JP2641575B2 - Glucose non-invasive measuring device - Google Patents
Glucose non-invasive measuring deviceInfo
- Publication number
- JP2641575B2 JP2641575B2 JP1313620A JP31362089A JP2641575B2 JP 2641575 B2 JP2641575 B2 JP 2641575B2 JP 1313620 A JP1313620 A JP 1313620A JP 31362089 A JP31362089 A JP 31362089A JP 2641575 B2 JP2641575 B2 JP 2641575B2
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- Prior art keywords
- glucose
- wavelength band
- blood
- light
- absorption
- Prior art date
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Description
【発明の詳細な説明】 産業上の利用分野 本発明は、グルコース（血糖値）の無侵襲的測定方法
に関する。Description: TECHNICAL FIELD The present invention relates to a non-invasive method for measuring glucose (blood glucose level).
従来の技術 人間の血液は次の表に示すような成分からなる。2. Description of the Related Art Human blood consists of components as shown in the following table.
血糖は血しょうおよび有形成分（赤血球，白血球，血
小板等）の水分中に一様に分布している。血液中の遊離
糖としてはグルコースの比率が極めて高くグルコースに
焦点を合わせて分析すれば他の糖はほとんど検出されな
い。グルコース（血糖値）の正常値は75〜110mg/d1とさ
れており、糖尿病の検査法の一つである負荷試験ではぶ
どう糖を経口投与し血液中のグルコース濃度の時間変動
を測定している。第８図に負荷試験の際の血液中のグル
コース濃度の時間変動の例を示す。ａは正常者、ｂは耐
糖能障害者、ｃは耐尿病患者の場合を示す。たゞしぶど
う糖75gr経口投与した場合である。 Blood sugar is uniformly distributed in the plasma and in the water of the formed components (red blood cells, white blood cells, platelets, etc.). As a free sugar in blood, the ratio of glucose is extremely high, and other sugars are hardly detected when the analysis is performed by focusing on glucose. The normal value of glucose (blood sugar level) is set to 75 to 110 mg / d1, and glucose is orally administered in a stress test, which is one of the diabetes testing methods, to measure the time variation of the glucose concentration in the blood. FIG. 8 shows an example of the time variation of the glucose concentration in blood during a load test. a shows a case of a normal person, b shows a case of glucose intolerance, and c shows a case of a urine-resistant patient. This is the case when orally administered 75 g of glucose.
注射器等を用いて人体より血液を採取しその採血試料
を分析してグルコース（血糖値）を求める破壊的または
侵襲的グルコース測定法は公知で分析には従来より酵素
電極法，比色法等種々の方法が実用化され多数の特許出
願も公開されている。一方非破壊的ないしは無侵襲的方
法としては皮膚を通して体表面に拡散して来るグルコー
スの濃度を皮膚表面に押しつけたセンサで測定する経皮
的方法や生体組織中をレーザ光を透過させて特定波長で
の吸光度を測定することによってグルコース濃度を求め
る方法が提案されている。A destructive or invasive glucose measurement method is known in which blood is collected from a human body using a syringe and the like, and the collected blood sample is analyzed to determine glucose (blood glucose level). Has been put to practical use and numerous patent applications have been published. On the other hand, non-destructive or non-invasive methods include a percutaneous method of measuring the concentration of glucose that diffuses to the body surface through the skin with a sensor pressed against the skin surface, or a specific wavelength by transmitting laser light through living tissue. There has been proposed a method of determining the glucose concentration by measuring the absorbance at a temperature.
