JP6551102B2 - Breath analyzer - Google Patents

Description

  The present invention relates to a breath analyzer for analyzing volatile components in breath.

  BACKGROUND ART Conventionally, a technique (breath analysis technique) for diagnosing a disease or the like by analyzing volatile components in breath has been known. As such a breath analysis technique, for example, by using a gas chromatograph (GC) or a gas chromatograph mass spectrometer (GC / MS), the breath together with the carrier gas is introduced into the column and separated in the process of passing through the column There is a thing of a structure which detects the volatile component in the exhaled breath by a detection part (for example, refer to the following patent documents 1).

  However, in the configuration in which only exhaled breath is introduced into the column, volatile components in exhaled breath can not be sufficiently separated, and high detection sensitivity may not be obtained. Therefore, as a breath analysis technique, for example, a solid phase adsorption method in which a volatile component in breath is adsorbed to an adsorbent such as a polymer and the volatile component is analyzed by thermal desorption is generally used.

Utility model registration 3135149 gazette

  However, when the solid phase adsorption method is used, volatile components in exhaled breath that can be adsorbed are limited depending on the adsorbent used. Therefore, there is a problem that it is difficult to simultaneously detect more volatile components in exhaled breath. In particular, when searching for specific components that can diagnose a disease from a small amount of volatile components in exhaled breath, it is important to be able to detect more volatile components in one analysis, Solid phase adsorption may not provide sufficient analytical results.

  The present invention has been made in view of the above circumstances, and an object thereof is to provide a breath analysis apparatus capable of detecting more volatile components in breath.

(1) The breath analysis apparatus according to the present invention includes a column, a carrier gas supply unit, a sample introduction unit, a cooling unit, a heating unit, and a detection unit. The carrier gas supply unit supplies a carrier gas into the column. The sample introduction unit introduces breath into the carrier gas supplied from the carrier gas supply unit into the column. The cooling unit traps volatile components in the breath into the column by cooling the breath introduced into the carrier gas from the sample introduction unit. The heating unit is desorbed by heating volatile components trapped in the column. The detection unit detects volatile components separated by the heating unit and separated in the process of passing through the column.

  According to such a configuration, more volatile components in the expiration can be trapped in the column by cooling the expiration introduced into the carrier gas from the sample introduction section by the cooling section. Then, the volatile components trapped in the column are heated by the heating unit, so that the volatile components having the lowest boiling points are desorbed in order, and the desorbed volatile components are separated in the column and sequentially detected by the detection unit. can do. Therefore, more volatile components in exhaled breath can be detected

The breath analysis apparatus is not limited to the configuration in which the cooling unit and the heating unit are separately provided, and the cooling unit and the heating unit may be configured by a temperature control unit having both a cooling function and a heating function. Good.

  According to such a configuration, after the volatile component in the exhalation is cooled by the cooling function and trapped in the column, the operation of the cooling function is stopped and the heating function is started to start trapping. The volatile components are heated. This allows the volatile components in the breath trapped in the column to be smoothly heated and released after the introduction of the breath by the sample introduction unit.

(2) The breath analysis apparatus may further include a column oven for housing the column. In this case, the cooling unit and the heating unit may be provided in the column oven.

  According to such a configuration, after the volatile component in the breath is cooled and trapped in the column by the cooling unit provided in the column oven, the operation of the cooling unit is stopped, the same as in the column oven. The volatile component trapped as it is is heated by the heating part provided in. This allows the volatile components in the breath trapped in the column to be smoothly heated and released after the introduction of the breath by the sample introduction unit.

(3) The breath analysis apparatus has a control unit that stops the operation of the cooling unit while maintaining the state in which the carrier gas is supplied into the column by the carrier gas supply unit after introduction of the exhalation by the sample introduction unit May be further provided.

  According to such a configuration, when the operation of the cooling unit is stopped after the introduction of exhalation by the sample introduction unit, the volatile components that are desorbed in the order of the low boiling point are kept in the column by the continuously supplied carrier gas. Pass through. As a result, the desorbed volatile component passes smoothly through the column, and the volatile component separated in the column is favorably detected by the detection unit.

(4) The control unit may stop the operation of the cooling unit after a predetermined time has elapsed after the introduction of the breath by the sample introduction unit.

  According to such a configuration, after the introduction of the exhalation by the sample introduction unit, oxygen or nitrogen contained in the exhalation passes through the column for a predetermined time, and thereafter the operation of the cooling unit is stopped. As a result, oxygen and nitrogen contained in the exhaled breath can be prevented from adversely affecting the detection result, so that a better detection result can be obtained.

