JP2008256680A - Method for measuring concentration of biogas in breathing and simplified measuring device for measuring biogas concentration in breathing - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method and simplified measuring device for measuring a biogas in breathing easily with high sensitivity. <P>SOLUTION: In the method for measuring the concentration of a biogas in breathing using a thermoelectric gas sensor, heat generated by a catalytic reaction between the biogas and a catalyst material is converted to a voltage signal by thermoelectric conversion, and the voltage signal is detected as a detection signal, thus measuring the concentration of the biogas in breathing. In the measurement method, human breathing is sampled, and the concentration of the biogas, such as hydrogen and carbon monoxide, contained in the breathing is quantitated. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for measuring the concentration of biological gases such as hydrogen and carbon monoxide gas in human exhalation and apparatus measurement thereof, and more particularly, as a gas sensor for collecting exhalation and measuring it. The heat generated by the catalytic reaction between a biological gas such as carbon monoxide gas and the catalytic material is converted into a voltage signal by the thermoelectric conversion effect, and these biological gases are increased using a gas detection sensor that detects it as a detection signal. The present invention relates to a method for measuring the concentration of biological gas such as hydrogen and carbon monoxide gas in exhaled gas, which is selectively measured and measured for sensitivity, and a simplified measuring device thereof. The present invention provides a method for measuring and measuring a biological gas such as hydrogen or carbon monoxide in human exhalation with high sensitivity and a simple measurement apparatus thereof, and allows easy pathophysiological analysis of a subject. The present invention also provides a new diagnostic technique that can be performed with high sensitivity.

  Usually, sugars such as lactose are digested in the stomach and absorbed in the small intestine. However, if there is a poor absorption of carbohydrates, the carbohydrates that are not absorbed in the small intestine reach the large intestine as they are. In the human large intestine, hundreds of intestinal bacteria are resident, and the intestinal flora (hydrogen-producing bacteria, methane-producing bacteria, etc.) is fermented with carbohydrates that have not been absorbed. Produces biogas such as (or methane). The hydrogen (or methane) gas generated here is excreted into the exhaled breath through the blood circulation. A method of diagnosing digestive insufficiency and the like of carbohydrates using this principle is a method for measuring a living gas in breath.

  By analyzing the concentration of biogas in the exhaled breath, the human health condition or stress can be evaluated. For example, hydrogen is absorbed from the intestinal tract and the gas produced by intestinal bacteria is released into the exhaled breath, so the hydrogen of the living gas in the breath clearly reflects the activity of the intestinal bacteria and decreases digestive function. It becomes a stress marker. Similarly, intestinal methane-producing bacteria produce methane, a biogas in exhaled breath, but the generation mechanism is unclear (in conjunction with hydrogen). Similarly, carbon monoxide in combustible gas in exhaled breath is known as an oxidative stress marker for free radical and biological damage (inflammation) caused by active oxygen.

  In this way, exhaled hydrogen is a gas produced by intestinal bacteria, which is produced by all humans, and the amount of hydrogen produced varies greatly depending on the quality of food intake and the state of absorption. It depends on. In addition, carbon monoxide in exhaled air is produced from Heme nucleus disruption by Heme oxygenase (HO), but heme oxidase is induced by oxidative stress, and the carbon monoxide concentration increases. Carbon monoxide in exhaled breath serves as an oxidative stress marker for free radicals, living body damage due to active oxygen, various inflammations, and the like. Furthermore, methane in the breath is a gas component produced by bacteria in the digestive tract, absorbed from the intestinal tract, and excreted in the breath. It is possible to analyze human pathophysiology by measuring the production of hydrogen, carbon monoxide and methane biogas contained in exhaled breath.

  For example, the test for hydrogen and methane in exhaled breath is a method that collects and measures end-tidal air, and is basically a non-invasive test method (a test without pain). Also, it does not matter at all for the subject. However, in order to analyze the collected gas, an expensive analysis facility is required, so that it is difficult to analyze it simply in the clinic.

  In recent years, a simple expiratory device capable of analyzing collected gas in an outpatient treatment room or the like has been developed (for example, Taiyo Corporation, biological gas measurement system Tri riser mBA-3000). Unlike an expensive analytical instrument, this apparatus is configured as shown in FIG. 1 and has been developed as a simple breath analysis apparatus based on the principle of gas chromatography analysis.

  In addition, this apparatus can analyze the gas species and their amounts from the peak of gas chromatography as shown in FIG. 2, and the carrier gas for analysis uses indoor air, so a dedicated gas is used. Is unnecessary, and the measurement time is about 4 to 10 minutes. FIG. 2 is an analysis and measurement of the concentration of hydrogen, methane, and carbon monoxide from the peak intensity of the time difference from gas chromatography.

  In the measurement technique described above, the sensor used in the gas detector uses a semiconductor sensor element that is highly sensitive to flammable gas. Typical products are sensor elements such as TGS821 and TGS2600 from Figaro Giken. Since these use semiconductor type sensor elements, there is a problem that the detection signal is greatly influenced by humidity, and is subject to change with time (drift) in the measurement technique. Because of these problems, in the above measurement technique, it is necessary to calibrate the instrument with a dedicated calibration gas, particularly in order to accurately and quantitatively measure the low concentration hydrogen / methane at the ppm level. In addition, in order to provide gas selectivity, this type of apparatus has a large equipment configuration including a gas chromatography portion, and becomes an expensive apparatus.

