Multi-channel Detection Method for Mass Spectrometer with Discontinuous Sampling

Abstract

The present invention relates to the technical field of mass spectrometers, and specifically provides a multi-channel detection method for a mass spectrometer with discontinuous sample injection. The method includes: feeding multiple compounds of a target sample into an ion mass analyzer; screening multiple target ions of the ion current of the compounds through a preset multi-channel screening waveform; performing fragmentation and analysis on the target ions in the ion trap one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high through a multi-channel resonance signal in a preset frequency band to obtain a mass spectrum containing multiple target ions. Thus, it solves the problem that in the related art, when a mass spectrometer with discontinuous sample injection performs analysis on target ions, only one target ion can be analyzed at a time, and when analyzing multiple target ions, it is necessary to analyze them one by one, resulting in a long analysis time and low analysis efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometers, and in particular, to a multi-channel detection method for a mass spectrometer with discontinuous sample injection. Background Art

[0002] In related technologies, the sampling frequency of a mass spectrometer with discontinuous sample injection is relatively low, and the number of analysis channels is limited. In particular, a single ion trap mass spectrometer with discontinuous sample injection usually can only achieve single-channel analysis. Therefore, when detecting multiple target substances or performing chromatographic tandem analysis, it is necessary to inject samples multiple times to separately isolate, fragment, and scan target ions one by one, which greatly increases the analysis time.

[0003] Regarding the problem that when analyzing target ions by a mass spectrometer with discontinuous sample injection for detecting multiple target substances or chromatographic tandem, only one target ion can be analyzed at a time, and when analyzing multiple target ions, they need to be analyzed one by one, resulting in a long analysis time and low analysis efficiency, no effective solution has been proposed yet. Summary of the Invention

[0004] The multi-channel detection method for a mass spectrometer with discontinuous sample injection provided by an embodiment of the present invention at least solves the problem that when analyzing target ions by a mass spectrometer with discontinuous sample injection for detecting multiple target substances or chromatographic tandem, only one target ion can be analyzed at a time, and when analyzing multiple target ions, they need to be analyzed one by one, resulting in a long analysis time and low analysis efficiency.

[0005] According to an aspect of an embodiment of the present invention, a multi-channel detection method for a mass spectrometer with discontinuous sample injection is provided, including: feeding multiple compounds of a target sample into an ion mass analyzer, where the compounds include target ions to be detected; inputting the ion current of the compounds into an ion trap, and screening multiple target ions in the ion trap through a preset multi-channel screening waveform and confining them in the ion trap, where the ion current includes multiple target ions to be detected; performing fragmentation and analysis on the target ions in the ion trap one by one in ascending order of mass-to-charge ratio according to a multi-channel resonance signal of a preset frequency band to obtain a mass spectrum corresponding to this mass spectrometry and including multiple target ions.

[0006] As an alternative embodiment, the ion current of the output compound is input into an ion trap, and multiple target ions in the ion trap are screened and trapped by a preset multi-channel screening waveform, including: inputting the ion current into the ion trap and performing trapping; resonantly ejecting impurity ions other than the multiple target ions in the ion trap through the multi-channel screening waveform, where the impurity ions are ions other than the target ions in the injected ion current; and trapping the multiple target ions in the ion trap.

[0007] As an alternative embodiment, before resonantly ejecting the impurity ions other than the multiple target ions in the ion trap through the multi-channel screening waveform, the method further includes: calculating the motion frequencies of various ions in the ion current in the ion trap according to the motion equation of the ion trap and relevant parameters, where the motion equation is used to describe the motion of ions with different mass-to-charge ratios in the ion trap under different relevant parameters, and the relevant parameters include the electric field potential and geometric dimensions of the ion trap; determining a spectral signal in a frequency range according to the motion frequencies of various ions in the ion current, and setting a uniform energy distribution within the frequency range; and reducing the energy corresponding to the frequency range of the spectral signal to below a preset energy threshold according to the motion frequencies of multiple target ions to generate the multi-channel screening waveform.

[0008] As an alternative embodiment, calculating the motion frequencies of various ions in the ion current in the ion trap according to the motion equation of the ion trap and relevant parameters includes: determining the corresponding Mathieu equation as the motion equation according to the type of the ion trap; calculating the ion motion parameters of the corresponding electric field using the Mathieu equation according to the mass and charge of the ion and the relevant parameters of the ion trap; calculating the stability parameters according to the ion motion parameters; and calculating the motion frequency of the ion according to the stability parameters.

[0009] As an alternative embodiment, before fragmenting and analyzing the target ions in the ion trap one by one in ascending order of mass-to-charge ratio through a multi-channel resonance signal in a preset frequency band to obtain a mass spectrum corresponding to the current mass spectrometry and including multiple target ions, the method further includes: determining the preset frequency band according to the motion frequencies of multiple target ions and the required frequency margin; determining the amplitude and duration of the target ions according to the kinetic energy of the target ions and the background gas pressure; and generating a corresponding multi-channel resonance signal according to the preset frequency band, the amplitude, and the duration.

[0010] As an alternative embodiment, by using multi-channel resonance signals in a preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one in ascending order of mass-to-charge ratio from low to high, and a mass spectrum corresponding to this mass spectrometry and including multiple target ions is obtained, including: by using multi-channel resonance signals in a preset frequency band, the target ions in the ion trap are fragmented one by one in ascending order of mass-to-charge ratio from low to high; the successively fragmented target ions are transmitted to a detector for detection, and the detector outputs a mass spectrum of multiple target ions, wherein the mass spectrum includes ion peaks of multiple target ions.

[0011] As an alternative embodiment, multiple compounds of a target sample are fed into an ion mass analyzer, including: feeding multiple compounds of the target sample into the ion mass analyzer by direct injection or chromatographic separation; in the case of feeding multiple compounds of the target sample into the ion mass analyzer by chromatographic separation, after obtaining a mass spectrum corresponding to this mass spectrometry and including multiple target ions, the method further includes: performing cyclic mass spectrometry when the chromatographic separation is not completed until the chromatographic separation is completed, and obtaining a sequence of mass spectra in chronological order, wherein the sequence of mass spectra includes multiple mass spectra obtained by performing cyclic mass spectrometry multiple times and is used to characterize the multi-channel detection results of multiple target ions.

[0012] As an alternative embodiment, before performing cyclic mass spectrometry when the chromatographic separation is not completed to obtain a corresponding mass spectrum until the chromatographic separation is completed and obtaining a sequence of mass spectra in chronological order, it includes: determining the number of mass spectrometry cycles according to the chromatographic separation duration and the single mass spectrometry duration; determining whether the chromatographic separation is completed according to whether the number of cycles reaches the number of mass spectrometry cycles; and determining that the chromatographic separation is completed when the number of cycles reaches the number of mass spectrometry cycles.

[0013] As an alternative embodiment, after performing cyclic mass spectrometry when the chromatographic separation is not completed to obtain a corresponding mass spectrum until the chromatographic separation is completed and obtaining a sequence of mass spectra in chronological order, it includes: confirming the mass-to-charge ratio of the target ions at the corresponding time and the mass-to-charge ratio tolerance, and determining the mass-to-charge ratio range of the target ions; for the mass spectrum at the corresponding time, extracting the signal intensity data within the mass-to-charge ratio range of each target ion; and statistically analyzing the extracted signal intensity data corresponding to the target ions in chromatographic order to obtain a chromatogram including chromatographic curves of each target ion, wherein the chromatographic curve includes the signal intensity changing with the chromatographic order.

[0014] As an alternative embodiment, before separating multiple compounds of a target sample by chromatographic separation, the method further includes: determining an internal standard for target ions; performing multi-channel detection on the internal standard as the target ions; after statistically processing the signal intensity data corresponding to the extracted target ions in chromatographic order to obtain a chromatogram including chromatographic curves of respective target ions, the method further includes: determining the concentration of the target ions according to the ratio of the area of the chromatographic peak of the target ions on the chromatographic curve to the area of the chromatographic peak of the internal standard and the concentration.

[0015] According to an aspect of an embodiment of the present invention, there is also provided a mass spectrometer with discontinuous sample injection, including: a processor, and a memory storing a program, characterized in that the program includes instructions which, when executed by the processor, cause the processor to execute the method according to the above.

[0016] In the multi-channel detection method of the mass spectrometer with discontinuous sample injection provided by the embodiments of the present invention, after separating multiple compounds of a target sample, the ion current thereof is input into an ion trap, and multiple target ions in the ion trap are screened through a preset multi-channel screening waveform and confined in the ion trap, realizing multi-channel synchronous confinement of multiple target ions.

[0017] Then, through multi-channel resonance signals in a preset frequency band, in the order of increasing frequency, the target ions in the ion trap are fragmented and analyzed one by one according to the increasing order of mass-to-charge ratio, obtaining a mass spectrum corresponding to this mass spectrometry and including multiple target ions, realizing multi-channel synchronous fragmentation detection of multiple target ions to characterize the multi-channel detection results of multiple target ions.

