JP2004313554A

JP2004313554A - Non-invasive measurement device for blood sugar level

Info

Publication number: JP2004313554A
Application number: JP2003113497A
Authority: JP
Inventors: Yoshiaki Shimomura; 義昭下村
Original assignee: Nagasaki Prefectural Government
Current assignee: Nagasaki Prefectural Government
Priority date: 2003-04-17
Filing date: 2003-04-17
Publication date: 2004-11-11
Anticipated expiration: 2023-04-17
Also published as: JP4052461B2

Abstract

<P>PROBLEM TO BE SOLVED: To provide a small-sized and easily portable non-invasive measurement device for a blood sugar level which can non-invasively measure a blood sugar level of a human body without errors. <P>SOLUTION: The device is provided with a light source control part 220, which is for irradiating a measuring site of a finger 1 with two irradiating lights 11 and 12 with different near-infrared wavelength regions, and light detectors 51 and 61 for detecting a transmitting light amount by receiving transmitting lights 12, 22 and 13, 23 which are the irradiation lights 11 and 12 transmitting through the measuring site of the finger 1 at two places apart at different distances. The relative transmittance, which is a ratio of the detected transmitting light amounts with the same wavelength at the two places, is calculated for each wavelength. The blood sugar level is calculated by using the relative transmittance of each wavelength. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

【０００１】
【発明の属する技術分野】
本発明は、人体の血糖値を非侵襲的に測定する装置に関し、詳しくは特定波長の単色光を人体に照射して得られる人体からの透過光から人体の血糖値を非侵襲的に誤差なく測定する技術に関する。
【０００２】
【従来の技術】
糖尿病では、肝臓から分泌されるインスリンの不足、あるいは体の細胞がインスリンに反応しなくなることで筋肉や肝臓への糖の蓄積が行われなくなり、血糖中のグルコース濃度、つまり血糖値が高くなり、これにより網膜症・神経障害・腎症等様々な合併症が引き起こされる。糖尿病患者は国内に６９０万人、その予備軍を含め１３００万人以上にもなるといわれ、深刻な国民病となっている。現状、糖尿病治療では完全な治療方法がなく、血糖値測定を行いながらインスリンの投与、あるいは食事療法によって血糖値を適正なレベルに維持させている。
【０００３】
現状の血糖値測定は、採血した血液を用いて血糖に対するグルコース酸化酵素の反応を電気化学的に定量し、血糖値に換算するグルコースセンサー法を用いた測定器により行われており、糖尿病患者の日常での血糖値管理に用いる携帯型血糖値測定器などはすでに市販化されている。こうした血糖値検査では、１日数回の採血に伴う苦痛や採血針による感染等の問題があり、採血が不要で且つ血糖値の日内変動をリアルタイムで測定できる非侵襲の血糖値測定装置が望まれている。
【０００４】
そこで、近赤外領域の波長の光を人体に照射し、その人体からの拡散反射光又は透過光を分光器を用いて測定し、その拡散反射光又は透過光のスペクトルから人体の血糖値を算出しようとする技術が開示されている（例えば非特許文献１，特許文献１参照）。非特許文献１では近赤外領域の波長の光を下唇に照射し、その拡散反射光から分光器等を用いて拡散反射光のスペクトルを測定し、そのスペクトル値から血糖値を測定する方法を提案している。特許文献１では近赤外領域の波長の光を指等に照射し、その透過光を検出して特定波長９４４ｎｍと９６４ｎｍでの吸光度を求め、その値から血糖値を測定する方法を提案している。
【０００５】
ところで、非特許文献１の方法によれば、近赤外領域の波長の光を下唇に照射し、その拡散反射光のスペクトルを測定する為に回折格子等から構成される複雑な分光器を必要としている。これは、血糖値を算出する為には１０〜２０種類の波長の光の反射率データを必要とし、このためにはこうした領域の波長の光を有する白色光源からの光を人体に照射し、その反射スペクトルを得る為には前記した分光器が必要となる。こうした白色光源や分光器をベースとした血糖値の測定方法では、糖尿病患者が日常の血糖値管理を行う為に持ち運びが容易な血糖値測定装置の小型・携帯化が難しいものであった。
【０００６】
一方、特許文献１では特定の２波長の光を用い、その透過光により血糖値を測定する装置を提案している。この技術を図８に基づいて説明する。図８に示す測定装置は、近赤外光を発する光源１００とその光から所定の単色光のみを指１に照射する為の回折格子３４０，反射ミラー３６０を備え、また分光された単色光１０１の一部を検出する為のサンプリング用プリズム３７０，ＮＤフィルター３９０，光検出器３８０を備えている。さらに人の指１からの透過光１０２を検出するためのレンズ５０，光検出器５１を、また光検出器５１，３８０からの検出信号を増幅してデジタル化する信号処理部２３０、及び中央制御部２００を備えている。中央制御部２００は信号処理部２３０で増幅・デジタル化された光検出器５１，３８０からの検出信号をもとに指１の透過率Ｔを下記式で算出する。
Ｔ＝Ｉ_１／Ｉ_０・・・（１．１）
【０００７】
ここで、Ｉ_０は照射光１０１の照射光量で、光検出器３８０で検出された検出信号に一定数を乗じて算出される。またＩ_１は透過光１０２の光量で検出器５１で検出された検出信号に一定数を乗じて算出される。ここでは照射光１０１の波長として２つの９４４ｎｍ，９６４ｎｍを選択し、その各波長に対する前記透過率をそれぞれＴ_１，Ｔ_２として下記式により血糖値Ｃを算出する。
Ｃ＝ｋ_０＋ｋ_０＊ＡＢＳ_１／ＡＢＳ_２・・・（１．２）
【０００８】
ここで、ＡＢＳ_１＝−ｌｎ（Ｔ_１），ＡＢＳ_２＝−ｌｎ（Ｔ_２）をそれぞれ表す。またｋ_０，ｋ_１は実測した血糖値を用いて最小２乗法で決定された係数を示す。なお、ここでは光源に白色光源を用いたが、前記波長の異なる２つの波長に９４４ｎｍ，９６４ｎｍの半導体レーザー等を用いることができれば、回折格子等から構成される複雑な分光器を必要としない血糖値の非侵襲測定装置が実現できる。
【０００９】
しかしながら、この先願発明では、照射光１０１の照射位置Ｐ_０と透過光１０２の検出位置Ｐ_１との直線距離ｒ_１が指１の大きさに依存してわずかに変化する。そのわずかな変化量に対して、前記式による血糖値Ｃの算出において無視できない測定誤差が生じる問題があった。
【００１０】
【非特許文献１】
Ｈ．Ｍ．Ｈｅｉｓｅ，ｅｔａｌ．，ＡｒｔｉｆｉｃｉａｌＯｒｇａｎｓ，１８（６）ｐｐ．４３９−４４７，１９９４
【特許文献１】
特開平５−１７６９１７号公報
【００１１】
【発明が解決しようとする課題】
本発明が解決しようとする課題は、従来のこれらの問題点を解消し、人体の血糖値を非侵襲的に誤差なく測定できる小型で携帯容易な血糖値の非侵襲測定装置を提供することにある。
【００１２】
【課題を解決するための手段】
かかる課題を解決した本発明の構成は、
１）人体の測定部位に複数の異なる波長からなる光を照射する照射手段を設け、同照射手段の光が人体の測定部位を透過した透過光を異なる距離をおいた２箇所で受光してその透過光量を検出する透過光量検出手段を設け、同透過光量検出手段で検出した２箇所での同波長の透過光量の比である相対透過度を各波長毎に算出し、同各波長の相対透過度を用いて人体の血糖値を算定する演算手段を設けた血糖値の非侵襲測定装置
