JPH0533743B2 - - Google Patents
Info
- Publication number
- JPH0533743B2 JPH0533743B2 JP60190776A JP19077685A JPH0533743B2 JP H0533743 B2 JPH0533743 B2 JP H0533743B2 JP 60190776 A JP60190776 A JP 60190776A JP 19077685 A JP19077685 A JP 19077685A JP H0533743 B2 JPH0533743 B2 JP H0533743B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- gate electrode
- enzyme
- monomolecular film
- reactive
- 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 - Fee Related
Links
- 102000004190 Enzymes Human genes 0.000 claims description 27
- 108090000790 Enzymes Proteins 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 20
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 8
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 7
- 125000000524 functional group Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000002356 single layer Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 230000003100 immobilizing effect Effects 0.000 claims description 5
- 239000012528 membrane Substances 0.000 claims description 5
- 230000005669 field effect Effects 0.000 claims description 4
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical group Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 claims 1
- 239000002994 raw material Substances 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 claims 1
- 239000010408 film Substances 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 230000000694 effects Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229910000077 silane Inorganic materials 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 239000012190 activator Substances 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000005685 electric field effect Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y10/00—Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
-
- 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
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4145—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
Landscapes
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nanotechnology (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Electrochemistry (AREA)
- Pathology (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Composite Materials (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Materials Engineering (AREA)
- Mathematical Physics (AREA)
- Theoretical Computer Science (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
- Peptides Or Proteins (AREA)
- Insulated Gate Type Field-Effect Transistor (AREA)
Description
産業上の利用分野
本発明は、バイオセンサーおよびその製造方法
に関するものである。
さらに詳しくは、電解効果トランジスタのゲー
ト電極に任意のタンパク質と酵素を固定した生体
物質に特異的に感応するバイオセンサーに関する
ものであり、生体物質の計測に利用するものであ
る。
従来の技術
これまで、バイオセンサーは、ガラス電極表面
にタンパクや酵素を固定した方式のものや、電界
効果型トランジスタ（FET）のゲート電極上に
タンパクや酵素を固定した方式のものが知られて
いるが、従来の方法では酵素やタンパクの固定法
に問題があり、あまり高感度のものが得られてい
なかつた。
すなわち、従来のタンパクや酵素の固定法は、
FETの電極やガラス電極に直接酵素やタンパク
を塗布したり樹脂にタンパクや酵素を混入して塗
布したり、樹脂粒子に固定したものを塗布したり
あるいは、有機膜を介してタンパク質や酵素を固
定する方法が用いられていた。
発明が解決しようとする問題点
ところが、直接塗布する方法では、測定中にタ
ンパクや酵素が脱離したりして、耐久性に問題が
あつたし、樹脂中にタンパクを混入して塗布した
り樹脂粒子に固定したものを塗布する方法では活
性が低かつたり、有機膜を介してタンパク質を固
定する方法でもやはり耐久性に問題があつた。
問題点を解決するための手段
以上述べてきた従来法と欠点に鑑み、本発明は
FETゲート電極上に、このゲート電極と直接化
学結合で固定された反応性単分子膜を介して酵素
を反応固定する方法を提供するものである。すな
わち、一端に反応性官応基（例えば、CH2＝CH
−、CH≡Ｃ−基等）を有し他端にゲート電極上
の酸化膜と反応し吸着される活性基（例えば、−
SiCl3等）を有する有機分子を用いた化学吸着法
や、あるいは、一端に反応性基を有し、他端に親
水基（例えば−COOH等）を有する有機分子を
用いたラングシユアー・ブロジエツト法（以下
LB法という）により、反応性単分子膜を形成し
た後、前記反応性基を化学処理して−OH基を付
加し、さらに、シアノブロマイド法やアルデヒド
法を用いて単分子膜表面を酵素のアミノ基（−
NH2）と反応する基に変換する工程を経てアミ
ノ基を反応させて酵素を固定する方法を提供する
ものである。
作 用
本発明を用いることにより、酵素は、分子中に
多量に存在するアミノ基と単分子膜との反応によ
りゲート電極上に固定されるため、活性が高くし
かも強固に固定されることになる。また、ゲート
電極と酵素は、単分子膜を挾んだのみで固定され
るのできわめて電界効果のロスが少いものとな
る。
従つて、耐久性が高く高感度のバイオセンサー
を提供できることになる。
実施例
以下に本発明の一実施例について図面とともに
説明する。第１図に示すように、あらかじめ
FET１の形成された基板２上には、レジスト３
をコートしてゲート電極４上のみを露光現像して
開口する（第１図）。
次に、化学吸着法により前記開口部にシラン界
面活性剤、例えば、CH2＝CH−（CH2）o−SiCl3
（ｎは整数で10〜20が良い、またCH2＝CH−は、
CH≡Ｃ−でも良い）を化学吸着させる（第２
図）。
このとき、ゲート電極表面では選択的に金属表
面の酵素と−SiCl3が反応して、
の単分子膜５が形成される。例えば、2.0×10-3
〜5.0×10-2Mol／の濃度で80％ｎ−ヘキサン、
12％四塩化炭素、８％クロロホルム溶液に溶かし
た活性剤溶液中に２〜３分浸漬すると、金属界面
で
INDUSTRIAL APPLICATION FIELD The present invention relates to a biosensor and its manufacturing method. More specifically, the present invention relates to a biosensor that is specifically sensitive to biological substances, in which arbitrary proteins and enzymes are immobilized on the gate electrode of a field effect transistor, and is used for measuring biological substances. Conventional technology Until now, biosensors have been known to have a type in which proteins or enzymes are immobilized on the surface of a glass electrode, or a type in which proteins or enzymes are immobilized on the gate electrode of a field effect transistor (FET). However, conventional methods have had problems with the method of immobilizing enzymes and proteins, and have not been able to achieve very high sensitivity. In other words, conventional methods of immobilizing proteins and enzymes are
Enzymes and proteins can be applied directly to FET electrodes and glass electrodes, proteins and enzymes mixed with resin can be applied, proteins and enzymes can be immobilized on resin particles, or proteins and enzymes can be immobilized through organic films. The method was used. Problems to be Solved by the Invention However, with the direct coating method, proteins and enzymes may be detached during measurement, resulting in durability problems. Methods in which proteins are immobilized on particles and coated have low activity, and methods in which proteins are immobilized through organic membranes also have problems in durability. Means for Solving the Problems In view of the conventional methods and drawbacks described above, the present invention has been developed.
The present invention provides a method for reaction-immobilizing an enzyme on a FET gate electrode via a reactive monolayer film that is directly immobilized with the gate electrode through chemical bonds. That is, a reactive functional group (e.g., CH 2 =CH
-, CH≡C- group, etc.) and an active group (e.g., -
chemisorption method using an organic molecule that has a reactive group at one end and a hydrophilic group (e.g. -COOH , etc.) at the other end. below
After forming a reactive monolayer using the LB method, the reactive groups are chemically treated to add -OH groups, and the surface of the monolayer is coated with enzymes using the cyanobromide method or aldehyde method. Amino group (-
The present invention provides a method for immobilizing an enzyme by reacting an amino group through a step of converting it into a group that reacts with NH 2 ). Effect: By using the present invention, the enzyme is immobilized on the gate electrode through a reaction between the amino groups present in large amounts in the molecule and the monolayer, resulting in high activity and firm immobilization. . Further, since the gate electrode and the enzyme are fixed only by sandwiching the monomolecular film, the loss of electric field effect is extremely small. Therefore, a highly durable and highly sensitive biosensor can be provided. Embodiment An embodiment of the present invention will be described below with reference to the drawings. As shown in Figure 1,
A resist 3 is placed on the substrate 2 on which the FET 1 is formed.
is coated, and only the top of the gate electrode 4 is exposed and developed to form an opening (FIG. 1). Next, a silane surfactant, e.g., CH2 =CH-( CH2 ) o - SiCl3 , is added to the opening by chemisorption.
(n is an integer, preferably 10 to 20, and CH 2 = CH- is
CH≡C- may also be adsorbed (second
figure). At this time, the enzyme on the metal surface selectively reacts with -SiCl 3 on the gate electrode surface, A monomolecular film 5 is formed. For example, 2.0×10 -3
80% n-hexane at a concentration of ~5.0×10 -2 Mol/;
When immersed in an activator solution of 12% carbon tetrachloride and 8% chloroform for 2 to 3 minutes, the metal interface
【式】の結合６が形成される。しかもこ
のとき、シラン界面活性剤のビニル基７は、電極
４表面に並んで単分子膜５が成膜される（第３
図）。
次に、第２図に示したレジストパターン３′を
除去した後、室温でジボラン1Mol／のTHF溶
液を用い、単分子膜５の形成された基板を浸漬
し、さらにNaOH0.1Mol／30％H2O2水溶液に
浸漬することにより、単分子膜５の表面のビニル
基又は、アセチレン基に水酸基（−OH）8を付加
させる（第４図）。
続して、過沃素酸水溶液に浸漬し、次式(1)に従
つて表面のOH基をアルデヒド基９に酸化する
（第５図）。
R1−CH2OHHIO4
―――→
……(1)
さらに、特定の活性を持つ酵素を次式(2)に従つ
て付加反応させて固定させる。
従つて、酵素１０は、選択時にゲート電極４上
に単分子膜５を介して化学反応により酵素薄膜１
１として強固に固定される（第６，７図）。
最後に、基板をダイシングして電極の接続等の
組立を行うとバイオセンサが完成する。
なお、以上の実施例では、アルデヒド法を示し
たが、次式(3)のようなシアノブロマイド法を用い
た酵素の固定も同じように行なえる。
また、単分子膜の形成に化学吸着法を用いた例
を示したが、CH2＝CH−（CH2）oCOOHやCH≡
Ｃ−（CH2）oCOOH等を用い、ラングシユアー・
ブロジエツト（LB）法にてもゲート電極上に単
分子膜を形成できることが確認された。
さらにまた、上記例では、レジストを用いて選
択的にゲート電極上にのみ単分子膜を形成した
が、ビニル基やアセチレン基は、エネルギー線で
感応してポリマーを形成するので、全面に単分子
膜を形成した後、ゲート電極上のみを後して、エ
ネルギー線１２で露光し、ビニル基やアセチレン
基を部分的に死活（失活）１３させてから、残つ
たビニル基１４（またはアセチレン基）の部分に
−OH基を付加させることも可能である（第８
図）。
なお、本発明の方法、すなわち、LB膜へのタ
ンパク質の自己整合機構を応用し、分子素子の構
築が可能なことも明らかであろう。
発明の効果
以上のように本発明によれば、酵素は単分子膜
を介して選択的に、しかも強固に活性を失うこと
なく固定される。従つて、高感度でしかも信頼性
の高いバイオセンサーが提供できる。
さらにまた、製造工程も簡単なため、コストを
大幅に低減できる効果もある。A bond 6 of the formula is formed. Moreover, at this time, the vinyl groups 7 of the silane surfactant form a monomolecular film 5 in line with the surface of the electrode 4 (third
figure). Next, after removing the resist pattern 3' shown in FIG. 2, the substrate on which the monomolecular film 5 was formed was immersed in a THF solution containing 1Mol of diborane at room temperature, and then immersed in a THF solution containing 0.1Mol of diborane/30%H. Hydroxyl groups (-OH) 8 are added to the vinyl groups or acetylene groups on the surface of the monomolecular film 5 by immersion in a 2 O 2 aqueous solution (FIG. 4). Subsequently, it is immersed in an aqueous periodic acid solution, and the OH groups on the surface are oxidized to aldehyde groups 9 according to the following formula (1) (FIG. 5). R 1 −CH 2 OHHIO 4 ---→ ...(1) Furthermore, an enzyme having a specific activity is immobilized by an addition reaction according to the following formula (2). Therefore, when the enzyme 10 is selected, the enzyme thin film 1 is formed on the gate electrode 4 through the monomolecular film 5 by a chemical reaction.
1 and is firmly fixed (Figures 6 and 7). Finally, the biosensor is completed by dicing the substrate and performing assembly such as electrode connections. In addition, although the aldehyde method was shown in the above example, enzyme immobilization using the cyanobromide method as shown in the following formula (3) can also be carried out in the same way. We also showed an example of using chemisorption to form a monomolecular film, but CH 2 = CH- (CH 2 ) o COOH and CH≡
Using C-(CH 2 ) o COOH etc., Langsheur
It was confirmed that a monomolecular film can also be formed on the gate electrode using the Blodget (LB) method. Furthermore, in the above example, a monomolecular film was selectively formed only on the gate electrode using a resist, but since vinyl groups and acetylene groups are sensitive to energy rays and form polymers, monomolecular films are formed over the entire surface. After forming the film, only the gate electrode is exposed to energy rays 12 to partially inactivate the vinyl groups and acetylene groups 13, and then the remaining vinyl groups 14 (or acetylene groups ) It is also possible to add an -OH group to the part (8th
figure). It is also clear that it is possible to construct molecular devices by applying the method of the present invention, that is, the self-alignment mechanism of proteins to LB membranes. Effects of the Invention As described above, according to the present invention, enzymes are selectively and firmly immobilized through a monolayer without losing activity. Therefore, a highly sensitive and highly reliable biosensor can be provided. Furthermore, since the manufacturing process is simple, there is also the effect of significantly reducing costs.
第１図〜第８図は本発明の一実施例におけるバ
イオセンサとその製造工程を説明するための工程
図であり、特に第３，４，５，６，８図は第２図
のＡ部の分子オーダーでの拡大図である。
１……FET、２……基板、４……ゲート電極、
５……単分子膜、１１……酵素膜。
Figures 1 to 8 are process diagrams for explaining a biosensor and its manufacturing process in one embodiment of the present invention. In particular, Figures 3, 4, 5, 6, and 8 are part A of Figure 2. This is an enlarged view in molecular order. 1...FET, 2...Substrate, 4...Gate electrode,
5... Monomolecular membrane, 11... Enzyme membrane.
Claims (1)
ゲート電極と直接化学結合で固定された反応性単
分子膜を設け、前記反応性単分子膜の表面に酵素
を化学結合で固定してなるバイオセンサー。 ２ 反応性単分子膜にSiを含む特許請求の範囲第
１項記載のバイオセンサー。 ３ 電解効果トランジスターのゲート電極上に、
一端に反応性官応基を有し、他端にゲート電極上
の酸化膜と反応する活性基を有する有機分子より
成る単分子膜を形成し化学結合して前記ゲート電
極と直接結合固定する工程と、前記反応性官応基
を化学処理して水酸基を付加する工程と、前記水
酸基をさらに化学処理した後酵素を反応させ固定
する工程を含むバイオセンサーの製造方法。 ４ 単分子膜を形成する工程において化学吸着法
を用いる特許請求の範囲第３項記載のバイオセン
サーの製造方法。 ５ 単分子膜の原料として、一端に反応性の官応
基としてビニル基またはアセチレン基を有し他端
にクロルシラン基を有する直鎖状ハイドロカーボ
ン分子を用いる特許請求の範囲第４項記載のバイ
オセンサーの製造方法。 ６ 単分子膜を形成する工程においてラングミユ
アー・ブロジエツト法を用いる特許請求の範囲第
３項記載のバイオセンサーの製造方法。 ７ 反応性の官応基として、単分子膜表面にビニ
ル基またはアセチレン基を含む膜を用い、前記ビ
ニル基またはアセチレン基に水酸基を付加させた
後、シアノブロマイド法またはアルデヒド法によ
り酵素と反応する官応基を導入する工程と、前記
酵素と反応する官応基に前記酵素を固定させるこ
とを特徴とした特許請求の範囲第３項記載のバイ
オセンサーの製造方法。[Scope of Claims] 1. A reactive monomolecular film directly fixed to the gate electrode by chemical bonds is provided on the gate electrode of a field effect transistor, and an enzyme is fixed to the surface of the reactive monomolecular film by chemical bonds. A biosensor. 2. The biosensor according to claim 1, wherein the reactive monolayer contains Si. 3 On the gate electrode of the field effect transistor,
A process of forming a monomolecular film made of organic molecules having a reactive functional group at one end and an active group that reacts with the oxide film on the gate electrode at the other end, and chemically bonding the film to directly bond and fix the gate electrode. A method for producing a biosensor, comprising: a step of chemically treating the reactive functional group to add a hydroxyl group; and a step of further chemically treating the hydroxyl group and then reacting and immobilizing an enzyme. 4. The method for producing a biosensor according to claim 3, in which a chemical adsorption method is used in the step of forming a monomolecular film. 5. The biotechnology according to claim 4, in which a linear hydrocarbon molecule having a vinyl group or acetylene group as a reactive functional group at one end and a chlorosilane group at the other end is used as a raw material for the monomolecular film. How the sensor is manufactured. 6. The method for producing a biosensor according to claim 3, in which the Langmuir-Blodget method is used in the step of forming a monomolecular film. 7 Using a membrane containing a vinyl group or acetylene group on the surface of the monolayer as a reactive functional group, adding a hydroxyl group to the vinyl group or acetylene group, and then reacting with an enzyme by a cyanobromide method or an aldehyde method. 4. The method for producing a biosensor according to claim 3, comprising the steps of introducing a functional group and immobilizing the enzyme on the functional group that reacts with the enzyme.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60190776A JPS6250657A (en) | 1985-08-29 | 1985-08-29 | Biosensor and its production |
| US06/900,629 US4881109A (en) | 1985-08-29 | 1986-08-26 | Sensor using a field effect transistor and method of fabricating the same |
| EP86306571A EP0214805B1 (en) | 1985-08-29 | 1986-08-26 | Sensor using a field effect transistor and method of fabricating the same |
| DE8686306571T DE3688489T2 (en) | 1985-08-29 | 1986-08-26 | SENSORS USING A FIELD EFFECT TRANSISTOR AND THEIR PRODUCTION METHOD. |
| US07/353,326 US4960722A (en) | 1985-08-29 | 1989-05-15 | Sensor using a field effect transistor and method of fabricating the same |
| JP4311735A JP2563739B2 (en) | 1985-08-29 | 1992-11-20 | Protein immobilization method |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60190776A JPS6250657A (en) | 1985-08-29 | 1985-08-29 | Biosensor and its production |
| JP4311735A JP2563739B2 (en) | 1985-08-29 | 1992-11-20 | Protein immobilization method |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4311735A Division JP2563739B2 (en) | 1985-08-29 | 1992-11-20 | Protein immobilization method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6250657A JPS6250657A (en) | 1987-03-05 |
| JPH0533743B2 true JPH0533743B2 (en) | 1993-05-20 |
Family
ID=26506305
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60190776A Granted JPS6250657A (en) | 1985-08-29 | 1985-08-29 | Biosensor and its production |
| JP4311735A Expired - Fee Related JP2563739B2 (en) | 1985-08-29 | 1992-11-20 | Protein immobilization method |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4311735A Expired - Fee Related JP2563739B2 (en) | 1985-08-29 | 1992-11-20 | Protein immobilization method |
Country Status (1)
| Country | Link |
|---|---|
| JP (2) | JPS6250657A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6250657A (en) * | 1985-08-29 | 1987-03-05 | Matsushita Electric Ind Co Ltd | Biosensor and its production |
| JPH026488A (en) * | 1988-06-24 | 1990-01-10 | Shin Etsu Chem Co Ltd | Omega-alkynylsilane compound |
| JP4850854B2 (en) | 2007-03-22 | 2012-01-11 | 信越化学工業株式会社 | Manufacturing method of substrate for producing microarray |
| JP4512607B2 (en) * | 2007-03-22 | 2010-07-28 | 信越化学工業株式会社 | Manufacturing method of substrate for producing microarray |
| CN103052455A (en) | 2011-01-17 | 2013-04-17 | 松下电器产业株式会社 | Safety device and preliminary action determination method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61176845A (en) * | 1985-01-31 | 1986-08-08 | Nok Corp | Film deposited by evaporation for immobilization of physiologically active material and field effect transistor urea sensor using said film |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6250657A (en) * | 1985-08-29 | 1987-03-05 | Matsushita Electric Ind Co Ltd | Biosensor and its production |
-
1985
- 1985-08-29 JP JP60190776A patent/JPS6250657A/en active Granted
-
1992
- 1992-11-20 JP JP4311735A patent/JP2563739B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61176845A (en) * | 1985-01-31 | 1986-08-08 | Nok Corp | Film deposited by evaporation for immobilization of physiologically active material and field effect transistor urea sensor using said film |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6250657A (en) | 1987-03-05 |
| JPH069698A (en) | 1994-01-18 |
| JP2563739B2 (en) | 1996-12-18 |
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