Multi-modal based mass spectrometry apparatus and method

Abstract

The application provides a multi-mode-based mass spectrum analysis device and method, which comprises an ion source, a detector and a power supply; further comprises: a multi-stage transmission unit arranged between the ion source and the detector, the transmission unit comprising an ion lens and a multipole rod; an input end of a control unit is connected with the power supply, and an output end is connected with the multipole rod and the ion lens, so as to adjust the voltage of the multipole rod and the ion lens, so that the transmission unit is selectively in an ion transmission mode, an ion filtering mode and an ion storage mode. The application has the advantages of high sensitivity, simple structure and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to mass spectrometry, in particular to a multi-modal based mass spectrometry device and method. BACKGROUND

[0002] Ion trap mass spectrometer is widely used in mass spectrometers due to its high sensitivity, convenient processing, high working pressure and support for multi-stage tandem mass spectrometry function. In the mass spectrometer, the ion optical transmission system plays an important role, and its main function is to efficiently transmit the ions ionized in the ion source to the mass analyzer working in high vacuum. However, in the transmission channel from ion generation to the mass analyzer, the transmission efficiency of the ions is very low, and the ion transmission rate is less than 1%, so it is very important to optimize the ion optical transmission system.

[0003] The voltage parameters of the components of the ion transmission system will affect the transmission efficiency of the ion transmission system, and further affect the analysis results, wherein the voltage is generally divided into radio frequency voltage and direct current voltage, and how to effectively control them to achieve the optimal output voltage is a difficult problem.

[0004] The radio frequency voltage generally refers to the radio frequency voltage of each ion guide including ion funnel, quadrupole rod, multipole rod and other devices, which has a great influence on the relative abundance of ions of different mass-to-charge ratios and can better confine the ion beam.

[0005] The direct current voltage generally refers to the voltage of the ion guide device and its interface (ion gate). In ion trap mass spectrometry, in order to reduce the space charge effect, an ion gate is usually used to control the number of ions entering the ion trap. The ion gate is generally divided into two categories: one is a consumable ion gate (ions transmitted from the source end are continuously removed from the ion transmission channel when the ion gate is closed), and the other is a blocking ion gate (ions transmitted from the source end continue to advance by applying a higher potential barrier, but the ions remain in the ion transmission channel).

[0006] In the ion trap mass spectrometer using the consumable ion gate, the instrument is more likely to use the AGC (automatic gain control) method to adjust the number of ions in the ion trap, and the instrument quantitative capacity (linear response) is usually strong; however, the use of consumable ion gate will result in only part of the ions being available for mass spectrometry, which may result in a decrease in instrument sensitivity or detection limit and other performances. In contrast, in the ion trap mass spectrometer using the blocking ion gate, the number of ions in the ion trap cannot be accurately adjusted, and the quantitative capacity of the instrument is usually poor. However, the use of the blocking ion gate can have a high ion utilization rate, which can improve the instrument sensitivity or detection limit and other performances.

[0007] In practical application, sometimes the instrument needs to have high sensitivity and detection ability only when detecting low concentration sample, but the quantitative range requirement is not so wide, and sometimes the instrument needs to have large quantitative range with chromatography. In order to meet different detection requirements, new challenges are put forward to the voltage control system of ion trap mass spectrometer. The traditional single ion gate control in and out is not enough to solve the defect of limited ion trap capacity to meet various detection requirements, in addition, the length of ion gate opening time is also restricted by related factors, too long time is easy to be affected by space charge effect, and too short time has little effect on the signal intensity of low concentration sample. SUMMARY

[0008] In order to solve the above problems in the prior art, the present application provides a mass spectrometry device based on multiple modes.

[0009] The purpose of the present application is achieved by the following technical solutions:

[0010] A mass spectrometry device based on multiple modes, comprising an ion source, a detector and a power supply; the mass spectrometry device further comprises:

[0011] A multi-stage transmission unit, which is arranged between the ion source and the detector, and comprises an ion lens and a multipole rod;

[0012] A control unit, which is connected with the power supply at the input end and connected with the multipole rod and the ion lens at the output end, for adjusting the voltage of the multipole rod and the ion lens, so that the transmission unit is selectively in ion transmission mode, ion filtering mode and ion storage mode.

