JPS6331638A - Non-invasion biochemical substance measuring apparatus - Google Patents
Non-invasion biochemical substance measuring apparatusInfo
- Publication number
- JPS6331638A JPS6331638A JP61176074A JP17607486A JPS6331638A JP S6331638 A JPS6331638 A JP S6331638A JP 61176074 A JP61176074 A JP 61176074A JP 17607486 A JP17607486 A JP 17607486A JP S6331638 A JPS6331638 A JP S6331638A
- Authority
- JP
- Japan
- Prior art keywords
- sweat
- biochemical substance
- concentration
- glucose
- measuring
- 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
- 239000000126 substance Substances 0.000 title claims description 32
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 57
- 239000008103 glucose Substances 0.000 claims description 57
- 210000004243 sweat Anatomy 0.000 claims description 49
- 210000004369 blood Anatomy 0.000 claims description 35
- 239000008280 blood Substances 0.000 claims description 35
- 230000035900 sweating Effects 0.000 claims description 19
- 238000005102 attenuated total reflection Methods 0.000 claims description 16
- 238000010438 heat treatment Methods 0.000 claims description 9
- 238000005259 measurement Methods 0.000 claims description 9
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 8
- 239000011148 porous material Substances 0.000 claims description 7
- 239000012528 membrane Substances 0.000 claims description 6
- 239000011810 insulating material Substances 0.000 claims description 5
- 230000002452 interceptive effect Effects 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 4
- 238000004364 calculation method Methods 0.000 claims description 4
- 229910052697 platinum Inorganic materials 0.000 claims description 4
- 229910052709 silver Inorganic materials 0.000 claims description 4
- 239000004332 silver Substances 0.000 claims description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 239000004202 carbamide Substances 0.000 claims description 2
- 108010093096 Immobilized Enzymes Proteins 0.000 claims 1
- 239000008151 electrolyte solution Substances 0.000 claims 1
- 238000010586 diagram Methods 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- 239000007789 gas Substances 0.000 description 7
- 238000000862 absorption spectrum Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000008016 vaporization Effects 0.000 description 4
- 238000009834 vaporization Methods 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000006866 deterioration Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003792 electrolyte Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000003340 mental effect Effects 0.000 description 3
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 108010015776 Glucose oxidase Proteins 0.000 description 2
- 239000004366 Glucose oxidase Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 210000003722 extracellular fluid Anatomy 0.000 description 2
- 235000019420 glucose oxidase Nutrition 0.000 description 2
- 229940116332 glucose oxidase Drugs 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 238000007410 oral glucose tolerance test Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 2
- 238000001028 reflection method Methods 0.000 description 2
- 210000000434 stratum corneum Anatomy 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- CVOFKRWYWCSDMA-UHFFFAOYSA-N 2-chloro-n-(2,6-diethylphenyl)-n-(methoxymethyl)acetamide;2,6-dinitro-n,n-dipropyl-4-(trifluoromethyl)aniline Chemical compound CCC1=CC=CC(CC)=C1N(COC)C(=O)CCl.CCCN(CCC)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O CVOFKRWYWCSDMA-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000004299 exfoliation Methods 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/55—Specular reflectivity
- G01N21/552—Attenuated total reflection
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Abstract] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は無侵襲生化学物質計測装置に係り、特に生体内
グルコースあるいは血糖値を生体表面から無侵襲計測す
るのに好適な無侵襲生化学物質計測装置に関するもので
ある。[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a non-invasive biochemical substance measuring device, and particularly to a non-invasive biochemical substance measuring device suitable for non-invasively measuring in-vivo glucose or blood sugar levels from the surface of a living body. This invention relates to a substance measuring device.
従来の生体内グルコース濃度あるいは血糖値の連続測定
は、グルコースセンサを血管内あるいは組織内に挿入す
るかく特開昭５９−８９３９号公報、特開昭５９−８９
６９号公報、特開昭５９−１４８４３号公報。Conventional continuous measurement of in vivo glucose concentration or blood sugar level involves inserting a glucose sensor into a blood vessel or tissue.
No. 69, JP-A-59-14843.
特開昭５９−１４８５７号公報）、血管内へ挿入したカ
テーテルから体外へ導いた血液にセンサを接する（特開
昭５２−１３５５９９号公報、特開昭５４−８２８８５
号公報）かの方法がとられていた。また、間欠的なグル
コース濃度、血糖値の測定は、採血後にセンサで測定し
ていた。(Japanese Unexamined Patent Publication No. 59-14857), a sensor is brought into contact with blood led outside the body from a catheter inserted into a blood vessel (Japanese Unexamined Patent Publications No. 52-135599, Unexamined Japanese Patent Application No. 54-82885)
(No. Publication) was used. In addition, intermittent glucose and blood sugar levels were measured using a sensor after blood was collected.
