JPH10108857A - Biochemical measuring device - Google Patents
Biochemical measuring deviceInfo
- Publication number
- JPH10108857A JPH10108857A JP8264057A JP26405796A JPH10108857A JP H10108857 A JPH10108857 A JP H10108857A JP 8264057 A JP8264057 A JP 8264057A JP 26405796 A JP26405796 A JP 26405796A JP H10108857 A JPH10108857 A JP H10108857A
- Authority
- JP
- Japan
- Prior art keywords
- light
- living body
- transmitted
- sample
- optical fiber
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/21—Polarisation-affecting properties
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は光学的手段により体
内の生化学成分濃度、特に血中グルコース濃度を計測す
る医療用生化学計測装置に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical biochemical measuring device for measuring the concentration of a biochemical component in a body, particularly blood glucose concentration, by optical means.
【０００２】[0002]
【従来の技術】近赤外分光法を利用する、生体中のグル
コース濃度の無侵襲計測がアプライドスペクトロスコピ
ー第４７／７巻，１９９３年，第８７５頁から第８８１
頁（Applied Spectroscopy，Vol. 47，No.7，pp. 875−
881 ）に記載されている。本技術では光ファイバのイン
ターフェイスが装着された近赤外分光装置を用いて測定
対象者の唇からの近赤外拡散反射スペクトルを測定し、
同時に測定対象者の血中グルコース濃度の従来法による
測定を行い、得られた近赤外スペクトルと血中グルコー
ス濃度の測定値をもとに部分最小自乗（ＰＬＳ）多変量
解析法を用いて検量式を作成している。2. Description of the Related Art Noninvasive measurement of glucose concentration in a living body using near-infrared spectroscopy is described in Applied Spectroscopy, Volume 47/7, 1993, pp. 875 to 881.
Page (Applied Spectroscopy, Vol. 47, No. 7, pp. 875-
881). In this technology, the near-infrared diffuse reflection spectrum from the lips of the measurement subject is measured using a near-infrared spectroscope equipped with an optical fiber interface,
At the same time, the blood glucose concentration of the measurement subject is measured by the conventional method, and calibration is performed using a partial least squares (PLS) multivariate analysis method based on the obtained near-infrared spectrum and the measured value of the blood glucose concentration. You are creating an expression.
【０００３】[0003]
【発明が解決しようとする課題】原理的には広い波長範
囲でスペクトルを求めなくてもグルコースに固有の吸収
波長を適切に選んで、レーザを光源として減光度を測定
することによりランベルト・ベールの法則によりグルコ
ースの定量が可能である。減光度Ａは試料への入射光の
パワーＰi と透過光の強度Ｐt を用いて、数１と表され
る。In principle, Lambert-Beer's method can be achieved by appropriately selecting an absorption wavelength specific to glucose without measuring a spectrum in a wide wavelength range and measuring the degree of extinction using a laser as a light source. Glucose can be quantified according to the law. The dimming degree A is expressed by Equation 1 using the power P i of the light incident on the sample and the intensity P t of the transmitted light.
【０００４】[0004]
【数１】 (Equation 1)
【０００５】減光度Ａと試料中の吸光物質濃度ｃとはラ
ンベルト・ベールの法則によって結びつけられる。実際
にはＰi とＰt を同時に測定することはできない。一般
的にはＰi を一定だと見なしてＰt だけを測定する。し
かし、近赤外の領域におけるグルコースの吸収は非常に
小さい。例えば、光路長１０mmのセルにグルコース水溶
液を入れてグルコースの近赤外における吸収ピーク波長
である１５８０ｎｍの光を照射してＰt を測定したと
き、Ｐi が完全に一定だとした時のグルコース濃度５０
mg／dlの変化に対応するＰt の変化はわずか０.２％ で
しかない。Ｐi そのものの揺らぎをこの０.２％ より十
分小さい値に押さえない限り、この変化を検出すること
はできない。そのように高度に光源を安定化することは
不可能ではないが難しい。より簡単な解決策として、光
源から射出された光の一部をビームスプリッタなどで二
つに分け、一方を試料に照射してその透過光（信号光）
を測定し、もう一方は参照光として直接に単にその強度
だけを測定して、信号光強度と参照光強度の比を取る構
成、いわゆる２光束の吸収測定系を使用することがよく
行われる。ビームスプリッタの反射光を参照光とし、光
電変換型の光センサを用い、参照光を検出した光センサ
の出力電流をＩ1 、信号光を検出した光センサの出力電
流をＩ2 とすれば、数２となり、Ｐiの変動は結果に現
れなくなる。[0005] The light attenuation A and the concentration c of the light absorbing substance in the sample are linked by the Lambert-Beer law. Actually, P i and P t cannot be measured simultaneously. In general, to measure only the P t considers that it is constant P i. However, the absorption of glucose in the near infrared region is very small. For example, when measuring P t and the cell having an optical path length of 10mm putting glucose aqueous solution was irradiated with light of 1580nm which is the absorption peak wavelength in the near infrared glucose, glucose when P i is that it is completely constant Concentration 50
change of P t corresponding to the change of mg / dl is only a slight 0.2%. Unless pressing the fluctuation of P i itself sufficiently smaller than the 0.2%, it is impossible to detect this change. It is difficult, if not impossible, to stabilize the light source to such a high degree. As a simpler solution, a part of the light emitted from the light source is divided into two parts by a beam splitter or the like, and one is irradiated on the sample and the transmitted light (signal light)
, And the other is directly measured only as the intensity of the reference light, and a ratio between the signal light intensity and the reference light intensity, that is, a so-called two-beam absorption measurement system is often used. Using the reflected light of the beam splitter as reference light, using a photoelectric conversion type optical sensor, and letting the output current of the optical sensor detecting the reference light be I 1 and the output current of the optical sensor detecting the signal light be I 2 , number 2, and the variation of P i would not appear in the result.
