CN104766780A - A Method for Efficient and Fast Analysis in Ion Trap Mass Analyzer - Google Patents

Abstract

The invention belongs to the technical field of mass spectrum analytical testing, and particularly relates to a method for conducting efficient and rapid analysis in an ion trap mass analyzer. According to the method, when ions enter an ion trap, a dipole voltage is utilized to conduct resonance extrusion on the ions, and the ion mass analysis working process is achieved. Particularly, the frequency of a digital radio frequency working voltage is scanned, working voltages of a front end cover electrode and a back end cover electrode of the ion trap mass analyzer are rapidly adjusted, four timing sequence phases which are needed in mass analysis conducted by conventional ion trap spectra are not needed, the mass analysis of the ions can be rapidly completed only by conducting the ion resonance extrusion phase, the analysis time of the whole ion trap mass spectrometer can be shortened, and the testing efficiency is improved. By means of the method for conducting the efficient and rapid analysis in the ion trap mass analyzer, additional hardware change is not needed, and the rapid analysis can be achieved efficiently only through software control.

Description

A Method for Efficient and Fast Analysis in Ion Trap Mass Analyzer

technical field

The invention belongs to the technical field of mass analysis, and specifically relates to a method for realizing high-efficiency and rapid mass analysis in an ion trap mass spectrometer. By scanning the frequency of a digital radio frequency operating voltage and quickly adjusting the operating voltage on the front and rear end cover electrodes of an ion trap mass analyzer, only Performing one of the ion resonance ejection phases quickly completes the mass analysis of the ions.

Background technique

Mass spectrometer is currently one of the most important analytical scientific instruments in the field of analysis and testing. It is widely used in modern scientific research and production activities. It plays an indispensable role in the field of trace substance detection, and has become an indispensable analytical tool in the development of modern science and technology and in daily life.

Ion trap mass spectrometer is one of many mass spectrometers, which has the advantages of simple structure, small volume, and easy processing. The core key component of the ion trap mass spectrometer is the ion trap mass analyzer. The ion trap mass analyzer can realize the functions of ion storage and tandem mass spectrometry in a single mass analyzer at the same time, and can obtain more measured sample components at the same time. Multiple information on composition and molecular structure. In addition, due to the advantages of ion storage and tandem mass spectrometry at the same time, ion trap mass analyzers are often combined with other types of mass spectrometers such as time-of-flight mass spectrometry, quadrupole mass spectrometry, and orbital ion trap mass spectrometry to become more powerful complex mass spectrometers. Instrument system, get more sample information.

Although the quadrupole ion trap mass analyzer and the quadrupole mass analyzer both work on the same quadrupole field theory, that is, they both use the quadrupole electric field to distinguish ions with different mass-to-charge ratios, but they are performing When analyzing the mass of ions, the analysis process is quite different. Simply put, when a quadrupole mass analyzer is used for ion mass analysis in a sample, it changes the electric field distribution in the quadrupole electrode system by continuously changing the operating voltage loaded on the quadrupole electrode system, so that Ions with a single mass-to-charge ratio that can move stably within a certain spatial range in a specific electric field are detected by passing through the quadrupole electrode and reaching the rear ion detector, while other ions are detected because the moving range exceeds The geometrical spatial extent of the quadrupole cannot reach the ion detector. Theoretically, in order to achieve high-mass resolution ion mass analysis, the geometrical processing and assembly accuracy of the quadrupole electrodes are required to be very high, generally within a few microns. This is because the small geometric errors of the quadrupole electrodes will lead to the generation of high-order fields in the quadrupole electric field, and the high-order fields are the nemesis to obtain high-resolution mass analysis.

Although the quadrupole ion trap mass analyzer also utilizes the quadrupole electric field in a certain space to confine ions in the ion storage space of the ion trap, it is different from the quadrupole mass analyzer in that when the ion trap mass analyzer is used for In ion mass analysis, it does not use the stable motion of a specific ion corresponding to a specific electric field distribution to distinguish the ion mass, but uses the inherent long-term frequency of a certain ion under a specific quadrupole electric field, and uses an external dipole electric field to achieve The so-called resonance excitation between the frequency of the dipole electric field and the long-term frequency of the ion makes the movement of the ion unstable and is expelled from the ion trap, and is detected by an external ion detector.

