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- JP2020010880A5 JP2020010880A5 JP2018135768A JP2018135768A JP2020010880A5 JP 2020010880 A5 JP2020010880 A5 JP 2020010880A5 JP 2018135768 A JP2018135768 A JP 2018135768A JP 2018135768 A JP2018135768 A JP 2018135768A JP 2020010880 A5 JP2020010880 A5 JP 2020010880A5
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- 210000004369 Blood Anatomy 0.000 claims description 30
- 239000008280 blood Substances 0.000 claims description 30
- WQZGKKKJIJFFOK-GASJEMHNSA-N D-Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 23
- 239000008103 glucose Substances 0.000 claims description 23
- 238000010521 absorption reaction Methods 0.000 claims description 22
- 238000005259 measurement Methods 0.000 claims description 10
- 210000003491 Skin Anatomy 0.000 claims description 6
- 210000003722 Extracellular Fluid Anatomy 0.000 claims 2
- 238000002788 crimping Methods 0.000 claims 2
- 210000003811 Fingers Anatomy 0.000 description 6
- 210000003813 Thumb Anatomy 0.000 description 3
- 230000003287 optical Effects 0.000 description 3
- 210000002615 Epidermis Anatomy 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000000624 Ear Auricle Anatomy 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000000875 corresponding Effects 0.000 description 1
- 230000001419 dependent Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
Description
意図するところは Itを計測し（１）からαを算出するものである。
ところが実用的には全て失敗している。理由はαｄが大きすぎ或はItの信号レベルが小さすぎ現在の検出器ではα検知に至らないということである。
図2は従来例である。手指・耳朶の透過を狙ったものである。出典は下記の非特許文献である。
これも失敗例である。
そこで従来の透過例を鑑みて出来るだけｄを小さくする目的で図3のようなアイデアが考案されている。
図3のように入射光I０を指の肉厚面に接するが如く斜入射する。透過光Itは指の肉厚面に接するが如く斜め拡散出射する。これはｄの出来るだけ小さいことを狙って指の表皮に斜入射、斜拡散出射の構成になっている。
この場合 拡散反射光（＝透過光＝皮膚に入り再び皮膚から外の空気域に出る光）を計測している。この場合の最近出願公開されている例を下記の特許文献に示す。
その図４のなかで読み取れるように斜光線入射の工夫がされているが実用的には失敗している。
The intention is to measure It and calculate α from ( 1 ).
However, in practice, everything has failed. The reason is that αd is too large or the signal level of It is too small to reach α detection with the current detector.
FIG. 2 is a conventional example. It aims to penetrate the fingers and earlobe. The source is the following non-patent document.
This is also a failure example.
Therefore, an idea as shown in FIG. 3 has been devised for the purpose of making d as small as possible in view of the conventional transmission example.
As shown in FIG. 3, the incident light I0 is obliquely incident so as to be in contact with the thick surface of the finger. The transmitted light It diffuses and emits diagonally as if it touches the thick surface of the finger. This is configured so that d is obliquely incident on the epidermis of the finger and obliquely diffused and emitted with the aim of making d as small as possible.
In this case, diffuse reflected light (= transmitted light = light that enters the skin and exits the skin to the outside air area) is measured. An example of a recently published application in this case is shown in the following patent document.
Although a device for incident oblique rays has been devised so that it can be read in FIG. 4, it has failed in practical use.
M．Noda et al．：Diabetologia,35(suppl),pA204(1994)
近赤外センシング技術（株）サイエンス フォーラム
M. Noda et al. : Diabetologia, 35 (suppl), pA204 (1994)
Near Infrared Sensing Technology Co., Ltd. Science Forum
ここで
N＝n＋iK
N：複素屈折率
n：実部屈折率
K：K消衰係数：α＝４πK/λ：波長依存の吸収係数：濃度に比例
このKが求めたい血中糖濃度である。
Rp：入射光線、反射光線に紙面上垂直（図5の紙面上）の電界強度の反射率、
Rs：入射光線、反射光線に紙面垂直（図5の紙面垂直）の電界強度の反射率
定性的に（3.11）を理解するために
Ψ0＝０
垂直入射、垂直反射の場合をかんがえる。
すると(3.11) は
here
N ＝ n ＋ iK
N: Complex index of refraction
n: Refractive index of the real part
K: K extinction coefficient: α = 4πK / λ: wavelength-dependent absorption coefficient: proportional to concentration This K is the blood sugar concentration to be obtained.
