Electron capture dissociation apparatus

Abstract

An electron capture dissociation apparatus. The apparatus comprises a linear ion trap (3) consisting of an even number of strip electrodes (3.1), wherein an in-phase radio frequency voltage and an anti-phase radio frequency voltage are alternately applied to the strip electrodes (3.1) of the linear ion trap (3) in sequence, such that there is a saddle point potential at the central axis of an ion trapping space; and electrons emitted by an electron emission source (1) are accelerated by means of an accelerating electrode (2.1), are then focused by means of a focusing lens (2.2), and then enter the ion trapping space (3.2) through an electron introduction slot (3.3). The potential of the electron emission source (1) is set to change relative to the saddle point potential within a radio frequency cycle according to a predefined pattern, such that electrons enter the linear ion trap (3) through the electron introduction slot (3.3) when the radio frequency voltages on the strip electrodes (3.1) where the electron introduction slot (3.3) is located are in a positive half-cycle, and decelerate, before reaching the central axis of the ion trapping space (3.2), to an energy range where electron capture dissociation may occur, thereby improving the time window and dissociation efficiency of electron capture dissociation.

Description

An electron capture dissociation device

[0001] TECHNICAL FIELD

[0002] The present application relates to the technical field of mass spectrometry devices and methods, in particular to an electron capture dissociation device.

[0003] BACKGROUND

[0004] Various dissociation methods are required for analyzing the sequence of a peptide or protein by tandem mass spectrometry. Among them, electron capture dissociation (ECD) can provide a wider sequence coverage than collision-induced dissociation based on collision with neutral gas molecules, and it can preserve side chains and groups produced by post-translational modification, providing accurate information for post-translational modification site determination, and is a very useful technique. Electron capture dissociation requires the reaction of a polyvalent positive ion with an ion having an energy of less than 1-3 eV (depending on the ion to be dissociated), and the captured electron is released, causing chemical bond cleavage and ion dissociation.

[0005] Currently, electron capture dissociation devices mainly include ion transmission type and ion trapping type. In the ion transmission type device, the electrons generated by the electron source converge into a low-energy electron cloud with a high electron density, and the ions will capture electrons when passing through this region, causing cleavage; in the ion trapping type device, the ions are first trapped in the ion trap, and low-energy electrons are introduced into the ion trapping space, so that the ions react with the low-energy electrons. Research has found that the ion trapping type electron capture dissociation device can obtain better dissociation efficiency than the transmission type device. In the early stage, the ion trapping type electron capture dissociation device used a superconducting magnet ICR cell to trap ions, and at the same time, electrons were introduced into the ion trapping space along the magnetic field lines to make them react with each other; however, this device has a large volume, high cost and high maintenance cost, and there are fewer users who have the conditions to use such a device. In the ion trap using radio frequency electric field to trap ions, a large number of electron capture dissociation attempts have also been carried out; however, the ion trap using radio frequency electric field to trap ions has a very strong alternating electric field, which will cause the incident electron beam to be deflected or accelerated, resulting in that the energy of the electrons is difficult to be lower than 1 eV, and even not easy to be lower than 3 eV.

[0006] To solve the problem of the influence of the alternating electric field on the incident electron beam, some people have proposed new solutions; for example, Takashi Baba mentioned in Analytical Chemistry, No. 76 (2004) 4263-4266, introducing a magnetic field in the axis direction of the radio frequency ion trap, allowing electrons to enter the ion trap along the magnetic field direction. Because the electric field strength in the center of the radio frequency quadrupole field is almost zero, the electron transmission along the magnetic line of force in the center of the trapped quadrupole field will not be heated. This method requires an additional carefully designed magnetic field, which is difficult to process and install. Gregory S. J. Wells in US20090547358A uses a special waveform of the trapped electric field. The alternating voltage waveform of the trapped electric field has a short period of zero electric field, and during this period, the electron can enter the ion trapping space without disturbance. However, this special waveform is obtained by cutting the sine wave of the radio frequency power supply, which is extremely difficult to implement and is difficult to be applied in practice. In addition, US7755034B2 gives another method, which uses a digital square wave that can form three steps as the driving voltage of the ion trap. One of the steps has a zero electric field time period, and the electron is introduced into the ion trap during the zero electric field period. Ding Li et al. in Analytical Chemistry, No. 78 (2006) 1995-2000, uses a high-low digital square wave to drive a 3D ion trap. The electron is introduced from the end cover during the positive period, and the electron energy can be reduced to nearly zero under the action of the deceleration field when the electron is transported to the center of the 3D ion trap, achieving better electron capture and dissociation in the 3D ion trap. Although the digital square wave generated by the switch is not a problem in technology, most mass spectrometers currently use the sine wave generated by the radio frequency power supply to drive the ion trap. At the same time, the 3D ion trap is gradually eliminated because of its poor introduction efficiency and low ion storage capacity.

[0007] Therefore, the Chinese patent CN117594415A provides an electron capture and dissociation device, which sets the potential of the electron emission source close to the DC saddle point potential, so that the high frequency voltage of the electron on the strip electrode in the electron introduction slot is in the positive half cycle, and the electron enters the linear ion trap. The above patent does not consider the influence of the change of the radio frequency electric field in the ion trap on the energy of the electron when the electron enters the linear ion trap through the electron introduction slot, and does not take the necessary potential compensation, which may cause the actual energy of some phase incident electrons to be relatively high, and some phase electrons cannot reach near the axis of the ion trap.

[0008] In summary, it is highly expected in the art to enlarge the proportion of the electrons successfully introduced into the high-frequency driving waveform to cause electron capture dissociation, and to improve the introduction efficiency.

