Cascade mass spectrometry system and mass spectrometry equipment

Abstract

This application relates to a cascade mass spectrometry system and apparatus. By controlling the combined radio frequency and DC electric fields of a quadrupole mass filter, an ion control unit, an ion trap mass analyzer, and a time-of-flight mass analyzer, functions such as linear ion transport, diverted transport, ion selection, and ion dissociation can be achieved. Combined with voltage timing control of the control unit, switching between three different cascade operating modes—Q-LIT analysis mode, Q-TOF analysis mode, and Q-LIT-TOF analysis mode—can be realized. This mass spectrometry analysis scheme enables multi-stage mass spectrometry analysis and possesses high sensitivity, high resolution, and good qualitative capabilities. By combining the advantages of quadrupole, ion trap, and time-of-flight mass analysis, rapid switching between different operating modes is achieved, effectively expanding the application scenarios of mass spectrometry analysis and demonstrating strong reliability.

Description

Technical Field

[0001] This application relates to the field of mass spectrometry analysis technology, and in particular to a tandem mass spectrometry system and mass spectrometry equipment. Background Technology

[0002] Mass spectrometry (MS) is a method that uses electric and magnetic fields to separate and detect moving ions (charged atoms, molecules, or molecular fragments, including molecular ions, isotopic ions, fragment ions, rearranged ions, multiply charged ions, metastable ions, negative ions, and ions generated by ion-molecule interactions) according to their mass-to-charge ratio. As a key analytical technique, mass spectrometry has been widely applied in fields such as biomedicine, food safety, environmental science, and national defense. In recent years, with increasingly demanding requirements for the performance of mass spectrometers, general-purpose single-mass spectrometers can no longer meet the detection needs.

[0003] To meet detection needs, novel mass spectrometry instruments employing multiple mass analyzers in tandem have emerged. Currently, common tandem mass spectrometry instruments coupled with time-of-flight (TOF) mass spectrometers mainly include quadrupole-time-of-flight mass spectrometers (Q-TOF) and ion trap-time-of-flight mass spectrometers (IT-TOF). While Q-TOF can simultaneously perform qualitative and quantitative analysis of target compounds, it can only perform two-stage mass spectrometry analysis, and its resolution for compounds with unknown structures remains insufficient. IT-TOF combines the multi-stage mass spectrometry capabilities of an ion trap with the high-precision mass determination of a time-of-flight mass analyzer, making it suitable for detecting unknown samples. However, its dynamic range and quantitative capabilities are relatively poor, and its analysis speed is slower than that of Q-TOF. Therefore, it is evident that traditional novel mass spectrometry instruments employing multiple mass analyzers in tandem still have certain shortcomings, resulting in relatively poor reliability. Summary of the Invention

[0004] Therefore, it is necessary to provide a cascade mass spectrometry system and mass spectrometry equipment to address the problem of poor reliability in traditional mass spectrometry instruments that use multiple mass analyzers in series.

[0005] A tandem mass spectrometry system includes: a quadrupole mass filter for transporting and selecting input ions to obtain selected ions; an ion control device disposed at the ion outlet of the quadrupole mass filter for conveying the selected ions to an ion trap mass analyzer; or for performing ion collisions on the selected ions and conveying the colliding ions to a time-of-flight mass analyzer; and an ion trap mass analyzer disposed at the first ion outlet of the ion control device for performing ion trap mass spectrometry analysis on the selected ions; or for performing ion trap mass spectrometry analysis on the selected ions and then conveying them back to the ion control device. The ion control device delivers the returned ions to the time-of-flight mass spectrometry (TOFMS) device. The TOFMS device, located at the second ion outlet of the ion control device, is used to perform time-of-flight mass spectrometry analysis on the input ions. The quadrupole mass filter, ion control device, ion trap mass spectrometry device, and TOFMS device are each connected to the control device. The control device is used to control the quadrupole mass filter, ion control device, ion trap mass spectrometry device, and TOFMS device to start operation according to the selected mass spectrometry analysis mode.

[0006] In one embodiment, the tandem mass spectrometry system further includes an ion input device disposed at the ion inlet of the quadrupole mass filter.

[0007] In one embodiment, the ion input device includes a mass spectrometry interface device and a focusing device, wherein the focusing device is disposed at the ion inlet of the quadrupole mass filter device, and the mass spectrometry interface device is disposed at the ion inlet of the focusing device.

[0008] In one embodiment, the mass spectrometry interface device includes a capillary, a molecular ion reactor, and a focusing electrode. The capillary is used to input ions generated by an external ionization source, the focusing electrode is disposed at the ion inlet of the focusing device, and the molecular ion reactor is disposed between the capillary and the focusing electrode. Alternatively, the mass spectrometry interface device includes a capillary, an ion funnel, and a focusing electrode. The capillary is used to input ions generated by an external ionization source, the focusing electrode is disposed at the ion inlet of the focusing device, and the ion funnel is disposed between the capillary and the focusing electrode.

[0009] In one embodiment, the time-of-flight quality analysis device includes an ion focusing modulator and a time-of-flight quality analyzer. The ion focusing modulator is disposed at the second ion outlet of the ion control device, and the time-of-flight quality analyzer is disposed at the ion outlet of the ion focusing modulator. The time-of-flight quality analyzer is connected to the control device.

