CN116344323A - Tandem mass spectrometry system and mass spectrometry equipment - Google Patents

Abstract

The application relates to a tandem mass spectrometry system and mass spectrometry equipment, which can realize the functions of linear transmission, steering transmission, ion selection, ion dissociation and the like of ions through the combined action of a control device on a radio frequency and direct current electric field of a quadrupole filter device, an ion control device, an ion trap mass analysis device and a time-of-flight mass analysis device. The switching of three different cascade working modes of the Q-LIT analysis mode, the Q-TOF analysis mode and the Q-LIT-TOF analysis mode can be realized by combining the voltage time sequence control of the control device. The mass spectrometry scheme can realize multistage mass spectrometry, and has high sensitivity, high resolution and good definite capacity. By combining the advantages of quadrupole rod and ion trap mass analysis and flight time mass analysis, the rapid switching of different working modes is realized, the application scene of mass spectrometry is effectively expanded, and the method has stronger use reliability.

Description

Tandem mass spectrometry system and mass spectrometry equipment

technical field

The present application relates to the technical field of mass spectrometry, in particular to a tandem mass spectrometry system and mass spectrometry equipment.

Background technique

Mass spectrometry (Mass Spectrometry, MS) is a method that uses electric and magnetic fields to convert moving ions (charged atoms, molecules or molecular fragments, including molecular ions, isotopic ions, fragment ions, rearranged ions, multiple charged Ions, metastable ions, negative ions and ions produced by ion-molecular interactions) are separated according to their mass-to-charge ratios and then detected. As a key analytical technique, mass spectrometry has been widely used in fields such as biomedicine, food safety, environmental science, and national defense. In recent years, with the increasing requirements for the performance of mass spectrometers in applications, general-purpose single mass spectrometers have been unable to meet the detection needs.

In order to meet the detection requirements, a new type of mass spectrometer with multiple mass analyzers working in series came into being. The tandem mass spectrometers currently commonly used in conjunction with time-of-flight mass analyzers (TOF) mainly include quadrupole-time-of-flight mass spectrometers (Q-TOF) and ion trap-time-of-flight mass spectrometers (IT-TOF). Although Q-TOF can realize the qualitative and quantitative analysis of the target compound at the same time, it can only realize the secondary mass spectrometry analysis, and it is still insufficient for the analysis of compounds with unknown structures; IT-TOF combines the multi-stage mass spectrometry analysis function of the ion trap and flight The advantage of high accurate mass determination of time mass analyzer is suitable for the detection of unknown samples, but its dynamic range and quantitative ability are poor, and the analysis speed is not as good as Q-TOF. It can be seen that the new mass spectrometer with traditional multi-mass analyzers working in series still has certain defects, resulting in poor reliability in use.

Contents of the invention

Based on this, it is necessary to provide a tandem mass spectrometry system and mass spectrometry equipment to solve the problem of poor reliability of the new mass spectrometer in which traditional multi-mass analyzers work in series.

A tandem mass spectrometry system, comprising: a quadrupole mass filter device, used to transmit input ions and select ions to obtain selected ions; an ion control device, arranged at the ion extraction port of the quadrupole mass filter device, for Transport the selected ions to the ion trap mass analysis device; or transport the collided ions to the time-of-flight mass analysis device after performing ion collision on the selected ions; the ion trap mass analysis device is set in the ion control device The first ion extraction port is used to perform ion trap mass spectrometry analysis on the selected ions; or transport the selected ions back to the ion control device after performing ion trap mass spectrometry analysis on the selected ions, so that the ion control device will transport The returned ions are transported to the time-of-flight mass analysis device; the time-of-flight mass analysis device is arranged at the second ion extraction port of the ion control device, and is used to perform time-of-flight mass spectrometry analysis on the input ions; the control device, the The quadrupole mass filter device, the ion control device, the ion trap mass analysis device and the time-of-flight mass analysis device are respectively connected to the control device, and the control device is used to control the The quadrupole mass filter device, the ion control device, the ion trap mass analysis device and the time-of-flight mass analysis device are started to operate.

In one embodiment, the tandem mass spectrometry system further includes an ion input device, and the ion input device is arranged at the ion introduction port of the quadrupole mass filter device.

In one embodiment, the ion input device includes a mass spectrometer interface device and a focusing device, the focusing device is arranged at the ion introduction port of the quadrupole mass filter device, and the mass spectrometer interface device is arranged at the ion inlet of the focusing device. Inlet.

In one embodiment, the mass spectrometer 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, and the focusing electrode is arranged at the ion introduction port of the focusing device, The molecular ion reactor is arranged between the capillary and the focusing electrode; or, the mass spectrometer interface device includes a capillary, an ion funnel and a focusing electrode, and the capillary is used to input ions generated by an external ionization source, the The focusing electrode is arranged at the ion introduction port of the focusing device, and the ion funnel is arranged between the capillary and the focusing electrode.

In one embodiment, the time-of-flight mass analysis device includes an ion focus modulator and a time-of-flight mass analyzer, the ion focus modulator is arranged at the second ion extraction port of the ion control device, and the time-of-flight mass The analyzer is arranged at the ion extraction port of the ion focus modulator, and the time-of-flight mass analyzer is connected to the control device.

