JPH10197445A - Method for analyzing expiration gas and apparatus therefor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To correctly measure a ratio of<13> CO2 to the whole carbon dioxide in an expiration gas, by adjusting a pressure reduction state on real time so that a concentration of the whole carbon dioxide in the expiration gas in a cell is kept at a constant value. SOLUTION: A sample-sealing bag 112 is connected to an expiration-collecting apparatus 110, and a pressure in a cell 120 is reduced to a predetermined value. Then, a valve 124 and a check valve 128 are opened to send an expiration gas in the sample-sealing bag 112 into the cell 120. A detecting means monitors a concentration of the whole carbon dioxide in the cell 120 in real time. A control means 141 controls operations of the valve 124, a cylinder pump 118, check valves 126, 128, etc., to adjust a pressure-reduced state in the cell 120 in real time so that the concentration of the whole carbon dioxide monitored by the detecting means is kept at a constant value. the detecting means measures a ratio of<13> CO2 to the whole carbon dioxide in the expiration gas in the cell 120 where the pressure-reduced state is adjusted to maintain the concentration of the whole carbon dioxide in the cell 120 constant.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method and apparatus for expiration analysis, and more particularly to a method and apparatus for exhalation measurement capable of measuring the ratio of ¹³ CO _{2 to} total carbon dioxide in exhalation.

[0002]

2. Description of the Related Art Conventionally, many patients with indigestion secondary to peptic ulcer complaining of dyspepsia and gastritis and non-ulcer patients have been treated with gram-negative bacilli Helicobacter Pylori. It is known to be infected. This Helicobacter pylori has been found to adhere to the patient's gastric mucosa and to be found inside the gastric mucosa. Conventionally, in order to test for infection by Helicobacter pylori, it was necessary to perform endoscopy and biopsy of the stomach.

However, it has been difficult to quantify the invasion of Helicobacter pylori by conventional gastric endoscopy and biopsy. Therefore, it is easy to determine the presence or absence of bacterial urease, which is considered to be present in the patient's stomach and its vicinity, and its infection status, and to perform a test that does not damage the human body when performing the test. Development was strongly desired in this type of field. As a response to such a demand, the breath test method is currently receiving the most attention.

[0004] This breath test method is that, after urea labeled with a carbon isotope is administered to a subject and consumed, a breath sample is collected from the subject, and the carbon in the breath sample is collected. Urease urea enzyme activity in the stomach and its vicinity is measured by analyzing carbon dioxide containing isotopes. That is, when urea labeled with a carbon isotope is administered to a person infected with Helicobacter pylori, bacterial urease present in the stomach and its vicinity decomposes urea into ¹³ CO ₂ and ammonia. Therefore, when the ratio of ¹³ CO _{2 to} the total carbon dioxide in the sample gas after administration of urea labeled with a carbon isotope is higher than the ratio of ¹³ CO ₂ before administration, the subject Is determined to be positive.

[0005] Incidentally, the sample-filled bag is connected to a breath analyzer after the breath is sealed, and the breath in the sample-bag is transferred into the cell of the breath analyzer. Then, the measurement of the ratio of ¹³ CO _{2 to} the entire carbon dioxide gas in the breath filled in the cell is performed. Here, when transferring the exhaled breath from the sample encapsulation bag to the cell, it is necessary to dilute the exhaled breath so that the concentration of the entire carbon dioxide gas in the exhaled breath filled in the cell is kept constant in order to perform the measurement properly. There is.

Conventionally, as a technique for diluting such expiration, for example, the technique shown in FIG. 1 is known.
FIG. 1 shows a partial configuration of a conventional breath analyzer. A conventional breath analyzer 10 shown in FIG. 1 includes a nitrogen cylinder 1 in which the mouth of a sample-encapsulating bag 12 in which the breath of a subject is sealed is inserted into one side, and the other is filled with high-purity nitrogen gas.
A sample pump 16 into which the sample gas 4 is inserted, a syringe pump 18 provided downstream of the sample chamber 16 for transferring a sample gas, and a syringe pump 18 provided downstream of the syringe pump 18;
Cell 2 filled with sample gas by syringe pump 18
0.

