WO2012070646A1

WO2012070646A1 - Optical rotation measurement device, optical rotation measurement method that can be used in optical rotation measurement system, optical rotation measurement optical system, and sample cell for optical rotation measurement

Info

Publication number: WO2012070646A1
Application number: PCT/JP2011/077204
Authority: WO
Inventors: 博梶岡
Original assignee: 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
Priority date: 2010-11-26
Filing date: 2011-11-25
Publication date: 2012-05-31
Also published as: TW201239337A; JPWO2012070646A1

Abstract

[Problem] To provide a novel optical rotation measurement device and measurement method that, in order to treat or prevent diabetes, are able by a simple method to highly precisely and non-invasively estimate human blood sugar levels conventionally requiring the drawing of blood to measure blood sugar levels. [Solution] By means of adopting a method for hybridizing an EBC generating mechanism, an EBC collection mechanism, and an optical system section that highly precisely estimates blood sugar levels of a sample by highly precisely measuring the phase difference arising in perpendicular circularly polarized light on the basis of the optical rotation of the sample, a measurement device and measurement method that are able to simply and highly precisely estimate human blood sugar levels in a non-invasive manner and reduce the burden on a subject were developed, and the problem was resolved.

Description

Optical rotation measurement device, optical rotation measurement method usable in optical rotation measurement system, optical rotation measurement optical system, sample cell for optical rotation measurement

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)). The present invention relates to an optical rotation measurement apparatus and 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.

Recently, the increasing tendency of people who are said to be diabetic patients or pre-diabetes group has become a big social problem. Many of these people manage blood sugar, treat and prevent them. Blood glucose levels are currently measured at hospitals as needed and blood glucose levels are measured by chemical methods using reagents.

For patients whose blood glucose level is above a certain level, blood sampling and measurement multiple times a day are required. 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.

In the conventional 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. For example, due to the influence of fluctuations in the power of the light source, it is not possible to accurately measure 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. When the cell length is set to 10 mm by this method, a minute optical rotation angle of 0.00066 degrees can be measured. However, this method has problems such as a large-scale apparatus and being easily influenced by the temperature characteristics of lead glass. Also, with this method, 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.

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. In this method, 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. According to this method, the optical rotation angle can be measured with an accuracy of 0.0001 degrees when the length of the specimen is 10 mm. However, 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.

On the other hand, 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.

As an optical method for estimating blood glucose level without blood collection, a method of irradiating a living body with light and measuring the spectrum of the intensity of the scattered light has been proposed. The measurement result depends on the state of the, and the measurement cannot be performed stably. Moreover, a fluctuation of 0.1 g / dL occurs with a change of about 0.1 ° C. in body temperature. For this reason, this method has not been put into practical use until now.

As described above, there has been no optical rotation measuring device for measuring the optical rotation of a minute optical rotatory substance contained in exhaled breath condensate by an optical method, and there has been no idea of developing it.

JP 2002-318169 A JP 2005-274380 A

In view of the above circumstances, 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. Thus, 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. We found the possibility of measuring glucose concentration in human breath with high accuracy, which was previously considered impossible, and proceeded in different directions based on the EBC generation mechanism, the EBC collection mechanism, and the optical rotation of the specimen. By measuring the phase difference generated in orthogonal circularly polarized light with high accuracy and adopting a method that hybridizes with the optical system part that can estimate the blood glucose level of the sample 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. Hereinafter, means for solving the problems of the present invention will be described in detail.

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. 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. And 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. And circularly polarized light traveling in the different directions and orthogonal to each other through the specimen can be optically coupled to an optical fiber constituting the ring optical path to propagate the ring optical path. 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. In addition, 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. By measuring the change in phase difference of the circularly polarized light orthogonal to each other between the case where the sample is arranged in the sample arrangement unit and the case where pure water or a glucose solution having a known concentration is arranged in the sample arrangement unit instead of the sample It is an invention of an optical rotation measuring device characterized in that information on glucose contained in the EBC can be obtained.

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 rotated by a predetermined angle clockwise or counterclockwise in the traveling direction of the signal light, and a polarization beam as signal light is incident from the other side of the polarization plane rotating element, the polarization plane of the signal light And a quarter-wave plate that is a non-reciprocal element that acts to rotate the signal light in the direction of travel of the signal light from the one side by a predetermined angle in the opposite direction. 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). One or more sets), and in the opposite polarization conversion collimator set, 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 counter-polarization conversion collimator in which polarized light emitted from both collimators is circularly polarized light orthogonal to each other. It is.

A tenth invention as an example of the present invention developed from the first to ninth inventions (hereinafter referred to as the tenth invention) 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. .

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 (hereinafter referred to as invention 12) 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. Is an invention of an optical rotation measuring device.

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. It is an invention of 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. , 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.

According to a twenty-sixth aspect of the present invention (hereinafter referred to as "invention 26") as an example of the present invention made to solve the problem, 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. In the optical rotation measuring device, 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 An optical fiber, phase modulation means, and a sample placement unit for placing a sample placed in the middle of the loop optical path of the ring interferometer, and on the loop optical path of the ring interferometer, in the middle of the 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. Light is incident, circularly polarized light orthogonal to each other is guided to the specimen through a polarization conversion optical system including a 45-degree polarization rotation element and a quarter-wave plate, and a quarter-wave plate and a reflection are provided downstream of the specimen. The orthogonal circularly polarized light reflected by the total reflection mirror is again coupled to both ends of the polarization-preserving optical fiber via the sample, the polarization conversion optical system, and the PBS, and a signal light is transmitted to the sample. Is an invention of a double-pass optical rotation measuring device characterized in that the optical rotation of the specimen is measured by measuring the phase difference of light propagating in both directions by reciprocating to form a double pass.

