1. A tandem mass spectrometry apparatus comprising focussing means, a time of flight mass analyser, an ion trap mass analyser and control means;

the focusing device is used for focusing ions to be detected so that the ions to be detected reach the subsequent time-of-flight mass analyzer;

the control device is used for carrying out voltage time sequence control on electrodes in the flight time mass analyzer and the ion trap mass analyzer according to test requirements, adjusting the running track of the ions to be tested and realizing the switching of working modes of the flight time mass spectrometry or the ion trap mass spectrometry;

the time-of-flight mass analyzer is used for performing time-of-flight mass spectrometry on the ions to be detected when the working mode is time-of-flight mass spectrometry, and is also used for transmitting the ions to be detected to the ion trap mass analyzer at the later stage when the working mode is ion trap mass spectrometry;

and the ion trap mass analyzer is used for carrying out ion trap mass spectrometry on the ions to be detected which pass through the time-of-flight mass analyzer when the working mode is ion trap mass spectrometry.

2. The tandem mass spectrometry apparatus of claim 1, wherein the focusing device comprises a focusing unit and a deflecting unit;

the focusing unit is used for focusing ions to be detected so that the ions to be detected reach the deflection unit;

the deflection unit is used for refocusing the ions to be detected so as to enable the ions to be detected to reach the time-of-flight mass analyzer at the later stage.

3. The tandem mass spectrometry apparatus of claim 1, wherein the focusing device is a combination of one or more of a grignard type electrostatic quadrupole, a circular ring lens group, a dc quadrupole and a deflection electrode.

4. The tandem mass spectrometry apparatus of any of claims 1 to 3, wherein the time-of-flight mass analyser comprises modulation means, acceleration means, reflection means and detection means;

the modulation device is arranged in a modulation area and is used for modulating the running track of the ions to be detected so that the ions to be detected enter an acceleration area or reach the ion trap mass analyzer;

the accelerating device is arranged in the accelerating area and used for accelerating the ions to be detected entering the accelerating area, so that the ions to be detected pass through the field-free area after being accelerated and enter the reflecting area;

the reflecting device is arranged in the reflecting area and used for reflecting the ions to be detected entering the reflecting area, so that the ions to be detected pass through the field-free area to reach the detection area after being reflected;

the detection device is arranged in the detection area and used for detecting the ions to be detected entering the detection area.

5. The tandem mass spectrometry apparatus of claim 4, wherein the modulation device comprises a first slit electrode, a gate electrode, and a repulsion plate; the first slit electrode is arranged at the entrance of the modulation region; the gate electrode is arranged at the modulation region outlet, and an ion channel of the gate electrode is aligned with an ion inlet of the ion trap mass analyzer;

the repulsion plate is arranged between the first slit electrode and the gate electrode and used for modulating the running track of the ions to be detected when the working mode is flight time mass spectrometry so that the ions to be detected enter the acceleration area.

6. The tandem mass spectrometry apparatus of any of claims 1 to 3, wherein the ion trap mass analyser comprises a first end cap electrode, a reaction electrode, a second end cap electrode and an ion detection device; the first end cap electrode and the second end cap electrode are oppositely arranged, and the reaction electrode is arranged between the first end cap electrode and the second end cap electrode;

the first end cover electrode is arranged at an ion inlet of the ion trap mass analyzer, and the ion detection device is arranged at an ion outlet of the ion trap mass analyzer;

the first end cover electrode is used for opening the ion inlet when the working mode is ion trap mass spectrometry so that ions to be detected reach the ion trap through the ion inlet;

the reaction electrode is used for forming the ion trap and enabling the ion trap to act on the ions to be detected, and finally enabling the ions to be detected to reach the ion detection device;

the ion detection device is used for detecting the ions to be detected.

7. A mass spectrometry detection system, comprising a capillary, a focusing structure, a transmission quadrupole and a tandem mass spectrometry device according to any one of claims 1 to 6 arranged in sequence along an ion travel channel to be detected.

8. The mass spectrometry detection system of claim 7, further comprising a quadrupole mass filter and a collision cell, the quadrupole mass filter and the collision cell being sequentially disposed between the transport quadrupole and the tandem mass spectrometry device.

9. The mass spectrometry detection system of claim 7, wherein the capillary and the focusing structure are disposed in the same chamber, and the transfer quadrupole is disposed in another chamber; wherein the vacuum degree of different chambers is different.

10. The mass spectrometry detection system of any of claims 7 to 9, wherein the focusing structure is an ion funnel, a radio frequency quadrupole, or an ion mobility spectrometry structure.

