High-coverage exhaled air detection device and exhaled air detection method

Abstract

The invention discloses a high-coverage expired gas detection device which comprises an expired gas sample gas bag, a connecting pipeline, a multi-channel valve group, a gas source, an adsorption tube, a thermal desorption cavity, a sucking pump, a reagent gas source and a photochemical ionization mass spectrometry system. In the prior art, exhaled gas sample components are complex, and direct injection mass spectrometry has the problems of competing ionization of different types of compounds, influence on sensitivity and qualitative and quantitative accuracy and the like. Therefore, a high-coverage expired gas detection technology is designed, specific types of components are enriched in sequence through ingenious connection and control of an air extracting pump, an air source, a multi-way valve and enrichment-thermal desorption, and the components are matched with corresponding photochemical ionization modes during desorption. Compared with a traditional GC separation method, the multi-channel selective enrichment-desorption sample introduction mode has the advantages of high flux and large sample introduction amount, can effectively eliminate competitive ionization and matrix effect influences generated when all components enter a mass spectrum at the same time, and improves qualitative and quantitative accuracy.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometers, and in particular, to a high-coverage exhaled breath detection device and a method for detecting exhaled breath using the device. Background Art

[0002] Exhaled breath detection has the characteristics of non-invasiveness, simple sampling, and high 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, exhaled breath metabolomics still faces many challenges for large-scale clinical applications. To ensure the reproducibility and reliability of the analysis results, it is necessary to develop high-coverage and high-throughput detection methods to achieve a comprehensive analysis of exhaled breath markers.

[0003] Direct injection mass spectrometry methods based on soft ionization technology, such as proton transfer reaction ionization mass spectrometry (PTR-MS), selected ion flow tube mass spectrometry (SIFT-MS), and photoionization chemical ionization mass spectrometry (PI / CI-MS). Direct injection mass spectrometry has the advantages of easy desorption of spectra and high sensitivity, and can achieve high-throughput detection of exhaled breath VOCs. However, for complex components, due to the absence of chromatographic separation in direct injection mass spectrometry, there are problems such as matrix interference, which affect the qualitative and quantitative analysis of compounds under complex components.

[0004] Through patent and literature retrieval, the patents related to high-coverage injection of exhaled breath retrieved are as follows: 1. A portable system for collecting samples from a subject's exhaled breath was disclosed by Sussen Sabuys Company on March 11, 2015. Detect or determine drug substances in exhaled breath. Collect samples for further analysis using mass spectrometry. This method is mainly used for total sample collection, and high-coverage measurement depends on the backend detection system. There will be problems of complex components and matrix interference for high-throughput direct injection mass spectrometry, and high-coverage analysis cannot be achieved. 2. A detection system and method for metabolic differential substances in exhaled breath were disclosed by Shenzhen Buri Biotechnology Co., Ltd. on April 15, 2022. The system includes a sampling device and a detection device; the sampling device includes an exhaled breath collector, a disposable sampling tube, and a sampling gas bag; the detection device includes a photoionization source and a mass spectrometer. This method uses a gas bag for sampling and directly analyzes it by passing it completely into the photoionization mass spectrometer. There are also problems of matrix interference of complex components, which affect qualitative and quantitative analysis, and high-coverage analysis of exhaled breath components cannot be achieved. Therefore, there is currently no report on high-throughput injection technology for exhaled breath to improve the coverage and analysis throughput of VOCs detection. Summary of the Invention

[0005] Aiming at the problems existing in the prior art, the purpose of the present invention is to provide a high-coverage exhaled breath detection device and a method for detecting exhaled breath using this device. This method can effectively eliminate the competitive ionization and matrix effects of sample components, improve the accuracy of qualitative and quantitative analysis, and can be matched with different ionization modes of photoionization mass spectrometry to obtain better detection sensitivity.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] A high-coverage exhaled breath detection device includes an exhaled breath sample gas bag, a connecting pipeline, a first multi-channel valve group, a second multi-channel valve group, a multi-way valve, a gas source, a suction pump, a reagent gas source, and an ionization mass spectrometry system;

[0008] Two or more parallel enrichment and desorption devices are arranged between the first multi-channel valve group and the second multi-channel valve group; each enrichment and desorption device includes an adsorption tube and a thermal desorption cavity, and the adsorption tube is placed in the thermal desorption cavity; the adsorption tube is filled with an adsorbent; the adsorbents filled in the parallel adsorption tubes are the same or different; there are two or more reagent gas sources, and each reagent gas source contains a different gas;

