WO2007107106A1

WO2007107106A1 - Multipole linerar ion trap system and method of manufacturing the same with electrodes all-in-one

Info

Publication number: WO2007107106A1
Application number: PCT/CN2007/000887
Authority: WO
Inventors: Xiang Fang
Original assignee: Xiang Fang
Priority date: 2006-03-17
Filing date: 2007-03-19
Publication date: 2007-09-27
Also published as: CN101038852B; CN101038852A

Abstract

A multipole linear ion trap system and method of manufacturing such system with electrodes all-in-one are provided. The system comprise two or more sets of electrode assembly, wherein each of the electrode assembly defines a portion of a ion trap and is connected to RF and DC source, and a pair of end electrodes (5,6). The method of manufacturing electrodes all-in-one comprise processing an non-metallic substrate, covering a metal film on the surface of substrate, and removing a part of metal film on the insulation area. A scheme to developing the mass analyzer and the mass spectrographs with wide applications, multifunction, making easily and low cost is provided.

Description

Multi-stage line 3⁄4 away from the sub-trap system, the system and the integrated electrode processing method

The invention relates to the technical field of mass spectrometry, in particular to a multi-stage linear ion trap system, the system and a processing method of the integrated electrode. Background technique

The quadrupole ion trap is a special device that can be used as an ion storage device to confine gaseous ions to the quadrupole field in the ion trap for a certain period of time, and as a mass analyzer for the shield instrument. Mass spectrometry is performed with a considerable mass range and variable mass resolution. The quadrupole electrostatic field in the ion trap is generated by connecting an RF voltage, a DC voltage, or a combination of the two on each pole of the ion trap device. A conventional ion trap consists of two partial electrodes, a ring electrode and an end cap electrode. In order to produce a remarkable quadrupole field, a typical electrode shape is a hyperbolic type.

The early ion trap is a three-dimensional ion trap whose quadrupole field is generated in the direction of r and z (in the polar coordinate system). The ions are subjected to a linear force in the quadrupole field, so that a certain mass-to-charge ratio m/z range can be obtained. The ions inside are captured and stored in the ion trap. The most typical three-dimensional ion trap consists of three hyperbolic electrodes, a ring electrode and two end cap electrodes. Such devices are commonly referred to as Paul-type ion traps or quadrupole ion traps. The cylindrical ion trap is a simpler three-dimensional ion trap consisting of a ring electrode with a cylindrical inner surface and two end plate electrodes with a flat structure. The biggest drawback of the Paul-type ion trap and the cylindrical ion trap is that the number of ions trapped in the well is small, and the capture efficiency is low for incident ions ionized outside the well.

Another type of ion trap-one linear ion trap has emerged in recent years. The linear ion trap consists of a plurality of poles that are extended and placed in parallel. This pole will determine the volume of the ion trap. By connecting the RF voltage and the DC voltage to the pole, it is perpendicular to the center of the ion trap. A two-dimensional quadrupole field is created on the plane of the axis. Since the intense focusing of the ions is achieved only in two dimensions, the trapped ions can be distributed near the central axis, greatly increasing the number of ion traps. U.S. Patent No. 5,420,425 describes a two-dimensional linear ion trap consisting of three sets of quadrupoles, with a set of quadrupoles in the middle as the main quadrupole, wherein a pair of main poles are designed with slits through which ions can pass. The slit realizes injection and exit; the two sets of quadrupoles at both ends are both real Now the axial trapping trap captures the movement of ions and improves the quadrupole field of the main quadrupole. When each pole is a hyperbolic pole, a nearly ideal quadrupole field is obtained.

In each of the above ion traps, in addition to the cylindrical ion trap, accurate machining processes, such as machining, assembly, etc., are required, and such high-precision machining is quite complicated. Especially with the ion trap of the hyperboloid electrode, under the premise of ensuring the processing precision, the assembly technology becomes a major bottleneck that ultimately affects the analytical performance of the instrument, and thus becomes an ion trap that limits the development of the ion trap mass analyzer. The ability to selectively store, separate, and analyze the ion trap mass analyzer is uniquely positioned to perform mass-mass spectrometry (MS ⁿ ) experiments. Although the MS ⁿ experiment can be performed using a single ion trap, with the development of ionization methods such as electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), mass spectrometry has been extensively applied to the analysis of complex samples of macromolecules. This has placed new demands on ion trap mass analyzers, and the technology of combining ion traps using multiple ion traps has emerged. U.S. Patent No. 6,481,109 B2 proposes a multi-stage mass spectrometer in which a plurality of ion traps are arranged in series in a spatially connected manner, i.e., end to end, forming a multi-stage ion trap space, separated by end electrodes. The ions are sequentially circulated between the stages to achieve the functions of storage, separation, dissociation or analysis. U.S. Patent No. 6,838,666 B2 proposes a rectangular linear ion trap (RIT) surrounded by four rectangular plate electrodes, and proposes a RIT combined ion trap composed of three or more RITs, each of which contains four plate electrodes. And a pair of terminal electrodes, ions are circulated in the combined ion trap and the MS ⁿ experiment is performed. The combined ion trap provides a new powerful mass spectrometry tool for the study of complex samples, especially in the fields of ion chemistry, biomacromolecules and pharmaceuticals, using MS ^{n to} achieve molecular structure. However, the existing combined ion trap structure is relatively complicated, especially the terminal electrode is designed at both ends of each well unit, and the transmission and transfer of ions between the well units are realized by controlling the DC voltage on the terminal electrode. There is only a DC signal on the electrode, and there will be a severe fringing field effect between the ion trap and the terminal electrode, resulting in a significant decrease in ion transport efficiency. Ion ions often undergo significant ion loss as they pass through the terminal electrode region, with series series The increase will make the corresponding analysis process unable to carry out the corresponding analysis process due to the excessive ion loss. One of the main factors in the processing of the series; at the same time, the design process involves high-precision assembly problems between the multi-stage electrodes and the end caps, which ultimately affects the resolution and sensitivity of the ion trap mass analyzer.

