JP2011092613A - Method for obtaining information about blood glucose level - Google Patents
Method for obtaining information about blood glucose level Download PDFInfo
- Publication number
- JP2011092613A JP2011092613A JP2009251861A JP2009251861A JP2011092613A JP 2011092613 A JP2011092613 A JP 2011092613A JP 2009251861 A JP2009251861 A JP 2009251861A JP 2009251861 A JP2009251861 A JP 2009251861A JP 2011092613 A JP2011092613 A JP 2011092613A
- Authority
- JP
- Japan
- Prior art keywords
- blood glucose
- light
- polarized light
- glucose concentration
- concentration information
- 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.)
- Granted
Links
Landscapes
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
Abstract
Description
本発明は、生体における血中グルコース濃度情報の取得方法に関する。詳しくは、生体の表層組織の表面に近赤外光を照射して表層組織から拡散反射した光（拡散反射光）を分光手段を介して受光して、分光分析によって血中グルコースの濃度情報を取得する方法に関する。 The present invention relates to a method for acquiring blood glucose concentration information in a living body. Specifically, the surface of the living body tissue is irradiated with near-infrared light and diffusely reflected from the surface tissue (diffuse reflected light) is received through the spectroscopic means, and blood glucose concentration information is obtained by spectroscopic analysis. On how to get.
従来より、血中グルコース濃度の測定は、通常、指先を穿刺して実際に採血し、この血液を分析することにより血液中に含まれるグルコースの濃度（以下、単に血中グルコース濃度という）を測定することにより行われている。しかし、穿刺には痛みを伴うため、短い間隔で血中グルコース濃度をモニタする必要のある患者に対して、１日に何回も測定を強要するのは困難な状況にある。 Conventionally, blood glucose concentration is usually measured by puncturing a fingertip and actually collecting blood and analyzing the blood to measure the concentration of glucose contained in the blood (hereinafter simply referred to as blood glucose concentration). Is done by doing. However, since puncture is painful, it is difficult to force a measurement several times a day for a patient who needs to monitor blood glucose concentration at short intervals.
一方、このような欠点を有する上記侵襲型（侵入型）の測定に代えて、近赤外分光分析法を用いた、痛み等を伴わない非侵襲型（非侵入型）の測定方法が提案されている。 On the other hand, instead of the invasive (intrusive) measurement having the above-mentioned drawbacks, a non-invasive (non-intrusive) measuring method without pain or the like using near infrared spectroscopy is proposed. ing.
ここで、近赤外分光分析法とは、近赤外光を物質に照射し、透過あるいは反射した光のスペクトルより分析を行う手法であり、農業分野をはじめ様々な分野で利用されている。特に最近では、生体分野において非侵襲型の分析手法として注目されている。この近赤外分光分析法は、エネルギーの低い電磁波を用いるので試料を損傷することがなく、固体、液体、気体など様々な状態の試料に適用することが可能である。また、赤外光に比べて近赤外光では水の吸収強度が弱くなるので、水溶液での分析に適するなどの利点を有しており、血中グルコース濃度等の生体情報の定量・定性分析を非侵襲で行うことが可能である。 Here, the near-infrared spectroscopic analysis method is a technique for irradiating a substance with near-infrared light and analyzing from the spectrum of transmitted or reflected light, and is used in various fields including the agricultural field. In particular, it has recently attracted attention as a non-invasive analysis method in the biological field. This near-infrared spectroscopic analysis method uses an electromagnetic wave having low energy, so that the sample is not damaged and can be applied to samples in various states such as solid, liquid, and gas. In addition, the near-infrared light absorbs less water than the infrared light, so it has the advantage of being suitable for analysis in aqueous solutions. Quantitative and qualitative analysis of biological information such as blood glucose concentration Can be performed non-invasively.
しかし、近赤外光を用いる場合、吸収シグナルはグルコースの高調波を扱うために赤外光に比べて非常に微弱である上、バンドの帰属が明確でないという欠点を有しており、このために近赤外分光分析にはその定量・定性のためにいわゆるケモメトリクスと称される手法が用いられている。これは、多変量解析手法や統計的解析手法を用いて化学分析を行う手法で、コンピュータの発達とともに発展し、最近の近赤外分光分析では主成分分析あるいはＰＬＳ回帰分析といった多変量解析手法を用いて行われることが多い。 However, when using near-infrared light, the absorption signal is very weak compared to infrared light in order to handle the harmonics of glucose, and has the disadvantage that the band assignment is not clear. In the near-infrared spectroscopic analysis, a technique called so-called chemometrics is used for quantification and qualification. This is a method of performing chemical analysis using multivariate analysis methods and statistical analysis methods, and has evolved with the development of computers. In recent near infrared spectroscopy, multivariate analysis methods such as principal component analysis or PLS regression analysis have been developed. Often used.
ところで、人間の皮膚組織構造は、角質層を含む表皮層（表皮組織）、真皮層（真皮組織）、皮下組織層（皮下組織）の三層で構成される。真皮層には毛細血管、リンパ、神経組織が発達している。皮下組織層は主に脂肪組織で構成される。グルコースは水溶性のため脂肪組織中には存在しにくい。また、表皮層には毛細血管が発達していないため、血液で輸送されるグルコースが到達しにくい。そのため、血糖値の測定を皮膚の近赤外吸収スペクトル測定を用いて行うためには、真皮層の近赤外吸収スペクトルを測定する必要がある。 By the way, the human skin tissue structure is composed of three layers including an epidermis layer (skin tissue) including a stratum corneum, a dermis layer (dermis tissue), and a subcutaneous tissue layer (subcutaneous tissue). Capillaries, lymph, and nervous tissue develop in the dermis layer. The subcutaneous tissue layer is mainly composed of adipose tissue. Glucose is not soluble in adipose tissue due to its water solubility. In addition, since capillaries are not developed in the epidermis layer, glucose transported by blood is difficult to reach. Therefore, in order to measure the blood glucose level using the near infrared absorption spectrum measurement of the skin, it is necessary to measure the near infrared absorption spectrum of the dermis layer.
