JP2005351798A - Measuring method by surface elastic wave element - Google Patents

Measuring method by surface elastic wave element Download PDF

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JP2005351798A
JP2005351798A JP2004173925A JP2004173925A JP2005351798A JP 2005351798 A JP2005351798 A JP 2005351798A JP 2004173925 A JP2004173925 A JP 2004173925A JP 2004173925 A JP2004173925 A JP 2004173925A JP 2005351798 A JP2005351798 A JP 2005351798A
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load
surface acoustic
acoustic wave
frequency
viscous
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JP4504106B2 (en
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Atsushi Ito
敦 伊藤
Motoko Ichihashi
素子 市橋
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Ulvac Inc
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Priority to EP05012537A priority patent/EP1605257B1/en
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00Indexing codes associated with group G01N29/00
    • G01N2291/02Indexing codes associated with the analysed material
    • G01N2291/025Change of phase or condition
    • G01N2291/0256Adsorption, desorption, surface mass change, e.g. on biosensors
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00Indexing codes associated with group G01N29/00
    • G01N2291/02Indexing codes associated with the analysed material
    • G01N2291/028Material parameters
    • G01N2291/02809Concentration of a compound, e.g. measured by a surface mass change
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00Indexing codes associated with group G01N29/00
    • G01N2291/02Indexing codes associated with the analysed material
    • G01N2291/028Material parameters
    • G01N2291/02818Density, viscosity
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00Indexing codes associated with group G01N29/00
    • G01N2291/04Wave modes and trajectories
    • G01N2291/042Wave modes
    • G01N2291/0421Longitudinal waves
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00Indexing codes associated with group G01N29/00
    • G01N2291/04Wave modes and trajectories
    • G01N2291/042Wave modes
    • G01N2291/0422Shear waves, transverse waves, horizontally polarised waves

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Abstract

<P>PROBLEM TO BE SOLVED: To provide a measuring method capable of measuring accurately a mass load without being influenced by a viscous load even when a detection object having a different viscosity is added to buffer liquid on a surface elastic wave element, and shortening a time required for measurement by shortening a time until the liquid temperature of the buffer liquid is stabilized. <P>SOLUTION: In this method, a surface elastic wave is excited on a substrate, and a physical property of the detection object placed on a detection part on the substrate is measured by a characteristic change of the surface elastic wave. The method is characterized by evaluating the viscous load of the detection object on the basis of at least two different frequency fluctuations in frequencies of the surface elastic wave excited on the substrate, and measuring the mass load of the detection object separately from the viscous load. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

本発明は、基板上に表面弾性波を励起して、前記基板上の検出部に載置された被検出物の物性を前記表面弾性波の特性の変化により測定する方法に関する。   The present invention relates to a method for exciting a surface acoustic wave on a substrate and measuring a physical property of a detection object placed on a detection unit on the substrate by a change in characteristics of the surface acoustic wave.

DNA・タンパク質など生体物質の相互作用を測定する方法として、また、抗原抗体反応を応用した測定に表面弾性波素子が使用されている(例えば、特許文献1及び非特許文献1)。
この表面弾性波素子を使用した測定は、前記素子に励起された弾性波の中心周波数f0(測定系のコンダクタンスが最大となる点又は位相が0となる点)を連続して測定するか、ネットワークアナライザ等を用いて中心周波数f0を連続で測定し、この中心周波数f0の変動に基づいて、表面弾性波素子の質量負荷を測定するようにしている。
ところが、表面弾性波素子の検出部に被検出物を載せて測定をする場合に、中心周波数f0は、質量負荷以外に、粘性の変化による粘性負荷が生じ、これらの負荷を明確に区別して測定することができなかった。このような測定系で、DNA・タンパク質など生体物質の相互作用を調べようとしたり、周波数変動によって抗原抗体反応を調べようとする場合は、しばしば測定系に注入する被検出物と、使用されているバッファー液(生化学用緩衝液であり、主な含有物はNaClやKCl等である)の粘性が異なるために、測定された周波数変動が、DNA・タンパク質などの結合又は抗原抗体の結合による質量負荷によるものか、粘性負荷によるものか区別することができずに、正確な測定をすることができなかった。また、室温の変化や被検出物注入による液温変化に伴う液体の粘性変化によっても、やはり正確な測定ができないことがあった。
A surface acoustic wave device is used as a method for measuring the interaction of biological substances such as DNA and protein, and for measurement using an antigen-antibody reaction (for example, Patent Document 1 and Non-Patent Document 1).
The measurement using this surface acoustic wave element is performed by continuously measuring the center frequency f 0 (the point where the conductance of the measurement system becomes maximum or the phase becomes 0) of the elastic wave excited by the element, The center frequency f 0 is continuously measured using a network analyzer or the like, and the mass load of the surface acoustic wave element is measured based on the fluctuation of the center frequency f 0 .
However, when the object to be detected is mounted on the detection unit of the surface acoustic wave device and measured, the center frequency f 0 has a viscous load due to a change in viscosity in addition to the mass load, and these loads are clearly distinguished. It could not be measured. In such a measurement system, when trying to investigate the interaction of biological substances such as DNA and protein, or to examine the antigen-antibody reaction by frequency fluctuation, it is often used with the target to be injected into the measurement system. The measured frequency fluctuation is due to the binding of DNA / protein or the binding of antigen / antibody because the viscosity of the buffer solution (the buffer for biochemistry, the main content is NaCl, KCl, etc.) is different. It was impossible to distinguish between mass load and viscous load, and accurate measurements could not be made. In addition, accurate measurement may not be possible due to a change in the viscosity of the liquid accompanying a change in the room temperature or a change in the liquid temperature due to the injection of the detection object.

特開平06−133759号公報Japanese Patent Laid-Open No. 06-133759 "A Love wave sensor for (bio)chemical sensing in liquids" Sensors and Actuators A,43(1994)38-43"A Love wave sensor for (bio) chemical sensing in liquids" Sensors and Actuators A, 43 (1994) 38-43

そこで、本発明は、表面弾性波素子上のバッファー液に対して、粘性が異なる被検出物を加えた場合であっても、その粘性負荷の影響を受けず、正確に質量負荷を測定すること、また、バッファー液の液温が安定するまでの時間を短縮して測定までにかかる時間を短縮することができる測定方法を提供することを目的とする。   Therefore, the present invention can accurately measure the mass load without being affected by the viscous load even when a detection object having a different viscosity is added to the buffer liquid on the surface acoustic wave device. It is another object of the present invention to provide a measurement method that can shorten the time required for the measurement by shortening the time until the liquid temperature of the buffer solution is stabilized.

