JP2006145512A - Measuring instrument for detecting substance contained in fluid with high sensitivity and measuring method using it - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a measuring instrument for detecting and quantifying a substance in a fluid with high detection sensitivity in terahertz spectral measurement, and a measuring method using it. <P>SOLUTION: This terahertz spectrometric instrument is constituted so that a fluid to be measured is introduced into a terahertz measuring fluid cell 1, the component in the fluid to be measured is separated by a filter 2 and the filter is irradiated with a frequency variable irradiation terahertz wave 4 to detect the transmitted terahertz wave 5, reflected terahertz wave or scattered terahertz wave from the filter to obtain a terahertz spectrum. By analyzing the measuring result of this measuring instrument, the detection or quantification of a very small amount of the component in the fluid to be measured is enabled. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to the use of terahertz electromagnetic waves.

  Conventional methods for identifying and quantifying contained substances in fluids such as liquids and gases are mainly GC-MS (gas chromatograph mass spectrometer), LC-MS (liquid chromatograph mass spectrometer), FT- IR (Fourier transform infrared spectrophotometer) or the like is used.

  However, these substances limit the substances that can be measured for each measurement method due to intrinsic causes due to physical properties such as the weight and polarization characteristics of the target substance, or causes due to detection inhibition by coexisting substances. Moreover, in order to measure a very small amount of a substance with high sensitivity, a complicated pretreatment for making the measurement sample into an appropriate shape or state is necessary, and there is a drawback that it takes time for the measurement.

  For example, when a substance contained in water is detected by FT-IR using near-infrared light or mid-infrared light, the measurement is difficult because of the large absorption by water itself. The present invention provides a technique for detecting a substance in a fluid that could not be identified and quantified by a conventional method with high sensitivity.

  The natural vibration frequency of various molecules such as molecules constituting a living body and gas molecules contained in the atmosphere exists in the terahertz band. If an absorption spectrum in this terahertz region is measured, it can be used for substance identification and composition analysis. Terahertz spectroscopic measurement is performed to identify a substance from the wavelength dependence of the transmittance or reflectance intensity of terahertz waves. Terahertz waves can also pass through many materials such as paper and plastic that cannot be transmitted by visible light or infrared light. Spectrometers using such terahertz wave generators are non-destructive and can be used for any measurement object. An absorption spectrum can be obtained over a wide frequency band with high resolution.

  As a wavelength tunable terahertz spectroscopic light source, for example, a terahertz wave generator using a polariton mode in a semiconductor GaP crystal is known. That is, the pump light and the signal light are incident on the GaP crystal at a minute angle so as to satisfy the angle phase matching condition, and a coherent terahertz wave is generated by the difference frequency generation. By narrowing the line width of the pump light and the signal light by injection seeding technology or etalon insertion, the line width of the obtained terahertz wave is narrowed and a higher output can be obtained, which is a light source suitable for a spectroscopic device.

  If this light source is used in a spectroscopic device, it is effective for measuring substances at arbitrary positions from short to long distances, measuring substances that exist continuously at long distances, and detecting substances that exist at very low density. It is.

  By separating and condensing trace contents contained in fluids such as liquids, gases, and supercritical fluids depending on the size of the constituents or the nature of chemical bonds, and by examining the terahertz absorption, which is the fingerprint region for molecular discrimination, Sensitivity can be detected or quantified. This method can reduce the influence of coexisting substances and is suitable for discriminating substances.

  In general, blood tests are widely used to check for the presence of disease. For example, arteriosclerosis can be diagnosed from cholesterol / neutral fat content, diabetes can be diagnosed from fasting blood glucose, and bacterial infection, anemia, jaundice, etc. can be examined. He also tests for viral hepatitis, syphilis, etc. based on bloody reactions. However, the amount of proteins, viruses, sugars, and the like contained in the blood to be examined is about 1 to 1000 ppm (eg, hemoglobin standard value: 11 to 17 g / dl), which is a trace amount. For drug poisoning and doping tests, it is necessary to detect drugs in blood or urine with high sensitivity.