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 The middle electrode and the detection device are respectively connected to the control device, the first end cap electrode and the second end cap electrode are arranged oppositely, and the first end cap electrode is arranged on the first ion ion of the ion control device. An outlet, the middle electrode is arranged between the first end cap electrode and the second end cap electrode, and the detection device is arranged on the middle electrode.

In one embodiment, the ion control device includes a cavity, an ion introduction electrode, an ion control electrode and an ion extraction electrode, and the ion introduction electrode, the ion control electrode and the ion extraction electrode are respectively connected to the control device The side of the cavity close to the quadrupole mass filter device is provided with an ion introduction port, the side of the cavity close to the ion trap mass analysis device is provided with a first ion extraction port, and the cavity is close to One side of the time-of-flight mass analysis device is provided with a second ion extraction port, and the side of the cavity opposite to the side where the first ion extraction port is opened is also provided with a buffer gas introduction port; the ion introduction The electrode, the ion control electrode and the ion extraction electrode are all arranged inside the cavity, the ion introduction electrode is arranged at the ion introduction port of the ion control device, and the ion extraction electrode is arranged at the ion The second ion extraction port of the control device, the ion control electrode is arranged between the ion introduction electrode and the ion extraction electrode.

In one embodiment, the ion control electrode includes a first direction control assembly, a second direction control assembly and a switching electrode assembly, and the first direction control assembly, the second direction control assembly and the switching electrode assembly are respectively The control device is connected, the ion introduction electrode is arranged at the first end of the first direction control assembly, the ion extraction electrode is arranged at the second end of the first direction control assembly, and the first end and The second ends are oppositely arranged, 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 arranged on the The first ion extraction port of the ion control device.

In one embodiment, the second direction control component is vertically arranged to the first direction control component.

A mass spectrometry device, comprising the above-mentioned tandem mass spectrometry system.

The above-mentioned tandem mass spectrometry system and mass spectrometry equipment are sequentially provided with a quadrupole mass filter device, an ion control device, an ion trap mass analysis device and a time-of-flight mass analysis device. The quadrupole mass filter device, the ion control device, the ion trap mass analysis device and the time-of-flight mass analysis device perform start-up control. When the quadrupole-time-of-flight mass spectrometry mode (Q-TOF) is selected, the control device controls the quadrupole mass filter device, the ion control device, and the time-of-flight mass spectrometry device to start operation simultaneously, and the quadrupole mass filter device is used for the input ion After performing ion selection, the selected ions are obtained and transmitted to the ion control device. The ion control device works in the collision mode. Perform time-of-flight mass spectrometry. When the quadrupole-ion trap mass spectrometry mode (Q-LIT) is selected, the control device controls the quadrupole mass filter device, the ion control device and the ion trap mass analysis device to start running at the same time. After ion selection is performed to obtain selected ions, the selected ions are transmitted to the ion trap mass analysis device, and the ion trap mass spectrometry analysis is directly realized in the ion trap mass analysis device. When the quadrupole-ion trap-time-of-flight mass spectrometry mode (Q-LIT-TOF) is selected, the control device controls the quadrupole mass filter device, ion control device, ion trap mass analysis device and time-of-flight mass spectrometry device to start running simultaneously , at this time, the quadrupole mass filter device performs ion selection on the input ions to obtain selected ions, and then transmits them to the ion trap mass analysis device, first realizes ion trap mass spectrometry analysis in the ion trap mass analysis device, and then sends them back to the ion control device The time-of-flight mass spectrometry is realized through the ion control device and then transmitted to the time-of-flight mass analysis device. Through the above scheme, three different mass spectrometry analysis modes, Q-LIT, Q-TOF and Q-LIT-TOF, can be selected according to different mass spectrometry analysis requirements. With high sensitivity and high resolution, it has good qualitative ability. By combining the advantages of quadrupole, ion trap mass analysis and time-of-flight mass analysis, the rapid switching of different working modes can be realized, the application scenarios of mass spectrometry can be effectively expanded, and it has strong reliability.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present application or the conventional technology, the following will briefly introduce the accompanying drawings that need to be used in the description of the embodiments or the traditional technology. Obviously, the accompanying drawings in the following description are only the present invention For some embodiments of the application, those skilled in the art can also obtain other drawings based on these drawings without creative work.

Fig. 1 is a schematic structural diagram of a tandem mass spectrometry system in an embodiment;

FIG. 2 is a schematic structural diagram of a tandem mass spectrometry system in another embodiment;

Fig. 3 is a schematic structural diagram of a tandem mass spectrometry system in another embodiment;

FIG. 4 is a schematic structural diagram of a tandem mass spectrometry system in another embodiment;

FIG. 5 is a schematic structural diagram of a tandem mass spectrometry system in another embodiment;

Fig. 6 is a schematic structural diagram of an ion trap mass analysis device in an embodiment;

Fig. 7 is a schematic structural diagram of an ion control device in an embodiment;

FIG. 8 is a schematic diagram of applying voltage to the first direction control component in an embodiment;

FIG. 9 is a schematic diagram of applying voltage to a second direction control component in an embodiment;

Fig. 10 is a schematic structural diagram of a Q-LIT working mode mass spectrometry system in an embodiment;

Fig. 11 is a schematic structural diagram of a Q-TOF working mode mass spectrometry system in an embodiment;

Fig. 12 is a schematic structural diagram of a mass spectrometry system in Q-LIT-TOF working mode in an embodiment.

