Method for eliminating space charge effect in ion trap based on selective collision induced dissociation

Abstract

The invention discloses a method for eliminating a space charge effect in an ion trap based on selective collision induced dissociation. According to the method, a rectangular ion trap mass spectrometer equipped with a reagent-assisted photochemical ionization source and a continuous atmospheric pressure interface is used as a detection instrument, and the continuous sample injection ion trap mass spectrometer has the advantages that the sensitivity can be improved by prolonging the sample injection time to accumulate target ions; however, interference ions occupy the charge capacity in the ion trap in practical application. When the sample introduction time is too long, a space charge effect is introduced, so that peak broadening and peak position offset are caused. Selective collision induced dissociation can be realized by utilizing different voltages required by collision induced dissociation of target ions and interference ions, the interference ions are broken, fragment ions cannot be stabilized in an ion trap, and the space charge effect caused by the interference ions is eliminated.

Description

Technical Field

[0001] The present invention relates to the field of mass spectrometry analysis methods, and more specifically, to a method for eliminating space charge effects in an ion trap based on selective collision-induced dissociation. This method uses a rectangular ion trap mass spectrometer equipped with a reagent-assisted photochemical ionization source and a continuous atmospheric pressure interface as a detection instrument. A major advantage of a continuous injection ion trap mass spectrometer is that the sensitivity can be improved by accumulating target ions by extending the injection time, but in practical applications, the presence of interfering ions will occupy the charge capacity in the ion trap. When the injection time is too long, a space charge effect will be introduced, resulting in peak broadening and peak position shift. Selective collision-induced dissociation can be achieved by utilizing the different voltages required for collision-induced dissociation of target ions and interfering ions, thereby breaking up interfering ions and preventing fragment ions from being stabilized in the ion trap, thereby eliminating the space charge effect caused by interfering ions. Background Art

[0002] One of the major advantages of a micro-continuous injection ion trap mass spectrometer is that the signal strength can be improved by extending the injection time, especially for trace samples. Since the charge capacity in an ion trap of fixed size is fixed, when the injection time is too long, the presence of high-abundance interfering ions will introduce a space charge effect, causing the peak position to shift and the half-peak width to increase. Thermal desorption reagent-assisted photochemical ionization is a highly efficient ionization technology that ionizes the sample by reacting a large number of reagent ions generated by photoionization with the sample, but the presence of reagent ions makes the above-mentioned space charge effect more obvious when the injection time is extended.

[0003] In order to solve the above-mentioned space charge effect, Xu Wei et al. (Xu, Z.; Jiang, T.; Xu, Q.; Zhai, Y.; Li, D.; Xu, W.) from Beijing Institute of Technology proposed a Pseudo-Multiple Reaction Monitoring (Pseudo-MRM) Mode on the "Brick" Mass Spectrometer, using the

[0004] Grid-SWIFT Waveform. Anal. Chem. 2019, 91, 13838-13846.) proposed the Grid-Swift technology, which uses the Grid-Swift waveform to screen the target ions while injecting the sample, eliminating the influence of other interfering ions. When the injection time is extended, the signal intensity of the target ions can be increased without introducing space charge effects. This method uses the different resonance frequencies of different ions to achieve ion screening by constructing a resonance excitation waveform with a gap.

[0005] In addition to the above methods, since different ions require different energies for bond breaking, i.e., collision-induced dissociation, it is also possible to achieve ion screening by breaking interfering ions into fragment ions that cannot exist stably in the trap through selective collision-induced dissociation. Summary of the invention

[0006] The present invention discloses a method for eliminating space charge effects in an ion trap based on selective collision-induced dissociation. In this method, a rectangular ion trap mass spectrometer equipped with a reagent-assisted photochemical ionization source and a continuous atmospheric pressure interface is used as a detection instrument. A major advantage of a continuous injection ion trap mass spectrometer is that the sensitivity can be improved by accumulating target ions by extending the injection time, but in practical applications, the presence of interfering ions will occupy the charge capacity in the ion trap. When the injection time is too long, the space charge effect will be introduced, resulting in peak broadening and peak position shift. Selective collision-induced dissociation can be achieved by utilizing the different voltages required for collision-induced dissociation of target ions and interfering ions, so that the interfering ions are broken up and the fragmented ions cannot be stabilized in the ion trap, thereby eliminating the space charge effect caused by the interfering ions.

