High-flux charge detection mass spectrometer

Abstract

The invention relates to the technical field of mass spectrum analyzers, in particular to a high-flux charge detection mass spectrometer. Comprising an ion source module, a first fan-shaped circular ring deflector, a second fan-shaped circular ring deflector, a first charge signal detection module and a second charge signal detection module, the first fan-shaped circular ring deflector and the second fan-shaped circular ring deflector are oppositely arranged, and the first fan-shaped circular ring deflector and the second fan-shaped circular ring deflector are respectively provided with a first fan-shaped well and a second fan-shaped well. A first charge signal detection module is arranged between the first upper outlet and the second upper outlet, a second charge signal detection module is arranged between the first lower outlet and the second lower outlet, the first fan-shaped circular ring deflector is provided with a horizontal circular through hole, and the ion source module is arranged at the horizontal circular through hole. Ions generated by the ion source module enter from the horizontal circular through hole and are trapped in the first fan-shaped well and / or the second fan-shaped well, and inductive charges formed by charged ions are detected through the first charge signal detection module and / or the second charge signal detection module.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometers, and in particular to a high-throughput charge detection mass spectrometer. Background Art

[0002] Mass spectrometry has always been considered the core technology for analyzing the quality of substances. In particular, the development of matrix-assisted laser desorption ionization and electrospray ionization sources has expanded the application of mass spectrometry to the field of biomolecules. However, traditional mass spectrometry does not measure mass but mass-to-charge ratio (m / z). For small ions, they usually carry a single charge, so the mass number can be converted according to m / z. However, for biomolecules produced by electrospray, they often carry multiple charges. Therefore, it is necessary to determine the charge number based on the isotope spacing or the charge envelope peak spacing, and then derive the molecular mass. However, with the continuous increase in the quality of the analyzed substances, especially for biomacromolecules, the heterogeneity of the samples will gradually increase. This will cause peak overlap, broadening and offset in the mass spectrum, making it impossible to determine the charge state of the sample ions. Therefore, how to accurately measure the charge state of biomacromolecules after ion formation is a difficult problem that needs to be solved urgently.

[0003] Through searching patents and papers, the relevant patents related to charge detection mass spectrometers retrieved are: On January 11, 2020, the Board of Trustees of Indiana University in the United States disclosed a charge detection mass spectrometer, including: an ion trap and an electrostatic linear ion trap (ELIT), the electrostatic linear ion trap (ELIT) is separated from the ion trap, and the ELI T includes a first ion mirror and a second ion mirror and a charge detection cylinder positioned between them; the mass-to-charge ratio and charge are measured by ions repeatedly passing through the charge detection cylinder and inducing current thereon. Its shortcomings are that the structure of the two electrostatic reflectors requires that the ions in the electrostatic trap must go through a deceleration and acceleration process in each cycle, which greatly increases the detection time and reduces the analysis speed. It subsequently disclosed a number of related patents on how to manipulate ions, control mass spectrometry timing and signal analysis, but the hardware structure is still an electrostatic trap based on two sets of electrostatic reflectors, and the analysis speed is defective. Therefore, it is necessary to develop a new electrostatic trap structure to avoid the reduction in analysis speed caused by deceleration during ion oscillation. Summary of the invention

[0004] In view of the problems existing in the prior art, an object of the present invention is to provide a high-throughput charge detection mass spectrometer to solve the problem of reduced analysis speed caused by ion deceleration during ion oscillation.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] The present invention provides a high-throughput charge detection mass spectrometer, comprising an ion source module, a first sector-shaped circular deflector, a second sector-shaped circular deflector, a first charge signal detection module and a second charge signal detection module, wherein the first sector-shaped circular deflector and the second sector-shaped circular deflector are arranged relative to each other, the first sector-shaped circular deflector and the second sector-shaped circular deflector respectively have a first sector-shaped well and a second sector-shaped well, the two ends of the first sector-shaped well are respectively a first upper outlet and a first lower outlet, the two ends of the second sector-shaped well are respectively a second upper outlet and a second lower outlet, and a first upper outlet and a second lower outlet are arranged between the first upper outlet and the second upper outlet. A first charge signal detection module, the first charge signal detection module has a first ion channel, a second charge signal detection module is arranged between the first lower outlet and the second lower outlet, the second charge signal detection module has a second ion channel, the first fan-shaped ring deflector is provided with a horizontal circular through hole connected to the first fan-shaped trap, the ion source module is arranged at the horizontal circular through hole, the ions generated by the ion source module enter through the horizontal circular through hole and are trapped in the first fan-shaped trap and / or the second fan-shaped trap, and the induced charge formed by the charged ions is detected by the first charge signal detection module and / or the second charge signal detection module.