ここで、特許文献１には、「生体の表層組織表面に光を照射して表層組織からの反射光を分光手段を介して受光して分光分析によって生体情報を得るにあたり、生体の表層組織表面に照射する光として直線偏光の光を用いるとともに、偏光角可変とした偏光板を介して上記反射光の受光を行ってスペクトル分布を求め、該偏光角が異なるスペクトル分布に基づいて上記表層組織への上記光の到達深度を解析し、この解析結果に応じて上記偏光板の偏光角を設定して分光分析のための光を受光することを特徴とする光学的生体情報測定方法。」が記載されており、発明の効果として「本発明に係る光学的生体情報測定方法は、偏光角が異なるスペクトル分布に基づいて表層組織への光の到達深度を解析するものであり、この解析結果から適切な深度からの反射光（透過光）を得られる偏光角に偏光板をセットした状態で分光分析することから、求める深度からの反射光を基にした生体情報の測定を行うことができる。しかも、生体に対しては単に光の照射と反射光の受光を行うだけで人体に対して非接触で構成することができ、接触圧等の影響を受けることがない。」とある。 Here, Patent Document 1 states that “in order to obtain biological information by spectroscopic analysis by irradiating light on the surface tissue of a living body and receiving reflected light from the surface tissue through a spectroscopic means, In addition to using linearly-polarized light as the light to be radiated, the reflected light is received through a polarizing plate having a variable polarization angle to obtain a spectrum distribution, and the surface layer structure is obtained based on the spectrum distribution having a different polarization angle. The optical living body information measuring method characterized by analyzing the depth of arrival of the light and receiving the light for spectroscopic analysis by setting the polarization angle of the polarizing plate according to the analysis result. As an effect of the invention, the optical biological information measuring method according to the present invention analyzes the depth of light reaching the surface tissue based on the spectral distributions with different polarization angles. Na Since the spectroscopic analysis is performed in a state where the polarizing plate is set at the polarization angle at which the reflected light (transmitted light) can be obtained, the biological information can be measured based on the reflected light from the desired depth. The living body can be configured to be non-contact with the human body simply by irradiating light and receiving reflected light, and is not affected by contact pressure or the like. "
しかし、上記従来の光学的生体情報測定（取得）方法では、非侵襲で血中グルコース濃度情報を得ることができるものの、感度の面で改善する必要があった。 However, although the conventional optical biological information measurement (acquisition) method can obtain blood glucose concentration information non-invasively, it needs to be improved in terms of sensitivity.
本発明は、上述の事柄に留意してなされたものであって、非侵襲で且つ感度よく血中グルコース濃度情報を取得する方法を提供することを目的とする。 The present invention has been made in consideration of the above-described matters, and an object of the present invention is to provide a method for acquiring blood glucose concentration information non-invasively and with high sensitivity.
上記課題を解決するために、本発明の血中グルコース濃度情報の取得方法は、交流用ハロゲンランプからの発光を回転自在に設置された半波長板に透過させ、この半波長板を透過した透過光を直線偏光とした後、この直線偏光の光を被照射面である生体の表層組織の表面に対してＳ偏光の光で、かつ入射角が概ね４５°になるように照射し、生体の表層組織からの拡散反射光のうちＰ偏光の光を取り出して分光分析して血中グルコース濃度情報を得る、血中グルコース濃度情報の取得方法であって、生体の表層組織の表面に照射されるＳ偏光の光がグルコース吸収帯（グルコース吸収波長帯）で最大強度となるように、半波長板の回転角度を予め設定しておくことを特徴とする。
ここで、交流用ハロゲンランプからの発光を２０〜３０ｍｍ２の面積ビームとしたものを半波長板に透過させることが好ましい。また、半波長板は、概ね１５００ｎｍに中心を置くものを用いることが好ましい。
In order to solve the above-described problem, the blood glucose concentration information acquisition method of the present invention transmits light emitted from an AC halogen lamp through a half-wave plate that is rotatably installed, and transmits through the half-wave plate. After making the light into linearly polarized light, this linearly polarized light is irradiated onto the surface of the surface tissue of the living body, which is the surface to be irradiated, with S-polarized light so that the incident angle is approximately 45 °. A method for acquiring blood glucose concentration information, in which P-polarized light out of diffusely reflected light from a surface tissue is extracted and spectrally analyzed to obtain blood glucose concentration information, which is irradiated on the surface of the surface tissue of a living body The rotation angle of the half-wave plate is set in advance so that the S-polarized light has the maximum intensity in the glucose absorption band (glucose absorption wavelength band).
Here, it is preferable to transmit the light emitted from the AC halogen lamp into an area beam of 20 to 30 mm 2 through the half-wave plate. Moreover, it is preferable to use a half-wave plate whose center is approximately 1500 nm.