一方、生体内グルコースを生体表面がら無侵襲測定する
方法については、「臨床病理」３３巻１０号（１９８５
年）第１０９３頁から第１０９９頁において論じられて
いるが、これは、角質層を剥離し、間質液を生体表面に
吸引後、血液と類似の成分からなる間質液のグルコース
を内部減衰全反射法で測定している。On the other hand, regarding a method for non-invasively measuring in-vivo glucose on the surface of a living body, "Clinical Pathology" Vol. 33, No. 10 (1985
2007), pages 1093 to 1099, this method involves exfoliating the stratum corneum and sucking the interstitial fluid onto the biological surface, and then internally attenuating the glucose in the interstitial fluid, which has components similar to blood. Measured using total internal reflection method.
上記従来技術は、採血針、カテーテルあるいはセンサを
生体内に挿入するもので、侵襲性の点については配慮が
なされておらず、感染、失血、患者の精神的および肉体
的苦痛、生体成分付着によるセンサの性能劣化および間
欠的測定による情報不足などの問題点があった。The above conventional technology involves inserting a blood collection needle, catheter, or sensor into the living body, and does not take into account invasiveness, which can lead to infection, blood loss, mental and physical pain for the patient, and adhesion of biological components. There were problems such as deterioration of sensor performance and lack of information due to intermittent measurements.
また、吸引内部減衰全反射法は、侵襲度を低下させてい
るものの、角質層の剥離、生体表面の防圧にともなう侵
襲性は除去できないという問題があった。In addition, although the suction internal attenuated total reflection method reduces the degree of invasiveness, it has the problem that the invasiveness associated with exfoliation of the stratum corneum and pressure-proofing of the biological surface cannot be eliminated.
本発明の目的は、生体内のグルコース濃度あるいは血糖
値を生体表面から無侵襲に測定することができる無侵襲
生化学物質計測装置を堤供することにある。An object of the present invention is to provide a non-invasive biochemical substance measuring device that can non-invasively measure glucose concentration or blood sugar level in a living body from the surface of a living body.
上記目的は、生体表面から発汗を起こさせるための加温
手段と、この加温手段によって生じた汗の生化学物質の
濃度を測定する計測手段と、上記加温手段によって生ず
る発汗の速度を測定する発汗速度計測手段と、上記計測
手段によって測定した上記汗の生化学物質濃度と上記発
汗速度計測手段によって測定した発汗速度とから血液中
の必要生化学物質濃度を演算して表示する演算・表示手
段とより構成して達成するようにした。The above purpose is to provide a heating means for causing sweating from the surface of a living body, a measuring means for measuring the concentration of biochemical substances in the sweat produced by the heating means, and a measuring means for measuring the rate of sweat produced by the heating means. a sweating rate measuring means, and calculation/display for calculating and displaying the concentration of necessary biochemical substances in the blood from the biochemical substance concentration in the sweat measured by the measuring means and the sweating rate measured by the sweating rate measuring means. I tried to achieve it by structuring the means.
まず、生化学物質の１つであるグルコース濃度測定につ
いて説明する。加温手段により皮膚は局所的に加熱され
て発汗する。汗のグルコース濃度は血液中の濃度とよく
相関することは「糖尿病」２８巻１１号（１９８５年）
第１２７１頁がら第１２７３頁に示されている。したが
って、汗のグルコース濃度を測定すれば、血液中のグル
コース濃度を経皮的に測定できる。ただし、汗のグルコ
ース濃度は。First, measurement of glucose concentration, which is one of the biochemical substances, will be explained. The heating means locally heats the skin and causes sweating. ``Diabetes'' Vol. 28, No. 11 (1985) states that the glucose concentration in sweat correlates well with the concentration in blood.
It is shown on pages 1271 to 1273. Therefore, by measuring the glucose concentration in sweat, the glucose concentration in blood can be measured transcutaneously. However, the glucose concentration in sweat.
測定する。すなわち、光源からの光は、汗と接した内部
減衰全反射プリジム中で汗のグルコースに特徴的な吸収
を生じるから、この吸収スペクトルを光検出器で経時的
に測定するようにする。したがって、血液中のグリコー
ス濃度を継続的、無侵襲的に計測することができる。Measure. That is, since the light from the light source causes absorption characteristic of glucose in sweat in the internally attenuated total reflection prism that comes into contact with sweat, this absorption spectrum is measured over time with a photodetector. Therefore, the glucose concentration in blood can be measured continuously and non-invasively.
