JPH0426427B2 - - Google Patents
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- Publication number
- JPH0426427B2 JPH0426427B2 JP59122345A JP12234584A JPH0426427B2 JP H0426427 B2 JPH0426427 B2 JP H0426427B2 JP 59122345 A JP59122345 A JP 59122345A JP 12234584 A JP12234584 A JP 12234584A JP H0426427 B2 JPH0426427 B2 JP H0426427B2
- Authority
- JP
- Japan
- Prior art keywords
- electrode
- mesh
- voltage
- glucose concentration
- blood
- 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.)
- Expired - Lifetime
Links
- 210000004369 blood Anatomy 0.000 claims description 30
- 239000008280 blood Substances 0.000 claims description 30
- 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 29
- 239000008103 glucose Substances 0.000 claims description 29
- 108010093096 Immobilized Enzymes Proteins 0.000 claims description 25
- 102000004169 proteins and genes Human genes 0.000 claims description 23
- 108090000623 proteins and genes Proteins 0.000 claims description 23
- 210000000601 blood cell Anatomy 0.000 claims description 22
- 210000001772 blood platelet Anatomy 0.000 claims description 22
- 238000001514 detection method Methods 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 10
- 210000002700 urine Anatomy 0.000 claims description 10
- 108090000790 Enzymes Proteins 0.000 claims description 9
- 102000004190 Enzymes Human genes 0.000 claims description 9
- 239000007853 buffer solution Substances 0.000 claims description 8
- 238000001962 electrophoresis Methods 0.000 claims description 5
- 238000012360 testing method Methods 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims 1
- 238000010586 diagram Methods 0.000 description 20
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 11
- 238000005259 measurement Methods 0.000 description 10
- 230000035945 sensitivity Effects 0.000 description 10
- 230000006866 deterioration Effects 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000001179 sorption measurement Methods 0.000 description 6
- 108010015776 Glucose oxidase Proteins 0.000 description 5
- 239000004366 Glucose oxidase Substances 0.000 description 5
- 239000000306 component Substances 0.000 description 5
- 229940116332 glucose oxidase Drugs 0.000 description 5
- 235000019420 glucose oxidase Nutrition 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 229910052697 platinum Inorganic materials 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 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 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 235000012208 gluconic acid Nutrition 0.000 description 2
- 239000000174 gluconic acid Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000005669 field effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000758 substrate Substances 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
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/38—Cleaning of electrodes
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Molecular Biology (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)
Description
【発明の詳細な説明】
〔技術分野〕
本発明は、生体生理物質計測並びに電気泳動に
よる妨害物質除去技術における固定化酵素電極を
用いたグルコース濃度検出装置に関するものであ
る。DETAILED DESCRIPTION OF THE INVENTION [Technical Field] The present invention relates to a glucose concentration detection device using an immobilized enzyme electrode in the measurement of biological physiological substances and the removal of interfering substances by electrophoresis.
近年酵素電極の名称のもとに生体内の成分を迅
速簡便に測定のできる電極が広く用いられるよう
になつてきた。
In recent years, electrodes that can quickly and easily measure components in living organisms have come into wide use under the name enzyme electrodes.
酵素電極は酵素の固定化技術の進歩とイオン電
極やガス感応電極の発展とが相まつて出現したも
のである。その構造は特定の基質と特異的に反応
する酵素膜の部分と系の濃度変化に対応する従来
型の電極部分（下地電極）とから成る二重構造の
電極である。この固定化酵素電極を用いて生体液
中の成分を迅速かつ簡便正確に測定が可能となつ
た。 Enzyme electrodes emerged from the combination of advances in enzyme immobilization technology and developments in ion electrodes and gas-sensitive electrodes. Its structure is a double-structured electrode consisting of a part of the enzyme membrane that specifically reacts with a specific substrate and a conventional electrode part (base electrode) that responds to changes in the concentration of the system. Using this immobilized enzyme electrode, it has become possible to quickly, simply and accurately measure components in biological fluids.
