JPH01152357A - Biosensor - Google Patents
BiosensorInfo
- Publication number
- JPH01152357A JPH01152357A JP62312857A JP31285787A JPH01152357A JP H01152357 A JPH01152357 A JP H01152357A JP 62312857 A JP62312857 A JP 62312857A JP 31285787 A JP31285787 A JP 31285787A JP H01152357 A JPH01152357 A JP H01152357A
- Authority
- JP
- Japan
- Prior art keywords
- enzyme
- immobilized membrane
- membrane
- crosslinking agent
- albumin
- 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
- 239000012528 membrane Substances 0.000 claims abstract description 40
- 102000004190 Enzymes Human genes 0.000 claims abstract description 27
- 108090000790 Enzymes Proteins 0.000 claims abstract description 27
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 18
- 102000009027 Albumins Human genes 0.000 claims abstract description 15
- 108010088751 Albumins Proteins 0.000 claims abstract description 15
- 239000000126 substance Substances 0.000 claims description 11
- 229940088598 enzyme Drugs 0.000 abstract description 22
- 102000016938 Catalase Human genes 0.000 abstract description 8
- 108010053835 Catalase Proteins 0.000 abstract description 8
- 108010015776 Glucose oxidase Proteins 0.000 abstract description 5
- 239000004366 Glucose oxidase Substances 0.000 abstract description 5
- 229940116332 glucose oxidase Drugs 0.000 abstract description 5
- 235000019420 glucose oxidase Nutrition 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 3
- 238000006911 enzymatic reaction Methods 0.000 abstract description 2
- -1 glyconolactnase Proteins 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract description 2
- 238000000605 extraction Methods 0.000 abstract 1
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 102100030262 Regucalcin Human genes 0.000 description 3
- 108050007056 Regucalcin Proteins 0.000 description 3
- 239000012491 analyte Substances 0.000 description 3
- 239000004065 semiconductor Substances 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 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 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000005669 field effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、酵素電極と参照電極の差動出力によって測定
する電気化学センサに関し、特に血液等の体液、発酵溶
液、果実などの多様な成分を含む系を測定する酵素セン
サの酵素固定化膜の構造に関するものである。Detailed Description of the Invention (Field of Industrial Application) The present invention relates to an electrochemical sensor that measures various components such as body fluids such as blood, fermented solutions, and fruits using differential outputs of an enzyme electrode and a reference electrode. The present invention relates to the structure of an enzyme-immobilized membrane of an enzyme sensor that measures a system containing.
（従来の技術）
従来、溶液中の特定の有機物の濃度を測定する半導体バ
イオセンサの一種に半導体電界効果型イオンセンサ（以
下ｒ Ｉ ５ＦＥＴ、という）の表面に酸素を固定化し
た膜が設けられたものが知られている（宮原裕二、塩用
祥子、森泉豊栄、松岡英明、軽部征夫、鈴木周−：半導
体技術を用いたバイオセンサ」電子通信学会、電子部品
材料研究会資料（ＰＭ、８１−９３．６１ （１９８１
）） 。(Prior Art) Conventionally, a film on which oxygen is fixed is provided on the surface of a semiconductor field-effect ion sensor (hereinafter referred to as rI5FET), which is a type of semiconductor biosensor that measures the concentration of a specific organic substance in a solution. (Yuji Miyahara, Shoko Shioyo, Toyosaka Moriizumi, Hideaki Matsuoka, Yukio Karube, Shu Suzuki: Biosensors using semiconductor technology, Materials from the Institute of Electronics and Communication Engineers, Electronic Components and Materials Study Group (PM, 81) -93.61 (1981
)).