[0007] The first sector-shaped circular ring deflector comprises a first sector-shaped circular ring deflector outer ring electrode and a first sector-shaped circular ring deflector inner ring electrode;

[0008] The outer ring electrode of the first sector-shaped circular deflector and the inner ring electrode of the first sector-shaped circular deflector are both semicircular structures with different radii, the outer ring electrode of the first sector-shaped circular deflector and the inner ring electrode of the first sector-shaped circular deflector are arranged concentrically from outside to inside and the end faces are flush, and the first sector-shaped well is formed between the outer ring electrode of the first sector-shaped circular deflector and the inner ring electrode of the first sector-shaped circular deflector;

[0009] The horizontal circular through hole is arranged at the upper end of the outer ring electrode of the first sector-shaped circular deflector and is coaxial with the first upper outlet.

[0010] The second sector-shaped circular deflector comprises a second sector-shaped circular deflector outer ring electrode and a second sector-shaped circular deflector inner ring electrode;

[0011] The outer ring electrode of the second sector-shaped circular deflector and the inner ring electrode of the second sector-shaped circular deflector are both semicircular structures with different radii. The outer ring electrode of the second sector-shaped circular deflector and the inner ring electrode of the second sector-shaped circular deflector are arranged concentrically from outside to inside and the end surfaces are flush. The second sector-shaped well is formed between the outer ring electrode of the second sector-shaped circular deflector and the inner ring electrode of the second sector-shaped circular deflector.

[0012] The second upper outlet and the second lower outlet of the second fan-shaped trap are coaxial with the first upper outlet and the first lower outlet of the first fan-shaped trap, respectively.

[0013] Applying direct current voltages with the same amplitude and opposite polarities to the outer ring electrode of the first sector-shaped circular deflector and the inner ring electrode of the first sector-shaped circular deflector, respectively, so that ions fly losslessly along the central area of ​​the first sector-shaped trap;

[0014] A DC voltage with the same amplitude and opposite polarity is applied to the outer ring electrode of the second sector-shaped circular deflector and the inner ring electrode of the second sector-shaped circular deflector, respectively, so that ions fly losslessly along the central area of ​​the second sector-shaped trap; a pulse voltage is applied to the outer ring electrode of the first sector-shaped circular deflector and the inner ring electrode of the first sector-shaped circular deflector to control the introduction of ions.

[0015] The first charge signal detection module includes a first ion manipulation lens, a first charge detection cylinder, and a second ion manipulation lens that are coaxially and sequentially arranged. The first ion manipulation lens, the first charge detection cylinder, and the second ion manipulation lens all have a central hole to form the first ion channel; the first ion channel is coaxial with the first upper outlet and the second upper outlet.

[0016] The second charge signal detection module comprises a third ion manipulation lens, a second charge detection cylinder and a fourth ion manipulation lens which are arranged in sequence and coaxially, the third ion manipulation lens, the second charge detection cylinder and the fourth ion manipulation lens all have a central hole to form the second ion channel, and the second ion channel is coaxial with the first lower outlet and the second lower outlet;

[0017] The charge signal is detected using the first charge detection cylinder and / or the second charge detection cylinder.

[0018] The first ion manipulation lens, the second ion manipulation lens, the third ion manipulation lens and the fourth ion manipulation lens are all composed of three identical circular electrodes, which are coaxial and spaced apart; three adjustable DC voltages are applied to the three circular electrodes in each group of ion manipulation lenses, and the same voltage is applied to the first and last circular electrodes in each group of ion manipulation lenses, and the DC voltage application range is 0-±2000V;

[0019] The first charge detection cylinder and the second charge detection cylinder are both hollow cylindrical electrodes.

[0020] The ion source module comprises an ion generating source, an acceleration zone and an ion gate which are coaxial with the horizontal circular through hole and arranged in sequence and spaced apart from each other. The ion gate is close to the horizontal circular through hole. The ion gate comprises two identical rectangular plate electrodes which are parallel to each other and spaced apart from each other. An adjustable DC voltage is applied to the two rectangular plate electrodes of the ion gate. When the voltages of the two rectangular plate electrodes are the same, ions pass through. When there is a pressure difference between the two rectangular plate electrodes, ions are deflected and cannot enter the horizontal circular through hole.

[0021] The acceleration zone includes more than three flat electrodes with circular holes in the center. The center holes of the flat electrodes are coaxial and spaced apart. Adjacent flat electrodes are separated by insulating pads and connected in series through resistors. A uniform accelerating electric field is formed by applying a DC voltage at both ends to accelerate the ions introduced by the ion generating source.

