CN114628220A - Vacuum ion enrichment method - Google Patents

Vacuum ion enrichment method Download PDF

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CN114628220A
CN114628220A CN202210103061.5A CN202210103061A CN114628220A CN 114628220 A CN114628220 A CN 114628220A CN 202210103061 A CN202210103061 A CN 202210103061A CN 114628220 A CN114628220 A CN 114628220A
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唐飞
张一鸣
张泽森
霍新明
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Tsinghua University
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    • HELECTRICITY
    • H01ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/0027Methods for using particle spectrometers
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    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N27/62Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
    • HELECTRICITY
    • H01ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/0027Methods for using particle spectrometers
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Abstract

The invention relates to the technical field of mass spectrometry, and provides a vacuum ion enrichment method, which realizes periodic sample injection ionization by control; the contradiction between the air pressure vacuum degree and the sample injection amount can be effectively solved, and the effect of improving the sensitivity of the instrument is achieved; and further provides a vacuum ion screening and enriching method, which can effectively reduce the space charge effect of the ion trap mass spectrometer and achieve the technical effect that the capacity utilization rate of the ion trap reaches the maximum.

Description

Vacuum ion enrichment method
Technical Field
The invention relates to the technical field of mass spectrometry, and relates to a vacuum ion enrichment method.
Background
Mass Spectrometry (MS) has been widely used in a variety of fields such as chemistry, biology, environmental science, pharmaceutical industry, space exploration, etc., as a qualitative and quantitative method. Mass spectrometers can not only measure the mass-to-charge ratio (m/z) of ions, but also detect ion structure by tandem MS.
The mass analyzer is a core device in a mass spectrometer and is a component for separating ions according to mass-to-charge ratio under the action of a magnetic field or an electric field. Currently, a variety of mass analyzers have been invented, such as magnetic mass spectrometry (sector) analyzers, time-of-flight (TOF) analyzers, linear ion trap analyzers, fourier transform ion cyclotron resonance (FT-ICR) cells (ceII), and orbital ion trap (Orbi trap) analyzers, to name a few. The linear ion trap can be used as an ion storage, ion guide and ion reaction device besides a mass analyzer, and can be even combined with other mass analyzers to form a powerful hybrid MS instrument.
The existing linear ion trap structure generally includes an x-direction electrode pair and a y-direction electrode pair (the motor type is a hyperbolic motor or a flat electrode) for generating radio frequency voltages in the x-direction and the y-direction, and also includes end cap electrodes, wherein an ion entrance port is disposed at a central position of one of the end cap electrodes. However, the existing testing method for the ion erosion resistance of the concrete material has the following disadvantages:
1) the sample injection amount is small;
2) the space charge effect causes the utilization rate of the ion trap to be low, and further causes the sensitivity of the ion trap mass spectrometer to be low;
3) in order to improve the sensitivity of some existing ion trap mass spectrometers, a membrane sample introduction device or an active carbon adsorption material is arranged in front of the spectrometer; although sensitivity can be improved, adding hardware results in higher retrofit costs.
Therefore, a vacuum ion enrichment method capable of improving the sensitivity of an ion trap mass spectrometer without hardware modification is needed.
Disclosure of Invention
The present invention provides a vacuum ion enrichment method to solve the problems in the prior art.
In order to achieve the aim, the vacuum ion enrichment method provided by the invention comprises the steps of opening a sample injection valve to enter a sample injection stage, and sucking gas into a cavity of an ion trap;
opening an ionization source, an ion gate and an RF signal to enter an ionization stage, ionizing gas sucked into the cavity into an ion state, and binding the ion beam in the ion trap cavity under the action of axial and radial electric fields;
cutting off the ionization source, keeping the ion gate and the RF signal to enter a cooling stage, so that the motion state of the ions bound in the ion trap cavity tends to be stable;
taking the sample introduction stage, the ionization stage and the cooling stage as an enrichment action period, and circularly executing the enrichment action period until the capacity of the ion trap is filled by newly-entered ions, and then entering a scanning stage;
applying an RF signal and an AC sinusoidal signal with amplitude controlled by a ramp voltage to enter a scanning stage, scanning and emitting ions stably bound in an ion trap cavity in a cooling stage in a resonance excitation mode, and processing the ions by a signal receiving electrode at the rear end;
and (5) setting all signals to zero, keeping entering an idle stage, and ending the analysis period.