この血中グルコース濃度情報の取得方法は、ハロゲンランプのなかでも水の吸収帯に対する発光光度が強く、またグルコース吸収帯の発光光度も強い交流用のハロゲンランプを光源に用いているため、直流用ハロゲンランプを用いた場合と比較して感度が向上する。
また、交流用ハロゲンランプからの発光を直線偏光（Ｓ偏光）とするため、グルコース吸収帯の偏光による損失を抑えることができ、より感度が向上する。
さらに、Ｓ偏光の光を生体の表層組織の表面に照射するため、構造的に皮膚表面と平行成分からなる表層組織から屈折率の変化を受けにくくＰ偏光を用いた場合よりも散乱が少なくなり、より感度が向上する。
加えて、入射角が概ね４５°であるため、表層組織の深い部分（真皮層）まで光が潜って戻ることにより、より感度が向上する。
さらに加えて、表層組織からの反射光のうちＰ偏光を取り出して、表面または表面浅部から反射された光を除いて分光分析することにより、皮膚から深い部分（真皮層）の情報を選択的に取り込むことができ、より感度が向上する。
またさらに加えて、生体の表層組織の表面に照射されるＳ偏光の光が、グルコース吸収帯（域）で最大強度となるように前記半波長板の回転角度を予め設定しておくことで、より感度が向上する。
なお、交流用ハロゲンランプからの発光を、ファイバ出射光でなく、２０〜３０ｍｍ２のの面積ビームとすることで、グルコース量の積分効果により、感度が向上する。
This method of acquiring blood glucose concentration information uses a halogen lamp for alternating current with a strong light emission intensity in the water absorption band and a light emission intensity in the glucose absorption band as a light source. Sensitivity is improved compared to the case of using a halogen lamp.
In addition, since light emitted from the AC halogen lamp is linearly polarized light (S-polarized light), loss due to polarization in the glucose absorption band can be suppressed, and sensitivity is further improved.
Furthermore, since the surface of the surface tissue of the living body is irradiated with S-polarized light, scattering is less than when using P-polarized light, which is structurally less susceptible to changes in refractive index from the surface tissue composed of components parallel to the skin surface. , Improve the sensitivity more.
In addition, since the incident angle is approximately 45 °, the sensitivity is further improved by the light diving back to a deep part (dermis layer) of the surface tissue.
In addition, the P-polarized light is extracted from the reflected light from the surface tissue, and the light reflected from the surface or shallow surface is removed for spectroscopic analysis. The sensitivity can be improved.
In addition, by setting the rotation angle of the half-wave plate in advance so that the S-polarized light irradiated on the surface tissue of the living body has the maximum intensity in the glucose absorption band (region), Sensitivity is improved.
In addition, the light emission from the AC halogen lamp is not a fiber emission light but an area beam of 20 to 30 mm 2 , so that the sensitivity is improved due to the integration effect of the glucose amount.
生体の表層組織が、手の甲の表層組織である、血中グルコース濃度情報の取得方法とすることが好ましい。 It is preferable to use a blood glucose concentration information acquisition method in which the surface tissue of the living body is the surface tissue of the back of the hand.
この血中グルコース濃度情報の取得方法は、表面が凸面で滑らかであり血管が近い手の甲の表層組織の表面にＳ偏光の光を照射するため、掌や手首内側で測定するよりも設置誤差や異なる時刻におけるデータ変動が少なく感度が向上する。 This method of acquiring blood glucose concentration information irradiates the surface of the surface tissue of the back of the hand with a convex and smooth surface and close to the blood vessel with S-polarized light. Sensitivity is improved with little data fluctuation at the time.
分光分析では、主成分分析を用い、この主成分分析で得られた第三主成分に基づいて血中グルコース濃度情報を得る、血中グルコース濃度情報の取得方法とすることも好ましい。 In the spectroscopic analysis, it is also preferable to use a blood glucose concentration information acquisition method that uses principal component analysis and obtains blood glucose concentration information based on the third principal component obtained by the principal component analysis.
この血中グルコース濃度情報の取得方法は、主成分分析で得られた第三主成分に基づいて血中グルコース濃度情報を得ることによって、血中グルコース濃度の実測値とよく相関する情報を得ることができる。 This blood glucose concentration information acquisition method obtains information that correlates well with the actual measured value of blood glucose concentration by obtaining blood glucose concentration information based on the third principal component obtained by principal component analysis. Can do.
このとき、主成分分析は、概ね９００〜１７００ｎｍの波長帯を用いて行う、血中グルコース濃度情報の取得方法とすることが好ましい。 At this time, the principal component analysis is preferably a blood glucose concentration information acquisition method that is performed using a wavelength band of approximately 900 to 1700 nm.
この血中グルコース濃度情報の取得方法は、水のクラスタの間にグルコース分子が入り込んで近赤外吸収スペクトルがシフトする現象も取り込んで評価するため、従来よりも安定して血中グルコース濃度情報を得ることができる。また感度もより向上する。従来の主成分分析では、グルコースの高調波吸収帯である概ね１５００ ｎｍ〜１７００ｎｍの波長帯を用いて行われていた。 This method of acquiring blood glucose concentration information is evaluated by taking in the phenomenon that glucose molecules enter between water clusters and shifting the near-infrared absorption spectrum. Therefore, blood glucose concentration information is more stable than before. Obtainable. Moreover, the sensitivity is further improved. Conventional principal component analysis has been performed using a wavelength band of approximately 1500 nm to 1700 nm, which is a harmonic absorption band of glucose.
本発明により、非侵襲で且つ感度よく血中グルコース濃度情報を取得する方法を提供することができる。 According to the present invention, it is possible to provide a method for acquiring blood glucose concentration information non-invasively and with high sensitivity.
