Semiconductor refrigeration and dehumidification ion mobility spectrometry for detecting NO in exhaled gas

Abstract

The utility model relates to a semiconductor refrigeration and dehumidification ion mobility spectrometry for detecting NO (nitric oxide) in exhaled air, which comprises an ion migration tube, a sampling nozzle, a three-way electromagnetic valve, a semiconductor refrigeration and dehumidification device, a first mass flow meter, an air exhaust sampling pump, a second mass flow meter, a two-stage dehumidification filter, a three-way connector and a data acquisition system. According to the present invention, the exhaled gas is subjected to refrigeration dehumidification through the semiconductor, the interference of high humidity in the exhaled gas is eliminated, no sample pretreatment or other processes is required, the high sensitivity detection of the exhaled gas NO can be achieved, the quantitative equation of the exhaled gas NO under the relative humidity of 95% is y = 0.48 x + 4.95, the linear range is 10-150 ppbv, the quantitative detection limit is 3.63 ppbv, and the method is used for the detection of the exhaled gas NO of the patient during the clinical operation process.

Description

Technical Field

[0001] This invention belongs to the field of analytical chemistry instruments, specifically relating to a semiconductor cooling dehumidification ion mobility spectrometer for detecting NO in exhaled breath. Background Technology

[0002] Ion mobility spectrometry (IMS) boasts numerous advantages, including high sensitivity, fast detection speed, simple operation, easy miniaturization, and low cost, and has been widely applied in clinical exhaled breath detection. However, exhaled breath contains up to 6% water vapor. High humidity not only reduces the detection sensitivity of IMS but also generates other related interference peaks, complicating the spectrum and hindering qualitative and quantitative analysis of analytes. Therefore, reducing humidity interference is a prerequisite for using IMS to detect NO in exhaled breath. To date, hydrophobic polydimethylsiloxane (PDMS) membranes, MCC technology, or gas chromatography are favored dehumidification or separation techniques by researchers. However, these methods require relatively long separation times: PDMS membranes require approximately 100 seconds of separation reaction time, while the entire detection time for GC or MCC can be even longer, exceeding 600 seconds. These limitations restrict their application in clinical testing.

[0003] While nonsteady-state dilution ion mobility spectrometry (NMP) can achieve online monitoring of exhaled NO and has been successfully applied to the detection of exhaled NO in healthy individuals, and can be combined with a 2CM model to analyze the distribution and source of NO in the respiratory system, it still suffers from insufficient sensitivity when applied to the detection of exhaled NO in patients during clinical surgery. Intraoperative patients' exhaled air originates from the lower respiratory tract (alveoli), where NO content is extremely low. After mixing and diluting with the air in the ventilator, the concentration is even lower, increasing the difficulty of detection. Furthermore, nonsteady-state dilution ion mobility spectrometry uses radioactive... 63 Ni ionization sources, to some extent, limit their application in clinical practice. Therefore, developing a method based on non-radioactive ionization sources to enhance the sensitivity of exhaled NO detection is of great significance for intraoperative IMS monitoring of exhaled NO in clinical practice. Eliminating issues such as humidity interference encountered in photoionization detection of exhaled NO is also an urgent problem to be solved. Utility Model Content

[0004] To address the problems existing in the prior art, the purpose of this utility model application is to provide a semiconductor cooling dehumidification ion mobility spectrometry for detecting exhaled NO. This ion mobility spectrometry includes a semiconductor cooling dehumidification device designed based on the Peltier effect. Based on the difference in liquefaction temperature between the substance and water vapor, water vapor in the exhaled breath sample can be separated from the target substance. Through semiconductor cooling and the unsteady dilution effect of drift gas, the influence of water vapor in the exhaled breath sample on the detection can be reduced online, and highly sensitive quantitative detection of exhaled NO can be achieved.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A semiconductor-cooled dehumidified ion mobility spectrometer for detecting exhaled NO includes an ion mobility tube, a sampling nozzle, a three-way solenoid valve, a semiconductor-cooled dehumidification device, a first mass flow meter, an air sampling pump, a second mass flow meter, a two-stage dehumidification filter, a three-way connector, and a data acquisition system.