発明が解決しようとする課題 採血試料を分析してグルコース濃度を求める侵襲的ま
たは破壊的な方法は患者に苦痛を与えるため論外であ
る。無侵襲的な測定法として、例えば特開昭61−25541
号公報「経皮グルコースセンサ」は皮膚加温機構を有す
るセンサを人体の皮膚表面に押し付けて体内から皮膚を
通して拡散して来るグルコースの濃度を測定する方法で
あるが、加温加圧することによって皮膚表面に跡形が長
く残ることがある上にこの方法では組織血管中を現在循
環しつつある血液を直接測定するわけではないので組織
中拡散のための時間遅れ、拡散中の変化等の問題を避け
ることができなかった。SUMMARY OF THE INVENTION Invasive or destructive methods for analyzing blood samples to determine glucose levels are out of the question because they are painful for the patient. As a non-invasive measuring method, for example, JP-A-61-25541
The patent publication “Transdermal glucose sensor” is a method of measuring the concentration of glucose that diffuses from the body through the skin by pressing a sensor having a skin warming mechanism against the skin surface of a human body. This method does not directly measure the blood currently circulating in the blood vessels of the tissue and avoids problems such as time delay for diffusion in the tissue and changes during the diffusion because the trace may remain on the surface for a long time I couldn't do that.
また例えば米国特許4,169,676号公報（血液中の代謝
産物の測定方法）「Method for determining of metabo
lic products in the blood」では、炭酸ガスレーザ光
を用い内部多重全反射吸収スペクトル法（ATR）法によ
って皮膚表面部のグルコース濃度を求めている。この方
法ではレーザ光を用いるためにある程度、エネルギー強
度の強い光を用いることができるが、測定波長は10μｍ
近傍の水分を含んだ生体組織の吸収の非常に大なる赤外
領域にあって組織の限られた深さまで（約30μｍまでと
いう報告もある）しかし測定できないという問題があっ
た。For example, US Patent No. 4,169,676 (Method for determining metabolites in blood) "Method for determining of metabo
In "lic products in the blood," the glucose concentration at the skin surface is determined by an internal multiple total reflection absorption spectrum (ATR) method using a carbon dioxide laser beam. In this method, light having a high energy intensity can be used to some extent because laser light is used, but the measurement wavelength is 10 μm
There is a problem that the measurement cannot be performed at a limited depth of the tissue (some reports have been reported up to about 30 μm) in the infrared region where absorption of living tissue containing water in the vicinity is very large.
さらにまた特開昭60−236631号公報「グルコースの測
光検出方法とその装置」では、生体組織中も比較的良く
透過する近赤外領域の光を利用しているが、この特許出
願が測定に用いている波長では濃度と吸光度との間の直
線性が悪く実用上問題があった。Furthermore, Japanese Patent Application Laid-Open No. 60-236631, "Method and Apparatus for Photometric Detection of Glucose", uses light in the near-infrared region that is transmitted relatively well even in living tissue. At the wavelength used, the linearity between the concentration and the absorbance was poor and there was a practical problem.
課題を解決するための手段 本発明は上述の問題点を解決するため、生体組織中で
の吸収が大なる赤外領域を避け、生体組織中も比較的よ
く透過する近赤外線を利用して毛細血管の存在する深さ
まで測定光を透過させるとともに最適測定波長帯を選ぶ
ことによってグルコース濃度と吸光度との間に良好な直
線関係を得て実用的なグルコース無侵襲計測装置を可能
としたものである。Means for Solving the Problems In order to solve the above-mentioned problems, the present invention avoids an infrared region where absorption in living tissue is large, and utilizes near infrared rays which penetrate relatively well into living tissue to achieve capillary action. By transmitting the measurement light to the depth of the blood vessel and selecting the optimum measurement wavelength band, a good linear relationship between the glucose concentration and the absorbance was obtained, and a practical glucose-invasive measurement device was made possible. .