また、グルコース以外の生化学物質も汗の値と血液の値
が対応して変化すると考えられるから、無侵襲に測定で
きる。Furthermore, biochemical substances other than glucose can be measured non-invasively, since sweat values and blood values are thought to change correspondingly.
次に、血糖値測定について説明する。血糖値を一定に保
ったときの汗のグルコース濃度と発汗速度との関係は第
４図に示すようになるから、血糖値は汗のグリコース濃
度と発汗速度との積に比例することが考えられ、５０ｇ
経口糖負荷試験時の血糖値、汗のグリコース濃度、発汗
速度および汗のグルコース濃度と発汗速度との積である
汗の中のグルコース量の経時変化は第５図に示すように
なり、汗のグルコース濃度よりも汗中グルコース量、萱
なわち、汗のグルコース濃度と発汗速度とによって生体
表面上に浸出した汗のグルコース濃度は、グルコースセ
ンサ１０１で測定し、発汗速度は１発汗速度センサ１０
２で測定し１両センサ１０１．１０２の出力を演算・標
示回路１０３に入力し、汗のグルコース濃度と発汗速度
との積を求め、血糖値を表示するようにすれば、これに
より、血糖値を連続的、無侵襲的に計測することができ
る。Next, blood sugar level measurement will be explained. The relationship between the glucose concentration in sweat and the rate of sweating when the blood sugar level is kept constant is shown in Figure 4, so it can be considered that the blood sugar level is proportional to the product of the glucose concentration in sweat and the rate of sweating. ,50g
Figure 5 shows the changes over time in the blood glucose level during the oral glucose tolerance test, the glucose concentration in sweat, the sweating rate, and the amount of glucose in sweat, which is the product of the glucose concentration in sweat and the sweating rate. The amount of glucose in sweat is higher than the glucose concentration, that is, the glucose concentration of sweat leached onto the surface of the living body depending on the glucose concentration of sweat and the sweat rate is measured by the glucose sensor 101, and the sweat rate is measured by the sweat rate sensor 10.
2 and input the outputs of the two sensors 101 and 102 into the calculation/display circuit 103, calculate the product of the glucose concentration of sweat and the sweating rate, and display the blood sugar level. can be measured continuously and non-invasively.
また、血糖値以外の必要生化学物質濃度も汗の濃度と発
汗速度との演算値が血液の必要生化学物質値と対応して
変化するものと考えられるから、無侵襲に１ｉｌＮ定で
きる。In addition, the concentration of necessary biochemical substances other than the blood sugar level can be non-invasively determined at 1 ilN since the calculated value of sweat concentration and sweating rate is considered to change in correspondence with the value of necessary biochemical substances in blood.
以下本発明を第１図〜第３図に示した実施例を用いて詳
細に説明する。The present invention will be explained in detail below using the embodiments shown in FIGS. 1 to 3.
第１図は本発明の無侵襲生化学物質計測装置の一実施例
を示す一部断面構成図であり、生体表面に装着する部分
は断面図で示しである。この計測装置は、ヒータ１０、
温度センサ１１を含む温度色
制御回路１２、白金電極１３、銀電極１４、襦緑物貿１
５．電解液１６．妨害物質除去膜１７．固定化グルコー
スオキシダーゼ［１８、多孔質物質１９からなるグルコ
ースセンサ、ガス流入口２０、ガス流出口２１、温度セ
ンサ２２、気化室２３からなる発汗速度センサ、グルコ
ースセンサ、ヒータ１ｏを覆い皮膚９への伝熱効率を高
くする断熱材２４．上記両センサの出力をディジタル変
換するＡ−Ｄ変換器２５、その出力を演算するＣＰＴＪ
２６、演算された血糖値の表示部２７、記憶部２８から
構成しである。FIG. 1 is a partially sectional configuration diagram showing an embodiment of the non-invasive biochemical substance measuring device of the present invention, and the portion to be attached to the surface of a living body is shown in a sectional view. This measuring device includes a heater 10,
Temperature color control circuit 12 including temperature sensor 11, platinum electrode 13, silver electrode 14, green material trade 1
5. Electrolyte 16. Interfering substance removal membrane 17. immobilized glucose oxidase [18, a glucose sensor consisting of a porous material 19, a sweating rate sensor consisting of a gas inlet 20, a gas outlet 21, a temperature sensor 22, a vaporization chamber 23, a glucose sensor that covers the heater 1o, Insulating material that increases heat transfer efficiency 24. An A-D converter 25 that digitally converts the outputs of both the sensors, and a CPTJ that calculates the outputs.