  FIG. 1 shows an example of the size that can be separated according to the type of membrane separation as an example of the classification method, and the sizes of biomolecules and microorganisms. As can be seen from this graph, protein, virus, and sugar in blood can be separated by membrane separation such as ultrafiltration and microfiltration. In the terahertz measurement fluid cell 1 including the filtration filter 2 as shown in FIG. 2A, if the pore size of the filtration filter 2 is set to about 1 μm, the size is 7 to 8 μm and 6 respectively when blood is passed. Red blood cells and white blood cells 6 of about ˜25 μm cannot pass through and accumulate in the filtration filter 2. In contrast, sugars and proteins having a size of about 1 to 100 nm are transmitted. Therefore, if this filtration filter is made of a material having high terahertz transmittance such as polyethylene or Teflon, and terahertz transmission or reflection measurement is performed on this filtration filter 2, the accumulated amount of red blood cells, white blood cells, etc. is highly sensitive and real time. It becomes possible to measure. In addition, since the molecular state of erythrocytes and leukocytes appears in the terahertz absorption spectrum, it is possible to simultaneously diagnose structural abnormalities of blood cells.

  At this time, after the filtration filter 2 used for membrane separation is taken out from the blood flow path, it is possible to identify and quantify the substance from the terahertz spectrum for the components concentrated on the filtration filter 2. The filtration filter 2 taken out from the flow path may be dried by natural drying, vacuum drying, vacuum heat drying or freeze drying. In addition, glucose, cholesterol, virus antigens, virus antibodies, uric acid, and the like can be separated and appropriately measured with high sensitivity by appropriately selecting the type of filtration filter 2.

  When trace substances in the fluid are aggregated without being filtered in the filtration filter 2, if they are localized without agglomeration uniformly, there is a possibility that detection may fail or erroneous determination may be made. In order to avoid this, as shown in FIG. 2B, the fluid (blood) flow path direction 3 is perpendicular to the filtration filter 2 but is shifted by 45 ° from the irradiation terahertz wave 4 irradiation direction. From the frequency dependence of the intensity of the transmitted terahertz wave 5 or the reflected terahertz wave 7, it is possible to analyze a trace substance. In order to agglomerate trace substances in the fluid uniformly in the filtration filter 2, a stirrer may be installed immediately before the filtration.

  As in the first embodiment, high-sensitivity detection using terahertz spectroscopy can be used in urinalysis. In general, urine test items include “urine protein”, an indicator for detecting liver dysfunction, “urine creatinine”, an indicator for detecting renal dysfunction, and “urine sugar”, a quantitative indicator for diabetes. These values are about 10 to 200 ppm as a standard. For drug poisoning and doping tests, it is necessary to detect drugs in blood or urine with high sensitivity.

  In the urine test, there is a problem of bacterial growth and salt precipitation with the passage of time, so it is necessary to test immediately after collecting urine. For this reason, if it is installed in the toilet drainage, it can be inspected in real time every time urination. As shown in FIG. 3, if the terahertz measurement fluid cell 11 including the filtration filter 12 is provided in multiple stages on the drainage pipe connected to the toilet 10, and the filtration filter 12 of each stage is filtered for each molecular size, When urine passes there, it can be separated and aggregated into urine protein 16, urine creatinine 17, urine sugar 18, and the like. By detecting the transmitted terahertz wave 15 by terahertz spectroscopic measurement of the filtration filter 2 together with the separated / aggregated substance, it is possible to detect and quantify the contained substance with high sensitivity. In particular, if the incident terahertz wave 14 is incident perpendicularly to the surface of the filtration filter 12, the amount of the substance to be measured on the optical path can be increased, so that measurement with higher sensitivity is possible.

  Measurement of trace substances present in the environment (organic compound particles, atmospheric ion clusters, trace substances in solution, etc.) is an important technology for monitoring harmful substances and identifying unregulated substances. For example, highly sensitive detection of exhaust gas components COx, SOx, NOx, etc. contained in the atmosphere is desired for environmental pollution investigations. For these gas molecules and suspended particulate matter, the standard concentration is a standard notation such as “daily average value of 0.04 ppm or less”, and in actual measurement, it is necessary to detect a concentration lower than that. ing. In addition, for example, formaldehyde gas, which is a volatile organic compound (VOC) that is a cause of sick house syndrome, acetaldehyde gas, ammonia gas, hydrogen sulfide gas, etc. contained in a lot of tobacco smoke are Therefore, development of a highly sensitive detection and removal method is desired. In addition, there is a strong demand for highly sensitive analysis of trace organic gases, such as combustion gases, odorous substances, and organic substances in clean rooms. It is becoming desirable.

