Titration ion mobility spectrometry for detecting nitric oxide in exhaled gas

Abstract

The utility model relates to a titration ion mobility spectrometry for detecting nitric oxide (NO) in exhaled air and application thereof, the titration ion mobility spectrometry comprises an exhaled air sampling device, an ion migration tube, a titration reagent generating device and a data acquisition system, and used titration reagent molecules are reagent molecules which can react with water molecules but not react with O2-molecules, such as analytically pure-grade p-benzoquinone (PBQ), p-benzoquinone, p-benzoquinone, p-benzoquinone, p-benzoquinone, p-benzoquinone, p-benzoquinone, p-benzoquinone, p-benzoquinone, p-benzoquinone and p-benzoquinone. According to the present invention, high humidity in exhaled gas can be removed through titration during the detection process, and the titration reaction with the reacted reagent ion O < 2-> is continuously performed so as to eliminate the influence of the humidity in the exhaled gas and simplify the influence of the ion mobility spectrometry without any sample pretreatment process, and the detection sensitivity of the NO in the exhaled gas is as low as 3.83 ppbv; the quantitative equation of NO under 100% relative humidity is y = 0.68 x + 0.91, the linear range is 10-200 ppbv, the relative standard deviation (RSD) is 3.83%, and high-sensitivity detection of trace NO in exhaled air can be realized through the ion mobility spectrometry of the titration reaction.

Description

Technical Field

[0001] The utility model belongs to the field of analytical chemical instruments, and in particular relates to a titration ion migration spectrum for detecting NO in exhaled breath. Background Art

[0002] Exhaled nitric oxide (NO) is a signaling molecule produced by NO synthase in epithelial cells, endothelial cells, and inflammatory cells in the respiratory bronchial and alveolar regions. Its content is directly related to the degree of inflammation in the respiratory tract and can be used as a non-invasive biomarker for respiratory diseases. Literature shows that excessive NO in exhaled air is often associated with different types of diseases, including chronic obstructive pulmonary disease (COPD), acute lung injury, primary ciliary dyskinesia, and asthma. Therefore, the detection of NO in exhaled air is of great significance. However, the content of NO in exhaled air is extremely low, about ppbv level, and its own chemical properties are unstable, and it is easily oxidized to nitrogen dioxide (NO2). It is quite difficult to detect NO under high humidity conditions in exhaled air. Despite this, researchers have never stopped developing its detection methods over the past few decades.

[0003] So far, the chemiluminescence method of interaction with ozone is recognized as the standard method for detecting NO in exhaled breath. Its principle is that light of a specific wavelength will be emitted during the reaction between NO and ozone, and qualitative and quantitative analysis will be performed according to the wavelength and intensity of the light. This method has high sensitivity, with a detection limit of up to 1 ppb and a response time of less than 1 s. However, this method requires the use of a molybdenum-containing reactor to reduce all nitrogen oxides (NOx) in the exhaled breath to NO before detection, which increases the complexity of the operation, the volume and cost of the instrument, making it difficult to carry and miniaturize the instrument. In addition, the reaction of NO and ozone is easily interfered by substances such as ammonia, hydrogen sulfide, water vapor and carbon dioxide, which will affect the accuracy of the detection. Therefore, chemiluminescence technology is not suitable as an online detection technology for NO in the exhaled breath of patients during clinical surgery. Electrochemical sensors can use chemical reagents to convert the concentration of NO into a detectable electrical signal, which is another widely used detection technology. It can be made into a portable and miniaturized instrument, such as the handheld sensor NIOX-MINO. However, its shortcomings cannot be ignored, such as relatively low sensitivity, long reaction time, and sensitivity of only 5 ppb within 30 s reaction time. In addition, the service life of electrochemical reagents is limited, and they need to be replaced every 100-300 tests. This will increase the cost of using the instrument, resulting in poor instrument repeatability and unsuitable for long-term stable use. A series of detection methods based on the development of laser technology, such as tunable semiconductor laser absorption spectroscopy (TDLAS) and quantum cascade laser technology (QCL), have recently been widely developed and applied to the detection of ppb-level NO. It can perform highly sensitive detection of exhaled NO in a short response time, with a detection sensitivity of up to 0.1 ppb within 1 s. However, the high price, attenuation of the laser light source, and poor reproducibility make these methods only suitable for use in laboratories and cannot be applied to actual clinical detection.