Rp: Reflectance of electric field strength perpendicular to the incident ray and reflected ray on the paper surface (on the paper surface in Fig. 5),
Rs: Ψ0 = 0 to understand qualitatively (3.11) the reflectance of the electric field strength perpendicular to the paper surface (perpendicular to the paper surface in Fig. 5) to the incident and reflected rays.
Consider the case of vertical incident and vertical reflection.
Then (3.11) is
（７）の示唆するところはR0を前もって計測し（２）複素数Nの実数部nによらず計測時にはRから血中糖濃度Kを求めることができることをしめしている。
R0の意味するところは血中糖度（吸収係数）の波長依存性がゼロの場合の実数部屈折率に対応する反射率であり、糖分子を含めた他分子の総合実数部屈折率に対応する。吸収波長域Kが糖分子のみとすると 吸収域近傍のR０は吸収域の総合実数屈折に対応している。ここではnの波長に対する変化はKより小さいことを応用している。また（２）からnを消去する方法は 波長をパラメーターにしてRとKの独立式を実験的に複数求めることで得られる。血中糖の吸光係数（消衰係数）の波長依存性は8.5μ〜10.0μ（FrontiersMed.Bio.Engng,Vol.9,No.２,pp.137−153（1999）と示されている。これによりRの計測には8.5μ〜10.0μの波長を R0の計測には8.5μ未満か10.0μより長い波長を用いる。重要なことはＲ0が分かれば Ｒから総合実数屈折率を消去したＫを求め得るということである。（５）によるＲ0とnの関係は厳密には人種、性別、年齢、食物などによって変わることもあり得る。そこで実用上は血中糖濃度の計測範囲を前もって網羅する必要があり、実用上問題ないnの生体区分によるRとKの対応表を用意し、計測したRから Kを求めることもできる。或は表ではなくRとKの関係を関数近似しでも問題ない。事前の計測で 採血方式により血糖値とKの関係が値付けされる。
The suggestion of (7) is that R0 is measured in advance, and (2) the blood sugar concentration K can be obtained from R at the time of measurement regardless of the real part n of the complex number N.
The meaning of R0 is the reflectance corresponding to the real part refractive index when the wavelength dependence of the blood sugar content (absorption coefficient) is zero, and corresponds to the total real part refractive index of other molecules including sugar molecules. .. Assuming that the absorption wavelength region K is only sugar molecules, R0 near the absorption region corresponds to the total real number refraction in the absorption region. Here, it is applied that the change of n with respect to the wavelength is smaller than K. The method of eliminating n from (2) can be obtained by experimentally obtaining a plurality of independent equations of R and K with the wavelength as a parameter. The wavelength dependence of the extinction coefficient (extinction coefficient) of blood sugar is shown to be 8.5 μ to 10.0 μ (Frontiers Med. Bio. Engng, Vol. 9, No. 2, pp. 137-153 (1999)). As a result, a wavelength of 8.5 μ to 10.0 μ is used for the measurement of R, and a wavelength of less than 8.5 μ or longer than 10.0 μ is used for the measurement of R0. Importantly, if R0 is known, the total real refractive index is eliminated from R. Strictly speaking, the relationship between R0 and n according to (5) may change depending on race, gender, age, food, etc. Therefore, in practice, the measurement range of blood sugar concentration should be set in advance. must be exhaustive, it is prepared a correspondence table R and K by the biological section of no practical problem n, it is also as possible out to determine the K from the measured R. Alternatively function approximating the relationship between the R and K instead of a table no problem even teeth. relationships blood glucose and K are priced by blood collection system in advance of the measurement.