  Since rotational vibrations of gas molecules exist in the terahertz frequency region, steep and periodic absorption lines are clearly detected when the terahertz absorption spectrum is measured. Even if the fluid is a gas, the membrane can be separated by a single stage as in the first embodiment or a multistage structure as in the second embodiment. That is, sifting is possible depending on the size of the gas molecules.

For example, by thermally decomposing a polymer membrane, a dense molecular sieving carbon membrane free from pinholes can be obtained, and high selective permeability can be obtained. By heat-treating the polyimide film at 1000 ° C., a carbon film having ultrafine pores of about 4 mm is obtained, and the gas permeation characteristics of this carbon film are each 1000 times that of N ₂ molecules having larger H ₂ and CO ₂ molecules, It is known to transmit 100 times faster. By using such a microporous carbon film 22 to form a terahertz measurement atmospheric measurement cell 21 as shown in FIG. 4 and flowing the measurement target air 23, molecules of CO ₂ and other atmospheric trace substances 26 are It can be separated from N ₂ and O ₂ which are atmospheric components, and if terahertz spectroscopy is applied here, highly sensitive substances can be detected and quantified. Quantitative sensitivity of trace gases by classifying and aggregating substances in a fluid with a filter or channel tube made of a material with high terahertz wave permeability such as Teflon or polyethylene, and measuring the structure together with terahertz spectroscopy The measurement time can be increased and the measurement time can be shortened easily.

As a classification method, in addition to membrane separation, an electrostatic classification method using the electric mobility of charged particles in an electrostatic field varies depending on the particle size and the number of charges, and dialysis and chromatography using the difference in diffusion rate. Alternatively, methods such as distillation using ion exchange, vapor pressure difference, freeze concentration using phase change, absorption / solvent extraction using solubility difference, and centrifugation using mass difference may be used. Further, when the object to be measured is a highly symmetric molecule such as H ₂ or O ₂ , it does not become infrared active as it is. Therefore, activation is performed using plasma to form an infrared active structure by forming a combination of radical hydrogen and hydrogen, and trace detection and quantification can be performed by measuring this.

  As shown in FIG. 5A, a gas cooling baffle 32 is installed in the fluid flow path pipe 30 to flow the measurement target fluid 31. If the melting point of the contained component is lower than the baffle temperature, it will be liquefied and separated / aggregated there. Further, if the baffle temperature is below the freezing point, it solidifies. By measuring these adsorbed trace substances 33 in the fluid by terahertz spectroscopy, the contents in the gas can be detected and quantified with high sensitivity. In this method, it is not always necessary to absorb in the terahertz band in the gas phase or the liquid phase, and it is sufficient that absorption is observed in the solid phase.

  When the material of the baffle 32 is a metal, the reflected terahertz wave 35 with respect to the incident terahertz wave 34 may be measured.

  When the content in the gas is such that only the lattice vibration in the solid crystal state is absorbed in the terahertz band, the cooling baffle temperature is adjusted by the cooling device 36, and the gas flow rate is appropriately selected, so that the crystal Crystal growth should be good. In this method, if the baffle 32 is heated again after the measurement is completed, and the aggregated liquid or solid molecules are evaporated and desorbed, it can be reused any number of times.

  The yield can be increased by increasing the surface area. As shown in FIG. 5B, a large number of fins may be attached to the surface, or the cooling part may have a large number of capillary structures.

  As shown in FIG. 6, a filter 42 is arranged in a fluid channel pipe 41 made of a metal such as stainless steel or copper or an inner metal coating. The measurement target fluid 43 is flowed here, and selectively classified from the difference in molecular weight, and the measurement target trace substance 47 is captured. When the incident terahertz wave 44 is introduced into the pipe here, the terahertz wave does not diverge and proceeds while being reflected by the pipe wall through the pipe wall, and after passing through the filter 42 and the trace substance 47 to be measured, from the pipe end face. Therefore, if the detector is brought into close contact with the output end face so as to receive all of the terahertz wave output, highly sensitive measurement can be performed. In particular, when the particles of the target substance have the same wavelength as the terahertz wave, the influence of the scattered terahertz wave 46 appears. In this configuration, since the piping also serves as a terahertz wave waveguide, the terahertz wave is collected. There is little wave loss and even higher sensitivity can be obtained. Of course, the filter may be multistage at this time.