[0018] Thus, by applying different multi-channel screening waveforms and multi-channel resonance signals when the ion trap confines and fragments, synchronous screening and fragmentation detection of multiple target ions are realized, effectively improving the detection efficiency of multi-channel detection of multiple target ions using a discontinuous mass spectrometer, and solving the problem in the prior art that when a discontinuous-sample-injection mass spectrometer analyzes target ions, only one target ion can be mass-spectrometrically analyzed at a time, and when analyzing multiple target ions, they need to be analyzed one by one, resulting in a long analysis time and low analysis efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the following drawings are only some embodiments of the present invention, and those of ordinary skill in the art can also obtain other embodiments according to these drawings without creative efforts.

[0020] Figure 1It is a flowchart of a single-channel detection method for a discontinuous sampling mass spectrometer in the related art.

[0021] Figure 2 It is a flowchart of multi-target ion detection for a discontinuous sampling mass spectrometer in the related art.

[0022] Figure 3 It is a flowchart of a multi-channel detection method for a discontinuous sampling mass spectrometer according to an embodiment of the present invention.

[0023] Figure 4 It is a schematic diagram of a multi-channel detection process for a discontinuous sampling mass spectrometer according to an embodiment of the present invention.

[0024] Figure 5 It is a schematic diagram of specific steps of multi-channel detection for a discontinuous sampling mass spectrometer according to an embodiment of the present invention.

[0025] Figure 6 It is a schematic diagram of data analysis based on multi-channel detection results according to an embodiment of the present invention.

[0026] Figure 7 It is a schematic diagram of a SWIFT waveform of an amino acid internal standard analysis method according to an embodiment of the present invention.

[0027] Figure 8 It is a schematic diagram of a mass spectrum of an amino acid internal standard analysis method according to an embodiment of the present invention.

[0028] Figure 9 It is a schematic diagram of integrating multiple mass spectra of an amino acid internal standard analysis method into a multi-channel chromatogram according to an embodiment of the present invention.

[0029] Figure 10 It is a schematic diagram of a multi-channel detection device for a discontinuous sampling mass spectrometer according to an embodiment of the present invention.

[0030] Figure 11 It is a schematic diagram of the structure of an electronic device according to the present invention. Detailed implementation manners

[0031] Hereinafter, embodiments of the present invention will be described in more detail with reference to the accompanying drawings. Although some embodiments of the present invention are shown in the drawings, it should be understood that the present invention can be implemented in various forms and should not be construed as limited to the embodiments set forth herein. On the contrary, these embodiments are provided to more thoroughly and completely understand the present invention. It should be understood that the drawings and embodiments of the present invention are only for exemplary purposes and are not used to limit the protection scope of the present invention.

[0032] In the related art, mass spectrometry is a highly specific analytical technique with high sensitivity and specificity. It analyzes the target ions selected by a mass analyzer; or uses tandem techniques to dissociate precursor ions and further analyzes the generated fragment ions to achieve qualitative and quantitative analysis of the compound structure. When the concentration of the target compound is low, its low mass spectrometry response signal will affect the recognition and identification of the characteristic peaks of the target ions, which may lead to deviations in qualitative and quantitative results, thus affecting the use of the mass spectrometer in specific application fields.

[0033] Due to the high analytical sensitivity and specificity of mass spectrometry, the mass spectrometer has become one of the most widely used chemical analytical instruments in the world, and miniaturization and portability are the future development directions of mass spectrometers. It analyzes the target ions selected by a mass analyzer; or uses tandem techniques to dissociate precursor ions and further analyzes the generated fragment ions to achieve qualitative and quantitative analysis of the compound structure. Among them, the ion trap mass spectrometer is a research hotspot in the field of portable mass spectrometry due to its small size and tandem mass spectrometry ability over time.

[0034] To achieve the portability of ion trap mass spectrometers, most common portable ion trap mass spectrometers currently use atmospheric pressure ion sources, and their atmospheric pressure interfaces are generally divided into continuous atmospheric pressure interfaces or discontinuous atmospheric pressure interfaces. The differential cavity volume of the ion trap mass spectrometer equipped with a continuous atmospheric pressure interface is relatively large, and a relatively large vacuum pump combination is required to maintain the vacuum required by the mass spectrometer, resulting in certain limitations in its portability.

[0035] Tandem analysis is an important technique for mass spectrometry to identify the structure of substances. During a single tandem mass spectrometry scan analysis, it is usually necessary to generate a characteristic fragment ion spectrum corresponding to the substance structure through steps such as target ion isolation, excitation fragmentation, and ion scanning, and then obtain qualitative or quantitative detection results of the mass spectrometry.

[0036] In the related art, from the perspective of the structure form of the inlet of the mass spectrometer, it usually includes a conventional continuous injection structure mass spectrometer and a discontinuous injection structure mass spectrometer. The discontinuous injection structure mass spectrometry system reduces the dependence of the mass spectrometer on the vacuum system, is easy to miniaturize the mass spectrometer, and is beneficial to enabling point-of-care testing, precision medicine and other point-of-care testing scenarios.

[0037] However, the design of the discontinuous injection structure reduces the frequency of single analysis of the mass spectrometer, especially the frequency of tandem mass spectrometry scan analysis. Therefore, in the combination of continuous chromatography and discontinuous mass spectrometry tandem analysis, the sampling frequency of the discontinuous injection mass spectrometer is relatively low, and the number of tandem analysis channels is limited. In particular, the single ion trap mass spectrometer with discontinuous injection usually can only achieve single-channel analysis. Therefore, when performing tandem analysis of multiple target substances, it is necessary to perform multiple injections to separately isolate, fragment, and scan the target ions in sequence, which greatly increases the analysis time.

[0038] A mass spectrometer with discontinuous sample injection, that is, a mass spectrometer with an atmospheric pressure ion source implemented by a discontinuous atmospheric pressure interface, is portable and has a simple structure. To further reduce the volume and simplify the structure, a portable mass spectrometer with discontinuous sample injection usually has a single ion trap structure.

[0039] Figure 1 It is a flowchart of a single-channel detection method for a mass spectrometer with discontinuous sample injection in the related art. As Figure 1 shown, a mass spectrometer with discontinuous sample injection can only isolate a single target ion, and then perform mass spectrometry detection after fragmenting the target ion.

[0040] If a mass spectrometer with discontinuous sample injection is used to detect multiple target ions, mass spectrometry can only be performed one by one. Figure 2 It is a flowchart of a multi-target ion detection method for a mass spectrometer with discontinuous sample injection in the related art. As Figure 2 shown. For a single-channel mass spectrometer with discontinuous sample injection, when performing multi-target ion detection, it is necessary to inject samples one by one, screen, fragment, and detect, based on a large number of repetitions of the entire detection process.

[0041] Especially when combined with chromatography, the chromatographic time is longer and it also needs to be carried out before mass spectrometry. This leads to a longer detection time for multi-target ions when a chromatograph is connected in series with a mass spectrometer with discontinuous sample injection, resulting in a problem of low detection efficiency.

[0042] In the related art, both multi-channel chromatography and mass spectrometry need to rely on parallel hardware structures, which will inevitably increase the volume of the chromatograph or mass spectrometer and is not suitable for a portable mass spectrometer with discontinuous sample injection. There is currently no related technology for implementing multi-channel detection on a single ion trap mass spectrometer with discontinuous sample injection.

[0043] Figure 3 It is a flowchart of a multi-channel detection method for a mass spectrometer with discontinuous sample injection according to an embodiment of the present invention. As Figure 3 shown, to solve the problem in the related art that when a mass spectrometer with discontinuous sample injection analyzes target ions, it can only perform mass spectrometry analysis on one target ion at a time, and when analyzing multiple target ions, it needs to be analyzed one by one, with a long analysis time and low analysis efficiency. The embodiment of the present invention provides a multi-channel detection method for a mass spectrometer with discontinuous sample injection, and this method includes the following steps:

[0044] Step S301, sending multiple compounds of a target sample into an ion mass analyzer, where the compounds contain target ions to be detected;

[0045] Step S302: Input the ion current of the compound into the ion trap. Screen multiple target ions in the ion trap through a preset multi-channel screening waveform and confine them in the ion trap. Herein, the ion current includes multiple target ions to be detected.

[0046] Step S303: Through a multi-channel resonance signal in a preset frequency band, fragment and analyze the target ions in the ion trap one by one in ascending order of mass-to-charge ratio from low to high frequency, and obtain a mass spectrum corresponding to this mass spectrometry, which contains multiple target ions.

[0047] The multi-channel detection method of the mass spectrometer with discontinuous sample injection provided in this embodiment separates multiple compounds of the target sample, inputs their ion current into the ion trap, screens multiple target ions in the ion trap through a preset multi-channel screening waveform, and confines them in the ion trap, realizing the multi-channel synchronous confinement of multiple target ions.

[0048] Then, through a multi-channel resonance signal in a preset frequency band, fragment and analyze the target ions in the ion trap one by one in ascending order of mass-to-charge ratio from low to high frequency, and obtain a mass spectrum corresponding to this mass spectrometry, which contains multiple target ions, realizing the multi-channel synchronous fragmentation detection of multiple target ions.

[0049] Therefore, by applying different multi-channel screening waveforms and multi-channel resonance signals when the ion trap confines and fragments, synchronous screening and fragmentation detection of multiple target ions are realized, effectively improving the detection efficiency of multi-channel detection of multiple target ions using a discontinuous mass spectrometer.