Detailed ways

In order to facilitate the understanding of the present application, the present application will be described more fully below with reference to the relevant drawings. Preferred embodiments of the application are shown in the accompanying drawings. However, the present application can be embodied in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the application more thorough and comprehensive.

Please refer to FIG. 1 , a tandem mass spectrometry system, including: a quadrupole mass filter device 200, which is used to transmit the input ions and select ions to obtain selected ions; an ion control device 300 is arranged on the quadrupole mass filter device 200 The ion extraction port is used to transport the selected ions to the ion trap mass analysis device 400; or after performing ion collision on the selected ions, transport the collided ions to the time-of-flight mass analysis device 500; the ion trap mass analysis device 400 is set in The first ion extraction port of the ion control device 300 is used to carry out ion trap mass spectrometry analysis on selected ions; The ions are transported to the time-of-flight mass analysis device 500; the time-of-flight mass analysis device 500 is arranged at the second ion extraction port of the ion control device 300, and is used to perform time-of-flight mass spectrometry analysis on the input ions; the control device 600 is a quadrupole mass filter The device 200, the ion control device 300, the ion trap mass analysis device 400 and the time-of-flight mass analysis device 500 are respectively connected to the control device 600, and the control device 600 is used to control the quadrupole mass filter device 200, the ion control The device 300, the ion trap mass analysis device 400 and the time-of-flight mass analysis device 500 are started up.

Specifically, the quadrupole mass filter device 200 is a device that uses quadrupole rods to transmit and select ions input. The quadrupole mass filter device 200 uses high frequency and DC electric field to make ions with a specific mass-to-charge ratio take a stable orbit through the quadrupole field. By adjusting the radio frequency voltage or DC voltage input to the quadrupole mass filter device 200 , the quadrupole mass filter device 200 can select ions with different mass-to-charge ratios to pass through.

The ion control device 300 has two different functions of ion transmission and ion collision. According to the different working modes selected by the tandem mass spectrometry system, the voltage input from the control device 600 to the ion control device 300 will be different, and finally the ion Control device 300 is in different operating states.

Under the action of the control device 600, the ion trap mass analysis device 400 can form an ion trap by applying an appropriate voltage. According to the size of the applied radio frequency voltage, the ion trap can capture ions in a certain mass range and trap them in the trap to realize ion storage. After the ions in the ion trap undergo collision-induced dissociation (CID), different fragment ions can be formed, and the mass detection of different fragment ions can be performed to obtain a secondary spectrum. After the fragment ions are selected again, specific fragment ions can be selected to continue fragmentation to generate smaller fragment ions and achieve mass detection to obtain a tertiary spectrum. If subsequent fragmentation analysis is carried out, more mass analysis spectra can be obtained, so mass spectrometry above three levels can be realized through the ion trap mass analysis device 400 .

The principle of the time-of-flight mass analyzer 500 is: use a pulse to extract the ions in the modulation area instantaneously, and after being accelerated by the accelerating voltage, they enter the drift tube with the same kinetic energy, and the ion with the smallest mass-to-charge ratio has the fastest speed. The ions with the highest mass-to-charge ratio arrive at the detector first, and the ions with the highest mass-to-charge ratio arrive at the detector last, enabling mass analysis operation.

Depending on the working mode, the devices connected to the tandem mass spectrometry system are different, and the operating modes of each device will also be different. When working in the Q-LIT analysis mode, the quadrupole mass filter device 200, the ion control device 300, the ion trap mass analysis device 400 and the control device 600 operate simultaneously. Since the ion trap mass analysis device 400 itself can trap ions in the trap, and then detect them after being broken by CID (Collision Induced Dissociation, collision-induced dissociation), the ion control device 300 is in the transmission mode in this mode, and will select The ions are transmitted to the ion trap mass analyzer 400 for mass analysis.

When working in the Q-TOF mode, the quadrupole mass filtration device 200, the ion control device 300, the time-of-flight mass analysis device 500 and the control device 600 operate simultaneously. At this time, the time-of-flight mass analyzer 500 is used as the mass analyzer. At this time, the ion control device 300 enters the collision+transmission working mode under the output control of the control device 600, and the input selected ions are collided to obtain the ions after the collision. The ions are sent to the time-of-flight mass analyzer 500 for mass analysis, and the transmission path is different from the transmission path in the Q-LIT working mode, so as to ensure that the ions are transmitted to the corresponding device.

When working in the Q-LIT-TOF working mode, the quadrupole mass filter device 200 , the ion control device 300 , the ion trap mass analyzer 400 , the time-of-flight mass analyzer 500 and the control device 600 operate simultaneously. At this time, it is necessary to perform mass analysis in two ways on the selected ions. Under the control of the control device 600, the ion control device 300 performs the transmission mode, and first transmits the selected ions to the ion trap mass analysis device 400 for mass analysis, and then needs to perform mass analysis. By switching the transmission path, the ions analyzed by the ion trap mass analyzer 400 are transmitted to the time-of-flight mass analyzer 500 for mass analysis again.