２）照射手段が、２つの異なる波長の光を照射するもので、演算手段が、２箇所で検出した各透過光量のうち透過距離が短い方をＩ_１． _λ _１，Ｉ_１． _λ _２とし、透過距離が長い方をＩ_２． _λ _１，Ｉ_２． _λ _２とし、２つの異なる波長の相対透過度Ｒ_λ _１，Ｒ_λ _２を式Ｒ_λ _１＝Ｉ_２． _λ _１／Ｉ_１． _λ _１，Ｒ_λ _２＝Ｉ_２． _λ _２／Ｉ_１． _λ _２とし、予め実測した血糖値と相対透過度Ｒ_λ _１，Ｒ_λ _２を用いて次式の係数ｋ_０，ｋ_１を求め、血糖値Ｃを式Ｃ＝ｋ_０＋ｋ_１＊ｌｎ（Ｒ_λ _１）／ｌｎ（Ｒ_λ _２）に従って算定するようにしたものである前記１）記載の血糖値の非侵襲測定装置
３）照射手段が、２つの異なる波長の光を照射するもので、演算手段が、２箇所で検出した各透過光量のうち透過距離が短い方をＩ_１． _λ _１，Ｉ_１． _λ _２とし、透過距離が長い方をＩ_２． _λ _１，Ｉ_２． _λ _２とし、２つの異なる波長の相対透過度Ｒ_λ _１，Ｒ_λ _２を式Ｒ_λ _１＝Ｉ_２． _λ _１／Ｉ_１． _λ _１，Ｒ_λ _２＝Ｉ_２． _λ _２／Ｉ_１． _λ _２とし、同各相対透過度Ｒ_λ _１，Ｒ_λ _２に基づいて２つの異なる波長の吸光度Ａ_１，Ａ_２を式Ａ_１＝−１ｎ（Ｒ_λ _１），Ａ_２＝−１ｎ（Ｒ_λ２）とし、予め実測した血糖値と吸光度Ａ_１，Ａ_２を用いて次式の係数ｋ_０，ｋ_１を求め、血糖値Ｃを式Ｃ＝ｋ_０＋ｋ_１＊Ａ_１／Ａ_２に従って算定するようにしたものである前記１）記載の血糖値の非侵襲測定装置
４）照射手段が照射する２つの異なる波長の光が、９４０〜１０００ｎｍの範囲と１０４０〜１０９０ｎｍの範囲の近赤外領域の中から選ばれたものである前記２）又は３）記載の血糖値の非侵襲測定装置
５）照射手段が、３つの異なる波長の光を照射するもので、演算手段が、２箇所で検出した各透過光量のうち透過距離が短い方をＩ_１． _λ _１，Ｉ_１． _λ _２，Ｉ_１． _λ _３とし、透過距離が長い方をＩ_２． _λ _１，Ｉ_２． _λ _２，Ｉ_２． _λ _３とし、３つの波長の相対透過度Ｒ_λ _１，Ｒ_λ _２，Ｒ_λ _３を式Ｒ_λ _１＝Ｉ_２． _λ _１／Ｉ_１． _λ _１，Ｒ_λ _２＝Ｉ_２． _λ _２／Ｉ_１． _λ _２，Ｒ_λ _３＝Ｉ_２． _λ _３／Ｉ_１． _λ _３とし、予め実測した血糖値と相対透過度Ｒ_λ _１，Ｒ_λ _２，Ｒ_λ _３を用いて次式の係数ｋ_０，ｋ_１を求め、血糖値Ｃを式Ｃ＝ｋ_０＋ｋ_１＊ｌｎ（Ｒ_λ _１／Ｒ_λ _３）／ｌｎ（Ｒ_λ _２／Ｒ_λ _３）に従って算定するようにしたものである前記１）記載の血糖値の非侵襲測定装置
６）照射手段が、３つの異なる波長の光を照射するもので、演算手段が、２箇所で検出した各透過光量のうち透過距離が短い方をＩ_１． _λ _１，Ｉ_１． _λ _２，Ｉ_１． _λ _３とし、透過距離が長い方をＩ_２． _λ _１，Ｉ_２． _λ _２，Ｉ_２． _λ _３とし、３つの波長の相対透過度Ｒ_λ _１，Ｒ_λ _２，Ｒ_λ _３を式Ｒ_λ _１＝Ｉ_２． _λ _１／Ｉ_１． _λ _１，Ｒ_λ _２＝Ｉ_２． _λ _２／Ｉ_１． _λ _２，Ｒ_λ _３＝Ｉ_２． _λ _３／Ｉ_１． _λ _３とし、同各相対透過度Ｒ_λ _１，Ｒ_λ _２，Ｒ_λ３に基づいて３つの異なる波長の吸光度Ａ_１，Ａ_２，Ａ_３を式Ａ_１＝−１ｎ（Ｒ_λ _１），Ａ_２＝−１ｎ（Ｒ_λ２），Ａ_３＝−１ｎ（Ｒ_λ３）とし、予め実測した血糖値と吸光度Ａ_１，Ａ_２，Ａ_３を用いて次式の係数ｋ_０，ｋ_１を求め、血糖値Ｃを式Ｃ＝ｋ_０＋ｋ_１＊（Ａ_１−Ａ_３）／（Ａ_２−Ａ_３）に従って算定するようにしたものである前記１）記載の血糖値の非侵襲測定装置
７）照射手段が照射する３つの異なる波長の光が、その内２つが９４０〜１０００ｎｍの範囲と１０４０〜１０９０ｎｍの範囲の近赤外領域の中から選ばれたもので、残りの１つが９１０〜９３０ｎｍ又は１０１０〜１０３０ｎｍの範囲の近赤外領域の中から選ばれたものである前記５）又は６）記載の血糖値の非侵襲測定装置
にある。
【００１３】
【発明の実施の形態】
本発明において、光源から波長の異なる複数の単色光を発生し、照射手段により人体の測定部位（例えば指等）にその単色光を照射する。照射された単色光は人体内部で散乱して吸収し、人体外に放射されて透過光となる。この透過光を透過光量検出手段で単色光の照射位置からそれぞれ異なる一定の直線距離で検出する。検出した２つの透過光からその比である相対透過度を波長毎に算出し、同相対透過度から人体の血糖値を算定する。検出された透過光には人体内部の血糖値情報が含まれており、非侵襲による人体の血糖値測定が可能となる。
【００１４】
また、光源に２つ又は３つの単色光源を用いることで、白色光源を用いた従来の血糖値測定装置のように透過又は反射光スペクトルを検出するための複雑な分光器を必要としない装置が実現できる。さらに、測定部位である指の大きさに依存して単色光の照射位置と透過光の検出位置との直線距離が変化しても、血糖値の測定誤差への影響を少なくした血糖値の非侵襲測定装置が実現できる。
【００１５】
なお、本発明で用いている透過光量Ｉ_１． _λ _１，Ｉ_２． _λ _１、及び相対透過度Ｒ_λ _１の各記号において、Ｉ_１，Ｉ_２の数字は検出位置を示し、λ_１，λ_２，λ_３は波長の種類を示しているものである。以下、本発明の各実施例を図面に基づいて具体的に説明する。
【００１６】
【実施例】
実施例１（図１，２参照）：図１に示す実施例１の血糖値測定装置は、照射光１１，２１を指１に照射するための光源１０，２０と、反射プリズム４０，レンズ４１を備える。また指１からの透過光１２，２２を検出するためのレンズ５０と光検出器５１から構成される透過光量検出手段Ｉと、透過光１３，２３を検出するためのレンズ６０と光検出器６１から構成される透過光量検出手段ＩＩを備え、さらに信号処理部２３０，中央制御部２００，表示部２１０，光源制御部２２０を備えている。
【００１７】
中央制御部２００は、信号処理部２３０でデジタル化された光検出器５１，６１からの検出信号をもとに、後述する算定式で人体の血糖値を算出して表示部２１０で表示する。光源制御部２２０は、光源１０，２０に電流を供給するための図示しない電源，スイッチ部を有している。中央制御部２００からトリガ信号Ｔ_１０（Ｔ_２０）がスイッチ部に入力されると、トリガ信号Ｔ_１０（Ｔ_２０）の立ち上がりに同期してスイッチ部がＯＮとなり、光源１０（光源２０）に電流が供給される。
【００１８】
以上の構成を有する血糖値の非侵襲測定装置の動作を説明する。まず、中央制御部２００から送信されるトリガ信号Ｔ_１０がＨｉｇｈとなると、光源制御部２２０の図示しないスイッチ部がトリガ信号Ｔ_１０の立ち上がりに同期してＯＮとなり、光源１０に電流が供給されて照射光１１が発生する。一方、トリガ信号Ｔ_２０はＬｏｗのままとなっており、光源２０には電流が供給されず単色光２１は発生していない。
【００１９】
次に、光源１０から発した照射光１１はプリズム４０を透過してレンズ４１により指１上に照射され、照射光１１は指１内部で散乱・吸収を受けて指１外のあらゆる方向に放射されて透過光となる。その後、照射光１１の照射位置Ｐ_０から直線距離ｒ_１離れた指１上の位置Ｐ_１からの透過光１２はレンズ５０で光検出器５１の受光面に集められ、また照射光１１の照射位置Ｐ_０から直線距離ｒ_２離れた指１上の位置Ｐ_２からの透過光１３はレンズ６０で光検出器６１の受光面に集められる。なお、図１ではｒ_１＜ｒ_２とし、また光検出器５１，６１にはフォトダイオードを用いている。
【００２０】
光検出器５１，６１からはそれぞれ透過光１２，１３の光強度に比例した検出信号が出力されて、信号処理部２３０でデジタル化処理され、その検出信号を基に中央制御部２００で後述する算定式で相対透過度Ｒ_λ _１が算出される。相対透過度Ｒ_λ _１の算出演算が終わると、トリガ信号Ｔ_１０がＬｏｗに、またトリガ信号Ｔ_２０がＨｉｇｈになる。このトリガ信号Ｔ_１０（Ｔ_２０）に基づいて光源制御部２２０内の図示しないスイッチ部の開閉で、光源１０がＯＦＦ（消灯）し、光源２０がＯＮ（点灯）する。
【００２１】
続いて、前述した照射光１１による相対透過度Ｒ_λ _１の算出手順と同様に、照射光２１による相対透過度Ｒ_λ _２の算出が実行される。照射光２１による相対透過度Ｒ_λ _２の算出演算が終了するとトリガ信号Ｔ_１０，Ｔ_２０はともにＬｏｗとなり、光源１０，２０は共にＯＦＦ（消灯）して指１の血糖値計測作業が終了する。中央制御部２００では、算出した相対透過度Ｒ_λ _１，Ｒ_λ _２から指１の血糖値を後述する算定式で算出し、その結果を表示部２１０に表示する。
【００２２】
