JP2690849B2 - Manufacturing method of quartz oscillator type biosensor and quartz oscillator type biosensor - Google Patents
Manufacturing method of quartz oscillator type biosensor and quartz oscillator type biosensorInfo
- Publication number
- JP2690849B2 JP2690849B2 JP5158619A JP15861993A JP2690849B2 JP 2690849 B2 JP2690849 B2 JP 2690849B2 JP 5158619 A JP5158619 A JP 5158619A JP 15861993 A JP15861993 A JP 15861993A JP 2690849 B2 JP2690849 B2 JP 2690849B2
- Authority
- JP
- Japan
- Prior art keywords
- electrode
- crystal oscillator
- biosensor
- type biosensor
- ionic substance
- 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
Links
Description
【０００１】[0001]
【産業上の利用分野】本発明は水晶振動子式バイオセン
サの製法に関する。さらに詳しくは、本発明は水晶振動
子電極上にイオン性物質の固定化膜を形成するバイオセ
ンサの製法に関する。本発明はさらに当該製法で製造さ
れる水晶振動子式バイオセンサに関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for manufacturing a quartz oscillator type biosensor. More specifically, the present invention relates to a biosensor manufacturing method for forming an immobilization film of an ionic substance on a crystal oscillator electrode. The present invention further relates to a crystal resonator type biosensor manufactured by the manufacturing method.
【０００２】[0002]
【従来の技術】近年、酵素、抗原、抗体等の生体物質を
その活性を保ったまま利用するバイオセンサが開発され
ている。バイオセンサとは、測定物質の分子（リガン
ド）と特異的に反応する主に生物由来のレセプターを、
このレセプターとリガンドの反応を電気信号に変えるト
ランスデューサー部に固定化したセンサである。このよ
うなバイオセンサは特異性が高く、立体異性体や構造類
似体をほぼ完全に区別し、真にバイオアクティブな特定
の物質のみを定量でき、さらには生体試料等を精製する
ことなく微量成分を測定することができるため、医療、
臨床検査あるいは各種工業プロセスにおける分析、環境
監視等の分野で多用されている。2. Description of the Related Art In recent years, biosensors have been developed which utilize biological substances such as enzymes, antigens and antibodies while maintaining their activities. A biosensor is a biologically-derived receptor that specifically reacts with a molecule (ligand) of a measurement substance.
This is a sensor immobilized on a transducer unit that converts the reaction between the receptor and the ligand into an electric signal. Such biosensors have high specificity, can almost completely distinguish stereoisomers and structural analogs, can quantify only specific substances that are truly bioactive, and furthermore, trace components without purifying biological samples etc. Medical,
It is widely used in clinical inspection, analysis in various industrial processes, environmental monitoring, and the like.
【０００３】バイオセンサのレセプターとリガンドの反
応は、酸素濃度の変化を感知する酸素電極、特定のイオ
ンの消費量あるいは生成量を感知するイオン電極、電極
上での反応による重量変化を感知する水晶振動子あるい
は発光量を感知する光デバイス等様々なトランスデュー
サーによって検出される。このうち、水晶振動子電極に
レセプターの固定化膜を形成したセンサは、レセプター
とリガンドの結合や解離によるごくわずかな重量変化を
検出することができ、特に抗原抗体反応等の比較的分子
量の大きなリガンドの反応を利用したセンサの場合に有
用である。[0003] The reaction between a receptor and a ligand of a biosensor includes an oxygen electrode that senses a change in oxygen concentration, an ion electrode that senses the consumption or generation of specific ions, and a quartz crystal that senses a weight change due to a reaction on the electrode. It is detected by various transducers such as a vibrator or an optical device that senses the amount of emitted light. Among them, the sensor in which the receptor immobilization film is formed on the crystal oscillator electrode can detect a very small weight change due to the binding and dissociation of the receptor and the ligand, and in particular, it has a relatively large molecular weight such as an antigen-antibody reaction. This is useful in the case of a sensor that utilizes the reaction of a ligand.
