JP2969066B2 - Isotope gas spectrometer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The metabolic function of a living body can be measured by administering a drug containing an isotope to a living body and then measuring the change in the isotope concentration or the change in the concentration ratio. Body analysis has been used to diagnose diseases in the medical field. In addition to the fields of medicine, isotope analysis is used for studies of photosynthesis and metabolism of plants, and is used for tracing ecosystems in the field of geochemistry.

[0002] The present invention relates to an isotope gas spectrometry method and apparatus for measuring the concentration of an isotope gas by focusing on the difference in the light absorption characteristics of the isotopes.

[0003]

2. Description of the Related Art In general, it is known that bacteria other than stress include bacteria called Helicobacter pylori (HP) as a cause of gastric ulcer and gastritis. If HP is present in the patient's stomach, it is necessary to perform eradication treatment by administration of antibiotics or the like. Therefore, it is important to determine whether HP is present in the patient. HP is
It has strong urease activity and breaks down urea into carbon dioxide and ammonia.

[0004] On the other hand, carbon has a mass number of 12 and isotopes having a mass number of 13 and 14 in addition to a carbon atom having a mass number of 12. Among these, the isotope ¹³ C having a mass number of 13 has no radioactivity, Handling is easy because it exists stably. Therefore, after administering urea marked with the isotope ¹³ C to the living body, the concentration of ¹³ CO ₂ in the patient's breath, which is the final metabolite, specifically, the concentration ratio of ¹³ CO ₂ to ¹² CO ₂ is measured. If it can, the existence of the HP can be confirmed.

However, the concentration ratio of ¹³ CO ₂ to ¹² CO ₂ is as large as 1: 100 in nature, and it is difficult to accurately measure the concentration ratio in a patient's breath. Conventionally,
^As a method for determining the concentration ratio between ¹³ CO ₂ and ¹² CO ₂ , a method using infrared spectroscopy is known (Japanese Patent Publication No. Sho 61-42).
No. 219, and JP-B-61-42220).

[0006] The method described in JP-B-61-42220 is
Two long and short cells were prepared, and the length of the cell was set so that the absorption of ¹³ CO ₂ in one cell was equal to the absorption of ¹² CO _{2 in} one cell, and the cells were transmitted through the two cells. In this method, light is guided to both cells, and the light intensity at a wavelength that achieves the maximum sensitivity is measured. According to this method, the light absorption ratio at the concentration ratio in the natural world can be set to 1. If the concentration ratio deviates from this, the light absorption ratio deviates by the amount of the deviation. You can see the change in the ratio.

[0007]

In the above-mentioned conventional infrared spectroscopy method, a bag containing a gas to be measured is connected to a predetermined pipe, and the bag is contracted by hand to pass the gas to be measured through the pipe. It was flowing to the cell. However, in the measurement of the isotope gas, the optical absorption of ¹³ CO ₂ present in the measurement is measured. Therefore, even if there is a slight turbulence, the measurement accuracy is greatly deteriorated. Shrink the bag by hand as described above,
When the gas to be measured flows into the cell, the gas to be measured does not have a constant flow rate. Therefore, the gas flows non-uniformly in the cell, causing a local temperature change and a concentration change based on the temperature change, and the fluctuation of the light detection signal. Cause.

In order to keep the flow rate of the gas to be measured constant, it is conceivable to control the flow rate by combining a pump and a flow meter. However, since the capacity of the bag containing the gas to be measured is originally small and the flow rate is small, the flow rate is small. Control accuracy cannot be ensured. Also, if a device for electronic flow control called a mass flow meter is used as the flow control means, the accuracy is improved, but the device becomes complicated,
Costs also rise.

Accordingly, the present invention realizes an isotope gas spectrometer capable of conducting spectrometry by introducing a gas to be measured including a plurality of component gases into a cell at a constant flow rate with a simple apparatus configuration. With the goal.

