A method for eliminating space charge effects in ion traps based on selective collision-induced dissociation

Abstract

The present invention discloses 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 sampling ion trap mass spectrometer is that it can accumulate target ions and improve sensitivity 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 the interfering ions and making it impossible for the fragmented ions to be stabilized in the ion trap, thereby eliminating the space charge effect caused by the interfering ions.

Description

Technical Field

[0001] The present invention relates to the field of mass spectrometry analysis methods, specifically a method for eliminating space charge effects in ion traps 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 it can accumulate target ions and improve sensitivity by extending the injection time, but in actual 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 the interfering ions and making it impossible for the fragmented ions to be stabilized in the ion trap, thereby eliminating the space charge effect caused by the interfering ions. Background Art

[0002] A major advantage of micro-continuous-injection ion trap mass spectrometers is that they can increase signal intensity by extending the injection time, especially for trace samples. Because the charge capacity in a fixed-size ion trap is fixed, when the injection time is too long, the presence of high-abundance interfering ions can introduce space charge effects, causing peak position shifts and increasing the half-width of the peak. Thermal desorption reagent-assisted photochemical ionization is a highly efficient ionization technique that ionizes the sample through a reaction between a large number of reagent ions generated by photoionization and the sample. However, the presence of reagent ions makes this space charge effect more pronounced when the injection time is extended.

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

[0004] Grid-SWIFT Waveform (Anal. Chem. 2019, 91, 13838-13846). Grid-Swift technology was proposed. It uses the Grid-Swift waveform to screen target ions during injection, eliminating the influence of other interfering ions. Extending the injection time can enhance the signal intensity of target ions without introducing space charge effects. This method exploits the different resonant frequencies of different ions and constructs a resonant excitation waveform with a notch to achieve ion screening.

[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. 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 sampling ion trap mass spectrometer is that it can accumulate target ions and improve sensitivity 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 the interfering ions and making it impossible for the fragmented ions to 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 solutions:

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

[0009] In order to achieve the above objectives, 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 by:

[0011] The volatile reagent molecules carried by the carrier gas and the gaseous sample 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 was 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 the photoionization auxiliary reagent carried by the carrier gas generates a large number of reagent ions that chemically react 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. 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 electrode 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 achieve collision-induced dissociation of the reagent ions and / or reagent ion dimers and collision-induced dissociation of the sample, and record the critical pressure difference between V1 and V3 for collision-induced dissociation of the reagent ions and / or reagent ion dimers (i.e., the pressure difference between V1 and V3 when the fragment ions of the reagent ions account for 10% of the total ion number) as Vreagent, and the critical pressure difference between V1 and V3 for collision-induced dissociation of the sample (i.e., the pressure difference between V1 and V3 when the fragment ions of the reagent ions account for 10% of the total ion number) as Vsample;

[0015] Due to the varying energy required for bond breaking, different substances require different pressure differences between V1 and V3 for collision-induced dissociation (CID). To eliminate interference from a large number of reagent ions, Vreagent is required to be smaller than Vsample, meaning the pressure difference between V1 and V3 is controlled between Vreagent and Vsample. At this point, the reagent ions or reagent ion dimers undergo CID, while the sample does not. Selective CID is achieved by exploiting the difference in voltage required for CID between sample and reagent ions. This fragments interfering ions and prevents the fragmented ions from being stabilized in the ion trap, eliminating space charge effects caused by interfering ions that can lead to mass spectrometry peak broadening and peak position shifts.

[0016] When the voltage V1 is applied to the front cover for injection, it is adjustable from -10 to 0 V, preferably -2 V; except for the injection period, V2 is adjustable from 50 to 150 V, preferably 100 V; 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 900 kHz to 1200 kHz, preferably 940 kHz, and the peak-to-peak value Vpp1 is adjustable from 100 to 3000 Vpp, preferably 300 Vpp, to prevent the reagent ions or fragment ions of reagent ion dimers from being stably stored in the ion trap. The AC frequency f2 is adjustable from 3 kHz to 400 kHz, preferably 313 kHz, and the peak-to-peak value Vpp2 is adjustable from 0.2 to 5 Vpp, preferably 1 Vpp.

