The present invention relates to a carbon isotope analysis device and a carbon isotope analysis method. In particular, the present invention relates to a radioactive carbon isotope analysis device useful for analysis of radioactive carbon isotope 14C and a radioactive carbon isotope analysis method.
Carbon isotope analysis has been applied to a variety of fields, including assessment of environmental dynamics based on the carbon cycle, and historical and empirical research through radiocarbon dating. The natural abundances of carbon isotopes, which may vary with regional or environmental factors, are as follows: 98.89% for 12C (stable isotope), 1.11% for 13C (stable isotope), and 1×10−10% for 14C (radioisotope). These isotopes, which have different masses, exhibit the same chemical behavior. Thus, artificial enrichment of an isotope of low abundance and accurate analysis of the isotope can be applied to observation of a variety of reactions.
In the clinical field, in vivo administration and analysis of a compound labeled with, for example, radioactive carbon isotope 14C are very useful for assessment of drug disposition. For example, such a labeled compound is used for practical analysis in Phase I or Phase IIa of the drug development process. Administration of a compound labeled with radioactive carbon isotope 14C (hereinafter may be referred to as “14C”) to a human body at a very small dose (hereinafter may be referred to as “microdose”) (i.e., less than the pharmacologically active dose of the compound) and analysis of the labeled compound are expected to significantly reduce the lead time for a drug discovery process because the analysis provides findings on drug efficacy and toxicity caused by drug disposition.
Patent Document 1: Japanese Patent No. 6004412
The present inventors have proposed a carbon isotope analysis device that enables simple and rapid analysis of 14C, and a carbon isotope analysis method by use of the analysis device (see Patent Document 1). This has made simple and inexpensive studies of the microdose with 14C possible.
A distributed feedback (DFB) quantum cascade laser (hereinafter may be referred to simply as “QCL”.) system is increasingly demanded as one aspect of a mid-infrared (MIR) laser usable for analysis of 14C. The reason for this is because such a system is commercially available and can be simply handled with monomode emission having a broad mode-hop free tuning range of several nanometers and a typical line width of several MHz.
While QCL systems, which has the above performances, are satisfactorily used in many optical applications, the systems have been demanded to have a line width of 100 kHz or less in coupling of laser with a high-finesse optical resonator (reflectance R>99.9%) for use in CRDS. A solution for accomplishing such a reduction in line width is, for example, a high-speed electrical signal feedback (for example, PDH lock) using a frequency discriminator, but requires a high-speed signal processing system and has the problem of being expensive, and furthermore, high bandwidth modulation is required in a laser light source.
Thus, a further improvement in stability of a light source is demanded in analysis of 14C. An object of the present invention is to provide a carbon isotope analysis device improved in stability of a light source, and a carbon isotope analysis method by use of the analysis device.
(1) A carbon isotope analysis device including a carbon dioxide isotope generator provided with a combustion unit that generates gas containing carbon dioxide isotope from carbon isotope, and a carbon dioxide isotope purifying unit; a spectrometer including an optical resonator having a pair of mirrors and a photodetector that determines intensity of light transmitted from the optical resonator; and a light generator including a light source, a splitter that splits light from the light source, a focusing lens that focuses light from the splitter, and a mirror that reflects light from the focusing lens and sends the light back to the light source via the focusing lens and the splitter.
(2) The carbon isotope analysis device according to (1), wherein the light source includes a mid-infrared quantum cascade laser.
(3) The carbon isotope analysis device according to (1) or (2), wherein the carbon isotope is radioactive carbon isotope 14C and the carbon dioxide isotope is radioactive carbon dioxide isotope 14CO2.
(4) The carbon isotope analysis device according to any one of (1) to (3), wherein the light having an absorption wavelength of the carbon dioxide isotope is light of a 4.5-μm wavelength range.
(5) The carbon isotope analysis device according to any one of (1) to (4), wherein the spectrometer further includes a cooler that cools the optical resonator.
