Mass spectrometry interface structure and mass spectrometer

Abstract

The application provides a mass spectrum interface structure and a mass spectrum analyzer, the mass spectrum interface structure comprises a metal electrode, an electrospray ionization needle, a metal plate and an analyzer, the metal electrode is connected to the tail end of the electrospray ionization needle, the head end of the electrospray ionization needle is provided with a nozzle and faces the metal plate, the metal electrode and the metal plate have a positive voltage difference, so that the ions in the electrospray ionization needle are sprayed from the nozzle and generate a blocking current pulse, the electrospray ionization needle is electrically connected with the analyzer, so that the analyzer analyzes the blocking current pulse and obtains the size of the ions. The mass spectrum interface structure and the mass spectrum analyzer provided by the application, the ions in the electrospray ionization needle are sprayed from the nozzle under the action of the voltage, when the ions with a size corresponding to the size of the nozzle are sprayed, a blocking current pulse is generated, the length and the width of the ions can be calculated through the signal amplitude and the blocking time of the blocking current pulse, so that the specific size of the ions is obtained.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of mass spectrum analysis, and more particularly relates to a mass spectrum interface structure and a mass spectrum analyzer. BACKGROUND

[0002] Mass spectrum analysis has been widely applied in the fields of environmental detection, clinical analysis, organic synthesis, drug research and development, protein and metabolomics, etc. due to its advantages of high sensitivity, fast analysis speed and strong specificity. The principle of mass spectrum analysis is to analyze the mass and identify the structure of a sample by measuring the mass-to-charge ratio information of ions of the sample. The structure and composition of a protein molecule determine the function of the protein, and the analysis of the structure of the protein is crucial for proteomics, disease diagnosis and drug design. Based on different principles, ion mobility spectrum (IMS) and cascade mass spectrum technology (MSn) are two widely used mass spectrum technologies for ion structure measurement. Ion mobility spectrum obtains the size of the collision cross section (CCS) of a sample molecule by the speed of the molecule flying in a drift tube, and it is a simple and fast structure measurement method, but it cannot directly obtain the structure of the sample in the liquid phase, and it ignores the reaction between the ion and the buffer gas, the neutral ion collision angle, and it is a rough single-dimensional estimation. Cascade mass spectrum technology analyzes the sub-ion spectrum of the fragments formed by the collision between a sample molecule and a neutral gas, and obtains the structure of the parent ion by sub-ion reconstruction, which can analyze the structure of the target ion from the bonding angle, but for complex protein macromolecules, the fragment information is complex and difficult to completely resolve, and the three-dimensional structure information of the molecule cannot be obtained. Meanwhile, the operation is difficult, the instrument requires multiple analyzers, and the operation timing needs to be coordinated, which is complex. SUMMARY

[0003] The purpose of the embodiment of the application is to provide a mass spectrum interface structure to solve the technical problems of single measurement dimension and difficult operation when measuring the structure of a protein molecule in the prior art.

[0004] To achieve the above-mentioned purpose, the technical solution adopted by the application is to provide a mass spectrum interface structure, which comprises a metal electrode, an electrospray ionization needle, a metal plate and an analyzer, the metal electrode is connected to the tail end of the electrospray ionization needle, the head end of the electrospray ionization needle has a nozzle and is arranged opposite to the metal plate, the metal electrode and the metal plate have a positive voltage difference, so that the ions of the electrospray ionization needle are sprayed from the nozzle and generate a blocking current pulse, the electrospray ionization needle is electrically connected to the analyzer, so that the analyzer analyzes the blocking current pulse and obtains the size of the ions.

[0005] In one embodiment, the diameter of the nozzle is 2 nm to 2 μm.

[0006] In one embodiment, the diameter of the nozzle is 10 nm to 100 nm.

[0007] In one embodiment, the ion is ellipsoid, the long axis of the ion is a, and the short axis of the ion is b.

[0008] In one embodiment, the voltage difference between the metal electrode and the metal plate is 300 V to 1000 V.