Background

The mass spectrometry is an analysis method in which substance particles are ionized into ions, and they are separated into a mass-to-nuclear ratio by a stable or variable electric field or magnetic field in accordance with spatial position, time sequence, etc., and the intensity thereof is detected to perform qualitative and quantitative analysis. Tandem analysis, which is one of the methods of mass spectrometry, has been widely used in various fields in recent years.

In a conventional tandem Mass spectrometry apparatus, Ion traps are serially connected at a front stage of a Time-of-flight Mass Spectrometer (IT-TOFMS) to combine to obtain an Ion Trap Time-of-flight Mass Spectrometer (IT-TOFMS), wherein the Ion traps are used for selecting and holding ions, and the ions to be detected are cracked by CID (Collision-Induced Dissociation) so as to perform Time-of-flight Mass spectrometry later. Therefore, the mass analysis mode of the traditional tandem mass spectrometry equipment is still single flight time mass analysis, the passing distance from the generation of the ions to the detection is relatively long, the probability of ion loss is high, and the requirements of high resolution and high ion utilization rate cannot be met at the same time.

Therefore, the conventional tandem mass spectrometry device has the disadvantage of limited application scenarios.

Disclosure of Invention

Based on this, there is a need to provide a tandem mass spectrometry device and a mass spectrometry detection system, which overcome the limitation of the application scenario of the conventional tandem mass spectrometry device.

A tandem mass spectrometry apparatus comprising focussing means, a time of flight mass analyser, an ion trap mass analyser and control means;

the focusing device is used for focusing ions to be detected so that the ions to be detected reach the subsequent time-of-flight mass analyzer;

the control device is used for carrying out voltage time sequence control on electrodes in the flight time mass analyzer and the ion trap mass analyzer according to test requirements, adjusting the running track of the ions to be tested and realizing the switching of working modes of the flight time mass spectrometry or the ion trap mass spectrometry;

the time-of-flight mass analyzer is used for performing time-of-flight mass spectrometry on the ions to be detected when the working mode is time-of-flight mass spectrometry, and is also used for transmitting the ions to be detected to the ion trap mass analyzer at the later stage when the working mode is ion trap mass spectrometry;

and the ion trap mass analyzer is used for carrying out ion trap mass spectrometry on the ions to be detected which pass through the time-of-flight mass analyzer when the working mode is ion trap mass spectrometry.

In one embodiment, the focusing device comprises a focusing unit and a deflecting unit;

the focusing unit is used for focusing ions to be detected so that the ions to be detected reach the deflection unit;

the deflection unit is used for refocusing the ions to be detected so as to enable the ions to be detected to reach the time-of-flight mass analyzer at the later stage.

In one embodiment, the focusing device is a combination of one or more of a grid type electrostatic quadrupole, a circular lens group, a direct current quadrupole and a deflection electrode. In one embodiment, the time-of-flight mass analyser comprises modulating means, accelerating means, reflecting means and detecting means;

the modulation device is arranged in a modulation area and is used for modulating the running track of the ions to be detected so that the ions to be detected enter an acceleration area or reach the ion trap mass analyzer;

the accelerating device is arranged in the accelerating area and used for accelerating the ions to be detected entering the accelerating area, so that the ions to be detected pass through the field-free area after being accelerated and enter the reflecting area;

the reflecting device is arranged in the reflecting area and used for reflecting the ions to be detected entering the reflecting area, so that the ions to be detected pass through the field-free area to reach the detection area after being reflected;

the detection device is arranged in the detection area and used for detecting the ions to be detected entering the detection area.

In one embodiment, the modulation device comprises a first slit electrode, a gate electrode, and a repulsion plate; the first slit electrode is arranged at the entrance of the modulation region; the gate electrode is arranged at the modulation region outlet, and an ion channel of the gate electrode is aligned with an ion inlet of the ion trap mass analyzer;

the repulsion plate is arranged between the first slit electrode and the gate electrode and used for modulating the running track of the ions to be detected when the working mode is flight time mass spectrometry so that the ions to be detected enter the acceleration area.

In one embodiment, the ion trap mass analyser comprises a first end cap electrode, a reaction electrode, a second end cap electrode and an ion detection means; the first end cap electrode and the second end cap electrode are oppositely arranged, and the reaction electrode is arranged between the first end cap electrode and the second end cap electrode;

the first end cover electrode is arranged at an ion inlet of the ion trap mass analyzer, and the ion detection device is arranged at an ion outlet of the ion trap mass analyzer;

the first end cover electrode is used for opening the ion inlet when the working mode is ion trap mass spectrometry so that ions to be detected reach the ion trap through the ion inlet;

the reaction electrode is used for forming the ion trap and enabling the ion trap to act on the ions to be detected, and finally enabling the ions to be detected to reach the ion detection device;

the ion detection device is used for detecting the ions to be detected.