(6) The carbon isotope analysis device according to any one of (1) to (5), wherein the spectrometer further includes a vacuum device that accommodates the optical resonator.
(7) The carbon isotope analysis device according to any one of (1) to (6), wherein the spectrometer further includes a vibration dampener.
(8) The carbon isotope analysis device according to any one of (1) to (7), wherein the analysis device has a detection sensitivity of about 0.1 dpm/ml to the radioactive carbon isotope 14C.
(9) The carbon isotope analysis device according to any one of Claims 1 to 8, further including a sample inlet outlet controller including an inlet tube that connects the carbon dioxide isotope generator and the optical resonator, a three-port valve disposed on the inlet tube, closer to the carbon dioxide isotope generator, an inlet valve disposed on the inlet tube, closer to the optical resonator, an outlet tube that connects the optical resonator and a pump, and an outlet valve provided on the outlet tube.
(10) A carbon isotope analysis method, including the steps of: generating carbon dioxide isotope from carbon isotope; feeding the carbon dioxide isotope into an optical resonance atmosphere having a pair of mirrors; generating irradiation light at an absorption wavelength of the carbon dioxide isotope, from a light source; splitting light from the light source by use of a splitter, focusing the light split, on a focusing lens, reflecting the light focused, by use of a mirror, and sending the light back to the light source via the mirror and the splitter; measuring the intensity of the transmitted light generated by resonance of carbon dioxide isotope excited by the irradiation light; and calculating the concentration of the carbon isotope from the intensity of the transmitted light.
(11) The carbon isotope analysis method according to (10), wherein the carbon isotope is radioactive carbon isotope 14C and the carbon dioxide isotope is radioactive carbon dioxide isotope 14CO2.
(12) The carbon isotope analysis method according to (10) or (11), involving a first step of increasing pressure in a carbon dioxide generation atmosphere above atmospheric pressure, and decreasing pressure in an optical resonance atmosphere to less than atmospheric pressure; a second step of increasing temperature in the carbon dioxide generation atmosphere to a threshold temperature or higher; a third step of introducing carbon dioxide isotope into the optical resonance atmosphere at several seconds after the temperature in the carbon dioxide generation atmosphere reaches the threshold temperature; a fourth step of increasing the pressure in the carbon dioxide generation atmosphere above atmospheric pressure, and decreasing the pressure in the optical resonance atmosphere; and a fifth step of setting the pressure in the optical resonance atmosphere to 10 to 40 Torr.
(13) A light generator including a light source, a splitter that splits light from the light source, a focusing lens that focuses light from the splitter, and a mirror that reflects light from the focusing lens and sends the light back to the light source via the focusing lens and the splitter.
(14) A sample inlet/outlet controller including an inlet tube that connects a carbon dioxide isotope generator and an optical resonator; a three-port valve disposed on the inlet tube, closer to the carbon dioxide isotope generator; an inlet valve disposed on the inlet tube, closer to the optical resonator; an outlet tube that connects the optical resonator and a pump; and an outlet valve provided on the outlet tube.
(15) A carbon isotope analysis device including a spectrometer including an optical resonator having a pair of mirrors and a photodetector that determines intensity of light transmitted from the optical resonator; and a light generator including a light source, a splitter that splits light from the light source, a focusing lens that focuses light from the splitter, and a mirror that reflects light from the focusing lens and sends the light back to the light source via the focusing lens and the splitter.
The present inventors have made studies, and as a result, have focused on a method using optical feedback known as delayed self-infection, as an alternative of high-speed electrical signal feedback using a frequency discriminator. The inventors have found that such passive feedback can be applied to QCL, resulting in a reduction in laser line width at the minimum cost. The detail will be described below.
The present invention will now be described by way of embodiments, which should not be construed to limit the present invention. In the drawings, the same or similar reference signs are assigned to components having the same or similar functions without redundant description. It should be noted that the drawings are schematic and thus the actual dimensions of each component should be determined in view of the following description. It should be understood that the relative dimensions and ratios between the drawings may be different from each other.