[0010] In one embodiment, the ion trap mass analysis device includes a first end cap electrode, a second end cap electrode, an intermediate electrode, and a detection device. The first end cap electrode, the second end cap electrode, the intermediate electrode, and the detection device are respectively connected to the control device. The first end cap electrode and the second end cap electrode are disposed opposite to each other. The first end cap electrode is disposed at the first ion outlet of the ion control device. The intermediate electrode is disposed between the first end cap electrode and the second end cap electrode. The detection device is disposed at the intermediate electrode.

[0011] In one embodiment, the ion control device includes a cavity, an ion introduction electrode, an ion control electrode, and an ion extraction electrode. The ion introduction electrode, the ion control electrode, and the ion extraction electrode are respectively connected to the control device. The cavity has an ion introduction port on the side near the quadrupole mass filter device, a first ion extraction port on the side near the ion trap mass analyzer, and a second ion extraction port on the side near the time-of-flight mass analyzer. A buffer gas introduction port is also provided on the side of the cavity opposite to the side with the first ion extraction port. The ion introduction electrode, the ion control electrode, and the ion extraction electrode are all disposed inside the cavity. The ion introduction electrode is disposed at the ion introduction port of the ion control device, the ion extraction electrode is disposed at the second ion extraction port of the ion control device, and the ion control electrode is disposed between the ion introduction electrode and the ion extraction electrode.

[0012] In one embodiment, the ion control electrode includes a first direction control component, a second direction control component, and a switching electrode component. The first direction control component, the second direction control component, and the switching electrode component are respectively connected to the control device. The ion introduction electrode is disposed at a first end of the first direction control component, and the ion extraction electrode is disposed at a second end of the first direction control component. The first end and the second end are disposed opposite to each other. The first end of the second direction control component is connected to the first direction control component through the switching electrode component, and the second end of the second direction control component is disposed at a first ion outlet of the ion control device.

[0013] In one embodiment, the second direction control component is disposed perpendicularly to the first direction control component.

[0014] A mass spectrometry device, comprising the tandem mass spectrometry system described above.

[0015] The aforementioned cascade mass spectrometry system and equipment consist of a quadrupole mass filter, an ion control unit, an ion trap mass analyzer, and a time-of-flight mass analyzer, arranged in cascade. The control unit can activate each of these units separately based on the selected mass spectrometry mode. When the quadrupole-time-of-flight mass spectrometry (Q-TOF) mode is selected, the control unit simultaneously activates the quadrupole mass filter, ion control unit, and time-of-flight mass analyzer. In this mode, the quadrupole mass filter selects the input ions and transmits the selected ions to the ion control unit. The ion control unit operates in collision mode, colliding the selected ions and then transmitting the resulting ions to the time-of-flight mass analyzer for analysis. When the quadrupole-ion-trap mass spectrometry (Q-LIT) mode is selected, the control unit simultaneously activates the quadrupole mass filter, ion control unit, and ion trap mass analyzer. In this mode, the quadrupole mass filter performs ion selection on the input ions, obtaining selected ions, which are then transmitted to the ion trap mass analyzer for direct ion trap mass spectrometry analysis. Conversely, when the quadrupole-ion-trap-time-of-flight mass spectrometry (Q-LIT-TOF) mode is selected, the control unit simultaneously activates the quadrupole mass filter, ion control unit, ion trap mass analyzer, and time-of-flight mass analyzer. In this mode, the quadrupole mass filter performs ion selection on the input ions, obtaining selected ions, which are then transmitted to the ion trap mass analyzer for initial ion trap mass spectrometry analysis. The selected ions are then transmitted back to the ion control unit, and finally to the time-of-flight mass analyzer for further time-of-flight mass spectrometry analysis. The above scheme allows for the selection of three different mass spectrometry analysis modes—Q-LIT, Q-TOF, and Q-LIT-TOF—to meet various mass spectrometry analysis needs. This scheme enables multi-stage mass spectrometry analysis and provides high sensitivity, high resolution, and good qualitative capabilities. By combining the advantages of quadrupole, ion trap, and time-of-flight mass spectrometry, it achieves rapid switching between different operating modes, effectively expanding the application scenarios of mass spectrometry analysis and demonstrating strong reliability. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of this application or the conventional technology, the drawings used in the description of the embodiments or the conventional technology will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1This is a schematic diagram of a cascade mass spectrometry system in one embodiment;

[0018] Figure 2 This is a schematic diagram of the cascade mass spectrometry system structure in another embodiment;

[0019] Figure 3 This is a schematic diagram of the cascade mass spectrometry system structure in another embodiment;

[0020] Figure 4 This is a schematic diagram of the cascade mass spectrometry system structure in another embodiment;

[0021] Figure 5 This is a schematic diagram of the cascade mass spectrometry system structure in another embodiment;

[0022] Figure 6 This is a schematic diagram of the ion trap mass analysis device in one embodiment;

[0023] Figure 7 This is a schematic diagram of the ion control device in one embodiment;

[0024] Figure 8 This is a schematic diagram of the voltage application of the first direction control component in one embodiment;

[0025] Figure 9 This is a schematic diagram of the voltage application of the second direction control component in one embodiment;

[0026] Figure 10 This is a schematic diagram of the Q-LIT working mode mass spectrometry system in one embodiment;

[0027] Figure 11 This is a schematic diagram of a Q-TOF working mode mass spectrometry system in one embodiment;

[0028] Figure 12 This is a schematic diagram of the Q-LIT-TOF working mode mass spectrometry system in one embodiment. Detailed Implementation

[0029] To facilitate understanding of this application, a more complete description will be provided below with reference to the accompanying drawings. Preferred embodiments of this application are shown in the drawings. However, this application can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of this application.

