavelet transformation from the theoretical amplitude value of the substance at a given period; The method includes:

[0072] Embodiment 11: A method according to the preceding claims, further comprising generating a heat map of the wavelet transformed mass spectrum and determining the amplitude deviation at predetermined periods in the heat map.

[0073] Embodiment 12: A method according to any one of the previous two claims, further comprising determining the amplitude deviation in a given period depending on the wavelet power.

[0074] Embodiment 13: A method according to any one of the preceding claims, further comprising determining that the condition of the mass spectrometry instrument is unsuitable if the determined deviation in amplitude exceeds a predefined amplitude threshold.

[0075] Embodiment 14: A method according to any one of the preceding claims, wherein the mass spectrometry instrument comprises two or more mass spectrometry cells, and the method is performed for each mass spectrometry cell.

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

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

[0078] Embodiment 17: A method according to the preceding claims, wherein the time point comprises at least a start-up time of the mass spectrometry instrument.

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

[0080] Embodiment 19: A computer-implemented method according to any one of the preceding method claims.

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

[0082] Embodiment 21: A computer-readable storage medium comprising instructions, which when the program is executed by a mass spectrometry instrument comprising at least one mass spectrometry cell, causes the mass spectrometry instrument to perform a method according to any one of the preceding method-related claims. [Brief description of the drawings]

[0083] Further optional features and embodiments are disclosed in more detail in the following description of the embodiments, preferably in conjunction with the dependent claims, in which each optional feature may be realized in an independent manner as well as in any possible combination, as understood by a person skilled in the art. The scope of the present invention is not limited by the preferred embodiments. The embodiments are illustrated diagrammatically in the figures, where identical reference numbers in these figures refer to identical or functionally equivalent elements. In the figure,

[0084] [Figure 1] 1 shows a schematic diagram of a mass spectrometry instrument. [Diagram 2] 1 shows a flow chart of a method for characterization of a mass spectrometry instrument according to a first embodiment. [Figure 3A] 1 shows an exemplary first mass spectrum of a first analytical cell. [Figure 3B] 13 shows an exemplary second mass spectrum of a third analytical cell. [Figure 4A] 1 shows an exemplary first mass spectrum of a first analytical cell. [Figure 4B] 13 shows an exemplary second mass spectrum of a third analytical cell. [Figure 5A] 1 shows an exemplary diagram of the calculated squared difference as a function of the mass-to-charge ratio of a first analytical cell. [Figure 5B] 13 shows an exemplary diagram of the calculated squared difference as a function of the mass-to-charge ratio of a third analytical cell. [Figure 6] 4 shows a flow chart of a method for characterization of a mass spectrometry instrument according to a second embodiment. [Figure 7A] 13 shows an exemplary third mass spectrum of the first analytical cell. [Figure 7B] 13 shows an exemplary fourth mass spectrum of the third analytical cell. [Figure 8A] 1 shows an exemplary first heatmap of a first analysis cell. [Figure 8B]13 shows an exemplary second heatmap of a third analysis cell. [Figure 9A] FIG. 2 shows an exemplary first wavelet transform diagram of a first analysis cell. [Figure 9B] FIG. 13 shows an exemplary second wavelet transform diagram of a third analysis cell. [Figure 10A] 1 shows an exemplary first wavelet magnitude diagram of a first analysis cell. [Figure 10B] 13 shows an exemplary second wavelet magnitude diagram of a third analysis cell. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0085] Detailed Description of the Embodiments 1 shows a schematic diagram of a mass spectrometry instrument 100. The mass spectrometry instrument 100 comprises at least one mass spectrometry cell 102. In this exemplary embodiment, the mass spectrometry instrument 100 is a triple quadrupole mass spectrometer with three analytical cells 102, 104, 106. Each of the analytical cells 102, 104, 106 is therefore a quadrupole. In particular, the mass spectrometry instrument 100 comprises a first analytical cell 102, a second analytical cell 104 and a third analytical cell 106 arranged to build a tandem mass spectrometer consisting of two quadrupole mass filters 102, 106 in series, between which is located a (non-mass resolving) radio frequency (RF) only quadrupole serving as the cell 104 for collision induced dissociation. The mass spectrometry instrument 100 further comprises an ionization source 108, such as an electrospray ionization (ESI) source or an atmospheric pressure chemical ionization (APCI) source, arranged adjacent to the first analytical cell 102, to which a sample 110 may be input. The mass spectrometry instrument 100 further comprises a particle multiplication section 112 arranged adjacent to the third analytical cell 106 and configured to provide an output signal 114. In this configuration, the sample 110 is ionized in the ionization source. The first analytical cell 102 performs mass-to-charge selection (m / z selection) of the sample ions. The second analytical cell 104 fragments the sample ions. The third analytical cell 106 performs mass-to-charge selection (m / z selection) of the fragmented sample ions. The basic operating principle of such a mass spectrometry instrument is known to a person skilled in the art from the prior art, e.g. as described above, and therefore a further description of the operating principle is omitted. Some conventional mass spectrometry instruments have a rather low resolution of 20 points / Da. The determination of the maximum signal intensity (precision of mass calibration) and the full width at half maximum of the maximum signal intensity (separation efficiency to adjacent ions) can be performed quite easily. However, shifts or other changes in the signal are not precise enough to be monitored. In this embodiment, the mass spectrometry instrument 100 has a higher resolution limited to 0.0076 Da, allowing data evaluation with a higher precision of 1000 points / Da.