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, and the optical rotation measuring optical system 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. And 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 (hereinafter referred to as invention 32) 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 (hereinafter referred to as invention 33) 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. Is rotated by a predetermined angle clockwise or counterclockwise in the traveling direction of the signal light, and a polarization beam as signal light is incident from the other side of the polarization plane rotating element, the polarization plane of the signal light A polarization plane rotating element that is a non-reciprocal element that acts to rotate a predetermined angle in the direction opposite to the direction in which the signal light is incident from the one side toward the traveling direction of the signal light, and a quarter wave 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 (hereinafter referred to as the thirty-sixth aspect) 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). One or more sets), and in the opposite polarization conversion collimator set, 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 (hereinafter referred to as the thirty-eighth aspect) includes the first coupler in the optical rotation measuring method according to any of the twenty-eighth to thirty-seventh aspects. Is an optical rotation measuring method invention characterized by being an optical circulator.

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. Is an invention of a method of measuring the optical rotation, 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 40th invention as an example of the present invention developed from the inventions 28 to 39 (hereinafter referred to as invention 40) 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 (hereinafter referred to as invention 41) 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. In consideration of the volume, 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.

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.

According to a fifty-th invention as an example of the present invention developed from the present invention 49 (hereinafter referred to as invention 50), in the optical rotation measuring method according to the invention 49, 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. It forms a an invention of optical rotation measurement method and characterized.

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 (hereinafter referred to as invention 53) 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-preserving optical fiber via the specimen, the polarization conversion optical system, and the PBS. An invention of a double-pass optical rotation measurement method characterized in that the optical rotation of the specimen is measured by measuring the phase difference of the light propagating in both directions along the ring optical path by the signal light reciprocating in the specimen. It is.

The 54th invention as an example of the present invention developed from the invention 53 (hereinafter referred to as the invention 54) 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.

Furthermore, 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. More specifically, 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. And if 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.

It is a block diagram of the EBC production | generation part, the EBC collection part, the liquid feeding part, and the sample arrangement | positioning part in the embodiment of one invention concerning this invention. It is a whole block diagram of the optical rotation measuring optical system of EBC in the optical rotation measuring device as an example of this embodiment. It is a block diagram of the opposite polarization conversion collimator optical system used for the optical rotation measuring system as an example of this embodiment. 1 is an overall configuration diagram of an optical rotation measurement system as an embodiment of the present invention. It is a figure which shows the structure of a part of glass pipe cell used for the optical rotation measuring system as an example of this Embodiment, and a counter polarization conversion collimator. It is a graph which shows an example of the optical rotation measurement result of the pure water in this embodiment. It is a graph which shows an example of the optical rotation measurement result of the glucose solution as an example of this embodiment. (A) A graph showing an example of an optical rotation measurement result of EBC and pure water as an example of this embodiment, and (B) is another example of an optical rotation measurement result of EBC and pure water as an example of this embodiment. It is a graph which shows one example. It is a graph which shows another example of the optical rotation measurement result of EBC as an example of this Embodiment. It is a conceptual diagram for demonstrating polarization | polarized-light conversion in the multipass opposing collimator optical system used for the optical rotation measuring device as an example of this Embodiment. It is a figure explaining the optical rotation measuring apparatus as 2nd Embodiment of the multipath opposing collimator optical system which concerns on this invention. It is a figure explaining the double path | pass opposing collimator optical system as a 2nd embodiment. It is a figure explaining the optical rotation measuring apparatus as 3rd Embodiment of the double path | pass opposing collimator optical system which concerns on this invention. It is a graph of the calculation result which shows the distance dependence of the beam diameter of a Gaussian beam whose beam waist is Φ0.2 mm. It is a figure explaining the especially preferable example of the sample cell in the other embodiment which concerns on this invention. It is a figure explaining the double path | pass opposing collimator optical system as another example of embodiment which concerns on this invention. It is a figure explaining the double pass opposed collimator optical system as other example of an embodiment concerning the present invention. It is a figure explaining the double pass opposed collimator optical system as other example of an embodiment concerning the present invention.

1: 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: Polarizing plates 28-1, 28-2, 28-3: Faraday rotators 29-1, 29-2, 29-3, 29- 4: 1/4 wavelength plate 30-1, 30-2, 30-3, 30-4, 30-5: Lens 31: Base 32: V groove holder 33-1, 33-2: Optical connector 34: Light Part of the interference system (including components other than rings)
35: PC 36: RS232C cable 37-1, 38-1: linearly polarized light incident on multiple reflection optical system 37-2, 38-2: linearly polarized light emitted from multiple reflection optical system 39-1, 39-2: polarized light Storage reflection mirror 40: Polarizing beam splitter (PBS)
41, 45: Total reflection mirrors 42-1, 42-2: Right circularly polarized light 43-1, 43-2: Left circularly polarized light 46: Polarizing prism 47: 2-core collimator

Hereinafter, an example of an embodiment of the present invention will be described with reference to the drawings. The drawings used for the description schematically show the dimensions, shapes, arrangement relationships, and the like of each component to the extent that an example of the present invention can be understood. For convenience of explanation, there may be cases where the enlargement ratio is partially changed for illustration, and the drawings used for explanation of the present embodiment may not necessarily be similar to the actual thing or description of the embodiment. Moreover, in each embodiment, in the drawings cited in the description, the same constituent components are denoted by the same reference numerals, and redundant description may be omitted. Further, in the following description of the embodiment according to the present invention, 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.