上記課題を解決するために、本発明者等は鋭意検討の結果、基板上に表面弾性波を励起して、励起される表面弾性波の周波数のうち、少なくとも2つの異なる周波数変動に基づいて前記被検出物の粘性負荷を評価して、表面弾性波素子にかかる負荷から前記粘性負荷を取り除くことにより、前記被検出物の質量負荷を測定するという解決手段を見出した。
即ち、本発明の測定方法は、請求項1に記載の通り、基板上に表面弾性波を励起して、前記基板上の検出部に載置された被検出物の物性を前記表面弾性波の特性の変化により測定する方法であって、前記基板上に励起される表面弾性波の周波数のうち、少なくとも2つの異なる周波数変動に基づいて前記被検出物の粘性負荷を評価し、前記被検出物の質量負荷を前記粘性負荷から分離して測定することを特徴とする。
また、更なる有効な解決手段は、次に説明する原理に基づいてなされたものである。
In order to solve the above-mentioned problem, the present inventors, as a result of intensive studies, excited surface acoustic waves on the substrate, and based on at least two different frequency fluctuations among the excited surface acoustic wave frequencies. The solution of measuring the mass load of the detected object by evaluating the viscous load of the detected object and removing the viscous load from the load applied to the surface acoustic wave device was found.
That is, according to the measurement method of the present invention, as described in claim 1, the surface acoustic wave is excited on the substrate, and the physical property of the detection object placed on the detection unit on the substrate is changed to the surface acoustic wave. A method of measuring by a change in characteristics, wherein a viscous load of the detected object is evaluated based on at least two different frequency fluctuations among frequencies of surface acoustic waves excited on the substrate, and the detected object The mass load is measured separately from the viscous load.
Further, a further effective solution is made based on the principle described below.

1)まず、表面弾性波素子のSH波の粘性負荷と質量負荷の関係について説明する。
SH波の伝播定数の摂動の式α+jβと表面インピーダンスZとの関係は、下記数1の通りである。式中、αは減衰定数、βは実伝播定数、Sは素子の感度である。

Figure 2005351798
1) First, the relationship between the SH wave viscous load and the mass load of the surface acoustic wave device will be described.
The relationship between the perturbation expression α + jβ of the propagation constant of the SH wave and the surface impedance Z is as shown in the following equation (1). In the equation, α is an attenuation constant, β is an actual propagation constant, and S is a sensitivity of the element.
Figure 2005351798

SH波でのニュートン液体での粘性負荷による表面インピーダンスZは、下記数2の通りである。式中、ωは角周波数、ηは液体の粘性、ρは液体の密度である。

Figure 2005351798
The surface impedance Z due to the viscous load on the Newtonian liquid in the SH wave is as follows. Where ω is the angular frequency, η is the viscosity of the liquid, and ρ is the density of the liquid.
Figure 2005351798

数1と数2の関係から、次の数3に示す関係を導出することができる。

Figure 2005351798
From the relationship of Equation 1 and Equation 2, the relationship shown in Equation 3 below can be derived.
Figure 2005351798

また、質量負荷による表面インピーダンスZは、下記数4で示す通りである。式中、mは付加した質量、Aは検出部の面積を示す。

Figure 2005351798
Further, the surface impedance Z due to the mass load is as shown in the following formula 4. In the formula, m represents the added mass, and A represents the area of the detection unit.
Figure 2005351798

上記数1、数3及び数4から、次の数5に示す関係を導出することができる。

Figure 2005351798
From the above equations 1, 3, and 4, the relationship shown in the following equation 5 can be derived.
Figure 2005351798

2)次に、表面弾性波素子の等価回路について説明する。
2ポート型の表面弾性波素子の等価回路は、図1で表される。
これに粘性負荷と質量負荷が加わったときの等価回路は、図2で表される。
ここで、表面インピーダンスZと等価回路のパラメータとの対応は、上記1)から粘性負荷の場合には、下記数6の通りとなる。

Figure 2005351798
2) Next, an equivalent circuit of the surface acoustic wave device will be described.
An equivalent circuit of the 2-port surface acoustic wave device is shown in FIG.
An equivalent circuit when a viscous load and a mass load are added to this is shown in FIG.
Here, the correspondence between the surface impedance Z and the parameters of the equivalent circuit is expressed by the following equation 6 in the case of a viscous load from the above 1).
Figure 2005351798

尚、数6中、S'は表面インピーダンスZとモーショナルレジスタンスR2、モーショナルインダクタンスL2,L3を関係付ける値であり数7に示す通りである。また、νgは波の群速度、νは波の音速を示すものである。

Figure 2005351798
In Equation 6, S ′ is a value relating the surface impedance Z, the motional resistance R 2 , and the motional inductances L 2 and L 3, as shown in Equation 7. Further, ν g represents a wave group velocity, and ν represents a wave sound velocity.
Figure 2005351798

上記数6から、次の数8及び数9で示す関係を導出することができる。

Figure 2005351798
Figure 2005351798
From the above equation (6), the relationship represented by the following equations (8) and (9) can be derived.
Figure 2005351798
Figure 2005351798

一方、質量負荷についても、次の数10で表すことができる。

Figure 2005351798
On the other hand, the mass load can also be expressed by the following formula 10.
Figure 2005351798

従って、数10に数4を代入して、次の数11で示す関係を導出することができる。

Figure 2005351798
Therefore, by substituting Equation 4 into Equation 10, the relationship represented by the following Equation 11 can be derived.
Figure 2005351798

3)次に、表面弾性波素子の中心周波数f0について説明する。
図1の粘性負荷と質量負荷のない等価回路の伝達特性H(ω)は、ネットワークアナライザなどを使用してインピーダンスが50Ω(R50)の測定系(図3)で測定した場合に、次の数12で示す関係となる。

Figure 2005351798
3) Next, the center frequency f 0 of the surface acoustic wave device will be described.
The transfer characteristic H (ω) of the equivalent circuit without viscous load and mass load in FIG. 1 is as follows when measured with a measurement system (FIG. 3) having an impedance of 50Ω (R 50 ) using a network analyzer or the like. This is the relationship expressed by Equation 12.
Figure 2005351798