Further, preferably, the enrichment action cycle comprises a sample introduction stage, an ionization stage, a cooling stage, an isolation stage and a re-cooling stage which are sequentially performed;
the isolation stage is as follows: applying an AC sweep frequency signal, and screening the ions bound in the ion trap cavity to retain target ions and screen out non-target ions;
the sub-cooling stage is as follows: turning off the AC frequency sweep signal to stabilize the motion state of the screened ions
Further, preferably, in the isolation phase, the frequency range of the applied AC sweep signal is obtained by the following formula:
Figure BDA0003492869270000021
wherein, ω isxIs the resonant frequency of the ion in the ion trap; Ω is the resonance frequency of the mass spectrometer.
Further, it is preferable that the sample injection pressure is 0.02mbar to 0.5 mbar.
Further, preferably, in the scanning phase, the frequency of the RF signal is 3 to 5 times of the frequency of the AC sinusoidal signal.
According to the invention, by establishing the vacuum ion enrichment method with a simple structure, the sensitivity of the mass spectrometer is improved from the control method, and the hardware cost is not additionally increased; the method can effectively solve the contradiction between the air pressure vacuum degree and the sample injection amount, and achieves the effect of improving the sensitivity of the mass spectrometer. Meanwhile, a vacuum ion screening and enriching method is further provided, so that the space charge effect of the ion trap mass spectrometer can be effectively reduced, and the technical effect of maximizing the capacity utilization rate of the ion trap is realized.
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FIG. 1 is a schematic diagram of a conventional mass spectrometer analysis sequence in the prior art;
fig. 2 is a schematic analysis timing diagram of an ion trap vacuum enrichment analysis method provided in embodiment 1 of the present invention;
fig. 3 is a schematic analysis timing diagram of an ion trap vacuum enrichment analysis method according to embodiment 2 of the present invention;
FIG. 4 is a schematic diagram illustrating comparison of the effects of the ion trap vacuum enrichment analysis method provided in example 1 of the present invention;
FIG. 5 is a schematic diagram illustrating comparison of still another effect of the ion trap vacuum enrichment analysis method provided in embodiment 1 of the present invention;
fig. 6 is a schematic diagram illustrating comparison of the effects of the ion trap vacuum enrichment analysis methods provided in embodiment 2 and embodiment 1 of the present invention.
The implementation, functional features and advantages of the objects of the present invention will be further explained with reference to the accompanying drawings.
Detailed Description
It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The invention mainly aims to achieve the purpose of improving the signal sensitivity of the ion trap mass spectrometer by adopting a pulse type sample introduction method. The existing ion trap mass spectrometer is limited by vacuum degree, so that the sampling volume of gas and liquid cannot be increased, the number of target ions is small, and the signal is low. The invention provides a vacuum enrichment analysis method, which can effectively solve the contradiction between the air pressure vacuum degree and the sample injection amount and achieve the effect of improving the sensitivity of an instrument; and further provides a vacuum ion enrichment method, which can effectively reduce the space charge effect of the ion trap mass spectrometer and maximize the capacity utilization rate of the ion trap.
FIG. 1 is a general depiction of a conventional mass spectrometer analysis sequence of the prior art; fig. 1 is a schematic diagram of an analysis sequence of a conventional mass spectrometer in the prior art.
Referring to fig. 1, in the longitudinal dimension of the schematic diagram of the conventional mass spectrometer analysis sequence, the key control signals include a sample injection valve control signal, an ion gate control signal, an RF control signal, and an AC control signal. The sample introduction valve is a sample introduction device of a mass spectrometer, the ion gate is a front end cover electrode and a rear end cover electrode of an ion trap of a core analysis device of the mass spectrometer, and 100-200V voltage is applied to the electrodes to axially constrain ions in a cavity of the ion trap. The RF is a high-frequency sinusoidal signal applied to the upper and lower plates of the ion trap shown in FIG. 1, and the AC signal is a high-frequency sinusoidal signal applied to the left and right plates of the ion trap shown in FIG. 1; the function of the ion resonance excitation device is to control the radial motion of ions and realize the resonance excitation of the ions.