[0009] SUMMARY

[0010] The technical problem to be solved by the present application is how to enlarge the proportion of the phase interval successfully introducing electrons to cause electron capture dissociation in the radio frequency driving waveform relative to the entire radio frequency period, and to improve the electron capture dissociation efficiency.

[0011] The present application provides an electron capture dissociation device, comprising:

[0012] A linear ion trap for trapping parent ions and product ions to be dissociated, comprising an ion trapping space surrounded by an even number of strip electrodes, and at least one strip electrode having an electron introduction slot for introducing electrons from outside the linear ion trap into the ion trapping space;

[0013] An electron emission source for emitting electrons to the linear ion trap, the electron emission source being arranged corresponding to the electron introduction slot, and an electron emission path being formed between the electron emission source and the electron introduction slot;

[0014] An electrode group arranged on the electron emission path, the electrode group comprising an electron acceleration electrode for accelerating the electrons emitted by the electron emission source to form a flat electron beam, and a focusing lens for converging the electron beam, the electron acceleration electrode and the focusing lens being arranged in sequence and in parallel along the direction from the electron emission source to the linear ion trap;

[0015] A radio frequency power supply for generating a positive phase radio frequency voltage and an inverted phase radio frequency voltage with equal voltage amplitudes and opposite phases, the positive phase radio frequency voltage and the inverted phase radio frequency voltage being applied in sequence and alternately on the even number of strip electrodes, and an alternating radio frequency multipole field being formed in the ion trapping space, and a fixed direct current saddle point potential existing at the central axis in the ion trapping space;

[0016] A potential control unit electrically connected to the electron emission source for controlling the potential of the electron emission source; the potential control unit provides a varying potential to the electron emission source, and the potential difference between the varying potential and the direct current saddle point potential varies according to a preset voltage-phase function relationship when the radio frequency voltage of the strip electrode corresponding to the electron introduction slot is in the positive half cycle, so that the electrons emitted by the electron emission source enter the linear ion trap through the electron introduction slot, and are decelerated to the energy range causing electron capture dissociation before reaching the central axis of the ion trapping space, and react with the trapped parent ions to be dissociated and cause dissociation to generate product ions.

[0017] In order to compensate the energy loss of the electrons caused by the dynamic electric field of the radio frequency, the potential control unit provides a varying potential for the electron emission source, which varies according to a specific voltage-phase function when the radio frequency voltage of the bar electrode corresponding to the electron introduction slot is in the positive half cycle. Preferably, the varying potential is generated by playing the function data stored in advance by using a high-speed digital-to-analog conversion chip and an amplifier.

[0018] Compared with the prior art, the electron capture and dissociation device has the following advantages: the positive phase radio frequency voltage and the negative phase radio frequency voltage are alternately applied to the bar electrodes of the linear ion trap in sequence, so that a direct current saddle point potential exists at the central axis of the ion trapping space; the potential of the electron emission source is set to be different from the direct current saddle point potential, and varies according to a preset voltage-phase function in each radio frequency cycle, so that the electrons emitted by the electron emission source are accelerated by the accelerating electrode, focused by the focusing lens, introduced into the linear ion trap from the electron introduction slot when the radio frequency voltage of the bar electrode where the electron introduction slot is located is in the positive half cycle, and decelerated to the energy range where the electron capture and dissociation can occur before reaching the central axis of the ion trapping space. The design expands the time window for successfully introducing the electrons to occur the electron capture and dissociation in the radio frequency cycle, and improves the efficiency of the electron capture and dissociation.

[0019] In a possible implementation, the emission surface of the electron emission source is long strip-shaped, and the long strip-shaped emission surface of the electron emission source extends in parallel with the central axis of the ion trapping space.

[0020] In a possible implementation, the electron emission source is an inter-thermal hot cathode emission source.

[0021] Compared with the prior art, the above technical solution can avoid the voltage drop caused by the heating current, and ensure that the emission surface of the electron emission source has a consistent potential in the entire axial direction.

[0022] In a possible implementation, the electron emission source is a direct-thermal hot cathode emission source, and the electron emission source is formed by splicing a plurality of direct-thermal hot cathodes, and the alternating heating voltage connection method of positive, negative, positive, and the like is adopted, so that the emission surface of the electron emission source has a low voltage difference.

[0023] In a possible implementation, the electron emission source is a field emission electron emission source coated with carbon nanotubes, velvet, or the like, or a field emission electron emission source formed by a chemical etching method on a substrate to form micro-emission protrusions or emission blades.

[0024] In a possible implementation, the focusing lens includes at least two rectangular focusing electrodes, the focusing electrodes are parallel to each other, and rectangular openings are formed in the focusing electrodes to further converge the electron beam.

[0025] Compared with the prior art, the above technical scheme can ensure that the flat electron beam can smoothly pass through the electron introduction slot into the ion trapping space.

[0026] In a possible implementation, an electron emission slot is formed on the bar-shaped electrode in which the electron introduction slot is located and which has the same phase of voltage, a reflecting electrode is arranged at the corresponding electron emission slot outside the linear ion trap, and the potential of the reflecting electrode is a preset range of negative values relative to the voltage of the electron emission source.

[0027] Compared with the prior art, the above technical scheme can reflect and reuse the electrons passing through the center of the ion trapping space.

[0028] In a possible implementation, the radio frequency power supply includes an LC oscillation circuit; the LC oscillation circuit includes an inductor coil having a first output end, a second output end and a center tap, wherein the first output end and the second output end of the inductor coil are respectively used to generate positive-phase radio frequency voltage and anti-phase radio frequency voltage with opposite phases, and the first output end and the second output end of the inductor coil are respectively electrically connected with a balance adjustment variable capacitor, so as to ensure that the voltage amplitudes of the positive-phase radio frequency voltage and the anti-phase radio frequency voltage are equal by adjusting the balance adjustment variable capacitor; if the direct current saddle point potential is zero, the center tap is grounded; and if the linear ion trap needs to be suspended to a preset potential, the center tap is electrically connected with a power supply to provide a specific potential.