26, a display section 27 for displaying the calculated blood sugar level, and a storage section 28.
温度制御回路１２により４３℃前後に加温された生体表
面に浸出した汗は多孔質物質１９に吸収され、常に新し
い汗をグルコースセンサ表面に維持する。グルコースセ
ンサでは、よく知られているように、グルコース（Ｃｓ
Ｈｚ ｘ○６）、酸素、水が固定化グルコースオキシ
ダーゼ膜１８の中で酵素の働きによりグルコン酸（Ｃｅ
Ｈｉ ２０７）と過酸化水素（ＨｚＣ）ｚ）を生じ、
これらは平衡状態にある。Sweat seeped onto the surface of the living body heated to around 43° C. by the temperature control circuit 12 is absorbed by the porous material 19, and fresh sweat is constantly maintained on the surface of the glucose sensor. As is well known, glucose sensors use glucose (Cs
Hz x○6), oxygen, and water are converted into gluconic acid (Ce
produces Hi 207) and hydrogen peroxide (HzC)z),
These are in equilibrium.
ＣｅＨｚ２０ｅ＋○ｚ十Ｈｚｏ−）ＣｓＨｔｚ○７＋Ｈ
２Ｏ２白金電極１３、銀電極１４、絶縁物質１５、電解
液１６からなるポーラログラフ電極では、発生する過酸
化水素あるいは消費される酸素に比例した電流を得る。CeHz20e+○z10Hz-)CsHtz○7+H
A polarographic electrode consisting of a 2O2 platinum electrode 13, a silver electrode 14, an insulating material 15, and an electrolyte 16 generates a current proportional to hydrogen peroxide generated or oxygen consumed.
したがって、グルコース濃度に比例した電流が得られる
。なお、妨害物質除去膜１７は、尿素、アスコルビン酸
などの妨害物質を除去する反面、測定対象物質を通す。Therefore, a current proportional to the glucose concentration is obtained. Note that while the interfering substance removal membrane 17 removes interfering substances such as urea and ascorbic acid, it allows the substance to be measured to pass through.
次に１発汗法度センサの動作は、論文集「電子通信学会
技術研究報告Ｊ ＢＭＥ８５−１７ （１０００年）に
論じられているように、乾燥した窒素ガスをガス流入口
２０から気化室２３を経由してガス流出口２１に流すこ
とにより、発汗速度に対応した湿気が気化室２３内で得
られ、それを温度センサ２２で検出することにより発汗
速度が計測される。Next, the operation of the perspiration level sensor 1 is as discussed in the collection of papers "IEICE technical research report J BME85-17 (1000)," in which dry nitrogen gas is passed from the gas inlet 20 through the vaporization chamber 23. By causing the gas to flow through the gas outlet 21, moisture corresponding to the sweating rate is obtained in the vaporization chamber 23, and by detecting this with the temperature sensor 22, the sweating rate is measured.
このようにして得られたグルコースセンサおよび発汗速
度センサの出力をＡ−Ｄ変換器２５でディジタル化し、
ＣＰｔＪ２６で演算し、その結果得られた血糖値を表示
部２７に表示したり、記憶部２８に保存する。The outputs of the glucose sensor and sweat rate sensor thus obtained are digitized by the A-D converter 25,
The CPtJ 26 calculates and the resulting blood sugar level is displayed on the display section 27 or stored in the storage section 28.
第２図は本発明の他の実施例を示す第１図に相当する一
部断面構成図で、第１図と同一部分は同じ符号で示し、
ここでは説明を省略する。第２図におイテハ、光ｒＡ２
９、光路３０．ＡＴＲ（内部減衰全反射）プリズム３１
、光検出器３２、多孔質物質１９からなる内部減衰全反
射法によるグルコース測定装置が設けてあり、これが第
１図の白金電極１３、銀電極１４、絶縁物質１５、電解
液１Ｇからなるポーラログラフ電極に対応しており、さ
らに、皮膚９への伝熱をよくする熱の良導体３３が設け
である。FIG. 2 is a partial cross-sectional configuration diagram corresponding to FIG. 1 showing another embodiment of the present invention, and the same parts as in FIG. 1 are designated by the same reference numerals.
The explanation will be omitted here. Figure 2 shows Iteha, Hikari rA2
9. Optical path 30. ATR (internally attenuated total reflection) prism 31
, a photodetector 32, and a porous material 19. A glucose measuring device using an internally attenuated total reflection method is provided, which is a polarographic electrode shown in FIG. In addition, a good heat conductor 33 is provided to improve heat transfer to the skin 9.