ｌ５ＦＥＴを実際の測定に供した場合問題となるのは、
測定対象中に存在する被測定物質以外の物質がセンサの
出力に与える影響である。このような影響を回避する手
段として、センサの差動出力を計測することが一般に行
われている。すなわち２つの電気化学センサのうち、一
方を酵素固定化膜を形成した酵素電極とし、他方を何も
設けていない参照電極として測定に際しては、酵素電極
の出力と参照電極の出力との差、いわゆる差動出力を測
定するものである。この方式に従えば、被測定物質以外
の要因からの影響は消去され、差動出力は被測定物質の
濃度のみに依存すると考えられる。The problem when using 15FET for actual measurement is:
This is the effect that substances other than the measured substance present in the measurement object have on the output of the sensor. As a means to avoid such an influence, it is generally practiced to measure the differential output of the sensor. In other words, when measuring between two electrochemical sensors, using one as an enzyme electrode with an enzyme-immobilized membrane formed thereon and the other as a reference electrode without any, the difference between the output of the enzyme electrode and the output of the reference electrode, the so-called It measures differential output. According to this method, it is considered that the influence from factors other than the substance to be measured is eliminated, and the differential output depends only on the concentration of the substance to be measured.
（発明が解決しようとする問題点）
しかしながら、血液などの多様な成分を含む溶液中の測
定では、タンパク質成分の吸着や血液の凝固などが起こ
るため、差動出力にドリフトを生じたり、出力が不安定
となるなど、被測定物質以外の要因を完全に消去できな
いという問題が残っている。(Problem to be solved by the invention) However, when measuring in a solution containing various components such as blood, adsorption of protein components and coagulation of blood occur, which may cause drift in the differential output or decrease the output. There remains the problem that factors other than the substance to be measured cannot be completely eliminated, such as instability.
（問題点を解決するための手段）
本発明は、酵素電極と参照電極の差動出力によって測定
する電気化学センサにおいて、酵素電極側の酵素固定化
膜と同様の組成を有し酵素を含まない固定化膜を参照電
極に有することを特徴とするバイオセンサの酵素固定化
膜構造を提供するものである。(Means for Solving the Problems) The present invention provides an electrochemical sensor that measures by differential output between an enzyme electrode and a reference electrode, which has the same composition as the enzyme-immobilized membrane on the enzyme electrode side and does not contain enzyme. The present invention provides an enzyme-immobilized membrane structure for a biosensor characterized by having an immobilized membrane as a reference electrode.
（作用）
酵素電極側と参照電極側とに上記の酵素固定化膜構造を
設けることによって、血液などの多様な成分を含む溶液
中では、タンパク質などの吸着や被測定物質のｌ５ＦＥ
Ｔ上への拡散が画電極で同一となる。その結果、両者と
も同様に出力の°変化が起き、差動出力では、タンパク
質などの吸着や被測定物質以外のｌ５ＦＥＴ上への拡散
などがキャンセルされ安定した測定を実現することが出
来る。(Function) By providing the above-mentioned enzyme-immobilized membrane structure on the enzyme electrode side and the reference electrode side, in a solution containing various components such as blood, adsorption of proteins and l5FE of the analyte can be achieved.
The diffusion onto T is the same at the picture electrode. As a result, the output changes in the same way in both cases, and with differential output, adsorption of proteins and the like and diffusion of substances other than the substance to be measured onto the 15FET are canceled out, making it possible to realize stable measurement.
（実施例）
以下、本発明の実施例について説明する。第１図は、本
発明の一実施例を示すためのバイオセンサの断面図であ
る。酵素電極２には、グルコースオキシダーゼ、グリコ
ノラクトナーゼ、カタラーゼと架橋剤を含んだ固定化膜
３とその上にアルブミンと架橋剤による固定化膜４の２
層の固定化膜が形成されており、参照型８ｉ１は、カタ
ラーゼ、アルブミンと架橋剤から成る固定化膜５とその
上にアルブミンと架橋剤から成る固定化膜４の２層の固
定化膜が設けられている。再固定化膜のちがいは、酵素
活性の有無だけで物理化学的に同じ性質を持っている。(Example) Examples of the present invention will be described below. FIG. 1 is a sectional view of a biosensor showing one embodiment of the present invention. The enzyme electrode 2 includes an immobilized membrane 3 containing glucose oxidase, glyconolactonase, catalase, and a crosslinking agent, and an immobilized membrane 4 formed of albumin and a crosslinking agent thereon.
The reference type 8i1 has two layers of immobilization membranes: an immobilization membrane 5 made of catalase, albumin, and a crosslinking agent, and an immobilization membrane 4 made of albumin and a crosslinking agent thereon. It is provided. The only difference between reimmobilized membranes is the presence or absence of enzyme activity, and they have the same physicochemical properties.