以下、本発明の血中グルコース濃度情報の取得方法を例示説明する。本発明は、生体の表層組織の表面に近赤外光を照射して表層組織からの反射光を分光手段を介して受光して分光分析によって血中グルコースの濃度情報を取得する方法を前提とする。そして、光源の交流用ハロゲンランプの発光は、１５００ｎｍ付近で偏光方向の違いによって２倍程度強度が異なる。これを補正するため半波長板の回転により偏光強度分布を変える。さらに透過光を偏光子で直線偏光とした後、被照射面である生体の表層組織の表面に対してＳ偏光の光で、かつ入射角が概ね４５°になるように生体の表層組織の表面に照射し、前記表層組織からの拡散反射光のうちＰ偏光の光を取り出して分光分析して血中グルコース濃度情報を得るのである。そして、予め、生体の表層組織の表面に照射されるＳ偏光の光がグルコース吸収帯で最大強度となるように半波長板の回転角度を設定しておく、血中グルコース濃度情報の取得方法である。 Hereinafter, the method for acquiring blood glucose concentration information according to the present invention will be described by way of example. The present invention presupposes a method of irradiating the surface of a living body tissue with near infrared light, receiving reflected light from the surface tissue through a spectroscopic means, and obtaining blood glucose concentration information by spectroscopic analysis. To do. The intensity of the light emitted from the AC halogen lamp, which is the light source, is about twice as large as the difference in polarization direction around 1500 nm. In order to correct this, the polarization intensity distribution is changed by rotating the half-wave plate. Further, after the transmitted light is converted into linearly polarized light by a polarizer, the surface of the living body surface tissue is irradiated with S-polarized light with respect to the surface of the living body surface tissue, which is the irradiated surface, and the incident angle is approximately 45 ° The P-polarized light out of the diffusely reflected light from the surface tissue is taken out and spectrally analyzed to obtain blood glucose concentration information. The blood glucose concentration information is acquired in advance by setting the rotation angle of the half-wave plate so that the S-polarized light applied to the surface of the surface tissue of the living body has the maximum intensity in the glucose absorption band. is there.
また、以下の実施形態はあくまで本発明を例示説明するものであって、本発明は、以下の具体的な実施形態に限定されるものではない。 The following embodiments are merely illustrative of the present invention, and the present invention is not limited to the following specific embodiments.
まず、近赤外光を発生するための光源として交流用ハロゲンランプを用いた。これは、交流用ハロゲンランプは、水の吸収帯における発光や、グルコース吸収帯（概ね１５００ ｎｍ〜１７００ｎｍ）における発光が直流用のものと比較して強いことによる。本実施形態では、１１０Ｗの交流用ハロゲンランプを用いた。 First, an AC halogen lamp was used as a light source for generating near infrared light. This is because the halogen lamp for alternating current has stronger light emission in the water absorption band and light emission in the glucose absorption band (approximately 1500 nm to 1700 nm) than that for direct current. In this embodiment, a 110 W AC halogen lamp is used.
この交流用ハロゲンランプをファンで冷却しながら発光させ近赤外光を得た。得られた近赤外光は、発光部の中心部を選択するため２５ｍｍ２（５ｍｍ×５ｍｍ）の面積ビームとした。一般に、ビーム径が大きいほどグルコース量の積分効果によって感度が高くなる。 Near-infrared light was obtained by emitting light while cooling the AC halogen lamp with a fan. The obtained near-infrared light was an area beam of 25 mm 2 (5 mm × 5 mm) in order to select the central part of the light emitting part. In general, the larger the beam diameter, the higher the sensitivity due to the integration effect of the glucose amount.
次に、交流用ハロゲンランプからの発光（面積ビーム）を回転自在に設置された半波長板に透過させて透過光を得た。ここで、測定に先立っては、詳細は後述するように、生体の表層組織の表面に照射されるＳ偏光の光の強度がグルコース吸収帯（概ね１５００ ｎｍ〜１７００ｎｍ）において最大となるように、半波長板の回転角度を予め設定しておくことになる。 Next, the light (area beam) emitted from the AC halogen lamp was transmitted through a half-wave plate that was rotatably set to obtain transmitted light. Here, prior to measurement, as will be described in detail later, the intensity of S-polarized light irradiated on the surface of the living body surface tissue is maximized in the glucose absorption band (approximately 1500 nm to 1700 nm). The rotation angle of the half-wave plate is set in advance.
次に、半波長板を透過した透過光を、グラントムソンプリズム（偏光子）を用いて直線偏光の光とした。 Next, the transmitted light that passed through the half-wave plate was converted to linearly polarized light using a Glan-Thompson prism (polarizer).
そして、この直線偏光の光を、被照射面である生体（被検体）の表層組織の表面に対してＳ偏光の光で、かつ入射角θが概ね４５°になるように、生体の表層組織の表面に照射するのである。これは、皮膚に平行な成分が多いという表皮の構造を意識したものであり、Ｓ偏光の光を用いることでケラチン繊維の影響を受けにくくなりＰ偏光を用いた場合よりも散乱が少なくなることによって、より感度が向上する。なお、入射角は、入射光線と法線のなす角度を指す。 Then, the surface tissue of the living body is such that the linearly polarized light is S-polarized light with respect to the surface of the surface tissue of the living body (subject) that is the irradiation surface, and the incident angle θ is approximately 45 °. Irradiate the surface. This is conscious of the structure of the epidermis that there are many components parallel to the skin. By using S-polarized light, it is less affected by keratin fibers and less scattered than when using P-polarized light. The sensitivity is further improved. The incident angle refers to an angle formed between the incident light ray and the normal line.
