A method for square wave phase modulation of the mass window of linear ion trap-time of flight mass spectrometry

Abstract

The present invention discloses a method for square wave phase modulation of the mass window of a linear ion trap-time of flight mass spectrometer. Ions generated by an ion source inside the trap or an ion source outside the trap enter the linear ion trap, and the ions are cooled and stored under the action of a square wave radio frequency electric field. An extraction voltage is then applied at a specific phase point to extract the ions in the trap axially to a time-of-flight mass analyzer at the rear end and detect to obtain a mass spectrum. By adjusting the square wave phase during ion extraction, the mass window of the linear ion trap-time of flight mass spectrometer can be regulated. In the present invention, in a time-of-flight mass spectrometer having an ion trap pre-stage storage device, the radio frequency phase during ion extraction can be changed to regulate the mass window of the linear ion trap-time of flight mass spectrometer.

Description

Technical Field

[0001] The invention belongs to a mass spectrometry instrument, and in particular relates to a method for square wave phase modulation of a linear ion trap-time of flight mass spectrometry mass window. Background Art

[0002] The ion trap / time-of-flight tandem mass spectrometer (QIT / TOFMS) combines the ion selection, cooling, and enrichment capabilities of an ion trap with the fast analysis speed, high sensitivity, and high resolution of a time-of-flight mass spectrometer. It is a widely used tandem mass spectrometry technique. Compared to the point-distributed state of a three-dimensional ion trap, a two-dimensional linear ion trap (LIT) offers higher injection efficiency and greater ion storage capacity, leading to a rapid increase in the use of linear ion traps in tandem mass spectrometry. Patent (WO 03041107) proposes a three-dimensional ion trap driven by digital waves. The non-patent document "A strategy for simultaneously improving resolution and sensitivity of hybrid quadrupole ion trap / time-of-flight mass spectrometry using square waveform phase modulation" develops a square-wave driven linear ion trap. Compared to traditional sinusoidal wave ion traps, digital wave ion traps offer greater operational agility and can manipulate ion trap performance, including ion storage mass range, storage capacity, and ion beam phase space, by modulating the frequency, voltage, duty cycle, and phase of the digital wave.

[0003] A microchannel plate (MCP) is a planar, two-dimensional detector capable of detecting ions and amplifying the detection signal in a vacuum. It boasts fast response speed and high gain, making it a widely used time-of-flight mass spectrometer detector. A MCP is a flat-plate array of electron multipliers formed by pressing hollow glass fibers. The inner wall of each hollow fiber channel is coated with a material with a high electron emission coefficient. A voltage is applied across the MCP, creating an electric field within the microchannels. Ions with a certain energy bombard the MCP coating, generating a large number of secondary electrons. Accelerated by the electric field, these secondary electrons continue to bombard the channel coating, generating an increasing number of electrons, ultimately outputting a large number of electrons (called multiplied electrons) at the output. The ratio of the number of multiplied electrons ultimately output by the MCP to the number of incident particles is called the MCP gain. It is well known that the lifespan of a MCP is inversely correlated with the total number of electrons emitted from the MCP. At the same voltage, the MCP gain decreases with use. High-intensity non-target ions can induce a large number of multiplied ions, shortening the detector lifespan. Therefore, selectively filtering out high-abundance non-target ions and detecting only low-abundance target ions is beneficial to extending the detector life and ensuring a stable gain effect. Summary of the Invention

[0004] The present invention discloses a method for square wave phase modulation of the mass window of a linear ion trap-time of flight mass spectrometer. In a time of flight mass spectrometer with an ion trap pre-stage storage device, the mass window of the linear ion trap-time of flight mass spectrometer can be adjusted by changing the radio frequency phase during ion extraction.