[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 carrier gas carries the thermally desorbed sample and mixes with the reagent ions to undergo a chemical reaction; the carrier gas is nitrogen, helium, or air, preferably air; the carrier gas flow rate is adjustable between 50-250 ml / min, preferably 100 ml / min;

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

[0023] The continuous atmospheric pressure interface is a metal capillary tube with an adjustable length between 10 cm and 30 cm, preferably 10 cm; and an adjustable inner diameter 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 the continuous sampling ion trap mass spectrometer is that the sensitivity can be improved by accumulating target ions by extending the injection time. However, in actual 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. By utilizing the different voltages required for collision-induced dissociation of target ions and interfering ions, selective collision-induced dissociation can be achieved, which will break up the interfering ions and prevent the fragmented ions from being stabilized in the ion trap, eliminating the space charge effect caused by the 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 its promotion and use in on-site testing. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0029] Figure 1 This is a schematic diagram of the rectangular ion trap mass spectrometer structure of the present invention, equipped with a thermal desorption reagent-assisted photochemical ionization source and a continuous atmospheric pressure interface. 1 is a sampling pump, 2 is an auxiliary reagent bottle, 3 is a heating block, 4 is a sample cloth, 5 is a support, 6 is a vacuum ultraviolet lamp, 7 is an ionization zone, and 8 is an ion trap mass spectrometer. A liquid or solid sample is added dropwise to the sample injection step 4 and thermally desorbed into a gaseous sample. The sampling pump 1 draws carrier gas carrying the volatilized auxiliary reagent from the auxiliary reagent bottle 2 and the gaseous sample into the ionization zone 6, where a photochemical ionization reaction occurs. The sample then enters the ion trap mass spectrometer 8 through a capillary tube for detection.

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

[0031] Figure 3 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 sample 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 was 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 the photoionization auxiliary reagent carried by the carrier gas generates a large number of reagent ions that chemically react 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. 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 electrode 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 achieve collision-induced dissociation of the reagent ions and / or reagent ion dimers and collision-induced dissociation of the sample, and record the critical pressure difference between V1 and V3 for collision-induced dissociation of the reagent ions and / or reagent ion dimers (i.e., the pressure difference between V1 and V3 when the fragment ions of the reagent ions account for 10% of the total ion number) as Vreagent, and the critical pressure difference between V1 and V3 for collision-induced dissociation of the sample (i.e., the pressure difference between V1 and V3 when the fragment ions of the reagent ions account for 10% of the total ion number) as Vsample;

[0036] Due to the varying energy required for bond breaking, different substances require different pressure differences between V1 and V3 for collision-induced dissociation (CID). To eliminate interference from a large number of reagent ions, Vreagent is required to be smaller than Vsample, meaning the pressure difference between V1 and V3 is controlled between Vreagent and Vsample. At this point, the reagent ions or reagent ion dimers undergo CID, while the sample does not. Selective CID is achieved by exploiting the difference in voltage required for CID between sample and reagent ions. This fragments interfering ions and prevents the fragmented ions from being stabilized in the ion trap, eliminating space charge effects caused by interfering ions that can lead to mass spectrometry peak broadening and peak position shifts.

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

[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 at a flow rate of 100 ml / min, and the thermal desorption temperature was 160°C. Butanone was used as an auxiliary reagent to detect the headspace vapor of 2 μg / ml aniline. The continuous atmospheric pressure interface consisted of 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, and V4 was 100 V. The RF frequency f1 was 940 kHz, Vpp1 was 300 Vpp, the AC frequency f2 was 313 kHz, the peak-to-peak Vpp2 was 1 Vpp, and the injection time was 250 ms. When V3 was -5 V, neither the butanone dimer ion nor the aniline underwent collision-induced dissociation. When V3 was -15 V, the butanone dimer ion underwent collision-induced dissociation, while the aniline did not.

