Double helix ion funnel with auxiliary electrode

Abstract

The present invention relates to the field of mass spectrometry, and in particular to a double helix ion funnel with an auxiliary electrode in ion transmission. The double helix ion funnel with an auxiliary electrode comprises two spiral electrodes, wherein the spiral electrodes have a constant inner diameter section and a conical inner diameter section connected to each other along the ion transmission direction, and four auxiliary electrodes are arranged at the outlet of the conical inner diameter section. The four auxiliary electrodes cooperate with the double helix electrode so that the positive / negative electrodes are arranged alternately, and a hexapole structure is formed at the outlet of the double helix ion funnel to improve the edge field. With the cooperation of the auxiliary electrode and the double helix electrode, the present invention greatly improves the influence of the edge field on the double helix electrode structure. The transmission efficiency of low and medium mass-to-charge ratio ions in the rough vacuum region is enhanced, and is almost unaffected by potential traps. At the same time, the ion strength is also enhanced, which helps to achieve a lower detection limit and higher sensitivity.

Description

Technical Field

[0001] The invention relates to the field of mass spectrometry, in particular to a double helix ion funnel with auxiliary electrodes in ion transmission. Background Art

[0002] The coupling of electrospray ionization (ESI) and mass spectrometry has made mass spectrometry (MS) a powerful technique in an increasing number of analytical applications. However, the transfer efficiency of ions from atmospheric pressure to vacuum limits the improvement of the sensitivity of ESI-MS (electrospray ionization-mass spectrometry) systems. Previous studies have shown that only a small portion of the analyte ions generated by the ionization source will eventually reach the vacuum region and be detected by the mass spectrometer, while the vast majority of ions will be lost along the ion transfer route, especially in the rough vacuum region (usually 0.1Torr-30Torr). Affected by the complex supersonic gas flow in the rough vacuum region, the ion cloud will expand and diverge, resulting in a decrease in the number of ions entering the downstream vacuum and a decrease in analytical sensitivity. In order to improve the detection sensitivity of the ESI-MS system for small molecule organic compounds to large molecule biological samples, it is of great significance to develop an atmospheric pressure interface (API) with higher ion transfer efficiency and wider mass range.

[0003] Past research has developed a variety of ion optical devices for ion transmission in the rough vacuum region, including sampling cones, radio frequency ion guides, etc. The sampling cone is usually designed as a gas conductivity limiting orifice with a small aperture, which has no ion focusing function and can only sample part of the ions in the gas flow, so the transmission efficiency is low.

[0004] Since it was demonstrated that ions can be effectively confined by radio frequency electric fields, a large number of studies have focused on the development and improvement of radio frequency ion guides. Multipole ion guides, which consist of four or more electrode rods, are the most common ion guides. By applying opposite radio frequency voltages to adjacent electrode rods, a "pseudo-potential" that can confine ions in the radial direction can be generated. However, when the background pressure is greater than 1 torr, the collision between ions and the background gas intensifies, causing the ion motion to become complicated. At this time, the airflow has a significant effect on the ion motion, and the confinement effect of the multipole ion guide is often poor. Under the same radio frequency voltage, the larger the parameter q in the Mathieu equation of ions with a lower mass-to-charge ratio (m / z), the narrower the stable region, and the greater the impact of this deteriorated confinement. In order to improve the ion transfer efficiency in a rough vacuum, a dodecapole ion guide with a gradually decreasing field radius has been developed, which has an optimized flow field and an ion transfer efficiency that is 5-6 times higher than that of a conventional quadrupole. Recently, Shiyu Du et al. designed a field gradient focusing ion guide by combining the advantages of a dodecapole (ion trapping) and a quadrupole g-rod (ion focusing). Experiments have shown that this design of transitioning from a dodecapole field to a quadrupole field can effectively improve the transmission efficiency of low-mass ions, which provides a new idea for studying ion guide devices with a wide mass transmission range.