ここで、既に触れたように、測定に先立ち、グルコース吸収帯（概ね１５００ ｎｍ〜１７００ｎｍ）の偏光による損失を抑えて強度を高めるため、上記面積ビームを１５００ｎｍに中心を置く半波長板（λ/２ plate）を用いてグルコース吸収帯で後述するＳ偏光の光の強度が最大となるように、半波長板の回転角度を予め設定しておく。 Here, as already mentioned, prior to the measurement, in order to suppress the loss due to the polarization of the glucose absorption band (approximately 1500 nm to 1700 nm) and increase the intensity, the half-wave plate (λ / 2 plate), the rotation angle of the half-wave plate is set in advance so that the intensity of S-polarized light, which will be described later, becomes maximum in the glucose absorption band.
即ち、交流用ハロゲンランプの出射光は、偏光方向によって強度が２倍程度変わるため、半波長板（動作波長１５００ｎｍ）を回転させると、それに応じて、半波長板を透過した透過光の偏光面も回転し、その結果、Ｓ偏光の光の強度分布が変化する。そこで、測定に先立ち、グルコース吸収帯でＳ偏光の光の強度が最大となるように、半波長板の回転角度を設定して半波長板を透過した透過光の偏光面を回転させておくのである。必然的に９００〜１３００ｎｍの波長帯の照射発光強度は緩やかに抑えられる。 That is, since the intensity of the emitted light from the AC halogen lamp changes by about twice as much as the polarization direction, when the half-wave plate (operating wavelength 1500 nm) is rotated, the polarization plane of the transmitted light that has passed through the half-wave plate accordingly. As a result, the intensity distribution of the S-polarized light changes. Therefore, prior to measurement, the rotation angle of the half-wave plate is set so that the intensity of the S-polarized light is maximized in the glucose absorption band, and the polarization plane of the transmitted light transmitted through the half-wave plate is rotated. is there. Inevitably, the emitted light intensity in the wavelength band of 900 to 1300 nm is moderately suppressed.
具体的には、血中グルコース濃度情報の取得に先立ち、半波長板を、その中心を通る法線ベクトルを軸として回転させながらＳ偏光の光の強度を測定し、このＳ偏光の光がグルコース吸収帯（域）で最大強度となるような回転角度に半波長板を設定しておいた。
換言すれば、予め半波長板を回転させながら、生体（被検体）の表層組織の表面に照射されるＳ偏光の光の強度を測定しておき、この測定結果に基づいて、Ｓ偏光の光がグルコース吸収帯（域）で最も大きなピークが得られるような回転角度に半波長板を設定しておいたのである。
Specifically, prior to obtaining blood glucose concentration information, the intensity of S-polarized light is measured while rotating a half-wave plate about a normal vector passing through the center of the half-wave plate, and the S-polarized light is converted into glucose. The half-wave plate was set at a rotation angle that gives the maximum intensity in the absorption band (region).
In other words, the intensity of S-polarized light irradiated on the surface of the surface tissue of the living body (subject) is measured in advance while rotating the half-wave plate, and the S-polarized light is measured based on the measurement result. However, the half-wave plate was set at a rotation angle such that the largest peak was obtained in the glucose absorption band (range).
半波長板の回転角度を設定した後、まず最初に、Ｓ偏光の光を被検体（後述するように、手の甲）の前面に置かれたガラス板に照射し、反射光を分光器に取り込みバックグラウンド光として記憶した。 After setting the rotation angle of the half-wave plate, first, S-polarized light is irradiated onto the glass plate placed in front of the subject (the back of the hand, as will be described later), and the reflected light is taken back into the spectrometer. Memorized as ground light.
次に、ガラス板を取り除き、Ｓ偏光の光を、入射角θが４５°になるように被検体の表層組織の表面に照射した。これにより、ケラチン繊維の影響を受けにくくなって表層組織の深い部分（真皮層）まで光が潜って戻ることにより感度が向上する。また検出光学系に反射光が後方入射しにくくなる。 Next, the glass plate was removed, and the surface of the surface tissue of the subject was irradiated with S-polarized light so that the incident angle θ was 45 °. Thereby, it becomes difficult to be influenced by the keratin fiber, and the sensitivity is improved by the light diving back to the deep part (dermis layer) of the surface layer structure. Also, the reflected light is less likely to enter the detection optical system.
ここで、皮膚細胞の屈折率は概ね１．３７であるので、表面の乱反射を入れても反射光は５％程度であり、残りの９５％程度は皮膚内に進入する。入射光は最初に皮膚の角質層に入る。角質層は偏平層約１０層からなりケラチン繊維で満たされている。表面付近で散乱される光はあまり偏光せずＳ偏光の光として反射される。 Here, since the refractive index of the skin cells is approximately 1.37, the reflected light is about 5% even if the surface is irregularly reflected, and the remaining 95% enters the skin. Incident light first enters the stratum corneum of the skin. The stratum corneum consists of about 10 flat layers and is filled with keratin fibers. Light scattered near the surface is not polarized so much and is reflected as S-polarized light.
皮膚の角質層に入射した光は、表皮の顆粒層及び有棘層に到達する。ここの組織は５〜１０層の有棘細胞で表面に近いほど偏平になる。このように構造的に皮膚表面に平行成分であるので、Ｓ偏光は屈折率の変化を受けにくくＰ偏光より散乱が少ないと考えられる。 Light incident on the stratum corneum of the skin reaches the granular layer and the spinous layer of the epidermis. The tissue here is 5 to 10 layers of spinous cells, and becomes flatter as the surface is closer. Thus, since it is structurally a parallel component to the skin surface, it is considered that S-polarized light is less susceptible to changes in refractive index and is less scattered than P-polarized light.