A mass spectrum detection system comprises a capillary tube, a focusing structure, a transmission quadrupole rod and the tandem mass spectrum equipment which are sequentially arranged along an ion running channel to be detected.

In one embodiment, the mass spectrometer further comprises a quadrupole mass filter and a collision cell, wherein the quadrupole mass filter and the collision cell are sequentially arranged between the transmission quadrupole and the tandem mass spectrometry equipment.

In one embodiment, the capillary and the focusing structure are disposed in the same chamber, and the transfer quadrupole is disposed in another chamber; wherein the vacuum degree of different chambers is different.

In one embodiment, the focusing structure is an ion funnel, a radio frequency quadrupole, or an ion mobility spectrometry structure.

The tandem mass spectrometry equipment comprises a time-of-flight mass analyzer and an ion trap mass analyzer arranged at the rear stage of the time-of-flight mass analyzer, wherein the control device performs voltage time sequence control on electrodes in the time-of-flight mass analyzer and the ion trap mass analyzer according to test requirements, adjusts the running track of ions to be tested, can realize the switching of working modes of time-of-flight mass spectrometry or ion trap mass spectrometry, can realize time-of-flight mass spectrometry and ion trap mass spectrometry on the same mass spectrometry equipment, and is favorable for expanding the application scene of the tandem mass spectrometry equipment.

Drawings

In order to more clearly illustrate the technical solutions in the embodiments or the conventional technologies of the present application, the drawings used in the descriptions of the embodiments or the conventional technologies will be briefly introduced below, it is obvious that the drawings in the following descriptions are only some embodiments of the present application, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.

FIG. 1 is a block diagram of the components of a tandem mass spectrometry apparatus in one embodiment;

FIG. 2 is a block diagram of the components of a time-of-flight mass analyzer in one embodiment;

FIG. 3 is a schematic diagram of an embodiment of a tandem mass spectrometry apparatus;

FIG. 4 is a schematic diagram of the structure of a tandem mass spectrometry apparatus in another embodiment;

FIG. 5 is a schematic axial electric field at various locations in a tandem mass spectrometry apparatus in one embodiment;

FIG. 6 is a timing diagram of voltages on the repeller plate and the first cap electrode in one embodiment;

FIG. 7 is a timing diagram of voltages on the repelling plate and the first cap electrode according to another embodiment;

FIG. 8 is a schematic diagram showing the timing of voltages applied to the repelling plate and the first cap electrode in yet another embodiment;

FIG. 9 is a block diagram of the components of a mass spectrometry detection system in one embodiment;

FIG. 10 is a schematic diagram of a mass spectrometry detection system in one embodiment;

FIG. 11 is a block diagram of the components of a mass spectrometry detection system in another embodiment;

FIG. 12 is a schematic diagram of a mass spectrometry detection system in another embodiment.

Detailed Description

To facilitate an understanding of the present application, the present application will now be described more fully with reference to the accompanying drawings. Embodiments of the present application are set forth in the accompanying drawings. This application may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein in the description of the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

It will be understood that, as used herein, the terms "first," "second," and the like may be used herein to describe various elements, but these elements are not limited by these terms. These terms are only used to distinguish one element from another.

Spatial relational terms, such as "under," "below," "under," "over," and the like may be used herein to describe one element or feature's relationship to another element or feature as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements or features described as "below" or "beneath" other elements or features would then be oriented "above" the other elements or features. Thus, the exemplary terms "under" and "under" can encompass both an orientation of above and below. In addition, the device may also include additional orientations (e.g., rotated 90 degrees or other orientations) and the spatial descriptors used herein interpreted accordingly.

As used herein, the singular forms "a", "an" and "the" may include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises/comprising," "includes" or "including," etc., specify the presence of stated features, integers, steps, operations, components, parts, or combinations thereof, but do not preclude the presence or addition of one or more other features, integers, steps, operations, components, parts, or combinations thereof.

In one embodiment, as shown in fig. 1, there is provided a tandem mass spectrometry apparatus comprising a focusing means 110, a time-of-flight mass analyser 130, an ion trap mass analyser 140 and a control means 150. The focusing device 110 is used for focusing ions to be measured, so that the ions to be measured reach the time-of-flight mass analyzer 130 at the later stage; the control device 150 is configured to perform voltage timing control on the electrodes in the time-of-flight mass analyzer 130 and the ion trap mass analyzer 140 according to the test requirements, adjust the operation trajectory of the ions to be tested, and implement switching of the operation modes of the time-of-flight mass spectrometry or the ion trap mass spectrometry. The time-of-flight mass analyzer 130 is configured to perform time-of-flight mass spectrometry on the ions to be detected when the operating mode is time-of-flight mass spectrometry, and is further configured to transmit the ions to be detected to the subsequent ion trap mass analyzer 140 when the operating mode is ion trap mass spectrometry; the ion trap mass analyzer 140 is configured to perform ion trap mass analysis on the ions to be measured passing through the time-of-flight mass analyzer 130 when the operation mode is ion trap mass analysis.