血液や尿中のグルコース濃度を測定する為にグ
ルコースオキシダーゼ（GOD）を白金電極上に
固定化して成る固定化酵素電極は反応式に示す反
応によりグルコース濃度を測定する。グルコース
は溶液中に存在する酵素と共にグルコースオキシ
ダーゼに特異的に反応してグルコン酸と過酸化水
素になる。この過酸化水素が下地電極である白金
電極により酸化されてその電流値を測定すること
によりグルコース濃度を測定することができる。 An immobilized enzyme electrode, in which glucose oxidase (GOD) is immobilized on a platinum electrode, is used to measure the glucose concentration in blood or urine, and the glucose concentration is measured by the reaction shown in the reaction formula. Glucose reacts specifically with glucose oxidase together with enzymes present in the solution to form gluconic acid and hydrogen peroxide. This hydrogen peroxide is oxidized by a platinum electrode serving as a base electrode, and the glucose concentration can be measured by measuring the current value.
第１０図は血液の成分を示す図であり、血液は
細胞成分（40〜45％）と血漿（55〜60％）とから
構成され、細胞成分は赤血球、白血球および血水
板からなり、血漿は繊維素（原）と溶存タンパク
を含む血清とからなつている。そして、赤血球、
白血球、血小板および繊維素で血餅と称する。第
１１図、第１２図に示す様に従来血液中のグルコ
ース濃度を測定するには人体より採取した血液６
を遠心分離機で血餅６Ａと血清６Ｂに分離し、そ
の血清６Ｂに薬品を加えて反応色変化を測定した
り、血清６を固定化酵素センサのはいつた緩衝液
１中に滴下して測定する方法が一般的であつた。
尚、第１２図中の２１，２２は電極、５は両電極
２１，２２に電圧を印加するための電源、４は電
流計である。 Figure 10 is a diagram showing the components of blood. Blood is composed of cellular components (40-45%) and plasma (55-60%). The cellular components are composed of red blood cells, white blood cells, and water plates, and plasma is It consists of fibrin and serum containing dissolved proteins. And red blood cells,
A blood clot is made up of white blood cells, platelets, and fibrin. As shown in Figures 11 and 12, conventional methods for measuring glucose concentration in blood include blood collected from the human body.
Separate blood into blood clot 6A and serum 6B using a centrifuge, add a chemical to serum 6B and measure the reaction color change, or drop serum 6 into buffer solution 1 in an immobilized enzyme sensor. This method of measurement was common.
In FIG. 12, 21 and 22 are electrodes, 5 is a power source for applying voltage to both electrodes 21 and 22, and 4 is an ammeter.
しかしながらこの方法は遠心分離という手間を
かける為に、遠心分離を行なわないで血液そのま
まを用いて血中のグルコース濃度を求めることが
種々行なわれてきた。血液を直接用いて測定する
方法の模式図を第１３図に示す。緩衝液１中に浸
した固定化酵素電極からなる試料極（W.E）２と
対極（C.E）３間に酸化還元電流を得る為に電源
５により基準電圧Vrefを加えて血液６中のグル
コース濃度に応じた電流を電流計４によつて測定
するものである。２は試料極、３は対極である。 However, since this method requires the time and effort of centrifugation, various attempts have been made to determine the glucose concentration in blood using blood as it is without centrifugation. A schematic diagram of a method for measuring directly using blood is shown in FIG. In order to obtain a redox current between the sample electrode (WE) 2 consisting of an immobilized enzyme electrode immersed in the buffer solution 1 and the counter electrode (CE) 3, a reference voltage Vref is applied by the power supply 5 to adjust the glucose concentration in the blood 6. The corresponding current is measured by an ammeter 4. 2 is a sample electrode, and 3 is a counter electrode.
次式は固定化酵素電極による反応式である。 The following equation is a reaction equation using an immobilized enzyme electrode.
β−Ｄ− C6H12O6 グルコース＋O2GOD ―――――――――――――――→ グルコースオキシダーゼ C6H10O6 グルコン酸 ＋ H2O2 過酸化水素Pt ―――――→ 白金電極O2＋2H+＋2e- ↓ 電流値測定 但し、酸化還元電位は0.6〜0.7Vである。 β-D- C 6 H 12 O 6 Glucose + O 2 GOD ―――――――――――――――→ Glucose oxidase C 6 H 10 O 6 Gluconic acid + H 2 O 2 Hydrogen peroxide Pt ― ――――→ Platinum electrode O 2 +2H + +2e - ↓ Current value measurement However, the redox potential is 0.6 to 0.7V.