【０００４】[0004]
【従来技術の問題点】水晶振動子は高周波に対し、非常
に高感度であるため、レセプターの固定化膜が均一、安
定に形成されていない場合にはノイズの影響が大きくな
りすぎて定量が難しい。従来のように、生化学的手法に
より水晶振動子表面上にレセプターを共有結合させる場
合には均一な膜を得ることが困難であり、得られた固定
化膜も剥がれ易い。さらに生化学的方法は煩雑で時間が
かかり、自動化あるいは大量生産することが難しいとい
う問題もある。[Problems of the prior art] Since the crystal resonator is very sensitive to high frequencies, if the immobilization film of the receptor is not formed uniformly and stably, the influence of noise becomes too large and quantification becomes difficult. difficult. It is difficult to obtain a uniform film when the receptor is covalently bound to the surface of the crystal oscillator by a biochemical method as in the conventional case, and the obtained immobilization film is easily peeled off. Further, the biochemical method is complicated and time-consuming, and it is difficult to automate or mass-produce it.
【０００５】[0005]
【発明が解決しようとする課題】本発明は簡単で安定か
つ均一な固定膜を水晶振動子上に形成させる方法を提供
し、高感度のバイオセンサを簡易に提供することを目的
とする。SUMMARY OF THE INVENTION It is an object of the present invention to provide a method for forming a simple, stable and uniform fixed film on a crystal oscillator, and to easily provide a highly sensitive biosensor.
【０００６】[0006]
【課題を解決するための手段】すなわち本発明はレセプ
ター形成用イオン性物質を含有する溶液に正負電極の少
なくとも一方が水晶振動子電極である電極を浸し、両電
極間に直流電圧をかけて水晶振動子電極表面上に当該イ
オン性物質の固定化膜を形成する水晶振動子式バイオセ
ンサの製法及び当該製法で製造される水晶振動子式バイ
オセンサに関する。That is, according to the present invention, an electrode in which at least one of positive and negative electrodes is a crystal oscillator electrode is dipped in a solution containing an ionic substance for forming a receptor, and a DC voltage is applied between both electrodes to form a crystal. The present invention relates to a method of manufacturing a crystal resonator type biosensor in which an immobilization film of the ionic substance is formed on the surface of a resonator electrode, and a crystal resonator type biosensor manufactured by the manufacturing method.
【０００７】本発明に用いる水晶振動子は、特定の周波
数に対して電気的インピーダンスが低下する。この特定
の周波数は共振周波数とも呼ばれ、水晶振動子の密度や
厚さによって以下の式：The crystal oscillator used in the present invention has a low electrical impedance with respect to a specific frequency. This particular frequency is also called the resonance frequency, and depends on the density and thickness of the crystal unit, the following equation:
【０００８】[0008]
【数１】 (Equation 1)
【０００９】［△ｆ：共振周波数の変化（Ｈｚ）、△
ｍ：電極表面の重量変化（ｇ）、ｆ：基本共振周波数
（Ｈｚ）、Ａ：電極の面積（ｃｍ2）、ρ：水晶の密度
（g/cm3）、ｔ：水晶の厚さ（ｃｍ）］の関係を有す
る。ここで[Δf: Change in resonance frequency (Hz), Δ
m: weight change of electrode surface (g), f: fundamental resonance frequency (Hz), A: electrode area (cm 2 ), ρ: crystal density (g / cm 3 ), t: crystal thickness (cm) )]. here
【００１０】[0010]
【数２】 (Equation 2)
【００１１】とおくと（１）の式は △ｆ＝Ｋ・△ｍ （２） と表される。従って、電極表面にレセプターを固定化す
れば、リガンドの結合により重量が増加し、これが共振
周波数の変化となって現れる。In other words, the equation (1) is represented by Δf = K · Δm (2). Therefore, when the receptor is immobilized on the electrode surface, the weight increases due to the binding of the ligand, which appears as a change in the resonance frequency.