[0009] The first multi-channel valve group is provided with 2 inlets and more than 2 outlets, and any inlet and outlet can be selectively opened by electric control; the second multi-channel valve group is provided with more than 2 inlets and 2 outlets, and any inlet and outlet can be selectively opened by electric control; the multi-way valve includes more than 2 inlets and 1 outlet;

[0010] The two inlets of the first multi-channel valve group are respectively connected to the exhaled breath 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 different adsorption tube through a connecting pipeline, the outlet of an adsorption tube is respectively connected to a different inlet of the second multi-channel valve group through a connecting pipeline, and the two outlets of the second multi-channel valve group are respectively connected to the suction pump and the sample injection port of the ionization mass spectrometry system through connecting pipelines;

[0011] Each inlet of the multi-way valve is respectively connected to a different reagent gas source, and the only outlet of the multi-way valve is connected to the reagent gas injection port of the ionization mass spectrometry system through a pipeline.

[0012] Furthermore, the exhaled breath sample gas bag is a tedlar gas bag or a PEEK gas bag; the gas bag contains the exhaled breath sample; the connecting pipeline is usually made of tetrafluoroethylene, PEEK or stainless steel; the thermal desorption cavity is a closed cavity, and an electric heating device is arranged on the cavity wall to heat the adsorption tube, and the electric heating device is a resistance wire or a heating rod.

[0013] Further, the gas source is one or more of nitrogen, argon or helium gas sources with adjustable flow rate, and the flow rate is usually 5-500 mL / min.

[0014] Further, the adsorbent filled in the adsorption tube can be a porous organic polymer such as tenax to adsorb benzene series and alkanes with more than C5, or graphitized carbon black to adsorb alcohols, aldehydes and ketones with more than C5, or a molecular sieve adsorbent, such as Tsingcarbo 569 carbon molecular sieve adsorbent, which can adsorb hydrocarbons with less than C5.

[0015] Further, the first multi-channel valve group 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 multi-inlet multi-outlet valve island; when the first multi-channel valve group is composed of 1 two-way three-way valve and 1 multi-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 connecting pipelines, the outlet of the two-way three-way valve is connected to the only inlet of the multi-inlet multi-outlet valve island, and each outlet of the multi-inlet multi-outlet valve island is respectively connected to the inlet of a different adsorption tube.

[0016] The second multi-channel valve group can be composed of a number of 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 different adsorption tube (5) through pipelines, and the only outlet of the multi-inlet one-outlet valve island is connected to the inlet of the two-way three-way valve.

[0017] Further, the reagent gas source can be one or more of oxygen, nitric oxide, water vapor, dibromomethane, etc.

[0018] Further, the air pump is a diaphragm pump, a diaphragm pump, an oil pump, etc. with controllable pumping flow rate, preferably a diaphragm pump with controllable pumping flow rate; the ionization mass spectrometry system can be a photoionization mass spectrometry, a proton transfer reaction ionization mass spectrometry with a reaction reagent ion selection function, a reagent ion selectable chemical ionization mass spectrometry, etc., preferably a photoionization mass spectrometry.

[0019] A method for detecting exhaled gas by using the above high-coverage exhaled gas detection device, the specific working process of the method is as follows:

[0020] Control the inlet of the first multi-channel valve group to connect to the exhaled gas sample gas bag, and the outlet to connect to the Nth (N = 1, 2,... integer) enrichment and desorption device. Control the inlet of the second multi-channel valve group to connect to the corresponding enrichment and desorption device, and the outlet to connect to the air extraction pump. Under the action of the air extraction pump, the exhaled gas sample gas bag enters the Nth enrichment and desorption device. The adsorbent in the adsorption tube is used to specifically enrich the sample. After the sample enrichment is completed, turn on the heating device in the pyrolysis desorption cavity to heat and desorb the enriched sample. At the same time, control the inlet of the first multi-channel valve group to connect to the gas source, control the outlet of the second multi-channel valve group to connect to the sample injection port of the ionization mass spectrometry system, and control the multi-way valve to be connected to a suitable reagent gas source. The gas source carries the sample collected by the Nth enrichment and desorption device to the ionization mass spectrometry system for specific ionization and analysis, completing the enrichment, desorption of the exhaled gas sample in the Nth enrichment and desorption device, and the targeted photoionization mass spectrometry analysis;

[0021] According to the above process, select different enrichment and desorption devices and reagent gas sources, and sequentially complete the enrichment, desorption of the exhaled gas sample gas bag in different enrichment and desorption devices, and the targeted photoionization mass spectrometry analysis.