本発明の別例として（５）或は（10）を応用した血中糖の吸収波長8.5μ〜10.0μのいずれかの波長を用いて反射率を計測し、血中糖の吸収無しの波長として8.5μに近い8.5μより短波長の波長を用いるか 10.0μより長波長を用いてCO2ガスレーザーを使用し光入射角ゼロ近傍の３５度未満の入射角を持つ血中糖濃度を計測する非侵襲血糖計である。図６は本発明の別例の主要な構成ブロック図である。LはCO2ガスレーザー光源であり、波長9.2〜10.8μmの複数輝線状の光束径が数ｍｍ程度の発振周波数１ＫＨＺ〜100ＫＨＺで射出される。出射光のレベルはＭｓの分岐ミラーにより受光素子Ｍｒにより監視する。LはCO2レーザー光源に限定するものではない。別途光パラメトリック発振器であってもよい。FはLから必要な波長を取り出す装置である。血中糖の吸光係数（消衰係数）の波長依存性は8.5μ〜10.0μ（Frontiers
Med.Biol.Engng,Vol.9,No.2,pp.137−153（1999））と示されている。必要な波長は 例えば、図7に示すように 9.6μ、10.2μ、bl遮光の３種を選ぶ。rtb回転板に光通過窓をもたせ9.6μの回折フィルター、10.2μの回折フィルター、遮光の各選択が巡回する構成にする。rtb回転のサイクルは受光素子のレスポンにあわせる。熱電対の場合は概１Ｈｚにする。これらの回折フィルターは光量レベルの調整もＮＤフィルターなどで行う。これら回折フィルターは干渉フィルターであってもよい。あるいは回転板は横スライドの往復機構を持つ手段であってもよい。
あるいは電磁気か音響による回折格子の定数を変化さす不動型の光学フィルターであってもよい。或は9.6μと遮光の２種であってもよい。図７のLaserはレーザー光である。図６のM１、M2、M３は光路を変更するためのミラーで１枚〜複数枚使う。ＦＸは被測定物、例えば図8に示の固定装置であり 測定時間内固定される。例えば親指の第一関節から指先までの肉厚表皮を使う場合、図8に示すように入射光穴に抑え板で第一関節から指先が動かないように固定する。抑え板はバネ性の金属で方側は固定されており親指を挿入して他の側に例えば図のように回転ネジで圧迫固定する。親指を 固定し易くするため 固定板に 指肉厚の堀の形状を設け、略中央に入射光穴をあける。この抑え板はくりかえし使用が可能なテープで少なくとも片側で例えばマジック固定であってもよい。あるいは洗濯バサミ状の 指抑えであってもよい。また この固定装置は反射光Ｉｒが最大になるように 自動的或は手動により機構が３次元的に動かし得る。メカニズムは図示していないが 組み立てロボットなどの公知手段を使う。自動化のメカニズムの原理は 例えば図9にしめす。少なくともnn法線方向に動くstm直進手段（第一手段）と入射点を中心に紙面垂直の回転軸（rt1回転１）を有する手段（第二手段）と入射点を中心に 紙面上の法線直角の回転軸（rt2回転２）を有する手段（第三手段）をもち、これら手段を用いて自動あるいは手動で最適位置にfxb固定治具とD受光素子を固定する。最適化の方法は例えば一手段の微小変動でIr反射光の増減をみながら局部最大値をもとめ、次に第二手段の微小変動でIrの増減をみながら局部最大値をもとめ、次に第三手段の微小変動でIrの増減をみながら局部最大値をもとめ て位置を固定する。これらを自動あるいは手動でおこなう。pbは圧着板である。Ｄは受光素子である。入射角と反射角が出来るだけ０度になるようにしかつ受光量を多くする。そのために受光素子の縁近くを入射光が通り、受光部と被測定部を近接さす。受光素子は9.2μ〜10.8μに感度があり、高感度のものほどよい。強制冷却型素子でもいいしあるいは常温タイプの熱電対でもよい。Ｍは必要な表示を例えば血糖濃度 時刻時間などを算出表示するもので、又予め必要な生体区分ごとのRとKの対応表とか 測定ごとの記憶とか、測定ごとの出力などをする装置である。
9.6μ波長については
Ir＝反射率R×I9・・・・・（１１）
I9入射光はＭｒで計測し、IｒはＤで測定する。
（１１）によりＲが計測される。遮光については遮光によりノイズレベルを測定する。
夫々の計測値からノイズレベルを引いた値をIr、I9とする。
10.2μについては糖吸収外の近傍波長である。
As another example of the present invention, the reflectance is measured using any of the absorption wavelengths of blood sugar of 8.5 μ to 10.0 μ to which (5) or (10) is applied, and the wavelength without absorption of blood sugar is measured. Use a wavelength shorter than 8.5μ, which is close to 8.5μ, or use a CO2 gas laser with a wavelength longer than 10.0μ to measure the blood sugar concentration with an incident angle of less than 35 degrees near zero light incident angle. It is a non-invasive blood meter. FIG. 6 is a main block diagram of another example of the present invention. L is a CO2 gas laser light source, and is emitted at an oscillation frequency of 1 KHZ to 100 KHZ having a wavelength of 9.2 to 10.8 μm and a luminous flux diameter of a plurality of emission lines of about several mm. The level of the emitted light is monitored by the light receiving element Mr by the branch mirror of Ms. L is not limited to CO2 laser light sources. It may be an optical parametric oscillator separately. F is a device that extracts the required wavelength from L. The wavelength dependence of the absorption coefficient (extinction coefficient) of blood sugar is 8.5 μ to 10.0 μ ( Frontiers).