Then, the exhaled gas in the sample enclosing bag 12 is diluted with high-purity nitrogen gas in the nitrogen cylinder 14 so that the concentration of the entire carbon dioxide gas in the sample gas filled in the cell 20 is kept constant. It is transferred to the cell 20 as a sample gas.
That is, as shown in FIG. 2, when the syringe 18 a of the syringe pump 18 is lowered with the valve 24 open, the exhalation of the sample sealing bag 12 is collected in the syringe pump 18.

Then, as shown in FIG. 3, when the cock 22 is opened on the way, the nitrogen gas in the nitrogen cylinder 14 is also collected into the syringe pump 18 and the exhaled air is diluted with the nitrogen gas. The syringe 18a is lowered to the lower limit,
When the sample gas is collected in the syringe pump 18, FIG.
As shown in (2), when the opened valve 24 is closed and the syringe 18a is raised, the sample gas collected in the syringe pump 18 is transferred into the cell 20.

Then, the ratio of ¹³ CO _{2 to} the total carbon dioxide in the sample gas flowing in the cell 20 is measured. The concentration of the entire carbon dioxide gas in the sample gas in the cell 20 is monitored in real time by a detector (not shown).
The operations of the cock 22, the syringe pump 22, the valve 24, and the like are controlled so that the concentration of the entire carbon dioxide gas within 0 maintains a constant value.

[0010]

However, in the above-mentioned conventional breath analyzer 10, nitrogen gas for diluting breath is supplied so that the concentration of the entire carbon dioxide gas in the cell 20 is kept constant as described above. is necessary. Therefore, the configuration of the apparatus is complicated, and the operation is complicated. Further, it is very difficult to dilute the exhaled breath with the nitrogen gas so that the concentration of the entire carbon dioxide gas in the cell 20 maintains a constant value.

That is, the concentration of the entire carbon dioxide gas in the cell 20 is monitored in real time by a detector (not shown), and the cock 22 of the nitrogen cylinder 14 is maintained so that the concentration of the entire carbon dioxide gas in the cell 20 maintains a constant value. , Syringe pump 2
2. The operation of the valve 24 and the like is controlled. However, it has been very difficult to change the dilution state of the sample gas once diluted with nitrogen gas. Moreover,
Since the configuration of the apparatus is complicated, its response is not sufficient, and a satisfactory detection result has not always been obtained.

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned circumstances of the prior art, and an object of the present invention is to make it possible to more accurately measure the ratio of ¹³ CO _{2 to} the entire carbon dioxide gas in exhaled breath and to easily carry out the measurement. An object of the present invention is to provide a breath analysis method and a device thereof.

[0013]

In order to achieve the above object, a breath analysis method according to the present invention comprises a pressure reducing step, a transferring step, an adjusting step, and a detecting step. In the pressure reducing step, the pressure in the cell of the breath analyzer is reduced to a predetermined value. In the transferring step, the exhaled air is transferred into the cell that has been depressurized by the depressurizing step.

In the adjusting step, the depressurized state in the cell is adjusted in real time such that the concentration of the entire carbon dioxide in the exhaled gas transferred into the cell in the transferring step is maintained at a constant value. The detecting step detects a ratio of ¹³ CO _{2 to} the entire carbon dioxide in the cell, the concentration of which is adjusted so as to maintain a constant value in the exhaled carbon dioxide by the adjusting step. In order to achieve the above object, a breath analyzer according to the present invention includes a sample loading inlet, a cell, a carbon dioxide concentration detecting unit, a transfer unit, a ¹³ CO ₂ concentration detecting unit, and a control unit. .

The sample loading inlet is provided with a mouth portion of a sample sealing bag in which the breath of the subject is sealed, which is detachably provided. The cell is provided on the downstream side of the sample loading port, and expiration of the sample sealing bag is transferred through the sample loading port. The carbon dioxide concentration detecting means detects the concentration of the entire carbon dioxide in the breath in the cell.