[0005] The stacked ring ion guide (SRIG) is a variant of the multipole, which consists of a series of ring electrodes with opposite phases of RF signals applied to adjacent electrodes. The ion funnel (IF) evolved from the SRIG, with the inner diameter of the ring electrodes gradually decreasing. This funnel-shaped electrode effectively reduces the spatial divergence of the ion cloud, and the ion cloud is focused to a small radius when it passes through the conductivity limiting orifice plate into the downstream vacuum region. In many bioanalytical applications, the sensitivity of mass spectrometers has been significantly improved by using ion funnels or their modified devices. However, there are fluctuations or "traps" in the effective potential on the central axis of the stacked ring structure. The depth of the "trap" is inversely proportional to the m / z and proportional to the RF amplitude, which means that low-mass ions are more susceptible to axial traps, namely the mass q discrimination effect. In early studies, the mass discrimination effect was mainly improved by optimizing the electrode structure. Later, traveling waves were applied to the ring electrodes to help ions escape from the trap. This method has been proven to be feasible and effective in a variety of designs. Recently, a new focusing quadrupole ion funnel (FQ-IF) has been proposed, with 4 quarter rings on each electrode. Its RF application method is similar to that of a quadrupole, which greatly improves the effective potential distribution along the central axis. The results show that FQ-IF has better focusing effect and higher sensitivity, especially for the transmission of low-mass ions. Many similar structures have also achieved performance improvements. In summary, the optimization of the ion funnel is very necessary because it has strong ion capture and focusing properties in the rough vacuum region. Summary of the invention

[0006] The double-helix ion funnel with auxiliary electrodes provided by the present invention is used to enhance the transmission efficiency of low and medium mass-to-charge ratio ions in a rough vacuum region and to optimize the evaluation of ion transmission performance.

[0007] The double helix ion funnel with auxiliary electrodes of the present invention comprises a double helix electrode with positive / negative electrodes, wherein the double helix electrode has a constant inner diameter section and a tapered inner diameter section connected to each other along the ion transmission direction, and four auxiliary electrodes are arranged at the outlet of the tapered inner diameter section. The four auxiliary electrodes cooperate with the double helix electrode so that the positive / negative electrodes are arranged alternately, and a hexapole structure is formed at the outlet of the double helix ion funnel to improve the edge field.

[0008] Furthermore, the length ratio of the inner diameter of the constant inner diameter section to the inner diameter of the tapered inner diameter section is 0.4-3.

[0009] Preferably, the length ratio of the inner diameter of the constant inner diameter section to the inner diameter of the tapered inner diameter section is 0.7-1.2.

[0010] Furthermore, the inner diameter of the constant inner diameter section is 5 to 50 mm.

[0011] Preferably, the inner diameter of the constant inner diameter section is 20-30 mm.

[0012] Furthermore, the ratio of the maximum inner diameter to the minimum inner diameter of the tapered inner diameter section is 5-10.

[0013] The beneficial effects of the present invention include:

[0014] 1. With the cooperation of the auxiliary electrode and the double helix electrode, the edge field of the double helix electrode structure is greatly improved, reducing its hindering effect on ion transmission.

[0015] 2. Enhanced the transmission efficiency of low and medium mass-to-charge ratio (m / z) ions in the rough vacuum region.

[0016] 3. Because of the continuous funnel-shaped electrode structure, the divergence of ions can be effectively limited. Compared with the traditional ion funnel, it is almost unaffected by the potential trap. Therefore, the evaluation of the electrode structure and ion transmission performance is also optimized.

[0017] 4. Through the comparison experiment of mass spectrometry data with the conventional stacked ring ion funnel (stacked ring ion funnel), it is known that the present invention improves the mass discrimination effect of the conventional stacked ring ion funnel and improves the efficiency of simultaneous transfer of low and medium mass-to-charge ratio ions. In addition, it is observed that the ion intensity is enhanced, which helps to achieve a lower detection limit and higher sensitivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is a schematic diagram of the radio frequency signal application principle of the present invention.

[0019] Figure 2 Schematic diagram of the spiral equipotential surface of the double spiral electrode structure of the present invention.

[0020] Figure 3 Schematic diagram of the electrode structure of the double helix ion funnel.

[0021] Figure 4 Cross-sectional distribution diagram of the effective potential in the xy plane at z = 20 mm, 42 mm and 50 mm for the present invention.

[0022] Figure 5 Schematic diagram of the fringe field of the double spiral electrode structure of the present invention.

