JP6286768B2 - Surface acoustic wave sensor - Google Patents

Description

  The present invention relates to a surface acoustic wave sensor.

  A SAW (Surface Acoustic Wave) sensor described in Patent Document 1 is known as a liquid phase biosensor. In the surface acoustic wave sensor described in Patent Literature 1, two surface acoustic wave sensor elements are provided, a reference signal is individually given to each of the surface acoustic sensors, and output signals (first measurement signal and second measurement signal) are output. Based on the difference, a method for identifying an antigen contained in a liquid as a specimen is adopted.

FIG. 5 is a diagram showing a planar structure of the SAW sensor 100 used in a method for identifying an antigen contained in a liquid that is a specimen. FIG. 6 is a diagram for explaining a method for identifying an antigen contained in a liquid as a specimen.
In FIG. 5, the SAW sensor 100_1 includes IDT 11-1 (transmission electrode 11-1a, transmission electrode 11-1b), IDT 11-2 (reception electrode 11-2a, reception electrode 11-2b) formed on the piezoelectric element substrate. ) And a channel region (reaction region thin film) A. In addition, the SAW sensor 100_2 is formed on the piezoelectric element substrate, IDT 11-3 (transmission electrode 11-3a, transmission electrode 11-3b), IDT 11-4 (reception electrode 11-4a, reception electrode 11-4b), A channel region (reaction region thin film) B is included. Here, the piezoelectric element substrate is a substrate that propagates SAW, for example, a quartz substrate. In addition, the detection region (region that becomes the sensor surface) into which the liquid as the specimen is introduced is a portion where the piezoelectric element substrate and the reaction region thin film overlap, but here the entire surface of the reaction region thin film becomes the detection region. To do. That is, the SAW sensor 100 includes the SAW sensor 100_1 and the SAW sensor 100_2, and the channel region A and the channel region B are the detection regions.

Referring to FIG. 6, a sensor circuit 20 used for solution measurement using SAW sensor 100 includes an AC signal source 21, an RF switch 22, a phase / amplitude detection circuit 23, and a PC 24 (Personal Computer). . In FIG. 6, a SAW sensor 100 is attached to the sensor circuit 20 instead of the SAW sensor 1, and an antigen is specified.
The AC signal source 21 generates a sine wave AC signal and outputs it to the transmission electrode IDT 11-1 or the transmission electrode IDT 11-3 of the SAW sensor 100 and the phase / amplitude detection circuit 23 via the RF switch 22. .
The phase / amplitude detection circuit 23 detects based on the detection signal input from either the reception electrode IDT 11-2 or the reception electrode IDT 11-4 of the SAW sensor 100 and the sine wave AC signal from the AC signal source 21. Detects phase change and amplitude attenuation due to propagation time required for signal input. The phase / amplitude detection circuit 23 outputs the detected phase change and amplitude attenuation amount to the PC 24. The PC 24 specifies the amount and type of the antigen in the solution that specifically reacts with the surface antibody based on the phase change and the amplitude attenuation amount input from the phase / amplitude detection circuit 23.

  With the above configuration, the SAW sensor 100 can specify an antigen contained in a liquid that is a specimen, as described below. That is, SAW is an acoustic wave that propagates in the vicinity of the surface of the piezoelectric element substrate. When a substance is adsorbed on the surface of the piezoelectric element substrate, the mass and viscosity per unit volume of the surface change. As a result, the propagation speed and amplitude of the SAW change. Therefore, the propagation time of SAW changes, and the amount of amplitude attenuation changes. In order to identify the antigen contained in the liquid as the specimen, the antigen contained in the solution is measured using the amount of change in phase and the amount of change in amplitude attenuation.

  First, the measurer of the SAW sensor 100 drops a solvent not containing an antigen onto the channel region B of the SAW sensor 100, wets the reaction region thin film with the solvent, and measures the phase change due to the SAW propagation time (blank test). . Next, the measurer drops the solution containing the antigen onto the channel region A of the SAW sensor 100 and measures the phase change due to the propagation time. The difference between the phase change corresponding to the solvent and the phase change corresponding to the solution is the amount of phase change caused by the antigen-antibody conjugate produced in the reaction region thin film by the antigen-antibody reaction. The PC 24 stores the phase change at the time of the blank test in the memory, and calculates the difference in phase by calculating the difference between this phase change and the phase change obtained by dropping the solution. (Differential detection). The PC 24 identifies the antigen contained in the solution based on the phase change amount. The same applies to the amount of attenuation of the amplitude, and the antigen contained in the solution is specified based on the amount of change in the amount of attenuation of the amplitude (see, for example, Non-Patent Document 1).

