Multi-channel detection method of mass spectrometer with discontinuous sample injection

Abstract

The invention relates to the technical field of mass spectrometers, and particularly provides a multi-channel detection method of a non-continuous sample injection mass spectrometer, which comprises the following steps: feeding a plurality of compounds of a target sample into an ion mass analyzer; screening a plurality of target ions of the ion flow of the compound through a preset multi-channel screening waveform; according to the method, target ions in an ion trap are fragmented and analyzed one by one according to a sequence from low frequency to high frequency and a mass-to-charge ratio from small to large through a multi-channel resonance signal of a preset frequency band, and a mass spectrum containing a plurality of target ions is obtained. Therefore, the problems of long analysis time and low analysis efficiency due to the fact that mass spectrometry of only one target ion can be realized at a time when a non-continuous sample injection mass spectrometer in related technologies analyzes the target ions and the multiple target ions need to be analyzed one by one when the multiple target ions are analyzed are solved.

Description

Technical Field

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

[0002] In the related technology, the sampling frequency of the mass spectrometer with non-continuous injection is low and the number of analysis channels is limited. In particular, the single ion trap mass spectrometer with non-continuous injection can usually only realize single-channel analysis. Therefore, when detecting multiple targets or performing chromatographic cascade analysis, multiple injections are required to isolate, fragment, and scan the target ions separately and sequentially, which greatly increases the analysis time.

[0003] With regard to the related technologies of multi-target detection or chromatographic tandem discontinuous injection mass spectrometers, when performing target ion analysis, only one target ion can be analyzed at a time. When analyzing multiple target ions, they need to be analyzed one by one, resulting in long analysis time and low analysis efficiency. No effective solution has been proposed so far. Summary of the invention

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

[0005] According to one aspect of an embodiment of the present invention, a multi-channel detection method for a mass spectrometer with discontinuous injection is provided, comprising: sending multiple compounds of a target sample into an ion mass analyzer, wherein the compounds include target ions that need to be detected; inputting the ion flow of the compounds into an ion trap, screening the multiple target ions in the ion trap through a preset multi-channel screening waveform, and binding them in the ion trap, wherein the ion flow includes multiple target ions that need to be detected; and fragmenting and analyzing 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 of a preset frequency band, to obtain a mass spectrum containing multiple target ions corresponding to this mass spectrum.

[0006] As an optional embodiment, the ion flow of the output compound is input into an ion trap, and a plurality of target ions in the ion trap are screened and confined in the ion trap through a preset multi-channel screening waveform, including: inputting the ion flow into the ion trap and confining it; resonantly ejecting impurity ions other than the plurality of 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 flow; and confining the plurality of target ions in the ion trap.

[0007] As an optional embodiment, before resonantly ejecting impurity ions other than multiple target ions in the ion trap through the multi-channel screening waveform, the method also includes: calculating the movement frequencies of various ions of the ion flow in the ion trap according to the motion equation of the ion trap and related parameters, wherein the motion equation is used to describe the movement of ions with different mass-to-charge ratios in the ion trap under different related parameters, and the related parameters include the electric field potential and geometric dimensions of the ion trap; determining the frequency spectrum signal of the frequency range according to the movement frequencies of various ions of the ion flow, and setting the energy within the frequency range to be uniformly distributed; and reducing the corresponding energy within the frequency range of the frequency spectrum signal to below a preset energy threshold according to the movement frequencies of multiple target ions to generate the multi-channel screening waveform.

[0008] As an optional embodiment, the movement frequencies of various ions of the ion flow in the ion trap are calculated according to the motion equation of the ion trap and related parameters, including: determining the corresponding Matthew 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 Matthew equation according to the mass and charge of the ions and related parameters of the ion trap; calculating the stability parameters according to the ion motion parameters; and calculating the movement frequencies of the ions according to the stability parameters.

[0009] As an optional embodiment, by using a multi-channel resonance signal of a preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high, and before a mass spectrum containing multiple target ions corresponding to this mass spectrum is obtained, the method also 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; and generating corresponding multi-channel resonance signals according to the preset frequency band, the amplitude and duration.

[0010] As an optional embodiment, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio in an ascending order of frequency through a multi-channel resonance signal of a preset frequency band, so as to obtain a mass spectrum containing multiple target ions corresponding to this mass spectrum, including: through a multi-channel resonance signal of a preset frequency band, the target ions in the ion trap are fragmented one by one according to the mass-to-charge ratio in an ascending order of frequency through a multi-channel resonance signal of a preset frequency band; the successively fragmented target ions are transmitted to a detector for detection, and the detector outputs a mass spectrum of the multiple target ions, wherein the mass spectrum includes ion peaks of the multiple target ions.

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

[0012] As an optional embodiment, cyclic mass spectrometry is performed when the chromatographic separation is not completed to obtain a corresponding mass spectrum until the chromatographic separation is completed and a mass spectrum sequence in chronological order is obtained, including: determining the number of mass spectrometry cycles based on the chromatographic separation duration and the single mass spectrometry duration; determining whether the chromatographic separation is completed based on 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 optional embodiment, cyclic mass spectrometry is performed when the chromatographic separation is not completed to obtain a corresponding mass spectrum, until the chromatographic separation is completed and a sequence of mass spectra in chronological order is obtained, including: confirming the mass-to-charge ratio of the target ion at the corresponding time, and the mass-to-charge ratio tolerance, and determining the mass-to-charge ratio range of the target ion; for the mass spectrum at the corresponding time, extracting signal intensity data within the mass-to-charge ratio range of each target ion; and statistically analyzing the signal intensity data corresponding to the extracted target ions in accordance with the chromatographic order to obtain a chromatogram containing chromatographic curves of each target ion, wherein the chromatographic curve includes signal intensity that changes with the chromatographic order.

[0014] As an optional embodiment, before separating multiple compounds of the target sample through chromatographic separation, the method also includes: determining the internal standard of the target ion; performing multi-channel detection on the target ion using the internal standard; and performing statistics on the signal intensity data corresponding to the extracted target ions in chromatographic order to obtain a chromatogram containing chromatographic curves of each target ion. The method also includes: determining the concentration of the target ion based on the ratio and concentration 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.

[0015] According to one aspect of an embodiment of the present invention, there is also provided a discontinuous injection mass spectrometer, comprising: a processor, and a memory for storing a program, wherein the program comprises instructions, which, when executed by the processor, cause the processor to execute the above-mentioned method.

