An on-line mass spectrometry atmospheric pressure chemical ionization source and its application

Abstract

The present invention discloses an on-line mass spectrometry atmospheric pressure chemical ionization source and its application, belonging to the field of analytical instruments, which includes a halogen lamp, a mass spectrometer, an injection capillary, a four-way tube, a plasma stream, a radio frequency high-voltage electrode, and a central ground electrode; the entire device is integrated through the four-way tube. In the four-way tube, the main pipeline, the first and second branch pipelines of the four-way tube are perpendicular to each other and intersect with each other to form an intersection area, which connects the plasma stream, the thermal desorption optical path, the auxiliary reagent inlet, and the sample sampling cotton swab, and the halogen lamp is focused on the intersection area. The entire device integrates photo-thermal desorption-chemical ionization-injection, reduces the loss of samples during transmission, improves the sensitivity of on-line mass spectrometry analysis by using double auxiliary reagents to assist the desorption and ionization of samples, uses the sampling cotton swab to collect samples at any position, can quickly analyze both solids and liquids, is convenient and fast, and has a small device volume, which is convenient for on-site and on-line rapid analysis.

Description

Technical Field

[0001] The present invention belongs to the field of analytical instruments, and particularly relates to an on-line mass spectrometry atmospheric pressure chemical ionization source and its application. Background Art

[0002] Dielectric barrier discharge is an important technical branch in the field of atmospheric pressure ionization source technology. Dielectric barrier discharge is a kind of non-equilibrium gas discharge with an insulating medium inserted into the discharge space. Dielectric barrier discharge can work in a high-pressure and wide-frequency range, with the working pressure being 10 4 Pa - 10 5 Pa or higher, and the power supply frequency being 50 Hz - 1 MHz. The discharge gas can be helium, nitrogen, air, etc. The plasma generated by the discharge gas has an electron energy exceeding 15 eV, which can generate both positive and negative ions. When the analyte contacts the plasma, a series of chemical reactions will occur and it will be ionized. At present, a variety of ionization source devices have been developed based on dielectric barrier discharge, but the problems of low sensitivity and long analysis time when analyzing non-volatile compounds have not been completely overcome.

[0003] In 2007, Zhang Xinrong et al. used a dielectric barrier discharge device to ionize reaction gases that can be used for chemical ionization (CN200610011548.1), causing the reaction gases to ionize and produce reaction ions. These reaction ions undergo ion-molecule reactions with the organic compounds to be measured, achieving the effective ionization of the organic compounds to be measured. However, this device is mainly used for analyzing volatile organic compounds and halogenated hydrocarbons and cannot directly analyze non-volatile solid and liquid analytes. In 2011, Hou Keyong et al. designed a new type of dielectric barrier discharge mass spectrometry ionization source device (CN201110232457.1). The present invention discloses a dielectric barrier discharge ionization source. This ionization source uses a 30 kHz radio frequency power supply as the discharge electrode, and the other electrode is grounded. The discharge electrode uses quartz glass as the dielectric. The inner diameter of the quartz glass tube where the radio frequency high voltage electrode is located is 10 mm, and the diameter of the quartz glass tube where the ground electrode is located is 50 mm. When this ionization source is combined with an on-line mass spectrometer, an explosive sample within a range of 50 mm in diameter can be detected in 3 seconds. In 2012, a T-shaped dielectric barrier discharge mass spectrometry ionization source was designed (CN201210536370.8). This device mainly includes a T-shaped glass tube, a central ground electrode, a radio frequency high voltage electrode, and a front-end ground electrode. When this ionization device operates, two discharge regions are formed between the radio frequency high voltage electrode and the central ground electrode and the front-end ground electrode, which can generate more heat for sample thermal desorption. A reagent gas is introduced through the T-shaped tube to mix with the plasma to form a plasma beam. When the plasma beam impinges on the surface of the solid analyte, desorption and selective ionization occur. This device uses the plasma beam to directly contact the sample to complete desorption and ionization. The helium gas flow rate used is approximately 0.2 L / min. When auxiliary gas is added to the plasma beam by the purge gas in the discharge region, it will interfere with the plasma beam, resulting in a decrease in discharge efficiency. The large flow rate of gas introduced will dilute the analyte and reduce the sensitivity.

