JPH0422293Y2 - - Google Patents

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Publication number
JPH0422293Y2
JPH0422293Y2 JP1986174096U JP17409686U JPH0422293Y2 JP H0422293 Y2 JPH0422293 Y2 JP H0422293Y2 JP 1986174096 U JP1986174096 U JP 1986174096U JP 17409686 U JP17409686 U JP 17409686U JP H0422293 Y2 JPH0422293 Y2 JP H0422293Y2
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Japan
Prior art keywords
ion
gate bias
pseudo
electrode
source
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JP1986174096U
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Japanese (ja)
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JPS6379566U (en
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Description

【考案の詳細な説明】 産業上の利用分野 本考案は、バイオセンサに係わり、特に生体試
料中の特定成分濃度を簡単に測定できるようにし
たバイオセンサに関する。
[Detailed Description of the Invention] Industrial Application Field The present invention relates to a biosensor, and particularly to a biosensor that can easily measure the concentration of a specific component in a biological sample.

従来の技術 バイオセンサは、酵素や抗体、あるいは微生物
を用いたリセプタと、物理量、化学量を電気信号
に変換するトランデユーサとからなり、生物特有
の生化学反応を利用しようとするものである。
BACKGROUND ART Biosensors are comprised of receptors using enzymes, antibodies, or microorganisms, and transducers that convert physical and chemical quantities into electrical signals, and utilize biochemical reactions unique to living organisms.

このバイオセンサのトランデユーサとしてイオ
ン感応性電界効果トランジスタ(ISFET)が用
いられている。このISFETは、第4図に示すよ
うに、シリコン−オン−サフアイア基板a上のシ
リコン層bにこのシリコン層の表面からホウ素を
ドープする。さらに互いに隔離された平行な細長
形状にリンをドープしてソース層cとドレイン層
dを形成する。これらソース層cとドレイン層d
の間隙はチヤンネル層eが形成される。これらソ
ース層、ドレイン層、チヤンネル層の表面を酸化
して酸化ケイ素膜fを設け、さらにこの上を窒化
シリコン膜gで被覆する。そして上記基板の裏面
にAuを蒸着し、ゲートバイアス用の疑似比較電
極Gを設けたものである。
An ion-sensitive field effect transistor (ISFET) is used as a transducer for this biosensor. In this ISFET, as shown in FIG. 4, a silicon layer b on a silicon-on-sapphire substrate a is doped with boron from the surface of the silicon layer. Further, a source layer c and a drain layer d are formed by doping phosphorus into parallel elongated shapes separated from each other. These source layer c and drain layer d
A channel layer e is formed in the gap. The surfaces of the source layer, drain layer, and channel layer are oxidized to form a silicon oxide film f, which is further covered with a silicon nitride film g. Then, Au was deposited on the back surface of the substrate, and a pseudo comparison electrode G for gate bias was provided.

このような構成において、ソースとドレイン間
に電圧を印加し、チヤンネル層に酸化ケイ素膜及
び窒化ケイ素膜を介してゲート電圧を加えると、
このゲート電圧の大きさによりチヤンネル層に誘
起されるキヤリヤ濃度が変化し、これによりソー
ス、ドレイン間に流れる電流が変化するが、窒化
ケイ素膜は供給される生体試料のPHによりその表
面電位が変化するため実効ゲート電圧が変化す
る。これによりソース、ドレイン間に流れる電流
が変化し、この変化を検出することによつて生体
試料のPHを測定することができる。
In such a configuration, when a voltage is applied between the source and the drain and a gate voltage is applied to the channel layer through the silicon oxide film and the silicon nitride film,
The carrier concentration induced in the channel layer changes depending on the magnitude of this gate voltage, which changes the current flowing between the source and drain, but the surface potential of the silicon nitride film changes depending on the pH of the biological sample supplied. Therefore, the effective gate voltage changes. This changes the current flowing between the source and drain, and by detecting this change, the pH of the biological sample can be measured.