Ｓ偏光の光は、手の甲に照射した。これにより、表面が凸面で滑らかであり血管が近い手の甲の表層組織の表面にＳ偏光の光を照射するため、掌や手首内側で測定するよりも異なる時刻におけるデータ変動が少なく感度が向上する。 S-polarized light was applied to the back of the hand. Thereby, since the surface of the surface tissue of the back of the hand is convex and smooth and the surface of the hand is close to the surface, the S-polarized light is radiated, so that there is less data fluctuation at different times and the sensitivity is improved as compared with the measurement inside the palm or wrist.
そして、光の平均的な進入深さはモンテカルロシュミュレーションによって０．５〜１ｍｍであることが分かっており、表皮の平均厚み０．２ｍｍの組織から散乱を受けながらも５０％以上の光が真皮層内に到達進入する。真皮と表皮の境には乳頭層があり、毛細血管やリンパ管が入り組んで細胞に栄養分を供給している。真皮の概ね７０％はゼラチン質の膠原繊維で、その内部に水を閉じこめ、細胞間液には血中と同程度のグルコースが遊離浮遊しているものと考えられる。光はグルコースに吸収されながら繊維細胞に散乱され概ね３０〜４０％は表面に戻される。平均散乱回数は３０回以上で、散乱課程を経て偏光はほぼランダムになる。即ち、入射深さが浅い部位からの光は偏光成分に元の成分が多く、深く進んで多重反射を受けるとランダムになる。 The average penetration depth of light is found to be 0.5 to 1 mm by Monte Carlo simulation, and more than 50% of light is scattered from the tissue with an average thickness of 0.2 mm of the epidermis. Enter the layer and enter. There is a papillary layer at the boundary between the dermis and the epidermis, and capillaries and lymphatic vessels are involved to supply nutrients to the cells. Approximately 70% of the dermis is gelatinous collagen fibers, and water is confined in the inside of the dermis, and it is considered that glucose equivalent to that in blood is free floating in the intercellular fluid. Light is scattered by fiber cells while being absorbed by glucose, and approximately 30 to 40% is returned to the surface. The average number of scattering times is 30 times or more, and the polarization becomes almost random after the scattering process. That is, the light from the site where the incident depth is shallow has a large amount of the original component in the polarization component, and becomes random when it goes deep and undergoes multiple reflection.
以上の解析に基づき、本発明では、組織からの反射光のうちＰ偏光を取り出して分光器にかけて分光分析した。これによって、表面または表面浅部から反射された光が除かれ、細胞内で多重散乱された光のみを分光分析することができるため皮膚から深い部分（真皮層）の情報を選択的に取り込むことができ、より感度が向上するのである。 Based on the above analysis, in the present invention, P-polarized light was extracted from the reflected light from the tissue, and spectroscopically analyzed. As a result, light reflected from the surface or shallow surface is removed, and only the light scattered multiple times in the cell can be spectroscopically analyzed, so the information on the deep part (dermis layer) is selectively captured from the skin. This improves the sensitivity.
本実施形態では、分光器からのデータは概ね９００〜１７００ｎｍの波長帯を５１２点分割したもので、前４点後４点の重み付きローパスフィルタで平滑化した後、一般的な主成分分析を行った。 In the present embodiment, the data from the spectroscope is obtained by dividing the wavelength band of 900 to 1700 nm in approximately 512 points, and after smoothing with a four-point weighted low-pass filter after the previous four points, a general principal component analysis is performed. went.
ここで、グルコースの高調波吸収帯である概ね１５００ ｎｍ〜１７００ｎｍの波長帯を用いずに、概ね９００〜１７００ｎｍの波長帯を用いている理由を以下に説明する。 Here, the reason why the wavelength band of approximately 900 to 1700 nm is used without using the wavelength band of approximately 1500 nm to 1700 nm, which is the harmonic absorption band of glucose, will be described below.
通常、水は水素結合により水分子４個位から１万個位の大小のクラスターを形成して浮遊しており、その間にグルコース分子が入ると水分子の結合が変わってクラスターが変化し近赤外吸収スペクトルを変化させることになる。一般に水分子のクラスターサイズが小さくなれば、水スペクトルは短波長側にシフトする。換言すれば、このシフトした波長域においてもグルコース情報が含まれているのである。 Normally, water floats by forming large and small clusters of about 4 to 10,000 water molecules by hydrogen bonds, and when glucose molecules enter between them, the water molecules bond to change and the clusters change. The external absorption spectrum will be changed. Generally, when the cluster size of water molecules is reduced, the water spectrum is shifted to the short wavelength side. In other words, glucose information is also included in this shifted wavelength region.
即ち、グルコース自体の吸収以外に水のスペクトルの変化も用いるために、波長９００ ｎｍ〜１７００ ｎｍ 間のスペクトル変化プロファイル全てを使ってグルコース量を回帰しているのであり、グルコーススペクトルと体内の水スペクトルの吸収変化を主成分回帰（主成分分析）で見ているのである。これによって、従来よりも安定して血中グルコース濃度情報を得ることができる。また感度もより向上する。 That is, in order to use a change in the spectrum of water in addition to the absorption of glucose itself, the amount of glucose is regressed using all the spectrum change profiles between wavelengths 900 nm to 1700 nm. The change in absorption is observed by principal component regression (principal component analysis). As a result, blood glucose concentration information can be obtained more stably than in the prior art. Moreover, the sensitivity is further improved.
