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JP2614905B2 - Immunosensor - Google Patents

Immunosensor

Info

Publication number
JP2614905B2
JP2614905B2 JP63236496A JP23649688A JP2614905B2 JP 2614905 B2 JP2614905 B2 JP 2614905B2 JP 63236496 A JP63236496 A JP 63236496A JP 23649688 A JP23649688 A JP 23649688A JP 2614905 B2 JP2614905 B2 JP 2614905B2
Authority
JP
Japan
Prior art keywords
electrode
antigen
working electrode
antibody
immunosensor
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 - Lifetime
Application number
JP63236496A
Other languages
Japanese (ja)
Other versions
JPH0285755A (en
Inventor
昭明 勝部
武行 川口
尚志 城
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.)
Teijin Ltd
Original Assignee
Teijin Ltd
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Description

【発明の詳細な説明】 [発明の技術的分野] 本発明は新規な免疫センサ、および希薄濃度の抗原ま
たは抗体を短時間で検出できる免疫反応検出方法に関す
る。
Description: TECHNICAL FIELD [0001] The present invention relates to a novel immunosensor and an immunoreaction detection method capable of detecting a dilute concentration of an antigen or an antibody in a short time.

[発明の背景] 近年、被検体液中に含まれる微少量の抗原または抗体
を検出する種々の方法が提案されている。それらは大別
すると、標識剤を用いる方式と標識剤を用いない方式と
に分類される。標識方式の具体例としては、酵素免疫法
(EIA),放射性同位元素標識免疫法(RIA),蛍光色素
標識免疫法(FIA)などが知られている。これらは一般
に煩雑な操作手順や発色試薬または特殊な設備を必要と
する欠点があった。
[Background of the Invention] In recent years, various methods for detecting a minute amount of an antigen or an antibody contained in a test solution have been proposed. They are broadly classified into a method using a labeling agent and a method not using a labeling agent. Specific examples of the labeling method include enzyme immunoassay (EIA), radioisotope labeling immunoassay (RIA), and fluorescent dye immunoassay (FIA). These generally have the disadvantage of requiring complicated operation procedures, coloring reagents or special equipment.

一方、非標識免疫法としてはこれまで、膜表面に抗体
または抗原を固定化し、抗原抗体反応後の膜表面電位を
測定する膜電位方式(例えば、相沢,鈴木ら、J.Memb.S
ci.,2(1977)125参照)と金属電極表面に直接あたは膜
を介して抗体あるいは抗原を結合し、抗原抗体反応に伴
う電極電位の変動を電極電位測定法(例えば、山本,坪
村ら日本化学会誌、(1980)1562参照)とが提案されて
いる。これらの免疫電極は抗原または抗体を直接、簡便
に測定できるがいずれも応答時間が30分以上かかり、検
出される電気信号の強度も一般に低い。さらに具体的な
問題点として、抗体や抗原が固定された電極に被検体液
を触れさせて抗原抗体反応を起こすに際して、上記電極
を被検体液中に浸漬して攪拌すると、必要とされる被検
体量が多くなり、攪拌に伴う電気信号ノイズやドリフト
も発生しやすい。また、上記電極上に少量の被検体液を
滴下して検出を行う場合も、滴下に伴う電気信号ノイズ
の発生が見られ再現性の良い安定な検出を行うことが困
難であった。
On the other hand, as a non-labeled immunoassay, a membrane potential method in which an antibody or antigen is immobilized on the membrane surface and the membrane surface potential after the antigen-antibody reaction is measured (for example, Aizawa, Suzuki et al., J. Memb. S.
ci., 2 (1977) 125) and the antibody or antigen bound directly to the surface of the metal electrode via a membrane, and the fluctuation of the electrode potential accompanying the antigen-antibody reaction is measured by an electrode potential measurement method (eg, Yamamoto, Tsubo Mura et al., Journal of the Chemical Society of Japan, (1980) 1562). These immunoelectrodes can directly and easily measure an antigen or an antibody, but all require a response time of 30 minutes or more, and the intensity of the detected electric signal is generally low. As a more specific problem, when an antigen-antibody reaction is caused by bringing a test solution into contact with an electrode on which an antibody or an antigen is immobilized, if the electrode is immersed in the test solution and agitated, the required test solution is required. The amount of the sample increases, and electric signal noise and drift accompanying the stirring are likely to occur. In addition, even when a small amount of the sample liquid is dropped on the electrode to perform detection, electric signal noise is generated due to the drop, and it is difficult to perform stable detection with good reproducibility.