[0086] FIG. 2 shows a flow chart of a method for characterization of a mass spectrometry instrument 100 comprising at least one mass spectrometry cell 102 according to a first embodiment of the present disclosure. The method of the present disclosure starts with step S10, in which a sample 110 containing at least one substance with a known molecular weight is analyzed by the mass spectrometry instrument 100, resulting in a mass spectrum of the sample 110. The method then proceeds to step S12, in which an outer envelope and an inner envelope of the mass spectrum are determined. The method then proceeds to step S14, in which a squared difference between the outer envelope and the inner envelope is calculated. The method then proceeds to step S16, in which a deviation of the calculated squared difference from the theoretical mass-to-charge ratio value of the substance is determined. The method then proceeds to step S18, in which it is determined whether the deviation of the calculated difference from the theoretical mass-to-charge ratio value of the substance exceeds a predetermined difference threshold. If the deviation of the calculated difference exceeds a predetermined difference threshold, the method then proceeds to step S20, in which the state of the mass spectrometry instrument is determined to be inappropriate. Conversely, if the determined deviation for the calculated difference does not exceed the predefined difference threshold, the method proceeds further to step S22 of determining that the condition of the mass spectrometry instrument is adequate. The method may be performed for each mass spectrometry cell 102, 104, 106.

[0087] This method and its optional modifications are described in further detail below.

[0088] FIG. 3A shows an exemplary first mass spectrum 116 of the first analytical cell 102 for testosterone and its internal standard analyzed by the mass spectrometry instrument 100 of the present embodiment. FIG. 3B shows an exemplary second mass spectrum 118 of the third analytical cell 106 for testosterone and its internal standard analyzed by the mass spectrometry instrument 100 of the present embodiment. In FIGS. 3A and 3B, the mass-to-charge ratio (m / z ratio) is given as the x-axis 120. The signal intensity (in %) is given as the y-axis 122. A graph 124 shows the signal intensity as a function of the mass-to-charge ratio. As can be seen in FIG. 3A, a less pronounced front shoulder 126 can be seen, and there are multiple maxima 128 in the higher regions. Thus, a data evaluation with higher resolution and data points can lead to better calibration efficiency. As can be seen in FIG. 3B, the quadrupole differences can be seen, for example the left ascending flank 130 is noisier than the right descending flank 132. Thus, the method according to the present disclosure is based on the discovery that fingerprint characterization of a quadrupole is possible based on mass spectral behavior, such as monitoring system specific or long term effects.

