A method for reducing the matrix effect of photoionization ion mobility spectrometry for detecting complex samples

Abstract

The application discloses a method for reducing the matrix effect of photoionization ion mobility spectrometry for detecting complex samples. The ion mobility spectrometer comprises an ion mobility tube with good air tightness, a photoionization source and an ion receiving electrode oppositely arranged at the left and right ends of the ion mobility tube, and an ion gate between the photoionization source and the ion receiving electrode. The region between the photoionization source and the ion gate is an ionization zone, and the region between the ion gate and the ion receiving electrode is a migration zone. The method maintains the air pressure in the ion mobility tube in the range of 10-80 kPa, and at the same time, adjusts the isolated high-voltage power supply connected with the ionization zone to maintain the electric field in the ionization zone in the range of 300-600 V / cm, so that the ion-molecule reactions such as charge transfer and proton transfer of the ionized complex target compound in the ionization zone are inhibited, thereby being beneficial to eliminating the influence of the complex matrix on the accurate quantification and detection of the ion mobility spectrometer for low proton affinity or high ionization energy target compounds.

Description

Technical Field

[0001] This invention belongs to the field of analytical chemistry instruments, and specifically relates to a method for reducing the matrix effect in the detection of complex samples by photoionization ion mobility spectrometry. Background Technology

[0002] In recent years, with the development of atmospheric pressure ionization technology, the application scope of ion mobility spectrometry has expanded to many chemical analysis fields such as clinical exhaled breath detection, environmental pollutant detection, food safety detection, and process analysis.

[0003] However, as the application scope of IMS continues to expand, the matrix of the samples to be analyzed is becoming increasingly complex. This poses a significant challenge to the detection sensitivity, selectivity, and quantitative accuracy of IMS for target analytes, hindering its further development. When ion mobility spectrometry (IMS) operates under atmospheric pressure, molecules with higher proton affinity or lower ionization energy in multi-component samples can suppress the ionization of molecules with lower proton affinity or higher ionization energy. As a result, the latter, after being ionized, is rapidly converted through ionic-molecular reactions and cannot be detected, severely affecting the detection sensitivity of ion mobility spectrometry.

[0004] A method for using an ion migration tube for the separation and analysis of complex samples, invented by Chen Chuang et al. (patent number CN201811412003.0), generates H+(H2O)n with a strong proton affinity in positive ion mode. This allows for the suppression of ions with lower proton affinity in complex sample compositions, detecting only sample molecules with a proton affinity higher than H+(H2O)n, thus achieving high selectivity for target ions in complex samples. However, while this method suppresses interference from low proton affinity ions, it also fails to detect ions with low proton affinity. Furthermore, when multiple compounds with proton affinity higher than H+(H2O)n exist in a complex sample, it cannot eliminate the matrix effect interference of different compound ions on their respective detection results. Sun Jing et al. invented a method, kit, and application for detecting prohibited antibacterial drugs in cosmetics based on electrospray ion mobility spectrometry (patent number CN202111613766.3). By optimizing the pretreatment method of cation solid-phase extraction purification and concentration, it can effectively eliminate the matrix interference effect of other compounds on the detection of prohibited antibacterial drugs in cosmetics, reducing false positive results. However, most commonly used commercial solid-phase microextraction columns are selective only for a certain type of component, with a narrow range of applications, and cannot avoid non-selective adsorption of blood matrix. In addition, particle-packed solid-phase microextraction columns are prone to clogging and damage, are mostly for single use, and have relatively high analysis costs.

[0005] Ammonia, as a dopant, has been widely used in the detection of chemical warfare agents in organophosphorus mixtures (Anal. Chem. 2010, 82, 9594–960010), effectively eliminating false alarms caused by matrix interference with proton affinity lower than NH4+. However, this method also cannot detect target compound ions with low proton affinity. Xiao et al. (SensorActuat B-Chem: 2022, 350.) used CCl4 as an extractant to extract etomidate from biological samples and then detected it by ion mobility spectrometry in positive ion mode, effectively avoiding interference from complex matrices in biological samples. However, this method is also selective only for a specific type of component and lacks universality.