The difference between the ion trap mass analyzer and the quadrupole mass analyzer is that under the same mass resolution capability, the geometric processing accuracy and assembly accuracy of the electrodes that make up the ion trap can be lower, because even the quadrupole There is a small amount of high-order field components in the electric field, but the long-term frequency of ions in the electric field is still related to the electric field distribution. Therefore, the frequency of the dipole electric field and the resonance of specific ions can still be used to realize the resonance of ions. For example, a quadrupole mass analyzer with a geometric accuracy of 20 microns can only achieve a resolution of hundreds of masses at most, while an ion trap with the same geometric accuracy can achieve a mass resolution of at least 1000.

Ion trap mass analyzers also have some disadvantages compared to quadrupole mass analyzers. An obvious disadvantage is that its analysis cycle is relatively long. In the usual mass analysis process, when the ion trap mass analyzer is used for ion sample mass analysis, generally four stages are required, namely: ion introduction, ion cooling, ion mass analysis and ion trap emptying. Each stage The time is about 10 milliseconds, and it takes about 100 ms to complete an analysis process. This is obviously a gap for the actual needs such as high-speed, high-throughput, and online analysis that are increasingly pursued.

Contents of the invention

The purpose of the present invention is to propose a method for performing high-efficiency and rapid mass analysis in an ion trap mass analyzer with high detection efficiency and simple detection process.

The ion trap mass analysis method proposed by the present invention can be quickly completed by scanning the frequency of the digital radio frequency operating voltage and quickly adjusting the operating voltage on the front and rear end cover electrodes of the ion trap mass analyzer, and only performing one of the ion resonance ejection stages Mass analysis of ions.

The driving voltage of the ion trap is mainly radio frequency voltage (radio frequency, referred to as RF). Currently, there are two types of RF voltages for driving ion traps, one is traditional sine wave driving, and the other is digital square wave driving. The method proposed by the invention is mainly applied in the digital square wave driving mode. The following takes digital square wave as an example to illustrate.

In an ion trap driven by a digital square wave, the amplitude of the square wave used to trap ions is generally several hundred volts, and is a certain value. When the ion trap is working, by scanning the frequency of the digital square wave, the dipole resonance excitation signal is superimposed on the digital square wave during the scanning phase. Resonance pops. The dipole excitation square wave used for ion resonance excitation is generated and controlled in the same way as the bound square wave, but its amplitude is lower, generally within 10 volts, and its frequency maintains a fixed proportional relationship with the bound square wave . The waveforms of both the binding square wave and the dipole excitation square wave used for ion ejection are symmetrical, ie, have a 50% duty cycle.

Parameters (a, q) similar to those in Matthew's equation are used to describe the stabilization of ions in the digital square wave ion trap. When an ion with mass m and charge e moves in a pure quadrupole field, the parameters (a, q) can be expressed as:

, (1)

Among them, _r0 is the field radius of the ion trap, U is the DC component of the rectangular square wave, V is the AC component of the rectangular square wave, is the frequency of the rectangular wave. The duty cycle of rectangular square wave is 50% (square wave) in the experimental process of the present invention, and does not contain DC component, therefore =0, It is equal to half of the difference between the high level and low level of the square wave (half peak value). The digital ion trap parameter is mainly _qz value, and its expression is as follows:

(2)

where T _RWF is the period of the digital rectangular wave (binding voltage), when the ion is ejected The value is mainly affected by the period of the digital rectangular square wave. When the bound square wave voltage amplitude V is fixed, changing the period of the square wave can achieve different value.