The specific type of the control device 300 is not unique, it is specifically an electronic control system, as long as it can control the quadrupole mass filter device 200, the ion control device 300, the ion trap mass analysis device 400 or the flight control system according to the selected mass spectrometry mode. The time-mass analysis device 600 outputs different voltages to control the access of each device to the system, and can operate in the working state corresponding to the selected mass spectrometry mode when connected to the system.

The above tandem mass spectrometry system is sequentially provided with a quadrupole mass filter device 200, an ion control device 300, an ion trap mass analysis device 400, and a time-of-flight mass spectrometry device 500. The control device 600 can be different according to the selected mass spectrometry analysis mode, The quadrupole mass filter device 200 , the ion control device 300 , the ion trap mass analyzer 400 and the time-of-flight mass analyzer 500 are controlled to start up respectively. When the quadrupole-time-of-flight mass spectrometry mode (Q-TOF) is selected, the control device 600 controls the quadrupole mass filter device 200, the ion control device 300 and the time-of-flight mass spectrometry device 500 to start operation simultaneously, and the quadrupole mass filter device 200 performs ion selection on the input ions to obtain selected ions, and transmits them to the ion control device 300. The ion control device 300 works in the collision mode, and after performing ion collision on the selected ions, transports the collided ions to the time-of-flight mass analysis device 500 , so that time-of-flight mass spectrometry is performed in the time-of-flight mass analyzer 500 . When the quadrupole-ion trap mass spectrometry mode (Q-LIT) is selected, the control device 600 controls the quadrupole mass filter device 200, the ion control device 300 and the ion trap mass analysis device 400 to start operation simultaneously, and the quadrupole mass filter device 200 conducts ion selection on the input ions to obtain selected ions, and transmits them to the ion trap mass analysis device 400 , where ion trap mass spectrometry analysis is directly implemented in the ion trap mass analysis device 400 . When the quadrupole-ion trap-time-of-flight mass spectrometry mode (Q-LIT-TOF) is selected, the control device 600 controls the quadrupole mass filter device 200, the ion control device 300, the ion trap mass analysis device 400 and the time-of-flight mass spectrometry The device 500 starts running at the same time. At this time, the quadrupole mass filter device 200 performs ion selection on the input ions to obtain the selected ions, and transmits them to the ion trap mass analysis device 400. First, the ion trap mass spectrometry is implemented in the ion trap mass analysis device 400. After that, it is transported back to the ion control device 300 , and then transmitted to the time-of-flight mass analysis device 500 via the ion control device 300 to realize time-of-flight mass spectrometry analysis. Through the above scheme, three different mass spectrometry analysis modes, Q-LIT, Q-TOF and Q-LIT-TOF, can be selected according to different mass spectrometry analysis requirements. With high sensitivity and high resolution, it has good qualitative ability. By combining the advantages of quadrupole, ion trap mass analysis and time-of-flight mass analysis, the rapid switching of different working modes can be realized, the application scenarios of mass spectrometry can be effectively expanded, and it has strong reliability.

Please refer to FIG. 2 , in one embodiment, the tandem mass spectrometry system further includes an ion input device 100 , and the ion input device 100 is disposed at the ion introduction port of the quadrupole mass filter device 200 .

Specifically, in the technical solution of this embodiment, the tandem mass spectrometry system is also provided with an ion input device 100 at the front end of the quadrupole mass filter device 200, and the ions generated by the external ionization source are first transmitted to the quadrupole filter through the ion input device 100. The quality device 200 realizes the ion selection operation.

It should be noted that the specific type of the ion input device 100 is not exclusive, as long as the ions generated by the external ionization source for mass analysis can be accurately transmitted to the quadrupole mass filter device 200 . For example, in one embodiment, please continue to refer to FIG. 2, the ion input device 100 includes a mass spectrometer interface device 110 and a focusing device 120, the focusing device 120 is arranged at the ion introduction port of the quadrupole mass filter device 200, and the mass spectrometer interface device 110 is arranged on The ion introduction port of the focusing device 120 .

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. , so as to ensure the stable and accurate transmission of ions to the quadrupole mass filter device 200, thereby ensuring the detection reliability of the mass spectrometry system.

It should be noted that the specific type of the focusing device 120 is not exclusive. For example, in a more detailed embodiment, the focusing device 120 can be a quadrupole, a hexapole, or an octopole, as long as the input ion can be achieved. Cool focus is fine.

Similarly, the specific structure of the mass spectrometer interface device 110 is not unique. In a more detailed embodiment, please refer to FIG. For inputting ions generated by an external ionization source, the focusing electrode 113 is arranged at the ion introduction port of the focusing device 120 , and the molecular ion reactor 112 is arranged between the capillary 111 and the focusing electrode 113 . In another embodiment, please refer to FIG. 4, the mass spectrometer 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, and the focusing electrode 113 is arranged on the focusing device 120 The ion introduction port, the ion funnel 114 is arranged between the capillary 111 and the focusing electrode 113 .

