WO2012070646A1 - Dispositif de mesure de rotation optique, méthode de mesure de rotation optique pouvant être utilisée dans un système de mesure de rotation optique, système optique de mesure de rotation optique et cellule échantillon pour la mesure de rotation optique - Google Patents

Dispositif de mesure de rotation optique, méthode de mesure de rotation optique pouvant être utilisée dans un système de mesure de rotation optique, système optique de mesure de rotation optique et cellule échantillon pour la mesure de rotation optique Download PDF

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WO2012070646A1
WO2012070646A1 PCT/JP2011/077204 JP2011077204W WO2012070646A1 WO 2012070646 A1 WO2012070646 A1 WO 2012070646A1 JP 2011077204 W JP2011077204 W JP 2011077204W WO 2012070646 A1 WO2012070646 A1 WO 2012070646A1
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optical
ebc
optical rotation
specimen
polarization
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PCT/JP2011/077204
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English (en)
Japanese (ja)
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博 梶岡
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株式会社グローバルファイバオプティックス
塩野義製薬株式会社
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Priority to JP2012545804A priority Critical patent/JPWO2012070646A1/ja
Publication of WO2012070646A1 publication Critical patent/WO2012070646A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/21—Polarisation-affecting properties

Definitions

  • the present invention relates to a liquid substance containing a very small amount of optical rotatory material such as an optical rotatory substance contained in exhaled breath or a solution containing exhaled breath (hereinafter, exhaled breath containing solution is also referred to as exhaled breath condensate or EBC (Exhaled Breath Condensate)).
  • exhaled breath containing solution is also referred to as exhaled breath condensate or EBC (Exhaled Breath Condensate)
  • EBC Exhaled Breath Condensate
  • Blood sampling for blood glucose level measurement has many problems such as great pain for the person to be measured and high economic burden. For this reason, many attempts have been made to develop a measurement apparatus for realizing a non-invasive blood sugar level measurement.
  • a typical method is to use an optical rotation measurement method.
  • linearly polarized light is incident on the sample to be measured, and the optical rotation angle is measured by measuring the power of the light transmitted through the sample with an analyzer.
  • 0.005 degrees which is an optical rotation angle corresponding to 100 mg / dL (deciritta), which is a blood sugar level of a healthy person.
  • Another conventional optical rotation measurement method is to place a sample in a spatial ring interference system as shown in Patent Document 1 and to propagate orthogonally polarized light around both the left and right sides of the sample outside the ring optical path. This is a method for detecting a phase difference. Since this method does not modulate the phase of light, the optical rotation or birefringence cannot be measured stably.
  • Another conventional optical rotation measurement method uses the Verde constant of lead glass described in Non-Patent Document 1, modulates the incident polarization state, and detects the change of light passing through the analyzer with a lock-in amplifier. To do.
  • a minute optical rotation angle of 0.00066 degrees can be measured.
  • this method has problems such as a large-scale apparatus and being easily influenced by the temperature characteristics of lead glass.
  • the optical rotation angle cannot be measured with an accuracy of 0.0001 degrees or less, which is necessary for measuring the minute glucose concentration contained in the breath condensate that the inventor aims to realize.
  • Patent Document 2 As a conventional method for measuring the optical rotation other than the above, there is a method described in Patent Document 2 proposed by the present inventor.
  • a pair of nonreciprocal optical systems using a Faraday rotator is provided in a sensing loop of a ring interferometer or a fiber optic gyroscope, and a sample to be measured is placed therein to measure the birefringence. It is. It is described that if a quarter wave plate is added, it becomes a polarimeter.
  • This method is characterized in that it is smaller than the conventional optical rotation measuring method described above, can be configured at low cost, and can be measured with high accuracy.
  • the optical rotation angle can be measured with an accuracy of 0.0001 degrees when the length of the specimen is 10 mm.
  • Patent Document 2 does not have an idea of measuring EBC, and there is no description regarding a specific measurement method including a method for arranging a specimen in an optical system.
  • Non-Patent Document 2 shows that the glucose concentration contained in exhaled breath condensate is approximately 7% of 0.1 g / dL, which is a concentration contained in blood in healthy subjects. That is, in the optical rotation measurement using orange laser light, the optical rotation is 0.0035 degrees when the sample length is 10 cm. In order to measure this with sufficient accuracy, a measurement sensitivity of the order of 0.00035 degrees, which is one digit below, is required. Therefore, even with the measuring device described in Patent Document 2, which is the most sensitive measuring method in the past, the glucose concentration contained in the condensate of breath cannot be measured with sufficient accuracy.
  • the problem to be solved by the present invention is to provide a simple method for blood glucose level in humans, which conventionally had to be collected and measured for diabetes treatment or prevention.
  • it is intended to provide a novel optical rotation measurement apparatus that can be estimated non-invasively and with high accuracy, an optical rotation measurement method that can be used in an optical rotation measurement system, an optical rotation measurement optical system, and a sample cell for optical rotation measurement.
  • the present inventor has conducted a detailed study in order to achieve an optical rotation measurement apparatus, an optical rotation measurement method, and an optical rotation measurement optical system that can estimate blood glucose levels of humans in a noninvasive manner with high accuracy.
  • the burden on the subject is reduced.
  • the problem was solved by developing a measuring device and a measuring method that can easily estimate human blood glucose levels with high accuracy.
  • the first invention (hereinafter referred to as invention 1) as an example of the present invention made to solve the problem has an optical rotation measurement optical system, and can measure the optical rotation of a specimen using the optical rotation measurement optical system.
  • the optical rotation measurement device In an invention of an optical rotation measurement device and / or an optical rotation measurement system (hereinafter referred to as an optical rotation measurement device), the optical rotation measurement device generates an exhalation condensate (hereinafter referred to as EBC) from exhalation.
  • EBC exhalation condensate
  • an EBC collecting unit for collecting EBC generated by the EBC generating unit, an EBC liquid feeding system from the EBC collecting unit to the specimen unit, the optical rotation measuring optical system, and a signal processing system, and the optical rotation measuring optical
  • the system has an optical ring interference system having a specimen placement part inserted so as to constitute a part of the ring optical path in a part of the ring optical path, and the ring optical path receives the EBC collected by the EBC collection part.
  • Sample arrangement The circularly polarized light traveling in different directions and orthogonal to each other is incident on the specimen placed in the specimen placement section from the two different directions when placed in the specimen cell placed in the specimen cell and placed as a specimen.
  • the optical ring interference system has an optical measurement unit capable of measuring information on glucose contained in the specimen by measuring a phase difference of the circularly polarized light orthogonal to each other caused by the specimen.
  • the present invention is an invention of an optical rotation measuring device.
  • the optical rotation measuring system as used in the field of this invention means what constructed the measuring system which has the function similar to an optical rotation measuring device combining the substantial component contained in description of an optical rotating measurement device.
  • a second invention (hereinafter referred to as invention 2) as an example of the present invention developed by developing invention 1 is the optical rotation measuring device according to invention 1, wherein the optical rotation measuring device includes the specimen containing EBC.
  • the optical rotation measuring device includes the specimen containing EBC.
  • a third invention (hereinafter referred to as invention 3) as an example of the present invention developed by developing invention 1 or 2 is the optical rotation measuring apparatus according to invention 1 or 2, wherein the optical rotation measuring apparatus It is an invention of an optical rotation measuring device characterized in that a correspondence data table capable of making a phase difference correspond to a blood glucose level concentration or a glucose concentration is provided in a place where a storage unit or device can refer to it.
  • a fourth invention (hereinafter referred to as invention 4) as an example of the present invention developed by developing invention 3 is the optical rotation measuring device according to invention 3, wherein the corresponding data table is provided from the input unit of the device and / or Alternatively, the invention is an invention of an optical rotation measuring device configured and / or arranged so that it can be changed from the outside of the device and / or by a program.
  • a fifth invention (hereinafter referred to as invention 5) as an example of the present invention developed from inventions 1 to 4 is the optical rotation measuring device according to any one of inventions 1 to 4, wherein the specimen is subjected to ring interference.
  • An optical rotation measuring device according to the present invention is disposed between opposing lenses of an opposing polarization conversion optical system inserted in the middle of a ring optical path of the system.