  On the other hand, the present inventors have developed a thermoelectric gas sensor that uses a temperature difference generated by catalytic combustion of hydrogen as a signal of the element itself using an operating principle that combines a catalytic reaction and a thermoelectric conversion function. . This thermoelectric gas sensor can be made 1) a hydrogen (or carbon monoxide) selective sensor by selecting a catalyst (see Non-Patent Documents 1 and 2). 2) The catalyst temperature of the sensor is set to 100. It is possible to eliminate the influence of moisture as ° C (see Non-Patent Document 3), and 3) it is possible to efficiently convert heat generated by microsensor catalytic combustion into a voltage signal (see Non-Patent Document 4). ), Etc.

  For example, in order to measure hydrogen in exhaled breath, it is necessary to selectively detect hydrogen in a concentration range of several ppm to several hundred ppm with high sensitivity. In particular, since exhaled air contains many types of biological gases, for example, in order to extract only hydrogen information from them, it is very important that the selectivity for biological gases is high. It is.

Shin, W., Matsumiya, M., Izu, N., And Murayama, N., “Hydrogen-selective Thermoelectric Gas Sensor”, Sens. Actuators, B, 93 (2003) 304-308 Matsumiya, M., Shin, W., Izu, N., and Murayama, N., “Thermoelectric CO Gas Sensor Using Thin-film Catalyst of Au and Co3O4”, J. Electrochem. Soc., 151 (1), H7- H10 (2004) Sawaguchi, N., Tajima, K., Shin, W., Izu, N., Matsubara, I., and Murayama, N., “Effect of humidity on the sensing property ofthermoelectric hydrogen sensor”, Sens. Actuators, B, 108 (2005) 461-466 Nishibori M., Shin W., Houlet, L., Tajima, K., Izu, N., Itoh, T., Murayama, N. and Matsubara, I., “New Structural Design of Micro-thermoelectric Sensor for Wide range Hydrogen detection ”, J. Ceram. Soc. Japan, vol.114, p 853-856 (2006)

  In such a situation, in view of the prior art, the present inventors can measure the concentration of biogas such as hydrogen and carbon monoxide in exhaled breath with high sensitivity and overall measurement, As a result of accumulating earnest research with the goal of developing a new measurement method and measurement device capable of simplifying the measurement system, by using the thermoelectric gas sensor developed by the present inventors as a gas sensor, The present inventors have found that the biogas component can be measured with high sensitivity and high selectivity and can achieve the initial purpose, and the present invention has been completed.

  The present invention is a gas measuring method and apparatus for measuring and measuring biological gas concentrations such as hydrogen and carbon monoxide in expired gas with high sensitivity and high sensitivity. Has developed a thermoelectric gas sensor for measuring the concentration of living gases such as hydrogen and carbon monoxide in exhaled breath, and has made it possible to simplify the overall measurement and measurement system and its simplified measurement method. An object of the present invention is to provide a mold measuring apparatus.

The present invention for solving the above-described problems comprises the following technical means.
(1) A method for measuring the concentration of a living gas in exhaled air using a thermoelectric gas sensor, wherein the heat generated by the catalytic reaction between the exhaled living gas component and the catalyst material is converted into a voltage signal by thermoelectric conversion. A method for measuring a concentration of a biological gas in expired air, wherein the concentration of the biological gas component in the expired air is measured by detecting the detection signal as a detection signal.
(2) The method for measuring a concentration of a living gas in the breath according to (1), wherein human breath is collected and the concentration of a living gas component contained in the breath is quantified.
(3) Using a catalyst material that selectively catalyzes with a biogas component in exhaled air, heat generated by the catalytic reaction is converted into a voltage signal by thermoelectric conversion, and is detected as a detection signal. 2. A method for measuring a concentration of a living gas in exhaled breath according to 1.
(4) As a catalyst material that undergoes a catalytic reaction with a biogas component, a hydrogen, carbon monoxide, or methane gas is selectively used to selectively measure hydrogen, carbon monoxide, or methane concentration. The method for measuring a concentration of biological gas in exhaled breath according to (3) above.
(5) As a catalyst material, a platinum-based noble metal alloy, a composite of platinum and oxide, or a composite catalyst member made of a platinum-based noble metal alloy and oxide is used, and the concentration of hydrogen gas contained in exhaled air is adjusted. The method for measuring a concentration of biological gas in expired air according to (4), wherein the concentration is selectively measured.
(6) Carbon monoxide gas contained in exhaled air, using a gold-based noble metal alloy, a composite of gold and oxide, or a composite catalyst member made of a gold-based noble metal alloy and oxide as a catalyst material The method for measuring a concentration of biological gas in exhaled breath according to (4), wherein the concentration is selectively measured.
(7) Pt / oxide catalyst and Au / oxide catalyst are used as catalyst materials, and hydrogen and carbon monoxide concentrations contained in exhaled gas are selectively measured. Biogas concentration measurement method.
(8) The amount of exhaled gas required for measurement is reduced by controlling the temperature condition of the catalyst material that undergoes a catalytic reaction with the biogas component to any temperature in the range of 100 ° C. to 150 ° C. (4) 2. A method for measuring a concentration of a living gas in exhaled breath according to 1.
(9) A biogas component concentration measuring device used in the measurement method according to any one of (1) to (8), wherein the gas sensor generates heat due to a catalytic reaction between the biogas component and the catalyst material. An apparatus for measuring a concentration of a biological gas component in exhaled breath, comprising a gas detection sensor that converts a voltage signal by thermoelectric conversion and detects it as a detection signal.
(10) A dehumidifying filter, an air pump for taking in exhaled air, and a gas sensor unit are included as components, and the gas sensor unit converts heat generated by a catalytic reaction between a biological gas component and a catalyst material into a voltage signal by thermoelectric conversion. The apparatus for measuring a concentration of a biological gas component in exhaled breath according to (9), comprising a gas detection sensor for detecting the detection signal as a detection signal and not including a gas separation means using chromatography or a separation membrane. .
(11) A simple diagnostic method characterized by detecting a biogas concentration in human expiration using the measurement method according to any one of (1) to (8).