Specifically, in the technical solution of the present application, two typical structures of mass spectrometer interface devices 110 are used for explanation. To the external ionization source, the ions generated by the external ionization source enter the tandem mass spectrometry system through the capillary 111 for analysis, pass through the molecular ion reactor 112 and the focusing electrode 113, and are further transmitted to the focusing device 120 for focusing. The second is a mass spectrometry interface device 110 comprising a capillary 111, an ion funnel 114 and a focusing electrode 113, which is connected to an external ionization source through the capillary 111, and ions generated by the external ionization source enter the tandem mass spectrometry system through the capillary 111 for analysis, pass through the ion funnel 114 and the focusing electrode 113, it is further transmitted to the focusing device 120 for focusing.

Please refer to FIGS. 3-5 in conjunction. In one embodiment, the time-of-flight mass analysis device 500 includes an ion focus modulator 510 and a time-of-flight mass analyzer 520. The ion focus modulator 510 is arranged on the second ion of the ion control device 300 At the extraction port, the time-of-flight mass analyzer 520 is disposed at the ion extraction port of the ion focus modulator 510 , and the time-of-flight mass analyzer 520 is connected to the control device 600 .

Specifically, in order to improve the analytical reliability of time-of-flight mass spectrometry analysis, in the time-of-flight mass spectrometry device, not only a time-of-flight mass analyzer 520 is provided to realize time-of-flight mass spectrometry analysis, but at the front end of the time-of-flight mass analyzer 520, a An ion focus modulator 510 is used to focus and modulate the direction of the ions output by the ion control device 300 to ensure that they can be accurately transmitted to the time-of-flight mass analyzer 520 .

It can be understood that the specific type of the ion focus modulator is not unique, as long as the input ions can be focused and directionally modulated, for example, in a more detailed embodiment, the ion focus modulator is a ring lens group Or a DC quadrupole combined with a deflection lens group.

The specific structure of the time-of-flight mass analyzer 520 is not unique, as long as the time-of-flight mass spectrometry analysis of the input ions can be realized. In a more detailed embodiment, please refer to FIG. 3 or FIG. 4, the time-of-flight mass analyzer 520 includes an acceleration device, a reflection device and a detection device, wherein the acceleration device is arranged at the ion extraction port of the ion focus modulator for An accelerating electric field is applied to the ions output by the ion focusing modulator, so that they are transmitted along the flight tube and finally transmitted to the reflection device. Under the action of the reflected electric field applied by the reflective device, the ions change their transmission direction, travel along the flight tube toward the detection device, and are finally detected by the detection device.

Similarly, please refer to FIG. 3, FIG. 4 and FIG. 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. An end cap electrode 410, a second end cap electrode 420, an intermediate electrode 430 and a 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 oppositely, and the first end cap electrode 410 is arranged on For the first ion extraction port of the ion control device 300 , the middle electrode 430 is disposed between the first end cap electrode 410 and the second end cap electrode 420 , and the detection device 440 is disposed on the middle electrode 430 .

Specifically, in the scheme of this embodiment, the ion trap mass analysis device 400 specifically adopts a linear ion trap (LIT, Linear Ion Trap) structure, by inputting Different voltages can store and analyze the ions delivered by the ion control device 300 , and push back the stored and analyzed ions back to the ion control device 300 to realize the next step of time-of-flight mass analysis. It can be understood that the number of detection devices 440 is not unique, and specifically, one or more detection devices 440 may be provided at the middle electrode 430 according to actual detection requirements.

The specific structure of the ion control device 300 is not unique, as long as it can realize the above-mentioned ion transmission control in different directions and ion collision, for example, in a more detailed embodiment. Please refer to FIG. 3 , FIG. 4 and FIG. 7 in conjunction. In 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 , and the ion introduction electrode 320 and the ion control electrode 340 and the ion extraction electrode 330 are respectively connected to the control device 600, the side of the cavity 310 close to the quadrupole mass filter device 200 is provided with an ion introduction port 311, and the side of the cavity 310 close to the ion trap mass analysis device 400 is provided with a first ion Outlet 314, a second ion outlet 312 is provided on the side of the cavity 310 close to the time-of-flight mass analysis device 500, and a buffer gas inlet is also provided on the side opposite to the side where the first ion outlet 314 is opened in the cavity 310. The entrance 313; the ion introduction electrode 320, the ion control electrode 340 and the ion extraction electrode 330 are all arranged inside the cavity 310, the ion introduction electrode 320 is arranged at the ion introduction port 311 of the ion control device 300, and the ion extraction electrode 330 is arranged at the ion control The second ion extraction port 312 of the device 300 and the ion control electrode 340 are arranged between the ion introduction electrode 320 and the ion extraction electrode 330 .

Specifically, the ion control device 300 is provided with a chamber body 310, and an ion introduction port 311, a first ion extraction port 312, a second ion extraction port 314, and a buffer gas introduction port 313 are respectively opened on the cavity body 310. The inlet 311 can transmit ions into the cavity 310 , and operations such as ion transmission and ion collision are performed in the cavity 310 . In order to realize ion collision, the buffer gas needed for collision needs to be input through the buffer gas inlet 313 opened on the cavity 310 to provide a suitable environment for ion collision and ion cooling. It can be understood that the specific type of the buffer gas is not exclusive, and in one embodiment, the buffer gas may specifically be an inert gas. Further, the inert gas may be at least one of nitrogen, helium, and argon.