[0030] Please see Figure 1A tandem mass spectrometry system includes: a quadrupole mass filter 200 for transporting and selecting input ions to obtain selected ions; an ion control device 300 disposed at the ion outlet of the quadrupole mass filter 200 for conveying the selected ions to an ion trap mass analyzer 400; or for conveying the selected ions to a time-of-flight mass analyzer 500 after ion collision; and an ion trap mass analyzer 400 disposed at the first ion outlet of the ion control device 300 for performing ion trap mass spectrometry analysis on the selected ions; or for returning the selected ions to the ion control device 300 after ion trap mass spectrometry analysis. The control device 300 delivers the returned ions to the time-of-flight mass spectrometry (TOFMS) analyzer 500. The TOFMS analyzer 500, located at the second ion outlet of the ion control device 300, is used to perform time-of-flight mass spectrometry analysis on the input ions. The control device 600 connects the quadrupole mass filter device 200, the ion control device 300, the ion trap mass analyzer 400, and the TOFMS analyzer 500 to the control device 600. The control device 600 controls the quadrupole mass filter device 200, the ion control device 300, the ion trap mass analyzer 400, and the TOFMS analyzer 500 to start operation according to the selected mass spectrometry analysis mode.

[0031] Specifically, the quadrupole mass filter 200 is a device that uses a quadrupole to transport and select input ions. The quadrupole mass filter 200 uses a high-frequency and a DC electric field to allow ions with a specific mass-to-charge ratio to pass through the quadrupole field in a stable trajectory. By adjusting the radio frequency voltage or DC voltage input to the quadrupole mass filter 200, it is possible to select ions with different mass-to-charge ratios to pass through.

[0032] The ion control device 300 has two different functions: ion transport and ion collision. Depending on the operating mode selected by the cascade mass spectrometry system, the voltage input from the control device 600 to the ion control device 300 will be different, ultimately causing the ion control device 300 to be in different operating states.

[0033] Under the control of the control device 600, the ion trap mass analyzer 400 forms an ion trap by applying an appropriate voltage. Depending on the applied radio frequency voltage, the ion trap can capture ions within a specific mass range, confining them for ion storage. After collision-induced dissociation (CID) within the ion trap, the ions form different fragment ions, and the mass of these fragment ions can be detected to obtain a secondary spectrum. Further selection of fragment ions allows for further fragmentation, producing even smaller fragment ions for mass detection, resulting in a tertiary spectrum. If further fragmentation analysis is performed, even more levels of mass analysis spectra can be obtained. Therefore, the ion trap mass analyzer 400 can achieve mass spectrometry analysis at levels three and above.

[0034] The principle of the time-of-flight mass analyzer 500 is as follows: a pulse is used to instantly extract ions from the modulation zone. After being accelerated by an accelerating voltage, they have the same kinetic energy and enter the drift tube. The ions with the lowest mass-to-charge ratio have the fastest speed and thus reach the detector first, while the ions with the highest mass-to-charge ratio reach the detector last, thereby realizing the mass analysis operation.

[0035] Depending on the operating mode, different devices are connected to the cascade mass spectrometry system, and the operating modes of each device also differ. When operating in Q-LIT analysis mode, the quadrupole mass filter 200, ion control device 300, ion trap mass analyzer 400, and control device 600 operate simultaneously. Since the ion trap mass analyzer 400 itself can trap ions within the trap, and then break them up via CID (Collision Induced Dissociation) for detection, in this mode, the ion control device 300 is in transport mode, transmitting selected ions to the ion trap mass analyzer 400 for mass analysis.

[0036] When operating in Q-TOF mode, the quadrupole mass filter 200, ion control device 300, time-of-flight mass analyzer 500, and control device 600 operate simultaneously. In this mode, the time-of-flight mass analyzer 500 serves as the mass analyzer. Under the output control of the control device 600, the ion control device 300 enters a collision + transport mode, colliding the input selected ions and then transporting the resulting ions to the time-of-flight mass analyzer 500 for mass analysis. The transport path differs from that in Q-LIT mode to ensure that the ions are transported to the corresponding devices.

[0037] When operating in Q-LIT-TOF mode, the quadrupole mass filter 200, ion control device 300, ion trap mass analyzer 400, time-of-flight mass analyzer 500, and control device 600 operate simultaneously. In this mode, the selected ions require two types of mass analysis. Under the control of control device 600, ion control device 300 operates in transfer mode, first transferring the selected ions to ion trap mass analyzer 400 for analysis. Then, the transfer path is switched, transferring the analyzed ions from ion trap mass analyzer 400 to time-of-flight mass analyzer 500 for further analysis.

[0038] The specific type of control device 300 is not unique. Specifically, it can be an electronic control system, as long as it can output different voltage magnitudes to the quadrupole mass filter device 200, ion control device 300, ion trap mass analyzer 400 or time-of-flight mass analyzer 600 according to the selected mass spectrometry analysis mode, so as to realize the control of each device connected to the system and operate in the working state corresponding to the selected mass spectrometry analysis mode when connected to the system.