  • a sixth invention (hereinafter referred to as invention 6) as an example of the present invention developed by developing the inventions 1 to 5 is the optical rotation measuring device according to any one of the inventions 1 to 5, wherein the counter polarization conversion optical
  • the system has at least a lens and a polarizer between the end face of the optical fiber and the specimen on the optical path in the vicinity of the end face of the optical fiber, and a polarization plane of the signal light when the polarized beam as the signal light is incident from one side.
  • Is placed And optical fiber optics are is an invention of optical rotation measuring device, characterized in that the opposing optical fiber optical system are opposed to each other across the said specimen placement unit in the optical path.
  • the seventh invention (hereinafter referred to as invention 7) as an example of the present invention developed by developing invention 6 is the optical rotation measuring device according to invention 6, wherein the polarization plane rotating element is a Faraday rotating element. It is invention of the optical rotation measuring device characterized by these.
  • An eighth invention (hereinafter referred to as invention 8) as an example of the present invention developed from inventions 1 to 7 is the optical rotation measuring device according to any one of inventions 1 to 7, wherein the counter polarization conversion optical
  • An optical rotation measuring device according to the invention is characterized in that the system is a counter polarization conversion collimator optical system.
  • a ninth invention (hereinafter referred to as invention 9) as an example of the present invention developed from the invention 8 is the optical rotation measuring device according to the invention 8, wherein the opposite polarization conversion collimator is a polarization maintaining optical fiber.
  • An optical system in which a polarization conversion collimator in which a lens, a polarizer, a Faraday rotator, and a quarter-wave plate are arranged at the emission end of the lens is opposed to each other in the optical path of the signal light with the specimen portion interposed therebetween (hereinafter referred to as a counter polarization conversion collimator).
  • the signal light emitted from the polarization-preserving optical fibers at both ends is in the same intrinsic linear polarization mode and propagates through the specimen section.
  • a tenth invention as an example of the present invention developed from the first to ninth inventions is the optical rotation measuring apparatus according to any one of the first to ninth inventions.
  • the laser beam as the signal light emitted from the light source is guided to the second optical coupler through the first optical coupler and the polarizer, and the signal light branched by the second coupler is mainly used as the polarization plane preserving light.
  • a ring light path formed by connecting the counter-polarization conversion collimator optical system in the middle of the ring optical path made of a fiber is branched as signal light propagating in both directions along the ring optical path, and light is transmitted in the vicinity of the second coupler of the ring optical path.
  • a phase modulator is provided, and the signal light propagating in both directions on the ring optical path is guided to a light receiver and a signal processing circuit via the second coupler, the polarizer, and the first coupler, and the ring optical path is An optical rotation measuring device according to the present invention, wherein a phase difference of signal light propagating in a direction is extracted as a signal synchronized with the phase modulation signal, and the sugar concentration of the specimen is estimated by measuring the optical rotation of the specimen. .
  • invention 11 An eleventh invention (hereinafter referred to as invention 11) as an example of the present invention developed from the inventions 1 to 10 is the optical coupler according to any one of the inventions 1 to 10, wherein the first coupler Is an optical rotation measuring device according to the invention.
  • a twelfth invention as an example of the present invention developed from the inventions 1 to 11 is the optical rotation measurement apparatus according to any one of the inventions 1 to 11, wherein the optical rotation measurement apparatus Is an invention of an optical rotation measuring device characterized in that it has a mechanism part for finely adjusting the angle of the specimen part with respect to the propagation signal light.
  • a thirteenth invention (hereinafter referred to as invention 13) as an example of the present invention developed from inventions 1 to 12 is the optical rotation measuring device according to any one of inventions 1 to 12, wherein The volume of the specimen portion through which the signal light is transmitted is 0.1 cc or less.
  • a fourteenth invention (hereinafter referred to as an invention 14) as an example of the present invention developed by developing the inventions 1 to 13 is the optical rotation measuring device according to any one of the inventions 1 to 13, wherein the sample cell is Glass plates at both ends are bonded to the specimen cell with optical contacts, and are glass cells having an EBC inlet and an EBC outlet.
  • the EBC inlet is connected to the end of the pipe for supplying EBC to the specimen cell.
  • the EBC discharge port is an invention of an optical rotation measuring device characterized in that each EBC discharge port is disposed perpendicularly to the optical path of the signal light at the end of the pipe for discharging EBC from the sample cell.
  • a fifteenth invention (hereinafter referred to as invention 15) as an example of the present invention developed by developing the inventions 1 to 13 is the optical rotation measuring device according to any one of the inventions 1 to 13, wherein the sample cell comprises: A plastic cell having an EBC inlet and an EBC outlet in which glass plates at both ends are fixed by an adhesive, and the EBC inlet and the EBC outlet are at the end of the pipe and with respect to the optical path of the signal light It is an invention of an optical rotation measuring device characterized by being arranged almost vertically.
  • a sixteenth invention (hereinafter referred to as an invention 16) as an example of the present invention developed from the inventions 1 to 15 is an optical rotation measurement apparatus according to any one of the inventions 1 to 15, wherein the EBC of the sample cell is the EBC.
  • the injection port is an invention of an optical rotation measuring device characterized in that the injection port is disposed at a position closer to the center of the wall surface of the cell than the EBC discharge port.
  • a seventeenth invention (hereinafter referred to as an invention 17) as an example of the present invention developed by developing the inventions 1 to 16 is an optical rotation measurement apparatus according to any one of the inventions 1 to 16, wherein the EBC of the sample cell is the EBC. It is an invention of an optical rotation measuring device characterized by having means for reducing the pressure of the discharge port to a reduced pressure state with respect to the EBC injection port.
  • An eighteenth invention (hereinafter referred to as invention 18) as an example of the present invention developed from the inventions 1 to 17 is the optical rotation measuring device according to any one of the inventions 1 to 17, wherein the sample cell The volume of the EBC is 0.1 cc or less.
  • a nineteenth invention (hereinafter referred to as an invention 19) as an example of the present invention developed from the inventions 1 to 18 is the optical rotation measuring device according to any one of the inventions 1 to 18, wherein the EBC generator is A pipe for allowing exhalation to pass through and a cooling means for cooling the exhalation in the pipe in a temperature range of 0 ° C. to 5 ° C. and a plastic pipe through which the EBC flows are arranged up to the EBC collecting section.
  • the EBC generator is A pipe for allowing exhalation to pass through and a cooling means for cooling the exhalation in the pipe in a temperature range of 0 ° C. to 5 ° C. and a plastic pipe through which the EBC flows are arranged up to the EBC collecting section.
  • the twentieth invention (hereinafter referred to as invention 20) as an example of the present invention developed by developing the invention 19 is the optical rotation measurement device according to the invention 19, wherein the optical rotation measurement device is connected to the EBC collection unit.
  • the plastic pipe is connected to the glass pipe for storing the specimen, and the volume from the collecting unit to the glass pipe for storing the specimen is set to a predetermined amount in advance, and the EBC collection is performed in consideration of the volume.
  • the optical rotation measuring device characterized in that the EBC of the section is configured to be fed to the glass pipe containing the specimen.
  • a twenty-first invention (hereinafter referred to as invention 21) as an example of the present invention developed by developing inventions 1 to 20 is the optical rotation measuring device according to any one of inventions 1 to 20, wherein the counter polarization conversion optical
  • the system is capable of allowing circularly polarized light traveling in different directions and orthogonal to each other to be incident on the specimen arranged in the specimen placement unit from the two different directions of the specimen.
  • the circularly polarized light traveling in different directions and orthogonal to each other can be optically coupled to an optical fiber constituting the ring optical path to propagate the ring optical path, and Signal light is arranged between the polarization conversion optical systems so as to face each other across the specimen placement section on the optical path, and signal light enters and exits the specimen of the specimen placement section a plurality of times.
  • a multipath counter collimator optical system, and the multipath counter collimator optical system includes a lens, a polarizer, a non-reciprocal polarization plane rotation element, and a polarization conversion element at each tip of the polarization plane preserving optical fiber facing each other. It is an invention of an optical rotation measuring device characterized in that a multipath is formed by providing an optical unit having an optical path changing means between a pair of collimators having a configuration.
  • a twenty-second invention (hereinafter referred to as invention 22) as an example of the present invention developed by developing invention 21 is the optical rotation measuring device according to invention 21, wherein the optical part having the optical path changing means is opposed to the optical part. It is an invention of an optical rotation measuring device characterized by having an arranged multiple reflection optical part.
