WO2020184474A1 - Analyzing device - Google Patents

Abstract

Provided is an analyzing device provided with: a light source; an optical resonator that is filled with gas to be analyzed and that receives light radiated from the light source; a photodetector that detects the intensity of light radiated from the optical resonator; a passive feedback unit for stabilizing the wavelength of the light radiated from the light source by optically feeding the light radiated from the light source back to the light source; a PDH locking unit for locking the frequency of the light radiated from the light source to the resonant frequency of the optical resonator; and a feedback control unit that outputs a control signal having a first frequency for PDH locking to the light source and that outputs a control signal having a second frequency for passive feedback to the passive feedback unit, wherein the first frequency is higher than the second frequency.

Description

Analysis equipment

The present invention relates to an analyzer.

Carbon isotopes have been widely applied to various fields such as environmental dynamics evaluation based on the carbon cycle and empirical research on history by dating. Although the carbon isotopes differ slightly depending on the region and environment, the stable isotopes ¹² C and ¹³ C are 98.89% and 1.11%, respectively, and the radioactive isotope ¹⁴ C is 1 × ^10-10 % natural. Exists in. Since isotopes have the same chemical behavior except for the difference in weight, the concentration of isotopes with a low abundance ratio is increased by artificial manipulation, and accurate measurement is performed to perform various reaction processes. Observation becomes possible.

In particular, in the clinical field, it is extremely useful to administer, for example, radiocarbon isotope ^14C as a labeling compound to a living body and analyze it in order to evaluate the pharmacokinetics of pharmaceuticals. For example, in Phase I and Phase IIa, It has been analyzed. As a labeled compound at a dose (hereinafter, also referred to as "microdose") that does not exceed the dose (drug discovery level) estimated to exert a pharmacological action in humans, a very small amount of radiocarbon isotope ¹⁴ C (hereinafter, " ¹⁴ C") Administering and analyzing the drug (also called) to the human body is expected to significantly shorten the development lead time in the drug discovery process because it provides insight into the efficacy and toxicity of drugs caused by pharmacological problems. ing.

Japanese Patent No. 6004412

The present inventors have proposed a carbon isotope analyzer capable of simple and rapid analysis of ¹⁴ C and a carbon isotope analysis method using the same (see Patent Document 1). As a result, research on microdose using ^14C can be carried out easily and inexpensively.
Here, there is an increasing demand for a distributed feedback (DFB) quantum cascade laser (hereinafter, also referred to as “QCL”) system as one aspect of a mid-infrared (MIR) laser that can be used for ^14C analysis. The reason is that these systems are commercially available and can be easily handled with a wide mode hop-free tuning range of a few nanometers and a single mode emission with a typical line width of a few MHz.

However, although the above performance is sufficient for many spectroscopic applications in the QCL system, the coupling between the laser and the high finesse optical resonator (reflectance R> 99.9%) used in the CRDS is sufficient. A line width of 100 kHz or less has been required.
As described above, in conducting the analysis of ^14C , further improvement in the stability of the light source was required. Therefore, an object of the present invention is to provide an analyzer and an analysis method using the analyzer, in which the stability of the light source is improved.

The above issues apply not only to carbon isotopes but also to the analysis target of any gas phase.

[1] A light source; an optical resonator filled with a gas to be analyzed and receiving light emitted from the light source; an optical detector for detecting the intensity of light emitted from the optical resonator; optically emitting light emitted from the light source A passive feedback section for stabilizing the wavelength of the light emitted from the light source by feeding it back to the light source; and a PDH lock section for locking the frequency of the light emitted from the light source to the resonance frequency of the optical resonator. A feedback control unit that outputs a control signal having a first frequency for PDH lock to a light source and outputs a control signal having a second frequency for passive feedback to a passive feedback unit; the first frequency is a first frequency. An analyzer that is higher than 2 frequencies.
[2] The analyzer according to [1], wherein the light source is a quantum cascade laser.
[3] The analyzer according to [1] or [2], wherein the gas to be analyzed is a carbon dioxide isotope containing a radiocarbon isotope 14C.
[4] The analyzer according to any one of [1] to [3], wherein the light having an absorption wavelength of carbon dioxide isotope is light in the 4.5 μm band.
[5] The analyzer according to any one of [1] to [4], further comprising a cooling device for cooling the optical resonator.
[6] The analyzer according to any one of [1] to [5], further comprising a vacuum device for accommodating an optical resonator.
[7] The analyzer according to any one of [1] to [6], further comprising a vibration absorbing means.
[8] Detection sensitivity for radiocarbon ¹⁴ C, is about 0.1dpm / ml [1] analyzer according to any one of - [7].
[9] A step of producing a carbon dioxide isotope from a carbon isotope; a step of filling the carbon dioxide isotope into an optical cavity having a pair of mirrors; and an irradiation having an absorption wavelength of the carbon dioxide isotope from a light source. The step of generating light; the step of irradiating the irradiation light into the optical cavity through the λ / 4 wavelength plate; and the step of irradiating the light returned from the optical cavity through, for example, the λ / 4 wavelength plate and the polarizer. PDH lock process that outputs the feedback control voltage to the feedback control unit, sends the high wavelength component directly to the light source, and sends the low frequency component to the light source via passive feedback; the carbon dioxide isotope is irradiated with irradiation light to resonate. An analysis method comprising a step of measuring the intensity of transmitted light obtained at the time; and a step of calculating the carbon isotope concentration from the intensity of transmitted light.
[10] The analysis method according to [9], wherein the carbon isotope is radiocarbon isotope 14C and the carbon dioxide isotope is radiocarbon dioxide isotope ¹⁴ CO ₂ .

FIG. 1 is a conceptual diagram of a carbon isotope analyzer according to an embodiment. FIG. 2 is a conceptual diagram of the carbon isotope analyzer according to the embodiment. 3A and 3B are a histogram of the beat RF spectrum and the beat line width measured when passive feedback is used. FIG. 4 is a diagram showing the intensity of the return light from the optical resonator and the error signal obtained by stabilization by passive feedback. FIG. 5 is a diagram showing the intensity of the return light from the resonator and the error signal when stabilization by passive feedback is not used. FIG. 6 is a diagram showing the time change of the light intensity transmitted through the optical resonator. FIG. 7 is a diagram showing the frequency drift of the quantum cascade laser. FIG. 8 is a diagram showing a 4.5 μm band absorption spectrum of ¹⁴ CO ₂ and a competing gas. 9A and 9B are diagrams showing the principle of high-speed scanning cavity ring-down absorption spectroscopy using laser light. FIG. 10 is a diagram showing the temperature dependence of the absorption amounts Δβ of ¹³ CO ₂ and ¹⁴ CO ₂ in CRDS. FIG. 11 is a conceptual diagram of a modified example of the optical resonator. FIG. 12 is a diagram showing the relationship between the absorption wavelength and the absorption intensity of the analysis sample. 13 (a) and 13 (b) are diagrams showing the time change of the ringdown rate and the pressure inside the cell due to the difference in the automatic valve opening / closing operation method when the sample gas is introduced into the gas cell.