[0029] In a possible implementation, each of the bar-shaped electrodes is divided into a front section, a middle section and a rear section along the direction of the central axis in the ion trapping space, and the front section and the middle section and the middle section and the rear section of the bar-shaped electrode are insulated; the space surrounded by the middle sections of the even number of bar-shaped electrodes is the actual trapping space of the ions, and the radio frequency power supply provides the same amplitude of radio frequency voltage to the front section, the middle section and the rear section of the same bar-shaped electrode; the electron capture and dissociation device further includes a direct current power supply, the direct current power supply provides direct current voltage to the front section, the middle section and the rear section of the bar-shaped electrode respectively, and the direct current voltage of the front section and the rear section of the bar-shaped electrode is higher than that of the middle section of the bar-shaped electrode.

[0030] Compared with the prior art, the above technical scheme can generate a potential barrier for trapping ions along the central axis in the linear ion trap.

[0031] In a possible implementation, the potential control unit includes a high-speed digital-to-analog conversion chip for storing preset voltage-phase function data and an amplifier, and the amplifier is electrically connected with the high-speed digital-to-analog conversion chip for outputting a potential difference varying according to the preset voltage-phase function relationship.

[0032] BRIEF DESCRIPTION OF DRAWINGS

[0033] Figure 1 is a structural schematic diagram of embodiment 1 of the present application;

[0034] Figure 2(a) is a waveform diagram of the sinusoidal function of the varying potential applied to the strip electrodes in the linear ion trap of embodiment 1 of the present application;

[0035] Figure 2(b) is a graph of the relationship between the emission source compensation voltage and the phase of the radio frequency power supply in embodiment 1 of the present application;

[0036] Figure 3(b) is a graph of the trajectory of the electron emitted from the position x0 = 0.4 mm on the electron emission source when the radio frequency voltage of the linear ion trap of embodiment 1 of the present application reaches 5 V;

[0037] Figure 4 is a graph of the trajectory of the electron at x0 = 0.4 mm in embodiment 1 of the present application;

[0038] Figure 5 is a side view of the trajectory of the electron emitted from the electron emission source in embodiment 1 of the present application;

[0039] Figure 6 is a structural schematic diagram of a direct heating type hot cathode emission source in embodiment 4 of the present application;

[0040] Figure 7 is a structural schematic diagram of embodiment 2 of the present application;

[0041] Figure 8 is a structural schematic diagram of embodiment 3 of the present application;

[0042] Figure 9 is a first structural schematic diagram of the coupling of the ion dissociation device of the present application with other parts of the mass spectrometer;

[0043] Figure 10 is a second structural schematic diagram of the coupling of the ion dissociation device of the present application with other parts of the mass spectrometer;

[0044] Figure 11 is a structural schematic diagram of the radio frequency power supply in embodiment 1 of the present application;

[0045] Figure 12 is a structural schematic diagram of the cross-sectional structure of the six-electrode linear ion trap of the present application.

[0046] Explanation of reference numerals:

[0047] 1, electron emission source; 2, electrode group; 2.1, electron acceleration electrode; 2.2, focusing lens; 2.2.1, focusing electrode; 2.3, rectangular opening; 3, linear ion trap; 3.1, strip electrode; 3.1a, X strip electrode; 3.1b, Y strip electrode; 3.2, ion trapping space; 3.3, electron introduction slot; 3.4, electron extraction slot; 4, radio frequency power supply; 4.1, inductive coil; 4.1a, output terminal; 4.1b, center tap; 4.2, power supply; 5, potential control unit; 6, direct current power supply; 7, reflecting electrode; 8, balance adjustment variable capacitor; 9, front end cover; 10, rear end cover.

[0048] DETAILED DESCRIPTION

[0049] First, those skilled in the art should understand that the embodiments are only used to explain the technical principles of the embodiments of the present application, and are not intended to limit the protection scope of the embodiments of the present application. Those skilled in the art can adjust them as needed in order to adapt to specific application occasions.

[0050] In the description of the embodiments of the present application, it should be noted that, unless otherwise explicitly specified and limited, the terms "connected", "connected" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium. For those skilled in the art, the specific meaning of the above terms in the embodiments of the present application can be understood according to specific circumstances.

[0051] In the embodiments of the present application, unless otherwise explicitly specified and limited, the first feature is "on" or "under" the second feature, which can be that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, the first feature "above", "over" and "on" the second feature can be that the first feature is directly above or obliquely above the second feature, or it only means that the horizontal height of the first feature is higher than that of the second feature. The first feature "below", "under" and "under" the second feature can be that the first feature is directly below or obliquely below the second feature, or it only means that the horizontal height of the first feature is less than that of the second feature.

[0052] The present application will be further described in detail below in combination with the drawings and specific embodiments.

[0053] Implementation principle

[0054] The key of electron capture dissociation in linear ion trap is to prevent low-energy electrons from being heated, that is, there is no too large energy range, and the energy of the electrons is not more than 3eV in the embodiment of the application. The electrons emitted by the hot cathode electron emission source are difficult to be introduced out and become a focused electron beam without acceleration. The method of accelerating first and then decelerating is adopted in the embodiment of the application, so that the energy of the electron beam is reduced to the energy range required for electron capture dissociation when the electron beam reaches the central axis of the ion trapping space.