この実成分(コンダクタンスG)は、次の数13に示す通りとなる。

Figure 2005351798
This real component (conductance G) is as shown in the following equation (13).
Figure 2005351798

上記数13において、コンダクタンスGは、ωL1=1/ωC1のとき最大値をとる。このときの中心周波数f0は、次の数14の通りとなる。

Figure 2005351798
In Equation 13, the conductance G takes the maximum value when ωL 1 = 1 / ωC 1 . The center frequency f 0 at this time is as shown in the following equation ( 14).
Figure 2005351798

また、コンダクタンスGの最大値GMAXは、次の数15の通りとなる。

Figure 2005351798
Further, the maximum value G MAX of the conductance G is as shown in the following Expression 15.
Figure 2005351798

数15における最終式は、R1に対してR50は極めて小さいため無視したものである。これは、例えば、125MHzのラブ波デバイスでは、純水を検出部に載せたときに、R1は約16kΩと極めて大きい値をとることからわかる。 The final equation in Equation 15 is neglected because R 50 is very small relative to R 1 . For example, in a 125 MHz Love wave device, R 1 takes a very large value of about 16 kΩ when pure water is placed on the detection unit.

次に、粘性負荷と質量負荷があるときの中心周波数の変化Δf0は、L1はL1+L2+L3となり、C1は変化しないため、次の数16が得られる。

Figure 2005351798
Next, as for the change Δf 0 in the center frequency when there is a viscous load and a mass load, since L 1 is L 1 + L 2 + L 3 and C 1 does not change, the following equation 16 is obtained.
Figure 2005351798

従って、Δf0とf0との比は、次の数17の通りになる。

Figure 2005351798
Therefore, the ratio between Δf 0 and f 0 is expressed by the following equation ( 17).
Figure 2005351798

数17の第1項は粘性負荷、第2項は質量負荷を表す。粘性負荷では、2)よりL2=R2/ωなる関係があるため、数17の第1項は、下記数18に示す通りになる。

Figure 2005351798
The first term of Equation 17 represents a viscous load, and the second term represents a mass load. In the viscous load, since there is a relationship of L 2 = R 2 / ω from 2), the first term of Expression 17 is as shown in Expression 18 below.
Figure 2005351798

従って、粘性負荷Δf0は、次の数19に示す通りである。

Figure 2005351798
Therefore, the viscous load Δf 0 is as shown in the following equation ( 19).
Figure 2005351798

これにより、中心周波数の変化Δf0は、次の数20に示すようになる。

Figure 2005351798
As a result, the change Δf 0 in the center frequency is as shown in the following equation ( 20).
Figure 2005351798

4)最後に、粘性負荷と質量負荷の分離について説明する。
粘性負荷と質量負荷が生じている場合にコンダクタンスGの最大値GMAXの半分の値を与えるω1とω2を次の数21に示すようにして求める。尚、次式中、R1'=R1+R2とし、L1'=L1+L2+L3とする。

Figure 2005351798
4) Finally, separation of viscous load and mass load will be described.
Ω 1 and ω 2 giving half the maximum value G MAX of conductance G when viscous load and mass load are generated are obtained as shown in the following equation (21). In the following formula, R 1 ′ = R 1 + R 2 and L 1 ′ = L 1 + L 2 + L 3 .
Figure 2005351798

上記数21において、R50は、R1'に比べて非常に小さいため無視できるので、数21は、次の数22のように変形することができる。

Figure 2005351798
In the above equation 21, R 50 is very small compared to R 1 ′ and can be ignored. Therefore, the equation 21 can be transformed into the following equation 22.
Figure 2005351798

上記数22を満足するωは、ω1(数23)とω2(数24)である(ω1<ω2)。

Figure 2005351798
Figure 2005351798
Ω satisfying the above equation 22 is ω 1 (Equation 23) and ω 2 (Equation 24) (ω 12 ).
Figure 2005351798
Figure 2005351798

上記数23及び数24をf1,f2(f1<f2)で表すと次の数25及び数26に示す通りとなる。

Figure 2005351798
Figure 2005351798
When Expression 23 and Expression 24 are expressed as f 1 and f 2 (f 1 <f 2 ), the following Expression 25 and Expression 26 are obtained.
Figure 2005351798
Figure 2005351798

ここで、SH波の表面弾性波素子の例として、125MHzのラブ波デバイスの純水を載せたときの等価回路パラメータの実測値は、C1'=5.4×10-7F,L1'=3.0×10-2H,R1'=1.6×104Ω程度であるので、数25及び数26のR1'21'2の項は、4L1'C1に比べて十分小さいので、次の数27及び数28に示すように変形することができる。

Figure 2005351798
Figure 2005351798
Here, as an example of the surface acoustic wave element of SH wave, the measured value of the equivalent circuit parameter when pure water of a 125 MHz Love wave device is placed is C 1 ′ = 5.4 × 10 −7 F, L 1 Since '= 3.0 × 10 −2 H, R 1 ′ = 1.6 × 10 4 Ω, the terms of R 12 C 12 in Equations 25 and 26 are 4L 1 ′ C 1 Therefore, it can be modified as shown in the following equations 27 and 28.
Figure 2005351798
Figure 2005351798

上記数27及び数28の第2項は、粘性負荷と質量負荷のある場合の中心周波数f0'に等しいので、f1及びf2は、下記数29及び数30のようになる。

Figure 2005351798
Figure 2005351798
Since the second terms of the above equations 27 and 28 are equal to the center frequency f 0 ′ when there is a viscous load and a mass load, f 1 and f 2 are expressed by the following equations 29 and 30.
Figure 2005351798
Figure 2005351798

ここで、L1'=L1+L2+L3、R1’=R2+R3を代入し、粘性負荷と質量負荷によるf1,f2の変化Δf1とΔf2を求めると、次の数31及び数32に示すようになる。式中、Δf0=f'0−f0とし、L2とL3はL1に比べて非常に小さいものとする。