Throughout the specification, the term “carbon isotope” includes stable isotopes 12C and 13C and radioactive isotopes 14C, unless otherwise specified in the case that the elemental signature “C” is designated, the signature indicates a carbon isotope mixture in natural abundance.
Stable isotopic oxygen includes 16O, 17O and 18O and the elemental signature “O” indicates an isotopic oxygen mixture in natural abundance.
The term “carbon dioxide isotope” includes 12CO2, 13CO2 and 14CO2, unless otherwise specified. The signature “CO2” includes carbon dioxide molecules composed of carbon isotope and isotopic oxygen each in natural abundance.
Throughout the specification, the term “biological sample” includes blood, plasma, serum, urine, feces, bile, saliva, and other body fluid and secretion; intake gas, oral gas, skin gas, and other biological gas; various organs, such as lung, heart, liver, kidney, brain, and skin, and crushed products thereof. Examples of the origin of the biological sample include ail living objects, such as animals, plants, and microorganisms; preferably, mammals, preferably human beings. Examples of mammals include, but should not be limited to, human beings, monkey, mouse, rat, marmot, rabbit, sheep, goat, horse, cattle, hog, canine, and cat.
The carbon dioxide isotope generator 40 may be of any type that can convert carbon isotope to carbon dioxide isotope. The carbon dioxide isotope generator 40 should preferably have a function to oxidize a sample and to convert carbon contained in the sample to carbon dioxide.
The carbon dioxide isotope generator 40 may be a carbon dioxide generator (G) 41, for example, a total organic carbon (TOC) gas generator, a sample gas generator for gas chromatography, a sample gas generator for combustion ion chromatography, or an elemental analyzer (EA).
It is preferred to minimize the contents of at least carbon, nitrogen, and sulfur elements in the carrier gas used in an organic elemental analyzer. An example of such gas is helium (He). The flow rate of the carrier gas preferably ranges from 50 mL/min to 500 mL/min, more preferably from 100 mL/min to 300 mL/min.
Gas containing carbon dioxide isotope 14CO2 (hereinafter merely “14CO2”) can be generated through combustion of a pretreated biological sample; however, gaseous contaminants, such as CO and N2O are generated together with 14CO2 in this process. CO and N2O each exhibit a 4.5-μm wavelength range absorption spectrum as illustrated in
A typical process of removing CO and N2O involves collection and separation of 14CO2 as described below. The process may be combined with a process of removing or reducing CO and N2O with an oxidation catalyst or platinum catalyst.
With reference to
A laser beam incident on and confined in the optical resonator 11 repeatedly reflects between the mirrors over several thousand to ten thousand times while the optical resonator 11 emits light at an intensity corresponding to the reflectance of the mirrors. Thus, the effective optical path length of the laser beam reaches several tens of kilometers, and a trace amount of analyte gas contained in the optical resonator can yield large absorption intensity.
As illustrated in
In the case of the absence of a light-absorbing substance in the optical resonator, the dotted curve in
The light leaked from the optical resonator is detected with the photodetector, and the concentration of 14CO2 is calculated with the arithmetic device. The concentration of 14C is then calculated from the concentration of 14CO2.
The distance between the mirrors 12a and 12b in the optical resonator 11, the curvature radius of the mirrors 12a and 12b, and the longitudinal length and width of the body should preferably be varied depending on the absorption wavelength of the carbon dioxide isotope (i.e., analyte). The length of the optical resonator is adjusted from 1 mm to 10 m, for example.
In the case of carbon dioxide isotope 14CO2, an increase in length of the optical resonator contributes to enhancement of the effective optical path length, but leads to an increase in volume of the gas cell, resulting in an increase in amount of a sample required for the analysis. Thus, the length of the optical resonator is preferably 10 cm to 60 cm. Preferably, the curvature radius of the mirrors 12a and 12b is equal to or slightly larger than the length of the optical resonator.