[0055] Embodiment 1

[0056] Referring to FIG. 1, an electron capture dissociation device includes:

[0057] A linear ion trap 3 for trapping parent ions and product ions to be dissociated includes an ion trapping space 3.2 surrounded by an even number of strip electrodes 3.1, and at least one strip electrode 3.1 is provided with an electron introduction slot 3.3 for introducing electrons from outside the linear ion trap 3 into the ion trapping space 3.2. In this embodiment, the electron introduction slot 3.3 is provided on one of the strip electrodes 3.1. The linear ion trap 3 in this embodiment is a two-dimensional four-stage ion trap, as shown in FIG. 1, having four strip electrodes 3.1. The four strip electrodes 3.1 in this embodiment are divided into a pair of X strip electrodes 3.1a and a pair of Y strip electrodes 3.1b. The inner sides of the corresponding ion trapping spaces 3.2 of the X strip electrodes 3.1a and the Y strip electrodes 3.1b are both hyperboloid-shaped. The four strip electrodes 3.1 are distributed in rotational symmetry.

[0058] An electron emission source 1 for emitting electrons to the linear ion trap 3, the electron emission source 1 is arranged corresponding to the electron introduction slot 3.3, and an electron emission path is formed between the electron emission source 1 and the electron introduction slot 3.3. The emission surface of the electron emission source 1 is long-strip-shaped, and the extension direction of the emission surface of the electron emission source 1 is parallel to the central axis of the ion trapping space 3.2. The electron emission source 1 in this embodiment adopts a self-heating hot cathode, and the heating current of the electron emission source 1 does not affect the potential of the cathode emission surface, avoiding the voltage drop formed by the heating current, and ensuring that the emission surface of the electron emission source 1 has a consistent potential in the entire axial direction.

[0059] The electrode group 2 is arranged on the electron emission path, and the electrode group 2 comprises an electron acceleration electrode 2.1 for accelerating the electron emission of the electron emission source 1 to form a flat electron beam and a focusing lens 2.2 for converging the electron beam, and the electron acceleration electrode 2.1 and the focusing lens 2.2 are sequentially arranged along the electron emission source 1 to the linear ion trap 3; the focusing lens 2.2 comprises at least two groups of rectangular focusing electrodes 2.2.1, the focusing electrodes 2.2.1 are arranged along the electron emission path, the focusing electrodes 2.2.1 are arranged in parallel between the focusing electrodes 2.2.1, and rectangular openings 2.3 are formed in the focusing electrodes 2.2.1, which are beneficial to converging the electron beam and ensuring that the flat electron beam can smoothly pass through the electron introduction slot 3.3 into the ion trapping space 3.2.

[0060] The radio frequency power supply 4 is used for generating positive phase radio frequency voltages and reverse phase radio frequency voltages with equal voltage amplitudes and opposite phases, and the positive phase radio frequency voltages and the reverse phase radio frequency voltages are alternately applied to each of the strip electrodes 3.1 in a circumferential order, and an alternating radio frequency multipole field is formed in the ion trapping space 3.2, and the radio frequency multipole field has a fixed direct current saddle point potential at the central axis of the ion trapping space 3.2; in the embodiment, the X strip electrodes 3.1a are provided with the positive phase radio frequency voltages, and the Y strip electrodes 3.1b are provided with the reverse phase radio frequency voltages; thus, the potential of the central axis of the ion trapping space 3.2 always remains zero; in the embodiment, the radio frequency power supply 4 comprises an LC oscillation circuit, and the LC oscillation circuit is a prior art and will not be described in detail here, as shown in FIG. 11, the LC oscillation circuit comprises an inductor coil 4.1, the inductor coil 4.1 has a first output end 4.1a, a second output end 4.1c and a center tap 4.1b, wherein the first output end 4.1a and the second output end 4.1c of the inductor coil 4.1 are respectively used for generating positive phase radio frequency voltages and reverse phase radio frequency voltages with opposite phases, and the first output end 4.1a and the second output end 4.1c of the inductor coil 4.1 are respectively electrically connected with a balance adjusting variable capacitor 8, and the balance adjusting variable capacitor 8 is adjusted to ensure that the positive phase radio frequency voltages and the reverse phase radio frequency voltages have equal voltage amplitudes; the center tap 4.1b of the inductor coil 4.1 is grounded; thus, the voltage of the radio frequency power supply 4 driving the Y strip electrodes 3.1a is , the voltage of the radio frequency power supply 4 driving the X strip electrodes 3.1b is , the pair of X strip electrodes 3.1a and the pair of Y strip electrodes 3.1b in the embodiment are geometrically symmetrically arranged, and the output coils of the X strip electrodes 3.1a and the Y strip electrodes 3.1b are symmetric, and the potential at the direct current saddle point potential of the ion trapping space 3.2 is zero;

[0061] The potential control unit 5 is electrically connected with the electron emission source 1 to control the potential of the electron emission source 1; the potential control unit provides a variable potential for the electron emission source, the potential difference between the variable potential and the saddle point potential changes according to a preset voltage-phase function when the radio frequency voltage of the strip electrode corresponding to the electron introduction slot is in the positive half cycle, the voltage in the voltage-phase function is the potential difference between the variable potential and the saddle point potential, so that the electrons emitted by the electron emission source enter the linear ion trap through the electron introduction slot; when the radio frequency voltage of the strip electrode 3.1 corresponding to the electron introduction slot 3.3 is in the positive half cycle, the electrons emitted by the electron emission source 1 are accelerated before entering the linear ion trap, and after entering the linear ion trap, the electrons are accelerated, and before reaching the central axis of the ion trapping space 3.2, the electron energy is reduced to nearly zero, which belongs to the energy range in which electron capture dissociation is easy to occur; the low-energy electrons react with the trapped parent ions to be dissociated and cause the dissociation to generate product ions;

[0062] Sometimes it is necessary to suspend the linear ion trap 3 to a preset potential, which can be provided by electrically connecting the center tap 4.1b to a specific power supply 4.2 to provide a specific potential V0; at this time, the potential on the DC saddle point potential of the ion trapping space 3.2 is V0; at this time, the potential V s of the electron emission source 1 is V 0 - V s , and the electron energy E k = e(V 0 - V s ); for most electron capture dissociation E k < 1 eV, at most not more than 3 eV.