【０００６】[0006]
【数２】 (Equation 2)
【０００７】Ｒ，Ｔはそれぞれビームスプリッタの反射
率と透過率である。光学系の位置安定度がよければ、Ｒ
／Ｔの変動は０.０１％ 程度に押さえられるから、この
方法によれば減光度の０.１％ の相対的変化を検出する
ことも必ずしも困難ではない。[0007] R and T are the reflectivity and the transmissivity of the beam splitter, respectively. If the position stability of the optical system is good, R
Since the variation of / T is suppressed to about 0.01%, it is not always difficult to detect a relative change of 0.1% in the dimming degree by this method.
【０００８】しかし生体を無侵襲的に測定しようとする
ような場合、適当な測定部位に光源を設置することは現
実的でないことが多く、また、自由空間を伝搬する光線
を生命活動を維持する生体の一定の部位に長時間にわた
って安定に精度よく照射することは不可能に近い。その
ため、多くの場合、生体を無侵襲で測定する場合は、従
来技術のように光源から光ファイバを介して、光ファイ
バの出射側を生体に固定して生体に光を照射している。
光ファイバと光源のカップリングは不安定なので生体に
照射した光の強度を正確にモニタするにはファイバから
光が射出された後に、ビームスプリッタなどで光を分割
し、一方を試料を通さず参照光直接に計測することが望
ましい。しかし、光ファイバから射出される光の偏光面
はごくわずかなファイバのゆれなどで大きく変動し、ビ
ームスプリッタに代表される分波素子は反射率・透過率
が偏光面に依存する。したがって偏光面が揺らぐと参照
光と照射光の強度比が変化してしまい、照射光強度の正
確なモニタができなくなってしまう。However, in a case where a living body is to be measured non-invasively, it is often not practical to install a light source at an appropriate measurement site, and light beams propagating in free space are maintained in vital activity. It is almost impossible to stably and accurately irradiate a fixed part of a living body for a long time. Therefore, in many cases, when measuring a living body non-invasively, light is radiated to the living body with the emission side of the optical fiber fixed to the living body via an optical fiber from a light source as in the related art.
Since the coupling between the optical fiber and the light source is unstable, to accurately monitor the intensity of the light irradiated on the living body, after the light is emitted from the fiber, the light is split by a beam splitter or the like, and one of them is referenced without passing through the sample It is desirable to measure light directly. However, the plane of polarization of the light emitted from the optical fiber fluctuates greatly due to a slight fluctuation of the fiber, and the reflectivity and transmittance of the demultiplexing element represented by the beam splitter depend on the plane of polarization. Therefore, when the polarization plane fluctuates, the intensity ratio between the reference light and the irradiation light changes, and it becomes impossible to accurately monitor the irradiation light intensity.
【０００９】従来技術では波長１.１μｍから１.８μｍ
の範囲における近赤外拡散反射スペクトルを測定したう
えで多変量解析を利用している。照射光強度や偏光面が
変動するよりも速く多波長の減光度スペクトルを測定す
れば照射光強度の変動等はスペクトルにおけるベースラ
イン変動の形で現れ、グルコース濃度変化による減光度
スペクトルの変化とは異なるため、グルコース濃度変動
に関する情報をスペクトル形から抽出することができ
る。しかしこのように波長一点における測定精度が不十
分であると、多くの波長における測定という代償が必要
であるばかりか、たまたま波長走査中にファイバや光源
の変動などが生じた場合、誤った測定結果を生む。In the prior art, the wavelength is 1.1 μm to 1.8 μm.
After measuring the near-infrared diffuse reflectance spectrum in the range, the multivariate analysis is used. If a multi-wavelength extinction spectrum is measured faster than the irradiating light intensity or polarization plane fluctuates, the irradiating light intensity fluctuations etc. will appear in the form of baseline fluctuations in the spectrum. Due to the difference, information on the glucose concentration fluctuation can be extracted from the spectral form. However, if the measurement accuracy at a single wavelength is insufficient as described above, the cost of measurement at many wavelengths is not only compensated, but if the fiber or light source fluctuates during wavelength scanning, an erroneous measurement result may occur. Spawn.
【００１０】本発明は光ファイバを利用した減光度測定
において、減光度の測定を高精度化し、より少ない波長
で高精度かつ信頼性が高い血中グルコース等の生体中に
おける吸光物質濃度の測定ができ、なおかつ小型化・軽
量化・低価格化が可能な無侵襲生化学計測装置を提供す
ることを目的とする。[0010] The present invention provides a method for measuring the density of a light-absorbing substance in a living body, such as blood glucose, which is highly accurate and highly reliable with a smaller wavelength in the dimming degree measurement using an optical fiber. It is an object of the present invention to provide a non-invasive biochemical measurement device which can be manufactured, and which can be reduced in size, weight and cost.
【００１１】[0011]
【課題を解決するための手段】光ファイバから射出され
た光を偏光板を通したうえでビームスプリッタで２分割
し、一方を参照光として第一の光センサで検出し、他方
を試料に照射してその透過光を第二の光センサで検出
し、第一と第二の光センサの出力の比を取る。The light emitted from the optical fiber passes through a polarizing plate and is split into two by a beam splitter, one of which is detected as reference light by a first optical sensor, and the other is irradiated on a sample. Then, the transmitted light is detected by the second optical sensor, and the ratio between the outputs of the first and second optical sensors is calculated.