[0007] In order to achieve the above object, the present invention adopts the following technical solution:

[0008] The object of the present invention is to provide a collision induced dissociation method in an ion trap mass spectrometer which is simple to operate.

[0009] In order to achieve the above purpose, the technical solution adopted by the present invention is:

[0010] A method for eliminating space charge effects in an ion trap based on selective collision-induced dissociation, characterized in that:

[0011] The volatile reagent molecules carried by the carrier gas and the gaseous samples thermally decomposed by the thermal desorber are photochemically ionized and then passed into the detection instrument for detection;

[0012] A rectangular ion trap mass spectrometer equipped with a thermal desorption reagent assisted photochemical ionization source and a continuous atmospheric pressure interface is used as the detection instrument;

[0013] The solid and / or liquid samples in the thermal desorption reagent-assisted photochemical ionization source are thermally decomposed into gaseous samples by the thermal desorber, and a large number of reagent ions are generated by the photoionization auxiliary reagent carried by the carrier gas to react chemically with the gaseous sample to achieve efficient ionization of the sample; the ionized sample enters the rectangular ion trap mass analyzer through a continuous atmospheric pressure interface for mass spectrometry analysis; the rectangular ion trap mass analyzer consists of a front cover electrode (which is a plate-shaped electrode with a through hole in the middle), a rear cover electrode (which is a plate-shaped electrode, arranged parallel to the front cover electrode and spaced apart), a pair of x electrodes arranged parallel to each other and spaced apart, and a pair of y electrodes arranged parallel to each other and spaced apart, three The normals of the parallel electrode pairs are perpendicular to each other; a time-varying DC voltage is applied to the front cover electrode, which is V1 during sample injection and V2 during other periods except sample injection; a constant DC voltage of V3 is applied to the x pair of electrodes and the y electrode, and a constant DC voltage of V4 is applied to the rear cover electrode; in addition to the DC voltage, a radio frequency confinement voltage RF with a frequency of f1 and a peak-to-peak value of Vpp1 is applied to the x electrode, and a resonance excitation voltage AC with a frequency of f2 and a peak-to-peak value of is applied to the y electrode; during detection, RF and AC are kept constant, V1, V2 and V4 are fixed, and the pressure difference between V1 and V3 is increased to achieve collision-induced dissociation;

[0014] Adjust the pressure difference between V1 and V3 to respectively realize the collision induced dissociation of reagent ions and / or reagent ion dimers and the collision induced dissociation of samples, and record the critical pressure difference between V1 and V3 for collision induced dissociation of reagent ions and / or reagent ion dimers (i.e., the pressure difference between V1 and V3 when the fragment ions of reagent ions account for 10% of the total ions) as Vreagent, and the critical pressure difference between V1 and V3 for collision induced dissociation of samples (i.e., the pressure difference between V1 and V3 when the fragment ions of reagent ions account for 10% of the total ions) as Vsample;

[0015] Due to the different energies required for bond breaking, different substances require different pressure differences between V1 and V3 to achieve collision-induced dissociation; in order to eliminate the interference caused by a large number of reagent ions, Vreagent is required to be smaller than Vsample, that is, the pressure difference between V1 and V3 is controlled between Vreagent and Vsample. At this time, the reagent ions or reagent ion dimers undergo collision-induced dissociation, while the sample does not undergo collision-induced dissociation. Selective collision-induced dissociation is achieved by using the different voltages required for collision-induced dissociation of sample ions and reagent ions, breaking up interfering ions and making it impossible for fragment ions to be stabilized in the ion trap, eliminating the space charge effect caused by interfering ions that leads to mass spectrum peak broadening and peak position shift.