したがって、酵素反応による出力変化だけが取り出せる
。第５図の７（実線）は、本発明のセンサによって測定
した血漿の出力特性である。Therefore, only output changes due to enzyme reactions can be extracted. 7 (solid line) in FIG. 5 is the output characteristic of plasma measured by the sensor of the present invention.
第２図は、従来のバイオセンサの断面図である。この従
来型センサを用いて測定した場合は、第５図の８（波線
）の出力特性である。FIG. 2 is a cross-sectional view of a conventional biosensor. When measured using this conventional sensor, the output characteristic is 8 (broken line) in FIG. 5.
このように、本発明によるバイオセンサの酵素膜構造に
よって多様な成分系を含む測定の効果は、明らかである
。As described above, it is clear that the enzyme membrane structure of the biosensor according to the present invention is effective in measuring various component systems.
第３図は、参照電極側にアルブミンと架橋剤から成る固
定化膜４を、酵素電極側には第１図の酵素電極上に形成
された２層構造の固定化膜３．４と同じ固定化酵素膜を
形成した場合である。Figure 3 shows an immobilization membrane 4 consisting of albumin and a cross-linking agent on the reference electrode side, and an immobilization membrane 4 of the same two-layer structure formed on the enzyme electrode in Figure 1 on the enzyme electrode side. This is the case when a conjugated enzyme membrane is formed.
このような構造でも本発明による効果は得られる。Even with such a structure, the effects of the present invention can be obtained.
第４図は、参照電極側にアルブミンと架橋剤から成る固
定化膜を、酵素電極側にはグルコースオキシダーゼ、グ
ルコノラクトナーゼ、カタラーゼ、アルブミンと架橋剤
から成る固定化膜である。このような−層構造によって
も本発明による効果は得られる。なお以上の実施例は、
２層構造までに限定するものではない、３層以上も可能
である。FIG. 4 shows an immobilized membrane consisting of albumin and a crosslinking agent on the reference electrode side, and an immobilized membrane consisting of glucose oxidase, gluconolactonase, catalase, albumin, and a crosslinking agent on the enzyme electrode side. Even with such a layered structure, the effects of the present invention can be obtained. Note that the above embodiments are
The structure is not limited to two layers, but three or more layers are also possible.
（発明効果）
従来のセンサでは、多様な成分を含む溶液系の測定に際
して、被測定物質以外の影響を消去できなかったのに対
し、本発明によるバイオセンサの酵素固定化膜構造では
、物理化学的に同一な酵素を含まない膜を参照電極上に
設けるために、多様な成分を含む溶液系においても、被
測定物質だけの変化を取り出すことが可能である。(Effect of the invention) Conventional sensors could not eliminate the effects of substances other than the analyte when measuring solution systems containing various components, whereas the enzyme-immobilized membrane structure of the biosensor of the present invention Since a membrane that does not contain the same enzyme is provided on the reference electrode, it is possible to extract changes in only the analyte even in a solution system containing various components.
第１図、第３図、第４図は、本発明の一実施例を示すセ
ンサの断面図、第２図は従来の構造を示す断面図である
。第４図は、本発明と従来のセンサによる血漿測定の出
力特性を比較した図である。
図において、
１・・・参照電極 ２・・・酵素電極
３・・・グルコースオキシダーゼ、グルコノラクトナー
ゼ、カタラーゼと架橋剤から成る固定化膜４・・・アル
ブミンと架橋剤から成る固定化膜５・・・カタラーゼ、
アルブミンと架橋剤から成る固定化膜
６・・・グルコースオキシダーゼ、グルコノラクトナー
ゼ、カタラーゼ、アルブミンと架橋剤から成る固定化膜
７・・・本発明を用いたグルコースセンサによって血漿
を測定した際の出力特性
８・・・従来のグルコースセンサによって血漿を測定し
た際の出力特性1, 3, and 4 are cross-sectional views of a sensor showing an embodiment of the present invention, and FIG. 2 is a cross-sectional view showing a conventional structure. FIG. 4 is a diagram comparing the output characteristics of blood plasma measurement by the sensor of the present invention and the conventional sensor. In the figure, 1... Reference electrode 2... Enzyme electrode 3... Immobilized membrane made of glucose oxidase, gluconolactonase, catalase and a crosslinking agent 4... Immobilized membrane 5 made of albumin and a crosslinking agent ... Catalase,
Immobilized membrane 6 consisting of albumin and a crosslinking agent...Immobilized membrane 7 consisting of glucose oxidase, gluconolactonase, catalase, albumin and a crosslinking agent...When plasma is measured by the glucose sensor using the present invention Output characteristics 8: Output characteristics when measuring plasma with a conventional glucose sensor
Claims (3)
を測定するバイオセンサにおいて、酵素電極上に酵素固
定化膜が形成され、該酵素固定化膜から被測定物質に反
応する酵素を除いた膜が参照電極上に形成されているこ
とを特徴とするバイオセンサ。(1) In a biosensor that measures a specific substance using differential output between an enzyme electrode and a reference electrode, an enzyme-immobilized membrane is formed on the enzyme electrode, and the enzyme that reacts with the substance to be measured is removed from the enzyme-immobilized membrane. A biosensor characterized in that a membrane is formed on a reference electrode.