【００１２】[0012]
【発明の実施の形態】本発明の第一の実施例のブロック
図を図１に示す。図１で、１は電源、２は光源、３は光
ファイバ、４はレンズ、５は波長板、６は偏光板、７は
ビームスプリッタ、８は試料、９，１０は光センサ、１
１，１２は電流計、１３はコンピュータ、１４は温度セ
ンサ、１５は電子クーラ、１６は温度制御装置である。
本実施例では水溶液試料中のグルコース濃度の測定が目
的であり、光源２として近赤外におけるグルコースの吸
収ピークの一つである波長１５８０ｎｍの準単色光を出
力する光通信用半導体レーザを電源１で駆動して使用し
た。FIG. 1 is a block diagram showing a first embodiment of the present invention. In FIG. 1, 1 is a power supply, 2 is a light source, 3 is an optical fiber, 4 is a lens, 5 is a wave plate, 6 is a polarizing plate, 7 is a beam splitter, 8 is a sample, 9 and 10 are optical sensors, 1
Reference numerals 1 and 12 denote an ammeter, 13 denotes a computer, 14 denotes a temperature sensor, 15 denotes an electronic cooler, and 16 denotes a temperature control device.
The purpose of the present embodiment is to measure the glucose concentration in the aqueous solution sample, and a light source 2 is connected to a semiconductor laser for optical communication that outputs quasi-monochromatic light having a wavelength of 1580 nm, which is one of the absorption peaks of glucose in the near infrared. Driven and used.
【００１３】光源２を出た光は光ファイバ３に直接導入
され、レンズ４で空間中を伝搬する並行光束に変換さ
れ、１／２波長板５と偏光板６を透過させて偏光面を一
定にしたうえでビームスプリッタ７で反射光と透過光に
分割される。測定を開始するときは波長板５によって反
射光が最大となるように偏光面を設定する。反射光は直
接第一の光センサ９で検出され、透過光は試料８に照射
され、その透過光が第二の光センサ９で検出される。光
センサ９，１０は波長１５８０ｎｍで分光感度０.９４
Ａ／Ｗ のInGaAsフォトダイオードである。温度センサ
１４は試料の温度を図るためのサーミスタで、１５〜４
０度の範囲で１０ｍＫ刻みで抵抗−温度特性の校正がさ
れている。温度制御装置１６は温度センサ１４の出力を
もとに電子クーラ１５に適当な電流を流し、試料８の温
度を２５±０.０２℃ に制御している。光センサ８，９
の出力電流はそれぞれ電流計１１，１２で測定され、コ
ンピュータ１３は電流計１１，１２の測定値を取り込ん
で、光センサ９の出力電流と光センサ１０の出力電流の
比log(Ｉ1／Ｉ2）を測定する。The light emitted from the light source 2 is directly introduced into the optical fiber 3, converted into a parallel light beam propagating in space by the lens 4, and transmitted through the half-wave plate 5 and the polarizing plate 6 to keep the polarization plane constant. Then, the light is split by the beam splitter 7 into reflected light and transmitted light. When the measurement is started, the polarization plane is set so that the light reflected by the wave plate 5 is maximized. The reflected light is directly detected by the first optical sensor 9, the transmitted light is applied to the sample 8, and the transmitted light is detected by the second optical sensor 9. The optical sensors 9 and 10 have a wavelength of 1580 nm and a spectral sensitivity of 0.94.
A / W InGaAs photodiode. The temperature sensor 14 is a thermistor for measuring the temperature of the sample.
The resistance-temperature characteristics are calibrated at intervals of 10 mK in the range of 0 degrees. The temperature controller 16 controls the temperature of the sample 8 to 25 ± 0.02 ° C. by supplying an appropriate current to the electronic cooler 15 based on the output of the temperature sensor 14. Optical sensors 8, 9
Is measured by the ammeters 11 and 12, respectively. The computer 13 takes in the measured values of the ammeters 11 and 12, and outputs the ratio log (I 1 / I) of the output current of the optical sensor 9 and the output current of the optical sensor 10. 2 ) Measure.
【００１４】本実施例では血中グルコース濃度の無侵襲
測定を目的としたためグルコースの吸収波長である１５
８０ｎｍの光源を使用したが、他の成分、例えば、アル
ブミンや尿素、コレステロール等の濃度を測定しようと
する場合はそれぞれに固有の近赤外における吸収波長の
光を用いればよい。光源はレーザと限らず、ハロゲンラ
ンプ等の白色光源を干渉計や回折格子で分光して用いれ
ば、たやすく多波長測定を構成することができる。もし
波長１μｍ以下の近赤外光を使用する場合には光センサ
としてシリコンフォトダイオードを用いれば実施例と同
様に小型かつ安価かつ高感度な測定系を構成することが
できる。In this embodiment, since the purpose is to measure blood glucose concentration noninvasively, the absorption wavelength of glucose is 15
Although a light source of 80 nm is used, when it is intended to measure the concentration of other components, for example, albumin, urea, cholesterol, etc., light having a specific absorption wavelength in the near infrared may be used. The light source is not limited to a laser, but if a white light source such as a halogen lamp is spectrally used by an interferometer or a diffraction grating, multi-wavelength measurement can be easily configured. If near-infrared light having a wavelength of 1 μm or less is used, a small, inexpensive, and highly sensitive measurement system can be constructed as in the embodiment by using a silicon photodiode as an optical sensor.