Next, the present invention will be described in more detail.
The present invention relates to a method for measuring the concentration of a living gas in exhaled air using a thermoelectric gas sensor, wherein heat generated by a catalytic reaction between the living gas and a catalyst material is converted into a voltage signal by thermoelectric conversion, and this is detected signal. It is characterized by measuring the concentration of biological gas in exhaled breath by detecting as.

  In the present invention, human breath is collected, the concentration of the biogas contained in the exhalation is quantified, and a catalytic material that selectively catalyzes with the biogas component in the exhalation is used to generate heat generated by the catalytic reaction. It is a preferred embodiment that a voltage signal is converted by thermoelectric conversion and detected as a detection signal.

  In the present invention, the concentration of hydrogen, carbon monoxide, or methane is selectively measured by using a catalyst material that selectively reacts with hydrogen, carbon monoxide, or methane gas as a catalyst material that undergoes a catalytic reaction with a biogas component. The catalyst material is a platinum-based precious metal alloy, a composite catalyst member made of a platinum-oxide composite or a platinum-based precious metal alloy-oxide composite, and the concentration of hydrogen gas contained in the breath is selected. Is a preferred embodiment.

  In the present invention, as the catalyst material, a gold-based noble metal alloy, a composite catalyst member made of a gold-oxide composite or a gold-based precious metal alloy-oxide composite is used, and carbon monoxide contained in exhaled air. It is preferable to selectively measure the gas concentration, and to selectively measure the concentration of hydrogen and carbon monoxide contained in exhaled air using Pt / oxide catalyst and Au / oxide catalyst as the catalyst material. This is an embodiment.

  Further, the present invention controls the temperature condition of the catalyst material that undergoes a catalytic reaction with the biological gas component to any temperature within the range of 100 ° C. to 150 ° C. when measuring the concentration of the biological gas in the expiration using the above method. By doing so, the amount of exhaled gas required for measurement is reduced.

  Furthermore, the present invention is a measuring apparatus used in the above method, and as a gas sensor, heat generated by a catalytic reaction between a biological gas component and a catalyst material is converted into a voltage signal by thermoelectric conversion and detected as a detection signal. A detection sensor is included, and includes a dehumidification filter, an air pump for taking in exhaled air, and a gas sensor unit as constituent elements, and the gas sensor unit generates heat due to a catalytic reaction between a biological gas component and a catalyst material. Is a gas detection sensor that converts the signal into a voltage signal by thermoelectric conversion and detects it as a detection signal, and does not include gas separation means using chromatography or a separation membrane.

  The thermoelectric gas sensor developed by the present inventors is based on an operating principle that combines a catalytic reaction and a thermoelectric conversion function (see FIG. 3). For example, a temperature difference generated by catalytic combustion of hydrogen is used as a signal for the element itself. Therefore, it has the following characteristics as compared with the conventional semiconductor type or catalytic combustion type hydrogen sensor.

  That is, a thermoelectric gas sensor is a sensor that enables biogas selectivity such as hydrogen (or carbon monoxide) by selecting a catalyst, and 2) the sensor temperature of the sensor is set to 100 ° C. to influence the humidity. 3) It is less susceptible to changes in ambient temperature, 4) has a wide measurable concentration range, and 5) has no drift. When used as a means for measuring the concentration of biological gases such as hydrogen and carbon monoxide, the entire measurement system can be made simple.

  In order to achieve high sensitivity, high selection, and high speed response of this thermoelectric gas sensor element, it is effective to make the element into a micro element. The present inventors have developed a micro device in which a thin film thermoelectric film, catalyst film, electrode, wiring, and heater are integrated on a silicon wafer. A microelement is manufactured by a process in which a thermoelectric element, a heater, an electrode, wiring, a catalyst, and the like are integrated on a silicon substrate, and the back side of the substrate is selectively removed.