[発明の構成] 本発明はかかる状況に鑑みてなされたものである。す
なわち、本発明者らは抗原や抗体を直接、簡便に検出す
るに当り、電気信号ノイズの発生を伴わないようにする
方法を鋭意検討の結果、本発明に到達したものである。
すなわち、本発明は 1. 抗原または抗体を固定した電極上に更にゲル状電解
質層が設けられた作用電極を有する免疫センサ, 2. 当該作用電極が、金属電極、およびその上に形成さ
れたピロール,アニリン,チオフェンおよびそれらの誘
導体から選ばれた化合物のポリマーから成る導電性高分
子、およびそのポリマーに包括固定された抗原または抗
体からなる上記免疫センサ, 3. 当該作用電極が、MOSFETのゲート領域に設けられた
ピロール,アニリン,チオフェンおよびそれらの誘導体
から選ばれる化合物のポリマーから成る導電性高分子、
およびそのポリマーに包括固定さた抗原または抗体かな
る上記免疫センサ, 4. 当該作用電極がMOSFETのゲート部分以外に導電性配
線を介して分離して設けられている上記1〜3項記載の
免疫センサ, 5. 比較電極が当該作用電極の抗体または抗原物質を不
活性化したものである上記1〜3項記載の免疫センサ,
および 6. 当該作用電極と比較電極との間の電位差を増幅し
て、電圧,電流または電荷量として検出する手段を有す
る上記1〜5項記載の免疫センサである。
[Configuration of the Invention] The present invention has been made in view of such circumstances. That is, the inventors of the present invention have intensively studied a method for directly and simply detecting an antigen or an antibody without causing the occurrence of electric signal noise, and have reached the present invention.
That is, the present invention provides: 1. an immunosensor having a working electrode in which a gel electrolyte layer is further provided on an electrode on which an antigen or an antibody is immobilized; 2. the working electrode is a metal electrode; and pyrrole formed thereon. Conductive polymer consisting of a polymer of a compound selected from aniline, thiophene and their derivatives, and the above immunosensor consisting of an antigen or antibody immobilized on the polymer, 3. The working electrode is a gate region of a MOSFET A conductive polymer comprising a polymer of a compound selected from pyrrole, aniline, thiophene and their derivatives provided in
And the immunosensor comprising an antigen or an antibody entrapped in the polymer thereof. 4. The immunosensor according to any one of the above items 1 to 3, wherein the working electrode is provided separately from the gate portion of the MOSFET via a conductive wiring. 5. The sensor according to any one of the above items 1 to 3, wherein the reference electrode is obtained by inactivating antibodies or antigenic substances of the working electrode.
6. The immunosensor according to any one of the above items 1 to 5, further comprising means for amplifying a potential difference between the working electrode and the reference electrode to detect the voltage, current or charge amount.

本発明によれば、電極,その上又は中に形成された抗
原又は抗体含有層及び更にその上に形成されたゲル状電
解質層からなる作用電極と参照電極とを抗原または抗体
を含む被検体水溶液と接触させ、当該作用電極上での抗
原抗体反応に伴う電位変化を電位変化,電流変化または
電荷量変化として検出することができる。
According to the present invention, a working aqueous solution and a reference electrode comprising an electrode, an antigen or antibody-containing layer formed thereon or therein, and a gel electrolyte layer further formed thereon are provided with an aqueous solution of an analyte containing the antigen or antibody. And a potential change accompanying the antigen-antibody reaction on the working electrode can be detected as a potential change, a current change, or a charge amount change.