[0022] The ion generating source is an ion trap analyzer that traps ions and can selectively extract ions and enter a fan-shaped trap for m / z and charge state measurement; the ion trap analyzer is a linear ion trap, rectangular ion trap or Paul trap with trapping and ion excitation functions.

[0023] The working method of the high-throughput charge detection mass spectrometer is as follows:

[0024] 1) The ion gate is set to an open state, and the outer ring electrode of the first sector-shaped circular deflector and the inner ring electrode of the first sector-shaped circular deflector are at a low level;

[0025] 2) The ions excited by the ion generating source enter the acceleration zone, and under the action of the accelerating electric field of the acceleration zone, they pass through the ion gate in the open state and the upper circular through hole in turn to enter the first sector-shaped well of the first sector-shaped circular deflector, and under the action of the first ion manipulation lens, they pass through the first charge detection cylinder and the second ion manipulation lens in turn and enter the second sector-shaped well of the second sector-shaped circular deflector; at this time, the outer ring electrode of the first sector-shaped circular deflector and the inner ring electrode of the first sector-shaped circular deflector are set to a high level in the trapped state;

[0026] 3) After being drawn out from the second sector trap of the second sector ring deflector, the ions sequentially pass through the fourth ion manipulation lens, the second charge detection cylinder and the third ion manipulation lens, enter the first sector trap of the first sector ring deflector, and are drawn out again to the first ion manipulation lens;

[0027] 4) The ions are trapped in the first and second fan-shaped traps to form a closed-loop ion trajectory, and an induced charge signal is generated each time the ions pass through the first charge detection cylinder and the second charge detection cylinder;

[0028] 5) Performing fast Fourier transformation on the time domain signals collected by the first charge detection cylinder and the second charge detection cylinder can obtain frequency domain signals, thereby obtaining the m / z and charge state of the ion to be detected.

[0029] The advantages and beneficial effects of the present invention are: the present invention cleverly uses two groups of symmetrical semicircular fan-shaped deflectors to imprison high-speed flying ions in a fan-shaped trap, and detects the induced charge formed after the charged ions pass through the fan-shaped trap through a charge detection cylinder. Since the ions are always in a high-speed state in the fan-shaped trap, the charge measurement speed can be greatly improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The accompanying drawings further illustrate the present invention, but the contents in the accompanying drawings do not constitute any limitation to the present invention.

[0031] Figure 1 The figure is a schematic diagram of the structure of a high-throughput charge detection mass spectrometer of the present invention.

[0032] In the figure: 1 is an ion generating source, 2 is an acceleration zone, 3 is an ion gate, 41 is an outer ring electrode of a first fan-shaped circular deflector, 42 is an outer ring electrode of a second fan-shaped circular deflector, 51 is an inner ring electrode of a first fan-shaped circular deflector, 52 is an inner ring electrode of a second fan-shaped circular deflector, 61 is a first ion manipulation lens, 62 is a second ion manipulation lens, 63 is a third ion manipulation lens, 64 is a fourth ion manipulation lens, 71 is a first charge detection cylinder, 72 is a second charge detection cylinder, 8 is a circular through hole of the outer ring electrode of the first fan-shaped circular deflector, and 9 is an ion trajectory. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] In the description of the present invention, it is necessary to understand that the directions or positional relationships indicated by directional words such as "front, back, up, down, left, right", "lateral, vertical, perpendicular, horizontal" and "top, bottom" are usually based on the directions or positional relationships shown in the drawings. They are only for the convenience of describing the present invention and simplifying the description. Unless otherwise specified, these directional words do not indicate or imply that the device or element referred to must have a specific direction or be constructed and operated in a specific direction. Therefore, they cannot be understood as limiting the scope of protection of the present invention: the directional words "inside and outside" refer to the inside and outside relative to the contours of each component itself.

[0035] like Figure 1As shown, the present invention provides a high-throughput charge detection mass spectrometer, including an ion source module, a first fan-shaped ring deflector, a second fan-shaped ring deflector, a first charge signal detection module and a second charge signal detection module, wherein the first fan-shaped ring deflector and the second fan-shaped ring deflector are arranged relatively to each other, the first fan-shaped ring deflector and the second fan-shaped ring deflector respectively have a first fan-shaped well and a second fan-shaped well, the two ends of the first fan-shaped well are respectively a first upper outlet and a first lower outlet, the two ends of the second fan-shaped well are respectively a second upper outlet and a second lower outlet, a first charge signal detection module is arranged between the first upper outlet and the second upper outlet, the first charge signal detection module has a first ion channel, a second charge signal detection module is arranged between the first lower outlet and the second lower outlet, the second charge signal detection module has a second ion channel, and the first fan-shaped ring deflector is provided with a horizontal circular through hole 8 connected with the first fan-shaped well, and the horizontal circular through hole 8 is used to introduce ions. The ion source module is arranged at the horizontal circular through hole 8. The ions generated by the ion source module enter through the horizontal circular through hole 8 and are trapped in the first sector trap and / or the second sector trap. The induced charge formed by the charged ions is detected by the first charge signal detection module and / or the second charge signal detection module.

