CN116598188A - A gradient multipole ion guide device and its mass spectrometry system - Google Patents

Abstract

The application provides a graded multipole ion guide device and a mass spectrometry system. The device is provided with a through hole with an aperture which is changed from large to small along the direction of an ion inlet and outlet, wherein the through hole is divided into a multipolar electric field region and a quadrupole electric field region, the multipolar electric field region is in a round table shape, and the quadrupole electric field region is in a cylindrical shape; the multipolar electric field region is surrounded by a plurality of electrode rods which are uniformly distributed, the electrode rods comprise 4 electrode rods I and 4 electrode rods II, n is more than or equal to 1 and less than or equal to 3, the electrode rods I are symmetrically distributed along the circumference, and the electrode rods II are uniformly distributed between the electrode rods I; the four-stage electric field region is surrounded by 4 electrode rods. The device of the application obviously improves the transmission efficiency of low-mass ions, reduces the 'low-mass discrimination effect' in the ion transmission process, and further improves the accuracy of analysis of the mixed sample in a wide mass range.

Description

A gradient multipole ion guide device and its mass spectrometry system

technical field

The invention relates to the technical field of mass spectrometry, in particular to a gradient multipole ion guide device and a mass spectrometry system.

Background technique

With the advantages of high sensitivity, fast analysis speed and strong specificity, mass spectrometer has been widely used in environmental detection, clinical analysis, organic synthesis, drug research and development, forensic science and other fields. A mass spectrometer is mainly composed of several parts such as an ion source, an ion transmission system, a mass analyzer, a detector, and a vacuum system.

Atmospheric pressure ionization has been widely used in the field of mass spectrometry. However, due to the "supersonic expansion" of ions in the process of transporting from the atmospheric environment to the vacuum environment and the collision with neutral gases, the ion sampling efficiency is greatly reduced, and the number of ions that finally reach the mass analyzer is extremely small. This reduces the sensitivity of the mass spectrometer. Therefore, for the high-efficiency ion focusing guide device, how to improve the sampling efficiency is the key to improving the sensitivity of the instrument. In addition, as another common phenomenon in the ion transmission process, the "mass discrimination effect" refers to the differential transmission of ions with different mass numbers (that is, the transmission efficiency of ions of different sizes is different), resulting in low transmission efficiency of low-mass ions. It also affects the highly sensitive and accurate analysis of mixed samples with different molecular masses.

Electrostatic lenses, ion funnels, and multipole guiding devices are common ion focusing transmission devices at present. The electrostatic lens ion guiding method has no mass discrimination against the transmitted ions and can maintain ion kinetic energy. It is suitable for use in conjunction with other ion guiding devices. It has the disadvantages of low transmission efficiency and limited transmission distance. The ion funnel has a good focusing effect and is suitable for ion transmission under high pressure conditions, but it also has the problems of "low mass discrimination effect", low transmission efficiency and poor sensitivity of small mass ions. The most common multipole ion guide devices are hexapoles and octopoles with a constant field radius. The high-order electric field (such as the hexapole field and octopole field) is used to achieve efficient capture and transmission of ions. It has a wide range of working pressures. , Low-quality discrimination effect and low advantage. However, due to the wider and flatter distribution of the electric field in the radial direction of the multipole ion transmission device, it cannot finally focus the ions into a smaller ion beam, and the focusing ability of the ions is not good. Therefore, the ions pass through the cone hole A defect in which the transfer efficiency into the next level of vacuum drops drastically.

Therefore, the current development of ion transmission technology and devices with high transmission efficiency, good focusing effect, and low low-mass discrimination effect has become one of the key issues to be solved in the development of high-performance mass spectrometers.

Contents of the invention

In order to solve the problems of low ion transmission efficiency, poor focusing effect and low mass discrimination effect existing in the existing mass spectrometry system, a gradient multipole ion guide device is provided.

Another object of the present invention is to provide a mass spectrometry system including the gradient multipole ion guide device.

