Sequential sampling device for expired gas detection and analysis method

Abstract

The invention discloses a sequential sampling device for expired gas detection. The sequential sampling device comprises an expired gas sample, a connecting pipeline, a first multi-channel valve group, a second multi-channel valve group, a gas source, a compound removal device, a quantitative loop, a sucking pump and a direct sampling mass spectrum system. The problem that qualitative and quantitative accuracy is affected due to competitive ionization of different types of compounds when a complex exhaled gas sample is analyzed by direct injection mass spectrometry is solved. Therefore, a sequential sampling technology is designed, specific types of components are sequentially removed through ingenious connection and control of an air pump, an air source, a multi-way valve, a compound removal device and a quantitative loop, and then the components enter a direct mass spectrum to be analyzed. Compared with a traditional GC separation method, the multi-channel selective removal sample introduction mode has the advantages of high flux and large sample introduction amount, competitive ionization and matrix effect influences generated when all components enter an ionization area at the same time can be effectively eliminated, and qualitative and quantitative accuracy is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometers, and particularly to a sequential injection device for exhaled breath detection and a method for performing sequential injection analysis on exhaled breath samples using the device. Background Art

[0002] Exhaled breath detection has the characteristics of non-invasiveness, simple sampling, and fast speed, and has unique advantages in non-invasive and high-throughput diagnosis of diseases, and is used to deeply study many endogenous biochemical processes and disease causes in the human body. Exhaled breath metabolomics has demonstrated excellent discrimination ability and great clinical application prospects in the diagnosis of major diseases such as tuberculosis, COPD, and lung cancer. However, there are still many challenges in the large-scale clinical application of exhaled breath metabolomics. To ensure the reproducibility and reliability of analysis results, it is necessary to develop high-coverage and high-throughput detection methods to achieve a comprehensive analysis of exhaled breath markers.

[0003] Through patent and literature retrieval, the patents related to exhaled breath injection found are as follows: 1. Suzhou Medicon Import and Export Co., Ltd. applied for and disclosed a nasal oxygen tube with an ETCO2 sampling port on February 14, 2012, for non-invasive continuous sampling of exhaled breath carbon dioxide while supplying oxygen to monitor the alveolar carbon dioxide pressure or concentration of patients. However, these methods cannot improve the high-coverage and high-throughput measurement of VOCs in exhaled breath, and there is no report on high-throughput injection technology for exhaled breath to improve the coverage and analysis throughput of VOCs detection. Summary of the Invention

[0004] Aiming at the defects of the prior art, the purpose of the present invention is to provide a sequential injection device for exhaled breath detection and a method for performing sequential injection analysis on exhaled breath using the device, which can effectively eliminate the competitive ionization and matrix effects of sample components and improve the accuracy of qualitative and quantitative analysis.

[0005] To achieve the above purpose, the present invention adopts the following technical solutions:

[0006] A sequential injection device for exhaled breath detection includes an exhaled breath sample gas bag, a connecting pipeline, a first multi-channel valve group, a second multi-channel valve group, a gas source, a compound removal device, a quantitative loop, a suction pump, and a direct injection mass spectrometry system; the first multi-channel valve is provided with two inlets and more than two outlets, and any inlet and outlet can be selectively opened by electric control; the second multi-channel valve is provided with more than two inlets and two outlets, and any inlet and outlet can be selectively opened by electric control; between the first multi-channel valve group and the second multi-channel valve group, more than two parallel compound removal devices are provided, and different types of compound removal materials are placed in each of the parallel compound removal devices for the removal of different compounds.

[0007] The two inlets of the first multi-channel valve group are respectively connected to the exhaled gas sample gas bag and the gas source through pipelines. Each outlet of the first multi-channel valve group is respectively connected to the inlet of a compound removal device through a pipeline. The outlet of each compound removal device is respectively connected to an inlet of the second multi-channel valve group through a quantitative loop after passing through a pipeline. The two outlets of the second multi-channel valve group are respectively connected to the inlet of the direct injection mass spectrometry system and the suction port of the suction pump through pipelines.