[0013] Another purpose of the present application is to provide a mass spectrometry method, and the purpose of the present application is achieved by the following technical solutions:

[0014] According to the mass spectrometry method of the mass spectrometry device of the present application, the mass spectrometry method is:

[0015] According to the sample state and sample concentration, the control unit adjusts the voltage of the multipole rod and the ion lens in the multi-stage transmission unit, so that the transmission unit is selectively in ion transmission mode, ion filtering mode and ion storage mode.

[0016] The sample is ionized, and the ions pass through the multi-stage transmission unit into the detector in turn.

[0017] Compared with the prior art, the present application has the following beneficial effects:

[0018] 1. Good quantitative ability;

[0019] Different working modes are realized in the same mass spectrum analysis device, which can be applied to different scenes, and provides better quantitative ability and detection ability;

[0020] 2. Simple structure;

[0021] Without additional devices, the selected multi-pole transmission rod is low in cost, effectively reduces cost, and is simple in structure and convenient to operate;

[0022] 3. High sensitivity;

[0023] The control unit is used to realize the switching of multiple working modes, and the switching is fast, the detection range is wide, and the sensitivity is high. BRIEF DESCRIPTION OF DRAWINGS

[0024] The disclosure of the present application will become more apparent with reference to the drawings. It is easy for those skilled in the art to understand that the drawings are only used to illustrate the technical solutions of the present application, and are not intended to limit the protection scope of the present application. In the drawings:

[0025] Fig. 1 is a structural schematic diagram of a multi-mode-based mass spectrum analysis device according to an embodiment of the present application;

[0026] Fig. 2 is a timing diagram of a working mode according to an embodiment of the present application. DETAILED DESCRIPTION

[0027] Figs. 1-2 The optional specific embodiments of the present application are described in the following description to teach those skilled in the art how to implement and reproduce the present application. Some conventional aspects have been simplified or omitted in order to teach the technical solutions of the present application. Those skilled in the art should understand that variations or substitutions derived from these specific embodiments will be within the scope of the present application. Those skilled in the art should understand that the following features can be combined in various ways to form multiple variations of the present application. Therefore, the present application is not limited to the following optional specific embodiments, but is only limited by the claims and their equivalents.

[0028] Embodiment 1

[0029] The multi-mode-based mass spectrum analysis device of the present application embodiment 1, as shown in Fig. 1 includes:

[0030] an ion source 1, a detector 210, and a power supply;

[0031] a multi-stage transmission unit 2, which is arranged between the ion source 1 and the detector 210, and includes an ion lens and a multi-pole rod;

[0032] A control unit, an input end of the control unit being connected to the power supply, an output end of the control unit being connected to the multipole rod and the ion lens, for adjusting the voltage of the multipole rod and the ion lens, so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode.

[0033] In order to accurately match the mode, further, the working mode of the control unit is:

[0034] According to the sample state and the sample concentration, the mode of the transmission unit is adjusted.

[0035] In order to improve the detection ability and sensitivity, further, as the sample concentration increases, the transmission unit changes from the ion storage mode or the ion filtering mode to the ion transmission mode, and the change of the downstream transmission unit is earlier than that of the upstream transmission unit; wherein, when the sample concentration is the smallest, the multi-stage transmission unit from upstream to downstream is in the ion transmission mode, the ion filtering mode and the ion storage mode in turn.

[0036] In order to accurately match the mode, further, the working mode of the control unit is:

[0037] According to the sample mass-to-charge ratio, the radio frequency voltage of the multipole rod is adjusted.

[0038] In order to improve the sensitivity, further, if the mass-to-charge ratio is less than a first threshold value, the radio frequency voltage is 0.5m+50;

[0039] If the mass-to-charge ratio is between the first threshold value and a second threshold value, the radio frequency voltage is 0.325m+67.5;

[0040] If the mass-to-charge ratio is between the second threshold value and a third threshold value, the radio frequency voltage is 0.24m+110;

[0041] If the mass-to-charge ratio is greater than the third threshold value, the radio frequency voltage is 350V.