  FIG. 4 shows a manufacturing process of a micro thermoelectric hydrogen sensor. Specifically, the present invention includes, for example, a substrate on which a plurality of different catalyst materials are disposed, and a thermoelectric conversion unit that converts a temperature difference of heat generated by the catalytic reaction between the gas and the catalyst material into an electrical signal. A sensor element is used. Thereby, it is possible to detect the specific gas component of the biological gas contained in the exhalation with high sensitivity and high selectivity. Examples of the catalyst material include a platinum / gold noble metal alloy, a composite of platinum / gold and an oxide, or a composite catalyst material made of a platinum / gold noble metal alloy and an oxide composite.

  The catalyst can be produced, for example, by forming a paste-like material on the element surface and then heat-treating and baking. In this case, for example, the raw material composition and its microstructure are previously set so that the final catalyst structure is a composite in which oxide nanoparticles and a noble metal having a size of several nanometers are dispersed on the surface. Design, prepare a raw material paste, form a paste on the element surface, and fire.

  Examples of the oxide nanoparticles include alumina, silica, and tin oxide nanoparticles, and examples of the noble metals include Pt, Pd, and Au. An example is a structure in which nanoparticles are dispersed in a predetermined dispersion state. Further, for example, the catalyst is formed on a membrane having low heat conduction so that the heat generated from the catalyst is not transmitted to the periphery.

  In the present invention, the catalyst powder and paste material can be prepared, for example, by preparing a commercially available platinum chloride or palladium chloride aqueous solution, directly mixing it with the oxide powder, and heating and drying this for the catalyst of the starting material. A powder is prepared and mixed with a vehicle made of, for example, terpineol and ethyl cellulose to prepare a paste-like material.

  The formation of the fine pattern is performed, for example, by applying a catalyst to a predetermined position of the element by using a dispenser and heating at 300 ° C. for 1 hour to produce the catalyst. The size of the catalyst can be formed, for example, as a circular pattern having a diameter of about 0.5 to 2.0 mm or a square pattern having a width of 0.5 to 1.5 mm.

Examples of the catalyst for detecting carbon monoxide include an Au / TiO ₂ catalyst in which gold particles having a particle diameter of 5 nm or less are supported on titanium oxide, iron oxide, or the like. Examples of the catalyst for detecting hydrogen include a Pt-based Pt / Al ₂ O ₃ catalyst. In these catalysts, for example, a chloroauric acid aqueous solution in which a metal oxide support is immersed is kept constant within a range of pH 6 to 10, and aged to precipitate and precipitate gold hydroxide only on the support. Then, after washing and drying, it can be produced by firing in air at 25 ° C. for 30 minutes.

As this Au / TiO ₂ catalyst, for example, a catalyst material having a catalyst composition of 3 wt% Au / TiO ₂ and a gold particle diameter of 2.8 nm (TEM standard deviation 0.8 nm) is exemplified. In this case, the catalyst material can be applied and integrated on the element by using a paste manufacturing method described in the literature (for example, JP-A-2006-047276).

  In the present invention, a microsensor element can be constructed and used. For example, in a thermoelectric gas sensor element, a micro element can be produced by forming a fine pattern of a catalyst using a dispenser on a membrane having low thermal conductivity so that heat generated from the catalyst is not transmitted to the surroundings. it can. In this case, the fabrication process of the micro thermoelectric gas sensor element basically includes a step of forming a membrane for heat shielding on the substrate, a thermoelectric conversion material film pattern, a heater pattern, a wiring pattern, and the like on the membrane. It consists of the process of forming a catalyst material pattern.

  FIG. 5 shows a photograph of the produced micro thermoelectric hydrogen sensor. The design of the hydrogen sensor element is appropriately determined for the purpose of 1) minimizing the element heat capacity and 2) efficiently preventing thermal diffusion. A heater, a thermoelectric thin film, and an electrode are integrated in the surface of the membrane formed for heat shielding. For the production of the membrane, for example, an anisotropic wet etching technique for a silicon substrate using a KOH solution can be used. A SiGe thermoelectric thin film having a thickness of about 300 nm is formed by sputtering, and a high temperature heat treatment process is performed for crystallization.

  As a hydrogen combustion catalyst, a microsensor element in which a ceramic catalyst in which platinum is supported on alumina is integrated (see FIG. 5), the signal voltage for hydrogen is dramatically improved as compared with an element using a thin film catalyst. FIG. 6 shows the dependence of the voltage signal of the micro thermoelectric hydrogen sensor with the catalyst temperature of 100 ° C. on the hydrogen concentration. This micro thermoelectric sensor can efficiently convert heat generated by catalytic combustion of a micro sensor into a voltage signal as compared with a conventional bulk type sensor.

  For this reason, in particular, the characteristics when the hydrogen concentration is low are improved, and response characteristics with excellent linearity are exhibited from a low concentration of 0.5 ppm to a high concentration of 5%. As shown in FIG. 7, the entire system for measuring the concentration of living biological gas in the breath using the thermoelectric gas sensor of the present invention is composed of a simple dehumidification filter in which silica gel is packed in a cylinder, an air pump and a sensor for taking in the breath. It is a simple structure.

  In this invention, it turned out that the stable performance which does not depend on moisture can be exhibited by using a thermoelectric gas sensor. However, in an actual environment, human exhalation is a hot and humid gas with a relative humidity of 95% or higher at 36 ° C, and when this is put into the system as it is, the temperature of the system is usually around 25 ° C at room temperature. Problems such as the occurrence of condensation in the system occur. In the measuring apparatus of the present invention, it is not necessary to carefully remove the humidity as in the above-described commercially available apparatus. However, for example, by providing a simple dehumidifying unit of about silica gel, the stability of the measuring system can be ensured. Is possible.