In order to achieve the above technical purpose, the gradient multipole ion guide device of the present invention has a through hole whose aperture is changed from large to small along the direction of ion import and export, and the through hole is divided into a multipole electric field area and a quadrupole electric field area , the multipole electric field area is in the shape of a circular frustum, and the quadrupole electric field area is cylindrical; the multipole electric field area is surrounded by a number of electrode rods evenly distributed, and the electrode rods include 4 electrode rods one and 4n Two electrode rods, n being greater than or equal to 1 and less than or equal to 3, the first electrode rods are symmetrically distributed along the circumference, and the second electrode rods are evenly distributed between the two electrode rods one; the quadrupole electric field area consists of four The electrode rods are surrounded by one.

Further, the minimum diameter of the through hole of the multi-electric field area is the same as the diameter of the four-level electric field area.

Further, in the multi-pole electric field region, the cross-sectional widths of the first electrode rod and the second electrode rod gradually change from wide to narrow along the direction of the ion inlet and outlet, and the cross-sectional width is toward the center of the inscribed circle of the guide assembly. direction of the electrode face width.

Further, the initial cross-sectional widths of the first electrode rod and the second electrode rod are consistent.

Further, the sectional width lapse rate of the first electrode rod is less than or equal to the lapse rate of the width of the second electrode rod.

Further, the number of the second electrode rods is 8.

Further, a sine wave radio frequency signal with the same amplitude and opposite phase is respectively applied to each two adjacent electrode rods, the adjustable range of the amplitude is 0-500V _0p , and the adjustable range of the frequency is 400kHz-2MHz. At the same time, the same DC voltage is applied to all electrode rods, and its adjustable range is -100V ~ 100V.

Further, the gradient multipole ion guide device also includes a housing for placing the electrode rods in the housing. The shell is fixed on the insulating support.

In order to achieve another object of the present invention, the present invention provides a mass spectrometry system including the gradient multipole ion guide device.

The main structure of the mass spectrometry system of the present invention is composed of an atmospheric pressure ion interface, a gradient multipole ion guide device, a mass analyzer and a detector. The gradient multipole ion guide device is integrated in the primary cavity of the small mass spectrometer, and is located between the outlet of the sampling capillary and the tapered hole lens. An ion trap is installed in the secondary vacuum chamber as a mass analyzer and an electron multiplier as a detector. Under the maintenance of the vacuum pump group, the air pressures of the two-stage vacuum chambers are 5Torr and 4mTorr respectively.

The gradient multipole ion guide device and the mass spectrometry system described in the present invention have the following advantages:

1) The device of the present invention adopts an electrode structure different from the traditional multipole ion guide, through the gradual electrode structure and spatial arrangement, different multipolar electric fields are organically combined to form a multipolar field to a quadrupole field Gradient gradient electric field. The multipole field is used to trap the expanded ion beam into the ion guide rod and transport the ions, and the focusing characteristics of the quadrupole field are used to finally realize the efficient focusing and transmission of the ion beam.

2) The present invention is different from the ion funnel plasma transmission device, utilizes multipole and quadrupole electric fields to realize the focusing and transmission of ions, and will not form a potential energy barrier that hinders ion movement in the transmission path of ions, and this potential energy barrier is harmful to small mass The hindering effect of number ions is particularly significant. Therefore, the device of the present invention can effectively reduce the low-mass discrimination effect in the ion transmission process, and improve the transmission efficiency of the low-mass number ions.

3) The present invention realizes efficient trapping, focusing and transmission of ions in the sub-vacuum region of the mass spectrometer by adopting a combination of mechanical structure and high-order field gradient gradient. In particular, the device of the present invention improves the transmission efficiency of low-mass ions, lays a foundation for mass spectrometers to realize high-efficiency detection of samples with different molecular weights, improves the accuracy of analysis of mixed samples with a wide range of mass, and is applicable to various traditional Mass spectrometers and small mass spectrometer systems.