The distance between the mirrors can be adjusted by, for example, several micrometers to several tens of micrometers through the drive of the piezoelectric element 13. The distance between the mirrors can be finely adjusted by the piezoelectric element 13 for preparation of an optimal resonance state.
The mirrors 12a and 12b (i.e., a pair of concave mirrors) may be replaced with combination of a concave mirror and a planar mirror or combination of two planar mirrors that can provide a sufficient optical path.
The mirrors 12a and 12b may be composed of sapphire glass.
The cell 16 to be filled with the analyte gas preferably has a small volume because even a small amount of the analyte effectively provides optical resonance. The volume of the cell 16 may be 8 mL to 1,000 mL. The cell volume can be appropriately determined depending on the amount of a 14C source to be analyzed. For example, the cell volume is preferably 80 mL to 120 mL for a 14C source that is available in a large volume (e.g., urine), and is preferably 8 mL to 12 mL for a 14C source that is available only in a small volume (e.g., blood or tear fluid).
The 14CO2 absorption and the detection limit of CRDS were calculated based on spectroscopic data. Spectroscopic data on 12CO2 and 13CO2 were retrieved from the high-resolution transmission molecular absorption database (HITRAN), and spectroscopic data on 14CO2 were extracted from the reference “S. Dobos, et al., Z. Naturforsch, 44a, 633-639 (1989)”.
A Modification (Δβ) in ring-down rate (exponential decay rate) caused by 14CO2 absorption (Δβ=β−β0 where β is a decay rate in the presence of a sample, and β0 is a decay rate in the absence of a sample) is represented by the following expression:
Δβ=σ14(λ, T, P)N (T, P, X1)c
where σ14 represents the photoabsorption cross section of 14CO2, N represents the number density of molecules, c represents the speed of light, and σ14 and N are the function of λ (the wavelength of laser beam), T (temperature), P (pressure), and X14=ratio 14C/TotalC.
If a Modification (Δβ0) in ring-down rate (corresponding to noise derived from the optical resonator) can be reduced to a level on the order of 101 s−1, the analysis could be performed at a ratio 14C/TotalC on the order of 10−11. Thus, cooling at about −40° C. is required during the analysis. In the case of a ratio 14C/TotalC of 10−11 as a lower detection limit, the drawing suggests that requirements involve an increase (for example, 20%) in partial pressure of CO2 gas due to concentration of the CO2 gas and the temperature condition described above.
Since the absorption intensity of 14CO2 has temperature dependence as described above, the temperature in the optical resonator 11 is preferably adjusted to a minimum possible level. In detail, the temperature in the optical resonator 11 is preferably adjusted to 273K (0° C.) or less. The temperature may have any lower limit. In view of cooling effect and cost, the temperature in the optical resonator 11 is adjusted to preferably 173K to 253K (−100° C. to −20° C.), more preferably about 233K (−40° C.)
A cooler (not illustrated in
The optical resonator 11 of the
A preferred dehumidification condition is as follows: when the CRDS analytical cell is cooled to −40° C. or less (233K or less), the gas has a low moisture content not causing dewing or freezing at this temperature. Dehumidification may be carried out with a cooling means, such as a Peltier element, or by membrane separation using a polymer membrane, such as a fluorinated ion-exchange membrane, for removing moisture. A dehumidifying agent or a gas drier should preferably be positioned in a carbon dioxide generator (sample inlet unit).
Examples of the dehumidifying agent include CaH2, CaSO4, Mg(ClO4)2, molecular sieve, H2SO4, Sicacide, phosphorus pentoxide, Sicapent (registered trade mark), and silica gel. Among these preferred are phosphorus pentoxide, Sicapent (registered trade mark) , CaH2, Mg(ClO4)2 and molecular sieve. More preferred is Sicapent (registered trade mark). A preferred gas drier is Nafion (registered trade mark) drier (made by Perma Pure Inc.). The dehumidifying agent and the gas drier may be used alone or in combination. The “moisture content not causing dewing or freezing at this temperature” was determined through measurement of the dew point. In other words, dehumidification is carried out such that the dew point is −40° C. or less (233K or less). The dew point may be an instantaneous dew point or an average dew point in unit time. The dew point can be measured with a commercially available dew point sensor. Examples of the dew point sensor include a Xentaur (registered trade mark) dew point sensor HTF Al2O3 (available from Mitsubishi Chemical Analytech Co., Ltd.) and Vaisala DRYCAP (registered trade mark) DM70 handy dew point sensor.