[0006] To reduce the matrix effect associated with ion mobility spectrometry (IMS) detection of complex samples, this invention adjusts the working gas pressure within the migration tube to suppress interference from multi-component samples in the ionization region on the detection results of a single component. Furthermore, this invention can simultaneously detect multi-component compounds in complex samples and effectively suppresses the matrix effect caused by most ions, demonstrating broad applicability. Summary of the Invention

[0007] The purpose of this invention is to provide a method for reducing matrix effects in the detection of complex samples using photoionization ion mobility spectrometry. This method utilizes the different collision frequencies between ions and molecules under different gas pressures. Under reduced gas pressure, the collision frequency between ions is lower, thus suppressing charge transfer and proton transfer reactions that can occur between ions and molecules. Simultaneously, the electric field strength in the ionization region of the ion mobility tube is increased. This increased electric field strength shortens the residence time of ions within the ionization region, thereby reducing the reaction time for ion-molecule reactions. Ultimately, this significantly suppresses the negative impact of matrix effects on ion detection, thereby achieving the goal of significantly reducing matrix effects in ion mobility spectrometry.

[0008] To achieve the above objectives, the technical solution adopted in this invention application is as follows:

[0009] A method for reducing matrix effects in complex samples using photoionization mobility spectrometry (PMA) is disclosed. The PMA includes a photoionization source and an ion receiver positioned opposite each other at the left and right ends, respectively, and an ion gate located between the photoionization source and the ion receiver. The region between the photoionization source and the ion gate is the ionization region, and the region between the ion gate and the ion receiver is the migration region. The method is characterized by: a sample gas inlet located on the upper wall of the ionization region near the photoionization source, connected to a sample gas source via a first mass flow meter; an outlet located on the upper wall of the ionization region near the ion gate, connected to the atmosphere via a pressure gauge, a needle valve, and a mechanical pump sequentially arranged on a connecting pipeline; and a drift gas inlet located above the ion receiver on the right wall of the migration region, connected to a drift gas source via a second mass flow meter.

[0010] The ionization region, ion gate, and migration region are all controlled by independent isolated high-voltage power supplies, enabling independent adjustment of the electrostatic field in each region without affecting the electrostatic field strength in other regions.

[0011] The method is specifically as follows:

[0012] 1) By adjusting the needle valve and the mechanical pump, the outflow rate in the ion migration tube is controlled to maintain the gas pressure in the ion migration tube within the range of 10 to 80 kPa, preferably 10 to 50 kPa, and more preferably 10 to 20 kPa;

[0013] Meanwhile, 2) by adjusting the isolation high-voltage power supply connected to the ionization region, the electric field in the ionization region is maintained in the range of 300 to 600 V / cm, preferably 300 to 500 V / cm, and most preferably 400 to 500 V / cm.

[0014] A needle valve is installed at the front end of the mechanical pump interface to work with the mechanical pump to control the gas pressure conditions throughout the migration tube. Under atmospheric pressure, the sample gas to be tested is carried into the ionization region of the migration tube by clean compressed air through the sample gas inlet and undergoes ionization. Subsequently, the sample ions of each component undergo further charge transfer and proton transfer reactions within the ionization region according to their respective proton affinity or ionization energy differences, forming final product ions under different gas pressure conditions. This results in the loss of some difficult-to-detect target compound ions, making them undetectable. By reducing the operating gas pressure of the ion migration tube, the mean free path of ions in the ionization region increases, the ion-molecule collision frequency decreases significantly, and ion-molecule reactions such as charge transfer and proton transfer are suppressed. Different molecular ions generated in the ionization region are then introduced into the migration region and can be detected.

[0015] An adjustable voltage isolation high-voltage power supply is applied separately to the ionization region to control the electric field conditions within the ionization region. The increased electric field strength in the ionization region will shorten the residence time of ions in the ionization region, thereby shortening the reaction time in which ion-molecule reactions can occur, and ultimately significantly suppressing the negative impact of matrix effects on ion detection.

[0016] To ensure high-throughput detection by ion mobility spectrometry, the flow rate range of the carrier gas inlet of the migration tube is 50–200 mL / min, and the flow rate range of the drift gas inlet is 50–200 mL / min.