[0016] The multi-channel detection method of the discontinuous injection mass spectrometer provided in the embodiment of the present invention separates multiple compounds of the target sample, inputs their ion flow into the ion trap, screens the multiple target ions in the ion trap through a preset multi-channel screening waveform, and binds them in the ion trap, thereby realizing multi-channel synchronous binding of multiple target ions.

[0017] Then, through the multi-channel resonance signal of the preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large, in the order of frequency from low to high, to obtain a mass spectrum corresponding to this mass spectrum containing multiple target ions, to achieve multi-channel synchronous fragmentation detection of multiple target ions, to characterize the multi-channel detection results of multiple target ions.

[0018] Therefore, by adding different multi-channel screening waveforms and multi-channel resonance signals to the ion trap during binding and fragmentation, 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, and solving the problem in the prior art that a discontinuous injection mass spectrometer can only perform mass spectrometry analysis of one target ion at a time when performing target ion analysis, 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 briefly introduces the drawings required for use in the embodiments or the prior art descriptions. Obviously, the drawings described below are only some embodiments of the present invention, and for ordinary technicians in this field, other embodiments can be obtained based on these drawings without creative work.

[0020] Figure 1The present invention is a flow chart of a single-channel detection method of a mass spectrometer with discontinuous injection in the related art.

[0021] Figure 2 The present invention is a flow chart of a mass spectrometer with discontinuous injection in the related art for performing multi-target ion detection.

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

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

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

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

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

[0027] 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.

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

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

[0030] Fig.11 It is a structural schematic diagram of the electronic device created by the present invention. DETAILED DESCRIPTION

[0031] The embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. Although certain embodiments of the present invention are shown in the accompanying drawings, it should be understood that the present invention can be implemented in various forms and should not be construed as being limited to the embodiments described herein, which are instead provided to provide a more thorough and complete understanding of the present invention. It should be understood that the drawings and embodiments of the present invention are only for exemplary purposes and are not intended to limit the scope of protection of the present invention.

[0032] Among the related technologies, mass spectrometry is a highly specific analytical technology with high sensitivity and specificity. It analyzes the target ions screened by the mass analyzer; or uses tandem technology to dissociate the parent 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 cause deviations in the qualitative and quantitative results, thereby affecting the use of the mass spectrometer in specific application fields.

[0033] Due to the high analytical sensitivity and specificity of mass spectrometry technology, mass spectrometers have become the most widely used chemical analysis instruments in the world, and miniaturization and portability are the future development direction of mass spectrometers. It analyzes the target ions screened by the mass analyzer; or uses tandem technology to dissociate the parent ions and further analyze the generated fragment ions to achieve qualitative and quantitative analysis of the compound structure. Among them, ion trap mass spectrometers are currently a hot research topic in the field of portable mass spectrometry because of their small size and time-tandem mass spectrometry capabilities.

[0034] In order 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 used in ion trap mass spectrometers equipped with continuous atmospheric pressure interfaces is large in volume, requiring a larger vacuum pump combination to maintain the vacuum required by the mass spectrometer, resulting in certain limitations on its portability.

[0035] Tandem analysis is an important technology for mass spectrometry identification of material structure. In a single tandem mass spectrometry scanning analysis process, it is usually necessary to produce a characteristic fragment ion spectrum corresponding to the material structure through the steps of target ion isolation, excitation fragmentation, and ion scanning, and then obtain the qualitative or quantitative detection results of the mass spectrometry.

[0036] In related technologies, mass spectrometers are differentiated based on the structural form of the injection port, usually including conventional continuous injection structure mass spectrometers and discontinuous injection structure mass spectrometers. The discontinuous injection structure mass spectrometer system reduces the dependence of the mass spectrometer on the vacuum system, facilitates the miniaturization of the mass spectrometer, and is conducive to enabling instant detection scenarios such as bedside detection and precision medicine.

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

[0038] A discontinuous injection mass spectrometer, that is, a mass spectrometer that uses a discontinuous atmospheric pressure interface to realize an atmospheric pressure ion source, is easy to carry and has a simple structure. In order to further reduce the volume and simplify the structure, a portable discontinuous injection mass spectrometer is usually a single ion trap structure.

[0039] Figure 1 is a flow chart of a single-channel detection method of a mass spectrometer with discontinuous injection in the related art, such as Figure 1 As shown, a discontinuous injection mass spectrometer can only isolate a single target ion and then perform mass spectrometry detection after retrograde fragmentation of the target ion.

[0040] If you want to use a non-continuous injection mass spectrometer to detect multiple target ions, you can only perform mass spectrometry one by one. Figure 2 is a flow chart of a mass spectrometer with discontinuous injection in the related art for multi-target ion detection, such as Figure 2 As shown in the figure, a single-channel non-continuous injection mass spectrometer needs to inject, screen, fragment and detect multiple target ions one by one when performing multi-target ion detection, based on a large number of repetitions of the entire detection process.

[0041] Especially when combined with chromatography, the chromatography time is longer and needs to be performed before the mass spectrometer. This results in a longer detection time for multiple target ions when the chromatography is connected in series with a mass spectrometer with non-continuous injection, resulting in a problem of low detection efficiency.

[0042] In the related technologies, multi-channel chromatography and mass spectrometry both rely on parallel hardware structures, which will inevitably increase the volume of chromatography or mass spectrometry and are not suitable for portable non-continuous injection mass spectrometers. There is currently no related technology for implementing multi-channel detection on a non-continuous injection single ion trap mass spectrometer.

[0043] Figure 3 Flow chart of a multi-channel detection method of a mass spectrometer with discontinuous injection according to an embodiment of the present invention, such as Figure 3 As shown, in order to solve the problem that a mass spectrometer with discontinuous injection in the related art can only perform mass spectrometry analysis of one target ion at a time when performing target ion analysis, and when multiple target ions are analyzed, they need to be analyzed one by one, resulting in a long analysis time and low analysis efficiency. The embodiment created by the present invention provides a multi-channel detection method for a mass spectrometer with discontinuous injection, the method comprising the following steps:

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

[0045] Step S302, inputting the ion flow of the compound into the 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 flow includes multiple target ions that need to be detected;

[0046] Step S303, using the multi-channel resonance signal of the preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high, to obtain a mass spectrum corresponding to this mass spectrum containing multiple target ions.

[0047] The multi-channel detection method of the above-mentioned non-continuous injection mass spectrometer provided in this embodiment separates multiple compounds of the target sample, inputs their ion flow into the ion trap, and screens multiple target ions in the ion trap through a preset multi-channel screening waveform and binds them in the ion trap, thereby realizing multi-channel synchronous binding of multiple target ions.