[0009] In one embodiment, there is a current amplifier between the metal plate and the analyzer.

[0010] The present application also provides a mass spectrometer comprising the mass spectrometer interface structure described above, and further comprising a mass spectrometer analysis structure.

[0011] The mass spectrometer interface structure and the mass spectrometer provided by the present application have the following beneficial effects: compared with the prior art, the mass spectrometer interface structure comprises a metal electrode, an electrospray ionization needle, a metal plate, and an analyzer, the metal electrode is connected to the tail end of the electrospray ionization needle, the metal plate is opposite to the head end of the electrospray ionization needle, a voltage is applied between the metal electrode and the metal plate, so that the ions in the electrospray ionization needle are sprayed from the nozzle under the action of the voltage, when the ions with a size equivalent to the nozzle are sprayed, a blocking current pulse is generated, the length and the width of the ions can be calculated through the signal amplitude and the blocking time of the blocking current pulse, and thus the specific size of the ions can be obtained. The mass spectrometer interface structure provided by the present application is simple to operate, and the size of the ions in two directions can be obtained, so that the detection is more accurate. BRIEF DESCRIPTION OF DRAWINGS

[0012] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without any creative labor.

[0013] Figure 1 The structural schematic diagram of the mass spectrometer interface structure provided by the embodiments of the present application;

[0014] Figure 2 The schematic diagram of the current blocking signal provided by the embodiments of the present application;

[0015] Figure 3 The size distribution of Escherichia coli detected by the mass spectrometer interface structure provided by the embodiments of the present application;

[0016] Figure 4 The size distribution of Pseudomonas aeruginosa detected by the mass spectrometer interface structure provided by the embodiments of the present application;

[0017] Figure 5 Size distribution of Staphylococcus aureus detected by the mass spectrometry interface structure provided by the embodiment of the present application;

[0018] Figure 6 Size distribution of Bacillus cereus detected by the mass spectrometry interface structure provided by the embodiment of the present application;

[0019] Figure 7 Mass spectrum of Escherichia coli detected by the mass spectrometer provided by the embodiment of the present application;

[0020] Figure 8 Mass spectrum of Pseudomonas aeruginosa detected by the mass spectrometer provided by the embodiment of the present application;

[0021] Figure 9 Mass spectrum of Staphylococcus aureus detected by the mass spectrometer provided by the embodiment of the present application;

[0022] Figure 10 Mass spectrum of Bacillus cereus detected by the mass spectrometer provided by the embodiment of the present application. DETAILED DESCRIPTION

[0023] In order to make the technical problems to be solved by the present application, technical solutions and beneficial effects more clearly, the present application will be further described in detail below in combination with the drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application, and are not used to limit the present application.

[0024] It should be noted that when an element is referred to as being "fixed to" or "set on" another element, it can be directly on the other element or indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or indirectly connected to the other element.

[0025] It should be understood that the terms "length", "width", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only used to facilitate the description of the present application and simplify the description, and therefore cannot be understood as indicating or implying that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application.

[0026] In addition, the terms "first", "second", "third", etc. are used only for descriptive purposes and are not to be construed as indicating or implying relative importance or an ordered ranking of the indicated technical features. Thus, a feature defined with "first", "second" or "third" can explicitly or implicitly include one or more of the features. In the description of the present application, the meaning of "a plurality" is two or more, unless otherwise expressly and specifically limited.

[0027] The mass spectrometry interface structure provided by the embodiments of the present application will be described.