[0004] In 2016, Jiang Jie et al. developed a mass spectrometry ion source device (CN201610491641.0), which mainly includes a tip electrode, an insulating medium, a power supply, an instrument interface, and a gas conduit. The tip electrode is connected to an AC and DC power supply, and the instrument interface is grounded. A strong electric field will be formed between them. The insulating medium with the sample adheres to the tip part of the tip electrode. The discharge gas fills the space between the insulating medium and the instrument interface through the gas conduit. Under the action of the strong electric field, a plasma will be formed. This device uses the direct interaction between the solid analyte and the plasma to achieve its ionization, with low efficiency and inconvenient operation. In 2016, Wen Luhong et al. developed an open atmospheric pressure ionization device and method (CN201610991572.X), including a dielectric barrier discharge ion source, a container, a conveying unit, a spray head, a power supply, and a sampler. This device uses a plasma source to ionize the auxiliary liquid ejected from the spray head, and the analyte sample ejected from the sampler is ionized by the ionized auxiliary liquid. By combining electrospray with dielectric barrier discharge, the ionization efficiency of non-polar compounds can be enhanced, which is suitable for post-ionization of liquid samples.

[0005] Therefore, there is an urgent need to develop an ionization source suitable for the analysis of non-volatile compounds, and to improve the analysis sensitivity and shorten the analysis time. Summary of the Invention

[0006] In order to solve the deficiencies of the prior art, the purpose of the present invention is to provide an on-line mass spectrometry atmospheric pressure chemical ionization source and its application. The ionization source provided by the present invention integrates photo-thermal desorption - chemical ionization - sampling into one area, reducing the loss of the sample during the transmission process. Two auxiliary reagents are respectively used to enhance the desorption and ionization efficiency of the sample, improving the analysis sensitivity. A cotton swab is used to quickly collect liquid and solid samples at any position, with convenient operation, wide applicability, and fast analysis speed.

[0007] In order to achieve the above purpose, the technical solution of the present invention is as follows:

[0008] On the one hand, an on-line mass spectrometry atmospheric pressure chemical ionization source includes: a photo-thermal desorption - chemical ionization - sampling area and a plasma generation area;

[0009] The photo-thermal desorption - chemical ionization - sampling area includes a mass spectrometer, an injection capillary, a four-way tube, a heating device, and a plasma flow;

[0010] The plasma generation area is used to generate a plasma flow;

[0011] The photo-thermal desorption - chemical ionization - sampling area and the plasma generation area are integrated into one through a four-way tube;

[0012] The four-way pipe is composed of one main pipeline and three branch pipelines. The first branch pipeline and the second branch pipeline of the four-way pipe are arranged in the photo-thermal desorption-chemical ionization-sampling area, and the third branch pipeline of the four-way pipe is arranged in the plasma generation area; the main pipeline of the four-way pipe, the first branch pipeline of the four-way pipe and the second branch pipeline of the four-way pipe are perpendicular to each other and intersect with each other to form an intersection area.

[0013] The heating device is focused on the intersection area.

[0014] The mass spectrometer is connected to the main pipeline of the four-way pipe through an injection capillary.

[0015] On the other hand, the application of the above-mentioned on-line mass spectrometry atmospheric pressure chemical ionization source in the on-site mass spectrometry analysis of non-volatile organic compounds.

[0016] Based on dielectric barrier discharge, the present invention designs an on-line mass spectrometry atmospheric pressure chemical ionization source, which integrates photo-thermal desorption-chemical ionization-sampling into one area, reduces the loss of samples during the transmission process, respectively uses two auxiliary reagents to enhance the desorption and ionization efficiency of samples, improves the analysis sensitivity, can use cotton swabs to quickly collect liquid and solid samples at any position, is convenient to operate, and has a fast analysis speed and high sensitivity.

[0017] The beneficial effects of the present invention are as follows:

[0018] Based on dielectric barrier discharge, the present invention designs an on-line mass spectrometry atmospheric pressure chemical ionization source, which integrates photo-thermal desorption-chemical ionization-sampling into one area, reduces the loss of samples during the transmission process, respectively uses two auxiliary reagents to enhance the desorption and ionization efficiency of samples, improves the analysis sensitivity, can use cotton swabs to quickly collect liquid and solid samples at any position, is convenient to operate, and has a fast analysis speed, high sensitivity and wide applicability.

[0019] The ionization source of the present invention designs a dual-reagent-assisted dielectric barrier discharge chemical ionization of an ionization auxiliary reagent and a volatilization auxiliary reagent. By adding the ionization auxiliary reagent, soft ionization is achieved, the sample ionization efficiency is improved, and the volatilization auxiliary reagent improves the sample desorption efficiency. The dual-reagent assistance is beneficial to improving the chemical ionization sensitivity. The present invention adopts the photo-radiation heating method and integrates the photo-radiation thermal desorption area and the chemical ionization area, reducing the device volume and sample transmission loss.