[0004] Ion mobility spectrometry has many advantages such as high sensitivity, fast detection speed, simple operation, easy miniaturization and low cost, and has been widely used in clinical exhaled breath detection. However, the water vapor content in exhaled breath is as high as 6%. High humidity will not only reduce the detection sensitivity of IMS, but also produce other related interference peaks, making the spectrum complex, which is not conducive to the qualitative and quantitative analysis of the analyte. Therefore, the premise of using IMS to detect NO in exhaled breath is to reduce the interference of humidity. So far, hydrophobic polydimethylsiloxane (PDMS) membrane, MCC technology or gas chromatography are the dehumidification or separation technologies favored by researchers. However, these methods require a long separation time: the PDMS membrane requires a separation reaction time of about 100s, while the entire detection time of GC or MCC takes longer, up to more than 600s, which will limit its application in clinical detection. Utility Model Content

[0005] In view of the problems existing in the prior art, the purpose of the utility model is to provide a titration ion mobility spectrometer for detecting nitric oxide in exhaled breath. The titration ion mobility spectrometer adopts suitable titration reagent molecules to realize the processing of the sample in the chemical ionization process in the ionization-reaction zone, shielding or eliminating the influence of interference caused by up to 100% relative humidity in the exhaled breath on the detection, realizing high-sensitivity detection of NO in exhaled breath, and applying it to continuous online monitoring in clinical surgery.

[0006] In order to achieve the above purpose, the utility model adopts the following technical solutions:

[0007] A titration ion mobility spectrometer for detecting exhaled nitric oxide, comprising an exhaled breath sampling device, an ion migration tube, a titration reagent generating device, a data acquisition system,

[0008] The exhaled air sampling device comprises an air sampling pump 1, a sampling quantitative bottle 2, a first three-way two-position solenoid valve 3, a second three-way two-position solenoid valve 4, an exhaled air sampler 7, and a sampling port 6 of the exhaled air sampler, wherein the sampling quantitative bottle 2 is a closed container, and an exhaled air inlet and an exhaled air outlet are respectively arranged at upper and lower relative positions on its side wall surface, the exhaled air inlet is connected to the outlet of the exhaled air sampler 7 through a pipeline, and the sampling port 6 of the exhaled air sampler is arranged at a relative position of the outlet of the exhaled air sampler 7; the side wall surface of the sampling quantitative bottle 2 is relatively A purge carrier gas inlet and an exhaled breath sample outlet are respectively arranged at the positions, the purge carrier gas inlet of the sampling and quantitative bottle 2 is connected to the first outlet of the second three-way two-position solenoid valve 4, the inlet of the second three-way two-position solenoid valve 4 is connected to the purge carrier gas source, the second outlet of the second three-way two-position solenoid valve 4 is connected to the second inlet of the first three-way two-position solenoid valve 3 through a pipeline, the first inlet of the first three-way two-position solenoid valve 3 is connected to the exhaled breath sample outlet of the sampling and quantitative bottle 2, and the outlet of the first three-way two-position solenoid valve 3 is connected to the inlet of the ion migration tube;

[0009] The ion transfer tube includes a photoionization source and a Faraday plate 14 which are arranged opposite to each other at the left and right ends, and an ion gate located between the photoionization source and the Faraday plate 14. The area between the photoionization source and the ion gate is an ion molecule reaction area 8, and the area between the ion gate and the Faraday plate 14 is a migration area 9. The Faraday plate 14 is connected to a data acquisition system through an amplifier 15.

[0010] An inlet is provided at the left end of the ion transfer tube near the photoionization source, a titration reagent molecule inlet is provided on the upper wall of the ion transfer tube near the photoionization source, and an air outlet 16 is provided on the upper wall of the ion transfer tube near the ion gate, and the air outlet 16 is connected to the atmosphere through a vacuum pump;

[0011] A drift gas inlet 12 is provided above the Faraday disk 14 at the right end of the ion transfer tube, and the drift gas inlet 12 is connected to a drift gas source through a pipeline;

[0012] The titration reagent generating device comprises a sealed container and a reagent bottle. The reagent bottle has an opening on the top and a silicone bottle cap with a through hole at the opening. The reagent bottle is filled with titration reagent molecules and the reagent bottle is placed in the sealed container. Two interfaces are arranged on the top of the sealed container, which are respectively connected to the titration reagent molecule inlet of the ion migration tube and the carrier gas source through pipelines.