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

The specific structure of the ion control electrode 340 is also not unique, as long as it can realize the control of different transmission paths of ions. For example, in a more detailed embodiment, please refer to FIG. 7, the ion control electrode 340 includes a first direction control assembly 341, a second direction control assembly 342 and a switching electrode assembly 343, the first direction control assembly 341, the second direction control assembly 341 The control assembly 342 and the switching electrode assembly 343 are respectively connected to the control device 600, the ion introduction electrode 320 is arranged at the first end of the first direction control assembly 341, the ion extraction electrode 330 is arranged at the second end of the first direction control assembly 341, and the first The first end of the second direction control assembly 342 is connected to the first direction control assembly 341 through the switching electrode assembly 343, and the second end of the second direction control assembly 342 is arranged on the second end of the ion control device 300. An ion extraction port 314 .

Specifically, the first direction control assembly 341 is used for the first direction transmission control of ions, the second direction control assembly 342 is used for the second direction transmission control of ions, and the switching electrode assembly 343 is used for ion transmission in the first direction. To switch between transmission in the second direction. It can be understood that the first direction and the second direction are not unique. In one embodiment, for ease of understanding, the direction from the ion control device 300 to the time-of-flight mass analysis device 500 is taken as the first direction, that is, Z in the diagram As for the direction, the direction from the ion control device 300 to the ion trap mass analyzer 400 is taken as the second direction, that is, the Y direction in the figure. Correspondingly, in the solution of this embodiment, the second direction control component 342 is vertically arranged on the first direction control component 341 .

At this time, the first direction control electrode and the first direction control electrode can be set as T-shaped, and the ion control electrode 340 is composed of two groups of T-shaped printed circuit boards placed in parallel, and the electrodes on each printed circuit board are divided into 3 components, including Z direction control component (first direction control component 341), switching electrode component 343 and Y direction control component (second direction control component 342).

In a more detailed embodiment, the Z-direction control component includes a first guide electrode 3412 and a first guard electrode 3411 . The first guiding electrode 3412 includes a sequence of multiple (n1) electrodes, adjacent electrodes are applied with alternating phase RF voltages and gradient-changed DC voltages, and the RF electric field is used to control the selection of ions in the direction perpendicular to the circuit board ( X direction) trajectory to prevent ion loss; the DC electric field is used to provide the selected ions with transmission kinetic energy in the Z direction. The first guard electrode 3411 includes a sequence composed of multiple (m1) electrodes. At this time, a DC voltage is applied to the electrodes to provide a focusing electric field for the selected ions in the Y direction. The ions can be transmitted in the Z direction through the Z direction control component.

The Y-direction control component includes a second guard electrode 3421 and a second guide electrode 3422 . Similarly, the second guiding electrode 3422 includes a sequence of multiple (n1) electrodes, adjacent electrodes are applied with alternating phase RF voltages and gradient-changed DC voltages, and the RF electric field is used to control the selection of ions in a direction perpendicular to the circuit board The running trajectory in the direction (X direction) prevents the loss of ions; the DC electric field is used to provide the transport kinetic energy in the Y direction for the selected ions. The second guard electrode 3421 includes a sequence of multiple (m2) electrodes, on which a DC voltage is applied to provide a focusing electric field for the selected ions in the Z direction; and the switching electrode assembly 343 specifically includes a switching guard electrode 3431 and a switching guide electrode 3432, by setting an appropriate voltage value, the trajectory switching and collision-induced dissociation of ions can be realized.

In order to facilitate the understanding of the specific operating principle of the ion control device 300 , detailed explanations will be given below in conjunction with specific embodiments. The Z-direction control component voltage application is shown in FIG. 8 , the adjacent electrodes of the first guide electrode 3412 are applied with alternating phase radio frequency voltage and gradient-changed DC voltage, and the voltage applied to the i-th electrode is U ₂ -(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, dU is the DC voltage drop across two adjacent electrodes, and _VRF is the magnitude of the applied RF voltage. The generated radio frequency electric field is used to control the trajectory of the selected ions in the direction perpendicular to the circuit board (X direction) to prevent ion loss; the DC electric field is used to provide the selected ions with transmission kinetic energy in the Z direction. The voltage applied to the first guard electrode 3411 is U ₂ +U; wherein, U ₂ is the DC voltage applied to the first electrode of the first guide electrode 3412 , and U is the first guard electrode 3411 relative to the first guide electrode 3412 DC bias voltage of the first electrode, which is used to provide focusing electric field in Y direction for selected ions.

For the second direction control component 342 (Y direction control component), its voltage application is as shown in FIG. The voltage applied to j electrodes is U ₃ -(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 guide electrode 3422, dU is the DC voltage drop across two adjacent electrodes, and _VRF is the magnitude of the applied RF voltage. The generated radio frequency electric field is used to control the trajectory of the selected ions in the direction perpendicular to the circuit board (X direction) to prevent ion loss; the DC electric field is used to provide the selected ions with transmission kinetic energy in the Y direction. The voltage applied by the second guard electrode 3421 is U ₃ +U; wherein, U ₃ is a DC voltage applied to the first electrode of the second guide electrode 3422, and U is the relative voltage of the second guard electrode 3421 to the second guide electrode 3422 The DC bias voltage of the first electrode is used to provide a focusing electric field in the Z direction for selected ions.