[0020] During the detection and analysis process of the ionization source of the present invention, cotton swabs can be directly used for sampling and injection analysis of non-volatile samples, both solid and liquid samples can be detected, samples at any position can be collected, the operation is convenient, the analysis speed is fast, and the analysis time of the whole analysis process is less than 1 minute. Description of the Drawings

[0021] The accompanying drawings forming a part of the present invention are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention.

[0022] Figure 1 It is a two-dimensional structure diagram of an on-line mass spectrometry atmospheric pressure chemical ionization source according to Embodiment 1 of the present invention;

[0023] Figure 2 It is a three-dimensional structure diagram of an on-line mass spectrometry atmospheric pressure chemical ionization source according to Embodiment 1 of the present invention.

[0024] Figure 3 It is a mixture spectrogram obtained by using the on-line mass spectrometry atmospheric pressure chemical ionization source in Embodiment 2 of the present invention;

[0025] Figure 4 It is a comparison spectrogram of 0.5 ng ketamine samples with and without dual reagent assistance obtained by using the on-line mass spectrometry atmospheric pressure chemical ionization source in Embodiment 3 of the present invention;

[0026] Figure 5 It is a spectrogram of 100 ng / ml ketamine saliva sample obtained by using the on-line mass spectrometry atmospheric pressure chemical ionization source in Embodiment 3 of the present invention;

[0027] Figure 6 It is a signal comparison spectrogram of the same concentration of MDMA obtained by using the on-line mass spectrometry atmospheric pressure chemical ionization source and nano-ESI in the comparative example of the present invention.

[0028] Among them, 1: photo-thermal desorption-chemical ionization-sampling area, 2: plasma generation area, 3: halogen lamp, 4: mass spectrometer, 5: main pipeline of four-way pipe, 6: first branch pipeline of four-way pipe, 7: second branch pipeline of four-way pipe, 8: plasma flow, 9: radio frequency high voltage electrode, 10: third branch pipeline of four-way pipe, 11: central ground electrode, 12: sampling capillary. Detailed Description of the Invention

[0029] It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs.

[0030] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular forms are also intended to include the plural forms. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0031] In order to improve the analysis sensitivity of non-volatile compounds and shorten their analysis time, the present invention proposes an on-line mass spectrometry atmospheric pressure chemical ionization source and its application.

[0032] A typical embodiment of the present invention provides an on-line mass spectrometry atmospheric pressure chemical ionization source, including: a photo-thermal desorption-chemical ionization-sampling zone and a plasma generation zone;

[0033] The photo-thermal desorption-chemical ionization-sampling zone includes a mass spectrometer, a sampling capillary, a four-way tube, a heating device, and a plasma flow;

[0034] The plasma generation zone is used to generate a plasma flow;

[0035] The photo-thermal desorption-chemical ionization-sampling zone and the plasma generation zone are integrated through a four-way tube;

[0036] The four-way tube is composed of a main pipeline and three branch pipelines. The first four-way tube branch pipeline and the second four-way tube branch pipeline are arranged in the photo-thermal desorption-chemical ionization-sampling zone, and the third four-way tube branch pipeline is arranged in the plasma generation zone; the main four-way tube pipeline, the first four-way tube branch pipeline and the second four-way tube branch pipeline are perpendicular to each other and intersect with each other to form an intersection area;

[0037] The heating device is focused on the intersection area;

[0038] The mass spectrometer is connected to the main four-way tube pipeline through a sampling capillary.

[0039] In some embodiments of this typical embodiment, the first four-way tube branch pipeline is the inlet for the sample to be measured and the volatilization auxiliary reagent; the volatilization auxiliary reagent includes one or more of methanol, ethanol, and butanol.

[0040] In some embodiments of this typical embodiment, the second four-way tube branch pipeline is the inlet for the ionization auxiliary reagent; the ionization auxiliary reagent includes one or more of acetone, butanone, toluene, anisole, ethanol, or chlorobenzene.

[0041] In some embodiments of this typical embodiment, the third four-way tube branch pipeline is the inlet for the discharge gas; the discharge gas includes one or more of helium, nitrogen, and air.