[0048] Then, through the multi-channel resonance signal of the preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large, in the order of frequency from low to high, to obtain the mass spectrum corresponding to this mass spectrum containing multiple target ions, thereby realizing multi-channel synchronous fragmentation detection of multiple target ions.

[0049] Therefore, by adding different multi-channel screening waveforms and multi-channel resonance signals to the ion trap during confinement and fragmentation, simultaneous screening and fragmentation detection of multiple target ions can be achieved, 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 a controller or a host computer of a mass spectrometer with discontinuous injection, or an external controller of a mass spectrometer with discontinuous injection, through which the working parameters of the mass spectrometer can be collected and various parts can be controlled.

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

[0052] The above ion flow is obtained by applying high voltage to the target compound solution through an electrospray ion source (ESI) to generate charged ions, and the ion flow includes the target ions of the compound and, if the internal standard method is used, the ions of the internal standard. The speed of the ion flow can be equivalent to the speed of the electron.

[0053] The higher the speed of the ion flow, the greater the kinetic energy of the ions. When the target ions in the ion flow are trapped in the ion trap, the greater the electric field strength required, that is, the greater the voltage applied to the ion trap. When injecting samples, theoretically, it is only necessary to ensure that the ion flow can be effectively trapped in the ion trap.

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

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

[0056] Then, high energy is maintained at other frequencies so that impurity ions other than the target ions can resonate out. The spectrum signal is converted into time domain to obtain a multi-channel screening waveform.

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

[0058] Since there are multiple target ions, different target ions are large and small. In order to avoid the fragmentation of larger ions, secondary fragmentation may easily occur when smaller ions are fragmented, resulting in reduced accuracy of the detection results.

[0059] To this end, this embodiment designs a multi-channel resonance signal, and within a preset frequency band, the target ions in the ion trap are fragmented one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high. 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 ions. After multiple target ions are fragmented and input into the detector, the detector can record the signal intensity of multiple target ions and finally generate the mass spectra of multiple target ions of this mass spectrum. For example, the mass spectra of multiple amino acid target ions are as follows: Figure 8 shown.

[0061] It should be noted that the target ions in this embodiment may be detected by an ion detector in the prior art, such as an electron multiplier (EM), a Faraday cup (FC), a photomultiplier electrode, an array detector, and the like.

[0062] The target ions can be detected by the ion detector, and the amplified ion signals can be output to form a mass spectrum corresponding to this mass spectrum containing multiple target ions.

[0063] Through the above steps, different multi-channel screening waveforms and multi-channel resonance signals are added to the ion trap during binding and fragmentation, so as to realize the simultaneous screening and fragmentation detection of multiple target ions, effectively improving the detection efficiency of multi-channel detection of multiple target ions using a discontinuous mass spectrometer, and solving the problem that in the prior art, a discontinuous injection mass spectrometer can only realize mass spectrometry analysis of one target ion at a time when performing target ion analysis, and when analyzing multiple target ions, they need to be analyzed one by one, resulting in a long analysis time and low analysis efficiency.

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

[0065] After the ion flow enters the ion trap, all ions in the ion flow will be bound in the ion trap by the electric field of the ion trap, and the ions other than the target ions are impurity ions. Impurity ions need to be removed.

[0066] Considering the different masses and kinetic energies of impurity ions and target ions, the impurity ions and target ions have different motion frequencies in the ion trap. By using the different frequencies of the impurity ions and target ions, an AC voltage with the impurity ions' own frequencies superimposed can be applied to resonate with the impurity ions, thereby ejecting all impurity ions from the ion trap and retaining 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 requires that the applied AC voltage has the characteristics of superimposing the motion frequencies of multiple target ions and having lower energy at the frequency of the target ions. When applied to the ion trap, the motion frequency of the impurity ions has higher energy, which can resonate with the impurity ions and eject them.

[0068] Specifically, the multi-channel screening signal can be converted into an AC voltage, which is superimposed on the ion trap to generate an AC signal, which is then used to resonate and eject impurity ions in the ion trap, thereby screening out target ions and retaining them in the ion trap.

[0069] It should be noted that the AC voltage will also produce vibrations on the target ions, but it will not produce resonance. However, it will still cause vibrations on the target ions. The purpose of applying the AC voltage is mainly to eject the impurity ions and retain the target ions. In other words, the effect of the AC voltage on the target ions should not be enough to eject the target ions from the ion trap. This requires that the amplitude of the AC voltage should also be appropriately set.

[0070] The setting of the amplitude needs to consider the kinetic energy of the target ions and impurity ions, and the size of the ion trap. This ensures that under the action of the preset AC voltage, the impurity ions resonate, causing their amplitude to increase exponentially, and the vibration amplitude can exceed the ion trap, thereby ejecting them. 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, thereby screening the target ions and confining them in the ion trap.

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

[0072] As an optional embodiment, before resonantly ejecting impurity ions other than multiple target ions in the ion trap through a multi-channel screening waveform, the method also includes: calculating the movement frequencies of various ions of the ion flow in the ion trap based on the motion equation of the ion trap and related parameters, wherein the motion equation is used to describe the movement of ions with different mass-to-charge ratios in the ion trap under different related parameters, and the related parameters include the electric field potential and geometric dimensions of the ion trap; determining the frequency spectrum signal of the frequency range based on the movement frequencies of various ions in the ion flow, and setting the energy within the frequency range to be uniformly distributed; and reducing the corresponding energy within the frequency range of the frequency spectrum signal to below a preset energy threshold based on the movement frequencies of multiple target ions to generate a multi-channel screening waveform.

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

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

[0075] According to the motion equation of the ion trap and related parameters, the motion frequencies of various ions in the ion flow in the ion trap are calculated. That is, according to the Matthew equation and related parameters, the motion frequencies of various ions in the ion trap can be calculated.

[0076] According to the movement frequencies of various ions in the ion flow, the frequency spectrum signal of the frequency range can be determined, that is, the frequency range can be determined according to the minimum movement frequency and the maximum movement frequency to cover the frequency range of the target ions and impurity ions in the ion trap.

[0077] In other embodiments, considering that the motion frequencies of ions in the ion trap vary greatly and generally do not exceed the motion frequency of the ion trap, in this embodiment, the spectrum signal can be directly set to zero to the motion frequency of the ion trap. This also avoids the calculation and selection of the frequency range, which can further improve the data processing efficiency.