In summary, existing linear ion trap mass analyzers, whether single ion traps or combined ion traps, require high precision machining and assembly. The MS^ energy of a single ion trap is relatively simple, and it is complicated or even impossible to perform analysis tasks in applications such as complex samples and ion/ion reactions of multiple samples. The combined ion trap can be used for multi-stage series analysis of complex samples and multiple samples by different combinations, but its structure is complex, ion transport efficiency is also affected, and processing assembly is relatively complicated. With the development of biology, pharmacy, ion chemistry and other disciplines, ion trap mass analyzers have more or less exposed their limitations. Therefore, exploring a linear ion trap with relatively simple structure and multiple analytical functions and a pole processing method that is easy to assemble with a pole will strongly promote the development of small ion trap mass analyzers, thus promoting biology, The development of pharmaceutical, ion chemistry and other disciplines. Summary of the invention

One of the technical problems to be solved by the present invention is to provide a multi-stage linear ion trap system which is relatively simple in structure and can be used for various analysis purposes.

The second technical problem to be solved by the present invention is to provide a processing method for an integrated electrode which is easy to realize high precision and high precision processing and assembly.

The third technical problem to be solved by the present invention is to provide a processing method for a multi-stage linear ion trap system which is easy to realize high precision and high precision processing and assembly.

In order to solve the above first technical problem, the present invention proposes a linear ion trap system, the system comprising:

Two or more electrode sets, each of which includes an electrode pair and a y electrode pair to define an ion trapping region; the electrode sets are arranged along the central axis z-axis of the ion trap system; At least one of the electrodes of the set is provided with a slit that can be used to radially introduce the sample or ions into the ion trap system, or for the sample or ions to exit the ion trap system radially; and on each electrode set A combined signal of a radio frequency signal and a direct current signal is connected; The terminal electrodes are connected to a direct current signal, and the terminal electrodes are disposed to have only one pair and are respectively disposed at the two outermost ends of the electrode groups along the Z axis of the central axis of the ion trap system.

The X electrode pair and the y electrode pair in the present invention are parallel to the central axis z axis, and the electrodes are alternately spaced by 90 degrees in an xyxy manner to define an ion trapping region; the RF power source is connected to the X and/or y electrode pair, thereby An RF ion trapping electric field is generated in the xy plane; the pair of terminal electrodes at both ends are connected to a DC direct current source to provide a DC trapping potential well between the two terminal electrodes in the z-axis direction. For two or more electrode sets, there are two or more ion trapping regions, each of which is connected to an RF signal and/or a DC DC signal.

An AC voltage is connected to the pair of X poles or the pair of y poles for exciting or ejecting ions in the X direction or the y direction, or an AC voltage is connected to the terminal electrodes to be excited in the z direction. Or expel ions. According to the analysis needs, the electrical parameters (such as RF/DC/AC parameters) of each sub-RF electrode can be provided to provide corresponding analysis functions, such as selective storage, separation, ion reaction or analysis, and at the same time, Item function.

The terminal electrode of the multi-purpose large-capacity multi-stage linear ion trap system may be a plate electrode placed along the xy plane, a multipole rod parallel to the z-axis, or a combination of a plate and a multipole. In the case where the terminal electrode is a flat electrode, a small hole or a slit may be formed in one of the flat end electrodes, or a small hole or a slit may be formed in both of the flat end electrodes, and the small hole or slit is opened. It can be used for the introduction of samples or ions, and it can also be used for samples or ions to leave the ion trap.

There are various opening schemes for the slits of each electrode group, and slits may be formed on the X electrode pairs of each sub-RF electrode group, or slits may be formed on the y-electrode pairs of each sub-RF electrode group. Under the premise of ensuring at least one slit for each sub-RF electrode group, a combined slit is used between each sub-electrode group, either at the X electrode or at the y electrode, to achieve any combination as needed. As an alternative example, slits of two or more electrode sets may be placed on electrodes located in the same circumferential position. Further, the slits of the two or more electrode groups may be arranged in a line so as to integrally process the two or more slits. The slits on each electrode group and the small holes or slits on the terminal electrodes can be used as inlets or outlets for samples or ions. By combining, it is possible to achieve along x, y. Or multi-inlet or multi-outlet analysis mode in the Z direction.

The versatile large-capacity multi-stage linear ionization 'sub-trap system of the present invention can use an ionization method of an external ion source, an ionization method using an internal ion source, or an ionization method combining an internal and external ion source. The multiple inlet mode of the ion trap allows for connection to two or more ion sources. In the case of multiple external ion sources, the ion transport system of the ion source can introduce ions into the well through small holes/slits on the terminal electrodes, or ions can be introduced into the well through slits in the electrode set. When the ion trap is used for mass analysis, multiple detectors can be used for ion detection.