温度制御回路１２により加温されて生体表面に浸出した
汗は、第１図に示した実施例と同様に、多孔質物質１９
に吸収され、常に新しい汗をＡＴＲプリズム３１表面に
維持する。汗の成分によ゛り光の吸収スペクトルは異な
り、グルコースでは赤外領域の１０００ｃ＋＋−”近傍
で特徴的な吸収を示すが。Sweat heated by the temperature control circuit 12 and leached onto the surface of the living body is absorbed into the porous material 19 as in the embodiment shown in FIG.
The sweat is absorbed by the ATR prism 31, and new sweat is always maintained on the surface of the ATR prism 31. The absorption spectrum of light differs depending on the components of sweat, and glucose exhibits a characteristic absorption near 1000c++-'' in the infrared region.
これはグルコース分子中のピラン環および環状へジアセ
タールの振動に起因すると考えられている。This is thought to be due to the vibration of the pyran ring and cyclic hediacetal in the glucose molecule.
グルコースを測定対象とするときは、光源２９として炭
酸ガスレーザを使用する。赤外線は光路３０にしたがい
、生体表面上のＡＴＲプリズムた
３１中で汗のグルコース濃度にビた吸収を受け、へ
光検出器３２に到達する。光検出器３２としては、例え
ば、フーリエ変換型赤外分光器を使用すれば、多数回の
測定データを積算してランダｔ１ノイズを低減すること
が可能である。得られた吸収スペクトルからは区間精算
法などによりグルコース濃度が求められるが、これにつ
いては、雑誌「臨床病理」３３巻１０号（１９８５年）
第１０９３頁から第１０９９頁に詳しく述べられている
。このようにして得られた汗のグルコース濃度と発汗速
度はＡ−Ｄ変換器２５に入力され、前述の実施例と同様
に処理される。When measuring glucose, a carbon dioxide laser is used as the light source 29. The infrared rays follow the optical path 30, are absorbed by the glucose concentration of sweat in the ATR prism 31 on the surface of the living body, and reach the photodetector 32. If, for example, a Fourier transform infrared spectrometer is used as the photodetector 32, it is possible to reduce the random t1 noise by integrating measurement data from a large number of times. Glucose concentration can be determined from the obtained absorption spectrum using the interval calculation method, etc., as described in the magazine "Clinical Pathology", Vol. 33, No. 10 (1985).
It is described in detail on pages 1093 to 1099. The sweat glucose concentration and sweat rate thus obtained are input to the A/D converter 25 and processed in the same manner as in the previous embodiment.
第３図は第２図の内部減衰全反射法によるグルコース測
定装置を単独で用いる場合の一実施例を示す一部断面構
成図で、生体物質測定の場合を示しである。第３図にお
いて、２９は光源、３０は光路、３１は内部減衰全反射
プリズム、３２は光検出器で、これらが主要構成要素と
なっていることは第２図と同様である。ところで、第３
図においては、内部減衰全反射プリズム３１の下の皮膚
９を加温して局所的に発汗させる目的で、加温用ヒータ
３３と温度制御用温度センサ３４を熱伝導率の高い材料
３５で囲い、これで内部減衰全反射プリズム３１を覆う
構造とし、プリズム３１と皮膚９との間に汗保持材３６
を設置しである。FIG. 3 is a partial cross-sectional configuration diagram showing an embodiment of the glucose measuring device based on the internally attenuated total reflection method shown in FIG. 2 used alone, and shows the case of biological substance measurement. In FIG. 3, 29 is a light source, 30 is an optical path, 31 is an internally attenuated total reflection prism, and 32 is a photodetector, which are the main components as in FIG. 2. By the way, the third
In the figure, a heating heater 33 and a temperature control temperature sensor 34 are surrounded by a material 35 with high thermal conductivity in order to heat the skin 9 under the internally attenuated total reflection prism 31 and cause local sweating. This structure covers the internally attenuated total reflection prism 31, and a sweat retaining material 36 is placed between the prism 31 and the skin 9.
It is installed.
て、内部減衰全反射プリズム３１と一体化している加温
用ヒータ３３とサーミスタなどからなる温度センサ３４
は、温度制御回路に組み込んであり、熱伝導率の高い材
料３５を介して皮膚９の表面を４３℃程度に加温する。A temperature sensor 34 consisting of a heating heater 33 integrated with the internally attenuated total reflection prism 31 and a thermistor, etc.
is incorporated in the temperature control circuit, and heats the surface of the skin 9 to about 43° C. via the material 35 having high thermal conductivity.
