JPH0339648A - Glucose biosensor - Google Patents
Glucose biosensorInfo
- Publication number
- JPH0339648A JPH0339648A JP1174941A JP17494189A JPH0339648A JP H0339648 A JPH0339648 A JP H0339648A JP 1174941 A JP1174941 A JP 1174941A JP 17494189 A JP17494189 A JP 17494189A JP H0339648 A JPH0339648 A JP H0339648A
- Authority
- JP
- Japan
- Prior art keywords
- membrane
- glucose
- calibration range
- working electrode
- electrode
- 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.)
- Pending
Links
- 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 title claims description 38
- 239000008103 glucose Substances 0.000 title claims description 38
- 239000012528 membrane Substances 0.000 claims abstract description 45
- 239000000126 substance Substances 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 10
- 108010015776 Glucose oxidase Proteins 0.000 abstract description 9
- 239000004366 Glucose oxidase Substances 0.000 abstract description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 abstract description 9
- 229940116332 glucose oxidase Drugs 0.000 abstract description 9
- 235000019420 glucose oxidase Nutrition 0.000 abstract description 9
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 abstract description 8
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 abstract description 7
- 229910052697 platinum Inorganic materials 0.000 abstract description 4
- 229920005989 resin Polymers 0.000 abstract description 4
- 239000011347 resin Substances 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 abstract description 4
- YVXDRFYHWWPSOA-BQYQJAHWSA-N 1-methyl-4-[(e)-2-phenylethenyl]pyridin-1-ium Chemical group C1=C[N+](C)=CC=C1\C=C\C1=CC=CC=C1 YVXDRFYHWWPSOA-BQYQJAHWSA-N 0.000 abstract description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 229910052737 gold Inorganic materials 0.000 abstract description 3
- 239000010931 gold Substances 0.000 abstract description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 abstract description 3
- 229910021607 Silver chloride Inorganic materials 0.000 abstract description 2
- 239000002861 polymer material Substances 0.000 abstract description 2
- 229910052709 silver Inorganic materials 0.000 abstract description 2
- 239000004332 silver Substances 0.000 abstract description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 abstract description 2
- 239000007788 liquid Substances 0.000 abstract 3
- 239000002904 solvent Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 14
- 238000010438 heat treatment Methods 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 239000002131 composite material Substances 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 229920002301 cellulose acetate Polymers 0.000 description 3
- 238000001223 reverse osmosis Methods 0.000 description 3
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000007772 electrode material Substances 0.000 description 2
- 235000012209 glucono delta-lactone Nutrition 0.000 description 2
- 229960003681 gluconolactone Drugs 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003411 electrode reaction Methods 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 150000002303 glucose derivatives Chemical class 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- -1 or the like is used Chemical compound 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920002037 poly(vinyl butyral) polymer Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、グルコースバイオセンサに関する。[Detailed description of the invention] [Industrial application field] The present invention relates to glucose biosensors.
更に詳しくは、検量範囲を拡大せしめたグルコースバイ
オセンサに関する。More specifically, the present invention relates to a glucose biosensor with an expanded calibration range.
従来のグルコースオキシダーゼ（ＣＯＤ）を用いたグル
コースバイオセンサにおいては、次の反応式に示される
ように、０□もしくは！（，０□を検知することにより
、間接的にグルコース量を測定することが行われており
、理論的に限界がみられる。In the conventional glucose biosensor using glucose oxidase (COD), as shown in the following reaction formula, 0□ or ! (,0□ is used to indirectly measure the amount of glucose, and there is a theoretical limit.
ＣＯＤ
グルコース＋０２ → グルコノラクトン＋Ｈ，０□
つまり、溶存酸素量は３７℃において約０．２μＭ／ｒ
ｓＱであり、これをグルコース量に換算すると約４０ｍ
ｇ／ａとなる。上記式は等モル反応であるから。COD Glucose +02 → Gluconolactone +H,0□
In other words, the amount of dissolved oxygen is approximately 0.2 μM/r at 37°C.
sQ, which is approximately 40 m when converted to glucose amount.
g/a. The above formula is an equimolar reaction.
これが検量上限値となる。This becomes the upper limit of calibration.