  When a gas is flowed on the surface of a substrate such as metal or glass or other solid particles or powder, adsorption of a specific substance occurs on the surface. For example, it is well known that the hygroscopic action of silica gel is due to the fact that hydroxyl groups (-OH groups) that are present on the silica gel surface adsorb water molecules by hydrogen bonds. A relatively weak bond such as a hydrogen bond vibrates in the terahertz band. The substance can be detected by detecting not the substance to be measured itself but the hydrogen bond or intermolecular force of adsorption between the substances such as the substrate. As shown in FIG. 7, the target molecule itself is applied to the substrate 51 to be adsorbed by applying transmission terahertz spectroscopy measurement or reflection terahertz spectroscopy measurement before and after adsorption of the molecule to be measured 52 bonded by the hydrogen bond 53. The target substance can be detected and identified from the terahertz wave absorption and the terahertz wave absorption spectrum of the target molecule adsorbed.

  It is a figure which shows the example of the magnitude | size of separable magnitude | size by the kind of membrane separation, and the magnitude | size of a biomolecule or a microorganism.   It is a figure which shows the blood component isolation | separation terahertz spectroscopy measurement by membrane separation.   It is a figure which shows the application to the urine test | inspection of the terahertz spectroscopy measurement using membrane separation.   It is a figure which shows the terahertz spectroscopy measurement of the trace component in air | atmosphere by membrane separation.   It is a figure which shows the terahertz spectroscopy measurement which aggregates the trace amount substance in a fluid using a cooling baffle.   It is a figure which shows the terahertz spectroscopy measurement which condenses a scattered terahertz wave in a waveguide.   It is a figure which shows the terahertz spectroscopy measurement with respect to the coupling | bonding of surface molecule adsorption.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Terahertz measurement fluid cell 2 ... Filtration filter 3 ... Blood 4 ... Incident terahertz wave 5 ... Transmission terahertz wave 6 ... Red blood cell and leukocyte 7 ... Reflection terahertz wave 10 ... Toilet 11 ... Terahertz measurement fluid cell 12 ... Filtration filter 13 ... Fluid to be measured (urine)
DESCRIPTION OF SYMBOLS 14 ... Incident terahertz wave 15 ... Transmission terahertz wave 16 ... Urine protein 17 ... Urine creatinine 18 ... Urine sugar 21 ... Terahertz measurement atmospheric analysis cell 22 ... Microporous carbon film 23 ... Measurement object atmosphere 24 ... Incident terahertz wave 25 ... Transmission terahertz Wave 26 ... Trace substance 27 in the atmosphere 27 ... Reflected terahertz wave 30 ... Fluid flow channel 31 ... Fluid to be measured 32 ... Baffle 33 ... Trace substance 34 in adsorbed fluid ... Incident terahertz wave 35 ... Reflected terahertz wave 36 ... Cooling device 37 ... cooling fin 41 ... metal or inner surface metal coating fluid flow pipe 42 ... filtration filter 43 ... measurement target fluid 44 ... incident terahertz wave 45 ... transmission terahertz wave 46 ... scattered terahertz wave 47 ... measurement target trace substance 51 ... substrate 52 ... molecule to be measured 53 ... hydrogen bond 54 ... incident terahertz wave 55 ... transmitted terahertz wave 56 ... anti Terahertz waves

Claims (4)

  Regarding the measurement using terahertz waves, the terahertz wave frequency sweep that can limit the range, or the function of irradiating terahertz waves with at least one arbitrary single frequency specified, and at least the contents in the fluid A device and method for performing physical property identification, substance quantification, or composition analysis based on a structure for selectively separating and at least transmitted wave intensity of terahertz waves irradiated on the separated inclusions.   The selective separation of inclusions in the fluid according to claim 1 is a separation based on a difference in particle size, mass, electrostatic attraction, diffusion rate, vapor pressure, or phase change between substances. Measuring device and method.   3. The measuring apparatus and method according to claim 1, wherein the measuring apparatus has a structure that does not at least localize inclusions in the fluid.   4. The measuring apparatus and method according to claim 1, wherein the measuring apparatus has a structure for collecting at least scattered waves of the irradiated terahertz wave.

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