The focusing device 110 may be a lens set or a quadrupole rod, and is a hardware device capable of focusing and deflecting ions to be detected. In one embodiment, the focusing device 110 is a combination of one or more of a grid-type electrostatic quadrupole, a circular lens set, a dc quadrupole, and a deflection electrode. The time-of-flight mass analyser 130 is a mass analyser which calculates the mass to charge ratio of ions by measuring the time taken for ions accelerated by the same voltage to pass through the flight channel to reach the detection means. The time-of-flight mass analyzer 130 may be a unipolar time-of-flight mass analyzer or a bipolar time-of-flight mass analyzer. The ion trap mass analyzer 140 implements mass spectrometry of ions to be detected by forming an ion trap and then using the ion trap to perform cooling, trapping, isolating, collision induced dissociation and other processes on the ions to be detected. The ion trap mass analyzer 140 may be a linear ion trap mass analyzer or a three-dimensional ion trap mass analyzer. The control device 140 may be a device including various types of controllers or control chips and peripheral circuits thereof.

Specifically, the focusing device 110 is disposed at a front stage of the time-of-flight mass analyzer 130, and is used for focusing the ions to be measured, so as to ensure that the ions to be measured reach the time-of-flight mass analyzer 130. The control device 150 is configured to perform voltage timing control on the electrodes in the time-of-flight mass analyzer 130 and the ion trap mass analyzer 140 according to the specific test requirements of the sample to be tested, adjust the movement trajectory of the ions to be tested, and implement switching of the working modes of the time-of-flight mass spectrometry or the ion trap mass spectrometry. The control device 140 can control the output of the power supply device to control the voltage of the electrode.

Further, when the operation mode is time-of-flight mass spectrometry, the time-of-flight mass analyzer 130 performs time-of-flight mass spectrometry on the ions to be detected. When the working mode is ion trap mass spectrometry, ions to be detected pass through the time-of-flight mass analyzer 130 and reach the ion trap mass analyzer 140 at the subsequent stage of the time-of-flight mass analyzer 130, and the ion trap mass analyzer 140 performs ion trap mass spectrometry on the ions to be detected.

It can be understood that, for the same ion to be detected, the control device 150 may switch the operation mode to implement time-of-flight mass spectrometry or ion trap mass spectrometry. And aiming at the same sample to be detected, the control device 150 carries out fast switching of working modes in real time, so that flight time mass spectrometry and ion trap mass spectrometry of different ions to be detected can be respectively carried out at different time nodes, and the requirements of high resolution and high ion utilization rate are considered at the same time.

The tandem mass spectrometry device comprises the time-of-flight mass analyzer 130 and the ion trap mass analyzer 140 arranged at the rear stage of the time-of-flight mass analyzer 130, so that time-of-flight mass spectrometry and ion trap mass spectrometry can be realized on the same mass spectrometry device, and the requirements of high resolution and high ion utilization rate are met. In addition, the control device 150 performs voltage sequential control on the electrodes in the time-of-flight mass analyzer 130 and the ion trap mass analyzer 140 according to the test requirements, adjusts the running track of the ions to be tested, can realize the switching of the working modes of the time-of-flight mass spectrometry or the ion trap mass spectrometry, equivalently can match different working modes according to different test requirements, and is beneficial to expanding the application scene of the tandem mass spectrometry equipment.

In one embodiment, the focusing device 110 includes a focusing unit 111 and a deflecting unit 112 as shown in fig. 3. The focusing unit 111 is used for focusing the ions to be measured so that the ions to be measured reach the deflection unit; the deflection unit 112 is used to refocus the ions to be measured so that the ions to be measured reach the subsequent stage of the time-of-flight mass analyzer 130.

Among them, the focusing unit 111 and the deflecting unit 112 are sequentially disposed at a front stage of the time-of-flight mass analyzer 130. The focusing unit 111 may be a circular ring lens group or a dc quadrupole. The deflection unit 112 may be a deflection lens group or a deflection electrode. In one embodiment, the deflection unit 112 is a deflection lens set that can be adjusted up and down to align the ions to be measured with the entrance of the time-of-flight mass analyzer 130, ensuring that the ions to be measured enter the time-of-flight mass analyzer 130. The ion movement direction in the above description is the left-right direction.