第１５図にフロー方式による測定を示す。７は
試料極、対極より成る固定化酵素電極であり、８
は血液注入シリンジである。第１６図は第１５図
に示すフロー方式による従来の検出波形である。
試料極と対極間に基準電圧（0.6〜0.7V）を加え
ると両電極間の酸化還元状態が定常状態におちつ
く為に２〜５分程度かかる。定常状態におちつい
た後、注入シリンジ８により血液６を注入するこ
とにより測定が行なわれる。しかしながら同一グ
ルコース濃度の血液を注入しても時間経過と共に
検出レベルが減少する結果が示される。これは試
料極、対極間に酸化還元電流を得る為に基準電圧
（0.6〜0.7V）を加えてある為に血液中の血球、血
小板、各種タンパク質等の物質が電気的に吸着す
る為である。第１４図に電極表面上での状態を模
式図として示す。第１４図に示される固定化酵素
電極２において、１０は白金膜、９は固定化酵素
膜である。また、e-は電子、gulはグルコース、
Ａは血球、血小板、各種タンパク等を示す。測定
を終了し基準電圧をオフした後再度測定する為に
電源５の基準電圧をオンすると以前と同様に定常
状態におちつくまでしばらく時間がかかり、グル
コース濃度検出能力はもとにもどつているのがわ
かる。これは電極表面上に吸引され血球、血小
板、タンパクが洗い流された為である。従つて血
球、血小板、各種タンパク吸着による感度劣化を
防ぐ為に基準電圧のオン、オフを行なえば良いの
であるが、基準電圧のオン、オフを行なうと定常
状態におちつくまで時間を要する為、連続的な測
定ができない状態になる。従つて電源５の基準電
圧はオン状態のままで血球、血小板、各種タンパ
クの吸着による感度劣化を防ぐ手段を用いる必要
がある。 FIG. 15 shows measurement using the flow method. 7 is an immobilized enzyme electrode consisting of a sample electrode and a counter electrode;
is a blood injection syringe. FIG. 16 shows a conventional detection waveform using the flow method shown in FIG.
When a reference voltage (0.6 to 0.7 V) is applied between the sample electrode and the counter electrode, it takes about 2 to 5 minutes for the redox state between the two electrodes to settle to a steady state. After settling into a steady state, measurement is performed by injecting blood 6 using the injection syringe 8. However, the results show that even if blood with the same glucose concentration is injected, the detection level decreases over time. This is because a reference voltage (0.6 to 0.7V) is applied between the sample electrode and the counter electrode to obtain a redox current, so substances such as blood cells, platelets, and various proteins in the blood are electrically adsorbed. . FIG. 14 schematically shows the state on the electrode surface. In the immobilized enzyme electrode 2 shown in FIG. 14, 10 is a platinum membrane and 9 is an immobilized enzyme membrane. Also, e - is electron, gul is glucose,
A indicates blood cells, platelets, various proteins, etc. After completing the measurement and turning off the reference voltage, when we turn on the reference voltage of the power supply 5 to measure again, it takes a while to reach a steady state as before, and the glucose concentration detection ability has returned to its original state. Recognize. This is because blood cells, platelets, and proteins that were attracted onto the electrode surface were washed away. Therefore, in order to prevent deterioration of sensitivity due to adsorption of blood cells, platelets, and various proteins, it is sufficient to turn the reference voltage on and off, but since turning the reference voltage on and off takes time to reach a steady state, It becomes impossible to make measurements. Therefore, it is necessary to use a means to prevent deterioration of sensitivity due to adsorption of blood cells, platelets, and various proteins while keeping the reference voltage of the power supply 5 in the ON state.
本発明は上述の点に鑑みて提供したものであつ
て、血液、尿中のグルコース濃度を検出する際、
感度劣化の要因となる血球、血小板、各種タンパ
ク質の物質を電気泳動により吸着除去して、感度
劣化を防ぎ、安定した感度特性を得ることを目的
としたグルコース濃度検出装置を提供するもので
ある。
The present invention has been provided in view of the above-mentioned points, and when detecting glucose concentration in blood or urine,
The present invention provides a glucose concentration detection device that prevents sensitivity deterioration and obtains stable sensitivity characteristics by electrophoretically adsorbing and removing substances such as blood cells, platelets, and various proteins that cause sensitivity deterioration.