【００１２】本発明に用いる水晶振動子としては、共振
周波数の温度による変化が極めて少ないＡＴカットのも
のが好ましい。例えば面積０.５０ｃｍ2（直径８ｍｍ）
の水晶片に０.２０ｃｍ2（直径５ｍｍ）の電極を取り付
けた共振周波数９ＭＨｚの振動子を用いれば、１ｎｇの
重量変化で１Ｈｚの周波数変化が得られ、測定限界が１
０ｎｇオーダーの感度のセンサが得られる。The crystal oscillator used in the present invention is preferably an AT-cut one in which the resonance frequency changes little with temperature. For example, an area of 0.50 cm 2 (diameter 8 mm)
If a resonator with a resonance frequency of 9 MHz, in which a 0.20 cm 2 (diameter 5 mm) electrode is attached to the quartz piece, a frequency change of 1 Hz can be obtained with a weight change of 1 ng, and the measurement limit is 1
A sensor having a sensitivity on the order of 0 ng can be obtained.
【００１３】水溶液による水晶振動子電極の腐食を防ぐ
ために本発明の製法に用いる水晶振動子には金製の電極
と金メッキを施したリード線を取り付けるのが好まし
い。すなわち、例えば図２に示したような形状となる。In order to prevent corrosion of the crystal resonator electrode by the aqueous solution, it is preferable to attach a gold electrode and a gold-plated lead wire to the crystal resonator used in the manufacturing method of the present invention. That is, for example, the shape is as shown in FIG.
【００１４】本発明のバイオセンサの製法においては、
まず固定化膜を形成させるレセプター形成用イオン性物
質を適当な緩衝液に溶解あるいは懸濁してイオン性物質
の溶液を作成する。In the method for producing a biosensor of the present invention,
First, an ionic substance for forming a receptor for forming an immobilized film is dissolved or suspended in an appropriate buffer solution to prepare a solution of the ionic substance.
【００１５】本発明の方法に用いられるイオン性物質
は、バイオセンサにおいてレセプターの役割を果すもの
であり、検出しようとする物質と特異的に反応し、かつ
イオン性を有する物質であれば特に限定はない。例えば
酵素、抗体、抗原、各種ホルモンレセプター、レクチ
ン、アビジン、レチノール結合タンパク等が好適に用い
られる。反対にレセプターに対するリガンドである、例
えば基質、ホルモン等を本発明の製法により水晶振動子
電極表面に固定化し、酵素、あるいはホルモンレセプタ
ーの検出、定量に用いることも可能である。The ionic substance used in the method of the present invention plays the role of a receptor in the biosensor, and is not particularly limited as long as it is a substance that specifically reacts with the substance to be detected and has ionicity. There is no. For example, enzymes, antibodies, antigens, various hormone receptors, lectins, avidins, retinol binding proteins and the like are preferably used. On the contrary, it is also possible to immobilize a ligand for the receptor, for example, a substrate, a hormone, etc. on the surface of the crystal oscillator electrode by the method of the present invention and use it for the detection or quantification of the enzyme or the hormone receptor.
【００１６】緩衝液は固定化させるイオン性物質の性質
によって適宜選択する。イオン性物質の活性発現に悪影
響を及ぼさない組成、ｐＨあるいは緩衝能を有するもの
を選択しなくてはならない。例えばイオン性物質がイム
ノグロブリンＧである場合には、ｐＨ７付近のリン酸緩
衝液が特に好適に用いられる。必要に応じてイオン性物
質の活性を保持するための冷却等の処置を行う。The buffer solution is appropriately selected depending on the properties of the ionic substance to be immobilized. It is necessary to select one having a composition, pH or buffering capacity that does not adversely affect the activity expression of the ionic substance. For example, when the ionic substance is immunoglobulin G, a phosphate buffer solution having a pH of about 7 is particularly preferably used. If necessary, a treatment such as cooling is performed to maintain the activity of the ionic substance.