[0016] When a voltage is applied to the front cover for sample injection, V1 is adjustable from -10 to 0 V, preferably -2 V; V2 is adjustable from 50 to 150 V, preferably 100 V, in other time periods except for sample injection; the constant DC voltage V3 on the x counter electrode and the y counter electrode is adjustable from -5 V to -50 V, which is -5 V when there is no collision induced dissociation, and is adjusted as needed when collision induced dissociation occurs.

[0017] The RF frequency f1 is adjustable from 900kHz to 1200kHz, preferably 940kHz, and the peak-to-peak value Vpp1 is adjustable from 100-3000Vpp, preferably 300Vpp, so that the reagent ions or fragment ions of reagent ion dimers cannot be stably stored in the ion trap. The AC frequency f2 is adjustable from 3kHz to 400kHz, preferably 313kHz, and the peak-to-peak value Vpp2 is adjustable from 0.2-5Vpp, preferably 1Vpp.

[0018] The injection time is adjustable from 10ms to 30s, and is controlled by the timing-varying voltage on the front cover;

[0019] The signal intensity of trace samples can be improved by extending the injection time of the rectangular ion trap mass spectrometer.

[0020] The auxiliary reagent in the thermal desorption reagent-assisted photochemical ionization source is one or more of acetone, butanone, and anisole, preferably butanone;

[0021] The auxiliary reagent in the thermal desorption reagent-assisted photochemical ionization source is ionized by a vacuum ultraviolet lamp; the function of the carrier gas is to carry the thermally desorbed sample and mix with the reagent ions to undergo a chemical reaction; the carrier gas is one of nitrogen, helium or air, preferably air; the carrier gas flow rate is adjustable within the range of 50-250 ml / min, preferably 100 ml / min;

[0022] The temperature of thermal desorption can be adjusted within the range of 120-200°C, preferably 160°C.

[0023] The continuous atmospheric pressure interface is a metal capillary tube, the length of which is adjustable between 10 cm and 30 cm, preferably 10 cm; the inner diameter of which is adjustable between 0.25 mm and 0.5 mm, preferably 0.25 mm.

[0024] The present invention uses a rectangular ion trap mass spectrometer equipped with a reagent-assisted photochemical ionization source and a continuous atmospheric pressure interface as a detection instrument. A major advantage of a continuous injection ion trap mass spectrometer is that the sensitivity can be improved by accumulating target ions by extending the injection time, but in practical applications, the presence of interfering ions will occupy the charge capacity in the ion trap. When the injection time is too long, a space charge effect will be introduced, resulting in peak broadening and peak position shift. Selective collision-induced dissociation can be achieved by utilizing the different voltages required for collision-induced dissociation of target ions and interfering ions, breaking up interfering ions and making it impossible for fragmented ions to be stabilized in the ion trap, thereby eliminating the space charge effect caused by interfering ions.

[0025] The advantages of the present invention are:

[0026] 1. The outstanding advantages of the present invention are: selective collision-induced dissociation is achieved by adjusting the DC voltage on the x-electrode and the y-electrode, so that excess reagent ions are fragmented and cannot be stably stored in the ion trap. When the injection time is extended to increase the sample signal intensity, there will be no obvious space charge effect, thereby improving the detection sensitivity.

[0027] 2. This method is simple to operate and does not require precise control of the resonance excitation voltage frequency. It is suitable for non-professionals and is conducive to promotion and use in on-site detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments:

[0029] Figure 1 It is a schematic diagram of the rectangular ion trap mass spectrometer structure equipped with a thermal desorption reagent assisted photochemical ionization source and a continuous atmospheric pressure interface in the present invention, wherein 1 is a sampling pump, 2 is an auxiliary reagent bottle, 3 is a heating block, 4 is a sample introduction cloth, 5 is a support, 6 is a vacuum ultraviolet lamp, 7 is an ionization zone, and 8 is an ion trap mass spectrometer. The liquid or solid sample is dripped on the sample introduction step 4 and thermally decomposed into a gaseous sample. The sampling pump 1 extracts the carrier gas carrying the volatilized auxiliary reagent and gaseous sample in the auxiliary reagent bottle 2 into the ionization zone 6, and a photochemical ionization reaction occurs, and then enters the ion trap mass spectrometer 8 through the capillary for detection;

[0030] Figure 2 When butanone is used as a reagent to detect aniline, butanone dimer ions undergo collision-induced dissociation, while aniline does not.