[0036] like Figure 1 As shown, the X direction is the right side, and the Y direction is the top; in an embodiment of the present invention, the first sector-shaped circular deflector includes a first sector-shaped circular deflector outer ring electrode 41 and a first sector-shaped circular deflector inner ring electrode 51; the first sector-shaped circular deflector outer ring electrode 41 and the first sector-shaped circular deflector inner ring electrode 51 are both semicircular structures with different radii, the first sector-shaped circular deflector outer ring electrode 41 and the first sector-shaped circular deflector inner ring electrode 51 are arranged concentrically from outside to inside and the end faces are flush, and a first sector-shaped well is formed between the first sector-shaped circular deflector outer ring electrode 41 and the first sector-shaped circular deflector inner ring electrode 51; a horizontal circular through hole 8 is arranged at the upper end of the first sector-shaped circular deflector outer ring electrode 41, and is coaxial with the first upper outlet, along the X direction.

[0037] Specifically, the first sector-shaped circular deflector outer ring electrode 41 and the first sector-shaped circular deflector inner ring electrode 51 are respectively formed by dividing circular ring electrodes with different radii into two equal parts along the radial direction, that is, the sector angle is 180°.

[0038] like Figure 1As shown, in an embodiment of the present invention, the second sector-shaped circular deflector includes a second sector-shaped circular deflector outer ring electrode 42 and a second sector-shaped circular deflector inner ring electrode 52; the second sector-shaped circular deflector outer ring electrode 42 and the second sector-shaped circular deflector inner ring electrode 52 are both semicircular structures with different radii, the second sector-shaped circular deflector outer ring electrode 42 and the second sector-shaped circular deflector inner ring electrode 52 are arranged concentrically from outside to inside and the end faces are flush, and a second sector-shaped well is formed between the second sector-shaped circular deflector outer ring electrode 42 and the second sector-shaped circular deflector inner ring electrode 52; the second upper outlet and the second lower outlet of the second sector-shaped well are coaxial with the first upper outlet and the first lower outlet of the first sector-shaped well, respectively, along the X direction.

[0039] Specifically, the second sector-shaped circular deflector outer ring electrode 42 and the second sector-shaped circular deflector inner ring electrode 52 are respectively formed by dividing circular ring electrodes with different radii into two equal parts along the radial direction, that is, the sector angle is 180°.

[0040] In an embodiment of the present invention, the first charge signal detection module includes a first ion manipulation lens 61, a first charge detection cylinder 71 and a second ion manipulation lens 62 which are coaxially and spaced apart in sequence. The first ion manipulation lens 61, the first charge detection cylinder 71 and the second ion manipulation lens 62 all have a central hole to form a first ion channel; the first ion channel is coaxial with the first upper outlet and the second upper outlet and are spaced apart.

[0041] In an embodiment of the present invention, the second charge signal detection module includes a third ion manipulation lens 63, a second charge detection cylinder 72 and a fourth ion manipulation lens 64 which are arranged in sequence and coaxially, the third ion manipulation lens 63, the second charge detection cylinder 72 and the fourth ion manipulation lens 64 all have a central hole to form a second ion channel, and the second ion channel is coaxial with the first lower outlet and the second lower outlet and arranged at intervals; the first charge detection cylinder 71 and / or the second charge detection cylinder 72 are used to detect the charge signal.

[0042] Further, the charge signal is detected on the first charge detection cylinder 71 and the second charge detection cylinder 72; when analyzing, any charge detection cylinder signal can be used, or two charge detection cylinder signals can be used simultaneously; when two charge detection cylinder signals are used simultaneously, they can be averaged or accumulated. Preferably, two charge detection cylinder signals are used simultaneously, and their measurement results are averaged.

[0043] Specifically, the first ion manipulation lens 61, the second ion manipulation lens 62, the third ion manipulation lens 63 and the fourth ion manipulation lens 64 are all composed of three identical circular electrodes, and the three circular electrodes are coaxial and spaced apart.