このように、０２もしくはＨ２０□を測定する方法には
欠点があり、こうした欠点のない方法として、近年反応
が溶存酸素に依存しないメデイエータ型グルコースバイ
オセンサが開発されており、その例としてフェロセンタ
イブのものが挙げられる。As described above, there are drawbacks to the methods of measuring 02 or H20□, but as a method that does not have these drawbacks, mediator-type glucose biosensors whose reactions do not depend on dissolved oxygen have been developed in recent years. Things can be mentioned.
これの電極反応は、以下に示される如くであり、０□の
代わりにメデイエータ（この場合にはフェロセン）を電
子受容体としたものであり、溶存酸素には律速されない
。This electrode reaction is as shown below, and uses a mediator (ferrocene in this case) as an electron acceptor instead of 0□, and is not rate-limited by dissolved oxygen.
しかしながら、このタイプの場合には、グルコースオキ
シダーゼは電子受容体としてメデイエータ、０□と共に
用いられ、このときこれら両者が共存すると、０□の割
合によって出力が変化するので、その都度出力の補正（
０□の補正）を必要とするようになる。However, in this type of case, glucose oxidase is used together with the mediator, 0□, as an electron acceptor, and if these two coexist, the output changes depending on the ratio of 0□, so the output is corrected each time.
0□ correction) is now required.
本発明の目的は、このような欠点がみられず。 The object of the present invention is to avoid such drawbacks.
検量範囲を拡大せしめたグルコースバイオセンサを提供
することにある。An object of the present invention is to provide a glucose biosensor with an expanded calibration range.
〔課題を解決するための手段〕。[Means for solving problems].
かかる本発明の目的は、作用極面上のグルコースオキシ
ダーゼ固定化膜上に、高分子物質の乾湿式膜またはそれ
の加熱処理膜よりなる基質透過膜を形成せしめたグルコ
ースバイオセンサによって遠戚される。The object of the present invention is distantly related to a glucose biosensor in which a substrate-permeable membrane made of a dry-wet membrane of a polymeric material or a heat-treated membrane thereof is formed on a glucose oxidase-immobilized membrane on a working electrode surface. .
このグルコースバイオセンサでは１作用極以外に、対極
あるいは対極と参照極とがいずれも線状体などの電極と
して用いられる０作用極材料としては金、チタン、カー
ボンなどが用いられ、対極材料としては白金、金などが
用いられ、また参照極としては、銀／塩化銀電極などが
用いられる。In this glucose biosensor, in addition to the working electrode, the counter electrode or both the counter electrode and the reference electrode are used as electrodes such as linear bodies. Gold, titanium, carbon, etc. are used as the working electrode material, and the counter electrode material is Platinum, gold, or the like is used, and a silver/silver chloride electrode or the like is used as the reference electrode.
作用極面上へのグルコースオキシダーゼ固定化膜の形成
は、線状体電極の端部に、任意の方法で行うことができ
るが、好ましくは水溶性光架橋性樹脂を用いて行われる
。即ち、逆浸透水０．４ｍＮに約１０〜５０ｍｇ、好ま
しくは約３０ｍｇ程度のグルコースオキシダーゼおよび
約０．１〜Ｉｇ、好ましくは約０．５ｇ程度の水溶性光
架橋性樹脂、例えば感光性基としてスチルバゾリウム基
を有するポリビニルアルコール系、ポリエチレングリコ
ール系、ポリプロピレングリコール系のものなどを添加
した溶液中に、線状体電極端部を浸漬し、室温下で乾燥
させた後光照射して架橋させることにより行われる。The glucose oxidase-immobilized membrane can be formed on the working electrode surface at the end of the linear electrode by any method, but preferably by using a water-soluble photocrosslinkable resin. That is, about 10 to 50 mg, preferably about 30 mg, of glucose oxidase and about 0.1 to Ig, preferably about 0.5 g of a water-soluble photocrosslinkable resin, for example, as a photosensitive group, are added to 0.4 mN of reverse osmosis water. By immersing the end of the linear body electrode in a solution containing polyvinyl alcohol, polyethylene glycol, or polypropylene glycol having a stilbazolium group, drying it at room temperature, and then irradiating it with light to crosslink it. It will be done.
この他、グルタルアルデヒド／アルブミン／酵素系、ポ
リアクリルアミド／酵素系など、一般に用いられている
方法でも酵素固定化膜の形成が行われる。In addition, commonly used methods such as glutaraldehyde/albumin/enzyme system and polyacrylamide/enzyme system can also be used to form the enzyme-immobilized membrane.