Although not illustrated
The vacuum device may be of any type that can accommodate the optical resonator 11, apply light from the light generator 20 to the optical resonator 11, and transmit light to the photodetector.
The method of introducing the carbon dioxide isotope generated in the carbon dioxide isotope generator 40 of
One automatic valve opening/closing system design can be a sample inlet/outlet unit 60 illustrated in
The cell can be filled with gas by determining the timing of opening of the three-port valve 63a and the like of the sample inlet/outlet unit 60. Specifically, control can be made at the following timings.
In a first step, the three-port valve 63a is first closed to increase the pressure in the carbon dioxide generator to atmospheric pressure or more. The inlet valve 63b and the outlet valve 63c are opened to decrease the pressure in the cell to atmospheric pressure or less, specifically, 30 Torr or less, more preferably 10 Torr or less.
In a second step, the column temperature is then increased to a threshold temperature or higher. The threshold temperature is specifically, 80° C. to 200° C., preferably 90° C. to 120° C., more preferably 90° C. to 110° C.
When the column temperature exceeds a certain temperature, CO2 gas is released in a pulsed manner, and thus the time until the CO2 gas released in a pulsed manner reaches the gas cell can be seen by finding the timing where the CO2 gas is released. The present inventors have found that the CO2 gas reaches the gas cell after several seconds after the column temperature monitored exceeds a predetermined temperature (threshold temperature). The present inventors have specifically found that the CO2 gas reaches the gas cell at a threshold temperature of 100° C. after 20 seconds to 30 seconds, preferably 25 seconds to 27 seconds.
In a third step, the three-port valve 63a is opened and the inlet valve 63b is closed for introduction of gas (carbon dioxide isotope) into the gas cell, after several seconds after the column temperature reaches the threshold temperature. The time for such introduction is preferably less than 1 second, although varies depending on the changes in size and the like of the gas cell. The outlet valve 63c is here closed.
In a fourth step, the pressure in the gas cell is decreased by closing the three-port valve 63a with the inlet valve 63b being closed and increasing the pressure in the carbon dioxide generator to atmospheric pressure or more.
In the third step, the gas pressure is increased from 0 Torr to 60 Torr for a period of 1 second from opening of the three-port valve 63a for introduction of gas into the gas cell from the carbon dioxide generator, to then closing of the inlet valve. The pressure in the gas cell is here too high to be suitable for absorption line determination. Thus, the pressure in the gas cell is decreased in the fourth step.
In a fifth step, the outlet valve 63c is opened until the pressure in the gas cell reaches about 10 to 40 Torr (about 1 second), and thereafter the outlet valve 63c is closed. The pressure in the gas cell is preferably 18 to 22 Torr.
The pressure in the gas cell is gradually decreased because gas in the gas cell is discharged by opening the outlet valve 63c with the inlet valve 63b being closed. After the pressure in the gas cell is decreased to about 20 Torr, the outlet valve 63c is closed.
The top (
In comparison with this, the bottom (
The data illustrated in
The light generator 20 of
The light generator 20 includes a light source 23, a splitter (delay line) 28 that splits light from the light source 23, a focusing lens 25b that focuses light from the splitter 28, and CATEYE 25 including a mirror 25a that reflects light from the focusing lens 25 and sends the light back to the light source 23 via the focusing lens 25 and the splitter 28. The light generator 20 further includes an optical separator 29.
The CATEYE 25 decreases the dependence of back reflection on the adjustment of angle, thereby enabling easy re-incidence to QCL to be made. The optical separator 29 enables light to be shielded.