Figure 2005351798
Figure 2005351798
Here, substituting L 1 ′ = L 1 + L 2 + L 3 and R 1 ′ = R 2 + R 3 to obtain changes Δf 1 and Δf 2 of f 1 and f 2 due to viscous load and mass load, As shown in Equation 31 and Equation 32. In the equation, Δf 0 = f ′ 0 −f 0, and L 2 and L 3 are very small compared to L 1 .
Figure 2005351798
Figure 2005351798

ここで、

Figure 2005351798
であるので、数31と数32は、次に示す数34と数35のようになる。
Figure 2005351798
Figure 2005351798
here,
Figure 2005351798
Therefore, Expressions 31 and 32 become Expressions 34 and 35 shown below.
Figure 2005351798
Figure 2005351798

上記数34と数35において、次の数36で示す項は、1.6×10-4と十分小さい。

Figure 2005351798
In the above equations 34 and 35, the term represented by the following equation 36 is sufficiently small as 1.6 × 10 −4 .
Figure 2005351798

従って、数34と数35は、次に示す数37と数38に変形することができる。

Figure 2005351798
Figure 2005351798
Therefore, the equations 34 and 35 can be transformed into the following equations 37 and 38.
Figure 2005351798
Figure 2005351798

ここで、3)で求めた粘性負荷と質量負荷のある場合のΔf0を代入すると、数37と数38は、次の数39と数40に示す通りになる。

Figure 2005351798
Figure 2005351798
Here, when Δf 0 in the case of the viscous load and the mass load obtained in 3) is substituted, Expressions 37 and 38 become as shown in the following Expressions 39 and 40.
Figure 2005351798
Figure 2005351798

従って、Δf2は質量負荷のみとなることがわかる。
更に、次の数41により、

Figure 2005351798
Therefore, it can be seen that Δf 2 is only the mass load.
Furthermore, by the following equation 41,
Figure 2005351798

下記数42は、粘性負荷のみとなることがわかる。

Figure 2005351798
It can be seen that the following formula 42 is only a viscous load.
Figure 2005351798

以上より、表面弾性波素子の中心周波数f0ではなく、コンダクタンスGの最大値の1/2となる2つの周波数f1,f2を用いることで中心周波数f0のみの測定では区別のつかなかった質量負荷と粘性負荷の分離測定が可能となる。 From the above, it is indistinguishable to measure only the center frequency f 0 by using the two frequencies f 1 and f 2 which are ½ of the maximum value of the conductance G, instead of the center frequency f 0 of the surface acoustic wave device. Separate measurement of mass load and viscous load.

従って、更なる有利な解決手段は、請求項2に記載の通り、請求項1に記載の測定方法において、前記2つの異なる周波数は、前記表面弾性波素子の中心周波数f0を与える測定系のコンダクタンスの半分のコンダクタンスを与える第1及び第2の周波数f1,f2(f1<f2)であることを特徴とする。 Accordingly, a further advantageous solution is as described in claim 2, wherein in the measurement method according to claim 1, the two different frequencies are of a measurement system that gives a center frequency f 0 of the surface acoustic wave device. The first and second frequencies f 1 and f 2 (f 1 <f 2 ) giving a conductance half the conductance are characterized.

また、これら2つの周波数f1及びf2は、中心周波数f0の表面弾性波に対して位相がそれぞれ、−45°、+45°ずれた表面弾性波の周波数で代用することもできる。
従って、請求項3に記載の本発明は、請求項1に記載の測定方法において、前記2つの異なる周波数は、前記基板上に励起される中心周波数f0に対して位相を、±45°ずらした第1及び第2の周波数f1,f2(f1<f2)であることを特徴とする。
また、請求項4に記載の本発明は、請求項2又は3に記載の測定方法において、前記第1及び第2の周波数f1,f2の差の変動に基づいて前記粘性負荷を評価することを特徴とする。
また、請求項5に記載の本発明は、請求項2乃至4のいずれかに記載の測定方法において、前記質量負荷は、前記中心周波数f0に近く、且つ、前記中心周波数f0よりも大きな周波数である第2の周波数f2の変動に基づいて測定することを特徴とする。
また、請求項6に記載の本発明は、請求項1乃至5のいずれかに記載の測定方法において、前記表面弾性波素子は、ラブ波デバイス、SH−SAWデバイス、STWデバイス又はSH−APMデバイスであることを特徴とする。
Further, these two frequencies f 1 and f 2 can be substituted by the surface acoustic wave frequencies whose phases are shifted by −45 ° and + 45 ° with respect to the surface acoustic wave of the center frequency f 0 , respectively.
Therefore, according to a third aspect of the present invention, in the measurement method according to the first aspect, the two different frequencies are shifted in phase by ± 45 ° with respect to a center frequency f 0 excited on the substrate. The first and second frequencies are f 1 and f 2 (f 1 <f 2 ).
According to a fourth aspect of the present invention, in the measurement method according to the second or third aspect, the viscous load is evaluated based on a variation in the difference between the first and second frequencies f 1 and f 2. It is characterized by that.
Big Further, the present invention according to claim 5, in the measurement method according to any one of claims 2 to 4, the mass load is close to the center frequency f 0, and than the center frequency f 0 The measurement is based on the fluctuation of the second frequency f 2 which is the frequency.
Further, the present invention according to claim 6 is the measurement method according to any one of claims 1 to 5, wherein the surface acoustic wave element is a Love wave device, an SH-SAW device, an STW device, or an SH-APM device. It is characterized by being.

本発明の測定方法によれば、測定中に被検出物の添加により、粘性負荷が生じた場合であっても、質量負荷と粘性負荷とを独立して測定することができる。従って、この粘性負荷を評価することで、粘性の高い血液の検査や食品に含まれる菌の検査において極めて正確に質量負荷を測定することが可能となる。また、バッファー液等に対して添加する被検出物の温度が異なっているために粘性が変化したとしても同様である。バッファー液の入ったセルを装置にセットした後、温度が一定になるまでの時間を短縮することができる。   According to the measurement method of the present invention, the mass load and the viscous load can be measured independently even when a viscous load is generated due to the addition of the detection object during the measurement. Therefore, by evaluating this viscous load, it is possible to measure the mass load very accurately in the inspection of highly viscous blood and the inspection of bacteria contained in food. The same applies to the case where the viscosity changes because the temperature of the detection object added to the buffer solution or the like is different. After the cell containing the buffer solution is set in the apparatus, the time until the temperature becomes constant can be shortened.