It can be understood that the arrangement of the switch electrode assembly 343 is not unique, the switch electrode can be set independently of the first direction control assembly 341 and the second direction control assembly 342, or can be set based on the first direction control assembly 342 described in the above embodiments. The direction control component 341 and the second direction control component 342 select a part of the electrodes as the switching electrode component 343 . For example, in a more detailed embodiment, please refer to FIG. 7, select the first guard electrode 3411 at the intersection of the Z-direction control component and the Y-direction control component as the switching guard electrode 3431, select the second guide electrode 3422 component The electrode closest to the first guide electrode 3412 serves as the switching guide electrode 3432 .

The voltage applied to the switching protection electrode 3431 is U ₄ , the voltage applied to the switching guide electrode 3432 is U ₃ +V _RF , and the voltage on the switching protection electrode 3431 is controlled separately. When the ion control device 300 is in the linear transmission mode (transmission mode in the first direction or the Z direction), that is, when the ions introduced by the ion introduction port are directly transmitted to the second ion extraction port opposite to it, the voltage applied by the switching guard electrode 3431 is U ₄ =U ₂ +U, switch the DC voltage U ₃ =U ₂ +U applied on the leading electrode 3432 . And when the ion control device 300 is in non-linear transmission (corresponding to the T-shaped ion control electrode 340, it is in the 90° transmission mode at this time), the voltage applied by the switching guard electrode 3431 is U ₄ =U ₂ +U+U _switch1 , wherein, 30V≤U _switch1 ≤150V, the DC voltage U ₃ =U ₂ +UU _switch2 applied to the switching guide electrode 3432 , wherein, 5V≤U _switch2 ≤20V.

When the ion control device 300 is used as a collision cell, the voltage applied by the switching guard electrode 3431 is U ₄ =U ₂ +UU _CID , where U _CID ≥ 10V, and the DC voltage U ₃ =U ₄ applied on the switching guide electrode 3432 . The U _CID accelerates the ions in the axial direction and collides 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 area 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 _CID is applied, debris is minimized and the ion control device 300 operates in linear transport mode.

Therefore, in the actual operation process, the tandem mass spectrometry system can be operated in three different analysis modes of Q-LIT, Q-TOF and Q-LIT-TOF only by controlling the voltage timing of each electrode through the control device 600. model.

Please refer to FIG. 10 , when working in the Q-LIT mode, after the ions are introduced from the mass spectrometer interface device 110, they are cooled by the focusing device 120, enter the quadrupole mass filter device 200 for ion selection, and then enter the ion control device 300, and the device works In the 90° turn transmission mode, ions will be turned and transmitted into the ion trap mass analyzer 400 for multi-stage mass spectrometry analysis.

Please refer to FIG. 11 , when working in the Q-TOF mode, after the ions are introduced from the mass spectrometer interface device 110, they are cooled by the focusing device 120, enter the quadrupole mass filter device 200 for ion selection, and then enter the ion control device 300, the device Working in the collision cell mode, the incoming ions are subjected to collision-induced dissociation to generate fragment ions. Afterwards, the ion control device 300 enters the linear transmission mode, and transmits the fragment ions to the ion focusing modulator for focusing and direction modulation, and finally transmits them to the time-of-flight mass analyzer 520 for high-resolution analysis.

Please refer to FIG. 12 , when working in the Q-LIT-TOF mode, after the ions are introduced from the mass spectrometer interface device 110, they are cooled by the focusing device 120, enter the quadrupole mass filter device 200 for ion selection, and then enter the ion control device 300, The device works in the 90° transmission mode. By setting the appropriate switching electrode voltage and the voltage of the first end cap electrode 410 and the second end cap electrode 420 of the ion trap, the ions are sent to the ion trap for storage and analysis by 90° transmission. , and then the ions are pushed out for 90° transmission, and sent to the time-of-flight mass analyzer 520 for high-sensitivity and high-resolution tandem mass spectrometry analysis.

When working in Q-LIT-TOF mode, first set the switching electrode voltage > the voltage U6 of the first end cap electrode 410 < the voltage U7 of the second end cap electrode 420, and the ions will enter the ion trap at this time. In the next stage, U6 is raised, ions will be trapped in the ion trap, and then CID can be performed and a part of ions released for LIT detection and analysis (during analysis, U7<U6, ions are pushed out). Then in the next stage, by raising U7 and lowering U6, finally U7>U6>switching the electrode voltage, the ions are pushed back to the ion control device 300, and only under the operation of the ion control device 300, they are transported to the time-of-flight mass analysis device 500.

A mass spectrometry device, comprising the above-mentioned tandem mass spectrometry system.