[0005] The technical solution adopted by the present invention to achieve the above-mentioned purpose is: a method for square wave phase modulation of the linear ion trap-time of flight mass spectrometer mass window, comprising the following steps:

[0006] Applying a square wave radio frequency voltage to the radio frequency electrode of the linear ion trap through a square wave generating device; applying a DC voltage to the entrance electrode and the exit electrode of the linear ion trap respectively;

[0007] By controlling the voltage parameters of the entrance and exit electrodes through the working sequence, ion injection, cooling and extraction are achieved in the linear ion trap;

[0008] The working sequence is realized by a pulse delay generator, and one working sequence cycle consists of three stages: ion injection, ion cooling, and ion extraction. The radio frequency phase value during ion extraction is regulated by setting the initial phase of the square wave generating device to adjust the mass window of the linear ion trap-time of flight mass spectrometer.

[0009] Ions of different charge-to-mass ratios are separated by a time-of-flight mass analyzer and fly to a detector to amplify the ion signals into electronic signals.

[0010] The method of implementing ion injection, cooling, and extraction in a linear ion trap by sequentially controlling voltage parameters of an entrance electrode and an exit electrode comprises the following steps:

[0011] During the ion injection period, ion injection is achieved through a DC electric field, which reduces the entrance electrode voltage to -5 V, forming a potential energy gradient with the voltage at the front end of the entrance electrode, and injecting ions into the linear ion trap. At the same time, the exit electrode is raised to +3 V to prevent ion outflow, and the injected ions are captured by a square wave radio frequency electric field.

[0012] During the ion cooling period, the entrance and exit electrodes are simultaneously modulated to +10 V to achieve axial confinement of the ions. The square-wave radio frequency electric field binds the ions radially. After a set cooling time, the ion cloud is spatially concentrated on the central axis of the quadrupole.

[0013] During the ion extraction period, at a certain RF phase moment, pulsed high voltages of +300 V and -300 V were applied to the entrance electrode and exit electrode, respectively, to extract ions from the linear ion trap into the time-of-flight mass analyzer at the rear end. The extraction time was set to 10 μs.

[0014] The gas pressure in the linear ion trap is regulated within the range of 0.1 to several tens of Pa.

[0015] The amplitude of the square wave radio frequency voltage is 80-500 V.

[0016] The frequency of the square wave radio frequency voltage is 0.5-2.5 MHz.

[0017] The double pulses are applied at different radio frequency phases, and the phase range is 0-360 degrees.

[0018] The ion source includes an internal source and an external ion source, and the external ion source includes various ion sources of normal pressure and negative pressure.

[0019] A square wave phase modulation linear ion trap-time of flight mass spectrometry mass window system, comprising:

[0020] A linear ion trap is composed of an entrance electrode, an exit electrode, and a radio frequency electrode; the DC power supplies of the entrance and exit electrodes are connected to a pulse delay generator, which is used to perform timing control and trigger the DC power supply;

[0021] a square wave generating device connected to the radio frequency electrode and used for applying a square wave radio frequency voltage;

[0022] A time-of-flight mass analyzer is provided at the rear end of the ion trap and is used to distinguish the masses of ions; the inlet corresponds to the outlet of the linear ion trap, and the axis of the time-of-flight mass analyzer coincides with the axis of the linear ion trap;

[0023] Detector, used to detect and amplify ion signals.

[0024] The detector is used to detect and amplify ion signals, including but not limited to a microchannel plate and an electron multiplier.

[0025] The present invention has the following beneficial effects and advantages:

[0026] 1. The present invention provides an axially tandem linear ion trap-time-of-flight mass spectrometer. The ion trap and time-of-flight mass spectrometer are coaxially placed, and the ion cloud is axially extracted from the ion trap to the time-of-flight mass analyzer. By varying the radio frequency phase during ion extraction, the mass window of the linear ion trap-time-of-flight mass spectrometer can be controlled in a simple and rapid manner.

[0027] 2. This method can adjust the detection abundance of different substances, effectively prevent high-peak non-target ions from damaging the detector life, and ensure long-term stable gain effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Schematic diagram of the linear ion trap-TOF structure;

[0029] 1. Inlet electrode, 2. Outlet electrode, 3. Radio frequency electrode, 4. Square wave generator, 5. Time-of-flight mass analyzer, 6. Detector;

[0030] Figure 2 Schematic diagram of the axially extracted segmented linear ion trap-TOF structure;

[0031] Figure 3 Ion trap working timing diagram;

[0032] Figure 4 X-axis phase space distribution diagram of ions of different m / z at square wave RF phase 0°;

[0033] Figure 5a Trends of the relative peak areas of ion peaks with mass-to-charge ratios of m / z 106, m / z 164, and m / z 258 versus square wave phase;

[0034] Figure 5b Mass-to-charge ratio-optimal extracted phase line diagram;

[0035] Figure 5c Mass spectrum of p-xylene / 1,3-hexachlorobutadiene mixed standard gas at 47° and 347°. DETAILED DESCRIPTION

[0036] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments.

