Cascade mass spectrometry system adopting multi-component gas and application

Abstract

The invention provides a cascade mass spectrometry system adopting multi-component gas and application, and belongs to the technical field of analytical instruments. The cascade mass spectrometry system comprises an atmospheric pressure interface module, a guide module, a mass analysis module and a detection module, wherein the atmospheric pressure interface module, the guide module, the mass analysis module and the detection module are connected in sequence; the guide module is a double-ion guide channel; and the mass analysis module comprises a quadrupole rod mass analyzer and an ion trap mass analyzer. The triple quadrupole mass spectrometer has high resolution and high sensitivity, has the advantages of high fragmentation efficiency of the triple quadrupole mass spectrometer and cascade mass spectrometry of the ion trap mass spectrometer, can effectively meet the analysis requirements of specific biological and drug samples, and has industrial utilization value.

Description

Technical Field

[0001] The present invention relates to the technical field of analytical instruments, and in particular, to a tandem mass spectrometry analysis system using multi-component gases and applications thereof.

Background Art

[0002] Mass spectrometry is an important instrumental method and is playing an increasingly important role in scientific research fields such as physics, chemistry, life sciences, and geology, as well as in cutting-edge application fields such as environmental protection, food hygiene, biopharmaceuticals, and clinical medicine. In recent years, with the continuous improvement of the accuracy requirements for the detection of trace and ultra-trace small molecule markers in industries such as environmental monitoring, food safety, and clinical diagnosis, traditional mass spectrometry instruments such as single quadrupole mass spectrometers can no longer meet the needs of highly accurate and sensitive qualitative and quantitative detection. The tandem mass spectrometry analysis method has the characteristics of high precision, strong specificity, high sensitivity, low cost, high throughput, etc., and can realize the rapid qualitative and quantitative analysis of multi-component and low-content compounds in complex matrices. Therefore, tandem mass spectrometry analysis technology has gradually become the "gold standard" for the detection of trace and ultra-trace substances in complex samples and is playing an increasingly important role in the detection field.

[0003] Currently, the most widely used commercial tandem analysis mass spectrometry instrument is the triple quadrupole mass spectrometer. The triple quadrupole mass spectrometer consists of three spatially connected quadrupole mass analyzers in series. Among them, the first and third quadrupole mass analyzers have the function of mass analysis, and the purpose of mass selection is achieved by combining radio frequency and direct current potentials. The second quadrupole serves as a collision cell and only applies a radio frequency voltage. There is usually a relatively high gas pressure in the collision cell, and the gas in the collision cell can collide with ions, resulting in ion dissociation and the generation of fragment ions. To ensure the collision efficiency, the gas used in the collision cell is usually nitrogen, and other heavier noble gases such as argon and xenon can also be used, which can provide higher collision energy and higher ion dissociation efficiency.

[0004] In recent years, the prior art has developed a new type of tandem mass spectrometry instrument (Q-LIT) that directly couples and connects a quadrupole and an ion trap mass analyzer in series. The main feature is to spatially connect and synchronously couple the quadrupole and the ion trap. The quadrupole is used to select the analyte ions with specific mass-to-charge ratios to enter the ion trap, and the ion trap is used to enrich, dissociate, and detect the analyte ions. Compared with the triple quadrupole, there is no need for a dedicated collision cell to implement dissociation, the system structure is simple, and the ion transmission and utilization efficiency are high. In addition, the ion trap can perform multi-stage tandem (MSn, n≥3) tandem mass spectrometry analysis, which is very suitable for qualitative and quantitative analysis of samples with a large variety, low content, and complex matrix.