[0089] FIG 4A shows an exemplary first mass spectrum 116 of the first analytical cell 102 for testosterone and its internal standard analyzed with the mass spectrometry instrument 100 of the present embodiment. FIG 4B shows an exemplary second mass spectrum 118 of the third analytical cell 106 for testosterone and its internal standard analyzed with the mass spectrometry instrument 100 of the present embodiment. In the following, only the differences from FIG 3A and FIG 3B will be described, and similar features will be indicated by similar reference numerals. As shown in FIG 4A and FIG 4B, the method according to the present disclosure can be used to obtain the outer envelope f of the mass spectra 116, 118. o and the inner envelope f i The y-axis 122 represents the signal intensity of the mass spectra 116, 118, the outer envelope f o , and the inner envelope f i The outer envelope f o and the inner envelope fi The difference between the left and right relative spectra results in a left relative spectrum that can further characterize the state of the quadrupole. Variations in environmental conditions such as humidity, temperature, and pressure, or matrix contamination provided by the sample 110, can be visualized by characterizing this "macroscopic" fingerprint. As can be seen by comparing Figures 4A and 4B, the envelope f of the first mass spectrum 116 of the first analytical cell 102 is o and f i is the outer envelope f o is more symmetrical than the second mass spectrum 118 of the third analytical cell 106 which exhibits a bulge 134 on the left side.

[0090] The method according to the present disclosure comprises the steps of: o and the inner envelope f i The squared difference between the outer envelope and the inner envelope is calculated as (f o -f i ) 2 It is calculated as f o is the outer envelope and f i is the inner envelope.

[0091] Figure 5A shows an exemplary diagram of the squared difference thus calculated as a function of the mass-to-charge ratio (m / z ratio) of the first analytical cell 102. Figure 5B shows an exemplary diagram of the squared difference thus calculated as a function of the mass-to-charge ratio (m / z ratio) of the third analytical cell 106. In the following, only the differences from Figures 3A and 3B are described, and similar features are indicated by similar reference numerals. In Figures 5A and 5B, the mass-to-charge ratio (m / z ratio) is given as the x-axis 120. The calculated outer envelope f o and the inner envelope f i The squared difference between is given as y-axis 122. Graph 136 shows the calculated squared difference as a function of mass-to-charge ratio (m / z ratio) from the theoretical value to the left. Graph 138 shows the calculated squared difference as a function of mass-to-charge ratio (m / z ratio) from the theoretical value to the right. As can be seen from a comparison of Figures 5A and 5B, the envelope f o , fi The squared difference between α, β and β is much larger for the third analysis cell 106.

[0092] The method according to the present disclosure further comprises a 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 position to the left and the position to the right of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum. The determination of the deviation includes determining the ratio of the peak at the position to the left and the peak at the position to the right 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 the right in the symmetrical case, as shown by the line 140 in FIG. 5A. In the asymmetrical case, this is not the case, and the height difference can be determined as shown by the line 142 in FIG. 5B. Thus, if the deviation determined for the calculated difference does not exceed a predetermined difference threshold, as shown, for example, by the approximately same peak heights in FIG. 5A, the condition of the mass spectrometry instrument 100 is determined to be adequate. Conversely, if the determined deviation in the calculated differences, as shown, for example, by different peak heights in FIG. 5B, exceeds a predetermined difference threshold, then the condition of the mass spectrometry instrument 100 is determined to be improper.

[0093] FIG. 6 shows a flow chart of a method for characterization of a mass spectrometry instrument 100 comprising at least one mass spectrometry cell 102 according to a second embodiment of the present disclosure. It is 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 predefined difference threshold. Needless to say, the method of the second embodiment may be performed independently of the method of the first embodiment. The method of the present disclosure starts with a step S30 in which a sample 110 containing at least one substance having a known molecular weight is analyzed by a mass spectrometry instrument 100, resulting in a mass spectrum of the sample 110. The method then proceeds to a step S32 in which a wavelet transform of the mass spectrum is performed. The method then proceeds to a step S34 in which the deviation of the amplitude of the wavelet transformed mass spectrum from the theoretical amplitude value of the substance in a given period is determined. The method then proceeds to a step S36 in which the deviation of the amplitude of the wavelet transformed mass spectrum from the theoretical amplitude value of the substance in a given period determined exceeds a predefined amplitude threshold. If the deviation of the amplitude of the mass spectrum after the wavelet transform from the theoretical amplitude value of the substance in the predetermined period exceeds the predetermined amplitude threshold, the method further proceeds to step S38, in which the mass spectrometry device is determined to be in an inappropriate state. Conversely, if the deviation of the amplitude of the mass spectrum after the wavelet transform from the theoretical amplitude value of the substance in the predetermined period does not exceed the predetermined amplitude threshold, the method further proceeds to step S40, in which the mass spectrometry device is determined to be in an appropriate state. The method may be performed for each mass spectrometry cell 102, 104, 106.