次に、中央制御部２００で行われる相対透過度Ｒ_λ _１，Ｒ_λ _２の算出方法について説明する。波長毎の照射光１１，透過光１２，１３の光量をそれぞれＩ_０． _λ _１，Ｉ_１． _λ _１，Ｉ_２． _λ _１とする。照射光１１に対する指１の相対透過度Ｒ_λ _１は下記式で表される。
Ｒ_λ _１＝Ｉ_２． _λ _１／Ｉ_１． _λ _１・・・（１．３）
【００２３】
光検出器５１，６１における光量−電圧変換係数をそれぞれβ_５１，β_６１とすると、光検出器５１，６１で検出される検出信号（電圧）Ｖ_５１，Ｖ_６１は下記式で表される。
Ｖ_５１＝β_５１＊Ｉ_１． _λ _１・・・（１．４）
Ｖ_６１＝β_６１＊Ｉ_２． _λ _１・・・（１．５）
【００２４】
前記各式より、指１の相対透過度Ｒ_λ _１は下記式で算出され、照射光１１の光量Ｉ_０． _λ _１に依存しない形で表される。
Ｒ_λ _１＝（β_５１／β_６１）＊Ｖ_６１／Ｖ_５１・・・（１．６）
【００２５】
ここで、（）内の値は血糖値測定装置固有の定数で、光量が分かった光源を用いて簡単に校正することができる。照射光２１に対する指１の相対透過度Ｒ_λ _２の算出も前記照射光１１に対する指１の相対透過度Ｒ_λ _１と同様にして求めることができる。指１の血糖値Ｃは、算出した相対透過度Ｒ_λ _１，Ｒ_λ _２を用いて下記式で算出する。
Ｃ＝ｋ_０＋ｋ_１＊ｌｎ（Ｒ_λ _１）／ｌｎ（Ｒ_λ _２）・・・（１．７）
【００２６】
ここでｋ_０，ｋ_１は実測血糖値を用いて最小２乗法で決定された係数を示す。また、血糖値推定を行うための異なる２つの波長として、実施例１では９４０〜１０００ｎｍの範囲と１０４０〜１０９０ｎｍの範囲の中からそれぞれ選ばれた波長としている。
【００２７】
なお、前記した波長範囲にある照射光１１，２１を発する光源１０，２０としてレーザーを用いることができる。このレーザーに半導体レーザーを用いれば、小型の血糖値測定装置が実現できる。また、発光ダイオード等の発光素子を光源１０，２０に用いることも可能である。また、近赤外領域の波長の光を連続的に発する白色光源を光源１０，２０に用いる場合、光源１０，２０からの光を前述した波長のみを透過させる光学フィルターを用いることで実現しても良い。さらに、図２に示すように光源１０，２０からの照射光１１，２１を光ファイバー７００を用いて指１に照射し、さらに指１上の検出点Ｐ_１，Ｐ_２からの透過光１２，１３（２２，２３）を光ファイバー７０１，７０２を用いて前記透過光量検出手段Ｉ，ＩＩに導光してもよい。
【００２８】
実施例２（図３参照）：図３に示す実施例２は３つの波長を用いた血糖値の非侵襲測定装置の例である。図３に示す実施例２の血糖値測定装置は、照射光１１，２１，３１を指１に照射するための光源１０，２０，３０と、レンズ４１０，４２０，４３０と、光ファイバー７１０，７２０，７３０及び同各光ファイバー７１０，７２０，７３０を束ねて指１に照射光１１，２１，３１を照射する光ファイバー７００を備える。また、指１からの透過光１２，２２，３２を検出するための光ファイバー７０１，レンズ５０，光検出器５１から構成される透過光量検出手段Ｉと、透過光１３，２３，３３を検出するための光ファイバー７０２，レンズ６０，光検出器６１から構成される透過光量検出手段ＩＩを備え、さらに信号処理部２３０，中央制御部２００，表示部２１０，光源制御部２２０を備えている。
【００２９】
中央制御部２００は、信号処理部２３０でデジタル化された光検出器５１，６１からの検出信号をもとに後述する算定式で人体の血糖値を算出し、表示部２１０で表示する。光源制御部２２０は、光源１０，２０，３０に電流を供給するための図示しない電源，スイッチ部を有している。中央制御部２００からトリガ信号Ｔ_１０（Ｔ_２０，Ｔ_３０）がスイッチ部に入力されると、トリガ信号Ｔ_１０（Ｔ_２０，Ｔ_３０）の立ち上がりに同期してスイッチ部がＯＮとなり、光源１０（光源２０，光源３０）に電流が供給される。各照射光１１，２１，３１に対応した指１の相対透過度Ｒ_λ _１，Ｒ_λ _２，Ｒ_λ _３は実施例１と同様の手順で算出することができる。指１の血糖値Ｃは、算出した相対透過度Ｒ_λ _１，Ｒ_λ _２，Ｒ_λ _３を用いて下記式で算出する。
Ｃ＝ｋ_０＋ｋ_１＊ｌｎ（Ｒ_λ _１／Ｒ_λ _３）／ｌｎ（Ｒ_λ _２／Ｒ_λ _３）・・・（１．８）
【００３０】
ここで、ｋ_０，ｋ_１は実測血糖値を用いて最小２乗法で決定された係数を示す。前記式（１．８）を用いて血糖値測定を行うための異なる３つの波長として、実施例２では照射光１１，２１が９４０〜１０００ｎｍの範囲と１０４０〜１０９０ｎｍの範囲の中からそれぞれ選ばれたものであり、また残りの照射光３１が９１０〜９３０ｎｍ又は１０１０〜１０３０ｎｍの範囲の中から選ばれた波長としている。
【００３１】
実施例３（図４参照）：実施例１，２では人体に照射する光を波長の異なる２つ又は３つの単色光に限定して説明した。これにより、白色光源を用いた従来の血糖値測定装置のように透過又は反射光スペクトルを検出するための複雑な分光器を必要としない装置が実現できる。また、指等の測定部位の大きさに依存して単色光の照射位置と透過光の検出位置との直線距離が変化しても、血糖値の測定誤差への影響を少なくした血糖値の非侵襲測定装置が実現できる。
【００３２】
一方、従来の白色光源と分光器を用いた血糖値の非侵襲測定装置においても、指等の測定部位の大きさに依存して単色光の照射位置と透過光の検出位置との直線距離が変化しても、血糖値の測定誤差への影響を少なくすることができる。従来の白色光源と分光器を用いた血糖値の非侵襲測定装置に適用した例を図４に基づいて説明する。
【００３３】
図４に示す血糖値の非侵襲測定装置では、近赤外領域の波長の光を含むハロゲンランプ等の白色光源１００とその電源１１０を備え、光源１００からの光１０１をレンズ１２０と光ファイバー７００を介して指１に照射する。指１に照射された光１０１は指１内部で散乱・吸収を受けて指１外のあらゆる方向に放射されて透過光となる。光ファイバー７００による光１０１の指１上の照射位置Ｐ_０から直線距離ｒ_１，ｒ_２にある指１上の位置Ｐ_１，Ｐ_２からの透過光１０２，１０３を光ファイバー７０１，７０２により分光器３００まで導光する。
【００３４】
分光器３００は、レンズ３１０，３２０と、シャッター３１１，３２１と、プリズム３３０，回折格子３４０，多チャンネル検出器３５０から構成される。多チャンネル検出器３５０にはＣＣＤ等のリニアアレイセンサーが用いられる。位置Ｐ_１から放射された透過光１０２の透過スペクトルを計測する場合、シャッター３１１が開き、多チャンネル検出器３５０上に透過光１０２の透過スペクトルＳ_１が得られる。この場合、シャッター３２１は閉まっている。同様にして位置Ｐ_２から放射された透過光１０３の透過スペクトルＳ_２を測定する場合、シャッター３２１が開き、多チャンネル検出器３５０上に透過光１０３の透過スペクトルＳ_２が得られる。この場合、シャッター３１１は閉まっている。以上のようにして測定した前記透過スペクトルＳ_１，Ｓ_２から透過率スペクトルＴ＝Ｓ_２／Ｓ_１を算出する。得られた透過率スペクトルから前記各式に従い血糖値Ｃを算出することができる。
【００３５】
各実施例の非侵襲血糖値測定方法について検討した結果を図５〜７に示す。図５は透明な石英セル容器入れたグルコース水溶液に種々の波長の単色光を照射し、その透過率スペクトルＴを算出して下記式により算出される吸光度比γと糖濃度の相関について相関係数の自乗値Ｒ^２＞０．９９５となる波長の組み合わせ領域を斜線で示している。
γ＝ｌｎ（Ｔ（λ_１））／ｌｎ（Ｔ（λ_２））・・・（１．９）
【００３６】
図５より９４０〜１０００ｎｍの範囲と１０４０〜１０９０ｎｍの範囲を四角で囲んだ領域は、前記吸光度比γで糖濃度を推定する為の最適な波長の組み合わせであることがわかる。
【００３７】
一方、人体などの散乱体に対しても、グルコース水溶液で得られた最適な波長の組み合わせがそのまま成り立つ。図６は人体を模した散乱体に対して、吸光度比γと糖濃度の相関について図１で示した非侵襲測定装置で測定した場合について理論解析し、その相関係数の自乗値Ｒ^２＞０．９９５となる波長の組み合わせ領域を斜線で示している。理論解析は文献「Ａ．Ｉｓｈｉｍａｒｕ：ＷａｖｅＰｒｏｐａｇａｔｉｏｎａｎｄＳｃａｔｔｅｒｉｎｇｉｎＲａｎｄｏｍＭｅｄｉａ，ＡｃａｄｅｍｉｃＰｒｅｓｓ，ＮｅｗＹｏｒｋ（１９７８）」を参考に行った。ここでの理論計算では図１中、直線距離ｒ_１，ｒ_２をそれぞれ１５ｍｍ，２５ｍｍに設定した。また等価散乱係数はグルコース濃度・波長によらず一定とし、ここでは人体の一般値１．０ｍｍ^−１（参考：機論、５９，５６１Ｂ（１９９３）、ＰＰ．３３８−３４０）を用いた。また波長・グルコース濃度に依存した吸収係数はグルコース水溶液を用いて実測した結果を用いた。図６より水溶液と同じ波長の組み合わせにおいて吸光度比γと糖濃度の相関が高いことがわかる。
【００３８】