[0013] An electric heating device is arranged on the outer side of the bottom of the sealed container of the titration reagent generating device. The electric heating device is a heating film, a resistance wire or a heating rod.

[0014] The photoionization source is 63 Ni ionization source (555MBq), the heating temperature of the electric heating device is 30-60℃.

[0015] The titration reagent used is a molecule that reacts with water molecules but not with O2 - Reagent molecules for molecular reactions, such as analytical grade p-benzoquinone (PBQ, 99%).

[0016] The electron affinity of the titration reagent molecule is higher than that of O2 in negative ion mode - The electron affinity of the reagent ion is lower than that of the product ion NO2 of the analyte NO. - The electron affinity of 2.28 eV.

[0017] The purge carrier gas, titration reagent molecule purge carrier gas and float gas are all clean air that has been purified by silica gel, activated carbon and 13X molecular sieve in sequence.

[0018] The invention discloses an application of titration ion mobility spectrometry for detecting exhaled nitric oxide in improving the detection sensitivity of exhaled nitric oxide (NO). The working mode of the titration ion mobility spectrometry is negative ion mode.

[0019] The specific detection process is as follows:

[0020] 1) During the sampling process, the first three-way two-position solenoid valve is connected to the second inlet, the second three-way two-position solenoid valve is connected to the second outlet, and the air extraction sampling pump is started. The tester first takes a deep breath of purified clean air and then exhales toward the sampling port of the exhaled breath sampler. Under the action of the sampling pump, the exhaled breath sample enters the sampling quantitative bottle, and at the same time, another purge carrier gas enters the migration spectrometer tube through the second outlet of the second three-way two-position solenoid valve, the second inlet and outlet of the first three-way two-position solenoid valve, so as to ensure that the migration tube is clean and the air pressure in the tube is stable;

[0021] 2) In the sampling detection process, the first three-way two-position solenoid valve is switched to be connected to the first inlet, and the second three-way two-position solenoid valve is connected to the first outlet. The exhaled breath sample in the sampling quantitative bottle enters the ion migration tube under the carrier action of the purge carrier gas, and reacts with the titration reagent molecules to obtain the migration spectrum of nitric oxide (NO) in the exhaled breath.

[0022] During the detection process, the detection conditions of the ion migration tube are as follows: Step 1) During the sampling process, the flow rate of the vacuum sampling pump is 500-1000ml min -1 , step 2) during the sample injection test, the electric field strength of the migration tube is: 200-450V cm -1 The temperature of the migration tube is 30-80℃, the concentration of the titration reagent molecules entering the ion mobility spectrometry reaction zone is 1-3ppm, and the flow rate of the purge carrier gas is 200-500ml min -1 The flow rate of the drift gas is 500-850 ml / min, and the injection flow rate of the ion migration tube is 200-500 ml min -1 .

[0023] The concentration of the titration reagent molecules can be calculated by adjusting the size of the hole on the silica gel bottle cap and using the weighing method. The specific operation method is to purge with clean air at a constant flow rate, and mix with the gaseous titration reagent molecules diffused from the reagent bottle. After a certain period of time, the weight loss of the reagent bottle is obtained by weighing. The formula is as follows:

[0024] Where C is the concentration of the titrant molecule (ppbv), M is the molar mass of the titrant molecule (g mol -1 ), f is the flow rate of the purge carrier gas of the titration reagent molecules (L min-1), t is the purge time of the purge carrier gas, m is the weight loss of the reagent bottle during the period t (g), and T is the heating temperature of the reagent bottle (K). Finally, by adjusting f, gaseous samples of titration reagent molecules with different concentrations can be obtained.

[0025] Compared with the prior art, the advantages of the utility model are: ion mobility spectrometry has many advantages such as high sensitivity, fast detection speed, simple operation, easy miniaturization and low cost, and is very suitable for clinical exhaled breath detection. PBQ is used to successfully titrate and transform humidity-related interference peaks, without the need for complex sample pretreatment, and the interference of humidity in exhaled breath is eliminated online, achieving accurate qualitative identification and detection of exhaled NO. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1The utility model is a structural schematic diagram of a titration ion migration spectrometer for improving NO sensitivity in exhaled breath, wherein 1 is an air extraction sampling pump, 2 is a sampling quantitative bottle, 3 is a first three-way two-position solenoid valve, 4 is a second three-way two-position solenoid valve, 5 is a purge carrier gas, 6 is a sampling port of an exhaled breath sampler, 7 is an exhaled breath sampler, 8 is an ion molecule reaction zone, 9 is a migration zone, 10 is a titration reagent molecule purge carrier gas, 11 is a reagent bottle in a titration reagent molecule generating device, 12 is a floating gas inlet, 13 is a heating and heat preservation sleeve, 14 is a Faraday disk, 15 is an amplifier, and 16 is an air outlet.