In the lateral dimension of the schematic diagram of the conventional mass spectrometer analysis sequence, the stages of the conventional analysis sequence include initialization, sample introduction, ionization, cooling, scanning, and idle stages, and the time of each stage is adjustable. Wherein, the initialization is the resetting stage of each module of the instrument. The sample introduction stage is a process that the sample introduction valve is opened by the instrument, and gas is sucked into the cavity due to the negative pressure of the instrument. The ionization stage is that the instrument opens the ionization source, ionizes the gas molecules which are taken into the instrument in the sample introduction stage into the ion state; wherein, the ion gate and the RF are opened simultaneously in the stage, and the ions are bound in the ion trap cavity under the action of the axial and radial electric fields. In the cooling stage, the ionization source opened in the ionization stage is closed, and the ion gate and the RF signal are reserved, so that the motion state of ions bound in the ion trap cavity gradually tends to be stable. And in the scanning stage, an RF (radio frequency) ramp high-frequency signal and an AC (alternating current) sinusoidal signal are applied, ions stably bound in the ion trap in the cooling stage are scanned and emitted in a resonance excitation mode, and the ions are processed by a signal receiving electrode at the rear end. The idle phase is to zero all signals and hold and the analysis period is finished.
In order to solve the contradiction between small quantity of ions in single sample injection and the requirement of vacuum degree of an instrument, the invention provides an ion trap vacuum enrichment analysis method on the basis of the traditional analysis time sequence. Unlike conventional ionization at atmospheric pressure (i.e., ionization outside the trap), i.e., ionization is performed first and then ions are introduced; the mass spectrometer adopts in-trap ionization, namely an ionization mode under vacuum, namely directly gas intake and ionization in an ion trap; the invention adopts the in-trap ionization mode, so that the mass spectrometer has the characteristics of more compact structure and more miniaturized instrument, and is more convenient to realize periodic sample injection ionization by control; in addition, after the cooling stage of the traditional time sequence, the scanning stage is not continued, but the ions bound at the front section are retained in the ion trap, the sampling stage is returned again, the sampling valve is opened, the sampling-ionization-cooling stage is sequentially performed, the sampling-ionization-cooling stage is repeatedly performed for n times until the ion trap capacity is filled up by the newly-fed ions, and finally the scanning stage is opened, so that the analysis period is completed.
Example 1
FIG. 2 is a diagram illustrating the analysis timing sequence of the ion trap vacuum enrichment analysis method provided in example 1 of the present invention; fig. 2 is a schematic analysis timing diagram of the ion trap vacuum enrichment analysis method provided in embodiment 1 of the present invention. As shown with reference to figure 2 of the drawings,
s1, opening a sample injection valve to enter a sample injection stage, and sucking gas into the cavity of the ion trap; wherein the size LWH of the ion trap is 41mm multiplied by 46mm multiplied by 50 mm; working air pressure < 8X 10-4mbar; the sample injection pressure is less than 0.5mbar and less than 0.02 mbar.
S2, opening an ionization source, an ion gate and an RF signal to enter an ionization stage, ionizing gas sucked into the cavity into an ion state, and constraining the ions in the ion trap cavity under the action of axial and radial electric fields;
s3, cutting off the ionization source, keeping the ion gate and the RF signal to enter a cooling stage, so that the motion state of the ions bound in the ion trap cavity tends to be stable; the ionization source is cut off, and the opening and closing of the ionization process are indirectly realized through the opening and closing of a shutter; and "remain" means that the state continues the previous stage unchanged.
S4, taking the sample feeding stage, the ionization stage and the cooling stage as an enrichment action period, circularly executing the enrichment action period until the capacity of the ion trap is filled by newly-fed ions, and then entering a scanning stage;
s5, applying an RF signal and an AC sinusoidal signal with amplitude controlled by a ramp voltage to enter a scanning stage, scanning and emitting ions stably bound in the ion trap cavity in the cooling stage in a resonance excitation mode, and processing the ions by a signal receiving electrode at the rear end; it should be noted that the RF signal is a high frequency signal, the frequency of the RF binding voltage depends on the resonant frequency of the circuit system, and is about 800kHz to 1300kHz, the amplitude is about 300 to 500V, the frequency of the AC is about an integral multiple (e.g., 3 to 5 times) of the frequency of the RF is about 200kHz to 500kHz, and the voltage is about 0.1 to 2V.
And S6, setting all signals to zero, keeping entering an idle stage, and ending the analysis period.
In conclusion, before the scanning stage, the enrichment action period of the sample injection stage, the ionization stage and the cooling stage which can be executed circularly is increased; after the traditional cooling stage is finished, the sampling valve is opened again in the sampling stage, sampling, ionization and cooling actions are sequentially carried out, the action cycle can be repeatedly executed for N times until the capacity of the ion trap is filled with newly-fed ions, namely the total quantity of the newly-fed ions reaches the ion capacity suitable for analysis; the ion capacity suitable for analysis is specifically set according to the actual application scenario. And finally, starting a scanning stage to finish the ion analysis period. It should be noted that, unlike the conventional timing sequence, the ion gate is kept in a normally open state in the subsequent sample injection stage, so as to ensure that the ions accumulated in the ion trap in the previous stages are not lost.