[0094] This method and its optional modifications are described in further detail below.

[0095] FIG. 7A shows an exemplary third mass spectrum 144 of the first analytical cell 102 for testosterone analyzed by the mass spectrometry instrument 100 of the present embodiment. FIG. 7B shows an exemplary fourth mass spectrum 146 of the third analytical cell 106 for testosterone analyzed by the mass spectrometry instrument 100 of the present embodiment. In FIGS. 7A and 7B, the mass-to-charge ratio (m / z ratio) is given as the x-axis 120. The signal intensity and the running average of the signal intensity are given as the y-axis 122. The graph 148 shown at the top of FIGS. 7A and 7B shows the signal intensity as a function of the mass-to-charge ratio. The graph 150 shown at the bottom of FIGS. 7A and 7B shows the running average of the signal intensity as a function of the mass-to-charge ratio.

[0096] The method of the second embodiment is based, inter alia, on the discovery that an alternative way to characterize a mass spectrum is to "microscopically" examine the wavelet transform of the signal. At noise frequencies, one can expect a larger amplitude in the fourth mass spectrum 146 of the third analytical cell 106 compared to the third mass spectrum 144 of the first analytical cell 102.

[0097] The method further includes generating a heat map of the wavelet transformed mass spectrum and determining an amplitude deviation at a given period in the heat map, wherein the amplitude deviation at a given period is determined as a function of the wavelet power.

[0098] FIG. 8A shows an exemplary first heat map 152 of the first analytical cell 102 for testosterone analyzed with the mass spectrometry instrument 100 of the present embodiment. FIG. 8B shows an exemplary second heat map 154 ​​of the third analytical cell 106 for testosterone analyzed with the mass spectrometry instrument 100 of the present embodiment. In FIGS. 8A and 8B, the mass-to-charge ratio (m / z ratio) is given as the x-axis 120. The period (mz) is given as the y-axis 156 on the left side. The wavelet power level is shown as the y-axis 158 on the right side, with high wavelet power levels shown as white and low or even lower wavelet power levels shown as grey or black for simplicity. The area with the highest amplitude for a given period can be observed in the second heat map 154 ​​of the third analytical cell 106, as shown by the circle 160 in the second heat map 154 ​​of the third analytical cell 106.

[0099] FIG. 9A shows an exemplary first wavelet transform diagram 162 of the first analytical cell 102 for testosterone analyzed with the mass spectrometry instrument 100 of the present embodiment. FIG. 9B shows an exemplary second wavelet transform diagram 164 of the third analytical cell 106 for testosterone analyzed with the mass spectrometry instrument 100 of the present embodiment. In FIGS. 9A and 9B, the average wavelet power is given as the x-axis 120. The period (mz) is given as the y-axis 122. Graph 166 shown in FIG. 9A shows the third mass spectrum 144 after the wavelet transform of the first analytical cell 102. Graph 168 shown in FIG. 9B shows the fourth mass spectrum 146 after the wavelet transform of the third analytical cell 106. As shown by graph 166, there are no significant signals of less than one period in the first wavelet transform diagram 162 of the first analytical cell 102. At a given period thus marked, a larger amplitude can be observed only for the third analytical cell 106, with a prominent signal at 0.02 periods / 5 kHz, as indicated by circle 170.

[0100] FIG. 10A shows an exemplary first wavelet amplitude diagram 172 of the first analytical cell 102 for testosterone analyzed with the mass spectrometry instrument 100 of the present embodiment. FIG. 10B shows an exemplary second wavelet amplitude diagram 174 of the third analytical cell 106 for testosterone analyzed with the mass spectrometry instrument 100 of the present embodiment. In FIGS. 10A and 10B, the mass-to-charge ratio m / z is given as the x-axis 120. The wavelet amplitude is given as the y-axis 122. Graph 176 shown in FIG. 10A shows the wavelet amplitude of the third mass spectrum 144 of the first analytical cell 102 as a function of the mass-to-charge ratio m / z. Graph 178 shown in FIG. 10B shows the wavelet amplitude of the fourth mass spectrum 146 of the third analytical cell 106 as a function of the mass-to-charge ratio m / z. As shown by graph 176, the wavelet amplitude does not show a significant signal at 0.02 cycles / 5 kHz. As indicated by circle 180, there is a large wavelet amplitude at approximately 0.02 periods / 5 kHz since the signal is highest at the location of the mass spectral peak.