なお、主成分分析とは、多数の変量によって構成された測定データに対して、それらの情報量をできるだけ損なわず、かつ、情報をより把握し易くするために合成変量（主成分）を求めて解析する統計的手法である。生体光計測装置の複数チャンネルのヘモグロビン信号について、主成分分析を施して主成分を求める手法については、例えば特開２００５−１４３６０９号公報等に詳細に記載され、広く知られた手法であるので、ここでは詳細な分析手法については説明を省略する。 Principal component analysis refers to measurement data composed of a large number of variables, and seeks a composite variable (principal component) to make the information easier to grasp without losing the amount of information as much as possible. It is a statistical method to analyze. The method for obtaining the principal component by performing principal component analysis on the multi-channel hemoglobin signals of the biological light measurement device is described in detail in, for example, Japanese Patent Application Laid-Open No. 2005-143609, and is a widely known method. Here, the detailed analysis method will not be described.
但し、本実施形態では、この主成分分析で得られた第三主成分に基づいて血中グルコース濃度情報を得る。これによって、血中グルコース濃度の実測値とよく相関する情報を得ることができる。 However, in this embodiment, blood glucose concentration information is obtained based on the third principal component obtained by this principal component analysis. As a result, information that correlates well with the actually measured value of the blood glucose concentration can be obtained.
以上述べた方法によって、実際に、生体の手の甲による近赤外分光分析と採血による血糖値測定を行い比較した。測定は平成２０年１１月７日、食事前２０分から直前まで１０分毎、食後１時間は５分毎、１時間〜２時間は１０分毎、採血は２０分間隔で行った。測る度に鏡を用いて光源照射光強度と皮膚の温度を非接触温度計で測定した。被験者は血糖値が境界領域の男性（６２歳）である。 By the method described above, the comparison was made by actually performing near-infrared spectroscopic analysis with the back of a living body and blood glucose measurement by blood collection. Measurement was carried out on November 7, 2008, every 10 minutes from 20 minutes before meal to immediately before, every 5 minutes for 1 hour after meal, every 10 minutes for 1 to 2 hours, and blood sampling at 20 minute intervals. Each time it was measured, the light source irradiation light intensity and the skin temperature were measured with a non-contact thermometer using a mirror. The test subject is a male (62 years old) whose blood glucose level is in the boundary region.
図２は２２個の分光吸収データの主成分分析を行って各成分のスコア値を描いたグラフであり、図３は各主成分負荷量の負荷係数（重み）を求めて食後時間変化を示したグラフである。また、図４は採血血糖値と第３主成分の類似性（相関性）を示すグラフである。図３及び図４に示すように、第三主成分は、第一主成分や第二主成分と比較して、採血血糖値と良好な相関を示していることがわかる。 FIG. 2 is a graph in which the principal component analysis of 22 spectral absorption data is performed and the score value of each component is drawn. FIG. 3 shows the change in time after meal by obtaining the load coefficient (weight) of each principal component load. It is a graph. FIG. 4 is a graph showing the similarity (correlation) between the collected blood glucose level and the third principal component. As shown in FIG.3 and FIG.4, it turns out that the 3rd main component has shown favorable correlation with the blood-collecting blood glucose level compared with a 1st main component and a 2nd main component.
以上、特定の実施形態を参照して本発明を説明したが、本発明は上記実施形態に限定されるものではなく、当該技術分野における熟練者等により、本出願の願書に添付された特許請求の範囲から逸脱することなく、種々の変更及び修正が可能である。 Although the present invention has been described above with reference to specific embodiments, the present invention is not limited to the above-described embodiments, and claims attached to the application of the present application by those skilled in the art or the like. Various changes and modifications can be made without departing from the scope.
Claims (4)
前記表層組織の表面に照射される前記Ｓ偏光の光がグルコース吸収帯で最大強度となるように、前記半波長板の回転角度を予め設定しておく、血中グルコース濃度情報の取得方法。
The light emitted from the AC halogen lamp is transmitted through a half-wave plate that is rotatably installed, and the transmitted light that has passed through the half-wave plate is converted into linearly polarized light. Irradiate the surface of the surface tissue with S-polarized light so that the incident angle is approximately 45 °, extract P-polarized light from the diffusely reflected light from the surface tissue of the living body, and perform spectroscopic analysis to obtain blood. A method for obtaining blood glucose concentration information, which obtains blood glucose concentration information,
A method for acquiring blood glucose concentration information, wherein a rotation angle of the half-wave plate is set in advance so that the S-polarized light irradiated on the surface of the surface tissue has a maximum intensity in a glucose absorption band.
請求項１記載の血中グルコース濃度情報の取得方法。
The surface tissue of the living body is the surface tissue of the back of the hand.
The blood glucose concentration information acquisition method according to claim 1.
この主成分分析で得られた第三主成分に基づいて、
血中グルコース濃度情報を得る、
請求項１又は２記載の血中グルコース濃度情報の取得方法。
Spectral analysis uses principal component analysis,
Based on the third principal component obtained by this principal component analysis,
Obtain blood glucose concentration information,
The method for acquiring blood glucose concentration information according to claim 1 or 2.
概ね９００〜１７００ｎｍの波長帯を用いて行う、
請求項３記載の血中グルコース濃度情報の取得方法。 Principal component analysis
It is performed using a wavelength band of approximately 900 to 1700 nm.