[0010]

According to a first aspect of the present invention, there is provided an isotope gas spectrometer for measuring a gas to be measured by sucking the gas to be measured and mechanically extruding the gas at a constant speed. Gas injection means for injecting gas into the cell, and measures the amount of transmitted light having a wavelength suitable for each component gas
Means for taking measurements while the gas to be measured is being injected into the cell.
Do. According to the above configuration, the gas to be measured is injected into the cell at a constant flow rate. Therefore, the gas to be measured flows uniformly during the measurement in the cell, and the light detection signal becomes accurate without fluctuation. Note that a plurality of component gases are
Carbon ¹² CO ₂ and carbon dioxide ¹³ CO ₂ .

As a gas injection means for mechanically extruding the gas at a constant speed, a mechanism having a piston and a cylinder and moving the piston at a constant speed is employed. Further, the isotope gas spectrometer according to the second aspect further includes a temperature holding means for keeping the temperature of the cell for guiding the gas to be measured constant.
By keeping the temperature inside the cell for introducing the gas to be measured constant, the temperature condition of the gas to be measured can be made uniform.
Therefore, in combination with the structure of the first aspect, an accurate light detection signal without fluctuation can be obtained.

[0012]

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, after a urea diagnostic agent marked with isotope ¹³ C is administered to humans, ¹³ CO _{2 in} exhaled breath
When spectroscopically measuring the concentration of the embodiment of the present invention,
This will be described in detail with reference to the accompanying drawings. I. Breath test First, the breath of the patient before administration of the urea diagnostic agent is collected in a breath bag. The capacity of the exhalation bag may be about 250 ml. Thereafter, a urea diagnostic agent was orally administered and 10-1
Five minutes later, the breath is collected in a breath bag in the same manner as before administration.

The exhalation bags before and after administration are respectively set in predetermined nozzles of an isotope gas spectrometer, and the following automatic measurement is performed. II. FIG. 1 is a block diagram showing the overall configuration of an isotope gas spectrometer. The exhalation bag that collects exhaled air after administration (hereinafter referred to as “sample gas”) and the exhalation bag that collects exhaled air before administration (hereinafter referred to as “base gas”) are set in nozzles N ₁ and N ₂ , respectively. The nozzle N ₁ is connected to a three-way valve V ₁ through a transparent resin pipe (hereinafter simply referred to as “pipe”), and the nozzle N ₂ is connected to a 30,000 valve V ₂ through a pipe.

On the other hand, a reference gas (any gas having no absorption in the wavelength range to be measured, for example, nitrogen gas) is supplied from a gas cylinder. Reference gas divided into two-way, one enters a reference cell 11c through the flow meter M _1, the other leads to the three-way valve V ₃ through the flow meter M _2. The reference gas enters the reference cell 11c and exits from the reference cell 11c and is discharged as it is.

[0016] While the divided from way valve V ₃ leads to the three-way valve V _1, and the other thereof is connected to the first sample cell 11a for measuring the absorption of ¹² CO _2.
Also, while the divided from way valve V ₂ are two-way leads to the first sample cell 11a through a valve V _4, the other is connected to the three-way valve V _1. Furthermore, between the three-way valve V ₃ and the first sample cell 11a, the gas injector 21 for quantitatively injecting the sample gas or base Sugasu (volume 60 cc) is interposed. This gas injector 21 is shaped like a syringe having a piston and a cylinder, and the piston is driven by the cooperation of a motor, a feed screw connected to the motor, and a nut fixed to the piston. (See below).

As shown in FIG. 1, the cell chamber 11 contains ¹² CO 2.
Short first sample cell 11 for measuring the absorption of ₂
a, comprising a long second sample cell 11b for measuring the absorption of ¹³ CO ₂ and a reference cell 11c for flowing a reference gas, the first sample cell 11a and the second sample cell 11b are in communication with each other, Cell 1
The gas led to the first sample cell 11a
b and is exhausted. The reference gas is guided to the reference cell 11c and exhausted. The length of the first sample cell 11a is specifically 13 mm, and the length of the second sample cell 11a is 11 mm.
The length of b is specifically 250 mm, and the length of the reference cell 11c is specifically 236 mm.