上記の通り、本発明では、基板上に表面弾性波を励起して、前記基板上の検出部に載置された被検出物の物性を前記表面弾性波の特性の変化により測定するものである。以下に本発明の測定方法について具体的に説明する。
本発明では、例えば、櫛形電極を組み合わせたIDTにより圧電基板に表面弾性波を生じさせ、前記表面弾性波の中心周波数を含む所定の周波数範囲で測定することにより質量負荷を測定するものである。所定の周波数範囲については、前記弾性波速度の変動を測定できる範囲であれば特に制限はないが、ノイズ等の影響を考慮すると、表面弾性波素子の中心周波数f0近傍の周波数を範囲とすることが好ましい。
前記周波数範囲において、少なくとも2つの異なる周波数を決定する。ここでは、説明のために2つの周波数faとfbを使用して説明する。これらの周波数変動は、同じ粘性負荷に対して異なる変動を示すので、各周波数fa,fbの粘性負荷の比率を決定することができる。この粘性負荷の比率に基づいて、測定中に表面弾性波素子に対する粘性負荷を決定することができる。その結果として、例えば、faの変動を測定することで、表面弾性波素子にかかる全体負荷を測定しておいて、faとfbとの関係から粘性負荷を決定し、前記全体負荷から粘性負荷を引くことで、質量負荷と粘性負荷とを分離して測定することが可能となる。尚、上記粘性負荷の評価のための演算等の処理は、上記測定後又は測定中のどちらでも行うことができる。
As described above, in the present invention, the surface acoustic wave is excited on the substrate, and the physical property of the detection object placed on the detection unit on the substrate is measured by the change in the characteristic of the surface acoustic wave. . The measurement method of the present invention will be specifically described below.
In the present invention, for example, a surface acoustic wave is generated on a piezoelectric substrate by IDT combined with a comb-shaped electrode, and the mass load is measured by measuring in a predetermined frequency range including the center frequency of the surface acoustic wave. The predetermined frequency range is not particularly limited as long as the variation of the elastic wave velocity can be measured, but considering the influence of noise and the like, the frequency near the center frequency f 0 of the surface acoustic wave element is set as the range. It is preferable.
At least two different frequencies are determined in the frequency range. Here, the description uses the two frequencies f a and f b for explanation. Since these frequency fluctuations show different fluctuations with respect to the same viscous load, the ratio of the viscous loads at the respective frequencies f a and f b can be determined. Based on the ratio of the viscous load, the viscous load on the surface acoustic wave element can be determined during the measurement. As a result, for example, by measuring the variation of f a, in advance by measuring the total load on the surface acoustic wave device, to determine the viscous load from the relationship between f a and f b, from the total load By pulling the viscous load, the mass load and the viscous load can be measured separately. Note that processing such as calculation for evaluation of the viscous load can be performed either after the measurement or during the measurement.

上記測定に関して、表面弾性波素子の中心周波数f0と以下に説明する特定の周波数f1,f2を用いて測定することにより本発明ではより精度の高い測定できるようにしている。次に、このf1及びf2の取得方法について説明する。
まず、基板上に表面弾性波を励起して、中心周波数f0を含む所定周波数帯で、図4に示されるように、周波数とコンダクタンスGの関係を測定する。そして、同図から、コンダクタンスGの値の1/2の値を与える周波数、即ち、周波数f1及びf2(f1<f2)を求める。尚、中心周波数f0では、コンダクタンスGは極値をとる。そして、コンダクタンスGの極値は最大値となるため、測定された最大コンダクタンスGMAXを与える周波数が中心周波数f0であることが容易にわかる。また、本発明において中心周波数f0は、IDTピッチによって決定される表面弾性波の波長をλ、表面弾性波速度をvとした場合に、f0=v/λで表される周波数を中心周波数f0としている。
With respect to the above measurement, the present invention enables measurement with higher accuracy by measuring using the center frequency f 0 of the surface acoustic wave device and specific frequencies f 1 and f 2 described below. Next, a method for obtaining f 1 and f 2 will be described.
First, a surface acoustic wave is excited on the substrate, and the relationship between the frequency and the conductance G is measured in a predetermined frequency band including the center frequency f 0 as shown in FIG. Then, determined from the figure, the frequencies giving the value half of the value of the conductance G, i.e., the frequency f 1 and f 2 a (f 1 <f 2). At the center frequency f 0 , the conductance G takes an extreme value. Since the extreme value of the conductance G is the maximum value, it can be easily seen that the frequency giving the measured maximum conductance G MAX is the center frequency f 0 . In the present invention, the center frequency f 0 is the frequency represented by f 0 = v / λ, where λ is the surface acoustic wave wavelength determined by the IDT pitch, and v is the surface acoustic wave velocity. It is set to f 0.

次に表面弾性波素子の検出部に、必要に応じて、バッファー液を滴下しておき、そこに、被検出物である特性成分を含む試料溶液を注入すると、周波数f0,f1,f2に変動が生じる。測定の開始から終了に至るまで、これらの周波数f1及びf2を所定の時間間隔で記録し、f2の変動量を質量負荷に基づく変化として、f2−f1の変動量を粘性負荷に基づく変化とすれば、これらの値に基づいて、質量負荷と粘性負荷とを分離して測定することができる。そして、これらの質量負荷、更には、粘性負荷も含めてバッファー液中の被検出物の成分の濃度がわかることになる。 Next, when a buffer solution is dropped onto the detection unit of the surface acoustic wave element as necessary, and a sample solution containing a characteristic component as a detection object is injected into the buffer solution, the frequencies f 0 , f 1 , f Variation occurs in 2 . From the start to the end of measurement, these frequencies f 1 and f 2 are recorded at predetermined time intervals, and the fluctuation amount of f 2 is defined as a change based on the mass load, and the fluctuation amount of f 2 −f 1 is the viscous load. Based on these values, the mass load and the viscous load can be separated and measured based on these values. Then, the concentration of the component of the detected substance in the buffer solution including the mass load and the viscous load can be known.