[0008] Further, the compound removal device is a sealed container, in which compound removal materials can be placed. The compound removal materials can be one or more of a packed column, a polymer removal tube, a solid particle adsorbent, etc.

[0009] Further, the packed column placed in the compound removal device can be 2,4-dinitrophenylhydrazine (DNPH) for the removal of aldehyde and ketone compounds. When the polymer removal tube is placed in the compound removal device, the material of the removal tube can be perfluorosulfonic acid-based polymer for the removal of water and ammonia. When the solid particle adsorbent is placed in the compound removal device, the adsorbent can be granular diethanolamine, soda lime, etc. for the removal of acid compounds.

[0010] Further, the exhaled gas sample gas bag is a tedlar gas bag or a PEEK gas bag for accommodating the exhaled gas sample; the connecting pipelines are usually made of tetrafluoroethylene, PEEK or stainless steel; the gas source is one or more of nitrogen, argon or helium with adjustable flow rate, and the usually used flow rate is 5 - 500 mL / min.

[0011] Further, the quantitative loop is usually made of tetrafluoroethylene, PEEK or stainless steel, and the volume of the quantitative loop is 2 - 50 mL.

[0012] Further, the first multi-channel valve group is composed of several two-way three-way valves connected in series in sequence or composed of 1 two-way three-way valve and 1 one-inlet multi-outlet valve island. When the first multi-channel valve group is composed of 1 two-way three-way valve and 1 one-inlet multi-outlet valve island, the two inlets of the two-way three-way valve are respectively connected to the exhaled gas sample gas bag and the gas source through pipelines, the outlet of the two-way three-way valve is connected to the only inlet of the one-inlet multi-outlet valve island, and each outlet of the one-inlet multi-outlet valve island is respectively connected to the inlet of a compound removal device.

[0013] The second multi-channel valve group can be composed of several two-way three-way valves connected in series in sequence or composed of 1 multi-inlet one-outlet valve island and 1 two-way three-way valve. When the second multi-channel valve group is composed of 1 multi-inlet one-outlet valve island and 1 two-way three-way valve, each inlet of the multi-inlet one-outlet valve island is respectively connected to the outlet of a compound removal device through a pipeline, and the only outlet of the multi-inlet one-outlet valve island is connected to the inlet of the two-way three-way valve.

[0014] Further, the air extraction pump is a diaphragm pump, a membrane pump, an oil pump, etc. with controllable air extraction flow rate; preferably, the air extraction pump is a diaphragm pump with controllable air extraction flow rate, and the direct injection mass spectrometry system is a photoionization mass spectrometry, a proton transfer reaction ionization mass spectrometry, a selected ion flow tube reaction ionization mass spectrometry, a chemical ionization mass spectrometry, etc.

[0015] The present invention also provides a method for analyzing exhaled breath by using the above sequential injection device, and the specific analysis process is as follows:

[0016] Control the inlet of the first multi-channel valve group to connect to the exhaled breath sample gas bag, and the outlet is connected to the inlet of the Nth (N = 1, 2,... integer) compound removal device through a connecting pipeline. The outlet of the compound removal device is connected to the Nth quantitative loop; control the inlet of the second multi-channel valve group to connect to the Nth quantitative loop, and the outlet is connected to the air extraction pump. The exhaled breath sample gas bag enters the Nth compound removal device under the action of the air extraction pump, and the compounds in the sample are specifically removed by the compound removal device. The removed sample is collected through the Nth quantitative loop; after the sample collection is completed, control the inlet of the first multi-channel valve group to connect to the gas source, and control the outlet of the second multi-channel valve group to connect to the inlet of the direct injection mass spectrometry system. The gas source carries the sample collected by the Nth quantitative loop into the direct injection mass spectrometry system for specific mass spectrometry analysis, and completes the removal of the exhaled breath sample in the Nth compound removal device and the mass spectrometry analysis of the remaining compounds;

[0017] Then, according to the above process, sequentially select other different compound removal devices, and sequentially complete the removal of the exhaled breath sample in different compound removal devices and the targeted mass spectrometry analysis of the remaining compounds.