[0005] However, to ensure a high scanning speed and resolution during ion trap mass spectrometry detection, the working pressure of the buffer gas in the ion trap mass analyzer is usually relatively low, which affects the ion capture efficiency and fragmentation efficiency. In addition, helium is usually used as the buffer gas in the ion trap. As a traditional collision gas, helium has advantages such as high detection sensitivity and resolution. However, in the collision-induced dissociation process (CID) of ion trap tandem mass spectrometry analysis, helium usually has a poor fragmentation effect. The reason is that the maximum internal energy that can be converted into the internal energy of an ion in a single collision between an ion and a collision gas molecule can be calculated by the following formula (1):

[0006]

[0007] Where E Com is the maximum internal energy that the parent ion can obtain in a single collision, M n represents the mass of the collision gas molecule or atom, M p represents the mass of the ion, and E Lab represents the kinetic energy of the ion in the laboratory coordinate system of the ion. Because of its small mass, helium can transfer less internal energy to the parent ion in a single collision, resulting in a poor fragmentation efficiency of the parent ion. If a large molecular weight gas such as nitrogen or argon is used as the collision gas, a stronger collision force can be provided, so that more internal energy is generated when the parent ion collides, thereby enriching the fragment ions. In addition, larger mass collision gas molecules also contribute to the improvement of the low mass cut-off effect of the ion trap. However, large molecular weight gases such as nitrogen and argon have a more obvious scattering effect on the analyte ions during ion trap scanning detection, seriously reducing the resolution and sensitivity of the spectrum.

[0008] Therefore, it is necessary to study a tandem mass spectrometry analysis system and application using multi-component gases to address the deficiencies of the prior art and solve or mitigate one or more of the above problems.

Summary of the Invention

[0009] In view of this, the present invention provides a tandem mass spectrometry analysis system and application using multi-component gases. This device can be used for analysis in the fields of analytical chemistry, physical chemistry, biomedicine, energy environment, etc. While having high-resolution and high-sensitivity performance, it also has the performance advantages of high fragmentation efficiency of triple quadrupole mass spectrometers and the ability to perform tandem mass spectrometry analysis of ion trap mass spectrometers, and can effectively meet the analysis requirements for specific biological and drug samples, having industrial utilization value.

[0010] On the one hand, the present invention provides a tandem mass spectrometry analysis system using multi-component gases. The tandem mass spectrometry analysis system includes an atmospheric pressure interface module, a guiding module, a mass analysis module, and a detection module, and the atmospheric pressure interface module, the guiding module, the mass analysis module, and the detection module are connected in sequence;

[0011] The guiding module is a dual-ion guiding channel;

[0012] The mass analysis module includes a quadrupole mass analyzer and an ion trap mass analyzer;

[0013] The dual-ion guiding channel is connected to the quadrupole mass analyzer and the ion trap mass analyzer.

[0014] In the above-described aspects and any possible implementation, a further implementation is provided. The atmospheric pressure interface module includes a heated capillary, a lens barrel lens, and a sampling cone. One end of the lens barrel lens is connected to the sampling cone, and the other end is connected to the heated capillary.

[0015] In the above-described aspects and any possible implementation, a further implementation is provided. The tandem mass spectrometry analysis system further includes a pulse valve. The pulse valve is located on the right side of the ion trap mass analyzer and is used to ensure that the gas generated by the pulse valve enters the ion trap mass analyzer, and at the same time, the pulse valve does not affect the operation of the ion trap mass analyzer.

[0016] In the above-described aspects and any possible implementation, a further implementation is provided. A continuous buffer gas is introduced into the ion trap, and the continuous buffer gas includes, but is not limited to, helium.

[0017] In the above-described aspects and any possible implementation, a further implementation is provided. An application of a tandem mass spectrometry analysis system using a multi-component gas is realized through the described tandem mass spectrometry analysis system. The application specifically includes: performing tandem mass spectrometry analysis through the tandem mass spectrometry analysis system and performing molecular ion reactions through the tandem mass spectrometry analysis system.

[0018] In the above-described aspects and any possible implementation, a further implementation is provided. When performing tandem mass spectrometry analysis through the tandem mass spectrometry analysis system, through the adjustment of the pulse valve controller, the pulsed collision gas enters the ion trap during the cooling and collision-induced dissociation time segments and collides with the ions in the trap, and is pumped away by the vacuum pump during the cooling time segment before the sampling time segment.