[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 at a flow rate of 100 ml / min and the thermal desorption temperature was 160°C. Butanone was used as an auxiliary reagent to detect the headspace vapor of 2 μg / ml aniline. The continuous atmospheric pressure interface consisted of 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, the RF frequency f1 was 940 kHz, Vpp1 was 300 Vpp, the AC frequency f2 was 313 kHz, and the peak-to-peak value Vpp2 was 1 Vpp. When V3 was -5 V, neither the butanone dimer ion nor the aniline underwent collision-induced dissociation. When V3 was -15 V, the butanone dimer ion underwent collision-induced dissociation, while the aniline did not. 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 up 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 sample thermally decomposed by the thermal desorber are photochemically ionized and then passed into the detection instrument for detection; The detection instrument is a rectangular ion trap mass spectrometer equipped with a thermal desorption reagent-assisted photochemical ionization source and a continuous atmospheric pressure interface; 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 the photoionization auxiliary reagent carried by the carrier gas generates a large number of reagent ions that chemically react with the gaseous sample to achieve efficient ionization of the sample; the ionized sample enters the rectangular ion trap mass spectrometer through a continuous atmospheric pressure interface for mass spectrometry analysis; the rectangular ion trap mass spectrometer includes a front cover electrode, a rear cover electrode, 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; the electrode surface normals of the three pairs of electrodes, the front cover electrode and the rear cover electrode, the x electrode, and the y electrode, are perpendicular to each other, the front cover electrode is a plate electrode with a through hole in the middle, and the rear cover electrode is a plate electrode with a through hole in the middle. The cover electrode is a plate-shaped electrode arranged parallel to and spaced apart from the front cover electrode; 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-electrode 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 trapping 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 Vpp2 is applied to the y-electrode; during detection, RF and AC are kept constant, V1, V2 and V4 are fixed, and the voltage difference between V1 and V3 is increased to achieve collision-induced dissociation; Adjust the pressure difference between V1 and V3 to achieve collision-induced dissociation of reagent ions and / or reagent ion dimers and 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, that is, the pressure difference between V1 and V3 when the fragment ions of the reagent ions account for 10% of the total ion number, as V 试剂 The critical pressure difference between V1 and V3 for collision-induced dissociation of the sample, that is, when the fragment ions of the reagent ions account for 10% of the total ion number, is taken as V 样品 ; In order to eliminate the interference caused by a large number of reagent ions, the pressure difference between V1 and V3 is controlled to be between V 试剂 and V 样品 The reagent ions or reagent ion dimers undergo collision-induced dissociation, while the sample does not undergo collision-induced dissociation. The different voltages required for collision-induced dissociation of sample ions and reagent ions are used to achieve selective collision-induced dissociation, which breaks up the interfering ions and makes the fragment ions unable to stabilize in the ion trap, eliminating the space charge effect caused by the interfering ions that leads to mass spectrum peak broadening and peak position shift. When the voltage V1 is applied to the front cover electrode during sample injection, it is adjustable from -10 to 0 V; V2 is adjustable from 50 to 150 V during other periods except during sample injection; the constant DC voltage V3 on the x-electrode and y-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.

2. The method according to claim 1, wherein: When the voltage applied to the front cover electrode is injected, V1 is -2V; except for the injection, V2 is 100V at other times.

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

4. The method according to claim 1, wherein: The injection time is adjustable from 10ms to 30s and is controlled by the time-varying voltage on the front cover electrode; The signal intensity of trace samples was enhanced by extending the injection time of the rectangular ion trap mass spectrometer.

5. The method according to claim 1, wherein: The auxiliary reagent in the thermal desorption reagent-assisted photochemical ionization source is one or more of acetone, butanone, and anisole; The auxiliary reagent in the thermal desorption reagent-assisted photochemical ionization source is ionized by a vacuum ultraviolet lamp; the carrier gas carries the thermally desorbed sample and mixes with the reagent ions to undergo a chemical reaction; the carrier gas is nitrogen, helium, or air; and the carrier gas flow rate is adjustable between 50-250 ml / min. The temperature of thermal desorption is adjustable between 120-200℃.

6. The method according to claim 1, wherein: The continuous atmospheric pressure interface is a metal capillary tube with an adjustable length of 10cm-30cm and an adjustable inner diameter of 0.25mm-0.5mm.

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