As mentioned above, there is currently no device for measuring the optical rotatory substance contained in exhaled breath, and no idea has been developed to develop it. However, the present inventor has included in exhalation from the expectation that if the optical rotatory substance contained in exhalation can be measured with high accuracy, it should be possible to estimate human blood glucose levels non-invasively. A detailed study on the improvement of the measurement accuracy of the optical rotatory materials was conducted. As a result, the inventors have found that human blood glucose levels can be estimated in a non-invasive manner, leading to the present invention. Hereinafter, the details will be described with reference to the embodiment.

Hereinafter, an embodiment of one invention according to the present invention will be described with reference to FIGS. 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. In FIG. 1, 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. When a certain amount of EBC 4 is accumulated in the collecting unit 2, the electromagnetic valve of the automatic valve 6 is switched, and a sufficient amount of EBC is filled from the collecting unit 2 by the pipe 5-3 by the control unit 7 of the flow system. The glass pipe cell 11 is filled through the pipe 5-5 and the cell injection portion 12-1. In FIG. 1, 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. In FIG. 2, 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. 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. Each passes through the specimen 4 from the glass plates 13-1 and 13-2 at both ends of the specimen cell 11, enters the collimator on the opposite side of the opposed polarization conversion collimator optical system, and propagates through the ring optical path. Here, the glass plates 13-1 and 13-2 were bonded to the glass pipe cell 11 for specimen by optical contact. 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, and 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. In this method, 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. For convenience of explanation, 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. Further, according to the present invention, 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.

In 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. When 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. Opposite polarization conversion using two polarization conversion optical systems as optical fiber optical systems having 45-degree rotation Faraday elements as polarization plane rotation elements that are non-reciprocal optical elements acting in this manner and facing each other with the specimen 4 interposed therebetween 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. In the optical rotation measuring device of the present embodiment, 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. In FIG. 2, 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.

If the sample 4 in the sample cell 11 has optical rotation, a phase difference is generated between the right and left circularly polarized light propagating through the sample. As is well known, 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. 2, 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. With this function, 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 Δθ represents a phase difference (unit: : Degree), the horizontal axis is the same as in FIG. 6, and the full scale is 1 minute. In the example of FIG. 7, 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.

As a result, it was found that when the specimen 4 was 0.1 g / dL glucose, the phase difference was measured as 0.1 degree.
The theoretical value of the optical rotation when the cell length at a wavelength of 780 nm = 10 cm and the glucose concentration is 0.1 g / dL is about 0.05 degree, and the phase difference between the left and right circularly polarized light is 0.1 degree, which is twice that value. It is. That is, the experiment shows that this is almost the same.
Thus, when the cell length is 100 mm, the values of the phase difference between the left and right light due to optical rotation and the glucose concentration coincide. Therefore, in the following measurement data, the phase difference (degree) and concentration (mg / dL) of the optical rotatory substance from pure water are not distinguished.

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. In FIG. 8A, FIG. 8B, and FIG. 9, 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. When EBC was measured using a measuring device, the value before meal was 0.026 degrees, the value after 30 minutes after meal was 0.033 degrees, and the value after 60 minutes after meal was 0.038 degrees. As a result, also in this experiment, the result that EBC contained approximately one-tenth of an optical rotatory substance in blood was obtained. In the same manner as in the experiment of Table 1, the blood glucose level was also measured for subjects in a normal range of 100 mg / dL. In this case, EBC contains about one-tenth glucose of blood. I found out that

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 Thus, 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. Further, in the optical rotation measuring device as the present embodiment, 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. It can be used by inputting it to an external storage device such as a memory or storage means such as its own USB. These 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
Overall, the loss was 17 dB, and the light receiving level was 20 μW.

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. In the experiment, 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. For EBC collection, it is not so difficult for many subjects to generate EBC by breathing intermittently into a breath collection pipe or the like for about 1 minute, but there are many patients who are unable to do so. Therefore, it is preferable to set the time for breathing into a breath collection pipe or the like in order to generate EBC to 30 seconds or less, and more preferably 20 seconds or less. As described above, the smaller the inner diameter of the sample cell, the shorter the time required for collecting EBC. From such a viewpoint, the volume of the specimen cell is desirably 0.1 cc or less.

In the experiment, it was found that the opposing polarization conversion collimator optical systems 22-1 and 22-2 cannot be coupled if bubbles are mixed in the specimen portion. In order to cope with this, it is effective that the EBC inlet 12-1 and the EBC outlet 12-2 of the present invention are arranged substantially perpendicularly to the end of the pipe.

In the present embodiment, 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) disposed opposite each other in the optical path of the signal light are used, and 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. In FIG. 10, 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. Similarly, 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. Then, when 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. By making the container a transparent container, 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. In FIG. 10, 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. As described above, 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. These orthogonal LPs propagate through the specimen 4 accommodated in the glass cell 11 via the Faraday rotator 28-3 as a 45-degree polarization plane rotator and the quarter-wave plate 29-3, and advance the fast axis. Is coupled to the specific polarization axis of the polarization-maintaining optical fiber 19-3 through a quarter-wave plate 29-4 and a lens 30-5 that are 90 degrees different from the polarization-plane rotating element 28-3. The light is reflected by the total reflection mirror 41 provided at the end portion 19-3.