この温熱により、汗腺は局所的に発汗を生じ、血液中の
成分が汗の成分となり、生体表面に浸出してくる。浸出
した汗は、薄い（１０μｍ〜１ｍ）ステンレス鋼のメツ
シュや多孔体などの汗保持材３６に吸収され、常に新し
い汗をプリズム３１の表面に維持する。これにより、血
液と相関がよい汗の成分を安定に測定することができる
。汗の成分により光の吸収スペクトルが異なり、グルコ
ースでは赤外領域の１０００ｄｌｌ −’近傍で特徴的
な吸収を示すが、これはグルコース分子中のピラン環お
よび環状へジアセタールの振動に起因すると考えられて
おり、グルコースを測定対象とするときは、光源２９と
して炭酸ガスレーザを使用する。赤外光は光路３０にし
たがい、生体表面上の内部減衰全反射プリズム３１の中
で汗のグルコース濃度に応じた吸収を受け、光検出器３
２に到達し、光検出器３２としては、例えば、フーリエ
変換型赤外分光器を使用すれば、多数回の測定データを
積算してランダムノイズを低減することが可能であり、
得られた吸収スペクトルからは、区間積算法などにより
グルコース濃度が求められることは第２図と同様である
。This heat causes the sweat glands to locally sweat, and components in the blood become sweat components and ooze out onto the surface of the body. The leached sweat is absorbed by a sweat retaining material 36 such as a thin (10 μm to 1 m) stainless steel mesh or a porous body, and new sweat is constantly maintained on the surface of the prism 31. This makes it possible to stably measure sweat components that have a good correlation with blood. The light absorption spectrum differs depending on the components of sweat, and glucose exhibits a characteristic absorption near 1000 dll-' in the infrared region, which is thought to be caused by the vibrations of the pyran ring and cyclic hediacetal in the glucose molecule. However, when glucose is to be measured, a carbon dioxide laser is used as the light source 29. The infrared light follows an optical path 30 and is absorbed in an internally attenuated total reflection prism 31 on the surface of the living body according to the glucose concentration of sweat, and is detected by a photodetector 3.
2, and if a Fourier transform infrared spectrometer is used as the photodetector 32, for example, it is possible to integrate the measurement data of many times and reduce random noise.
As in FIG. 2, the glucose concentration can be determined from the obtained absorption spectrum by the interval integration method or the like.
上記した実施例によれば、簡便な方法により体内のグル
コース濃度を生体表面から無侵襲に測定できるので、感
染、患者の精神的・肉体的苦痛、失血を除くことができ
、また、センサに血液や組織の生体成分が付着しないの
で、性能劣化が少なく、長期に亘すグルコース濃度を安
定に測定できる。また、グルコース濃度を常に知ること
により血糖値を生理的に正常な値に保てるので、高血糖
による合併症や低血糖の事故を防ぐことができ、血糖測
定装置や人工膵臓のセンサとして利用できる。According to the above embodiment, the glucose concentration in the body can be measured non-invasively from the surface of the body using a simple method, thereby eliminating infection, mental and physical pain of the patient, and blood loss. Since biocomponents of tissues and tissues do not adhere to the sensor, there is little performance deterioration and glucose concentration can be measured stably over a long period of time. Furthermore, by constantly knowing the glucose concentration, the blood sugar level can be maintained at a physiologically normal value, thereby preventing complications due to hyperglycemia and accidents due to hypoglycemia, and can be used as a sensor for blood sugar measuring devices and artificial pancreas.
以上説明したように、本発明によれば、簡便な方法によ
り血糖値を生体表面から無侵襲に計測できるので、感染
、失血、患者の精神的・肉体的苦痛を除くことができ、
しかも、センサに血液や組織の生体成分が付着しないの
で、性能劣化が少なく、長期に亘すグルコース濃度を安
定に測定できる。また、グルコース濃度を常に知ること
により。As explained above, according to the present invention, blood sugar levels can be measured non-invasively from the surface of a living body using a simple method, thereby eliminating infections, blood loss, and mental and physical pain for patients.
Moreover, since biological components such as blood and tissue do not adhere to the sensor, there is little performance deterioration and glucose concentration can be stably measured over a long period of time. Also, by always knowing your glucose concentration.
血糖値を生理的に正常な値に保てるので、高血糖による
合併症や低温糖の事故を防ぐことができるという効果が
ある。Since it can maintain blood sugar levels at physiologically normal levels, it has the effect of preventing complications caused by hyperglycemia and accidents caused by low-temperature sugar.