  According to the present invention, when the breath introduced into the carrier gas from the sample introduction section is cooled by the cooling section, more volatile components in the breath are trapped and detected by desorbing those volatile components. Can be detected by

It is the schematic which showed the structural example of the breath analyzer which concerns on one Embodiment of this invention. It is the flowchart which showed the flow of the process by the control part at the time of breath analysis.

1. Configuration of Breath Analysis Device FIG. 1 is a schematic diagram illustrating a configuration example of a breath analysis device according to an embodiment of the present invention. The breath analysis apparatus is configured of a gas chromatograph mass spectrometer (GC / MS) including a gas chromatograph unit (GC unit 1) and a mass analysis unit (MS unit 2).

  The GC unit 1 includes, for example, a column 11, a sample introduction unit 12, a column oven 13, a carrier gas supply unit 14, a heater 16, and a cooling unit 17. The column 11 is, for example, a capillary column, and the upstream end thereof is connected to the sample introduction unit 12 and the downstream end thereof is connected to the MS unit 2.

  The column 11 is housed in the column oven 13 together with the heater 16 and the cooling unit 17. The column oven 13 is for heating the column 11, and the analysis is performed while heating the column 11 by driving the heater 16 at the time of analysis.

  A sample vaporization chamber (not shown) is formed in the sample introduction unit 12. The breath to be analyzed is introduced into the sample vaporization chamber of the sample introducing unit 12. Further, the carrier gas is supplied from the carrier gas supply unit 14 to the sample vaporization chamber. As a carrier gas, for example, an inert gas such as He gas is used. In the sample vaporizing chamber, exhaled air is introduced into the carrier gas supplied from the carrier gas supply unit 14, and the carrier gas mixed with exhaled air is introduced into the column 11 from the sample vaporizing chamber.

  Although not shown in FIG. 1, a split flow path for discharging a part of the gas in the sample vaporization chamber to the outside at a predetermined split ratio is connected to the sample introduction unit 12. When the carrier gas is introduced into the column 11 together with the sample, the sample can be introduced into the column 11 using the split introduction method by discharging a part thereof from the split flow path to the outside. For example, when injecting a sample having a low concentration of the ppb order, a splitless introduction method in which the entire amount of the sample is introduced into the column 11 by closing the split flow path using a valve (not shown) is used. There is also. When analysis of exhaled breath is performed as a sample, it is necessary to introduce the entire amount of the sample (the latter) into the column 11 because the concentration of volatile components in exhaled breath is low. In this embodiment, since the cooling unit 17 is used, for example, 10 ml or more of exhaled air is injected into the sample vaporizing chamber using a syringe or the like in the sample introducing unit 12, and the entire amount of exhaled air is introduced into the column 11.

  The breath introduced into the carrier gas is cooled by the cooling unit 17 immediately after being supplied into the column 11. The cooling unit 17 is provided near the upstream end of the column 11. Specifically, the cooling unit 17 is provided at a position within 50 cm, more preferably within 30 cm, from the upstream end to the downstream end of the column 11.

  The cooling unit 17 cools the column 11 from the outside. For example, a gas cooled by a coolant such as liquid nitrogen is supplied to the cooling unit 17, and the column 11 is cooled by heat exchange between the gas and the column 11. Although the temperature of the column 11 of the part cooled by the cooling unit 17 is, for example, -160 to -190 ° C., it is not limited thereto. The said temperature changes according to the kind of coolant, for example, it is preferable that it is -60 degrees C or less, and it is more preferable if it is -100 degrees C or less.

  Thus, the cooling unit 17 functions as a cryofocusing unit that traps volatile components in exhaled breath in the column 11 of the cooled portion by cooling the column 11. That is, some or all of the volatile components in exhaled breath are collected near the upstream end of the column 11 and are retained without flowing downstream. On the other hand, oxygen and nitrogen in exhaled breath are not trapped even when cooled by the cooling unit 17, and flow downstream in the column 11.

  When the operation of the cooling unit 17 is stopped, the column 11 is heated by the heater 16 including the portion cooled by the cooling unit 17. That is, since the column 11 is provided in the column oven 13 together with the heater 16 and the cooling unit 17, when the cooling unit 17 is operating, the vicinity of the upstream end of the column 11 is cooled even if the heater 16 is operating. However, when the operation of the cooling unit 17 is stopped, the vicinity of the upstream end of the column 11 is heated by the operating heater 16.