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. Here, 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. In the case of multipaths of three or more passes, there is a problem that the volume of the specimen increases because the beam expands. However, in the case of double passes, the signal light reciprocates through the same specimen, so that the specimen quantity can be reduced. Furthermore, in the case of FIG. 12 and FIG. 13, since 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.

In addition, the measuring apparatus of FIG. 13 requires the reflection mirror 41, but has an advantage that only one Faraday element is required.

As a trial calculation example, the following conditions were examined.
Cell diameter: Φ0.5mm
Cell length: 25-100mm
Medium refractive index: 1.33
Incident side beam waist radius: 2.5 μm (NA = 0.1)
Design wavelength: 780 nm
The calculation was performed by approximating the light emitted from the fiber as a Gaussian beam under the above conditions.
The beam diameter at which vignetting does not occur is a range obtained by multiplying the Gaussian beam diameter (the diameter at which the intensity falls to 1 / square of e) by 1.3, and includes 99% of the light energy. If the margin is 1.5 times, the maximum beam radius without vignetting is as follows.
0.5 ÷ 1.5 ÷ 2 = 167μm
FIG. 14 shows the calculation results when the beam radius is changed from 0.1 mm to 0.01 mm steps. From this calculation result, it is appropriate that the beam waist radius is about 100 mm, and the beam radius at the cell exit end is 137 μm, which is smaller than the above-mentioned maximum beam radius, so that light can be transmitted without vignetting.

If the cell length is 50 mm and the inner diameter of the cell is Φ0.5 mm with a double-pass optical system, 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. By using the method of filling the cell with EBC due to the phenomenon and / or the method of filling the cell with EBC while taking in air from the outlets 12-2 provided at both ends of the figure, the burden on the subject can be reduced and the measurement time can be reduced. Shortening can be achieved. In this experiment, 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.

For example, if the cell length of the sample cell in FIG. 15 is 50 mm and the cell inner diameter is Φ0.5 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.

In the above experiments and considerations, the phase difference of EBC of a healthy person corresponds to approximately 0.01 degrees, and 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. Initially, 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. Here, 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.

As described above, it is experimentally proved that 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. In addition to 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.

As mentioned above, although 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.

Since 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. In particular, in the medical field, the health equipment field, and the like, blood glucose level can be estimated non-invasively. First, 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.