[0044] Furthermore, three adjustable DC voltages are applied to the three annular electrodes in each group of ion manipulation lenses. Usually, the same voltage is applied to the first and last annular electrodes in each group of ion manipulation lenses, and the DC voltage application range is 0-±2000V; the first charge detection cylinder 71 and the second charge detection cylinder 72 are both hollow cylindrical electrodes. Preferably, under positive ion conditions, 0V voltage is applied to the first and last annular electrodes of each group of ion manipulation lenses, and -1000V voltage is applied to the center.

[0045] like Figure 1 As shown, in an embodiment of the present invention, the ion source module includes an ion generating source 1, an acceleration zone 2 and an ion gate 3 which are coaxial with the horizontal circular through hole 8 and arranged in sequence. The ion gate 3 is close to the horizontal circular through hole 8. The center of the ion generating source 1, the axis of the acceleration zone 2, the center of the ion gate 3, and the axis of the horizontal circular through hole 8 of the first fan-shaped ring deflector are all on a straight line.

[0046] In an embodiment of the present invention, the ion gate 3 includes two completely identical rectangular plate electrodes, which are parallel to each other and spaced apart from each other. An adjustable DC voltage is applied to the two rectangular plate electrodes of the ion gate 3. When the voltages of the two rectangular plate electrodes are the same, the ions pass through. When there is a pressure difference between the two rectangular plate electrodes, the ions are deflected and cannot enter the horizontal circular through hole 8.

[0047] The acceleration zone 2 includes more than three flat electrodes with circular holes in the center. The center holes of the flat electrodes are coaxial and spaced apart. Adjacent flat electrodes are separated by insulating pads and connected in series through resistors. A uniform accelerating electric field is formed by applying a DC voltage at both ends to accelerate the ions introduced by the ion generating source 1.

[0048] Specifically, the acceleration zone 2 is composed of a plurality of 0.1-5 mm thin annular pole pieces, which are separated by PEEK or ceramic insulating pads and connected in series by resistors with a resistance of 1-100 MΩ. Preferably, the acceleration zone 2 uses 1 mm thick thin annular pole pieces, which are separated by ceramic insulating pads and connected in series by resistors with a resistance of 5 MΩ.

[0049] The ion generation source 1 is an ion trap analyzer that traps ions, and can selectively extract ions and enter a fan-shaped trap for more accurate m / z and charge state measurement; the ion trap analyzer can be a linear ion trap, a rectangular ion trap, or a Paul trap, etc., which has trapping and ion excitation functions. Preferably, a linear ion trap is selected to trap ions, and ions are ejected by axial excitation.

[0050] Furthermore, a DC voltage (±100-±10000V) with the same amplitude and opposite polarity is applied to the outer ring electrode 41 of the first sector-shaped circular deflector and the inner ring electrode 51 of the first sector-shaped circular deflector, respectively, so that the ions fly losslessly along the central area of ​​the first sector-shaped trap of the first sector-shaped circular deflector. A DC voltage (±100-±10000V) with the same amplitude and opposite polarity is applied to the outer ring electrode 42 of the second sector-shaped circular deflector and the inner ring electrode 52 of the second sector-shaped circular deflector, respectively, so that the ions fly losslessly along the central area of ​​the second sector-shaped trap of the second sector-shaped circular deflector; in addition, a pulse voltage is applied to the outer ring electrode 41 of the first sector-shaped circular deflector and the inner ring electrode 51 of the first sector-shaped circular deflector to control the introduction of ions.

[0051] Preferably, under positive ion conditions, a voltage of 2000V is applied to the outer ring electrode 41 and the second fan-shaped circular deflector outer ring electrode 42 when working, and a voltage of -2000V is applied to the inner ring electrode 51 and the second fan-shaped circular deflector inner ring electrode 52 when working normally; when ions are introduced, a voltage of 0V is applied to the outer ring electrode 41 and the inner ring electrode 51 of the first fan-shaped circular deflector.

[0052] The present invention provides a high-throughput charge detection mass spectrometer, and its specific working method is as follows:

[0053] 1) The ion gate 3 is set to an open state, and the first sector-shaped circular deflector outer ring electrode 41 and the first sector-shaped circular deflector inner ring electrode 51 are at a low level;

[0054] 2) The ions excited by the ion generating source 1 enter the acceleration zone 2, and under the action of the accelerating electric field of the acceleration zone 2, they sequentially pass through the ion gate 3 in the open state and the upper circular through hole 8 to enter the first sector-shaped well of the first sector-shaped circular deflector, and under the action of the first ion manipulation lens 61, they sequentially pass through the first charge detection cylinder 71 and the second ion manipulation lens 62 and enter the second sector-shaped well of the second sector-shaped circular deflector; at this time, the outer ring electrode 41 of the first sector-shaped circular deflector and the inner ring electrode 51 of the first sector-shaped circular deflector are set to a high level in the trapped state;