[0007] The semiconductor cooling and dehumidification device is a sealed cavity. On the two opposite side walls of the cavity, there are semiconductor cooling plates for cooling and electric heating plates for heating. An air inlet for the semiconductor cooling and dehumidification device is set on the upper bottom surface of the cavity. The air inlet of the semiconductor cooling and dehumidification device is connected to the sampling nozzle through a three-way solenoid valve and a sampling tube. An air outlet for the semiconductor cooling and dehumidification device is set on the lower bottom surface of the cavity. The air outlet of the semiconductor cooling and dehumidification device is connected to the ion migration tube through a pipeline.

[0008] An upper baffle plate, parallel to the left and right side walls, is vertically downwards on the upper bottom surface of the cavity. An airflow channel is formed between the top of the upper baffle plate and the lower bottom surface. A lower baffle plate, parallel to the upper baffle plate, is vertically upwards on the lower bottom surface of the cavity. The lower baffle plate and the upper baffle plate are alternately arranged. An airflow channel is formed between the top of the lower baffle plate and the upper bottom surface of the cavity. A gas cooling channel is formed between the upper bottom surface, side walls, upper baffle plate, lower baffle plate, and lower bottom surface of the cavity. Hydrophobic particles are filled in the gas cooling channel.

[0009] The ion migration tube includes a photoionization source and a Faraday disk arranged opposite each other at the left and right ends, and an ion gate located between the photoionization source and the Faraday disk. The region between the photoionization source and the ion gate is the ion molecular reaction region, and the region between the ion gate and the Faraday disk is the migration region. The Faraday disk is connected to the data acquisition system through an amplifier.

[0010] An ion migration tube inlet is provided on the upper wall of the reaction zone of the ion migration tube near the ion gate. The ion migration tube inlet is connected to the outlet of the semiconductor refrigeration dehumidification device through a connecting pipe.

[0011] An ion migration tube outlet is provided on the upper wall of the reaction zone of the ion migration tube near the photoionization source. The ion migration tube outlet is connected to the inlet of the sampling pump through a first mass flow meter. A drift gas inlet is provided above the Faraday disk at the right end of the ion migration tube. The drift gas inlet is connected to the outlet of the sampling pump through a pipeline via a second mass flow meter, a three-way connector, and a two-stage dehumidification filter.

[0012] Furthermore, the hydrophobic particles are hydrophobic microspheres, and the materials of the hydrophobic microspheres are polytetrafluoroethylene, polypropylene, nylon 66, and perfluoroethylene propylene, with a particle size of 3-5 cm.

[0013] Furthermore, the upper and lower partitions are made of stainless steel or aluminum, and the distance between adjacent upper and lower partitions is 3-7 centimeters.

[0014] Furthermore, the two-stage dehumidification filter consists of two sealed containers, each filled with a molecular sieve. One dehumidification filter contains alumina molecular sieve, while the other contains silica molecular sieve. The dehumidification filters are primarily used to remove H₂O, CO₂, and hydrocarbons with a critical diameter of 10 Å from the adsorbed gas, thus purifying and drying the air. The gas filtered through the two-stage dehumidification filters enters the ion migration tube via a three-way connector and a second mass flow meter, in the form of drift gas, through the drift gas inlet.

[0015] Furthermore, the ion mobility spectrum is a photoionization ion mobility spectrum; the photoionization source is a vacuum ultraviolet lamp.

[0016] Furthermore, the temperature range of the semiconductor refrigeration dehumidification device is 24°C to -10°C, and the refrigeration time is 10-25 seconds.

[0017] Furthermore, the heating element in the semiconductor cooling dehumidification device is heated to a temperature of 100 to 150°C for a heating time of 10 to 25 seconds.

[0018] During the exhaled gas sampling and detection process, the sample gas is directly introduced into the semiconductor cooling and dehumidification device through a three-way solenoid valve by the action of the sampling pump. The water vapor in the sample gas condenses into liquid water under the low temperature conditions of the cooling chip. The liquid water is trapped on the surface of the hydrophobic microspheres. After cooling and dehydration, the sample gas enters the IMS and is detected to obtain the migration spectrum.

[0019] During the heating and backflushing process, after sampling is completed, the vacuum sampling pump is turned off, and the three-way solenoid valve is switched. The semiconductor cooling chip stops cooling, and the electric heating element of the semiconductor cooling dehumidification device starts to heat the semiconductor cooling dehumidification device. At the same time, the gas in the ion migration spectrum enters the semiconductor cooling device, and the moisture in the cavity is backflushed and flows out through the third port of the three-way solenoid valve.