[0063] In the above analysis, the effect of the change of the radio frequency electric field in the ion trap on the energy of the electron when the electron passes through the electron introduction slot into the linear ion trap is not considered, because the accelerated electron speed is very fast, and the time of crossing the dynamic radio frequency electric field is only a few nanoseconds, and for a radio frequency field of about 1 MHz, the change is not much. Compared with the static conservative field, the additional energy obtained or lost by the electron in the dynamic electric field is not large, only a few electron volts. However, if the change of the electric field is considered, the above energy formula needs to be compensated. The following simulation experiment will analyze the additional energy caused by the dynamic electric field.

[0064] Simulation experiment

[0065] Through simulation, we can study the law of electron motion, and Fig. 2(a) is the driving voltage applied to the Y strip electrode 3.1b in the linear ion trap 3, which is a sine wave (V); Fig. 3 is the electron trajectory calculated by the commercially available SIMION ion simulation program (Scientific Instrument Services, Inc., Ringoes, New Jersey); the potential of the electron emission source 1 is assumed to be 0 V, the electrons emitted from the electron emission source 1 are first accelerated by the acceleration electrode, then focused into an electron beam by the focusing lens 2.2, and finally pass through the Y-bar electrode 3.1b into the linear ion trap 3; if the Y-bar electrode 3.1b at this time is the negative half cycle of the sine wave, the electron will be repelled and cannot enter the linear ion trap 3; if the Y-bar electrode 3.1b at this time is the positive half cycle of the sine wave, the electron will easily pass through the Y-bar electrode 3.1b and enter the linear ion trap 3. Since the Y-bar electrode 3.1b of the linear ion trap 3 is positive and the potential of the central axis of the ion trapping space 3.2 is zero, this will cause the electrons that have just entered the linear ion trap 3 to decelerate. At the same time, in the X direction, due to the repulsive effect of the two negative electrodes, the electron beam entering the linear ion trap 3 will be subjected to a converging force in the X direction; if the dynamic change of the Y-bar electrode voltage is not considered, when the potential of the electron emission source 1 is 0 V, the kinetic energy of the electron decays to nearly 0 when it reaches the central axis position of the linear ion trap 3, and electron reflection phenomenon occurs; at this time, the low-energy electrons, if captured by polyvalent ions, will undergo electron capture dissociation reactions; if not captured by ions, the electrons will return and may again enter the linear ion trap 3 near the ion cloud, until they diverge in the X and Z directions and cannot be utilized; if the potential of the electron emission source 1 is a relatively low negative value, the electron may pass through the area near the central axis of the linear ion trap 3 with a relatively low energy, and such an electron is also likely to undergo electron capture dissociation reactions.

[0066] However, in the process of the electron passing through the introduction slot in the Y-bar electrode and moving towards the central axis of the trap, the voltage of the Y-bar electrode is dynamically changing, that is, the electron experiences a region of changing electric field, and the kinetic energy of the electron cannot be calculated according to the potential difference between the starting point and the end point.

[0067] Fig. 3(a) shows the trajectories of the electrons emitted from different positions on the electron emission source 1 entering the linear ion trap when the RF voltage of the Y-bar electrode is 500 V; the majority of the ions with an initial maximum displacement of + / - 0.4 mm in the X direction can smoothly pass through the electron introduction slot 3.3 to reach the ion trapping space 3.2; through simulation calculation, it can be known that the energy of the electrons entering the ion trapping space 3.2 at a distance of 0.5 mm from the central axis of the trap is mostly less than 1 eV, and they will have a relatively large probability of being captured by polyvalent ions.

[0068] This indicates that when electrons enter at a radio frequency voltage phase of approximately π / 2, their kinetic energy is relatively high, and the field change is minimal during their journey to the center of the trap, closely resembling a conservative field.

[0069] Figure 3(b) shows the instantaneous value of the radio frequency voltage of the linear ion trap 3 just reaching 5 V, i.e., when the radio frequency phase is 0.0032π, from the electron emission source 1. 0 The trajectory of an electron emitted from a position of 0.4 mm. Due to the change in electric field, the electron loses kinetic energy more quickly after entering the ion trap due to the increase in the retardation field, and thus cannot reach the vicinity of the central axis of the ion trap. Figure 3(c) shows that when the instantaneous value of the radio frequency voltage of the linear ion trap 3 reaches 5 V, the potential of the electron emission source 1 becomes -9 V accordingly. In this way, the electron emitted from the electron emission source has a higher initial potential energy. Even if the retardation field strength increases dynamically, the electron can still reach the vicinity of the central axis of the ion trap, and the energy decays to below 1 eV when it arrives.