[0022] Furthermore, the adsorption time of each adsorption tube is set to 1 - 2 min, and the adsorption temperature is 25 - 50 °C; the pyrolysis desorption time is 1 - 2 min, and the desorption temperature is set to 200 - 300 °C, and the entire cycle time is 6 - 12 min.

[0023] This method can achieve the enrichment, desorption of different types of compounds in the exhaled gas sample and targeted photoionization mass spectrometry analysis, effectively eliminate the influence of competitive ionization and matrix effects caused by all components in the exhaled gas sample entering the mass spectrometry simultaneously, and can be matched with different ionization modes of photoionization mass spectrometry to obtain better detection sensitivity and analysis speed.

[0024] Compared with the prior art, the advantages of the present invention are:

[0025] The present invention cleverly connects and controls the air extraction pump, gas source, multi-way valve, enrichment-pyrolysis desorption, sequentially enriches specific types of components, and matches the corresponding photoionization mode during desorption. Compared with the traditional GC separation method, this multi-channel selective enrichment-desorption injection method has the advantages of high throughput and large injection volume, can effectively eliminate the influence of competitive ionization and matrix effects caused by all components entering the mass spectrometry simultaneously, and improve the accuracy of qualitative and quantitative analysis; and can be matched with different ionization modes of photoionization mass spectrometry to obtain better detection sensitivity. The invention has broad application prospects in the fields of exhaled gas medical diagnosis, complex gas component analysis, etc. Description of the Drawings

[0026] The accompanying drawings further illustrate the present invention, but the content in the drawings does not constitute any limitation to the present invention.

[0027] Figure 1 It is a schematic structural diagram of the high-coverage exhaled breath detection device of the present invention.

[0028] 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 an adsorption tube, 6 is a thermal desorption cavity, 7 is a second multi-channel valve group, 8 is an ionization mass spectrometry system, 9 is a reagent gas source, 10 is a suction pump, and 11 is a multi-way valve.

[0029] Figure 2 It is a schematic structural diagram of a high-coverage exhaled breath detection technology of one embodiment of the present invention.

[0030] Figure 3 It is an exhaled breath mass spectrometry diagram obtained by the high-coverage exhaled breath detection technology developed using this embodiment. Detailed implementation manners

[0031] 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 accompanying drawings and in combination with the embodiments.

[0032] 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 accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some of the embodiments of the present invention, rather than all the embodiments. The description of at least one exemplary embodiment below is actually only illustrative and in no way restrictive of the present invention and its application or use. Based on the embodiments in 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.

[0033] It should be noted that the terms used here are only for describing specific implementation manners and are not intended to limit the exemplary embodiments according to the present invention. As used here, 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 "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or their combinations.

[0034] 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, such 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, and thus, once an item is defined in one drawing, it does not need to be further discussed in subsequent drawings.

[0035] 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" are generally based on the orientation or positional relationships shown in the drawings. These are only for the convenience of describing the present invention and simplifying the description. Without contrary explanations, these orientation words do not indicate or imply that the devices or elements referred to must have a specific orientation or be constructed and operated in a specific orientation. Therefore, they 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 contours of the respective components.

[0036] As Figure 1 shown, the present invention provides a high-coverage exhaled gas detection device, which includes an exhaled gas sample gas bag 1, a connecting pipeline 2, a first multi-channel valve group 3, a second multi-channel valve group 7, a multi-way valve 11, a gas source 4, an air extraction pump 10, a reagent gas source 9, and an ionization mass spectrometry system 8.

[0037] Two or more parallel enrichment and desorption devices are arranged between the first multi-channel valve group 3 and the second multi-channel valve group 7; each enrichment and desorption device includes an adsorption tube 5 and a thermal desorption cavity 6, and the adsorption tube 5 is placed in the thermal desorption cavity 6; the adsorption tube 5 is filled with an adsorbent; the adsorbents filled in the parallel adsorption tubes 5 are the same or different; the adsorbent filled in the adsorption tube 5 can be a porous organic polymer such as tenax for adsorbing benzene series compounds and alkanes with more than C5, or graphitized carbon black for adsorbing alcohols, aldehydes, and ketones with more than C5, or a molecular sieve adsorbent, such as Tsingcarbo 569 carbon molecular sieve adsorbent, which can adsorb hydrocarbons with less than C5.