Reference symbol L indicates an infrared light source device. The infrared light source device L has two waveguides 23 for irradiating infrared light.
a and 23b. The method of generating infrared rays may be any method, for example, a ceramic heater (surface temperature 45 ° C).
0 ° C.) can be used. In addition, a rotating chopper 22 that cuts off and passes infrared rays at a constant cycle is provided. Of the infrared rays emitted from the infrared light source device L,
An optical path formed by an object passing through the first sample cell 11a and the reference cell 11c is referred to as a “first optical path”,
The optical path formed by the object passing through the sample cell 11b is referred to as “second
(See FIG. 2).

Symbol D detects infrared light passing through the cell.
FIG. The infrared detector D is
A first wavelength filter 24a placed in a first optical path and a first wavelength filter 24a;
Of the second wavelength filter placed in the second optical path.
It has a filter 24b and a second detection element 25b. No.
One wavelength filter 24a is¹²CO_TwoMeasuring absorption
For this reason, it passes infrared light with a wavelength of about 4280 nm (bandwidth about
20 nm), the second wavelength filter 24b ¹³CO_Twoof
Pass infrared light at a wavelength of about 4412 nm to measure absorption.
(Bandwidth about 50 nm). First
Detection element 25a and second detection element 25b detect infrared rays.
Any element can be used as long as the element emits, for example, PbSe.
Such a semiconductor infrared sensor is used.

The first wavelength filter 24a and the first detection element 25a are contained in a package 26a filled with an inert gas such as Ar,
b, the second detection element 25b is also contained in a package 26b filled with an inert gas. The whole infrared detecting device D is maintained at a constant temperature (25 ° C.) by a heater and a Peltier element, and the inside of the packages 26a and 26b is maintained at 0 ° C. by a Peltier element.

FIG. 2 is a sectional view showing the detailed structure of the cell chamber 11. As shown in FIG. The cell chamber 11 is itself made of stainless steel, and is vertically and horizontally sandwiched between metal plates (for example, a brass plate) 12, and is provided with a heat insulating material 1 such as styrene foam via a heater 13.
Sealed with 4. Although not shown in the figure, a temperature sensor (for example, a platinum temperature sensor) for measuring the temperature of the cell chamber 11 is attached.

The inside of the cell chamber 11 is divided into two stages, one of which is a first sample cell 11a and the other is a reference cell 1.
1c and the second sample cell 11
b is arranged. A first optical path passes in series between the first sample cell 11a and the reference cell 11c.
A second optical path passes through the sample cell 11b. Reference numerals 15, 16 and 17 are sapphire transmission windows for transmitting infrared rays.

FIG. 9 is a block diagram showing a mechanism for adjusting the temperature of the cell chamber 11. As shown in FIG. The temperature adjustment mechanism is provided in the cell chamber 11.
Temperature sensor 32 attached to the
And a heater 13. As a method of adjusting the temperature of the temperature adjustment substrate 31, any method may be employed. For example, a method of changing a duty ratio of a pulse current flowing through the heater 13 based on a temperature measurement signal of the temperature sensor 32 may be used. Based on this temperature adjustment method, the cell chamber 11 is controlled by the heater 13 so as to be maintained at a constant temperature (40 ° C.).

FIG. 10 is a plan view (FIG. 10 (a)) and a side view (FIG. 10 (b)) showing a gas injector 21 for quantitatively injecting the gas to be measured. The gas injector 21 includes a base 21a.
A cylinder 21b containing a piston 21c is disposed on the upper surface of the cylinder 21. A movable nut 21d connected to the piston 21c, a feed screw 21e meshing with the nut 21d, and a motor 2 for rotating the feed screw 21e are provided below the base 21a.
1f is a structure in which it is arranged.

The motor 21f is driven forward and reverse by a drive circuit (not shown). When the feed screw 21e is rotated by the rotation of the motor 21f, the nut 21d moves back and forth according to the rotation direction, whereby the piston 21c moves back and forth to the position indicated by the two-dot chain line in FIG. Therefore, introduction of the gas to be measured into the cylinder 21b and derivation of the gas to be measured from the cylinder 21b can be freely controlled. III. Measurement procedure Measurement is performed in the order of reference gas measurement → base gas measurement → reference gas measurement → sample gas measurement → reference gas measurement →.