尚、上記説明では、f1及びf2を、所定の周波数帯をスキャンすることにより得たものであるが、f1及びf2は、次に示すもので代用することもできる。即ち、本発明の測定方法は、これらf1及びf2の周波数を有する表面弾性波のみを表面弾性波素子上に励起することによっても行うことができる。
1)中心周波数f0に対して、位相が、+45°,−45°となる2つの周波数をf1及びf2とする。
2)表面弾性波素子に外部から信号を加えたときの挿入損失が、最大値から所定値分下がった値の2つの周波数f1及びf2とする。尚、前記所定値は、特に制限はないが、例えば、3dB等とすることができる。
3)サセプタンスBを、角周波数ωで微分したδB/δωが0となる2つの周波数をf1及びf2とする。
4)スミスチャートのアドミタンス平面上において測定点G+jBが描く円の周上での1対の象限周波数をf1及びf2とする。
In the above description, f 1 and f 2 are obtained by scanning a predetermined frequency band, but f 1 and f 2 can be substituted by the following. That is, the measurement method of the present invention can also be performed by exciting only surface acoustic waves having the frequencies of f 1 and f 2 on the surface acoustic wave device.
1) Two frequencies having phases of + 45 ° and −45 ° with respect to the center frequency f 0 are defined as f 1 and f 2 .
2) The insertion loss when a signal is applied to the surface acoustic wave element from the outside is set to two frequencies f 1 and f 2 that are values that are lower than the maximum value by a predetermined value. The predetermined value is not particularly limited, but may be 3 dB, for example.
3) Let f 1 and f 2 be two frequencies at which δB / δω obtained by differentiating the susceptance B with the angular frequency ω is 0.
4) A pair of quadrant frequencies on the circumference of a circle drawn by the measurement point G + jB on the admittance plane of the Smith chart is defined as f 1 and f 2 .

次に、本発明において表面弾性波素子として使用されるデバイスについて説明する。
まず、ラブ波デバイスは、STカット水晶等からなる基板表面にIDTを設け、前記基板表面に前記基板の横波の伝播速度より遅い速度を有する材質(SiO2、ポリマー等)を層状に設け、波の伝播方向に垂直で、基板表面に平行な横波の成分の表面波(ラブ波)を励起することができるものをいう。
また、SH−SAWデバイスは、IDTをLiTaO3(36°回転Y板X伝播、Xカット150°伝播)等上に設け、波の伝播方向に垂直で、基板表面に平行な横波成分の表面波(圧電表面すべり波等)を励起することができるものをいう。
また、STWデバイスは、ATカット水晶基板等にIDTのグレーティング(溝)を設けたものであり、基板を伝播するSSBW(surface skimming bulkwave)をグレーティングにより基板表面にトラップし、表面横波(surface transverse wave)を励起するものである。
また、SH−APMデバイスは、STカット水晶基板等上にIDTを設けたものであり、基板表面に沿って基板に平行に伝播する板波を励起するものである。
Next, a device used as a surface acoustic wave element in the present invention will be described.
First, a Love wave device is provided with an IDT on a substrate surface made of ST cut quartz or the like, and a layer of a material (SiO 2 , polymer, etc.) having a speed slower than the propagation speed of the transverse wave of the substrate on the substrate surface. A surface wave (love wave) of a transverse wave component that is perpendicular to the propagation direction and parallel to the substrate surface can be excited.
In addition, the SH-SAW device is provided with IDT on LiTaO 3 (36 ° rotation Y plate X propagation, X cut 150 ° propagation), etc., and is a surface wave of a transverse wave component that is perpendicular to the wave propagation direction and parallel to the substrate surface. A thing that can excite (piezoelectric surface slip wave, etc.).
In addition, the STW device is an AT-cut quartz substrate or the like provided with an IDT grating (groove), and traps SSBW (surface skimming bulkwave) propagating through the substrate on the surface of the substrate by the grating. ) Is excited.
In addition, the SH-APM device is provided with an IDT on an ST cut quartz substrate or the like, and excites a plate wave propagating parallel to the substrate along the substrate surface.

次に、本発明の一実施例について図面に基づいて説明する。
図5は、本発明の測定に使用される装置の構成例である。
符号40で示される表面弾性波素子は、分析装置20に接続され、分析装置20は所望の交流信号を表面弾性波素子40に出力し、表面弾性波素子40のコンダクタンスGを測定できるように構成されている。制御装置30は、分析装置20の動作を制御し、分析装置20が表面弾性波素子40に出力する信号の周波数を変化させるとともに、周波数と測定結果とを対応させ、演算結果とともに記憶するように構成されている。尚、分析装置20は、ネットワークアナライザやインピーダンスアナライザー等として市販されているものである。
Next, an embodiment of the present invention will be described with reference to the drawings.
FIG. 5 is a configuration example of an apparatus used for the measurement of the present invention.
The surface acoustic wave element denoted by reference numeral 40 is connected to the analyzer 20, and the analyzer 20 is configured to output a desired AC signal to the surface acoustic wave element 40 and measure the conductance G of the surface acoustic wave element 40. Has been. The control device 30 controls the operation of the analysis device 20, changes the frequency of the signal output from the analysis device 20 to the surface acoustic wave element 40, associates the frequency with the measurement result, and stores it together with the calculation result. It is configured. The analyzer 20 is commercially available as a network analyzer, impedance analyzer, or the like.