次に、実施例１，２記載の血糖値測定装置において、図２中、指１の厚みを変化させた場合の血糖値の測定誤差について解析した結果を図７に示す。ここでは透過光検出位置Ｐ_１，Ｐ_２間の距離を２０ｍｍで一定とした。また、縦軸の血糖値の測定誤差は、従来技術における指１の厚みの変化量０．１ｍｍに対する血糖値の測定誤差に対する相対値で表示した。実施例１では、従来技術に比べ血糖値の測定誤差が約１／１０に、また実施例２では従来技術に比べ血糖値の測定誤差が約１／１００にそれぞれ低減していることがわかる。
【００３９】
【発明の効果】
以上説明したように、本発明によれば複数の異なる特定波長の単色光を人体に照射し、その透過光を前記単色光の照射位置からの直線距離が異なる位置でそれぞれ検出する。検出された透過光には人体内部の血糖値情報が含まれており、人体の血糖値測定が可能となる。また、白色光源を用いた従来の血糖値測定装置のように透過又は反射光スペクトルを検出するための複雑な分光器を必要としない装置が実現でき、また光源に小型の半導体レーザー等を用いることができるため、小型・軽量の血糖値測定装置が実現できる。さらに、指等の測定部位の大きさに依存して単色光の照射位置と透過光の検出位置との直線距離が変化しても、血糖値の測定誤差への影響を少なくした血糖値の非侵襲測定装置が実現できる。
【図面の簡単な説明】
【図１】実施例１の血糖値の非侵襲測定装置の説明図である。
【図２】実施例１の他の例の光ファイバーを用いた血糖値の非侵襲測定装置の説明図である。
【図３】実施例２の血糖値の非侵襲測定装置の説明図である。
【図４】実施例３の血糖値の非侵襲測定装置の説明図である。
【図５】グルコース水溶液での最適波長の組み合わせ領域を示す図である。
【図６】人体を模した散乱体での最適波長の組み合わせ領域を示す図である。
【図７】指の厚みの変化量と血糖値測定誤差との関係を示す図である。
【図８】従来の血糖値の非侵襲測定装置の説明図である。
【符号の説明】
１指
１０，２０，３０光源
１１，２１，３１照射光
１２，１３透過光
２２，２３透過光
３２，３３透過光
４１レンズ
５０，６０レンズ
４０プリズム
５１，６１光検出器
１００白色光源
１０１照射光
１０２，１０３透過光
１１０白色光源用電源
１２０レンズ
２００中央制御部
２１０表示部
２２０光源制御部
２３０信号処理部
３００，３０１分光器
３１０，３２０レンズ
３１１，３２１シャッター
３３０プリズム
３４０回転格子
３５０多チャンネル検出器
３６０ミラー
３７０サンプル用プリズム
３８０光検出器
３９０ＮＤフィルター
４１０，４２０，４３０レンズ
７００，７０１，７０２光ファイバー
７１０，７２０，７３０光ファイバー[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a device for non-invasively measuring the blood sugar level of a human body, and more particularly, non-invasively measuring the blood sugar level of a human body from transmitted light from a human body obtained by irradiating a monochromatic light of a specific wavelength to the human body without error. Related to measuring technology.
[0002]
[Prior art]
In diabetes, the lack of insulin secreted from the liver or the inability of cells in the body to respond to insulin prevents sugar from accumulating in muscles and liver, increasing the glucose concentration in blood sugar, that is, increasing blood sugar levels, This causes various complications such as retinopathy, neuropathy and nephropathy. The number of diabetics is said to be 6.9 million in Japan and more than 13 million including the reserve army, which is a serious national illness. At present, there is no complete treatment method in the treatment of diabetes, and the blood sugar level is maintained at an appropriate level by administering insulin or diet while measuring the blood sugar level.
[0003]
The current blood sugar level measurement is performed using a glucose sensor method that electrochemically quantifies the reaction of glucose oxidase to blood sugar using blood collected and converts it into a blood sugar level. Portable blood glucose meters used for daily blood glucose management are already commercially available. In such a blood glucose test, there are problems such as pain associated with blood collection several times a day and infection with a blood collection needle, and a noninvasive blood glucose measurement device that does not require blood collection and can measure the daily fluctuation of blood glucose level in real time is desired. ing.
[0004]
Therefore, the human body is irradiated with light having a wavelength in the near-infrared region, and diffuse reflected light or transmitted light from the human body is measured using a spectroscope, and the blood glucose level of the human body is determined from the spectrum of the diffuse reflected light or transmitted light. A technique to be calculated is disclosed (for example, see Non-Patent Document 1 and Patent Document 1). Non-Patent Document 1 discloses a method of irradiating light having a wavelength in the near-infrared region to the lower lip, measuring the spectrum of the diffuse reflection light from the diffuse reflection light using a spectroscope or the like, and measuring the blood glucose level from the spectrum value. Has been proposed. Patent Document 1 proposes a method of irradiating a finger or the like with light having a wavelength in the near-infrared region, detecting the transmitted light, obtaining absorbance at specific wavelengths of 944 nm and 964 nm, and measuring a blood glucose level from the values. I have.