【００１７】次に、固定化しようとするイオン性物質の
イオン性に応じて正または負極の少なくとも一方または
両方が水晶振動子に金電極を取り付けた水晶振動子電極
である電極を、上記イオン性物質の緩衝液溶液へ浸し、
両電極間へ直流電圧を印加する。電極の一方のみが水晶
振動子電極である場合には、他方は金電極とするのが好
ましい。電極は一対のみであっても複数個つないだもの
であってもよい。Next, depending on the ionicity of the ionic substance to be immobilized, at least one or both of positive and negative electrodes is a crystal oscillator electrode in which a gold electrode is attached to the crystal oscillator, and Soak the substance in a buffer solution,
DC voltage is applied between both electrodes. When only one of the electrodes is a crystal oscillator electrode, the other is preferably a gold electrode. The electrodes may be only one pair or a plurality of electrodes.
【００１８】一対の電極間の電圧は、固定化するイオン
性物質のイオン性、緩衝液のｐＨにもよるが０.５〜３
Ｖ、より好ましくは０.５〜２Ｖとする。電圧が０.５Ｖ
以下であると時間がかかり、また電圧が３Ｖを越えると
付着物が剥がれ、ついには電極まで剥がれ落ちるため好
ましくない。電圧を印加する時間は３０分程度とするの
が好ましい。電圧の印加が終了した後、水晶振動子を引
き揚げ、洗浄して本発明のバイオセンサを得る。The voltage between the pair of electrodes is 0.5 to 3 depending on the ionicity of the ionic substance to be immobilized and the pH of the buffer solution.
V, and more preferably 0.5 to 2V. Voltage is 0.5V
If it is below, it will take time, and if the voltage exceeds 3 V, the adhered matter will be peeled off, and finally the electrode will be peeled off, which is not preferable. The time for applying the voltage is preferably about 30 minutes. After the application of the voltage is completed, the crystal oscillator is pulled up and washed to obtain the biosensor of the present invention.
【００１９】本発明のバイオセンサを用いて、例えば図
３に示した如く、発振部、周波数カウンターおよびデー
タ処理部をつなぎ、バイオセンサシステムを構成するこ
とができる。発振部としては、安定した高周波数が得ら
れる水晶発振回路が好ましく、具体的にはＮＡＮＤゲー
トと水晶発振子を用いた水晶発振回路が好適に用いられ
る。周波数カウンターとしては、微小な変化を正確に読
み取ることの可能なカウンターであることが望ましく、
具体的には１００ＭＨｚまで測定できる精度が１Ｈｚ以
上のカウンターが例示される。The biosensor of the present invention can be used to construct a biosensor system by connecting an oscillator, a frequency counter and a data processor as shown in FIG. 3, for example. As the oscillating unit, a crystal oscillating circuit capable of obtaining a stable high frequency is preferable, and specifically, a crystal oscillating circuit using a NAND gate and a crystal oscillator is preferably used. As the frequency counter, it is desirable to be a counter that can accurately read minute changes,
Specifically, a counter having an accuracy of 1 Hz or higher that can measure up to 100 MHz is exemplified.
【００２０】本発明の製法においては、電気泳動によっ
てイオン性物質を電極表面上に固定化するため、簡単で
安定かつ均一な固定膜を形成させることが可能である。
また、操作に要する時間が短く手順が単純であるため、
バイオセンサの製造を自動化し、さらには大量生産する
ことも可能である。In the production method of the present invention, since the ionic substance is immobilized on the electrode surface by electrophoresis, a simple, stable and uniform immobilization film can be formed.
Also, because the time required for operation is short and the procedure is simple,
It is possible to automate the production of biosensors and even mass-produce them.
【００２１】[0021]
【実施例１】ヒト血清アルブミン（以下ＨＳＡ）を認識
する抗体を水晶振動子電極表面に固定化したバイオセン
サを製造した。水晶振動子としては、ＡＴカット、面積
０.５０ｃｍ2(直径８ｍｍ）基本周波数９ＭＨｚのもの
を用いた。この水晶振動子に面積０.２０ｃｍ2（直径５
ｍｍ）の金電極および金メッキを施したリード線を取り
付けて水晶振動子電極とした。ＨＳＡを認識する抗体と
して、ウサギ抗ヒト血清アルブミンＩｇＧ（25mg/ml、
米国Organon Teknika社製)を用い、緩衝液としてはリン
酸緩衝生理的食塩水（Phosphate-Buffered Saline ＝Ｐ
ＢＳ）ｐＨ７.０を用いた。Example 1 A biosensor in which an antibody recognizing human serum albumin (hereinafter, HSA) was immobilized on the surface of a quartz oscillator electrode was manufactured. As the crystal unit, an AT-cut unit having an area of 0.50 cm 2 (diameter 8 mm) and a fundamental frequency of 9 MHz was used. Area of 0.20 cm 2 (diameter 5
(mm) gold electrode and a gold-plated lead wire were attached to form a crystal oscillator electrode. As an antibody that recognizes HSA, rabbit anti-human serum albumin IgG (25 mg / ml,
Phosphate-Buffered Saline = P is used as a buffer solution using Organon Teknika (US).