以下、本発明の実施例を図面により詳述する。
第１図は構成図を示すものであり、２は固定化酵
素電極（試料電極）で、下地電極である白金膜１
０と固定化酵素膜９とからなつている。３は固定
化酵素電極２と対になる対極である。１１は試料
電極（W.E）２の全面に設けたメツシユ状電極
で、このメツシユ状電極１１は第２図に示すよう
にメツシユ状に形成されていて、感度劣化の要因
となる血球、血小板、各種タンパクを電気泳動に
より吸着せしめるものである。１２はメツシユ状
電極１１と対になる電極である。５は両電極２，
３に基準電圧を印加するための電源であり、４は
電流計である。また、メツシユ状電極１１には上
記基準電圧より少し高い1V程度の電圧が電源２
３により印加される。この電極表面上での状態を
模式的に示したものが第３図である。すなわち従
来感度劣化の要因であつた血球、血小板、各種タ
ンパクをメツシユ状電極１１に基準電圧より少し
高い1V程度の電圧を加えることにより吸着させ
て感度劣化を防ぐものである。
Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
Figure 1 shows a configuration diagram, in which 2 is an immobilized enzyme electrode (sample electrode), and platinum film 1 is the base electrode.
0 and an immobilized enzyme membrane 9. 3 is a counter electrode paired with the immobilized enzyme electrode 2. Reference numeral 11 denotes a mesh-shaped electrode provided on the entire surface of the sample electrode (WE) 2. As shown in FIG. Proteins are adsorbed by electrophoresis. Reference numeral 12 denotes an electrode paired with the mesh-like electrode 11. 5 is both electrodes 2,
3 is a power source for applying a reference voltage, and 4 is an ammeter. In addition, a voltage of about 1V, which is slightly higher than the above reference voltage, is applied to the mesh electrode 11 from the power source 2.
3. FIG. 3 schematically shows the state on the electrode surface. That is, by applying a voltage of about 1V, which is slightly higher than the reference voltage, to the mesh electrode 11, blood cells, platelets, and various proteins, which have conventionally caused deterioration of sensitivity, are adsorbed, thereby preventing deterioration of sensitivity.
第４図は特許請求の範囲第２項に対応する具体
回路図を示すものであり、これはグルコース濃度
検出装置に於て検査と検査の間にメツシユ状電極
１１への電圧印加を中止するスイツチ手段を設け
ものである。第５図は第４図に示す回路によつて
得られる出力波形であり検査と検査の間にメツシ
ユ状電極１１への電圧印加をオン、オフさせるこ
とによりメツシユ状電極１１上での吸着による血
球、血小板、各種タンパクの目づまりを防ぐもの
である。 FIG. 4 shows a specific circuit diagram corresponding to claim 2, which shows a switch for stopping the voltage application to the mesh electrode 11 between tests in the glucose concentration detection device. Means are provided. FIG. 5 shows an output waveform obtained by the circuit shown in FIG. 4. By turning on and off the voltage application to the mesh electrode 11 between examinations, blood cells are absorbed by the mesh electrode 11. , platelets, and various proteins from clogging.