作用 周知のごとく簡単な光学素子を用いれば、集光したり
光路を任意の方向に向けることができる。これによって
測定したい部位に集中的に光を照射する。照射された光
は生体組織表面で一部は反射され、一部は組織中で吸収
される。残余が生体組織中を透過し再び組織外へ出てく
る。一般に水を含んだ生体組織では近赤外領域における
光の透過率は他の領域に比べてかなり大きく実測によれ
ば約2mm厚みの組織で10-5から10-3にも達する。一方こ
の領域においてよく用いられるPbS赤外線検出素子の感
度は80V/W・cm-2程度のものは現在市販されており、容
易に入手可能である。また10-6V程度の電圧も測定容易
である。したがって生体組織に何等の損傷を与えない程
度のエネルギー量照射で生体組織の透過光測定は容易に
可能である。Operation As is well known, if a simple optical element is used, light can be condensed or the optical path can be directed to an arbitrary direction. In this way, light is intensively applied to a portion to be measured. The irradiated light is partially reflected on the surface of the living tissue and partially absorbed in the tissue. The residue permeates through the living tissue and comes out of the tissue again. Generally, in living tissue containing water, the transmittance of light in the near-infrared region is considerably larger than that in other regions, and according to actual measurement, it reaches 10 -5 to 10 -3 for a tissue having a thickness of about 2 mm. On the other hand, the sensitivity of a PbS infrared detector frequently used in this region is about 80 V / W · cm −2 , which is currently commercially available and easily available. Also, a voltage of about 10 -6 V can be easily measured. Therefore, it is possible to easily measure the transmitted light of the living tissue by irradiating an amount of energy that does not cause any damage to the living tissue.
水分を含んだ生体組織の分光吸収スペクトルを測定す
ると、1.4〜1.5および1.9〜２μｍ付近に水による吸収
のピークが見られると同時に他の波長でも組織中に含ま
れている物質の種類と濃度に関係した吸収のパターンが
観測される。実験の結果、水溶液のグルコースによる吸
収波長帯としては、1600〜1750nmの波長帯を用い、グル
コースの吸収に関係のない基準波長帯としては1200〜13
00nmを用いるのが実用上望ましいことが判明した。When the spectral absorption spectrum of a biological tissue containing water is measured, absorption peaks due to water are found around 1.4 to 1.5 and 1.9 to 2 μm, and at the same time, the type and concentration of the substance contained in the tissue at other wavelengths A related absorption pattern is observed. As a result of the experiment, a wavelength band of 1600 to 1750 nm was used as an absorption wavelength band of glucose in the aqueous solution, and a wavelength band of 1200 to 13
It has been found that the use of 00 nm is practically desirable.
実 施 例 以下本発明の実施例について説明する。EXAMPLES Examples of the present invention will be described below.
実施例１ 実施した計測系の概念的なブロック図を第３図に示
す。Example 1 FIG. 3 shows a conceptual block diagram of the measurement system implemented.
ハロゲン電球よりなる光源１より発した光束は光学系
２を通りチョッパ３で規則的に断続された後、回折格子
型分光器４に入り、この分光器４の射出スリットの直後
に置かれた試料５を透過してPbS赤外線検出器よりなる
センサ６に入射する。チョッパ３に取り付けられたセン
サ７によりチョッパ回転数が検出され、得られた信号を
参照信号としてセンサ６の出力信号がロックインアンプ
８により増幅されてコンピュータ９により演算記録さ
れ、演算結果は必要に応じて試料の分光透過特性，吸光
度などの形で出力される。A light beam emitted from a light source 1 composed of a halogen lamp passes through an optical system 2 and is regularly interrupted by a chopper 3 and then enters a diffraction grating type spectroscope 4 where a sample placed immediately after an exit slit of the spectroscope 4 is placed. 5 and enters a sensor 6 comprising a PbS infrared detector. The sensor 7 attached to the chopper 3 detects the number of rotations of the chopper, the output signal of the sensor 6 is amplified by the lock-in amplifier 8 using the obtained signal as a reference signal, and is calculated and recorded by the computer 9. Accordingly, the data is output in the form of the spectral transmission characteristics, absorbance, etc. of the sample.