[0027] Figure 2 Schematic diagram of the exhaled NO sampling and injection detection process, where (a) is a schematic diagram of the sampling process, and (b) is a schematic diagram of the injection detection process.

[0028] Figure 3 The ion migration spectra of standard NO (50 ppbv) at 100% RH detected by conventional ion migration spectrometry and ion migration spectrometry of the titration reagent in the utility model in Comparative Example 1, wherein (a) is the ion migration spectra of NO detected by conventional ion migration spectrometry, and (b) is the ion migration spectra of NO detected by the ion migration spectrometry of the titration reagent in the utility model.

[0029] Figure 4 This is the standard quantitative curve of exhaled NO at 100% RH humidity.

[0030] Figure 5 The ion mobility spectra of NO in the exhaled breath of a healthy volunteer are detected by using the ion mobility spectra of the titration reagent in the utility model and the traditional ion mobility spectrometry in Example 2 and Comparative Example 2, respectively; wherein (a) is the ion mobility spectra of NO when the traditional ion mobility spectrometry is used for detection, and (b) is the ion mobility spectra of NO when the ion mobility spectrometry of the titration reagent in the utility model is used for detection. DETAILED DESCRIPTION

[0031] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0032] like Figure 1 As shown, the utility model provides a titration ion mobility spectrometer for detecting exhaled nitric oxide, including an exhaled breath sampling device, an ion migration tube, a titration reagent generating device, and a data acquisition system.

[0033] The exhaled air sampling device comprises an air extraction sampling pump 1, a sampling quantitative bottle 2, a first three-way two-position solenoid valve 3, a second three-way two-position solenoid valve 4, an exhaled air sampler 7, and a sampling port 6 of the exhaled air sampler, wherein the sampling quantitative bottle 2 is a closed container, and an exhaled air inlet and an exhaled air outlet are respectively arranged at upper and lower relative positions on its side wall surface, the exhaled air inlet is connected to the outlet of the exhaled air sampler 7 through a pipeline, and the sampling port 6 of the exhaled air sampler is arranged at a relative position to the outlet of the exhaled air sampler 7; the side wall surface of the sampling quantitative bottle 2 is arranged at the upper and lower relative positions on the side wall surface of the sampling quantitative bottle 2. A clean air purge carrier gas inlet and an exhaled breath sample outlet are respectively arranged at the positions, the clean air purge carrier gas inlet is connected to the outlet of the second three-way two-position solenoid valve 4, the first inlet of the second three-way two-position solenoid valve 4 is connected to the clean air purge carrier gas source, the second inlet of the second three-way two-position solenoid valve 4 is connected to the second outlet of the first three-way two-position solenoid valve 3 through a pipeline, the inlet of the first three-way two-position solenoid valve 3 is connected to the exhaled breath sample outlet, and the first outlet of the first three-way two-position solenoid valve 3 is connected to the injection port of the ion migration tube;

[0034] The ion transfer tube includes a photoionization source and a Faraday plate 14 which are arranged opposite to each other at the left and right ends, and an ion gate located between the photoionization source and the Faraday plate 14. The area between the photoionization source and the ion gate is an ion molecule reaction area 8, and the area between the ion gate and the Faraday plate 14 is a transfer area 9.

[0035] An inlet is provided at the left end of the ion transfer tube near the photoionization source, a titration reagent molecule inlet is provided on the upper wall of the ion transfer tube near the photoionization source, and an air outlet 16 is provided on the upper wall of the ion transfer tube near the ion gate, and the air outlet 16 is connected to the atmosphere through a vacuum pump;

[0036] A drift gas inlet 12 is provided above the Faraday disk 14 at the right end of the ion transfer tube, and the drift gas inlet 12 is connected to a drift gas source through a pipeline;

[0037] The titration reagent generating device comprises a sealed container and a reagent bottle. The reagent bottle has an opening on the top and a silicone bottle cap with a through hole at the opening. The reagent bottle is filled with titration reagent molecules and the reagent bottle is placed in the sealed container. Two interfaces are arranged on the top of the sealed container, which are respectively connected to the titration reagent molecule inlet of the ion migration tube and the carrier gas source through pipelines.