BS) pH 7.0 was used.
【００２２】上記の水晶振動子電極を一対用い、図１に
示す如き回路を組んだ。上記のウサギＩｇＧ５０μｌと
ＰＢＳ８mlを、直径３ｃｍ、深さ１.５ｃｍの小型シャ
ーレ内で混合し、室温に保った。ここへ水晶振動子電極
一対を浸し、両電極間に１.０Ｖの直流電圧を３０分間
印加してＩｇＧの固定化膜を水晶振動子電極表面上に形
成した。ＩｇＧは陰イオン性を有するため、陽極表面上
に固定化される。固定化終了後、蒸留水約５ｍｌで５回
洗浄し、実施例１のバイオセンサを得た。A circuit as shown in FIG. 1 was assembled by using a pair of the above crystal oscillator electrodes. 50 μl of the above rabbit IgG and 8 ml of PBS were mixed in a small petri dish having a diameter of 3 cm and a depth of 1.5 cm and kept at room temperature. A pair of crystal oscillator electrodes was immersed therein, and a DC voltage of 1.0 V was applied between both electrodes for 30 minutes to form an IgG immobilization film on the surface of the crystal oscillator electrodes. Since IgG has an anionic property, it is immobilized on the surface of the anode. After the immobilization was completed, the biosensor of Example 1 was obtained by washing 5 times with about 5 ml of distilled water.
【００２３】[0023]
【実施例２】実施例１で得られたバイオセンサを用いて
図３に示したごときバイオセンサシステムを構築した。
発振部はＮＡＮＤゲートを用いたパルス発生回路を用
い、９ＭＨｚの周波数の高周波を印加した。周波数カウ
ンターの出力は、ＧＰ−ＩＢインターフェースを介して
データ処理部に入力し、△ｆを求めた。Example 2 A biosensor system as shown in FIG. 3 was constructed using the biosensor obtained in Example 1.
A pulse generation circuit using a NAND gate was used as the oscillating unit, and a high frequency of 9 MHz was applied. The output of the frequency counter was input to the data processing unit via the GP-IB interface, and Δf was calculated.
【００２４】蒸留水中にＨＳＡの濃度が１０、５０、１
００および２００ｎｇ／ｍｌとなるように溶解させた。
各溶液に上記バイオセンサのセンサ部分を浸し、３０分
間静置したのちに周波数の変化量△ｆを測定した。結果
を図４に示す。本実施例の結果から、ＨＳＡ量と周波数
変化量には相関関係があり、抗原であるＨＳＡとバイオ
センサ上のＩｇＧとの反応により増加した重量が周波数
変化量として得られたことがわかる。The concentration of HSA in distilled water is 10, 50, 1
It was dissolved at a concentration of 00 and 200 ng / ml.
The sensor part of the biosensor was dipped in each solution and allowed to stand for 30 minutes, after which the amount of frequency change Δf was measured. FIG. 4 shows the results. From the results of this example, it can be seen that there is a correlation between the HSA amount and the frequency change amount, and the weight increased by the reaction between the antigen HSA and the IgG on the biosensor was obtained as the frequency change amount.