The light source 23 may be a mid-infrared quantum cascade laser (Quantum Cascade Laser: QCL).
It is preferred that the first optical fiber 21 can transmit high intensity of ultrashort light pulses without deterioration of the optical properties of the pulses. The first optical fiber 21 should preferably be composed or fused silica.
The arithmetic device 30 of
The arithmetic device 30 includes an arithmetic controller 31, such as an arithmetic unit used in a common computer system (e.g., CPU); an input unit 32, such as a keyboard or a pointing device (e.g., a mouse); a display unit 33, such as an image display (e.g., a liquid crystal display or a monitor); an output unit 34, such as a printer; and a memory unit 35, such as a RCM, a RAM, or a magnetic disk.
In the case that the carbon isotope analysis device 1 is used in a microdose test, the prospective detection sensitivity to the radioactive carbon isotope 14C in the sample is approximately 0.1 dpm/ml. Such a detection sensitivity “0.1 dpm/ml” requires not only use of “narrow-spectrum laser” as a light source, but also the stability of wavelength or frequency of the light source. In other words, the requirements include no deviation from the wavelength of the absorption line and a narrow line width. In this regard, the carbon isotope analysis device 1 has an advantage in that the analysis device can determine a low concentration of radioactive carbon isotope in the analyte.
The detection sensitivity of the radioactive carbon isotope 14C in the sample of the carbon isotope analysis device 1 is about “0.1 dpm/ml”, more preferably “0.1 dpm/ml” or less.
The earlier literature (Hiromoto Kazuo et al., “Designing of 14C continuous monitoring based on cavity ring down spectroscopy”, preprints of Annual Meeting, the Atomic Energy Society of japan, Mar. 19, 2010, p. 432) discloses determination of the concentration of 14C in carbon dioxide by CRDS in relation to monitoring of the concentration of spent fuel in atomic power generation. Although the signal processing using the fast Fourier transformation (FET) disclosed in the literature has a high processing rate, the fluctuation of the baseline increases, and thus a detection sensitivity of 0.1 dpm/ml cannot be readily achieved.
Although the carbon isotope analysis device of the present invention has been described with reference to the embodiment, the configuration of the carbon isotope analysis device should not be limited to the analysis device described above, and various modifications may be made. Several modifications of the carbon isotope analysis device will now be described by focusing on modified points.
The spectrometer may further be provided with a vibration damper. The vibration damper can prevent a perturbation in distance between the mirrors due to the external vibration, resulting in an improvement in analytical accuracy. The vibration damper may be an impact absorber (polymer gel) or a seismic isolator. The seismic isolator may be of any type that can provide the spectrometer with vibration having a phase opposite to that of the external vibration.
In the aforementioned embodiment, the distance between the mirrors is adjusted with the piezoelectric element 13 for generation of ring-down signals in the spectrometer 10. For generation of ring-down signals, a light shield may be provided in the light generator 20 for ON/OFF control of light incident on the optical resonator 11. The light shield may be of any type that can promptly block light having the absorption wavelength of the carbon dioxide isotope. The light shield is, for example, an optical switch. The excitation light should be blocked within a time much shorter than the decay time of light in the optical resonator.
The pretreatment of the biological sample is categorized into a step of removing carbon sources derived from biological objects and a step of removing or separating the gaseous contaminant in a broad sense. In this embodiment, the step of removing carbon sources derived from biological objects will now be mainly described.
A microdose test analyzes a biological sample, for example, blood, plasma, urine, feces, or bile containing an ultratrace amount of 14C labeled compound. Thus, the biological sample should preferably be pretreated to facilitate the analysis. Since the ratio 14C/TotalC of 14C to total carbon in the biological sample is one of the parameters determining the detection sensitivity in the measurement due to characteristics of the CRDS unit, it is preferred to remove the carbon source derived from the biological objects contained in the biological sample.
The analysis of radioisotope 14C as an example of the analyte will now be described.