[0042] In some embodiments of this exemplary embodiment, the specific operations for the sample to be measured and the volatilization auxiliary reagent to enter the first branch pipeline of the four-way pipe are as follows: Use a cotton swab to sample the sample to be measured, drop the volatilization auxiliary reagent on the top of the cotton swab for auxiliary analysis, and then insert the cotton swab into the main pipeline of the four-way pipe from the first branch pipeline of the four-way pipe, and place the sample in the cross-region of the three pipelines. Sampling with a cotton swab can quickly collect liquid and solid samples at any position, with convenient operation and wide universality. And dropping a certain volume of volatilization auxiliary reagent on the sampling cotton swab can improve the gasification efficiency of the sample and the sensitivity of on-line mass spectrometry analysis.

[0043] In some embodiments of this exemplary embodiment, the specific operation for the ionization auxiliary reagent to enter the second branch pipeline of the four-way pipe is as follows: Drop the ionization auxiliary reagent on the top of the cotton swab, and then insert the cotton swab into the second branch pipeline of the four-way pipe. The gas formed by the volatilization of the ionization auxiliary reagent enters the cross-region and mixes with the plasma to be ionized to form reagent ions. The second branch pipeline of the four-way pipe is used to insert the cotton swab dropped with the ionization auxiliary reagent, which can improve the ionization efficiency. And the ionization auxiliary reagent has high volatility. Dip the required ionization auxiliary reagent with a cotton swab and insert it into the second branch pipeline of the four-way pipe. Without additional purge gas, the gas formed by the self-volatilization of the ionization auxiliary reagent at room temperature enters the main pipeline of the four-way pipe, which can reduce the dilution and interference of the sample.

[0044] In some embodiments of this exemplary embodiment, the flow rate of the discharge gas is 90 - 110 ml / min.

[0045] In some embodiments of this exemplary embodiment, the heating device includes a halogen lamp, an infrared heating lamp or an ultraviolet heating lamp.

[0046] In some embodiments of this exemplary embodiment, the heating device is a halogen lamp; the halogen lamp has a focusing heating function, and the light emitted by the halogen lamp passes through the four-way pipe and focuses on the cross-region to gasify the sample through the focused light and heat.

[0047] In some embodiments of this exemplary embodiment, the material of the four-way pipe is quartz or glass.

[0048] In some embodiments of this exemplary embodiment, the cross-region is 1 - 10 mm away from the connection end of the main pipeline of the four-way pipe and the mass spectrometer.

[0049] In some embodiments of this exemplary embodiment, the third branch pipeline of the four-way pipe is perpendicular to the main pipeline of the four-way pipe and parallel to the first branch pipeline of the four-way pipe.

[0050] The third branch pipeline of the four-way pipe is 1 - 10 mm away from the end of the main pipeline of the four-way pipe far from the mass spectrometer.

[0051] In some embodiments of this exemplary embodiment, the plasma generation region includes a radio frequency high voltage electrode and a central ground electrode.

[0052] The radio frequency high-voltage electrode is a metal ring with an inner diameter adapted to the main pipeline of the four-way pipe, and is sleeved between the first branch pipeline and the third branch pipeline of the four-way pipe. The radio frequency high-voltage electrode is as close as possible to the first branch pipeline of the four-way pipe, so that the plasma density in the cross region is the largest.

[0053] The central ground electrode is a metal rod, which is inserted into the four-way pipe at the end of the main pipeline of the four-way pipe far from the mass spectrometer, and partially overlaps with the radio frequency high-voltage electrode.

[0054] The radio frequency high-voltage electrode is connected to the high-voltage output terminal of the radio frequency power supply, and the central ground electrode is connected to the grounded terminal of the radio frequency voltage.

[0055] The radio frequency high-voltage electrode will ionize the introduced discharge gas, generating excited ions, electrons, etc., to form a plasma flow. The gas generated by the volatilization of the ionization auxiliary reagent enters the main pipeline of the four-way pipe through the second branch pipeline of the four-way pipe, and is mixed with the plasma flow in the cross region and thus ionized to form reagent ions. A cotton swab with a sample to be measured is inserted into the first branch pipeline of the four-way pipe, and the sample to be measured and the focus of the halogen lamp are placed in the cross region of the three pipelines. The sample is rapidly heated by the halogen lamp and volatilizes to form a gas. The formed gaseous sample molecules directly collide with the plasma and reagent ions, and processes such as proton transfer, charge transfer or molecular fragmentation occur to ionize the sample, and then enter the mass spectrometer through the outlet for analysis.