[0037] The present invention can adjust the mass window of a linear ion trap-time of flight mass spectrometer by changing the radio frequency phase during ion extraction in a time of flight mass spectrometer with an ion trap front-stage storage device.

[0038] The phase space distribution of the ion cloud in the trap changes with the square wave radio frequency phase moment, and at the same phase moment, the phase space distribution of ions with different mass-to-charge ratios is also different. The optimal radio frequency extraction phase corresponding to ions with different mass-to-charge ratios must be different. Therefore, by changing the radio frequency phase during ion extraction, the mass window of the linear ion trap-time-of-flight mass spectrometer can be controlled.

[0039] The method operates as follows: ions generated by an internal or external ion source enter a linear ion trap, where they are cooled and stored under the influence of a square-wave radio frequency electric field. An extraction voltage is then applied at a specific phase point to extract the ions axially from the trap into a time-of-flight mass analyzer at the rear end, where they are detected and detected as a mass spectrum. Adjusting the square wave phase during ion extraction can control the mass window of the linear ion trap-TOF mass spectrometer.

[0040] like Figure 1 A method for square-wave phase modulation of the mass window of a linear ion trap-time-of-flight mass spectrometer is shown. The system structure includes an ion source, an ion trap consisting of an entrance electrode, an exit electrode, and a radio frequency electrode, a square-wave generating device, and a time-of-flight mass spectrometer. The square-wave generating device generates a square-wave radio frequency voltage and applies it to the radio frequency electrode of the linear ion trap.

[0041] Ions are generated by an internal or external ion source and enter a linear ion trap, where they are cooled and stored under the action of a square-wave radio frequency electric field. A double-pulsed voltage is then applied at a specific phase point to extract the ions from the trap axially to the time-of-flight mass analyzer at the rear end.

[0042] The driving RF voltage of the linear ion trap is a periodic digital RF wave, such as a square wave, a triangle wave, etc.

[0043] Linear ion systems include but are not limited to rectangular ion traps, quadrupoles, and segmented quadrupole structures.

[0044] The storage time of the linear ion trap can be adjusted in the range of 0 to 1000 ms.

[0045] The square wave phase can be modulated at any phase point between 0 and 360°.

[0046] The background gas in the linear ion trap is one or more of helium, argon, krypton, nitrogen, oxygen or dry air.

[0047] The gas pressure in the linear ion trap can be controlled in the range of 0.1 to tens of Pa.

[0048] Ion sources include internal sources and external sources. External sources include normal pressure and negative pressure ion sources.

[0049] The ion trap extraction method is axial extraction. Example

[0050] A method for square-wave phase modulation of the mass window of a linear ion trap-time-of-flight mass spectrometer is disclosed. The method comprises a linear ion trap, a square-wave generating device, and a time-of-flight mass spectrometer. The square-wave generating device generates a square-wave radio frequency voltage, which is applied to the radio frequency electrodes of the linear ion trap.

[0051] Ions are generated by an internal or external ion source and enter a linear ion trap, where they are cooled and stored under the action of a square-wave radio frequency electric field. An extraction voltage is then applied at a specific phase point to extract the ions from the trap axially to the time-of-flight mass analyzer at the rear end.