表面弾性波素子40は、図6に示すように、STカット水晶(33度33分)からなる圧電基板4上に、夫々75対の櫛形電極5a,5bからなる送信用IDT5と、同様に、一対の櫛形電極6a,6bからなる受信用IDT6と、IDT5,6間の弾性波伝播路の表面に形成された検出部7とを有している。
前記櫛形電極5a,5b,6a,6bは、圧電基板4上に、厚み150nmの電極Au金属膜をスパッタリング法で形成した後、フォトリソグラフィにより不要な金属膜部分をドライエッチングにより除去して形成される。各櫛形電極5a等の幅w及び間隔sは夫々10μmに形成され、励起される表面弾性波の波長λは2(w+s)で求まり40μmとなる。そして、IDT5,6の上からSiO2を3μm前後成膜することで、中心周波数f0=125MHzのラブ波デバイスとして構成される。
この構成において、分析装置20の出力側から出力される交流信号が送信用IDT5に入力されると、圧電基板4の表面に所定の周波数fの波が伝わる。そして、この周波数fは、検出部7において変動し、受信用IDT6で検波され電気信号に変換され、分析装置20の入力側に入力され分析装置20で記録される。
As shown in FIG. 6, the surface acoustic wave element 40 is formed on the piezoelectric substrate 4 made of ST-cut quartz (33 degrees 33 minutes), similarly to the transmission IDT 5 made of 75 pairs of comb-shaped electrodes 5a and 5b, respectively. The receiving IDT 6 includes a pair of comb-shaped electrodes 6 a and 6 b, and a detection unit 7 formed on the surface of the elastic wave propagation path between the IDTs 5 and 6.
The comb electrodes 5a, 5b, 6a and 6b are formed by forming an electrode Au metal film having a thickness of 150 nm on the piezoelectric substrate 4 by sputtering, and then removing unnecessary metal film portions by dry etching by photolithography. The The width w and interval s of each comb-shaped electrode 5a and the like are each formed to be 10 μm, and the wavelength λ of the surface acoustic wave to be excited is 2 (w + s) and is 40 μm. Then, a SiO 2 film having a thickness of about 3 μm is formed on the IDTs 5 and 6 to constitute a Love wave device having a center frequency f 0 = 125 MHz.
In this configuration, when an AC signal output from the output side of the analyzer 20 is input to the transmission IDT 5, a wave having a predetermined frequency f is transmitted to the surface of the piezoelectric substrate 4. The frequency f varies in the detection unit 7, detected by the reception IDT 6, converted into an electric signal, input to the input side of the analyzer 20, and recorded by the analyzer 20.

次に、上記構成により測定した具体例を説明する。
まず、表面弾性波素子40の検出部7に150μlの純水を載置する。
測定開始時間から60秒後に第1の試料であるアビジン(濃度70μg/ml)を1μl投入し、700秒後に第2の試料である濃度30%グリセロールとアビジンの混合物(アビジン濃度は上記と同じ)を2μl投入し、1400秒後に第3の試料である濃度30%のグリセロールを1μl注入した。この測定期間中、分析装置20により1秒毎に1MHzの周波数帯域を掃引して、表面弾性波素子40の中心周波数f0を記録するとともに、中心周波数f0の近傍におけるコンダクタンスGの最大値を求め、このコンダクタンスGの1/2となる第1の周波数f1及び第2の周波数f2(f1<f2)を求めて、これらの値f0,f1,f2を記録した。
尚、前記試料のアビジンは検出部7に付着して質量負荷を与えるが、グリセロールは検出部7に付着せず粘性負荷だけを与えるものである。
Next, a specific example measured by the above configuration will be described.
First, 150 μl of pure water is placed on the detection unit 7 of the surface acoustic wave device 40.
1 μl of the first sample avidin (concentration 70 μg / ml) was added 60 seconds after the measurement start time, and after 700 seconds, the mixture of the second sample 30% glycerol and avidin (the avidin concentration is the same as above) After 1400 seconds, 1 μl of glycerol having a concentration of 30%, which is a third sample, was injected. During this measurement period, the analyzer 20 sweeps the frequency band of 1 MHz every second to record the center frequency f 0 of the surface acoustic wave device 40 and to determine the maximum conductance G in the vicinity of the center frequency f 0. Then, a first frequency f 1 and a second frequency f 2 (f 1 <f 2 ) that are ½ of the conductance G were obtained, and these values f 0 , f 1 , and f 2 were recorded.
The avidin of the sample adheres to the detection unit 7 and gives a mass load, but glycerol does not adhere to the detection unit 7 and gives only a viscous load.

記録されたデータのf0及びf2と、本実施例では、f1とf2の差に基づくパラメータとしてΔf1,2/2(Δf1,2=f2−f1)を算出し、これらをプロットしたものを図5に示す。
図5から明らかなように、第1の試料を投入すると、アビジンが表面弾性波素子40の検出部7に付着して質量負荷が変動するため、これを検知したf0及びf2が2000Hz変動する。これに対して、Δf1,2/2は、質量負荷の影響を受けないため一定値を維持する。
F 0 and f 2 of the recorded data, and in this embodiment, Δf 1,2 / 2 (Δf 1,2 = f 2 −f 1 ) is calculated as a parameter based on the difference between f 1 and f 2 . A plot of these is shown in FIG.
As can be seen from FIG. 5, when the first sample is introduced, avidin adheres to the detection unit 7 of the surface acoustic wave element 40 and the mass load fluctuates. Therefore, f 0 and f 2 detected by this change fluctuate by 2000 Hz. To do. On the other hand, Δf 1,2 / 2 maintains a constant value because it is not affected by the mass load.

次に、第2の試料を投入すると、中心周波数f0は、質量負荷の変動に加えて、グリセロールにより検出部が淀むことにより生じる粘性負荷の変動を受けている。このため、一旦周波数が大きく下がり、安定するまでに時間がかかっている。これに対して、f2は、グリセロールによる粘性負荷の変動を受けずに、質量負荷の変動を明確に示すように減少し、f0に比べて安定するまでの時間が短いことがわかる。また、Δf1,2/2は、グリセロールによる粘性負荷の変動のみを表していることがわかる。 Next, when the second sample is introduced, the center frequency f 0 is subject to a change in the viscous load caused by the glycerol stagnation in addition to the change in the mass load. For this reason, it takes time until the frequency is once lowered and stabilized. On the other hand, it can be seen that f 2 is decreased to clearly show the change in mass load without being affected by the change in viscous load due to glycerol, and is shorter in time to stabilize than f 0 . Further, it can be seen that Δf 1,2 / 2 represents only a change in viscous load due to glycerol.

最後に、第3の試料を投入すると、中心周波数f0は、質量負荷の変動に加えて、グリセロールによる粘性負荷の変動も受けて、大きく周波数が減少してから元に戻っていることがわかる。これに対して、f2は、グリセロールによる粘性負荷の変動を受けず、一定値を維持している。また、Δf1,2/2は、グリセロールによる粘性負荷の変動を検出し周波数が減少していることがわかる。 Finally, when the third sample is added, it can be seen that the center frequency f 0 returns to its original state after a large frequency decrease due to the fluctuation of the viscous load due to glycerol in addition to the fluctuation of the mass load. . On the other hand, f 2 is not affected by the viscous load due to glycerol and is maintained at a constant value. Further, Δf 1,2 / 2 shows that the frequency is decreased by detecting the fluctuation of the viscous load due to glycerol.

