Method of characterizing mass spectrometry instrument comprising at least one mass analyzing 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 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 signature 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 sample's molecules to break down into positively charged fragments, or simply become positively charged without fragmentation. 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 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 their mass-to-charge ratio. Atoms or molecules in the sample can be identified by correlating known masses, e.g., whole molecules, with identified masses, or by characteristic fragmentation patterns.

[0005] Mass spectrometry instruments, including at least one mass analysis cell, have many different electronic potentials for directing, filtering, and at least detecting ions. System parameters should match the behavior of the same ion across different systems. Mass calibration parameters correlate the mass of ions and their resolution to the applied voltage. Due to changing environmental conditions and system contamination 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 The object is to provide a mass analyzer comprising at least one mass analysis cell having the features of the independent claims. The present invention is addressed by a method, a computer program, and a computer-readable storage medium for characterization of analytical instruments. Advantageous embodiments, which may be realized alone or in any combination, are set out in the dependent claims as well as in the specification as a whole.

[0008] When used below, the terms "having," "comprising," or "including," or any grammatical variants thereof, are used in a non-exclusive manner. These terms can therefore refer both to a situation in which, besides the features introduced by these terms, no further features are present in the entity described in this context, and to a situation in which one or more further features are present. For example, the expressions "A has B," "A comprises B," and "A includes B" can refer both to a situation in which no other elements are present in A besides B (i.e., a situation in which A consists exclusively of B), and to a situation in which, besides B, one or more further elements are present in 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," "even more particularly," "particularly," "more particularly," or similar terms are used in conjunction with optional features without limiting the possibilities for substitution. Features introduced by these terms are therefore optional features and are not intended to limit the scope of the claims in any way. The present invention may be implemented by using alternative features, as would be understood by one skilled in the art. Similarly, features introduced by "in an embodiment of the invention" or similar phrases 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 possibility of combining a feature introduced in this manner 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, and it is expressly stated that these terms are not intended to define any particular order of importance or relevance.

[0012] In a first aspect, a method for 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 common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but is not limited to, a mass analyzer used for mass analysis. 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. 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 can be used to analyze molecules and other compounds. MS is used to reveal the chemical identity or structure of a substance. 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 sample's molecules to break down into positively charged fragments, or to simply become positively charged without fragmentation. 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 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 their 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 fragmentation patterns.

[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 refer to, but is not limited to, the portion of a mass spectrometer involved in mass resolution. Thus, the analysis cell is capable of resolving the mass of a sample or prepares for or facilitates 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 state of a mass spectrometry instrument. In simple applications, the determination or detection can reveal a normal or abnormal state.

[0016] The method includes the following method steps, which may be performed in particular in the given order. However, other orders are possible. Furthermore, two or more method steps may be performed completely 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 containing at least one substance of known molecular weight with a mass spectrometer 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; Includes:

[0018] As used herein, the term "analysis" 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 specific or particular meaning. The term may specifically, 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, tissues, cells, etc. Samples can be prepared by preparing plasma from blood, diluting viscous fluids, Prior to use, samples may be pretreated, such as by dissolution, and methods of treatment may include filtration, centrifugation, distillation, concentration, inactivation of interfering components, and addition of reagents. Samples may be used directly from the source in some cases, or may be used after pretreatment and / or sample preparation workflows to alter the sample's properties, such as adding an internal standard, diluting with another solution, or mixing with a reagent, to enable the performance of one or more in vitro diagnostic tests, enrich (extract / separate / enrich) the analyte of interest, and / or remove matrix components that may interfere with the detection of the analyte of interest. While the term "sample" is often used to refer to a sample before sample preparation, the term "sample after preparation" is also used to refer to a sample after sample preparation. In non-specific cases, the term "sample" may broadly refer to either or both the sample before sample preparation or the sample after sample preparation. Examples of analytes of interest are commonly 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 common and ordinary meaning to those skilled in the art, without being limited to any particular or special meaning. Specifically, but not exclusively, the term may refer to a curve that touches each member of a family of curves at some point, with these tangent points collectively forming the entire envelope. Classically, a point on an envelope can be thought of as the intersection of two "near-minima" curves, signifying the limit of intersection of the adjacent curves. This idea can be generalized to the envelope of a surface in space, and also to higher dimensions. To have an envelope, each member of a family of curves must be a differentiable curve (otherwise the concept of tangency does not apply), and there must be a smooth transition running through the members. However, these conditions are not sufficient, and a given family may not have an envelope. A simple example of this is provided 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 status, for example, during the start-up process, automatic classification of the system status (normal / abnormal) is possible using a "noise limit." Identifying abnormal conditions can prevent erroneous patient results. Furthermore, proper insulation of electrical circuits or the quality of used electrical components can be checked. Correct labeling of the status (e.g., position shift, resolution, and envelope) can be used to trigger correct maintenance actions, thus reducing system downtime and maintenance costs. From a manufacturer's perspective, 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 can be calculated as f ois the outer envelope and f i is the inner envelope. This particular calculation of the squared difference weights the difference between the outer and inner envelopes more than a simple difference formation. Therefore, 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 region surrounding the ion.