In order to solve the foregoing second technical problem, the present invention provides an integrated electrode processing method, the basic steps of the method comprising: firstly using a non-metallic material as a substrate, processing into an electrode substrate having a desired electrode shape, and then A metal conductor film is coated on the surface of the non-metal electrode substrate, and finally the metal film is ground or removed at a portion where insulation is required, thereby forming two or more sub-electrodes insulated from each other.

The integrated electrode processing method is especially suitable for the case where the electrode needs to be divided into a plurality of parts. The RF electrode of the multi-purpose large-capacity linear ion trap proposed in the present application can be processed by this method. Therefore, in order to solve the aforementioned third technical problem, the present invention provides a processing method of a multi-stage linear ion trap system, the method comprising the following steps:

Forming a pair of integrated electrodes as a pair of X electrodes, forming a pair of integrated electrodes as a pair of y electrodes, wherein each integrated electrode is formed by the above-described integrated electrode processing method;

A pair of terminal electrodes are provided on both sides of the outermost ends of the pair of X electrodes and the pair of y electrodes.

The present invention also provides a method of processing a multi-stage linear ion trap system, the method comprising the steps of:

Forming a pair of integrated electrodes as a pair of electrodes, forming a pair of integrated electrodes as a pair of y electrodes, wherein each integrated electrode is formed by the above-described integrated electrode processing method;

The pair of X electrodes and the sub-electrodes on both sides of the outermost end of the pair of y electrodes are provided as a pair of terminal electrodes.

The invention also provides a processing method of a multi-stage linear ion trap system, the method comprising the following Steps:

Forming a pair of integrated electrodes as a pair of X electrodes, forming a pair of integrated electrodes as a pair of y electrodes, wherein each integrated electrode is formed by a method of processing the integrated electrodes;

Providing a pair of plate electrodes on both sides of the outermost end of the pair of X electrodes and the pair of y electrodes, the pair of plate electrodes and the adjacent sub-electrodes on the corresponding integrated electrodes A pair of terminal electrodes are formed.

In the above-described method for processing an integrated electrode and a method for processing a multi-stage linear ion trap system, the non-metal material may be a ceramic material, and the metal film may be a conductor material containing gold as a main component.

In the existing processing method, the electrode of each part is usually directly processed by a metal material, and then the parts are assembled by using an insulating material, which requires precise assembly technology, and this technology has become the current ion trap. A major bottleneck in manufacturing. The processing method using the integrated electrode and the processing method of the multi-stage linear ion trap system using the integrated electrode processing method can ensure the uniformity of the respective portions (sub-electrodes) on the same body electrode, thereby reducing the assembly technique Difficulty.

The multi-purpose large-capacity multi-stage linear ion trap system proposed in the present application can realize the ion trap analysis function by providing two or more electrode groups defining ion trapping regions in an ion trap having only one pair of terminal electrodes. The extension, according to the needs of the analysis, set up the analytical method to carry out the required analytical experiments. The ion trap has wide adaptability. When only the ion trapping region defined by one of the electrode groups is used as the analysis region, or the same signal is connected to all the electrode groups, it is equivalent to the existing single ion trap shield. A volume analyzer; when multiple ion capture regions defined by multiple electrode sets work together, by defining the function of each ion capture region, such as selective storage, separation, ion reaction or analysis regions, or a combination thereof, A variety of working modes are provided, including existing spatial sequential flow MS ⁿ analysis experiments, spatial series and time series combination MS ⁿ array analysis experiments. The combined working mode not only implements the existing MS ⁿ analysis technology, but also provides a powerful tool for exploring MS ⁿ analysis methods to help scientists conduct material structure research.

Compared with a combined ion trap composed of a plurality of ion traps that are directly connected in series, the present application proposes The structure of the multi-purpose large-capacity multi-stage linear ion trap system is more simplified, and only the structural aspect is compared. It seems that the terminal electrodes are omitted and the plurality of electrode groups are directly connected in series. However, such an omission can be an ion trap. Control, commissioning and manufacturing bring great change. Connected to each electrode group

The combined signal of RF+DC has significant advantages in the control of ion motion. When the control of the ion transport transfer process is performed, the function of the terminal electrode as in the prior art can be realized by adjusting the DC component, and the electric field force focused on the central axis can be applied to the ion assist during the ion transport process by adjusting the RF component. , so that the ions are controlled both in the axial direction and in the radial direction during the transfer process. In the prior art, only the DC signal is present on the terminal electrode, and there is a severe fringing field effect between the ion trap and the terminal electrode, resulting in a significant decrease in ion transport efficiency. As the number of series stages increases, ion loss will occur. Being too serious to carry out the corresponding analysis process has become one of the main factors limiting the number of ion treatment stages. By adopting the scheme proposed by the invention, the ion transmission path can be shortened, the influence of the fringe field effect can be reduced, the ion can be controlled in three dimensions, and the ion transmission efficiency can be effectively improved, thereby improving the sensitivity of the instrument for performing multi-level ion analysis, which is carried out Combined process analysis is critical. In addition, in the control circuit, the DC or AC signal on the terminal electrode between adjacent electrode groups can be omitted, and when there are only two electrode groups, the signal of one terminal electrode can be omitted, and the superiority does not seem to be sufficient. Obvious, but with the increase in the number of electrode groups, this advantage is particularly significant. In the debugging of the instrument, if there is one terminal electrode, the loss in the ion well will be reduced accordingly, thus reducing the influence factor on the performance of the instrument. In terms of manufacturing, without the separation of the end caps, the integrated electrode processing method can be used to reduce the difficulty of assembly.