本発明において用いられる作用電極としては数μV〜
数mVの電位変化を検出でき、界面電位の安定したもので
あれば使用できる。具体的な例としては、白金,金,パ
ラジウム,ニッケル,カーボン,クロム,タンタル,イ
リジウムなどが挙げられる。これらの金属電極の形態は
平板,多孔質体,フィラメントおよびスポンジなどのい
ずれでも構わない。また、これらの金属は直接,作用電
極として用いることはもちろん、電解効果型トランジス
タ(FET)のソースおよびドレイン電極として用いるこ
とも可能である。本発明の作用電極としては金および白
金が好ましい。また、ゲート部に金属を用いる場合は
金,白金以外にイリジウムも好適に用いられる。これら
のゲート金属はFETチップから分離されたいわゆる分離
ゲート型FETとして用いることも可能である。本発明に
用いられる比較電極用の金属としては、本質的には上記
作用電極に用いた金属が使用できる。好ましくは、比較
電極と作用電極の金属は同一である。作用電極上には抗
体または抗原が固定されており、比較電極上には活性を
無くした上記の抗体および抗原が固定される。
As the working electrode used in the present invention, several μV to
A change in potential of several mV can be detected, and any device having a stable interface potential can be used. Specific examples include platinum, gold, palladium, nickel, carbon, chromium, tantalum, iridium, and the like. The form of these metal electrodes may be any of a flat plate, a porous body, a filament and a sponge. In addition, these metals can be used not only directly as working electrodes but also as source and drain electrodes of a field effect transistor (FET). Gold and platinum are preferred for the working electrode of the present invention. When a metal is used for the gate, iridium is preferably used in addition to gold and platinum. These gate metals can be used as a so-called separated gate type FET separated from the FET chip. As the metal for the comparison electrode used in the present invention, essentially the metal used for the above working electrode can be used. Preferably, the metal of the comparison electrode and the working electrode is the same. Antibodies or antigens are immobilized on the working electrode, and the above-mentioned antibodies and antigens having no activity are immobilized on the reference electrode.

次に、本発明に用いられる抗体や抗原物質は、免疫反
応に関わるものであって分子内にイオン性基を有し、10
0μV以上、好ましくは1mV以上の膜電位を示すIgG,IgA,
IgE,IgM等の免疫グロブリンや絨毛性性腺刺激ホルモン
(HCG),ガン胎児性抗原(CEA)などが挙げられ、抗体
としては、これらの抗原に対するポリクローナル又はモ
ノクローナルな抗体が用いられる。
Next, antibodies and antigenic substances used in the present invention are related to an immune reaction and have an ionic group in the molecule.
IgG, IgA, showing a membrane potential of 0 μV or more, preferably 1 mV or more,
Examples include immunoglobulins such as IgE and IgM, chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), and the like, and polyclonal or monoclonal antibodies against these antigens are used.

これらの抗原および抗体分子は、単独でまたは他の脂
質分子と組み合わせて薄膜状にしたのち前記の作用電極
上に固定される。該電極上への抗体および抗原の固定化
法としては、浸漬吸着法,流延法,ラングミュア・ブロ
ージェット法や導電性高分子の形成と同時に該高分子中
に包括固定する方法などが採用される。かくして、作用
電極上に抗体または抗原が固定された素子が、抗原また
は抗体を含む被検体液と接触すると、該作用電極上での
抗原−抗体反応に伴って、その表面膜電位が変化する。
その結果、該膜電位変化量を直接、または電流に変換し
て検出することにより抗原や抗体の検出が原理的には可
能となる。しかしながら、前述したとおりこの膜電位変
化を検出するに当り、ノイズやドリフトの発生が見ら
れ、特に微少信号の検出の際にはこのノイズ発生による
S/N比の低下が問題であった。これを解決するために、
上記の作用電極上にゲル状電解質層を設けることが本発
明の特徴である。
These antigen and antibody molecules are made into a thin film alone or in combination with other lipid molecules, and then immobilized on the working electrode. Examples of a method for immobilizing the antibody and the antigen on the electrode include a dip adsorption method, a casting method, a Langmuir-Blowjet method, and a method in which a conductive polymer is formed and immobilized in the polymer at the same time. You. Thus, when the element on which the antibody or antigen is immobilized on the working electrode comes into contact with a test solution containing the antigen or antibody, the surface membrane potential changes with the antigen-antibody reaction on the working electrode.
As a result, antigens and antibodies can be detected in principle by detecting the change in the membrane potential directly or by converting it into a current. However, as described above, in detecting this change in the membrane potential, generation of noise and drift is observed.
The problem was the decrease in S / N ratio. To solve this,
It is a feature of the present invention to provide a gel electrolyte layer on the working electrode.