[0042] In order to improve the detection ability and sensitivity, further, as Fig. 2 As shown in the ion transmission mode, the direct current voltage of the ion lens 24 of the second stage transmission unit remains unchanged in the pre-scan, ion injection cooling, mass analysis and ion emptying four stages, and the value range is 10V-20v; the direct current voltage of the ion lens 26 of the third stage transmission unit remains unchanged in the pre-scan, ion injection cooling, mass analysis and ion emptying four stages, and the voltage range is 0-10v; the direct current voltage in front of the ion gate between the multi-stage transmission unit and the detector 210 remains unchanged in the pre-scan, ion injection cooling, mass analysis and ion emptying four stages, and the voltage range is -50V--40V;

[0043] In the ion storage mode, the ion lens 24 of the second stage transmission unit has a high voltage in the pre-scan stage, the voltage range is 400-500V, and the voltage is reduced after the 1 / 3 pre-scan stage and remains unchanged in the subsequent stage until the ions are emptied; the ion lens 26 of the third stage transmission unit has a high voltage in the pre-scan 1 / 3 stage, the voltage range is 400-500V, and the voltage is reduced after the 1 / 3 pre-scan stage and remains unchanged in the subsequent stage until the ions are emptied; the direct current voltage in front of the ion gate 28 is raised to a high voltage after the pre-scan 2 / 3 stage, the voltage range is 90-100V, and the voltage is reduced after the 1 / 3 pre-scan stage and remains unchanged in the subsequent stage until the ions are emptied.

[0044] In the ion storage mode, the ion lens 24 of the second stage transmission unit has a high voltage in the pre-scan stage, the voltage range is 400-500V, and the voltage is reduced after the 1 / 3 pre-scan stage and remains unchanged in the subsequent stage until the ions are emptied; the ion lens 26 of the third stage transmission unit has a high voltage in the pre-scan 1 / 3 stage, the voltage range is 400-500V, and the voltage is reduced after the 1 / 3 pre-scan stage and remains unchanged in the subsequent stage until the ions are emptied; the direct current voltage in front of the ion gate 28 is raised to a high voltage after the pre-scan 2 / 3 stage, the voltage range is 90-100V, and the voltage is reduced after the 1 / 3 pre-scan stage and remains unchanged in the subsequent stage until the ions are emptied.

[0045] The mass spectrometry method of the embodiment of the application, i.e., the mass spectrometry method of the mass spectrometry device of the embodiment, is as follows:

[0046] According to the sample state and sample concentration, the control unit adjusts the voltage of the multipole rod and the ion lens in the multi-stage transmission unit 2, so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode;

[0047] The sample is ionized, and the ions pass through the multi-stage transmission unit 2 into the detector 210 in turn.

[0048] Embodiment 2

[0049] Application example of the multi-mode based mass spectrometry device and method according to the embodiment 1 of the application in the detection of methamphetamine in hair.

[0050] In this application example, as shown in Fig. 1 The multi-stage transmission unit 2 is three stages and is between the ion source 1 and the detector 210. The ion source includes an atmospheric pressure inlet and an ion funnel 21, and a (ion trap) mass analyzer 29 is connected to the detector 210. The multipole rod 23 of the first stage transmission unit is a single quadrupole rod, the multipole rod 25 of the second stage transmission unit is a curved quadrupole rod, and the multipole rod 27 of the third stage transmission unit is an octupole rod.

[0051] According to the sample state and sample concentration, the control unit adjusts the voltage of the transmission unit (multipole rod and ion lens), so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode.

[0052] If the sample is a complex matrix, when the sample concentration is ≤10ppb, the three-stage transport unit sequentially selects the normal transport, ion filtration and ion storage working modes.

[0053] When the sample concentration is >10ppb but <1ppm, the three-stage transmission unit sequentially selects the normal transmission, ion filtration and normal transmission working modes.

[0054] When the sample concentration is ≥1ppm, the three-level transmission unit sequentially selects the normal transmission, normal transmission and normal transmission working modes.

[0055] If the sample is a standard, when the sample concentration is ≤1ppb, the three-stage transmission unit sequentially selects the normal transmission, ion filtration and ion storage working modes.

[0056] When the sample concentration is >1 ppb but <100 ppb, the three-stage transmission unit sequentially selects the normal transmission, ion filtration and normal transmission working modes.

[0057] When the sample concentration is ≥100ppb, the three-stage transmission unit sequentially selects the normal transmission, normal transmission and normal transmission working modes.

[0058] The radio frequency voltage of the multipole is adjusted according to the mass-to-charge ratio of the sample.