In summary, the multi-purpose large-capacity multi-stage linear ion trap system proposed in the present application can combine the functions of the existing single ion trap and the combined ion trap, has wide applicability, and can effectively improve ion transport efficiency. Improve the sensitivity of multi-level ion analysis, providing a powerful research tool for the development of biological, pharmaceutical, and ion chemistry. At the same time, the ion trap with combined function proposed by the present invention is not based on a design scheme of multiple ion traps in series. As a whole, it is only a linear ion trap itself, and the ion is realized by designing a plurality of ion trap capture regions. The combined analysis function of the well. Invention design based on such "one ion trap realizes combined function" The solution makes the multi-stage linear ion trap structure relatively simple, reduces the work complexity of the quality control and debugging of the instrument, and extends the integrated electrode processing method proposed by the invention, thereby reducing the assembly difficulty of the ion trap. The multi-stage linear ion trap system provides a practical and versatile solution for the development of ion trap mass analyzers and mass spectrometers, which is adaptable, versatile, easy to process and assemble, and relatively inexpensive. Development of analytical techniques in the fields of pharmaceuticals, ion chemistry, etc. DRAWINGS

Figure 1: Schematic diagram of a multi-stage linear ion trap system with two electrode sets;

Figure 2: Schematic diagram of a multi-stage linear ion trap system with three electrode sets;

Figure 3a - Figure 3d: Schematic cross-section of a typical electrode;

Figure 4: Schematic diagram of a multi-stage linear ion trap system with a quadrupole of f as the terminal electrode;

Figure 5: Schematic diagram of a multi-stage linear ion trap system with plate electrodes and quadrupole as the terminal electrode; Figure 6: Schematic diagram of the dual ion source dual detector ion trap mass analysis system;

Figure 7: Schematic diagram of a multi-ion source multi-detector ion trap mass analysis system;

Figure 8: Schematic diagram of a multi-stage linear ion trap system with integrated processing;

Figure 9: A schematic cross-sectional view of an integrated electrode shown in Figure 8. detailed description

The present application will be further described in detail below with reference to the accompanying drawings. .

As shown in FIG. 1-9, the present invention provides a multi-purpose large-capacity multi-stage linear ion trap system, the system comprising:

Two or more electrode groups 10, wherein each electrode group 10 includes an X electrode pair and a y electrode pair to define an ion trapping region; the electrode groups 10 are arranged along the central axis z-axis of the ion trap system; Providing a slit on at least one electrode of each electrode group 10, the slit being used to introduce a sample or ions into the ion trap system in a radial direction, or to radially or away from the ion trap system; And a combined signal of a radio frequency signal and a direct current signal is connected to each of the electrode groups 10; the terminal electrodes 5, 6 are connected with a direct current signal, and the end electrodes 5, 6 are arranged to have only one pair and are respectively set At the two outermost ends of the electrode groups 10 along the z-axis of the central axis of the ion trap system.

Figure 1 shows a specific example of a multi-purpose high-capacity multi-stage linear ion trap system with two electrode sets. The DC, AC and RF voltages are connected to the electrode set 10 and the terminal electrodes 5, 6 respectively for capture. And analyzing ions. The X electrodes 1, 2 and y electrodes 3, 4 are placed parallel to the z-axis, and are placed at intervals of 90 degrees in the xy plane in the 1-3-2-4 clockwise direction, and the electrode group 10 is arranged in two along the z-square, each The X electrode pair 1, 2 and y electrodes 3, 4 of the electrode group 10 define an ion trapping region, and the two electrode groups 10 correspond to the ion trapping region I and the ion trapping region II, respectively. Slits 7 and 8 are formed on the X electrode pairs of the two electrode sets. The slits 7, 8 can be used to introduce the sample or ions into the ion trap in the radial direction, or to separate the sample or ions from the ion trap in the radial direction. The RF RF voltage is connected to the y electrode pair 3, 4, respectively, and can also be connected to the X and y electrode pairs 1, 2, and the RF ion trapping electric field in the xy plane is generated in the ion trapping region corresponding to the electrode group. DC DC signals are also connected to both electrode sets. The terminal electrodes 5, 6 are respectively located at the two outer ends of the two ion trapping regions defined by the two electrode groups 10; the terminal electrodes 5, 6 are connected to the DC voltage of the DC. Adjusting the DC DC voltage values on the terminal electrodes 5, 6 and the electrode group, the DC trapping electric field in the z-axis direction of the region between the two terminal electrodes 5, 6 can be obtained, and the DC potentials of the two electrode groups can be the same, or Different, thereby generating a differential capture sub-region, it is possible to simultaneously capture ions of different polarities or ions from two samples simultaneously in the two ion capture regions. The AC voltage is connected to the X electrode pair 1, 2 or y electrode 3, 4 pair, as an AC resonance excitation signal between the pair of x electrode pairs 1, 2 or y electrodes 3, 4, thereby implementing the well in the X direction or the y direction Internally excited ions. According to the analysis needs, the electrical parameters (such as RF/DC/AC parameters) of each electrode can be provided to provide corresponding analysis functions, such as selective storage, separation, ion reaction or analysis area, or an ion capture area. Multiple features.