In the digital ion trap, mass analysis is realized by scanning the frequency of the square wave signal, in order to ensure that all ions are in the same The value is resonantly excited out of the ion trap, and the frequency of the resonant excitation signal is also swept along with the frequency of the square wave signal. The resonance excitation signal can be generated by the frequency division of the square wave signal, if the frequency division number is , then the frequency of the resonant excitation signal for:

(3)

Ion resonance frequency (secular frequency) frequency with a digitally bound voltage signal The relationship between the parameters can be used To represent:

(4)

When the digital tie voltage signal is a square wave, and The following relationship exists:

(5)

When the frequency of the external resonance excitation signal is equal to the resonance frequency of the ion, the ion will be expelled from the ion trap due to the resonance excitation phenomenon. According to formulas (3) and (4), it can be obtained:

(6)

when frequency division When determined, the ion ejection can be calculated by formulas (5) and (6) value, denoted as . At this time, the mass-to-charge ratio of the ion can be expressed as:

(7)

in Indicates the period of the digital tie voltage.

It can be seen that when the amplitude When held constant, a linear sweep over the frequency of the digital confinement voltage is not a linear sweep over the mass-to-charge ratio. In order to realize the linear scanning of the mass-to-charge ratio, the following periodic scanning method can be implemented: the initial period of the digital confinement voltage is set as ,continued After cycles, increase the cycle by a fixed step , at this time the period of the digital tie voltage becomes + . then continue cycles, and so on. then for any step in the scanning process ,have:

(8)

(9)

in Indicates the first The time elapsed during the step, in order of The middle moment of the step (ie step continues cycles) shall prevail. Variables can be eliminated by combining equations (8) and (9) ,get:

(10)

Represents the period of the digital pinning voltage corresponding to the moment when ions are ejected from the ion trap. Bundle Substituting it into Equation 7, it can be seen that the mass-to-charge ratio and time A linear relationship is achieved, that is, a linear scan of the mass-to-charge ratio of ions is realized.

Regardless of whether digital square wave or sine wave voltage is used to bind ions in the ion trap, as long as the ions are ejected from the ion trap by resonance excitation, a dipole excitation voltage needs to be applied, that is, a pair of excitation voltages with the same amplitude and completely opposite phases. An alternating voltage is applied to a pair of electrodes of the ion trap, respectively, and ions are ejected from the direction in which the electrodes are located.

For the currently known conventional ion trap mass spectrometers, four stages are required to realize the mass analysis of ions: ion introduction, ion cooling, ion resonance expulsion and ion emptying. The entire mass analysis process takes a relatively long time, making it impossible for ion trap mass spectrometers to detect in some areas of efficient and rapid analysis and testing. This leads to limitations in the application field of ion trap mass spectrometers.

The ion trap high-efficiency and rapid mass analysis method proposed by the present invention realizes the entire working process of the ion trap mass analyzer by only one stage of ion resonance eviction, replacing the ion introduction, ion cooling, ion resonance eviction, Four stages of ion emptying save the time of three stages, realize fast mass analysis and improve detection efficiency.

The ion trap high-efficiency and rapid analysis method of the present invention uses only one ion resonance to drive out the stage to realize the entire ion trap mass analyzer working process, and the specific process is as follows: in the ion resonance to drive out the stage, apply a radio frequency operating voltage signal with a symmetrical waveform , the ions are trapped in the ion trap by colliding with neutral gas molecules under the action of the electric field generated by the ion trap radio frequency operating voltage; in the digital square wave driving ion trap operating mode, the frequency of the digital radio frequency operating voltage and the fast Adjust the working voltage on the front and rear end cover electrodes of the ion trap mass analyzer, and apply a dipole excitation voltage signal during the scanning process. The ion detector is installed outside the ion trap to detect and obtain the mass spectrum signal of the ion.

In the present invention, in the ion resonance expulsion stage, the applied RF operating voltage with a symmetrical waveform is a digital square wave voltage signal, or a sine wave voltage signal, or other waveform signals.

In the present invention, in the ion resonance ejection stage, the time of the entire mass analysis process is determined by experimental requirements.

In the present invention, the cooling gas is a neutral gas in the ion resonance ejection stage.

In the present invention, in the ion resonance ejection stage, the frequency ratio of the dipole excitation voltage to the confinement voltage is an arbitrary value.