[0059] If the mass-to-charge ratio is less than 100, the multipole RF voltage of the three-stage transmission unit is (0.5m+50)V;

[0060] If the mass-to-charge ratio is between 100 and 500, the RF voltage is (0.325m + 67.5)V;

[0061] If the mass-to-charge ratio is between 500 and 1000, the radio frequency voltage is (0.24m+110)V;

[0062] If the mass-to-charge ratio is greater than 1000, the radio frequency voltage is 350V.

[0063] like Fig. 2 As shown, in ion transport mode, the DC voltage of the ion lens 24 (middle ion lens) of the second-stage transport unit remains constant during the four stages of pre-scan, ion implantation cooling, mass analysis, and ion clearance, with a value range of 10V-20V; the DC voltage of the ion lens 26 (rear ion lens) of the third-stage transport unit remains constant during the four stages of pre-scan, ion implantation cooling, mass analysis, and ion clearance, with a voltage range of 0-10V; the DC voltage before the ion gate between the multi-stage transport unit and the detector 210 remains constant during the four stages of pre-scan, ion implantation cooling, mass analysis, and ion clearance, with a voltage range of -50V to -40V.

[0064] In ion filtering mode, the voltage of the multipole rod is raised after 1 / 3 of the pre-scan stage, the voltage range is 2000V-3000V, and remains unchanged in the subsequent stage until the ions are emptied, the conventional voltage range is 100V-500V.

[0065] In ion storage mode, the ion lens 24 of the second-stage transmission unit has a high voltage in the pre-scan stage, the voltage range is 400V-500V, and the voltage is lowered after 1 / 3 of the pre-scan stage and remains unchanged in the subsequent stage until the ions are emptied; the ion lens 26 of the third-stage transmission unit has a high voltage in the pre-scan stage, the voltage range is 400V-500V, and the voltage is lowered after 1 / 3 of the pre-scan stage and remains unchanged in the subsequent stage until the ions are emptied; the DC voltage in front of the ion gate 28 is raised to a high voltage after 2 / 3 of the pre-scan stage, the voltage range is 90V-100V, and the voltage is lowered after 1 / 3 of the pre-scan stage and remains unchanged in the subsequent stage until the ions are emptied.

[0066] The mass spectrometry method of the embodiment of the application, i.e., the mass spectrometry method of the mass spectrometry device of the embodiment, is as follows:

[0067] Hair is a complex matrix, and the content of methamphetamine in hair is very low, less than 10ppb, and the three-stage transmission unit selects the normal transmission, ion filtering and ion storage working modes in turn.

[0068] As shown in Fig. 2 the ion lens 24 of the second-stage transmission unit always maintains a stable voltage unchanged in the pre-scan, ion injection cooling, mass analysis and ion emptying four stages, and the voltage is 13V; the DC voltage of the ion lens 26 of the third-stage transmission unit is the same as that of the ion lens 24, and always maintains a stable voltage unchanged in the pre-scan, ion injection cooling, mass analysis and ion emptying four stages, and the DC voltage of the ion lens 26 is 5V at this time, while the RF of the Q guide rod is raised to a high voltage of 140V after 1 / 3 of the pre-scan stage, and remains unchanged in the subsequent stage until the ions are emptied; the DC voltage in front of the ion gate 28 is raised to a high voltage of 0V after 2 / 3 of the pre-scan stage, and is lowered to a low voltage of -40V after 1 / 3 of the pre-scan stage, and remains unchanged in the subsequent stage until the ions are emptied.

[0069] The mass-to-charge ratio of methamphetamine is 150, and the optimal radio frequency voltage obtained is 98.75V, i.e., the radio frequency voltages of the ion funnel 21, the quadrupole rod 23, the hyperbolic quadrupole rod 25 and the octupole rod 27 fluctuate in the range of 98.75V, and the fluctuation range is not more than 50V.

[0070] In the ion pre-scan stage, the ions generated by the atmospheric pressure sampling port enter the multi-stage transmission unit 2 through the transmission capillary, and each stage of ion lens and ion gate 28 is controlled according to the ion pre-scan program. Fig. 2The voltage and mode are set.