[0020] During the sampling process, the test subject first takes a deep breath of purified clean air and then exhales into the breathing-sampling device to eliminate the interference of NOx in the air on the results.

[0021] The experimental conditions for ion mobility spectrometry detection are as follows: the inter-ring voltage in the migration region is 200-300V, the migration tube temperature is 60-110℃, the flow rate of the first mass flow meter is 600-1200mL / min, the flow rate of the second mass flow meter is set to 400-700mL / min, and the flow rate of the sample gas drawn into the migration tube is 100-400mL / min.

[0022] Compared with the prior art, the advantages of this utility model are: by using semiconductor cooling dehumidification, the influence of high humidity in exhaled air is effectively eliminated, and no complicated sample pretreatment process is required. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of the semiconductor cooling dehumidification ion mobility spectrometry for detecting exhaled NO provided by this utility model; wherein, 1 is exhaled air, 2 is sampling nozzle, 3 is air outlet, 4 is three-way solenoid valve, 5 is semiconductor cooling dehumidification device, 6 is [missing information], 8 is ion migration tube inlet, 9 is ion migration tube outlet, 10 is photoionization source, 11 is ion molecule reaction zone, 12 is migration zone, 13 is heat insulation heating jacket, 14 is Faraday disk, 15 is first mass flow meter, 16 is air sampling pump, 17 is two-stage dehumidification filter, 19 is three-way connector, 20 is drift gas inlet, 21 is second mass flow meter, 22 is amplifier, and 23 is data acquisition system.

[0024] Figure 2 A schematic diagram of the internal structure of a semiconductor refrigeration dehumidification device. 6 is the air inlet of the semiconductor refrigeration dehumidification device, 7 is the air outlet of the semiconductor refrigeration dehumidification device, 102 is the airflow channel, 104 is the upper baffle plate, 105 is the lower baffle plate, 106 is the hydrophobic particles, 107 is the semiconductor refrigeration element, and 108 is the electric heating element.

[0025] Figure 3 The quantitative curve of NO at 100% RH.

[0026] Figure 4 The image shows the ion mobility spectrum of exhaled NO detected by the ion mobility spectrometry of the present invention in a healthy subject during a physical examination, as described in Example 2.

[0027] Figure 5 The comparative example uses traditional ion mobility spectrometry to detect the ion mobility spectrum of NO in the exhaled breath of a healthy subject. Detailed Implementation

[0028] To make the objectives, technical solutions, and advantages of this utility model clearer, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0029] like Figure 1 , Figure 2 As shown, this utility model provides a semiconductor cooling dehumidification ion mobility spectrum for detecting exhaled NO, including an ion mobility tube, a sampling nozzle 2, a three-way solenoid valve 4, a semiconductor cooling dehumidification device 5, a first mass flow meter 15, an air sampling pump 16, a second mass flow meter 21, a two-stage dehumidification filter 17, a three-way connector 19, and a data acquisition system 23.

[0030] The semiconductor cooling dehumidification device 5 is a rectangular sealed cavity with a length of 60cm, a width of 55cm, and a height of 55cm. A semiconductor cooling chip 107 for cooling and an electric heating chip 108 for heating are provided on one side wall of the cavity. An air inlet 6 of the semiconductor cooling dehumidification device is provided on the upper bottom surface of the cavity. The air inlet 6 of the semiconductor cooling dehumidification device is connected to the sampling nozzle 2 through a three-way solenoid valve 4 and a sampling tube. An air outlet 7 of the semiconductor cooling dehumidification device is provided on the lower bottom surface of the cavity. The air outlet 7 of the semiconductor cooling dehumidification device is connected to the ion migration tube through a pipeline.

[0031] Six upper baffles 104, each 45cm high, are installed vertically downwards from the top surface of a rectangular sealed cavity and are parallel to the left and right side walls. An airflow channel 102 is formed between the top of the upper baffle 104 and the bottom surface. Six lower baffles 105, each 45cm high, are installed vertically upwards from the bottom surface of the cavity and are parallel to the upper baffles. The lower baffles 105 are installed alternately with the upper baffles 104, and an airflow channel is formed between the top of the lower baffle and the top surface of the cavity.