  Conventionally, a thermoelectric gas sensor is known as a sensor for measuring a combustible gas. However, no thermoelectric gas sensor has been used for analysis of biological gas in human exhalation, and the relative humidity is not less than 95% at 36 ° C. It was completely unknown whether biogas components can be detected with high sensitivity and high selectivity. As a result of repeated experiments shown in the examples described later, the present invention has demonstrated that biogas components in human breath can be analyzed with high sensitivity and high selectivity even under high humidity conditions. Yes, these findings are new and exceptionally unexpected from the literature.

  As described above, in the present invention, as a catalyst material that selectively detects hydrogen in the breath, for example, a platinum-based noble metal alloy, a platinum-oxide composite, or a platinum-based noble metal alloy-oxide composite The composite catalyst member which consists of a body is illustrated. Examples of the catalyst material that selectively detects carbon monoxide in the breath include, for example, a gold-based noble metal alloy, a composite of gold and an oxide, or a composite catalyst composed of a composite of a gold-based noble metal alloy and an oxide. The member is exemplified. In addition, examples of the catalyst material that selectively detects hydrogen and carbon monoxide in exhaled air include Pt / oxide catalyst and Au / oxide catalyst. It is possible to use it, but it is not limited to these.

  In the present invention, the temperature condition of the catalyst material that undergoes a catalytic reaction with the biogas component is controlled to any temperature in the range of 100 ° C. to 150 ° C. when the biogas concentration in the exhaled breath is measured using the above method. Thus, it is possible to improve the response speed and the stabilization time for the low-concentration gas, reduce the amount of exhaled gas collected from the subject necessary for measurement, and shorten the measurement time. In the present invention, it is possible to construct and provide a simple diagnostic technique and means that can detect a biogas concentration in human breath.

  In the present invention, the measurement device used in the above method includes a dehumidifying filter, an air pump for taking in exhaled air, and a gas sensor unit as constituent elements, and the gas sensor unit generates heat due to a catalytic reaction between a biological gas component and a catalyst material. An apparatus for measuring a concentration of a living body gas in a breath, comprising a gas detection sensor that converts a voltage signal by thermoelectric conversion and detects it as a detection signal, and does not include a gas separation means using chromatography or a separation membrane Used. The specific configurations of the dehumidifying filter, the air pump, and the gas sensor unit that constitute the device are not particularly limited, and can be arbitrarily designed as necessary.

The present invention has the following effects.
(1) It is possible to provide a method for measuring and measuring a biological gas such as hydrogen or carbon monoxide in human exhalation with high sensitivity and high sensitivity, and a simple measuring device thereof.
(2) It is sufficient to provide a simple dehumidifying unit of about silica gel without providing a special dehumidifying mechanism and reducing the humidity of the breath sampling gas as in the above-mentioned commercially available apparatus.
(3) Since a gas chromatography or the like for selecting and selecting a gas is not required, the system can be configured in a simple structure.
(4) Since the response speed and the stabilization time for low-concentration gas are short, the amount of exhaled gas collected from the subject necessary for measurement is small and the burden is small.
(5) Since a complicated dehumidifying part and gas chromatography part are not required, the air pump for controlling the gas flow is simple and small enough to be measured.
(6) The conventional simple analyzer analyzes the gas species and their amounts from the peak of gas chromatography as shown in FIG. 2. In the thermoelectric hydrogen sensor system of the present invention, the sensor itself selects the gas. Therefore, the gas chromatography part is unnecessary.
(7) From these things, it is possible to measure and measure the concentration of biological gas such as hydrogen (or carbon monoxide) with high accuracy within a few dozen seconds with a compact device.
(8) It is possible to provide a simple diagnostic technique that can detect the concentration of biological gas in human breath.

  EXAMPLES Next, although this invention is demonstrated concretely based on an Example, this invention is not limited at all by the following Examples.

  The gas concentration measurement was performed on the simplified breath analysis apparatus shown in FIG. 8 using a semiconductor gas sensor and a thermoelectric hydrogen sensor, and the difference was confirmed by experiments. As a sensor element used, a semiconductor sensor is a commercially available sensor element TGS821 (manufactured by Figaro Giken), and a thermoelectric hydrogen sensor is a micro thermoelectric hydrogen sensor (an element manufactured by a process similar to Non-Patent Document 4). there were.

(1) Details of the experiment Indoor air (same as after dehumidification with silica gel) is collected in a gas collection bag, hydrogen is metered into the bag, and the mixed simulated gas prepared to become (hydrogen / air) Got ready. This mixed gas was passed through the gas sensor section at a flow rate of 300 ccm, and a signal from the gas sensor was recorded. Two gases, a sampling gas and a flow gas, were also put in the sampling bag and switched to flow. The humidity of the gas was about 20% relative humidity at room temperature.

(2) Quantitative detection performance As shown in FIG. 9, a signal capable of quantitative measurement up to 1000 ppm level was obtained from the thermoelectric hydrogen sensor. By drawing a calibration curve based on this, the hydrogen concentration in the breath was quantitatively evaluated.