[0039] The aforementioned cascade mass spectrometry system comprises a quadrupole mass filter 200, an ion control unit 300, an ion trap mass analyzer 400, and a time-of-flight mass analyzer 500, arranged sequentially in cascade. The control unit 600 can control the activation of each of these devices according to the selected mass spectrometry analysis mode. When the quadrupole-time-of-flight mass spectrometry (Q-TOF) mode is selected, the control unit 600 simultaneously activates the quadrupole mass filter 200, ion control unit 300, and time-of-flight mass analyzer 500. In this mode, the quadrupole mass filter 200 selects the input ions and transmits the selected ions to the ion control unit 300. The ion control unit 300 operates in collision mode, colliding the selected ions and then transmitting the resulting ions to the time-of-flight mass analyzer 500 for analysis. When the quadrupole-ion trap mass spectrometry (Q-LIT) mode is selected, the control device 600 controls the quadrupole mass filter device 200, the ion control device 300 and the ion trap mass analyzer 400 to start operating simultaneously. At this time, the quadrupole mass filter device 200 performs ion selection on the input ions to obtain selected ions, and then transmits them to the ion trap mass analyzer 400, where ion trap mass spectrometry analysis is directly performed. When the quadrupole-ion trap-time-of-flight mass spectrometry (Q-LIT-TOF) mode is selected, the control device 600 simultaneously activates the quadrupole mass filter 200, ion control device 300, ion trap mass analyzer 400, and time-of-flight mass analyzer 500. The quadrupole mass filter 200 selects the input ions, which are then transmitted to the ion trap mass analyzer 400 for ion trap mass spectrometry analysis. The ions are then returned to the ion control device 300 and transmitted to the time-of-flight mass analyzer 500 for further time-of-flight mass spectrometry analysis. This scheme allows for the selection of three different mass spectrometry analysis modes—Q-LIT, Q-TOF, and Q-LIT-TOF—to meet various analysis requirements. This mass spectrometry approach enables multi-stage mass spectrometry analysis and provides high sensitivity, high resolution, and excellent qualitative capabilities. By combining the advantages of quadrupole, ion trap, and time-of-flight mass analysis, it enables rapid switching between different working modes, effectively expanding the application scenarios of mass spectrometry analysis and exhibiting strong reliability.

[0040] Please see Figure 2 In one embodiment, the tandem mass spectrometry system further includes an ion input device 100, which is disposed at the ion inlet of the quadrupole mass filter 200.

[0041] Specifically, in this embodiment, the tandem mass spectrometry system is further provided with an ion input device 100 at the front end of the quadrupole mass filter device 200. The ion input device 100 first transmits the ions generated by the external ionization source to the quadrupole mass filter device 200 to realize the ion selection operation.

[0042] It should be noted that the specific type of ion input device 100 is not unique, as long as it can ensure the accurate transmission of ions generated by the external ionization source that require mass analysis to the quadrupole mass filter device 200. For example, in one embodiment, please refer to [reference needed]. Figure 2 The ion input device 100 includes a mass spectrometry interface device 110 and a focusing device 120. The focusing device 120 is disposed at the ion inlet of the quadrupole mass filter device 200, and the mass spectrometry interface device 110 is disposed at the ion inlet of the focusing device 120.

[0043] Specifically, the mass spectrometry interface device 110 is used to connect to an external ionization source and transmit the ions generated by the external ionization source to the focusing device 120. By inputting a certain amount of radio frequency voltage on the focusing device 120, the ions are cooled and focused on the focusing device 120 to ensure that the ions are stably and accurately transmitted to the quadrupole mass filter device 200, thereby ensuring the detection reliability of the mass spectrometry system.

[0044] It should be noted that the specific type of focusing device 120 is not unique. For example, in a more detailed embodiment, the focusing device 120 can be a quadrupole, hexapole, or octapole, as long as it can achieve cooling and focusing of the input ions.

[0045] Similarly, the specific structure of the mass spectrometry interface device 110 is not unique. For a more detailed embodiment, please refer to [reference needed]. Figure 3 The mass spectrometry interface device 110 includes a capillary 111, a molecular ion reactor 112, and a focusing electrode 113. The capillary 111 is used to input ions generated by an external ionization source. The focusing electrode 113 is disposed at the ion inlet of the focusing device 120, and the molecular ion reactor 112 is disposed between the capillary 111 and the focusing electrode 113. In another embodiment, please refer to [reference needed]. Figure 4 The mass spectrometry interface device 110 includes a capillary 111, an ion funnel 114, and a focusing electrode 113. The capillary 111 is used to input ions generated by an external ionization source. The focusing electrode 113 is disposed at the ion inlet of the focusing device 120. The ion funnel 114 is disposed between the capillary 111 and the focusing electrode 113.

[0046] Specifically, the technical solution of this application is explained using two typical mass spectrometry interface device 110 structures. The first type includes a capillary tube 111, a molecular ion reactor 112, and a focusing electrode 113. The capillary tube 111 connects to an external ionization source. Ions generated by the external ionization source enter the tandem mass spectrometry system through the capillary tube 111 for analysis. After passing through the molecular ion reactor 112 and the focusing electrode 113, they are further transported to the focusing device 120 for focusing. The second type includes a capillary tube 111, an ion funnel 114, and a focusing electrode 113. The capillary tube 111 connects to an external ionization source. Ions generated by the external ionization source enter the tandem mass spectrometry system through the capillary tube 111 for analysis. After passing through the ion funnel 114 and the focusing electrode 113, they are further transported to the focusing device 120 for focusing.

[0047] Please refer to the following: Figures 3-5 In one embodiment, the time-of-flight quality analysis device 500 includes an ion focusing modulator 510 and a time-of-flight quality analyzer 520. The ion focusing modulator 510 is disposed at the second ion outlet of the ion control device 300, and the time-of-flight quality analyzer 520 is disposed at the ion outlet of the ion focusing modulator 510. The time-of-flight quality analyzer 520 is connected to the control device 600.