[0023] Figure 6 This is a schematic diagram of a structure approximating a hexapole formed by four auxiliary electrodes and a double-helix electrode arranged at the DHE-IF outlet of the present invention.

[0024] Figure 7 This is a schematic diagram of the structure in which four auxiliary electrodes are arranged on a circuit board at a DHE-IF outlet in the present invention.

[0025] Figure 8 (a) is a comparison of the edge fields of a double helix ion funnel with and without an auxiliary electrode (FPC).

[0026] Figure 8 (b) is a comparison diagram of the edge fields of the DHE-IF of the present invention and the traditional stacked annular ion funnel (IF).

[0027] Fig. 9 (a) is a diagram of the flow field distribution of a traditional stacked annular ion funnel (IF).

[0028] Fig. 9 (b) is a diagram of the flow field distribution of DHE-IF.

[0029] Fig. 9 (c) is a graph showing the simulated ion transmission efficiency of a traditional stacked annular ion funnel (IF) for different ions as a function of RF amplitude.

[0030] Fig. 9 (d) is a graph showing the change in the simulated ion transmission efficiency of DHE-IF for different ions as the RF amplitude increases.

[0031] Fig.10 (a) is a graph showing the relationship between the relative abundance of ions with different mass-to-charge ratios and the DC bias voltage.

[0032] Fig.10 (b) is a graph showing the relationship between the relative abundance of ions with different mass-to-charge ratios and the amplitude of the RF voltage applied to the DHE-IF electrode.

[0033] Fig.11 (a) is the mass spectrum obtained using DHE-IF at 90 Vpp.

[0034] Fig.11 (b) is the mass spectrum obtained using IF at 60 Vpp.

[0035] Fig.11 (c) is the mass spectrum obtained using DHE-IF at 140 Vpp.

[0036] Fig.11 (d) is the mass spectrum obtained using IF at 120 Vpp.

[0037] Fig.11 (e) is a comparison of the optimal transmission point intensities of caffeine ions and reserpine ions between DHE-IF and IF.

[0038] Description of reference numerals:

[0039] 1: Double helix electrode, 2: Hexapole structure, 3: Auxiliary electrode, 4: Flexible circuit board. DETAILED DESCRIPTION

[0040] To make the purpose, technical scheme and advantages of the embodiments of the present application clearer, the technical scheme in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all of the embodiments. The components of the embodiments of the present application usually described and shown in the drawings here can be arranged and designed in various configurations. Therefore, the following detailed description of the embodiments of the present application provided in the drawings is not intended to limit the scope of the application claimed for protection, but merely represents the selected embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without making creative work belong to the scope of protection of the present application.

[0041] like Figure 6 As shown, the double helix ion funnel (DHE-IF) with auxiliary electrodes of the present invention comprises a double helix electrode 1 with positive and negative poles, wherein the double helix electrode has a constant inner diameter section and a conical inner diameter section connected along the ion transmission direction, and four auxiliary electrodes 3 are arranged at the outlet of the conical inner diameter section, wherein the four auxiliary electrodes 3 cooperate with the double helix electrode 1 so that the positive and negative electrodes are arranged alternately, and a hexapole structure 2 is formed at the outlet of the double helix ion funnel to improve the edge field. The working pressure range of the DHE-IF of the present invention is 100~3000 Pa.

[0042] Because the spiral electrode is continuous rather than segmented from the constant inner diameter section and the tapered inner diameter section, and the positive and negative electrodes of the radio frequency (RF) are symmetrical in the radial cross section, there is no floating or fluctuation in the potential along the central axis. Therefore, the double-helix ion funnel of the present invention has almost no axial potential traps, which will be beneficial to the transmission of ions, especially low-mass ions.

[0043] The length ratio of the inner diameter of the constant inner diameter section to the inner diameter of the tapered inner diameter section is 0.4-3, preferably 0.7-1.2. The inner diameter of the constant inner diameter section is 5-50 mm, preferably 20-30 mm. The ratio of the maximum inner diameter to the minimum inner diameter of the tapered inner diameter section is 5-10.