すなわち、第４図において、１３はツエナーダ
イオードZD、電界効果トランジスタFET、オペ
アンプOP1等から構成される定電圧回路で、１４
はオペアンプOP2等から構成される電流・電圧変
換回路である。この両回路１３，１４にて固定化
酵素電極２と対極３との間に電圧が印加されるこ
とになる。また、メツシユ状電極１１と電極１２
との間には電源V1がスイツチSW1を介して接続
され、スイツチSW1がオンの時にメツシユ状電極
１１に電源V1の電圧が印加されるようにしてい
る。しかして、第５図ａに示すように時刻t0でス
イツチSW2をオンにすると、両回路１３，１４に
より固定化酵素電極２と対極３との間には電源
V2により基準電圧が印加される。その後定常状
態に落ち着いた後に、時刻t1でスイツチSW1をオ
ンにしてメツシユ状電極１１に基準電圧より少し
高い電圧を印加し、時刻t2で血液を注入して測定
する。この時に電流・電圧変換回路１４に流れる
電流を電圧に変換し、緩衝液中のグルコース濃度
に相当する電圧レベルを得るようにしている。そ
して、時刻t3でスイツチSW1をオフにしてメツシ
ユ状電極１１への電源V1からの電圧の印加を停
止し、メツシユ状電極１１上での吸着による血
球、血小板、各種タンパクの目づまりを防止す
る。このように、血液を注入してグルコース濃度
を測定する時はある一定時間スイツチSW1をオン
にしてメツシユ状電極１１に電源V1の電圧を印
加するが、測定以外の時にはスイツチSW1をオフ
にして電圧の印加を停止するようにしている。
尚、オペアンプOP2に電源が印加されてオン状態
の時には、第４図中のＡ点はグランドレベルとな
つて、AB間には基準電圧Vrefが印加されるが、
上記電源が印加されないオペアンプOP2がオフ状
態の時はＡ点はグランドレベルに落ちない。従つ
て、オフ状態からオン状態にした際に、試料電極
２と対極３間に定常状態になるまでの時間を回避
するために、両電極２，３間に電源V2による基
準電圧を与えるために連動するスイツチSW2SW3
を設けている。 That is, in FIG. 4, 13 is a constant voltage circuit composed of a Zener diode ZD, a field effect transistor FET, an operational amplifier OP 1 , etc.;
is a current/voltage conversion circuit consisting of an operational amplifier OP2 , etc. A voltage is applied between the immobilized enzyme electrode 2 and the counter electrode 3 in both circuits 13 and 14. In addition, the mesh-like electrode 11 and the electrode 12
A power source V1 is connected between the two electrodes through a switch SW1 , and the voltage of the power source V1 is applied to the mesh electrode 11 when the switch SW1 is on. When the switch SW 2 is turned on at time t 0 as shown in FIG.
A reference voltage is applied by V2 . Thereafter, after settling into a steady state, the switch SW 1 is turned on at time t 1 to apply a voltage slightly higher than the reference voltage to the mesh electrode 11, and at time t 2 blood is injected and measured. At this time, the current flowing through the current/voltage conversion circuit 14 is converted into voltage to obtain a voltage level corresponding to the glucose concentration in the buffer solution. Then, at time t3 , the switch SW 1 is turned off to stop applying voltage from the power supply V1 to the mesh electrode 11 , thereby preventing clogging of blood cells, platelets, and various proteins due to adsorption on the mesh electrode 11. do. In this way, when blood is injected and the glucose concentration is measured, the switch SW 1 is turned on for a certain period of time and the voltage of the power supply V 1 is applied to the mesh electrode 11, but when other than measurement, the switch SW 1 is turned off. to stop applying voltage.
Note that when power is applied to the operational amplifier OP 2 and it is in the on state, point A in FIG. 4 becomes the ground level, and the reference voltage Vref is applied between AB.
When the operational amplifier OP 2 is in the OFF state to which the above power is not applied, the point A does not fall to the ground level. Therefore, in order to avoid the time required for the sample electrode 2 and the counter electrode 3 to reach a steady state when the state is changed from the off state to the on state, a reference voltage from the power supply V 2 is applied between the sample electrode 2 and the counter electrode 3 between the two electrodes 2 and 3. Switch SW 2 SW 3 linked to
has been established.