Description of drawings

Fig. 1 is a schematic cross-sectional view of the structure of the gradient multipole ion guide device according to the present invention;

Fig. 2 is the structural representation of electrode rod described in the present invention;

Fig. 3a and Fig. 3b are respectively the composition of the electrode rods at the ion inlet port and the outlet port of the present invention and the principle diagrams for applying electrical signals;

Fig. 4 is a schematic diagram of the principle of the small mass spectrometer system of the gradient multipole ion guide device of the present invention;

Fig. 5a is the ion transmission characteristics of the gradient multipole ion guide device of the present invention under different radio frequency voltage conditions;

Fig. 5b is the ion transmission characteristics of the gradient multipole ion guide device of the present invention under different DC voltage conditions;

Fig. 6a is a mass spectrogram of mixed samples with different mass numbers analyzed by the gradient multipole ion guide device of the present invention when the radio frequency voltage is 170V _pp ;

Fig. 6b is a mass spectrogram of mixed samples with different mass numbers analyzed by the gradient multipole ion guide device of the present invention when the radio frequency voltage is 210V _pp ;

Figure 7a is the mass spectrum of mixed samples with different mass numbers analyzed by the traditional ion funnel device when the RF voltage is 60V _pp ;

Figure 7b is the mass spectrum of mixed samples with different mass numbers analyzed by the traditional ion funnel device when the RF voltage is 150V _pp ;

Figure 8a and Figure 8b are respectively the detection limit curves of the small mass spectrometer of the gradient multipole ion guide device of the present invention for different substances.

Detailed ways

In order to make the purpose, technical solutions and advantages of the present invention clearer, the technical solutions of the exemplary embodiments of the present invention are described below in conjunction with the accompanying drawings. Elements and features described in one drawing or one embodiment of the present invention may be combined with elements and features shown in one or more other drawings or embodiments. It should be noted that representation and description of components or processes that are not related to the present invention and known to those of ordinary skill in the art are omitted from the drawings and descriptions for the purpose of clarity.

The present invention will be further described below in conjunction with the accompanying drawings.

As shown in Figures 1 to 3, the gradient multipole ion guide device of this embodiment has a through hole whose aperture changes from large to small along the direction of ion import and export, and the through hole is divided into a multipole electric field area and a quadrupole electric field area . The multi-pole electric field area is in the shape of a circular frustum, and the quadruple electric field area is in the shape of a cylinder.

The multi-pole electric field area is surrounded by several electrode rods evenly distributed, and the electrode rods include 4 electrode rods 1 and 8 electrode rods 2 .

The four electrode rods one 1 are symmetrically distributed along the circumference, and the two electrode rods two 2 are evenly distributed between the two electrode rods one 1; the quadrupole electric field area is surrounded by four electrode rods one 1.

The cross-sectional width of the four electrode rods 1 gradually decreases in the length interval of L1, and then remains unchanged in the length of L2; there are 8 electrode rods 2 and 2, and the cross-sectional width gradually shrinks to be very thin in the length interval of L1. Finally, the assembly forms a "funnel"-shaped electrode group structure in which the radius of the inscribed circle first gradually decreases from Rin to Rout (length L1), and then keeps Rout constant (length L2).

The length of the electrode rod one 1 used in this embodiment is 85mm, and the section width gradually decreases from 2.2mm-1mm to 1.2mm-0.5mm. The length of the electrode rod two 2 is 65mm, and the section width gradually decreases from 2.2mm-1mm to 0-0.1mm, specific specifications can be adjusted according to actual needs.

Preferably, the initial width ratios of the first electrode rod 1 and the second electrode rod 2 are consistent. The cross-sectional width decrease rate of electrode rod one 1 is less than or equal to the width decrease rate of electrode rod two 2 .

The radius of the inscribed circle area of the device in this embodiment gradually decreases from 6 mm to 2 mm in the 65 mm length interval of the front section, and remains constant at 2 mm in the 20 mm length interval of the rear section. The radius of the inscribed circle area can also be adjusted as required.

The number of electrode rods 2 of this device can be adjusted according to needs, such as 4, 12, etc. The diameters and diameter changes of electrode rod 1 and electrode rod 2 can also be adjusted according to needs, as long as the ion import and export direction is gradually changed from thick to thin That's it.

The device adopts the multi-pole to quadrupole method to more effectively capture and focus the expanding ion beam, the free electric field area of the high-order electric field is larger, the ability to capture ions is strong, and the space charge effect is small, and there is no discrimination against low-mass ions effect. The ion focusing characteristics of the quadrupole field are stronger, which can focus the ions into a finer ion beam, and improve the transmission efficiency of the ions through the cone hole into the next vacuum.