[0019] In the above-described aspects and any possible implementation, a further implementation is provided. When performing molecular ion reactions through the tandem mass spectrometry analysis system, through the adjustment of the pulse valve controller, the pulsed reaction gas enters the ion trap during the reaction time segment and collides and reacts with the ions in the trap, and is pumped away by the vacuum pump before the sampling time segment.

[0020] In the above-described aspects and any possible implementation, a further implementation is provided. When performing tandem mass spectrometry analysis through the tandem mass spectrometry analysis system, only the continuous buffer gas is in the ion trap during sampling.

[0021] In the aspects and any possible implementation manners described above, an implementation manner is further provided. In the tandem mass spectrometry analysis performed by the tandem mass spectrometry system, according to the requirements of the tandem stage number, the pulse valve can be opened multiple times within a single working cycle to implement multi-stage tandem MSn (n≥3) tandem mass spectrometry analysis of the analyte.

[0022] In the aspects and any possible implementation manners described above, an implementation manner is further provided. In the molecular ion reaction performed by the tandem mass spectrometry system, only continuous buffer gas is present in the ion trap during sampling.

[0023] Compared with the prior art, the present invention can achieve the following technical effects:

[0024] Through the development of the device and method, the present invention realizes the tandem mass spectrometry analysis of multi-component gas by an ion trap mass analyzer. Compared with the traditional method, the present invention can simultaneously achieve high fragmentation efficiency, high resolution, and high-sensitivity mass spectrometry analysis. In addition, the present invention also provides a reaction device and reaction method for molecular ion reactions.

[0025] Of course, it is not necessary for any product implementing the present invention to achieve all the above-described technical effects simultaneously.

Description of the Drawings

[0026] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention, and those of ordinary skill in the art can also obtain other drawings based on these drawings without creative efforts.

[0027] Figure 1 is a structural diagram of a tandem mass spectrometry analysis device using multi-component gas provided by an embodiment of the present invention;

[0028] Figure 2 is a timing diagram of a tandem mass spectrometry analysis method using multi-component gas provided by an embodiment of the present invention;

[0029] Figure 3 is a timing diagram of a multi-stage tandem (MS n n≥3) tandem mass spectrometry analysis method using multi-component gas provided by an embodiment of the present invention;

[0030] Figure 4 is a timing diagram of a molecular ion reaction method using multi-component gas provided by an embodiment of the present invention;

[0031] Figure 5 is a diagram of helium continuous gas fragmentation of triphenylmethyl cation provided by an embodiment of the present invention;

[0032] Figure 6 It is a diagram of the fragmentation of triphenylmethyl cation by continuous helium gas and pulsed carbon dioxide gas provided by an embodiment of the present invention;

[0033] Figure 7 It is a diagram of the daughter ion m / z 108 of triphenylmethyl cation provided by an embodiment of the present invention;

[0034] Figure 8 It is a diagram of the reaction of the daughter ion m / z 108 of triphenylmethyl cation with acetone provided by an embodiment of the present invention.

[0035] Among them, in the figure: A: heating capillary, B: tube lens, C: Skimmer, D: first ion guide, E: second ion guide, F: quadrupole mass analyzer, G: ion trap mass analyzer, H: detector, I: continuous gas, J: pulsed valve.

Detailed implementation manners

[0036] For a better understanding of the technical solution of the present invention, the embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0037] It should be clear that the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0038] The terms used in the embodiments of the present invention are only for the purpose of describing specific embodiments, and are not intended to limit the present invention. The singular forms "a", "the" and "said" used in the embodiments of the present invention and the appended claims are also intended to include the plural forms, unless the context clearly indicates otherwise.

[0039] The present invention provides a tandem mass spectrometry analysis system using multi-component gases. The tandem mass spectrometry analysis system includes an atmospheric pressure interface module, a guiding module, a mass analysis module and a detection module, and the atmospheric pressure interface module, the guiding module, the mass analysis module and the detection module are connected in sequence;

[0040] The guiding module is a dual ion guiding channel;

[0041] The mass analysis module includes a quadrupole mass analyzer and an ion trap mass analyzer;

[0042] The dual ion guiding channel is connected to the quadrupole mass analyzer and the ion trap mass analyzer.