このようにして形成されたグルコースオキシダーゼ固定
化膜上への基質透過膜の形成は、ポリビニルブチラール
、酢酸セルロース、ポリスルホンなどの膜形成性高分子
物質の有機溶媒溶液、好ましくはジメチルホルムアミド
、ジメチルアセトアミドなどの水溶性有機溶媒の溶液よ
りなるドープ液中に浸漬し、それを引き上げて十分に乾
燥しない前にそれのゲル化浴、例えば水中に浸漬してゲ
ル化させることにより行われる。Formation of a substrate-permeable membrane on the thus formed glucose oxidase-immobilized membrane is carried out using an organic solvent solution of a membrane-forming polymeric substance such as polyvinyl butyral, cellulose acetate, or polysulfone, preferably dimethylformamide, dimethylacetamide, etc. This is done by immersing the dope in a dope solution consisting of a solution of a water-soluble organic solvent, and before pulling it out and drying it sufficiently, immersing it in a gelling bath, for example water, to gel it.
この際のドープ液の濃度は、グルコースバイオセンサの
検量範囲を大きく左右するので重要であり、一般に約１
〜３０重量２、好ましくは約５〜２０重量２の濃度で調
製され、用いられる。このドープ液濃度が高くなるに従
って、その検量範囲は拡大するが、約３０重量２以上で
は定常出力値が極端に低下するようになり、一方これ以
下の濃度で用いられると、検量範囲の制御が不可能とな
る。The concentration of the dope solution at this time is important because it greatly influences the calibration range of the glucose biosensor, and is generally about 1
A concentration of ~30 wt 2 is prepared and used, preferably about 5-20 wt 2 . As the concentration of this dope solution increases, its calibration range expands; however, when it exceeds about 30 wt. It becomes impossible.
検量範囲の拡大はまた、−旦形成させた乾湿式膜を加熱
処理することによっても行われる。加熱処理は、水浴中
あるいは空気中などで約４０〜７０℃に加熱することに
よって行われる。この熱処理温度が高い程、検量範囲は
拡大するが、加熱処理温度を高めすぎると酵素の失活を
招く可能性があるので、ドープ液濃度を調節する方法を
とる方が安全ではある。The calibration range can also be expanded by heat-treating the wet-dry membrane once formed. The heat treatment is performed by heating to about 40 to 70°C in a water bath or in the air. The higher the heat treatment temperature is, the wider the calibration range will be, but if the heat treatment temperature is too high, the enzyme may be deactivated, so it is safer to adjust the concentration of the dope solution.
〔作用〕および〔発明の効果〕
前述の如く、溶液中の溶存酸素濃度には限界があるので
、検知グルコース量をこれと同濃度レベル迄低下させれ
ばよいことになる。この場合の溶液−基質透過膜−酵素
固定化膜中の酸素およびグルコース濃度レベルは、基質
透過膜によるグルコース濃度レベルを溶存酸素と等モル
付近に迄下げることにより、検量範囲上限を拡大できる
ことになる。この検量範囲上限の制御は、基質透過膜の
グルコース拡散能力制御による。[Function] and [Effects of the Invention] As mentioned above, since there is a limit to the dissolved oxygen concentration in the solution, it is sufficient to reduce the detected glucose amount to the same concentration level. In this case, the upper limit of the calibration range can be expanded by lowering the oxygen and glucose concentration levels in the solution-substrate-permeable membrane-enzyme immobilization membrane to around equimolar levels of dissolved oxygen in the glucose concentration level in the substrate-permeable membrane. . The upper limit of the calibration range is controlled by controlling the glucose diffusion ability of the substrate permeable membrane.
酵素固定化膜の表面および内部に達したグルコースは、
グルコースオキシダーゼによって直ちにグルコノラクト
ンとＨ２０□とに変換され、反応は定常状態となり、溶
液−基質透過膜−酵素固定化膜中の濃度レベルも定常と
なる。Glucose that reaches the surface and inside of the enzyme-immobilized membrane is
It is immediately converted into gluconolactone and H20□ by glucose oxidase, and the reaction becomes steady state, and the concentration level in the solution-substrate-permeable membrane-enzyme immobilization membrane also becomes steady.