  • a twenty-third invention (hereinafter referred to as invention 23) as an example of the present invention developed by developing invention 22 is the optical rotation measuring apparatus according to invention 19, wherein the multiple reflection optical unit has polarization condition storage means.
  • the present invention is an optical rotation measuring device according to the present invention.
  • a twenty-fourth invention (hereinafter referred to as an invention 24) as an example of the present invention developed by developing the inventions 1 to 20 is an optical rotation measuring apparatus according to any one of the inventions 1 to 20, wherein the ring interferometer On the loop optical path, a polarizing beam splitter (PBS) is provided in the middle of the loop optical path, and linearly polarized light orthogonal to the PBS is incident from both ends of the polarization-maintaining optical fiber constituting the loop optical path via the PBS.
  • PBS polarizing beam splitter
  • a 45-degree polarization plane rotation element guides the circularly polarized light orthogonal to the specimen through a polarization conversion optical system including a quarter-wave plate, and arranges a quarter-wave plate and a reflection mirror at the subsequent stage of the specimen. Then, the reflected orthogonal circularly polarized light is coupled to both ends of the polarization-preserving optical fiber again through the specimen, the polarization conversion optical system, and the PBS, and the signal light reciprocates to the specimen and doubles. It is the invention of optical rotation measuring device according to claim forming the scan.
  • a twenty-fifth invention (hereinafter referred to as invention 25) as an example of the present invention developed by developing the invention 24 is an optical rotation measuring apparatus according to the invention 24, which is arranged in the rear stage of the specimen instead of the reflecting mirror.
  • Optical rotation measurement characterized in that the light linearly polarized by the quarter-wave plate formed is coupled to the intrinsic polarization axis of a short knitted wavefront-preserving optical fiber with a lens, and a total reflection mirror is provided on its exit end face It is an invention of the device.
  • invention 26 the optical rotation of the specimen is measured using an optical fiber ring interferometer that measures the phase difference between the left and right light.
  • the optical rotation measuring device includes, as its constituent elements, at least an optical coupler that branches light from a light source into a ring optical path, and a polarization plane preserving that constitutes the ring optical path, that is, a loop optical path
  • a polarization beam splitter (PBS) is provided, and straight lines orthogonal to the PBS from both ends of the polarization-maintaining optical fiber constituting the loop via the PBS.
  • PBS polarization beam splitter
  • a twenty-seventh invention (hereinafter referred to as an invention 27) as an example of the present invention developed by developing the invention 26 is an optical rotation measuring apparatus according to the invention 26, which is arranged in the rear stage of the specimen instead of the reflecting mirror.
  • Optical rotation measurement characterized in that the light linearly polarized by the quarter-wave plate formed is coupled to the intrinsic polarization axis of a short knitted wavefront-preserving optical fiber with a lens, and a total reflection mirror is provided on its exit end face It is an invention of the device.
  • the twenty-eighth invention (hereinafter referred to as invention 28) as an example of the present invention made to solve the problem is an EBC generation unit that generates EBC from exhaled breath and an EBC collection that collects EBC generated by the EBC generation unit
  • An optical rotation measurement method capable of measuring the optical rotation of a specimen using an optical rotation measurement system having a liquid feeding system, an optical rotation measurement optical system, and a signal processing system from the head section and the EBC collection section,
  • the optical rotation measurement method includes a step of collecting EBC using the EBC generation unit and an EBC collection unit, a step of supplying EBC as a sample to a sample arrangement unit via the liquid feeding system, and the optical rotation measurement optical system.
  • a step of measuring the optical rotation of the specimen using the optical ring includes an optical ring unit having a specimen arrangement part inserted into a part of the ring optical path so as to constitute a part of the ring optical path.
  • the ring optical path of the optical rotation measurement optical system has the specimen placement when the EBC collected by the EBC collection section is placed in a specimen cell placed in the specimen placement section and placed as a specimen.
  • the circularly polarized light that travels in different directions to the specimen arranged in the section and is orthogonal to each other can be incident from two different directions of the specimen, and travels in the different directions through the specimen and
  • An orthogonal circularly polarized light is optically coupled to an optical fiber constituting the ring optical path so as to be propagated through the ring optical path, and the optical ring interference system is orthogonal to each other caused by the specimen.
  • An optical measurement unit capable of measuring information on glucose contained in the specimen by measuring a phase difference of circularly polarized light. It is the invention of optical rotation measuring method comprising.
  • a twenty-ninth invention (hereinafter referred to as invention 29) as an example of the present invention developed by developing the invention 28 is the optical rotation measuring method according to the invention 28, wherein the optical rotation measuring optical system includes the EBC. Measuring the change in phase difference of the circularly polarized light orthogonal to each other between the case where the sample is placed in the sample placement unit and the case where pure water or a glucose solution having a known concentration is placed in the sample placement unit instead of the sample. It is an invention of the optical rotation measuring method characterized in that it is an optical system that can obtain information on glucose contained in the EBC.
  • a thirtieth invention (hereinafter referred to as invention 30) as an example of the present invention developed by developing the invention 28 or 29 is the optical rotation measurement method according to the invention 28 or 29, wherein the optical rotation measurement method is the phase difference.
  • a blood glucose level concentration or a glucose concentration can be associated with each other by using a correspondence data table.
  • a thirty-first invention (hereinafter referred to as invention 31) as an example of the present invention developed by developing invention 30 is the changing means capable of changing the corresponding data table in the optical rotation measuring method according to invention 30. It is invention of the optical rotation measuring method characterized by using this.
  • a thirty-second invention as an example of the present invention developed from the inventions 28 to 31 is the optical rotation measurement method according to any one of the inventions 28 to 31, wherein the optical system includes the optical system described above.
  • the optical rotation measuring method invention is characterized in that the specimen is an optical system disposed between the opposing lenses of the opposing polarization conversion optical system inserted in the middle of the ring optical path of the ring interference system.
  • a thirty-third invention as an example of the present invention developed from the inventions 28 to 32 is the optical rotation measurement method according to any of the inventions 28 to 32, wherein the counter polarization conversion optical
  • the system has at least a lens and a polarizer between the end face of the optical fiber and the specimen on the optical path in the vicinity of the end face of the optical fiber, and a polarization plane of the signal light when the polarized beam as the signal light is incident from one side.
  • An invention of optical rotation measurement wherein the optical fiber optics plate is located is a counter optical fiber optical system are opposed to each other across the said specimen placement unit in the optical path.
  • a thirty-fourth invention (hereinafter referred to as invention 34) as an example of the present invention developed by developing the invention 33 is the optical rotation measuring method according to the invention 33, wherein the polarization plane rotation element is a Faraday rotation element. It is invention of the optical rotation measuring method characterized by these.
  • a thirty-fifth invention (hereinafter referred to as invention 35) as an example of the present invention developed by developing the inventions 28 to 34 is the optical polarization measuring method according to any one of the inventions 28 to 34, wherein The invention is an invention of a method of measuring the optical rotation, wherein the system is a counter polarization conversion collimator optical system.
  • a thirty-sixth aspect of the present invention developed as an example of the present invention is the optical rotation measurement method according to the thirty-fifth aspect, wherein the counter polarization conversion collimator is a polarization-maintaining optical fiber.
  • An optical system in which a polarization conversion collimator in which a lens, a polarizer, a Faraday rotator, and a quarter-wave plate are arranged at the emission end of the lens is opposed to each other in the optical path of the signal light with the specimen portion interposed therebetween (hereinafter referred to as a counter polarization conversion collimator).
  • the signal light emitted from the polarization-preserving optical fibers at both ends is in the same intrinsic linear polarization mode and propagates through the specimen section.
  • Optical rotation measurement characterized in that it is a counter-polarization conversion collimator in which the polarized light emitted from both collimators is circularly polarized light orthogonal to each other The law is of the invention.
  • a thirty-seventh invention (hereinafter referred to as invention 37) as an example of the present invention developed from the inventions 28 to 36 is the optical rotation measuring optical method according to any one of the inventions 28 to 36, wherein
  • the system guides laser light as signal light emitted from a light source to a second optical coupler via a first optical coupler and a polarizer, and mainly preserves the polarization plane of the signal light branched by the second coupler.