[0018] The removal time of a single compound removal device is 0.1 - 1 min, and the mass spectrometry acquisition time of the remaining compounds after passing through a single compound removal device is 0.1 - 2 min.

[0019] This method can achieve the removal of different types of compounds in the exhaled breath sample and the analysis of the remaining compounds, can effectively eliminate the competitive ionization and matrix effect caused by all components in the exhaled breath sample entering the mass spectrometry simultaneously, and does not sacrifice the high detection sensitivity and analysis speed of the direct injection mass spectrometry.

[0020] Compared with the prior art, the advantages of the present invention are as follows: through the ingenious connection and control of the air extraction pump, the gas source, the multi-way valve, the compound removal device and the quantitative loop, the present invention removes specific types of components and then enters the direct mass spectrometry analysis, with the advantages of high throughput and large sample injection volume. It can not only effectively eliminate the competitive ionization and matrix effect generated when all components enter the ionization region simultaneously, improve the accuracy of qualitative and quantitative analysis, but also does not sacrifice the high detection sensitivity of the direct mass spectrometry. This technology has broad application prospects in the fields of exhaled breath medical diagnosis, complex gas component analysis, etc. Brief Description of the Drawings

[0021] The drawings further illustrate the present invention, but the content in the drawings does not constitute any limitation to the present invention.

[0022] Figure 1 It is a schematic structural diagram of a sequential injection device for exhaled breath detection provided by the present invention;

[0023] Among them, 1 is an exhaled breath sample gas bag, 2 is a connecting pipeline, 3 is a first multi-channel valve group, 4 is a gas source, 5 is a compound removal device, 6 is a quantitative loop, 7 is a second multi-channel valve group, 8 is a direct injection mass spectrometry system, and 9 is a suction pump.

[0024] Figure 2 It is a schematic structural diagram of a sequential injection device for exhaled breath detection in Embodiment 1 of the present invention;

[0025] Figure 3 It is a mass spectrometry diagram of the real exhaled breath obtained by sequential injection analysis of the exhaled breath in Example 3. Detailed Embodiments

[0026] It should be noted that, without conflict, the embodiments in the present invention and the features in the embodiments can be combined with each other. The present invention will be described in detail below with reference to the drawings and in combination with the embodiments.

[0027] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. The description of at least one exemplary embodiment below is actually only illustrative and in no way restricts the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0028] It should be noted that the terms used here 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 form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0029] Unless otherwise specifically stated, the relative arrangements, numerical expressions, and numerical values of the components and steps set forth in these embodiments do not limit the scope of the present invention. At the same time, it should be clear that, for the sake of convenience of description, the dimensions of the various parts shown in the drawings are not drawn in actual proportional relationships. Technologies, methods, and devices known to those of ordinary skill in the relevant art may not be discussed in detail, but where appropriate, the said technologies, methods, and devices should be regarded as part of the authorized specification. In all the examples shown and discussed here, any specific values should be construed as merely exemplary and not as a limitation. Therefore, other examples of the exemplary embodiments may have different values. It should be noted that: Similar reference numerals and letters denote similar items in the following drawings. Therefore, once an item is defined in one drawing, it does not need to be further discussed in subsequent drawings.

[0030] In the description of the present invention, it should be understood that the orientation or positional relationships indicated by orientation words such as "front, rear, upper, lower, left, right", "lateral, vertical, perpendicular, horizontal", and "top, bottom", etc. are generally based on the orientation or positional relationships shown in the drawings. It is only for the convenience of describing the present invention and simplifying the description. Without contrary instructions, these orientation words do not indicate and imply that the device or element referred to must have a specific orientation or be constructed and operated in a specific orientation. Therefore, it should not be construed as limiting the protection scope of the present invention: The orientation words "inside, outside" refer to the inside and outside relative to the contour of each component itself.

