Double helix ion funnel with auxiliary electrode

Abstract

The invention relates to the field of mass spectrometry, in particular to a double-helix ion funnel with an auxiliary electrode in ion transmission. The double-spiral ion funnel with the auxiliary electrodes comprises two spiral electrodes, each spiral electrode is provided with a constant inner diameter section and a conical inner diameter section which are connected in the ion transmission direction, the four auxiliary electrodes are arranged at an outlet of the conical inner diameter section, the four auxiliary electrodes are matched with the double-spiral electrodes, positive electrodes and negative electrodes are alternately arranged, and the two spiral electrodes are arranged in a staggered mode. And a hexapole rod structure is formed at the outlet of the double-helix ion funnel to improve a fringing field. Under the cooperation of the auxiliary electrode and the double-helix electrode, the influence of a fringing field on the double-helix electrode structure is greatly improved. And the transmission efficiency of ions with low and medium mass-to-charge ratios in a coarse vacuum region is enhanced, and the transmission efficiency is hardly influenced by potential traps. Meanwhile, the ionic strength is enhanced, and lower detection limit and higher sensitivity can be realized.

Description

Technical Field

[0001] The present invention relates to the field of mass spectrometry analysis, 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 for a growing number of analytical applications. However, the efficiency of ion transfer from atmospheric pressure to vacuum limits the sensitivity of ESI-MS (electrospray ionization-mass spectrometry) systems. Previous studies have shown that only a small fraction of the analyte ions generated by the ionization source ultimately reach the vacuum region and are detected by the mass spectrometer, while the vast majority are lost along the ion transfer path, particularly in the rough vacuum region (typically between 0.1 Torr and 30 Torr). The complex supersonic gas flow in the rough vacuum region causes the ion cloud to expand and diverge, reducing the number of ions entering the downstream vacuum and lowering analytical sensitivity. To improve the sensitivity of ESI-MS systems for detecting samples ranging from small organic molecules to large biological molecules, the development of an atmospheric pressure interface (API) with higher ion transfer efficiency and a wider mass range is crucial.

[0003] Past research has developed a variety of ion optical devices for ion transmission in rough vacuum regions, including sampling cones and radio frequency ion guides. Sampling cones are typically designed as gas conductivity-limiting orifices with small apertures. These have no ion focusing function and can only sample a portion of the ions in the gas flow, resulting in low transmission efficiency.

[0004] Since the demonstration that ions can be effectively confined by radio frequency (RF) fields, extensive research has focused on the development and improvement of RF ion guides. Multipole ion guides, consisting of four or more electrode rods, are the most common ion guides. Applying opposite RF voltages to adjacent rods generates a "pseudopotential" that can confine ions radially. However, when the background pressure exceeds 1 Torr, ion collisions with the background gas intensify, complicating ion motion. At this point, airflow significantly influences ion motion, and the confinement effectiveness of multipole ion guides is often poor. At the same RF voltage, a larger parameter q in the Mathieu equation for ions with lower mass-to-charge ratios (m / z) results in a narrower stability region, making them more susceptible to this degraded confinement. To improve ion transfer efficiency in a rough vacuum, a dodecapole ion guide with a gradually decreasing field radius has been developed. This guide features an optimized flow field and achieves ion transfer efficiency 5-6 times higher than a conventional quadrupole. Recently, Shiyu Du et al. designed a field-gradient focusing ion guide, 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 new ideas for the study of ion guide devices with a wide mass transmission range.

[0005] The stacked ring ion guide (SRIG) is a variant of the multipole, consisting of a series of ring electrodes with oppositely phased RF signals applied to adjacent electrodes. The ion funnel (IF), an evolution of the SRIG, features ring electrodes with gradually decreasing inner diameters. This funnel-shaped electrode effectively reduces the spatial divergence of the ion cloud, focusing it into a small radius as it passes through a conductivity-limiting orifice into the downstream vacuum region. In many bioanalytical applications, the use of ion funnels or their modifications has significantly improved mass spectrometry sensitivity. However, along the central axis of the stacked ring structure, there is a fluctuation in the effective potential, or "trap." The depth of this "trap" is inversely proportional to the m / z and directly proportional to the RF amplitude, meaning that low-mass ions are more susceptible to axial trapping, a phenomenon known as mass-q discrimination. Early efforts to improve mass discrimination primarily focused on optimizing the electrode structure. Later, traveling waves were applied to the ring electrodes to aid ion escape from the trap. This approach has been proven feasible and effective in various designs. Recently, a novel focusing quadrupole ion funnel (FQ-IF) has been proposed, featuring four quarter rings per electrode. Its radio frequency application method, similar to that of a quadrupole, significantly improves the effective potential distribution along the central axis. Results demonstrate that the FQ-IF offers improved focusing and higher sensitivity, particularly for the transmission of low-mass ions. Many similar structures have also achieved performance improvements. In summary, optimization of the ion funnel is essential, as it offers robust ion trapping 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 includes a double-helix electrode with positive / negative poles. The double-helix electrode has a constant inner diameter section and a tapered inner diameter section connected along the ion transmission direction. Four auxiliary electrodes are provided 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, forming a hexapole structure 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, and its obstruction to ion transmission is reduced.