The basic working process of mass analysis using a single capture region of a multi-purpose large-capacity multi-stage linear ion trap system is that the sample gas to be analyzed is ionized in the well to generate ions to be analyzed, or samples to be analyzed After the ionization outside the well, the ions to be analyzed are injected into the well, and the ions collide with the buffer gas to attenuate the kinetic energy, and are limited by the RF trapping electric field and the DC trapping electric field in the ion trapping region in the well, when the ions are captured, AC or The signals of other waveforms are connected to the electrodes of the electrode group 10 or to the terminal electrodes 5, 6 to achieve mass selective separation or excitation of the ions. The excitation of the target ion can be selectively excited by AC excitation, and the kinetic energy is increased. The collision-induced dissociation (CID) of the ion can be achieved after the target ion acquires kinetic energy and collides with the buffer gas. The MS ⁿ experiment can be carried out by using CID. When the AC voltage is applied to the terminal electrodes 5, 6, the scanning RF amplitude allows ions to be ejected out of the ion trap through the apertures or slits 9 in the terminal electrodes 5, 6 along the z-axis. When the AC voltage is connected to the X or y electrode pair, scanning the RF amplitude allows ions to be ejected out of the ion trap through the slits on the X or y electrodes in the X or y direction. The ion detector outside the trap detects the ejected ions to obtain the corresponding grammar map.

The basic operating principle of a single capture region for a multi-purpose, high-capacity, multi-stage linear ion trap system is the same as for the existing linear ion trap theory. When the DC portion of the RF signal to which the electrode group 10 is connected is zero, the operating state corresponds to the q-axis in the stability map. The initial RF amplitude will determine the lower limit of the stable ion mass-to-charge ratio. All ions with a mass-to-charge ratio greater than or equal to this lower limit can be captured by the ion trap and stored in the ion trap. The lower limit of the mass of ions stored in this region can be adjusted by setting the initial RF amplitude on the electrode set.

There are two ways to achieve ion separation: RF/DC separation and AC waveform separation. The RF/DC separation is based on the ion motion stability map, and the unstable ions are emitted out of the ion trap by changing the state of the ions from stable to unstable at the boundary of the stability map. The working process of RF/DC separation is to select the ions to be retained in the ion trap according to the separation needs, and calculate the state parameter ( a _{i 5 qi} ) of the retained ions so that the state point ^ cii ) falls near the apex of the stable triangle. Then, according to the calculation result, the RF component on the y-pole is adjusted and the DC component is simultaneously input, so that the target ion state point becomes (aq, ), and at this time, other ions fall into the unstable region, thereby the target ion and other The ions are separated.

The AC waveform separation is based on the relationship between the fundamental frequency of the ion motion and the ion state. The amplitude response in the z direction after excitation is proportional to the Fourier transform of the excitation waveform itself. The ion response is independent of the ion axis oscillation frequency, and also with the ion. The mass-to-charge ratio has nothing to do. The excitation of ions with a mass-to-charge ratio of m/z is determined only by the magnitude of the excitation amplitude at the corresponding frequency of the shield-to-charge ratio. Using the ion motion fundamental frequency as a link, It is not necessary to accurately calculate the ion trajectory to determine the axial amplitude of the excited ions. As long as the AC waveform corresponding to the separation purpose is connected to the corresponding electrode pair, multiple target ions can be simultaneously realized. Selective excitation and eviction.

In a multi-purpose large-capacity linear ion trap, it is often necessary to perform selective resonance excitation and eviction of a single target ion, that is, AC resonance excitation and eviction. On the shield, a special case of AC waveform separation is the target ion motion fundamental frequency. Is a certain frequency value, not a certain frequency band. In the linear ion trap shown in Figure 6, the AC signal is applied to the two X poles to achieve resonant excitation and eviction of the ions along the X direction.

The mass analysis of the multi-purpose large-capacity multi-stage linear ion trap system is performed by selecting ions to make the target ions from stable to unstable, thereby driving them out of the ion trap for ion detection. Selective instability detection can be divided into two ways: boundary emission and AC resonance eviction. The boundary emission is based on the stable boundary point on the q-axis of the stability diagram as the operating point. The DC voltage amplitude is zero. By scanning the RF voltage amplitude (rising scan), the ions enter the unstable state according to the mass-to-charge ratio from small to large. The unstable ions will be ejected from the ion trap, reach the ion detection system outside the well, receive and amplify the corresponding electrical signal, and the corresponding mass spectrum can be obtained. The AC resonance eviction utilizes the relationship between the fundamental frequency of the ion motion and the state of the ion. By scanning RF, the fundamental frequency of the ion is changed. When the fundamental frequency of the ion is equal to the frequency of the AC signal, the amplitude of the ion in the X direction. It will increase rapidly, leaving the ion trap from the slit in the center of the X-plate and entering the external detection circuit.

It is often necessary to identify the structure of a substance during mass spectrometry. The MS ⁿ experiment is the basis of this analysis. In the MSn experiment, it is necessary to cleave the target ions into fragment ions, and determine the type of the fragment ions by performing a qualitative scan on the fragment ions to determine the composition structure of the target ions. There are many ways to achieve the cleavage of target ions. Commonly used are: CID generated by collision of ions with buffer gas, electron capture cleavage (ECD) and electron transfer cleavage (ETD) by ion-ion reaction. In a multi-purpose, large-capacity multi-stage linear ion trap system, each ion trapping region can be used as a separate reaction chamber. The design of multiple ion trapping regions provides sufficient conditions for MS ⁿ by assigning regions. The ability to perform MS ⁿ experiments on a variety of processes.