このように、検量範囲上限を制御するには、基質透過膜
の特性を制御すればよく、このために本発明においては
、ドープ液濃度によって特性の制御可能な高分子物質の
乾湿式膜が基質透過膜として選択され、更に必要に応じ
てそれの加熱処理による膜特性の制御が行われている。In this way, in order to control the upper limit of the calibration range, it is sufficient to control the characteristics of the substrate-permeable membrane, and for this purpose, in the present invention, a wet-dry membrane of a polymer material whose characteristics can be controlled by the concentration of the dope solution is used as the substrate. It is selected as a permeable membrane, and its membrane properties are further controlled by heat treatment as necessary.
検量範囲を拡大させた本発明のグルコースバイオセンサ
は、人工膵臓用血糖値センサ、家庭用自己管理血糖値セ
ンサ、発酵槽用グルコースセンサなどとして有効に使用
することができる。The glucose biosensor of the present invention with an expanded calibration range can be effectively used as a blood sugar sensor for artificial pancreas, a self-management blood sugar sensor for home use, a glucose sensor for fermenters, and the like.
次に、実施例について本発明を説明する。 Next, the present invention will be explained with reference to examples.
比較例１
直径０．２■、長さ４ｃ閣の金線（フルウチ化学製品、
純度９９．９９％）の両端部をそれぞれ０．５ｏ＋ａず
つ残し。Comparative Example 1 Gold wire with a diameter of 0.2 cm and a length of 4 cm (Furuuchi Chemical Products,
(purity 99.99%) with 0.5o+a left on each end.
エポキシ樹脂で絶縁した。この一端側を、グルコースオ
キシダーゼ（シグマ社製品、ＥＣ１，１，３，４、タイ
プ■、１５．３０００／ｇ、 Ａｓｐｅｒｇｉｌｌｕｓ
ｎｉｇｅｒ由来）３０ＩＩ１ｇ、水溶性光架橋性樹脂
（スチルバゾリウム基含有ポリビニルアルコール）０．
５ｇおよび逆浸透水０．４ｍＱよりなる溶液中に浸漬し
、引き上げた後２５℃に６０分間放置して乾燥させた。Insulated with epoxy resin. Glucose oxidase (Sigma product, EC1, 1, 3, 4, type ■, 15.3000/g, Aspergillus
niger origin) 30II1 g, water-soluble photocrosslinkable resin (stilbazolium group-containing polyvinyl alcohol) 0.
It was immersed in a solution consisting of 5 g and 0.4 mQ of reverse osmosis water, pulled up, and left at 25° C. for 60 minutes to dry.
次いで、マスクアライナ（ミカサ製ＭＡ−１０）を用い
、紫外線（波長４０００Ａ）による露光を、５秒間。Next, exposure to ultraviolet light (wavelength 4000A) was performed for 5 seconds using a mask aligner (Mikasa MA-10).
１０秒間、３０秒間または６０秒間行い、金線の一端に
グルコースオキシダーゼ固定化膜を形成させた。This was carried out for 10 seconds, 30 seconds, or 60 seconds to form a glucose oxidase-immobilized membrane at one end of the gold wire.
この金線を、外径１．０間、内径０．８ｍ麿、長さ３ｃ
ｍの白金チューブ（フルウチ化学製、純度９９．９９％
）中に入れ、金線を作用極、白金チューブを対極とする
２極の針状グルコースバイオセンサを作製し、電流検出
計（ＢＡＳ社製ＬＣ−４Ｂ）を用いて、グルコースの測
定を行った。即ち、参照極は対極とショートさせ、作用
極と対極との間の電位は、Ｈ，Ｏ，の酸化電位を０．８
Ｖとし、ＰＨ７，０，５ＩＩＭトリスーマレイン酸緩衝
液を測定溶液として用い、３７℃の測定温度で測定した
。This gold wire has an outer diameter of 1.0 mm, an inner diameter of 0.8 m, and a length of 3 cm.
m platinum tube (manufactured by Furuuchi Chemical, purity 99.99%)
), a bipolar needle-shaped glucose biosensor was prepared with a gold wire as a working electrode and a platinum tube as a counter electrode, and glucose was measured using a current detector (LC-4B manufactured by BAS). . That is, the reference electrode is short-circuited with the counter electrode, and the potential between the working electrode and the counter electrode is set to the oxidation potential of H, O, by 0.8
The measurement was carried out at a measurement temperature of 37° C. using a pH 7,0,5 IIM tris-maleic acid buffer as a measurement solution.