[0078] Since resonance ejection of impurity ions requires a certain amount of energy, the energy distribution within the frequency range can be set to be uniform. The energy corresponding to the movement frequency of the target ions within the frequency range of the spectrum signal can be reduced to below the preset energy threshold, generating a multi-channel screening waveform to avoid resonance ejection of the target ions.

[0079] As an optional embodiment, the movement frequencies of various ions in the ion flow in the ion trap are calculated based on the motion equation of the ion trap and related parameters, including: determining the corresponding Matthew equation as the motion equation based on the type of the ion trap; calculating the ion motion parameters of the corresponding electric field using the Matthew equation based on the mass, charge, and related parameters of the ion trap; calculating the stability parameters based on the ion motion parameters; and calculating the movement frequency of the ions based on the stability parameters.

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

[0081]

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

[0083] And, the ion motion parameter q in the AC (RF) electric field u The calculation formula is:

[0084]

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

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

[0087]

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

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

[0090]

[0091] As an optional embodiment, by using a multi-channel resonance signal of a preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high, and before a mass spectrum containing multiple target ions corresponding to this mass spectrum is obtained, the method also includes: determining a 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; and generating a corresponding multi-channel resonance signal 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] The setting of amplitude and duration needs to consider the kinetic energy of the target ion and the background gas pressure, and calculate the amplitude and duration of the target ion fragmentation, so as to ensure that the target ion fragments under the resonance of the multi-channel resonance signal.

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

[0095] By superimposing an AV voltage on the RF voltage, which is the above-mentioned multi-channel resonance signal, the target ion can be made to resonate and have a larger kinetic energy, in order to increase the probability of the target ion being collided with the background gas ion. It can be understood that the larger the amplitude of the AV voltage, the higher the kinetic energy of the target ion. However, the kinetic energy of the target ion cannot be too high, which will cause the ion to resonate and pop out of the ion trap before it collides and breaks.

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

[0097] In the process of determining the 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 bounce out of the ion trap.

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

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

[0100] The frequency of the multi-channel resonance signal can be a superposition of the motion frequencies of the target ions, or a preset frequency band covering multiple target ion motion frequencies. When determining the preset frequency band, the preset frequency band of the multi-channel resonance signal can be determined based on the maximum and minimum values ​​of the motion frequencies of the multiple target ions and the required frequency margin.

[0101] After the preset frequency band, amplitude and duration are determined, 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, that is, the SWIFT waveform, to achieve the purpose of removing excess ions. SWIFT is a method of creating waveforms. The excitation waveform in the time domain is obtained by inverse Fourier transforming the waveform after frequency domain excitation. The selection is based on the resonance frequency of the ion.

[0102] As an optional embodiment, through a multi-channel resonance signal of a preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high, so as to obtain a mass spectrum containing multiple target ions corresponding to this mass spectrum, including: through a multi-channel resonance signal of a preset frequency band, the target ions in the ion trap are fragmented one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high; the successively fragmented target ions are transmitted to a detector for detection, and the detector outputs a mass spectrum of the multiple target ions, wherein the mass spectrum includes ion peaks of the multiple target ions.

[0103] As mentioned above, in order to avoid the fragmentation of the larger target ions first, secondary fragmentation occurs when the smaller ions are fragmented, which affects the detection accuracy. This embodiment adopts the order of frequency from small to large for fragmentation. Each time the fragmented ions are directly transmitted to the detector, so that as the target ions are fragmented one by one, the detector can obtain the mass spectra of multiple target ions of this mass spectrum. Figure 8 As shown, the mass spectrum includes ion peaks of multiple target ions.

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

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

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

[0107] When detecting target ions of multiple compounds by chromatographic serial discontinuous injection mass spectrometer, due to the single-channel characteristics of the discontinuous injection mass spectrometer, it is necessary to first use chromatography to separate different compounds, and then inject different compounds separately to screen, fragment and detect their single target ions. As a result, the entire detection process needs to repeat the entire process of chromatography and mass spectrometry, especially because the chromatographic analysis takes a long time, resulting in extremely low analysis efficiency.

[0108] The output port of the above-mentioned chromatographic separation device and the input port of the mass spectrometer may not be directly connected. In the related art, there is also a method of indirectly inputting the compounds at the chromatographic separation site into the mass spectrometer for mass spectrometry.

[0109] The output port of the chromatographic separation device of this embodiment is directly connected to the input port of the mass spectrometer, and the chromatographically separated compounds are directly input into the mass spectrometer. When performing mass spectrometry, the discontinuous atmospheric pressure interface of the mass spectrometer is first opened to inject the ion flow of the target sample into the ion trap of the mass spectrometer.

[0110] The target ions can be detected by the ion detector, and the amplified ion signals can be output to form a mass spectrum corresponding to the mass spectrum containing multiple target ions. The required statistical graphs can also be generated according to other parameters. Figure 8 is the mass spectrum, Fig. 9 A chromatogram generated using multiple mass spectra.

[0111] As an optional embodiment, cyclic mass spectrometry is performed when chromatographic separation is not completed to obtain a corresponding mass spectrum until the chromatographic separation is completed and a mass spectrum sequence in chronological order is obtained, including: determining the number of mass spectrometry cycles based on the chromatographic separation duration and the single mass spectrometry duration; determining whether the chromatographic separation is completed based on 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.

[0112] The chromatographic separation time can be understood as the time from the start of the chromatographic device to the completion of the separation of all compounds, or the time from the start of the chromatographic device to the completion of the separation of all compounds. Considering that there may be no compound output for a period of time after the start of the chromatographic device, when the mass spectrometer is turned on, the mass spectrometer is in an idle state, and although it is turned on, it will not work.

[0113] The chromatographic separation time of this embodiment can be the time from the start of the chromatographic device outputting the separated compounds until all compounds are separated. A certain time margin can also be combined. The single mass spectrometry time is the time for the compound to enter the mass spectrometer, undergo ion bombardment, and then be sampled, screened, fragmented, and detected.

[0114] Chromatographic separation time is usually in the order of minutes, for example, 5 minutes. Single mass spectrometry time is usually in the order of seconds, for example, 5 seconds. Therefore, multi-compound chromatographic tandem mass spectrometry is more limited by the duration of the chromatographic separation.

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

[0116] The multi-channel detection of the mass spectrometer combined with discontinuous injection greatly reduces the detection time of multiple compounds by chromatography-tandem mass spectrometry and improves 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 mass spectrometry needs to be determined according to the progress of chromatographic separation. In this example, the number of mass spectrometry cycles is determined according to the chromatographic separation time and the single mass spectrometry time, and whether the chromatographic separation is completed is determined according to whether the number of cycles reaches the number of mass spectrometry cycles.