The present invention will be described with reference to embodiments, but the present invention is not limited to the following embodiments. In the figure, those having the same function or similar functions are designated by the same or similar reference numerals and the description thereof will be omitted. However, the drawings are schematic. Therefore, the specific dimensions and the like should be determined in light of the following explanations. In addition, it goes without saying that the drawings include parts having different dimensional relationships and ratios from each other.

(Analysis equipment)
As a result of research, the present inventors have focused on a method using optical feedback known as delayed self-injection. It was found that the laser beam width can be reduced by applying this passive feedback to the QCL.

That is, the analyzer according to the embodiment includes a light source; an optical resonator filled with a gas to be analyzed and receiving light emitted from the light source; and an optical detector that detects the intensity of light emitted from the optical resonator; A passive feedback unit for stabilizing the wavelength of the light emitted from the light source by optically feeding back the light emitted from the light source to the light source; and locking the frequency of the light emitted from the light source to the resonance frequency of the optical resonator. PDH (Pound Drever Hall) lock unit for PDH lock; feedback control that outputs the control signal with the first frequency for PDH lock to the light source and outputs the control signal with the second frequency for passive feedback to the passive feedback unit. With respect to the analyzer, the first frequency is higher than the second frequency.

Here, the light source is preferably a quantum cascade laser. The gas to be analyzed is preferably a carbon dioxide isotope containing the radioactive carbon isotope ¹⁴ C. That is, the gas to be analyzed is preferably a gas containing the radioactive carbon dioxide isotope ¹⁴ CO ₂ . The light having the absorption wavelength of the carbon dioxide isotope is preferably light in the 4.5 μm band.

It is preferable that the spectroscope further includes a cooling device for cooling the optical resonator. It is preferable that the spectroscope further includes a vacuum device that houses an optical resonator. The spectroscope is preferably further provided with vibration absorbing means. Detection sensitivity for radiocarbon ¹⁴ C, is preferably about 0.1dpm / ml.
Hereinafter, a carbon isotope analyzer whose analysis target is the radioactive isotope ¹⁴ C will be described in more detail by taking as an example.

(Carbon isotope analyzer)
FIG. 1 is a conceptual diagram of a carbon isotope analyzer according to an embodiment. The carbon isotope analyzer 1 includes a light generator 20, a carbon dioxide isotope generator 40, a spectroscopic device 10, and an arithmetic unit 30. Here, as an analysis target, the radioactive isotope ¹⁴ C, which is a carbon isotope, will be described as an example. The light having an absorption wavelength of the carbon dioxide isotope ¹⁴ CO ₂ produced from the radioisotope ¹⁴ C is light in the 4.5 μm band. Although the details will be described later, it is possible to realize high sensitivity by the selectivity of the absorption line of the substance to be analyzed, the light generator, and the optical resonator mode.

As used herein, the term "carbon isotope" means stable carbon isotopes ¹² C, ¹³ C, and radiocarbon isotopes ¹⁴ C, unless otherwise specified. Also, when simply displayed as the element symbol "C", it means a carbon isotope mixture in the natural abundance ratio.
There are ¹⁶ O, ¹⁷ O and ¹⁸ O stable isotopes of oxygen, but when the element symbol "O" is displayed, it means an oxygen isotope mixture in the natural abundance ratio.
"Carbon dioxide isotope" means ¹² CO ₂ , ¹³ CO ₂ and ¹⁴ CO ₂ unless otherwise noted. When simply displayed as "CO ₂ ", it means a carbon dioxide molecule composed of carbon and oxygen isotopes having a natural abundance ratio.

As used herein, the term "biological sample" refers to blood, plasma, serum, urine, feces, bile, saliva, other body fluids and secretions, exhaled gas, oral gas, skin gas, other biological gas, and even the liver. It means any sample that can be collected from a living body, such as various organs such as heart, liver, kidney, brain, and skin, and their crushed substances. Furthermore, the origin of the biological sample includes all organisms including animals, plants and microorganisms, preferably mammals, and more preferably humans. Mammals include, but are not limited to, humans, monkeys, mice, rats, guinea pigs, rabbits, sheep, goats, horses, cows, pigs, dogs, cats and the like.

<Light generator>
As the light generator 20 of FIG. 1, various devices can be used without particular limitation as long as they can generate light having an absorption wavelength of carbon dioxide isotope. Here, a light generator that simply generates light in the 4.5 μm band, which is the absorption wavelength of the radioactive carbon isotope ¹⁴ C, and has a compact device size will be described as an example.

The light generator 20 uses a light source 23, a waveguide 21 that guides light emitted from the light source 23, a branching means (beam splitter) 27 provided on the waveguide 21, and a luminous flux branched by the branching means 27. A passive feedback unit 25 for receiving is provided. The passive feedback unit 25 reflects the light from the condenser lens 25 and transmits the light to the light source 23 via the condenser lens 25 and the branch means 27, and the condenser lens 25b that collects the light corresponding to the branch means 27. It has a mirror 25a to be sent back. Since the passive feedback unit 25 reduces the dependence of the rear reflection on the angle adjustment, it is possible to easily re-enter the QCL described later.

As the light source 23, a quantum cascade laser (Quantum Cascade Laser: QCL) capable of emitting light having a wavelength in the mid-infrared region can be used. As the waveguide 21, it is preferable to use an optical fiber capable of transmitting the generated high-intensity ultrashort pulsed light without deteriorating the characteristics. As the material, a fiber made of molten quartz can be used.

The light generator 20 further includes an optical separator 29, a polarizer 22, a λ / 4 wave plate, a detector 24, a mixer 26a, a low bus filter 26b, and a PID (Proportional-Integral-Differential). A PDH lock unit including a control servo 28 is provided. As the optical separator 29, an electro-optical phase modulator (EOM) can be used. A photodiode can be used as the detector 24. The PID control servo 28 is an example of a feedback control unit.

Although not shown, it is preferable to arrange an isolator between the optical separator 29 and the light source 23 to prevent the return light from the resonator. Further, it is preferable to arrange a laser current controller that corrects the frequency by modulating the current.

The light from the optical separator 29 is sent to the optical resonator 11 through the λ / 4 wave plate. The light (error signal) reflected by the optical resonator 11 passes through the λ / 4 wave plate again, is polarized by the polarizer 22, is sent to the detector 24, and is mixed by the mixer 26a. Will be done.