[0070] Simulations show that during the process of the RF voltage phase changing from 0 to 0.98π, and the RF voltage rising from 0V to 500V and then falling back to around 30V, by adjusting the potential of the electron emission source accordingly, the electron beam emitted by the 0.8mm wide emitter can successfully reach the vicinity of the central axis of the ion trapping space; during this time period T... r Occupying 98% of the positive half-cycle, this means that when the device is driven by a sinusoidal RF power supply, the effective phase interval provided for electron capture and dissociation during the positive half-cycle accounts for 49% of the total cycle. Simulations show that, in order to compensate for the energy gain and loss of electrons caused by the dynamic electric field, the range of the changing potential provided to the electron emission source is not large. Figure 2(b) shows the relationship between the emission source compensation voltage and the RF power supply phase. As can be seen from the figure, in the RF phase 0... During the rise of π / 2, the compensation voltage is negative, making the electron emission source potential more negative and giving electrons more initial energy. This negative compensation voltage gradually decreases to 0. During the fall of the RF phase from π / 2 to π, the compensation voltage becomes positive, making the electron emission source potential more positive and reducing the initial acceleration energy of the electrons. In summary, by changing the electron emission source potential, when the RF voltage of the strip electrode corresponding to the electron introduction slot is in the positive half-cycle, electrons can reach the central axis of the linear ion trap, resulting in E... k < 1 eV, to meet the conditions for electron capture and dissociation. As can be seen in Figure 2(b), when electrons are introduced from the electron emission source, the phase of the RF power supply corresponding to the strip electrode of the slot is even at the end of the negative half-cycle (1.98π in the example given in the figure). As long as the RF enters the positive half-cycle after the electrons enter the linear ion trap, and the electron emission source compensation voltage is appropriate, they can still reach the vicinity of the field axis and undergo ECD reactions with the ions. In the RF phase... During the negative half cycle of the RF voltage, the electrons cannot enter the linear ion trap, so the voltage of the electron source is set to a constant value of +12V as shown in the table of Fig. 2, without a complicated function. Therefore, in principle, the effective phase interval for electron capture dissociation provided by the present method can reach 50%.

[0071] The relationship between the compensation voltage of the electron source and the phase of the RF power source shown in Fig. 2(b) can be a preset specific periodic function curve, which has the same frequency as the RF power source. In order to generate this specific signal, the optimized function curve can be stored and then played out through high-speed digital-to-analog conversion, and output to the electron source through an amplifier. Of course, it can also be approximately considered that one segment of the voltage curve is a straight line, and a signal generator is used to generate an approximate trapezoidal wave instead. This is a common technique in electronic technology, which will not be described here.

[0072] Fig. 4 shows the trajectories of a plurality of electrons emitted from x 0 = -0.4 to 0.4 mm; it can be seen that some electrons that fail to pass through the center of the linear ion trap will be bounced back and re-bounced in front of the electron source; under the voltage settings of the present simulation, the transit time of the electrons is only 4.2 ns, so the electrons that are not captured by the ions have multiple opportunities for reuse, thereby improving the efficiency of electron capture dissociation.

[0073] Fig. 5 shows the trajectories of the electrons emitted from the long strip-shaped electron source in a side view; this is the trajectories of 50 electrons randomly emitted by the electron source at x = -0.4~0.4, z = -4~4 mm; at this time, the front and rear end covers 9, 10 of the linear ion trap have a suspension voltage of 10 V, which is sufficient to ensure that the cooled ions cannot escape in the axial direction; obviously, most of the electrons have a small velocity component in the z direction, and the trajectories are basically vertical downward, injecting into the linear ion trap 3 and reaching the central axis region of the ion trapping space 3.2; through simulation verification, the electrons provided by the electron source 1 can be efficiently utilized.

[0074] Specific Embodiment 2

[0075] The embodiment is based on embodiment 1 with the addition of an electron reflection device. As shown in Figure 7, the embodiment has an electron extraction slot 3.4 on the strip electrode 3.1 opposite the electron introduction slot 3.3 in the y direction, and the linear ion trap 3 has a reflection electrode 7 corresponding to the electron extraction slot 3.4. A -35V voltage is applied to the reflection electrode, which reflects the electrons passing through the center of the linear ion trap 3.2 back to the center of the ion trapping space 3.2, where the energy of the electrons is reduced to about 0 eV, and the electrons can react with the ions to cause dissociation. The strip electrode 3.1 with the electron introduction slot is opposite the strip electrode 3.1 with the electron extraction slot 3.3, and is present in the 4-pole and 8-pole ion traps. In a broad sense, the strip electrode 3.1 with the electron introduction slot and the strip electrode 3.1 with the electron extraction slot 3.3 are strip electrodes with the same phase of the radio frequency voltage, and do not necessarily have to be opposite each other in geometry. For example, for a 6-pole field ion trap, the strip electrode with the electron introduction slot and the strip electrode with the electron extraction slot are arranged at an angle of 120 degrees.

[0076] Embodiment 3

[0077] The difference between the embodiment and embodiment 2 is that the linear ion trap 3 has electron introduction slots 3.3 on the strip electrodes 3.1, and corresponding to each electron introduction slot 3.3, there is an electron emission source 1 on the outside of the strip electrode 3.1, and an electrode group 2 for accelerating and converging the electrons emitted from the electron emission source 1. The electrons emitted by each electron emission source 1 enter the interior of the linear ion trap 3 through the electron introduction slot 3.3 when the corresponding strip electrode 3.1 is in the positive phase, and react with the trapped ions to cause dissociation. As shown in Figure 8, four sets of electron emission sources 1 are used for an electron capture and dissociation device for a linear four-pole ion trap.

[0078] Of course, the reflection device of Figure 7 can also be combined with an X-direction electron emission source and a Y-direction electron emission source to achieve the function of efficient electron capture and dissociation.

[0079] Embodiment 4

[0080] The difference between the embodiment and embodiment 1 is that the electron emission source 1 of the embodiment is a direct heating type hot cathode emission source formed by splicing a plurality of direct heating type hot cathodes, and an alternating heating voltage connection method of positive, negative, positive is adopted, resulting in a low voltage difference of the emission surface of the electron emission source. As shown in FIG. 6, the cathode filaments 11.1 and 11.2 are connected together and are respectively led out by the leads 13, 14 and 16 fixed on the ceramic substrate 12; the lead 14 is connected to a potential control unit, and the leads 13 and 16 provide a large current filament power source with a potential of 0.5 V higher than that of the electron emission source; that is, the filaments 11.1 and 11.2 are heated in parallel on the large current filament power source. Although this heating method requires a large current (tens of amperes), the potential difference between the two ends of the electron emission source can be controlled to be much less than 1 V, ensuring that the potential of the electron emission source is controllable.