[0031] As Figure 1 shown, the present invention provides a sequential injection device for exhaled breath detection, including an exhaled breath sample gas bag 1, a connecting pipeline 2, a first multi-channel valve group 3, a second multi-channel valve group 7, a gas source 4, a compound removal device 5, a quantitative loop 6, a suction pump 9, and a direct injection mass spectrometry system 8;

[0032] The first multi-channel valve 3 is provided with two inlets and more than two outlets, and any inlet and outlet can be selectively opened by electric control; the second multi-channel valve 7 is provided with more than two inlets and two outlets, and any inlet and outlet can be selectively opened by electric control; More than two parallel compound removal devices 5 are arranged between the first multi-channel valve group 3 and the second multi-channel valve group 7. Different types of compound removal materials are placed in each of the parallel compound removal devices 5 for the removal of different compounds.

[0033] Two inlets of the first multi-channel valve group 3 are respectively connected to the exhaled gas sample gas bag 1 and the gas source 4 through pipelines 2. Each outlet of the first multi-channel valve group 3 is respectively connected to the inlet of a compound removal device 5 through a pipeline. The outlet of each compound removal device 5 is respectively connected to an inlet of a second multi-channel valve group 7 through a pipeline after passing through a quantitative loop 6. Two outlets of the second multi-channel valve group 7 are respectively connected to the injection port of the direct injection mass spectrometry system 8 and the pumping port of the air extraction pump 9 through pipelines.

[0034] Further, the compound removal device 5 is a sealed container, in which a compound removal material can be placed. The compound removal material can be one or more of a packed column, a polymer removal tube, and a solid particle adsorbent.

[0035] Further, when a packed column is placed in the compound removal device 5, the packing material can be 2,4-dinitrophenylhydrazine (DNPH) for removing aldehyde and ketone compounds; when a polymer removal tube is placed in the compound removal device 5, the tube material can be a perfluorosulfonic acid-based polymer for removing water and ammonia; when a solid particle adsorbent is placed in the compound removal device 5, the adsorbent can be granular diethanolamine, soda lime, etc. for removing acid compounds.

[0036] Further, the exhaled gas sample gas bag 1 is a tedlar gas bag or a PEEK gas bag for containing the exhaled gas sample; the connecting pipeline 2 is usually made of tetrafluoroethylene, PEEK or stainless steel; the quantitative loop 6 is usually made of tetrafluoroethylene, PEEK or stainless steel, and the volume of the quantitative loop is 2 - 50 mL.

[0037] Preferably, the gas bag for placing the exhaled gas sample 1 is a PEEK gas bag; the connecting pipeline 2 is made of stainless steel; the quantitative loop 6 is made of stainless steel, and the volume of the quantitative loop is 5 mL.

[0038] Further, the gas source 4 is one or more of a nitrogen gas source, an argon gas source or a helium gas source with adjustable flow rate, and the usually used flow rate is 5 - 500 mL / min.

[0039] Preferably, the gas source 4 is a nitrogen gas source with adjustable flow rate, and the usually used flow rate is 20 - 50 mL / min.

[0040] Further, the first multi-channel valve group 3 is composed of a number of two-way three-way valves connected in series in sequence or composed of 1 two-way three-way valve and 1 one-inlet multi-outlet valve island; when the first multi-channel valve group is composed of 1 two-way three-way valve and 1 one-inlet multi-outlet valve island, the two inlets of the two-way three-way valve are respectively connected to the exhaled gas sample gas bag and the gas source through pipelines, the outlet of the two-way three-way valve is connected to the only inlet of the one-inlet multi-outlet valve island, and each outlet of the one-inlet multi-outlet valve island is respectively connected to the inlet of a compound removal device;

[0041] The second multi-channel valve group 7 can be composed of several two-way three-way valves connected in series in sequence or composed of one multi-inlet and one-outlet valve island and one two-way three-way valve; when the second multi-channel valve group is composed of one multi-inlet and one-outlet valve island and one two-way three-way valve, each inlet of the multi-inlet and one-outlet valve island is respectively connected to the outlet of a compound removal device through a pipeline, and the only outlet of the multi-inlet and one-outlet valve island is connected to the inlet of the two-way three-way valve.