  In addition to the measurement by the blank test, the following method can be used as the differential detection. In the channel region A, in order to detect an antigen as a specimen, an antibody that performs molecular recognition corresponding to the antigen is immobilized. In addition, the channel B region fixes a membrane that does not perform molecular recognition corresponding to the antigen, or inactivates the function of the antibody as an antibody after fixing the antibody corresponding to the antigen that performs molecular recognition. Keep the membrane fixed.

  The measurer drops the solution containing the antigen together with the channel region A and the channel region B of the SAW sensor 100, and measures the phase change due to the propagation time. Since the channel region B does not perform molecular recognition, only the solvent not containing the antigen changes, and the channel region A becomes the amount of change in the solvent in the channel region B and the phase change caused by the antigen-antibody conjugate. The change in the channel region A and the channel region B can be detected only as a phase change amount caused by the antigen-antibody conjugate (differential detection).

JP 2013-96866 A

Japanese Journal Applied Physics 49 (2010) 07HD15

  However, the above-described method has a problem that a change amount for specifying the target antigen cannot be detected due to a change amount due to a large disturbance. The large disturbance here refers to a change that occurs when the SAW sensor 100 is changed from an air-loaded state in which the SAW sensor 100 is exposed to air to a state in which a sample (solution containing an antigen) is dropped. Since the surface acoustic wave sensor detects the density and viscosity of the solution, a large change, that is, a disturbance always occurs when the sample is dropped. In the above-described method for identifying the antigen contained in the liquid that is the specimen, the channel region A and the channel region B cause substantially the same amount of disturbance. Therefore, if there is no variation in the amount of change due to this disturbance, the difference between the amount of change in the antigen-antibody reaction that does not occur in the channel region B is calculated from the amount of change in the antigen-antibody reaction that occurs in the channel region A. It becomes possible.

  However, since the amount of change due to the disturbance is larger than the amount of change in the antigen-antibody reaction that occurs in the channel region A, the variation in the amount of change due to the disturbance is also larger than the variation in the amount of change in the antigen-antibody reaction. Therefore, if the amount of change due to disturbance is large and the same amount as the amount of change in the antigen-antibody reaction, the amount of change in the antigen-antibody reaction cannot be detected, and the amount of change to identify the target antigen can be detected. It will disappear.

Further, the above-described differential detection has a problem that the measurement is complicated because separate surface structures are required for the channel region A and the channel region B. That is, in the channel region A, a solution containing an antigen is dropped, while in the channel region B, a solvent that does not contain an antigen is dropped. Therefore, it is necessary to replace the dropped one, and the measurement becomes complicated. There was a problem.
Further, since the conversion amount due to the substantially same amount of disturbance is canceled as it is, it is necessary to configure the channel region A and the channel region B with the same area.

  The present invention has been made in view of the above points, and provides a surface acoustic wave sensor that can improve measurement accuracy, can be easily measured, and has a small detection region.

(1) The present invention has been made to solve the above-described problems, and one aspect of the present invention provides differential detection when a target change amount in a measurement target is small relative to a change amount due to a disturbance. In order to carry out, a first surface acoustic wave element and a second surface acoustic wave element are provided, and the propagation distance of the second surface acoustic wave element is set to the propagation distance of the first surface acoustic wave element. The surface acoustic wave sensor is characterized in that a change amount of a measurement object in the two surface acoustic wave elements is set smaller than a detection limit of the surface acoustic wave sensor.
( 2 ) Further, according to one aspect of the present invention, the first surface acoustic wave element and the second elasticity are used to perform differential detection when the target change amount in the measurement target is small relative to the change amount due to the disturbance. A surface acoustic wave element, a propagation distance of the second surface acoustic wave element with respect to a propagation distance of the first surface acoustic wave element, a ratio of a change amount of a disturbance and a measurement object, and the second surface acoustic wave The surface acoustic wave sensor is characterized in that a change amount of a measurement object in the element is set to be smaller than a detection limit of the surface acoustic wave sensor.
( 3 ) Further, one embodiment of the present invention is characterized in that the surface acoustic wave sensor includes one input electrode and two output electrodes.
( 4 ) One embodiment of the present invention is characterized in that the surface acoustic wave sensor includes one input / output electrode and a reflector.
( 5 ) Further, according to one aspect of the present invention, the target change amount in the measurement target is a change due to the antigen-antibody reaction, and the change amount due to the disturbance is a state in which the load is air and a state in which the load is sample water. It is a change between.