The ion trap high-efficiency and fast analysis method in the present invention has no requirements on the type of ion trap, and it can be a three-dimensional ion trap, a two-dimensional linear ion, and a rectangular ion trap of various structures, it can be an ion trap array, and it can also be a field-adjusted ion trap wait.

In the high-efficiency and rapid analysis method of the ion trap in the present invention, the amplitude of the radio frequency operating voltage and the amplitude of the dipole excitation voltage are not limited, and are determined by the needs of experiments.

The advantage of the method of the present invention is that it only scans the frequency of the digital radio frequency operating voltage and quickly adjusts the operating voltage on the front and rear end cover electrodes of the ion trap mass analyzer, thereby realizing that for the same ion trap mass analyzer, it can realize both traditional The ion storage, mass analysis, and tandem mass spectrometry functions of the ion trap can also perform rapid sample analysis like a quadrupole mass analyzer, which can significantly simplify experimental devices and methods.

Description of drawings

Figure 1. Schematic diagram of the square and sine waves used to drive the ion trap. Among them, (a) the schematic diagram of the waveform of the symmetrical square wave, and (b) the schematic diagram of the waveform of the symmetrical sine wave.

Fig. 2 is the structural representation of the instrument experiment platform of embodiment 1.

Fig. 3 is a schematic diagram of the digital radio frequency square wave working voltage application method adopted in embodiment 1.

Figure 4 is a schematic diagram of the working sequence of the ion trap in Example 1.

Figure 5 shows the experimental results of Example 1, the sample uses reserpine (m/z=609). Among them, (a) is the ion trap mass analysis working spectrogram of the traditional method, and (b) is the spectrogram of the inventive method.

Figure 6 is a schematic diagram of ion confinement voltage and dipole excitation voltage application method when the traditional sine wave voltage is used to drive the ion trap, and the dipole excitation voltage is also sine wave.

Fig. 7 is a schematic diagram of ion confinement voltage and dipole excitation voltage application mode when the digital square wave voltage is used to drive the linear ion trap and the dipole excitation voltage is digital square wave.

Detailed ways

Example 1

This technical solution uses a digital square wave voltage to drive the ion trap, and realizes efficient and rapid analysis by scanning the frequency of the digital radio frequency operating voltage and quickly adjusting the operating voltage on the front and rear end cover electrodes of the ion trap mass analyzer. This scheme has been verified experimentally, and the details are as follows.

The ion trap in this scheme selects the rectangular ion trap for testing. The instrument experiment platform is shown in Figure 2, which is an electrospray ionization source-rectangular ion trap mass spectrometer system (ESI-RIT-MS). The instrument is composed of a three-stage differential vacuum system, and the vacuum degree in the third-stage vacuum chamber where the ion trap is located can reach 3×10 ^-3 Pa. The ions generated by the electrospray ionization source enter the secondary vacuum chamber through the sampling cone, and then enter the rectangular ion trap through a quadrupole ion guide with a length of 200 mm to complete the mass analysis. Helium gas is introduced as a cooling gas through a small hole on the electrode in the rear end cap of the trap for ion cooling. Reagent: Reserpine (Reserpine, m/z=175, Shanghai Aladdin Reagent Co., Ltd.), prepared into a 5×10 ^-5 M solution, the solvent is methanol:water=50:50, which contains 0.05% acetic acid.

The direct digital synthesis (DDS) method generates a low-level square wave voltage, generally a TTL level of 5V. After fast switches (switches) and MOSFET field effect tube amplification, a high-voltage square wave with continuously adjustable amplitude in the range of 0-500V _0-p is obtained as the tie-in voltage. The dipole excitation voltage is obtained by dividing the frequency of the binding voltage, that is, there is a proportional relationship between the dipole excitation voltage and the frequency of the binding voltage, and the coefficient is β/2, and the value of β is less than 1. The period, sweep speed, symmetry and timing of the square wave of the RF working voltage can be precisely controlled by software. The way of applying the square wave voltage on the rectangular ion trap is shown in Figure 3. A pair of square-wave confinement voltages with the same amplitude and opposite phases are respectively applied to the two pairs of electrodes in the x and y directions of the ion trap. Ions are ejected from the x-direction, and the dipole excitation voltage is coupled with the square-wave confinement voltage and applied to a pair of x-direction electrodes.