It is shown as Med.Biol.Engng , Vol.9, No.2, pp.137-153 (1999)). For example, as shown in Fig. 7, select three types of required wavelengths: 9.6μ, 10.2μ, and bl shading. The rtb rotating plate is provided with a light passing window so that the 9.6μ diffraction filter, 10.2μ diffraction filter, and shading selection can be circulated. The cycle of rtb rotation is adjusted to the response of the light receiving element. In the case of a thermocouple, it should be approximately 1 Hz. With these diffraction filters, the light intensity level is also adjusted with an ND filter or the like. These diffraction filters may be interference filters. Alternatively, the rotating plate may be a means having a reciprocating mechanism for lateral sliding.
Alternatively, it may be an immovable optical filter that changes the constant of the diffraction grating by electromagnetic or acoustic. Alternatively, there may be two types, 9.6μ and shading. The Laser in FIG. 7 is a laser beam. M1, M2, and M3 in FIG. 6 are mirrors for changing the optical path, and one or more mirrors are used. The FX is an object to be measured, for example, a fixing device shown in FIG. 8, and is fixed within the measurement time. For example, when using a thick epidermis from the first joint of the thumb to the fingertip, fix it in the incident light hole with a holding plate so that the fingertip does not move from the first joint as shown in FIG. The holding plate is fixed on one side with spring-loaded metal, and a thumb is inserted and pressed and fixed on the other side with a rotating screw, for example, as shown in the figure. To make it easier to fix the thumb, make a moat with a thick finger wall on the fixing plate, and make an incident light hole in the center. This holding plate is a tape that can be used repeatedly and may be fixed, for example, by magic on at least one side. Alternatively, it may be a clothespin-like finger holder. In addition, the mechanism of this fixing device can be moved three-dimensionally automatically or manually so as to maximize the reflected light Ir. Although the mechanism is not shown, a known means such as an assembly robot is used. The principle of the automation mechanism is shown in Fig. 9 for example. At least the stm straight-ahead means (first means) that moves in the normal direction of nn, the means (second means) that has a rotation axis (rt1 rotation 1) perpendicular to the paper surface around the incident point, and the normal on the paper centering on the incident point. It has means (third means) having a right-angled rotation axis (rt2 rotation 2), and uses these means to automatically or manually fix the fxb fixing jig and the D light receiving element at the optimum positions. The optimization method is, for example, to find the local maximum value while observing the increase / decrease of Ir reflected light by the minute fluctuation of one means, then to find the local maximum value while observing the increase / decrease of Ir by the minute fluctuation of the second means. The position is fixed by finding the local maximum value while observing the increase / decrease of Ir by the minute fluctuation of the three means. Do these automatically or manually. pb is a crimp plate. D is a light receiving element. The incident angle and the reflection angle should be 0 degrees as much as possible, and the amount of light received should be increased. Therefore, the incident light passes near the edge of the light receiving element, and the light receiving portion and the measured portion are brought close to each other. The light receiving element has a sensitivity of 9.2μ to 10.8μ, and the higher the sensitivity, the better. It may be a forced cooling type element or a room temperature type thermocouple. M is a device that calculates and displays the necessary display, for example, blood glucose concentration, time, time, etc., and also outputs the necessary R and K correspondence table for each biological category, memory for each measurement, output for each measurement, etc. ..
For 9.6μ wavelength
Ir = reflectance R × I9 ・ ・ ・ ・ ・ (11)
I9 incident light is measured by Mr, and Ir is measured by D.
R is measured according to (11). For shading, the noise level is measured by shading.
Let Ir and I9 be the values obtained by subtracting the noise level from each measured value.
For 10.2μ, it is a near wavelength outside the sugar absorption.
Claims (19)
内部に間質液が存在する部位の皮膚面の反射率を計測する計測部と、式１の
Rp と式２のRsが等しくなると仮定して式３から得られた計算式に基づいて
消衰係数Kから血中の糖濃度を算出する演算算出部を備えた非侵襲血糖計
A measuring unit that measures the reflectance of the skin surface where interstitial fluid exists inside, and the formula 1
Based on the formula obtained from formula 3 assuming that Rp and Rs in formula 2 are equal
Non-invasive glucose meter equipped with an arithmetic calculation unit that calculates the sugar concentration in blood from the extinction coefficient K
血中糖の吸収無しの波長として8.5μに近い8.5μより短波長の波長を使うか
10.0μに近い10.0μより長波長を使用するCO2ガスレーザーを使用する請求
項３に記載の非侵襲血糖計。 The reflectance was measured using one of the absorption wavelengths of blood sugar of 8.5 μ to 10.0 μ.