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

[0016] 3. The continuous funnel-shaped electrode structure effectively limits ion dispersion and is virtually unaffected by potential traps compared to traditional ion funnels. This optimizes the evaluation of electrode structure and ion transport performance.

[0017] 4. Comparison of mass spectrometry data with that of a conventional stacked ring ion funnel (STAF) indicates that the present invention improves the mass discrimination effect of conventional stacked ring ion funnels and increases the efficiency of simultaneous transfer of low and medium mass-to-charge ratio ions. Furthermore, enhanced ion intensity was observed, contributing to lower detection limits 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-helix 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-helix 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 structural diagram of the present invention in which four auxiliary electrodes are arranged on a circuit board at the DHE-IF outlet.

[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 fringe fields of the DHE-IF of the present invention and the traditional stacked annular ion funnel (IF).

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

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

[0029] Figure 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] Figure 9 (d) is a curve showing the change of the simulated ion transmission efficiency of DHE-IF for different ions with the RF amplitude.

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

[0032] Figure 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] Figure 11 (a) is the mass spectrum obtained using DHE-IF at 90 Vpp.

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

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

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

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

[0038] Description of reference numerals:

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

[0040] In order to make the purpose, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions 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 generally described and shown in the drawings here can be arranged and designed in various different 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 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 are within the scope of protection of this application.

[0041] like Figure 6 As shown, the present invention's double-helix ion funnel with auxiliary electrodes (DHE-IF) includes a double-helix electrode 1 with positive and negative poles. The double-helix electrode has a constant inner diameter section and a tapered inner diameter section connected along the ion transmission direction. Four auxiliary electrodes 3 are located at the exit of the tapered inner diameter section. These four auxiliary electrodes 3 work in conjunction with the double-helix electrode 1 to alternate the positive and negative electrodes, forming a hexapole structure 2 at the exit of the double-helix ion funnel to improve the fringe field. The operating pressure range of the DHE-IF is 100 to 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 electric 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 to 3, preferably 0.7 to 1.2. The inner diameter of the constant inner diameter section is 5 to 50 mm, preferably 20 to 30 mm. The ratio of the maximum inner diameter to the minimum inner diameter of the tapered inner diameter section is 5 to 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 first studied. Figure 1 The coordinates r and z represent the radial and axial directions, respectively, with o representing the origin. RF signals of opposite phases are applied to the two spiral electrodes, forming an alternating positive and negative RF (radio frequency) electric field on the axial cross section. This structure, similar to a conventional stacked ring ion guide (SRIG), generates an effective potential (also known as a "pseudopotential"), effectively confining 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 demonstrates the ability of the double-helix electrode structure to radially confine ions.

[0048] like Figure 3 The double-spiral electrode of the DHE-IF of the present invention is shown as a schematic diagram, 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 in the radial XY plane of the DHE-IF of the present invention is presented (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 broad and flat near the central axis; however, a steep potential gradient is observed near the electrodes, which is beneficial for capturing diverging ion clouds in supersonic gas flows. As the inner diameter of the helical electrode decreases, the near-field free zone decreases, the potential well narrows, and ions are focused toward 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 rings. 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, as shown in the figure. 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 dipole field to hexapole field at the ion outlet is beneficial to the improvement of the fringe field to a certain extent. Figure 8 (a) shows a comparison of the fringe fields of a double-helix ion funnel with and without an auxiliary electrode (FPC). The results show that the axisymmetric hexapole, consisting of an FPC (flexible printed circuit) with four auxiliary electrodes and the double-helix electrodes, effectively reduces the fringe fields at the ion exit, significantly improving the ion transfer rate.

[0051] After the electrode optimization was completed, the electric fields of DHE-IF and IF were compared. Figure 8Figure (b) shows a comparison of the fringe fields of the DHE-IF (DHE-IF) of the present invention and an IF (conventional stacked annular ion funnel). It can be seen that the effective potential of the conventional IF fluctuates or "traps," which hinder ion transport, particularly for low-mass ions, a phenomenon known as mass discrimination. The DHE-IF of the present invention features continuous, symmetrical spiral electrodes, making it virtually immune to potential traps. With the optimized exit electrode configuration, the fringe fields of the DHE-IF are effectively reduced by over 90% compared to the IF, further improving ion transport 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 carried out. Figure 9 (a) and Figure 9 (b) shows the velocity distribution of the flow field within the IF and DHE-IF, respectively. The results show that the compressible gas flow forms a supersonic jet and a complex shock wave structure upon entering the first vacuum chamber, due to the large pressure difference between the rough vacuum region and atmospheric pressure. Analyte ions radially expand with the gas flow after leaving the capillary, which is the primary cause of most ion losses. Notably, the recirculation region observed within the DHE-IF is more pronounced than that observed within the IF. Due to the gradual decrease in pressure toward the center of the jet, eddies in this region eventually rejoin the jet. For electrospray ionization mass spectrometry (ESI-MS), this recirculation mechanism increases the residence time of charged droplets and improves the desolvation efficiency of charged droplets within the API. Therefore, it can be preliminarily determined that DHE-IF can achieve higher signal intensity.