  • a ring light path formed by connecting the opposite polarization conversion collimator optical system in the middle of the ring optical path made of an optical fiber branches as signal light propagating in both directions along the ring optical path, and is near the second coupler of the ring optical path.
  • An optical phase modulator is provided, and the signal light propagating in both directions on the ring optical path is guided to a light receiver and a signal processing circuit via the second coupler, the polarizer, and the first coupler, and
  • the optical system is characterized in that the phase difference of the signal light propagating in both directions along the optical path is extracted as a signal synchronized with the phase modulation signal, and the sugar concentration of the specimen can be estimated by measuring the optical rotation of the specimen. It is invention of the optical rotation measuring method to do.
  • a thirty-eighth invention as an example of the present invention developed from the twenty-eighth to thirty-seventh aspects includes the first coupler in the optical rotation measuring method according to any of the twenty-eighth to thirty-seventh aspects.
  • a thirty-ninth invention (hereinafter referred to as invention 39) as an example of the present invention developed by developing the inventions 28 to 38 is the optical rotation measurement optical system according to any one of the inventions 28 to 38.
  • a 40th invention as an example of the present invention developed from the inventions 28 to 39 is the optical rotation measurement optical system according to any one of the inventions 28 to 39, wherein the optical rotation measurement optical system Is an optical rotation measuring method invention characterized by being an optical system in which the volume of the specimen portion through which the signal light of the specimen placement section passes is 0.1 cc or less.
  • a forty-first invention as an example of the present invention developed from the inventions 28 to 40 is the optical rotation measurement method according to any one of the inventions 28 to 40, wherein the sample cell comprises: Glass plates at both ends are bonded to the specimen cell with optical contacts, and are glass cells having an EBC inlet and an EBC outlet.
  • the EBC inlet is connected to the end of the pipe for supplying EBC to the specimen cell.
  • the EBC discharge port is an invention of the optical rotation measurement method, characterized in that each EBC discharge port is arranged perpendicularly to the optical path of the signal light at the end of the pipe for discharging EBC from the sample cell.
  • a forty-second invention (hereinafter referred to as an invention 42) as an example of the present invention developed by developing the inventions 28 to 41 is the optical rotation measurement method according to any one of the inventions 28 to 41, wherein the sample cell comprises: A plastic cell having an EBC inlet and an EBC outlet in which glass plates at both ends are fixed by an adhesive, and the EBC inlet and the EBC outlet are at the end of the pipe and with respect to the optical path of the signal light
  • the optical rotation measuring method is characterized by being arranged substantially vertically.
  • a forty-third invention (hereinafter referred to as an invention 43) as an example of the present invention developed by developing the inventions 28 to 42 is the optical rotation measurement method according to any of the inventions 28 to 43, wherein the EBC of the sample cell is the EBC.
  • the injection port is an invention of an optical rotation measurement method characterized in that the injection port is disposed at a position closer to the center of the cell wall than the EBC discharge port.
  • a forty-fourth invention (hereinafter referred to as an invention 44) as an example of the present invention developed by developing the inventions 28 to 43, in the optical rotation measurement method according to any one of the inventions 28 to 43, is the sample cell. It is invention of the optical rotation measuring method characterized by having a means to make the pressure of EBC discharge port of this pressure-reduced state with respect to EBC injection port.
  • a forty-fifth invention (hereinafter referred to as an invention 45) as an example of the present invention developed by developing the inventions 28 to 44, in the optical rotation measurement method according to any one of the inventions 28 to 44, is the sample cell.
  • the volume of the EBC is 0.1 cc or less.
  • a forty-sixth invention (hereinafter referred to as invention 46) as an example of the present invention developed by developing inventions 28 to 45 is the optical rotation measurement method according to any one of inventions 28 to 45, wherein the EBC generator is A pipe for allowing exhalation to pass through and a cooling means for cooling the exhalation in the pipe in a temperature range of 0 ° C. to 5 ° C. and a plastic pipe through which the EBC flows are arranged up to the EBC collecting section. It is invention of the optical rotation measuring method.
  • a forty-seventh invention (hereinafter referred to as invention 47) as an example of the present invention developed by developing inventions 28 to 46 is the optical rotation measurement method according to any one of inventions 28 to 46, wherein
  • the measurement system has a plastic pipe connecting the EBC collection unit to the glass pipe for storing the sample, and the volume from the collection unit to the glass pipe for storing the sample is set to a predetermined amount in advance.
  • the EBC collection unit is configured to send the EBC to the glass pipe that houses the specimen, and is an invention of an optical rotation measurement method.
  • a forty-eighth invention (hereinafter referred to as invention 48) as an example of the present invention developed by developing inventions 28 to 47 is the optical polarization measuring method according to any of the inventions 28 to 47, wherein The system is capable of allowing circularly polarized light traveling in different directions and orthogonal to each other to be incident on the specimen arranged in the specimen placement unit from the two different directions of the specimen.
  • the circularly polarized light traveling in different directions and orthogonal to each other can be optically coupled to an optical fiber constituting the ring optical path to propagate the ring optical path, and
  • the signal light is arranged between the polarization conversion optical systems so as to oppose each other with the specimen placement part sandwiched on the optical path, and the signal light enters and exits the specimen in the specimen placement part a plurality of times.
  • a multipath counter collimator optical system, and the multipath counter collimator optical system includes a lens, a polarizer, a nonreciprocal polarization plane rotation element, and a polarization conversion element at each tip of the polarization plane preserving optical fiber.
  • An optical rotation measuring method according to the invention is characterized in that a multipath is formed by providing an optical unit having an optical path changing means between a pair of collimators configured to include.
  • invention 49 A forty-ninth aspect of the present invention (hereinafter referred to as "invention 49") as an example of the present invention developed by developing the invention 48 is the optical rotation measuring method according to the aspect 48, wherein the optical section having the optical path changing means is opposed to the optical section. It is an invention of an optical rotation measuring method characterized by having a multiple reflection optical part arranged.
  • the multiple reflection optical unit has a polarization condition storage means. It is an invention of the optical rotation measuring method characterized by being a multilayer mirror.
  • a fifty-first invention (hereinafter referred to as invention 51) as an example of the present invention developed from the inventions 28 to 47 is the optical rotation measurement method according to any of the inventions 28 to 47, wherein the ring interferometer On the loop optical path, a polarization beam splitter (PBS) is provided in the middle of the loop optical path, and linearly polarized light orthogonal to the PBS is incident from both ends of the polarization-maintaining optical fiber constituting the loop via the PBS, 45-degree polarization plane rotation element guides circularly polarized light orthogonal to the specimen through a polarization conversion optical system including a quarter-wave plate, and arranges a quarter-wave plate and a reflection mirror downstream of the specimen, The reflected orthogonally circularly polarized light is coupled again to both ends of the polarization-preserving optical fiber via the specimen, the polarization conversion optical system, and the PBS, and the signal light reciprocates to the specimen to double pass.
  • PBS polarization beam splitter
  • a fifty-second invention (hereinafter referred to as invention 52) as an example of the present invention developed by developing the invention 51 is an optical rotation measurement method according to the invention 51, which is arranged in the rear stage of the specimen instead of the reflecting mirror.
  • Optical rotation measurement characterized in that the light linearly polarized by the quarter-wave plate formed is coupled to the intrinsic polarization axis of a short knitted wavefront-preserving optical fiber with a lens, and a total reflection mirror is provided on its exit end face It is a method invention.
  • the 53rd invention as an example of the present invention made to solve the problem includes an EBC generation unit that generates EBC from exhaled breath and an EBC collection that collects EBC generated by the EBC generation unit.
  • An optical rotation measurement method capable of measuring the optical rotation of a specimen using an optical rotation measurement system having a liquid feeding system from the head and the EBC collection part to the specimen part, an optical rotation measurement optical system, and a signal processing system, The optical rotation measurement method includes a step of collecting EBC using the EBC generation unit and an EBC collection unit, a step of supplying EBC as a sample to a sample arrangement unit via the liquid feeding system, and the optical rotation measurement optical system.