上記構造はイオン感応部に窒化シリコン膜を設
けたが、この窒化シリコン膜上に酵素や抗体等を
固定すると、それぞれが検出できる特有な生体中
の特定成分の濃度を測定することができる。
In the above structure, a silicon nitride film is provided in the ion-sensing part, but by immobilizing enzymes, antibodies, etc. on this silicon nitride film, it is possible to measure the concentration of specific components in living organisms that can be detected by each enzyme.

考案が解決しようとする問題点 しかしながら、このようなバイオセンサは、シ
リコン−オン−サファイア基板aの半導体基板の
表裏にそれぞれ電極を設けているので、生体試料
の特定成分の濃度を測定するときは、これらの両
方の電極を生体試料に浸漬する必要がある。その
ため生体試料を多く必要とするという問題点があ
り、その改善が望まれていた。
Problems to be Solved by the Invention However, since such a biosensor has electrodes on the front and back sides of the silicon-on-sapphire semiconductor substrate, it is difficult to measure the concentration of a specific component in a biological sample. , both of these electrodes need to be immersed in the biological sample. Therefore, there is a problem that a large amount of biological samples are required, and an improvement has been desired.

問題点を解決するための手段 本考案は、上記問題点を解決するために、ゲー
トバイアス用疑似比較電極とイオン感応性電界効
果型トランジスタのイオン感応部を該イオン感応
性電界効果型トランジスタの基板とは別体の絶縁
基板の同一面上に近接して設け、かつ上記イオン
感応部とこれに相応する上記ゲートバイアス用疑
似比較電極の近接する側縁部を除いた周辺を絶縁
膜で被覆して試料滴下窓部を設けたことを特徴と
するバイオセンサを提供するものである。
Means for Solving the Problems In order to solve the above-mentioned problems, the present invention provides a gate bias pseudo comparison electrode and an ion-sensitive part of an ion-sensitive field-effect transistor on the substrate of the ion-sensitive field-effect transistor. The electrode is provided adjacently on the same surface of an insulating substrate separate from the electrode, and the periphery of the ion-sensing portion and the corresponding pseudo comparison electrode for gate bias except for adjacent side edges is covered with an insulating film. The present invention provides a biosensor characterized in that a sample dropping window is provided.

作 用 ゲートバイアス用疑似比較電極とイオン感応性
電界効果型トランジスタのイオン感応部を近接し
て設け、その相対する両端部を除いて周辺を絶縁
膜で覆うようにしたので、疑似比較電極とイオン
感応部の両端部が露出した窓が形成され、ここに
生体試料の少量を供給することにより生体試料中
の特定成分濃度が測定される。
Function: The pseudo reference electrode for gate bias and the ion sensitive part of the ion sensitive field effect transistor are placed close to each other, and the periphery is covered with an insulating film except for the opposite ends, so that the pseudo reference electrode and the ion sensitive part are covered with an insulating film. A window is formed in which both ends of the sensitive part are exposed, and by supplying a small amount of the biological sample to the window, the concentration of a specific component in the biological sample is measured.

実施例 次に本考案の一実施例を第1図及び第2図に基
づいて説明する。
Embodiment Next, an embodiment of the present invention will be described based on FIGS. 1 and 2.

1はガラス基板で、このガラス基板上には
ISFET2が設けられ、これを挟んだ位置にゲー
トバイアス用疑似比較電極3及びこれに接続され
た外部接点3aと、ソース用外部接点4a,4b
及びその中間にドレイン用外部接点4cがそれぞ
れAl等の金属蒸着により形成されている。
1 is a glass substrate, and on this glass substrate
An ISFET 2 is provided, and a pseudo comparison electrode 3 for gate bias, an external contact 3a connected to this, and external contacts 4a and 4b for source are provided on both sides of the ISFET 2.
An external drain contact 4c is formed between the two by vapor deposition of a metal such as Al.