Each ion capture region of a multi-purpose, high-capacity, multi-stage linear ion trap system is self-contained The function of selective ion storage, separation, reaction/cracking, and analysis, when multiple ion trapping regions work together, can combine a variety of analytical processes/methods, which also makes the multistage linear ion trap system widely available. Adaptable and versatile.

Figure 2 shows a multi-purpose, high-capacity multi-stage linear ion trap system with three electrode sets. The structure and voltage signal connections are similar to those of Figure 1, except that an electrode group 10 is added to Figure 1, which is increased accordingly. An ion trapping region III and a set of voltage signals connected to the electrode group 10. Due to the addition of an ion trapping region 111, the multi-purpose, high-capacity multi-level ion trap system works in a more diverse manner. In the present invention, the structure of the multi-stage linear ion trap system having three or more electrode groups 10 is similar to that of the above-described FIGS. 1 and 2, except that the number of electrode groups 10 changes, and the number of electrode groups 10 increases. The more diverse the multi-purpose, high-capacity multi-stage ion trap system works, it is no longer detailed.

The electrode of the electrode group 10 of the multi-purpose large-capacity multi-stage linear ion trap system can adopt various electrode shapes capable of generating a quadrupole field, as shown in Figures 3a to 3d, a hyperbolic electrode, a cylindrical electrode, and a cross-sectional edge Graded shrinkage electrode, rectangular plate electrode, etc.

In a multi-purpose large-capacity multi-stage linear ion trap system, the terminal electrodes 5, 6 may be plate electrodes placed along the xy plane, as shown in Figures 1 and 2; or may be composed of four electrodes parallel to the z-axis. The multipole rods, such as the terminal electrodes 5, 6 of Fig. 4, are quadrupole rods, and the electrodes are placed at intervals of 90 degrees in the xy plane; it may also be a combination of a plate electrode and a multipole rod, as shown in Fig. 5. The DC voltage can be connected to the flat-end electrode, and the RF voltage or DC voltage or a combination of the two can be connected to the multi-pole rod electrode. The main function of the terminal electrodes 5, 6 is to generate a potential well along the z-axis direction, confining the ions in the trapping region of the ion trap in the z-direction.

As shown in Figures 1, 2, 4 and 5, slits (7 and 8) parallel to the z-axis can be formed in at least one electrode of the electrode group 10 in the linear ion trap and connected to the sub-X or y electrode pairs. Injecting an AC signal to excite ions in the X or y direction or to eject ions out of the ion trap; or to create a small hole or slit in the end electrode of the plate to excite ions in the z direction or to eject ions out of the ion trap; Each of the above modes is arbitrarily combined to realize multi-directional excitation of ions or ejection of ions from the ion trap. There are various openings for the slits on the electrode group 10, and slits may be formed on the X electrode pairs of each electrode group 10, or slits may be formed on the y electrode pairs of each electrode group 10. Under the premise of ensuring that at least one slit is formed in each electrode group 10, a combination slit is used between each of the sub-electrode groups 10, or is opened on the X electrode or on the y electrode, and is arbitrarily combined as needed. As an alternative example, the slits of two or more electrode sets 10 can be placed on electrodes located in the same circumferential position (as shown in Figures 1, 2). Further, as shown in FIG. 8, the slits of the two or more electrode groups 10 may be arranged in a line so as to integrally process the two or more slits. The slits on the electrodes and the small holes or slits in the terminal electrodes 5, 6 can be used as inlets or outlets for the sample or ions, and a multi-inlet or multi-outlet analysis mode in the x, y or z direction can be achieved by combination.

The multi-purpose large-capacity linear ion trap can be ionized by an external ion source, or ionized by an internal ion source, or ionized by a combination of internal and external ion sources. The multiple inlet mode of the ion trap allows for connection to two or more ion sources. In the case of multiple external ion sources, the ion transport system of the ion source can introduce ions into the well through small holes/slits in the end cap, or can introduce ions into the well through slits in the RF electrode. Figure 6 shows a dual-ion source dual detector multi-purpose high-capacity linear ion trap. The ions generated by the two ion sources enter the well from the small holes on the two flat-end electrodes, respectively. The radial ions are ejected, and detectors are disposed outside the two slits to detect ions ejected from the two ion trapping regions, respectively. Figure 7 shows a combination of a multi-source multi-detector multi-purpose high-capacity multi-stage linear ion trap system. The corresponding device can be connected to each ion source or detector position according to specific needs, and the combination can be realized in space three-dimensional. Multi-ion source multi-detection shield analysis program.

In the multi-purpose large-capacity multi-stage linear ion trap system of the above structure, by providing two or more electrode groups 10 in the z direction, the ion trap analysis function can be expanded, and the analysis method can be set according to the needs of the analysis purpose. The required analytical experiments can be carried out. The ion trap has wide adaptability. When only one of the ion trapping regions is used as the analysis region, or all ion trap units are connected to the same signal, it is equivalent to the existing single ion trap mass analyzer; By working with multiple sub-areas, by defining the functions of each ion-trapping area, such as selective storage, separation, The ion reaction or analysis region, or a combination thereof, provides a variety of modes of operation, including existing spatial sequential flow MS ⁿ analysis experiments, spatial series and time series combination MS ⁿ array analysis experiments. The combined working mode not only implements the existing MS ⁿ analysis technology, but also provides a powerful tool for exploring MS ⁿ analysis methods to help scientists verify or implement more possible technical routes for material structure research.