[0118] The mass spectrometer can simply set the number of mass spectrometry cycles, and 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, and the mass spectrometry is continued.

[0119] As an optional embodiment, cyclic mass spectrometry is performed before chromatographic separation is completed to obtain a corresponding mass spectrum, and after the chromatographic separation is completed and a sequence of mass spectra in chronological order is obtained, the method includes: confirming the mass-to-charge ratio of the target ion at the corresponding time, and the mass-to-charge ratio tolerance, and determining the mass-to-charge ratio range of the target ion; 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 signal intensity data corresponding to the extracted target ions in accordance with the chromatographic order to obtain a chromatogram containing chromatographic curves of each target ion, wherein the chromatographic curve includes the signal intensity that changes with the chromatographic order.

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

[0121] Therefore, this embodiment sets a mass-to-charge ratio tolerance and can determine a mass-to-charge ratio range based on the mass-to-charge ratio of the target ion. The signal intensity within this mass-to-charge ratio range can be considered to be that of the target ion. This can effectively avoid errors in mass spectrum analysis caused by mass spectrum errors and improve the accuracy of mass spectrum analysis.

[0122] Since multiple mass spectra are generated in chronological order, the signal intensities of different extracted target ions in different mass spectra are in chronological order. The signal intensities of the same target ions are arranged in chronological order and fitted into curves. Multiple target ions can be fitted into multiple curves to characterize the temporal changes in the signal intensity of the corresponding target ions.

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

[0124] As an optional embodiment, before separating multiple compounds of the target sample through chromatographic separation, the method also includes: determining the internal standard of the target ion; performing multi-channel detection on the internal standard as the target ion; and performing statistics on the signal intensity data corresponding to the extracted target ions according to the chromatographic order to obtain a chromatogram containing chromatographic curves of each target ion. The method also includes: determining the concentration of the target ion based on the ratio and concentration 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.

[0125] When the internal standard method is used for multi-channel detection of multiple target ions, the ion of the internal standard can be used as a target ion alone to finally form a chromatographic curve of the internal standard. The concentration of the target ion compound in the original mixed solution can then be determined by comparing the area of ​​the target peak of the chromatographic curve of the target ion with the area of ​​the target peak of the chromatographic curve of the internal standard, as well as the known concentration of the internal standard.

[0126] In addition, as an optional embodiment, during the process of cyclic mass spectrometry performed by the mass spectrometer, 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, wherein the pressure of the vacuum chamber will increase when the discontinuous atmospheric pressure interface is opened for sampling.

[0127] When the pressure reaches the working pressure, the discontinuous atmospheric pressure interface of the mass spectrometer is opened to perform cyclic mass spectrometry. This ensures that the vacuum pressure of the ion trap is maintained in an appropriate range, and prevents the vacuum pressure from gradually deteriorating during cyclic mass spectrometry, which results in ineffective injection. This ensures the effectiveness of each injection of cyclic mass spectrometry.

[0128] Since the injection and ion trap have high requirements for vacuum, when the instrument is turned on, the vacuum system of the mass spectrometer is always controlled to perform vacuum operation, so that the vacuum environment of the ion trap for ion screening and confinement is always at a high quality, thereby improving the accuracy and efficiency of screening and confinement of target ions in the ion trap.

[0129] The reason why the pressure reaches the working pressure range and maintains the preset time is that only a small amount of air will enter each time the sample is injected, and the actual pressure fluctuation in the vacuum chamber will not be too large. This places too high a precision requirement on the detection device of the vacuum system. Therefore, by limiting the pressure maintenance time, the accuracy of pressure detection can be improved, and the use of more accurate pressure detection equipment can be avoided, reducing the cost of the mass spectrometer.

[0130] As an optional embodiment, the ion trap of the mass spectrometer with discontinuous injection is a quadrupole linear ion trap, including a front cover electrode, a quadrupole and a rear cover electrode. When the discontinuous atmospheric pressure interface of the mass spectrometer is opened and the ion flow of the target sample is injected into the ion trap of the mass spectrometer, the electric potential of the front cover electrode can be adjusted to the target potential so that the electric field strength of the ion trap reaches the required electric field strength, and the ion flow 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, and the electric field strength in the quadrupole linear ion trap is achieved by adjusting the potential of the front cover electrode during sample injection to meet the requirements of the bound ion flow. In the subsequent repeated sample injection process, the electric field strength in the quadrupole linear ion trap can also be adjusted by the potential of the front cover electrode.

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

[0133] In real analysis scenarios, there is a need for simultaneous detection of multiple targets by tandem mass spectrometry. In order to improve the efficiency of analysis and detection, avoid the accumulation of errors that may be caused by individual detection, and improve the accuracy of the detection results,

[0134] This embodiment provides a chromatography-discontinuous mass spectrometry multi-channel cascade analysis technology, combined with a discontinuous injection portable mass spectrometry system, to achieve the joint detection of multi-target cascade mass spectrometry, which can meet the requirements of efficient, accurate and comprehensive analysis and detection technology for multiple targets in a sample with one injection. In addition to the identification and analysis of substances through secondary mass spectrometry data matching, quantitative analysis can be achieved through the introduction of isotope internal standards and other methods.

[0135] Figure 4 Schematic diagram of a multi-channel detection process of a mass spectrometer with discontinuous injection according to an embodiment of the present invention, such as Figure 4 As shown, the detection process of this embodiment can simultaneously achieve n target ion selection, synchronous fragmentation and synchronous detection, and finally obtain multi-channel analysis results.

[0136] This embodiment first provides a multi-channel ion simultaneous isolation operation mode based on the ion operation characteristics of the ion trap, which can simultaneously bind the precursor ions of multiple target objects in the ion trap and remove the remaining matrix interference ions. A multi-channel screening waveform is calculated by inverse Fourier transform to include the frequencies of other ions in the ion trap except the target ions, and only multiple target ions are selectively bound in the ion trap.

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

[0138] Then, the ion source of the mass spectrometer is used to ionize and inject the compounds output by the chromatogram. The multi-channel SWIFT waveform is used to synchronously screen and isolate n target ions. Resonance excitation energy, that is, the multi-channel resonance signal mentioned above, is applied to the ion trap in the form of radio frequency RF voltage. The n target ions are fragmented in order from low to high according to the mass-to-charge ratio m / z from low to high.