The light that has passed through the low bus filter 26b is output by the PID control servo 28 as two PID control voltages, a higher frequency component and a lower frequency component. Here, by sending a higher frequency component (laser current (PID _fast )) to the light source 23, instability in a frequency band having a high laser frequency can be corrected and stabilized. Further, by sending a lower frequency component to the mirror 25a of the passive feedback unit 25 and correcting the mirror distance (PID _slow ), the instability of the low frequency band is stabilized. Although the correction of the mirror distance is not shown, it can be controlled by using a piezo element or the like.
As a result, the light is phase-modulated and the reflected light intensity is demodulated at that modulation frequency to obtain signals with different codes before and after the resonance frequency, which is fed back as an error signal to resonate the light frequency. It can be locked to the resonance frequency of the vessel.

By providing the PDH lock unit, the frequency of light can be stabilized and the line width of light can be narrowed.

Next, the effects of the PDH lock unit and the passive feedback unit will be described in more detail with reference to FIG. FIG. 2 is a conceptual diagram showing an example of a layout including a PDH lock unit and a passive feedback unit. Here, an example using a QCL driver and a distributed feedback type (DFB) quantum cascade laser (QCL) as a light source is shown.

The electro-optical phase modulator EOM modulates the phase frequency of the laser with a line width of several tens to several hundreds of kHz of the resonator. The modulated laser passes through the polarizing plate and the λ / 4 wave plate, and is incident on the optical resonator to be stabilized. Since the return light from the optical resonator passes through the λ / 4 wave plate twice and rotates 90 degrees with the incident light, it can be taken out by a polarizing plate and detected by a photodetector. The output of the photodetector and the EOM modulation frequency signal are mixed by a mixer and passed through a low-pass filter to obtain an error signal. The output for PID control of the laser current based on the high frequency component of this error signal (PID _fast ) and the output for PID control of the mirror distance of passive feedback based on the low frequency component (PID _slow ) are servoed. generate. It can be stabilized by feeding back the PID _fast and PID _slow to the piezo element that changes the mirror distance between the laser current and the passive feedback, and matching the laser frequency to the resonance frequency of the optical resonator. The obtained results are shown in FIGS. 3 to 7.

<Carbon dioxide isotope generator>
As the carbon dioxide isotope generating device 40, various devices can be used without particular limitation as long as the carbon isotope can be converted into the carbon dioxide isotope. The carbon dioxide isotope generator 40 preferably has a function of oxidizing the sample and converting carbon contained in the sample into carbon dioxide.
For example, carbon dioxide such as a total organic carbon (hereinafter referred to as "TOC") generator, a sample gas generator for gas chromatography, a sample gas generator for combustion ion chromatography, and an elemental analyzer (EA). A carbon generator (G) 41 can be used.

When using an organic element analyzer, the carrier gas is preferably a gas containing at least carbon, nitrogen and sulfur elements as much as possible, and helium gas (He) can be exemplified. The flow rate of the carrier gas is preferably in the range of 50 mL / min to 500 mL / min, more preferably in the range of 100 mL / min to 300 mL / min.

FIG. 8 shows ¹⁴ CO ₂ and ¹³ CO competing gas under the conditions of 273 K, CO ₂ partial pressure 20%, CO partial pressure 1.0 × 10 ^-4 %, and N ₂ O partial pressure 3.0 × 10 ^-8 %. The 4.5 μm band absorption spectra of ₂ , CO, and N ₂ O are shown.
By burning the biological sample after the pretreatment, a gas containing the carbon dioxide isotope ¹⁴ CO ₂ (hereinafter, also referred to as “ ¹⁴ CO ₂ ”) can be generated. However, with the generation of ¹⁴ CO ₂ , contaminant gases such as CO and N ₂ O are also generated. As shown in FIG. 8, these CO and N ₂ O each have an absorption spectrum in the 4.5 μm band, and therefore compete with the absorption spectrum in the 4.5 μm band of ¹⁴ CO ₂ . Therefore, it is preferable to remove CO and N ₂ O in order to improve the analysis sensitivity.
Examples of the method for removing CO and N ₂ O include a method for collecting and separating ¹⁴ CO ₂ as follows. Further, the oxidation catalyst or platinum catalyst, CO, a method of removing and reducing the N 2 _O, and the combined use of the collection and separation methods used.

<Spectroscopic device>
As shown in FIG. 1, the spectroscopic device 10 includes an optical resonator 11 and a photodetector 15 that detects the intensity of transmitted light from the optical resonator 11. The optical resonator or optical cavity 11 is arranged so that the cylindrical main body in which the carbon dioxide isotope to be analyzed is encapsulated and the concave surfaces face each other at one end and the other end in the longitudinal direction inside the main body. A pair of mirrors 12a and 12b with high reflectance (high reflectance: preferably 99.99% or more), a piezo element 13 arranged at the other end of the main body and adjusting the interval between the mirrors 12a and 12b, and a gas to be analyzed A cell 16 to be filled is provided. Although not shown here, it is preferable to provide a gas injection port for injecting carbon dioxide isotope and a pressure adjusting port for adjusting the air pressure in the main body on the side of the main body.
When the laser beam is incident on the inside 11 of the optical resonator and confined, the laser beam repeats multiple reflections on the order of several thousand times to 10,000 times while outputting light having an intensity corresponding to the reflectance of the mirror. Therefore, since the effective optical path extends to several tens of kilometers, a large amount of absorption can be obtained even if the amount of gas to be analyzed enclosed inside the optical resonator is extremely small.

9A and 9B are diagrams showing the principle of cavity ring-down spectroscopy (hereinafter, also referred to as “CRDS”) using a laser beam.
As shown in FIG. 9A, when the piezo element 13 is operated and the mirror spacing satisfies the resonance condition, a high-intensity signal is transmitted from the optical resonator. On the other hand, when the incident light is blocked, the light accumulated in the optical resonator decreases exponentially with time. By measuring the output light intensity from the optical resonator, an exponential attenuation signal [Ringdown signal] as shown in FIG. 9A can be observed. Another method of observing the ringdown signal is to quickly block the input laser beam with an optical switch.

When the inside of the optical resonator is not filled with an absorbent substance, the transmitted time-dependent ringdown signal has a curve as shown by the dotted line in FIG. 9A. On the other hand, when the optical resonator is filled with an absorbent substance, as shown by the solid line in FIG. 9A, the laser beam is absorbed each time it reciprocates in the optical resonator, so that the light attenuation time is shortened. Since the decay time of this light depends on the concentration of the light-absorbing substance in the optical cavity and the wavelength of the incident laser light, the absolute concentration of the absorbing substance can be calculated by applying Beer-Lambert's law. Further, the concentration of the absorbent substance in the optical cavity can be measured by measuring the amount of change in the attenuation rate (ring down rate) which is proportional to the concentration of the absorbent substance in the optical cavity.

The transmitted light leaked from the optical resonator is detected by a photodetector, the ¹⁴ CO ₂ concentration is calculated using an arithmetic unit, and then the ¹⁴ C concentration can be calculated from the ¹⁴ CO ₂ concentration.