(3) Interference characteristics of methane gas As shown in FIG. 10, the interference characteristics of methane gas (only methane gas) of a thermoelectric hydrogen sensor and a semiconductor gas sensor were examined. The thermoelectric hydrogen sensor hardly responded to 100 ppm of methane gas. The methane concentration in normal exhalation is about 100 ppm at the maximum, and it may be considered that the thermoelectric hydrogen sensor does not respond to methane in this application.

  Response to 1000 ppm methane gas was also observed with a thermoelectric hydrogen sensor. However, the magnitude of the response signal is 5 ppm or less in terms of hydrogen gas, and is considered negligible. The semiconductor sensor responded to methane. Moreover, it was small compared with the response of hydrogen gas, and the signal was about 1/10.

  However, in the case of actual exhalation, hydrogen and methane are in a mixed state, and if the amount of methane is adjusted to the hydrogen concentration measurement in this state, accurate measurement cannot be performed. FIG. 11 shows interference characteristics of a thermoelectric hydrogen sensor and a semiconductor gas sensor due to methane gas when hydrogen gas and methane gas are mixed. In the case of a thermoelectric hydrogen sensor, it was found that there was almost no influence by methane gas. However, the semiconductor sensor has interference characteristics even at 100 ppm of methane.

(4) Humidity effects / Gas sensor differences Indoor air (same as after dehumidification with silica gel) is collected in a gas collection bag, and hydrogen is metered into the bag to reach 20 ppm (hydrogen / air). The prepared mixed gas was prepared. Further, a high-humidity gas was separately prepared and prepared so as to be 20 ppm (hydrogen / air). These mixed gases were passed through the gas sensor section at a flow rate of 300 ccm, and signals from the thermoelectric hydrogen sensor and the semiconductor gas sensor were recorded. Two gases, a sampling gas and a flow gas, were also put in the sampling bag and switched to flow.

(5) Thermoelectric hydrogen sensor Thermoelectric hydrogen sensors and semiconductor sensors are affected by high humidity gases. In the case of a thermoelectric hydrogen sensor, there is almost no influence in the case of high concentration hydrogen measurement, but when the PPM level is reached, the influence shown in FIG. 10 occurs. Therefore, even in a simple procedure, if the gas to be measured is passed through a desiccant such as silica gel and the humidity is lowered, the measurement like the dry state in FIG. 10 is repeated with good reproducibility and quantitatively as shown in FIG. It was found that accurate calibration was possible.

(6) Semiconductor type sensor The semiconductor type sensor shows the characteristic of responding to high sensitivity even at low concentrations of ppm level, although the selectivity of combustible gas is poor. However, due to its operating principle, it responds sensitively to the humidity contained in the analysis gas in the entire detected concentration range. As the tendency, as shown in FIG. 10, when the humidity is high, the response voltage increases.

  As other problems, as shown in FIG. 10, when the gas flow is switched, the response is slow, and even when switching from the measurement gas to the air, the signal remains, and it is not possible to quickly return to the baseline. The problem can be confirmed. In the case of a breath analyzer that combines this sensor and gas chromatography, gas chromatography uses the principle of gas separation based on time difference, so such problems of rising and falling response characteristics are fatal problems for gas concentration measurement. It becomes.

  Breath measurement was performed using a thermoelectric hydrogen sensor. Specifically, exhaled gas concentration was measured using a thermoelectric hydrogen sensor in a simple analysis system as shown in FIG. As for exhalation collection, a 30-year-old man (the present inventors) infused exhalation into an exhalation collection bag and lost the breath. The sampling gas was flowed through the gas sensor section at a flow rate of 300 ccm, and the signal from the gas sensor was recorded. Two gases, sampling gas and flow gas, were also put in the sampling bag and switched to flow. FIG. 13 shows the result of measuring the hydrogen concentration in the breath by a simple breath analyzer using the thermoelectric hydrogen sensor of the breath. The response of the thermoelectric hydrogen sensor was 2.6 μV in response at an elapsed time of 100 s, and it was measured to be 6.5 ppm of hydrogen when considered from the calibration curve.

  The gas concentration was measured using a thermoelectric hydrogen sensor in a simple analysis system as shown in FIG. At that time, the catalyst temperature was changed from 100 ° C. to 150 ° C. and the gas flow rate was changed from 300 ccm to 100 ccm, and the difference in response speed depending on the catalyst temperature and the gas flow rate was confirmed.

(1) Details of the experiment The mixed simulated gas was prepared so that air adjusted to a temperature of 25 ° C and a relative humidity of 55% was collected in a gas collection bag, and hydrogen was metered into the bag to become (hydrogen / air). Prepared. This mixed gas was passed through the gas sensor section at a flow rate of 300 ccm to 100 ccm, and a signal from the gas sensor was recorded. Two gases of sampling gas and flow gas were put in the same sampling bag, and measurement was performed by switching between air 30 seconds, mixed simulation gas 150 seconds, and air 60 seconds.