【００２５】[0025]
【実施例３】蒸留水中にＢＳＡの濃度が１０、５０、１
００および２００ｎｇ／ｍｌとなるように溶解させた。
各溶液に実施例１で構築したバイオセンサを浸し、３０
分間静置したのちに周波数の変化量△ｆを測定した。結
果を図５に示す。ＢＳＡ添加による周波数の変化は少な
く、実施例２の結果と併せて本発明の製法により得られ
たセンサが、ＨＳＡのみを認識していることを示す。Example 3 A BSA concentration of 10, 50, 1 in distilled water
It was dissolved at a concentration of 00 and 200 ng / ml.
Immerse the biosensor constructed in Example 1 in each solution, and
After standing for a minute, the frequency change Δf was measured. Results are shown in FIG. The frequency change due to the addition of BSA is small, and together with the result of Example 2, it is shown that the sensor obtained by the manufacturing method of the present invention recognizes only HSA.
【００２６】[0026]
【発明の効果】本発明の製法により、高感度で安定の良
いバイオセンサを簡易に得ることができた。According to the manufacturing method of the present invention, a highly sensitive and stable biosensor can be easily obtained.
【図１】 本発明の製法の一例を示す概略図である。FIG. 1 is a schematic view showing an example of a production method of the present invention.
【図２】 本発明の水晶振動子式バイオセンサの一例を
示す概略図である。FIG. 2 is a schematic diagram showing an example of a quartz oscillator type biosensor of the present invention.
【図３】 本発明のバイオセンサを用いて構築されるバ
イオセンサシステムの一例である。FIG. 3 is an example of a biosensor system constructed using the biosensor of the present invention.
【図４】 本発明の実施例２の結果を示すグラフであ
る。FIG. 4 is a graph showing the results of Example 2 of the present invention.
【図５】 本発明の実施例３の結果を示すグラフであ
る。FIG. 5 is a graph showing the results of Example 3 of the present invention.
１：電極、２：水晶振動子、３：リード線、４：直流電
圧1: Electrode, 2: Crystal oscillator, 3: Lead wire, 4: DC voltage
───────────────────────────────────────────────────── フロントページの続き (72)発明者 チャウ ビン ダック 大阪府大阪市淀川区三国本町１丁目10番 40号 和泉電気株式会社内 (72)発明者 北浦 博己 大阪府大阪市淀川区三国本町１丁目10番 40号 和泉電気株式会社内 (56)参考文献 特開 昭62−288546（ＪＰ，Ａ) ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Chow Bin Duck 1-10-40 Mikuni Honcho, Yodogawa-ku, Osaka City, Osaka Prefecture Izumi Electric Co., Ltd. 10-40, Izumi Electric Co., Ltd. (56) Reference JP-A-62-288546 (JP, A)
Claims (5)
る溶液に正負電極の少なくとも一方が水晶振動子電極で
ある電極を浸し、両電極間に直流電圧をかけて水晶振動
子電極表面上に当該イオン性物質の固定化膜を形成する
水晶振動子式バイオセンサの製法。1. An electrode in which at least one of positive and negative electrodes is a crystal oscillator electrode is immersed in a solution containing an ionic substance for forming a receptor, and a DC voltage is applied between both electrodes to apply the ion to the surface of the crystal oscillator electrode. A method of manufacturing a crystal oscillator-type biosensor that forms an immobilization film of a volatile substance.
１記載の製法。2. The method according to claim 1, wherein the ionic substance is a protein.
の製法。3. The method according to claim 1, wherein the ionic substance is an antibody.
ミンＩｇＧである請求項３記載の製法。4. The method according to claim 3, wherein the ionic substance is rabbit anti-human serum albumin IgG.