Claims

An optical rotation measurement apparatus having an optical rotation measurement optical system and capable of measuring the optical rotation of a specimen using the optical rotation measurement optical system, wherein the optical rotation measurement apparatus is configured to extract exhaled breath condensate (hereinafter referred to as EBC). An EBC generating unit to generate, 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, The optical rotation measuring optical system has an optical ring interference system having a specimen arrangement part inserted so as to constitute a part of the ring optical path in a part of the ring optical path, and the optical ring interference system is in the phosphor optical path. And a counter polarization conversion optical system that is inserted and opposed to sandwich the sample placement unit, and the ring optical path stores the EBC collected by the EBC collection unit in a sample cell arranged in the sample placement unit. As a sample When arranged, circularly polarized light traveling in different directions and orthogonal to each other can be incident on the specimen placed in the specimen placement section from the two different directions of the specimen. The optical ring interference system is configured to be able to propagate the ring optical path by optically coupling the circularly polarized light traveling in the different directions passing through and orthogonal to each other to an optical fiber constituting the ring optical path. An optical rotation unit comprising an optical measurement unit capable of measuring information on glucose contained in the specimen by measuring a phase difference between the circularly polarized lights orthogonal to each other caused by the specimen. measuring device.
2. The optical rotation measuring device according to claim 1, wherein the specimen is arranged between opposing lenses of the opposing polarization conversion optical system inserted in the middle of the ring optical path of the ring interference system. .
3. The optical rotation measuring apparatus according to claim 2, wherein the opposite polarization conversion optical system includes at least a lens and a polarizer between one end of the optical fiber and the specimen on an optical path in the vicinity of the end face of the optical fiber. When the polarization beam as the signal light is incident, the polarization plane of the signal light is rotated by a predetermined angle clockwise or counterclockwise in the traveling direction of the signal light, and from the other side of the polarization plane rotating element. When a polarized beam as signal light is incident, the polarization plane of the signal light acts to rotate by a predetermined angle in the opposite direction to the direction of incidence of the signal light from the one side. This is a counter optical fiber optical system in which a polarization plane rotating element that is a nonreciprocal element and an optical fiber optical system in which a quarter-wave plate is disposed are opposed to each other with the specimen arrangement portion interposed therebetween on the optical path. Optical rotation measurement device comprising and.
4. The optical rotation measuring apparatus according to claim 3, wherein a polarization beam splitter (PBS) is provided in the middle of the loop optical path on the ring optical path of the ring interferometer, that is, the loop optical path, and the loop is configured via the PBS. Linearly polarized light orthogonal to the PBS is incident from both ends of the polarization-preserving optical fiber, and circularly polarized light orthogonal to the specimen is passed through a polarization conversion optical system including a 45-degree polarization plane rotating element and a quarter-wave plate. Then, a quarter-wave plate and a reflecting mirror are arranged at the subsequent stage of the specimen, and the reflected orthogonal circularly polarized light is again transmitted to the polarization-preserving optical fiber via the specimen, the polarization conversion optical system, and the PBS. An optical rotation measuring apparatus, characterized in that it is coupled to both ends, and signal light reciprocates in the specimen to form a double path.
5. The optical rotation measuring apparatus according to claim 4, wherein light that has been linearly polarized by a quarter-wave plate disposed downstream of the specimen instead of the reflecting mirror is converted into a short knitted wavefront-preserving optical fiber by a lens. An optical rotation measuring apparatus, characterized in that a total reflection mirror is provided on the exit end face coupled to the intrinsic polarization axis.
The optical rotation measurement apparatus according to claim 3, wherein the optical fiber constituting the ring optical path, that is, the loop optical path is a polarization-preserving optical fiber, and the counter-polarization conversion optical system is disposed on the specimen arranged in the specimen placement unit. Circularly polarized light traveling in different directions and orthogonal to each other can be incident from the two different directions of the specimen, and circularly polarized light traveling in the different directions through the specimen and orthogonal to each other The specimen placement unit is configured to be able to propagate through the ring optical path by being optically coupled to an optical fiber constituting the ring optical path, and on the optical path between the two polarization conversion optical systems arranged opposite to each other. A multi-pass opposed collimator that is arranged so as to face each other with the signal light entering and exiting the specimen of the specimen placement section a plurality of times. The multipath opposed collimator optical system includes a lens, a polarizer, a non-reciprocal polarization plane rotation element, and a polarization conversion element at each end of the polarization-maintaining optical fiber facing each other. An optical rotation measuring device characterized in that an optical unit having an optical path changing means is provided between the pair to form a multipath.
7. An optical rotation measuring apparatus according to claim 6, wherein the optical part having the optical path changing means has a multiple reflection optical part arranged so as to face each other.
8. The optical rotation measuring device according to claim 7, wherein the multiple reflection optical unit is a multilayer mirror having polarization condition storage means.
9. The optical rotation measurement apparatus according to claim 1, wherein the optical rotation measurement apparatus has a configuration in which pure water or concentration is used instead of the specimen when the specimen containing the EBC is placed in the specimen placement unit. Information on glucose contained in the EBC can be obtained by measuring a change in phase difference of circularly polarized light orthogonal to each other when a known glucose solution is placed in the specimen placement portion. measuring device.
10. The optical rotation measurement device according to claim 1, wherein the optical rotation measurement device has a correspondence data table that can associate the phase difference with a blood glucose level concentration or a glucose concentration. An optical rotation measuring device characterized by that.
11. The optical rotation measuring apparatus according to claim 10, wherein the correspondence data table can be changed from an input unit of the apparatus and / or from the outside of the apparatus and / or by a program.
The optical rotation measuring apparatus according to any one of claims 3 to 11, wherein the polarization plane rotating element is a Faraday rotating element.
13. The optical rotation measuring apparatus according to claim 1, wherein the counter polarization conversion optical system is a counter polarization conversion collimator optical system.