The transfer means is provided on the downstream side of the cell, reduces the pressure in the cell to a predetermined value, and maintains the concentration of the entire carbon dioxide in the exhaled gas in the cell at a constant value.
The depressurized state in the cell is adjusted in real time, and the expiration of the sample sealing bag is transferred into the cell. The ¹³ CO ₂ concentration detecting means detects the ratio of ¹³ CO _{2 to} the entire carbon dioxide in the cell in which the pressure reduction state is adjusted by the transfer means so that the concentration of the entire carbon dioxide in the exhaled air keeps a constant value. .

The control means adjusts the depressurized state in the cell by the transfer means so that the entire concentration of carbon dioxide in the exhaled air detected by the carbon dioxide concentration detecting means maintains a constant value.

[0018]

An embodiment of the present invention will be described below with reference to the drawings. FIG. 5 shows a schematic configuration of the breath analyzer according to the first embodiment of the present invention. In addition,
Parts corresponding to those in FIG. 1 are denoted by reference numeral 100, and description thereof is omitted. The breath analyzer 110 shown in FIG. 1 includes a sample loading port 116 into which the mouth of a sample encapsulating bag 112 in which the breath of a subject is sealed, and a cell 120 provided downstream of the sample loading port 116. And a transfer means including a syringe pump 118 provided on the downstream side of the cell 120.

The cell 120 includes a cell inner chamber 120e filled with expiration, an inlet pipe 120a for introducing expiration into the cell inner chamber 120e, and an outlet pipe 120b for discharging the measured sample gas from the cell inner chamber 120e to the outside. It has. The syringe pump 118 adjusts the reduced pressure state in the cell 120 so that the concentration of the entire carbon dioxide gas in the expiration in the cell 120 maintains a constant value. In addition, the breath analyzer 110 shown in the figure has a light source 132 that irradiates an infrared light beam L, a rotating sector 134 that uses the infrared light beam L from the light source 132 as intermittent light, A detector 136 for measuring the ratio of ¹³ CO _{2 to} the whole carbon dioxide in the exhaled air, an amplifier 138 for amplifying a signal from the detector 136, and ¹³ CO ₂ for the whole carbon dioxide based on a signal from the amplifier 138. Indicator 14 for indicating the ratio of
0.

The detecting means monitors the concentration of the entire carbon dioxide in the exhaled gas in the cell 120 in real time. Then, the control means 14 controls the operation of the valve 124, the syringe pump 22, the check valves 126 and 128 and the like so that the concentration of the entire carbon dioxide in the cell 120 monitored by the detection means keeps a constant value. Cell 1
The decompression state in 20 is adjusted. That is, ¹³ CO ₂
During the measurement of the ratio, when the concentration of the entire carbon dioxide gas monitored by the detection means falls below a predetermined value, the control means 141 controls the valve 124, the syringe pump 118,
The check valves 126 and 128 are operated to increase the pressure in the cell 120 until the concentration of the entire carbon dioxide gas monitored by the detection means rises to a predetermined value.

On the other hand, when the concentration of the entire carbon dioxide gas monitored by the detection means rises above a predetermined value, the control means 141 controls the valve 124, the syringe pump 11
8. Activate the check valves 126, 128, etc., and reduce the pressure in the cell 120 until the concentration of the entire carbon dioxide gas monitored by the detection means drops to a predetermined value. The breath analyzer 110 according to the first embodiment is configured as outlined above, and its operation will be described next.

First, the exhaled breath before urea administration labeled with a carbon isotope is collected in the sample enclosing bag 112,
Twelve mouths are connected to the sample inlet 116 of the breath test apparatus 110. When the sample sealing bag 112 is connected to the breath collection device 110, the pressure inside the cell 120 is reduced to a predetermined value. That is, as shown in FIG.
When the check valve 126 is opened and the syringe of the syringe pump 118 is lowered with the valve 28 closed, the cell 1
The air in 20 is collected in syringe pump 118, and the pressure in cell 120 is reduced. And the syringe pump 11
When the syringe No. 8 drops to the lower limit, the check valve 128 is opened as shown in FIG. 7 and the syringe pump 118 is raised by raising the syringe of the syringe pump 118.
Air can be exhausted from inside to outside. This is repeated to reduce the pressure inside the cell 120 to a predetermined value.