[0038] The photoionization source is 63 Ni ionization source (555MBq); the titration reagent molecule is analytical grade p-benzoquinone (PBQ, 99%); the carrier gas and the float gas are clean air purified by silica gel, activated carbon and 13X molecular sieve in sequence; the electric heating device is a heating film, and the heating temperature is 30-60°C.

[0039] Comparative Example 1

[0040] The results of the detection of standard NO (50 ppbv) at 100% RH using conventional ion mobility spectrometry and the titration ion mobility spectrometry in the utility model application were compared.

[0041] The exhaled breath sampling device, ion migration tube and data acquisition system of the conventional ion migration spectrometer are the same as those of the ion migration spectrometer in the utility model application, and the difference from the ion migration spectrometer in the utility model application is that the titration reagent generating device is not included.

[0042] The specific detection process is as follows: (1) Sampling process: keep the first three-way two-position solenoid valve connected to the second inlet, the second three-way two-position solenoid valve connected to the second outlet, start the air sampling pump, and draw 100% RH NO sample gas into the sampling quantitative bottle. The sampling time is 4 seconds, and the flow rate of the air sampling pump is 1000 ml min -1 At the same time, another purge carrier gas enters the migration spectrometer tube through the second outlet of the second three-way two-position solenoid valve (4) and the second inlet and outlet of the first three-way two-position solenoid valve (3) to ensure that the migration tube is clean and the gas pressure in the tube is stable. The flow rate of the purge carrier gas is 400 ml min -1 ;like Figure 2 (a)

[0043] (2) Sampling test process: the first three-way two-position solenoid valve is switched to be connected to the first inlet, and the second three-way two-position solenoid valve is switched to be connected to the first outlet. The exhaled breath sample in the sampling quantitative bottle enters the ion transfer tube for detection under the action of the purge carrier gas. Figure 2 (b)

[0044] The working mode of ion mobility spectrometry is negative ion mode, and the electric field strength of the migration tube is: 350Vcm -1 The temperature of the migration tube was 40°C and the flow rate of the purge gas was 400 ml min -1 The flow rate of the drift gas is 800 ml / min, and the flow rate of the reagent molecule purge gas is 200 ml min -1 The concentration of the titration reagent molecules entering the ion mobility spectrometry reaction zone is 2ppm, and the injection flow rate of the ion mobility tube is 300ml min -1 , the sampling time is 3s, and the migration spectrum of nitric oxide (NO) in exhaled breath is obtained.

[0045] The migration spectrum of traditional ion mobility spectrometry, such as Figure 3As shown in (a); due to the high humidity in the NO sample gas at 100% RH, the high humidity participates in the ion-molecule reaction, and the migration times of the three interference peaks related to humidity are 7.72ms, 8.00ms and 8.24ms, respectively. They are all located near the RIP peak (8.52ms) and the PIP peak of NO (7.68ms), which seriously interferes with the accurate qualitative identification of the NO ion peak. In the negative ion mode, substances are successively reacted by the reactive ion O2 based on their electron affinity (EA). – Ionization and the corresponding product ions are generated, and substances with higher EA are ionized first. Under high humidity conditions, it is very difficult to accurately identify and quantify NO in the negative ion mode of traditional ion mobility spectrometry.

[0046] The migration spectrum detected by the titration ion migration spectrometry in the utility model application is shown in 3(b). The RIP (O2 – ) has been completely converted into the titration reagent ion peak (PIP) of PBQ, the migration time of which is 9.60 ms and the reduced mobility K0 is 1.93 cm 2 V -1 s -1 , the product ion corresponding to PBQ is C6H4O2(H2O) n – The product ion of NO is still NO2, the same as that of conventional ion mobility spectrometry. – Therefore, the introduction of the titration reagent PBQ can reduce the generation of interfering ions related to water vapor. The three interfering peaks (7.72ms, 8.00ms and 8.24ms) that interfere with NO identification disappear during direct detection, and will not affect the detection of NO. The migration spectrum obtained by the detection is significantly simplified, and the PIP (7.68ms) of NO can be clearly and accurately identified.