[0005]
By the way, according to the method of Non-Patent Document 1, a complex spectroscope including a diffraction grating or the like is used to irradiate light having a wavelength in the near-infrared region to the lower lip and measure the spectrum of the diffusely reflected light. In need of. This requires reflectance data of 10 to 20 wavelengths of light to calculate the blood sugar level, and for this purpose, irradiates the human body with light from a white light source having light in wavelengths in these regions, To obtain the reflection spectrum, the above-mentioned spectroscope is required. With such a method of measuring blood glucose level based on a white light source or a spectroscope, it is difficult to make a small and portable blood glucose level measuring apparatus that is easy to carry in order for a diabetic patient to perform daily blood glucose level management.
[0006]
On the other hand, Patent Literature 1 proposes an apparatus that uses two specific wavelengths of light and measures a blood glucose level using the transmitted light. This technique will be described with reference to FIG. The measuring device shown in FIG. 8 includes a light source 100 that emits near-infrared light, a diffraction grating 340 for irradiating the finger 1 with only a predetermined monochromatic light from the light, and a monochromatic light 101 that has been dispersed. ND filter 390 and photodetector 380 for detecting a part of. Further, a lens 50 and a photodetector 51 for detecting the transmitted light 102 from the human finger 1, a signal processing unit 230 for amplifying and digitizing detection signals from the photodetectors 51 and 380, and central control A section 200 is provided. The central control unit 200 calculates the transmittance T of the finger 1 based on the detection signals from the photodetectors 51 and 380 that have been amplified and digitized by the signal processing unit 230 using the following equation.
T = I ₁ / I ₀ (1.1)
[0007]
Here, I ₀ is the irradiation light amount of the illumination light 101, is calculated by multiplying a predetermined number of detection signals detected by the optical detector 380. The I ₁ is calculated by multiplying a predetermined number of detection signals detected by the detector 51 in the amount of transmitted light 102. Here, two wavelengths of 944 nm and 964 nm are selected as the wavelength of the irradiation light 101, and the blood glucose level C is calculated by the following equation, with the transmittances for the respective wavelengths being T ₁ and T ₂ , respectively.
C = k ₀ + k ₀ * ABS ₁ / ABS ₂ (1.2)
[0008]
Here, ABS ₁ = −In (T ₁ ) and ABS ₂ = −In (T ₂ ) are represented. K ₀ and k ₁ indicate coefficients determined by the least-squares method using actually measured blood sugar levels. Here, a white light source is used as the light source. However, if a semiconductor laser of 944 nm and 964 nm can be used for the two different wavelengths, blood glucose that does not require a complicated spectroscope including a diffraction grating or the like is used. A non-invasive measurement device of the value can be realized.
[0009]
However, in the invention of the prior application, the linear distance r ₁ between the irradiation position P ₀ of the irradiation light 101 and the detection position P ₁ of the transmitted light 102 slightly changes depending on the size of the finger 1. There is a problem that a measurement error that cannot be ignored in the calculation of the blood sugar level C by the above equation occurs for the slight change amount.
[0010]
[Non-patent document 1]
H. M. Heise, et al. , Artifical Organs, 18 (6) pp. 439-47, 1994
[Patent Document 1]
JP-A-5-176917
[Problems to be solved by the invention]
The problem to be solved by the present invention is to solve the conventional problems and to provide a small and portable non-invasive blood glucose level measuring device capable of non-invasively measuring the blood glucose level of a human body without error. is there.
[0012]
[Means for Solving the Problems]
The configuration of the present invention that has solved such a problem includes:
1) Irradiation means for irradiating light having a plurality of different wavelengths to a measurement site of the human body is provided, and the light of the irradiation means receives transmitted light transmitted through the measurement site of the human body at two places at different distances. A transmitted light amount detecting means for detecting the transmitted light amount is provided, and a relative transmittance, which is a ratio of a transmitted light amount of the same wavelength at two places detected by the transmitted light amount detecting means, is calculated for each wavelength, and a relative transmittance of each wavelength is calculated. Non-invasive measuring device for blood glucose level provided with calculating means for calculating blood sugar level of human body using degree 2) Irradiating means irradiates light of two different wavelengths, and calculating means detects at two places The shorter of the transmission distance among the respective transmitted light amounts is I1 _. _λ ₁ , I _1. _λ _2, and the longer transmission distance I _2. _λ ₁ , I _2. _λ _2, and the relative transmittances R _λ ₁ and R _λ ₂ of two different wavelengths are represented by the formula R _λ ₁ = I2 _. _λ ₁ / I _1. _λ ₁ , R _λ ₂ = I _2. _λ ₂ / I _1. _λ ₂ , the coefficients k ₀ and k ₁ of the following equation are obtained using the blood glucose level measured in advance and the relative transmittances R _λ ₁ and R _λ ₂ , and the blood glucose level C is calculated by the equation C = k ₀ + k ₁ * ln (R _λ ₁ ) / ln (R _λ ₂ ) The non-invasive blood sugar level measuring apparatus according to the above 1), wherein the irradiating means irradiates light of two different wavelengths. The means determines which one of the transmitted light amounts detected at two locations has a shorter transmission distance as I1 _. _λ ₁ , I _1. _λ _2, and the longer transmission distance I _2. _λ ₁ , I _2. _λ _2, and the relative transmittances R _λ ₁ and R _λ ₂ of two different wavelengths are represented by the formula R _λ ₁ = I2 _. _λ ₁ / I _1. _λ ₁ , R _λ ₂ = I _2. _λ ₂ / I _1. _λ _2, and based on the respective relative transmittances R _λ ₁ , R _λ ₂ , the absorbances A ₁ , A ₂ of two different wavelengths are expressed by the following formula: A ₁ = −1 n (R _λ ₁ ), A ₂ = −1 n (R _λ2 ), the coefficients k ₀ and k ₁ of the following equation are obtained using the blood sugar level and the absorbances A ₁ and A ₂ measured in advance, and the blood sugar level C is calculated according to the equation C = k ₀ + k ₁ * A ₁ / A _2. The non-invasive blood glucose level measuring apparatus according to the above 1), wherein the two different wavelengths of light emitted by the irradiating means are in a near infrared region in a range of 940 to 1000 nm and a range of 1040 to 1090 nm. 5) The blood glucose level non-invasive measuring apparatus according to 2) or 3) above, which is selected from among 5) The irradiating means irradiates light of three different wavelengths, and the calculating means detects at two places. The shorter of the transmission distances of the respective transmitted light amounts I1 _. _λ ₁ , I _1. _λ ₂ , I _1. _λ _3, and the longer transmission distance is I2 _. _λ ₁ , I _2. _λ ₂ , I _2. _{Assuming that λ} ₃ , the relative transmittances R _λ ₁ , R _λ ₂ , and R _λ ₃ of the _three _wavelengths are represented by the formula R _λ ₁ = I _2. _λ ₁ / I _1. _λ ₁ , R _λ ₂ = I _2. _λ ₂ / I _1. _λ ₂ , R _λ ₃ = I2 _. _λ ₃ / I _1. _λ ₃ , the coefficients k ₀ , k ₁ of the following equation are obtained using the blood glucose level measured in advance and the relative transmittances R _λ ₁ , R _λ ₂ , R _λ ₃ , and the blood glucose level C is calculated by the equation C = k ₀ + k ₁ _{_{* ln (R λ 1 / R}} λ 3) / ln (R λ 2 / R λ 3) is obtained so as to calculate in accordance with said 1) non-invasive measuring device 6) means for irradiating blood sugar described, 3 The operation means irradiates light of two different wavelengths, and the arithmetic means determines which one of the transmitted light amounts detected at two locations has a shorter transmission distance as I1 _. _λ ₁ , I _1. _λ ₂ , I _1. _λ _3, and the longer transmission distance is I2 _. _λ ₁ , I _2. _λ ₂ , I _2. _{Assuming that λ} ₃ , the relative transmittances R _λ ₁ , R _λ ₂ , and R _λ ₃ of the _three _wavelengths are represented by the formula R _λ ₁ = I _2. _λ ₁ / I _1. _λ ₁ , R _λ ₂ = I _2. _λ ₂ / I _1. _λ ₂ , R _λ ₃ = I2 _. _λ ₃ / I _1. and _lambda _3, the respective relative transmittance _{_{_{_{R λ 1, R λ 2,}}}} R λ3 absorbance _A 1 for three different wavelengths on the basis _of, A 2, _{A 3} Equation _{_{_{A 1 = -1n (R λ 1}}} ), A _₂ = _-1n (R _{_λ2),} and _{a 3 = -1n (R λ3)} , determine the coefficients _k 0, _{k 1} of the following equation using the previously measured blood glucose level and the absorbance _{_{_{a 1, a 2, a 3}}} , The blood glucose level non-invasive measuring device 7) according to 1), wherein the blood glucose level C is calculated according to the formula: C = k ₀ + k ₁ * (A ₁ −A ₃ ) / (A ₂ −A ₃ ). The light of three different wavelengths irradiated by the irradiation means, two of which are selected from the near infrared region in the range of 940 to 1000 nm and 1040 to 1090 nm, and the other one is 910 to 930 nm or The above 5 which is selected from the near infrared region in the range of 1010 to 1030 nm ) Or 6).