In order to realize the repeated execution of the enrichment action period, the invention provides the pulse valve, the opening time is adjustable within the range of 5-20 ms, and the opening time is set according to the required sample volume.
Acquiring a signal after 4 enrichment action cycles are executed according to the ion trap vacuum enrichment analysis method in the embodiment 1 and a signal according to a single sample injection method of a mass spectrometer in the prior art; the two signals were compared.
FIG. 4 is a schematic diagram illustrating comparison of the effects of the ion trap vacuum enrichment analysis method provided in example 1 of the present invention; as shown in fig. 4, the left side is the signal strength and the right side is the air pressure monitoring plot. By comparison, the signal is obviously improved after 4 cycles of enrichment action.
Fig. 5 is a schematic diagram for comparing still another effect of the ion trap vacuum enrichment analysis method provided in embodiment 1 of the present invention. Again taking anisole (mass number 108) as an example, fig. 5 is a line graph after processing with matlab derived from the raw data of the set of experiments; as can be seen from the observation of FIG. 5, the signal intensity of the control group without enrichment was about 100; the signal intensity after enrichment in 2 times of enrichment action periods is more than 200; the signal intensity after enrichment in 4 times of enrichment action periods is about 400, and the signal is obviously improved; therefore, the ion trap vacuum enrichment analysis method realizes ion enrichment from the aspects of ion control and ion screening, thereby realizing that the sensitivity of a mass spectrometer is improved on the basis of not improving hardware.
Example 2
FIG. 3 is a diagram illustrating the analysis timing sequence of the ion trap vacuum enrichment analysis method provided in example 2 of the present invention; fig. 3 is a schematic analysis timing diagram of the ion trap vacuum enrichment analysis method provided in embodiment 2 of the present invention. As shown with reference to figure 3 of the drawings,
s1, opening a sample injection valve to enter a sample injection stage, and sucking gas into the cavity of the ion trap;
s2, opening an ionization source, an ion gate and an RF signal to enter an ionization stage, ionizing gas sucked into the cavity into an ion state, and constraining the ions in the ion trap cavity under the action of axial and radial electric fields;
s3, cutting off the ionization source, keeping the ion gate and the RF signal to enter a cooling stage, so that the motion state of the ions bound in the ion trap cavity tends to be stable;
and S4, applying an AC sweep frequency signal to enter an isolation stage, and screening the ions bound in the ion trap cavity to retain target ions and screen out non-target ions. In particular, the theoretical basis for the "isolation" phase is based on the resonance excitation theory, the resonance frequency ω of the ions in the ion trapxThe calculation formula is as follows:
Figure BDA0003492869270000061
Wherein, betaxIs a complex function inversely proportional to the mass number M of the ion and Ω is the resonance frequency of the mass spectrometer. Due to betaxIs obtained by derivation according to quadrupole field theory, and is equivalent to a coefficient related to the mass M; and are difficult to calculate or obtain in practical applications. Ω is the resonant frequency of the mass spectrometer, and Ω can also be said to be the angular frequency of the RF power supply. Therefore, in a specific implementation, it is generally selected
Figure BDA0003492869270000062
For the ion resonance range, the specific implementation method is to apply a frequency sweeping signal or a frequency mixing signal to the left and right polar plates of the ion trap, for example, the scanning starting frequency is 1kHz, the termination frequency is 500kHz, the frequency band of 140 k-150 kHz is lacked in the middle, and the amplitude is 0.1-1V. The purpose of this operation is to retain target ions (frequency between 140kHz and 150kHz) that have been bound in the ion trap within the trap, interfering ions being scanned out of the ion trap in advance, facilitating the filling of the ion trap chamber with target ions during the subsequent scanning phase.
S5, turning off the AC frequency sweeping signal to enter a re-cooling stage so that the motion state of the screened ions tends to be stable;
s6, taking the sample feeding stage, the ionization stage, the cooling stage, the isolation stage and the re-cooling stage as an enrichment action period, and circularly executing the enrichment action period until the capacity of the ion trap is filled by the newly-fed ions, and then entering the scanning stage;
s7, applying a high-frequency RF signal and an AC sinusoidal signal with amplitude controlled by a ramp voltage to enter a scanning stage, scanning and emitting ions stably bound in the ion trap cavity in the cooling stage in a resonance excitation mode, and processing the ions by a signal receiving electrode at the rear end;
and S8, setting all signals to zero, keeping the signals to enter an idle stage, and ending the analysis period.