【００１５】偏光板６の消光比は完全ではないから、偏
光板６に入射する光の偏光面が変動すると透過光の偏光
面も入射光の変動の数％程度は変動してしまう。わずか
な変動であっても、ビームスプリッタの（反射率／透過
率）の変動を０.０１％ に押さえようとする場合には無
視できない。しかし、偏光板の偏光方向を透過光線と反
射光線で張られる平面に対して適当な角度にしておけば
偏光方向の変動が１次の微少量である時に（反射率／透
過率）の変動を２次の微少量にすることができる。Since the extinction ratio of the polarizing plate 6 is not perfect, if the plane of polarization of the light incident on the polarizing plate 6 fluctuates, the plane of polarization of the transmitted light also fluctuates by about several percent of the fluctuation of the incident light. Even a slight change cannot be ignored when trying to suppress the change in (reflectance / transmittance) of the beam splitter to 0.01%. However, if the polarization direction of the polarizing plate is set to an appropriate angle with respect to the plane stretched by the transmitted light and the reflected light, the change in (reflectance / transmittance) can be reduced when the change in the polarization direction is very small in the first order. It can be reduced to a second minute amount.
【００１６】図２に透過光線と反射光線で張られる平面
に対する偏光面の角度とビームスプリッタの（反射率／
透過率）の関係を示す。この曲線は９０度と１８０度で
極大，極小となるので、もともとの角度を９０度、ある
いは１８０度にしておけばわずかな偏光面の変動に対す
る（反射率／透過率）の変動は２次の微少量となり、無
視できるようになる。本実施例では偏光板６を、透過光
の偏光面が透過光線と反射光線で張られる平面に対して
直角になるように設置したが、平行になるようにしても
明らかに同等の効果を得ることができる。なお、本実施
例ではビームスプリッタ７の反射光を参照光としたが、
逆に透過光を参照光として反射光を試料８に照射してそ
の透過光を測定しても同一の効果が得られることは同様
である。FIG. 2 shows the angle of the plane of polarization relative to the plane spanned by the transmitted and reflected rays and the (reflectance /
(Transmittance). Since this curve becomes maximum and minimum at 90 degrees and 180 degrees, if the original angle is set to 90 degrees or 180 degrees, a change in (reflectance / transmittance) with respect to a slight change in the polarization plane is quadratic. It is very small and can be ignored. In this embodiment, the polarizing plate 6 is installed such that the plane of polarization of the transmitted light is perpendicular to the plane spanned by the transmitted light and the reflected light. be able to. In this embodiment, the reflected light from the beam splitter 7 is used as the reference light.
Conversely, the same effect can be obtained by irradiating the sample 8 with reflected light using transmitted light as reference light and measuring the transmitted light.
【００１７】本実施例における偏光板の効果を調べるた
め、空気を試料として行ったlog （Ｉ1／Ｉ2）の測定の
結果を図３と図４に示す。空気の吸収は無視できるの
で、この測定は装置そのものの安定度，精度を示す。図
３は偏光板６を取り外して行った測定の結果であり、フ
ァイバ３のわずかなゆれによって偏光面が変動し、（反
射率／透過率）が変動したため、log(Ｉ1／Ｉ2）の値が
大きく変動している。図４は元通り偏光板６を取り付け
て行った測定の結果である。図３に示した測定のときと
同様に光ファイバ３にゆれを加わえたにもかかわらず、
log（Ｉ1／Ｉ2）の値はほとんど変動していない。平均
値に対する標準偏差は０.０５％であり、グルコース５
０mg／dlの変化を検出可能な精度が本実施例によって達
成されている。FIGS. 3 and 4 show the results of the log (I 1 / I 2 ) measurement using air as a sample to examine the effect of the polarizing plate in this embodiment. Since air absorption is negligible, this measurement indicates the stability and accuracy of the device itself. FIG. 3 shows the result of measurement performed with the polarizing plate 6 removed. The polarization plane fluctuated due to slight fluctuation of the fiber 3 and (reflectance / transmittance) fluctuated, so that log (I 1 / I 2 ) The value fluctuates greatly. FIG. 4 shows the result of the measurement performed with the polarizing plate 6 attached. Although the optical fiber 3 was shaken similarly to the case of the measurement shown in FIG.
The value of log (I 1 / I 2 ) hardly fluctuates. The standard deviation from the mean is 0.05% and glucose 5
The accuracy with which a change of 0 mg / dl can be detected is achieved by this embodiment.
【００１８】既知濃度のグルコース水溶液を試料として
本実施例によるlog(Ｉ1／Ｉ2）の測定を行った結果を図
５に示す。log(Ｉ1／Ｉ2）とグルコース濃度ｃ（mg／d
l）は次の数３のような直線的関係を持つことがわかっ
た。FIG. 5 shows the result of measurement of log (I 1 / I 2 ) according to the present embodiment using a glucose aqueous solution having a known concentration as a sample. log (I 1 / I 2 ) and glucose concentration c (mg / d
l) was found to have a linear relationship as shown in the following Equation 3.
【００１９】[0019]
【数３】 (Equation 3)
【００２０】図５における回帰直線をlog(Ｉ1／Ｉ2）の
値からグルコース濃度を定量する検量線とした場合、濃
度０mg／dlの試料（純水）の繰り返し測定から求めたグ
ルコースの検出限界は３４mg／dlとなった。When the regression line in FIG. 5 is a calibration curve for quantifying the glucose concentration from the value of log (I 1 / I 2 ), the detection of glucose obtained from repeated measurement of a sample (pure water) having a concentration of 0 mg / dl. The limit was 34 mg / dl.
【００２１】本発明の第二の実施例のブロック図を図６
に示す。本実施例では基本的には第一の実施例と同一の
構成を用いるが、本実施例では生体２２中のグルコース
濃度の測定が目的であり、光源の電源１に交流電流源を
用いて一定周波数１ｋＨｚで出力光を変調している。ま
た、ファイバ中を伝搬する光に対して偏光面制御をする
ため光ファイバに応力を与えて偏光面を変化させる偏光
面制御装置２１を使用した。FIG. 6 is a block diagram showing a second embodiment of the present invention.