[0013]
BEST MODE FOR CARRYING OUT THE INVENTION
In the present invention, a plurality of monochromatic lights having different wavelengths are generated from a light source, and the measurement unit (for example, a finger) of a human body is irradiated with the monochromatic lights by an irradiation unit. The irradiated monochromatic light is scattered and absorbed inside the human body, and radiated outside the human body to become transmitted light. The transmitted light is detected by the transmitted light amount detecting means at different linear distances from the irradiation position of the monochromatic light. A relative transmittance, which is a ratio between the two detected transmitted lights, is calculated for each wavelength, and a blood sugar level of a human body is calculated from the relative transmittance. The detected transmitted light contains blood sugar level information inside the human body, which enables non-invasive measurement of the blood sugar level of the human body.
[0014]
In addition, by using two or three monochromatic light sources as light sources, there is a device that does not require a complicated spectroscope for detecting a transmitted or reflected light spectrum like a conventional blood glucose measurement device using a white light source. realizable. Furthermore, even if the linear distance between the irradiation position of the monochromatic light and the detection position of the transmitted light changes depending on the size of the finger that is the measurement site, the influence of the blood sugar level on the measurement error of the blood sugar level is reduced. An invasive measurement device can be realized.
[0015]
Note that the amount of transmitted light I1 _. _λ ₁ , I _2. _lambda _1, and in each symbol relative transmittance R _lambda _{_1,} numerals I 1, _{I 2} represents the detected _{_{position, λ 1, λ 2, λ}} 3 are those showing the kinds of wavelengths. Hereinafter, embodiments of the present invention will be specifically described with reference to the drawings.
[0016]
【Example】
Example 1 (see FIGS. 1 and 2): The blood glucose level measuring device of Example 1 shown in FIG. 1 includes light sources 10 and 20 for irradiating irradiation light 11 and 21 to a finger 1, a reflecting prism 40, and a lens 41. Is provided. Further, a transmitted light amount detecting means I comprising a lens 50 for detecting the transmitted lights 12 and 22 from the finger 1 and a photodetector 51, a lens 60 for detecting the transmitted lights 13 and 23, and a photodetector 61. And a signal processing unit 230, a central control unit 200, a display unit 210, and a light source control unit 220.
[0017]
The central control unit 200 calculates the blood sugar level of a human body by a calculation formula described later based on the detection signals from the photodetectors 51 and 61 digitized by the signal processing unit 230, and displays the blood sugar level on the display unit 210. The light source control unit 220 has a power supply and a switch unit (not shown) for supplying current to the light sources 10 and 20. When the trigger signal T ₁₀ (T ₂₀ ) is input from the central control unit 200 to the switch unit, the switch unit is turned on in synchronization with the rise of the trigger signal T ₁₀ (T ₂₀ ), and the current is supplied to the light source 10 (light source 20). Is supplied.
[0018]
The operation of the non-invasive blood sugar level measuring device having the above configuration will be described. First, a trigger signal T ₁₀ transmitted from the central control unit 200 becomes High, ON next in synchronization with the rise of the switch unit is a trigger signal T ₁₀ (not shown) of the light source control unit 220, a current is supplied to the light source 10 Irradiation light 11 is generated. On the other hand, the trigger signal T ₂₀ is a left Low, monochromatic light 21 current is not supplied to the light source 20 is not generated.
[0019]
Next, the irradiation light 11 emitted from the light source 10 passes through the prism 40 and is irradiated on the finger 1 by the lens 41. The irradiation light 11 is scattered and absorbed inside the finger 1 and radiates in all directions outside the finger 1. It becomes transmitted light. Thereafter, the transmitted light 12 from the position P ₁ on the finger 1, which is a linear distance r ₁ away from the irradiation position P _{0 of the} irradiation light 11, is collected on the light receiving surface of the photodetector 51 by the lens 50, and the irradiation of the irradiation light 11 The transmitted light 13 from the position P ₂ on the finger 1 that is a linear distance r ₂ away from the position P ₀ is collected by the lens 60 on the light receiving surface of the photodetector 61. In FIG. 1, r ₁ <r ₂ and photodiodes are used for the photodetectors 51 and 61.
[0020]
Detection signals proportional to the light intensities of the transmitted lights 12 and 13 are output from the photodetectors 51 and 61, respectively, are digitized by the signal processing unit 230, and based on the detection signals, the central control unit 200 described later. relative permeability R _lambda ₁ is calculated by the calculation formula. When calculating operation of a relative transmittance R _lambda ₁ is completed, the trigger signal _{T 10} Low, also the trigger signal _{T 20} becomes High. The light source 10 is turned off (turned off) and the light source 20 is turned on (turned on) by opening and closing a switch unit (not shown) in the light source control unit 220 based on the trigger signal T ₁₀ (T ₂₀ ).
[0021]
Then, in analogy to the procedure calculates the relative transmittance R _lambda ₁ by irradiation light 11 described above, the calculation of the relative transmittance R _lambda ₂ by the irradiation light 21 is performed. Trigger signal _T 10 the calculating operation of the relative transmittance R _lambda ₂ by the irradiation light 21 is _{completed, T 20} are both Low, and the light source 10 and 20 OFF (dark) by blood glucose measurement tasks of the finger 1 is completed both . The central control unit 200 calculates the blood glucose level of the finger 1 from the calculated relative transmittances R _λ ₁ , R _λ ₂ using a calculation formula described later, and displays the result on the display unit 210.
[0022]
Next, a method of calculating the relative transmittances R _λ ₁ and R _λ ₂ performed by the central control unit 200 will be described. The light amounts of the irradiation light 11 and the transmission lights 12 and 13 for each wavelength are respectively set to I _0. _λ ₁ , I _1. _λ ₁ , I _2. and _{λ _1.} Relative permeability R _lambda ₁ of the finger 1 with respect to the irradiation light 11 is represented by the following formula.
R _λ ₁ = I _2. _λ ₁ / I _1. _λ ₁ ... (1.3)
[0023]
Assuming that the light quantity-voltage conversion coefficients in the photodetectors 51 and ₆₁ are β ₅₁ and β ₆₁ , detection signals (voltages) V ₅₁ and V ₆₁ detected by the photo detectors ₅₁ and ₆₁ are represented by the following equations.
V ₅₁ = β ₅₁ * I _1. _λ ₁ ... (1.4)
V ₆₁ = β ₆₁ * I _2. _λ ₁ ... (1.5)
[0024]
From the above equations, the relative transmittance R _λ ₁ of the finger 1 is calculated by the following equation, and the light amount I _0. It is expressed in a manner independent of _λ ₁ .
_{_{_{R λ 1 = (β 51 /}}} β 61) * V 61 / V 51 ··· (1.6)
[0025]
Here, the values in parentheses are constants unique to the blood sugar level measuring device, and can be easily calibrated using a light source whose light amount is known. Can calculate the relative transmittance R _lambda ₂ of the finger 1 with respect to the irradiation light 21 obtained in the same manner as the relative transmittance R _lambda ₁ of the finger 1 with respect to the irradiation light 11. Blood sugar level C of the finger 1 is calculated by the following equation using the calculated relative transmittance R λ _1, R λ _{_{_2.}}
C = k ₀ + k ₁ * ln ( _Rλ ₁ ) / ln ( _Rλ ₂ ) (1.7)
[0026]
Here, k ₀ and k ₁ indicate coefficients determined by the least square method using the actually measured blood glucose level. In the first embodiment, the two different wavelengths for performing the blood sugar level estimation are wavelengths selected from a range of 940 to 1000 nm and a range of 1040 to 1090 nm, respectively.