When the pressure in the cell 120 is reduced to a predetermined value, the valve 124 and the check valve 128 are opened as shown in FIG. Here, the detecting means monitors the concentration of the entire carbon dioxide gas in the cell 120 in real time. Then, the control means 141 controls the operation of the valve 124, the syringe pump 118, the check valves 126 and 128 and the like so that the concentration of the entire carbon dioxide gas monitored by the detection means keeps a constant value. Condition is being adjusted.

That is, during the measurement of the ¹³ CO ₂ ratio, if the concentration of the entire carbon dioxide gas monitored by the detection means falls below a predetermined value, the control means 141 sets the valve 1
24, syringe pump 118, check valve 126,
128, etc., until the concentration of the entire carbon dioxide gas monitored by the detecting means rises to a predetermined value.
Increase pressure inside 0. On the other hand, when the concentration of the entire carbon dioxide gas monitored by the detection means rises above a predetermined value,
The control means 141 includes the valve 124, the syringe pump 11
8. Activate the check valves 126, 128, etc., and reduce the pressure in the cell 120 until the concentration of the entire carbon dioxide gas monitored by the detecting means drops to a predetermined value.

As described above, in the first embodiment, as shown in FIG. 9, the control means 124 controls and opens the valve 124 with time, closes the check valve 128, and adjusts the concentration of the entire carbon dioxide gas in the cell 120 to a constant value. To keep the cell 120
The decompression state inside is adjusted in real time. And
As described above, the detecting means controls the ¹³ C for the entire carbon dioxide in the exhaled gas in the cell 120, the pressure of which has been adjusted to keep the concentration of the entire carbon dioxide in the cell 120 constant.
It measures the O ₂ ratio. By the way, for example, the syringe pump 118 is connected to the sample sealing bag 112 and the cell 12.
When it is arranged between 0, the dead volume becomes large, and as a result, contamination by the syringe pump 118 is likely to occur.

Therefore, in the first embodiment, the syringe pump 118 is arranged downstream of the cell 120 in order to prevent contamination. When the measurement is completed, the valve 124 and the check valves 126 and 128 are opened, and the measured gas is discharged from the inner chamber 120e of the cell 120 to the outside.

Next, in the same way as before the administration of the urea labeled with the carbon isotope, the exhaled air after the administration of the urea labeled with the carbon isotope is collected in the sample enclosing bag, and then the exhaled air is subjected to the entire carbon dioxide gas in the sample gas. ^{The 13} CO ₂ ratio is measured by the breath analyzer 110. And, before and after the administration of urea labeled with carbon isotope, ¹³ CO
The ratio of ₂ is compared to determine whether the subject is infected with Gram-negative bacilli Helicobacter pylori or the like. That is, when urea labeled with a carbon isotope is administered to a person infected with Helicobacter pylori, bacterial urease present in the stomach and its vicinity decomposes urea into ¹³ CO ₂ and ammonia. Therefore, the ratio of ¹³ CO _{2 to} the total carbon dioxide in the sample gas after the administration of urea labeled with carbon isotope,
If it is increased compared to the ratio of ¹³ CO ₂ before administration,
The subject is determined to be positive.

As described above, the breath analyzer 110 according to the first embodiment employs a decompression method as a method for diluting the sample gas, instead of diluting the breath with nitrogen gas as in the conventional method. That is, the ratio of ¹³ CO _{2 to} the entire carbon dioxide in the exhaled gas is detected in the cell 120 in which the depressurized state is adjusted in real time so that the concentration of the entire carbon dioxide in the exhaled gas in the cell 120 is kept constant. ¹³ CO _{2 to the} entire carbon dioxide gas
Can be more accurately measured, and this can be easily performed.