[0050] The execution subject of the above steps can be the controller of the mass spectrometer with discontinuous sample injection, the upper computer, or an external controller of the mass spectrometer with discontinuous sample injection. Through this controller and upper computer, the working parameters of the mass spectrometer can be collected and each part can be controlled.

[0051] The above-mentioned mass spectrometer with discontinuous sample injection is also a mass spectrometer with a discontinuous atmospheric pressure interface. It should be noted that this kind of mass spectrometer with discontinuous sample injection is generally portable, and for the convenience of carrying, the smaller its size, the better. Therefore, the general mass spectrometer with discontinuous sample injection is a single ion trap mass spectrometer. The single ion trap it has is the above-mentioned target ion trap.

[0052] The above ion current is obtained by applying a high voltage to the target compound solution through an electrospray ionization source (ESI) to generate charged ions. The ion current includes the target ions of the compound. If the internal standard method is used, it can also include the ions of the internal standard. The velocity of the ion current can be equivalent to the velocity of electrons.

[0053] The higher the velocity of the ion flow, the greater the kinetic energy of the ions. When confining the target ions in the ion trap, the higher the required electric field strength, that is, the higher the voltage applied to the ion trap. During sample injection, theoretically, it is only necessary to ensure that the ion flow can be effectively confined in the ion trap.

[0054] After the ion flow is confined in the ion trap, since multiple target ions need to be retained, a multi-channel screening waveform is required to screen multiple target ions and resonantly eject impurity ions other than the target ions.

[0055] Since different ions in the ion flow have different mass-to-charge ratios, their movement frequencies in the ion trap electric field are different. The movement frequencies of ions with different mass-to-charge ratios can be calculated, and then a frequency spectrum signal can be designed to have low or zero energy at the frequencies corresponding to the target ions to avoid resonance of the target ions.

[0056] Then maintain high energy at other frequencies so that impurity ions other than the target ions can all resonate out. By performing time-domain conversion on this frequency spectrum signal, a multi-channel screening waveform can be obtained.

[0057] The multi-channel screening waveform can accurately and effectively screen multiple target ions and retain them confined in the ion trap.

[0058] Since there are multiple target ions, and different target ions are of different sizes, to avoid the larger ions from being prone to secondary fragmentation when the smaller ions fragment, resulting in a decrease in the accuracy of the detection results.

[0059] For this reason, in this embodiment, a multi-channel resonance signal is designed. Within a preset frequency band, in the order of increasing frequency, the target ions in the ion trap are fragmented one by one according to the increasing mass-to-charge ratio. The fragmented target ions can be directly input into the ion detector for detection.

[0060] After the fragmented ions are input into the detector, the detector records the signal intensity of the target ion. After multiple target ions are fragmented and input into the detector respectively, the detector can record the signal intensities of multiple target ions, and finally generate a mass spectrum diagram of multiple target ions in this mass spectrometry. For example, a primary mass spectrum diagram of multiple target ions of amino acids, as Figure 8 shown.

[0061] It should be noted that the method for detecting target ions in this embodiment can be one of the existing ion detectors. For example, an electron multiplier (EM), a Faraday cup (FC), a photomultiplier electrode, an array detector, etc.

[0062] The target ions can be detected by an ion detector, and an amplified ion signal is output to form a mass spectrum corresponding to this mass spectrometry, which contains multiple target ions.

[0063] When the ion trap is in the processes of confinement and fragmentation through the above steps, different multi-channel screening waveforms and multi-channel resonance signals are applied, so as to realize the synchronous screening and fragmentation detection of multiple target ions, effectively improving the detection efficiency of multi-channel detection of multiple target ions by using a discontinuous mass spectrometer, and solving the problem that in the prior art, when a discontinuous injection mass spectrometer analyzes target ions, only the mass spectrometry analysis of one target ion can be realized at a time. When analyzing multiple target ions, it is necessary to analyze them one by one, resulting in a long analysis time and low analysis efficiency.

[0064] As an optional embodiment, the ion current of the output compound is input into the ion trap. Through a preset multi-channel screening waveform, multiple target ions in the ion trap are screened and confined in the ion trap, including: inputting the ion current into the ion trap and confining it; through the multi-channel screening waveform, resonantly ejecting impurity ions other than the multiple target ions in the ion trap, where the impurity ions are the ions other than the target ions in the injected ion current; confining the multiple target ions in the ion trap.

[0065] After the ion current enters the ion trap, all the ions in the ion current will be confined in the ion trap under the action of the electric field of the ion trap, and the ions other than the target ions are impurity ions. The impurity ions need to be removed.

[0066] Considering that the masses and kinetic energies of the impurity ions and the target ions are different, resulting in different motion frequencies of the impurity ions and the target ions in the ion trap. Utilizing the characteristic that the frequencies of the impurity ions and the target ions are different, the impurity ions can be resonantly ejected from the ion trap by applying an alternating voltage that is the superposition of the own frequencies of the impurity ions, so as to retain the target ions.

[0067] The screening method for multiple target ions is the same as the screening principle for a single target ion. It only needs to make the applied alternating voltage have the characteristic of the superposition of the motion frequencies of multiple target ions and have a lower energy at the frequencies of the target ions. When applied to the ion trap, it has a higher energy at the motion frequencies of the impurity ions, so that it can resonate with the impurity ions and eject them.

[0068] Specifically, the above multi-channel screening signal can be converted into an alternating voltage, an alternating voltage is superimposed on the ion trap to generate an alternating signal, and then the alternating signal is used to resonantly eject the impurity ions in the ion trap, and the target ions are screened out and retained in the ion trap.

[0069] It should be noted that since the alternating voltage also has a vibrating effect on the target ions, although it will not produce resonance, it will still cause the vibration of the target ions. The purpose of applying the alternating voltage is mainly to eject the impurity ions while retaining the target ions. That is, the effect of the alternating voltage on the target ions is not sufficient to eject the target ions from the ion trap. Therefore, it is necessary to appropriately set the amplitude of the alternating voltage.

[0070] When setting the amplitude, it is necessary to consider the kinetic energies of the target ions and the impurity ions, as well as the size of the ion trap. To ensure that under the action of the preset alternating voltage, the impurity ions resonate, causing their amplitudes to increase exponentially, and the vibrating amplitude can exceed the ion trap, so as to eject them. While the amplitude of the target ions will not exceed the confinement range of the ion trap under the action of the non-resonant single amplitude, so as to screen and confine the target ions in the ion trap.

[0071] It can be simply set that the amplitude of the multi-channel screening signal at the motion frequency of the target ions does not exceed the first amplitude, and the amplitude at the motion frequency of the impurity ions is not less than the second amplitude, and the first amplitude is significantly less than the second amplitude.

[0072] As an alternative embodiment, before resonantly ejecting the impurity ions other than the multiple target ions in the ion trap through the multi-channel screening waveform, the method further includes: according to the motion equation of the ion trap and related parameters, calculating the motion frequencies of various ions in the ion current in the ion trap, where the motion equation is used to describe the motion of ions with different mass-to-charge ratios in the ion trap under different related parameters, and the related parameters include the electric potential of the ion trap and the geometric size; determining the spectral signal in the frequency range according to the motion frequencies of various ions in the ion current, and setting the energy to be evenly distributed within the frequency range; reducing the energy corresponding to the frequency range of the spectral signal below a preset energy threshold according to the motion frequencies of the multiple target ions to generate the multi-channel screening waveform.

[0073] The motion equations corresponding to different types of ion traps are different. There are mainly two types of ion traps, namely Penning trap and Paul trap. The Paul trap uses a radio frequency electric field to trap ions, and its motion equation is the Mathieu equation. The Penning trap uses a combination of a static electric field and a magnetic field to trap ions, and its motion equation is calculated in another way. The ion trap in the discontinuous sampling mass spectrometer of this embodiment can be a Penning trap, and its motion equation is the Mathieu equation.

[0074] The Mathieu equation is related to the size of the ion trap and the radio frequency voltage, that is, the above-mentioned relevant parameters. It should be noted that the size of the ion trap can be in various aspects and is specifically selected according to the requirements of the Mathieu equation. For example, the radius of an ion trap with a circular interface, or the shortest distance to the geometric center, etc. The above radio frequency voltage can also be in other forms, such as the corresponding electric field, the induced force generated by ions, etc.

[0075] According to the motion equation of the ion trap and the relevant parameters, calculate the motion frequencies of various ions in the ion current in the ion trap. That is, according to the Mathieu equation and the relevant parameters, the motion frequencies of various ions in the ion trap can be calculated.

[0076] According to the motion frequencies of various ions in the ion current, a spectral signal within a frequency range can be determined. That is, according to the minimum motion frequency and the maximum motion frequency, this frequency range can be determined to cover the frequency ranges of the target ions and impurity ions in the ion trap.

[0077] In some other embodiments, considering that the motion frequency differences of the ions in the ion trap are relatively large and generally do not exceed the motion frequency of the ion trap, in this embodiment, the spectral signal can be directly set from zero to the motion frequency of the ion trap. This also avoids calculating and selecting the frequency range, which can further improve the data processing efficiency.