[0032] A gas cooling channel is formed between the upper bottom surface, side wall surface, upper baffle plate, lower baffle plate and lower bottom surface of the cavity, and 106 hydrophobic polytetrafluoroethylene microspheres with a particle size of 4cm are filled in the gas cooling channel.

[0033] The ion migration tube includes a photoionization source 10 and a Faraday disk 14 arranged opposite to each other at the left and right ends, respectively, and an ion gate located between the photoionization source and the Faraday disk. The region between the photoionization source and the ion gate is the ion molecular reaction region 11, and the region between the ion gate and the Faraday disk is the migration region 12. The Faraday disk is connected to the data acquisition system 23 through an amplifier 22.

[0034] An ion migration tube inlet 8 is provided on the upper wall of the reaction zone of the ion migration tube near the ion gate. The ion migration tube inlet is connected to the outlet 7 of the semiconductor refrigeration dehumidification device through a connecting pipe.

[0035] An ion migration tube outlet 9 is provided on the upper wall of the reaction zone of the ion migration tube near the photoionization source. The ion migration tube outlet 9 is connected to the inlet of the sampling pump 16 through the first mass flow meter 15.

[0036] A drift gas inlet 20 is provided above the Faraday disk on the right side of the ion migration tube. The drift gas inlet 20 is connected to the outlet of the suction sampling pump 16 via a pipeline through a second mass flow meter 21, a three-way connector 19, a two-stage dehumidification filter 17.

[0037] The two-stage dehumidifier filter 17 consists of two sealed containers, each filled with a molecular sieve. One dehumidifier filter is filled with aluminum oxide molecular sieve, while the other dehumidifier filter is filled with a different type of molecular sieve.

[0038] The ionization source for the ion mobility spectrometer is a vacuum ultraviolet lamp. The cooling temperature range of the semiconductor refrigeration dehumidification device 5 is 24℃ to -10℃, and the cooling time is 10-25 seconds. The heating element in the semiconductor refrigeration dehumidification device 5 heats at a temperature of 100 to 150℃ for a heating time of 10-25 seconds.

[0039] Example 1

[0040] Ion mobility spectrometry was used for the quantitative analysis of NO at 100% RH after semiconductor refrigeration and dehumidification. Different concentrations of NO standard samples, including 10 ppb, 20 ppb, 40 ppb, 60 ppb, 80 ppb, 100 ppb, 120 ppb, 150 ppb, 180 ppb, and 200 ppb, were detected under 100% RH conditions. For each concentration, a certain volume of 0.1% NO (containing 0.1% NO in N2 standard gas) was diluted with clean, humidified air at 100% RH. The volume of the dilution glass bottle used for sample preparation was 600 mL. A certain volume of 0.1% NO standard sample and clean, humidified air at 100% RH were respectively injected into the dilution bottle using a glass syringe and allowed to stand for approximately 5 minutes. After mixing, the sampled air enters a semiconductor refrigeration and dehumidification device under the action of a sampling pump, and then enters an IMS for detection. A quantitative curve of NO in exhaled air can be obtained by plotting the NO concentration at 100% RH on the x-axis and the NO signal intensity on the y-axis. Figure 3 As shown in Table 1, the quantitative equation is y = 0.48x + 4.95, where x is the concentration of NO in exhaled air in ppbv and y is the signal intensity of NO in mV.

[0041] Table 1. Quantitative equations for NO in exhaled air at different humidity levels after dehumidification by the semiconductor refrigeration dehumidification device.

[0042]

[0043] Example 2

[0044] The ion mobility spectrometry of this invention was used to detect NO in the exhaled breath of a healthy subject during a physical examination. The ion mobility spectrum is as follows: Figure 4 As shown, the NO intensities obtained from three breath tests were 34.58 mV, 33.77 mV, and 34.97 mV, respectively, with average intensity and relative standard deviation of 34.44 mV and 1.78%, respectively. The NO content in the volunteer's exhaled breath was 10.64 ppbv, as determined by the quantitative curve at 100% RH.

[0045] Comparative Example

[0046] The ion mobility spectra of exhaled NO from the same healthy subject in Example 2 were detected using a conventional ion mobility spectrometer (without a semiconductor cooling and dehumidification device) (compared with Example 1). Figure 5 As shown, the migration times of the humidity-related interference peaks are 8.00 ms and 8.24 ms, respectively, both located near the RIP peak (8.52 ms) and the NO product ion peak (7.68 ms), which seriously interfere with the accurate qualitative identification of the exhaled NO product ion peak. Therefore, it is difficult to perform accurate qualitative and quantitative analysis of NO under high humidity conditions.