  According to the present invention, it is possible to provide a surface acoustic wave sensor that can improve measurement accuracy, can be easily measured, and has a small detection region.

It is a schematic top view of SAW sensor 1 (surface acoustic wave sensor) concerning this embodiment. 1 is a schematic cross-sectional view of a SAW sensor 1. FIG. It is a schematic diagram which shows the structure of the SAW sensor 2 which concerns on the 2nd Embodiment of this invention. It is a schematic diagram which shows the structure of the SAW sensor 3 which concerns on the 3rd Embodiment of this invention. It is a figure which shows the planar structure of the SAW sensor 100 used for the system which identifies the antigen contained in the liquid which is a test substance. It is a figure for demonstrating the system which identifies the antigen contained in the liquid which is a test substance.

(First embodiment)
Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
FIG. 1 is a schematic top view of a SAW sensor 1 (surface acoustic wave sensor) according to the present embodiment. FIG. 2 is a schematic cross-sectional view of the SAW sensor 1. In FIG. 1, the same parts as those in FIG. FIG. 2 shows a cross-sectional view of the SAW sensor 1_1 (first surface acoustic wave element) shown in FIG. 1 cut along the SAW propagation direction.
As shown in FIG. 1, the SAW sensor 1 includes a SAW sensor 1_1 and a SAW sensor 1_2 (second surface acoustic wave element) formed on the same piezoelectric element substrate 10. 1 and 2, the SAW sensor 1_1 includes a transmission electrode 11-1a, a transmission electrode 11-1b, a reception electrode 11-2a, a reception electrode 11-2b, a reaction region thin film 12 (channel region A). ), A porous substrate 13, a sealing structure 14_1, and a sealing structure 14_2. The SAW sensor 1_2 includes a transmission electrode 11-3a, a transmission electrode 11-3b, a reception electrode 11-4a, a reception electrode 11-4b, a reaction region thin film (channel region R), a porous substrate 13, and a sealing structure 14_3. (Not shown in FIGS. 1 and 2) and a sealing structure 14_4 (not shown in FIGS. 1 and 2).
The piezoelectric element substrate is a substrate that propagates SAW, for example, a quartz substrate.

The transmission electrode 11-1a and the transmission electrode 11-1b are metal electrodes formed by a comb-like pattern constituting the transmission-side electrode unit. The transmission electrode 11-3a and the transmission electrode 11-3b are metal electrodes formed by a comb-like pattern that constitutes the transmission-side electrode unit. Hereinafter, the transmission electrode 11-1a and the transmission electrode 11-1b are collectively referred to as IDT 11-1, and the transmission electrode 11-3a and the transmission electrode 11-3b are collectively referred to as IDT 11-3.
In addition, the reception electrode 11-2a and the reception electrode 11-2b are metal electrodes formed by a comb-like pattern constituting the reception-side electrode unit. The reception electrode 11-4a and the reception electrode 11-4b are metal electrodes formed by a comb-like pattern that constitutes the reception-side electrode unit. Hereinafter, the reception electrode 11-2a and the reception electrode 11-2b are collectively referred to as IDT 11-2, and the reception electrode 11-4a and the reception electrode 11-4b are collectively referred to as IDT 11-4.
IDT11-1, IDT11-2 (collectively referred to as IDT11_1), IDT11-3, and IDT11-4 (collectively referred to as IDT11_2) are electrodes configured on the piezoelectric element substrate, respectively. IDT11_1 and IDT11_2 are a pair of electrodes facing each other. IDT11_1, IDT11_2, IDT11-3, and IDT11-4 are each made of, for example, an aluminum thin film.