[0042] Furthermore, the air extraction pump 9 is a diaphragm pump, a membrane pump, an oil pump, etc. with controllable air extraction flow; the direct injection mass spectrometry system 8 is a photoionization mass spectrometry, a proton transfer reaction ionization mass spectrometry, a selected ion flow tube reaction ionization mass spectrometry, a chemical ionization mass spectrometry, etc.

[0043] Preferably, the air extraction pump 9 is a diaphragm pump with controllable air extraction flow; the direct injection mass spectrometry system 8 is a photoionization mass spectrometry or a proton transfer reaction ionization mass spectrometry.

[0044] Example 1

[0045] As Figure 2 shown, Figure 2 A sequential injection device for exhaled breath detection according to the present invention includes an exhaled breath sample gas bag 1, a connecting pipeline 2, a first multi-channel valve group 3, a second multi-channel valve group 7, a gas source 4, a compound removal device 5, a quantitative loop 6, an air extraction pump 9, and a direct injection mass spectrometry system 8;

[0046] The first multi-channel valve 3 is provided with two inlets and three outlets, and any inlet and outlet can be selectively opened through electric control; the second multi-channel valve 7 is provided with three inlets and two outlets, and any inlet and outlet can be selectively opened through electric control; three parallel compound removal devices 51, 52, and 53 are arranged between the first multi-channel valve group 3 and the second multi-channel valve group 7;

[0047] The first multi-channel valve 3 is composed of a two-way three-way valve (3V100 series of Zhejiang Oulikai Pneumatic Company) and a 1-inlet and 3-outlet valve island (2V025 series of Zhejiang Oulikai Pneumatic Company). Among them, the two inlet ends of the two-way three-way valve of the first multi-channel valve group 3 are respectively connected to the exhaled breath sample gas bag 1 and the gas source 4 through the connecting pipeline 2, the outlet end is connected to the only inlet of the 1-inlet and 3-outlet valve island, and the 3 outlets of the valve island are respectively connected to the inlets of the compound removal devices 51, 52, and 53 through the connecting pipeline 2. The outlets of the compound removal devices 51, 52, and 53 are respectively connected to the inlets of the quantitative loops 61, 62, and 63 through pipelines;

[0048] Three different types of compound removal materials are placed in the compound removal devices 51, 52, and 53 respectively. Among them, a packed column is placed in the compound removal device 51, and the packing material is 1000 mg of 2,4-dinitrophenylhydrazine (DNPH), which can remove aldehyde and ketone compounds; a polymer removal tube is placed in the compound removal device 52. The removal tube selects the MD-050 series of Bochen Company, a 30-cm-long perfluorosulfonic acid-based polymer Nafion tube, which can remove a large amount of water and ammonia in exhaled breath; a solid particle adsorbent is placed in the compound removal device 53, and the adsorbent is 50 g of analytical pure calcium oxide (CaO) particles, which can remove acid compounds.

[0049] The exhaled breath sample gas bag 1 uses a PEEK film to press a gas bag with a volume of 5 L. The gas bag contains the collected exhaled breath sample to be measured. The purge and desorption gas source 4 uses high-purity (99.999%) nitrogen, and the purge flow rate is controlled to 50 mL / min by a mass flow meter with a range of 100 sccm.

[0050] The quantitative loops 61, 62, and 63 are all 20-mL stainless steel quantitative loops.

[0051] The second multi-channel valve group 7 is composed of a 3-in-1-out valve island (2V025 series of Zhejiang Oulekai Pneumatic Company) and a two-way three-way valve (3V100 series of Zhejiang Oulekai Pneumatic Company). Among them, the 3 inlets of the 3-in-1-out valve island of the second multi-way valve group 7 are connected to the outlets of the quantitative loops 61, 62, and 63 respectively through pipelines. The only outlet of the valve island is connected to the inlet end of the two-way three-way valve, and the two outlet ends of the two-way three-way valve are respectively connected to the sampling pump 9 and the photoionization chemical ionization mass spectrometry system 8.