The intervals between the mirrors 12a and 12b of the optical resonator 11, the radius of curvature of the mirrors 12a and 12b, the length and width in the longitudinal direction of the main body, and the like are preferably changed according to the absorption wavelength of the carbon dioxide isotope to be analyzed. The assumed optical resonator length is 1 mm to 10 m.
In the case of carbon dioxide isotope ¹⁴ C, a long optical cavity length is effective in securing the optical path length, but as the optical resonator length increases, the volume of the gas cell increases and the required sample amount increases. The optical resonator length is preferably between 10 cm and 60 cm. Further, the radius of curvature of the mirrors 12a and 12b is preferably the same as or longer than the optical resonator length.

By driving the piezo element 13, the mirror spacing can be adjusted on the order of several micrometers to several tens of micrometers as an example. Fine adjustment by the piezo element 13 can also be performed in order to create the optimum resonance condition.
As the pair of mirrors 12a and 12b, a pair of concave mirrors has been illustrated and described, but if a sufficient optical path can be obtained, a combination of a concave mirror and a plane mirror or a combination of plane mirrors can be used. It doesn't matter if there is.

Sapphire glass can be used as the material constituting the mirrors 12a and 12b.
The cell 16 filled with the gas to be analyzed preferably has a smaller volume. This is because the resonance effect of light can be effectively obtained even with a small number of analytical samples. The capacity of the cell 16 can be exemplified by 8 mL to 1000 mL. The cell volume can be appropriately selected depending on the amount of ¹⁴ C source that can be used for measurement, for example, and 80 mL to 120 mL of cells are suitable for ¹⁴ C sources that can be obtained in large quantities such as urine, such as blood and For ¹⁴ C sources with limited availability, such as tears, 8 mL-12 mL cells are suitable.

(Evaluation of stability conditions of optical resonator)
Calculations based on spectroscopic data were performed to evaluate the ¹⁴ CO ₂ absorption and detection limit in CRDS. ^For spectroscopic data on ¹² CO ₂ , ¹³ CO _2, etc., the atmospheric absorption line database (HITRAN) was used, and for ¹⁴ CO ₂ , literature values (“S. Dobos et al., Z. Naturforsch, 44a, 633-639 (1989)) )")It was used.
Here, the amount of change Δβ (= β-β ₀ , β: attenuation rate with sample, β ₀ : attenuation rate without sample) of the ringdown rate (rate of exponential decay) due to absorption of ¹⁴ CO ₂ is ¹⁴ CO ₂ can be expressed as follows by the light absorption cross section σ ₁₄ , the molecular number density N, and the light velocity c.
Δβ = σ ₁₄ (λ, T, P) N (T, P, X ₁₄ ) c
(In the equation, σ ₁₄ , N are functions of the laser light wavelength λ, the temperature T, the pressure P, and the X ₁₄ = ¹⁴ C / ^Total C ratio.)

FIG. 10 is a diagram showing the temperature dependence of Δβ due to the absorption of ¹³ CO ₂ and ¹⁴ CO ₂ obtained by calculation. From FIG. ^{10, 14} C / ^Total C ^{10 -10,} 10 ^-11, in ^{10 -12,} for a equal to or absorption by ¹³ CO ₂ at room temperature 300K exceeds the absorption of ¹⁴ CO _2, the cooling I found that I needed to do it.
On the other hand, it can be seen that if the variation Δβ ₀ to 10 ¹ s ^{-1 of the} ringdown rate, which is a noise component derived from the optical resonator, can be realized, the measurement of ¹⁴ C / ^Total C ratio to ^10-11 can be realized. From this, it became clear that cooling of about -40 degrees Celsius is required as the temperature at the time of analysis. For example, when the ¹⁴ C / ^Total C and ^10-11 as the lower limit of quantification, increase of CO ₂ gas partial pressure by concentration of CO ₂ gas (e.g. 20%), suggesting that it is necessary and the temperature ..

Although the optical resonator 11 has been described, FIG. 13 shows a conceptual diagram (partially cutaway diagram) of a specific embodiment of the optical resonator. As shown in FIG. 13, the optical resonator 51 is arranged at both ends of a cylindrical heat insulating chamber 58 as a vacuum device, a measuring gas cell 56 arranged in the heat insulating chamber 58, and a measuring gas cell 56. Cools the pair of high-reflectivity mirrors 52, the mirror drive mechanism 55 arranged at one end of the measurement gas cell 56, the ring piezo actuator 53 arranged at the other end of the measurement gas cell 56, and the measurement gas cell 56. A Peltier element 59 is provided, and a water-cooled heat sink 54 having a cooling pipe 54a connected to a circulation cooler (not shown). The water-cooled heat sink 54 can dissipate heat generated from the Peltier element 59.

<Cooling system>
Figure 12 (quoted from Applied Physics Vol.24, pp.381-386, 1981) shows the absorption wavelengths of analytical samples ¹² C ¹⁶ O ₂ , ¹³ C ¹⁸ O ₂ , ¹³ C ¹⁶ O ₂ , and ¹⁴ C ¹⁶ O _2. The relationship of absorption strength is shown. As shown in FIG. 12, carbon dioxide containing each carbon isotope has a unique absorption line. In actual absorption, each absorption line has a finite width due to the spread due to the pressure and temperature of the sample. Therefore, it is preferable that the pressure of the sample is atmospheric pressure or less and the temperature is 273K (0 ° C.) or less.

^Since the absorption intensity of ¹⁴ CO ₂ is temperature-dependent, it is preferable to set the set temperature in the optical resonator 11 as low as possible. The specific set temperature in the optical resonator 11 is preferably 273 K (0 ° C.) or less. The lower limit is not particularly limited, but from the viewpoint of cooling effect and economy, it is preferable to cool to 173K to 253K (-100 ° C to -20 ° C), particularly to about 233K (-40 ° C).

Although not shown in FIG. 1, a cooling device for cooling the optical resonator 11 may be provided in the spectroscopic device 10. ^Since the light absorption of ¹⁴ CO ₂ is temperature-dependent, by lowering the set temperature in the optical resonator 11 with a cooling device, the absorption line of ¹⁴ CO _{2 and} the absorption line of ¹³ CO ₂ and ¹² CO ₂ can be separated. This is because it becomes easier to distinguish and the absorption intensity of ¹⁴ CO ₂ becomes stronger. Examples of the cooling device for cooling the optical resonator 11 include a Peltier element. In addition to the Peltier element, for example, a liquid nitrogen tank, a dry ice tank, or the like can be used. From the viewpoint of miniaturizing the spectroscopic device 11, it is preferable to use a Peltier element, and from the viewpoint of reducing the manufacturing cost of the device, it is preferable to use a liquid nitrogen water tank or a dry ice tank.