[0048] Specifically, in order to improve the reliability of time-of-flight mass spectrometry analysis, the time-of-flight mass spectrometry analysis device is equipped with not only a time-of-flight mass analyzer 520 to realize time-of-flight mass spectrometry analysis, but also an ion focusing modulator 510 at the front end of the time-of-flight mass analyzer 520 to focus and modulate the direction of the ions output by the ion control device 300, so as to ensure that they can be accurately transmitted to the time-of-flight mass analyzer 520.

[0049] It is understood that the specific type of ion focusing modulator is not unique, as long as it can focus and modulate the direction of the input ions. For example, in a more detailed embodiment, the ion focusing modulator is a circular lens group or a DC quadrupole combined with a deflecting lens group.

[0050] The specific structure of the time-of-flight mass analyzer 520 is not unique; any structure capable of performing time-of-flight mass spectrometry analysis of input ions is acceptable. For a more detailed embodiment, please refer to [reference needed]. Figure 3 or Figure 4The time-of-flight quality analyzer 520 includes an accelerating device, a reflecting device, and a detection device. The accelerating device is located at the ion outlet of the ion focusing modulator and applies an accelerating electric field to the ions output from the ion focusing modulator, causing them to travel along the flight tube and eventually reach the reflecting device. Under the influence of the reflected electric field applied by the reflecting device, the ions change their travel direction and travel along the flight tube towards the detection device, where they are finally detected.

[0051] Similarly, please refer to the following: Figure 3 Figure 4 as well as Figure 6 In one embodiment, the ion trap mass analysis device 400 includes a first end cap electrode 410, a second end cap electrode 420, an intermediate electrode 430, and a detection device 440. The first end cap electrode 410, the second end cap electrode 420, the intermediate electrode 430, and the detection device 440 are respectively connected to the control device 600. The first end cap electrode 410 and the second end cap electrode 420 are arranged opposite to each other. The first end cap electrode 410 is disposed at the first ion outlet of the ion control device 300. The intermediate electrode 430 is disposed between the first end cap electrode 410 and the second end cap electrode 420. The detection device 440 is disposed on the intermediate electrode 430.

[0052] Specifically, in this embodiment, the ion trap mass analysis device 400 adopts a linear ion trap (LIT) structure. By inputting different voltage magnitudes to the first end cap electrode 410, the second end cap electrode 420, and the intermediate electrode 430, it can perform storage and analysis operations on the ions delivered by the ion control device 300. Furthermore, the stored and analyzed ions can be fed back to the ion control device 300 for subsequent time-of-flight mass analysis. It is understood that the number of detection devices 440 is not unique; one or more detection devices 440 can be set at the intermediate electrode 430 according to actual detection requirements.

[0053] The specific structure of the ion control device 300 is not unique; any device capable of achieving the aforementioned control of ion transport in different directions and ion collisions is acceptable. For example, in a more detailed embodiment, please refer to [the relevant documentation / reference]. Figure 3 , Figure 4 as well as Figure 7In one embodiment, the ion control device 300 includes a cavity 310, an ion introduction electrode 320, an ion control electrode 340, and an ion extraction electrode 330. The ion introduction electrode 320, the ion control electrode 340, and the ion extraction electrode 330 are respectively connected to the control device 600. An ion introduction port 311 is provided on the side of the cavity 310 near the quadrupole mass filter device 200, a first ion extraction port 314 is provided on the side of the cavity 310 near the ion trap mass analyzer 400, and a second ion extraction port 314 is provided on the side of the cavity 310 near the time-of-flight mass analyzer 500. The cavity 310 has a buffer gas inlet 313 on the side opposite to the side where the first ion outlet 314 is located. The ion introduction electrode 320, the ion control electrode 340, and the ion extraction electrode 330 are all located inside the cavity 310. The ion introduction electrode 320 is located at the ion introduction port 311 of the ion control device 300, the ion extraction electrode 330 is located at the second ion outlet 312 of the ion control device 300, and the ion control electrode 340 is located between the ion introduction electrode 320 and the ion extraction electrode 330.

[0054] Specifically, the ion control device 300 is provided with a cavity 310, on which are respectively provided an ion inlet 311, a first ion outlet 312, a second ion outlet 314, and a buffer gas inlet 313. Ions can be transferred into the cavity 310 through the ion inlet 311, and ion transport and ion collision operations can be performed within the cavity 310. To achieve ion collision, a buffer gas required for collision is input through the buffer gas inlet 313 on the cavity 310, providing a suitable environment for ion collision and ion cooling. It is understood that the specific type of buffer gas is not unique; in one embodiment, the buffer gas can be an inert gas. Further, the inert gas can be at least one of nitrogen, helium, and argon.

[0055] The ion introduction electrode 320, ion control electrode 340, and ion extraction electrode 330 are respectively connected to the control device 600. Under the action of the voltage input to the control device 600, each electrode is in a different working state and can transport ions through different transmission paths so that the ions can enter the back-end time-of-flight mass analyzer 500 or the ion trap mass analyzer 400 to achieve different mass spectrometry analysis operations.

[0056] The specific structure of the ion control electrode 340 is not unique; any structure that enables control of different ion transport paths is acceptable. For example, in a more detailed embodiment, please refer to... Figure 7The ion control electrode 340 includes a first direction control component 341, a second direction control component 342, and a switching electrode component 343. The first direction control component 341, the second direction control component 342, and the switching electrode component 343 are respectively connected to the control device 600. The ion introduction electrode 320 is disposed at the first end of the first direction control component 341, and the ion extraction electrode 330 is disposed at the second end of the first direction control component 341. The first end and the second end are disposed opposite to each other. The first end of the second direction control component 342 is connected to the first direction control component 341 through the switching electrode component 343. The second end of the second direction control component 342 is disposed at the first ion outlet 314 of the ion control device 300.