[0038] The thermal desorption cavity 6 is a closed cavity, and an electric heating device is arranged on the cavity wall to heat the adsorption tube 5. The electric heating device is a resistance wire or a heating rod.

[0039] The first multi-channel valve group 3 is provided with 2 inlets and more than 2 outlets, and 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, and any inlet and outlet can be selectively opened through electric control; the second multi-channel valve group 7 is provided with more than 2 inlets and 2 outlets, and is composed of a number of 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, and any inlet and outlet can be selectively opened through electric control.

[0040] The 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 the pipeline 2. Each outlet of the first multi-channel valve group 3 is respectively connected to the inlet of a different adsorption tube 5 through a connecting pipeline. The outlet of one adsorption tube 5 is respectively connected to a different inlet of the second multi-channel valve group 7 through a connecting pipeline. The two outlets of the second multi-channel valve group 7 are respectively connected to the sampling pump 10 and the sample injection port of the ionization mass spectrometry system 8 through connecting pipelines;

[0041] The exhaled gas sample gas bag 1 is a tedlar gas bag or a PEEK gas bag, and the exhaled gas sample is accommodated in the gas bag; the connecting pipeline 2 is made of tetrafluoroethylene, PEEK or stainless steel; the gas source 4 is one or more of nitrogen, argon or helium gas sources with adjustable flow rate, and the usually used flow rate is 5 - 500 mL / min;

[0042] Preferably, the gas source 4 is nitrogen with adjustable flow rate, and the usually used flow rate is 20 - 50 mL / min to match the mass spectrometry sample injection volume.

[0043] The sampling pump 10 is a diaphragm pump, a membrane pump, an oil pump, etc. with controllable sampling flow rate; preferably, the sampling pump 10 is a diaphragm pump with controllable sampling flow rate; the ionization mass spectrometry system 8 can be a photoionization mass spectrometry, a proton transfer reaction ionization mass spectrometry with the function of selecting reaction reagent ions, a chemical ionization mass spectrometry with selectable reagent ions, etc., and has the advantage of convenient screening of reagent ions.

[0044] There are more than 2 reagent gas sources 9, and the reagent gas sources 9 are one or more of oxygen, nitric oxide, water vapor, dibromomethane, etc., and each reagent gas source 9 contains different gases;

[0045] The multi-way valve 11 includes more than 2 inlets and 1 outlet; each inlet of the multi-way valve 11 is respectively connected to a different reagent gas source 9, and the only outlet of the multi-way valve 11 is connected to the reagent gas injection port of the ionization mass spectrometry system 8 through a pipeline.

[0046] Example 1

[0047] Such as Figure 2A high-coverage exhaled breath detection device provided by 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 multi-way valve 11, a gas source 4, a suction pump 10, a reagent gas source 9, and a photoionization mass spectrometry system 8.

[0048] Three parallel enrichment and desorption devices are arranged between the first multi-channel valve group 3 and the second multi-channel valve group 7; the first enrichment and desorption device consists of an adsorption tube 51 and a thermal desorption cavity 61. The adsorption tube 51 is filled with solid granular Tenax TA porous polymer adsorbent, and the particle size of the adsorbent is 60-80 mesh, which can enrich benzene series compounds and alkanes above C5. The adsorption tube 51 is placed in the thermal desorption cavity 61, and a heating rod is arranged on the wall of the thermal desorption cavity 61; the second enrichment and desorption device consists of an adsorption tube 52 and a thermal desorption cavity 62. The adsorption tube 52 is filled with solid granular graphitized carbon black adsorbent with a specific surface area of 70 m 2 / g, which can adsorb polar compounds such as alcohols, aldehydes, and ketones above C5. The adsorption tube 52 is placed in the thermal desorption cavity 62, and a heating rod is arranged on the wall of the thermal desorption cavity 62; the third enrichment and desorption device consists of an adsorption tube 53 and a thermal desorption cavity 63. The adsorption tube 53 is filled with solid granular Tsingcarbo569 carbon molecular sieve adsorbent with a specific surface area of 500 m 2 / g, an average pore diameter of 5-8 Å, and a bulk density of 0.5 ml / g, which can adsorb hydrocarbons below C5. The adsorption tube 53 is placed in the thermal desorption cavity 63, and a heating rod is arranged on the wall of the thermal desorption cavity 63.