上記ISFET2は第2図に示すように、幅1mm、
長さ4mm、厚さ0.35mmのシリコン−オン−サフア
イア基板2a上のシリコン膜2bにホウ素をドー
プし、このホウ素がドープされたシリコン膜2b
にリンをドープした細長形状のソース層2c,2
d及びその中間のドレイン層2eをそれぞれ間隔
を保つて形成する。これらのドレイン層、ソース
層の一端、すなわち上記ゲートバイアス用疑似比
較電極側端部の間隙のシリコン膜2bにチヤンネ
ル層2f,2′fが形成される。
As shown in Figure 2, the above ISFET2 has a width of 1 mm,
A silicon film 2b on a silicon-on-sapphire substrate 2a having a length of 4 mm and a thickness of 0.35 mm is doped with boron, and the silicon film 2b doped with boron is
An elongated source layer 2c, 2 doped with phosphorus
d and the drain layer 2e located therebetween are formed with intervals maintained between them. Channel layers 2f and 2'f are formed in the silicon film 2b in the gap between one end of these drain and source layers, that is, the end on the gate bias pseudo comparison electrode side.

上記ソース層2c,2d及びドレイン層2eと
これらの間隙のシリコン膜2b表面に加熱酸化に
よつて酸化ケイ素膜2gを形成し、さらにこの上
を窒化シリコン膜2hで被覆する。ただし、ソー
ス層2c,2d及びドレイン層2eの他端部は酸
化ケイ素膜2g、窒化シリコン膜2hで覆わない
部分を設け、この部分にAl等の金属蒸着により
上記ソース用外部接点4a,4b、ドレイン用外
部接点4cに対応するソース電極2′c,2′d及
びドレイン電極2′eを形成し、それぞれと対応
する電極外部接点をワイヤーボンデイング法によ
り電気的に接続する。
A silicon oxide film 2g is formed by thermal oxidation on the source layers 2c, 2d and drain layer 2e, and on the surface of the silicon film 2b in the gap therebetween, and is further covered with a silicon nitride film 2h. However, the other end portions of the source layers 2c, 2d and the drain layer 2e are provided with a portion not covered with the silicon oxide film 2g and the silicon nitride film 2h, and the external contacts 4a, 4b for the source are formed by vapor deposition of a metal such as Al on this portion. Source electrodes 2'c, 2'd and drain electrode 2'e corresponding to the drain external contact 4c are formed, and the corresponding electrode external contacts are electrically connected by wire bonding.

一方、上記ホウ素をドープした層及びこれに隣
接するソース層及びドレイン層の相対する側縁を
除いた部分に対応する窒化シリコン膜2hに光硬
化性エポキシ樹脂等の耐水性絶縁性樹脂膜2iを
設け、この樹脂膜で覆われない一方の間隙にポリ
パラキシリレンのポリ塩化ビニル樹脂溶液を塗
布、乾燥させて参照用電極2kを形成し、他方の
間隙はそのままにして窒化シリコン膜のイオン感
応部2lとする。
On the other hand, a water-resistant insulating resin film 2i, such as a photocurable epoxy resin, is applied to the silicon nitride film 2h corresponding to the portions of the boron-doped layer and the adjacent source and drain layers excluding the opposing side edges. A polyvinyl chloride resin solution of polyparaxylylene is applied to one gap not covered by the resin film and dried to form a reference electrode 2k, while the other gap is left as it is and the ion sensitivity of the silicon nitride film is applied. Section 2l.

さらに第1図において、上記イオン感応部2
l、参照用電極2kとゲートバイアス用疑似比較
電極3の相対する側縁を除いたその周辺に対応す
る表面をエポキシ樹脂等の耐水性絶縁性膜で覆つ
て試料滴下窓部5を形成する。
Furthermore, in FIG. 1, the ion sensing section 2
l. The sample dropping window portion 5 is formed by covering the surfaces of the reference electrode 2k and gate bias pseudo comparison electrode 3, excluding their opposing side edges, with a water-resistant insulating film such as epoxy resin.