[0139] The fragmented ions of n target ions are sent to the detector for detection, and the detector can output a MS / MS mass spectra of the n target ions arranged in chronological order. Each MS / MS mass spectrum can include the signal intensity of some target ions among the n target ions, or no signal intensity of any target ions.

[0140] Furthermore, 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 sweep waveform with a frequency from low to high (the frequency range will include the resonance frequencies of all target ions), resonance excitation energy is applied, and collision gas is introduced to fragment the multiple target ions in the ion trap in order of mass-to-charge ratio from low to high.

[0141] Finally, all fragment ions are scanned out of the ion trap in sequence and detected by the detector, and fragment ion detection and analysis are realized. Multiple target ions are selected and analyzed simultaneously, and multiple target objects can be analyzed by MS / MS simultaneously in one injection, solving the problem of limited number of cascade analysis channels in the combination of continuous chromatography and discontinuous mass spectrometry, thereby improving analysis efficiency.

[0142] In order to avoid the interference of fragment ions with the same mass-to-charge ratio that may exist when multiple target ions are fragmented at the same time, a chromatographic technology with separation performance is introduced to separate the target objects before the samples enter the mass spectrometry analysis, so that they enter the mass spectrometry analysis at different times, thereby achieving differentiation of fragment ions with the same mass-to-charge ratio at the peak time, thus retaining the qualitative analysis capability of the mass spectrometry.

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

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

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

[0146] Calculate the ion motion parameter a of the DC electric field in the ion trap u ;

[0147] In an ion trap without a DC field, the ion motion parameter a u The value is 0, directly calculating the ion motion parameter q of the AC (RF) electric field u ;

[0148] The stability parameter β of the ion is calculated by the above continued fraction uAs mentioned above, β can be obtained by numerical methods such as recursion from the ion frequency u .

[0149] Based on β u Calculate the angular frequency ω of the ion's motion u .

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

[0151] Multi-ion resonance excitation fragmentation implementation method: It is known that the minimum resonance frequency of the ions of the multiple targets is f min , the maximum value is f max , set the frequency margin to n, determine the energy amplitude to cd V, and generate and load a period of 5-1000 ms in the ion trap with a sweep range of (f min -n) kHz ~ (f max +n) kHz multi-channel resonance signals, with frequencies from low to high to avoid overlapping interference; in the collision gas background, isolated ions will be excited in turn and collide with the background gas, thereby achieving multi-channel fragmentation of target substances.

[0152] When analyzing multiple targets in a sample, the multi-target ions separated by chromatography are detected at the mass spectrometer end. Under the action of the imported SWIFT waveform, the selected n target ions are simultaneously bound in the ion trap. Subsequently, under the action of the applied resonance excitation energy, they are fragmented in order from low to high in mass-to-charge ratio, and the fragment ions are detected, thereby achieving simultaneous MS / MS analysis of multiple targets.

[0153] In actual application scenarios, the analysis of n targets using traditional methods requires n injections, while the above method only requires one injection to achieve simultaneous analysis of n targets.

[0154] Related operations involving ion trap mass spectrometry analysis process, such as Figure 6 As shown, Figure 6 Schematic diagram of data analysis based on multi-channel detection results according to the embodiment of the present invention. As described above, after completing a chromatography-mass spectrometry analysis, a MS / MS mass spectra of n target ions can be obtained, such as Figure 8 As described, the 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 target ions can be considered as daughter ions of the target substance. And the mass-to-charge ratio tolerance tol. The corresponding mass-to-charge ratio range is m / z1±tol, m / z2±tol, ..., m / zn±tol.

[0156] The signal intensity in different mass spectra is extracted according to the mass-to-charge ratio range of each target ion, and then statistics are performed based on the chromatographic time and fitted into the corresponding chromatographic curve. The chromatographic peak area can be obtained by integrating the area of ​​the target peak of the chromatographic curve for quantitative analysis. For example, the concentration of the compound corresponding to the target ion can be determined based on the ratio of the chromatographic peak area corresponding to the internal standard with a known concentration to the chromatographic peak area of ​​the target ion of the corresponding compound.

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

[0158] The present embodiment is further described in detail below in conjunction with a specific multi-channel mass spectrometry example of multiple amino acids. This example provides a chromatography-discontinuous mass spectrometry multi-channel tandem analysis method for 14 amino acids and amino acid internal standards.

[0159] The samples used contain 14 kinds of amino acids to be tested and internal standards, including 7 kinds of amino acids: proline, valine, leucine, methionine, phenylalanine, citrulline, and tyrosine. And their corresponding internal standards: 13 C5-proline; 15 N, 13 C5-valine; d3-leucine; d3-methionine; 13 C6-phenylalanine; d2-citrulline; 13 C6-Tyrosine.

[0160] First, the mass-to-charge ratios of the target ions of 14 amino acids were determined, as shown in Table 1 below, and the selected 14 target ions were set to generate a specific SWIFT waveform for the ion trap. The time required for a chromatographic analysis is 5 minutes, and the time required for the mass spectrometer to complete an analysis process is 5 seconds. Therefore, it is determined that 60 mass spectrometry injections are required. A mass spectrometry analysis process includes the following steps:

[0161] Mass spectrometer ion source ionization injection;

[0162] The 14 amino acid target ions were isolated simultaneously by generating and loading a multi-channel SWIFT waveform. Figure 7 As shown, Figure 7This is a schematic diagram of the SWIFT waveform of the amino acid internal standard analysis method of the embodiment of the invention, the SWIFT waveform has energy reduction of multiple position frequencies to ensure that the target ions corresponding to multiple motion frequencies can be effectively screened and bound in the ion trap. The impurity ions corresponding to other motion frequencies are uniformly resonated and ejected from the ion trap.

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

[0164] The chromatography-mass spectrometry analysis process is completed, and 60 MS / MS mass spectrometry data containing 14 target ion fragment ions are obtained. The data is based on the mass-to-charge ratio m / z as the x-axis and the ion signal intensity Intensity as the y-axis, such as Figure 8 As 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] The mass-to-charge ratio information of the fragment ions of the 14 target ions was confirmed, as shown in Table 1 below. Table 1 is a table of mass-to-charge ratio information of the target ions and the fragment ions.

[0166] Table 1 Mass-to-charge ratio information 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 for each mass-to-charge ratio ion, and plot it in sequence according to the chromatographic time sequence to form a chromatogram with the time sequence as the x-axis and the intensity as the y-axis. Perform Gaussian fitting on the chromatogram to obtain the final chromatogram result for each target m / z, such as Fig. 9 As shown, Fig. 9 It is a schematic diagram of integrating multiple mass spectra of the amino acid internal standard analysis method according to the embodiment of the present invention into a multi-channel chromatogram.