[0056] Based on dielectric barrier discharge, the present invention designs an on-line mass spectrometry atmospheric pressure chemical ionization source, integrating photo-thermal desorption - chemical ionization - sampling into one region, reducing the loss of the sample during the transmission process, respectively using two kinds of auxiliary reagents to enhance the desorption and ionization efficiency of the sample, improving the analysis sensitivity, and enabling the use of a cotton swab to rapidly collect liquid and solid samples at any position, with convenient operation, fast analysis speed and high sensitivity.

[0057] Another typical embodiment of the present invention provides an application of the above on-line mass spectrometry atmospheric pressure chemical ionization source in the on-site mass spectrometry analysis of non-volatile organic compounds.

[0058] In some embodiments of this embodiment, the specific operation of the application is as follows:

[0059] Introduce the discharge gas;

[0060] Adjust the halogen lamp to adjust its focus just on the cross region of the three pipelines;

[0061] Turn on the radio frequency power supply and adjust the voltage frequency. The radio frequency high-voltage electrode will ionize the introduced discharge gas, generating excited ions, electrons, etc., to form a plasma flow;

[0062] Add an ionization auxiliary reagent to the top of the cotton swab, and then insert the cotton swab into the second branch pipe of the four-way pipe. The gas generated by the volatilization of the ionization auxiliary reagent enters the intersection area and mixes with the plasma to be ionized to form reagent ions;

[0063] Use a cotton swab to take a sample of the sample to be tested, add a volatile auxiliary reagent to the top of the cotton swab for auxiliary analysis, and then insert the cotton swab from the branch line of the four-way pipe into the main line of the four-way pipe, and place the sample at the intersection of the three pipes;

[0064] Turn on the mass spectrometer analysis system, turn on the halogen lamp, and the sample on the cotton swab evaporates to form a gas, mixes with the plasma flow and reagent ions, and undergoes proton transfer, charge transfer or molecular fragmentation to be ionized, and then is sucked into the mass spectrometer through the mass spectrometer injection tube for analysis.

[0065] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0066] Example 1

[0067] An online mass spectrometry atmospheric pressure chemical ionization source

[0068] like Figure 1 As shown, an online mass spectrometry atmospheric pressure chemical ionization source includes a photothermal desorption-ionization-injection area 1 and a plasma generation area 2.

[0069] The photothermal desorption / ionization (PTD)-injection zone 1 includes a mass spectrometer 4, an injection capillary 12, a four-way pipe, a halogen lamp 3, and a plasma stream 8. The plasma generation zone 2 includes a radio frequency high-voltage electrode 9 and a central ground electrode 11. The PTD-CCI-injection zone 1 and the plasma generation zone 2 are integrated via a four-way pipe. The injection capillary 12 connects the mass spectrometer 4 to the four-way pipe, with one end of the injection capillary 12 inserted 3 mm into the main pipe 5 through a 2 mm diameter hole on the left side of the four-way pipe.

[0070] The cross-over pipe consists of a main line and three branch lines, specifically, a main line 5, a branch line 1 6, a branch line 2 7, and a branch line 3 10. Branch lines 1 6 and 7 are located in the photothermal desorption-chemical ionization-injection area 1, while branch line 3 10 is located in the plasma generation area 2. The main line 5, branch line 1 6, and branch line 2 7 are perpendicular to each other and intersect, forming an intersection. Branch line 3 10 is perpendicular to the main line 5 and parallel to branch line 1 6.

[0071] The main pipeline 5 of the four-way pipe used is a quartz cylinder with a length of 36 mm, an outer diameter of 6 mm, and an inner diameter of 4 mm. The first branch pipeline 6 of the four-way pipe, the second branch pipeline 7 of the four-way pipe, and the third branch pipeline 10 of the four-way pipe are all quartz cylinders with an outer diameter of 6 mm, an inner diameter of 4 mm, and a length of 27 mm.

[0072] The radio frequency high-voltage electrode 8 is a metal ring with an inner diameter of 6.1 mm, a wall thickness of 0.1 mm, and a length of 16 mm. It is sleeved on the main pipeline 5 of the four-way pipe and is located between the first branch pipeline 6 and the third branch pipeline 7 of the four-way pipe. The radio frequency high-voltage electrode 9 is connected to the output end of the adjustable AC high-voltage power supply. The central ground electrode 11 is a metal round tube with an outer diameter of 1.58 mm and a length of 100 mm. It is inserted into the pipe on the right side of the main pipeline 5 of the four-way pipe, partially overlaps with the radio frequency high-voltage electrode, and is connected to the ground electrode of the adjustable AC high-voltage power supply.