[0078] Since a certain amount of energy is required to resonantly eject impurity ions, the energy within the frequency range can be set to be evenly distributed. The energy corresponding to the motion frequency of the target ions within the frequency range of the spectral signal is reduced to below a preset energy threshold to generate a multi-channel screening waveform, which can avoid the resonant ejection of the target ions.

[0079] As an optional embodiment, according to the motion equation of the ion trap and the relevant parameters, calculate the motion frequencies of various ions in the ion current in the ion trap, including: determining the corresponding Mathieu equation as the motion equation according to the type of the ion trap; calculating the ion motion parameters of the corresponding electric field using the Mathieu equation according to the mass, charge of the ion, and the relevant parameters of the ion trap; calculating the stability parameters according to the ion motion parameters; and calculating the motion frequency of the ion according to the stability parameters.

[0080] Taking the quadrupole linear ion trap as an example, after solving based on the Mathieu equation, the ion motion parameter a of the direct current electric field of the ion trap is obtained u The calculation formula:

[0081]

[0082] Among them, z is the ion charge number, e is the unit charge, U is the potential intensity of the direct current electric field, m is the ion mass, Ω a is the angular frequency of the quadrupole direct current field of the ion trap, and r0 is the field radius of the ion trap.

[0083] and the ion motion parameter q of the alternating (radio frequency) electric field u Calculation formula:

[0084]

[0085] where z is the ion charge number, e is the unit charge, V is the potential intensity of the quadrupole alternating (radio frequency) electric field, m is the ion mass, Ω q is the angular frequency of the quadrupole alternating (radio frequency) electric field of the ion trap, and r0 is the field radius of the ion trap.

[0086] In an ion trap without a DC field, the ion motion parameter a u value is 0, while the ion stability parameter β u can be given by the following continued fraction:

[0087]

[0088] The stability parameter β of the ion frequency can be obtained by numerical methods such as recursion u .

[0089] The motion frequency ω of the ion is calculated by the following formula u :

[0090]

[0091] As an alternative embodiment, before obtaining a mass spectrometry corresponding to the current mass spectrometry, which includes a mass spectrometry diagram containing multiple target ions by fragmenting and analyzing the target ions in the ion trap one by one in ascending order of mass-to-charge ratio according to the multi-channel resonance signals of a preset frequency band in ascending order of frequency, the method further includes: determining the preset frequency band according to the motion frequencies of the multiple target ions and the required frequency margin; determining the amplitude and duration of the target ions according to the kinetic energy of the target ions and the background gas pressure; generating corresponding multi-channel resonance signals according to the preset frequency band, amplitude and duration.

[0092] When setting the multi-channel resonance signal, it mainly includes frequency setting and amplitude setting.

[0093] When setting the amplitude and duration, it is necessary to consider the kinetic energy of the target ions and the background gas pressure situation, and calculate the amplitude and duration of the fragmentation of the target ions. To ensure that under the action of the multi-channel resonance signal, the target ions are fragmented under the resonance effect.

[0094] The specific process of the fragmentation of the target ions is as follows: First, the target ions are trapped in the ion trap by the electric field of the radio frequency voltage RF.

[0095] The target ions can be made to resonate with relatively large kinetic energy by superimposing an AV voltage, i.e., the multi-channel resonance signal described above, on the RF voltage, so as to increase the probability of the target ions being collided by the background gas ions. It can be understood that the larger the amplitude of the AV voltage, the higher the kinetic energy of the target ions. However, the kinetic energy of the target ions should not be too high, otherwise the ions will resonate and eject out of the ion trap before they are collided and fragmented.

[0096] The above-mentioned background gas includes but is not limited to air / nitrogen / helium, etc. The ions of the background gas have relatively stable chemical properties. The molecules of the background gas can be injected into the ion trap by opening the ion trap to collide and fragment the target ions trapped in the ion trap. In order to increase the kinetic energy of the background gas and the probability of fragmentation of the target ions, the gas pressure of the background gas before entering the ion trap can be increased to increase the kinetic energy of the background gas, thereby increasing the fragmentation probability of the target ions.

[0097] In the process of determining the above-mentioned amplitude and duration, a suitable amplitude and duration can be adjusted through multiple experiments to generate a multi-channel resonance signal. The generated multi-channel resonance signal needs to ensure that the target ions resonate as much as possible, but at the same time will not eject out of the ion trap.

[0098] At the same time, when the pressure of the background gas is relatively high, the fragmentation requirements can be met at a relatively low amplitude level of the multi-channel resonance signal. Therefore, it will also be used as a determining factor for the amplitude and duration of the multi-channel resonance signal.

[0099] In some embodiments, a mathematical model can also be established to model the above influencing factors as various constraints. Through an iterative optimization algorithm, an optimal solution can be obtained to determine the amplitude and duration of the multi-channel resonance signal.

[0100] The frequency of the multi-channel resonance signal can be the superposition of the motion frequencies of the target ions, or cover a preset frequency band that includes the motion frequencies of multiple target ions. When determining the preset frequency band, the maximum and minimum values of the motion frequencies of multiple target ions can be combined with the required frequency margin to determine the preset frequency band of the multi-channel resonance signal.

[0101] After the amplitude and duration are determined in the preset frequency band, the corresponding multi-channel resonance signal can be generated. Specifically, the Stored Waveform Inverse Fourier Transform (SWIFT) can be used to generate the required multi-channel resonance signal, i.e., the SWIFT waveform, so as to achieve the purpose of removing redundant ions. SWIFT is a method of creating waveforms. The excitation waveform in the time domain is obtained by performing an inverse Fourier transform on the waveform excited in the frequency domain, and the selection is based on the resonance frequency of the ions.

[0102] As an alternative embodiment, by using multi-channel resonance signals in a preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one in ascending order of mass-to-charge ratio from low to high, and a mass spectrum corresponding to this mass spectrometry containing multiple target ions is obtained, including: using multi-channel resonance signals in a preset frequency band to fragment the target ions in the ion trap one by one in ascending order of mass-to-charge ratio from low to high; transmitting the successively fragmented target ions to a detector for detection, and the detector outputs a mass spectrum of multiple target ions, where the mass spectrum includes ion peaks of multiple target ions.

[0103] As described above, in order to avoid the larger target ions from fragmenting first and causing secondary fragmentation when the smaller ions fragment, which affects the detection accuracy. In this embodiment, the fragmentation is carried out in ascending order of frequency. Each ion after fragmentation is directly transmitted to the detector, so that as the target ions are fragmented one by one, the detector can obtain a mass spectrum of multiple target ions for this mass spectrometry. As Figure 8 shown, the mass spectrum includes ion peaks of multiple target ions.

[0104] As an alternative embodiment, sending multiple compounds of a target sample into an ion mass analyzer includes: sending multiple compounds of the target sample into the ion mass analyzer by direct injection or chromatographic separation; in the case of sending multiple compounds of the target sample into the ion mass analyzer by chromatographic separation, after obtaining a mass spectrum corresponding to this mass spectrometry containing multiple target ions, the method further includes: performing cyclic mass spectrometry when the chromatographic separation is not completed until the chromatographic separation is completed, and obtaining a sequence of mass spectra in chronological order, where the sequence of mass spectra includes multiple mass spectra obtained by cyclic mass spectrometry multiple times and is used to characterize the multi-channel detection results of multiple target ions.

[0105] That is, the above non-continuous mass spectrometer can be used in series with a chromatographic separation device, and the execution subject of the above steps can also be a non-continuous mass spectrometer in series with a chromatographic separation device.

[0106] A mass spectrometer with chromatographic series non-continuous injection is a mass spectrometer with a chromatographic separation device in series at the inlet. The chromatographic device can separate different compounds in the mixture, and combined with a non-continuous injection mass spectrometer, it can detect the target ions of multiple compounds in the same mixture.

[0107] When detecting the target ions of multiple compounds by a mass spectrometer with chromatographic tandem discontinuous injection, due to the single-channel characteristic of the mass spectrometer with discontinuous injection, it is necessary to first use chromatography to separate different compounds, inject them separately for different compounds, and screen, fragment, and detect their individual target ions. This results in the need to continuously repeat the entire processes of chromatography and mass spectrometry throughout the detection process. Especially because the chromatographic analysis time is relatively long, this leads to extremely low analysis efficiency.

[0108] The output port of the above chromatographic separation device and the input port of the mass spectrometer may not be directly connected. In related technologies, there are also methods to indirectly input the compounds separated by chromatography into the mass spectrometer for mass spectrometry.

[0109] The output port of the chromatographic separation device in this embodiment is directly connected to the input port of the mass spectrometer, and the compounds separated by chromatography are directly input into the mass spectrometer. When the mass spectrometer with discontinuous injection performs mass spectrometry, first open the discontinuous atmospheric pressure interface of the mass spectrometer, and inject the ion current of the target sample into the ion trap of the mass spectrometer.

[0110] The target ions can be detected through an ion detector, and an amplified ion signal is output. After forming a mass spectrum diagram corresponding to this mass spectrometry and containing multiple target ions, statistical charts required can also be generated according to other parameters. For example Figure 8 is a mass spectrum diagram, Figure 9 is a chromatogram generated using multiple mass spectrum diagrams.