成人男性の指爪の1.2μｍ〜2.4μｍの近赤外領域での
分光吸収特性測定結果を第４図に示す。縦軸に透過率の
逆数の常用対数すなわち吸光度を、横軸に波長をとって
示してある。1.4〜1.5および1.9〜２μｍ帯での水によ
る吸収のピークが示されていると同時に爪中に含まれて
いる成分物質による多数の吸収ピークが見られる。FIG. 4 shows the results of measuring the spectral absorption characteristics of an adult male fingernail in the near infrared region of 1.2 μm to 2.4 μm. The vertical axis shows the common logarithm of the reciprocal of the transmittance, that is, the absorbance, and the horizontal axis shows the wavelength. The absorption peaks due to water in the 1.4 to 1.5 and 1.9 to 2 μm bands are shown, and at the same time, a large number of absorption peaks due to the component substances contained in the nail are observed.
純水の分光吸収特性（試料透過距離0.5mm）を第５図
に、グルコース粉末試料（若干の水分を含む）の分光吸
収特性を第６図にそれぞれ示す。FIG. 5 shows the spectral absorption characteristics of pure water (sample transmission distance 0.5 mm), and FIG. 6 shows the spectral absorption characteristics of a glucose powder sample (containing some water).
希釈法により各種濃度のグルコース水溶液を調製し、
これらと水との分光吸光度差を測定した結果を第７図に
示す。1200〜1300nmの波長領域では吸光度差はグルコー
スの濃度が変化してもほとんど変化せず、1600〜1750nm
の波長領域ではグルコース濃度とともに吸光度差が変化
していく様子が明確に認められる。1600〜1750nmを測定
波長領域とし、1200〜1300nmを基準波長領域として吸光
度差より演算処理した数値と水溶液のグルコース濃度と
の関係を第１図において実線で示す。図の縦軸における
PGはグルコース水溶液の1600〜1750nm範囲における分光
透過率の平均値を表わし、PGRは同じくグルコース水溶
液の基準波長1200〜1300nmの場合を示す。またPWは純水
の1600〜1750nm範囲における分光透過率の平均値を表わ
し、PWRは同じく純水の基準波長1200〜1300nmの場合を
示す。このような演算処理を行った数値はグルコース濃
度に対して直線性を示すことがわかる。この際の演算処
理の方法は公知であり、基本原理としてLambert−Beer
の法則を用いている。なお、同図中点線で示した曲線は
測定波長領域を1575±15nmとした場合である。Prepare glucose aqueous solution of various concentrations by dilution method,
FIG. 7 shows the results of measuring the spectral absorbance difference between these and water. In the wavelength region of 1200 to 1300 nm, the absorbance difference hardly changes even if the concentration of glucose changes, and 1600 to 1750 nm
In the wavelength region of, it can be clearly seen that the absorbance difference changes with the glucose concentration. The solid line in FIG. 1 shows the relationship between the numerical value calculated from the absorbance difference and the glucose concentration of the aqueous solution, with 1600 to 1750 nm as the measurement wavelength region and 1200 to 1300 nm as the reference wavelength region. On the vertical axis of the figure
P G represents the average value of the spectral transmittance in 1600~1750nm range of aqueous glucose solution, P GR is also shown a case of a reference wavelength 1200~1300nm glucose solution. The P W represents the average value of the spectral transmittance in 1600~1750nm range of pure water, P WR is also shown a case of a reference wavelength 1200~1300nm of pure water. It can be seen that the numerical value obtained by performing such an arithmetic processing shows linearity with respect to the glucose concentration. The arithmetic processing method at this time is known, and the fundamental principle is Lambert-Beer
Is used. It should be noted that the curve shown by the dotted line in the figure is the case where the measurement wavelength region is set to 1575 ± 15 nm.
なお、補正値（0.01）とは光学測定系に対する実験装
置固有の補正定数である。Note that the correction value (0.01) is a correction constant unique to the experimental apparatus with respect to the optical measurement system.