[0052] like Figure 2 As shown in the example, the linear ion trap is a segmented quadrupole structure consisting of an entrance electrode, a segmented RF electrode, and an exit electrode. The segmented RF electrodes are composed of four parallel electrode arrays; each electrode array consists of one or more concentric cylindrical electrodes evenly spaced apart, with a cylinder diameter of 9.04 mm. The centers of the four electrode arrays are evenly spaced on a circle with a radius of 8.52 mm. The cylindrical electrodes are 4 mm thick and spaced 0.5 mm apart. The entrance electrode aperture and exit electrode are both circular ring electrodes with an inner diameter of 1.5 mm, an outer diameter of 28 mm, and a thickness of 1 mm. A DC voltage is applied to each of the four segmented RF electrode arrays. The concentric cylindrical electrodes in each group are evenly divided by a voltage divider resistor. Each segmented RF electrode is connected to an equivalent capacitor. The cylindrical electrodes in each segmented RF electrode array are applied the same RF voltage, and alternate segmented RF electrode array groups are applied the same RF voltage. Adjacent cylindrical electrode groups are applied RF voltages of opposite polarity but the same absolute value. The RF voltage is a digital square wave RF voltage (RF voltage amplitude is 200 V, frequency is 1.5 MHz, and duty cycle is 0.5). Figure 3As shown in the figure, by sequentially controlling the voltage parameters of the above electrodes, ion injection, cooling, and extraction can be achieved in a linear ion trap. The mass spectrometry analysis cycle is controlled by the main trigger frequency, which in turn regulates the storage time of the linear ion trap. Each trigger cycle consists of three stages: ion injection, ion cooling, and ion extraction. During the ion injection stage, ion injection is achieved via a DC electric field. The voltage at the entrance electrode is reduced to -5 V, forming a potential energy gradient with the voltage at the front end of the entrance electrode, enabling ion injection into the linear ion trap. Simultaneously, the voltage at the entrance electrode is raised to +3 V to prevent ion outflow, and the RF power supply is turned on to capture the injected ions. Finally, in the cooling stage, the entrance and exit electrodes are simultaneously modulated to +10 V to achieve axial confinement of the ions. The square wave RF field radially confines the ions. After a period of cooling, the ion cloud gradually converges spatially onto the central axis of the quadrupole. During the ion extraction period, dual-pulse extraction was adopted. Pulsed high voltages of +300 V and -300 V were applied to the entrance electrode and exit electrode, respectively. The extraction time was set to 10 μs. Dual pulses were applied at different RF phases to extract ions from the trap to the time-of-flight mass analyzer at the rear end. After passing through the time-of-flight mass analyzer, ions with different charge-to-mass ratios were distinguished and flew to the detector, which amplified the ion signal into an electronic signal.

[0053] like Figure 4 As shown in the figure, simion software was used to perform collision cooling of three different m / z ions m / z 106, 260 and 800 in square wave radio frequency (1.5 MHz-200 V) for 2 ms, and the phase space distribution of the cloud in the X direction was recorded at 0° phase. It can be seen that there are differences in the phase space distribution of the three mass-to-charge ratio ions. This was then verified experimentally. 10 ppbv acetone-benzene-p-xylene-tetrachloroethylene-1,3-hexachlorobutadiene was used as the sample standard gas and ionized by a VUV lamp. The mass spectrum signal intensity and resolution of m / z 106, m / z 164 and m / z 258 ions were tested as the square wave extraction radio frequency phase changed. The experimental results are shown in the figure. Figure 5a to Figure 5c The relative peak areas of the four mass-to-charge ratio ions m / z 78, 106, 164 and 258 change with the square wave RF phase. The optimal RF extraction phases for different mass-to-charge ratios are different, namely 63°, 47°, 17° and 345°. Based on this, we can get Figure 5b There is a linear relationship between the mass-to-charge ratio of an ion and its optimal extraction radio frequency phase; in addition, Figure 5c The mass spectra at square wave RF phases of 47° and 327° are shown. It can be seen that at 47°, xylene ions can be well detected, while 1,3-hexachlorobutadiene cannot be effectively detected. On the contrary, at 327°, 1,3-hexachlorobutadiene ions can be detected, while xylene cannot be detected.