[0044] In order to understand the ion focusing characteristics of the double helix ion funnel (DHE-IF) of the present invention, the electric field distribution in the double helix electrode structure was firstly studied. Figure 1 The coordinates r and z represent radial and axial directions respectively, and o is the origin. RF signals with opposite phases are applied to the two spiral electrodes, forming an RF electric field with alternating positive and negative RF (RF voltage) on the axial section. This structure is similar to the traditional stacked ring ion guide (SRIG), which can generate an effective potential (i.e., "pseudo-potential") and effectively limit ions radially.

[0045] The effective potential is calculated by the following formula:

[0046] ;

[0047] In the above formula, E is the amplitude of the radio frequency field, ω is the angular frequency of the radio frequency field, Q is the charge of the ion, and m is the mass of the ion. Using this formula to calculate the equivalent distribution of the effective potential, a closed spiral equipotential surface is obtained, such as Figure 2 As shown, Figure 2 The coordinates r and z represent the radial and axial directions respectively, and o is the origin. This proves that the double helix electrode structure has the ability to radially confine ions.

[0048] like Figure 3 The schematic diagram of the double-helix electrode of the DHE-IF of the present invention is shown, which consists of two parts with a constant inner diameter and a gradually decreasing inner diameter, wherein RF+ and RF- represent the positive / negative voltage of the radio frequency, respectively. Figure 4The cross-sectional distribution of the effective potential of the DHE-IF of the present invention in the radial XY plane is given (Z = 20 mm, 42 mm and 50 mm; f = 1 MHz; V_pp = 100 V; M / z = 195). The results show that the potential well formed by the RF signal acting on the double helical electrode structure is wide and flat near the central axis; while a steep potential change gradient is observed near the electrode, which is conducive to capturing the divergent ion cloud in the supersonic gas flow. As the inner diameter of the helical electrode decreases, the area of ​​the near-field free zone decreases, the potential well becomes narrower, and the ions are focused to the center of the ion guide.

[0049] It is known from common knowledge in the art that the fringe field existing at the exit of multipole and stacked ring ion guides cannot be ignored. Figure 5 As shown in the figure, the present invention is a combination of multipole and stacked ring, and the double helix electrode structure is also affected by the fringe field. Under the same RF voltage, the fringe field of the double helix ion funnel is much weaker than that of the traditional stacked ring ion funnel (IF). Therefore, the present invention further optimizes the electrode structure of the double helix ion funnel to improve the influence of the fringe field, such as Figure 6 As shown, the present invention sets four auxiliary electrodes 3 at the outlet of the double helix ion funnel (i.e., the outlet of the conical inner diameter section) to cooperate with the double helix electrode 1, so that the positive / negative electrodes are arranged alternately. Figure 7 As shown, the four auxiliary electrodes 3 can be arranged on a circuit board (PCB). Taking a flexible circuit board 4 (FPC) as an example, the four auxiliary electrodes 3 on the flexible circuit board 4 cooperate with the double helix electrode 1 to form an approximate hexapole structure 2 at the outlet of the double helix ion funnel, which can improve the edge field.

[0050] The smooth transition from the dipole field to the hexapole field at the ion outlet is beneficial to the improvement of the edge field to a certain extent. Figure 8 (a) shows the comparison of the edge field of the double helix ion funnel with and without auxiliary electrodes (FPC). The results show that the axisymmetric hexapole composed of FPC (flexible printed circuit) with four auxiliary electrodes and double helix electrodes effectively weakens the edge field of the ion outlet and can significantly improve the ion transfer rate.

[0051] After the electrode optimization was completed, the electric fields of DHE-IF and IF were compared. Figure 8As shown in (b), the edge field comparison between the DHE-IF of the present invention and IF (traditional stacked annular ion funnel) is shown. It can be seen that the effective potential of the traditional IF has fluctuations or "traps", which hinder the transmission of ions, especially for low-mass ions, that is, the mass discrimination effect. The DHE-IF of the present invention has continuous symmetrical spiral electrodes and is therefore almost unaffected by potential traps. Under the optimized exit electrode configuration, the edge field of the DHE-IF is effectively weakened by more than 90% compared with the IF, which is conducive to further improving the ion transfer efficiency.