<Dehumidifier>
When cooling the optical resonator 11 of FIG. 1, it is preferable to dehumidify the inside of the optical resonator 11 with a dehumidifying device.
The dehumidifying condition is preferably a gas condition (moisture content) that does not cause dew condensation or freezing under the temperature condition when the CRDS analysis cell is cooled to −40 ° C. or lower (233 K or lower). Dehumidification may be performed by a cooling means such as a Peltier element, but dehumidification may also be performed by a membrane separation method using a polymer film for removing water vapor such as a fluorine-based ion exchange resin film. Further, a hygroscopic agent or a gas dryer may be arranged in the carbon dioxide generation unit (sample introduction unit).

As the hygroscopic agent, for example, CaH ₂ , CaSO _4, Mg (ClO ₄ ) ₂ , molecular sieve, H ₂ SO ₄ , Sicacide, phosphorus pentoxide, Sicapent (registered trademark) or silica gel should be used. Can be done. Of these, phosphorus pentoxide, sikapent (registered trademark), CaH ₂ , Mg (ClO ₄ ) ₂ or molecular sieves are preferable, and sikapent (registered trademark) is more preferable. As the gas dryer, a Nafion (registered trademark) dryer (manufactured by Perma Pure Inc.) is preferable. The hygroscopic agent and the gas dryer may be used alone or in combination. The above-mentioned "gas condition (moisture content) that does not condense or freeze under the temperature condition" was confirmed by measuring the dew point. In other words, it is preferable that the dehumidification can be performed so that the dew point is −40 ° C. or lower (233K or lower). The dew point display may be an instantaneous dew point or an average dew point per unit time. The dew point can be measured using a commercially available dew point sensor. For example, the Zentor dew point sensor HTF Al2O3 (registered trademark) (manufactured by Mitsubishi Chemical Analytech), Vaisala DRYCAP (registered trademark) DM70 handy type dew point meter ( (Made by Vaisala) can be used.

<Vacuum device>
Although not shown in FIG. 1, the optical resonator 11 may be arranged in the vacuum apparatus. This is because the analysis accuracy is improved by preventing the optical resonator 11 from being exposed to the outside air and reducing the influence of the external temperature.
The vacuum device is not particularly limited as long as it can accommodate the optical resonator 11, irradiate the irradiation light from the light generator 20 into the optical resonator 11, and transmit the transmitted light to the light detector. Vacuum device can be used.

<Carbon dioxide isotope introduction emission control device>
As a method of introducing the carbon dioxide isotope generated by the carbon dioxide isotope generation device 40 of FIG. 1 into the spectroscopic device 10, there are a flow through method (Flow through) and a stopped flow method (Stopped flow). The flow-through method does not require a complicated introduction mechanism, so sample analysis can be performed relatively easily, but it is not suitable for high-sensitivity measurement. On the other hand, the stopped flow method enables high-sensitivity measurement, but has a drawback that introduction control is required and sample loss is likely to occur. Therefore, the present inventors have studied the problem of introduction control in the stopped flow method capable of high-sensitivity measurement. As a result, the above-mentioned problems have been solved by optimizing the design of the automatic valve opening / closing system and the gas filling method.

As one of the automatic valve opening / closing system designs, the carbon dioxide isotope introduction / discharge device 60 as shown in FIG. 1 can be used. The carbon dioxide isotope introduction / emission control device 60 of FIG. 1 is provided on the introduction pipe 61a connecting the carbon dioxide isotope generation device 40 and the optical resonator 11 and on the upstream side (carbon dioxide isotope generation device 40 side) of the introduction pipe 61a. On the three-port valve 63a arranged, the introduction valve 63b arranged on the downstream side (optical resonator 11 side) of the introduction pipe 61a, the discharge pipe 61b connecting the optical resonator 11 and the pump 65, and the discharge pipe 61b. It is provided with a discharge valve 63c provided.

The gas can be sealed in the cell by timing the opening of the three-port valve 63a of the carbon dioxide isotope introduction / discharge device 60. Specifically, it can be controlled at the following timing.

First, in the first step, the three-port valve 63a is closed to make the pressure in the carbon dioxide generator higher than the atmospheric pressure. Further, the introduction valve 63b and the discharge valve 63c are opened to make the pressure in the cell lower than the atmospheric pressure. Specifically, it is set to 30 Torr or less, more preferably 10 Torr or less.
The carbon dioxide generator used as a sample introduction system needs to keep flowing the carrier gas at a constant flow rate. In this case, by closing the three-port valve 63a and opening it to the atmosphere, it is possible to prevent the carrier gas from the carbon dioxide generator before the CO ₂ gas is released from being introduced into the gas cell. Further, by opening the introduction valve 63b and the discharge valve 63c, the gas from the three port valve 63a to the inside of the gas cell is discharged, so that the pressure in the gas cell can be reduced.

Next, in the second step, the column temperature is heated to the threshold temperature or higher. Specifically, the threshold temperature is 80 ° C. to 200 ° C., preferably 90 ° C. to 120 ° C., and more preferably 90 ° C. to 110 ° C.
Since the column temperature CO ₂ gas exceeds a certain temperature is emitted in pulses, by any timing CO ₂ gas to grasp whether released, CO ₂ gas discharged in pulses within the gas cell You can see the time to reach it. By monitoring the column temperature, the present inventors have found that the CO ₂ gas reaches the gas cell several seconds after the column temperature exceeds a predetermined temperature (threshold temperature). Specifically, it was found that when the threshold temperature is 100 ° C., the CO ₂ gas reaches the gas cell after 20 to 30 seconds, preferably 25 to 27 seconds.

In the third step, a few seconds after the column temperature reaches the threshold temperature, the three-port valve 63a is opened, the introduction valve 63b is closed, and the gas (carbon dioxide isotope) is introduced into the gas cell. The introduction time varies depending on the size of the gas cell and the like, but is preferably less than 1 second. The valve 63c is closed.

In the fourth step, with the introduction valve 63b closed, the three-port valve 63a is closed, the pressure in the carbon dioxide generator is made higher than the atmospheric pressure, and the pressure in the gas cell is lowered.
In the third step, the gas pressure rises from 0 Torr to 60 Torr in 1 second until the three-port valve 63a is opened to introduce the gas from the carbon dioxide generator into the gas cell and then the introduction valve is closed. If nothing is done, the gas cell pressure is too high and it is not suitable for measuring the absorption line. Therefore, the pressure in the gas cell is reduced in the fourth step.

In the fifth step, the discharge valve 63c is opened (for about 1 second) until the pressure in the gas cell reaches about 10 to 40 Torr, and then the discharge valve 63c is closed. The pressure in the gas cell is preferably 18-22 Torr.
When the discharge valve 63c is opened with the introduction valve 63b closed, the pressure in the gas cell gradually decreases because the gas in the gas cell is discharged. After the pressure in the gas cell drops to about 20 Torr, the discharge valve 63c is closed.