  • the optical rotation measurement system includes, as a component thereof, at least an optical coupler that branches light from a light source into a ring optical path, and A ring preserving optical fiber constituting a ring optical path, that is, a loop optical path, a phase modulation means, and a specimen placement section for placing a specimen placed in the middle of the loop optical path of the ring interferometer,
  • a polarization beam splitter (PBS) is provided in the middle of the loop optical path on the loop optical path, and linearly polarized light orthogonal to the PBS is incident from both ends of the polarization-maintaining optical fiber constituting the loop via the PBS, 45-degree polarization rotation element guides circularly polarized light orthogonal to each other through a polarization conversion optical system including a quarter-wave plate, and arranges a quarter-wave plate and a reflection mirror at the subsequent stage of the sample, The orthogonal circularly polarized light reflected by the total reflection mirror is again coupled to both ends of the polarization
  • the 54th invention as an example of the present invention developed from the invention 53 is an optical rotation measuring method according to the invention 53, which is arranged in the rear stage of the specimen instead of the reflecting mirror.
  • Optical rotation measurement characterized in that the light linearly polarized by the quarter-wave plate formed is coupled to the intrinsic polarization axis of a short knitted wavefront-preserving optical fiber with a lens, and a total reflection mirror is provided on its exit end face It is a method invention.
  • the 55th invention (referred to as invention 55) as an example of the present invention made to solve the problem is an optical rotation measurement optical system having the characteristics of the optical rotation measurement optical system according to any one of inventions 1 to 27. It is an invention of the system.
  • a fifty-sixth invention (referred to as invention 56) as an example of the present invention made to solve the problem is an invention of a specimen cell that can be used in the optical rotation measuring device according to any one of inventions 1 to 28.
  • the EBC injection port of the sample cell is an invention of a sample cell for optical rotation measurement, characterized in that the EBC injection port is disposed at a position closer to the center of the cell wall surface than the EBC discharge port.
  • the fifty-seventh invention (hereinafter referred to as invention 57) as an example of the present invention developed by developing the invention 56 is the sample cell for optical rotation measurement according to any one of the inventions 1 to 16, wherein It is an invention of a sample cell for optical rotation measurement, characterized by having means for reducing the pressure of the EBC discharge port relative to the EBC injection port.
  • the 58th invention (referred to as invention 58) as an example of the present invention developed by developing the inventions 56 and 57 includes the EBC of the sample cell in the sample cell for optical rotation measurement according to the invention 56 and 57. It is an invention of a sample cell for optical rotation measurement, characterized in that the volume to be measured is 0.1 cc or less.
  • the present invention can provide a number of inventions by developing inventions 1 to 58.
  • the optical path changing means including the polarization condition storing means can be provided on the outer wall of the sample cell, or can be provided inside the sample cell. These are also included in the present invention, and can be applied to, for example, a multipath opposed collimator optical system to be described later with reference to FIGS. 10 and 11 to reduce the size of the apparatus and improve the measurement accuracy.
  • the present invention employs a method of hybridizing a part that aggregates exhaled breath and an optical part that measures the optical rotation of the specimen, thereby measuring the glucose concentration of the breath condensate with high accuracy and increasing the blood glucose level non-invasively.
  • the present invention provides a novel optical rotation measuring device that can be estimated with high accuracy, and has an extremely large effect that blood glucose level of the living body can be estimated with high accuracy without collecting blood from the living body.
  • the present invention includes, firstly, no annoyance and pain associated with blood collection by the subject's needle, second, no sanitary disposal of the blood collection needle, and third, simple
  • the blood glucose level can be measured and the blood glucose level monitor can be performed any number of times a day, so that it can be used for the health management of diabetics and healthy persons, and has a great effect that could not be expected at all.
  • the optical rotation measuring device of the present invention is used in ordinary households, the number of diabetic patients and the number of people called diabetic reserves, which are currently increasing worldwide, can be greatly reduced, and medical expenses can be greatly reduced. Can be reduced.
  • Cooling device 2 EBC collection device 3: Cooling temperature control device 4: Sample (EBC, exhaled breath condensate) 5-1, 5-2, 5-3, 5-4, 5-5, 5-6: Plastic pipe 6: Automatic valve 7: Control unit of flow system 8: Pump 9: Pure water tank and pure water 10: Inlet 11: Glass pipe cell 12-1, 44: EBC inlet 12-2: EBC outlet 13-1, 13-2: Glass plate (adhesion by optical contact) 14-1, 14-2: Signal light 15: Drain 16: Light source (SLD) 17-1, 17-2: first and second couplers 18: optical fiber polarizers 19-1, 19-2, 19-3: polarization-maintaining optical fibers 20: Optical phase modulators 21-1, 21-2: Clockwise and counterclockwise linearly polarized light 22-1 and 22-2: Opposing polarization conversion collimator optical system 23: Light receiver 24: Signal processing circuit 25: Phase modulation Signals 26-1, 26-2: Fiber ferrules 27-1, 27-2: Polar
  • the optical rotation measuring method and the optical system that can be used in the optical rotation measuring device and the optical rotation measuring system of the present embodiment are duplicated. There are many. Therefore, in order to avoid duplication of explanation, while avoiding misunderstandings, the explanation of the optical system also serves as a partial explanation of the optical rotation measurement device and optical rotation measurement method, and vice versa, without any particular mention. is there.
  • FIG. 1 is a configuration diagram of an EBC generation unit, an EBC collection unit, an EBC liquid feeding unit, and a sample placement unit in an embodiment of the present invention.
  • the subject blows into the exhalation infusion pipe 5-1.
  • the exhaled air blown into the exhalation injecting pipe 5-1 passes through the pipe 5-1, is cooled by the cooling device 1, and condensed EBC (exhaled breath condensate) is stored in the EBC collecting unit 2.
  • Reference numeral 3 in the figure denotes a cooling temperature control unit.
  • reference numeral 14 denotes signal light that propagates through the specimen 4 in both directions.
  • the buffer solution 9 is pure water, and when the sample cell 11 is washed, it is guided to the sample cell via the pipe 5-4, the electromagnetic valve 6, and the pipe 5-5.
  • the phase difference of light propagating in pure water in both directions is measured, the value is switched to EBC as a reference value, the difference from the phase difference of signal light propagating in both directions is obtained, and the optical rotation of EBC is obtained.
  • FIG. 2 is an overall configuration diagram of an EBC optical rotation measurement optical system in an optical rotation measurement apparatus as an embodiment of the present invention.
  • the sample cell 11 is arranged at the center of the ring optical path of the optical fiber ring interference system.
  • the light source 16 is an SLD (Super Luminescent Diord) having a wavelength of 780 nm as a central wavelength.
  • SLD Super Luminescent Diord
  • the signal light emitted from the light source 16 is guided to the second optical coupler 17-2 through the first optical coupler 17-1 and the polarizer 18, and the polarization plane preserving optical fiber 19- by the second coupler 17-2.
  • 1 and 19-2 are branched into linearly polarized light 21-1 and 22-2, respectively.
  • the linearly polarized light 21-1 that is the branched light is modulated by the optical phase modulator 20 placed in the vicinity of the second coupler, and is converted from the polarization-maintaining optical fiber 19-1 to the opposite polarization conversion collimator optical system 22-1.
  • the linearly polarized light 21-2 which is the branched light, is guided from the polarization-maintaining optical fiber 19-2 to the opposite polarization conversion collimator optical system 22-1, and emitted from the opposite polarization conversion collimator optical systems 22-1 and 22-2.
  • the optical rotation measurement optical system of FIG. 2 includes a polarization plane preserving optical fiber 19-1, a counter polarization conversion collimator optical system 22-1, a specimen 4, a counter polarization conversion collimator optical system 22-2, and a polarization plane preserving optical fiber 19-2. Configure the ring optical path.
  • the signal light propagated through the EBC 4 in the sample cell 11 and propagated in both directions along the ring optical path is converted into an electric signal by the light receiver 23 via the second coupler 17-2, the polarizer 18, and the first coupler 17-1. Is done.
  • a 20 KHz modulation signal 25 is applied from the signal processing circuit 24 to the optical phase modulator 20.
  • the optical rotation of the specimen 4 can be measured by extracting the phase difference of the light propagating in the ring optical path in both directions as a signal synchronized with the phase modulation signal.
  • the optical fiber interference system used here is used in the optical fiber gyro described in Non-Patent Document 3, except that the counter polarization conversion collimator optical system in which the specimen is placed in the specimen placement portion is inserted into the ring optical path. The same method is used.