[0017] The photoionization source can be either a laser light source or a vacuum ultraviolet lamp.

[0018] The ion gate is either a Tyndall-Powell type ion gate or a Bradbury-Nielsen type ion gate.

[0019] The drift gas source and carrier gas source are clean compressed air, which is air that has been filtered through 13X molecular sieve and activated carbon in sequence.

[0020] This invention achieves the suppression of the influence of matrix effect during photoionization spectroscopy detection through two approaches.

[0021] This invention firstly controls the outflow velocity within the migration tube by adjusting the needle valve at the exhaust port of the mechanical pump, in conjunction with the pump. This allows for arbitrary adjustment of the working gas pressure within the migration tube within a pressure range of 10–80 kPa. By adjusting the working gas pressure, the frequency of charge transfer and proton transfer reactions between ions and molecules is reduced, thereby suppressing the matrix effect. Secondly, by increasing the electric field strength in the ionization region of the migration tube within the range of 300–600 V / cm, the negative impact of the matrix effect on ion mobility spectrometry detection is also reduced. This invention has low requirements for adjusting the gas pressure and electric field, and can significantly improve the detection performance of ion mobility spectrometry under easily achievable experimental conditions, demonstrating universal applicability to ion mobility spectrometry. Attached Figure Description

[0022] Figure 1 A schematic diagram of an ion mobility spectrometer structure with adjustable gas pressure. Wherein: 1. Photoionization source; 2. Sample gas inlet; 3. First mass flow meter; 4. Gas outlet; 5. Needle valve; 6. Mechanical pump; 7. Drift gas inlet; 8. Ion receiving electrode; 9. Ion gate; 10. Ionization region; 11. Migration region; 12. Second mass flow meter; 13. Pressure gauge.

[0023] Figure 2 Ion migration spectrum of a mixed standard gas of benzene, toluene and xylene at a concentration of 1 ppmv, with a pressure of 100 kPa and an electric field strength of 200 V / cm in the ionization region.

[0024] Figure 3 Ion migration spectrum of a mixed standard gas of benzene, toluene and xylene at a concentration of 1 ppmv, with a pressure of 50 kPa and an electric field strength of 200 V / cm in the ionization region.

[0025] Figure 4 Ion migration spectrum of a mixed standard gas of benzene, toluene and xylene at a concentration of 1 ppmv, with a pressure of 10 kPa and an electric field strength of 200 V / cm in the ionization region.

[0026] Figure 5 Ion migration spectrum of a mixed standard gas of benzene, toluene and xylene at a concentration of 1 ppmv, with a pressure of 10 kPa and an electric field strength of 450 V / cm in the ionization region. Detailed Implementation

[0027] The photoionization ion mobility spectrum structure used in the method of this invention is as follows: Figure 1 As shown. The photoionization ion mobility spectrum includes an ion migration tube composed of annular electrodes and annular insulators coaxially stacked alternately. Inside the ion migration tube, a photoionization source 1 and an ion receiving electrode 8 are respectively arranged opposite each other at the left and right ends, and an ion gate 9 is located between the photoionization source 1 and the ion receiving electrode 8. The region between the photoionization source 1 and the ion gate 9 is the ionization region 10, and the region between the ion gate 9 and the ion receiving electrode 8 is the migration region 11. A sample gas inlet 2 is provided on the upper wall of the ionization region 10 near the photoionization source 1, and the sample gas inlet 2 is connected to the sample gas source through a first mass flow meter 3. An outlet 4 is provided on the upper wall of the ionization region 10 near the ion gate 9, and the outlet 4 is connected to the atmosphere through a pressure gauge 13, a needle valve 5, and a mechanical pump 6 arranged sequentially on the connecting pipeline. A drift gas inlet 7 is provided on the right wall of the migration region 11 above the ion receiving electrode 8, and the drift gas inlet 7 is connected to the atmosphere through the ion receiving electrode 8. The second mass flow meter 12 is connected to the drift gas source; the ionization zone 10, ion gate 9, and migration zone 11 are all controlled by independent isolated high-voltage power supplies, so that the electrostatic field of each zone can be independently adjusted without affecting the electrostatic field strength of other zones; the ion gate used inside the ion migration tube is a Tyndall-Powell type ion gate, which consists of two parallel metal grids separated by a circular insulating ring (polytetrafluoroethylene insulating ring) with a thickness of 0.5 mm; the ion source 1 is a 10.6 eV VUV photoionization source; the ion receiving electrode 8 is a Faraday disk with a diameter of 6 mm, fixed on a metal shielding cylinder with an outer diameter of 30 mm; the ionization zone 10 and the migration zone 11 are both composed of annular conductive electrode plates with an axial length of 5 mm and an outer diameter of 30 mm and annular insulating electrode plates with an axial length of 5 mm and an outer diameter of 30 mm, which are coaxially alternately stacked.