[0101] Thus, if the determined deviation in amplitude does not exceed a predefined amplitude threshold, for example as shown by the absence of peaks or amplitudes in Figure 9A, the condition of the mass spectrometry instrument 100 is determined to be adequate. Conversely, if the determined deviation in amplitude exceeds a predefined amplitude threshold, for example as shown by the peaks or amplitudes in Figure 9B, the condition of the mass spectrometry instrument 100 is determined to be inadequate.

[0102] The methods according to each of the embodiments described herein may use the following example parameters to classify the condition of the mass spectrometry instrument 100 as adequate / normal or improper / abnormal.

[0103] For resolution in Da, a suitable condition can be defined as 0.8±0.1, and an unsuitable condition can be defined as <0.7 and >0.9. For precision, i.e. mass axis position (units Da), a suitable condition can be defined as a tolerance on the shift of ±0.1, and an unsuitable condition can be defined as a shift >0.1. For high precision characterization, i.e. multiple systems with machine learning, a suitable condition can be defined as comparable to other systems and no shift or environmental change over time, and an unsuitable condition can be defined as the quadrupole is not comparable to other systems and there is a shift or environmental change over time. For envelope characterization, a suitable condition can be defined as a symmetric arrangement of the outer and inner envelopes, and an unsuitable condition can be defined as an asymmetric arrangement of the outer and inner envelopes. For wavelet or Fourier transform, a suitable condition can be defined as the absence of characteristic frequencies, and an unsuitable condition can be defined as interference between the signal and noise frequencies.

[0104] The method according to each embodiment described herein is performed at predetermined times. In particular, these times include at least the start-up of the mass spectrometry instrument 100. For example, the method is performed as a predictive maintenance measure. The method 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. Instead of a wavelet transform, a Fourier transform may be performed. [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 multiplier 114 Signal 116 First mass spectrum of the first analytical cell 118 Second mass spectrum of the third analytical cell 120 x axis 122 y-axis 124 Signal Intensity as a Function of Mass-to-Charge Ratio 126 Front Shoulder 128 Maximum 130 Left Upward Flank 132 Right Down Flank 134 Bulge 136 Squared difference calculated as a function of mass-to-charge ratio on the left side from the theoretical value 138 Squared difference calculated according to mass-to-charge ratio on the right side from the theoretical value 140 Symmetric peak height ratio 142 Asymmetric peak height ratio 144 Third mass spectrum of the first analytical cell 146 Fourth mass spectrum of the third analytical cell 148 Signal Intensity as a Function of Mass-to-Charge Ratio 150 Moving average of signal intensity according to mass-to-charge ratio 152 Exemplary First Heatmap of First Analysis Cell 154 Exemplary second heat map of third analysis cell 156 Left y-axis 158 right y-axis 160 Area of ​​maximum amplitude in a given 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 transformation of the first analytical cell 168 Fourth mass spectrum after wavelet transformation of the third analytical 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 analytical cell as a function of mass-to-charge ratio m / z 178 Wavelet amplitude of the fourth mass spectrum of the third analytical cell 180 Large Wavelet Amplitude S10 Analyze the sample S12 Determine the outer and inner envelopes of mass spectra S14 Calculate the squared difference between the outer and inner envelopes S16 Determine the deviation of the calculated squared difference from the theoretical mass-to-charge ratio value of the substance S18 Determine whether the deviation of the calculated difference from the theoretical mass-to-charge ratio value of the determined substance exceeds a predetermined difference threshold. S20 Mass spectrometry instrument is determined to be in an unsuitable condition S22 Determine that the mass spectrometry instrument is in good condition S30 Analyzing a sample containing at least one substance having a known molecular weight S32 Perform wavelet transform of mass spectrum S34 Determine the deviation of the amplitude of the mass spectrum after wavelet transformation from the theoretical amplitude value of the substance at a given period. S36 Determine whether the deviation of the amplitude of the mass spectrum after the wavelet transform from the theoretical amplitude value of the substance in a given period exceeds a given amplitude threshold value. S38 Mass spectrometry instrument is determined to be in an unsuitable condition S40 Determine that the mass spectrometry instrument is in good condition