すなわち、半固体状の電解質層を電極上に設けると、
検体液中のイオン濃度が低くてもスパイクノイズが発生
しない。従って抗原・抗体反応により生じた膜の表面電
位変化が検体液中のイオンによって低減される、いわゆ
るイオンシールド効果が押えられる結果、センサーとい
ての感度の向上につながることが判明した。このゲル状
層を形成する物質とは、親水性高分子ゲルが代表的なも
のであり、具体的には寒天,アルギン酸ナトリウム,グ
アーガム,カラギーナン,ゼラチンなどの天然高分子化
合物;およびポリアクリル酸イオン架橋体,グルタルア
ルベヒドとポリアミンの架橋反応物,ポリアクリルアミ
ドゲル,塩基性ポリカチオンと強酸性ポリアニオンとの
ポリイオンコンプレックスが挙げられる。これらはゲル
化する前に作用電極上に塗布してゲル層を形成させる。
このゲル層形成に先立って、上記ゲル層形成性物質の水
溶液中には、予め緩衝液成分や血清アルブミンが添加さ
れる。該ゲル層の形成は通常、常温〜50℃で30分以内に
完了する。作用電極上に固定した抗体または抗原の活性
低下を避けるために、ゲルの形成条件はなるべく温和な
方が良い。また、ゲル層の厚みはとくに制限されない
が、好ましくは0.1〜10μm、さらに好ましくは0.5〜5
μmの範囲が採用される。ゲル層の厚みがこれ以上にな
ると被検出成分の拡散が遅くなり、検出に時間がかか
る。また、ゲル層の厚みが0.1μm未満になるとゲル層
を設けた効果が観測されなくなる。かくして、電解質を
含んだゲル層が前記作用電極上に形成される。このゲル
層上で抗原抗体反応を行うと、後述の実施例にも見られ
る様に電気信号ノイズが発生しにくい。抗原抗体反応を
該作用電極上で行うに際しては、被検体液中に上記電極
を挿入して検出を行うことも可能であるが、好ましくは
少量の上記検体液を該作用電極上に滴下して検出を行う
方が効率的である。
That is, when a semi-solid electrolyte layer is provided on the electrode,
No spike noise occurs even if the ion concentration in the sample solution is low. Therefore, it has been found that the change in the surface potential of the membrane caused by the antigen-antibody reaction is reduced by the ions in the sample solution, that is, the so-called ion shield effect is suppressed, leading to an improvement in the sensitivity of the sensor. The substance forming the gel-like layer is typically a hydrophilic polymer gel, specifically, a natural polymer compound such as agar, sodium alginate, guar gum, carrageenan, gelatin; and polyacrylate ion A crosslinked product, a crosslinked reaction product of glutaraldehyde and polyamine, polyacrylamide gel, and a polyion complex of a basic polycation and a strongly acidic polyanion are exemplified. These are applied on the working electrode before gelling to form a gel layer.
Prior to the formation of the gel layer, a buffer component or serum albumin is added to the aqueous solution of the gel layer-forming substance in advance. The formation of the gel layer is usually completed at room temperature to 50 ° C. within 30 minutes. In order to avoid a decrease in the activity of the antibody or antigen immobilized on the working electrode, the conditions for forming the gel should be as mild as possible. The thickness of the gel layer is not particularly limited, but is preferably 0.1 to 10 μm, more preferably 0.5 to 5 μm.
A range of μm is employed. When the thickness of the gel layer is more than this, the diffusion of the component to be detected becomes slow, and it takes time for detection. When the thickness of the gel layer is less than 0.1 μm, the effect of providing the gel layer is not observed. Thus, a gel layer containing an electrolyte is formed on the working electrode. When an antigen-antibody reaction is carried out on this gel layer, electrical signal noise hardly occurs as seen in the examples described later. When performing an antigen-antibody reaction on the working electrode, it is possible to perform detection by inserting the electrode into the test solution, but preferably, a small amount of the sample solution is dropped on the working electrode. Performing the detection is more efficient.

かくして、本発明によれば実質的に10〜100μの被
検体液で検出を行うことも充分可能であり、その検出感
度領域も10-9〜10-3g/mlと極めて広い。また、検出に要
する時間も5〜30分間と比較的短い。以下、実施例によ
り本発明をさらに詳しく説明する。
Thus, according to the present invention, it is sufficiently possible to perform detection with a sample liquid of substantially 10 to 100 μm, and the detection sensitivity range is as wide as 10 −9 to 10 −3 g / ml. The time required for detection is relatively short, 5 to 30 minutes. Hereinafter, the present invention will be described in more detail with reference to examples.