Shown in In this embodiment, basically the same configuration as that of the first embodiment is used. However, in this embodiment, the purpose is to measure the glucose concentration in the living body 22, and the constant is obtained by using an AC current source as the power source 1 of the light source. The output light is modulated at a frequency of 1 kHz. Further, in order to control the plane of polarization of the light propagating in the fiber, a polarization plane controller 21 for applying a stress to the optical fiber to change the plane of polarization was used.
【００２２】第一の実施例と同様に、測定を開始すると
きは偏光面制御装置２１によって反射光が最大となるよ
うに偏光面を設定し、反射光は直接第一の光センサ９で
検出され、透過光は生体２２に照射され、その透過光が
第二の光センサ１０で検出される。ここでは生体２２を
ヒトの耳朶とした。温度センサ１４は耳朶の温度を図る
ためのサーミスタで、３５〜４０度の範囲で１０ｍＫ刻
みで抵抗−温度特性の校正がされている。レンズ４，偏
光板６，ビームスプリッタ７，光センサ９は筺体２０に
固定され、筺体２０は板２３に接続されている。As in the first embodiment, when the measurement is started, the polarization plane is set by the polarization plane controller 21 so that the reflected light is maximized, and the reflected light is directly detected by the first optical sensor 9. Then, the transmitted light is applied to the living body 22, and the transmitted light is detected by the second optical sensor 10. Here, the living body 22 was a human earlobe. The temperature sensor 14 is a thermistor for measuring the temperature of the earlobe, and the resistance-temperature characteristics are calibrated at intervals of 10 mK in a range of 35 to 40 degrees. The lens 4, the polarizing plate 6, the beam splitter 7, and the optical sensor 9 are fixed to a housing 20, and the housing 20 is connected to a plate 23.
【００２３】光センサ１０と温度センサ１４は板２４に
固定されている。板２３と板２４で生体２２を挟んで固
定し、生体２２に対する相対的位置関係の一定性を確保
する。光センサ９，１０の出力と温度センサ１４の出力
はそれぞれ電線２５，２６，２７を介して筺体３２内の
装置に伝達される。電線２５，２６，２７は光ファイバ
３とともに被覆２８によって１本のケーブル束に束ねら
れている。光センサ９，１０の出力電流はそれぞれ電流
増幅器１７，１８で電圧信号に変換される。電流増幅器
１７と１８の変換ゲインはそれぞれ、Ｇ１，Ｇ２であ
る。The optical sensor 10 and the temperature sensor 14 are fixed to a plate 24. The living body 22 is sandwiched and fixed between the plate 23 and the plate 24, and the relative positional relationship with the living body 22 is kept constant. The outputs of the optical sensors 9 and 10 and the output of the temperature sensor 14 are transmitted to devices in the housing 32 via electric wires 25, 26 and 27, respectively. The electric wires 25, 26, and 27 are bundled together with the optical fiber 3 by a coating 28 into one cable bundle. Output currents of the optical sensors 9 and 10 are converted into voltage signals by current amplifiers 17 and 18, respectively. The conversion gains of the current amplifiers 17 and 18 are G1 and G2, respectively.
【００２４】電流増幅器１７の出力はロックインアンプ
１９の参照入力に、電流増幅器１８の出力信号は信号入
力にそれぞれ入力され、電流増幅器１７の出力の振幅と
電流増幅器１８の出力の振幅との比を測定する。この比
はlog(Ｉ1／Ｉ2）＋log(Ｇ１／Ｇ２）に等しい。Ｇ１，
Ｇ２は既知であるから、測定値からlog(Ｇ１／Ｇ２）を
引けば、log(Ｉ1／Ｉ2）の値が求められる。温度センサ
であるサーミスタ１４の抵抗は抵抗計２９で測定され
る。信号処理装置３０はロックインアンプから比の値を
読みとってlog(Ｉ1／Ｉ2）を求め、抵抗計２９からサー
ミスタの抵抗を読みとってメモリ上に記憶された抵抗−
温度校正表に従って生体２２の温度Ｔ(℃)を求め、これ
らの測定値とあらかじめ記録された式に基づいて生体２
２中の血中グルコース濃度を計算し、計算結果を表示パ
ネル３１に送る。電源１，光源２，偏光面制御装置２
１，電流増幅器１７，１８，ロックインアンプ１９，抵
抗計２９，信号処理装置３０，表示パネル３１は筺体３
２に一体化されている。The output of the current amplifier 17 is input to the reference input of the lock-in amplifier 19, and the output signal of the current amplifier 18 is input to the signal input, and the ratio of the amplitude of the output of the current amplifier 17 to the amplitude of the output of the current amplifier 18 is obtained. Is measured. This ratio is equal to log (I 1 / I 2) + log (G1 / G2). G1,
Since G2 is known, by pulling the log (G1 / G2) from the measured value, the value of log (I 1 / I 2) is obtained. The resistance of the thermistor 14, which is a temperature sensor, is measured by a resistance meter 29. The signal processing device 30 reads the value of the ratio from the lock-in amplifier to obtain log (I 1 / I 2 ), reads the resistance of the thermistor from the ohmmeter 29, and reads the resistance −
The temperature T (° C.) of the living body 22 is determined according to the temperature calibration table, and the living body 2 is determined based on these measured values and a previously recorded equation.
The blood glucose concentration in 2 is calculated, and the calculation result is sent to the display panel 31. Power supply 1, light source 2, polarization plane controller 2
1, current amplifiers 17, 18, lock-in amplifier 19, resistance meter 29, signal processing device 30, display panel 31
2 are integrated.