Claims

1. A semiconductor-based refrigerated dehumidification ion mobility spectrometry method for detecting exhaled NO, characterized in that, Includes ion migration tube, sampling nozzle (2), three-way solenoid valve (4), semiconductor refrigeration dehumidification device (5), first mass flow meter (15), air sampling pump (16), second mass flow meter (21), two-stage dehumidification filter (17), three-way connector (19), and data acquisition system (23). The semiconductor cooling dehumidification device (5) is a closed cavity. On the two opposite side walls of the cavity, there are semiconductor cooling plates for cooling and electric heating plates for heating. An air inlet (6) of the semiconductor cooling dehumidification device is provided on the upper bottom surface of the cavity. The air inlet (6) of the semiconductor cooling dehumidification device is connected to the sampling nozzle (2) through a three-way solenoid valve (4) and a sampling tube. An air outlet (7) of the semiconductor cooling dehumidification device is provided on the lower bottom surface of the cavity. The air outlet (7) of the semiconductor cooling dehumidification device is connected to the ion migration tube through a pipeline. An upper baffle plate is set vertically downward on the upper bottom surface of the cavity and parallel to the left and right side walls. An airflow channel is formed between the top of the upper baffle plate and the lower bottom surface. A lower baffle plate is set vertically upward on the lower bottom surface of the cavity and parallel to the upper baffle plate. The lower baffle plate and the upper baffle plate are set alternately. An airflow channel is formed between the top of the lower baffle plate and the upper bottom surface of the cavity. A gas cooling channel is formed between the upper bottom surface, side wall surface, upper baffle plate, lower baffle plate and lower bottom surface of the cavity, and hydrophobic particles are filled in the gas cooling channel; The ion migration tube includes a photoionization source (10) and a Faraday disk (14) respectively arranged opposite to each other at the left and right ends, and an ion gate located between the photoionization source and the Faraday disk. The region between the photoionization source and the ion gate is the ion molecular reaction region (11), and the region between the ion gate and the Faraday disk is the migration region (12). The Faraday disk is connected to the data acquisition system (23) through an amplifier (22). An ion migration tube inlet (8) is provided on the upper wall of the reaction zone of the ion migration tube near the ion gate. The ion migration tube inlet is connected to the outlet (7) of the semiconductor refrigeration dehumidification device through a connecting pipe. An ion migration tube outlet (9) is provided on the upper wall of the ion migration tube reaction zone near the photoionization source. The ion migration tube outlet (9) is connected to the inlet of the gas sampling pump (16) through the first mass flow meter (15). A drift gas inlet (20) is provided above the Faraday disk on the right side of the ion migration tube. The drift gas inlet (20) is connected to the outlet of the gas sampling pump (16) via a pipeline through a second mass flow meter (21), a three-way connector (19), and a two-stage dehumidification filter (17).

2. The ion mobility spectrum according to claim 1, characterized in that, The hydrophobic particles are hydrophobic microspheres made of polytetrafluoroethylene, polypropylene, nylon 66, or perfluoroethylene propylene, with a particle size of 3-5 cm.

3. The ion mobility spectrometry according to claim 1, characterized in that, The upper and lower partitions are made of stainless steel or aluminum, and the distance between adjacent upper and lower partitions is 3-7 centimeters.

4. The ion mobility spectrum according to claim 1, characterized in that, The two-stage dehumidifier (17) consists of two sealed containers filled with molecular sieves, one of which is filled with aluminum oxide and the other with silicon dioxide.

5. The ion mobility spectrometry according to claim 1, characterized in that, The ion mobility spectrum is a photoionization ion mobility spectrum; the photoionization source is a vacuum ultraviolet lamp.

6. The ion mobility spectrum according to claim 1, characterized in that, The temperature range of the semiconductor refrigeration dehumidification device (5) is from 24°C to -10°C.

7. The ion mobility spectrum according to claim 1, characterized in that, The heating element in the semiconductor refrigeration dehumidification device (5) is heated to a temperature of 100 to 150°C.

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