[0028] Please refer to Figure 1 In one of the embodiments of the present application, the mass spectrometry interface structure includes a metal electrode 2, an electrospray ionization needle 1 (abbreviated as ESI needle), a metal plate 3 and an analyzer. The metal electrode 2 is connected to the tail end of the electrospray ionization needle 1, the metal plate 3 is opposite to the head end of the electrospray electrode needle, and the head end of the electrospray electrode needle has a nozzle. There is a positive voltage difference between the metal electrode 2 and the metal plate 3, that is, the voltage of the metal electrode 2 is greater than the voltage of the metal plate 3, so that the charged ions between the metal electrode 2 and the metal plate 3 can move in the direction of the metal plate 3. That is, the ions in the electrospray ionization needle 1 can be sprayed from the nozzle towards the metal plate 3. The electrospray ionization needle 1 is electrically connected to the analyzer, and when the ions with a size comparable to the nozzle pass through the nozzle, a blocking current pulse is formed, which breaks the loop of the electrospray ionization needle 1 and the analyzer. The analyzer obtains a blocking current pulse, and the analyzer analyzes each parameter of the blocking current pulse and finally calculates the size of the ion structure. After a positive voltage difference is applied between the metal electrode 2 and the metal plate 3, the ions in the electrospray ionization needle 1 are turned under the action of the generated electric field, and the length direction of the ions is always the same as the direction of ion ejection.

[0029] The mass spectrometry interface structure in the above embodiment includes a metal electrode 2, an electrospray ionization needle 1, a metal plate 3 and an analyzer, the metal electrode 2 is connected to the tail end of the electrospray ionization needle 1, the metal plate 3 is opposite to the head end of the electrospray ionization needle 1, and a voltage is applied between the metal electrode 2 and the metal plate 3. The mass spectrometry provided by the present application sprays the ions in the electrospray ionization needle 1 from the nozzle under the action of the voltage. When the ions with a size comparable to the nozzle are sprayed, a blocking current pulse is generated. The length and width of the ions can be calculated from the signal amplitude and blocking time of the blocking current pulse, so as to obtain the specific size of the ions. The interface structure is simple, easy to draw, and can be used for protein structure estimation. When it is combined with mass spectrometry analysis structure, structural information can be obtained at the same time of mass spectrometry measurement of the mass spectrometer.

[0030] Optionally, a current amplifier is arranged between the metal plate 3 and the analyzer to increase the amplitude of the blocking current pulse signal, so as to facilitate the analysis of the analyzer. The current amplifier is used to amplify the blocking current pulse signal, and the input end of the current amplifier is connected with the electrospray ionization needle 1, and the output end of the current amplifier is connected with the analyzer. The current amplifier is a prior art, and is usually realized by a current amplification circuit. Any type of current amplifier in the prior art is suitable for the embodiment.

[0031] Optionally, the voltage difference between the metal electrode 2 and the metal plate 3 is 300V to 1000V, such as 400V, 600V, 800V, etc. The voltage difference between the metal electrode 2 and the metal plate 3 is not limited here, and can be selected according to the size of the ion structure to be measured.

[0032] In one embodiment of the present application, the diameter of the nozzle is 2nm to 2μm, preferably 10nm to 100nm, and specifically 100nm, 80nm, 60nm, etc. The diameter of the nozzle is equivalent to the width of the ion to be detected, such as the diameter of the nozzle being equal to or slightly larger than the width of the ion to be detected, so that each ion can generate a blocking current pulse when it is sprayed out.

[0033] In one embodiment of the present application, please refer to Figure 2 , the signal amplitude of the blocking current pulse is ΔI, and the blocking time of the blocking current pulse is t. Specifically, when the ion passes through the nozzle, the analyzer detects a blocking current pulse amplified by the current amplifier, and further, the analyzer obtains a fitting waveform according to a fitting formula, compares the fitting waveform with the detected blocking current pulse, and adjusts the values of a and b to make the fitting waveform and the detected blocking current pulse waveform the same. At this time, the values of a and b are the size of the ion obtained by experiment. Wherein, is the system function of the current amplifier, and is the scale factor. The length of the ion is 2a, and the width of the ion is 2b. When the microorganism or the protein macromolecule passes through the nozzle with a cross-sectional radius of, the cross-sectional area of the embedded ion causes a change in current, v I is the initial current when the blocking current pulse is not detected. The shape of the ion is indefinite, for example, the shape of the ion is ellipsoidal, such as a microorganism or a protein macromolecule, etc. The long axis radius of the ion is a, and the short axis radius of the ion is b. According to the above formula, the sizes of a and b can be calculated.