  • the optical fiber length of the ring optical path is 100 m
  • the optical phase modulator 20 uses a cylindrical PZT (lead zirconate titanate) element to which a sine wave modulation signal 25 of about 20 KHz is applied from the signal processing circuit 21. 1 is phase-modulated.
  • the optical fiber gyro described in Non-Patent Document 3 modulates the modulator with a sine wave, detects the fundamental wave, the second harmonic wave, and the fourth harmonic wave component in the light receiving unit, and determines the amplitude ratio of the fundamental wave and the second harmonic wave.
  • the phase difference is controlled by arc tangent (tan-1), and the modulation degree is controlled to be constant by the ratio of the second harmonic and the fourth harmonic components.
  • FIG. 3 is a configuration diagram of the opposite polarization conversion collimator optical systems 22-1 and 22-2 used in the optical rotation measurement system according to the present embodiment.
  • the front ends of the polarization-maintaining optical fibers 19-1 and 19-2 are shown in FIG. Respectively held by ferrules 26-1 and 26-2, the tips are obliquely polished by 8 degrees.
  • the light emitted from the polarization-preserving fiber 19-1 passes through the polarizing plate 27-1, the 45-degree rotating Faraday element 28-1, and the quarter-wave plate 29-1, and is collimated by the lens 30-1.
  • Light 14-1 passes through the specimen 4 and is optically coupled to the polarization-maintaining optical fiber 19-2.
  • the light emitted from the polarization-maintaining optical fiber 19-2 is polarized by the polarizing plate 27-2, the 45-degree rotating Faraday element 28-2, and the like.
  • the light passes through the quarter-wave plate 29-2, is collimated by the lens 30-2, passes through the specimen 4 as signal light 14-2 from the right side in the drawing, and is optically coupled to the polarization-maintaining optical fiber 19-1.
  • the signal light 14-1 and the signal light 14-2 are shown apart from each other in the figure, but both are beams that travel in the opposite directions at the same position.
  • the intrinsic polarization axis of the polarization-maintaining optical fiber 19-1 and the intrinsic polarization axis of the polarization-maintaining optical fiber 19-2 are orthogonal to each other, and 45-degree rotating Faraday elements 28-1 and 28-2 are of the same standard. Use. Thus, by using the Faraday element and the quarter-wave plate, circularly polarized light orthogonal to each other can be propagated in the specimen 4 in both the left and right directions.
  • the relative intrinsic polarization axes of the polarizing plate, the 45-degree rotating Faraday element, the wave plate, and the polarization-maintaining optical fiber are adjusted to propagate in the left-right direction through the polarization-maintaining optical fiber constituting the ring optical path. Only the phase difference of the signal light propagating in the left and right directions without causing the phase difference of the signal light propagating in both directions in the polarization plane preserving optical fiber so that the signal light propagates in the same polarization mode. Can be detected.
  • FIG. 4 is an overall configuration diagram of an optical rotation measurement system as an example of the present embodiment.
  • the specimen cell 11 is fixed on a stainless steel V groove 32.
  • the opposite polarization conversion collimators 22-1 and 22-2, the cell 11, and the V-groove 32 are disposed on the base 31 and are aligned and fixed.
  • the opposite polarization conversion collimators 22-1 and 22-2 are aligned via the cell 11. Are combined.
  • Reference numeral 34 denotes components other than the ring optical path of the ring interference system, that is, includes the light source 16, the first coupler 17-1, the second coupler 17-2, the polarizer 18, the light receiver 23, and the signal processing circuit 24 of FIG. It is connected to the personal computer 35 by an RS232C cable 36.
  • FIG. 2 as a polarization plane rotating element, when a polarized beam as signal light is incident on the specimen 4 from one side, the polarization plane of the signal light is rotated clockwise or counterclockwise in the traveling direction of the signal light.
  • the polarization beam is incident as signal light from the other side of the polarization plane rotating element, the polarization plane of the signal light is incident from the one side toward the traveling direction of the signal light.
  • a polarization plane rotating element which is a nonreciprocal optical element that acts to rotate by 45 degrees in the opposite direction, that is, counterclockwise or clockwise, is used.
  • the specimen 4 created as described above is arranged between the collimator optical systems, and the present invention, which will be described in detail below, makes it possible to obtain information on glucose in the breath that has not been conceived conventionally such as development of a measuring instrument.
  • An optical rotation measuring device that can be used has become possible.
  • the measurement circuit having the configuration shown in FIG. 2 is based on a so-called phase modulation type optical fiber gyro, but in this embodiment, a counter polarization conversion collimator optical system is installed near the center of the ring optical path of the phase modulation type optical fiber gyro. Is.
  • the phase modulation type optical fiber gyro can measure the rotation angular velocity of the ring optical path in the inertial space with high accuracy, but cannot measure the rotation of the polarization angle, that is, the optical rotation in principle.
  • a set of nonreciprocal optical systems 22-1 and 22-2 is provided in the ring optical path of the ring interferometer, while maintaining the highly sensitive phase measurement characteristics of the optical fiber gyro.
  • the optical rotation can be measured.
  • the half length of the polarization-preserving optical fiber in the ring optical path is wound in the opposite direction so as not to detect the rotational angular velocity.
  • the polarization-maintaining optical fiber used in the optical path of the ring interferometer of this embodiment is an optical fiber having an elliptical core, but an optical fiber having a structure in which anisotropic stress is applied to the core is also used. Can be used.
  • phase difference is generated between the right and left circularly polarized light propagating through the sample.
  • the phase difference generated as described above is twice the angle of optical rotation received when linearly polarized light passes through the specimen 4.
  • the generated phase difference depends on the specific rotation of the specimen 4, wavelength, temperature, specimen length, and the like. When the generated phase difference is small, it is necessary to increase the specimen length. In the experiment, the length of the sample cell 11 was set to 10 cm.
  • FIG. 5 is a photograph showing a part of the configuration of the glass pipe cell and the counter polarization conversion collimator used in the optical rotation measurement system as the present embodiment.
  • FIG. 6 is a graph showing an example of the optical rotation measurement result of pure water as an embodiment of the present invention, where the vertical axis Y is the glucose concentration (unit: g / dL) and the horizontal axis T is the time. The full scale on the horizontal axis is 1 minute. That is, FIG. 6 shows the time characteristics of the glucose concentration in the case of pure water, and the graph shows that the value of the vertical axis is zero throughout the measurement recording time, and the glucose concentration in pure water is the measurement recording time. In the figure, it is 0 g / dL. In the measurement system of FIG.
  • a mechanism for finely adjusting the incident / exit angle and position of the signal light beam in a direction perpendicular to the signal light beams 14-1 and 14-2 is added to the input / output portion of the specimen cell 11.
  • the glucose concentration in the case of pure water can be manually adjusted to 0 while viewing the output screen of the personal computer. This can be used as a reference for the glucose concentration in the measurement of the specimen 4
  • FIG. 7 is an example of a graph showing the optical rotation measurement results of a 0.1 g / dL glucose solution and pure water measured using the optical rotation measuring apparatus as an embodiment of the present invention.
  • the vertical axis ⁇ represents a phase difference (unit: : Degree), the horizontal axis is the same as in FIG. 6, and the full scale is 1 minute.
  • the specimen is switched from the glucose solution to pure water near the center of the horizontal axis that is the time axis of the graph.
  • FIG. 8A shows a graph showing an example of the optical rotation measurement result of EBC as the present embodiment.
  • the vertical axis Y is the glucose concentration (unit: g / dL), and the horizontal axis T is the time. is there.
  • EBC100 means the phase difference of EBC of a subject whose blood glucose level measured with a blood glucose meter of a conventional blood collection system is 100 mg / dL. The concentration difference between pure water and EBC100 was 0.01 g / dL.
  • the measurement is based on the level of the EBC 100.
  • FIG. 8B shows a graph showing another measurement example of the optical rotation measurement result of EBC as the present embodiment.
  • the vertical axis and the horizontal axis are the same as those in FIG. 8A. is there.
  • the difference in concentration of EBC326 between the pure water and the subject with high blood glucose level was 0.0345 g / dL.