[0047] Example 1

[0048] Quantitative analysis of 100% RH NO by ion mobility spectrometry. NO standard samples with different concentrations, including 10ppb, 20ppb, 40ppb, 60ppb, 80ppb, 100ppb, 120ppb, 150ppb, 180ppb, 200ppb, and 220ppb, were tested under 100% RH conditions. During the test, standard samples of different concentrations were obtained by diluting a certain volume of 0.1% NO (N2 standard gas containing 0.1% NO) with clean wet air at 100% RH. The volume of the dilution glass bottle used to prepare the sample was 600mL. A certain volume of 0.1% NO standard sample and 100% RH clean wet air were drawn with a glass syringe, injected into the dilution bottle, and left to stand for about 5 minutes. After mixing, the sample enters the quantitative bottle under the action of the sampling pump and is carried by the carrier gas into the IMS detection. The quantitative curve of NO in the exhaled breath can be obtained with the concentration of 100% RH NO as the horizontal axis and the signal intensity of NO as the vertical axis, as shown in the figure: Figure 4 As shown, the quantitative equation is y=0.68x+0.91, as shown in Table 1, wherein x is the concentration of NO in exhaled breath, in ppbv, and y is the signal intensity of NO, in mV.

[0049] Table 1. Quantitative equations for exhaled NO at 100% RH

[0050]

[0051]

[0052] Example 2

[0053] The titration ion mobility spectrometry in the utility model application was used to detect the NO content in the exhaled breath of a healthy volunteer, aged 24 years old. (1) Sampling process: Keep the first three-way two-position solenoid valve connected to the second inlet, and the second three-way two-position solenoid valve connected to the second outlet. The volunteer first takes a deep breath of purified clean air and then exhales toward the sampling port of the exhaled breath sampler. Start the air sampling pump. Start sampling at the 5th second of the volunteer's exhalation. The sampling time is 4 seconds. The volunteer's exhaled air is sucked into the sampling quantitative bottle. The flow rate of the air sampling pump is 1000ml min -1 At the same time, another purge carrier gas enters the migration spectrometer tube through the second outlet of the second three-way two-position solenoid valve, the second inlet and outlet of the first three-way two-position solenoid valve to ensure the cleanliness of the migration tube and the stability of the gas pressure in the tube. The flow rate of the purge carrier gas is 400 ml min -1 (2) Sampling test process: switch the first three-way two-position solenoid valve to communicate with the first inlet, and the second three-way two-position solenoid valve to communicate with the first outlet, and the exhaled breath sample in the sampling quantitative bottle enters the ion transfer tube for detection under the carrier action of the purge carrier gas;

[0054] The working mode of ion mobility spectrometry is negative ion mode, and the electric field strength of the migration tube is: 350Vcm -1 The temperature of the migration tube was 40°C and the flow rate of the purge gas was 400 ml min -1 The flow rate of the drift gas is 800 ml / min, and the flow rate of the reagent molecule purge gas is 200 ml min -1 The concentration of the titration reagent molecules entering the ion mobility spectrometry reaction zone is 2ppm, and the injection flow rate of the ion mobility tube is 300ml min -1 , the sampling time is 3s, and the migration spectrum of nitric oxide (NO) in exhaled breath is obtained, such as Figure 5 As shown in (b), the signal intensity of NO in the exhaled breath is 45.6 mV. Through the quantitative equation of NO in the exhaled breath y=0.68x+0.91, the concentration of NO in the exhaled breath of the volunteer is obtained to be 65 ppb.

[0055] Comparative Example 2

[0056] The content of NO in the exhaled breath of healthy volunteers in Example 2 was detected by conventional ion mobility spectrometry (no titration of ion reagents during the detection process). The difference from Example 2 is that no titration of ion reagents was involved in the detection process. The other processes were the same as in Example 2. The migration spectrum of nitric oxide (NO) in the exhaled breath was obtained by detection, as shown in FIG. Figure 5 As shown in (a); the signal intensity of NO in exhaled breath is 11.8 mV. Through the quantitative equation of NO in exhaled breath y=0.68x+0.91, the concentration of NO in the exhaled breath of the volunteer is obtained to be 9 ppbv.

[0057] pass Figure 5 (a) and Figure 5 It can be clearly observed in (b) that the PIP of NO in the exhaled breath is located at 7.68 ms. However, the signal intensity of NO in the exhaled breath detected by the titration ion mobility spectrometry in the present application in Example 2 is significantly higher than the signal intensity of NO in the exhaled breath detected by the ordinary ion mobility spectrometry in Comparative Example 2. In addition, the interference peaks of common substances in the exhaled breath such as acetone, amines and alcohols disappear in Example 2, and will not interfere with the detection.