第６図は併合発明の構成図を示すものであり、
プラス、マイナスの電圧が印加される一対のメツ
シユ状電極１１，１１′を固定化酵素電極２の前
面に配し、印加電圧のプラス、マイナスを反転さ
せるものである。これは固定化酵素電極２での感
度劣化はマイナスに帯電した血球、血小板、各種
タンパクが電気的に吸着したものと他の血球、血
小板、各種タンパクが酵素膜との接触により機械
的に付着したものにより発生する為である。従つ
てプラス、マイナスに印加されたメツシユ状電極
１１，１１′によつてその両方とも電気的吸着に
よつて除去しようとするものである。第７図は第
６図電極面上での模式図であり、スイツチ切換手
段を構成するスイツチSW4により電圧V3V4をメ
ツシユ状電極１１，１１′に交互に印加するよう
にしている。第７図ａはメツシユ状電極１１に電
圧V3のプラスを、電極１１′にマイナスを印加
し、また同図ｂは電極１１′に電圧V4のプラス
を、他方の電極１１にはマイナスを印加するよう
にした場合を示している。すなわち、第７図ａは
測定中であり、この測定中においてはメツシユ状
電極１１，１１′にプラス、マイナスの電荷を有
する血球、血小板、タンパク等が夫々吸着され
る。そして、スイツチSW4を切り換えてメツシユ
状電極１１，１１′に上記とは反対の極性の電圧
を印加してその反発力にて血球等を除去せしめる
ものである。 Figure 6 shows the configuration diagram of the merged invention,
A pair of mesh-like electrodes 11, 11' to which positive and negative voltages are applied are placed in front of the immobilized enzyme electrode 2, and the positive and negative voltages applied are reversed. This is because the sensitivity deterioration of the immobilized enzyme electrode 2 is due to electrical adsorption of negatively charged blood cells, platelets, and various proteins, and mechanical adhesion of other blood cells, platelets, and various proteins due to contact with the enzyme membrane. This is because it is caused by certain things. Therefore, the mesh electrodes 11, 11' to which positive and negative voltages are applied are used to remove both of them by electrical adsorption. FIG. 7 is a schematic view of the electrode surface shown in FIG. 6, in which a voltage V 3 V 4 is alternately applied to the mesh electrodes 11 and 11' by a switch SW 4 constituting a switch switching means. In FIG. 7a, a positive voltage V 3 is applied to the mesh electrode 11 and a negative voltage is applied to the electrode 11', and in FIG. 7b, a positive voltage V 4 is applied to the electrode 11' and a negative voltage is applied to the other electrode 11. This shows the case where the voltage is applied. That is, FIG. 7a shows the measurement in progress, and during this measurement, positively and negatively charged blood cells, platelets, proteins, etc. are adsorbed to the mesh-like electrodes 11 and 11', respectively. Then, the switch SW 4 is switched to apply a voltage of opposite polarity to the mesh electrodes 11, 11', and the repulsive force is used to remove blood cells and the like.
第８図は具体回路図を示すものであり、スイツ
チ切換発振回路１５により上記スイツチSW4を切
り換えるようにしている。第９図は第８図によつ
て得られる出力波形である。血液を注入してグル
コース濃度を測定するある時間内に一方の電極１
１又は１１′に電圧V3又はV4を印加するようにし
ている。このように、プラス、マイナスを印加す
る両メツシユ状電極１１，１１′を配しそれをス
イツチングさせることにより血球、血小板、各種
タンパクを電気的に吸引させて除去し検査と検査
の間（この間は血液は流れてこず、緩衝液のみが
流れている）にスイツチングによる吸着物質を放
出し、絶えず酵素電極表面上に血球、血小板、各
種タンパクが付着しない状態を保つておくことが
できるものである。 FIG. 8 shows a specific circuit diagram, in which the switch SW 4 is switched by a switch switching oscillation circuit 15. FIG. 9 shows the output waveform obtained by FIG. One electrode 1 within a certain period of time when blood is injected and the glucose concentration is measured.
A voltage V 3 or V 4 is applied to the terminal 1 or 11'. In this way, by arranging the mesh-like electrodes 11, 11' that apply positive and negative voltages and switching them, blood cells, platelets, and various proteins are electrically attracted and removed, and between examinations (during this period) By switching, an adsorbent is released into the enzyme electrode (no blood is flowing, only the buffer is flowing), and it is possible to constantly keep blood cells, platelets, and various proteins free from adhering to the surface of the enzyme electrode.
本発明は上述のように、電気泳動により血液、
尿中の血球、血小板、各種タンパク質等の物質を
除去するメツシユ状の電極を固定化酵素電極の前
面に設け、試料電極と対極とに印加される電圧よ
りも高い電圧を前記メツシユ状の電極に印加する
ようにしたものであるから、血液中のグルコース
濃度を測定する時、血球、血小板、タンパク等は
メツシユ状電極に吸着されることになつて、これ
ら血球等は固定化酵素電極にはほとんど付着しな
くなつて、経時的感度劣化を防ぐことができる効
果を奏する。
As described above, the present invention provides blood,
A mesh-shaped electrode for removing substances such as blood cells, platelets, and various proteins in urine is provided in front of the immobilized enzyme electrode, and a voltage higher than the voltage applied to the sample electrode and the counter electrode is applied to the mesh-shaped electrode. Therefore, when measuring the glucose concentration in blood, blood cells, platelets, proteins, etc. are adsorbed to the mesh electrode, and almost none of these blood cells are attached to the immobilized enzyme electrode. This has the effect of preventing deterioration of sensitivity over time by preventing adhesion.