第１図は本発明の無侵襲生化学物質計測装置の一実施例
を示す一部断面構成図、第２図は本発明の他の実施例を
示す第１図に相当する一部断面構成図、第３図は第２図
の内部減衰全反射法によるグリコース測定装置を単独で
用いる場合の一実施例を示す一部断面構成図、第４図は
空腹時の汗のグルコース濃度と発汗速度との関係線図、
第５図は５０ｇ経口糖負荷試験時の血糖値、汗のグルコ
ース濃度１発汗速度、汗中グルコース量の経時変化を示
す線図、第６図は無侵襲生化学物質針？１１１Ｉ装置の
基本構成図である。
１０・・・ヒータ、１１・・・温度センサ、１２・・・
温度制御回路、１３・・・白金電極、１４・・・銀電極
、１５・・・絶縁物質、１６・・・電解液、１７・・・
妨害物質除去膜、１８・・固定化グルコースオキシダー
ゼ膜、１９・・・多孔質物質、２ｏ・・・ガス流入口、
２１・・・ガス流出浸−
口、２２・・・せ度センサ、２３・・・気化室、２４・
・・断熱材、２５・・・Ａ−Ｄ変換器、２６・・・ＣＰ
Ｕ、２７・・・表示部、２８・・記憶部、２９・・・光
源、３ｏ・・・光路、３１・・・ＡＴＲプリズム、３２
・・・光検出器。FIG. 1 is a partial cross-sectional configuration diagram showing one embodiment of the non-invasive biochemical substance measuring device of the present invention, and FIG. 2 is a partial cross-sectional configuration diagram corresponding to FIG. 1 showing another embodiment of the present invention. , FIG. 3 is a partially cross-sectional configuration diagram showing an example of the case where the glucose measuring device using the internally damped total reflection method shown in FIG. 2 is used alone, and FIG. relationship diagram,
Figure 5 is a diagram showing the blood glucose level during a 50g oral glucose tolerance test, glucose concentration in sweat, sweat rate, and glucose amount in sweat over time, and Figure 6 is a non-invasive biochemical needle? 111I is a basic configuration diagram of an 111I device. 10... Heater, 11... Temperature sensor, 12...
Temperature control circuit, 13... Platinum electrode, 14... Silver electrode, 15... Insulating material, 16... Electrolyte, 17...
Interference substance removal membrane, 18...immobilized glucose oxidase membrane, 19...porous material, 2o...gas inlet,
21... Gas outflow immersion port, 22... Temperature sensor, 23... Vaporization chamber, 24...
...Insulating material, 25...A-D converter, 26...CP
U, 27...Display unit, 28...Storage unit, 29...Light source, 3o...Optical path, 31...ATR prism, 32
...Photodetector.
Claims (1)
該加温手段によつて生じた汗の生化学物質の濃度を測定
する計測手段と、前記加温手段によつて生ずる発汗の速
度を測定する発汗速度計測手段と、前記計測手段によつ
て測定した前記汗の生化学物質濃度と前記発汗速度計測
手段によつて測定した発汗速度とから血液中の必要生化
学物質濃度を演算して表示する演算、表示手段とを備え
たことを特徴とする無侵襲生化学物質計測装置。 ２、前記計測手段は、白金電極と、銀電極と、絶縁物質
と、電解液とからなるポーラログラフ電極と、尿素、ア
スコルビン酸などの妨害物質を除去して測定対象物質の
みを通す妨害物質除去膜と固定化酵素膜および汗を吸収
する多孔質物質よりなる特許請求の範囲第１項記載の無
侵襲生化学物質計測装置。 ３、前記計測手段は、光源と、該光源からの光を入射す
る汗を吸収する多孔質物質上に設けた内部減衰全反射プ
リズムと、該プリズムからの光を検出する光検出器とよ
りなる特許請求の範囲第１項記載の無侵襲生化学物質計
測装置。 ４、前記生化学物質濃度はグルコース濃度であり、前記
必要生化学物質濃度は血糖値である特許請求の範囲第１
項または第２項または第３項記載の無侵襲生化学物質計
測装置。[Claims] 1. A heating means for causing sweating from the surface of a living body;
a measuring means for measuring the concentration of biochemical substances in sweat produced by the heating means; a sweating rate measuring means for measuring the rate of sweat produced by the heating means; The invention is characterized by comprising calculation and display means for calculating and displaying the necessary biochemical substance concentration in the blood from the biochemical substance concentration of the sweat and the sweating rate measured by the sweating rate measuring means. Non-invasive biochemical substance measuring device. 2. The measurement means includes a polarographic electrode consisting of a platinum electrode, a silver electrode, an insulating material, and an electrolytic solution, and an interfering substance removal membrane that removes interfering substances such as urea and ascorbic acid and allows only the substance to be measured to pass through. 2. The non-invasive biochemical substance measuring device according to claim 1, comprising: an immobilized enzyme membrane; and a porous material that absorbs sweat. 3. The measurement means includes a light source, an internally attenuated total reflection prism provided on a porous material that absorbs the sweat incident on the light from the light source, and a photodetector that detects the light from the prism. A non-invasive biochemical substance measuring device according to claim 1. 4. Claim 1, wherein the biochemical substance concentration is glucose concentration, and the necessary biochemical substance concentration is blood sugar level.