That is, during the measurement of the ¹³ CO ₂ ratio,
Even if the concentration of the entire carbon dioxide gas in the cell 120 deviates from a predetermined value, the control means 141 controls the valve 12
4. Syringe pump 118, check valve 126, 1
Only 28 such actuates adjusting the vacuum of cell 120, it is possible to quickly and easily correct this, compared to the conventional, ¹³ CO ₂ to the whole carbon dioxide
Can be measured more accurately, and the configuration of the device can be simplified.

Further, the syringe pump 118 is connected to the cell 12
0, the dead volume can be reduced, and the syringe pump 118
Contamination can be prevented. In addition,
The breath analyzer of the present invention is not limited to the above configuration, and various modifications can be made within the scope of the present invention.

FIG. 10 shows a schematic configuration of a cell used in a breath analyzer according to another embodiment. Note that the portions corresponding to those in FIG. 5 are denoted by reference numeral 100, and description thereof is omitted. In the figure, a light source 232 that irradiates an infrared light beam, a rotating sector 234 that uses the infrared light beam from the light source 232 as intermittent light, a cell 220, a detector 236a in which ¹² CO ₂ is sealed, and ¹³ CO ₂ 236b, a detector 236b in which is enclosed, an amplifier 238 for amplifying a signal from the detector 236, and an indicator 240 for indicating the ratio of ¹³ CO _{2 to} the entire carbon dioxide based on the signal from the amplifier 238. .

Further, these detecting means monitor the concentration of the entire carbon dioxide gas in the cell 220 in real time. Then, the control unit controls the operation of the valve, the syringe pump, the check valve, and the like to adjust the reduced pressure state in the cell 220 so that the concentration of the entire carbon dioxide gas monitored by the detection unit maintains a constant value. . In the second embodiment, the cell 220 includes a short optical path section 220c and a long optical path section 220c.
and each optical path length is configured to correspond to a mixing ratio of ¹² CO ₂ and ¹³ CO ₂ .

That is, the cell 220 stores the ¹² CO
The mixing ratio of ₂ and ¹³ CO ₂ is, for example, A: B (where A >>
In the case of B), the short optical path section 220c and the long optical path section 220d
Are configured such that the optical path length of the light-emitting device becomes B: A.

Further, a detector 236 in which ¹² CO ₂ is sealed is provided.
a has sensitivity only to an infrared light beam in the same wavelength range as the wavelength range specific to ¹² CO ₂ , and can detect the absorption of ¹² CO ₂ . In contrast, ¹³ detector 236b which CO ₂ has been filled are those with only sensitivity infrared light beam of the specific wavelength region in the same wavelength range ¹³ CO _2, to detect the absorption of ¹³ CO ₂ it can. In the second embodiment, it is preferable that the cell 220 be provided with plano-convex condensing lenses 242 and 244 on the passage courses L1 and L2 of the infrared light flux. That is, the incident light to the cell 220 can be satisfactorily transmitted, and the incident light can be satisfactorily focused on the detectors 236a and 236b.

The filters 246 and 2 selectively absorb light having a wavelength unique to carbon dioxide gas sealed in the other detector.
Preferably, 48 is provided. That is, when the wavelength specific to ¹² CO ₂ is about 4.2 μm, the detector 236 a is provided with a filter 146 for selectively absorbing light having a wavelength of 4.2 μm. In contrast, ¹³ C
When the wavelength specific to O ₂ is about 4.4 microns (μm), the detector 236b is provided with a filter 248 that selectively absorbs light having a wavelength of 4.4 microns (μm).

As a result, even if a component other than the object to be measured is mixed in the detector, a measurement error due to light absorption of the component other than the object to be measured can be greatly reduced. Can be further improved. As described above, even when the cell 220 shown in the figure is used as the cell, the same effect as in the first embodiment can be obtained. Moreover, one of the forked parts of the cell 220 is dark
¹² In the case of CO _2, shortened constituting the optical path length, a thin ¹³
In the case of CO ₂ , the other optical path length is compared with the one optical path length and is configured to be longer, so that the detectors 236a, 236
Since the output from 36b is balanced, the detection sensitivity is improved as compared with the first embodiment.