[0052] In order to evaluate the transmission performance of DHE-IF in the rough vacuum region, especially its potential to enhance the transmission of small mass ions, gas dynamics simulations and ion trajectory simulations were performed. Fig. 9 (a) and Fig. 9 (b) shows the velocity distribution of the flow field inside IF and DHE-IF, respectively. The results show that the compressible gas flow forms a supersonic jet and a complex shock wave structure when entering the first vacuum chamber, which is caused by the huge pressure difference between the rough vacuum region and the atmospheric pressure. The analyte ions expand radially with the gas flow after leaving the capillary, which is the main reason for most ion losses. It is worth noting that the recirculation zone observed in DHE-IF is more significant than that observed in IF. Due to the gradual decrease in pressure toward the center of the jet, the vortex in this area will eventually rejoin the jet. For electrospray ionization mass spectrometry (ESI-MS), this recycling mechanism increases the residence time of the charged droplets and improves the desolvation efficiency of the charged droplets inside the API. Therefore, it can be preliminarily judged here that higher signal intensity can be obtained using DHE-IF.

[0053] The random collisions of ions with buffer gas molecules were analyzed using the Monte Carlo collision model. All calculations were performed using the CPT module of COMSOL Multiphysics 6.0 software. In the ion trajectory simulations, the total number of ion releases of each type was 2000. Fig. 9 Middle (c), Fig. 9 (d) shows the transmission efficiency of ions of different m / z obtained by IF and DHE-IF as a function of the RF voltage amplitude. For the transmission of large mass ions, DHE-IF and IF show similar trends. However, the transmission of small mass ions is significantly different. Fig. 9 (c) and Fig. 9 (d) shows that compared with IF, as the RF voltage amplitude increases, DHE-IF has a higher transmission efficiency for ions with m / z of 68 and 203, which indicates that DHE-IF not only has comparable performance to IF in transmitting large mass ions, but also has an enhanced effect on the transmission of small mass ions.

[0054] RF voltage amplitude and DC bias are two key factors affecting ion transmission. In order to ensure maximum ion transmission efficiency, the DC bias (DC_bias) between the ion inlet and outlet is first optimized. During the optimization process, the RF voltage is set to a constant 100Vpp. Fig.10 (a) records different DC biases bias Normalized ion abundance of four polymer ions in PPG solution under voltage. As the DC bias voltage increases, the abundance of each ion first increases to a maximum value and then gradually decreases. Under weak DC bias, the ions lose kinetic energy due to collisions with buffer gas molecules and do not have sufficient axial momentum to enter the lower vacuum. After reaching the maximum value, the decrease in abundance is believed to be caused by the ions being over-pushed and unable to focus on the central axis in a limited transfer path, ultimately annihilating on the electrode surface. When the optimized DC_bias value is 28 V, the functional relationship between the normalized ion abundance of the four ions and the RF voltage is obtained ( Fig.10 (b)). The RF voltage was adjusted in the range of 0 V_pp-140 V_pp with a step size of 10 V_pp. The ion abundance at each voltage point was recorded 10 times and then averaged. The results show that the m / z175 ion has the highest abundance at 90 V_pp, while high-mass m / z ions require a higher RF amplitude for optimal transmission (m / z 382: 100 V_pp, m / z 847: 140 V_pp). This result is similar to the RF-dependent trend observed in the simulation. We also found that when the RF voltage is higher than the optimal transmission RF value for small-mass ions, the ion abundance curve obtains a plateau rather than a rapid decline. This indicates that DHE-IF can efficiently transfer ions over a wide mass range. The high consistency of the abundance curves of m / z382 and m / z559 ions may be due to similar molecular structures or collision cross sections.