[0031] Figure 3 It is the mass spectra of different injection times when the injection time is extended, with selective collision-induced dissociation and without selective collision-induced dissociation; DETAILED DESCRIPTION

[0032] The volatile reagent molecules carried by the carrier gas and the gaseous samples thermally decomposed by the thermal desorber are photochemically ionized and then passed into the detection instrument for detection;

[0033] A rectangular ion trap mass spectrometer equipped with a thermal desorption reagent assisted photochemical ionization source and a continuous atmospheric pressure interface is used as the detection instrument;

[0034] The solid and / or liquid samples in the thermal desorption reagent-assisted photochemical ionization source are thermally decomposed into gaseous samples by the thermal desorber, and a large number of reagent ions are generated by the photoionization auxiliary reagent carried by the carrier gas to react chemically with the gaseous sample to achieve efficient ionization of the sample; the ionized sample enters the rectangular ion trap mass analyzer through a continuous atmospheric pressure interface for mass spectrometry analysis; the rectangular ion trap mass analyzer consists of a front cover electrode (which is a plate-shaped electrode with a through hole in the middle), a rear cover electrode (which is a plate-shaped electrode, arranged parallel to the front cover electrode and spaced apart), a pair of x electrodes arranged parallel to each other and spaced apart, and a pair of y electrodes arranged parallel to each other and spaced apart, three The normals of the parallel electrode pairs are perpendicular to each other; a time-varying DC voltage is applied to the front cover electrode, which is V1 during sample injection and V2 during other periods except sample injection; a constant DC voltage of V3 is applied to the x pair of electrodes and the y electrode, and a constant DC voltage of V4 is applied to the rear cover electrode; in addition to the DC voltage, a radio frequency confinement voltage RF with a frequency of f1 and a peak-to-peak value of Vpp1 is applied to the x electrode, and a resonance excitation voltage AC with a frequency of f2 and a peak-to-peak value of is applied to the y electrode; during detection, RF and AC are kept constant, V1, V2 and V4 are fixed, and the pressure difference between V1 and V3 is increased to achieve collision-induced dissociation;

[0035] Adjust the pressure difference between V1 and V3 to respectively realize the collision induced dissociation of reagent ions and / or reagent ion dimers and the collision induced dissociation of samples, and record the critical pressure difference between V1 and V3 for collision induced dissociation of reagent ions and / or reagent ion dimers (i.e., the pressure difference between V1 and V3 when the fragment ions of reagent ions account for 10% of the total ions) as Vreagent, and the critical pressure difference between V1 and V3 for collision induced dissociation of samples (i.e., the pressure difference between V1 and V3 when the fragment ions of reagent ions account for 10% of the total ions) as Vsample;

[0036] Due to the different energies required for bond breaking, different substances require different pressure differences between V1 and V3 to achieve collision-induced dissociation; in order to eliminate the interference caused by a large number of reagent ions, Vreagent is required to be smaller than Vsample, that is, the pressure difference between V1 and V3 is controlled between Vreagent and Vsample. At this time, the reagent ions or reagent ion dimers undergo collision-induced dissociation, while the sample does not undergo collision-induced dissociation. Selective collision-induced dissociation is achieved by using the different voltages required for collision-induced dissociation of sample ions and reagent ions, breaking up interfering ions and making it impossible for fragment ions to be stabilized in the ion trap, eliminating the space charge effect caused by interfering ions that leads to mass spectrum peak broadening and peak position shift.

[0037] Air was used as carrier gas, the flow rate was 100 ml / min, and the thermal desorption temperature was 160°C. Butanone was used as an auxiliary reagent to detect the headspace vapor of 2ug / ml aniline. The continuous atmospheric pressure interface was a metal capillary with a length of 10 cm and an inner diameter of 0.25 mm. V1 was -2V, V2 was 100V, V4 was 100V, RF frequency f1 was 940kHz, Vpp1 was 300Vpp, AC frequency f2 was 313kHz, peak-to-peak value Vpp2 was 1Vpp, and the injection time could be adjusted according to demand.