[0049] The first multi-channel valve group 3 consists of a two-position three-way valve (3V100 series of Zhejiang Oulikai Pneumatic Co., Ltd.) and a 1-inlet 3-outlet valve island (2V025 series of Zhejiang Oulikai Pneumatic Co., Ltd.). The two inlets NO and NC of the two-position three-way valve of the first multi-way valve group 3 are respectively connected to the exhaled breath sample gas bag 1 and the gas source 4 through the connecting pipeline 2, and the outlet COM is connected to the only inlet of the 1-inlet 3-outlet valve island. The 3 outlets of the valve island are respectively connected to the inlets of the adsorption tubes 51, 52, and 53 through the connecting pipeline 2 passing through the walls of the thermal desorption cavities 61, 62, and 63.

[0050] The exhaled breath sample gas bag 1 is a 5L gas bag pressed by PEEK film, which accommodates the collected exhaled breath sample. The gas source 4 uses high-purity (99.999%) nitrogen as the purge and desorption carrier gas, and the purge flow rate is controlled to be 50 mL / min by a mass flow meter with a range of 100 sccm; the connecting pipeline 2 is a stainless steel pipeline with an outer diameter of 3 mm and an inner diameter of 2 mm.

[0051] The second multi-way valve group 7 consists of a two-position three-way valve (3V100 series of Zhejiang Oulekai Pneumatic Company) and a 3-inlet 1-outlet valve island (2V025 series of Zhejiang Oulekai Pneumatic Company). Among them, the 3 inlets of the 3-inlet 1-outlet valve island of the second multi-way valve group 7 are respectively connected to the outlets of the adsorption tubes 51, 52, and 53 through pipelines. The only outlet of the valve island is connected to the inlet COM terminal of the two-position three-way valve. The two outlets NO and NC of the two-position three-way valve are respectively connected to the sampling pump 10 and the sample injection port of the ionization mass spectrometry system 8.

[0052] The desorption sampling pump 10 is a diaphragm pump with controllable pumping flow rate. The flow rate is controlled to be 100 mL / min by a mass flow meter with a range of 500 sccm. The ionization mass spectrometry system 8 uses a photoionization time-of-flight mass spectrometer.

[0053] Three reagent gas sources are correspondingly set, namely 91, 92, and 93. Among them, the reagent gas source 91 is a dibromomethane reagent gas with 1000 ppmv balance gas of nitrogen. The flow rate is controlled to be 100 mL / min by a mass flow meter with a range of 500 sccm. Using dibromomethane reagent ions, efficient ionization of benzene series compounds and alkanes above C5 is achieved; the reagent gas source 92 is high-purity helium (99.999%). The flow rate is controlled to be 100 mL / min by a mass flow meter with a range of 500 sccm, and water vapor with a flow rate of 100 mL / min is generated by the bubbling method for the ionization of polar compounds such as alcohols, aldehydes, and ketones above C5; the reagent gas source 93 is high-purity oxygen (99.999%). The flow rate is controlled to be 100 mL / min by a mass flow meter with a range of 500 sccm for the ionization of hydrocarbons below C5.

[0054] The multi-way valve 11 is a 3-inlet 1-outlet valve island (2V025 series of Zhejiang Oulekai Pneumatic Company). Among them, the 3 inlets of the valve island are respectively connected to the reagent gas sources 91, 92, and 93 through pipelines. The only outlet of the valve island is connected to the reagent gas injection port of the photoionization time-of-flight mass spectrometer 8 through a pipeline.

[0055] Example 2

[0056] Using the method for detecting exhaled breath by the high-coverage exhaled breath detection device provided in Example 1 (i.e., Figure 2 )