In the above embodiment, the focusing unit 111 and the deflecting unit 112 are respectively arranged to realize focusing and deflecting of the detected ions, which is beneficial to improving the focusing quality of the detected ions and improving the ion utilization rate.

In one embodiment, as shown in fig. 2, the time-of-flight mass analyzer 130 includes a modulating device 131, an accelerating device 132, a reflecting device 133, and a detecting device 134. The modulation device 131 is disposed in the modulation region and is configured to modulate the trajectory of the ions to be measured, so that the ions to be measured enter the acceleration region or the ion trap mass analyzer 140. The accelerating device 132 is disposed in the accelerating region, and is configured to accelerate the ions to be detected entering the accelerating region, so that the ions to be detected pass through the field-free region after being accelerated and enter the reflecting region. The reflection device 133 is disposed in the reflection region, and configured to perform reflection processing on the ions to be detected entering the reflection region, so that the ions to be detected pass through the field-free region to reach the detection region after being reflected. The detection device 134 is disposed in the detection area and is used for detecting the ions to be detected entering the detection area.

The modulation device 131 may be a device including a deflection electrode, and modulates the movement trajectory of the ions to be measured by applying a deflection electric field to the ions to be measured. The accelerating device 132 may be a device including an accelerating electrode, which increases the moving speed of the ions to be measured by applying an accelerating electric field to the ions to be measured, so that the ions to be measured can pass through the field-free region to reach the reflection region. The reflecting device 133 may be a device including a mirror or a reflecting plate, and may push back the ions to be measured in flight to the field-free region. Detection device 134 is a device that contains a detector for receiving and detecting ions to be detected that reach a detection zone.

Specifically, the control device 150 changes the trajectory of the ions to be measured by controlling the voltage timing sequence of the deflection electrode in the modulation device 131. When the working mode is ion trap mass spectrometry, the running track of the ions to be detected passes through the modulation region and enters the ion trap mass analyzer 140; when the working mode is time-of-flight mass spectrometry, the movement trajectory of the ions to be detected sequentially passes through the modulation region, the acceleration region and the field-free region, reaches the reflection region, is reflected by the reflection device 133, and then passes through the field-free region to reach the detection region.

Furthermore, the modulation process of the modulation device 131 on the ions to be detected may be that only when one of the two working modes, i.e. ion trap mass spectrometry or time-of-flight mass spectrometry, a deflection electric field is applied to modulate the movement trajectory of the ions to be detected, so that the movement direction of the ions to be detected changes and reaches a subsequent ion trap mass analyzer or an acceleration region; or applying different deflection electric fields to perform operation track modulation on the ions to be detected respectively in two working modes of ion trap mass spectrometry and time-of-flight mass spectrometry so that the movement direction of the ions to be detected is changed in different degrees and reaches the ion trap mass analyzer 140 or the acceleration region at the later stage.

In the above embodiment, the modulation device 131 is arranged to modulate the movement trajectory of the ions to be detected, so that the ions to be detected reach the ion trap mass analyzer or the acceleration region, thereby realizing ion trap mass spectrometry or time-of-flight mass spectrometry, and the ion trap mass spectrometer has a simple structure, and is beneficial to reducing the cost of tandem mass spectrometry equipment.

In one embodiment, as shown in fig. 3, the modulation device 131 includes a first slit electrode 1311, a gate electrode 1312, and a repulsive plate 1313; the first slit electrode 1311 is disposed at the modulation region entrance; a gate electrode 1312 is disposed at the modulation region exit, and the ion channel of the gate electrode 1312 is aligned with the ion entrance of the ion trap mass analyzer 140. The repulsion plate 1313 is disposed between the first slit electrode 1311 and the gate electrode 1312, and is configured to modulate a moving trajectory of the ions to be detected when the working mode is time-of-flight mass spectrometry, so that the ions to be detected enter the acceleration region.

Specifically, the first slit electrode 1311 is disposed at an inlet of the modulation region, and an ion channel of the first slit electrode 1311 is an entrance channel of the modulation region 1 for ions to be detected; the gate electrode 1312 is disposed at the exit of the modulation region, and the ion channel of the gate electrode 1312 is aligned with the ion entrance of the ion trap mass analyzer 140, so that when the operation mode is ion trap mass analysis, the ions to be measured can reach the ion trap mass analyzer 140 through the ion channel. The repulsion plate 1313 is disposed between the first slit electrode 1311 and the gate electrode 1312, and the control device 150 changes the movement trajectory of the ions to be detected according to the voltage timing sequence of the repulsion plate 1313. When a high-level voltage is applied to the repulsion plate 1313, the operation mode is flight time mass spectrometry, and the ions to be detected are modulated and then deflected to enter the acceleration region 2. Further, the repulsion plate 1313 may be a circular arc electrode, a planar electrode, a grid electrode or a strip electrode, and the repulsion plate 1313 may be located at any position of the upper, lower, front or rear of the modulation region. That is, the shape and the specific orientation of the repulsion plate 1313 are not unique, and only the function of modulating the movement trajectory of the ions to be measured and making the ions to be measured enter the acceleration region 2 is required.