[0052] The sampling pump 9 is a diaphragm pump with a controllable pumping flow rate. The flow rate is controlled to 100 mL / min by a mass flow meter with a range of 500 sccm. The photoionization chemical ionization mass spectrometry system 8 uses a photoionization time-of-flight mass spectrometer PI-TOFMS.

[0053] Example 2

[0054] In this example, the sequential injection device provided in Example 1 is used to analyze exhaled breath. The specific process is as follows:

[0055] First, the inlet of the first multi-channel valve group 3 is controlled to be connected to the exhaled breath sample bag 1, and the outlet is connected to the inlet of the first compound removal device 51, and the inlet of the second multi-channel valve group 7 is controlled to be connected to the outlet of the first quantitative loop 61, and the outlet is connected to the suction pump 9. The exhaled breath sample enters the first compound removal device 51 under the action of the suction pump 9, and the sample is subjected to aldehyde and ketone compound removal by the first compound removal device 51 and collected by the first quantitative loop 61. This process lasts for 0.5 minutes to complete the collection of the remaining compound samples in the exhaled breath sample; then the inlet of the first multi-channel valve group 3 is controlled to be connected to the gas source 4, and the outlet of the second multi-channel valve group 7 is controlled to be connected to the direct injection mass spectrometry system 8. The gas source 4 carries the sample collected by the first quantitative loop 6 to the direct injection mass spectrometry system 8 for analysis of the remaining compounds in the sample, and mass spectrometry signal acquisition is performed at the same time. The acquisition time is 1 minute, and the total time for removal and mass spectrometry analysis by a single compound removal device is 1.5 minutes;

[0056] According to the above process, the second compound removal device 52 and the third compound removal device 53 are selected in sequence to remove the compounds in the exhaled breath sample and analyze the remaining compounds, respectively, so that the aldehydes, ketones, water, ammonia, and acid compounds in the exhaled breath sample can be removed in sequence and analyzed by mass spectrometry.

[0057] The total time for removal and mass spectrometry analysis of a single compound removal device is 1.5 minutes; the entire detection and analysis cycle time is 4.5 minutes.

[0058] Finally, the spectra obtained by the three sequence analyses are summed up to obtain the following Figure 3 The exhaled breath mass spectrometry signals shown in the figure show that this method can be used to achieve highly sensitive detection of dozens of compounds in exhaled breath, such as acetone, isoprene, acetic acid, ethanol, dimethyl sulfide, allyl methyl sulfide, limonene, etc. It has high coverage and sensitivity and has broad application prospects in the field of medical diagnosis based on exhaled breath detection.

[0059] The technical principle of the present invention is described above in conjunction with specific embodiments. These descriptions are only for explaining the principle of the present invention and cannot be interpreted as limiting the scope of protection of the present invention in any way. Based on the explanations herein, those skilled in the art can associate other specific embodiments of the present invention without creative work, and these equivalent variations or substitutions are all included in the scope defined by the claims of this application.

[0060] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A sequential injection device for exhaled breath detection, comprising an exhaled breath sample gas bag (1), a connecting pipeline (2), a first multi-channel valve group (3), a second multi-channel valve group (7), a gas source (4), a compound removal device (5), a quantitative loop (6), a suction pump (9) and a direct injection mass spectrometry system (8); Characterized in that: The first multi-channel valve (3) is provided with two inlets and more than two outlets, the second multi-channel valve (7) is provided with more than two inlets and two outlets, and more than two parallel compound removal devices (5) are arranged between the first multi-channel valve group (3) and the second multi-channel valve group (7), and different types of compound removal materials are placed in each of the parallel compound removal devices (5) for the removal of different compounds; The two inlets of the first multi-channel valve group (3) are respectively connected to the exhaled breath sample gas bag (1) and the gas source (4) through pipelines (2), each outlet of the first multi-channel valve group (3) is respectively connected to the inlet of a compound removal device (5) through a pipeline, the outlet of each compound removal device (5) is respectively connected to an inlet of the second multi-channel valve group (7) through a pipeline via a quantitative loop (6), and the two outlets of the second multi-channel valve group (7) are respectively connected to the injection port of the direct injection mass spectrometry system (8) and the suction port of the suction pump (9) through pipelines.