また、併合発明にあつては、電気泳動により血
液、尿中の血球、血小板、各種タンパク質等の物
質を除去するメツシユ状の電極を固定化酵素電極
の前面に設け、試料電極と対極とに印加される電
圧よりも高い電圧を前記メツシユ状の電極に印加
する電源を設け、上記メツシユ状の電極と固定化
酵素電極との間に第２のメツシユ状の電極を配設
し、両メツシユ状の電極にプラス、マイナスの電
圧を交互に印加するスイツチ切換手段を設けたも
のであるから、血液、尿中のプラス、マイナスの
夫々の電荷を有する血液、血小板、各種タンパク
質等の物質を吸引と反発により、メツシユ状の電
極への血液、尿中の血球、血小板、各種タンパク
質の吸着を除去することが可能となり、安定した
感度特性を得ることができる効果を奏するもので
ある。 In addition, in the combined invention, a mesh-shaped electrode that removes substances such as blood, blood cells, platelets, and various proteins in blood and urine by electrophoresis is provided in front of the immobilized enzyme electrode, and an electric current is applied to the sample electrode and the counter electrode. A power source is provided to apply a voltage higher than the voltage applied to the mesh-shaped electrode to the mesh-shaped electrode, a second mesh-shaped electrode is disposed between the mesh-shaped electrode and the immobilized enzyme electrode, and a second mesh-shaped electrode is provided between the mesh-shaped electrode and the immobilized enzyme electrode. Since it is equipped with a switch that alternately applies positive and negative voltages to the electrodes, it attracts and repels substances such as blood, platelets, and various proteins that have positive and negative charges in blood and urine. This makes it possible to remove adsorption of blood, blood cells in urine, platelets, and various proteins to the mesh-shaped electrode, and has the effect of obtaining stable sensitivity characteristics.
第１図は本発明の実施例の構成図、第２図は同
上のメツシユ状電極の正面図、第３図は同上の電
極面上での模式図、第４図は同上の具体回路図、
第５図は同上の動作波形図、第６図は同上の併合
発明の実施例の構成図、第７図ａ，ｂは同上の模
式図、第８図は同上の具体回路図、第９図は同上
の動作波形図、第１０図は血液の成分を示す図、
第１１図および第１２図は従来例の遠心分離を行
つてグルコース濃度を測定する場合の説明図、第
１３図は同上の構成図、第１４図は同上の模式
図、第１５は同上のフロー方式による測定方法を
示す図、第１６図は同上の動作波形図である。
１は緩衡液、２は固定化酵素電極（試料電極）、
３は対極、１１はメツシユ状の電極、１１′は第
２のメツシユ状の電極を示す。
Fig. 1 is a configuration diagram of an embodiment of the present invention, Fig. 2 is a front view of the mesh-like electrode as above, Fig. 3 is a schematic diagram on the electrode surface of the above, Fig. 4 is a specific circuit diagram of the same as above,
Fig. 5 is an operation waveform diagram of the same as above, Fig. 6 is a configuration diagram of an embodiment of the combined invention of the above, Fig. 7 a and b are schematic diagrams of the same as the above, Fig. 8 is a specific circuit diagram of the above, and Fig. 9 is the same operating waveform diagram as above, Figure 10 is a diagram showing blood components,
Figures 11 and 12 are explanatory diagrams of conventional centrifugal separation to measure glucose concentration, Figure 13 is a configuration diagram of the same as above, Figure 14 is a schematic diagram of the same as above, and Figure 15 is a flowchart of the same as above. FIG. 16, which is a diagram showing a measurement method based on the method, is an operation waveform diagram of the same as above. 1 is a buffer solution, 2 is an immobilized enzyme electrode (sample electrode),
3 is a counter electrode, 11 is a mesh-like electrode, and 11' is a second mesh-like electrode.