In one embodiment, the repulsion plate 1313 is perpendicular to the first slit electrode 1311 and the gate electrode 1312, and is disposed above the modulation region 1, the acceleration region 2 is disposed below the modulation region 1, and after a high voltage is applied to the repulsion plate 1313, the ions to be measured entering the modulation region 1 can be deflected downward to reach the acceleration region 2. Further, an isolation grid 1314 is provided between the modulation region 1 and the acceleration region 2 to perform electric field isolation.

In one embodiment, with continued reference to fig. 3, the acceleration device 132 includes a first acceleration grid 1321, a second acceleration grid 1322, and an acceleration zone pole piece 1323, the acceleration zone pole piece 1323 being disposed between the first acceleration grid 1321 and the second acceleration grid 1322. The reflection device 133 includes a primary reflection grid 1331, a secondary reflection grid 1332, and a reflection plate 1333, which are sequentially disposed, and a reflection region pole piece 1334 disposed between the primary reflection grid 1331 and the reflection plate 1333. The detection device 134 includes a detection zone grid 1341 and a detector 1342.

Specifically, as shown in fig. 3, after entering the modulation region 1, the ions to be detected are deflected by the repulsion plate 1313, enter the acceleration region 2, pass through the field-free region 3 along the operation track 6 to reach the reflection region 4 under the action of the acceleration electric field, pass through the field-free region 3 to reach the detection region 5 after being reflected by the reflection region 4, and finally reach the detector 1342 in the detection region 5, and are subjected to ion detection by the detector 1342, thereby completing the time-of-flight mass spectrometry. Further, in one embodiment, the first accelerating grid 1321 is further configured to cooperate with the repelling plate 1313 to deflect the ions to be detected. Specifically, a pulse signal with a polarity opposite to that of the repulsion plate 1313 may be applied to the first acceleration grid 1321, so that the electric field gradient between the repulsion plate 1313 and the first acceleration grid 1321 is increased, the deflection force of the ions to be detected is increased, and the action effect of the deflection electric field is improved.

In the above embodiment, the specific structural composition of each component in the time-of-flight mass analyzer 130 is given, and the structure is simple, which is beneficial to reducing the cost of the tandem mass spectrometer.

In one embodiment, continuing to refer to fig. 3, the ion trap mass analyzer 140 includes a first end cap electrode 141, a reaction electrode 142, a second end cap electrode 143, and an ion detection device 144. The first and second cap electrodes 141 and 143 are disposed opposite to each other, and the reaction electrode 142 is disposed between the first and second cap electrodes 141 and 143. The first end cap electrode 141 is disposed at an ion entrance of the ion trap mass analyzer 140 and the ion detection device 144 is disposed at an ion exit of the ion trap mass analyzer 140. The first end cover electrode 141 is used for opening an ion inlet when the working mode is ion trap mass spectrometry, so that ions to be detected reach the ion trap through the ion inlet; the reaction electrode 142 is used for forming an ion trap, and is also used for making the ion trap act on ions to be detected, and finally making the ions to be detected reach the ion detection device 144; the ion detection device 144 is used to detect ions to be detected.

The ion trap can limit ions in a limited space through an electromagnetic field, and comprises a three-dimensional ion trap and a linear ion trap. The first cap electrode 141, the reaction electrode 142, and the second cap electrode 143 are also different based on the type of the ion trap. For example, when the first and second end cap electrodes 141 and 143 are hyperboloid-shaped end cap electrodes and the reaction electrode 142 is a ring electrode, a three-dimensional ion trap may be formed; when the first and second end cap electrodes 141 and 143 are flat end cap electrodes and the reaction electrode 142 is two sets of hyperbolic rods, a linear ion trap can be formed. The present embodiment is not limited to a specific type of ion trap. Further, the ion trap mass analyzer 140 is also provided with a gas inlet to facilitate injection of the assist gas required for ion cooling and collision by the gas supply means from the gas inlet. The position of the gas inlet is not exclusive and may be disposed above or below the reaction electrode 142, for example. In one embodiment, the second end cap electrode 142 is disposed at the gas inlet of the ion trap mass analyzer 140.