[0071] In the ion injection and cooling stage, the small amplitude radio frequency voltage is increased and maintained due to the decrease of the gas pressure and the increase of the vacuum degree in the vacuum chamber, so that the ions are maximally injected and effectively captured by the mass analyzer 29 after the decrease of kinetic energy by the buffer gas collision in the mass analyzer 29; in the mass scanning stage, the ions are sequentially ejected from the mass analyzer 29 according to the mass-to-charge ratio as the radio frequency voltage gradually increases, and the detector 210 starts to detect the ions and generate a spectrum; in the ion emptying stage, the radio frequency voltage is reduced to zero, and the ions in the mass analyzer 29 are emptied, preparing for the analysis of the next stage, and the analysis process repeats the above steps.

Claims

1. A multi-modal based mass spectrometry device comprising an ion source, a detector and a power supply; characterized in that, The mass spectrometry device further comprises a multi-stage transmission unit arranged between the ion source and the detector, the transmission unit comprising an ion lens and a multipole rod; The multi-stage transmission unit comprises a first-stage transmission unit, a second-stage transmission unit, and a third-stage transmission unit; The multipole rod of the first-stage transmission unit is a single quadrupole rod, the multipole rod of the second-stage transmission unit is a double curved quadrupole rod, and the multipole rod of the third-stage transmission unit is an octupole rod; In the ion transmission mode, the direct current voltage of the ion lens of the second-stage transmission unit remains unchanged in the four stages of pre-scan, ion injection cooling, mass analysis, and ion emptying, and the voltage range is 10V-20V; The direct current voltage of the ion lens of the third-stage transmission unit remains unchanged in the four stages of pre-scan, ion injection cooling, mass analysis, and ion emptying, and the voltage range is 0-10V; The direct current voltage in front of the ion gate between the multi-stage transmission unit and the detector remains unchanged in the four stages of pre-scan, ion injection cooling, mass analysis, and ion emptying, and the voltage range is -50V--40V; In the ion filtering mode, the voltage of the multipole rod is raised after 1 / 3 of the pre-scan stage, and the voltage range is 2000V-3000V, and remains unchanged in the subsequent stages until ion emptying, and the conventional voltage range is 100V-500V; In the ion storage mode, the direct current voltage of the ion lens of the second-stage transmission unit is raised to a high voltage before pre-scan, and the voltage range is 400V-500V, and the voltage is lowered after 1 / 3 of the pre-scan stage, and remains unchanged in the subsequent stages until ion emptying; The direct current voltage of the ion lens of the third-stage transmission unit is raised to a high voltage after 1 / 3 of the pre-scan stage, and the voltage range is 400V-500V, and the voltage is lowered after 1 / 3 of the pre-scan stage, and remains unchanged in the subsequent stages until ion emptying; The direct current voltage in front of the ion gate is raised to a high voltage after 2 / 3 of the pre-scan stage, and the voltage range is 90V-100V, and the voltage is lowered after 1 / 3 of the pre-scan stage, and remains unchanged in the subsequent stages until ion emptying; A control unit, the input end of the control unit is connected to the power supply, and the output end is connected to the multipole rod and the ion lens, for adjusting the voltage of the multipole rod and the ion lens, so that the transmission unit selectively operates in the ion transmission mode, the ion filtering mode, and the ion storage mode.

2. The multi-modal based mass spectrometric analysis device of claim 1, wherein, The working mode of the control unit is to adjust the mode of the transmission unit according to the sample state and the sample concentration.

3. The multi-modal based mass spectrometric analysis device of claim 2, wherein, As the sample concentration increases, the transmission unit changes from the ion storage mode or the ion filtering mode to the ion transmission mode, and the change of the downstream transmission unit is earlier than that of the upstream transmission unit.

4. The multi-modal based mass spectrometry device of claim 3, wherein, When the sample concentration is the smallest, the multi-stage transmission unit from upstream to downstream is in the ion transmission mode, the ion filtering mode, and the ion storage mode in turn.

5. The multi-modal based mass spectrometry device of claim 2, wherein, The working mode of the control unit is to adjust the radio frequency voltage of the multipole rod according to the sample mass-to-charge ratio.

6. The mass spectrometry method of claim 1-5, wherein the mass spectrometry method is: according to the sample state and the sample concentration, the control unit adjusts the voltage of the multipole rods and the ion lens in the multi-stage transmission unit, so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode; the sample is ionized, and the ions pass through the multi-stage transmission unit into the detector in turn.

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