グルコース（関東化学製品、特級）は、逆浸透水を所定
量加えることにより、測定溶液（全容４０ｍｎ）中で最
終濃度がそれぞれ１．５．１０．２０．３０．４０゜５
０、１００．２００．３００．４００または５００ｍｇ
／ａｌｔとなるように添加されて、ｍ定試料が調製され
た。Glucose (Kanto Kagaku Products, special grade) was adjusted to a final concentration of 1.5, 10, 20, 30, and 40°5 respectively in the measurement solution (total volume 40 mm) by adding a predetermined amount of reverse osmosis water.
0, 100.200.300.400 or 500mg
/alt, and a constant sample was prepared.
測定は、センサ応答の定常出力で行い、検量範囲は直線
領域とした６露光時間に応じた検量範囲は、次の如くで
ある。The measurement was performed using the steady output of the sensor response, and the calibration range was set as a linear region.The calibration range corresponding to the six exposure times is as follows.
艷光膨延麹吐 遺１蔦Ｉ力ｌ【１
５ １〜５０
０
０
０
この結果から分かるように、この範囲内の露光時間は検
量範囲には影響せず、上限値も５０ｍｇ／ｄＱとほぼ理
論値に近かった。即ち、酵素固定化膜のみでは、検量範
囲の上限には限界のあることが示された。As can be seen from this result, the exposure time within this range does not affect the calibration range, and the upper limit is 50 mg/dQ. It was almost close to the theoretical value. That is, it was shown that there is a limit to the upper limit of the calibration range using only the enzyme-immobilized membrane.
実施例１
比較例１で作製された露光時間３０秒の針状グルコース
センサを３本準備し、酵素固定化膜上に以下の方法で酢
酸セルロース膜を形成させ、複合膜化させた。Example 1 Three needle-shaped glucose sensors prepared in Comparative Example 1 with an exposure time of 30 seconds were prepared, and a cellulose acetate membrane was formed on the enzyme-immobilized membrane by the following method to form a composite membrane.
即ち、酢酸セルロース（イーストマンコダック社製品Ｅ
−３９８）を、ジメチルホルムアミド中に濃度が５．１
０または１５重量算になるように溶解させたドープ液を
調製し、このドープ液中に酵素固定化膜部分を浸漬し、
引き上げて３０秒後、２５℃の水中に１時間浸漬してゲ
ル化させ、基質透過膜を酵素固定化膜上に形成させた。That is, cellulose acetate (Eastman Kodak Company Product E)
-398) in dimethylformamide at a concentration of 5.1
Prepare a dope solution dissolved to a weight of 0 or 15, immerse the enzyme-immobilized membrane part in this dope solution,
After 30 seconds of lifting, it was immersed in water at 25° C. for 1 hour to gel, and a substrate-permeable membrane was formed on the enzyme-immobilized membrane.
この複合膜形成針状グルコースセンサについて。About this composite membrane-forming needle-shaped glucose sensor.
比較例１と同一条件でグルコースの測定を行い、定常出
力値を求めた。測定結果は、ドープ液濃度毎に第１図の
グラフに示される。なお、このグラフには、比較例１に
おける露光時間３０秒の測定結果も併記されている。Glucose was measured under the same conditions as in Comparative Example 1, and a steady output value was determined. The measurement results are shown in the graph of FIG. 1 for each dope concentration. Note that this graph also shows the measurement results for Comparative Example 1 with an exposure time of 30 seconds.
この結果から、ドープ液濃度に応じた検量範囲は次の如
くであり、ドープ液濃度に応じて検量範囲上限が拡大す
ることが分かる。From this result, it can be seen that the calibration range depending on the dope concentration is as follows, and the upper limit of the calibration range expands depending on the dope concentration.
ドープ ° 重量％ 曵１（１山阻８０５
１〜２００１０
１〜４００１５
１〜５００比較例２
比較例１で作製された露光時間３０秒の針状グルコース
センサを３本準備し、酵素固定化膜部分を５５°、６０
°または６５℃の温水中で１０分間それぞれ熱処理した
後、比較例１と同一条件でグルコース量範囲が１〜５０
ｍｇ／ｄＱで、酵素固定化膜の熱処理は検量範囲には影
響を及ぼさないことが分った。Dope ° Weight % 1 (1 mountain 805
1~20010
1~40015
1 to 500 Comparative Example 2 Three needle-shaped glucose sensors prepared in Comparative Example 1 with an exposure time of 30 seconds were prepared, and the enzyme-immobilized membrane portion was tilted at 55° and 60°.