As a result, the temperature near the upstream end of the column 11 gradually increases and approaches the temperature in the column oven 13. At this time, the volatile components in the breath trapped in the vicinity of the upstream end of the column 11 are volatilized in order from the volatile component having the lowest boiling point. Thereby, the volatile component is desorbed from the state trapped in the column 11 and flows to the downstream side of the column 11. That is, the heater 16 constitutes a heating unit that desorbs the volatile component trapped in the column 11 by heating. Examples of volatile components having a low boiling point include hydrogen sulfide (H ₂ S), formaldehyde (CH ₂ O) and the like, but are not limited thereto.

  Volatile components in exhaled air desorbed by the heating of the heater 16 are separated in the process of passing through the column 11, and are sequentially guided to the MS unit 2 as a detection unit. The MS unit 2 performs mass spectrometry on volatile components sequentially introduced from the column 11. The method of mass analysis by the MS unit 2 is not particularly limited, but for example, a method using a quadrupole mass spectrometer can be adopted.

  In this case, volatile components sequentially introduced from the column 11 are ionized in the ionization section (not shown), and the ions are sent to the quadrupole mass spectrometer. In the quadrupole mass spectrometer, only ions having a specific m / z (mass-to-charge ratio) selectively pass between the four electrodes, and the passed ions are detected by the detector. Thereby, the relationship between m / z and the detection intensity in the detector is measured as a mass spectrum, and mass analysis is realized.

  The operations of the sample introduction unit 12, the carrier gas supply unit 14, the heater 16, the cooling unit 17, and the MS unit 2 are controlled by the control unit 3 including, for example, a CPU (Central Processing Unit). The control unit 3 may be provided in either the GC unit 1 or the MS unit 2, or may be configured by a control device provided separately from the GC unit 1 and the MS unit 2.

2. Operation During Breath Analysis FIG. 2 is a flowchart showing the flow of processing by the control unit 3 during breath analysis.

  When analyzing the volatile components in the exhaled breath, the supply of the carrier gas from the carrier gas supply unit 14 is started (step S101), and the heating of the column 11 by the heater 16 is started (step S102). During the subsequent analysis, the supply of the carrier gas and the heating of the column 11 are maintained.

  Then, first, the cooling by the cooling unit 17 is started (step S103), whereby the vicinity of the upstream end of the column 11 is cooled. The vicinity of the upstream end of the column 11 is sufficiently cooled, and when the temperature of the portion is stabilized, exhalation is introduced from the sample introduction unit 12 into the carrier gas supplied into the column 11 (step S104).

  Thereafter, the cooling unit 17 is maintained in the operating state until the predetermined time passes, and when the predetermined time passes (Yes in step S105), the cooling by the cooling unit 17 is stopped (step S106). That is, after the introduction of the exhalation by the sample introduction unit 12, the operation of the cooling unit 17 is stopped after a predetermined time has elapsed while maintaining the state of the carrier gas supply unit 14 supplying the carrier gas into the column 11.

  Although the said predetermined time is not specifically limited, For example, it is preferable that it is 180 to 500 seconds, and if it is 450 to 500 seconds, it is more preferable. The predetermined time is obtained based on, for example, the length of the column 11 or the flow rate of the carrier gas, and exhaled air (oxygen, nitrogen, etc.) after trapping volatile components in the column 11 passes through the column 11. Set to a value sufficient for

  When cooling by the cooling unit 17 is stopped (step S106), the temperature in the vicinity of the upstream end of the column 11 gradually increases due to the heating of the heater 16, and volatile components in the exhaled breath trapped in the column 11 are The volatile components of lower boiling point are desorbed in order and flow to the downstream side of the column 11. Then, the volatile components separated in the process of passing through the inside of the column 11 are sequentially detected by the MS unit 2 (step S107), and mass spectrometry is performed.

3. Operation and Effect (1) In the present embodiment, as shown in FIG. 1, by cooling the exhalation introduced into the carrier gas from the sample introduction part 12 by the cooling part 17, more volatile components in the exhalation can be reduced 11 can be trapped. Then, the volatile components trapped in the column 11 are heated by the heater 16 to sequentially desorb the volatile components having a lower boiling point, and the desorbed volatile components are separated in the column 11 to form the MS portion 2 Can be detected sequentially. Thus, more volatile components in exhaled breath can be detected.