[0043] The atmospheric pressure interface module includes a heating capillary, a tube lens and a skimmer, and one end of the tube lens is connected to the skimmer, and the other end is connected to the heating capillary.

[0044] The tandem mass spectrometry analysis system further includes a pulse valve, which is located on the right side of the ion trap mass analyzer and is used to ensure that the gas generated by the pulse valve enters the ion trap mass analyzer, and at the same time, the pulse valve does not affect the operation of the ion trap mass analyzer.

[0045] Continuous buffer gas is introduced into the ion trap, and the continuous buffer gas includes but is not limited to helium.

[0046] The present invention also provides an application of a tandem mass spectrometry analysis system using multi-component gases, which is realized by the described tandem mass spectrometry analysis system. The application specifically includes: performing tandem mass spectrometry analysis through the tandem mass spectrometry analysis system and performing molecular ion reactions through the tandem mass spectrometry analysis system.

[0047] For the tandem mass spectrometry analysis through the tandem mass spectrometry analysis system, through the adjustment of the pulse valve controller, the pulsed collision gas enters the ion trap during the cooling and collision-induced dissociation time segments and collides with the ions in the trap, and is pumped away by the vacuum pump during the cooling time segment before the sampling time segment.

[0048] For the molecular ion reaction through the tandem mass spectrometry analysis system, through the adjustment of the pulse valve controller, the pulsed reaction gas enters the ion trap during the reaction time segment and collides and reacts with the ions in the trap, and is pumped away by the vacuum pump before the sampling time segment.

[0049] During sampling, only the continuous buffer gas is in the ion trap.

[0050] Example 1:

[0051] Based on the Q-LIT mass spectrometer, the present invention designs a tandem mass spectrometry analysis device that can use multi-component gases and develops related analysis methods. While having high-resolution and high-sensitivity performance, it also has the performance advantages of high fragmentation efficiency of triple quadrupole mass spectrometers and the ability to perform tandem mass spectrometry analysis of ion trap mass spectrometers, and can effectively meet the analysis requirements for specific biological and drug samples, and has industrial utilization value.

[0052] As Figure 1 shown, a tandem mass spectrometry analysis device using multi-component gases according to the present invention is composed of a heated capillary, a tube lens, a Skimmer, a first ion guide, a second ion guide, a quadrupole mass analyzer, an ion trap mass analyzer, continuous gas, a pulse valve, a detector, etc.

[0053] Continuous buffer gas is introduced into the ion trap, usually helium.

[0054] When the pulse valve is opened, pulsed collision gas can be introduced into the ion trap, usually large molecular weight gases such as nitrogen, argon, carbon dioxide, etc., or pulsed reaction gas can also be introduced into the ion trap.

[0055] The pulse valve is located on one side of the ion trap mass analyzer to ensure that the gas generated by the pulse valve effectively enters the ion trap mass analyzer, and at the same time, the pulse valve does not affect the normal operation of the ion trap mass analyzer.

[0056] The pulse valve is driven by a pulse valve controller, which can adjust basic parameters such as the working timing, frequency, and pulse width of the pulse valve.

[0057] The present invention provides a tandem mass spectrometry analysis method using multi-component gases. The tandem mass spectrometry analysis method is operated based on the tandem mass spectrometry analysis device using multi-component gases described in any of the foregoing aspects. The method includes a tandem mass spectrometry analysis method and a molecular ion reaction method.

[0058] In a specific embodiment, as Figure 3 shown, during tandem mass spectrometry analysis, through the adjustment of the pulse valve controller, the pulsed collision gas enters the ion trap during the cooling and CID (Collision Induced Dissociation) time segments and collides with the ions in the trap, and is pumped away by the vacuum pump during the Cooling time segment before the sample time segment. During sampling, the gas in the ion trap is only the continuous buffer gas.