In the gradient multipole ion guide device of this embodiment, the electrode rods are placed in the shell of the shell 3 . The shell 3 is fixed on the insulating support. Insulating support comprises front end support 4 and rear end support 9, is convenient to the stability of device like this.

In order to form a gradually focused multi-pole electric field, an alternating radio frequency voltage signal and a direct current voltage signal are simultaneously applied to the electrodes of the device of the present invention. Fig. 3a, Fig. 3b are respectively the electrode composition and electrical signal application schematic diagram of the ion inlet port and the outlet port of the present invention; Wave radio frequency signal with adjustable amplitude and frequency; at the same time, the same adjustable DC voltage is applied to all electrodes. Among them, the role of the radio frequency signal is to form a multipolar electric field in the x-y plane to realize the trapping and confinement of ions, and the role of the DC voltage is to realize the transmission of ions in the z direction.

A sinusoidal radio frequency signal with the same amplitude and opposite phase is respectively applied to every two adjacent electrode rods, the adjustable range of the amplitude is 0-500V _0p , and the adjustable range of the frequency is 400kHz-2MHz. At the same time, the same DC voltage is applied to all electrode rods, and its adjustable range is -100V ~ 100V.

A sine wave radio frequency signal with the same amplitude and opposite phase is respectively applied to every two adjacent electrodes of the 12 electrodes. The adjustable range of the amplitude is 0-500V _0p , and the adjustable range of the frequency is 400kHz-2MHz. At the same time, the same DC voltage is applied to all electrodes, and its adjustable range is -100V ~ 100V.

The device of the present invention can generate two sections of ion guiding regions in which the multipole electric field changes continuously and gradually, that is, the multipole field region and the quadrupole field region. In the multipole field region, due to the changes in the mechanical and arrangement structure of the electrode group as shown above, the multipole field components gradually decrease, and the quadrupole field components gradually increase, realizing the gradual change from the multipole field to the quadrupole field, which is beneficial to the The expanded ion beam is trapped into the multi-pole field area; in the quadrupole field area, the structure and arrangement of the four electrodes will no longer change, so a stable quadrupole field is formed in this area, which can further focus the ions and transmit them into the Next level vacuum.

This embodiment also provides a mass spectrometry system including the gradient multipole ion guide device.

Fig. 4 is a schematic diagram of the principle of the small mass spectrometer system of the gradient multipole ion guide device of the present invention. As shown in Figure 4, the main structure of the mass spectrometry system consists of an atmospheric pressure ion interface, a gradient multipole ion guide, a mass analyzer, and a detector. Including but not limited to two-stage vacuum chambers, wherein the primary vacuum chamber is connected to the atmospheric pressure through the atmospheric pressure sampling interface, and connected to the secondary vacuum chamber through the cone lens. The two-stage vacuum is maintained by a set of mechanical and molecular pumps.

The aforementioned ion guide device of the present invention is integrated in the first-stage vacuum cavity, and is located between the capillary of the atmospheric pressure sampling interface and the tapered lens, and the relative positions of the three can be adjusted freely. An ion trap is placed in the secondary cavity as a mass analyzer and an electron multiplier as a detector for ion mass analysis and signal detection. The invention also includes an integrated circuit and measurement and control software, etc., which provide required electrical signals for each part of the system, and perform communication control and result collection and analysis.

In the mass spectrometry system of this embodiment, under the maintenance of the vacuum pump group, the air pressures of the two-stage vacuum chambers are respectively 5 Torr and 4 mTorr. During the analysis process, the ions enter the first-stage vacuum chamber through the sampling capillary of the atmospheric pressure sampling interface, and are captured, transmitted and focused by the gradient multipole ion guide device, and finally enter the ion trap through the tapered hole lens to complete the quality analysis. analysis, and finally enter the detector to complete the detection of the signal.

The following is a study of the ion transmission performance of the graded multipole ion guide device.