[0073] The power of the halogen lamp 3 is 100 W. It can form a focus with a diameter of 2 mm at 35 mm. The temperature at the focus can rise to 250 °C within 2 s, and the focus is adjusted to just fall on the intersection area of the three pipelines.

[0074] Turn on the radio frequency power supply, adjust the voltage frequency, and provide an AC high voltage with a peak-to-peak value of 1.6 kVp-p and a frequency of 25 kHz to the radio frequency high-voltage electrode 9 for generating dielectric barrier discharge to generate plasma.

[0075] In the application of the on-line mass spectrometry atmospheric pressure chemical ionization source in the on-site analysis of non-volatile organic compounds, the specific steps are as follows:

[0076] Introduce the discharge gas, and the flow rate of the helium gas used as the discharge gas is 100 ml / min.

[0077] Adjust the halogen lamp so that its focus just falls on the intersection area of the three pipelines.

[0078] Turn on the radio frequency power supply, adjust the voltage frequency, and the radio frequency high-voltage electrode will ionize the introduced discharge gas to generate excited ions, electrons, etc., forming a plasma flow.

[0079] Drop the ionization auxiliary reagent on the top of the cotton swab, and then insert the cotton swab into the second branch pipeline of the four-way pipe. The gas formed by the volatilization of the ionization auxiliary reagent enters the intersection area and mixes with the plasma to be ionized to form reagent ions.

[0080] Use the cotton swab to sample the sample to be measured, drop the volatilization auxiliary reagent on the top of the cotton swab for auxiliary analysis, and then insert the cotton swab from the first branch pipeline of the four-way pipe into the main pipeline of the four-way pipe, and place the sample in the intersection area of the three pipelines.

[0081] Turn on the mass spectrometer analysis system, turn on the halogen lamp, and the sample on the cotton swab volatilizes to form a gas state, which is mixed with the plasma flow and reagent ions, and is ionized by proton transfer, charge transfer or molecular fragmentation, and then is inhaled into the analyzer by the mass spectrometer sampling tube for analysis.

[0082] Example 2

[0083] Application of the on-line mass spectrometry atmospheric pressure chemical ionization source of Example 1 in the on-site analysis of non-volatile organic compounds. The on-line mass spectrometry atmospheric pressure chemical ionization source of Example 1 is used, and a continuous injection type ion trap mass spectrometer is used as the analysis instrument. In the positive ion mode, a mixture of amphetamine, methamphetamine and MDMA is measured, and the concentration of the three drugs is 10 ppm.

[0084] Among them, a pipette is used to suck the mixture solution with a concentration of 10 ppm and drop it on the top of the cotton swab, and then a pipette is used to suck 5 μl of butanol solvent and drop it at the same position. After that, the cotton swab is inserted into the cross region from the first branch of the four-way tube; a pipette is used to suck 20 μl of acetone solvent and drop it on the top of another cotton swab, and it is inserted at the second branch of the four-way tube. The rest are the same as the steps of Example 1.

[0085] The analysis results are shown in Figure 3 , Figure 3 is the mixture spectrogram obtained in the full spectrum mode. The ion with a mass-to-charge ratio of 117 is the dimer ion peak formed by the auxiliary reagent acetone gas, the ion with a mass-to-charge ratio of 136 is the protonated molecular ion peak of amphetamine, the ion with a mass-to-charge ratio of 150 is the protonated molecular ion peak of methamphetamine, and the ion with a mass-to-charge ratio of 194 is the protonated molecular ion peak of MDMA.

[0086] Example 3

[0087] Application of the on-line mass spectrometry atmospheric pressure chemical ionization source of Example 1 in the on-site analysis of non-volatile organic compounds.

[0088] The on-line mass spectrometry atmospheric pressure chemical ionization source of Example 1 is used in combination with an analysis instrument, and a continuous injection type ion trap mass spectrometer is used as the analysis instrument. The multi-reaction monitoring mode of the continuous injection type ion trap mass spectrometer is used to perform more accurate qualitative analysis on the analyte.