Claims (1)
この試料電極と対になる対極とを浸し、両電極間
に電圧を印加して試料電極からの出力にて緩衝液
中に投入された血液、尿中のグルコース濃度を検
出するグルコース濃度検出装置において、電気泳
動により血液、尿中の血球、血小板、各種タンパ
ク質等の物質を除去するメツシユ状の電極を固定
化酵素電極の前面に設け、試料電極と対極とに印
加される電圧よりも高い電圧を前記メツシユ状の
電極に印加して成ることを特徴とするグルコース
濃度検出装置。 ２ グルコース濃度検出の検査休止期間中メツシ
ユ状の電極への電圧印加を中止するスイツチ手段
を有していることを特徴とする特許請求の範囲第
１項記載のグルコース濃度検出装置。 ３ 緩衝液中に固定化酵素電極である試料電極と
この試料電極と対になる対極とを浸し、両電極間
に電圧を印加して試料電極からの出力にて緩衝液
中に投入された血液、尿中のグルコース濃度を検
出するグルコース濃度検出装置において、電気泳
動により血液、尿中の血球、血小板、各種タンパ
ク質等の物質を除去するメツシユ状の電極を固定
化酵素電極の前面に設け、試料電極と対極とに印
加される電圧よりも高い電圧を前記メツシユ状の
電極に印加する電源を設け、上記メツシユ状の電
極と固定化酵素電極との間に第２のメツシユ状の
電極を配設し、両メツシユ状の電極にプラス、マ
イナスの電圧を交互に印加するスイツチ切換手段
を設けて成ることを特徴とするグルコース濃度検
出装置。[Claims] 1. A sample electrode, which is an immobilized enzyme electrode, and a counter electrode paired with the sample electrode are immersed in a buffer solution, and a voltage is applied between both electrodes, so that the output from the sample electrode is adjusted to the buffer solution. In a glucose concentration detection device that detects the glucose concentration in blood and urine input into the bloodstream, an enzyme electrode with an immobilized mesh electrode is used to remove substances such as blood cells, platelets, and various proteins from blood and urine by electrophoresis. What is claimed is: 1. A glucose concentration detecting device, characterized in that the glucose concentration detecting device is provided in front of the mesh-shaped electrode, and a voltage higher than the voltage applied to the sample electrode and the counter electrode is applied to the mesh-shaped electrode. 2. The glucose concentration detection device according to claim 1, further comprising a switch means for stopping the application of voltage to the mesh-shaped electrode during a test suspension period for glucose concentration detection. 3. Immerse a sample electrode, which is an immobilized enzyme electrode, and a counter electrode paired with the sample electrode in a buffer solution, and apply a voltage between the two electrodes to detect the blood injected into the buffer solution based on the output from the sample electrode. In a glucose concentration detection device that detects glucose concentration in urine, a mesh-shaped electrode is installed in front of an immobilized enzyme electrode to remove substances such as blood, blood cells in urine, platelets, and various proteins by electrophoresis. A power source is provided to apply a voltage higher than the voltage applied to the electrode and the counter electrode to the mesh-shaped electrode, and a second mesh-shaped electrode is disposed between the mesh-shaped electrode and the immobilized enzyme electrode. 1. A glucose concentration detection device comprising: a switch for alternately applying a positive voltage and a negative voltage to both mesh-shaped electrodes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59122345A JPS61750A (en) | 1984-06-14 | 1984-06-14 | Glucose concentration detector |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59122345A JPS61750A (en) | 1984-06-14 | 1984-06-14 | Glucose concentration detector |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61750A JPS61750A (en) | 1986-01-06 |
| JPH0426427B2 true JPH0426427B2 (en) | 1992-05-07 |
Family
ID=14833649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59122345A Granted JPS61750A (en) | 1984-06-14 | 1984-06-14 | Glucose concentration detector |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61750A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06481U (en) * | 1992-06-16 | 1994-01-11 | 株式会社学習研究社 | Slingshot toys |
| KR20010067623A (en) * | 2001-02-23 | 2001-07-13 | 홍영표 | Noninvasive Glucose Extraction through Skin by Reverse Iontophoresis or Electroosmosis |
| KR100453483B1 (en) * | 2001-10-26 | 2004-10-20 | 케이엠에이치 주식회사 | Patch for glucose extraction apparatus and manufacturing process for the same |
| KR20090118314A (en) * | 2008-05-13 | 2009-11-18 | 케이엠에이치 주식회사 | A apparatus and method for measuring a blood glucose using a electrophoresis phenomenon without blood gathering |
-
1984
- 1984-06-14 JP JP59122345A patent/JPS61750A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61750A (en) | 1986-01-06 |
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