[0027]
Note that lasers can be used as the light sources 10 and 20 that emit the irradiation lights 11 and 21 in the above-described wavelength range. If a semiconductor laser is used as this laser, a small-sized blood sugar level measuring device can be realized. Further, a light emitting element such as a light emitting diode can be used for the light sources 10 and 20. When a white light source that continuously emits light having a wavelength in the near-infrared region is used for the light sources 10 and 20, this is realized by using an optical filter that transmits light from the light sources 10 and 20 only at the wavelengths described above. Is also good. Further, as shown in FIG. 2, irradiation light 11 and 21 from light sources 10 and 20 are irradiated on finger 1 using optical fiber 700, and transmitted light 12 and 13 from detection points P ₁ and P ₂ on finger 1 are further transmitted. (22, 23) may be guided to the transmitted light amount detecting means I, II using optical fibers 701, 702.
[0028]
Embodiment 2 (see FIG. 3): Embodiment 2 shown in FIG. 3 is an example of a non-invasive blood glucose level measuring device using three wavelengths. The blood glucose level measuring device according to the second embodiment shown in FIG. 3 includes light sources 10, 20, 30 for irradiating irradiation light 11, 21, 31, 31 to the finger 1, lenses 410, 420, 430, optical fibers 710, 720, 730 and an optical fiber 700 for bundling the optical fibers 710, 720, 730 and irradiating the finger 1 with irradiation light 11, 21, 31. Also, a transmitted light amount detecting means I composed of an optical fiber 701, a lens 50, and a photodetector 51 for detecting the transmitted light 12, 22, 32 from the finger 1, and for detecting the transmitted light 13, 23, 33. , A transmitted light amount detecting means II including an optical fiber 702, a lens 60, and a photodetector 61, and a signal processing unit 230, a central control unit 200, a display unit 210, and a light source control unit 220.
[0029]
The central control unit 200 calculates the blood glucose level of the human body based on the detection signals from the photodetectors 51 and 61 digitized by the signal processing unit 230 using a calculation formula described later, and displays the blood sugar level on the display unit 210. The light source control unit 220 has a power supply and a switch unit (not shown) for supplying current to the light sources 10, 20, and 30. When the trigger signal _T 10 from the central control unit 200 _{_(T 20,} T ₃₀₎ is inputted to the switching unit, the switch unit is turned ON in synchronization with the rising edge of the trigger signal _{_{_{T 10 (T 20, T 30}}} ), the light source 10 (Light source 20, light source 30) is supplied with electric current. The relative transmittances R _λ ₁ , R _λ ₂ , R _λ ₃ of the finger 1 corresponding to the irradiation lights 11, 21, 31 can be calculated in the same procedure as in the first embodiment. The blood sugar level C of the finger 1 is calculated by the following equation using the calculated relative transmittances R _λ ₁ , R _λ ₂ , and R _λ ₃ .
_{_{C = k 0 + k 1 *}} ln (R λ 1 / R λ 3) / ln (R λ 2 / R λ 3) ··· (1.8)
[0030]
Here, k ₀ and k ₁ indicate coefficients determined by the least square method using the actually measured blood glucose level. In Example 2, the irradiation light 11 or 21 is selected from the range of 940 to 1000 nm and the range of 1040 to 1090 nm as three different wavelengths for performing the blood sugar level measurement using the formula (1.8). The remaining irradiation light 31 has a wavelength selected from the range of 910 to 930 nm or 1010 to 1030 nm.
[0031]
Third Embodiment (see FIG. 4): In the first and second embodiments, the light to be irradiated on the human body is limited to two or three monochromatic lights having different wavelengths. This makes it possible to realize a device that does not require a complicated spectroscope for detecting a transmitted or reflected light spectrum, unlike a conventional blood glucose level measuring device using a white light source. Further, even if the linear distance between the irradiation position of monochromatic light and the detection position of transmitted light changes depending on the size of the measurement site such as a finger, the influence of the blood glucose level on the measurement error of the blood glucose level is reduced. An invasive measurement device can be realized.
[0032]
On the other hand, even in a conventional non-invasive blood glucose measurement device using a white light source and a spectroscope, the linear distance between the irradiation position of monochromatic light and the detection position of transmitted light depends on the size of the measurement site such as a finger. Even if it changes, the influence on the measurement error of the blood sugar level can be reduced. An example in which the present invention is applied to a conventional non-invasive blood sugar level measuring apparatus using a white light source and a spectroscope will be described with reference to FIG.
[0033]
The non-invasive blood sugar level measuring apparatus shown in FIG. 4 includes a white light source 100 such as a halogen lamp including light having a wavelength in the near-infrared region and a power supply 110. The light 101 from the light source 100 is transmitted through a lens 120 and an optical fiber 700. Irradiate finger 1 through The light 101 applied to the finger 1 is scattered / absorbed inside the finger 1 and emitted in all directions outside the finger 1 to be transmitted light. The transmitted light 102, 103 from the positions P ₁ , P ₂ on the finger 1 at linear distances r ₁ , r ₂ from the irradiation position P ₀ of the light 101 on the finger 1 by the optical fiber 700, and the spectroscope 300 by the optical fibers 701, 702. To light.
[0034]
The spectroscope 300 includes lenses 310 and 320, shutters 311 and 321, a prism 330, a diffraction grating 340, and a multi-channel detector 350. As the multi-channel detector 350, a linear array sensor such as a CCD is used. When measuring the transmission spectrum of the transmitted light 102 emitted from the position P ₁ , the shutter 311 is opened, and the transmission spectrum S ₁ of the transmitted light 102 is obtained on the multi-channel detector 350. In this case, the shutter 321 is closed. When measuring the transmission spectrum _{S 2} of transmitted light 103 emitted from the position _{P 2} in the same manner, the shutter 321 is opened, the transmission spectrum _{S 2} of transmitted light 103 onto the multi-channel detector 350 is obtained. In this case, the shutter 311 is closed. A transmittance spectrum T = S ₂ / S ₁ is calculated from the transmission spectra S ₁ and S ₂ measured as described above. From the obtained transmittance spectrum, the blood sugar level C can be calculated according to the above equations.
[0035]
The results of examining the non-invasive blood glucose level measurement method of each example are shown in FIGS. FIG. 5 shows that a glucose solution placed in a transparent quartz cell container is irradiated with monochromatic light of various wavelengths, its transmittance spectrum T is calculated, and the correlation coefficient between the absorbance ratio γ calculated by the following equation and the sugar concentration is shown. The combination region of the wavelengths satisfying the square value R ² > 0.995 is indicated by oblique lines.
γ = ln (T (λ ₁ )) / ln (T (λ ₂ )) (1.9)
[0036]
From FIG. 5, it can be seen that the region in which the range of 940 to 1000 nm and the range of 1040 to 1090 nm are surrounded by a square is an optimal combination of wavelengths for estimating the sugar concentration by the absorbance ratio γ.
[0037]
On the other hand, for a scatterer such as a human body, the optimum combination of wavelengths obtained with an aqueous glucose solution holds as it is. FIG. 6 is a theoretical analysis of the correlation between the absorbance ratio γ and the sugar concentration of a scatterer simulating a human body, when the non-invasive measurement device shown in FIG. 1 is used to perform a theoretical analysis, and the square value R ^{2 of the} correlation coefficient> The combination region of the wavelength of 0.995 is shown by oblique lines. The theoretical analysis was performed with reference to the document “A. Ishimaru: Wave Propagation and Scattering in Random Media, Academic Press, New York (1978)”. In the theoretical calculation here, the linear distances r ₁ and r ₂ in FIG. 1 were set to 15 mm and 25 mm, respectively. The equivalent scattering coefficient is constant regardless of the glucose concentration and the wavelength, and here, a general value of the human body of 1.0 mm ^-1 (reference: mechanical theory, 59, 561B (1993), PP. 338-340) was used. In addition, the absorption coefficient depending on the wavelength and the glucose concentration was obtained from the result of measurement using an aqueous glucose solution. FIG. 6 shows that the correlation between the absorbance ratio γ and the sugar concentration is high in the same combination of wavelengths as in the aqueous solution.
[0038]
Next, FIG. 7 shows the result of analyzing the measurement error of the blood sugar level when the thickness of the finger 1 is changed in FIG. 2 in the blood sugar level measuring devices described in the first and second embodiments. Here, the distance between the transmitted light detection positions P ₁ and P ₂ was fixed at 20 mm. The measurement error of the blood sugar level on the vertical axis is represented by a relative value with respect to the measurement error of the blood sugar level with respect to the change in the thickness of the finger 1 of 0.1 mm in the conventional technique. It can be seen that in Example 1, the measurement error of the blood glucose level was reduced to about 1/10 as compared with the prior art, and in Example 2, the measurement error of the blood glucose level was reduced to about 1/100 as compared to the conventional technique.