実施例２ 他の実施例について第２図を用いて詳細に説明する。Embodiment 2 Another embodiment will be described in detail with reference to FIG.
第２図において、光源21より射出し、一部は直接に指
23の爪と反対側（指腹部側）を照射し、他の一部は指組
織中を透過して指爪付近で焦点を結ぶように調整された
凹面反射鏡22によって反射された後、同じく指面を照射
し、指組織中を拡散しながら透過し指爪24に達し、これ
を透過して外部に出る。このように指組織中を透過した
光線の一部はレンズ25およびフィルタ27を通ってPbSセ
ンサ29に達し、増幅器31を経て演算装置33に信号が送ら
れる。他の一部は同様にレンズ26およびフィルタ28を通
ってPbSセンサ30に達し、増幅器32を経て演算装置33に
信号が送られる。フィルタ27および28はそれぞれ前述の
グルコース吸収波長領域，基準波長領域に対応する波長
帯の近赤外線を透過する特性を有するものである。これ
によって指先端部の毛細血管中の血液に含まれているグ
ルコース濃度（血糖値）が無侵襲的に測定される。In FIG. 2, light is emitted from a light source 21 and a part is directly
After irradiating the opposite side of the fingernail (finger side) of 23, another part is transmitted through the finger tissue and is reflected by the concave reflecting mirror 22 adjusted to focus near the fingernail. The finger surface is irradiated and diffused through the finger tissue, penetrates and reaches the fingernail 24, penetrates the fingernail 24, and exits. Part of the light beam transmitted through the finger tissue as described above reaches the PbS sensor 29 through the lens 25 and the filter 27, and a signal is sent to the arithmetic unit 33 via the amplifier 31. The other part similarly reaches the PbS sensor 30 through the lens 26 and the filter 28, and a signal is sent to the arithmetic unit 33 via the amplifier 32. The filters 27 and 28 have characteristics of transmitting near-infrared rays in the wavelength bands corresponding to the aforementioned glucose absorption wavelength region and reference wavelength region, respectively. Thus, the glucose concentration (blood sugar level) contained in the blood in the capillary at the tip of the finger is measured non-invasively.
発明の効果 以上の説明から明らかなように本発明は、1600〜1750
nmの帯域と1200〜1300nmの帯域の近赤外光を利用するこ
とによって、生体組織を透過させることができ、かつ生
体中に含まれているグルコースによる分光吸収特性がグ
ルコース濃度と一定の関係にあるため、生体を破壊する
ことなく無侵襲で生体内のグルコース濃度を測定するこ
とができるという効果を有するものである。Effect of the Invention As is clear from the above description, the present invention
By using near-infrared light in the band of 1200 nm and the band of 1200 to 1300 nm, it is possible to transmit biological tissues, and the spectral absorption characteristics of glucose contained in the living body have a certain relationship with the glucose concentration. Therefore, the present invention has an effect that the glucose concentration in a living body can be measured noninvasively without destroying the living body.
第１図は吸光度よりの演算値とグルコース濃度との関係
を示す図、第２図は本発明によるグルコース無侵襲計測
装置の一実施例の概略構成図、第３図は本発明の一実施
例における計測系の概念的なブロック図、第４図は成人
爪の近赤外線領域における分光吸収特性の測定結果の一
例を示す図、第５図は実施例において使用した純水の分
光吸収特性を示す図、第６図は同じく近赤外領域でのグ
ルコースの分光吸収特性を示す図、第７図は種々の濃度
のグルコース水溶液と水との分光吸光度差を示す図、第
８図はぶどう糖経口投与時の血液中のグルコース濃度の
時間経過を示す特性図である。 21……光源、23……指。FIG. 1 is a diagram showing a relationship between a calculated value from absorbance and a glucose concentration, FIG. 2 is a schematic configuration diagram of an embodiment of a glucose-invasive measuring apparatus according to the present invention, and FIG. 3 is an embodiment of the present invention. FIG. 4 is a diagram showing an example of a measurement result of a spectral absorption characteristic of an adult nail in a near infrared region, and FIG. 5 is a diagram showing a spectral absorption characteristic of pure water used in Examples. Fig. 6, Fig. 6 shows the spectral absorption characteristics of glucose in the near-infrared region, Fig. 7 shows the spectral absorbance difference between various concentrations of glucose aqueous solution and water, and Fig. 8 shows oral administration of glucose. FIG. 7 is a characteristic diagram showing a time course of blood glucose concentration at the time. 21 ... light source, 23 ... finger.