[0111] As an alternative embodiment, before performing cyclic mass spectrometry when the chromatographic separation is not completed to obtain the corresponding mass spectrum diagram until the chromatographic separation is completed to obtain a sequence of mass spectrum diagrams in chronological order, it includes: determining the number of mass spectrometry cycles according to the chromatographic separation duration and the single mass spectrometry duration; determining whether the chromatographic separation is completed according to whether the number of cycles reaches the number of mass spectrometry cycles; determining that the chromatographic separation is completed when the number of cycles reaches the number of mass spectrometry cycles.

[0112] The chromatographic separation duration can be understood as the time from when the chromatographic device starts to output separated compounds until all compounds are completely separated, or it can also be the time from the start of chromatography until all compounds are completely separated. Considering that no compounds may be output for some time after the start of chromatography, if the mass spectrometer is turned on at this time, the mass spectrometer is in an idle state and will not work although it is turned on.

[0113] The chromatographic separation duration in this embodiment can be the time from when the chromatographic device starts to output separated compounds until all compounds are completely separated. It can also have a certain time margin. The single mass spectrometry duration is also the time for a complete set of processes in which the compound enters the mass spectrometer, undergoes ion bombardment, and then injection, screening, fragmentation, and detection.

[0114] The chromatographic separation duration is generally in the order of minutes, such as 5 min. The single mass spectrometry duration is generally in the order of seconds, such as 5 s. Therefore, the chromatographic tandem mass spectrometry of multiple compounds is more mainly limited by the chromatographic duration.

[0115] For this reason, in this embodiment, the chromatography is only performed once, and the separated compounds are input into the mass spectrometer of the cyclic mass spectrometry to achieve multi-channel detection of multiple target ions. Finally, a plurality of mass spectra in chronological order are output. By analyzing the plurality of mass spectra, the signal intensities of the multiple target ions over time can be obtained, that is, as Figure 9 shown in the chromatogram.

[0116] Thus, the multi-channel detection of a mass spectrometer with discontinuous injection is combined, greatly reducing the detection time of multiple compounds in chromatographic tandem mass spectrometry and improving the detection efficiency.

[0117] However, mass spectrometry is a microscopic operation and the inside of the mass spectrometer is not visible. When to control the end of the mass spectrometry needs to be determined according to the progress of chromatographic separation. In this actual example, according to the chromatographic separation duration and the single mass spectrometry duration, the number of mass spectrometry cycles is determined. Whether the chromatographic separation is completed is determined according to whether the number of cycles reaches the number of mass spectrometry cycles.

[0118] The number of mass spectrometry cycles can be simply set by the mass spectrometer. When the number of cycles reaches the number of mass spectrometry cycles, it is determined that the chromatographic separation is completed. When the number of cycles does not reach the number of mass spectrometry cycles, it is determined that the chromatographic separation is not completed. Then the mass spectrometry continues.

[0119] As an alternative embodiment, when the chromatographic separation is not completed, cyclic mass spectrometry is performed to obtain the corresponding mass spectra until the chromatographic separation is completed. After obtaining the mass spectrometry sequence in chronological order, it includes: confirming the mass-to-charge ratio of the target ions at the corresponding time, as well as the mass-to-charge ratio tolerance, and determining the mass-to-charge ratio range of the target ions; for the mass spectra at the corresponding time, extracting the signal intensity data within the mass-to-charge ratio range of each target ion; statistically analyzing the extracted signal intensity data corresponding to the target ions in chromatographic order to obtain a chromatogram including the chromatographic curves of each target ion, where the chromatographic curves include the signal intensities changing with the chromatographic order.

[0120] The mass-to-charge ratio range of the target ions is determined by the mass-to-charge ratio of the target ions and the mass-to-charge ratio tolerance. The corresponding signal intensities are extracted from the multiple mass spectra according to this range. This is because there are different errors in different mass spectra, and there may be a certain deviation in the mass-to-charge ratio detected for the same target ion.

[0121] Therefore, in this embodiment, by setting a mass-to-charge ratio tolerance, a mass-to-charge ratio range can be determined based on the mass-to-charge ratio of the target ion. The signal intensities within this mass-to-charge ratio range can be considered as those of the target ion, which effectively avoids the problem of incorrect analysis of the mass spectrum caused by mass spectrometry errors and improves the accuracy of mass spectrum analysis.

[0122] Since multiple mass spectra are generated in chronological order, the signal intensities of different target ions extracted from different mass spectra have a chronological order. Arrange the signal intensities of the same target ion in chronological order and fit them into a curve. Multiple target ions can be fitted into multiple curves, which characterize the change in the signal intensity of the corresponding target ion over time.

[0123] As Figure 9 shown, each curve corresponds to a target ion. The horizontal axis is time, and the vertical axis is signal intensity, which can characterize the change in the signal intensities of multiple detected target ions over time. The concentration of the compound corresponding to the target ion in the original mixed solution can also be determined according to the ratio of the area of the target peak of the curve to the area of the internal standard. That is, quantitative analysis.

[0124] As an alternative embodiment, before separating multiple compounds of the target sample by chromatographic separation, the method further includes: determining the internal standard of the target ion; performing multi-channel detection on the internal standard as a target ion; after statistically analyzing the signal intensity data corresponding to the extracted target ions in chromatographic order to obtain a mass spectrum containing chromatographic curves of each target ion, the method further includes: determining the concentration of the target ion according to the ratio of the area of the chromatographic peak of the target ion on the chromatographic curve to the area of the chromatographic peak of the internal standard and the concentration.

[0125] When performing multi-channel detection of multiple target ions using the internal standard method, the ions of the internal standard can be regarded as a separate target ion to finally form a chromatographic curve of the internal standard. Then, based on the ratio of the area of the target peak of the chromatographic curve of the target ion to the area of the target peak of the chromatographic curve of the internal standard, and the known concentration of the internal standard, the concentration of the compound of the target ion in the original mixed solution can be determined.

[0126] In addition, as an alternative embodiment, during the process of the mass spectrometer performing cyclic mass spectrometry, after the target ions in the ion trap are fragmented, the vacuum system of the mass spectrometer can be controlled to evacuate the vacuum chamber of the mass spectrometer and detect the pressure of the vacuum chamber. Among them, the pressure of the vacuum chamber will increase when the non-continuous atmospheric pressure interface is opened for sample injection.

[0127] When the pressure reaches the working pressure, continue to open the discontinuous atmospheric pressure interface of the mass spectrometer for cyclic mass spectrometry. This can ensure that the vacuum pressure in the ion trap is maintained within an appropriate range, avoiding the gradual deterioration of the vacuum pressure during cyclic mass spectrometry, which may lead to ineffective sample injection. This ensures the effectiveness of each sample injection during cyclic mass spectrometry.

[0128] Since the sample injection and the ion trap have high requirements for vacuum, during the power-on state, the vacuum system of the mass spectrometer is always controlled to perform vacuum pumping operations, so that the vacuum environment for ion screening and confinement in the ion trap is always of high quality, thereby improving the accuracy and efficiency of target ion screening and confinement in the ion trap.

[0129] The reason for reaching the working pressure range and maintaining the preset time is that only a small amount of air enters during each sample injection, and the actual pressure fluctuation in the vacuum chamber is not too large. In this case, the accuracy requirement for the pressure detection device of the vacuum system is too high. Therefore, by limiting through the pressure maintenance time, the accuracy of pressure detection can be improved, and the use of more precise pressure detection equipment can be avoided, reducing the cost of the mass spectrometer.

[0130] As an optional embodiment, the ion trap of the above-mentioned discontinuous injection mass spectrometer is a quadrupole linear ion trap; it includes a front end cap electrode, a quadrupole, and a rear end cap electrode. When opening the discontinuous atmospheric pressure interface of the mass spectrometer and injecting the ion current of the target sample into the ion trap of the mass spectrometer, the electric potential of the front end cap electrode can be adjusted to the target electric potential so that the electric field strength in the ion trap reaches the required electric field strength, and the ion current of the target sample is injected into the ion trap of the mass spectrometer.

[0131] The above ion trap is a quadrupole linear ion trap. During sample injection, by adjusting the electric potential of the front end cap electrode, the electric field strength in the quadrupole linear ion trap can reach the requirement for confining the ion current. During subsequent repeated sample injection processes, the electric field strength in the quadrupole linear ion trap can also be adjusted by the electric potential of the front end cap electrode.

[0132] It should be noted that this embodiment also provides an optional implementation manner, which will be described in detail below.

[0133] In real analysis scenarios, there are requirements for simultaneous detection of tandem mass spectrometry of multiple targets. To improve the analysis and detection efficiency, and at the same time avoid the cumulative error that may be brought by separate detections and improve the accuracy of the detection results.

[0134] This embodiment provides a chromatographic - discontinuous mass spectrometry multi - channel tandem analysis technique. Combining with a discontinuous injection portable mass spectrometry system, it can realize the combined detection of multi - target tandem mass spectrometry, and can meet the requirements of efficient, accurate and comprehensive analysis and detection of multiple targets in a sample in one injection. In addition to identifying and analyzing substances through secondary mass spectrometry data matching, quantitative analysis can be achieved by introducing isotope internal standards and other methods.