To sum up, in example 2, based on the ion trap vacuum enrichment analysis method of example 1, an "isolation-cooling" section is added after each "sample injection-ionization-cooling" cycle section. The isolation is to carry out specific screening on all ions bound in the ion trap cavity in an AC frequency sweeping signal mode, retain target ions in the ion trap cavity, scan impurity ions of non-target objects out of the ion trap in advance, enable the ion trap to leave more storage space for the target ions, repeat the sample introduction, ionization, cooling, isolation and cooling for n times until the capacity of the ion trap is filled up with the target ions, further improve the storage quantity of the target ions, and further improve the signal intensity of the target ions.
Taking toluene (mass number 92) and anisole (mass number 108) as examples, screening toluene ions; FIG. 6 is a schematic diagram illustrating comparison of the effects of the ion trap vacuum enrichment analysis methods provided in example 2 and example 1 of the present invention; FIG. 6 is a line graph after matlab processing for raw data derivation from the set of experiments; as can be seen from the observation of FIG. 6, the signal intensity of the control group without screening and enrichment means was about 100; the signal intensity after enrichment of 4 times of enrichment action periods without screening is more than 500; while the signal intensity after enrichment for 4 cycles of enrichment action comprising the screen was close to 1000. The signal boost is significant.
The vacuum ion enrichment method can realize ion enrichment from the aspects of ion control and ion screening, thereby achieving the technical effect of improving the sensitivity of a mass spectrometer instrument.
Finally, it should be noted that the above embodiments are only intended to illustrate the technical solutions of the present invention and not to limit the same, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims (5)

1. A vacuum ion enrichment method is characterized by comprising the following steps,
opening a sample injection valve to enter a sample injection stage, and sucking gas into the cavity of the ion trap;
opening an ionization source, an ion gate and an RF signal to enter an ionization stage, ionizing the gas sucked into the ion trap cavity into an ion state, and constraining the ions in the ion trap cavity under the action of axial and radial electric fields;
cutting off an ionization source, and keeping an ion gate and an RF signal to enter a cooling stage so as to enable the motion state of ions bound in the ion trap cavity to tend to be stable;
taking the sample introduction stage, the ionization stage and the cooling stage as an enrichment action period, and circularly executing the enrichment action period until the capacity of the ion trap is filled by newly-entered ions, and then entering a scanning stage;
applying an RF signal and an AC sinusoidal signal with the amplitude controlled by a ramp voltage to enter a scanning stage, scanning and emitting ions stably bound in an ion trap cavity in the cooling stage in a resonance excitation mode, and processing the ions by a signal receiving electrode at the rear end;
and (5) setting all signals to zero, keeping entering an idle stage, and ending the analysis period.
2. The vacuum ion enrichment method of claim 1,
the enrichment action cycle comprises a sample introduction stage, an ionization stage, a cooling stage, an isolation stage and a re-cooling stage which are sequentially carried out;
the isolation stage is as follows: applying an AC sweep frequency signal, and screening the ions bound in the ion trap cavity to retain target ions and screen out non-target ions;
the sub-cooling stage is as follows: and turning off the AC frequency sweep signal to enable the motion state of the screened ions to tend to be stable.
3. The vacuum ion enrichment method of claim 1,
in the isolation phase, the frequency range over which the AC sweep signal is applied is obtained by the following equation:
Figure FDA0003492869260000011
wherein, ω isxIs the resonant frequency of the ion in the ion trap; Ω is the resonance frequency of the mass spectrometer.
4. The vacuum ion enrichment method of claim 1, wherein the sample injection pressure is 0.02mbar to 0.5 mbar.
5. The vacuum ion enrichment method of claim 1,
in the scanning phase, the frequency of the RF signal is 3-5 times of the frequency of the AC sinusoidal signal.
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CN105655224A (en) * 2016-03-09 2016-06-08 清华大学 Small two-stage vacuum rectangular ion trap mass spectrometer and detection method thereof
CN106908511A (en) * 2017-03-07 2017-06-30 清华大学 A kind of method that Miniature ion trap mass spectrum carries out ion continual analysis on a large scale
CN112992646A (en) * 2021-02-08 2021-06-18 清华大学深圳国际研究生院 Radio frequency voltage applying method of small ion trap mass spectrometer

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20010000618A1 (en) * 1996-04-03 2001-05-03 Hitachi, Ltd. Mass spectrometer
JP2009009863A (en) * 2007-06-29 2009-01-15 Hitachi Ltd Ion trap, mass spectrometer, ion mobility analyzer
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