このような構成において、上記ゲートバイアス
用疑似比較電極の外部接点3a、ソース電極の外
部接点4a,4b、ドレイン電極の外部接点4c
に所定の電源をつなぎ、ソースとドレイン間に電
圧を印加すると、上記チヤンネル層に誘発される
キヤリヤ濃度が高いほどソースとドレインの間に
流れる電流が大きくなる。この状態でゲート電圧
がイオン感応部2lに印加されると、その電界に
より上記キヤリヤ濃度が変化し、上記ソースとド
レイン間に流れる電流が変化する。
In such a configuration, the external contact 3a of the pseudo comparison electrode for gate bias, the external contacts 4a and 4b of the source electrode, and the external contact 4c of the drain electrode.
When a predetermined power source is connected to and a voltage is applied between the source and drain, the higher the carrier concentration induced in the channel layer, the greater the current flowing between the source and drain. When a gate voltage is applied to the ion sensitive portion 2l in this state, the carrier concentration changes due to the electric field, and the current flowing between the source and drain changes.

この際、生体試料がピペツト等で上記試料滴下
窓部5に一滴落され、この生体試料を介してイオ
ン感応部2lにゲート電圧が印加されると、ゲー
ト電圧が一定であつても窒化シリコン膜に対する
生体試料の及ぼす影響により実効ゲート電圧が変
化する。すなわち、窒化シリコン表面では、窒化
珪素の一部が加水分解を受けてSiOHとなつて、
SiO-とH+の間に平衡が成立し、この平衡は試料
のPHにより変化し、これにより表面電位が異なる
ことになつてチヤンネル層のキヤリヤ濃度が変化
する。これによりソースとドレイン間に流れる電
流の大きさが変わり、これが検出されることによ
つて試料のPHが測定される。
At this time, when a drop of a biological sample is dropped into the sample dropping window 5 using a pipette or the like, and a gate voltage is applied to the ion sensing section 2l through this biological sample, even if the gate voltage is constant, the silicon nitride film The effective gate voltage changes depending on the influence of the biological sample on the In other words, on the silicon nitride surface, a portion of silicon nitride undergoes hydrolysis and becomes SiOH.
An equilibrium is established between SiO - and H + , and this equilibrium changes depending on the pH of the sample, resulting in a difference in surface potential and a change in the carrier concentration in the channel layer. This changes the magnitude of the current flowing between the source and drain, and by detecting this, the pH of the sample is measured.

上記は生体試料のPHを測定するバイオセンサに
ついて述べたが、上記ポリパラキシリレンの参照
用電極2kはそのままにしてイオン感応部2lに
次の左側の物質膜を用いることにより右側の生体
試料の特定成分濃度を測定することができる。
The above describes a biosensor that measures the pH of a biological sample. By leaving the reference electrode 2k of polyparaxylylene as is and using the material film on the left side in the ion sensing part 2l, the biosensor on the right side can be measured. Specific component concentration can be measured.

バリノマイシン/PVC K+イオン bis−12−クラウン−4/PVC Na+イオン また、参照用電極2kに牛血清アルブミンを用
いイオン感応部2に下記左側の物質膜を用いる
ことにより右側の生体試料濃度を測定できる。
Valinomycin / PVC K + ion bis-12-crown-4 / PVC Na + ion In addition, by using bovine serum albumin as the reference electrode 2k and using the material membrane shown on the left side below as the ion sensing part 2, the concentration of the biological sample on the right side can be determined. Can be measured.

グリコースオキシダーゼ グルコース ウレアーゼ 尿素 リポプロテインリパーゼ 中性脂質 なお、PVCはポリ塩化ビニル樹脂を表し、こ
の樹脂溶液を用いてバリノマイシン等を成膜化す
ることを示す。
Glyose oxidase Glucose Urease Urea Lipoprotein lipase Neutral lipid Note that PVC represents polyvinyl chloride resin, and indicates that this resin solution is used to form a film of valinomycin, etc.