(2) In particular, in the present embodiment, as shown in FIG. 1, the cooling unit 17 and the heater 16 are provided in the column oven 13 together with the column 11. Therefore, after the volatile components in the exhalation are cooled by the cooling unit 17 provided in the column oven 13 and trapped in the column 11, the operation of the cooling unit 17 is stopped, the same as in the column oven 13. The volatile component trapped as it is is heated by the heater 16 provided. As a result, after the introduction of the exhalation by the sample introduction unit 12, the volatile component in the exhalation trapped in the column 11 can be smoothly heated and released.

(3) Further, in the present embodiment, as shown in FIG. 2, after the introduction of exhalation by the sample introduction unit 12 (step S <b> 104), the cooling unit 17 maintains the state where the carrier gas is supplied into the column 11. The operation is stopped (step S106). Accordingly, when the operation of the cooling unit 17 is stopped after the introduction of exhaled gas by the sample introduction unit 12, the volatile components that are desorbed in the order of the low boiling point pass through the column 11 by the continuously supplied carrier gas. . Thereby, the desorbed volatile component smoothly passes through the column 11, and the volatile component separated in the column 11 is detected well by the MS unit 2.

(4) In particular, in this embodiment, as shown in FIG. 2, after the expiration is introduced by the sample introduction unit 12 (step S104), after a predetermined time has elapsed (Yes in step S105), the operation of the cooling unit 17 is performed. Are stopped (step S106). That is, after the introduction of exhalation by the sample introduction unit 12, oxygen, nitrogen, etc. contained in the exhalation pass through the column 11 for a predetermined time, and thereafter the operation of the cooling unit 17 is stopped. Thereby, since oxygen, nitrogen, etc. contained in exhalation can prevent a detection result from being adversely affected, a better detection result can be obtained.

4. Modification Example In the above embodiment, the case where the breath analyzer is configured by the gas chromatograph mass spectrometer in which the volatile component separated in the process of passing through the column 11 is detected by the MS unit 2 has been described. However, the present invention is not limited to such a configuration. For example, another detector such as a hydrogen flame ionization detector (FID) may be configured to detect the volatile component separated in the process of passing through the column 11 Also good. In this case, the breath analysis apparatus is not limited to the gas chromatograph mass spectrometer including the GC unit 1 and the MS unit 2, and may be a gas chromatograph including only the GC unit 1.

  Further, in the above embodiment, the configuration in which the operation of the breath analysis apparatus for analyzing volatile components in the breath is automatically performed by the processing of the control unit 3 as illustrated in FIG. 2 has been described. However, the present invention is not limited to such a configuration, and at least a part of the processing as illustrated in FIG. 2 may be manually performed by a worker.

  The heater 16 and the cooling unit 17 are not limited to the separately provided configuration, and the heating unit and the cooling unit may be configured by, for example, a temperature control unit having both a cooling function and a heating function. In this case, after the volatile component in the exhalation is cooled by the cooling function and trapped in the column 11, the operation of the cooling function is stopped and the volatile component trapped as it is by starting the operation of the heating function. Is heated. Thereby, after the introduction of the exhalation by the sample introduction unit 12, the volatile components in the exhalation trapped in the column 11 can be smoothly heated and desorbed.

DESCRIPTION OF SYMBOLS 1 GC part 2 MS part 3 Control part 11 Column 12 Sample introduction part 13 Column oven 14 Carrier gas supply part 16 Heater 17 Cooling part

Claims (3)

Columns,
A carrier gas supply unit for supplying a carrier gas into the column;
A sample introduction part for introducing exhaled breath into the carrier gas supplied into the column from the carrier gas supply part;
A cooling unit that traps volatile components in the exhalation in the column by cooling exhalation introduced into the carrier gas from the sample introduction unit;
A heating unit for desorbing the volatile component trapped in the column by heating;
A detection unit for detecting volatile components separated in the process of being desorbed by the heating unit and passing through the column ;
A control unit for stopping the operation of the cooling unit while maintaining the state of supplying the carrier gas into the column by the carrier gas supply unit after the introduction of exhalation by the sample introduction unit;
The control unit may stop the operation of the cooling unit after a predetermined time for oxygen and nitrogen contained in the breath to pass through the column after the introduction of the breath by the sample introduction unit. Breath analysis device.   The breath analysis apparatus according to claim 1, wherein the predetermined time is 180 to 500 seconds. A column oven containing the column;
The breath analysis apparatus according to claim 1 or 2 , wherein the cooling unit and the heating unit are provided in the column oven.

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