(A) Carbon isotope analysis device 1 illustrated in
(B) The biological sample is pretreated to remove protein and thus to remove the biological carbon source. Examples of deproteinization include insolubilization of protein with acid or organic solvent; ultrafiltration and dialysis based on a difference in molecular size; and solid-phase extraction. As described below, deproteinization with organic solvent is preferred, which can extract the 14C labeled compound and in which the organic solvent can be readily removed after treatment.
The deproteinization with organic solvent involves addition of the organic solvent to a biological sample to insolubilize protein. The 14C labeled compound adsorbed on the protein is extracted to the organic solvent in this process. To enhance the recovery rate of the 14C labeled compound, the solution is transferred to another vessel and fresh organic solvent is added to the residue to further extract the labeled compound. The extraction operations may be repeated several times. In the case that the biological sample is feces or an organ such as lung, which cannot be homogeneously dispersed in organic solvent, the biological sample should preferably be homogenized. The insolubilized protein may be removed by centrifugal filtration or filter filtration, if necessary.
The organic solvent is then removed by evaporation to yield a dry 14C labeled compound. The carbon source derived from the organic solvent can thereby be removed. Preferred examples of the organic solvent include methanol (MeOH), ethanol (EtOH), and acetonitrile (ACN). Particularly preferred is acetonitrile.
(C) The pretreated biological sample was combusted to generate gas containing carbon dioxide isotope 14CO2 from the radioactive isotope 14C source. N2O and CO are then removed from the resulting gas.
(C) Moisture is removed from the resultant 14CO2 gas. For example, moisture is preferably removed from the 14CO2 gas in the carbon dioxide isotope generator 40 by allowing the 14CO2 gas to pass through a desiccant (e.g., calcium carbonate) or cooling the 14CO2 gas for moisture condensation. Formation of ice or frost on the optical resonator 11, which is caused by moisture contained in the 14CO2 gas, may lead to a reduction in reflectance of the mirrors, resulting in low detection sensitivity. Thus, removal of moisture improves analytical accuracy. The 14CO2 gas is preferably cooled and then introduced into the spectrometer 10 for the subsequent spectroscopic process. Introduction of the 14CO2 gas at room temperature significantly varies the temperature of the optical resonator, resulting is a reduction is analytical accuracy.
(E) The 14CO2 gas is fed into the optical resonator 11 having the pair of mirrors 12a and 12b. The 14CO2 gas is preferably cooled to 273K (0° C.) or less to enhance the absorption intensity of excitation light. The optical resonator 11 is preferably maintained under vacuum because a reduced effect of the external temperature on the optical resonator improves analytical accuracy.
(F) A laser beam is generated from the light source 23, and the resulting light is transmitted through the optical fiber 21. The light source to be used is preferably QCL. The light from the light source 23 is split with the splitter 28, the light split is focused on the focusing lens 25b, and the light focused is reflected with the mirror 25a and sent back to the light source 23 via the mirror 25a and the splitter 28 (feedback step).
The foregoing generates excitation light of 4.5 μm, which is the absorption wavelength of the carbon dioxide isotope 14CO2.
(G) The carbon dioxide isotope 14CO2 is in resonance with the light. To improve analytical accuracy, the external vibration of the optical resonator 11 is preferably reduced by a vibration absorber to prevent a perturbation in distance between the mirrors 12a and 12b. During resonance, the downstream end of the first optical fiber 21 should preferably abut on the mirror 12a to prevent the light from coming into contact with air. The intensity of light transmitted from the optical resonator 11 is then determined. To generate ring-down signals, the length of the resonator is changed at a high speed or light incident to the optical resonator 11 is shielded so as to turn resonance to non-resonance. The light incident to the optical resonator 11 is here shielded by the optical separator (switch) 29.
(H) The concentration of carbon isotope 14C is calculated from the intensity of the transmitted light.
Although the embodiment of the present invention has been described above, the descriptions and drawings as part of this disclosure should not be construed to limit the present invention. This disclosure will enable those skilled in the art to find various alternative embodiments, examples, and operational techniques.