In each of the above structures, it is preferable to use a cell whose inside is optically polished. This allows the infrared light beam L to pass efficiently. Each of the above-mentioned components includes a constant temperature means 150 for keeping the temperature of the cell 120 at a constant value, for example, as shown in FIG. Is preferred. Thereby, the measurement error caused by the temperature change around the cell can be significantly reduced, and the reliability of the analysis result can be improved. Furthermore, in each of the above-described configurations, the case where the flow of exhalation is stopped in a state where the exhalation is filled in the cell has been described.However, the present invention is not limited to this. If the concentration can be maintained at a constant value, it is possible to make the expiration flow continuously.

[0038]

As described above, according to the expiration analysis method and apparatus according to the present invention, a decompression method is adopted as a method for diluting expiration. That is, in a cell in which the decompression state is adjusted in real time so that the concentration of carbon dioxide in the cell is maintained at a constant value, the ratio of ¹³ CO _{2 to} the entire carbon dioxide in exhalation is detected, The ratio of ¹³ CO _{2 to} the whole can be measured more accurately and this can be done easily. In addition, by providing the transfer means at the subsequent stage of the cell, the dead volume can be reduced and contamination by the transfer means can be prevented.

[Brief description of the drawings]

FIG. 1 is a block diagram illustrating a schematic configuration of a conventional breath analyzer.

FIG. 2 is an explanatory view of the operation of the device shown in FIG.

FIG. 3 is an explanatory view of the operation of the device shown in FIG. 1;

FIG. 4 is an explanatory view of the operation of the device shown in FIG. 1;

FIG. 5 is a block diagram showing a schematic configuration of a breath analyzer according to the first embodiment;

FIG. 6 is an explanatory view of the operation of the device shown in FIG. 5;

FIG. 7 is an explanatory view of the operation of the device shown in FIG. 5;

FIG. 8 is an explanatory view of the operation of the device shown in FIG. 5;

FIG. 9 is an explanatory view of the operation of the device shown in FIG. 5;

FIG. 10 is an explanatory diagram of a cell used in the breath analyzer according to the second embodiment.

[Explanation of symbols]

110 ... breath analyzer 116 ... sample spout 118 ... syringe pump (transfer means) 120 ... cell 132 ... light source (carbon dioxide concentration detection means, ¹³ CO ₂ concentration detector) 136 ... detector (carbon dioxide concentration detection means, ¹³ CO ₂
Concentration detection means)

Claims (2)

[Claims] A pressure reducing step of reducing the pressure in the cell of the breath analyzer to a predetermined value; a transferring step of transferring the expired gas into the cell in a state where the pressure is reduced by the pressure reducing step; Adjusting the depressurized state in the cell in real time so that the concentration of the entire carbon dioxide in the exhaled gas keeps a constant value; and A detection step of detecting a ratio of ¹³ CO _{2 to} the entire carbon dioxide in the cell being adjusted, comprising: 2. A sample loading port in which a mouth portion of a sample sealing bag in which the breath of a subject is sealed is provided detachably, and a sample loading port is provided downstream of the sample loading port, and the sample loading bag is provided through the sample loading port. A cell in which the exhalation of the sample-encapsulated bag is transferred, a carbon dioxide concentration detecting means for detecting the concentration of the entire carbon dioxide in the exhaled gas in the cell, provided on the downstream side of the cell to a predetermined value in the cell. At the same time as the pressure is reduced, the pressure in the cell is adjusted in real time so that the concentration of the entire carbon dioxide in the breath in the cell maintains a constant value, and the breath in the sample sealing bag is transferred into the cell. Transfer means, and ¹³ CO ₂ concentration detection for detecting the ratio of ¹³ CO _{2 to} the total carbon dioxide in the cell in which the reduced pressure state is adjusted by the transfer means so that the concentration of the entire carbon dioxide in the exhaled air keeps a constant value. Means, and the carbon dioxide concentration detecting means A breathing analyzer, comprising: control means for adjusting the reduced pressure state in the cell by the transfer means so that the concentration of the entire carbon dioxide gas detected in the breath keeps a constant value.