[0023] The method may further include determining a deviation of the calculated difference along the mass-to-charge ratio axis of the mass spectrum, such that rather than just observing a single point of the signal, a range along the mass-to-charge ratio axis of the mass spectrum is observed, thus allowing for more accurate monitoring of the state 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 peak of the theoretical mass value of the substance in the mass spectrum, thereby observing possible asymmetric signals (which may give a hint of an improper state of the mass spectrometry instrument).

[0025] Determining the deviation may include determining the 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. This allows the left and right sides of the peak of the theoretical mass value of the substance in the mass spectrum to be observed. If the peak is symmetrical, the ratio of the signal heights at the left and right positions should be approximately 1. In the case of an asymmetric signal peak, the ratio of the signal heights at the left and right positions may be significantly different from 1, such as 2, 3, or even greater.

[0026] The method may further include determining that the condition of the mass spectrometry instrument is unsuitable if the determined deviation in the calculated difference exceeds a predetermined 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 substance at a given period, thereby allowing for a fairly microscopic observation 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, without being limited to any special or particular meaning. Specifically, but not exclusively, the term may refer to the representation of a square-integrable (real- or complex-valued) function by a specific 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-term oscillation," such as the vibrations recorded by a seismograph or heart monitor. In general, wavelets are intentionally created to have specific 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 selecting appropriate basis functions that enable 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 predetermined period may be performed if the determined deviation of the calculated difference does not exceed a predetermined 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 made, making it possible to detect even smaller deviations from the target state of the mass spectrometry instrument.

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

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

[0031] The method comprises in particular the following method steps which may be performed in the given order: However, other orders are possible. Moreover, two or more method steps can be performed completely or partially simultaneously. Moreover, one or more, or all, of the method steps can be performed once or repeatedly, e.g., repeated one or more times. Furthermore, the method may include additional method steps not listed.

[0032] The method comprises the following steps: - analyzing a sample containing at least one substance of known molecular weight with a mass spectrometer to provide a mass spectrum of the sample; performing a wavelet transform of the mass spectrum; - determining the deviation of the amplitude of the wavelet transformed mass spectrum 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, when the deviation of the calculated squared difference from the theoretical mass-to-charge ratio value of the substance does not have to be determined in the method of the first aspect. The method of the second aspect therefore allows for a closer observation of the state of the mass spectrometer.

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

[0035] As used herein, the term "heat map" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but 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, providing a clear visual cue to the reader as to how the phenomena are clustered or vary in space. There are two fundamentally different categories of heat maps: cluster heat maps and spatial heat maps. In cluster heat maps, the magnitudes are laid out in a matrix with a fixed cell size, the rows and columns of the matrix are discrete phenomena and categories, and the sorting of the rows and columns is intentional 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 heat map is constrained by their location in space; there is no concept of cells; the phenomena are considered to vary continuously.

[0036] When using wavelets, a heat map is also known as a scalogram. In a scalogram, the results of a wavelet transform are visualized as a three-dimensional graph. The first spatial dimension is the signal's defined range, which is the mass-to-charge ratio (m / z) on the x-axis used herein. The second spatial dimension is the signal's frequency or period on the y-axis. The third spatial dimension represents the amplitude of a specific period associated with a specific position (m / z) within the defined range, i.e., the wavelet power. The latter is represented not in a spatial manner but in a colored manner, 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 common and ordinary meaning to those skilled in the art, and should not be construed as a specific or special meaning. The term should not be limited in meaning. Specifically, but without limitation, the term can refer to a frequency range of a signal and a periodic signal portion located within a defined range. Thus, it can indicate potential variations in frequency within a frequency range, and prominent frequencies can be clearly associated with specific portions of the defined range.

[0038] The method may further include 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 specific or special meaning. This 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 wavelet-transformed mass spectrum. 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 within a signal to be derived.