る溶液に正負電極の少なくとも一方が水晶振動子電極で
ある電極を浸し、両電極間に直流電圧をかけて水晶振動
子電極表面上に当該イオン性物質の固定化膜を形成して
なる、水晶振動子式バイオセンサ。5. An electrode in which at least one of positive and negative electrodes is a crystal oscillator electrode is dipped in a solution containing an ionic substance for forming a receptor, and a DC voltage is applied between both electrodes to deposit the ion on the crystal oscillator electrode surface. A crystal oscillator-type biosensor formed by forming an immobilization film of a volatile substance.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5158619A JP2690849B2 (en) | 1993-06-29 | 1993-06-29 | Manufacturing method of quartz oscillator type biosensor and quartz oscillator type biosensor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5158619A JP2690849B2 (en) | 1993-06-29 | 1993-06-29 | Manufacturing method of quartz oscillator type biosensor and quartz oscillator type biosensor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0712694A JPH0712694A (en) | 1995-01-17 |
| JP2690849B2 true JP2690849B2 (en) | 1997-12-17 |
Family
ID=15675675
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5158619A Expired - Lifetime JP2690849B2 (en) | 1993-06-29 | 1993-06-29 | Manufacturing method of quartz oscillator type biosensor and quartz oscillator type biosensor |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2690849B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001098919A (en) | 1999-09-29 | 2001-04-10 | Nitto Kohki Co Ltd | Pipe joint for oil replacement |
| JP6004470B2 (en) * | 2012-09-03 | 2016-10-05 | 国立大学法人大阪大学 | Sample immobilization method |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62288546A (en) * | 1986-06-06 | 1987-12-15 | Seiko Instr & Electronics Ltd | Crystal oscillator biosensor and analysis of living body-related substances using same |
-
1993
- 1993-06-29 JP JP5158619A patent/JP2690849B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0712694A (en) | 1995-01-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4735906A (en) | Sensor having piezoelectric crystal for microgravimetric immunoassays | |
| US4789804A (en) | Analytical device and method utilizing a piezoelectric crystal biosensor | |
| US4072576A (en) | Method for studying enzymatic and other biochemical reactions | |
| JPH10504100A (en) | Sensor and method for detecting a predetermined chemical sample in a solution | |
| Cavalcanti et al. | A label-free immunosensor based on recordable compact disk chip for early diagnostic of the dengue virus infection | |
| US20090078023A1 (en) | Detection And Quantification Of Biomarkers Via A Piezoelectric Cantilever Sensor | |
| Luong et al. | Analytical applications of piezoelectric crystal biosensors | |
| JPH03503567A (en) | Enzymatically amplified piezospecific binding assay | |
| Bizet et al. | Immunodetection by quartz crystal microbalance: A new approach for direct detection of rabbit IgG and peroxidase | |
| Suri et al. | Development of piezoelectric crystal based microgravimetric immunoassay for determination of insulin concentration | |
| Liu et al. | Comparative analysis of static and non-static assays for biochemical sensing using on-chip integrated field effect transistors and solidly mounted resonators | |
| Wong-ek et al. | Cardiac troponin T detection using polymers coated quartz crystal microbalance as a cost-effective immunosensor | |
| JP2690849B2 (en) | Manufacturing method of quartz oscillator type biosensor and quartz oscillator type biosensor | |
| US20110236877A1 (en) | Biosensor and method using the same to perform a biotest | |
| JP2647790B2 (en) | Manufacturing method of quartz oscillator type biosensor and quartz oscillator type biosensor | |
| Hu et al. | Piezoelectric immunosensor for detection of complement C6 | |
| Shao et al. | Determination of bovine haemoglobin by a piezoelectric crystal immunosensor | |
| JP4127192B2 (en) | Receptor fixing method on crystal oscillator electrode surface and manufacturing method of receptor fixed crystal oscillator | |
| CN111811983A (en) | Biological sensing detection by quartz crystal shearing vibration amplitude modulation frequency modulation throwing-off method | |
| JPH07260782A (en) | Measurement of human serum albumin | |
| JPH07225233A (en) | Immunoassay using crystal vibrator | |
| Chunta et al. | A piezoelectric-based immunosensor for high density lipoprotein particle measurement | |
| RU2032908C1 (en) | Device for determination of biologically active compounds in biological fluids and process of manufacture of sensitive element | |
| KR100921237B1 (en) | Quartz crystal microbalance immunosensor Apparatus for C-reactive protein detection and High-sensitivity detection method for C-reactive protein using quartz crystal microbalance immunosensor | |
| SHEN et al. | The Fabrication of Electrochemical Impedance Immunosensor Based on Aldehyde-containing Self-assembled Monolayers for Hepatitis B Surface Antigen Detection |