  • FIG. 9 is a result showing the concentration difference between EBC 100 and EBC 326 used in FIGS. 8A and 8B and pure water. As a result, it was experimentally revealed that the optical rotation or concentration of EBC is approximately one tenth of the value measured with a conventional blood glucose meter.
  • Table 1 shows a comparison experiment result of the optical rotation measurement result of EBC according to the present embodiment and the blood glucose level measurement result by the conventional blood collection method.
  • the experiment was conducted using the EBC collected from the same subject before meal, 30 minutes after meal, and 60 minutes after meal, using the phase difference measured using the optical rotation measuring apparatus (interferometer method) of the present invention and conventional blood sampling at each time.
  • the relationship of blood glucose levels measured by the method was compared.
  • the measurement results were 254 mg / dL before meal, 323 mg / dL after 30 minutes, 395 mg / dL after 60 meals, and 395 mg / dL after the meal.
  • the present inventor for many subjects, data that can associate the phase difference resulting from EBC measured using the optical rotation measuring device of the present invention with the blood glucose level measurement result measured by the conventional blood sampling method.
  • a table is created for each subject, each healthy person, and each degree of medical condition, stored as a corresponding data table in the memory of the signal processing circuit of the ring interferometer, and using the optical rotation measurement device of this embodiment
  • an optical rotation measuring device capable of estimating the blood glucose level of the subject from the phase difference caused by the measured EBC was prepared.
  • the corresponding data table is created by the subject himself or herself or measured by an expert or the like, and an appropriate portion of the optical rotation measuring device is created.
  • optical rotation measuring devices of the present invention can exert extremely remarkable effects on the health management of diabetic patients and people called diabetic reserves, and can be widely used as easy-to-use health management devices. .
  • Non-Patent Document 2 chemically indicates that the glucose concentration contained in EBC is approximately 7% of 0.1 g / dL, which is the concentration contained in the blood of a healthy person. In the experiment of the present inventor, it was found that normal and abnormal blood glucose levels can be estimated with extremely high accuracy although the results are slightly different from the results of this document.
  • the 780 nm SLD light source output and loss level in this experiment were approximately as follows.
  • Light source output ⁇ 1mW
  • Optical interference system loss -10 dB (coupler 6 dB, polarizer 3 dB, other 1 dB)
  • Loss of opposed polarization conversion collimator set 7 dB
  • the loss was 17 dB
  • the light receiving level was 20 ⁇ W.
  • the collection rate of EBC in the experiment was usually 0.3 cc in 1 minute. Collecting EBC in as short a time as possible will reduce the burden on the subject.
  • a pipe having an inner diameter of 1 mm was used for the specimen cell 11. If it does in this way, it will be measurable if it is a net 0.075cc. That is, net EBC can be collected in about 15 seconds.
  • the volume of the specimen cell is desirably 0.1 cc or less.
  • the counter-polarization conversion collimator is connected to the specimen portion of the polarization-conversion collimator in which a lens, a polarizer, a Faraday rotator, and a quarter-wave plate are arranged at the exit end of the polarization-maintaining optical fiber.
  • One or more optical systems hereinafter referred to as an opposite polarization conversion collimator set
  • the opposite polarization conversion collimator set is emitted from the polarization plane preserving optical fibers at both ends.
  • the signal light beams having the same intrinsic linear polarization mode and the polarized light emitted from both collimators so as to propagate through the specimen portion can be made into opposite polarization conversion collimators in which the polarized lights are circularly polarized lights orthogonal to each other. By doing so, it is possible to prevent a phase difference from occurring due to a temperature change, and it is possible to realize an optical rotation measuring device that can estimate a blood glucose level more accurately.
  • FIG. 10 is a diagram for explaining the polarization conversion in the multipath opposed collimator optical system used in the optical rotation measuring apparatus as the embodiment.
  • the incident linearly polarized light 37-1 becomes right circularly polarized light 42-1 that is incident on the specimen 4 by the polarization conversion optical system 22-1 and propagates between the counter collimator optical systems 22-1 and 22-2.
  • 4 is repeatedly transmitted through the specimen 4, and is linearly polarized by the polarization conversion optical system 22-2 as the right circularly polarized light 42-2 emitted from the specimen 4 to become the outgoing linearly polarized light 37-2.
  • the incident linearly polarized light 38-1 becomes the left circularly polarized light 43-1 in the polarization conversion optical system 22-2, propagates through the counter collimator optical system, and exits from the specimen 4 as the left circularly polarized light 43-2.
  • the light is linearly polarized by the system 22-1 to become output linearly polarized light 38-2.
  • the multipath opposed collimator optical system of FIG. 10 is inserted into the ring optical path of FIG. 11
  • the linearly polarized light 37-1 and the linearly polarized light 38-2 are respectively transmitted counterclockwise through the optical fiber 19-2 in the same intrinsic polarization mode.
  • the linearly polarized light 37-2 and the linearly polarized light 38-1 are propagated as the counterclockwise signal light and the clockwise signal light through the optical fiber 19-1 in the same intrinsic polarization mode, respectively.
  • a part of the optical rotation measuring device of the present invention can be constructed.
  • the specimen in the optical rotation measuring device as an embodiment of the present invention can take various forms.
  • the sample may be a gas, for example, exhaled into the space, may be exhaled into the container, or may be an aqueous solution in which the gas stored in the container is dissolved. In some cases, it may be an aqueous solution containing a chemical that generates an optical rotatory material.
  • an optical path changing means such as a mirror provided with the quarter-wave plate on the surface can be arranged outside the container, and an apparatus can be easily produced. Further, the optical path changing means can be formed inside the container, and the size can be reduced.
  • reference numerals 39-1 and 39-2 denote polarization preserving mirrors as optical path changing means, which prevent changes in the polarization state due to reflection.
  • FIG. 11 is a diagram for explaining an optical rotation measuring apparatus as a second embodiment according to the present invention, in which the multipath opposed collimator optical system is provided in the optical path of the ring optical path of the optical fiber ring interference system. is there.
  • the optical rotation measuring apparatus according to the second embodiment shown in FIG. 11 inserts the multipath opposed collimator optical system into a so-called optical fiber ring interference system, that is, an optical fiber gyro loop,
  • the phase difference between left and right circularly polarized light propagating in both directions is measured by a phase modulation type optical fiber ring interference system.
  • the optical rotation measuring device having a multi-pass optical system can collect abundant amounts of specimens, and is effective when downsizing and high sensitivity of the device are required.
  • FIG. 12 is a diagram for explaining polarization conversion in a double-pass collimator optical system used in the optical rotation measuring apparatus according to the second embodiment of the present invention. That is, collimated light is generated from the polarization plane preserving optical fibers 19-1 and 19-2 constituting the ring via the lenses 30-3 and 30-4, and linearly polarized light (LP) orthogonal to each other is guided to the polarization beam splitter 40. That is, the LP emitted from the polarization-maintaining optical fiber 19-1 passes through the polarization beam splitter 40, and the LP emitted from the polarization-maintaining optical fiber 19-2 is reflected by the polarization beam splitter 40.
  • LP linearly polarized light
  • the light reflected by the total reflection mirror 41 in the left direction in FIG. 12 is the lens 30-5, the wave plate 29-4, the specimen 4 accommodated in the glass cell 11, the quarter wave plate 29-3, 45 degrees.
  • Light incident from the polarization-maintaining optical fiber 19-2 via the polarization rotating element 28-3 enters the polarization-maintaining optical fiber 19-1, and light incident from the polarization-maintaining optical fiber 19-1 is the polarization-maintaining optical fiber.
  • Each of the beams enters the polarization plane preserving optical fibers 19-1 and 19-2 in the same direct polarization mode.
  • the light exiting from the polarization-maintaining optical fiber 19-1 reciprocates the sample with right (left) circular polarization, and the light exiting from the polarization-maintaining optical fiber 19-2 passes through the sample to the left (right) circle. Since it reciprocates with polarized light, the optical rotation of the specimen can be measured by measuring the phase difference of the light propagating in both directions along the ring optical path.
  • FIG. 13 is a diagram for explaining an optical rotation measuring device as a third embodiment of the double-pass collimator optical system according to the present invention.
  • the volume of the specimen increases because the beam expands.
  • the signal light reciprocates through the same specimen, so that the specimen quantity can be reduced.