Specifically, the structure and operating principle of the tandem mass spectrometry system are as shown in the above-mentioned embodiments and drawings, and will not be repeated here. The mass spectrometry equipment is also equipped with molecular pumps, mechanical pumps and other devices, which cooperate with the above-mentioned tandem mass spectrometry system to provide a stable vacuum environment for mass spectrometry detection, so as to realize different mass spectrometry detection requirements. The above-mentioned mass spectrometry equipment, its mass spectrometry system can realize the functions of ion linear transmission, 90° turning transmission, ion selection and ion dissociation through the combined action of radio frequency and DC electric field on the electrode and specific buffer gas. Combined with the voltage sequence control of the control device 600, the switching of three different cascade working modes of Q-LIT analysis mode, Q-TOF analysis mode and Q-LIT-TOF analysis mode can be realized, which is beneficial to expand the application scenarios of mass spectrometry equipment.

The technical features of the above-mentioned embodiments can be combined arbitrarily. To make the description concise, all possible combinations of the technical features in the above-mentioned embodiments are not described. However, as long as there is no contradiction in the combination of these technical features, should be considered as within the scope of this specification.

The above-mentioned embodiments only express several implementation modes of the present application, and the description thereof is relatively specific and detailed, but should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make several modifications and improvements without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the scope of protection of the patent application should be based on the appended claims.

Claims (10)

1. A tandem mass spectrometry system, characterized in that, comprising: The quadrupole mass filter device is used to transmit the input ions and select the ions to obtain selected ions; The ion control device is arranged at the ion extraction port of the quadrupole mass filter device, and is used to transport the selected ions to the ion trap mass analysis device; or after performing ion collision on the selected ions, transport the ion after collision To the time-of-flight mass analysis device; The ion trap mass analysis device is arranged at the first ion extraction port of the ion control device, and is used to perform ion trap mass spectrometry on the selected ions; or transport the selected ions back to the an ion control device, such that the ion control device delivers ions back to the time-of-flight mass analysis device; The time-of-flight mass analysis device is arranged at the second ion extraction port of the ion control device, and is used to perform time-of-flight mass spectrometry analysis on the input ions; The control device, the quadrupole mass filter device, the ion control device, the ion trap mass analysis device and the time-of-flight mass analysis device are respectively connected to the control device, and the control device is used to analyze according to the selected mass spectrum Mode, respectively controlling the quadrupole mass filter device, the ion control device, the ion trap mass analysis device and the time-of-flight mass analysis device to start running. 2. The tandem mass spectrometry system according to claim 1, further comprising an ion input device, the ion input device is arranged at the ion introduction port of the quadrupole mass filter device. 3. The tandem mass spectrometry system according to claim 2, wherein the ion input device comprises a mass spectrometer interface device and a focusing device, and the focusing device is arranged at the ion introduction port of the quadrupole mass filter device, so The mass spectrometry interface device is arranged at the ion introduction port of the focusing device. 4. tandem mass spectrometry system according to claim 3, is characterized in that, described mass spectrometer interface device comprises capillary, molecular ion reactor and focusing electrode, and described capillary is used for inputting the ion that external ionization source produces, and described focusing An electrode is arranged at the ion introduction port of the focusing device, and the molecular ion reactor is arranged between the capillary and the focusing electrode; Or, the mass spectrometer 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 arranged at the ion introduction port of the focusing device, and the ion funnel is arranged at between the capillary and the focusing electrode. 5. The tandem mass spectrometry system according to claim 1, wherein the time-of-flight mass analysis device comprises an ion focus modulator and a time-of-flight mass analyzer, and the ion focus modulator is arranged on the ion control device The second ion extraction port of the time-of-flight mass analyzer is arranged at the ion extraction port of the ion focus modulator, and the time-of-flight mass analyzer is connected to the control device. 6. The tandem mass spectrometry system according to claim 1, wherein the ion trap mass analysis device comprises a first end cap electrode, a second end cap electrode, an intermediate electrode and a detection device, and the first end cap The 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 arranged oppositely, and the first end cap electrode The electrodes are arranged at the first ion extraction port 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 according to 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 extraction electrode, the ion introduction electrode, The ion control electrode and the ion extracting electrode are respectively connected to the control device, and the side of the cavity close to the quadrupole mass filter device is provided with an ion introduction port, and the cavity is close to the ion trap mass analyzer. A first ion extraction port is provided on one side of the device, a second ion extraction port is provided on the side of the cavity close to the time-of-flight mass analysis device, and a second ion extraction port is provided on the side of the cavity and the first ion extraction port On the opposite side, there is also a buffer gas inlet; The ion introduction electrode, the ion control electrode and the ion extraction electrode are all arranged inside the cavity, the ion introduction electrode is arranged at the ion introduction port of the ion control device, and the ion extraction electrode is arranged In the second ion extraction port of the ion control device, the ion control electrode is arranged between the ion introduction electrode and the ion extraction electrode. 8. The tandem mass spectrometry system according to 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 The second direction control assembly and the switching electrode assembly are respectively connected to the control device, the ion introduction electrode is arranged at the first end of the first direction control assembly, and the ion extraction electrode is arranged at the first end of the first direction control assembly. The second end of the component, the first end is opposite to the second end, the first end of the second direction control component is connected to the first direction control component through the switching electrode component, the first direction control component The second end of the two-direction control assembly is arranged at the first ion extraction port of the ion control device. 9. The tandem mass spectrometry system according to claim 8, wherein the second direction control component is vertically arranged to the first direction control component. 10. A mass spectrometry device, comprising the tandem mass spectrometry system according to any one of claims 1-9.

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