参考例1 (ヒトIgGとアラキン酸メチルとの混合単分子膜および
ラングミュア・ブロージェット膜の作成) テフロンコートした水槽中に二回蒸留水を満たし、そ
の表面にアラキン酸メチルのクロロホルム溶液(0.5mg/
ml)を100μ展開し、単分子膜を形成した。その後、
水槽中にヒトIgGを全体の濃度が10μg/mlになる様に注
入したのち、上記単分子膜を10mN/mに圧縮した状態で1
時間整地した。かくして水中にヒトIgGの一部を上記単
分子膜中に吸着固定した後、ラングミュア・ブロージェ
ット法により該単分子膜を本発明の電極基板上に転写し
た。
Reference Example 1 (Preparation of a mixed monomolecular film of human IgG and methyl arachiate and a Langmuir-Blowjet membrane) A double-distilled water was filled in a Teflon-coated water tank, and the surface of the tank was mixed with a chloroform solution of methyl arachiate (0.5 mg). /
ml) was developed by 100 μ to form a monomolecular film. afterwards,
After injecting human IgG into the aquarium so that the total concentration becomes 10 μg / ml, the above monomolecular film is compressed to 10 mN / m, and
Time was leveled. Thus, after a part of human IgG was adsorbed and fixed in the monomolecular film in water, the monomolecular film was transferred onto the electrode substrate of the present invention by the Langmuir-Blowjet method.

実施例1 スライドガラス基板上に白金を薄膜状にスパッタして
電極板とした。この上に、前記参考例1に示した方法に
よって作成したヒトIgGとアラキン酸メチルとの混合単
分子膜をラングミュア・ブロージェット法で二層累積
し、リン酸緩衝液で充分洗浄し。同一寸法の上記電極を
二枚作成し、一方の電極はそのまま作用電極用として用
い、もう一方の電極はその上に固定したヒトIgGを紫外
線照射により失活させた後、比較電極として用いた。次
に、25mlのリン酸緩衝液(pH6.8)と牛血清アルブミン
を混合した0.7重量%の寒天水溶液を上記作用電極用電
極上に塗布したのち、室温にて放置することによりゲル
化させた。このゲル上に10-9モル/の抗イトIgG溶液
を5μ滴下したところ、何らノイズ信号の発生を伴わ
ずに10分後に1mVの表面電位変化が観測された。
Example 1 An electrode plate was formed by sputtering platinum on a slide glass substrate in a thin film form. On top of this, two layers of a mixed monolayer of human IgG and methyl arachiate prepared by the method shown in the above-mentioned Reference Example 1 were accumulated in two layers by the Langmuir-Blowjet method, and sufficiently washed with a phosphate buffer. Two electrodes having the same dimensions were prepared, and one electrode was used as it was for a working electrode, and the other electrode was used as a reference electrode after human IgG immobilized thereon was inactivated by ultraviolet irradiation. Next, a 0.7% by weight agar aqueous solution obtained by mixing 25 ml of a phosphate buffer (pH 6.8) and bovine serum albumin was applied on the working electrode, and then left at room temperature to gel. . When 5 μl of an anti-ito IgG solution of 10 −9 mol / was dropped on this gel, a change in surface potential of 1 mV was observed after 10 minutes without any generation of a noise signal.

比較例1 実施例において寒天ゲルを用いる事なく、同一の実験
を行ったところ、非常に大きなスパイク状のノイズ信号
が発生し、抗IgGの検出は不可能であった。
Comparative Example 1 When the same experiment was performed without using agar gel in the example, a very large spike-like noise signal was generated, and it was impossible to detect anti-IgG.

実施例2 実施例1において、ヒトIgGを混合単分子膜方で電極
上に固定する代わりに、ヒトIgG(10mg/ml),ピロール
(0.5モル/)および塩化カリ(0.1モル/)を常法
に従い定電位重合(0.65V,通電量0.2クローン/cm2,重合
温度25℃)を行うことにより、電極上に形成したポリピ
ロール膜中に固定した。この作用電極用電極上に実施例
1と同様に寒天ゲル層を設けて、抗ヒトIgGの検出を行
ったところ、ノイズ信号の発生を伴うことなく、10-10
モル/の濃度まで検出可能であった。
Example 2 In Example 1, human IgG (10 mg / ml), pyrrole (0.5 mol /) and potassium chloride (0.1 mol /) were used in a conventional manner instead of immobilizing human IgG on a mixed monomolecular membrane. The polymer was fixed in a polypyrrole film formed on the electrode by performing constant potential polymerization (0.65 V, 0.2 clones / cm 2 of electricity, polymerization temperature of 25 ° C.) according to the procedure described in Example 1. This likewise provided agar gel layer as in Example 1 on the working electrode for the electrode, was subjected to detection of anti-human IgG, without occurrence of the noise signal, 10 -10
It was detectable up to a concentration of mol /.