[0057] First, control the inlet of the first multi-channel valve group 3 to be connected to the exhaled gas sample bag 1, and the outlet to be connected to the first enrichment and desorption device. Control the inlet of the second multi-channel valve group 7 to be connected to the first enrichment and desorption device, and the outlet to be connected to the air extraction pump 10. Start the air extraction pump 10. Under the action of the air extraction pump 10, the exhaled gas sample 1 enters the adsorption tube 51 of the first enrichment and desorption device through the connecting pipeline. Set the temperature of the pyrolysis desorption cavity 61 to 35 °C, and perform adsorption enrichment for 1.5 min. The adsorbent 51 is used for targeted enrichment of the high-efficiency ionization of benzene series compounds and alkanes with more than C5; after the sample enrichment is completed, switch the position of the two-way three-way valve, control the inlet of the first multi-channel valve group 3 to be connected to the gas source 4, control the outlet of the second multi-channel valve group 7 to be connected to the sample inlet of the photoionization time-of-flight mass spectrometer 8, and control the temperature of the pyrolysis desorption cavity 61 to 250 °C for heating and desorption. Thus, the gas source 4 can carry the sample collected by the first enrichment and desorption device through pyrolysis desorption to the photoionization time-of-flight mass spectrometer 8. At the same time, control the inlet of the multi-way valve 11 to be connected to the reagent gas source 91, and use dibromomethane reagent ions to complete the specific ionization and analysis of the exhaled gas sample after enrichment and desorption in the first enrichment and desorption device. The pyrolysis desorption and analysis time is 1.5 min, and the total detection time is 3 min;

[0058] Select the second enrichment and desorption device and the third enrichment and desorption device in turn according to the above process to enrich and desorb the exhaled gas sample respectively. During the mass spectrometry analysis of the exhaled gas sample enriched and desorbed in the second enrichment and desorption device, control the inlet of the multi-way valve 11 to be connected to the reagent gas source 92, and use helium reagent ions to complete the specific ionization and analysis of the exhaled gas sample after enrichment and desorption in the second enrichment and desorption device; during the mass spectrometry analysis of the exhaled gas sample enriched and desorbed in the third enrichment and desorption device, control the inlet of the multi-way valve 11 to be connected to the reagent gas source 93, and use oxygen reagent ions to complete the specific ionization and analysis of the exhaled gas sample after enrichment and desorption in the third enrichment and desorption device. After going through the above detection process in turn, the enrichment, desorption and targeted photoionization mass spectrometry analysis of different types of compounds in the exhaled gas sample can be realized.

[0059] The set adsorption time for each adsorbent is 1.5 min; the desorption time is 1.5 min, the temperature during adsorption is 35 °C; the temperature during desorption is set to 250 °C, and the entire cycle time is 9 min.

[0060] Finally, add the intensities of the spectra obtained from the three process analyses to obtain as Figure 3The high coverage spectrum of exhaled breath shown in the figure shows that the technology can achieve high coverage ionization and detection of more than 150 compounds within a mass-to-charge ratio of 200, and can also perform quantitative analysis on individual spectrum components, and integrate the quantitative results of each sequence to obtain the overall compound concentration data. The present invention can effectively eliminate the competitive ionization and matrix effect caused by all components entering the mass spectrometer at the same time, and can match different ionization modes of photochemical ionization mass spectrometry to obtain better detection sensitivity and analysis speed, with high coverage and sensitivity, and has broad application prospects in the field of exhaled breath detection and analysis.

[0061] 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.

[0062] 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 it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, 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 high-coverage exhaled breath detection device, 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 multi-way valve (11), a gas source (4), an air extraction pump (10), a reagent gas source (9), and an ionization mass spectrometry system (8); It is characterized in that: Two or more parallel enrichment and desorption devices are arranged between the first multi-channel valve group (3) and the second multi-channel valve group (7); each enrichment and desorption device includes an adsorption tube (5) and a thermal desorption cavity (6), and the adsorption tube (5) is placed in the thermal desorption cavity (6); an adsorbent is filled in the adsorption tube (5); the adsorbents filled in the parallel adsorption tubes (5) are the same or different; two or more reagent gas sources (9) are provided, and each reagent gas source (9) contains different gases; The first multi-channel valve group (3) is provided with 2 inlets and more than 2 outlets, the second multi-channel valve group (7) is provided with more than 2 inlets and 2 outlets, and the multi-way valve (11) includes more than 2 inlets and 1 outlet; 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 different adsorption tube (5) through a connecting pipeline, the outlet of an adsorption tube (5) is respectively connected to a different inlet of the second multi-channel valve group (7) through a connecting pipeline, and the two outlets of the second multi-channel valve group (7) are respectively connected to the sample inlet of the air extraction pump (10) and the ionization mass spectrometry system (8) through connecting pipelines; Each inlet of the multi-way valve (11) is respectively connected to a different reagent gas source (9), and the only outlet of the multi-way valve (11) is connected to the reagent gas inlet of the ionization mass spectrometry system (8) through a pipeline.