上記測定からわかるように、f2を質量負荷の測定のために使用し、Δf1,2/2を粘性負荷の測定のために使用すれば、測定の際に、質量負荷と粘性負荷を分離して測定することができることになる。従って、表面弾性波素子40にかかる負荷全体から粘性負荷を評価して質量負荷のみを正確に測定することができる。 As can be seen from the above measurement, if f 2 is used for measuring the mass load and Δf 1,2 / 2 is used for measuring the viscous load, the mass load and the viscous load are separated during the measurement. Can be measured. Therefore, it is possible to evaluate the viscous load from the entire load applied to the surface acoustic wave element 40 and accurately measure only the mass load.

尚、上記実施例は測定系を限定するものでなく、中心周波数f0を利用せずに直接f1及びf2を求めることができる測定系としてもよい。
また、上記実施例において、より正確な測定とするためには、表面弾性波素子40及び分析装置20の測定系を測定の前に校正することが好ましい。
The above embodiment does not limit the measurement system, and may be a measurement system that can directly determine f 1 and f 2 without using the center frequency f 0 .
Moreover, in the said Example, in order to set it as a more exact measurement, it is preferable to calibrate the measurement system of the surface acoustic wave element 40 and the analyzer 20 before a measurement.

2ポート型表面弾性波素子の等価回路の説明図Illustration of equivalent circuit of 2-port surface acoustic wave device 図1の等価回路に粘性負荷及び質量負荷が加わったときの等価回路の説明図Illustration of equivalent circuit when viscous load and mass load are added to the equivalent circuit of FIG. 同回路の作動図Operation diagram of the circuit 信号の周波数と表面弾性波素子のコンダクタンスとの関係を示すグラフGraph showing the relationship between signal frequency and surface acoustic wave element conductance 本発明の一実施例の測定装置の構成例を示す説明図Explanatory drawing which shows the structural example of the measuring apparatus of one Example of this invention. 本発明の一実施例の表面弾性波素子を示す説明図Explanatory drawing which shows the surface acoustic wave element of one Example of this invention 質量負荷及び粘性負荷と周波数変動の関係を説明するためのグラフGraph for explaining the relationship between mass load and viscous load and frequency fluctuation

符号の説明Explanation of symbols

4 圧電基板
5 送信用IDT
6 受信用IDT
7 検出部
20 分析装置
30 制御装置
40 表面弾性波素子
4 Piezoelectric substrate 5 IDT for transmission
6 IDT for reception
7 detector 20 analyzer 30 controller 40 surface acoustic wave element

Claims (6)

基板上に表面弾性波を励起して、前記基板上の検出部に載置された被検出物の物性を前記表面弾性波の特性の変化により測定する方法であって、前記基板上に励起される表面弾性波の周波数のうち、少なくとも2つの異なる周波数変動に基づいて前記被検出物の粘性負荷を評価し、前記被検出物の質量負荷を前記粘性負荷から分離して測定することを特徴とする測定方法。   A method of exciting a surface acoustic wave on a substrate and measuring a physical property of a detection object placed on a detection unit on the substrate by a change in characteristics of the surface acoustic wave, wherein the surface acoustic wave is excited on the substrate. The viscous load of the detected object is evaluated based on at least two different frequency fluctuations of the surface acoustic wave frequency, and the mass load of the detected object is measured separately from the viscous load. Measuring method to do. 前記2つの異なる周波数は、前記表面弾性波素子の中心周波数f0を与える測定系のコンダクタンスの半分のコンダクタンスを与える第1及び第2の周波数f1,f2(f1<f2)であることを特徴とする請求項1に記載の測定方法。 The two different frequencies are first and second frequencies f 1 and f 2 (f 1 <f 2 ) that provide a conductance that is half the conductance of the measurement system that provides the center frequency f 0 of the surface acoustic wave device. The measuring method according to claim 1. 前記2つの異なる周波数は、前記表面弾性波素子の中心周波数f0に対して位相を、±45°ずらした第1及び第2の周波数f1,f2(f1<f2)であることを特徴とする請求項1に記載の測定方法。 The two different frequencies are first and second frequencies f 1 and f 2 (f 1 <f 2 ) with a phase shifted by ± 45 ° with respect to the center frequency f 0 of the surface acoustic wave element. The measurement method according to claim 1. 前記第1及び第2の周波数f1,f2の差の変動に基づいて前記粘性負荷を評価することを特徴とする請求項2又は3に記載の測定方法。 The measurement method according to claim 2 or 3, wherein the viscous load is evaluated based on a variation in a difference between the first and second frequencies f 1 and f 2 . 前記質量負荷は、前記中心周波数f0に近く、且つ、前記中心周波数f0よりも大きな周波数である第2の周波数f2の変動に基づいて測定することを特徴とする請求項2乃至4のいずれかに記載の測定方法。 The mass load is close to the center frequency f 0, and, according to claim 2 to 4, characterized in that measured based on the center frequency f 0 the second variation of the frequency f 2 is a frequency greater than The measuring method in any one. 前記表面弾性波素子は、ラブ波デバイス、SH−SAWデバイス、STWデバイス又はSH−APMデバイスであることを特徴とする請求項1乃至5のいずれかに記載の測定方法。
The measurement method according to claim 1, wherein the surface acoustic wave element is a Love wave device, an SH-SAW device, an STW device, or an SH-APM device.
JP2004173925A 2004-06-11 2004-06-11 Measuring method using surface acoustic wave device Expired - Lifetime JP4504106B2 (en)

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US11/149,530 US7398685B2 (en) 2004-06-11 2005-06-10 Measuring method using surface acoustic wave device, and surface acoustic wave device and biosensor device
AT05012537T ATE439583T1 (en) 2004-06-11 2005-06-10 DUAL-FREQUENCY MEASURING METHOD FOR A SURFACE WAVE SENSOR, AS WELL AS SURFACE WAVE SENSOR AND BIOSENSOR WITH MEANS FOR MIXING THE ANALYSIS FLUID
DE602005015913T DE602005015913D1 (en) 2004-06-11 2005-06-10 Two-frequency measuring method for a surface wave sensor, as well as surface wave sensor and biosensor with means for mixing the analysis fluid
EP05012537A EP1605257B1 (en) 2004-06-11 2005-06-10 Two-frequency measuring method using surface acoustic wave device, and surface acoustic wave device and biosensor device with analysis liquid agitating means

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