び架橋剤より形成された膜である事を特徴とする特許請
求の範囲第１項に記載のバイオセンサ。(2) The biosensor according to claim 1, wherein the enzyme-immobilized membrane is a membrane formed of at least an enzyme, albumin, and a crosslinking agent.
び架橋剤より構成され下側に位置する第１の膜と少なく
ともアルブミンと架橋剤より構成され上側に位置する第
２の膜より構成される２層構造であることを特徴とする
特許請求の範囲第２項に記載のバイオセンサ。(3) The enzyme-immobilized membrane is a two-layered film consisting of a first membrane located on the lower side and composed of at least an enzyme, albumin, and a crosslinking agent, and a second membrane located on the upper side and composed of at least albumin and a crosslinking agent. The biosensor according to claim 2, characterized in that the biosensor has a structure.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62312857A JPH0750063B2 (en) | 1987-12-09 | 1987-12-09 | Biosensor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62312857A JPH0750063B2 (en) | 1987-12-09 | 1987-12-09 | Biosensor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01152357A true JPH01152357A (en) | 1989-06-14 |
| JPH0750063B2 JPH0750063B2 (en) | 1995-05-31 |
Family
ID=18034272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62312857A Expired - Lifetime JPH0750063B2 (en) | 1987-12-09 | 1987-12-09 | Biosensor |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0750063B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1182456A3 (en) * | 2000-07-21 | 2003-02-05 | i-SENS, INC. | Biosensors with porous chromatographic membranes |
| WO2008093494A1 (en) * | 2007-01-30 | 2008-08-07 | Nikkiso Co., Ltd. | Monitor and living body measuring device |
| JP2017531157A (en) * | 2014-06-05 | 2017-10-19 | アヴェイルズ メディカル，インコーポレイテッド | System and method for detecting substances in body fluids |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61231454A (en) * | 1985-04-08 | 1986-10-15 | Nok Corp | Physiologically active substance immobilized membrane and electric field effect type transistor-urea sensor using the same |
-
1987
- 1987-12-09 JP JP62312857A patent/JPH0750063B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61231454A (en) * | 1985-04-08 | 1986-10-15 | Nok Corp | Physiologically active substance immobilized membrane and electric field effect type transistor-urea sensor using the same |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1182456A3 (en) * | 2000-07-21 | 2003-02-05 | i-SENS, INC. | Biosensors with porous chromatographic membranes |
| WO2008093494A1 (en) * | 2007-01-30 | 2008-08-07 | Nikkiso Co., Ltd. | Monitor and living body measuring device |
| JP2008183250A (en) * | 2007-01-30 | 2008-08-14 | Nikkiso Co Ltd | Monitor and artificial pancreas apparatus |
| US8340739B2 (en) | 2007-01-30 | 2012-12-25 | Nikkiso Co., Ltd. | Monitor device and biological component-measuring device |
| JP2017531157A (en) * | 2014-06-05 | 2017-10-19 | アヴェイルズ メディカル，インコーポレイテッド | System and method for detecting substances in body fluids |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0750063B2 (en) | 1995-05-31 |
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