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

図1は本発明の免疫センサの1例を示すものである。図
中、1はヒトIgGが固定された電極,2はゲル状電解質層,
3は電極リード線,4は被検液体である。
FIG. 1 shows an example of the immunosensor of the present invention. In the figure, 1 is an electrode on which human IgG is immobilized, 2 is a gel electrolyte layer,
3 is an electrode lead, and 4 is a test liquid.

Claims (6)

(57)【特許請求の範囲】(57) [Claims] 【請求項1】電極,その上又は中に形成された抗原又は
抗体含有層及び更にその上に形成されたゲル状電解質層
からなる作用電極を有する免疫センサ。
1. An immunosensor comprising a working electrode comprising an electrode, an antigen or antibody-containing layer formed thereon or therein, and a gel electrolyte layer further formed thereon.
【請求項2】当該電極が金属成形物及びその上に形成さ
れたピロール,アニリン,チオフェンおよびそれらの誘
導体から選ばれた化合物の重合体層からなり;かつ抗原
又は抗体含有層が、上記重合体層が抗原又は抗体を含有
せしめられてなる層である請求項1の免疫センサ。
2. The electrode according to claim 1, wherein said electrode comprises a polymer layer of a compound selected from pyrrole, aniline, thiophene and derivatives thereof formed on the metal molded product; 2. The immunosensor according to claim 1, wherein the layer is a layer containing an antigen or an antibody.
【請求項3】当該作用電極がMOSFETのゲート領域を構成
している請求項1の免疫センサ。
3. The immunosensor according to claim 1, wherein said working electrode forms a gate region of a MOSFET.
【請求項4】当該作用電極がMOSFETのゲート部分以外に
導電性配線を介して分離して設けられている請求項1に
記載の免疫センサ。
4. The immunosensor according to claim 1, wherein the working electrode is provided separately from the gate portion of the MOSFET via a conductive wiring.
【請求項5】比較電極が当該作用電極の抗体または抗原
物質を不活性化したものである請求項1〜4記載のいず
れかの免疫センサ。
5. The immunosensor according to claim 1, wherein the reference electrode is obtained by inactivating antibodies or antigen substances of the working electrode.
【請求項6】当該作用電極と比較電極との間の電位差を
増幅して、電圧,電流または電荷量として検出する手段
を有する請求項1〜5記載のいずれかの免疫センサ。
6. The immunosensor according to claim 1, further comprising means for amplifying a potential difference between the working electrode and the reference electrode, and detecting the amplified potential difference as a voltage, a current, or a charge amount.
JP63236496A 1988-09-22 1988-09-22 Immunosensor Expired - Lifetime JP2614905B2 (en)

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JP2614905B2 true JP2614905B2 (en) 1997-05-28

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US5328847A (en) * 1990-02-20 1994-07-12 Case George D Thin membrane sensor with biochemical switch
US5547555A (en) * 1993-02-22 1996-08-20 Ohmicron Technology, Inc. Electrochemical sensor cartridge
US6180288B1 (en) * 1997-03-21 2001-01-30 Kimberly-Clark Worldwide, Inc. Gel sensors and method of use thereof
AU2003261568B2 (en) * 2002-09-13 2006-12-07 Hitachi Chemical Co., Ltd Fixation carrier and solid phase
JP2011102729A (en) * 2009-11-10 2011-05-26 Sharp Corp Analyzing chip device, chemical sensor chip housing adaptor used analyzing chip device analyzer, and analyzing method using the analyzing chip device
CN104297473B (en) * 2014-09-26 2015-10-21 济南大学 A kind of unmarked pig parvoviral transducer production method of three-dimensional structure rGO-MWCNT-Pd and application
CN109490284B (en) * 2018-12-03 2020-06-19 青岛大学 Dual-catalysis luminol electrochemical luminescence biosensor based on gold nanoparticles and titanium carbide MXenes
JP6977705B2 (en) * 2018-12-19 2021-12-08 日本電信電話株式会社 Biomolecule measuring device and method

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