[0034] In one embodiment of the present application, please refer to Figure 3 , Figure 3 is the size distribution of E. coli detected by the mass spectrometry interface structure provided by the embodiment of the present application. Figure 3 ​The longitudinal coordinate is b, the horizontal coordinate is a, and the dot array in the first quadrant is the size distribution dot array of each E. coli obtained after multiple tests. In this embodiment, the diameter of the nozzle is 0.75 μm, the sample solution is a suspension of E. coli, and the size distribution dot array of the E. coli obtained by the method of the present application is shown in FIG. 5. Figure 3 As shown in the dot array in FIG. 5, the experimental average value a = 1.8155 and b = 0.6935 obtained by testing and calculation are within the error range of the actual size of the E. coli (a = 1 to 3 and b = 0.5), thereby proving the feasibility of the embodiment of the present application.

[0035] In one embodiment of the present application, please refer to Figure 4 , Figure 4 The size distribution of P. aeruginosa detected by the mass spectrometry interface structure provided by the embodiment of the present application. Figure 4 The longitudinal coordinate is b, the horizontal coordinate is a, and the dot array in the first quadrant is the size distribution dot array of each P. aeruginosa obtained after multiple tests. In this embodiment, the diameter of the nozzle is 0.75 μm, the sample solution is a suspension of P. aeruginosa, and the size distribution dot array of the P. aeruginosa obtained by the method of the present application is shown in FIG. 6. Figure 4 As shown in the dot array in FIG. 6, the experimental average value a = 2.4538 and b = 0.5990 obtained by testing and calculation are within the error range of the actual size of the P. aeruginosa (a = 1.5 to 5 μm and b = 0.5 to 1 μm), thereby proving the feasibility of the embodiment of the present application.

[0036] In one embodiment of the present application, please refer to Figure 5 The size distribution of S. aureus detected by the mass spectrometry interface structure provided by the embodiment of the present application. Figure 5 The longitudinal coordinate is b, the horizontal coordinate is a, and the dot array in the first quadrant is the size distribution dot array of each S. aureus obtained after multiple tests. In this embodiment, the diameter of the nozzle is 0.75 μm, the sample solution is a suspension of S. aureus, and the size distribution dot array of the S. aureus obtained by the method of the present application is shown in FIG. 7.

[0037] In one embodiment of the present application, please refer to Figure 6 The size distribution of B. cereus detected by the mass spectrometry interface structure provided by the embodiment of the present application. Figure 6The longitudinal coordinate in the graph is b, the transverse coordinate is a, and the dot matrix in the first quadrant is the size distribution dot matrix of each Bacillus cereus obtained after the test. In this embodiment, the diameter of the nozzle is 0.75 μm, and the sample solution is a suspension of Bacillus cereus. As shown in the dot matrix in 6, the experimental average value obtained by the test and calculation is a = 0.9479 μm and b = 0.9340 μm, and the actual size of Staphylococcus aureus is a = b = 1 μm, both of which are within the error range, thereby proving the feasibility of the embodiment of the present application.

[0038] The present application also provides a mass spectrometer, which comprises the mass spectrometer interface structure in any of the above embodiments, and further comprises a mass spectrometer analysis structure for mass spectrometer analysis. The ions sprayed on the metal plate 3 are ionized by the laser, and the mass spectrometry information is obtained by the action of the mass spectrometer analysis structure. The mass spectrometer analysis structure is the same as the mass spectrometer analysis structure in the prior art, and the specific structure is not described here.