Claims

1. A titration ion mobility spectrometer for detecting exhaled nitric oxide, characterized in that: Including exhaled breath sampling device, ion migration tube, titration reagent generator, data acquisition system, The exhaled air sampling device comprises an air extraction sampling pump (1), a sampling quantitative bottle (2), a first three-way two-position solenoid valve (3), a second three-way two-position solenoid valve (4), an exhaled air sampler (7), and a sampling port (6) for the exhaled air sampler, wherein the sampling quantitative bottle (2) is a closed container, and an exhaled air inlet and an exhaled air outlet are respectively arranged at upper and lower relative positions on the side wall surface of the sampling quantitative bottle, the exhaled air inlet is connected to the outlet of the exhaled air sampler (7) through a pipeline, and the sampling port (6) for the exhaled air sampler is arranged at a position relative to the outlet of the exhaled air sampler (7); the sampling quantitative bottle (2) has a left side wall surface and a right side wall surface. A purge carrier gas inlet and an exhaled gas sample outlet are respectively arranged at the right relative positions, the purge carrier gas inlet of the sampling and quantitative bottle (2) is connected to the first outlet of the second three-way two-position solenoid valve (4), the inlet of the second three-way two-position solenoid valve (4) is connected to the purge carrier gas source, the second outlet of the second three-way two-position solenoid valve (4) is connected to the second inlet of the first three-way two-position solenoid valve (3) through a pipeline, the first inlet of the first three-way two-position solenoid valve (3) is connected to the exhaled gas sample outlet of the sampling and quantitative bottle (2), and the outlet of the first three-way two-position solenoid valve (3) is connected to the inlet of the ion migration tube; The ion transfer tube comprises a photoionization source and a Faraday plate (14) which are arranged opposite to each other at the left and right ends respectively, and an ion gate located between the photoionization source and the Faraday plate (14); the area between the photoionization source and the ion gate is an ion molecule reaction area (8); the area between the ion gate and the Faraday plate (14) is a transfer area (9); and the Faraday plate (14) is connected to a data acquisition system via an amplifier (15); An inlet is provided at the left end of the ion transfer tube near the photoionization source, a titration reagent molecule inlet is provided on the upper wall of the ion transfer tube near the photoionization source, and an air outlet (16) is provided on the upper wall of the ion transfer tube near the ion gate, and the air outlet (16) is connected to the atmosphere through an air pump; A drift gas inlet (12) is provided above the Faraday disk (14) at the right end of the ion transfer tube, and the drift gas inlet (12) is connected to a drift gas source through a pipeline; The titration reagent generating device comprises a sealed container and a reagent bottle. The reagent bottle has an opening on the top and a silicone bottle cap with a through hole at the opening. The reagent bottle is filled with titration reagent molecules and the reagent bottle is placed in the sealed container. Two interfaces are arranged on the top of the sealed container, which are respectively connected to the titration reagent molecule inlet of the ion migration tube and the carrier gas source through pipelines.

2. The titration ion mobility spectrometry according to claim 1, characterized in that: An electric heating device is arranged on the outer side of the bottom of the sealed container of the titration reagent generating device. The electric heating device is a heating film, a resistance wire or a heating rod.

3. The titration ion mobility spectrometry according to claim 1, characterized in that: The photoionization source is 555 MBq 63 Ni ionization source, the heating temperature of the electric heating device is 30-60 ℃.

4. The titration ion mobility spectrometry according to claim 1, characterized in that: The titration reagent used is a molecule that reacts with water molecules but not with O2 - Reagent molecules for molecular reactions.

5. The titration ion mobility spectrometry according to claim 1, characterized in that: The titration reagent used was p-benzoquinone of analytical grade.

6. The titration ion mobility spectrometry according to claim 1, characterized in that: The electron affinity of the titration reagent molecule is higher than that of O2 in negative ion mode - The electron affinity of the reagent ion is lower than that of the product ion NO2 of the analyte NO. - The electron affinity is 2.28 eV.

7. The titration ion mobility spectrometry according to claim 1, characterized in that: The purge carrier gas, titration reagent molecule purge carrier gas and float gas are all clean air that has been purified by silica gel, activated carbon and 13X molecular sieve in sequence.

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