The non-invasive biochemical substance measuring device according to item 1 or 2 or 3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61176074A JPH06121B2 (en) | 1986-07-26 | 1986-07-26 | Non-invasive biochemical substance measuring device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61176074A JPH06121B2 (en) | 1986-07-26 | 1986-07-26 | Non-invasive biochemical substance measuring device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6331638A true JPS6331638A (en) | 1988-02-10 |
| JPH06121B2 JPH06121B2 (en) | 1994-01-05 |
Family
ID=16007265
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61176074A Expired - Lifetime JPH06121B2 (en) | 1986-07-26 | 1986-07-26 | Non-invasive biochemical substance measuring device |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06121B2 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02236168A (en) * | 1989-03-09 | 1990-09-19 | New Japan Radio Co Ltd | Contact type sample collector and analyser |
| US5050604A (en) * | 1989-10-16 | 1991-09-24 | Israel Reshef | Apparatus and method for monitoring the health condition of a subject |
| US5890489A (en) * | 1996-04-23 | 1999-04-06 | Dermal Therapy (Barbados) Inc. | Method for non-invasive determination of glucose in body fluids |
| JP2006043120A (en) * | 2004-08-04 | 2006-02-16 | Nippon Telegr & Teleph Corp <Ntt> | Animate sensor and method of measuring |
| JP2007532183A (en) * | 2004-04-07 | 2007-11-15 | センシス メディカル インク | A compact instrument for non-invasive measurement of glucose by near infrared spectroscopy |
| JP2008504881A (en) * | 2004-07-01 | 2008-02-21 | ヴィヴォメディカル， インコーポレイテッド | Noninvasive glucose measurement |
| JP2010172588A (en) * | 2009-01-30 | 2010-08-12 | Omron Healthcare Co Ltd | Blood component concentration change measuring instrument |
| JP2014001946A (en) * | 2012-06-15 | 2014-01-09 | Seiko Epson Corp | Concentration measurement device and control method for the same |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6175752B1 (en) * | 1998-04-30 | 2001-01-16 | Therasense, Inc. | Analyte monitoring device and methods of use |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4073713A (en) * | 1975-09-24 | 1978-02-14 | The Yellow Springs Instrument Company, Inc. | Membrane for enzyme electrodes |
| JPS5766741A (en) * | 1980-10-11 | 1982-04-23 | Aloka Co Ltd | Analysing device for biochemical component through lasre |
-
1986
- 1986-07-26 JP JP61176074A patent/JPH06121B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4073713A (en) * | 1975-09-24 | 1978-02-14 | The Yellow Springs Instrument Company, Inc. | Membrane for enzyme electrodes |
| JPS5766741A (en) * | 1980-10-11 | 1982-04-23 | Aloka Co Ltd | Analysing device for biochemical component through lasre |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02236168A (en) * | 1989-03-09 | 1990-09-19 | New Japan Radio Co Ltd | Contact type sample collector and analyser |
| US5050604A (en) * | 1989-10-16 | 1991-09-24 | Israel Reshef | Apparatus and method for monitoring the health condition of a subject |
| US5890489A (en) * | 1996-04-23 | 1999-04-06 | Dermal Therapy (Barbados) Inc. | Method for non-invasive determination of glucose in body fluids |
| JP2007532183A (en) * | 2004-04-07 | 2007-11-15 | センシス メディカル インク | A compact instrument for non-invasive measurement of glucose by near infrared spectroscopy |
| JP2008504881A (en) * | 2004-07-01 | 2008-02-21 | ヴィヴォメディカル， インコーポレイテッド | Noninvasive glucose measurement |
| JP2006043120A (en) * | 2004-08-04 | 2006-02-16 | Nippon Telegr & Teleph Corp <Ntt> | Animate sensor and method of measuring |
| JP2010172588A (en) * | 2009-01-30 | 2010-08-12 | Omron Healthcare Co Ltd | Blood component concentration change measuring instrument |
| JP2014001946A (en) * | 2012-06-15 | 2014-01-09 | Seiko Epson Corp | Concentration measurement device and control method for the same |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH06121B2 (en) | 1994-01-05 |
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