[0169] Quantitative analysis can be achieved by introducing isotope internal standards. The area of ​​each target peak is integrated to obtain the chromatographic peak area, and further quantitative analysis can be performed based on the chromatographic peak area data.

[0170] Perform chromatography-mass spectrometry injection, start the analysis process and perform chromatography-mass spectrometry data acquisition, and collect mass spectrometry data by the ion trap mass spectrometer. During the mass spectrometry data acquisition process, under the action of the SWIFT waveform, only the 14 selected 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 RF voltage and scanning in sequence from high to low energy, the 14 target ions are sequentially excited and fragmented. The fragmented ions after fragmentation are collected and detected by the ion trap mass spectrometer to obtain a mass spectrum such as Figure 8 According to the continuously collected mass spectrometry data, the chromatogram can be obtained as shown in Fig. 9 shown.

[0171] Fig.10 Schematic diagram of a multi-channel detection device of a mass spectrometer with discontinuous injection according to an embodiment of the present invention, Fig.10 As shown, an embodiment of the invention provides a multi-channel detection device for a mass spectrometer with non-continuous injection, the device comprising: an input module 1001, a mass spectrum screening module 1002, and a mass spectrum detection module 1003. The device is described in detail below.

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

[0173] The mass spectrometry screening module 1002 is connected to the input module 1001 and is used to input the ion flow of the separated compound into the ion trap, screen multiple target ions in the ion trap through a preset multi-channel screening waveform, and bind them in the ion trap, wherein the ion flow includes multiple target ions that need to be detected;

[0174] The mass spectrometer detection module 1003 is connected to the mass spectrometer screening module 1002, and is used to fragment and analyze 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 the multi-channel resonance signal of the preset frequency band, so as to obtain a mass spectrum containing multiple target ions corresponding to this mass spectrum.

[0175] The multi-channel detection device of the above-mentioned non-continuous sampling mass spectrometer provided in this embodiment separates multiple compounds of the target sample, inputs their ion flow into the ion trap, screens multiple target ions in the ion trap through a preset multi-channel screening waveform, and binds them in the ion trap, thereby realizing multi-channel synchronous binding of multiple target ions.

[0176] Then, through the multi-channel resonance signal of the preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large, in the order of frequency from low to high, to obtain the mass spectrum corresponding to this mass spectrum containing multiple target ions, thereby realizing multi-channel synchronous fragmentation detection of multiple target ions.

[0177] Therefore, by adding different multi-channel screening waveforms and multi-channel resonance signals to the ion trap during confinement and fragmentation, simultaneous screening and fragmentation detection of multiple target ions can be 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 an embodiment of the present invention, there is also provided a mass spectrometer with discontinuous injection, comprising: a processor, and a memory for storing a program, wherein the program comprises instructions, and when the instructions are executed by the processor, the processor executes the above method.

[0179] And, according to one aspect of an embodiment of the present invention, there is also provided a chromatographic tandem discontinuous injection mass spectrometer, comprising: a processor, and a memory for storing a program, wherein the program comprises instructions, which, when executed by the processor, cause the processor to execute the above method.

[0180] Since the mass spectrometer, or the mass spectrometer with chromatographic series discontinuous injection, works according to the above control method, the 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 repeated here.

[0181] The embodiments of the present invention also provide a non-transitory machine-readable medium storing 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.

[0182] The embodiments of the present invention further 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] The embodiment of the invention also provides an electronic device, comprising: at least one processor; and a memory connected to the at least one processor in communication. The memory stores a computer program that can be executed by the at least one processor, and the computer program is used to enable the electronic device to perform the method of the embodiment of the invention when executed by the at least one processor.

[0184] refer to Fig.11, a block diagram of an electronic device that can be used as a server or client of an embodiment of the invention will now be described, which is an example of hardware devices that can be applied to various aspects of the invention. The electronic device is intended to represent various forms of digital electronic computer devices, such as laptop computers, desktop computers, workbenches, 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 processing, 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 invention described and / or required herein.

[0185] like Fig.11 As 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 to 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 to the electronic device, and the input unit 1106 can receive input digital or character information, and generate key signal input related to user settings and / or function control 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 a disk, an optical disk. The communication unit 1109 allows the electronic device to exchange information / data with other devices through 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 may be a variety of general and / or special 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 dedicated artificial intelligence (AI) computing units, various computing units running machine learning model algorithms, digital signal processors (DSPs), and any appropriate processors, controllers, microcontrollers, etc. The computing unit 1101 performs the various methods and processes described above. For example, in some embodiments, the method embodiments created by the present invention may be implemented as a computer program, which is tangibly contained in a machine-readable medium, such as a storage unit 1108. In some embodiments, part or all of the computer program may be loaded and / or installed on an electronic device via ROM 1102 and / or a communication unit 1109. In some embodiments, the computing unit 1101 may be configured to perform the above method in any other appropriate manner (e.g., by means of firmware).

[0188] The computer program for implementing the method 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, so that the computer program, when executed by the processor or controller, enables the functions / operations specified in the flow chart and / or block diagram to be implemented. The computer program can be executed entirely on the machine, partially on the machine, partially on the machine as a stand-alone software package and partially on a remote machine, or entirely on a remote machine or server.

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

[0190] It should be noted that the term "including" and its variations used in the embodiments of the present invention are open inclusions, that is, "including but not limited to". The term "based on" means "based at least in part on". The term "one embodiment" means "at least one embodiment"; the term "another embodiment" means "at least one other embodiment"; the term "some embodiments" means "at least some embodiments". The modifications of "one" and "multiple" mentioned in the embodiments of the present invention are illustrative and not restrictive. Those skilled in the art should understand that unless otherwise clearly indicated 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 used for analysis, stored data, displayed data, etc.) involved in the embodiments of the present invention are all information and data authorized by the user or fully authorized by all parties, and the collection, use and processing of relevant data must comply with the relevant laws, regulations and standards of relevant countries and regions, and provide corresponding operation entrances for users to choose to authorize or refuse.