[0055] 3) After being drawn out from the second sector trap of the second sector ring deflector, the ions sequentially pass through the fourth ion manipulation lens 64, the second charge detection cylinder 72 and the third ion manipulation lens 63, and enter the first sector trap of the first sector ring deflector, and are drawn out again to the first ion manipulation lens 61;

[0056] 4) The ions are trapped in the first and second fan-shaped traps to form a closed-loop ion trajectory 9, and an induced charge signal is generated each time the ions pass through the first charge detection cylinder 71 and the second charge detection cylinder 72;

[0057] 5) Performing fast Fourier transformation on the time domain signals collected by the first charge detection cylinder 71 and the second charge detection cylinder 72 can obtain frequency domain signals, thereby obtaining the m / z and charge state of the ion to be detected.

[0058] Embodiment 1

[0059] like Figure 1 As shown, the present invention provides a high-throughput charge detection mass spectrometer, in which the ion generation source 1 adopts a linear ion trap. When working, first, the upper and lower rectangular plate electrodes of the ion gate 3 are set to 0V and are in an open state, and the first fan-shaped circular ring deflector outer ring electrode 41 and the first fan-shaped circular ring deflector inner ring electrode 51 are set to 0V level; the second fan-shaped circular ring deflector outer ring electrode 42 and the second fan-shaped circular ring deflector inner ring electrode 52 are set to 2000V and -2000V levels respectively; then, the positive ions generated by the axial excitation of the linear ion trap enter the acceleration zone 2, which is composed of ten 1mm thick circular ring thin pole pieces, adjacent circular ring thin pole pieces are separated by 3mm ceramic insulating pads, and are connected in series through 5MΩ resistors, and a 2000 voltage difference voltage is applied at the beginning and end of the acceleration zone 2 to accelerate the ions. Under the action of the accelerating electric field, the ions pass through the ion gate 3 in the open state and the horizontal circular through hole 8 on the first fan-shaped circular ring deflector outer ring electrode 41 in turn to enter the first fan-shaped trap; A voltage of 0V is applied to the first and last circular electrodes of the group ion manipulation lens, and -500V is applied to the center circular electrode for ion shaping; under the action of the first ion manipulation lens 61, the ions pass through the first charge detection cylinder 71, the second ion manipulation lens 62 in turn and enter the second fan-shaped circular deflector; at this time, the outer ring electrode 41 of the first fan-shaped circular deflector and the inner ring electrode 51 of the first fan-shaped circular deflector are set to a high level in the trapped state, that is, 2000V and -2000V are set respectively; then, after the ions are drawn out from the second fan-shaped circular deflector, they pass through the fourth ion manipulation lens 64, the second charge detection cylinder 72 and the third ion manipulation lens 63 in turn and enter the first fan-shaped circular deflector, and are drawn out again to the first ion manipulation lens 61; in this way, the ions are trapped in the fan-shaped trap to form a closed-loop ion trajectory 9, and an induced charge signal is generated each time they pass through the first charge detection cylinder 71 and the second charge detection cylinder 72.

[0060] The present invention cleverly uses two sets of symmetrical semicircular sector deflectors to trap high-speed flying ions in a sector trap, and uses a charge detection cylinder to detect the induced charge formed after the charged ions pass through. Since the ions are always in a high-speed state in the sector trap, the charge measurement speed can be greatly improved; finally, the frequency domain signal can be obtained by performing a fast Fourier transform on the time domain signal collected by the two charge detection cylinders, in which the frequency is related to the m / z and the amplitude is related to the charge state, thereby obtaining the m / z and charge state of the ion to be measured.

[0061] At present, traditional mass spectrometry is not mass but mass-to-charge ratio (m / z), and it is necessary to know the charge state to accurately obtain mass number information. For multi-charged biomacromolecules produced by electrospray, even if ultra-high resolution mass spectrometry is used, its charge state cannot be determined. Therefore, the present invention designs a high-throughput charge detection mass spectrometer, which cleverly imprisons high-speed flying ions in a fan-shaped trap through two sets of symmetrical semicircular fan-shaped deflectors, and detects the induced charge formed after the charged ions pass through the charge detection cylinder; finally, the time domain signal collected by the two charge detection cylinders is subjected to fast Fourier transformation to obtain a frequency domain signal, wherein the frequency is related to m / z, and the amplitude is related to the charge state, so as to obtain the m / z and charge state of the ion to be measured. Since the ions are always in a high-speed state in the fan-shaped trap, the charge measurement speed is greatly improved.