[0028] Comparative Example 1

[0029] The electric field strength in the fixed ionization region was 200 V / cm, and the electric field strength in the migration region was 400 V / cm. The needle valve was adjusted to stabilize the gas pressure in the migration tube at 100 kPa, and the reading was recorded from the pressure gauge. The drift gas flow rate was 200 mL / min. A mixed standard gas of benzene, toluene, and xylene at a flow rate of 100 mL / min was introduced into the ionization region and ionized by the vacuum ultraviolet lamp. The final stable product ions in the ionization region were then introduced into the migration region by the electric field and detected by the detector. The ion migration spectrum of the mixed sample was recorded at this time, as shown below. Figure 2 As shown, it can be found that when the electric field strength in the ionization region is 200 V / cm and the working gas pressure in the migration tube is 100 kPa, only the xylene molecular ion with the lowest ionization energy can be detected. The toluene and benzene ions with higher ionization energy will continue to take away the charge of the xylene molecule and convert it into toluene and benzene molecules through charge transfer reaction.

[0030] Under atmospheric pressure, the sample gas to be tested is carried into the ionization region of the migration tube by clean compressed air through the sample gas inlet and is ionized first. Then, the sample ions of each component undergo further charge transfer and proton transfer reactions between ions and molecules in the ionization region according to the differences in their proton affinity or ionization energy, forming the final product ions under different gas pressure conditions. This results in the loss of some target compound ions that are difficult to detect and cannot be detected.

[0031] Example 1

[0032] The electric field strength in the fixed ionization region was 200 V / cm, and the electric field strength in the migration region was 400 V / cm. The needle valve was adjusted to stabilize the gas pressure inside the migration tube at 50 kPa and 10 kPa, respectively, and the readings were recorded from the pressure gauge. The drift gas flow rate was 200 mL / min. A mixed standard gas of benzene, toluene, and xylene at a flow rate of 100 mL / min was introduced into the ionization region and ionized by the vacuum ultraviolet lamp. The final stable product ions in the ionization region were then introduced into the migration region by the electric field and detected by the detector. The ion migration spectrum of the mixed sample was recorded at this time, as shown below. Figure 3 and Figure 4 As shown,

[0033] Combination Figures 2 to 4 The results show that reducing the working pressure of the ion migration tube can suppress the matrix effect of xylene molecules on the detection of benzene and toluene ions. When the working pressure of the ion migration tube is 10 kPa, the mean free path of ions in the ionization region increases, the ion-molecule collision frequency decreases significantly, and ion-molecule reactions such as charge transfer and proton transfer are suppressed. This can effectively suppress the charge transfer reaction process between benzene, toluene, and xylene, and effectively suppress the matrix effect of xylene molecules on the detection of benzene and toluene ions.

[0034] Example 2

[0035] The working gas pressure for the fixed ion mobility spectrometer was 10 kPa. The isolation high-voltage power supply connected to the ionization region was adjusted to increase the electric field strength in the ionization region from 200 V / cm to 450 V / cm, while keeping the electric field strength in the migration region fixed at 400 V / cm. The drift gas flow rate was 200 mL / min. A mixed standard gas of benzene, toluene, and xylene (1 ppmv) was introduced into the ionization region through an inlet flow rate of 100 mL / min, and the signal response intensity of each was recorded under the condition of an electric field strength of 450 V / cm in the ionization region. Figure 5 As shown.