上記は生体試料中の特定成分濃度は同時には1
種類しか測定できなかつたが、第3図に示すよう
に、ガラス基板11上にゲートバイアス用疑似比
較電極12を設け、これを囲むようにして例えば
4箇所に上記PH測定用ISFET素子、K+イオン測
定用ISFET素子、Na+イオン測定用ISFET素子、
酵素測定用ISFET素子13,14,15,16
を配設し、これらのISFET素子に対応してそれ
ぞれソース用外部接点及びその中間のドレイン接
点からなる外部接点13a,14a,15a,1
6aを設け、さらに上記バイアス用疑似比較電極
12と各ISFETのイオン感応部13b,14b,
15b,16b及び参照電極13c,14c,1
5c,16cを残してその周辺をエポキシ樹脂等
の耐水性絶縁性材料で被覆し、試料滴下窓17を
設けるようにしても良い。
The above shows that the concentration of the specific component in the biological sample is 1 at the same time.
However, as shown in Figure 3, a pseudo reference electrode 12 for gate bias is provided on a glass substrate 11, and surrounding it, for example, the above ISFET element for PH measurement, K + ion measurement ISFET element for Na + ion measurement, ISFET element for Na + ion measurement,
ISFET elements for enzyme measurement 13, 14, 15, 16
External contacts 13a, 14a, 15a, 1 are provided corresponding to these ISFET elements, respectively, consisting of an external contact for source and a drain contact in between.
6a, and furthermore, the bias pseudo comparison electrode 12 and the ion sensing parts 13b, 14b of each ISFET,
15b, 16b and reference electrodes 13c, 14c, 1
5c and 16c may be left and the periphery thereof may be covered with a water-resistant insulating material such as epoxy resin, and the sample dropping window 17 may be provided.

このようにすると、試料滴下窓17に生体試料
をそれぞれの電極が液に浸る程度に滴下するだけ
で、同時に4つの特定成分濃度を測定することが
できる。
In this way, the concentrations of four specific components can be measured at the same time by simply dropping the biological sample into the sample dropping window 17 to the extent that each electrode is immersed in the liquid.

考案の効果 以上説明したように、本考案によれば、
ISFETのイオン感応部とバイアス用疑似比較電
極とを近接して設け、その相対する側縁を残して
その周辺を絶縁膜で覆い試料滴下窓部を形成した
ので、生体試料の測定のための必要量は試料滴下
窓部内の上記のイオン感応部とバイアス用疑似比
較電極とを浸す程度で良く、少量の生体試料で生
体の特定成分濃度を測定することができる。
Effects of the invention As explained above, according to the invention,
The ion sensing part of the ISFET and the pseudo reference electrode for bias are placed close together, and the periphery is covered with an insulating film leaving the opposing side edges to form a sample dropping window, which is necessary for measuring biological samples. The amount is sufficient to immerse the above-mentioned ion-sensing section in the sample dropping window and the pseudo comparison electrode for bias, and the concentration of a specific component in the living body can be measured with a small amount of the biological sample.

これは複数のイオン感応部をバイアス用疑似比
較電極を囲むようにして設け、検出に必要な部分
を残して周辺を覆うことにより少量の生体試料で
複数の生体試料の特定成分濃度を同時に測定する
ことを可能にし、測定能率を高めることができ
る。
This allows multiple ion-sensing parts to surround a pseudo comparison electrode for bias, and by covering the periphery leaving only the part necessary for detection, it is possible to simultaneously measure the concentration of a specific component in multiple biological samples using a small amount of biological sample. It is possible to improve measurement efficiency.

また、上記イオン感応部とバイアス用疑似比較
電極をこのイオン感応部が設けられている例えば
シリコン−オン−サファイア等の半導体基板とは
別体の例えばガラス基板に設けることにより、半
導体に形成するイオン感応部を数mm程度の必要最
小限の大きさにして高価な半導体を有効に利用す
るとともに、その絶縁を行う煩わしさを軽減し、
さらにガラス基板等は電極を蒸着又は印刷等によ
り形成することも容易であり、安価であるから、
イオン感応部を形成した半導体をこのガラス基板
等に載せて上記電極と接続すれば、低コストでバ
イオセンサ全体をカード型の数cmの大きさにする
ことができ、試料をイオン感応部に滴下したり、
測定器にセツトする際等のハンドリングを行う際
の取扱いの利便性を高めることができるととも
に、使い捨ても可能な低価格の製品を提供するこ
とができる。
Furthermore, by providing the ion sensing section and the pseudo comparison electrode for bias on a glass substrate, for example, which is separate from the semiconductor substrate on which the ion sensing section is provided, such as silicon-on-sapphire, it is possible to By reducing the size of the sensitive part to the minimum necessary size of several millimeters, we can make effective use of expensive semiconductors and reduce the trouble of insulating them.
Furthermore, glass substrates and the like are easy to form electrodes on by vapor deposition or printing, and are inexpensive.
By placing the semiconductor with the ion-sensing part on this glass substrate and connecting it to the above electrodes, the entire biosensor can be made into a card-shaped several centimeters in size at low cost, and the sample can be dropped onto the ion-sensing part. or
It is possible to improve the convenience of handling when setting it in a measuring instrument, etc., and also to provide a disposable and low-cost product.