[0062] The technical principle of the present invention is described above in conjunction with specific embodiments. These descriptions are only for explaining the principle of the present invention and cannot be interpreted as limiting the scope of protection of the present invention in any way. Based on the explanations herein, those skilled in the art can associate other specific embodiments of the present invention without creative work, and these equivalent variations or substitutions are all included in the scope defined by the claims of this application.

Claims

1. A high-throughput charge detection mass spectrometer, characterized in that: The invention comprises an ion source module, a first sector-shaped circular deflector, a second sector-shaped circular deflector, a first charge signal detection module and a second charge signal detection module, wherein the first sector-shaped circular deflector and the second sector-shaped circular deflector are arranged relatively to each other, the first sector-shaped circular deflector and the second sector-shaped circular deflector respectively have a first sector-shaped well and a second sector-shaped well, two ends of the first sector-shaped well are respectively a first upper outlet and a first lower outlet, two ends of the second sector-shaped well are respectively a second upper outlet and a second lower outlet, a first charge signal detection module is arranged between the first upper outlet and the second upper outlet, and the first sector-shaped well is provided with a first charge signal detection module. The charge signal detection module has a first ion channel, a second charge signal detection module is arranged between the first lower outlet and the second lower outlet, the second charge signal detection module has a second ion channel, the first sector-shaped annular deflector is provided with a horizontal circular through hole (8) connected to the first sector-shaped trap, the ion source module is arranged at the horizontal circular through hole (8), the ions generated by the ion source module enter through the horizontal circular through hole (8) and are trapped in the first sector-shaped trap and / or the second sector-shaped trap, and the induced charge formed by the charged ions is detected by the first charge signal detection module and / or the second charge signal detection module.

2. The high-throughput charge detection mass spectrometer according to claim 1, characterized in that: The first sector-shaped circular deflector comprises a first sector-shaped circular deflector outer ring electrode (41) and a first sector-shaped circular deflector inner ring electrode (51); The first sector-shaped circular deflector outer ring electrode (41) and the first sector-shaped circular deflector inner ring electrode (51) are both semicircular structures with different radii, the first sector-shaped circular deflector outer ring electrode (41) and the first sector-shaped circular deflector inner ring electrode (51) are arranged concentrically from outside to inside and their end surfaces are flush, and the first sector-shaped well is formed between the first sector-shaped circular deflector outer ring electrode (41) and the first sector-shaped circular deflector inner ring electrode (51); The horizontal circular through hole (8) is arranged at the upper end of the outer ring electrode (41) of the first sector-shaped circular deflector and is coaxial with the first upper outlet.

3. The high-throughput charge detection mass spectrometer according to claim 2, characterized in that: The second sector-shaped circular deflector comprises a second sector-shaped circular deflector outer ring electrode (42) and a second sector-shaped circular deflector inner ring electrode (52); The second sector-shaped circular deflector outer ring electrode (42) and the second sector-shaped circular deflector inner ring electrode (52) are both semicircular structures with different radii, the second sector-shaped circular deflector outer ring electrode (42) and the second sector-shaped circular deflector inner ring electrode (52) are arranged concentrically from outside to inside and the end surfaces are flush, and the second sector-shaped well is formed between the second sector-shaped circular deflector outer ring electrode (42) and the second sector-shaped circular deflector inner ring electrode (52); The second upper outlet and the second lower outlet of the second fan-shaped trap are coaxial with the first upper outlet and the first lower outlet of the first fan-shaped trap, respectively.

4. The high-throughput charge detection mass spectrometer according to claim 3, characterized in that: Applying direct current voltages with the same amplitude and opposite polarities to the first sector-shaped circular ring deflector outer ring electrode (41) and the first sector-shaped circular ring deflector inner ring electrode (51) respectively, so that ions fly losslessly along the central area of ​​the first sector-shaped trap; Direct current voltages with the same amplitude and opposite polarity are applied to the outer ring electrode (42) of the second sector-shaped circular deflector and the inner ring electrode (52) of the second sector-shaped circular deflector, respectively, so that ions fly losslessly along the central area of ​​the second sector-shaped trap; and pulse voltages are applied to the outer ring electrode (41) of the first sector-shaped circular deflector and the inner ring electrode (51) of the first sector-shaped circular deflector, so as to control the introduction of ions.