[0081] Embodiment 5

[0082] The difference between the embodiment and embodiment 1 is that the electron emission source 1 is a field emission electron emission source coated with carbon nanotubes, velvet and other electron emission materials, or a field emission electron emission source formed by chemical etching method on the substrate to form micro emission protrusions or emission blades.

[0083] After the electron incidence and ion reaction reach a sufficient time and the cleaved ions are obtained, the direct current voltage at one end is removed so as to lead the ions to the subsequent mass spectrometer analyzer along the axial direction.

[0084] Embodiment 6

[0085] The embodiment is based on any one of the electron capture dissociation devices in embodiments 1 to 5, as shown in FIG. 10, each of the strip-shaped electrodes 3.1 is divided into a front section, a middle section and a rear section along the central axis direction of the ion trapping space 3.2, and the front section and the middle section of the strip-shaped electrode 3.1 and the middle section and the rear section are insulated; wherein the structure of the insulation between the front section and the middle section of the strip-shaped electrode 3.1 and the middle section and the rear section is a prior art, and the embodiment is realized by an internal hollow insulation sleeve. Specifically, the barrel wall of the insulation sleeve is provided with embedding windows for embedding the front section, the middle section and the rear end of the strip-shaped electrode 3.1, the embedding windows are communicated with the inside of the insulation sleeve, and the front section, the middle section and the rear section of the strip-shaped electrode 3.1 are embedded and fixed through the embedding windows, and the front section, the middle section and the rear section of the strip-shaped electrode 3.1 are inserted into the inside of the insulation sleeve from the embedding windows, so as to surround the ion trapping space 3.2;

[0086] The front section, the middle section and the rear section of the strip-shaped electrode (3.1) are connected with the radio frequency power source through capacitors, which is the prior art and will not be described in detail. The radio frequency power source (4) provides the same amplitude of radio frequency voltage to the front section, the middle section and the rear section of the same strip-shaped electrode (3.1). The electron capture dissociation device further comprises a direct current power source (6), which provides direct current voltage to the front section, the middle section and the rear section of the strip-shaped electrode (3.1) through resistors or inductors. The direct current voltage of the front section and the rear section of the strip-shaped electrode (3.1) is higher than that of the middle section of the strip-shaped electrode (3.1), so that a potential barrier for trapping ions along the central axis in the linear ion trap is formed, so as to axially bind the dissociated ions, and thus an actual ion trapping space 3.2 is formed around the middle section of the strip-shaped electrode. After the electron injection and ion reaction reach a sufficient time and the dissociated ions are obtained, the direct current voltage of the front end cover or the rear end cover is removed, so that the ions are led out along the axial direction to a subsequent mass spectrometer analyzer.

[0087] In addition, as part of the mass spectrometer, the electron capture dissociation device of any one of embodiments 1 to 5 of the present application must be coupled with other parts of the mass spectrometer, so that the cleavage products can be sent to an analyzer for mass spectrometric analysis. As shown in FIG. 9, the front end cover 9 and the rear end cover 10 are respectively arranged at the front end and the rear end of the linear ion trap 3 of the device, and the direct current power source 6 is electrically connected to the front end cover 9 and the rear end cover 10. A direct current potential higher than the axial potential in the linear ion trap 3 is added to the front end cover 9 and the rear end cover 10, and the direct current voltage here is 10 V, which is used to axially bind the dissociated ions.

[0088] In addition to the quadrupole linear ion trap using a pair of Y electrodes and a pair of X electrodes, a 6-pole, an 8-pole or more pole rod structure can also be used. FIG. 12 is a 6-pole linear ion trap. The above-mentioned positive phase radio frequency voltage and the negative phase radio frequency voltage are alternately applied to each strip-shaped electrode 3.1 in the circumferential order, that is, the electrodes 101, 103 and 105 are connected with the positive phase radio frequency, and the electrodes 102, 104 and 106 are connected with the negative phase radio frequency voltage.

[0089] In addition, the device itself of the present application can be directly used for mass spectrometric analysis after precise design and processing. At this time, one or two ion detectors arranged outside the linear ion trap are further required, which are arranged in the direction without placing the electron emission source, such as the X direction of FIG. 1. When the electron and ion reaction reaches a sufficient time and the dissociated ions are obtained, a dipole excitation is applied to the radial direction of the arranged ion detector, and the amplitude or frequency of the radio frequency voltage is scanned, so that the fragmented ions are thrown out along the radial direction according to their mass-to-charge ratio to the detector, so as to realize the mass spectrometric analysis of the fragmented ions.

[0090] Although the present disclosure discloses the above, the protection scope of the present disclosure is not limited to this. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present disclosure, and these changes and modifications will fall within the protection scope of the present disclosure.

[0091] In the description of the embodiments of the present application, it should be noted that in the description of the present application, the terms indicating the direction or positional relationship are based on the direction or positional relationship shown in the drawings, which is only for the convenience of description, and does not indicate or imply that the device or member must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation of the present application.

[0092] In the description of the present application, the description of the terms "one embodiment", "some embodiments", "in this embodiment", "specific examples", or "some examples" means that the specific features, mechanisms, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, mechanisms, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. Furthermore, those skilled in the art can combine and combine the features of different embodiments or examples and the features of different embodiments or examples described in the present specification without contradiction.