14. The optical rotation measuring apparatus according to claim 13, wherein the opposite polarization conversion collimator is a 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 counter polarization conversion collimator sets) arranged opposite to each other in the optical path of the signal light with the specimen portion interposed therebetween, and the polarization plane preserving optical fibers at both ends of the counter polarization conversion collimator set are used. The signal light emitted from the collimator is the same eigen linear polarization mode, and the polarized light emitted from both collimators is circularly polarized light orthogonal to each other so as to propagate through the specimen portion. Optical rotation measuring device characterized by.
The optical rotation measurement device according to any one of claims 1 to 14, wherein the optical rotation measurement device transmits a laser beam as a signal light emitted from a light source through a first optical coupler and a polarizer. The signal light branched to the second optical coupler and branched by the second coupler is connected to the ring optical path formed by connecting the opposite polarization conversion collimator optical system in the middle of the ring optical path mainly composed of a polarization-maintaining optical fiber. A signal light that propagates in both directions in the optical path is branched, an optical phase modulator is provided in the vicinity of the second coupler in the ring optical path, and the signal light that propagates in the bidirectional direction in the ring optical path is converted into the second coupler and the polarization A phase difference between the signal light propagating in both directions through the ring optical path is extracted as a signal synchronized with the phase modulation signal, and is detected. Optical rotation measurement device, characterized in that for estimating the glucose concentration of the analyte to the optical rotation was measured.
The optical rotation measuring apparatus according to any one of claims 1 to 15, wherein the first coupler is an optical circulator.
The optical rotation measurement apparatus according to any one of claims 1 to 16, wherein the optical rotation measurement apparatus includes a mechanism unit that finely adjusts an angle of the specimen unit with respect to the propagation signal light. Optical rotation measuring device.
The optical rotation measurement apparatus according to any one of claims 1 to 17, wherein the volume of the specimen portion through which the signal light of the specimen arrangement section is transmitted is 0.1 cc or less.
The optical rotation measuring apparatus according to any one of claims 1 to 18, wherein the specimen cell is a glass cell having glass plates at both ends bonded to the specimen cell by optical contact, and having an EBC inlet and an EBC outlet. The EBC inlet is perpendicular to the optical path of the signal light at the end of the pipe that supplies EBC to the sample cell, and the EBC outlet is at the end of the pipe that discharges EBC from the sample cell. An optical rotation measuring device characterized by being arranged.
The optical rotation measuring apparatus according to any one of claims 1 to 19, wherein the specimen cell is a plastic cell having an EBC inlet and an EBC outlet in which glass plates at both ends are fixed with an adhesive. The optical rotation measuring device is characterized in that the EBC inlet and the EBC outlet are arranged at the end of the pipe and substantially perpendicular to the optical path of the signal light.
The optical rotation measuring apparatus according to any one of claims 1 to 20, wherein the EBC injection port of the sample cell is disposed at a position closer to the center of the cell wall surface than the EBC discharge port. Optical rotation measuring device.
The optical rotation measurement apparatus according to any one of claims 1 to 21, further comprising means for reducing the pressure of the EBC discharge port of the sample cell relative to the EBC injection port. apparatus.
The optical rotation measurement apparatus according to any one of claims 1 to 22, wherein a volume of the specimen cell storing the EBC is 0.1 cc or less.
The optical rotation measuring device according to any one of claims 1 to 23, wherein the EBC generator cools a pipe through which exhaled gas passes and exhaled gas in the pipe in a temperature range of 0 ° C to 5 ° C. An optical rotation measuring apparatus characterized in that a plastic pipe through which the EBC flows is arranged to the EBC collecting part.
25. The optical rotation measurement device according to claim 24, wherein the optical rotation measurement device is connected with a plastic pipe from the EBC collection unit to a glass pipe that houses the sample, and the sample is collected from the collection unit. The volume between the glass pipe to be stored is set to a predetermined amount in advance, and the EBC of the EBC collecting unit is sent to the glass pipe to store the specimen in consideration of the volume. Optical rotation measuring device.
In the optical rotation measurement apparatus capable of measuring the optical rotation of the specimen using an optical fiber ring interferometer that measures the phase difference of both the right and left light, the optical rotation measurement apparatus includes at least a light source as a component. An optical coupler that branches light into a ring optical path, a polarization-preserving optical fiber that constitutes the ring optical path, that is, a loop optical path, a phase modulation means, and a specimen that arranges a specimen disposed in the middle of the loop optical path of the ring interferometer A polarization beam splitter (PBS) in the middle of the loop optical path on the loop optical path of the ring interferometer, and from both ends of the polarization-preserving optical fiber constituting the loop via the PBS Linearly polarized light that is orthogonal to each PBS is incident on the PBS, and the detection is performed via a polarization conversion optical system including a 45-degree polarization rotation element and a quarter-wave plate. The circularly polarized light orthogonal to each other is guided, a quarter-wave plate and a reflection mirror are arranged at the subsequent stage of the specimen, and the orthogonal circularly polarized light reflected by the total reflection mirror is again the specimen, the polarization conversion optical system, By coupling to both ends of the polarization-maintaining optical fiber via the PBS, the signal light reciprocates to the specimen to form a double path, and the phase difference of the light propagating in both directions through the ring optical path is measured. A double pass optical rotation measuring device characterized by measuring optical rotation.
27. The optical rotation measurement apparatus according to claim 26, wherein light that has been linearly polarized by a quarter-wave plate disposed downstream of the specimen instead of the reflecting mirror is converted into a short knitted wavefront-preserving optical fiber by a lens. An optical rotation measuring apparatus, characterized in that a total reflection mirror is provided on the exit end face coupled to the intrinsic polarization axis.
An EBC generator that generates exhaled breath condensate (hereinafter referred to as EBC), an EBC collector that collects EBC generated by the EBC generator, and a liquid feed system and an optical rotation measurement optical system from the EBC collector to the specimen And an optical rotation measurement method capable of measuring the optical rotation of a specimen using an optical rotation measurement system having a signal processing system, wherein the optical rotation measurement method uses an EBC generation unit and an EBC collection unit to perform EBC. A step of collecting, a step of supplying EBC as a specimen to the specimen placement section via the liquid feeding system, and a step of measuring the optical rotation of the specimen using the optical rotation measuring optical system. The degree measuring optical system has an optical ring interference system having a specimen arrangement 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 of the optical rotation measuring optical system includes: in front When the EBC collected by the EBC collection unit is stored in the sample cell arranged in the sample arrangement unit and arranged as a sample, the circles proceed in different directions to the sample arranged in the sample arrangement unit and are orthogonal to each other Polarized light can be incident from two different directions of the specimen, and circularly polarized light traveling through the specimen in different directions and orthogonal to each other is optically coupled to an optical fiber constituting the ring optical path. The optical ring interference system is configured to transmit information on glucose contained in the specimen by measuring a phase difference of the circularly polarized light that are caused by the specimen and are orthogonal to each other. An optical rotation measuring method comprising an optical measuring unit capable of measuring.