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

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

[0042] As used herein, the term "quadrupole mass analyzer" 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 any specific or special meaning. This 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, quadrupole mass filter, or quadrupole mass analyzer. As the name suggests, it consists of four cylindrical rods arranged parallel to each other. In a quadrupole mass spectrometer, the quadrupole is the mass analyzer and 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. A 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 specific mass-to-charge ratio reach the detector; other ions become unstable and collide with the rods. This allows for the selection of ions with a specific 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 specific ratio of rod diameter to spacing provide an easy-to-manufacture and sufficient approximation of the hyperbola. Small variations in the ratio have a significant effect on resolution and peak shape. Different manufacturers choose slightly different ratios to fine-tune operating characteristics in the context of 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. It should not be constrained to a specific or special meaning. The term may specifically, but not exclusively, refer 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, acting as a cell for collision-induced dissociation. This configuration is often abbreviated as QqQ, and will be abbreviated here as Q1q2Q3. Essentially, a triple quadrupole mass analyzer 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. While Q1 and Q3 are both controlled by direct current (dc) and radio frequency (rf) potentials, the collision cell (q) is subjected to RF potential only. 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 technology allows for sequential mass analysis in different regions of the instrument. TQMS follows a tandem spatial configuration, since ionization, primary mass selection, collision-induced dissociation (CID), mass analysis of 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 less expensive, easier to operate, and highly efficient. Furthermore, when operated in selected reaction monitoring mode, TQMS has 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] The method may be performed at predetermined times, which may in particular include at least the start-up of the mass spectrometry instrument, so that the status can be checked at regular intervals or the like.

[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 specific or special meaning. The term may specifically refer to a process that is fully or partially performed using data processing means, such as, but not limited to, data processing means comprising at least one processing unit, in particular, focus electronics and control systems. Thus, the term "computer" can 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 additional 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 analysis instrument comprising at least one mass analysis cell, cause the mass analysis instrument to carry out a method according to any one of the preceding claims relating to a method.

[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, cause 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 any special or particular meaning. This term can specifically, but is not limited to, refer to a calculation for analyzing data points by creating a series of averages of different subsets of the entire data set. Also known as a moving average (MM) or rolling average, it is a type of finite impulse response filter. Variations include simple, cumulative, and weighted forms. Given a series of numbers and a fixed subset size, the first element of the moving average is obtained by averaging the first fixed subset of the series. The subset is then modified by "forward shifting," 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 values ​​depends on the application, and the parameters of the moving average are set accordingly. For example, they are often used in the technical analysis of financial data such as stock prices, returns, or trading volumes. It is also used in economics to examine gross domestic product, employment, or other macroeconomic time series. Mathematically, a moving average is a type of convolution, and can therefore be thought of as an example of a low-pass filter used in signal processing. When used with 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 run 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. A 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, two or more 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 carrying out the method according to the present invention in one or more of the embodiments contained herein when the program is run 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 having stored thereon a data structure that is capable of performing the methods according to one or more of the embodiments disclosed herein after being loaded into a computer or computer network, for example into the working memory or main memory of the computer or computer network.

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

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

[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 to perform a method according to one of the embodiments described herein when it is executed on a computer, 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 the method according to one of the embodiments described herein when said computer program is run on a computer or 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 perform a method according to one of the embodiments described herein after being loaded into a main memory and / or a working memory of a computer or a computer network, 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 the program code means is 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 containing at least one substance having a known molecular weight with a mass spectrometer 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; A method comprising:

[0063] Embodiment 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 and f i is the inner envelope.

[0064] Embodiment 3: A 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: 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 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.

[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 unsuitable if the determined deviation of the calculated difference exceeds a predetermined 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: A 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 predetermined 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 containing at least one substance having a known molecular weight with a mass spectrometer 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 transform from the theoretical amplitude value of the substance at a given period; A method comprising:

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

[0073] Embodiment 12: Determining the deviation of amplitude at a given period depending on wavelet power 2. The method according to any one of the preceding two claims, further comprising:

[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 predetermined 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 analysis 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 points include at least the start-up of the mass spectrometry instrument.

[0079] Embodiment 18: A method according to any one of the preceding claims, further comprising performing 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 containing instructions, which when a 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 explanation of the drawings]