2. The sequential injection device according to claim 1, Characterized in that: The compound removal device (5) is a sealed container in which compound removal materials can be placed, and the compound removal materials can be one or more of a packed column, a polymer removal tube, a solid particle adsorbent, etc.

3. The sequential injection device according to claim 2, Characterized in that: The packed column can be a 2,4-dinitrophenylhydrazine (DNPH) packed column for the removal of aldehyde and ketone compounds; the polymer removal tube can be a perfluorosulfonic acid-based polymer removal tube for the removal of water and ammonia; the solid particle adsorbent can be a solid particle adsorbent such as diethanolamine and soda lime for the removal of acid compounds.

4. The sequential injection device according to claim 1, Characterized in that: The exhaled breath sample gas bag (1) is a tedlar gas bag or a PEEK gas bag; the connecting pipeline (2) is usually made of tetrafluoroethylene, PEEK or stainless steel; the quantitative loop (6) is usually made of tetrafluoroethylene, PEEK or stainless steel, and the volume of the quantitative loop is 2 - 50 mL.

5. The sequential injection device according to claim 1, Characterized in that: The gas source (4) is one or more of nitrogen, argon or helium with adjustable flow rate, and the usually used flow rate is 5 - 500 mL / min.

6. The sequential injection device according to claim 1, Characterized in that: The first multi-channel valve group (3) is composed of several two-way three-way valves connected in series in sequence or composed of 1 two-way three-way valve and 1 one-inlet multi-outlet valve island; the second multi-channel valve group (7) can be composed of several two-way three-way valves connected in series in sequence or composed of 1 multi-inlet one-outlet valve island and 1 two-way three-way valve.

7. According to the sequential injection technique of claim 1, It is characterized in that: The air extraction pump (9) is one or more of a diaphragm pump, a membrane pump, an oil pump, etc. with controllable air extraction flow rate; the direct injection mass spectrometry system (8) is a photoionization mass spectrometry, a proton transfer reaction ionization mass spectrometry, a selected ion flow tube reaction ionization mass spectrometry, a chemical ionization mass spectrometry, etc.

8. A method for analyzing exhaled breath by using the sequential injection device according to any one of claims 1-7, It is characterized in that: The analysis process of the method is as follows: controlling the inlet of the first multi-channel valve group (3) to be connected to the exhaled breath sample gas bag (1), and the outlet to be connected to the inlet of the Nth (N = 1, 2,... integer) compound removal device (5) through a pipeline, and the outlet of the compound removal device (5) to be connected to the Nth quantitative loop (6); controlling the inlet of the second multi-channel valve group (7) to be connected to the Nth quantitative loop (6), and the outlet to be connected to the air extraction pump (9), and the exhaled breath sample gas bag (1) enters the Nth compound removal device (5) under the action of the air extraction pump (9), and the compounds in the sample are specifically removed by the compound removal device (5), and the removed sample is collected through the Nth quantitative loop (6); after the sample collection is completed, controlling the inlet of the first multi-channel valve group (3) to be connected to the gas source (4), and controlling the outlet of the second multi-channel valve group (7) to be connected to the injection port of the direct injection mass spectrometry system (8), and the gas source (4) carries the sample collected by the Nth quantitative loop (6) into the direct injection mass spectrometry system (8) for specific mass spectrometry analysis, completing the removal of the exhaled breath sample in the Nth compound removal device (5) and the mass spectrometry analysis of the remaining compounds; According to the above process, different compound removal devices (5) are selected to sequentially complete the removal of the exhaled breath sample in different compound removal devices (5) and the targeted mass spectrometry analysis of the remaining compounds.

9. According to the method described in claim 8, It is characterized in that: This method can realize the removal of different types of compounds in the exhaled breath sample and the analysis of the remaining compounds, can effectively eliminate the influence of competitive ionization and matrix effect caused by all components in the exhaled breath sample entering the mass spectrometry at the same time, and does not sacrifice the high detection sensitivity and analysis speed of the direct injection mass spectrometry.

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