29. In the optical rotation measurement method according to claim 28, when the optical rotation measurement optical system arranges the specimen containing EBC in the specimen arrangement section, pure water or a glucose solution having a known concentration is used instead of the specimen. Optical rotation measurement characterized by being an optical system capable of obtaining information on glucose contained in the EBC by measuring a change in phase difference of the circularly polarized light orthogonal to each other when placed in the specimen placement unit Method.
30. The optical rotation measurement method according to claim 28 or 29, wherein the optical rotation measurement method includes a step of using a correspondence data table capable of making the phase difference correspond to a blood glucose level concentration or a glucose concentration. Optical rotation measurement method.
31. The optical rotation measurement method according to claim 30, wherein a change means capable of changing the corresponding data table is used.
The optical rotation measurement method according to any one of claims 28 to 31, wherein the optical system is disposed between opposing lenses of an opposing polarization conversion optical system in which the specimen is inserted in the middle of a ring optical path of a ring interference system. An optical rotation measuring method, characterized by comprising:
The optical rotation measurement method according to any one of claims 28 to 32, wherein the counter-polarization conversion optical system includes at least a lens and a polarization between an optical fiber end face and the specimen on an optical path in the vicinity of the end face of the optical fiber. When a polarized beam as signal light is incident from one side of the optical element, the polarization plane of the signal light is rotated by a predetermined angle clockwise or counterclockwise toward the traveling direction of the signal light, and the polarization plane When a polarized beam as signal light is incident from the other side of the rotating element, the polarization plane of the signal light is incident at a predetermined angle in a direction opposite to the direction of incidence from the one side toward the traveling direction of the signal light. A polarization plane rotating element, which is a non-reciprocal element that acts to rotate only, and an optical fiber optical system in which a quarter-wavelength plate is arranged are opposed to each other with the specimen arrangement portion interposed therebetween on the optical path Optical rotation measurement method which is a fiber optical system.
34. The optical rotation measurement method according to claim 33, wherein the polarization plane rotation element is a Faraday rotation element.
The optical rotation measurement method according to any one of claims 28 to 34, wherein the counter polarization conversion optical system is a counter polarization conversion collimator optical system.
36. The optical rotation measurement method according to claim 35, wherein the opposite polarization conversion collimator is a polarization conversion collimator in which a lens, a polarizer, a Faraday rotation element, and a quarter-wave plate are arranged at the output end of the polarization-maintaining optical fiber. One or more optical systems (hereinafter referred to as counter polarization conversion collimator sets) arranged opposite to each other in the optical path of the signal light with the specimen portion interposed therebetween, and the polarization plane preserving optical fibers at both ends of the counter polarization conversion collimator set are used. The signal light emitted from the collimator is the same eigen linear polarization mode, and the polarized light emitted from both collimators is circularly polarized light orthogonal to each other so as to propagate through the specimen portion. An optical rotation measuring method characterized by the above.
The optical rotation measurement method according to any one of claims 28 to 36, wherein the optical rotation measurement optical system transmits laser light as signal light emitted from a light source via a first optical coupler and a polarizer. The signal light branched to the second optical coupler and branched by the second coupler is connected to the ring optical path formed by connecting the opposite polarization conversion collimator optical system in the middle of the ring optical path mainly composed of a polarization-maintaining optical fiber. Branching as signal light propagating in both directions on the ring optical path, an optical phase modulator is provided in the vicinity of the second coupler of the ring optical path, and the signal light propagating in both directions on the ring optical path is transmitted to the second coupler, The light is guided to a light receiver and a signal processing circuit via a polarizer and the first coupler, and a phase difference of signal light propagating in both directions on the ring optical path is extracted as a signal synchronized with the phase modulation signal. Optical rotation measurement method is characterized in that an optical system as possible to estimate the glucose concentration of the analyte by measuring the optical rotation of the sample.
The optical rotation measurement method according to any one of claims 28 to 37, wherein the first coupler is an optical circulator.
The optical rotation measurement method according to any one of claims 28 to 38, wherein the optical rotation measurement optical system includes a mechanism unit for finely adjusting an angle of the specimen unit with respect to the propagation signal light. Optical rotation measurement method.
The optical rotation measurement optical system according to any one of claims 28 to 39, wherein the optical rotation measurement optical system is an optical system in which the volume of the specimen portion through which the signal light of the specimen placement section is transmitted is 0.1 cc or less. An optical rotation measuring method characterized by being.
41. The optical rotation measuring method according to claim 28, wherein the specimen cell is a glass cell having glass plates at both ends bonded to the specimen cell by optical contact and having an EBC inlet and an EBC outlet. The EBC inlet is perpendicular to the optical path of the signal light at the end of the pipe that supplies EBC to the sample cell, and the EBC outlet is at the end of the pipe that discharges EBC from the sample cell. An optical rotation measurement method characterized by being arranged.
The optical rotation measurement method according to any one of claims 28 to 41, wherein the specimen cell is a plastic cell having an EBC inlet and an EBC outlet in which glass plates at both ends are fixed with an adhesive. The optical rotation measuring method, wherein the EBC inlet and the EBC outlet are arranged at the end of the pipe and substantially perpendicular to the optical path of the signal light.
The optical rotation measurement method according to any one of claims 28 to 42, wherein the EBC inlet of the sample cell is disposed at a position closer to the center of the cell wall than the EBC outlet. To measure the optical rotation.