[0083] Further optional features and embodiments are disclosed in more detail in the subsequent description of the embodiments, preferably in conjunction with the dependent claims. Each optional feature therein may be realized in an independent manner as well as in any possible combination, as will be understood by those 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 numerals 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. [Figure 2] 1 shows a flowchart 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] 10 shows an exemplary second mass spectrum of the third analytical cell. [Figure 4A] 1 shows an exemplary first mass spectrum of a first analytical cell. [Figure 4B] 10 shows an exemplary second mass spectrum of the third analytical cell. [Figure 5A] 1 shows an exemplary diagram of the squared difference calculated as a function of the mass-to-charge ratio of a first analytical cell. [Figure 5B] 10 shows an exemplary diagram of the squared difference calculated as a function of the mass-to-charge ratio of the third analytical cell. [Figure 6] 4 shows a flowchart of a method for characterization of a mass spectrometry instrument according to a second embodiment. [Figure 7A] 10 shows an exemplary third mass spectrum of the first analytical cell. [Figure 7B] 10 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]10 shows an exemplary second heatmap of a third analysis cell. [Figure 9A] 1 shows an exemplary first wavelet transform diagram of a first analysis cell. [Figure 9B] 10 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] 10 shows an exemplary second wavelet magnitude diagram of a third analysis cell. DETAILED DESCRIPTION OF THE INVENTION

[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 comprising three analytical cells 102, 104, and 106. Thus, each of the analytical cells 102, 104, and 106 is 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 form 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 that serves as the cell 104 for collision-induced dissociation. The mass spectrometry instrument 100 further includes an ionization source 108, such as an electrospray ionization (ESI) source or an atmospheric pressure chemical ionization (APCI) source, positioned adjacent to the first analytical cell 102, to which a sample 110 may be input. The mass spectrometry instrument 100 further includes a particle multiplier 112 positioned 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 principles of such mass spectrometry instruments are known to those skilled in the art, for example, from the prior art described above, and therefore will not be further described. Some conventional mass spectrometry instruments have a fairly low resolution of 20 points / Da. Determination of the maximum signal intensity (accuracy of mass calibration) and full width at half maximum of the maximum signal intensity (efficiency of separation into adjacent ions) can be performed quite easily. However, signal shifts or other changes are not sufficiently accurate to monitor. In this embodiment, the mass analysis instrument 100 has a higher resolution limited to 0.0076 Da, allowing for data evaluation with a higher accuracy of 1000 points / Da.

[0086] 2 shows a flowchart of a method for characterization of a mass spectrometry instrument 100 including 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 including at least one substance having 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 a theoretical mass-to-charge ratio value of the substance is determined. The method then proceeds to step S17, 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, where it is determined whether the deviation between the calculated differences exceeds a predetermined difference threshold. If the determined deviation between the calculated differences exceeds the predetermined difference threshold, the method proceeds to step S20, where it is determined that the state of the mass analysis instrument is inappropriate. Conversely, if the determined deviation between the calculated differences does not exceed the predetermined difference threshold, the method proceeds to step S22, where it is determined that the state of the mass analysis instrument is appropriate. The method may be performed for each mass analysis 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 this 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 this embodiment. In FIGS. 3A and 3B, the mass-to-charge ratio (m / z ratio) is given as the x-axis 120. The signal intensity (unit: %) 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 region. Therefore, data evaluation with higher resolution and data points can result in better calibration efficiency. As can be seen in FIG. 3B, differences in the quadrupole 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 quadrupoles is possible based on mass spectral behavior, such as monitoring system-specific or long-term effects.

[0089] 4A 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 this embodiment. FIG. 4B 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 this embodiment. Hereinafter, only differences from FIGS. 3A and 3B will be described, with like features being indicated by like reference numerals. As shown in FIGS. 4A and 4B, the method according to the present disclosure provides an 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-hand and right-hand relative spectra provides a further characterization of the quadrupole state. 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 from a comparison of Figures 4A and 4B, the envelope f of the first mass spectrum 116 of the first analytical cell 102 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 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 will be described, and like features will be indicated by like reference numerals. 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 fo , f i The squared difference between σ and σ is much larger for the third analytical cell 106.

[0092] The method according to the present disclosure further includes 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. Specifically, the deviation of the calculated difference is determined based on the positions to the left and right 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 position to the left of the theoretical mass value of the substance along the mass-to-charge ratio axis of the mass spectrum to 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 right sides in the symmetric case, as shown by line 140 in FIG. 5A. In the asymmetric case, this is not the case, and a height difference can be determined as shown by line 142 in FIG. 5B. Therefore, if the deviation determined for the calculated difference does not exceed a predetermined difference threshold, as shown by the approximately identical peak heights in FIG. 5A, for example, the condition of the mass analysis instrument 100 is determined to be appropriate. Conversely, if the determined deviation in the calculated difference, as shown, for example, by different peak heights in FIG. 5B, exceeds a predetermined difference threshold, the condition of the mass spectrometry instrument 100 is determined to be unsuitable.