During the measurement, a reference gas is constantly flowing through the reference cell 11c, and its flow rate is measured by the flow meter M.
₁ is set so that it is always kept constant. III-1. Reference Measurement As shown in FIG. 3, a clean reference gas is flowed at 200 ml / min for about 15 seconds into the gas flow path and the cell chamber 11 of the isotope gas spectrometer to clean the gas flow path and the cell chamber 11. .

Next, as shown in FIG. 4, the gas flow path is changed to supply a reference gas, and the gas flow path and the cell chamber 11 are cleaned. After about 30 seconds, each detection element 25
The light quantity is measured by a and 25b. The reason for performing the reference measurement in this way is to calculate the absorbance. In this manner, the amount of light obtained by the first detection element 25a is ¹² R ₁ , and the amount of light obtained by the second detection element 25b is
¹³ written as R _1. III-2. Base Gas Measurement Next, the base gas is sucked from the expiration bag by the gas injector 21 so that the reference gas does not flow through the first sample cell 11a and the second sample cell 11b (FIG. 5).
reference).

After inhaling the base gas, as shown in FIG. 6, the base gas is mechanically pushed out at a constant flow rate using the gas injector 21 (80 ml / min). During this time, the light amounts are measured by the respective detection elements 25a and 25b. Thus, the light amount obtained by the first detection element 25a is
¹² B, the amount of light obtained by the second detection element 25b are the ¹³ B. III-3. Reference measurement The gas flow path and the cell are washed again, and the light quantity of the reference gas is measured again (see FIGS. 3 and 4).

Thus, the light amount obtained by the first detection element 25a is written as ¹² R ₂ , and the light amount obtained by the second detection element 25b is written as ¹³ R ₂ . III-4. Sample gas measurement The sample gas is sucked from the expiration bag by the gas injector 21 so that the reference gas does not flow through the first sample cell 11a and the second sample cell 11b (see FIG. 7).

After sucking in the sample gas, the sample gas is mechanically pushed out at a constant speed using a gas injector 21 (60 ml / min), as shown in FIG. During this time, the light amounts are measured by the respective detection elements 25a and 25b. In this way, the light amount obtained by the first detection element 25a is ¹² S, and the light amount obtained by the second detection element 25b is ¹³ S.
Write S. III-5. Reference measurement The gas flow path and the cell are washed again, and the light quantity of the reference gas is measured again (see FIGS. 3 and 4).

Thus, the light amount obtained by the first detection element 25a is written as ¹² R ₃ , and the light amount obtained by the second detection element 25b is written as ¹³ R ₃ . IV. Data processing IV-1. Calculation of absorbance of base gas First, the transmitted light amount of the reference gas ¹² R ₁ ,
^{Using 13} R ₁ , the transmitted light amount of the base gas ¹² B, ¹³ B, and the transmitted light amount of the reference gas ¹² R ₂ , ¹³ R ₂ , the absorbance of ¹² CO ₂ in the base gas, ¹² Abs (B) and ¹³ CO ₂ The absorbance is determined as ¹³ Abs (B).

[0032] Here, ¹² CO ₂ absorbance ¹² Abs (B) is, ¹² Abs (B) = -log _{^{[2 12 B / (12 R 1}} + 12 R 2) ] In sought, the ¹³ CO ₂ absorbance ¹³ abs (B) is obtained by ¹³ abs (B) = -log _{^{[2 13 B / (13 R 1}} + 13 R 2) ].

As described above, when calculating the absorbance, the average value (R ₁ + R) of the light amounts of the reference measurements performed before and after
₂ ) / 2, the absorbance is calculated using the average value and the light amount obtained by the base gas measurement, so that the influence of drift (time change affects the measurement) must be offset. Can be. Therefore, the measurement can be started immediately without waiting for the thermal equilibrium to be completely reached (usually several hours) when the apparatus is started. IV-2. Calculation of absorbance of sample gas Next, the transmitted light amount of the reference gas ¹² R ₂ ,
^{Using 13} R ₂ , the amount of transmitted light of the sample gas ¹² S, ¹³ S, and the amount of transmitted light of the reference gas ¹² R ₃ , ¹³ R ₂ , the absorbance of ¹² CO ₂ in the sample gas, ¹² Abs (S), and ¹³ CO ₂
Absorbance ¹³ Request and Abs (S).