Experimental example 1

The gradient multipole ion guide device of this embodiment is installed in the primary vacuum cavity of the miniature mass spectrometer, the air pressure is about 5 Torr, and the instrument adopts the continuous sampling method. Arginine (m/z 174), rhodamine (m/z 443), reserpine (m/z 609) and "N"-NNQQNY-"C" (m/z 780) were used at a concentration of 10ug/mL to treat Measure the sample, increase the radio frequency voltage from 0V _0p to 500V _0p to detect and record the relative abundance of different ions under various radio frequency voltage conditions. Keep the RF voltage unchanged, change the DC voltage from 0V to 50V, detect and record the relative abundance of different ions under various DC voltage conditions, as shown in Figure 5.

Fig. 5a shows the ion transmission characteristics of the gradient multipole ion guide device of the present invention under different radio frequency voltage conditions; as the radio frequency voltage increases, the ion signal intensity increases and finally tends to be constant. At the same time, it can be seen that the gradient multipole ion guide device of the present invention has similar transmission characteristics for ions with different mass numbers, and does not show obvious low-mass discrimination effect. Fig. 5b shows the ion transmission characteristics of the gradient multipole ion guide device of the present invention under different DC voltage conditions. It shows that the ion transmission efficiency first increases gradually and then decreases gradually with the increase of DC voltage.

Experimental example 2

This experimental example is to verify the transmission characteristics of the ion guide device of the present invention for samples with different molecular weights.

In this experimental example, a solution containing two ions with different mass-to-charge ratios: arginine (m/z=175, Arginine) and reserpine (m/z=609, Reserpine) was selected, and different sizes of ions under different RF voltages were explored. Transport properties of mass-to-charge ions. Specifically, a mixed solution of arginine and reserpine was used to apply a constant DC voltage of 15V to the gradient multipole ion guide device, and the radio frequency voltage amplitude was increased from 100Vpp to 210Vpp, and the optimal voltage of arginine was reached (~170Vpp). Spectra were recorded at the optimal voltage (~210Vpp) of reserpine and reserpine, as shown in Figure 6. Fig. 6a is the mass spectrum of two kinds of ions with the same charge and different mass numbers when the RF voltage is 170V. Fig. 6b is the mass spectrogram of two kinds of ions with the same charge amount but different mass numbers when the radio frequency voltage is 210V.

It can be seen from FIG. 6 that the absolute signal intensity of arginine ions with smaller mass numbers decreases by less than 20% during the increase of the radio frequency voltage amplitude from 100Vpp to 210Vpp. This shows that the "low mass discrimination effect" of the gradient multipole ion guide device of the present invention is small, and it has a good performance in dealing with complex mixed samples, especially when the samples contain ions with large mass-to-charge ratios.

Comparative example 1

Same as Example 2, the same solution containing two kinds of ions with different mass-to-charge ratios is selected: arginine (m/z=175, Arginine) and reserpine (m/z=609, Reserpine), the difference is to adopt the existing traditional The ion funnel device is used for ion guidance, and the spectral peaks are recorded when the ion passage rates of arginine and reserpine samples are the highest. Figure 7a is the mass spectrum of mixed samples with different mass numbers analyzed by the traditional ion funnel device when the RF voltage is 60V _pp ; Figure 7b is the traditional ion funnel device when the RF voltage is 150V _pp mixed samples with different mass spectrum analysis mass spectrum.

It can be seen from Figure 7a and Figure 7b that when the radio frequency amplitude is adjusted to 60V _pp , the arginine of the traditional ion funnel device reaches the peak, but the signal of reserpine is very weak. When the radio frequency amplitude is adjusted to 150V _pp , the traditional ion funnel Reserpine passage through the device peaked, but no arginine signal was detected.

It can be seen from Comparative Example 1 that the mass discrimination of the traditional ion funnel device is relatively large, which is not conducive to the detection requirements of low-quality samples in complex mixed samples.

Experimental example 3

This experimental example is to verify the sensitivity of the gradient multipole ion guide device and the mass spectrometry system of the present invention. The gradient quadrupole ion guide device of the present invention is integrated in a small mass spectrometer system, and after parameter optimization, the detection sensitivity of the small mass spectrometer system for ions with different mass numbers is measured.