【００２５】図７は本実施例の耳朶装着部分を耳朶の持
ち主の斜前方から見た図であり、図８は正面から見た図
である。また図９は耳朶装着部分を図２の耳朶の持ち主
の背面から見た場合の図である。３３，３４，３５はス
ペーサ、３６，３７，３８はばねである。板２３と２４
で耳朶を挟み、板同士が並行かつ間隔を一定に保つ機構
として３本のスペーサ３３，３４，３５と３本のばね３
６，３７，３８を使用する。スペーサ３６，３７，３８
は細目のねじが切られており、板２３に開けられたねじ
穴を利用して２３と２４の間隔を調製することが可能に
なっている。測定対象者の耳朶の厚さをあらかじめノギ
ス，マイクロメータ等で測定しておき、ねじが切られた
スペーサ３３，３４，３５の板２４から飛び出た部分の
長さを耳朶の厚さよりもやや小さい同一の値に調整して
おいたうえで、板２３と２４で耳朶を挟む。ばね３６，
３７，３８によって耳朶を押し付けるように板２３と２
４が引っ張られ、耳朶がスペーサの飛び出た長さまで縮
んだところでスペーサによって板が押さえられ、固定さ
れる。本実施例では測定対象者の耳朶の厚さが4.1mmで
あったため、スペーサで固定する板と板の間隔を３.９m
mに調整した。FIG. 7 is a view of the earlobe mounting portion of the present embodiment viewed obliquely from the front of the owner of the earlobe, and FIG. 8 is a view viewed from the front. FIG. 9 is a view when the earlobe-mounted portion is viewed from the back of the owner of the earlobe in FIG. 33, 34 and 35 are spacers, and 36, 37 and 38 are springs. Plates 23 and 24
The three spacers 33, 34, 35 and the three springs 3 serve as a mechanism for sandwiching the earlobe and keeping the boards parallel and at a constant interval.
6, 37, 38 are used. Spacers 36, 37, 38
Is threaded finely, and it is possible to adjust the distance between 23 and 24 using a screw hole formed in the plate 23. The thickness of the earlobe of the measurement subject is measured in advance with a caliper, a micrometer, or the like, and the length of the threaded spacers 33, 34, and 35 protruding from the plate 24 is slightly smaller than the thickness of the earlobe. After adjusting to the same value, the earlobe is sandwiched between the plates 23 and 24. Spring 36,
Plates 23 and 2 so that the earlobe is pressed by 37 and 38
When the earlobe 4 is pulled and the earlobe shrinks to the length where the spacer has protruded, the plate is pressed and fixed by the spacer. In this example, the thickness of the earlobe of the person to be measured was 4.1 mm, so the distance between the plates fixed by the spacers was 3.9 m.
Adjusted to m.
【００２６】特定の生体を対象として本実施例によるlo
g(Ｉ1／Ｉ2）、生体温度Ｔの測定と採血を伴う従来法に
よる血中グルコース濃度ｃ（mg／dl）の測定を多数回行
い、log(Ｉ1／Ｉ2）、生体温度Ｔを説明変数、ｃを目的
変数とする線形重回帰分析を行った結果、数４が得られ
た。According to the present embodiment, the lo
g (I 1 / I 2 ), the measurement of the living body temperature T and the measurement of the blood glucose concentration c (mg / dl) by the conventional method involving blood sampling were performed many times, and the log (I 1 / I 2 ) and the living body temperature T were measured. Was used as an explanatory variable, and linear multiple regression analysis was performed using c as an objective variable, and as a result, Equation 4 was obtained.
【００２７】[0027]
【数４】 (Equation 4)
【００２８】図１０に健常者を対象として糖負荷試験を
行った時の、数４を用いた本実施例による血糖値の連続
モニタリングの結果を示す。実線は本実施例による無侵
襲モニタリングの結果、白抜きの丸は１０分おきに採血
して従来法で測定した結果である。従来法によって測定
された血中グルコース濃度と本実施例による測定結果か
ら数４によって計算されたグルコース濃度との間では相
関係数が０.９３６０という非常に高い相関が得られて
いる。FIG. 10 shows the results of continuous monitoring of the blood glucose level according to the present embodiment using Equation 4 when a glucose tolerance test was performed on healthy subjects. The solid line is the result of non-invasive monitoring according to this example, and the white circle is the result of blood collection every 10 minutes and measurement by the conventional method. A very high correlation with a correlation coefficient of 0.9360 is obtained between the blood glucose concentration measured by the conventional method and the glucose concentration calculated by Expression 4 from the measurement result according to the present embodiment.
【００２９】また、第一の実施例では光検出を直流で行
っていたため、暗室中で測定を行う必要があった。本実
施例では光源を変調してロックイン検出をしているた
め、太陽の光や室内照明の影響がなくなり、通常の環境
下で測定が可能となっている。無侵襲であるため人目を
はばかる必要もなく、測定者は衆人環境での血中グルコ
ース濃度の自己測定が容易にできる。Further, in the first embodiment, since the light was detected by DC, the measurement had to be performed in a dark room. In this embodiment, the lock-in detection is performed by modulating the light source, so that there is no influence of the sun light or the indoor lighting, and the measurement can be performed in a normal environment. Since it is non-invasive, it does not need to be noticed, and the measurer can easily self-measure blood glucose concentration in a public environment.
【００３０】[0030]
【発明の効果】本発明によれば光源から光を照射する試
料まで光ファイバによって光を導いて試料による光の吸
収を測定する装置で、従来よりも一桁以上高精度化し、
減光度にして０.００１ 以下の変化を検出可能とし、そ
の結果血中グルコース濃度の５０mg／dlの変化の検出を
達成した。According to the present invention, there is provided an apparatus for measuring light absorption by a sample by guiding light from a light source to a sample to be irradiated with light by an optical fiber.