[0034] Here, ¹² CO ₂ absorbance ¹² Abs (S) is, ¹² Abs (S) = determined in -log _{^{[2 12 S / (12 R 2}} + 12 R 3) ], ¹³ CO ₂ absorbance ¹³ abs (S) is calculated by ¹³ abs (S) = -log _{^{[2 13 S / (13 R 2}} + 13 R 3) ].

As described above, when calculating the absorbance, the average value of the light amounts of the reference measurements performed before and after is taken, and the absorbance is calculated using the average value and the light amount obtained by the sample gas measurement. Therefore, the influence of the drift can be offset. IV-3. Calculation of Concentration The concentration of ¹² CO _{2 and} the concentration of ¹³ CO ₂ are determined using a calibration curve.

The calibration curve is created by using a measured gas having a known ¹² CO ₂ concentration and a measured gas having a known ¹³ CO ₂ concentration. In order to obtain a calibration curve, the absorbance of ¹² CO ₂ is measured by changing the concentration of ¹² CO _{2 in} the range of about 0% to 6%. The horizontal axis is ¹² CO ₂ concentration, and the vertical axis is ¹² C
Take the O ₂ absorbance, plot and determine the curve using least squares. Since the curve approximated by the quadratic equation has a relatively small error curve, the calibration curve approximated by the quadratic equation is employed in the present embodiment.

Further, the concentration of ¹³ CO _{2 is set} to 0.00% to 0.0%.
The absorbance of ¹³ CO ₂ is measured while changing it in the range of about 7%. The horizontal axis is taken as ¹³ CO ₂ concentration, the vertical axis is taken as ¹³ CO ₂ absorbance, plotted, and the curve is determined using the least squares method. Since the curve approximated by the quadratic equation has a relatively small error curve, the calibration curve approximated by the quadratic equation is employed in the present embodiment.

Strictly speaking, a gas containing ¹² CO ₂ and a gas containing ¹³ CO ₂ are measured independently, and a gas containing ¹² CO ₂ and ¹³ CO ₂ is mixed. , The absorbance of ¹³ CO ₂ will be different. This is because the wavelength filter used has a bandwidth and the absorption spectrum of ¹² CO _{2 and} the absorption spectrum of ¹³ CO ₂ partially overlap. In this measurement,
^Since a gas in which ¹² CO ₂ and ¹³ CO ₂ are mixed is to be measured, it is necessary to correct the overlap when determining a calibration curve. In this measurement, a calibration curve in which the overlap of the absorption spectra is partially corrected is actually used.

The base gas calculated using the calibration curve
In¹²CO_TwoThe concentration of¹²Conc (B) for base gas
Put¹³CO_TwoThe concentration of¹³Conc (B), sample gas
Kick ¹²CO_TwoThe concentration of¹²Conc (S) in sample gas
To¹³CO_TwoThe concentration of¹³Write Conc (S). IV-4. Calculation of concentration ratio¹³ CO_TwoWhen¹²CO_TwoThe concentration ratio is determined. For base gas
Concentration ratio¹³ Conc (B) /¹²Conc (B) The concentration ratio in the sample gas is¹³ Conc (S) /¹²Required by Conc (S).

The concentration ratio was ¹³ Conc (B) / ¹² Conc (B)
^{+ 13 Conc (B), 13} Conc (S) / 12 Conc (S) + 13 may be defined as Conc (S). ^{This is because} the concentration of ¹² CO ₂ is much higher than the concentration of ¹³ CO ₂ , so that both have substantially the same value. IV-5. ¹³ C ¹³ C variation in comparing the variation of the determined sample gas collected by base Sugasu of is obtained by the following expression. Δ ¹³ C = [concentration ratio of sample gas−concentration ratio of base gas] × 10 ³ / [concentration ratio of base gas] (unit: per mille (per thousand))

[0041]

As described above, according to the first aspect of the present invention, a gas injection means is provided for injecting the gas to be measured into the cell by sucking the gas to be measured and then mechanically extruding the gas at a constant speed. Thus, the gas to be measured can be injected into the cell at a constant flow rate. Therefore, the gas to be measured flows uniformly in the cell, an accurate light detection signal without fluctuation is obtained, and more accurate concentration measurement can be performed.