Whether to use a wavelength shorter than 8.5μ, which is close to 8.5μ, as the wavelength without absorption of blood sugar
The non-invasive glucose meter according to claim 3, wherein a CO2 gas laser using a wavelength longer than 10.0 μ, which is close to 10.0 μ, is used.
反射率を計測し、夫々の回折フィルターと遮光板を回転板に取り付けた請
求項８に記載の非侵襲血糖計。 Using the absorption wavelength of blood sugar 9.3μ, 9.4μ, 9.5μ or 9.6μ
The non-invasive glucose meter according to claim 8, wherein the reflectance is measured and each diffraction filter and light-shielding plate are attached to a rotating plate.
ィルターと遮光版を回転板に取り付けた請求項９に記載の非侵襲血糖計。 As a means of using 10.2μ as the wavelength without absorption of blood sugar, each diffraction pattern
The non-invasive glucose meter according to claim 9 , wherein the filter and the light-shielding plate are attached to a rotating plate.
り作り、反射率から血糖値を算出する請求項１０に記載の非侵襲血糖計。 The non-invasive glucose meter according to claim 10, wherein a correspondence table of the reflectance and the sugar concentration according to the absorption wavelength of blood sugar is prepared in advance according to the target biological classification, and the blood glucose level is calculated from the reflectance.
り作り、反射率から血糖値るを算出する請求項８に記載の非侵襲血糖計。 The non-invasive glucose meter according to claim 8, wherein a correspondence table of the reflectance and the sugar concentration according to the absorption wavelength of blood sugar is prepared in advance according to the target biological classification, and the blood glucose level is calculated from the reflectance.
り作り、反射率から血糖値を算出する請求項９に記載の非侵襲血糖計。 In advance, the correspondence table of reflectance and sugar concentration according to the absorption wavelength of blood sugar is based on the target biological classification.
The non-invasive glucose meter according to claim 9 , wherein the blood glucose level is calculated from the reflectance.
反射率を計測し、 夫々の回折フィルターと遮光板を回転板に取り付けた
請求項１４に記載の非侵襲血糖計。 Using the absorption wavelength of blood sugar 9.3μ, 9.4μ, 9.5μ or 9.6μ
The non-invasive glucose meter according to claim 14 , wherein the reflectance is measured and each diffraction filter and light-shielding plate are attached to a rotating plate.
り作り、反射率から血糖値を算出する請求項１５に記載の非侵襲血糖計。 In advance, the correspondence table of reflectance and sugar concentration according to the absorption wavelength of blood sugar is based on the target biological classification.
The non-invasive glucose meter according to claim 15, wherein the blood glucose level is calculated from the reflectance.
生体の表皮膚内部に間質液が存在する部位の皮膚面の反射率を計測する計測
部と、式１のRp と式２のRsが等しくなると仮定して式３から得られた計算
式に基づいて消衰係数Kから生体中の糖濃度を算出する演算算出部を備え
非侵襲糖度計
Measurement to measure the reflectance of the skin surface where interstitial fluid exists inside the surface skin of the living body
Part, and the calculation obtained from Equation 3 assuming that Rp in Equation 1 and Rs in Equation 2 are equal.
Equipped with an arithmetic calculation unit that calculates the sugar concentration in the living body from the extinction coefficient K based on the formula
Non-invasive sugar content meter
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| JP2020010880A5 true JP2020010880A5 (en) | 2021-09-09 |
| JP7080480B2 JP7080480B2 (en) | 2022-06-06 |
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| JP2018135768A Active JP7080480B2 (en) | 2018-07-19 | 2018-07-19 | Non-invasive blood sugar meter |
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| JPH09215679A (en) * | 1996-02-09 | 1997-08-19 | Matsushita Electric Works Ltd | Concentration measuring apparatus for humor component |
| JP2008175794A (en) * | 2007-01-17 | 2008-07-31 | Tohoku Univ | Reflection measuring apparatus and method |
| JP2009201852A (en) * | 2008-02-29 | 2009-09-10 | Panasonic Corp | Living body composition concentration measuring instrument |
| GB201011459D0 (en) * | 2010-07-07 | 2010-08-25 | Melys Diagnostics Ltd | Optical element, assembly and method for determining analyte concentration |
| JP2012191969A (en) * | 2011-03-14 | 2012-10-11 | Shinshu Univ | Biological information measuring apparatus |
| JP6600135B2 (en) | 2014-12-22 | 2019-10-30 | リンテック株式会社 | Sheet feeding apparatus and feeding method |
| WO2016117520A1 (en) * | 2015-01-21 | 2016-07-28 | 国立研究開発法人日本原子力研究開発機構 | Device for measuring concentration of substance in blood, and method for measuring concentration of substance in blood |
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