[0135] Figure 4 It is a schematic diagram of the multi - channel detection process of the discontinuous injection mass spectrometer according to the embodiment of the present invention. As Figure 4 shown, the detection process of this embodiment can synchronously achieve the selection of n target ions, synchronous fragmentation and synchronous detection, and finally obtain multi - channel analysis results.

[0136] This embodiment first provides an operation method for simultaneously isolating multi - channel ions based on the ion operation characteristics of the ion trap. It can simultaneously trap the precursor ions of multiple targets in the ion trap and remove the remaining matrix interference ions. By calculating an inverse Fourier transform of a multi - channel screening waveform, making it contain the frequencies of the ions other than the target ions in the ion trap, only selectively binding multiple target ions in the ion trap.

[0137] Figure 5 It is a schematic diagram of the specific steps of multi - channel detection of a chromatographic tandem discontinuous injection mass spectrometer according to the embodiment of the present invention. As Figure 5 shown, first determine the mass - to - charge ratio m / z information of the precursor ions of the n target ions to be detected. Then generate and load the multi - channel SWIFT waveforms corresponding to the n target ions, that is, the above - mentioned multi - channel screening waveforms. Determine the number of injections a according to the chromatographic analysis duration and the single - time mass spectrometry duration.

[0138] Then use the ion source of the mass spectrometer to ionize and inject the compounds output by the chromatograph. And perform synchronous screening and binding isolation of the n target ions through the multi - channel SWIFT waveforms. Apply resonance excitation energy, that is, the above - mentioned multi - channel resonance signal, generally in the form of an RF voltage applied to the ion trap. And in ascending order, for the n target ions, perform fragmentation in ascending order of the mass - to - charge ratio m / z.

[0139] Send the fragment ions after fragmenting the n target ions to the detector for detection. The detector can output a MS / MS mass spectrometry diagrams of the n target ions arranged in chronological order. Each MS / MS mass spectrometry diagram can include the signal intensities of some of the n target ions, or the signal intensities of no target ions.

[0140] Further, according to the mass-to-charge ratio characteristics of the selected multiple target ions, a multi-channel resonance signal is loaded into the ion trap, that is, a frequency-sweeping waveform with a frequency ranging from low to high (the frequency range will cover the resonance frequencies of all target ions) is applied with resonance excitation energy, and collision gas is introduced to fragment the multiple target ions in the ion trap in ascending order of mass-to-charge ratio.

[0141] Finally, all the fragment ions are sequentially scanned out of the ion trap and detected by the detector, and the detection and analysis of the fragment ions are realized. Multiple target ions can perform ion selection and analysis simultaneously, enabling multiple target substances to be analyzed by MS / MS simultaneously in one injection, solving the problem of limited number of tandem analysis channels in the coupling of continuous chromatography and discontinuous mass spectrometry, thereby improving the analysis efficiency.

[0142] To avoid the problem of interference from fragment ions with the same mass-to-charge ratio that may exist in the simultaneous fragmentation of multiple target ions, before the sample enters mass spectrometry analysis, a chromatographic technique with separation performance is introduced to separate the target substances so that they enter mass spectrometry analysis at different times, thereby differentiating fragment ions with the same mass-to-charge ratio in terms of elution time and retaining the qualitative analysis ability of the mass spectrometry.

[0143] In the chromatographic-discontinuous mass spectrometry multi-channel tandem analysis method described in this embodiment, multi-channel ion selection and detection are completed in a radio frequency ion trap, and both a linear ion trap and a 3D ion trap can be used. All operations can be completed in a single ion trap or in a dual ion trap. In the latter case, ion capture and ion selection are completed in the first ion trap, and fragmentation and ion detection can be completed in the second ion trap.

[0144] Multi-ion isolation embodiment: The present invention first designs an inverse Fourier transform waveform of a storage waveform, i.e., a SWIFT waveform, according to the frequencies of the target ions to be retained, and applies it to the ion trap in the form of a quadrupole field. The calculation method of the multi-channel SWIFT waveform for simultaneous selection of multiple target ions is as follows:

[0145] When designing the waveform for synchronous selection of multiple ions, it is necessary to first calculate the motion frequency of the ion trap according to the Mathieu equation, and the method is briefly as follows:

[0146] Calculate the ion motion parameter a of the direct current electric field of the ion trap u ;

[0147] In an ion trap without a direct current field, the ion motion parameter a u value is 0, and directly calculate the ion motion parameter q of the alternating current (radio frequency) electric field u ;

[0148] Calculate the stability parameter β of the ion through the above continued fraction u, as described above, β can be obtained for the ion frequency through numerical methods such as recursion u .

[0149] Then, based on β u calculate the angular frequency of motion ω of the ions u .

[0150] Furthermore, in this embodiment, a spectral signal will be designed according to the ion frequencies to be retained as the above-mentioned multi-channel screening waveform, that is, the energy within the range (0, Ω q ) is evenly distributed, and the energy is only 0 near the frequencies of each target ion. Furthermore, the frequency is converted into a time-domain signal through inverse Fourier transform and applied to the ion trap in the form of a dipole field.

[0151] Multi-ion resonance excitation fragmentation embodiment: It is known that the minimum resonance frequency corresponding to the multi-target ions is f min , and the maximum value is f max . Set the frequency margin to n, determine the energy amplitude to be c - d V, and thus generate and load a multi-channel resonance signal with a duration of 5 - 1000 ms and a frequency sweep range of (f min - n) kHz to (f max + n) kHz in the ion trap. The frequency increases from low to high to avoid overlapping interference; in the background of the collision gas, the isolated ions will be excited in turn and collide with the background gas, thereby realizing the fragmentation of multi-channel target substances.

[0152] When performing the analysis of multi-target substances in a sample, the multi-target substance ions separated by chromatography are detected at the mass spectrometry end. Under the action of the imported SWIFT waveform, the selected n target ions are simultaneously trapped in the ion trap. Subsequently, under the action of the applied resonance excitation energy, they are fragmented in turn according to the order of increasing mass-to-charge ratio, and the fragment ions are detected, thereby realizing the simultaneous MS / MS analysis of multiple target substances.

[0153] In an actual application scenario, using the traditional method to analyze n target substances requires n injections, while using the above method only requires one injection to achieve the synchronous analysis of n target substances.

[0154] Regarding the related operations of the ion trap mass spectrometry analysis process, as Figure 6 shown, Figure 6 is a schematic diagram of data analysis based on the multi-channel detection results in the embodiment of the present invention. As described above, after completing one chromatographic-mass spectrometric analysis, a MS / MS mass spectra of n target ions can be obtained, as Figure 8 described, this mass spectrum has the mass-to-charge ratio m / z as the x-axis and the signal intensity Intensity as the y-axis.

[0155] During analysis, first confirm the mass-to-charge ratio information of n target ions, including: m / z1, m / z2, …, m / zn. The target ions can be considered as the product ions of the target substance. Also, the mass-to-charge ratio tolerance tol is provided. The corresponding mass-to-charge ratio ranges are m / z1±tol, m / z2±tol, …, m / zn±tol.

[0156] Extract the signal intensities of each target ion's mass-to-charge ratio range in different mass spectra, then statistically analyze according to the chromatographic time and fit them into corresponding chromatographic curves. The chromatographic peak area can be obtained by integrating the target peak of the chromatographic curve for quantitative analysis. For example, according to the ratio of the chromatographic peak area corresponding to an internal standard with a known concentration to the chromatographic peak area of the target ion of the corresponding compound, the concentration of the compound corresponding to the target ion can be determined.

[0157] After obtaining the mass spectrometry data, through Figure 6 the analysis process, the chromatographic-mass spectrometry peak area results of multiple substances can be achieved, and subsequent quantitative information can be obtained based on these results.

[0158] The following further describes this embodiment in detail in combination with a multi-channel mass spectrometry example of specific multiple amino acids. This example provides a chromatographic-discontinuous mass spectrometry multi-channel tandem analysis method for 14 amino acids and amino acid internal standards.

[0159] The sample used contains 14 amino acids to be measured and internal standards, specifically including 7 amino acids: proline, valine, leucine, methionine, phenylalanine, citrulline, tyrosine. And their respective internal standards: 13 C5-proline; 15 N, 13 C5-valine; d3-leucine; d3-methionine; 13 C6-phenylalanine; d2-citrulline; 13 C6-tyrosine.

[0160] First, determine the mass-to-charge ratios of the target ions of 14 amino acids as shown in Table 1 below, and set the selected 14 target ions to generate specific SWIFT waveforms of the ion trap. The time required for one chromatographic analysis is 5 min, and the time for the mass spectrometry end to complete one analysis process is 5 s. Thus, it is determined that 60 mass spectrometry injection analyses need to be carried out. One mass spectrometry analysis process includes the following steps:

[0161] Ionization injection of the mass spectrometry ion source;

[0162] Simultaneously isolate the 14 amino acid target ions through the generated and loaded multi-channel SWIFT waveforms. The SWIFT waveforms are as Figure 7 shown, Figure 7It is a schematic diagram of the SWIFT waveform of the amino acid internal standard analysis method of the embodiment of the present invention. This SWIFT waveform has a reduced energy at multiple position frequencies to ensure that target ions corresponding to multiple motion frequencies can be effectively screened and trapped in the ion trap. Impurity ions corresponding to other motion frequencies are resonantly ejected from the ion trap uniformly.

[0163] According to the resonance frequencies corresponding to 14 target ions, the minimum resonance frequency is determined to be 235 kHz and the maximum is 316 kHz. A frequency margin of 10 kHz is set, and the energy amplitude is 1 - 2 V. A frequency-sweeping waveform and energy for 200 ms are loaded into the ion trap. Isolated ions will be excited in sequence and collide with the background gas, thereby achieving fragmentation of multi-channel target substances. The fragmented ions are collected by the detector to obtain the MS / MS mass spectrum of all fragment ions.

[0164] The chromatographic - mass spectrometric analysis process is completed, and 60 pieces of MS / MS mass spectrometry data containing fragment ions of 14 target ions are obtained. This data uses the mass - to - charge ratio m / z as the x - axis and the ion signal intensity Intensity as the y - axis, as Figure 8 shown. Figure 8 It is a schematic diagram of a mass spectrum of the amino acid internal standard analysis method of the embodiment of the present invention.

[0165] Confirm the mass - to - charge ratio information of the fragment ions of 14 target ions, as shown in Table 1 below. Table 1 is the mass - to - charge ratio information table of target ions and fragment ions.

[0166] Table 1 Mass - to - charge ratio information table of ions and fragment ions

[0167]

[0168] Confirm that the mass - to - charge ratio tolerance is 0.3. Extract the intensity of the signal within the range of ±0.3 of each mass - to - charge ratio ion and depict them in sequence according to the chromatographic time order, forming a chromatogram with the time order as the x - axis and the intensity as the y - axis. Perform Gaussian fitting on the chromatogram to obtain the final chromatogram result of each target substance's m / z, as Figure 9 shown. Figure 9 It is a schematic diagram of integrating multiple mass spectra of the amino acid internal standard analysis method of the embodiment of the present invention into a multi - channel chromatogram.

[0169] By introducing isotope internal standards, quantitative analysis can be achieved. Perform area integration on each target peak to obtain the chromatographic peak area, and further quantitative analysis can be carried out based on the chromatographic peak area data.

[0170] Chromatography-mass spectrometry injection is performed, and the analysis process starts and chromatographic-mass spectrometric data is collected. The data is collected by the ion trap mass spectrometry end for mass spectrometry data. During the mass spectrometry data collection process, under the action of the SWIFT waveform, only the selected 14 target ions are isolated in the ion trap. Subsequently, according to the fragmentation characteristics of the 14 target ions, a resonance excitation energy is superimposed on the ion trap, that is, by applying an RF voltage, and scanning is performed in sequence according to the energy from high to low to achieve the sequential excitation fragmentation of the 14 target ions. The fragment ions after fragmentation are collected and detected by the ion trap mass spectrometry, and a mass spectrum diagram is obtained as Figure 8 shown. According to the continuously collected mass spectrometry data, a chromatogram can be obtained as Figure 9 shown.

[0171] Figure 10 Figure 10 is a schematic diagram of a multi-channel detection device of a non-continuous injection mass spectrometer according to an embodiment of the present invention, as shown. The embodiment of the present invention provides a multi-channel detection device of a non-continuous injection mass spectrometer. The device includes: an input module 1001, a mass spectrometry screening module 1002, and a mass spectrometry detection module 1003. The device will be described in detail below.

[0172] The input module 1001 is used to send multiple compounds of a target sample into an ion mass analyzer, where the compounds contain target ions to be detected;

[0173] The mass spectrometry screening module 1002 is connected to the above input module 1001 and is used to input the ion current of the separated compounds into the ion trap, and screen multiple target ions in the ion trap through a preset multi-channel screening waveform and confine them in the ion trap, where the ion current includes multiple target ions to be detected;

[0174] The mass spectrometry detection module 1003 is connected to the above mass spectrometry screening module 1002 and is used to perform fragmentation and analysis on the target ions in the ion trap one by one according to the mass-to-charge ratio from small to large through a multi-channel resonance signal in a preset frequency band in the order of frequency from low to high, and obtain a mass spectrum diagram corresponding to this mass spectrometry containing multiple target ions.

[0175] For the above multi-channel detection device of the non-continuous injection mass spectrometer provided in this embodiment, after separating multiple compounds of the target sample, the ion current is input into the ion trap, and multiple target ions in the ion trap are screened through a preset multi-channel screening waveform and confined in the ion trap, realizing the multi-channel synchronous confinement of multiple target ions.

[0176] Then, by means of multi-channel resonance signals in a preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one in ascending order of mass-to-charge ratio from low to high, and a mass spectrometry corresponding to this mass spectrometry and containing multiple target ions is obtained, realizing multi-channel synchronous fragmentation detection of multiple target ions.

[0177] Thus, by applying different multi-channel screening waveforms and multi-channel resonance signals when the ion trap is in the trapping and fragmentation states, synchronous screening and fragmentation detection of multiple target ions are achieved, effectively improving the detection efficiency of multi-channel detection of multiple target ions using a discontinuous mass spectrometer.

[0178] According to one aspect of the embodiments of the present invention, there is also provided a discontinuous injection mass spectrometer, including: a processor, and a memory storing a program, wherein the program includes instructions that, when executed by the processor, cause the processor to execute the above method.

[0179] Moreover, according to one aspect of the embodiments of the present invention, there is also provided a chromatography tandem discontinuous injection mass spectrometer, including: a processor, and a memory storing a program, wherein the program includes instructions that, when executed by the processor, cause the processor to execute the above method.

[0180] Since this mass spectrometer, or the chromatography tandem discontinuous injection mass spectrometer operates according to the above control method, therefore, this mass spectrometer includes all the technical effects of the above method. Since the technical effects of the control method have been described in detail above, they will not be elaborated here.

[0181] Embodiments of the present invention also provide a non-transitory machine-readable medium storing a computer program, wherein the above computer program, when executed by a processor of a computer, is used to cause the computer to execute the method of the embodiments of the present invention.

[0182] Embodiments of the present invention also provide a computer program product, including a computer program, wherein the computer program, when executed by a processor of a computer, is used to cause the computer to execute the method of the embodiments of the present invention.

[0183] Embodiments of the present invention also provide an electronic device, including: at least one processor; and a memory communicatively connected to the at least one processor. The above memory stores a computer program capable of being executed by the at least one processor, and the above computer program, when executed by the at least one processor, is used to cause the electronic device to execute the method of the embodiments of the present invention.

[0184] Reference Figure 11, a block diagram of an electronic device of a server or a client that can be an embodiment of the present invention will now be described. It is an example of a hardware device that can be applied to various aspects of the present invention. The electronic device is intended to represent various forms of digital electronic computer devices, such as, laptop computers, desktop computers, workstations, personal digital assistants, servers, blade servers, mainframe computers, and other suitable computers. The electronic device can also represent various forms of mobile devices, such as, personal digital processors, cellular phones, smart phones, wearable devices, and other similar computing devices. The components shown herein, their connections and relationships, and their functions are merely examples and are not intended to limit the implementation of the present invention described and / or claimed herein.

[0185] As Figure 11 shown, the electronic device includes a computing unit 1101, which can perform various appropriate actions and processes according to a computer program stored in a read-only memory (ROM) 1102 or a computer program loaded from a storage unit 1108 into a random access memory (RAM) 1103. In the RAM 1103, various programs and data required for the operation of the electronic device can also be stored. The computing unit 1101, the ROM 1102, and the RAM 1103 are connected to each other via a bus 1104. An input / output (I / O) interface 1105 is also connected to the bus 1104.

[0186] Multiple components in the electronic device are connected to the I / O interface 1105, including: an input unit 1106, an output unit 1107, a storage unit 1108, and a communication unit 1109. The input unit 1106 can be any type of device that can input information into the electronic device. The input unit 1106 can receive input digital or character information, and generate key signal inputs related to the user settings and / or function controls of the electronic device. The output unit 1107 can be any type of device that can present information, and can include but is not limited to a display, a speaker, a video / audio output terminal, a vibrator, and / or a printer. The storage unit 1108 can include but is not limited to magnetic disks, optical disks. The communication unit 1109 allows the electronic device to exchange information / data with other devices via a computer network such as the Internet and / or various telecommunication networks, and can include but is not limited to a modem, a network card, an infrared communication device, and / or a wireless communication transceiver, such as a Bluetooth device, a WiFi device, a WiMax device, a cellular communication device, and / or the like.

[0187] The computing unit 1101 can be various general-purpose and / or special-purpose processing components with processing and computing capabilities. Some examples of the computing unit 1101 include, but are not limited to, a CPU, a graphics processing unit (GPU), various special artificial intelligence (AI) computing units, various computing units running machine learning model algorithms, a digital signal processor (DSP), and any suitable processor, controller, microcontroller, etc. The computing unit 1101 executes the various methods and processes described above. For example, in some embodiments, the method embodiments of the present invention can be implemented as a computer program, which is tangibly contained in a machine-readable medium, such as the storage unit 1108. In some embodiments, part or all of the computer program can be loaded and / or installed onto the electronic device via the ROM 1102 and / or the communication unit 1109. In some embodiments, the computing unit 1101 can be configured to execute the above-described method in any other suitable manner (e.g., by means of firmware).