[0057] Specifically, the first direction control component 341 is used for first-direction ion transport control, the second direction control component 342 is used for second-direction ion transport control, and the switching electrode component 343 is used for switching between first-direction transport and second-direction transport. It is understood that the first and second directions are not unique. In one embodiment, for ease of understanding, the direction from the ion control device 300 to the time-of-flight mass analyzer 500 is taken as the first direction, i.e., the Z direction shown in the figure, and the direction from the ion control device 300 to the ion trap mass analyzer 400 is taken as the second direction, i.e., the Y direction shown in the figure. Accordingly, in this embodiment, the second direction control component 342 is vertically disposed above the first direction control component 341.

[0058] At this time, the first direction control electrode can be set as a T-shape. The ion control electrode 340 is composed of two sets of parallel T-shaped printed circuit boards. The electrodes on each printed circuit board are divided into three components, including the Z-direction control component (first direction control component 341), the switching electrode component 343, and the Y-direction control component (second direction control component 342).

[0059] In a more detailed embodiment, the Z-direction control component includes a first guiding electrode 3412 and a first protective electrode 3411. The first guiding electrode 3412 comprises a sequence of multiple (n1) electrodes, with alternating phase radio frequency voltages and gradient-changing DC voltages applied to adjacent electrodes. The radio frequency electric field controls the trajectory of selected ions in the direction orthogonal to the circuit board (X-direction), preventing ion loss; the DC electric field provides the selected ions with transport kinetic energy in the Z-direction. The first protective electrode 3411 comprises a sequence of multiple (m1) electrodes, with a DC voltage applied to provide a focusing electric field for the selected ions in the Y-direction. The Z-direction control component enables ion transport in the Z-direction.

[0060] The Y-direction control component includes a second protection electrode 3421 and a second guiding electrode 3422. Similarly, the second guiding electrode 3422 comprises a sequence of multiple (n1) electrodes, with alternating phase radio frequency voltages and gradient-changing DC voltages applied to adjacent electrodes. The radio frequency electric field controls the trajectory of selected ions in the direction orthogonal to the circuit board (X-direction), preventing ion loss; the DC electric field provides the selected ions with transport kinetic energy in the Y-direction. The second protection electrode 3421 comprises a sequence of multiple (m2) electrodes, with DC voltage applied to them to provide a focusing electric field for the selected ions in the Z-direction. The switching electrode assembly 343 specifically includes a switching protection electrode 3431 and a switching guiding electrode 3432. By setting appropriate voltage values, the trajectory switching of ions and collision-induced dissociation can be achieved.

[0061] To facilitate understanding of the specific operating principle of the ion control device 300, a detailed explanation is provided below with reference to a specific embodiment. The voltage applied to the Z-direction control component is as follows: Figure 8 As shown, alternating phase radio frequency voltages and gradient-changing DC voltages are applied to adjacent electrodes of the first guiding electrode 3412, and the voltage applied to the i-th electrode is U2-(i-1)dU+(-1). i V RF Where i is the electrode number, 0≤i≤n1. U2 is the DC voltage applied to the first electrode, and dU is the DC voltage drop between two adjacent electrodes, V RF This refers to the amplitude of the applied radio frequency voltage. The generated radio frequency electric field is used to control the trajectory of selected ions in the direction orthogonal to the circuit board (X direction), preventing ion loss; the DC electric field is used to provide the selected ions with transport kinetic energy in the Z direction. A voltage of U2+U is applied to the first protection electrode 3411; where U2 is the DC voltage applied to the first electrode of the first guiding electrode 3412, and U is the DC bias voltage of the first protection electrode 3411 relative to the first electrode of the first guiding electrode 3412. This voltage is used to provide a focusing electric field in the Y direction for the selected ions.

[0062] As for the second direction control component 342 (Y direction control component), its voltage is applied as follows: Figure 9 As shown, alternating phase radio frequency voltages and gradient-changing DC voltages are applied to the adjacent electrodes of the second guiding electrode 3422, and the voltage applied to the j-th electrode is U3-(j-1)dU+(-1). j V RF Where j is the electrode number, 0≤j≤n2. U3 is the DC voltage applied to the first electrode of the second guiding electrode 3422, dU is the DC voltage drop across two adjacent electrodes, V RFThis refers to the amplitude of the applied radio frequency voltage. The generated radio frequency electric field is used to control the trajectory of selected ions in the direction orthogonal to the circuit board (X direction), preventing ion loss; the DC electric field is used to provide the selected ions with transport kinetic energy in the Y direction. The voltage applied to the second protection electrode 3421 is U3+U; where U3 is the DC voltage applied to the first electrode of the second guiding electrode 3422, and U is the DC bias voltage of the second protection electrode 3421 relative to the first electrode of the second guiding electrode 3422. This voltage is used to provide a focusing electric field in the Z direction for the selected ions.