According to the second aspect of the present invention, the temperature in the cell for introducing the gas to be measured can be kept constant, so that the temperature distribution of the gas to be measured can be made uniform.
Therefore, in combination with the structure of the first aspect, an accurate light detection signal without fluctuation can be obtained .

[Brief description of the drawings]

FIG. 1 is a block diagram showing an overall configuration of an isotope gas spectrometer.

FIG. 2 is a sectional view showing the structure of a cell chamber.

FIG. 3 is a view showing a gas flow of the isotope gas spectrometer and a gas flow path at the time of cleaning by flowing a clean reference gas through a cell chamber.

FIG. 4 is a diagram showing a gas flow path when a clean reference gas is flown through a gas flow path and a cell chamber of the isotope gas spectrometer for cleaning and reference measurement.

FIG. 5 is a diagram illustrating a first sample cell 11a having a reference gas;
FIG. 9 is a flow chart showing a state in which a base gas is inhaled by a gas injector 21 from an expiration bag without flowing through a second sample cell 11b.

FIG. 6 is a drawing illustrating a method of mechanically extruding a base gas at a constant speed using a gas injector 21 after inhaling a base gas. During this time, a gas flow path for measuring the amount of light from each of the detection elements 25a and 25b is formed. FIG.

FIG. 7 shows a first sample cell 11a having a reference gas;
FIG. 9 is a flow chart showing a state in which a sample gas is being sucked in from a breath bag by a gas injector 21 so as not to flow through a second sample cell 11b.

FIG. 8 shows a gas injector 21 after aspirating a sample gas.
Mechanically extruding the sample gas at a constant speed using
FIG. 4 is a diagram showing gas flow paths when measuring the amount of light by the detection elements 25a and 25b during this time.

FIG. 9 is a block diagram showing an outline of a mechanism for adjusting the temperature of the cell chamber.

10A is a plan view showing a gas injector for quantitatively injecting a gas to be measured, and FIG. 10B is a side view of the same.

[Explanation of symbols]

D Infrared detector L Infrared light source device M ₁ , M ₂ Flow meter N ₁ , N ₂ nozzle V ₁ -V ₄ valve 11a First sample cell 11b Second sample cell 11c Reference cell 21 Gas injector 21a Cylinder 21b Piston 24a First 1 wavelength filter 25a first detection element 24b second wavelength filter 25b second detection element 31 temperature adjustment board 32 temperature sensor

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Kazunori Tsutsui 38, 670, Mizuguchi, Mizuguchi-machi, Koka-gun, Shiga Prefecture (56) References JP-A-7-181134 (JP, A) JP-A-57-171836 (JP, A) (58) Field surveyed (Int. Cl. ⁶ , DB name) G01N 21/00-21/01 G01N 21/17-21/61 G01N 33/497

Claims (2)

(57) [Claims] 1. Carbon dioxide ¹² CO ₂ and carbon dioxide ¹³ CO ₂
In the isotope gas spectrometer that measures the concentration of the component gas by guiding the gas to be measured containing the component gas to the cell, measuring the amount of transmitted light having a wavelength suitable for each component gas and processing the data, It has a piston and a cylinder, and has gas injection means for injecting the gas to be measured into the cell by sucking the gas to be measured into the cylinder and then mechanically extruding the piston at a constant speed, suitable for each component gas. An isotope gas spectrometer, wherein the means for measuring the amount of transmitted light having a wavelength performs measurement while the gas to be measured is injected into the cell. 2. The isotope gas spectrometer according to claim 1, further comprising a temperature holding means for keeping a temperature of a cell for guiding the gas to be measured constant.