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

第1図は本考案の一実施例のバイオセンサの斜
視図、第2図イはそのISFETの平面図、同図ロ、
ハはそれぞれそのA−A断面図、B−B断面図、
第3図は他の実施例の斜視図、第4図は従来のバ
イオセンサの斜視図、断面図である。 図中3,12はゲートバイアス用疑似比較電
極、2l,13b,14b,15b,16bはイ
オン感応部、5,17は試料滴下窓部である。
Figure 1 is a perspective view of a biosensor according to an embodiment of the present invention, Figure 2A is a plan view of its ISFET,
C is a cross-sectional view along A-A, a cross-sectional view along B-B,
FIG. 3 is a perspective view of another embodiment, and FIG. 4 is a perspective view and a sectional view of a conventional biosensor. In the figure, 3 and 12 are pseudo comparison electrodes for gate bias, 2l, 13b, 14b, 15b, and 16b are ion sensing parts, and 5 and 17 are sample dropping windows.

Claims (1)

【実用新案登録請求の範囲】 (1) ゲートバイアス用疑似比較電極とイオン感応
性電界効果型トランジスタのイオン感応部を該
イオン感応性電界効果型トランジスタの半導体
基板とは別体の絶縁基板の同一面上に近接して
設け、かつ上記イオン感応部とこれに相対する
上記ゲートバイアス用疑似比較電極の近接する
側縁部を除いた周辺を絶縁膜で被覆して試料滴
下窓部を設けたことを特徴とするバイオセン
サ。 (2) 試料滴下窓部内に共通のゲートバイアス用疑
似比較電極とこれを取り巻く複数のイオン感応
部を有することを特徴とする実用新案登録請求
の範囲第1項記載のバイオセンサ。
[Scope of Claim for Utility Model Registration] (1) The pseudo reference electrode for gate bias and the ion sensitive part of the ion sensitive field effect transistor are formed on the same insulating substrate that is separate from the semiconductor substrate of the ion sensitive field effect transistor. A sample dropping window is provided close to the surface and covered with an insulating film around the ion sensing part and the gate bias pseudo comparison electrode facing thereto except for the adjacent side edges. A biosensor featuring: (2) The biosensor according to claim 1, which is characterized by having a common pseudo comparison electrode for gate bias and a plurality of ion sensing parts surrounding the common gate bias pseudo comparison electrode within the sample dropping window.
JP1986174096U 1986-11-14 1986-11-14 Expired JPH0422293Y2 (en)

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JPH0422293Y2 true JPH0422293Y2 (en) 1992-05-21

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Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07122620B2 (en) * 1986-11-18 1995-12-25 株式会社島津製作所 Device for concentration measurement

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5928647A (en) * 1982-08-09 1984-02-15 Mitsubishi Electric Corp Semiconductor sensor for liquid
JPS6056247A (en) * 1983-09-07 1985-04-01 Mitsubishi Electric Corp Insulation of semiconductor ion sensor

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5928647A (en) * 1982-08-09 1984-02-15 Mitsubishi Electric Corp Semiconductor sensor for liquid
JPS6056247A (en) * 1983-09-07 1985-04-01 Mitsubishi Electric Corp Insulation of semiconductor ion sensor

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