The optical rotation measurement method according to any one of claims 28 to 43, further comprising means for reducing the pressure of the EBC discharge port of the sample cell relative to the EBC injection port. Method.
45. The optical rotation measurement method according to any one of claims 28 to 44, wherein a volume in which the EBC of the sample cell is stored is 0.1 cc or less.
The optical rotation measurement method according to any one of claims 28 to 45, wherein the EBC generator cools a pipe through which exhaled gas passes and exhaled gas in the pipe in a temperature range of 0 ° C to 5 ° C. A method for measuring the optical rotation, characterized in that a plastic pipe through which the EBC flows is arranged up to the EBC collecting part.
The optical rotation measurement method according to any one of claims 28 to 46, wherein the optical rotation measurement system includes a plastic pipe connecting the EBC collection unit to the glass pipe storing the specimen, The volume from the collection unit to the glass pipe for storing the sample is set to a predetermined amount in advance, and the EBC of the EBC collection unit is sent to the glass pipe for storing the sample in consideration of the volume. An optical rotation measurement method characterized by comprising:
The optical rotation measurement method according to any one of claims 28 to 47, wherein the counter polarization conversion optical system travels in different directions to the sample arranged in the sample arranging unit and is orthogonal to each other. Circularly polarized light can be incident from two different directions of the specimen, and circularly polarized light traveling in the different directions through the specimen and orthogonal to each other is optically coupled to an optical fiber constituting the ring optical path. The light beam is configured to be able to propagate in the ring optical path, and is arranged so as to oppose each other with the specimen arrangement part sandwiched between the two polarization conversion optical systems arranged opposite to each other on the optical path. Has a multi-pass opposed collimator optical system that allows signal light to enter and exit the sample of the sample placement unit a plurality of times, and the multi-pass opposed collimator optical system An optical unit having an optical path changing means is provided between a pair of collimators including a lens, a polarizer, a nonreciprocal polarization plane rotation element, and a polarization conversion element at each tip of the polarization-maintaining optical fiber facing each other. An optical rotation measuring method characterized by forming a path.
49. The optical rotation measuring method according to claim 48, wherein the optical part having the optical path changing means has a multiple reflection optical part arranged so as to face each other.
50. The optical rotation measurement method according to claim 49, wherein the multiple reflection optical unit is a multilayer mirror having polarization condition storage means.
The optical rotation measurement method according to any one of claims 28 to 47, wherein a polarization beam splitter (PBS) is provided in the middle of the loop optical path on the loop optical path of the ring interferometer, and the Linearly polarized light orthogonal to the PBS is incident from both ends of the polarization-preserving optical fiber constituting the loop, and orthogonal to the specimen through a polarization conversion optical system including a 45-degree polarization plane rotating element and a quarter-wave plate. The circularly polarized light is guided, a quarter-wave plate and a reflection mirror are arranged at the rear stage of the specimen, and the orthogonal circular polarized light reflected again passes through the specimen, the polarization conversion optical system, and the PBS. An optical rotation measurement method, characterized in that the optical signal is coupled to both ends of a storage optical fiber, and signal light reciprocates to form a double path.
52. The optical rotation measurement method according to claim 51, wherein light that has been linearly polarized by a quarter-wave plate disposed downstream of the specimen instead of the reflecting mirror is converted into a short knitted wavefront-preserving optical fiber by a lens. A method of measuring optical rotation, characterized in that a total reflection mirror is provided on the exit end face coupled to the intrinsic polarization axis.
An EBC generator that generates exhaled breath condensate (hereinafter referred to as EBC), an EBC collector that collects EBC generated by the EBC generator, and a liquid feed system and an optical rotation measurement optical system from the EBC collector to the specimen And an optical rotation measurement method capable of measuring the optical rotation of a specimen using an optical rotation measurement system having a signal processing system, wherein the optical rotation measurement method uses an EBC generation unit and an EBC collection unit to perform EBC. A step of collecting, a step of supplying EBC as a specimen to the specimen placement section via the liquid feeding system, and a step of measuring the optical rotation of the specimen using the optical rotation measuring optical system. The degree measurement system includes, as its components, at least an optical coupler that branches light from a light source into a ring optical path, and a polarization-preserving optical fiber that constitutes the ring optical path, that is, a loop optical path. A phase modulation means and a sample placement section for placing a sample placed in the middle of the loop optical path of the ring interferometer, and a polarization beam splitter (in the middle of the loop optical path on the loop optical path of the ring interferometer) PBS), linearly polarized light orthogonal to the PBS is incident from both ends of the polarization-maintaining optical fiber constituting the loop via the PBS, and polarized light including a 45-degree polarization rotating element and a quarter-wave plate. Circular polarizations orthogonal to each other are guided to the specimen via a conversion optical system, a quarter-wave plate and a reflection mirror are arranged at the subsequent stage of the specimen, and the orthogonal circular polarization reflected by the total reflection mirror is again The sample is coupled to both ends of the polarization-maintaining optical fiber via the sample, the polarization conversion optical system, and the PBS, and the signal light reciprocates to the sample to form a double path. Double pass optical rotation measuring method characterized by measuring the optical rotation of the sample by measuring the phase difference of the light propagating direction.
54. The optical rotation measurement method according to claim 53, wherein light that has been linearly polarized by a quarter-wave plate disposed downstream of the specimen instead of the reflecting mirror is converted into a short knitted wavefront-preserving optical fiber by a lens. A method of measuring optical rotation, characterized in that a total reflection mirror is provided on the exit end face coupled to the intrinsic polarization axis.
An optical rotation measurement optical system having the characteristics of the optical rotation measurement optical system according to any one of claims 1 to 27.
The sample cell that can be used in the optical rotation measuring device according to any one of claims 1 to 27, wherein the EBC injection port of the sample cell is disposed closer to the center of the cell wall than the EBC discharge port. A sample cell for optical rotation measurement, characterized in that
57. The sample cell for optical rotation measurement according to claim 56, further comprising means for reducing the pressure of the EBC discharge port of the sample cell relative to the EBC injection port. .
58. A sample cell for optical rotation measurement according to claim 56 or 57, wherein the volume of EBC in the sample cell is 0.1 cc or less.