In addition, FIG. 13A and FIG. 13B show the relationship between the ringdown rate and the gas cell pressure change in the optical resonator when the carbon dioxide isotope introduction / emission control device of the present invention is used.
In the upper stage (FIG. 13 (a)), the three port valve 63a, the introduction valve 63b, and the discharge valve 63c are opened, and the carrier gas from the carbon dioxide generator before the CO ₂ gas is released is introduced into the gas cell. This is the relationship between the ringdown rate and the gas cell pressure change when the three-port valve 63a, the introduction valve 63b, and the discharge valve 63c are closed at the same time when the CO ₂ gas is released and reaches the gas cell. The pressure inside the cell after the introduction of CO ₂ gas is as high as about 60 Torr, which is not suitable for measuring absorption lines. In addition, since carrier gas exists in the cell when the CO ₂ gas reaches the gas cell, when the CO ₂ gas is confined in the gas cell, it is diluted with the carrier gas, the CO ₂ gas concentration in the cell decreases, and the CO ₂ gas The ring-down signal, which is proportional to the amount of carbon dioxide absorbed, becomes smaller.
In comparison with this, as shown in the lower part (FIG. 13 (b)), when the valve is appropriately opened and closed by using the carbon dioxide isotope introduction / emission control device of the present invention, the cell after the introduction of CO ₂ gas is used. The pressure inside is about 20 Torr, which is suitable for measuring the absorption line, and since dilution with the carrier gas hardly occurs, the CO ₂ gas concentration in the cell does not decrease, and the ring-down signal does not decrease.
When obtaining the data shown in FIG. 13, the wavelength of the laser was constantly swept, and the absorption line spectrum of CO ₂ was acquired approximately once every 5 seconds.

<Arithmetic logic unit>
The arithmetic unit 30 of FIG. 1 is particularly limited as long as it can measure the concentration of the absorbent substance in the optical resonator from the above-mentioned decay time and ring down rate and can measure the carbon isotope concentration from the concentration of the absorbent substance. Various devices can be used without.
The arithmetic control unit 31 may be configured by arithmetic means or the like used in a normal computer system such as a CPU. Examples of the input device 32 include a pointing device such as a keyboard and a mouse. Examples of the display device 33 include an image display device such as a liquid crystal display and a monitor. Examples of the output device 34 include a printer and the like. As the storage device 35, a storage device such as a ROM, RAM, or magnetic disk can be used.

When the above-mentioned carbon isotope analyzer 1 is used for microdose, the detection sensitivity for the radiocarbon isotope ¹⁴ C in the sample is assumed to be about "0.1 dpm / ml". In order to achieve this detection sensitivity of "0.1 dpm / ml", it is not enough to use a "narrow band laser" as a light source, and stability of the wavelength (frequency) of the light source is required. That is, it is a requirement that the wavelength of the absorption line does not deviate and that the line width is narrow. In this respect, the carbon isotope analyzer 1 has an advantageous effect that it can measure a sample containing a low concentration of radioactive carbon isotopes.
The detection sensitivity of the radiocarbon isotope ^{14C in} the sample of the carbon isotope analyzer 1 is about "0.1 dpm / ml", more preferably "0.1 dpm / ml" or less.

In addition, the prior literature (Kazuo Hiromoto et al., "Design study of 14C continuous monitoring based on cavity ring-down spectroscopy", Proceedings of the Atomic Energy Society of Japan Spring Annual Meeting, March 19, 2010, P432) is related to nuclear power generation. It is disclosed that CRDS measures the concentration of ¹⁴ C in carbon dioxide in connection with the monitoring of the concentration of spent fuel in Japan. However, the signal processing method using the fast Fourier transform (FFT) described in the prior art achieves a detection sensitivity of "0.1 dpm / ml" because the baseline fluctuation becomes large although the data processing becomes faster. It's difficult to do.

Although the carbon isotope analyzer has been described above with reference to embodiments, the carbon isotope analyzer is not limited to the apparatus according to the above-described embodiment, and various modifications can be made. A modified example of the carbon isotope analyzer will be described below, focusing on the changes.

The spectroscopic device may further include vibration absorbing means. This is because it is possible to prevent the mirror spacing from shifting due to vibration from the outside of the spectroscope and improve the measurement accuracy. As the vibration absorbing means, for example, a shock absorber (polymer gel) or a seismic isolation device can be used. As the seismic isolation device, a device capable of applying vibration of the opposite phase of the external vibration to the spectroscopic device can be used.

In the above-described embodiment, the mirror spacing is adjusted by the piezo element 13 in the spectroscopic device 10 as the ring-down signal acquisition means. However, in order to obtain the ring-down signal, the optical resonator in the light generator 20 is used. A light blocking device for blocking light to 11 may be provided to control on / off of the irradiation light applied to the optical resonator. As the light blocking device, various devices can be used without particular limitation as long as they can quickly block light having an absorption wavelength of carbon dioxide isotope, and for example, an optical switch can be used. It is necessary to block the light sufficiently faster than the decay time of the light in the optical resonator.

(Pretreatment of biological sample)
In a broad sense, the pretreatment of a biological sample includes a step of removing a carbon source derived from the living body and a step of removing (separating) a contaminant gas. However, here, the step of removing the carbon source derived from the living body will be mainly described.
The microdose test analyzes biological samples containing trace amounts of ¹⁴ C labeled compounds (eg, blood, plasma, urine, feces, bile, etc.). Therefore, in order to improve the analysis efficiency, it is preferable to perform pretreatment of the biological sample. Due to the characteristics of the CRDS device, the ratio of ¹⁴ C to total carbon in the biological sample ( ¹⁴ C / ^Total C) is one of the factors that determine the detection sensitivity of the measurement. Therefore, the carbon source derived from the biological sample is selected from the biological sample. It is preferable to remove it.
Pretreatment of biological samples also includes the significance of concentrating ¹⁴ C. In this case, there are a method using an organic solvent described later and a method of concentrating and drying the biological sample itself. The former is expected to improve ¹⁴ C / ^Total C, and the latter has the advantage of being able to measure without loss of ¹⁴ C.

(Carbon isotope analysis method)
Radioisotope ^14C will be described as an example for analysis.

[Step S1] First, a carbon isotope analyzer 1 as shown in FIG. 1 is prepared. As radioisotopes ¹⁴ C ^sources, biological sample containing ¹⁴ C, for example, prepared blood, plasma, urine, feces, bile and the like.