2. The exhaled breath detection device according to claim 1, It is characterized in that: The adsorbent filled in the adsorption tube (5) can be a porous organic polymer such as tenax to adsorb benzene series and alkanes with more than C5, or graphitized carbon black to adsorb alcohols, aldehydes and ketones with more than C5, or a molecular sieve adsorbent, such as Tsingcarbo 569 carbon molecular sieve adsorbent, which can adsorb hydrocarbons with less than C5.

3. The exhaled breath detection device according to claim 1, It is characterized in that: The thermal desorption cavity (6) is a closed cavity, and an electric heating device is arranged on the cavity wall to heat the adsorption tube (5), and the electric heating device is a resistance wire or a heating rod.

4. The exhaled breath detection device according to claim 1, It is 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.

5. The exhaled breath detection device according to claim 1, It is characterized in that: The gas source (4) is one or more of nitrogen, argon, or helium gas sources with adjustable flow rates, and the commonly used flow rate is 5 - 500 mL / min; the reagent gas source (9) can be one or more of oxygen, nitric oxide, water vapor, dibromomethane, etc.

6. According to the sequential injection technique described in 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 multi-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 exhaled breath detection technique described in claim 1, characterized in that: When the first multi-channel valve group (3) is composed of 1 two-way three-way valve and 1 multi-inlet multi-outlet valve island, the two inlets of the two-way three-way valve are respectively connected to the exhaled breath sample gas bag (1) and the gas source (4) through pipelines (2), the outlet of the two-way three-way valve is connected to the only inlet of the multi-inlet multi-outlet valve island, and each outlet of the multi-inlet multi-outlet valve island is respectively connected to the inlet of a different adsorption tube (5); When the second multi-channel valve group (7) 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 different adsorption tube (5) through pipelines, and the only outlet of the multi-inlet one-outlet valve island is connected to the inlet of the two-way three-way valve.

8. According to the exhaled breath detection device described in claim 1, characterized in that: The air extraction pump (10) is a diaphragm pump, a membrane pump, an oil pump, etc. with controllable air extraction flow rate; the ionization mass spectrometry system (8) can be photoionization mass spectrometry, proton transfer reaction ionization mass spectrometry with reaction reagent ion selection function, reagent ion selectable chemical ionization mass spectrometry, etc.

9. A method for detecting exhaled breath using the high-coverage exhaled breath detection device according to any one of claims 1 - 8, characterized in that: The specific working process of the method is as follows: Control 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 Nth (N = 1, 2,... integer) enrichment and desorption device. Control the inlet of the second multi-channel valve group (7) to be connected to the corresponding enrichment and desorption device, and the outlet to be connected to the air extraction pump (10). The exhaled breath sample gas bag (1) enters the Nth enrichment and desorption device under the action of the air extraction pump (10). The adsorbent in the adsorption tube (5) is used to specifically enrich the sample. After the sample enrichment is completed, turn on the heating device in the thermal desorption cavity (6) to heat and desorb the enriched sample. At the same time, control the inlet of the first multi-channel valve group (3) to be connected to the gas source (4), control the outlet of the second multi-channel valve group (7) to be connected to the sample inlet of the ionization mass spectrometry system (8), and control the multi-way valve (11) to be connected to a suitable reagent gas source (9). The gas source (4) carries the sample collected by the Nth enrichment and desorption device to the ionization mass spectrometry system (8) for specific ionization and analysis, completing the enrichment, desorption of the exhaled breath sample in the Nth enrichment and desorption device, and the targeted photoionization mass spectrometry analysis. According to the above process, different enrichment and desorption devices and reagent gas sources (9) are selected, and the enrichment, desorption of the exhaled gas sample gas bag (1) in different enrichment and desorption devices, and targeted ionization mass spectrometry analysis are completed in sequence.

10. The method according to claim 9, wherein: This method can achieve the enrichment, desorption and targeted ionization mass spectrometry analysis of different types of compounds in the exhaled gas sample, can effectively eliminate the influence of competitive ionization and matrix effect caused by all components in the exhaled gas sample entering the mass spectrometry simultaneously, and can be matched with different ionization modes of photoionization mass spectrometry to obtain better detection sensitivity and analysis speed.

Images