5. The high-throughput charge detection mass spectrometer according to claim 3, characterized in that: The first charge signal detection module comprises a first ion manipulation lens (61), a first charge detection cylinder (71) and a second ion manipulation lens (62) which are coaxially and sequentially arranged at intervals; the first ion manipulation lens (61), the first charge detection cylinder (71) and the second ion manipulation lens (62) all have a central hole to form the first ion channel; the first ion channel is coaxial with the first upper outlet and the second upper outlet.

6. The high-throughput charge detection mass spectrometer according to claim 5, characterized in that: The second charge signal detection module comprises a third ion manipulation lens (63), a second charge detection cylinder (72) and a fourth ion manipulation lens (64) which are arranged in sequence and coaxially, the third ion manipulation lens (63), the second charge detection cylinder (72) and the fourth ion manipulation lens (64) all having a central hole to form the second ion channel, and the second ion channel is coaxial with the first lower outlet and the second lower outlet; The charge signal is detected using a first charge detection cylinder (71) and / or a second charge detection cylinder (72).

7. The high-throughput charge detection mass spectrometer according to claim 6, characterized in that: The first ion manipulation lens (61), the second ion manipulation lens (62), the third ion manipulation lens (63) and the fourth ion manipulation lens (64) are all composed of three identical circular electrodes, which are coaxial and spaced apart; three adjustable DC voltages are applied to the three circular electrodes in each group of ion manipulation lenses, and the same voltage is applied to the first and last circular electrodes in each group of ion manipulation lenses, and the DC voltage application range is 0-±2000V; The first charge detection cylinder (71) and the second charge detection cylinder (72) are both hollow cylindrical electrodes.

8. The high-throughput charge detection mass spectrometer according to claim 6, characterized in that: The ion source module comprises an ion generating source (1), an acceleration zone (2) and an ion gate (3) which are coaxial with the horizontal circular through hole (8) and arranged in sequence and spaced apart. The ion gate (3) is close to the horizontal circular through hole (8). The ion gate (3) comprises two identical rectangular plate electrodes which are parallel to each other and spaced apart from each other. An adjustable DC voltage is applied to the two rectangular plate electrodes of the ion gate (3). When the voltages of the two rectangular plate electrodes are the same, ions pass through. When there is a pressure difference between the two rectangular plate electrodes, ions are deflected and cannot enter the horizontal circular through hole (8). The acceleration zone (2) comprises more than three flat plate electrodes with circular holes in the center, the center holes of each flat plate electrode are coaxial and spaced apart; adjacent flat plate electrodes are separated by insulating pads and connected in series through resistors, and a uniform accelerating electric field is formed by applying a DC voltage at both ends to accelerate the ions introduced by the ion generating source (1).

9. The high-throughput charge detection mass spectrometer according to claim 8, characterized in that: The ion generating source (1) is an ion trap analyzer that traps ions and can selectively extract ions and enter a fan-shaped trap for m / z and charge state measurement; the ion trap analyzer is a linear ion trap, a rectangular ion trap or a Paul trap with trapping and ion excitation functions.

10. The high-throughput charge detection mass spectrometer according to claim 9, characterized in that: The working method of the high-throughput charge detection mass spectrometer is as follows: 1) The ion gate (3) is set to an open state, and the first sector-shaped circular deflector outer ring electrode (41) and the first sector-shaped circular deflector inner ring electrode (51) are at a low level; 2) The ions excited by the ion generating source (1) enter the acceleration region (2), and under the action of the accelerating electric field of the acceleration region (2), sequentially pass through the ion gate (3) in the open state and the upper circular through hole (8) to enter the first sector-shaped well of the first sector-shaped circular deflector, and sequentially pass through the first charge detection cylinder (71) and the second ion manipulation lens (62) under the action of the first ion manipulation lens (61) and enter the second sector-shaped well of the second sector-shaped circular deflector; at this time, the outer ring electrode (41) of the first sector-shaped circular deflector and the inner ring electrode (51) of the first sector-shaped circular deflector are set to a high level in a trapped state; 3) After being drawn out from the second sector trap of the second sector ring deflector, the ions sequentially pass through the fourth ion manipulation lens (64), the second charge detection cylinder (72) and the third ion manipulation lens (63), enter the first sector trap of the first sector ring deflector, and are drawn out again to the first ion manipulation lens (61); 4) The ions are trapped in the first and second fan-shaped traps to form a closed-loop ion trajectory (9), and an induced charge signal is generated each time the ions pass through the first charge detection cylinder (71) and the second charge detection cylinder (72); 5) Performing fast Fourier transformation on the time domain signals collected by the first charge detection cylinder (71) and the second charge detection cylinder (72) to obtain frequency domain signals, thereby obtaining the m / z and charge state of the ion to be detected.

Images