[0038] Example 1

[0039] When butanone was used as a reagent to detect aniline, the butanone dimer ion underwent collision-induced dissociation, while aniline did not.

[0040] Air was used as the carrier gas with a flow rate of 100 ml / min and a thermal desorption temperature of 160°C. Butanone was used as an auxiliary reagent to detect the headspace vapor of 2 ug / ml aniline. The continuous atmospheric pressure interface was a metal capillary with a length of 10 cm and an inner diameter of 0.25 mm. V1 was -2 V, V2 was 100 V, V4 was 100 V, RF frequency f1 was 940 kHz, Vpp1 was 300 Vpp, AC frequency f2 was 313 kHz, peak-to-peak value Vpp2 was 1 Vpp, and injection time was 250 ms. When V3 was -5 V, collision-induced dissociation did not occur for both butanone dimer ions and aniline. When V3 was -15 V, collision-induced dissociation occurred for butanone dimer ions but no collision-induced dissociation occurred for aniline.

[0041] Example 2

[0042] Extending the injection time, mass spectra with selective collision-induced dissociation and non-selective collision-induced dissociation at different injection times

[0043] Air was used as the carrier gas with a flow rate of 100 ml / min and a thermal desorption temperature of 160°C. Butanone was used as an auxiliary reagent to detect the headspace vapor of 2 ug / ml aniline. The continuous atmospheric pressure interface was a metal capillary with a length of 10 cm and an inner diameter of 0.25 mm. V1 was -2 V, V2 was 100 V, V4 was 100 V, RF frequency f1 was 940 kHz, Vpp1 was 300 Vpp, AC frequency f2 was 313 kHz, and peak-to-peak value Vpp2 was 1 Vpp. When V3 was -5 V, collision-induced dissociation of both butanone dimer ion and aniline did not occur. When V3 was -15 V, collision-induced dissociation of butanone dimer ion occurred but collision-induced dissociation of aniline did not occur. The mass spectra were recorded when the injection time was 50ms, 500ms and 2500ms. It can be found that when V3 is -5V, as the injection time increases, a large number of reagent ions exist in the ion trap, resulting in serious space charge effect, causing peak broadening and peak shift. When V3 is set to -15V with selective collision induced dissociation, the reagent ions are broken and the fragmented ions cannot be stably stored in the ion trap. As the injection time increases, only the sample signal intensity increases while the reagent ion intensity does not increase, and the sample mass spectrum peak broadening and peak shift are eliminated.