(2) Response characteristics at a catalyst temperature of 100 ° C. FIG. 14 shows the response characteristics at a catalyst temperature of 100 ° C. At a hydrogen concentration of 1000 ppm, at 300 ccm, the rise was fast, but the voltage gradually decreased and it took about 60 seconds to stabilize after gas switching. Further, at 100 ccm, there is a time lag of gas replacement, but the voltage stabilizes in about 60 seconds after gas switching. Therefore, it can be said that the amount of gas necessary for stabilization is constant regardless of the flow rate. At a hydrogen concentration of 100 ppm, it took about 150 seconds for both 300 ccm and 100 ccm to stabilize after gas switching. Moreover, the maximum response value changed with the flow rate.

(3) Response characteristics at a catalyst temperature of 125 ° C. FIG. 15 shows the response characteristics at a catalyst temperature of 125 ° C. At a hydrogen concentration of 1000 ppm, at 300 ccm, the rise was fast and the voltage stabilized in about 20 seconds after gas switching. Further, at 100 ccm, there is a time lag of gas replacement, but the time until gas is stabilized after gas switching is about 40 seconds. At a hydrogen concentration of 100 ppm, at 300 ccm, the voltage stabilized after about 20 seconds after gas switching and there was a time lag for gas replacement, but even at 100 ccm, it stabilized after about 40 seconds after gas switching.

(4) Response characteristics at a catalyst temperature of 150 ° C. FIG. 16 shows the response characteristics at a catalyst temperature of 150 ° C. At a hydrogen concentration of 1000 ppm, at 300 ccm, the rise was fast and the voltage stabilized in about 20 seconds after gas switching. Further, at 100 ccm, there is a time lag of gas replacement, but the time until gas is stabilized after gas switching is about 40 seconds. At a hydrogen concentration of 100 ppm, at 300 ccm, the voltage stabilized within 20 seconds after gas switching, and there was a time lag for gas replacement, but even at 100 ccm, it stabilized at about 40 seconds after gas switching.

(5) Difference in response speed depending on catalyst temperature and flow rate It was found that when the catalyst temperature was set to 125 ° C, the response time and the time to stabilization became much faster after gas switching than when the temperature was 100 ° C. . However, when the catalyst temperature was 150 ° C., no significant improvement was observed compared to the case of 125 ° C.

(6) Gas amount required for measurement The gas amount required for measurement could be estimated as shown in Table 1 below from the above results.

  By changing the catalyst temperature, the reaction time (response speed) in low concentration measurement was increased, and the gas flow rate required for measurement could be reduced. For example, when the operating temperature is changed from 100 ° C. to 125 ° C., the gas amount necessary for measuring the hydrogen concentration of 100 ppm becomes 1/6 at the maximum. This means that the burden on the subject at the time of measurement, such as shortening the measurement time and reducing the amount of exhaled gas collected for measurement, is reduced.

  In order to examine the gas selectivity, the concentration of interference gas was measured using a thermoelectric hydrogen sensor in a simple analysis system as shown in FIG. Air adjusted to a temperature of 25 ° C. and a relative humidity of 55% was collected in a gas collection bag, and a mixed gas prepared by metering carbon monoxide or isobutane into the bag was prepared. This mixed gas was passed through the gas sensor section at a flow rate of 300 ccm, and a signal from the gas sensor was recorded. Two gases, a mixed gas and a flow gas, were also put in a sampling bag, and measurement was performed by switching between air 30 seconds, mixed simulation gas 150 seconds, and air 60 seconds.

(1) Carbon monoxide FIG. 17 shows the measurement results in the case of carbon monoxide. It was found that neither 100 ppm nor 10 ppm was detected at an operating temperature of 100 ° C. with respect to the carbon monoxide single gas. However, as the operating temperature increased, the detection sensitivity increased and the response was shown even at 10 ppm. Carbon monoxide can be poisoned by adsorbing on the catalyst surface and inhibit hydrogen combustion, but in this case, carbon monoxide is burned, so it is not poisoned and does not interfere with hydrogen detection. I understood.

(2) Isobutane FIG. 18 shows the measurement results for isobutane. For isobutane, no detection was made even at an operating temperature of 150 ° C., and a slight detection started at an operating temperature of 200 ° C. Therefore, it has been found that there is no risk of affecting the analysis of the present invention.

  As described above in detail, the present invention relates to a method for measuring a biological gas in exhaled breath and a simple measuring apparatus thereof. According to the present invention, exhaled breath can be obtained in a short time within a few tens of seconds with a compact apparatus. It is possible to provide a method for measuring the concentration of living body gas in exhaled breath and a simple measuring device thereof that can measure and measure the concentration of hydrogen or carbon monoxide gas in the chamber with high sensitivity. The present invention provides a method for measuring and measuring a biological gas such as hydrogen or carbon monoxide in human exhalation with high sensitivity and a simple measurement apparatus thereof, and allows easy pathophysiological analysis of a subject. In addition, it is useful for providing a new diagnostic technique that can be performed with high sensitivity.

  In the present invention, since the thermoelectric gas sensor is used, the sensor itself is gas-selective, so that the gas chromatography portion is unnecessary and the entire system can be simplified. The present invention provides a simple and low-cost simple diagnostic device that measures the concentration of hydrogen or carbon monoxide gas in human breath and is capable of diagnosing carbohydrate digestion and absorption failure. Useful for providing.