[0053] Random collisions between ions and buffer gas molecules were analyzed using a Monte Carlo collision model. All calculations were performed using the CPT module in COMSOL Multiphysics 6.0. A total of 2000 ions of each type were released in the ion trajectory simulations. Figure 9 (c) Figure 9 (d) shows the transmission efficiency of ions of different m / z obtained using IF and DHE-IF as a function of the RF voltage amplitude. For the transmission of high-mass ions, DHE-IF and IF show similar trends. However, the transmission of low-mass ions differs significantly. Figure 9 (c) and Figure 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. To ensure maximum ion transmission efficiency, we first optimized the DC bias (DC_bias) between the ion inlet and outlet. During the optimization process, the RF voltage was set to a constant 100 Vpp. Figure 10 (a) records different DC bias DC 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 enough axial power to enter the lower vacuum. After reaching the maximum value, the decrease in abundance is believed to be due to the ions being over-pushed and unable to focus on the central axis in time within the limited transfer path, and ultimately annihilated 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 ( Figure 10 (b)). The RF voltage was adjusted from 0 Vpp to 140 Vpp in 10 Vpp steps, and the ion abundance was recorded 10 times at each voltage point and then averaged. The results show that the m / z 175 ion is most abundant at 90 Vpp, while high-mass m / z ions require higher RF amplitudes for optimal transmission (m / z 382: 100 Vpp, m / z 847: 140 Vpp). 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 low-mass ions, the ion abundance curve forms 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 for m / z 382 and m / z 559 ions may be due to similar molecular structures or collision cross sections.

[0055] To further validate the improved mass discrimination and enhanced MS instrument sensitivity achieved by DHE-IF, mass spectra obtained using DHE-IF and IF as ion introduction devices were compared. The IF used for comparison had similar dimensions to the DHE-IF (inlet inner diameter: 20 mm; outlet inner diameter: 2 mm; electrode thickness: 0.5 mm; inter-electrode distance: 0.5 mm). To obtain clear mass spectra, a mixture of caffeine (m / z 195) and reserpine (m / z 609) was used as the sample due to their high ionization efficiency and significant m / z difference. The solvent was methanol and 1% formic acid. The mass spectra of the caffeine and reserpine ions were recorded at their respective optimal RF voltages and normalized. Figure 11 (a) and Figure 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 is increased 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, Figure 11 (b) and Figure 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 was continuously increased, the intensity of caffeine ions decreased rapidly. This sharp decrease is consistent with previously reported results and is caused by potential traps on the central axis of the IF. In addition, Figure 11 Figure (e) shows that the peak intensities of caffeine and reserpine increased by over 50% and 10%, respectively, with DHE-IF compared to IF. This enhanced intensity is hypothesized to be due to the more pronounced recirculation zone within DHE-IF, which enhances the desolvation efficiency of the charged droplets. Overall, DHE-IF outperforms IF in terms of simultaneous transmission of medium- and low-mass m / z ions and improved sensitivity.

[0056] The aforementioned tests demonstrate that the dual-helix electrode ion funnel (DHE-IF) with an auxiliary electrode, positioned at the exit of the funnel-shaped helical electrode, forms a nearly symmetrical hexapole structure with the dual helical electrode. This significantly improves the fringe field of the dual helical structure, reducing its hindrance to ion transmission and enhancing 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, which effectively limits ion divergence and is virtually unaffected by potential trapping compared to conventional ion funnels. After optimizing the DC bias and RF amplitude, mass spectrometric data from the DHE-IF were compared with those from a conventional stacked ring ion funnel (stacked ring ion funnel). The results demonstrate that the DHE-IF exhibits improved mass discrimination compared to IF and enhances the efficiency of simultaneous transmission of low- and medium-m / z ions. Furthermore, enhanced ion intensity was observed, contributing to lower detection limits and higher sensitivity.

[0057] The above-described embodiments merely represent specific implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of protection of the present application. It should be noted that those skilled in the art will be able to make relevant modifications and improvements without departing from the technical concept of the present application, and these modifications and improvements fall within the scope of protection 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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