By performing a mass scan, a complete spectrum of the sample ions can be obtained. At this time, the waveform of the dipole excitation voltage is a symmetrical waveform, and its frequency is one-third of the frequency of the bound square wave, that is, the value of β is 2/3, and the amplitude is a certain value. With the frequency scanning of the bound square wave, ions with different mass-to-charge ratios arrive at the resonance point in turn to resonate, and are ejected from the trap to be detected by the ion detector.

In the ion resonance ejection stage, the schematic diagram of the ion trap working sequence is shown in Fig. 4 . Under the cooling effect of neutral gas, the ions in the ion trap linearly scan the radio frequency working voltage signal from high frequency to low frequency. The beta value is 2/3. The fragment ions in the ion trap resonate under the action of the dipole excitation voltage, and finally pop out from the extraction hole or extraction groove of the electrode to be detected, complete the entire mass analysis, and obtain the sample mass spectrometry spectrum.

Preliminary experimental results show that with the same set of ion trap mass analyzer and working system power supply, the reserpine mass spectrum obtained by the inventive method is consistent with the reserpine mass spectrum obtained by the traditional ion trap operating mode, as shown in Figure 5 Show.

In the present invention, the traditional sine wave voltage can also be used to drive the ion trap, and the dipole excitation voltage also adopts a sine wave. The application of the radio frequency voltage and the dipole excitation voltage is shown in FIG. 6 .

In the present invention, when using an ion trap with a hyperboloid electrode, it can be a three-dimensional ion trap or a linear ion trap using a hyperboloid electrode. The central cross-sectional structure of the two is the same, and the radio frequency voltage and dipole excitation voltage are applied as follows As shown in Figure 7, a pair of digital square wave voltages with the same amplitude and opposite phase can also be applied to the two pairs of electrodes in the x direction and y direction of the hyperbolic ion trap respectively, by scanning the frequency of the digital radio frequency operating voltage and the fast Adjust the working voltage on the front and rear end cover electrodes of the ion trap mass analyzer to realize efficient and rapid analysis of the ion trap.

Claims (6)

1. A method for efficient and fast analysis in an ion trap mass analyzer, characterized in that: Only one ion resonance ejection stage is used to realize the working process of the entire ion trap mass analyzer, and the specific steps are as follows: In the ion resonance ejection stage, a symmetrical waveform RF operating voltage signal is applied, and the ions are bound in the ion trap by colliding with neutral gas molecules under the action of the electric field generated by the ion trap RF operating voltage; In the digital square wave driving ion trap working mode, scan the frequency of the digital radio frequency working voltage and quickly adjust the working voltage on the front and rear end cover electrodes of the ion trap mass analyzer, and apply a dipole excitation voltage signal during the scanning process, and the ions are in the dipole Under the action of the excitation voltage, resonant excitation occurs, and finally is expelled from the extraction hole or the extraction groove of the ion extraction electrode, and the ion detector placed outside the ion trap detects and obtains the mass spectrum signal of the ion. 2. The method according to claim 1, characterized in that: in the ion resonance ejection stage, the applied ion RF voltage signal waveform is a digital square wave or a sine wave, or other forms of waveform. 3. The method according to claim 1, characterized in that: in the ion resonance ejection stage, the cooling gas passed into the ion trap is a neutral gas. 4. The method according to claim 1, characterized in that: in the ion resonance ejection stage, the frequency ratio of the radio frequency operating voltage to the dipole resonance excitation voltage is an arbitrary value. 5. method according to claim 1, is characterized in that: described ion trap mass analyzer is any quadrupole ion trap mass analyzer, comprises three-dimensional ion trap, two-dimensional linear ion trap, or ion of any other geometry trap mass analyzer. 6. The method according to claim 1, characterized in that: the ion trap mass analyzer can realize the ion storage, mass analysis, and tandem mass spectrometry functions of the traditional ion trap, and can be combined with the quadrupole mass analyzer The same rapid analysis of samples.