[0093] The above is only a specific embodiment of the present application, but the protection scope of the present application is not limited to this. Any person skilled in the art can easily think of changes or replacements within the technical range disclosed by the present application, which should be covered within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. An electron capture dissociation device, comprising: The application relates to a linear ion trap (3) for trapping parent ions and product ions to be dissociated, comprising an ion trapping space (3.2) surrounded by an even number of strip electrodes (3.1), at least one strip electrode (3.1) being provided with an electron introduction slot (3.3) for introducing electrons from outside the linear ion trap (3) into the ion trapping space (3.2); an electron emission source (1) for emitting electrons towards the linear ion trap (3), the electron emission source (1) being arranged corresponding to the electron introduction slot (3.3), and an electron emission path being formed between the electron emission source (1) and the electron introduction slot (3.3); an electrode group (2) arranged on the electron emission path, the electrode group (2) comprising an electron acceleration electrode (2.1) for accelerating the electrons emitted by the electron emission source (1) to form a flat electron beam and a focusing lens (2.2) for converging the electron beam, the electron acceleration electrode (2.1) and the focusing lens (2.2) being arranged in sequence in the direction from the electron emission source (1) to the linear ion trap (3); an RF power supply (4) for generating a positive RF voltage and an inverted RF voltage with equal voltage amplitude and opposite phase, the positive RF voltage and the inverted RF voltage being applied in sequence and alternately on the even number of strip electrodes (3.1) so that an alternating RF multipole field is formed in the ion trapping space (3.2), and the RF multipole field has a fixed DC saddle point potential at the central axis in the ion trapping space (3.2); and a potential control unit (5) electrically connected to the electron emission source (1) for controlling the potential of the electron emission source (1), the potential control unit (5) providing a variable potential for the electron emission source, the potential difference between the variable potential and the DC saddle point potential varying according to a preset voltage-phase relationship function when the RF voltage of the strip electrode (3.1) corresponding to the electron introduction slot (3.3) is in the positive half cycle, so that the electrons emitted by the electron emission source (1) enter the linear ion trap through the electron introduction slot (3.3) and are decelerated to the energy range of electron capture dissociation before reaching the central axis of the ion trapping space (3.2), and react with the trapped parent ions to be dissociated and cause dissociation to generate product ions. The emission surface of the electron emission source (1) is in the shape of a long strip, and the extension direction of the emission surface of the electron emission source is parallel to the central axis of the ion trapping space (3.2). The electron emission source (1) is an inter-heating type hot cathode emission source. The electron emission source (1) is a direct-heating type hot cathode emission source, and the electron emission source (1) is formed by splicing a plurality of direct-heating type hot cathodes, and an alternating heating voltage connection method of positive, negative and positive is adopted, so that the emission surface of the electron emission source (1) is in the shape of a low voltage difference. The electron emission source (1) is a field emission electron emission source coated with carbon nanotubes, velvet or the like, or a field emission electron emission source formed by a chemical etching method on a substrate. ​ 2. The electron capture dissociation device of claim 1, wherein, ​ 3. The electron capture dissociation device of claim 2, wherein, ​ 4. The electron capture dissociation device of claim 2, wherein, ​ 5. The electron capture dissociation device of claim 2, wherein, ​ 6. The electron capture dissociation device of claim 1, wherein, The focusing lens (2.2) comprises at least two focusing electrodes (2.2.1) which are arranged in parallel between the focusing electrodes (2.2.1), and rectangular openings (2.3) are formed on the focusing electrodes (2.2.1).

7. The electron capture dissociation device of claim 1, wherein, The bar-shaped electrode (3.1) with the same phase of voltage as the electron introduction slot (3.3) is provided with an electron emission slot (3.4), and the linear ion trap (3) is provided with a reflecting electrode (7) corresponding to the electron emission slot (3.4), and the voltage potential of the reflecting electrode (7) is negative by a preset range value compared with the potential of the electron emission source (1).

8. The electron capture dissociation device of claim 1, wherein, The power supply (4) comprises an LC oscillation circuit; the LC oscillation circuit comprises an inductor coil (4.1) having a first output end (4.1a), a second output end (4.1c) and a center tap (4.1b), wherein the first output end (4.1a) and the second output end (4.1c) of the inductor coil (4.1) are respectively used to generate positive phase radio frequency voltage and reverse phase radio frequency voltage with opposite phases, and the first output end (4.1a) and the second output end (4.1c) of the inductor coil (4.1) are respectively electrically connected with a balance adjusting variable capacitor (8); if the direct current saddle point potential is zero, the center tap (4.1b) is grounded; if the linear ion trap (1) needs to be suspended to a preset potential, the center tap (4.1b) is electrically connected with a power supply (4.2) to provide a specific potential.

9. The electron capture dissociation device of claim 1, wherein, Each of the bar-shaped electrodes (3.1) is divided into a front section, a middle section and a rear section along the central axis direction of the ion trapping space (3.2), and the front section and the middle section and the middle section and the rear section of the bar-shaped electrode (3.1) are insulated; the actual ion trapping space (3.2) is surrounded by the middle sections of the even number of bar-shaped electrodes (3.1), and the radio frequency power supply (4) provides the same amplitude of radio frequency voltage to the front section, the middle section and the rear section of the same bar-shaped electrode (3.1); the electron capture and dissociation device further comprises a direct current power supply (6), which provides direct current voltage to the front section, the middle section and the rear section of the bar-shaped electrode (3.1) respectively, and the direct current voltage of the front section and the rear section of the bar-shaped electrode (3.1) is higher than that of the middle section of the bar-shaped electrode (3.1).

10. The electron capture dissociation device of claim 1, wherein, The potential control unit comprises a high-speed digital-to-analog conversion chip for storing preset voltage-phase function data and an amplifier, and the amplifier is electrically connected with the high-speed digital-to-analog conversion chip for outputting potential difference varying according to the preset voltage-phase function relationship.

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