[Step S2] The biological carbon source is removed by performing deproteinization as a pretreatment of the biological sample. Examples of the protein removal method include a protein removal method in which a protein is insolubilized with an acid or an organic solvent, a protein removal method by ultrafiltration or dialysis utilizing a difference in molecular size, and a protein removal method by solid phase extraction. As will be described later, the deproteinization method using an organic solvent is preferable because the ¹⁴ C-labeled compound can be extracted and the organic solvent itself can be easily removed.
In the case of the protein removal method using an organic solvent, the organic solvent is first added to the biological sample to insolubilize the protein. At this time, the ¹⁴ C-labeled compound adsorbed on the protein is extracted into the organic solvent-containing solution. ^{14 In} order to increase the recovery rate of the C-labeled compound, the organic solvent-containing solution may be collected in another container, and then an organic solvent may be further added to the residual to extract the solution. The extraction operation may be repeated a plurality of times. If the biological sample is feces, an organ such as a lung, or other form that is difficult to mix uniformly with an organic solvent, the biological sample and the organic solvent are uniformly mixed by homogenizing the biological sample. It is preferable to carry out a treatment for the above. If necessary, the insolubilized protein may be removed by centrifugation, filtration through a filter, or the like.
The extract containing the ¹⁴ C labeled compound is then dried by evaporating the organic solvent to remove the carbon source from the organic solvent. As the organic solvent, methanol (Methanol), ethanol (EtOH), or acetonitrile (ACN) is preferable, and acetonitrile is more preferable.

[Step S3] The pretreated biological sample is heated and burned to generate a gas containing carbon dioxide isotope ¹⁴ CO ₂ from a radioactive isotope ¹⁴ C source. Then, N ₂ O and CO are removed from the obtained gas.

[Step S4] Moisture is removed from the obtained ¹⁴ CO ₂ . For example at the carbon dioxide isotope generating apparatus 40, the ¹⁴ CO ₂ or passed over drying agent such as calcium carbonate, it is preferred to remove water by condensation of moisture by cooling the ¹⁴ CO _2. ^{14 This} is because the reduction in the mirror reflectance due to icing and frosting of the optical resonator 11 due to the water content contained in CO ₂ lowers the detection sensitivity, and therefore the analysis accuracy is improved by removing the water content. In consideration of the spectroscopic process, it is preferable to cool the ¹⁴ CO ₂ before introducing the ¹⁴ CO ₂ into the spectroscopic device 10. This is because when ¹⁴ CO ₂ at room temperature is introduced, the temperature of the resonator changes significantly and the analysis accuracy decreases.

[Step S5] ¹⁴ CO ₂ is filled in the optical resonator 11 having a pair of mirrors 12a and 12b as shown in FIG. Then, it is preferable to cool ¹⁴ CO ₂ to 273 K (0 ° C.) or less. This is because the absorption intensity of the irradiation light is increased. Further, it is preferable to keep the optical resonator 11 in a vacuum atmosphere. This is because the measurement accuracy is improved by reducing the influence of the external temperature.

[Step S6] Laser light is generated from the light source 23, and the obtained light is transmitted to the waveguide 21. It is preferable to use a QCL as a light source. The light from the light source 23 is branched by using the branching means 27, the branched light is focused on the condenser lens 25b, the condensed light is reflected by the mirror 25a, and the mirror 25a and the branching means 27 are combined. It is sent back to the light source 23 via the light source 23 (feedback step).
As described above, light in the 4.5 μm band of the absorption wavelength of the carbon dioxide isotope ¹⁴ CO ₂ is generated as irradiation light.

[Step S7] The irradiation light is sent into the optical resonator via the λ / 4 wave plate, and the carbon dioxide isotope ¹⁴ CO ₂ is irradiated with the irradiation light to resonate. At that time, in order to improve the measurement accuracy, it is preferable to absorb the vibration from the outside of the optical resonator 11 so that the intervals between the mirrors 12a and 12b do not deviate. Further, it is preferable to irradiate the mirror 12a with the other end on the downstream side of the waveguide 21 so as not to come into contact with the air. Then, the intensity of the transmitted light from the optical resonator 11 is measured. In order to obtain the ringdown signal, there is a method of changing the resonator length at high speed or blocking the light incident on the optical resonator 11 so as to be non-resonant from resonance. Here, the optical separator (switch) 29 blocks the light incident on the optical resonator 11.

[Step S8] The light returned from the optical resonator is sent to the PID controller via the λ / 4 wavelength plate and the polarizer to output the PID control voltage, the high frequency component is sent directly to the light source, and the low frequency component is sent. It is sent to the light source via the passive feedback unit (PDH lock process).

[Step S9] The ringdown signal obtained by irradiating the carbon dioxide isotope with the irradiation light is measured.

[Step S10] The carbon isotope ¹⁴ C concentration is calculated from the intensity of the transmitted light.

(Other embodiments)
As mentioned above, the present invention has been described by embodiment, but the statements and drawings that form part of this disclosure should not be understood to limit the invention. Various alternative embodiments, examples and operational techniques will be apparent to those skilled in the art from this disclosure.

In the carbon isotope analyzer according to the embodiment, the radioisotope ^14C has been mainly described as the carbon isotope to be analyzed. In addition to the radioactive isotope ¹⁴ C, stable isotope elements ¹² C and ¹³ C can be analyzed. As the irradiation light in that case, for example, when the ¹² C and ¹³ C analysis is performed as the absorption line analysis of ¹² CO ₂ and ¹³ CO ₂ , it is preferable to use the light in the 2 μm band or the 1.6 μm band.

^When performing absorption line analysis of ¹² CO ₂ and ¹³ CO ₂ , it is preferable that the mirror spacing is 10 to 60 cm and the radius of curvature of the mirror is the same as or greater than the mirror spacing.

Although ¹² C, ¹³ C, and ¹⁴ C each behave chemically the same, the natural abundance ratio of the radioactive isotope ¹⁴ C is lower than that of the stable isotope elements ¹² C and ¹³ C. ^It is possible to observe various reaction processes by increasing the concentration of ¹⁴ C by artificial manipulation and performing accurate measurements.

In addition, for example, a medical diagnostic device and an environmental measurement device including a part of the configuration described in the embodiment can be manufactured in the same manner. Further, the light generator described in the embodiment can be used as the measuring device.

As described above, it goes without saying that the present invention includes various embodiments not described here. Therefore, the technical scope of the present invention is defined only by the matters specifying the invention relating to the reasonable claims from the above description.

Here, an embodiment will be described with reference to FIG. 2 again. The numerical values and specific product names shown in this example are examples and should not be construed as limiting the present invention.

An experiment was conducted to apply passive feedback and frequency stabilization by PDH to a mid-infrared CRDS system. A DFB-QCL was used as the laser. The optical cavities to be stabilized by PDH are CRDS optical cavities (resonant length: 46 cm, resonance line width: 26 kHz) and short cavities (resonant length: 6 cm, resonance line width: 250 kHz). Was used. A passive feedback system was constructed by splitting the QCL light into two hands using a beam splitter (transmission vs. reflectance: 50:50), reflecting one of them with a mirror and returning it to the QCL.