A change of 0.001 or less in terms of extinction can be detected, and as a result, a change in blood glucose concentration of 50 mg / dl can be detected.
【図１】本発明の第一の実施例の装置構成を示すブロッ
ク図。FIG. 1 is a block diagram showing an apparatus configuration of a first embodiment of the present invention.
【図２】本発明の実施例で使用したビームスプリッタの
（反射率／透過率）の値の偏光面角度に対する依存性を
示す特性図。FIG. 2 is a characteristic diagram showing the dependence of the (reflectance / transmittance) value of the beam splitter used in the embodiment of the present invention on the polarization plane angle.
【図３】本発明の第一の実施例で試料，偏光板を取り除
いた状態で行ったlog（Ｉ1／Ｉ2 ）の測定の結果を示す
特性図。FIG. 3 is a characteristic diagram showing a result of measurement of log (I 1 / I 2 ) performed in a state where a sample and a polarizing plate are removed in the first embodiment of the present invention.
【図４】本発明の第一の実施例で試料だけを取り除いた
状態で行ったlog（Ｉ1／Ｉ2 ）の測定の結果を示す特性
図。FIG. 4 is a characteristic diagram showing a result of measurement of log (I 1 / I 2 ) performed in a state where only a sample is removed in the first embodiment of the present invention.
【図５】本発明の第一の実施例によるグルコース水溶液
の測定の結果の特性図。FIG. 5 is a characteristic diagram of a result of measurement of an aqueous glucose solution according to the first embodiment of the present invention.
【図６】本発明の第二の実施例の装置構成を示すブロッ
ク図。FIG. 6 is a block diagram illustrating a device configuration according to a second embodiment of the present invention.
【図７】本発明の第二の実施例の生体装着部の斜視図。FIG. 7 is a perspective view of a living body mounting portion according to a second embodiment of the present invention.
【図８】本発明の第二の実施例における耳朶装着部の正
面図。FIG. 8 is a front view of an earlobe mounting portion according to a second embodiment of the present invention.
【図９】本発明の第二の実施例における耳朶装着部の背
面図。FIG. 9 is a rear view of the earlobe mounting portion according to the second embodiment of the present invention.
【図１０】本発明の第二の実施例による血糖値の連続モ
ニタリングの特性図。FIG. 10 is a characteristic diagram of continuous monitoring of blood glucose level according to the second embodiment of the present invention.
１…電源、２…光源、３…光ファイバ、４…レンズ、５
…波長板、６…偏光板、７…ビームスプリッタ、８…試
料、９、１０…光センサ、１１，１２…電流計、１３…
コンピュータ、１４…温度センサ、１５…電子クーラ、
１６…温度制御装置。DESCRIPTION OF SYMBOLS 1 ... Power supply 2 ... Light source 3 ... Optical fiber 4 ... Lens 5
... Wavelength plate, 6 ... Polarizing plate, 7 ... Beam splitter, 8 ... Sample, 9, 10 ... Optical sensor, 11, 12 ... Ammeter, 13 ...
Computer, 14 temperature sensor, 15 electronic cooler,
16 ... temperature control device.
Claims (7)
記試料を透過した光を検出して上記試料の減光度を求
め、上記試料中の吸光物質濃度を計測する装置におい
て、少なくとも一個の光ファイバと、上記光ファイバか
ら射出された光を透過させる偏光子と、上記偏光子を透
過した光を２光束に分波する手段と、上記２光束の一方
を上記試料に照射する手段と、上記２光束の他の一方を
検出する光センサと、上記試料を透過した光を検出する
光センサを有することを特徴とする生化学計測装置。An apparatus for irradiating a sample with light emitted from a light source, detecting light transmitted through the sample, determining the degree of extinction of the sample, and measuring the concentration of a light-absorbing substance in the sample. An optical fiber, a polarizer that transmits light emitted from the optical fiber, a unit that splits the light transmitted through the polarizer into two light beams, and a unit that irradiates one of the two light beams to the sample. A biochemical measurement device, comprising: an optical sensor for detecting the other of the two light beams; and an optical sensor for detecting light transmitted through the sample.
記生体を透過，拡散した光を検出して上記生体の減光度
を求め、上記生体中の吸光物質濃度を計測する装置にお
いて、少なくとも一個の上記光源の光を導入する光ファ
イバと、上記光ファイバを伝搬した光を自由空間中の単
一光束に成形して射出するレンズと、上記光ファイバか
ら射出された上記光束の偏光面を制御する手段と、上記
光束を透過させる偏光子と、上記偏光子を透過した光束
を２光束に分波するビームスプリッタと、上記２光束の
一方を上記生体に照射する手段と、上記２光束の他の一
方を直接検出する光センサと、上記生体を透過，拡散し
た光を検出する光センサとを有することを特徴とする生
化学計測装置。2. An apparatus for irradiating a living body with light radiated from a light source, detecting light transmitted and diffused through the living body, obtaining the degree of extinction of the living body, and measuring the concentration of a light absorbing substance in the living body. An optical fiber for introducing the light of at least one of the light sources, a lens for shaping the light propagated through the optical fiber into a single light beam in free space and emitting the same, and a polarization plane of the light beam emitted from the optical fiber , A polarizer that transmits the light beam, a beam splitter that splits the light beam transmitted through the polarizer into two light beams, a unit that irradiates one of the two light beams to the living body, and the two light beams A biochemical measurement device comprising: an optical sensor for directly detecting the other one; and an optical sensor for detecting light transmitted and diffused through the living body.