[0063] It is understood that the configuration of the switching electrode assembly 343 is not unique. The switching electrode can be configured independently of the first direction control assembly 341 and the second direction control assembly 342, or it can be based on the first direction control assembly 341 and the second direction control assembly 342 described in the above embodiments, selecting a portion of the electrodes as the switching electrode assembly 343. For example, in a more detailed embodiment, please refer to [the relevant documentation / reference]. Figure 7 The first protection electrode 3411 at the orthogonal point of the Z-direction control component and the Y-direction control component is selected as the switching protection electrode 3431, and the electrode closest to the first guide electrode 3412 in the second guide electrode 3422 component is selected as the switching guide electrode 3432.

[0064] The voltage applied to the switching protection electrode 3431 is U4, and the voltage applied to the switching guide electrode 3432 is U3+V. RF The voltage on the switching protection electrode 3431 is controlled independently. When the ion control device 300 is in linear transmission mode (first direction or Z direction transmission mode), that is, when the ions introduced into the ion inlet are directly transmitted to the corresponding second ion outlet, the voltage applied to the switching protection electrode 3431 is U4 = U2 + U, and the DC voltage applied to the switching guide electrode 3432 is U3 = U2 + U. When the ion control device 300 is in non-linear transmission (corresponding to the T-type ion control electrode 340, which is the 90° transmission mode), the voltage applied to the switching protection electrode 3431 is U4 = U2 + U + U. switch1 Where 30V≤U switch1 ≤150V, switch the DC voltage U3 = U2 + UU applied to the switching guide electrode 3432 switch2 Where 5V≤U switch2 ≤20V.

[0065] When the ion control device 300 is used as a collision cell, the voltage applied by the switching protection electrode 3431 is U4 = U2 + UU. CID , among which, U CID ≥10V, switch the DC voltage U3 = U4 applied to the pilot electrode 3432.CID The axially propelled ions are accelerated and collide with the collision gas in the ion transport device to generate fragment ions. A higher electric field suitable for CID can be applied in two regions: between the front section of the Z-direction control assembly and the region of the switching electrode assembly 343, and between the switching electrode assembly 343 and the rear section of the Z-direction control assembly. When no U is applied... CID At this time, the fragments are minimized, and the ion control device 300 operates in linear transmission mode.

[0066] Therefore, in actual operation, the voltage timing of each electrode can be controlled by the control device 600 to enable the cascade mass spectrometry system to operate in three different analysis modes: Q-LIT, Q-TOF, and Q-LIT-TOF.

[0067] Please refer to the following: Figure 10 When operating in Q-LIT mode, ions are introduced from the mass spectrometry interface device 110, cooled by the focusing device 120, and enter the quadrupole mass filter device 200 for ion selection. Then, they enter the ion control device 300, which operates in 90° turn transmission mode. The ions will be turned and transmitted into the ion trap mass analyzer 400 for multi-stage mass spectrometry analysis.

[0068] Please refer to the following: Figure 11 When operating in Q-TOF mode, ions are introduced from the mass spectrometry interface device 110, cooled by the focusing device 120, and then enter the quadrupole mass filter 200 for ion selection. They then enter the ion control device 300, which operates in collision cell mode to induce collision-induced dissociation of the incoming ions, generating fragment ions. The ion control device 300 then enters a linear transport mode, transmitting the fragment ions to the ion focusing modulator for focusing and direction modulation, and finally to the time-of-flight mass analyzer 520 for high-resolution analysis.

[0069] Please refer to the following: Figure 12 When operating in Q-LIT-TOF mode, ions are introduced from the mass spectrometry interface device 110, cooled by the focusing device 120, and enter the quadrupole mass filter device 200 for ion selection. Then, they enter the ion control device 300, which operates in 90° transmission mode. By setting appropriate switching electrode voltages and the voltages of the first end cap electrode 410 and the second end cap electrode 420 of the ion trap, ions are first transmitted at 90° to the ion trap for storage and analysis. Then, the ions are ejected and transmitted at 90° to the time-of-flight mass analyzer 520 for high-sensitivity, high-resolution cascade mass spectrometry analysis.

[0070] In the Q-LIT-TOF mode of operation, first, the switching electrode voltage is set such that it is greater than the voltage U6 of the first end cap electrode 410 and less than the voltage U7 of the second end cap electrode 420. At this time, ions will enter the ion trap. In the next stage, U6 is raised, and the ions will be trapped in the ion trap. Then, CID can be performed and a part of the ions can be released for LIT detection and analysis (during analysis, U7 < U6, and the ions are ejected). Then, in the next stage, by raising U7 and lowering U6, finally, U7 > U6 > the switching electrode voltage, and the ions are pushed back to the ion control device 300 and are only transported to the time-of-flight mass analyzer 500 under the action of the ion control device 300.

[0071] A mass spectrometry device includes the tandem mass spectrometry system described above.

[0072] Specifically, the structure and operating principle of the tandem mass spectrometry system are as shown in the above-mentioned various embodiments and the drawings and will not be elaborated here. The mass spectrometry device is also provided with other devices such as a molecular pump and a mechanical pump, which cooperate with the above-mentioned tandem mass spectrometry system to provide a vacuum-stable environment for mass spectrometry detection to meet different mass spectrometry detection requirements. For the above-mentioned mass spectrometry device, its mass spectrometry system can achieve functions such as linear ion transmission, 90° turning ion transmission, ion selection, and ion dissociation through the combined action of radio frequency and DC electric fields on the electrodes and a specific buffer gas. Combined with the voltage timing control of the control device 600, the switching of three different tandem operation modes, namely the Q-LIT analysis mode, the Q-TOF analysis mode, and the Q-LIT-TOF analysis mode, can be achieved, which is beneficial to expanding the application scenarios of the mass spectrometry device.

[0073] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope recorded in this specification.