Specifically, when the operation mode is ion trap mass spectrometry, the control device 150 controls the first end cap electrode 141 to be at a low level, the ion entrance of the ion trap mass analyzer 140 is opened, and the ions to be detected reach the ion trap through the ion entrance. The ion trap is formed by applying a voltage across the reaction electrode 142. Through applying radio frequency voltage and resonance voltage of different sizes on the reaction electrode 142, processes of trapping, cooling, isolating, collision induced dissociation and the like of ions to be detected by the ion trap can be realized. After the ions to be detected are accumulated to a certain number, the ions to be detected with different masses can enter an unstable state in sequence by changing the parameters of the electric field, and are ejected from the ion outlet to reach the ion detection device 144, so that the ion trap mass spectrometry is completed.

Further, referring to fig. 3 and 4, the ion trap mass analyzer 140 and the time-of-flight mass analyzer 130 may be in the same chamber, or may be in different chambers, and different vacuum degrees may be achieved in different chambers by an external molecular pump. Channels are reserved among the chambers so as to allow ions to be measured to pass through.

In the above embodiment, a specific structure of the ion trap mass analyzer 140 is provided, and when the working mode is ion trap mass spectrometry, ion trap mass spectrometry is performed on ions to be detected, which is beneficial to expanding the application scenario of tandem mass spectrometry equipment.

For ease of understanding, the operation mode switching process of the tandem mass spectrometry apparatus will be described in detail below with reference to fig. 5 and 8. As shown in fig. 5, a schematic diagram of the axial electric field at different positions is shown, wherein the axial direction refers to the central axis direction of the first slit electrode 1311. Wherein U1 and U2 are voltages applied to the repulsion plate 1313 for controlling whether ions to be measured enter the acceleration region 2 of the time-of-flight mass analyzer 130. U3 and U4 are voltages applied to the first end cap electrode 141 for controlling whether ions to be measured enter the ion trap mass analyzer 140. Further, after the ions to be measured enter the acceleration region 2 or the ion trap mass analyzer 140, the control device 150 can control the operation of the acceleration device 132 or the ion trap mass analyzer 140, respectively, to perform the subsequent mass spectrometry operation. Under the condition that the low-level voltage U4 is applied to the first end cap electrode 141, when the high-level voltage U1 is applied to the repulsion plate 1313, the ions to be detected enter the acceleration region 2; when the low level voltage U2 is applied by the repulsion plate 1313, the ions to be measured pass through the modulation region 1 and enter the ion trap mass analyzer 140 for accumulation and cooling. Under the condition that the high-level voltage U3 is applied to the first end cap electrode 141, the ions to be detected do not enter the ion trap mass analyzer 130 any more, and the ion trap mass analyzer 130 performs ion trap mass spectrometry on the accumulated ions to be detected. At this time, if the repulsion plate 1313 applies the high-level voltage U1, the ions to be detected enter the acceleration region 2; if the repulsion plate 1313 applies the low-level voltage U2, the ions to be detected collide with the gate electrode 1312 or the first end cap electrode 141 and then are dissipated.

In one embodiment, as shown in fig. 6, a pulse voltage signal having a period T1 is applied to the repulsive plate 1313, and a square wave voltage signal having a period T2 is applied to the first cap electrode 141. When the repulsion plate 1313 is provided with a high-level voltage U1, ions to be detected deflect to enter the acceleration region 2, and time-of-flight mass spectrometry is performed, wherein the duration time is t 1; when a low level voltage U2 is applied to the repeller plate 1313, ions to be measured pass axially through the modulation region 1 to the ion entrance of the ion trap mass analyzer 140. When a low-level voltage U4 is applied to the first end cap electrode 141, the ion gate is opened, ions to be detected enter the ion trap, the opening duration is t3, and when a high-level voltage U3 is applied to the first end cap electrode 141, the ion gate is closed, the ions to be detected cannot enter the ion trap, and the ions to be detected are dissipated after colliding with the gate electrode 1312 or the first end cap electrode 141, and the closing duration is t 4.

In another embodiment, as shown in fig. 7, a low level voltage U2 is applied to the repulsive plate 1313, and a square wave voltage signal having a period T2 is applied to the first cap electrode 141. The ions to be measured do not enter the acceleration region 2 of the time-of-flight mass analyser 130 but pass through the modulation region 1 to the ion entrance of the ion trap mass analyser 140. When a low-level voltage U4 is applied to the first end cap electrode 141, the ion gate is opened, ions to be detected enter the ion trap, the opening duration is t3, when a high-level voltage U3 is applied to the first end cap electrode 141, the ion gate is closed, the ions to be detected cannot enter the ion trap and are lost after impacting the cavity or the gate electrode 1312, and the closing duration is t 4; ions trapped in the ion trap are analyzed.