After heat treatment for 10 minutes in warm water at 65 °C or 65 °C, the glucose amount range was 1 to 50
It was found that heat treatment of the enzyme-immobilized membrane did not affect the calibration range in mg/dQ.
実施例２
実施例１で作製されたドープ液濃度５％の複合膜形成針
状グルコースセンサを３本準備し、複合膜部分を５５°
、６０°または６５℃の温浴中で１０分間それぞれ熱処
理した後、比較例１と同一条件でグルコースの測定を行
い、定常出力値からその検量範囲を求めた。Example 2 Three composite membrane-forming acicular glucose sensors prepared in Example 1 with a dope concentration of 5% were prepared, and the composite membrane portion was tilted at 55°.
, 60° or 65° C. for 10 minutes, glucose was measured under the same conditions as in Comparative Example 1, and the calibration range was determined from the steady output value.
その結果１次に示されるように、複合膜全体を熱処理す
ることにより、検量範囲上限が拡大し。As a result, as shown in Figure 1, the upper limit of the calibration range was expanded by heat-treating the entire composite membrane.
その程度は熱処理温度に依存することが分かった。It was found that the degree depends on the heat treatment temperature.
糺ゑ星象え０ｕ 樵１（１カミ個吐 （なし） １〜２００ ５５ １〜３００ ６０ １〜４００ ６５ １〜５００Tadasu star image 0u woodcutter 1 (1 woodcutter) (None) 1-200 55 1~300 60 1~400 65 1~500
第１図は、 グルコース濃度と定常出力値との関 係を示すグラフである。 Figure 1 shows Relationship between glucose concentration and steady output value FIG.
Claims (1)
、高分子物質の乾湿式膜よりなる基質透過膜を形成せし
めてなるグルコースバイオセンサ。 ２、作用極面上のグルコースオキシダーゼ固定化膜上に
、高分子物質の乾湿式膜の加熱処理膜よりなる基質透過
膜を形成せしめてなるグルコースバイオセンサ。[Scope of Claims] 1. A glucose biosensor comprising a substrate-permeable membrane made of a dry-wet membrane of a polymer substance formed on a glucose oxidase-immobilized membrane on a working electrode surface. 2. A glucose biosensor in which a substrate-permeable membrane made of a heat-treated dry-wet membrane of a polymeric substance is formed on a glucose oxidase-immobilized membrane on a working electrode surface.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1174941A JPH0339648A (en) | 1989-07-06 | 1989-07-06 | Glucose biosensor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1174941A JPH0339648A (en) | 1989-07-06 | 1989-07-06 | Glucose biosensor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0339648A true JPH0339648A (en) | 1991-02-20 |
Family
ID=15987409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1174941A Pending JPH0339648A (en) | 1989-07-06 | 1989-07-06 | Glucose biosensor |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0339648A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5205496A (en) * | 1991-06-05 | 1993-04-27 | O.D.E. Investments Corporation | Universal grinder with reciprocal feeder |
| JP2011013072A (en) * | 2009-07-01 | 2011-01-20 | Nikkiso Co Ltd | Electrode structure for enzyme sensor, enzyme sensor, and artificial pancreas device |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6267442A (en) * | 1985-09-16 | 1987-03-27 | ザ・ヴィクトリア・ユニバーシティ・オブ・マンチェスター | Enzyme electrode type sensor |
| JPH0459055A (en) * | 1990-06-20 | 1992-02-25 | Nissan Motor Co Ltd | Manufacture of monolithick catalyst |
-
1989
- 1989-07-06 JP JP1174941A patent/JPH0339648A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6267442A (en) * | 1985-09-16 | 1987-03-27 | ザ・ヴィクトリア・ユニバーシティ・オブ・マンチェスター | Enzyme electrode type sensor |
| JPH0459055A (en) * | 1990-06-20 | 1992-02-25 | Nissan Motor Co Ltd | Manufacture of monolithick catalyst |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5205496A (en) * | 1991-06-05 | 1993-04-27 | O.D.E. Investments Corporation | Universal grinder with reciprocal feeder |
| JP2011013072A (en) * | 2009-07-01 | 2011-01-20 | Nikkiso Co Ltd | Electrode structure for enzyme sensor, enzyme sensor, and artificial pancreas device |
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