A piezo element is attached to the mirror, and the applied voltage of the piezo is modulated so that the QCL frequency becomes stable using the error signal from the PDH. In addition, the QCL driver current was modulated so that the QCL frequency became stable using the error signal from the PDH. A polarizing plate (Thorlabs, model number: WP12LM-IRA) and a λ / 4 plate (Thorlabs, model number: WPLQ05M-4500) were used to observe the reflected light from the optical resonator. A Vigo MCT photodetector PVI-3TE-5 (time constant: ≤20 ns) was used as the photodetector for the reflected light measurement. EO-12.5T3-MIR (resonance frequency: 11.0 to 13.8 MHz, AR coating: 3.0 to 4.5 μm) manufactured by QUBIG was used for the EOM. In addition, ADU (Analog to Digital Unit) manufactured by QUBIG, which is a dedicated RF driver, was also used. The output of the photodetector for measuring reflected light (light intensity signal of reflected light) is mixed with the modulated signal of EOM by a mixer, and an error signal for PDH is generated by passing through a low-pass filter.

The output for PID control of the laser current based on the high frequency component of this error signal (PID fast) and the output for PID control of the mirror distance of passive feedback based on the low frequency component (PID slow) are supplied to the Digilock module. Generated. PID fast and PID slow were fed back to the piezo element that changed the mirror distance of the laser current and passive feedback, and the laser frequency was matched to the resonance frequency of the optical cavity and stabilized.

The characteristics of frequency stabilization by passive feedback were evaluated using the beat signals of a mid-infrared optical frequency comb and a quantum cascade laser with stable frequencies. The RF spectrum of the beat measured when passive feedback is used is shown in FIG. 3A. It was observed that the passive feedback narrowed the beat line width and improved the strength. In order to compare each passive feedback condition in detail, the RF spectrum of the beat was repeatedly measured (RBW: 100 kHz, Sweep time: 1 ms, measurement time: 600 s). A histogram of the beat line width when passive feedback is used is shown in FIG. 3B. It can be seen that the beat line width is narrowed by using passive feedback. From now on, the QCL can be narrowed by passive feedback.

Fig. 4 shows the intensity of the return light from the optical resonator and the error signal obtained by stabilization by passive feedback. Due to the stabilization by passive feedback, the error signal is obtained with high S / N. On the other hand, when the stabilization by passive feedback shown in FIG. 5 is not used, it can be seen that noise is generated in the error signal due to the fluctuation of the laser frequency and the S / N is lowered. Since the hoodback control is performed on the laser frequency by the error signal, if the error signal can be acquired with a high S / N ratio, the laser frequency can be controlled more stably.

It was confirmed whether the resonance frequency of the optical resonator and the laser frequency could be maintained in agreement by PDH and passive feedback. FIG. 6 shows the time change of the light intensity transmitted through the optical resonator. When the laser current is modulated, a resonance peak can be seen according to the transmitted light characteristics of the FPI (Fabry-Perot interferometer). When stabilized only with the passive seat back, the optical resonator transmitted light intensity is maintained near the intensity of the resonance peak, but fluctuations in high frequency components are observed, and it cannot be said that the resonance state is always maintained. .. It was shown that when combined with passive feedback and PDH, the resonance state was maintained and there was no variation in high frequency components.

When the laser was stabilized in the optical resonator for CRDS by PDH without using passive feedback, the time change of the center frequency of the beat signal of the mid-infrared optical frequency comb and the quantum cascade laser, which are extremely stable in frequency, was measured. FIG. 7 shows the time change of the center wavelength of the RF spectrum of the measured beat. Without PDH frequency stabilization, the beat signal fluctuates significantly beyond ± about 20 MHz. On the other hand, it can be seen that the frequency fluctuation of the QCL can be suppressed to about ± 10 MHz by stabilizing the frequency by PDH. Also, from the change in the temperature of the optical cavity (CRDS cell) measured at the same time, the frequency fluctuation (± about 10 MHz) of the quantum cascade laser stabilized by PDH fluctuates with the temperature change of the resonator length of the optical resonator. It was suggested that it was derived from. When acquiring a ring-down signal with CRDS, the laser frequency only needs to match the resonance frequency determined by the resonator length of the optical resonator for CRDS, so fluctuations due to temperature changes in the resonator length of the optical resonator Does not have to be considered.

In the embodiments and examples described in the present specification, carbon was exemplified as an analysis target. The present invention is not limited to this, and any gas such as hydrogen (which may be deuterium) may be analyzed.

Further, in the embodiments and examples described in the present specification, an example in which the cavity is formed by two mirrors provided in the optical resonator has been described, but the present invention is not limited to this, and three or more mirrors are used. The cavity may be constructed of mirrors of.

1 Carbon isotope analyzer 10 Spectrometer 11 Optical resonator 12 Mirror 13 Piezo element 15 Photodetector 16 cell 20 Light generator 21 Optical fiber 22 Polarizer 23 Light source 24 Detector 25 Passive feedback 25a Mirror 25b Condensing lens 26a Mixer 26b Low bus filter 28 PID control servo 29 Optical separator 30 Arithmetic device 40 Carbon dioxide isotope generator 60 Carbon dioxide isotope introduction / discharge control device 61a Introduction pipe 61b Discharge pipe 63a Three port valve 63b Introduction valve 63c Discharge valve 65 Pump

Claims (8)

1. Light source and
   An optical resonator filled with the gas to be analyzed and receiving light emitted from the light source,
   An optical detector that detects the intensity of light emitted from the optical resonator, and
   A passive feedback unit for stabilizing the wavelength of the light emitted from the light source by optically feeding back the light emitted from the light source to the light source.
   A PDH lock unit for locking the frequency of light emitted from the light source to the resonance frequency of the optical resonator, and
   A feedback control unit that outputs a control signal having a first frequency for PDH lock to the light source and outputs a control signal having a second frequency for passive feedback to the passive feedback unit is provided.
   An analyzer in which the first frequency is higher than the second frequency.
2. The analyzer according to claim 1, wherein the light source is a quantum cascade laser.
3. The analyzer according to claim 1 or 2, wherein the gas to be analyzed is a carbon dioxide isotope containing a radiocarbon isotope ^14C .
4. The analyzer according to any one of claims 1 to 3, wherein the light having an absorption wavelength of the carbon dioxide isotope is light in the 4.5 μm band.
5. The analyzer according to any one of claims 1 to 4, further comprising a cooling device for cooling the optical resonator.
6. The analyzer according to any one of claims 1 to 5, wherein the spectroscopic device further includes a vacuum device accommodating the optical resonator.
7. The analyzer according to any one of claims 1 to 6, wherein the spectroscopic device further includes vibration absorbing means.
8. The detection sensitivity for radiocarbon ¹⁴ C, analysis device according to any one of claims 1 to 7 is about 0.1dpm / ml.

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