The method for acquiring blood glucose concentration information according to claim 3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009251861A JP5360718B2 (en) | 2009-11-02 | 2009-11-02 | Method for obtaining blood glucose concentration information |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009251861A JP5360718B2 (en) | 2009-11-02 | 2009-11-02 | Method for obtaining blood glucose concentration information |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011092613A true JP2011092613A (en) | 2011-05-12 |
| JP5360718B2 JP5360718B2 (en) | 2013-12-04 |
Family
ID=44110232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009251861A Expired - Fee Related JP5360718B2 (en) | 2009-11-02 | 2009-11-02 | Method for obtaining blood glucose concentration information |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP5360718B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015532445A (en) * | 2012-09-25 | 2015-11-09 | グーグル・インク | Information processing method |
| US11872032B2 (en) | 2019-02-19 | 2024-01-16 | Samsung Electronics Co., Ltd. | Apparatus and method for estimating analyte concentration |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH1170101A (en) * | 1996-11-26 | 1999-03-16 | Matsushita Electric Works Ltd | Analysis method for blood component density, device therefor and optical fiber bundle for the device |
| WO2005079661A1 (en) * | 2004-02-24 | 2005-09-01 | Waseda University | Apparent chemical species measuring method and measuring system |
| WO2005111583A1 (en) * | 2004-05-17 | 2005-11-24 | The New Industry Research Organization | Method for nondestructively examining component of vegetable or the like by near-infrared spectroscopy and its device |
| JP2007313286A (en) * | 2006-04-25 | 2007-12-06 | Matsushita Electric Works Ltd | Method and apparatus for measurement of optical organism information |
| JP2008132335A (en) * | 2001-01-26 | 2008-06-12 | Sensys Medical Inc | Non-invasive measurement of glucose through optical properties of tissue |
-
2009
- 2009-11-02 JP JP2009251861A patent/JP5360718B2/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH1170101A (en) * | 1996-11-26 | 1999-03-16 | Matsushita Electric Works Ltd | Analysis method for blood component density, device therefor and optical fiber bundle for the device |
| JP2008132335A (en) * | 2001-01-26 | 2008-06-12 | Sensys Medical Inc | Non-invasive measurement of glucose through optical properties of tissue |
| WO2005079661A1 (en) * | 2004-02-24 | 2005-09-01 | Waseda University | Apparent chemical species measuring method and measuring system |
| WO2005111583A1 (en) * | 2004-05-17 | 2005-11-24 | The New Industry Research Organization | Method for nondestructively examining component of vegetable or the like by near-infrared spectroscopy and its device |
| JP2007313286A (en) * | 2006-04-25 | 2007-12-06 | Matsushita Electric Works Ltd | Method and apparatus for measurement of optical organism information |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015532445A (en) * | 2012-09-25 | 2015-11-09 | グーグル・インク | Information processing method |
| JP2018146982A (en) * | 2012-09-25 | 2018-09-20 | ヴェリリー ライフ サイエンシズ エルエルシー | Information processing method |
| US11872032B2 (en) | 2019-02-19 | 2024-01-16 | Samsung Electronics Co., Ltd. | Apparatus and method for estimating analyte concentration |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5360718B2 (en) | 2013-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ghosh et al. | Tissue polarimetry: concepts, challenges, applications, and outlook | |
| Cherkasova et al. | Noninvasive blood glucose monitoring in the terahertz frequency range | |
| Ghosh et al. | Polarized Light Assessment of Complex Turbid Media Such as Biological Tissues Us-ing Mueller Matrix Decomposition | |
| US20070078312A1 (en) | Method and system for non-invasive measurements in a human body | |
| JP2013009963A (en) | Method for noninvasive human body component measurement with optional optical length | |
| Tseng et al. | Noninvasive evaluation of collagen and hemoglobin contents and scattering property of in vivo keloid scars and normal skin using diffuse reflectance spectroscopy: pilot study | |
| Wróbel | Non-invasive blood glucose monitoring with Raman spectroscopy: prospects for device miniaturization | |
| EP0957748A1 (en) | Apparatus for non-invasive analyses of biological compounds | |
| WO2002026152A8 (en) | A method for quantification of stratum corneum hydration using diffuse reflectance spectroscopy | |
| US7050842B2 (en) | Method of tissue modulation for noninvasive measurement of an analyte | |
| Pai et al. | A photoacoustics based continuous non-invasive blood glucose monitoring system | |
| Nazarov et al. | Terahertz tissue spectroscopy and imaging | |
| Lin et al. | Kinetics of optical clearing of human skin studied in vivo using portable Raman spectroscopy | |
| JP2007259967A (en) | Internal component measuring instrument | |
| He et al. | Effects of optical clearing agents on noninvasive blood glucose monitoring with optical coherence tomography: a pilot study | |
| Abdulhameed et al. | On the suitability of laser-Doppler flowmetry for capturing microvascular blood flow dynamics from darkly pigmented skin | |
| Kurakina et al. | Probing depth in diffuse reflectance spectroscopy of biotissues: a Monte Carlo study | |
| Ghosh et al. | Turbid medium polarimetry in biomedical imaging and diagnosis | |
| JP2003344279A (en) | Method for measuring hair moisture | |
| Pleitez et al. | Infrared reflectometry of skin: Analysis of backscattered light from different skin layers | |
| JP5360718B2 (en) | Method for obtaining blood glucose concentration information | |
| Yakimov et al. | Comparative analysis of the methods for quantitative determination of water content in skin from diffuse reflectance spectroscopy data | |
| JP2011232290A (en) | Skin horny layer component measurement method using terahertz wave | |
| WO2007060583A2 (en) | Method and apparatus for determining concentrations of analytes in a turbid medium | |
| JP4925278B2 (en) | Optical biological information measuring method and apparatus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20121026 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20121026 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121205 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20121205 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20130724 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130731 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20130807 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130807 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130826 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |