JPS58184540A - Biochemical detecting element and method for measuring concentration of compound using the same - Google Patents

Biochemical detecting element and method for measuring concentration of compound using the same

Info

Publication number
JPS58184540A
JPS58184540A JP57066981A JP6698182A JPS58184540A JP S58184540 A JPS58184540 A JP S58184540A JP 57066981 A JP57066981 A JP 57066981A JP 6698182 A JP6698182 A JP 6698182A JP S58184540 A JPS58184540 A JP S58184540A
Authority
JP
Japan
Prior art keywords
biochemical
isfet
immobilized
ion
solution
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
Application number
JP57066981A
Other languages
Japanese (ja)
Other versions
JPH037066B2 (en
Inventor
Yoshio Hanasato
善夫 花里
Satoru Shiono
悟 塩野
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mitsubishi Electric Corp
Original Assignee
Mitsubishi Electric Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Mitsubishi Electric Corp filed Critical Mitsubishi Electric Corp
Priority to JP57066981A priority Critical patent/JPS58184540A/en
Publication of JPS58184540A publication Critical patent/JPS58184540A/en
Publication of JPH037066B2 publication Critical patent/JPH037066B2/ja
Granted legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/403Cells and electrode assemblies
    • G01N27/414Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
    • G01N27/4145Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS specially adapted for biomolecules, e.g. gate electrode with immobilised receptors

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Engineering & Computer Science (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Electrochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)

Abstract

PURPOSE:To measure the concn. of a compound in solution to be measured, by providing immobilized ISFET obtained by immobilizing a biochemical substance by ISFET having an ion sensitive membrane, ISFET, a false electrode and a differential amplifier. CONSTITUTION:A biochemical sensor 1 is formed from ISFET 11 having an ion sensitive membrane formed thereto, immobilized ISFET 12 obtained by immobilizing ISFET 11 by the ion sensitive membrane and an artificial electrode 13. When GOD immobilized ISFET 12 is held in a solution 8 to be measured, the hydrogen ion concn. in a glucoseoxidase immobilized membrane 12a is changed by the action of glucoseoxidase of the GOD immobilized ISFET 12 but this variation amount is detected as the difference of each output voltages of the GOD immobilized ISFET 12 and PH-ISFET 11 and the concn. of the compound in the solution 8 to be measured is measured by the differential amplifier 16.

Description

【発明の詳細な説明】 この発明は、イオン感応膜を備えた電界効果型トランジ
スタに生化学物質を固定化して成る生化学的検知素子及
び皺生化学的検知素子を用いた化学物濃度の測定方法に
関する。
DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a biochemical sensing element in which a biochemical substance is immobilized on a field-effect transistor equipped with an ion-sensitive membrane, and measurement of chemical concentration using a wrinkled biochemical sensing element. Regarding the method.

先行技術として、電界効果型トランジスタより成り、化
学物質量を測定できる小形センサが特開%:52 26
292号で提案された。第1図はこの小形センサの断面
図を示したもので、図中、IFip型シリコン基板、2
,3は前記p型シリコン基枡1にn型不純物の拡散で形
成されたソース及びドレイン、4#iダート、5は熱酸
化シリコン膜、6Fi窒化シリコン膜である。種々のイ
オンに感応する前記小形センナは、さらにこの上にイオ
ン感応#7を形成するのが一般的である。
As a prior art, a small sensor made of a field effect transistor and capable of measuring the amount of chemical substances has been published in Japanese Patent Publication %: 52 26
It was proposed in No. 292. Figure 1 shows a cross-sectional view of this small sensor.
, 3 are sources and drains formed by diffusion of n-type impurities into the p-type silicon substrate 1, 4#i dirt, 5 are thermally oxidized silicon films, and 6Fi silicon nitride films. The small senna sensitive to various ions generally further has an ion sensitive sensor #7 formed thereon.

第2図は前記小形センサを用いたイオン濃度の測定装置
の一例を示すもので、図中、8は被測定溶液、9#i、
電界効果型トランジスタセンサ(以下l5FETという
)、10Fi比較11極テある。
FIG. 2 shows an example of an ion concentration measuring device using the above-mentioned small sensor. In the figure, 8 is the solution to be measured, 9#i,
There are 11 poles of field effect transistor sensors (hereinafter referred to as 15FET) compared to 10Fi.

次に動作について説明する。被測定溶液8にl5FET
9と比較電極1oを浸し、ドレイン電流−足の下で、l
5FET9のソースの電位をソースフォロア回路によっ
て直接読取るものである。
Next, the operation will be explained. 15FET in measurement solution 8
9 and reference electrode 1o, drain current - under foot, l
The source potential of the 5FET 9 is directly read by a source follower circuit.

すなわち、前記被測定溶液8中のイオン濃度の変化によ
り、前記イオン感応膜7とこの被測定溶液8との間に生
じる界面を位が変化し、これがソース211r圧の変化
として検出されるため、イオン濃度を側足できるもので
ある。
That is, due to a change in the ion concentration in the solution 8 to be measured, the position of the interface between the ion-sensitive membrane 7 and the solution 8 to be measured changes, and this is detected as a change in the source 211r pressure. It is something that can increase the ion concentration.

なお、ここで用いられる前記比較電極101を前iピ被
側足溶液8の種類に係わらず一定の重りを示すもので、
よく用いられるものに銀−塩化銀′11tk、カロメル
電極などがある。
The reference electrode 101 used here has a constant weight regardless of the type of the anterior foot solution 8,
Commonly used electrodes include silver-silver chloride '11tk and calomel electrodes.

また、前記l5FET9#′i広く知られている半導体
製造技術で製作されるため微小化は容易であるが、前記
比較電極10は小形化が困難である。それは骸比較電極
10では液絡部にて内部液を被測定溶液中に安定的に流
出させるようになっており、この部分がある程度の大き
さを必要とするからである。このため、従来の1!+ 
’?装置では、前記比較電極10を用いるため、センサ
自体を小形化できないことや、内部液の補充が必要であ
るなどの欠点があった。
Furthermore, since the 15FET9#'i is manufactured using a widely known semiconductor manufacturing technique, it is easy to miniaturize it, but the comparison electrode 10 is difficult to miniaturize. This is because the skeleton comparison electrode 10 is designed to allow the internal liquid to stably flow out into the solution to be measured at the liquid junction, and this portion requires a certain size. For this reason, the conventional 1! +
'? Since the device uses the reference electrode 10, there are drawbacks such as the inability to downsize the sensor itself and the need to replenish the internal liquid.

この発明は、上記の欠点を解消するために成されたもの
で、比較電極を用いないで被測定溶液の化合物濃度を測
定できる生化学的検知素子及びこの生化学的検知素子を
用いた測定方法を提供することを目的とするものである
The present invention was made in order to eliminate the above-mentioned drawbacks, and includes a biochemical detection element that can measure the concentration of a compound in a solution to be measured without using a reference electrode, and a measurement method using this biochemical detection element. The purpose is to provide the following.

以下、この発明の一実施例を図面と共に説明する。An embodiment of the present invention will be described below with reference to the drawings.

まず、生化学的検知素子は、上述の先行技術である第1
図に示す如きl5FET9と酵素や微生物等の生化学物
質とから構成されている。すなわち、この生化学的物質
としてグルコースオキシダーゼを用い、酪素固定化法と
し、てよく用いられるグルタルアルデヒドによる架橋反
応により前記l5FET9の第1図に示す如きイオン感
応膜7上に固定化I7て形成される。
First, the biochemical sensing element is based on the prior art described above.
It is composed of 15FET9 as shown in the figure and biochemical substances such as enzymes and microorganisms. That is, glucose oxidase is used as the biochemical substance, and I7 is immobilized on the ion-sensitive membrane 7 as shown in FIG. be done.

次に、上述の生化学的検知素子を用いた化合物濃度の測
定方法を笥3図と共KWit明する。
Next, a method for measuring compound concentration using the above-mentioned biochemical sensing element will be explained with reference to Figure 3.

図中、2社ソース、:・:□3はドレイン、8は被測定
溶液、l 1jIsFET、12は生化学的検知素子イ
オン感応膜7の上に生化学物質の膜12aを備える。1
3#i被測定溶液の11位を一定にするための疑似電極
、14.15は前記l5FET11及び生化学的検知素
子12各々のドレイン電流を一定にする定−流電源、1
6it差動増幅器で、前記l5FETII及び生化学的
検知素子12各々の出力電圧の差を出力する。17Fi
恒温水、18t=を恒温水槽である。
In the figure, 2 sources: 3 is a drain, 8 is a solution to be measured, l1jIsFET, 12 is a biochemical sensing element, and a biochemical substance film 12a is provided on the ion-sensitive film 7. 1
3 #i A pseudo electrode for keeping the 11th position of the solution to be measured constant; 14.15 a constant current power source for keeping the drain current of each of the 15FET 11 and the biochemical detection element 12 constant; 1
A 6-bit differential amplifier outputs the difference between the output voltages of the 15FET II and the biochemical sensing element 12. 17Fi
Constant temperature water, 18 tons = constant temperature water tank.

さて、本発明による生化学的検知素子を用いた測定方法
の作用は、被測定溶液8の中に前記生化学的検知素子を
保持すると、皺生化学的検知素子の生化学物質の作用で
、前記イオン感応膜7の水素イオン濃度(以下pHとい
う)が変化するが、この変化蓋をこの生化学的検知素子
12とpHの変化しない前記l5FET 11との各出
力電圧の差として検知し1、被iI+!定溶液中の化合
物濃度を1ll1足することである。
Now, the action of the measurement method using the biochemical sensing element according to the present invention is that when the biochemical sensing element is held in the solution 8 to be measured, the effect of the biochemical substance of the wrinkle biochemical sensing element is as follows. The hydrogen ion concentration (hereinafter referred to as pH) of the ion-sensitive membrane 7 changes, and this change is detected as a difference between the output voltages of the biochemical detection element 12 and the 15FET 11 whose pH does not change. Covered iI+! This is to add 1 1 1 to the concentration of the compound in the constant solution.

このi++足方法においては、被測定溶液81jiM記
生化学的検知素子12に固定化された生化学物質12a
K最適条件となるようにII!に適なpHと35℃の被
測定溶液8の温度に調整された。また、l5FET 1
1及び生化学的検知素子12は飽和領域で作動するよう
にドレイン3に定電圧を印加するように構成された。な
お、疑似電極13には白金線が用いられた。
In this i++ foot method, the biochemical substance 12a immobilized on the biochemical detection element 12 that records the solution to be measured 81jiM
K so that the optimum condition is achieved II! The pH of the solution 8 to be measured was adjusted to an appropriate pH and the temperature of the solution 8 to be measured was 35°C. Also, l5FET 1
1 and the biochemical sensing element 12 were configured to apply a constant voltage to the drain 3 so as to operate in the saturation region. Note that a platinum wire was used for the pseudo electrode 13.

まず、初期の出力電圧が安定するまで祉被測定溶液8と
してグルコースを含んだ酢11!M価溶液をMt L、
た。すると、グルコースオキシダーゼを固定化した膜1
2a中でダルコン酸が生成され、その結果、生化学的検
知素子12のイオン感応膜7中のpHが低下するが、l
5FET11のイオン感応膜中ではpHの変化はない。
First, vinegar 11 containing glucose is used as the solution 8 to be measured until the initial output voltage becomes stable. The M value solution is Mt L,
Ta. Then, membrane 1 with immobilized glucose oxidase
Dalconic acid is produced in 2a, and as a result, the pH in the ion-sensitive membrane 7 of the biochemical sensing element 12 decreases;
There is no change in pH in the ion sensitive membrane of 5FET11.

そこで、このpHの変化量を利用して、これを前記l5
FET11及び生化学的検知素子12の各出力電圧の差
として差動増幅器16の出力電圧を得ることができた。
Therefore, by using the amount of change in pH, this is
The output voltage of the differential amplifier 16 could be obtained as the difference between the output voltages of the FET 11 and the biochemical sensing element 12.

ところで、第4図はグルコースを含まない緩衝溶液とグ
ルコースを含んだ緩衝溶液をサンプルチェンソヤーにて
交互に流した時のグルコース濃度(M)に対するl5F
ET11と生化学的検知素子12との出力電圧差(ΔV
s)  の時間的変化を示すものである。但し、この場
合、グルコース溶液はト一タルで5分間流した。
By the way, Figure 4 shows the 15F versus glucose concentration (M) when a buffer solution that does not contain glucose and a buffer solution that contains glucose are alternately flowed through a sample chain soyer.
Output voltage difference (ΔV) between ET11 and biochemical detection element 12
s) shows the change over time. However, in this case, the glucose solution was allowed to flow for a total of 5 minutes.

この第4図の結果から、第5図に示すように前記出力電
圧差(ΔVs )のピーク値とグルコース濃度との間の
関係特性曲線が得られた。従って、この第5図の特性曲
線を用いることにより、前記出力電圧差(ΔVs)から
被測定溶液8中のグルコース濃度(M)が与えられる。
From the results shown in FIG. 4, a characteristic curve of the relationship between the peak value of the output voltage difference (ΔVs) and the glucose concentration was obtained as shown in FIG. Therefore, by using the characteristic curve shown in FIG. 5, the glucose concentration (M) in the solution to be measured 8 can be determined from the output voltage difference (ΔVs).

なお上記実施例では、生化学的検知素子を1個、l5F
ETを1個用いたが、生化学的検知素子を2個以上用い
ることも可能である。
In the above example, one biochemical detection element, 15F
Although one ET was used, it is also possible to use two or more biochemical sensing elements.

以上のように、この発明は、イオン感応膜を有するl5
FETに生化学物質を形成して成る生化学的検知素子と
l5FETと差動増幅器とを設けることにより、従来の
比較電極を用いないで被溶液中の化合物濃度を測定する
ことができ、その結果、測定装置を小形化し、しかも安
価に作ることができ、さらに前記比較電極の内部を袖先
の手間がいらないため操作を簡便にできるという顕著な
効果を奏するものである。
As described above, the present invention provides l5 having an ion-sensitive membrane.
By providing a biochemical detection element formed by forming a biochemical substance in an FET, an 15FET, and a differential amplifier, it is possible to measure the concentration of a compound in a solution without using a conventional reference electrode, and as a result, This has the remarkable effect that the measuring device can be miniaturized and manufactured at low cost, and that the operation can be simplified since there is no need to inspect the inside of the reference electrode.

【図面の簡単な説明】[Brief explanation of drawings]

第1図けl5FETの断面図、第2図は従来の1ll1
足装置を示す断面図、第3図はこの発明の一実施例を示
す第2図相当図、第4図は第3図の#I足装置で得られ
たl5FETの出力電圧の時間的変化を示す#1足デー
タ崗、第5図はグルコース濃度と出力電圧差の関係を示
す特性図である。 1・・・p型シリコン基板、2・・・ソース、3・・・
ドレイン、4・・・ダート、5・・・熱酸化シリコン膜
、6・・・窒化シリコン蒙、7・・・イオン感応膜、8
・・・被1Ii11足溶液、9 、 II ・l5FE
T、 10 ・・・比較lL12・・・生化学的検知素
子、13・・・疑似11極、16・・・差動増幅器。 なお、図中、同一符号は同一部分、又は相当部分を示す
。 代理人   葛  野  信  − □′1゜ (Al)5^v 8   9 (Al)%Aり 手続補正゛M(自発) 11 晶 1’l  長官−殿 l “11fl−の表、1′N      特願昭57
−86981号ヱ ≦C四力名称 生化学センナ及び生化学七ン1!に願出いた化合物−匿
の#M足方法 、、  ?!Ii+l、を+るh =I4f’FとJ)関係   持許出宿1人f!−所 
    東京都丁・r(ll1区丸0内−ロ12音、3
シJ名 f+ロ60し  云菱電機株式会社代表台片由
仁八部 1  代  理  )\ fl:1す「     東上;〔都丁−代111区丸の
内−1’l+2番3シ;三菱電機株式会社内 氏 名f5699+   弁理1: 葛  野  信 
 −5、補正の対象 願誓の[発明の名称1の欄、明細書の「特許請求の範囲
」、「発明の詳細な説明」及び(図面の簡単な説明」の
各欄、及び図面。 6、 補正の内容 (11l1ia曹の[発明の名称」の[生化学的検知素
子及び生化学的検知素子を用いた化合物11にの測定方
法]t−[生化学センサ及び生化学センサを用いた化合
物@度の測定方法]と訂正する。 (2)明細書の「特許請求の範囲」を別紙のとお9補正
する。 (31同書1頁20行〜2頁1行、2負1行、4頁2 
r+ + 3行、7行及び15行、及び5負7行の「生
化学的検知素子−、+ 11− r生化学センサ」と訂
正する5、 (4)同書2貞l〜2行の「化学物濃度」紮[化合vI
!縞1fJと訂正する。 (5)同頁3行〜4行の[電界効果型トランジスタよr
)成り、化学物質量kJt−r電界効果型トランジスタ
(以下l8FETという)より成9.#!液中のイオン
濃[14−Jと訂正する。 (6)同頁lO行〜12行の[穐々のイオンに・・・一
般的である。Jを下記のとお9訂正する。 配 [この窒化シリコン膜6tイオン感応験とすると、これ
は水素イオンに感応する水素イオン感応膜となり、そこ
で前記小形センサ扛水港液中の水素イオン濃[VC感応
するセンサになるが、さらにこの上に適当なイオン感応
膜7に形成すると種々のイオンに感応するセンサを形成
することが可能である。] (71四頁15〜16行の「電界効果型、トランジスタ
センサ(以下l8FKTという)、」ヲr l8FE’
I’ Jと訂正する。 (8)同頁17行の「・・・説明する。」の後に「この
イオン濃[測足装歇は、」會付加する。 1、:1 (9)−書3頁2行の「前記イオン感応膜7Jk[前記
イオン感応1lii!6 、7 Jと訂正する(1(l
llaJ員14行の「安定的に」會「安定に」と訂正す
る、 Uυ 同14頁5行の「−実施fil管」の後[rダル
コースセンサtNKとり」を付加する。 03  同頁9行の「生化学物質Ukr生化学物貧1r
向足化した固定化18FETと疑似電極」とdj止する
。 Q3 1fiJ負9行の「すなわち、この生化学的物質
として」會[この固定化l8FETは生化学物餉と(−
て」と訂正する。 圓 同頁13〜14行の[第]し1に示す・・・・・・
形成されている。Jkr第1−に示す如き水素イオン感
応映6上に該生化学物資【固定化したものである。」と
訂正する1、 (11同1it18−20行)r 11はI8に’BT
、、、。 を備える。Jt−[11は水素イオンに感剋するIfS
FET (以下p)1−I8)’ETという)、12は
グルコースオキシダーゼ固定化−−I8FET(J!T
(301)1.1f(kl、 IaFET 、!: イ
5 ) T**イオン感応′膜6の上にグルコースオキ
V / −−1!’固足化験12at−備える。」と訂
正する。。 08  pls5頁1行、4行、13行及び20行。 6負9行、12行及び18行のr ll9FET11J
IHr、H−I81?ET tt Jと訂正する。 071  同書5頁2行及び4行、8〜9行、9行。 12行、17行及び20行、6頁8行、12行及び18
行の「生化学的検知素子J’1irGOD固足化I8F
gT12Jと訂正する。 舖 同頁10行及び17行の「生化学物質」を「グルコ
ースオキシダーゼ」と訂正する。 (1’J  同頁10行の「前記イオン感応膜7の」會
「グルコースオキシダーゼを固定化した膜12a中の」
と訂正する。 (1) 同頁12〜13行の「、Hの変化しない」tM
#する。 (211PI員18〜19行のri2aK最適条件・・
・・・・に調製された。」を[に最適なpHvr持つ緩
術液と最適な温[に調整された。」と訂正する。 の 同頁20行の「12は」の後にr l8FETの」
を付加する。 (ハ)同書6頁5行の「#I液8として」の後に「グル
コースを含まない酢酸緩衝溶液tRしておき、電圧が安
定したら」を付加する。 (至)同頁8行の[イオン感応1j!7 Jt−r前記
固定化II 12a Jと訂正する。 (ハ)−j貞9〜lO行の「のイオン感応膜中1を削除
する。 (4)1「1頁20行〜7頁1行の[トータルで」【削
除する。 罰 同書7頁8行、9行、12〜13行の「生化学的検
知集子Jkr固定化l8FET Jと訂正する。 (至)−」頁9行の「1個用いたが、」の稜(「違った
穐類の」を付加する。 −同頁12行の[t−形成して成るJkrk固足化して
成る」と訂正する。 −同頁13行のr l8FETと」の後K「疑似電極と
It付加する。 eυ 同書8頁11行の「・・・生化学的検知素子、」
を[・−・固定化l8FET%12a・・・固定化膜、
」と訂正する。 ■ 第3図を別紙のとおり朱書訂正する。 7. 添付を類の目録 (11訂正特許請求の範!8%    1通(2)第3
図の訂正図面     1通以上 訂正特許請求の範囲 (1)イオン感応1Kを形成した$ *界効果型トラン
ジスタ)と、酸素や1生物等の生化学物質を前記I S
 F E Tのイオン感応膜上に固定化した固定化IS
F’ETと、疑似電極とから成ることt特徴とする生化
学センナ。 (2)生化学センサと、差動増幅器とt備え、前記疑似
電極を基準とした前記l8FET及び前記固定化I8F
’ET17)各々の出力電圧の差音前記差動増幅器で測
定して成ること11做とする生化学センナを用いた化合
物濃度の#1足方法。
Figure 1 is a cross-sectional view of the 15FET, Figure 2 is the conventional 1ll1
FIG. 3 is a cross-sectional view showing the foot device, FIG. 3 is a diagram corresponding to FIG. 2 showing an embodiment of the present invention, and FIG. Figure 5 is a characteristic diagram showing the relationship between glucose concentration and output voltage difference. 1...p-type silicon substrate, 2...source, 3...
Drain, 4... Dirt, 5... Thermal oxidation silicon film, 6... Silicon nitride film, 7... Ion sensitive film, 8
...1Ii11 foot solution, 9, II ・l5FE
T, 10... Comparison lL12... Biochemical detection element, 13... Pseudo 11 poles, 16... Differential amplifier. In addition, in the drawings, the same reference numerals indicate the same or equivalent parts. Agent Makoto Kuzuno − □′1゜(Al)5^v 8 9 (Al)%A procedure amendment゛M (voluntary) 11 Akira 1'l Director-General ``11fl- table, 1'N Special Gansho 57
No. -86981ヱ ≦ C four power names Biochemistry Senna and Biochemistry Seven 1! Compound applied for - Hidden #M foot method...? ! Ii + l, + h = I4f'F and J) Relationship One person f! -place
Tokyo cho・r(ll1 ward Marunouchi-ro 12 sounds, 3
shi J name f + ro 60 shi Yunryo Electric Co., Ltd. representative taichung kata yuni 8be 1 representative) \ fl: 1su `` Higashijo; Mr. Uchi Name f5699+ Patent attorney 1: Makoto Kuzuno
-5. Column 1 of Title of the Invention, "Claims", "Detailed Description of the Invention" and (Brief Description of Drawings) columns of the specification of the application to be amended, and the drawings.6. Contents of amendment ([Title of the invention] of 11l1ia Cao [Biochemical detection element and method for measuring compound 11 using biochemical detection element] t-[Biochemical sensor and compound using biochemical sensor @ (2) The "Claims" in the specification are amended by 9 in the appendix.
r + + Lines 3, 7, and 15, and 5 - Line 7, correct "biochemical sensing element -, + 11- r biochemical sensor" 5, (4) Lines 2 and 2 of the same book, " Chemical concentration” ligation [compound vI
! Correct it as stripe 1fJ. (5) Lines 3 and 4 of the same page [Field-effect transistor
), and the amount of chemical substance kJt-r is determined by the field effect transistor (hereinafter referred to as 18FET). #! The ion concentration in the liquid [14-J is corrected. (6) On the same page, lines 10 to 12, [In the ion of Aki... is common. Make the following 9 corrections to J. If this silicon nitride film 6t ion-sensitivity test is used, this will be a hydrogen ion-sensitive membrane that is sensitive to hydrogen ions, and therefore the small sensor will become a sensor that is sensitive to hydrogen ion concentration in the water in the water port [VC]. By forming a suitable ion-sensitive film 7 thereon, it is possible to form sensors sensitive to various ions. ] (Page 71, lines 15-16, “Field-effect transistor sensor (hereinafter referred to as 18FKT),” or 18FE'
Correct it as I' J. (8) On line 17 of the same page, after ``I will explain...'' add ``this ion concentration [foot measuring device is]''. 1, :1 (9)-Book, page 3, line 2, ``The ion-sensitive membrane 7Jk [the ion-sensitive membrane 1lii!6, 7J is corrected (1(l)
llaJ member "stablely" in line 14 is corrected to "stablely". Uυ Add [r Darcose sensor tNK control] after "-implementation fil tube" in line 5 of page 14. 03 On the same page, line 9, “Biochemical substances Ukr Biochemical substances poverty 1r
"Immobilized 18FET and pseudo electrode", the DJ stopped. Q3 1fiJ Negative 9th line “In other words, as this biochemical substance”
"I corrected myself." En Shown in line 13-14 of the same page, number 1...
It is formed. The biochemical substance [immobilized] on a hydrogen ion sensitive film 6 as shown in JKR No. 1-. ' Correct 1, (11 same 1 it lines 18-20) r 11 is 'BT' in I8
,,,. Equipped with Jt-[11 is IfS that is sensitive to hydrogen ions
FET (hereinafter referred to as p)1-I8)'ET), 12 is glucose oxidase immobilized--I8FET (J!T
(301) 1.1f (kl, IaFET,!: I5) Glucose oxygen V/--1! on the T** ion-sensitive membrane 6. 'Standing test 12at-Prepare. ” he corrected. . 08 pls page 5 lines 1, 4, 13 and 20. 6 negative 9th row, 12th row and 18th row r ll9FET11J
IHr, H-I81? Correct it as ET tt J. 071 Ibid., page 5, lines 2 and 4, lines 8-9, and lines 9. Lines 12, 17 and 20, page 6 lines 8, 12 and 18
"Biochemical sensing element J'1irGOD immobilized I8F"
Corrected to gT12J. Or Correct "biochemical substance" in lines 10 and 17 of the same page to "glucose oxidase."(1'J same page, line 10, "of the ion-sensitive membrane 7";"in the membrane 12a on which glucose oxidase is immobilized")
I am corrected. (1) "H does not change" tM on the same page, lines 12-13
#do. (ri2aK optimal conditions for 211PI members 18-19 lines...
... was prepared. ” was adjusted to the laxative fluid with the optimal pHvr and the optimal temperature. ” he corrected. On the same page, line 20, after "12 is" r l8FET's.
Add. (c) After "as #I liquid 8" on page 6, line 5 of the same book, add "add acetic acid buffer solution tR that does not contain glucose, and when the voltage stabilizes". (To) Line 8 of the same page [Ion Sensitivity 1j! 7 Jt-r The above immobilization II 12a J is corrected. (c) Delete "1 in the ion-sensitive membrane of 1" from lines 9 to 10 of -j Sada. (4) Delete 1 "in total" from line 20 on page 1 to line 1 on page 7. Punishment: ``Corrected to ``Biochemical detection collector Jkr immobilized 18FET J'' on page 7, lines 8, 9, and 12-13. (Add ``of a different kind of lizard.'' - Correct the line 12 of the same page as [t-formed Jkrk with a solid foot. - Line 13 of the same page, after the r l8FET'', K `` Add a pseudo electrode and It. eυ "...Biochemical sensing element," on page 8, line 11 of the same book.
[--immobilized l8FET%12a...immobilized membrane,
” he corrected. ■ Correct the red inscription in Figure 3 as shown in the attached sheet. 7. Attached is a list of types (11 amended patent claims! 8% 1 copy (2) No. 3
Corrected drawings for figures One or more corrected claims
Immobilized IS immobilized on the ion-sensitive membrane of FET
A biochemical senna characterized by comprising an F'ET and a pseudo electrode. (2) A biochemical sensor, a differential amplifier, and the I8FET and the immobilized I8F with the pseudo electrode as a reference.
'ET17) #1 method of determining compound concentration using a biochemical sensor, where the difference between the output voltages of each is measured with the differential amplifier.

Claims (1)

【特許請求の範囲】 +11イオン感応膜を形成した電界効果型トランジスタ
と、酵素や微生物郷の生化学物質とを有し、前記電界効
果型トランジスタのイオン感応膜上に前記生化学物質を
固定化して成ることを特徴とする生化学的検知素子。 (2)生化学的検知素子と、イオン感応膜を有する電界
効果型トランジスタと、疑似電極と、差動増幅器とを備
え、前記疑似電極を基準とした前記生化学的検知素子及
び前記電界効果型トランジスタの各々の出力電圧の差を
前−記差動増幅器で111足して成ることを特徴とする
生化学的検知素子を用いた化合物濃度の測定方法。
[Claims] A field-effect transistor having a +11 ion-sensitive membrane and a biochemical substance such as an enzyme or a microbial colony, wherein the biochemical substance is immobilized on the ion-sensitive membrane of the field-effect transistor. A biochemical sensing element characterized by comprising: (2) A biochemical sensing element, a field effect transistor having an ion-sensitive membrane, a pseudo electrode, and a differential amplifier, the biochemical sensing element and the field effect transistor having the pseudo electrode as a reference. 1. A method for measuring compound concentration using a biochemical sensing element, characterized in that the difference between the output voltages of each transistor is added by 111 using the differential amplifier.
JP57066981A 1982-04-21 1982-04-21 Biochemical detecting element and method for measuring concentration of compound using the same Granted JPS58184540A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP57066981A JPS58184540A (en) 1982-04-21 1982-04-21 Biochemical detecting element and method for measuring concentration of compound using the same

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP57066981A JPS58184540A (en) 1982-04-21 1982-04-21 Biochemical detecting element and method for measuring concentration of compound using the same

Publications (2)

Publication Number Publication Date
JPS58184540A true JPS58184540A (en) 1983-10-28
JPH037066B2 JPH037066B2 (en) 1991-01-31

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Family Applications (1)

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Country Link
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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6029657A (en) * 1983-07-28 1985-02-15 Mitsubishi Electric Corp Glucose sensor
JPS6279334A (en) * 1985-09-09 1987-04-11 オルド,インコ−ポレ−テツド Fluorescent immunity testing device and method
JPS62130349A (en) * 1985-11-22 1987-06-12 ソーン イーエムアイ ピーエルシー Device for measuring concentration of substance in solution
JPS62502061A (en) * 1985-01-14 1987-08-13 センサ− ダイアグナステイツクス インコ−ポレ−テツド Measurement of ligand/antiligand mutual interference using bulk conductivity
JPS63111454A (en) * 1986-10-29 1988-05-16 Nec Corp Production of immobilized enzyme film
JPH02280047A (en) * 1989-04-21 1990-11-16 Nec Corp One-chip semiconductor biosensor
JPH04254750A (en) * 1990-08-21 1992-09-10 Byung Ki Sohn Measuring circuit for biosensor utilizing ion sensitive field-effect transistor
EP1392860A1 (en) * 2001-04-23 2004-03-03 Samsung Electronics Co., Ltd. Molecular detection chip including mosfet, molecular detection device employing the chip, and molecular detection method using the device
JP2015099070A (en) * 2013-11-19 2015-05-28 大日本印刷株式会社 Built-in solution biosensor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ANALYTICAL CHEMISTRY=1980 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6029657A (en) * 1983-07-28 1985-02-15 Mitsubishi Electric Corp Glucose sensor
JPH0418624B2 (en) * 1983-07-28 1992-03-27 Mitsubishi Electric Corp
JPS62502061A (en) * 1985-01-14 1987-08-13 センサ− ダイアグナステイツクス インコ−ポレ−テツド Measurement of ligand/antiligand mutual interference using bulk conductivity
JPS6279334A (en) * 1985-09-09 1987-04-11 オルド,インコ−ポレ−テツド Fluorescent immunity testing device and method
JPS62130349A (en) * 1985-11-22 1987-06-12 ソーン イーエムアイ ピーエルシー Device for measuring concentration of substance in solution
JPS63111454A (en) * 1986-10-29 1988-05-16 Nec Corp Production of immobilized enzyme film
JPH02280047A (en) * 1989-04-21 1990-11-16 Nec Corp One-chip semiconductor biosensor
JPH04254750A (en) * 1990-08-21 1992-09-10 Byung Ki Sohn Measuring circuit for biosensor utilizing ion sensitive field-effect transistor
EP1392860A1 (en) * 2001-04-23 2004-03-03 Samsung Electronics Co., Ltd. Molecular detection chip including mosfet, molecular detection device employing the chip, and molecular detection method using the device
EP1392860A4 (en) * 2001-04-23 2006-11-29 Samsung Electronics Co Ltd Molecular detection chip including mosfet, molecular detection device employing the chip, and molecular detection method using the device
US7781167B2 (en) 2001-04-23 2010-08-24 Samsung Electronics Co., Ltd. Molecular detection methods using molecular detection chips including a metal oxide semiconductor field effect transistor
US7863140B2 (en) 2001-04-23 2011-01-04 Samsung Electronics Co., Ltd. Methods of making a molecular detection chip having a metal oxide silicon field effect transistor on sidewalls of a micro-fluid channel
JP2015099070A (en) * 2013-11-19 2015-05-28 大日本印刷株式会社 Built-in solution biosensor

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