料を透過，拡散した光を検出して上記生体の減光度を求
め、上記生体中の吸光物質濃度を計測する装置におい
て、少なくとも一個の上記光源の光を導入する光ファイ
バと、上記光ファイバを伝搬した光を自由空間中の単一
光束に成形して射出するレンズと、上記光ファイバから
射出された上記光束の偏光面を制御する手段と、上記光
束を透過させる偏光子と、上記偏光子を透過した光束を
透過光と反射光の２光束に分波するビームスプリッタ
と、上記２光束の一方を上記生体に照射する手段と、上
記生体を透過，拡散した光を検出する第一の光センサ
と、上記２光束のもう一方を直接検出する第二の光セン
サと、上記レンズと上記偏光子と上記ビームスプリッタ
と、上記生体の温度を測定する温度センサと、上記光セ
ンサと上記試料の相対的な空間的的配置を固定する手段
を有し、上記偏光子の透過光の偏光ベクトルの向きが上
記偏光ビームスプリッタの透過光と反射光の両方に対し
て垂直であるかまたは偏光面が上記偏光ビームスプリッ
タの透過光と反射光で張られる平面上にあるように上記
偏光子を設置し、上記第一の光検出器の出力電流と上記
第二の光センサの出力電流の比の対数と上記温度センサ
で測定された上記生体の温度の一次式から上記生体中の
吸光物質濃度を求めることを特徴とする生化学計測装
置。3. An apparatus for irradiating a living body with light radiated from a light source, detecting light transmitted and diffused through a sample to obtain the degree of extinction of the living body, and measuring the concentration of a light-absorbing substance in the living body. An optical fiber for introducing the light of the one light source, a lens for shaping the light propagated through the optical fiber into a single light beam in free space and emitting the same, and a polarization plane of the light beam emitted from the optical fiber. Controlling means, a polarizer for transmitting the light beam, a beam splitter for splitting the light beam transmitted through the polarizer into two light beams of transmitted light and reflected light, and means for irradiating the living body with one of the two light beams A first optical sensor for detecting light transmitted and diffused through the living body, a second optical sensor for directly detecting the other of the two light beams, the lens, the polarizer, the beam splitter, Measuring temperature of living body Temperature sensor, and means for fixing the relative spatial arrangement of the optical sensor and the sample, the direction of the polarization vector of the transmitted light of the polarizer is the direction of the transmitted light and reflected light of the polarizing beam splitter. Place the polarizer so that it is perpendicular to both or the plane of polarization is on the plane spanned by the transmitted and reflected light of the polarizing beam splitter, the output current of the first photodetector and the A biochemical measurement apparatus, wherein a concentration of a light-absorbing substance in a living body is obtained from a logarithm of a ratio of an output current of a second optical sensor and a linear expression of a temperature of the living body measured by the temperature sensor.
７００ｎｍから波長２５００ｎｍの近赤外光を出力する
光源を用いる生化学計測装置。4. A biochemical measurement apparatus using the light source according to claim 1, 2 or 3 for outputting near-infrared light having a wavelength of 700 nm to 2500 nm.
少なくとも一つに波長１０００ｎｍから波長１８００ｎ
ｍの、好ましくは波長１５５０ｎｍから１７５０ｎｍの
近赤外光を出力する半導体レーザまたは発光ダイオード
を用い、光センサの少なくとも一つにゲルマニウムフォ
トダイオードまたはインジウム・ガリウム・砒素フォト
ダイオードを用いる生化学計測装置。5. A light source according to claim 1, 2 or 3, wherein at least one of said light sources has a wavelength of 1000 nm to 1800 n.
A biochemical measurement device using a semiconductor laser or a light emitting diode that outputs near infrared light having a wavelength of 1550 nm to 1750 nm, and using a germanium photodiode or an indium gallium arsenide photodiode for at least one of the optical sensors.
タで分波された光の一方を上記生体の耳朶の一方の側に
照射し、上記耳朶の光を照射した面の反対側の表面上に
あるいはごく表面近傍に光センサを設ける生化学計測装
置。6. One of the lights split by the beam splitter according to claim 2 or 3 is applied to one side of the earlobe of the living body, and the light is applied to a surface of the earlobe opposite to the light-irradiated surface. A biochemical measurement device that has an optical sensor at or very near the surface.
リッタで分波された光の一方を前記生体の耳朶の一方の
側に照射し、上記耳朶の光を照射した面の反対側の表面
に密着あるいはごく表面近傍に光センサを設け、上記耳
朶を挟む２枚の板と、板のどちらか一つにだけ固定され
た、２枚の板についてあわせて少なくとも三つのスペー
サと、上記スペーサの長さを調節する手段と上記２枚の
板を結ぶ複数本のばね機構を備え、上記光ファイバと上
記光検出器を上記板に固定する生化学計測装置。7. One of the lights split by the beam splitter according to claim 2 or 3 is applied to one side of the earlobe of the living body, and a surface of the earlobe opposite to the surface to which the light is applied. An optical sensor is provided in close contact with or very near the surface, and two plates sandwiching the earlobe, at least three spacers for the two plates fixed to only one of the plates, A biochemical measurement device comprising: a length adjusting means; and a plurality of spring mechanisms connecting the two plates, and fixing the optical fiber and the photodetector to the plate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8264057A JPH10108857A (en) | 1996-10-04 | 1996-10-04 | Biochemical measuring device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8264057A JPH10108857A (en) | 1996-10-04 | 1996-10-04 | Biochemical measuring device |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH10108857A true JPH10108857A (en) | 1998-04-28 |
Family
ID=17397947
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8264057A Pending JPH10108857A (en) | 1996-10-04 | 1996-10-04 | Biochemical measuring device |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH10108857A (en) |
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- 1996-10-04 JP JP8264057A patent/JPH10108857A/en active Pending
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