[0089] Use a pipette to aspirate 1 μl of ketamine standard solution with a concentration of 500 ng / ml and drop it on the top of the cotton swab. Then, use the pipette to aspirate 5 μl of butanol solvent and drop it at the same position. After that, insert the cotton swab into the cross-region from branch one of the four-way tube, and ensure that the halogen lamp focus is concentrated on the surface of the cotton swab. The absolute amount of the sample on the cotton swab is 0.5 ng. Use a pipette to aspirate 20 μl of acetone solvent and drop it on the top of another cotton swab, and insert it at branch two of the four-way tube. Since acetone is volatile at room temperature, the formed acetone gas enters the cross-region and mixes with the plasma and is ionized to form reagent ions. The remaining steps are the same as those in Example 1.

[0090] Figure 4 Figure 4 is the comparative mass spectrometry diagram of the signals of 500 pg of ketamine standard samples with and without the addition of the double auxiliary reagent. 219 is the characteristic fragment ion of ketamine. a) is the intensity of the characteristic fragment ion of ketamine that appears when the double auxiliary reagent is added, and b) is the intensity of the characteristic fragment ion of ketamine that appears when the auxiliary reagent is not added. It can be seen that the signal intensity of the characteristic fragment ion peak of ketamine has increased by one order of magnitude.

[0091] Figure 5 Figure 8 is the spectrum obtained by analyzing the 100 ng / ml ketamine saliva sample with a cotton swab, and ketamine has been successfully detected. Since 100 ng / ml ketamine in saliva is the preliminary confirmation threshold for roadside rapid drug driving tests, it can be seen that the sensitivity of the on-line mass spectrometry atmospheric pressure chemical ionization source of the present invention in the on-site analysis of non-volatile organic compounds can be used for roadside rapid drug driving screening.

[0092] Table 1 shows the minimum detection limits of six common drugs obtained in this example. Among them, methamphetamine, methamphetamine hydrochloride, MDMA, MDA, and ketamine can be detected as low as 50 pg, and cocaine and benzoylecgonine can be detected as low as 100 pg. Table 1 can illustrate that the on-line mass spectrometry atmospheric pressure chemical ionization source of the present invention has high sensitivity and great potential in roadside drug driving rapid screening.

[0093] Table 1

[0094]

[0095] Comparative Example 1

[0096] The difference from Example 3 is that a commercial nano-ESI is used to analyze the MDMA standard solution. The same analytical instrument and parameters are used. Use a pipette to take 10 μl of MDMA amine standard solution with a concentration of 1 μg / ml and add it to the quartz glass capillary. Insert the metal electrode and apply a DC voltage of 1200 V. Due to the action of the DC high voltage, the liquid forms a spray and ionizes the analytes therein and is analyzed by the instrument.

[0097] Figure 6 This is the signal comparison mass spectrometry diagram of the online mass spectrometry atmospheric pressure chemical ionization source of the present invention and nano-ESI for analyzing MDMA standard solution. a) is the signal mass spectrometry diagram of the online mass spectrometry atmospheric pressure chemical ionization source for analyzing MDMA standard solution, and b) is the signal mass spectrometry diagram of nano-ESI for analyzing MDMA standard solution. Through Figure 6 It can be seen that when analyzing with the online mass spectrometry atmospheric pressure chemical ionization source of the present invention under the condition of using the same concentration and volume of standard solution and the same instrument and parameters, the signal intensity of the characteristic fragment ion peak of MDMA can be seen to increase by one order of magnitude.

[0098] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. An on-line mass spectrometry atmospheric pressure chemical ionization source, characterized in that, Comprising: A photo-thermal desorption-chemical ionization-injection zone and a plasma generation zone; The photo-thermal desorption-chemical ionization-injection zone includes a mass spectrometer, an injection capillary, a four-way tube, a heating device, and a plasma stream; The plasma generation zone is used to generate a plasma stream; The photo-thermal desorption-chemical ionization-injection zone and the plasma generation zone are integrally integrated through a four-way tube; The four-way tube consists of a main pipeline and three branch pipelines. The first four-way tube branch pipeline and the second four-way tube branch pipeline are arranged in the photo-thermal desorption-chemical ionization-injection zone, and the third four-way tube branch pipeline is arranged in the plasma generation zone; The main four-way tube pipeline, the first four-way tube branch pipeline, and the second four-way tube branch pipeline are perpendicular to each other and intersect to form an intersection area; The heating device is focused on the intersection area; The mass spectrometer is connected to the main four-way tube pipeline through an injection capillary; The first four-way tube branch pipeline is the inlet for the sample to be measured and the volatilization auxiliary reagent, the second four-way tube branch pipeline is the inlet for the ionization auxiliary reagent, and the third four-way tube branch pipeline is the inlet for the discharge gas; The plasma generation zone includes a radio frequency high voltage electrode and a central ground electrode; The radio frequency high voltage electrode is a metal ring with an inner diameter adapted to the main four-way tube pipeline, sleeved between the first four-way tube branch pipeline and the third four-way tube branch pipeline. The central ground electrode is a metal rod inserted into the four-way tube at the end of the main four-way tube pipeline far from the mass spectrometer and partially overlaps with the radio frequency high voltage electrode; The radio frequency high voltage electrode is connected to the high voltage output end of the radio frequency power supply, and the central ground electrode is connected to the grounded end of the radio frequency voltage.