The invention also proposes an integrated electrode processing method.

The basic steps of the integrated electrode processing method include: firstly, using a non-metal material as a substrate, processing into an electrode substrate having a desired RF electrode shape, such as a hyperbolic electrode, a cylindrical electrode, a rectangular plate electrode, and being analyzable into a plurality of thin layers The optimized field electrode of the unit is then coated with a metal conductor film on the surface of the non-metal electrode substrate, and finally the metal film is worn away or removed at the portion where insulation is required. In this processing method, a non-metallic material may be selected from a ceramic material, and a metal film may be selected from a conductor material containing gold as a main component, such as high-purity gold. The integrated electrode processing method is particularly suitable for the case where the electrode needs to be divided into a plurality of parts, and the electrode of the multi-purpose large-capacity linear ion trap proposed in the present application can be processed by the method.

For example, as an alternative example, the processing method of the multi-stage linear ion trap system of the present invention may include the following steps:

Thus, the X electrode pair and the y electrode pair are integrated electrodes, and each X integrated electrode forms two or more X sub-electrodes by removing the metal film, and each y-body electrode is removed by removing the metal film. Two or more y sub-electrodes are formed, and each of the corresponding X sub-electrode pairs and y sub-electrode pairs can define an ion trapping region, which constitutes an electrode group of the present invention, thereby forming a pair The X electrode and the pair of y electrodes can form two or more electrode groups between the terminal electrodes of the present invention.

As another optional example, the processing method of the multi-stage linear ion trap system of the present invention may be Including the following steps:

Thus, the terminal electrode and the electrode group of the multistage linear ion trap system of the present invention are formed by integrating electrodes, thereby omitting the assembly between the terminal electrode and the electrode group.

As still another alternative example, the processing method of the multi-stage linear ion trap system of the present invention may include the following steps:

A pair of plate electrodes are disposed on both sides of the outermost end of the pair of electrodes and the pair of y electrodes, and the pair of plate electrodes and the sub-electrodes adjacent thereto on the corresponding integrated electrodes are configured together A pair of terminal electrodes.

Figure 8 and Figure 9 show the multi-purpose large-capacity linear ion trap processed by the integrated method. The shape of the electrode is hyperbolic. Each integrated electrode is divided into three sub-electrodes, thus having three or More than three electrode groups 10, wherein the dark surface in Fig. 8 indicates that the gold film is covered, the white surface indicates the surface of the ceramic substrate from which the gold film is removed, and the slits of the X electrodes of the respective electrode groups are opened, the same X The three slits on the electrode are connected in one piece, that is, a long slit is opened during the processing of the ceramic base electrode, and the slit is divided into three parts while dividing the electrode into three parts in the subsequent step. This one-time slitting method greatly simplifies the machining process and ensures that the slits of each part are hooked and on the same line.

In the existing processing methods, the electrode of each part is usually directly processed by a metal material, and then the parts are assembled by using an insulating material, which requires precise assembly technology, and this technology has become the current ion trap processing. A big bottleneck in manufacturing.一体化Using an integrated processing method, the uniformity of each part on the same electrode can be ensured, thereby reducing the difficulty of assembly technology. The present invention is not limited to the specific structure of the above embodiment, wherein the number of end portions divided by the electrode group, the size and proportion of each part, the connection position of the ion source and the detector, and the like can be adjusted as needed, and the same idea based on the present invention All are within the scope of the invention.

The structure of the multi-purpose large-capacity linear ion trap proposed by the present application is more simplified than that of the combined ion traps in which a plurality of ion traps are directly connected in series. It is only a structural comparison, and it seems that only the terminal electrodes are omitted. Multiple RF electrode sets are connected in series directly, but such omissions can bring about revolutionary changes in the control, commissioning and manufacturing of ion traps. The combined signal of RF+DC is connected to each of the electrode groups defining the ion trapping region, which has significant advantages in the control of ion motion. When the control of the ion transport transfer process is performed, the function of the terminal electrode as in the prior art can be realized by adjusting the DC component, and the electric field force focused on the central axis can be applied to the ion assist during the ion transport process by adjusting the RF component. , so that the ions are controlled both in the axial direction and in the radial direction during the transfer process. In the prior art, only the DC signal is present on the terminal electrode, and there is a severe fringing field effect between the ion trap and the terminal electrode, resulting in a significant decrease in ion transport efficiency. As the number of series stages increases, ion loss will occur. Being too serious to carry out the corresponding analysis process has become one of the main factors limiting the number of ion treatment stages. By adopting the scheme proposed by the invention, the ion transmission path can be shortened, the influence of the fringe field effect can be reduced, the ion can be controlled in three dimensions, and the ion transmission efficiency can be effectively improved, thereby improving the sensitivity of the instrument for performing multi-level ion analysis, which is carried out Combined process analysis is critical. In addition, in the control circuit, the DC or AC signal on the terminal electrode between adjacent wells can be omitted, and when there are two electrode groups, the signal of one terminal electrode can be omitted, and the superiority does not seem obvious enough, but This advantage is particularly significant as the number of electrode sets increases. In the instrument debugging, the loss of the ion trap is reduced by one less electrode, which reduces the influence on the performance of the instrument. In terms of manufacturing, without the separation of the end caps, the integrated electrode can be processed to reduce the difficulty of assembly.