[0039]
【The invention's effect】
As described above, according to the present invention, a human body is irradiated with a plurality of monochromatic lights having different specific wavelengths, and the transmitted light is detected at positions having different linear distances from the irradiation position of the monochromatic light. The detected transmitted light contains blood sugar level information inside the human body, and the blood sugar level of the human body can be measured. In addition, a device that does not require a complicated spectroscope for detecting a transmitted or reflected light spectrum, such as a conventional blood glucose level measuring device using a white light source, can be realized, and a small semiconductor laser or the like is used as a light source. Therefore, a small and lightweight blood glucose measuring device can be realized. Furthermore, even if the linear distance between the irradiation position of monochromatic light and the detection position of transmitted light changes depending on the size of the measurement site such as a finger, the influence of the blood glucose level on the measurement error of the blood glucose level is reduced. An invasive measurement device can be realized.
[Brief description of the drawings]
FIG. 1 is an explanatory diagram of a non-invasive blood sugar level measuring device according to a first embodiment.
FIG. 2 is an explanatory diagram of a noninvasive blood sugar level measuring device using an optical fiber according to another example of the first embodiment.
FIG. 3 is an explanatory diagram of a non-invasive blood sugar level measuring device according to a second embodiment.
FIG. 4 is an explanatory view of a non-invasive blood sugar level measuring apparatus according to a third embodiment.
FIG. 5 is a diagram showing an optimum wavelength combination region in an aqueous glucose solution.
FIG. 6 is a diagram showing an optimum wavelength combination region in a scatterer imitating a human body.
FIG. 7 is a diagram showing a relationship between a change amount of a finger thickness and a blood sugar level measurement error.
FIG. 8 is an explanatory diagram of a conventional non-invasive blood sugar level measuring device.
[Explanation of symbols]
1 finger 10, 20, 30 light source 11, 21, 31 irradiation light 12, 13 transmission light 22, 23 transmission light 32, 33 transmission light 41 lens 50, 60 lens 40 prism 51, 61 photodetector 100 white light source 101 irradiation light 102, 103 Transmitted light 110 White light source power supply 120 Lens 200 Central control unit 210 Display unit 220 Light source control unit 230 Signal processing unit 300, 301 Spectroscope 310, 320 Lens 311, 321 Shutter 330 Prism 340 Rotation grating 350 Multi-channel detector 360 Mirror 370 Sample prism 380 Photodetector 390 ND filter 410, 420, 430 Lens 700, 701, 702 Optical fiber 710, 720, 730 Optical fiber

Claims

Irradiation means for irradiating light having a plurality of different wavelengths to the measurement site of the human body is provided, and the light of the irradiation means receives the transmitted light transmitted through the measurement site of the human body at two places at different distances, and the transmitted light amount Is provided, and the relative transmittance, which is the ratio of the amount of transmitted light of the same wavelength at two locations detected by the transmitted light amount detector, is calculated for each wavelength, and the relative transmittance of each wavelength is calculated. A non-invasive blood sugar level measuring device provided with an arithmetic means for calculating a blood sugar level of a human body using the same.

The irradiating means irradiates light of two different wavelengths, and the calculating means determines which one of the transmitted light amounts detected at two locations has a shorter transmission distance as I1 _. _λ ₁ , I _1. _λ _2, and the longer transmission distance I _2. _λ ₁ , I _2. _λ _2, and the relative transmittances R _λ ₁ and R _λ ₂ of two different wavelengths are represented by the formula R _λ ₁ = I2 _. _λ ₁ / I _1. _λ ₁ , R _λ ₂ = I _2. _λ ₂ / I _1. _λ ₂ , the coefficients k ₀ and k ₁ of the following equation are obtained using the blood glucose level measured in advance and the relative transmittances R _λ ₁ and R _λ ₂ , and the blood glucose level C is calculated by the equation C = k ₀ + k ₁ * ln (R _2. The non-invasive blood sugar level measuring apparatus according to claim 1, wherein the blood glucose level is calculated according to [ _lambda] ₁ ) / ln (R [ _lambda] ₂ ).

The irradiating means irradiates light of two different wavelengths, and the calculating means determines which one of the transmitted light amounts detected at two locations has a shorter transmission distance as I1 _. _λ ₁ , I _1. _λ _2, and the longer transmission distance I _2. _λ ₁ , I _2. _λ _2, and the relative transmittances R _λ ₁ and R _λ ₂ of two different wavelengths are represented by the formula R _λ ₁ = I2 _. _λ ₁ / I _1. _λ ₁ , R _λ ₂ = I _2. _λ ₂ / I _1. _λ _2, and based on the respective relative transmittances R _λ ₁ , R _λ ₂ , the absorbances A ₁ , A ₂ of two different wavelengths are expressed by the following formula: A ₁ = −1 n (R _λ ₁ ), A ₂ = −1 n (R _λ2 ), the coefficients k ₀ and k ₁ of the following equation are obtained using the blood sugar level and the absorbances A ₁ and A ₂ measured in advance, and the blood sugar level C is calculated according to the equation C = k ₀ + k ₁ * A ₁ / A _2. The non-invasive blood sugar level measuring device according to claim 1, wherein

The non-invasive blood glucose level non-invasive according to claim 2 or 3, wherein the two different wavelengths of light emitted by the irradiating means are selected from a near infrared region in a range of 940 to 1000 nm and a range of 1040 to 1090 nm. measuring device.

The irradiating means irradiates light of three different wavelengths, and the calculating means determines the shorter one of the transmitted light amounts of the transmitted light amounts detected at two points in I1 _. _λ ₁ , I _1. _λ ₂ , I _1. _λ _3, and the longer transmission distance is I2 _. _λ ₁ , I _2. _λ ₂ , I _2. _{Assuming that λ} ₃ , the relative transmittances R _λ ₁ , R _λ ₂ , and R _λ ₃ of the _three _wavelengths are represented by the formula R _λ ₁ = I _2. _λ ₁ / I _1. _λ ₁ , R _λ ₂ = I _2. _λ ₂ / I _1. _λ ₂ , R _λ ₃ = I2 _. _λ ₃ / I _1. _λ ₃ , the coefficients k ₀ , k ₁ of the following equation are obtained using the blood glucose level measured in advance and the relative transmittances R _λ ₁ , R _λ ₂ , R _λ ₃ , and the blood glucose level C is calculated by the equation C = k ₀ + k ₁ _{_{* ln (R λ 1 / R}} λ 3) / ln (R λ 2 / R λ 3) non-invasive measuring device for blood glucose level according to claim 1, wherein is obtained so as to calculate in accordance with.

The irradiating means irradiates light of three different wavelengths, and the calculating means determines the shorter one of the transmitted light amounts of the transmitted light amounts detected at two points in I1 _. _λ ₁ , I _1. _λ ₂ , I _1. _λ _3, and the longer transmission distance is I2 _. _λ ₁ , I _2. _λ ₂ , I _2. _{Assuming that λ} ₃ , the relative transmittances R _λ ₁ , R _λ ₂ , and R _λ ₃ of the _three _wavelengths are represented by the formula R _λ ₁ = I _2. _λ ₁ / I _1. _λ ₁ , R _λ ₂ = I _2. _λ ₂ / I _1. _λ ₂ , R _λ ₃ = I2 _. _λ ₃ / I _1. and _lambda _3, the respective relative transmittance _{_{_{_{R λ 1, R λ 2,}}}} R λ3 absorbance _A 1 for three different wavelengths on the basis _of, A 2, _{A 3} Equation _{_{_{A 1 = -1n (R λ 1}}} ), A _₂ = _-1n (R _{_λ2),} and _{a 3 = -1n (R λ3)} , determine the coefficients _k 0, _{k 1} of the following equation using the previously measured blood glucose level and the absorbance _{_{_{a 1, a 2, a 3}}} , blood sugar level C of the formula _{_{_{_{C = k 0 + k 1 *}}}} (a 1 -A 3) / non-invasive measuring device for blood glucose level according to claim 1, wherein is obtained so as to calculate in accordance with _(a 2 -A _3).

The light of three different wavelengths irradiated by the irradiation means, two of which are selected from the near infrared region in the range of 940 to 1000 nm and 1040 to 1090 nm, and the other one is 910 to 930 nm or 7. The non-invasive blood sugar level measuring device according to claim 5, wherein the device is selected from a near infrared region in a range of 1010 to 1030 nm.