The structure of a simple breath analysis apparatus is shown. Measurement example from a commercially available simple breath analyzer (H ₂ : 23.0 ppm, CO: 89 ppm, CH ₄ : 1.2 ppm) From the Taiyo Corporation website (http://www.t-taiyo.com/) An excerpt is shown. 1 shows a thermoelectric gas (hydrogen) sensor that detects hydrogen gas on the operating principle of converting a local temperature difference generated from catalyst heat generation between hydrogen gas and a Pt catalyst into a voltage signal by a thermoelectric conversion material. The manufacturing process of a micro thermoelectric hydrogen sensor is shown. A photograph of a micro thermoelectric hydrogen sensor is shown. The hydrogen concentration dependence of the voltage signal of a micro thermoelectric hydrogen sensor is shown. A configuration of a simple breath analysis apparatus using a thermoelectric hydrogen sensor is shown. A photograph of a simple breath analysis apparatus using a thermoelectric hydrogen sensor is shown. The dependence of the thermoelectric hydrogen sensor on the hydrogen gas concentration is shown. Interference characteristics (only methane gas) of methane gas between thermoelectric hydrogen sensor and semiconductor gas sensor are shown. Interference characteristics of thermoelectric hydrogen sensor and semiconductor gas sensor with methane gas (when hydrogen gas and methane gas are mixed) are shown. The humidity dependence of a thermoelectric hydrogen sensor and a semiconductor gas sensor is shown. The exhalation measurement result by a simple exhalation analyzer using a thermoelectric hydrogen sensor is shown. The response characteristics at a catalyst temperature of 100 ° C. are shown. The response characteristics at a catalyst temperature of 125 ° C. are shown. The response characteristics at a catalyst temperature of 150 ° C. are shown. Response characteristics with respect to carbon monoxide at operating temperatures of 100 ° C., 125 ° C., and 150 ° C. are shown. Response characteristics for isobutane at operating temperatures of 150 ° C. and 200 ° C. are shown.

Claims (11)

  A method for measuring the concentration of biological gas in exhaled air using a thermoelectric gas sensor, which converts the heat generated by the catalytic reaction between the exhaled biological gas component and the catalyst material into a voltage signal by thermoelectric conversion and detects it. A method for measuring a concentration of a biological gas in expired air, wherein the concentration of the biological gas component in expired air is measured by detecting as   The method for measuring a concentration of a living gas in exhaled breath according to claim 1, wherein human breath is collected and the concentration of a living gas component contained in the exhaled breath is quantified.   The exhalation according to claim 1, wherein a heat generation by the catalytic reaction is converted into a voltage signal by thermoelectric conversion and detected as a detection signal using a catalyst material that selectively catalyzes with a biological gas component in exhaled breath. Method for measuring the concentration of living body gas   The hydrogen, carbon monoxide, or methane concentration is selectively measured by using a catalyst material that selectively reacts with hydrogen, carbon monoxide, or methane gas as a catalyst material that catalyzes with a biogas component. 2. A method for measuring a concentration of a living gas in exhaled breath according to 1.   As a catalyst material, a platinum-based noble metal alloy, a composite catalyst member made of a platinum-oxide composite or a platinum-based noble metal alloy-oxide composite is used, and the concentration of hydrogen gas contained in exhaled gas is selectively selected. The method for measuring a concentration of biological gas in exhaled breath according to claim 4, which is measured.   The catalyst material is a gold-based noble metal alloy, a composite of gold and oxide, or a composite catalyst member made of a gold-based noble metal alloy and oxide, and the concentration of carbon monoxide gas contained in the exhaled air is selected. The method for measuring a concentration of biological gas in exhaled breath according to claim 4, wherein the concentration is measured automatically.   The biogas concentration measurement in exhaled breath according to claim 4, wherein Pt / oxide catalyst and Au / oxide catalyst are used as catalyst materials, and hydrogen and carbon monoxide concentrations contained in exhaled gas are selectively measured. Method.   The expiration | expired_air of Claim 4 which reduces the amount of expiration | expired_gas required for a measurement by controlling the temperature conditions of the catalyst material which carries out a catalytic reaction with a biogas component in any temperature of the range of 100 to 150 degreeC. Method for measuring the concentration of biogas in the body.   The biogas component concentration measuring apparatus used in the measurement method according to any one of claims 1 to 8, wherein the gas sensor generates heat generated by a catalytic reaction between the biogas component and the catalyst material, and a voltage signal is obtained by thermoelectric conversion. A device for measuring a concentration of a biological gas component in exhaled breath, comprising a gas detection sensor that converts the gas into a gas and detects it as a detection signal.   A dehumidifying filter, an air pump for taking in exhaled air, and a gas sensor unit are included as components, and the gas sensor unit converts heat generated by a catalytic reaction between a biogas component and a catalyst material into a voltage signal by thermoelectric conversion. The apparatus for measuring a concentration of a biological gas component in exhaled breath according to claim 9, comprising a gas detection sensor that detects a detection signal and does not include gas separation means using chromatography or a separation membrane.   A simple diagnostic method, wherein the biogas concentration in human breath is detected using the measurement method according to any one of claims 1 to 8.