In this experiment example, samples of arginine and reserpine at various concentrations were first prepared, and the concentration was increased by 10 times starting from 0.1ng/mL, and the concentration was gradually increased. When a signal with a signal-to-noise ratio of 3 was obtained, the signal of the sample to be tested was considered And tandem mass spectrometry was performed to obtain sample product ions for further confirmation of the sample. Each concentration is then measured step by step to obtain a linear relationship between concentration and relative abundance.

Figure 8a and Figure 8b are respectively the detection limit curves of the small mass spectrometer of the gradient multipole ion guide device of the present invention for different substances. Figure 8a is the detection limit calibration curve of the system for measuring arginine, and the MS/MS spectrum of the arginine sample at the minimum detection limit concentration of 1 ng/mL. Fig. 8b is the detection limit calibration curve of the system for measuring reserpine, and the MS/MS spectrum of the reserpine sample under the condition of the minimum detection limit concentration of 1 ng/mL.

The device of the present invention adopts a gradually changing electrode structure and spatial arrangement, uses the twelve-pole field to capture the expanded ion beam, enters the ion guide rod and transmits the ions, and utilizes the focusing characteristics of the quadrupole field to finally realize the efficient focusing and transmission of the ion beam, effectively Reduce the low-mass discrimination effect and improve the transmission efficiency of low-mass ions. It lays the foundation for mass spectrometers to realize efficient detection of samples with different molecular weights and sizes, and is suitable for various traditional mass spectrometers and small mass spectrometer systems.

Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made hereto without departing from the spirit and scope of the invention as defined by the appended claims. Moreover, the scope of the present application is not limited to the specific embodiments of the procedures, devices, means, methods and steps described in the specification. Those of ordinary skill in the art will readily appreciate from the disclosure of the present invention that existing and future devices that perform substantially the same function or obtain substantially the same results as the corresponding embodiments described herein can be used in accordance with the present invention. The developed process, device, means, method or steps. Accordingly, the appended claims are intended to include within their scope such processes, means, means, methods or steps.

Claims (10)

1. A progressive multipole ion guide device, characterized by having a through hole with an aperture from large to small in an ion inlet-outlet direction, the through hole being divided into a multipole electric field region and a quadrupole electric field region, the multipole electric field region being in a circular truncated cone shape, the quadrupole electric field region being in a cylindrical shape; the multipolar electric field region is surrounded by a plurality of electrode rods which are uniformly distributed, the electrode rods comprise 4 electrode rods I and 4 electrode rods II, n is more than or equal to 1 and less than or equal to 3, the electrode rods I are symmetrically distributed along the circumference, and the electrode rods II are uniformly distributed between the electrode rods I; the four-stage electric field region is surrounded by 4 electrode rods.

2. The graded multipole rod ion guide of claim 1, wherein the minimum diameter of the through-holes of the multipole electric field region is the same as the diameter of the quaternary electric field region.

3. The graded multipole rod ion guide apparatus of claim 1 or 2, wherein the cross-sectional widths of the first and second electrode rods in the multipole electric field region are graded from wide to narrow in the ion entrance and exit directions.

4. A graded multipole rod ion guide device according to claim 3, wherein the rate of decrease in cross-sectional width of the first electrode rod is less than or equal to the rate of decrease in cross-sectional width of the second electrode rod.

5. The graded multipole ion guide device of claim 1, wherein the number of electrode rods two is 8.

6. The ion guide device of claim 1, wherein the two adjacent electrode rods are respectively applied with sine wave radio frequency signals with the same amplitude and opposite phases, and the amplitude of the sine wave radio frequency signals is adjustable within the range of 0-500V _0p The adjustable frequency range is 400 kHzV-2 MHz.

7. The graded multipole rod ion guide of claim 1, wherein the same dc voltage is applied across all the electrode rods, with an adjustable range of-100V to 100V.

8. The graded multipole rod ion guide apparatus of any of claims 1-7, further comprising a housing in which the electrode rod is disposed within the housing.

9. The graded multipole ion guide of claim 8, wherein the housing is secured to an insulating support.

10. A mass spectrometry system comprising the graded multipole ion guide device of any of claims 1 to 9.