Claims

1. A method for eliminating space charge effects in an ion trap based on selective collision-induced dissociation, characterized in that: The volatile reagent molecules carried by the carrier gas and the gaseous samples thermally decomposed by the thermal desorber are photochemically ionized and then passed into the detection instrument for detection; A rectangular ion trap mass spectrometer equipped with a thermal desorption reagent assisted photochemical ionization source and a continuous atmospheric pressure interface is used as the detection instrument; The solid and / or liquid samples in the thermal desorption reagent-assisted photochemical ionization source are thermally decomposed into gaseous samples by the thermal desorber, and a large number of reagent ions generated by the photoionization auxiliary reagent carried by the carrier gas react chemically with the gaseous sample to achieve efficient ionization of the sample; The ionized sample enters the rectangular ion trap mass analyzer through a continuous atmospheric pressure interface for mass spectrometry analysis; the rectangular ion trap mass analyzer consists of a front cover electrode (a plate-shaped electrode with a through hole in the middle), a rear cover electrode (a plate-shaped electrode, arranged parallel to and spaced apart from the front cover electrode), a pair of x electrodes arranged parallel to and spaced apart from each other, and a pair of y electrodes arranged parallel to and spaced apart from each other, and the normals of the three pairs of parallel electrodes are perpendicular to each other; a time-varying DC voltage is applied to the front cover electrode, which is V1 during sample injection and V2 in other time periods except for sample injection; a constant DC voltage of V3 is applied to the x pair of electrodes and the y electrode, and a constant DC voltage of V4 is applied to the rear cover electrode; in addition to the DC voltage, a radio frequency trapped voltage RF with a frequency of f1 and a peak-to-peak value of Vpp1 is applied to the x electrode, and a resonance excitation voltage AC with a frequency of f2 and a peak-to-peak value of is applied to the y electrode; during detection, RF and AC are kept constant, V1, V2 and V4 are fixed, and the pressure difference between V1 and V3 is increased to achieve collision-induced dissociation; Adjust the pressure difference between V1 and V3 to respectively realize the collision induced dissociation of reagent ions and / or reagent ion dimers and the collision induced dissociation of samples, and record the critical pressure difference between V1 and V3 for collision induced dissociation of reagent ions and / or reagent ion dimers (i.e., the pressure difference between V1 and V3 when the fragment ions of reagent ions account for 10% of the total ions) as Vreagent, and the critical pressure difference between V1 and V3 for collision induced dissociation of samples (i.e., the pressure difference between V1 and V3 when the fragment ions of reagent ions account for 10% of the total ions) as Vsample; Due to the different energies required for bond breaking, different substances have different pressure differences between V1 and V3 required to achieve collision-induced dissociation. In order to eliminate the interference caused by a large number of reagent ions, Vreagent is required to be smaller than Vsample, that is, the pressure difference between V1 and V3 is controlled to be between Vreagent and Vsample. At this time, the reagent ions or reagent ion dimers undergo collision-induced dissociation, while the sample does not undergo collision-induced dissociation. Selective collision-induced dissociation is achieved by utilizing the different voltages required for collision-induced dissociation of sample ions and reagent ions, which breaks up interfering ions and makes the fragmented ions unable to stabilize in the ion trap, eliminating the space charge effect caused by interfering ions that leads to mass spectrum peak broadening and peak position shift.

2. The method according to claim 1, characterized in that: When a voltage is applied to the front cover for sample injection, V1 is adjustable from -10 to 0 V, preferably -2 V; V2 is adjustable from 50 to 150 V, preferably 100 V, in other time periods except for sample injection; the constant DC voltage V3 on the x counter electrode and the y counter electrode is adjustable from -5 V to -50 V, which is -5 V when there is no collision induced dissociation, and is adjusted as needed when collision induced dissociation occurs.

3. The method according to claim 1, characterized in that: The RF frequency f1 is adjustable from 900kHz to 1200kHz, preferably 940kHz, and the peak-to-peak value Vpp1 is adjustable from 100-3000Vpp, preferably 300Vpp, so that the reagent ions or fragment ions of reagent ion dimers cannot be stably stored in the ion trap. The AC frequency f2 is adjustable from 3kHz to 400kHz, preferably 313kHz, and the peak-to-peak value Vpp2 is adjustable from 0.2-5Vpp, preferably 1Vpp.

4. The method according to claim 1, characterized in that: The injection time is adjustable from 10ms to 30s, and is controlled by the timing-varying voltage on the front cover; The signal intensity of trace samples can be improved by extending the injection time of the rectangular ion trap mass spectrometer.

5. The method according to claim 1, characterized in that: The auxiliary reagent in the thermal desorption reagent-assisted photochemical ionization source is one or more of acetone, butanone, and anisole, preferably butanone; The auxiliary reagent in the thermal desorption reagent-assisted photochemical ionization source is ionized by a vacuum ultraviolet lamp; the function of the carrier gas is to carry the thermally desorbed sample and mix with the reagent ions to undergo a chemical reaction; the carrier gas is one of nitrogen, helium or air, preferably air; the carrier gas flow rate is adjustable within the range of 50-250 ml / min, preferably 100 ml / min; The temperature of thermal desorption can be adjusted within the range of 120-200°C, preferably 160°C.

6. The method according to claim 1, characterized in that: The continuous atmospheric pressure interface is a metal capillary tube, the length of which is adjustable between 10 cm and 30 cm, preferably 10 cm; the inner diameter of which is adjustable between 0.25 mm and 0.5 mm, preferably 0.25 mm.

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