In summary, the multi-purpose large-capacity linear ion trap proposed in the present application can combine the functions of the existing single ion trap and the combined ion trap, has wide applicability, and can effectively improve ion transport efficiency and thereby improve multi-level. Sensitivity of ion analysis for bio, pharmaceutical, ion chemistry, etc. The development of the domain provides a powerful research tool. At the same time, the ion trap with combined function proposed by the present invention is not based on a design scheme of multiple ion traps in series. As a whole, it is only a linear ion trap itself, and the ion trap is realized by designing a plurality of ion trapping regions. Combined analysis capabilities. Based on such an invention design scheme of "one ion trap realizes combined function", the ion trap structure is relatively simple, the work complexity of shield instrument control and debugging is reduced, and the integrated electrode processing proposed by the present invention is extended. The method thus reduces the assembly difficulty of the ion trap. The multi-stage linear ion trap system provides a practical and adaptable solution for the development of ion trap mass analyzers and mass spectrometers, which is adaptable, versatile, easy to process and assemble, and relatively low in cost. Development of analytical techniques in the fields of pharmaceuticals, ion chemistry, etc.

Claims

Claim

1. A multi-stage linear ion trap system, the system comprising:

Two or more electrode sets, wherein each electrode set includes an X electrode pair and a y electrode pair to define an ion trapping region; the electrode sets are arranged along the z axis of the central axis of the ion trap system; a slit is disposed on at least one electrode of the electrode group; and a combined signal of a radio frequency signal and a direct current signal is connected to each electrode group;

The terminal electrodes are connected to a direct current signal, and the terminal electrodes are disposed to have only one pair and are disposed at the two outermost ends of the electrode groups along the z-axis of the central axis of the ion trap system, respectively.

2. The multi-stage linear ion trap system of claim 1 wherein said slit is provided in either the X pole pair or the Y pole pair of the electrode set.

3. The multi-stage linear ion trap system of claim 1 wherein the two or more electrode sets open the slits in electrodes located at the same circumferential position.

The multi-stage linear ion trap system according to claim 3, wherein the slits on the electrodes of the two or more electrode groups are linearly arranged in the Z-axis direction.

5. The multi-stage linear ion trap system according to claim 1, wherein an AC voltage is connected to the X electrode pair or the y electrode pair for exciting or ejecting in the X direction or the y direction. On the ion; or an AC voltage is connected to the pair of terminal electrodes to excite or dislodge ions in the z direction.

6. The multi-stage linear ion trap system according to claim 1, wherein said pair of terminal electrodes are plate electrodes placed along an xy plane, or a multipole rod parallel to the z-axis, or a flat plate The combination of an electrode and a multipole.

7. The multi-stage linear ion trap system of claim 6 wherein at least one of said flat end electrodes has apertures or slits for injection or ejection of the sample or ions.

8. The multi-stage linear ion trap system of claim 1 wherein the ion source used in the linear ion trap system is an external ion source or an internal ion source, or a combination of the two.

9. The multi-stage linear ion trap system of claim 1 wherein said linear ion trap system uses at least two ion sources.

10. The multi-stage linear ion trap system according to claim 1, wherein the two or more electrode groups are formed such that the non-metallic material is used as a substrate to form an electrode having a desired electrode shape. a substrate; a metal film is coated on the surface of the electrode substrate; and a metal film is removed at a portion corresponding to a position between each two adjacent electrode groups, thereby forming the two or more electrode groups.

11. A method of processing an integrated electrode, the method comprising the steps of:

Processing an electrode substrate having a desired electrode shape with a metal material as a base;

Coating a metal film on the surface of the electrode substrate;

The metal film is removed at a portion where insulation is required, thereby forming two or more sub-electrodes insulated from each other.

The integrated electrode processing method according to claim 11, wherein the non-metallic material is ceramic.

The integrated electrode processing method according to claim 11, wherein the metal film is made of a conductor material containing gold as a main component.

14. A method of processing a multi-stage linear ion trap system, the method comprising the steps of: forming a pair of integrated electrodes as a pair of X electrodes, forming a pair of integrated electrodes as a pair of y electrodes, wherein each integrated electrode All formed by the method of claim 11;

The method of processing a multi-stage linear ion trap system according to claim 14, wherein the non-metallic material is ceramic.

The method of processing a multi-stage linear ion trap system according to claim 14, wherein the metal film is made of a conductor material containing gold as a main component.

17. A method of processing a multi-stage linear ion trap system, the method comprising the steps of: forming a pair of integrated electrodes as a pair of X electrodes, forming a pair of integrated electrodes as a pair of y electrodes, wherein each integrated electrode All formed by the method of claim 11;

Providing a pair of the pair of X electrodes and the pair of y electrodes on the outermost sides of the pair of y electrodes Terminal electrode.

18. A method of processing a multi-stage linear ion trap system according to claim 17, wherein said non-metallic material is ceramic.

The method of processing a multi-stage linear ion trap system according to claim 17, wherein the metal film is made of a conductor material containing gold as a main component.

20. A method of processing a multi-stage linear ion trap system, the method comprising the steps of: forming a pair of integrated electrodes as a pair of X electrodes, forming a pair of integrated electrodes as a pair of y electrodes, wherein each integrated electrode All formed by the method of claim 11;

A method of processing a multi-stage linear ion trap system according to claim 20, wherein said non-metallic material is ceramic.

The method of processing a multi-stage linear ion trap system according to claim 20, wherein the metal film is made of a conductor material containing gold as a main component.