Claims

1. A method for characterization of a mass spectrometry instrument (100) comprising at least one mass spectrometry cell (102, 104, 106), comprising: - analyzing a sample (110) containing at least one substance of known molecular weight by said mass spectrometry instrument (100) to provide a mass spectrum (116, 118, 144, 146) of said sample (110); - determining the outer and inner envelope of said mass spectrum (116, 118, 144, 146); - calculating the squared difference between the outer envelope and the inner envelope; - determining the deviation of said calculated squared difference from a theoretical mass-to-charge ratio value of said substance; The method includes:

2. The squared difference between the outer envelope and the inner envelope is (f ｏ -f ｉ ) ２ is calculated as f ｏ is the outer envelope, f ｉ The method of claim 1 , wherein: is the inner envelope.

3. The method of claim 2 or 3, further comprising determining the deviation of the calculated difference along a mass to charge ratio axis of the mass spectrum (116, 118, 144, 146).

4. 4. The method of claim 3, further comprising determining the deviation of the calculated difference based on a position to the left and a position to the right of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum.

5. 5. The method of claim 4, wherein determining the deviation comprises determining a ratio of a peak at a position to the left of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum (116, 118, 144, 146) to a peak at a position to the right of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum (116, 118, 144, 146).

6. The method of any one of claims 1 to 5, further comprising determining that a condition of the mass spectrometry instrument (100) is unsuitable if the determined deviation of the calculated difference exceeds a predetermined difference threshold.

7. 7. The method of claim 6, further comprising performing a wavelet transform of the mass spectrum (116, 118, 144, 146) and determining deviations of the amplitude of the wavelet transformed mass spectrum (116, 118, 144, 146) from a theoretical amplitude value for the material at a predetermined period.

8. 8. The method of claim 7, wherein performing the wavelet transform of the mass spectrum (116, 118, 144, 146) and determining the deviation of the amplitude of the wavelet transformed mass spectrum (116, 118, 144, 146) from a theoretical amplitude value for the material at a predetermined period is performed if the determined deviation of the calculated difference does not exceed the predetermined difference threshold.

9. 9. The method of claim 8, further comprising determining that a condition of the mass spectrometry instrument is improper if the determined deviation in the amplitude exceeds a predetermined amplitude threshold.

10. A method for characterization of a mass spectrometry instrument (100) comprising at least one mass spectrometry cell (102, 104, 106), comprising: - analyzing a sample (110) containing at least one substance of known molecular weight by said mass spectrometry instrument (100) to provide a mass spectrum (116, 118, 144, 146) of said sample (110); performing a wavelet transform of said mass spectrum (116, 118, 144, 146); determining the deviation of the amplitude of said wavelet transformed mass spectrum (116, 118, 144, 146) from the theoretical amplitude value of said substance in a given period (160); The method includes:

11. 11. The method of claim 10, further comprising generating a heat map (162, 164) of the wavelet transformed mass spectrum (116, 118, 144, 146) and determining the deviation in amplitude at the predetermined period (160) in the heat map (162, 164).

12. 12. The method of claim 10 or 11, further comprising determining the deviation in amplitude over the given period (160) in dependence on wavelet power.

13. The method of any one of claims 1 to 12, further comprising determining that a condition of the mass spectrometry instrument (100) is unsuitable if the determined deviation in amplitude exceeds a predefined amplitude threshold.

14. The method according to any one of claims 1 to 13, wherein the mass spectrometry instrument (100) comprises two or more mass spectrometry cells (102, 104, 106), and the method is performed for each mass spectrometry cell (102, 104, 106).

15. The method according to any one of the preceding claims, wherein the method is performed at a predetermined point in time, said point in time in particular comprising at least a start-up of the mass spectrometry instrument (100).

Images