Claims

1. A method for square wave phase modulation of a linear ion trap-time of flight mass spectrometer mass window, characterized in that: The following steps are involved: Applying a square wave radio frequency voltage to the radio frequency electrodes of the linear ion trap by a square wave generating device; Applying DC voltages to the entrance electrode and exit electrode of the linear ion trap respectively; By controlling the voltage parameters of the entrance and exit electrodes through the working sequence, ion injection, cooling and extraction are achieved in the linear ion trap; The working sequence is realized by a pulse delay generator, and one working sequence cycle consists of three stages: ion injection, ion cooling, and ion extraction. The radio frequency phase value during ion extraction is regulated by setting the initial phase of the square wave generating device to adjust the mass window of the linear ion trap-time of flight mass spectrometer. Ions of different charge-to-mass ratios are separated by a time-of-flight mass analyzer and fly to a detector to amplify the ion signals into electronic signals.

2. The method for square wave phase modulation of a linear ion trap-time of flight mass spectrometer mass window according to claim 1, characterized in that: The method of implementing ion injection, cooling, and extraction in a linear ion trap by sequentially controlling voltage parameters of an entrance electrode and an exit electrode comprises the following steps: During the ion injection period, ion injection is achieved through a DC electric field, which reduces the entrance electrode voltage to -5 V, forming a potential energy gradient with the voltage at the front end of the entrance electrode, and injecting ions into the linear ion trap. At the same time, the exit electrode is raised to +3 V to prevent ion outflow, and the injected ions are captured by a square wave radio frequency electric field. During the ion cooling period, the entrance and exit electrodes are simultaneously modulated to +10 V to achieve axial confinement of the ions. The square-wave radio frequency electric field binds the ions radially. After a set cooling time, the ion cloud is spatially concentrated on the central axis of the quadrupole. During the ion extraction period, at a certain RF phase moment, pulsed high voltages of +300 V and -300 V were applied to the entrance electrode and exit electrode, respectively, to extract ions from the linear ion trap into the time-of-flight mass analyzer at the rear end. The extraction time was set to 10 μs.

3. The method for square wave phase modulation of a linear ion trap-time of flight mass spectrometer mass window according to claim 1, characterized in that: The gas pressure in the linear ion trap is regulated within the range of 0.1 to several tens of Pa.

4. The method for square wave phase modulation of a linear ion trap-time of flight mass spectrometer mass window according to claim 1, characterized in that: The amplitude of the square wave radio frequency voltage is 80-500 V.

5. The method for square wave phase modulation of a linear ion trap-time of flight mass spectrometer mass window according to claim 1, characterized in that: The frequency of the square wave radio frequency voltage is 0.5-2.5 MHz.

6. The method for square wave phase modulation of a linear ion trap-time of flight mass spectrometer mass window according to claim 1, characterized in that: During the ion extraction phase, dual pulses were applied at different RF phases, ranging from 0 to 360°.

7. The method for square wave phase modulation of a linear ion trap-time of flight mass spectrometer mass window according to claim 1, characterized in that: The ion source generates ions and enters the linear ion trap. The ion source includes an internal ion source or an external ion source. The external ion source includes a normal pressure or negative pressure ion source.

8. A system of square wave phase modulation linear ion trap-time of flight mass spectrometry mass window, characterized in that: include: A linear ion trap is composed of an entrance electrode (1), an exit electrode (2) and a radio frequency electrode (3); the DC power supplies of the entrance electrode (1) and the exit electrode (2) are connected to a pulse delay generator, and the pulse delay generator is used to perform timing control and trigger the DC power supply; A square wave generating device (4) is connected to the radio frequency electrode (3) and is used to apply a square wave radio frequency voltage. The radio frequency phase value during ion extraction is regulated by setting the initial phase of the square wave generating device to regulate the mass window of the linear ion trap-time of flight mass spectrometer; A time-of-flight mass analyzer (5) is provided at the rear end of the ion trap and is used for mass differentiation of ions; the inlet corresponds to the outlet of the linear ion trap, and the axis of the time-of-flight mass analyzer coincides with the axis of the linear ion trap; The detector (6) is used to detect and amplify the ion signal.

9. The square wave phase modulation linear ion trap-time of flight mass spectrometry mass window system according to claim 8, characterized in that: The detector is used to detect and amplify ion signals, and includes a microchannel plate and an electron multiplier.

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