2. The on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 1, characterized in that: The volatilization auxiliary reagent includes one or more of methanol, ethanol, and butanol.

3. The on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 1, wherein: The ionization auxiliary reagent includes one or more of acetone, butanone, toluene, anisole, ethanol, or chlorobenzene.

4. The on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 1, characterized in that: The discharge gas includes one or more of helium, nitrogen, and air.

5. The on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 1, wherein: The specific operation for the sample to be measured and the volatilization auxiliary reagent to enter the first four-way tube branch pipeline is as follows: Use a cotton swab to sample the sample to be measured, drop the volatilization auxiliary reagent on the top of the cotton swab for auxiliary desorption, and then insert the cotton swab from the first four-way tube branch pipeline into the main four-way tube pipeline, and place the sample in the intersection area of the three pipelines; The specific operation for the ionization auxiliary reagent to enter the second four-way tube branch pipeline is as follows: Drop the ionization auxiliary reagent on the top of the cotton swab, and then insert the cotton swab into the second four-way tube branch pipeline. The gas formed by the volatilization of the ionization auxiliary reagent enters the intersection area and mixes with the plasma to be ionized to form reagent ions; The flow rate of the discharge gas is 90 - 110 ml / min.

6. The on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 1, characterized in that: The heating device includes a halogen lamp, an infrared heating lamp, or an ultraviolet heating lamp.

7. The on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 6, characterized in that: The heating device is a halogen lamp.

8. The on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 7, characterized in that: The halogen lamp has a focusing heating function. The light emitted by the halogen lamp passes through the four-way tube and is focused on the intersection area, and the sample is vaporized by the focused light and heat.

9. The on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 1, wherein: The material of the four-way tube is quartz or glass.

10. The on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 1, wherein: The intersection area is 1 - 10 mm away from the connection end of the main four-way tube pipeline and the mass spectrometer.

11. The online mass spectrometry atmospheric pressure chemical ionization source according to claim 1, characterized in that: The third four-way tube branch pipeline is perpendicular to the main four-way tube pipeline and parallel to the first four-way tube branch pipeline.

12. The online mass spectrometry atmospheric pressure chemical ionization source according to claim 11, characterized in that: The third four-way tube branch pipeline is 1 - 10 mm away from the end of the main four-way tube pipeline far from the mass spectrometer.

13. Use of the online mass spectrometry atmospheric pressure chemical ionization source according to any one of claims 1 to 12 in on-site analysis of non-volatile organic compounds.

14. Use of the on-line mass spectrometry atmospheric pressure chemical ionization source according to claim 13 in on-site analysis of non-volatile organic compounds, characterized in that: The specific operations are: introducing discharge gas; Adjust the halogen lamp so that its focus falls exactly on the intersection of the three pipes; Turn on the RF power supply and adjust the voltage frequency. The RF high-voltage electrode will ionize the discharged gas, generating excited ions and electrons, etc., forming a plasma flow. Add an ionization auxiliary reagent to the top of the cotton swab, and then insert the cotton swab into the second branch pipe of the four-way pipe. The gas generated by the volatilization of the ionization auxiliary reagent enters the intersection area and mixes with the plasma to be ionized to form reagent ions; Use a cotton swab to take a sample of the sample to be tested, add a volatile auxiliary reagent to the top of the cotton swab for auxiliary analysis, and then insert the cotton swab from the branch line of the four-way pipe into the main line of the four-way pipe, and place the sample at the intersection of the three pipes; Turn on the mass spectrometer analysis system, turn on the halogen lamp, and the sample on the cotton swab evaporates to form a gas, mixes with the plasma flow and reagent ions, and undergoes proton transfer, charge transfer or molecular fragmentation to be ionized, and then is sucked into the mass spectrometer through the mass spectrometer injection tube for analysis.

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