Claims (1)
帯域1600〜1750nmの光線とグルコースの吸収によらない
基準波長帯域1200〜1300nmの光線を発生させる手段と、
前記吸収波長帯域の光線および前記基準波長帯域の光線
を生体に照射させる手段と、前記生体を介した前記吸収
波長帯域の光線エネルギーと前記基準波長帯域の光線エ
ネルギーをそれぞれ電気信号に変換する第１第２の光電
変換手段と、前記第１第２の光電変換手段の出力の平均
値をもとに前記生体を介した前記吸収波長帯域の光線エ
ネルギーと前記基準波長帯域の光線エネルギーの差違を
演算処理する手段を具備し、前記演算手段の出力からグ
ルコース濃度を求めることを特徴とするグルコース無侵
襲計測装置。A means for generating a light beam having an absorption wavelength band of 1600 to 1750 nm specific to glucose in living tissue and a light beam having a reference wavelength band of 1200 to 1300 nm which does not depend on glucose absorption;
Means for irradiating the living body with the light beam in the absorption wavelength band and the light beam in the reference wavelength band, and a first means for converting the light energy in the absorption wavelength band and the light energy in the reference wavelength band through the living body into electric signals, respectively. The difference between the light energy of the absorption wavelength band and the light energy of the reference wavelength band via the living body is calculated based on the average value of the outputs of the second photoelectric conversion means and the first and second photoelectric conversion means. A non-invasive glucose measuring apparatus, comprising: means for processing; and obtaining a glucose concentration from an output of the calculating means.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1313620A JP2641575B2 (en) | 1989-12-01 | 1989-12-01 | Glucose non-invasive measuring device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1313620A JP2641575B2 (en) | 1989-12-01 | 1989-12-01 | Glucose non-invasive measuring device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03173535A JPH03173535A (en) | 1991-07-26 |
| JP2641575B2 true JP2641575B2 (en) | 1997-08-13 |
Family
ID=18043511
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1313620A Expired - Fee Related JP2641575B2 (en) | 1989-12-01 | 1989-12-01 | Glucose non-invasive measuring device |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2641575B2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL107396A (en) * | 1992-11-09 | 1997-02-18 | Boehringer Mannheim Gmbh | Method and apparatus for analytical determination of glucose in a biological matrix |
| US5529755A (en) * | 1994-02-22 | 1996-06-25 | Minolta Co., Ltd. | Apparatus for measuring a glucose concentration |
| WO1997033514A1 (en) * | 1996-03-13 | 1997-09-18 | Hitachi, Ltd. | Method and apparatus for circular dichromatic analysis |
| AUPS332802A0 (en) * | 2002-07-03 | 2002-07-25 | Iwrx Pty Ltd | Sucrose monitor |
| JP4834350B2 (en) * | 2005-08-18 | 2011-12-14 | 株式会社東芝 | Biological information measuring apparatus and calibration method thereof |
| WO2024034312A1 (en) * | 2022-08-09 | 2024-02-15 | バイオニクス株式会社 | Vital information measurement device, vital information measurement method, living body management system, and living body management method |
-
1989
- 1989-12-01 JP JP1313620A patent/JP2641575B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH03173535A (en) | 1991-07-26 |
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