[0036] Compared to Figure 4 The results show that, based on a gas pressure of 10 kPa, increasing the electric field in the ionization region can suppress proton transfer and charge transfer ion-molecule reactions by shortening the residence time of ions in the reaction region. This further effectively suppresses the matrix effect of xylene molecules on the detection of benzene and toluene ions, significantly improves the signal intensity of toluene and benzene that are suppressed by xylene, and enhances the detection sensitivity of ion mobility spectrometry.

Claims

1. A method for reducing matrix effects in complex samples using photoionization ion mobility spectrometry, wherein the photoionization ion mobility spectrometry includes a photoionization source (1) and an ion receiving electrode (8) respectively disposed opposite to each other at the left and right ends, and an ion gate (9) located between the photoionization source (1) and the ion receiving electrode (8), wherein the region between the photoionization source (1) and the ion gate (9) is an ionization region (10), and the region between the ion gate (9) and the ion receiving electrode (8) is a migration region (11); characterized in that: A sample gas inlet (2) is provided on the upper wall of the ionization region (10) near the photoionization source (1), and the sample gas inlet (2) is connected to the sample gas source through the first mass flow meter (3); an outlet (4) is provided on the upper wall of the ionization region (10) near the ion gate (9), and the outlet (4) is connected to the atmosphere through a pressure gauge (13), a needle valve (5) and a mechanical pump (6) arranged in sequence on the connecting pipeline; a drift gas inlet (7) is provided on the upper wall of the migration region (11) above the ion receiving electrode (8), and the drift gas inlet (7) is connected to the drift gas source through the second mass flow meter (12); The ionization region (10), ion gate (9) and migration region (11) are all controlled by independent isolated high-voltage power supplies, so that the electrostatic field of each region can be independently adjusted without affecting the electrostatic field strength of other regions. The method is specifically as follows: 1) By adjusting the needle valve (5) and the mechanical pump (6), the gas flow rate inside the ion migration tube is controlled, and the gas pressure inside the ion migration tube is maintained within the range of 10~80 kPa. Meanwhile, 2) by adjusting the isolation high-voltage power supply connected to the ionization region, the electric field in the ionization region is maintained within the range of 300~600 V / cm.

2. The method for reducing the matrix effect of complex samples in photoionization spectroscopy detection according to claim 1, characterized in that: The method is specifically as follows: 1) The gas flow rate inside the ion migration tube is controlled by adjusting the needle valve (5) and the mechanical pump (6) to maintain the gas pressure inside the ion migration tube at 10–50 kPa. Meanwhile, 2) by adjusting the isolation high-voltage power supply connected to the ionization region, the electric field in the ionization region is maintained at 300-500 V / cm.

3. The method for reducing the matrix effect of complex samples in photoionization spectroscopy detection according to claim 1, characterized in that: The method is specifically as follows: 1) By adjusting the needle valve (5) and the mechanical pump (6) together, the gas flow rate in the ion migration tube is controlled, and the gas pressure in the ion migration tube is maintained at 10-20 kPa; Meanwhile, 2) by adjusting the isolation high-voltage power supply connected to the ionization region, the electric field in the ionization region is maintained at 400-500 V / cm.

4. The method for reducing the matrix effect of complex samples in photoionization spectroscopy detection according to claim 1, characterized in that: The photoionization source includes a laser emitter and a vacuum ultraviolet lamp.

5. The method for reducing the matrix effect in complex samples using photoionization ion mobility spectrometry according to claim 1, characterized in that: The flow rate of the sample gas inlet (2) is controlled by the first mass flow meter to be 50~200 mL / min, and the flow rate of the drift gas inlet (7) is controlled by the second mass flow meter to be 50~200 mL / min. The electric field strength in the migration zone is 200~500 V / cm.

6. The method for reducing the matrix effect in detecting complex samples using photoionization ion mobility spectrometry according to claim 1, characterized in that: The ion gates used are Tyndall-Powell type ion gates and Bradbury-Nielsen type ion gates.

7. The method for reducing matrix effects in complex samples using photoionization spectroscopy according to claim 1, characterized in that: The drift gas source and carrier gas source are clean compressed air, which is air that has been filtered through 13X molecular sieve and activated carbon in sequence.

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