[0055] To further verify the improvement of mass discrimination effect and the enhancement of MS instrument sensitivity by DHE-IF, the mass spectra obtained by DHE-IF and IF as ion introduction devices were compared. The size of IF used for comparison was similar to that of DHE-IF (inlet inner diameter: 20 mm; outlet inner diameter: 2 mm; electrode thickness: 0.5 mm; distance between electrodes: 0.5 mm). In order to obtain clear mass spectra, a mixture of caffeine (m / z 195) and reserpine (m / z 609) was used as the sample because of their high ionization efficiency and significant m / z difference. The solvents were methanol and 1% formic acid. The mass spectra of caffeine ions and reserpine ions at their respective optimal RF voltages were recorded and normalized. Fig.11 (a) and Fig.11(c) shows the mass spectra obtained using DHE-IF at RF voltage amplitudes of 90 Vpp and 140 Vpp. The results show that the abundance of caffeine ions is the highest when the RF voltage is 90 Vpp. When the RF voltage increases from 90 V to 140 V, the relative abundance of reserpine ions increases by more than 50%, while the relative abundance of caffeine ions decreases by less than 40%. For comparison, Fig.11 (b) and Fig.11 (d) shows the mass spectra obtained when IF was used instead of DHE-IF at RF voltage amplitudes of 60 Vpp and 120 Vpp, respectively. When the optimal RF voltage for caffeine ions was reached and the RF amplitude potential was continuously increased, the intensity of caffeine ions dropped rapidly. This sharp drop is consistent with previously reported results and is caused by the potential trap on the central axis of IF. In addition, Fig.11 (e) shows that the peak intensities of caffeine and reserpine increased by more than 50% and 10%, respectively, in DHE-IF compared to IF. This enhanced intensity is speculated to be due to the more significant reflow zone inside DHE-IF, which improves the desolvation efficiency of the charged droplets. In summary, DHE-IF is superior to IF in terms of simultaneous transmission of medium and low mass m / z ions and improved sensitivity.

[0056] From the above tests, it is known that the double helix electrode ion funnel (DHE-IF) with auxiliary electrodes of the present invention, the auxiliary electrode arranged at the outlet of the funnel-shaped spiral electrode cooperates with the double helix electrode to approximately form a symmetrical hexapole structure, which greatly improves the edge field of the double helix structure, reduces its hindering effect on ion transmission, and can enhance the transmission of low and medium mass-to-charge ratio (m / z) ions in the rough vacuum region. This is due to the continuous funnel-shaped electrode structure. The DHE-IF can effectively limit the divergence of ions and is almost unaffected by potential traps compared to traditional ion funnels. After optimizing the DC bias and RF amplitude, the mass spectrometry data of the DHE-IF and the conventional stacked ring ion funnel (stacked ring ion funnel) were compared. The results show that the DHE-IF has an improved mass discrimination effect than IF, and improves the efficiency of simultaneous transmission of low and medium m / z ions. In addition, it is observed that the ion intensity is enhanced, which helps to achieve a lower detection limit and higher sensitivity.

[0057] The above-mentioned embodiments only express the specific implementation methods of the present application, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the protection scope of the present application. It should be pointed out that for ordinary technicians in this field, relevant deformations and improvements can be made without departing from the technical solution concept of the present application, and these all belong to the protection scope of the present application.

Claims

1. A double helical ion funnel with an auxiliary electrode, characterized by: The invention comprises a double helix electrode (1) having positive / negative electrodes, wherein the double helix electrode (1) has a constant inner diameter section and a conical inner diameter section connected to each other along the ion transmission direction, and four auxiliary electrodes (3) are arranged at the outlet of the conical inner diameter section. The four auxiliary electrodes (3) cooperate with the double helix electrode (1) so that the positive / negative electrodes are arranged alternately, thereby forming a hexapole structure (2) at the outlet of the double helix ion funnel to improve the edge field.

2. The double helical ion funnel with auxiliary electrode as claimed in claim 1, characterized in that: The length ratio of the inner diameter of the constant inner diameter section to the inner diameter of the tapered inner diameter section is 0.4-3.

3. The double helical ion funnel with auxiliary electrode as claimed in claim 2, characterized in that: The length ratio of the inner diameter of the constant inner diameter section to the inner diameter of the tapered inner diameter section is 0.7 to 1.

2.

4. The double helical ion funnel with auxiliary electrode as claimed in claim 1, characterized in that: The inner diameter of the constant inner diameter section is 5~50mm.

5. The double helical ion funnel with auxiliary electrode as claimed in claim 4, characterized in that: The inner diameter of the constant inner diameter section is 20~30mm.

6. The double helical ion funnel with auxiliary electrode as claimed in claim 1, characterized in that: The ratio of the maximum inner diameter to the minimum inner diameter of the tapered inner diameter section is 5 to 10.

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