[0074] The above-described embodiments only represent several implementation manners of the present application. Their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the patent application. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present application, several modifications and improvements can still be made, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A tandem mass spectrometry system, characterized by, The application relates to a mass spectrometer, comprising: a quadrupole mass filter for transmitting input ions and selecting ions to obtain selected ions; an ion control device arranged at an ion outlet of the quadrupole mass filter; an ion trap mass analyzer arranged at a first ion outlet of the ion control device; a time-of-flight mass analyzer arranged at a second ion outlet of the ion control device; a control device, the quadrupole mass filter, the ion control device, the ion trap mass analyzer and the time-of-flight mass analyzer are connected to the control device, and the control device is used for controlling the quadrupole mass filter, the ion control device, the ion trap mass analyzer and the time-of-flight mass analyzer to start operation according to a selected mass spectrum analysis mode; in a quadrupole rod-ion trap mass spectrum mode, the ion control device is used for transmitting the selected ions to the ion trap mass analyzer, and the ion trap mass analyzer is used for performing ion trap mass spectrum analysis on the selected ions; in a quadrupole rod-time-of-flight mass spectrum mode, the ion control device is used for transmitting the selected ions to the time-of-flight mass analyzer after ion collision, and the time-of-flight mass analyzer is used for performing time-of-flight mass spectrum analysis on the input ions; in a quadrupole rod-ion trap-time-of-flight mass spectrum mode, the ion control device is used for transmitting the selected ions to the ion trap mass analyzer, the ion trap mass analyzer is used for performing ion trap mass spectrum analysis on the selected ions, and the ion trap mass analyzer is used for transmitting the selected ions back to the ion control device after ion trap mass spectrum analysis, so that the ion control device transmits the selected ions back to the time-of-flight mass analyzer, and the time-of-flight mass analyzer is used for performing time-of-flight mass spectrum analysis on the input ions.

2. The tandem mass spectrometry system of claim 1, wherein, The application further comprises an ion input device arranged at an ion inlet of the quadrupole mass filter.

3. The tandem mass spectrometry system of claim 2, wherein, The ion input device comprises a mass spectrum interface device and a focusing device, the focusing device is arranged at the ion inlet of the quadrupole mass filter, and the mass spectrum interface device is arranged at an ion inlet of the focusing device.

4. The tandem mass spectrometry system of claim 3, wherein, The mass spectrum interface device comprises a capillary, a molecular ion reactor and a focusing electrode, the capillary is used for inputting ions generated by an external ionization source, the focusing electrode is arranged at the ion inlet of the focusing device, and the molecular ion reactor is arranged between the capillary and the focusing electrode. Or, the mass spectrum interface device comprises a capillary, an ion funnel and a focusing electrode, the capillary is used for inputting ions generated by an external ionization source, the focusing electrode is arranged at the ion inlet of the focusing device, and the ion funnel is arranged between the capillary and the focusing electrode.

5. The tandem mass spectrometry system of claim 1, wherein, The time-of-flight mass analyzer comprises an ion focusing modulator arranged at the second ion outlet of the ion control device and a time-of-flight mass analyzer arranged at an ion outlet of the ion focusing modulator, and the time-of-flight mass analyzer is connected to the control device.

6. The tandem mass spectrometry system of claim 1, wherein, The ion trap mass analysis device comprises a first end cap electrode, a second end cap electrode, a middle electrode and a detection device, the first end cap electrode, the second end cap electrode, the middle electrode and the detection device are connected to the control device respectively, the first end cap electrode and the second end cap electrode are oppositely arranged, the first end cap electrode is arranged at the first ion exit of the ion control device, the middle electrode is arranged between the first end cap electrode and the second end cap electrode, and the detection device is arranged at the middle electrode.

7. The tandem mass spectrometry system of any one of claims 1-6, wherein, The ion control device comprises a cavity, an ion introduction electrode, an ion control electrode and an ion exit electrode, the ion introduction electrode, the ion control electrode and the ion exit electrode are connected to the control device respectively, the cavity is provided with an ion introduction port on one side close to the quadrupole mass filter device, the cavity is provided with a first ion exit on one side close to the ion trap mass analysis device, the cavity is provided with a second ion exit on one side close to the time-of-flight mass analysis device, and the cavity is provided with a buffer gas introduction port on the side opposite to the side provided with the first ion exit. The ion introduction electrode, the ion control electrode and the ion exit electrode are all arranged in the cavity, the ion introduction electrode is arranged at the ion introduction port of the ion control device, the ion exit electrode is arranged at the second ion exit of the ion control device, and the ion control electrode is arranged between the ion introduction electrode and the ion exit electrode.

8. The tandem mass spectrometry system of claim 7, wherein, The ion control electrode comprises a first direction control assembly, a second direction control assembly and a switching electrode assembly, the first direction control assembly, the second direction control assembly and the switching electrode assembly are connected to the control device respectively, the ion introduction electrode is arranged at the first end of the first direction control assembly, the ion exit electrode is arranged at the second end of the first direction control assembly, the first end and the second end are oppositely arranged, the first end of the second direction control assembly is connected to the first direction control assembly through the switching electrode assembly, and the second end of the second direction control assembly is arranged at the first ion exit of the ion control device.

9. The tandem mass spectrometry system of claim 8, wherein, The second direction control assembly is arranged perpendicularly to the first direction control assembly.

10. A mass spectrometry apparatus characterized by comprising: The tandem mass spectrometry system comprises the ion control device according to any one of claims 1-9.

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