[0059] Furthermore, to maximize the collision induced dissociation effect of the pulsed collision gas, the time length of the cooling time segment before the CID and sample time segments is adjustable, ensuring that the parent ions fully interact with the pulsed collision gas during collision induced dissociation, improving the fragmentation efficiency, and at the same time, the pulsed gas is completely pumped away during ion trap scanning, ensuring the resolution and sensitivity of the spectrum.

[0060] Furthermore, according to the requirements of the tandem series, the pulse valve can be opened multiple times within a single working cycle to achieve multi-stage tandem (MSn n≥3) tandem mass spectrometry analysis of the analyte.

[0061] In a specific embodiment, during molecular ion reaction, through the adjustment of the pulse valve controller, the pulsed reaction gas enters the ion trap during the reaction time segment and collides and reacts with the ions in the trap, and is pumped away by the vacuum pump before the sample time segment. During sampling, the gas in the ion trap is only the continuous buffer gas.

[0062] Furthermore, according to the requirements of the molecular ion reaction, the pulse valve can be opened multiple times within a single working cycle to achieve continuous multiple reactions of the product ions and precisely control the reaction process.

[0063] Specifically, the tandem mass spectrometry analysis method:

[0064] Use helium continuous gas and carbon dioxide as pulsed gas to dissociate triphenylmethyl cation (m / z 277). Through the pulsed valve controller, adjust the pulse opening time to find the gas inlet position, so that it covers the fragmentation in the CID section but does not affect the scanning in the Sample section, as Figure 2 shown; adjust the pulse duration to control the gas intake, and introduce as much carbon dioxide as possible under the condition of ensuring that the vacuum degree is not affected. Trigger the pulsed valve in the Cooling section before CID to make carbon dioxide enter the ion trap, so that it collides and dissociates with triphenylmethyl cation. Its m / z = 108, FWHM = 0.40; m / z = 184, FWHM = 0.45; dissociation efficiency: 86.8%. Compare with pure helium: m / z = 108, FWHM = 0.40; m / z = 184, FWHM = 0.45; dissociation efficiency: 75.47%. The dissociation efficiency is improved under the condition of ensuring the full width at half maximum, as Figure 5 and Figure 6 shown.

[0065] Specifically, the molecular ion reaction method:

[0066] Use helium continuous gas to perform secondary fragmentation on triphenylmethyl cation (m / z 277), and extract the daughter ion m / z 108, which fully reacts with the neutral pulsed gas acetone in the reaction section, as Figure 4 shown. The daughter ion m / z 108 reacts with acetone to undergo substitution, addition and other reactions, generating new substances, which provides a new platform for the study of chemical reaction mechanisms, as Figure 7 and Figure 8 shown.

[0067] The above has introduced in detail a tandem mass spectrometry analysis system and its application using multi-component gases provided by the embodiments of the present application. The description of the above embodiments is only used to help understand the method and its core idea of the present application; at the same time, for those of ordinary skill in the art, according to the idea of the present application, there will be changes in the specific implementation manner and application scope. In summary, the content of this specification should not be construed as a limitation to the present application.

[0068] As used in the specification and claims, certain terms are used to refer to specific components. Those skilled in the art should understand that hardware manufacturers may use different terms to refer to the same component. The specification and claims do not distinguish components by the difference in names, but by the difference in functions. As used throughout the specification and claims, the terms "comprising" and "including" are open-ended terms and should be interpreted as "comprising / including but not limited to". "Substantially" means within an acceptable error range. Those skilled in the art can solve the technical problem within a certain error range and basically achieve the technical effect. The following description in the specification is the preferred embodiment for implementing the present application, but the description is for the purpose of explaining the general principles of the present application and not for limiting the scope of the present application. The protection scope of the present application shall be subject to that defined by the appended claims.