[0093] FIG. 6 shows a flowchart of a method for characterizing a mass spectrometry instrument 100 including at least one mass spectrometry cell 102 according to a second embodiment of the present disclosure. It should be noted 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 performed 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 spectrometry instrument 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 the 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 it is determined whether the deviation of the amplitude of the wavelet-transformed mass spectrum from the theoretical amplitude value of the substance at a predetermined period exceeds a predetermined amplitude threshold. If the deviation of the determined amplitude of the mass spectrum after the wavelet transform from the theoretical amplitude value of the substance in a given period exceeds a predetermined amplitude threshold, the method proceeds to step S38, where it is determined that the mass analysis device is in an improper state. Conversely, if the deviation of the determined amplitude of the mass spectrum after the wavelet transform from the theoretical amplitude value of the substance in a given period does not exceed the predetermined amplitude threshold, the method proceeds to step S40, where it is determined that the mass analysis device is in an appropriate state. This method may be performed for each mass analysis cell 102, 104, 106.

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

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

[0096] The method of the second embodiment is based, among other things, 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 the amplitude of the fourth mass spectrum 146 of the third analytical cell 106 to be larger 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 amplitude deviations at predetermined periods in the heat map, wherein the amplitude deviations at predetermined periods are determined as a function of wavelet power.

[0098] FIG. 8A shows an exemplary first heat map 152 of the first analytical cell 102 for testosterone analyzed by the mass spectrometry instrument 100 of this embodiment. FIG. 8B shows an exemplary second heat map 154 ​​of the third analytical cell 106 for testosterone analyzed by the mass spectrometry instrument 100 of this embodiment. In FIGS. 8A and 8B, mass-to-charge ratio (m / z ratio) is given as the x-axis 120. Period (mz) is given as the left-hand y-axis 156. Wavelet power level is shown as the right-hand y-axis 158, with high wavelet power levels shown as white and low or even lower wavelet power levels shown as gray or black for simplicity. Regions of highest amplitude for a given period can be observed within the second heat map 154 ​​of the third analytical cell 106, as indicated by circles 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 by the mass spectrometry instrument 100 of this embodiment. FIG. 9B shows an exemplary second wavelet transform diagram 164 of the third analytical cell 106 for testosterone analyzed by the mass spectrometry instrument 100 of this 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 the 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 the circle 170.

[0100] FIG. 10A shows an exemplary first wavelet amplitude plot 172 of the first analytical cell 102 for testosterone analyzed by the mass spectrometry instrument 100 of this embodiment. FIG. 10B shows an exemplary second wavelet amplitude plot 174 of the third analytical cell 106 for testosterone analyzed by the mass spectrometry instrument 100 of this 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 shown by circle 180, the signal is Since it is highest at the position of the sine wave, there is a large wavelet amplitude at approximately 0.02 periods / 5 kHz.

[0101] Thus, if the determined deviation in amplitude does not exceed a predetermined amplitude threshold, as indicated, for example, 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 predetermined amplitude threshold, as indicated, for example, 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 embodiment described herein may use the following exemplary parameters to classify the condition of the mass spectrometry instrument 100 as adequate / normal or unadequate / 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 for 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 symmetrical arrangement of the outer and inner envelopes, and an unsuitable condition can be defined as an asymmetrical 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 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 first analytical cell 118 Second mass spectrum of the third analytical cell 120 x axis 122 y-axis 124 Signal intensity according to mass-to-charge ratio 126 Front Shoulder 128 Maximum 130 Left uphill flank 132 Right Down Flank 134 Bulge 136 Squared difference calculated depending on the mass-to-charge ratio on the left side from the theoretical value 138 Squared difference calculated depending on the 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 according to 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 the 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 the 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 a mass spectrum 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 state S22 Determine that the mass spectrometry instrument is in good condition S30 Analyzing a sample containing at least one substance with a known molecular weight S32 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 at a predetermined period exceeds a predetermined amplitude threshold. S38 Determine that the mass spectrometry instrument is 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 the theoretical mass-to-charge ratio value of said substance; A method comprising:

2. The squared difference between the outer envelope and the inner envelope is (f ｏ -f ｉ ) ２ is calculated as ｏ is the outer envelope, and 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.

6. 6. The method of claim 1, further comprising determining that the mass spectrometry instrument (100) is in an unsuitable state 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 substance 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 substance 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 the mass spectrometry instrument is in an unsuitable state 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: - a sample (110) containing at least one substance with a known molecular weight is introduced into said mass spectrometer analyzing the sample (110) with a mass analyzer (100) to provide a mass spectrum (116, 118, 144, 146) of the 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); A method comprising:

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 the 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 of the amplitude in the given period (160) in dependence on wavelet power.

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

14. The method of 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 carried out at a predetermined time point, said time point in particular comprising at least the start-up of the mass spectrometry instrument (100).

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