The carbon isotope analysis device according to the embodiment has been described by focusing on the case where the analyte as a carbon isotope is radioisotope 14C. The carbon isotope analysis device can analyze stable isotopes 12C and 13C besides radioisotope 14C. In such a case, excitation light of 2 μm or 1.6 μm is preferably used in, for example, absorption line analysis of 12CO2 or 13CO2 based on analysis of 12C or 13C.
In the case of absorption line analysis of 12CO2 or 13CO2, the distance between the mirrors is preferably 10 to 60 cm, and the curvature radius of the mirrors is preferably equal to or longer than the distance therebetween.
Although the carbon isotopes 12C, 13C, and 14C exhibit the same chemical behaviors, the natural abundance of 14C (radioisotope) is lower than that of 12C or 13C (stable isotope). Artificial enrichment of the radioisotope 14C and accurate analysis of the isotope can be applied to observation of a variety of reaction mechanisms.
A medical diagnostic device or environmental measuring device including the configuration described above in the embodiment can be produced as in the carbon isotope analysis device. The light generator described in the embodiments can also be used as a measuring device.
As described above, the present invention certainly includes, for example, various embodiments not described herein. Thus, the technological range of the present invention is defined by only claimed elements of the present invention in accordance with the proper claims through the above descriptions.
The present invention will be described in more detail with reference to Examples below. The apparatus used in Examples may be any type, and other apparatus may be used as long as such an apparatus has the same function.
2. Experiment Procedure
In order to examine the effects of feedback on the laser output and the change in frequency, a Fabry-Perot resonator (FSR=1.86 GHz, fineness 4.5) configured from two 50:50 beam splitters was installed.
Two InAsSb photodiodes (Hamamatsu Photonics K.K., P13243-011MA) were used which were low in cost and wide in band (>1 MHz) and which could be operated at room temperature. One thereof was used for reference of an output power and the other thereof was used for detection of transmitted light from a low-fineness FPI. The results provided the signal of the transmitted light from FPI in scanning of a QCL current, which was normalized by the intensity of output light.
After coupling with a single mode fiber, the laser beam was introduced into a CRD resonator (reflectance >99.98, length=30 cm, the fineness experimentally evaluated was about 10,000). The length of the CRD resonator was scanned by a piezoelectric element. The light was transmitted through the resonator only in the case where the resonance condition of the resonator was near the length of the resonator L=nλ/2 (n=1,2 . . . , λ: wavelength).
The laser was rapidly shielded by an acousto-optical modulator (AOM, operating as a high-speed optical switch) in typical ring-down signal measurement. The AOM was normally “ON” in evaluation of a laser line width shown below. The transmitted light was subjected to measurement with a liquid nitrogen cooling InSb detector, and was amplified by a high-speed current amplifier.
3. Effect of Feedback
The QCL current was modulated by applying a ramp triangular wave voltage to the input of modulation of the current driver. A beam block was attached just behind a focusing lens of a CATEYE reflecting device, for the case of no optical feedback.
The effect of feedback on the laser line width was evaluated by monitoring the transmitted light from the CRD resonator. Thus, the current of QCL was fixed to 850 mA, and the length of the resonator was slowly scanned in the range of peak of the transmitted light.
1 carbon isotope analysis device
10 spectrometer
11 optical resonator
12 mirror
13 piezoelectric element
15 photodetector
16 cell
20 light generator
21 optical fiber
23 light source
25 CATEYE
25
a mirror
25
b focusing lens
29 optical separator
30 arithmetic device
40 carbon dioxide isotope generator
60 sample inlet/outlet controller
61
a inlet tube
61
b outlet tube 61b
63
a three-port valve
63
b inlet valve
63
c outlet valve
65 pump
Number | Date | Country | Kind |
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2017-008937 | Jan 2017 | JP | national |
2017-076595 | Apr 2017 | JP | national |
Filing Document | Filing Date | Country | Kind |
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PCT/JP2018/001590 | 1/19/2018 | WO | 00 |