  • the signal light that has passed through the specimen is once incident on the optical fiber by the lens and is emitted again from the incident end of the same fiber, there is a merit that the beam does not spread even when reciprocating, Furthermore, the amount of specimen can be reduced, and the EBC collection time can be shortened.
  • the measuring apparatus of FIG. 13 requires the reflection mirror 41, but has an advantage that only one Faraday element is required.
  • the beam waist radius is about 100 mm
  • the beam radius at the cell exit end is 137 ⁇ m, which is smaller than the above-mentioned maximum beam radius, so that light can be transmitted without vignetting.
  • the internal volume of the sample cell will be about 0.01 cc, and EBC collection for several seconds will allow the cell to be filled with EBC. And the optical rotation of the EBC can be measured in a short time.
  • FIG. 15 is a diagram for explaining a particularly preferable example of the sample cell in another embodiment according to the present invention.
  • An EBC injection port 44 is provided in the vicinity of the center of the sample cell, and the EBC is hung from the EBC injection port 44, and a capillary tube is provided.
  • the burden on the subject can be reduced and the measurement time can be reduced. Shortening can be achieved.
  • EBC collected in advance was poured from the EBC inlet 44. Note that the EBC inlet can be used as both ends of the cell, and air can be sucked in from the opposite end of the EBC inlet.
  • the cell length of the sample cell in FIG. 15 is 50 mm and the cell inner diameter is ⁇ 0.5 mm, the internal volume of the sample cell is 0.01 cc, and the EBC collection time required to fill the sample cell is several seconds. That's it. If this sample cell is used in the double-pass optical system of the present invention to measure the optical rotation of the breath, the burden on the subject can be reduced, and the accurate optical rotation measurement of EBC can be performed in a short time.
  • the phase difference of EBC of a healthy person corresponds to approximately 0.01 degrees
  • the concentration of the optical rotation substance corresponds to 0.01 g / dL. Therefore, the accuracy of the measurement system must be 10 to 30 times or less. Therefore, the required phase difference measurement accuracy is 0.001 to 0.0003 degrees.
  • the experiment was performed with a rectangular cell shape, but the coupling loss of the opposing optical system changed by 20 dB or more just by changing the temperature of the upper part of the cell to such an extent that the hand was brought closer. This was thought to be due to the temperature difference between the upper and lower parts of the cell, the refractive index of the sample liquid at the upper part of the cell changing, and the beam being refracted. From this experience, it was possible to prevent a partial change in the refractive index of the sample liquid even if there was a temperature change around the cell by placing the cell in a V-shaped groove. In other words, the optimal shape of the cell is a pipe.
  • FIG. 16 is a diagram for explaining a double-pass polarization conversion optical system as another embodiment according to the present invention.
  • FIG. 16 is a diagram in which a total reflection mirror 45 is disposed in place of the lens 30-5 of the double-pass collimator optical system, the polarization-maintaining optical fiber 19-3, and the total reflection mirror 41 provided at the end portion thereof, as described in FIG.
  • the orthogonal LP propagates through the specimen 4 stored in the glass cell 11 via the Faraday rotator 28-3 as a 45-degree polarization plane rotating element, and the quarter-wave plate 29-3, and passes through the sample 4 for 4 minutes.
  • the light passes through the one-wave plate 29-4 and is reflected by the total reflection mirror 45.
  • the light reflected by the total reflection mirror 45 is in the left direction in the figure, the wave plate 29-4, the specimen 4, the quarter wave plate 29-3 accommodated in the glass cell 11, and the 45-degree polarization rotation element 28-. 3 through the polarization plane preserving optical fiber 19-2, the light entering the polarization preserving optical fiber 19-1, and the light entering from the polarization preserving optical fiber 19-1 into the polarization preserving optical fiber 19-2.
  • Incident light enters and exits the polarization-maintaining optical fibers 19-1 and 19-2 with the same polarization polarization mode as the same polarization mode.
  • the light exiting from the polarization-maintaining optical fiber 19-1 reciprocates the sample with right (left) circular polarization, and the light exiting from the polarization-maintaining optical fiber 19-2 passes through the sample to the left (right) circle. Since it reciprocates with polarized light, the optical rotation of the specimen can be measured by measuring the phase difference of the light propagating in both directions along the ring optical path.
  • FIGS. 17 and 18 are diagrams for explaining a double-pass collimator optical system as still another embodiment according to the present invention.
  • FIG. 17 shows a modification of the double-pass polarization conversion optical system according to still another embodiment of the present invention.
  • the spatial light of the signal light that has passed through the specimen 4 in the left direction in the drawing is once condensed by the lens and is divided into four minutes.
  • This is a so-called cat's eye type in which a total reflection mirror is arranged at the condensing point and the signal light is folded back through the one-wave plate.
  • the quarter wave plate may be disposed on the incident side of the cat's eye. In this example, the position of the mirror was adjusted so as to be coupled to the incident side collimator at the maximum.
  • FIG. 18 shows another modification which is still another embodiment of the double-pass polarization conversion optical system, which uses a two-core collimator and a polarizing prism. Also in this case, the clockwise light and the counterclockwise light propagating in the ring optical path reciprocate the specimen with right (left) circularly polarized light and left (right) circularly polarized light, respectively.
  • the optical rotation measurement device that can be used for the optical rotation measurement device and the optical rotation measurement system of the EBC according to the embodiments of the present invention can estimate blood glucose levels non-invasively. It was done.
  • the EBC it can be used as an optical rotation measuring device for specimens that contain an extremely small amount of optical rotation component in the medical and bio fields, and can exert a great effect.
  • the EBC generator of the present invention the collection device, the liquid feeding device, the optical rotation measuring device, the counter polarization conversion collimator optical system, and the optical rotation measuring method of the present invention have been described with reference to the drawings. Even if each of the above-described configurations of the embodiment of the present invention is used alone, the effects of the present invention can be exhibited, and the effects of the present invention can be exhibited even in various combinations.
  • the present invention is not limited to the embodiments and drawings described above, and many variations are possible based on the technical idea of the present invention.
  • the optical rotation measuring device of the present invention can measure the optical rotation of a specimen having an EBC or an extremely small amount of optical rotation with high accuracy, it can be widely used in the medical field, health equipment field, agricultural field, food field and the like.
  • blood glucose level can be estimated non-invasively.
  • the subject is released from the pain of blood collection, and secondly, it is hygienic because no blood is collected. In addition, it is possible to prevent infection of diseases through blood collection devices, etc. Third, there is no waste such as injection needles and enzymes, and fourth, the cost of consumables (medical expenses) is unnecessary. It has a great effect.

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Abstract

[Problème] Fournir un nouveau dispositif de mesure de rotation optique et une méthode de mesure qui, afin de traiter ou de prévenir le diabète, peuvent estimer très précisément et de manière non invasive, par une méthode simple, les taux de sucre dans le sang humain, ce qui requiert normalement le prélèvement de sang. [Solution] Grâce à une méthode d'hybridation d'un mécanisme EBC (condensat d'expiration), à un mécanisme de collecte EBC et à une partie de système optique qui estime très précisément les taux de sucre dans le sang d'un échantillon en mesurant très précisément la différence de phase survenant dans la lumière polarisée de manière circulaire et perpendiculaire en fonction de la rotation optique de l'échantillon, on a mis au point un dispositif et une méthode de mesure capables d'estimer simplement et très précisément les taux de sucre dans le sang humain, de manière non invasive, et de réduire la charge sur le sujet, et on a résolu le problème.
PCT/JP2011/077204 2010-11-26 2011-11-25 Dispositif de mesure de rotation optique, méthode de mesure de rotation optique pouvant être utilisée dans un système de mesure de rotation optique, système optique de mesure de rotation optique et cellule échantillon pour la mesure de rotation optique WO2012070646A1 (fr)

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JP2021067659A (ja) * 2019-10-28 2021-04-30 株式会社グローバルファイバオプティックス 濃縮呼気凝縮液の旋光度測定装置及び測定方法

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JP2021067659A (ja) * 2019-10-28 2021-04-30 株式会社グローバルファイバオプティックス 濃縮呼気凝縮液の旋光度測定装置及び測定方法
JP7290319B2 (ja) 2019-10-28 2023-06-13 株式会社グローバルファイバオプティックス 濃縮呼気凝縮液の旋光度測定装置及び測定方法

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