[0039] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement and improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A mass spectrometry interface structure, characterized by, The mass spectrometry interface structure comprises a metal electrode, an electrospray ionization needle, a metal plate and an analyzer, the metal electrode is connected to the tail end of the electrospray ionization needle, the head end of the electrospray ionization needle has a nozzle and is arranged opposite to the metal plate, the metal electrode and the metal plate have a positive voltage difference, so that the ions of the electrospray ionization needle are ejected from the nozzle and generate a blocking current pulse, the electrospray ionization needle is electrically connected to the analyzer, so that the analyzer analyzes the blocking current pulse and obtains the size of the ions. The voltage of the metal electrode is greater than the voltage of the metal plate, and the charged ions between the metal electrode and the metal plate can move towards the metal plate; the metal plate and the analyzer have a current amplifier therebetween, the input end of the current amplifier is connected to the electrospray ionization needle, and the output end of the current amplifier is connected to the analyzer. The signal amplitude of the blocking current pulse is ΔI, and the blocking time of the blocking current pulse is t. When the ions pass through the nozzle, the analyzer detects a blocking current pulse amplified by the current amplifier; the analyzer obtains a fitting waveform according to a fitting formula, and compares the fitting waveform with the detected blocking current pulse in waveform; the ions are ellipsoidal, the long axis of the ions is a, and the short axis of the ions is b.

2. The mass spectrometry interface structure of claim 1, wherein: The diameter of the nozzle is 2 nm to 2 μm.

3. The mass spectrometry interface structure of claim 1, wherein: The diameter of the nozzle is 10 nm to 100 nm.

4. The mass spectrometry interface structure of claim 1, wherein: The voltage difference between the metal electrode and the metal plate is 300 V to 1000 V.

5. A mass spectrometer characterised by: The mass spectrometry interface structure comprises a metal electrode, an electrospray ionization needle, a metal plate and an analyzer, the metal electrode is connected to the tail end of the electrospray ionization needle, the head end of the electrospray ionization needle has a nozzle and is arranged opposite to the metal plate, the metal electrode and the metal plate have a positive voltage difference, so that the ions of the electrospray ionization needle are ejected from the nozzle and generate a blocking current pulse, the electrospray ionization needle is electrically connected to the analyzer, so that the analyzer analyzes the blocking current pulse and obtains the size of the ions. The voltage of the metal electrode is greater than the voltage of the metal plate, and the charged ions between the metal electrode and the metal plate can move towards the metal plate; the metal plate and the analyzer have a current amplifier therebetween, the input end of the current amplifier is connected to the electrospray ionization needle, and the output end of the current amplifier is connected to the analyzer. The signal amplitude of the blocking current pulse is ΔI, and the blocking time of the blocking current pulse is t. When the ions pass through the nozzle, the analyzer detects a blocking current pulse amplified by the current amplifier; the analyzer obtains a fitting waveform according to a fitting formula, and compares the fitting waveform with the detected blocking current pulse in waveform; the ions are ellipsoidal, the long axis of the ions is a, and the short axis of the ions is b. The diameter of the nozzle is 2 nm to 2 μm. The diameter of the nozzle is 10 nm to 100 nm. The voltage difference between the metal electrode and the metal plate is 300 V to 1000 V. The mass spectrometry interface structure comprises a metal electrode, an electrospray ionization needle, a metal plate and an analyzer, the metal electrode is connected to the tail end of the electrospray ionization needle, the head end of the electrospray ionization needle has a nozzle and is arranged opposite to the metal plate, the metal electrode and the metal plate have a positive voltage difference, so that the ions of the electrospray ionization needle are ejected from the nozzle and generate a blocking current pulse, the electrospray ionization needle is electrically connected to the analyzer, so that the analyzer analyzes the blocking current pulse and obtains the size of the ions. The voltage of the metal electrode is greater than the voltage of the metal plate, and the charged ions between the metal electrode and the metal plate can move towards the metal plate; the metal plate and the analyzer have a current amplifier therebetween, the input end of the current amplifier is connected to the electrospray ionization needle, and the output end of the current amplifier is connected to the analyzer. The signal amplitude of the blocking current pulse is ΔI, and the blocking time of the blocking current pulse is t. When the ions pass through the nozzle

Images