In yet another embodiment, as shown in fig. 8, a high level voltage U3 is applied to the first cap electrode 141, and a pulse voltage signal with a period T1 is applied to the repulsive plate 1313. When the repulsion plate 1313 is provided with a high-level voltage U1, ions to be detected deflect to enter the acceleration region 2, and time-of-flight mass spectrometry is performed, wherein the duration time is t 1; when the repulsion plate 1313 is under a low-level voltage U2, the ions to be detected pass through the modulation region 1 along the axial direction and then impact the cavity or the electrode to be lost, and the duration is t 2.

In the embodiment, different electrode voltage time sequence control modes in the flight time + ion trap mass spectrometry mode, the ion trap mass spectrometry mode and the flight time mass spectrometry mode are respectively provided, so that switching of multiple mass spectrometry modes can be realized, the requirements of high resolution and high sensitivity are met, and the application scene of tandem mass spectrometry equipment is further expanded.

In one embodiment, as shown in fig. 9, a mass spectrometry detection system is provided, which comprises a capillary 200, a focusing structure 300, a transmission quadrupole 400 and the tandem mass spectrometry apparatus 100 in the above embodiments, which are sequentially arranged along an ion travel channel to be detected.

For specific limitations of the tandem mass spectrometry apparatus 100, reference is made to the above description, which is not repeated herein. The focusing structure 300 may be an ion funnel, a radio frequency quadrupole, or an ion mobility spectrometry structure. Specifically, as shown in fig. 10, the ions to be detected sequentially pass through the capillary 200, the focusing structure 300 and the transmission quadrupole 400, and reach the tandem mass spectrometry device 100 for mass spectrometry. In one embodiment, the capillary 200 and the focusing structure 300 are disposed in the same chamber, and the transfer quadrupole 400 is disposed in another chamber; wherein, different vacuum degrees are realized by different cavities through an external molecular pump. Further, the transmission quadrupole 400 and the focusing unit 111 can be disposed in the same chamber, and a channel is reserved between the chambers for passing the ions to be measured. Slit electrodes 7 are disposed between the focusing structure 300 and the transmission quadrupole 400, and between the transmission quadrupole 400 and the focusing unit 111.

The mass spectrometry detection system forms a Q (Quadrupole) -TOF (Time of light) + ion trap structure, can realize the switching of the working modes of flight Time mass spectrometry or ion trap mass spectrometry, equivalently can match different working modes according to different test requirements, and is favorable for expanding the application scene of tandem mass spectrometry equipment.

In one embodiment, as shown in fig. 11, the mass spectrometry detection system further comprises a quadrupole mass filter 500 and a collision cell 600, the quadrupole mass filter 500 and the collision cell 600 being in turn arranged between the transfer quadrupole 400 and the tandem mass spectrometry device 100.

The quadrupole mass filter 500 is formed by a quadrupole field in which direct current and radio frequency are superimposed, and can filter ions to be detected, so that ions to be detected with specific mass enter the collision cell 600. The collision cell 600 may be a quadrupole collision cell, a six-pole collision cell, or an eight-pole collision cell, and is configured to convert ions to be detected into ions to be detected in a fragment state after collision, and enter the tandem mass spectrometry device 100.

Further, as shown in fig. 12, the collision cell 600 includes a third cap electrode 601, a multi-stage ion guide 602, and a fourth cap electrode 603, wherein the third cap electrode 601 and the fourth cap electrode 603 are oppositely disposed, and the multi-stage ion guide 602 is disposed between the third cap electrode 601 and the fourth cap electrode 603. The multi-stage ion guide 602 is used to provide an electric field to make the ions to be measured collide with the auxiliary gas and transform into the ions to be measured in a fragment state. Further, the collision cell 600 is further provided with a gas inlet for facilitating the gas supply device to inject the auxiliary gas required for ion collision from the gas inlet. The location of the gas inlet is not exclusive, for example in fig. 12, the gas inlet may be disposed above the multi-stage ion guide 602. In addition, the quadrupole mass filter 500 and the collision cell 600 are disposed in the same chamber as the focusing unit 111, and the transmission quadrupole 400 is disposed in another chamber, wherein a channel is reserved between the chambers for passing the ions to be measured.

In the above embodiment, an API (Atmospheric Pressure Ionization) -TOF (Time of light) + ion trap structure is formed, and mass spectrometry can be performed after filtering, which is beneficial to improving the detection accuracy of mass spectrometry.

The technical features of the above embodiments can be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the above embodiments are not described, but should be considered as the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present application, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the concept of the present application, which falls within the scope of protection of the present application. Therefore, the protection scope of the present patent shall be subject to the appended claims.