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

[0193] The term "embodiment" in this specification refers to specific features, structures or characteristics described in conjunction with the embodiment that can be included in at least one embodiment of the invention. The appearance of this phrase in various places in the specification does not necessarily mean the same embodiment, nor does it mean that it is mutually exclusive with other embodiments and is independent or optional. The various embodiments in this specification are described in a related manner, and the same and similar parts between the various embodiments refer to each other. In particular, for the device, equipment, and system embodiments, since they are basically similar to the method embodiments, the description is relatively simple, and the relevant parts refer to the partial description of the method embodiment.

[0194] The above-described embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of protection. It should be pointed out that, for a person of ordinary skill in the art, several modifications and improvements can be made without departing from the concept of the present invention, and these all belong to the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be subject to the attached claims.

Claims

1. A multi-channel detection method for a mass spectrometer with discontinuous injection, characterized in that: include: Sending multiple compounds of a target sample into an ion mass analyzer, wherein the compounds contain target ions to be detected; Inputting the ion flow of the compound into the ion trap, screening a plurality of target ions in the ion trap through a preset multi-channel screening waveform, and binding them in the ion trap, wherein the ion flow includes a plurality of target ions to be detected; By using the multi-channel resonance signal of the preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high, so as to obtain a mass spectrum corresponding to this mass spectrum containing multiple target ions.

2. The method according to claim 1, characterized in that Inputting the ion flow of the output compound into the ion trap, screening multiple target ions in the ion trap through a preset multi-channel screening waveform, and binding them in the ion trap, including: Inputting the ion flow into an ion trap and confining the ion flow; Resonantly ejecting impurity ions other than a plurality of target ions in the ion trap by using the multi-channel screening waveform, wherein the impurity ions are ions other than the target ions in the injected ion flow; A plurality of the target ions are trapped in the ion trap.

3. The method according to claim 2, characterized in that Before resonantly ejecting impurity ions other than a plurality of target ions in the ion trap by using the multi-channel screening waveform, the method further comprises: According to the motion equation of the ion trap and related parameters, the motion frequencies of various ions of the ion flow in the ion trap are calculated, wherein 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 field potential and geometric dimensions of the ion trap; Determine a frequency spectrum signal of a frequency range according to the movement frequencies of various ions in the ion flow, and set a uniform energy distribution within the frequency range; According to the movement frequencies of the multiple target ions, the energy corresponding to the frequency range of the spectrum signal is reduced to below a preset energy threshold to generate the multi-channel screening waveform.

4. The method according to claim 3, characterized in that According to the motion equation of the ion trap and related parameters, the motion frequencies of various ions of the ion flow in the ion trap are calculated, including: Determine the corresponding Matthew equation as the motion equation according to the type of the ion trap; According to the mass and charge of the ions and the related parameters of the ion trap, the ion motion parameters corresponding to the electric field are calculated using the Matthew equation; Calculating stability parameters according to the ion motion parameters; The movement frequency of the ions is calculated based on the stability parameter.

5. The method according to claim 1, characterized in that By using the multi-channel resonance signal of the preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high, and before obtaining the mass spectrum corresponding to the mass spectrum and containing multiple target ions, the method further includes: Determining the preset frequency band according to the movement frequencies of the plurality of target ions and the required frequency margin; Determining the amplitude and duration of the target ion according to the kinetic energy of the target ion and the background gas pressure; According to the preset frequency band, the amplitude and the duration, a corresponding multi-channel resonance signal is generated.

6. The method according to claim 5, characterized in that Through the multi-channel resonance signal of the preset frequency band, the target ions in the ion trap are fragmented and analyzed one by one according to the mass-to-charge ratio from small to large in the order of frequency from low to high, and a mass spectrum containing multiple target ions corresponding to this mass spectrum is obtained, including: By using a multi-channel resonance signal of a preset frequency band, the target ions in the ion trap are fragmented one by one in the order of frequency from low to high and in the order of mass-to-charge ratio from small to large; The successively fragmented target ions are transmitted to a detector for detection, and the detector outputs a mass spectrum of a plurality of target ions, wherein the mass spectrum includes ion peaks of a plurality of target ions.

7. The method according to claim 1, characterized in that Multiple compounds of the target sample are sent to the ion mass analyzer, including: Multiple compounds of a target sample are delivered to an ion mass analyzer by direct injection or chromatographic separation; In the case where the chromatographic separation sends multiple compounds of the target sample into the ion mass analyzer, after obtaining a mass spectrum corresponding to the current mass spectrum and containing multiple target ions, the method further includes: When chromatographic separation is not completed, cyclic mass spectrometry is performed until chromatographic separation is completed, thereby obtaining a mass spectrum sequence in chronological order, wherein the mass spectrum sequence includes multiple mass spectra obtained by cyclic mass spectrometry for characterizing multi-channel detection results of multiple target ions.

8. The method according to claim 7, characterized in that In the case where the chromatographic separation is not completed, a cyclic mass spectrometry is performed to obtain a corresponding mass spectrum, until the chromatographic separation is completed and a mass spectrum sequence in chronological order is obtained, comprising: Determine the number of mass spectrometry cycles based on the chromatographic separation time and the single mass spectrometry time; Determining whether the chromatographic separation is completed according to whether the number of cycles reaches the number of mass spectrometry cycles; When the cycle number reaches the mass spectrometry cycle number, it is determined that the chromatographic separation is completed.

9. The method according to claim 8, characterized in that When the chromatographic separation is not completed, performing cyclic mass spectrometry to obtain a corresponding mass spectrum, until the chromatographic separation is completed and a sequence of mass spectra in chronological order is obtained, comprising: Confirm the mass-to-charge ratio of the target ion at the corresponding time, as well as the mass-to-charge ratio tolerance, and determine the mass-to-charge ratio range of the target ion; For the mass spectrum at the corresponding time, extracting signal intensity data within the mass-to-charge ratio range of each target ion; The signal intensity data corresponding to the extracted target ions are statistically analyzed according to the chromatographic order to obtain a chromatogram containing chromatographic curves of each target ion, wherein the chromatographic curve includes signal intensities that vary with the chromatographic order.

10. The method according to claim 9, characterized in that Before separating the multiple compounds of the target sample by chromatographic separation, the method further comprises: Determine the internal standard of the target ion; Perform multi-channel detection using the internal standard as the target ion; After the signal intensity data corresponding to the extracted target ions are counted according to the chromatographic order to obtain a chromatogram containing chromatographic curves of each target ion, the method further comprises: The concentration of the target ion is determined based on 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.

11. A discontinuous injection mass spectrometer, comprising: A processor and a memory storing a program, wherein the program comprises instructions, which, when executed by the processor, cause the processor to perform the method according to any one of claims 1 to 10.

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