[0188] The computer program for implementing the method of the embodiments of the present invention can be written in any combination of one or more programming languages. These computer programs can be provided to a processor or controller of a general-purpose computer, a special-purpose computer, or other programmable data processing device, such that when the computer program is executed by the processor or controller, the functions / operations specified in the flowchart and / or block diagram are implemented. The computer program can be executed entirely on the machine, partially on the machine, as an independent software package partially on the machine and partially on a remote machine, or entirely on a remote machine or server.

[0189] In the context of the embodiments of the present invention, a machine-readable medium can be a tangible medium that can contain or store a program for use by or in connection with an instruction execution system, apparatus, or device. A machine-readable medium can be a machine-readable signal medium or a machine-readable storage medium. A machine-readable signal medium can include, but is not limited to, an electronic, magnetic, optical, electromagnetic, or infrared system, apparatus, or device, or any suitable combination of the foregoing. More specific examples of a machine-readable storage medium would include an electrical connection based on one or more wires, a portable computer disk, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing.

[0190] It should be noted that the term "including" and its variants used in the embodiments of the present invention are open-ended, that is, "including but not limited to". The term "based on" means "at least partially based on". The term "one embodiment" means "at least one embodiment"; the term "another embodiment" means "at least one additional embodiment"; the term "some embodiments" means "at least some embodiments". The modifications of "one" and "a plurality" mentioned in the embodiments of the present invention are illustrative rather than restrictive. Those skilled in the art should understand that unless clearly stated otherwise in the context, it should be understood as "one or more".

[0191] The user information (including but not limited to user device information, user personal information, etc.) and data (including but not limited to data for analysis, stored data, displayed data, etc.) involved in the embodiments of the present invention are all information and data that have been authorized by the user or fully authorized by all parties. And the collection, use, and processing of relevant data need to comply with the relevant laws, regulations, and standards of relevant countries and regions, and corresponding operation entrances are provided for users to choose to authorize or reject.

[0192] The steps described in the method embodiments provided by the embodiments of the present invention can be executed in different orders and / or executed in parallel. In addition, the method embodiments may include additional steps and / or omit the steps shown. The protection scope of the present invention is not limited in this regard.

[0193] The term "embodiment" in this specification means that the specific features, structures, or characteristics described in connection with the embodiment may be included in at least one embodiment of the present invention. The phrase appears in various positions in the specification does not necessarily mean the same embodiment, nor does it mean being independent or alternative to other embodiments and mutually exclusive. The various embodiments in this specification are described in a related manner, and the same or similar parts between the various embodiments are cross-referred to. In particular, for device, equipment, and system embodiments, since they are basically similar to method embodiments, the description is relatively simple, and the relevant parts refer to the partial description of the method embodiments.

[0194] The above-described embodiments only represent several implementation manners of the present invention, and the description is relatively specific and detailed, but it should not be understood as a limitation of the protection scope. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the appended claims.

Claims

1. A multi-channel detection method for a mass spectrometer with discontinuous sample injection, characterized in that, Comprising: Sending multiple compounds of a target sample into an ion mass analyzer of a mass spectrometer with discontinuous injection through chromatographic separation, wherein the compounds contain target ions to be detected; Inputting the ion current of the compounds into an ion trap, screening multiple target ions in the ion trap through a preset multi-channel screening waveform, and confining them in the ion trap, wherein the ion current includes multiple target ions to be detected; Fragmenting and analyzing the target ions in the ion trap one by one according to the mass-to-charge ratio from small to large through a multi-channel resonance signal in a preset frequency band in the order of frequency from low to high to obtain a mass spectrum corresponding to this mass spectrometry and containing multiple target ions; Performing cyclic mass spectrometry when the chromatographic separation is not completed until the chromatographic separation is completed to obtain a sequence of mass spectra in chronological order, wherein the sequence of mass spectra includes multiple mass spectra obtained by performing cyclic mass spectrometry multiple times and is used to characterize the multi-channel detection results of multiple target ions. When the number of cycles does not reach the number of mass spectrometry cycles, it is determined that the chromatographic separation is not completed, and the number of mass spectrometry cycles is determined according to the chromatographic separation duration and the single mass spectrometry duration.

2. The method according to claim 1, characterized in that, Inputting the ion current of the output compounds into an ion trap, screening multiple target ions in the ion trap through a preset multi-channel screening waveform, and confining them in the ion trap, including: Inputting the ion current into the ion trap and confining it; Resonantly ejecting impurity ions other than the multiple target ions in the ion trap through the multi-channel screening waveform, wherein the impurity ions are ions other than the target ions in the injected ion current; Confining multiple said target ions in the ion trap.

3. The method according to claim 2, wherein Before resonantly ejecting the impurity ions other than the multiple target ions in the ion trap through the multi-channel screening waveform, the method further includes: Calculating the motion frequencies of various ions in the ion current in the ion trap according to the motion equation of the ion trap and relevant parameters, wherein the motion equation is used to describe the motion of ions with different mass-to-charge ratios in the ion trap under different relevant parameters, and the relevant parameters include the electric field potential and geometric size of the ion trap; Determining a spectral signal in a frequency range according to the motion frequencies of various ions in the ion current and setting a uniform energy distribution within the frequency range; Reducing the energy corresponding to the frequency range of the spectral signal below a preset energy threshold according to the motion frequencies of multiple target ions to generate the multi-channel screening waveform.

4. The method according to claim 3, characterized in that, Calculating the motion frequencies of various ions in the ion current in the ion trap according to the motion equation of the ion trap and relevant parameters, including: Determining the corresponding Mathieu equation as the motion equation according to the type of the ion trap; Calculating the ion motion parameters of the corresponding electric field using the Mathieu equation according to the mass and charge of the ions and the relevant parameters of the ion trap; Calculating the stability parameters according to the ion motion parameters; Calculating the motion frequencies of the ions according to the stability parameters.

5. The method according to claim 1, characterized in that Before obtaining a mass spectrometry corresponding to this mass spectrometry and including a plurality of target ions by fragmenting and analyzing the target ions in the ion trap one by one in ascending order of mass-to-charge ratio according to a multi-channel resonance signal in a preset frequency band in ascending order of frequency, the method further includes: Determining the preset frequency band according to the motion frequencies of a plurality of target ions and the required frequency margin; Determining the amplitude and duration of the target ions according to the kinetic energy of the target ions and the background gas pressure; Generating a corresponding multi-channel resonance signal according to the preset frequency band, the amplitude, and the duration; 6. The method according to claim 5, wherein Obtaining a mass spectrometry corresponding to this mass spectrometry and including a plurality of target ions by fragmenting and analyzing the target ions in the ion trap one by one in ascending order of mass-to-charge ratio according to a multi-channel resonance signal in a preset frequency band in ascending order of frequency, including: Fragmenting the target ions in the ion trap one by one in ascending order of mass-to-charge ratio according to a multi-channel resonance signal in a preset frequency band in ascending order of frequency; Transmitting the successively fragmented target ions to a detector for detection, and outputting a mass spectrometry of a plurality of target ions by the detector, wherein the mass spectrometry includes ion peaks of a plurality of target ions.

7. The method according to claim 1, wherein Before performing a cyclic mass spectrometry when the chromatographic separation is not completed to obtain a corresponding mass spectrometry until the chromatographic separation is completed to obtain a sequence of mass spectrometries in chronological order, it includes: Determining whether the chromatographic separation is completed according to whether the number of cycles reaches the number of mass spectrometry cycles; Determining that the chromatographic separation is completed when the number of cycles reaches the number of mass spectrometry cycles.

8. The method according to claim 1, wherein After performing a cyclic mass spectrometry when the chromatographic separation is not completed to obtain a corresponding mass spectrometry until the chromatographic separation is completed to obtain a sequence of mass spectrometries in chronological order, it includes: Confirming the mass-to-charge ratio of the target ions at the corresponding time and the mass-to-charge ratio tolerance, and determining the mass-to-charge ratio range of the target ions; Extracting signal intensity data within the mass-to-charge ratio range of each target ion for the mass spectrometry corresponding to the corresponding time; Statistically analyzing the extracted signal intensity data corresponding to the target ions in chromatographic order to obtain a chromatogram including chromatographic curves of each target ion, wherein the chromatographic curves include signal intensities varying with the chromatographic order.

9. The method according to claim 8, wherein Before separating a plurality of compounds of a target sample by chromatographic separation, the method further includes: Determining an internal standard for the target ions; Performing multi-channel detection on the internal standard as the target ions; After statistically analyzing the extracted signal intensity data corresponding to the target ions in chromatographic order to obtain a chromatogram including chromatographic curves of each target ion, the method further includes: Determining the concentration of the target ions according to the ratio of the area of the chromatographic peak of the target ions on the chromatographic curve to the area of the chromatographic peak of the internal standard and the concentration; 10. A mass spectrometer with discontinuous sample introduction, comprising: A processor and a memory storing a program, wherein the program includes instructions that, when executed by the processor, cause the processor to execute the method according to any one of claims 1 to 9.

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