[0069] It should also be noted that the term "including", "comprising" or any other variant thereof is intended to cover non-exclusive inclusion, so that a commodity or system including a series of elements not only includes those elements, but also includes other elements not expressly listed, or also includes elements inherent to such commodity or system. Without further limitation, the element defined by the statement "including one..." does not exclude the existence of another identical element in the commodity or system including the said element.

[0070] It should be understood that the term "and / or" used herein is merely an associative relationship describing associated objects, indicating that three relationships may exist. For example, A and / or B may represent: A exists alone, A and B exist simultaneously, and B exists alone. In addition, the character " / " herein generally represents an "or" relationship between the associated objects before and after.

[0071] The above description shows and describes several preferred embodiments of the present application. However, as mentioned above, it should be understood that the present application is not limited to the form disclosed herein, should not be regarded as excluding other embodiments, but can be used in various other combinations, modifications and environments, and can be changed within the scope of the application concept described herein through the above teachings or the technology or knowledge in the relevant field. And the changes and variations made by those skilled in the art that do not depart from the spirit and scope of the present application shall all be within the protection scope of the appended claims of the present application.

Claims

1. A cascade mass spectrometry analysis system using multi-component gases, characterized in that: The tandem mass spectrometry analysis system comprises an atmospheric pressure interface module, a guide module, a mass analysis module and a detection module, wherein the atmospheric pressure interface module, the guide module, the mass analysis module and the detection module are connected in sequence; The guiding module is a dual ion guiding channel; The mass analysis module comprises a quadrupole mass analyzer and an ion trap mass analyzer, and the dual ion guide channel connects the quadrupole mass analyzer and the ion trap mass analyzer.

2. The tandem mass spectrometry system according to claim 1, characterized in that: The atmospheric pressure interface module comprises a heating capillary, a lens barrel and a sampling cone. One end of the lens barrel is connected to the sampling cone, and the other end is connected to the heating capillary.

3. The tandem mass spectrometry system according to claim 1, characterized in that: The tandem mass spectrometry system also includes a pulse valve, which is located on the right side of the ion trap mass analyzer and is used to ensure that the gas generated by the pulse valve enters the ion trap mass analyzer, while the pulse valve does not affect the operation of the ion trap mass analyzer.

4. The tandem mass spectrometry system according to claim 1, characterized in that: A continuous buffer gas is passed through the ion trap, and the continuous buffer gas includes but is not limited to helium.

5. An application of a tandem mass spectrometry system using a multi-component gas, implemented by the tandem mass spectrometry system according to any one of claims 1 to 4, characterized in that: The application specifically includes: performing tandem mass spectrometry analysis by the tandem mass spectrometry analysis system and performing molecular ion reaction by the tandem mass spectrometry analysis system.

6. The use according to claim 5, characterized in that: The tandem mass spectrometry analysis is performed by the tandem mass spectrometry analysis system. Through the adjustment of the pulse valve controller, the pulse collision gas enters the ion trap during the cooling and collision induced dissociation time period and collides with the ions in the trap, and is pumped away by the vacuum pump during the cooling time period before the sampling time period.

7. The use according to claim 5, characterized in that: The molecular ion reaction is carried out through the tandem mass spectrometry analysis system. Through the adjustment of the pulse valve controller, the pulse reaction gas enters the ion trap in the reaction time sequence and collides and reacts with the ions in the trap, and is pumped away by the vacuum pump before the sampling time sequence.

8. The use according to claim 6, characterized in that: The tandem mass spectrometry analysis is performed by the tandem mass spectrometry analysis system, and the gas in the ion trap during sampling is only continuous buffer gas.

9. The use according to claim 6, characterized in that: The tandem mass spectrometry analysis is performed by the tandem mass spectrometry analysis system. According to the requirement of the number of tandem stages, the pulse valve can be opened multiple times in a single working cycle to realize multi-stage tandem MSn n≥3 tandem mass spectrometry analysis of the object to be analyzed.

10. The use according to claim 7, characterized in that: The molecular ion reaction is carried out by the tandem mass spectrometry analysis system, and the gas in the ion trap during sampling is only continuous buffer gas.

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