With reference to FIG. 2, porous substrate 13 is a substrate provided in contact with reaction region thin film 12. The porous substrate 13 is made of a material such as nitrocellulose. The porous substrate 13 is fixed so as to completely cover the reaction region thin film 12. For example, the porous base material 13 is bonded and fixed to the outer four corners of the reaction region thin film 12. The porous substrate 13 holds the dropped solution, and infiltrates the solution into the inside and the surface thereof.
The porous substrate 13 transfers and holds the dropped solution to the inside of the porous substrate 13 and the surface of the reaction region thin film 12 by capillary action.
That is, the SAW sensor 1_1 holds the dropped solution inside the porous substrate 13 and the surface of the reaction region thin film 12.

In the SAW sensor 1_1, the solution transferred in the porous substrate 13 wets a specific region of the reaction region thin film 12. Here, the specific region is a region whose area is determined by the overlapping portion of the porous substrate 13 and the reaction region thin film 12. For example, when the entire surface of the reaction region thin film 12 is covered with the porous substrate 13, the entire region of the reaction region thin film 12 is obtained. In the present embodiment, the entire region of the reaction region thin film 12 is referred to as a channel region A as shown in FIG.
The antigen in the solution reacts with the antibody carried on the channel region A to generate an antigen-antibody conjugate in a specific region on the channel region A.
That is, in the channel region A, an antigen-antibody reaction occurs between the antibody carried on the channel region A and the antigen in the liquid sample by dropping a liquid sample containing the antigen on the surface thereof. As a result, an antigen-antibody conjugate in which the antibody carried on the channel region A and the antigen are bound to each other is generated on the channel region A. The channel region A may be anything other than gold as long as it can carry antibodies.

In the SAW sensor 1_2, similarly to the SAW sensor 1_1, the solution transferred through the porous substrate 13 wets a specific region of the reaction region thin film. For example, when the entire surface of the reaction region thin film is covered with the porous substrate 13, the entire region of the reaction region thin film is formed. In the present embodiment, the entire region of the reaction region thin film is referred to as a channel region R as shown in FIG.
Similar to the channel region A, the antigen in the solution reacts with the antibody carried on the channel region R to generate an antigen-antibody conjugate in a specific region on the channel region R.
That is, in the channel region R, as in the channel region A, a liquid sample containing an antigen is dropped on the surface thereof, so that an antibody supported on the channel region R and an antigen in the liquid sample are separated. An antigen-antibody reaction occurs. As a result, an antigen-antibody conjugate in which an antibody carried on the channel region R and an antigen are bound to each other is generated on the channel region R. The channel region R may be anything other than gold as long as it can carry an antibody.

  In this embodiment, the length of the channel region A and the channel region R in the SAW propagation direction is set shorter in the channel region R than in the channel region A. In the following, as shown in FIG. 1, the length of the SAW propagation direction in the channel region A is defined as length L1, and the length of the SAW propagation direction in the channel region R is defined as length L2. A method of setting the ratio of the length L2 to the length L1 will be described later.

With reference to FIG. 2, the sealing structure 14-1 on the transmission electrode side in the SAW sensor 1 </ b> _ <b> 1 includes a sealing wall 15-1 and a sealing ceiling 16-1. In addition, although the contact bonding layer for adhere | attaching both is provided between the sealing wall 15-1 and the sealing ceiling 16-1, it is abbreviate | omitting in FIG. The sealing wall 15-1 is a wall that covers the IDT 11-1 and is formed in a rectangular shape on the piezoelectric element substrate 10. The sealing wall 15-1 is made of, for example, a photosensitive resin.
Moreover, the sealing ceiling 16-1 is a ceiling for closing the upper side of the sealing wall 15-1 and sealing the IDT 11-1 from the outside. The sealing ceiling 16-1 is disposed on the upper side of the sealing wall 15-1 so that the sealing wall 15-1 is accommodated in the planar area of the sealing ceiling 16-1. The sealed ceiling 16-1 is made of, for example, a glass substrate. An adhesive layer (not shown) is provided between the sealing wall 15-1 and the sealing ceiling 16-1, and the space between the sealing wall 15-1 and the sealing ceiling 16-1 is sealed. Glue.
The sealing structure 14-1 is a sealing structure that covers the IDT 11-1 from the outside so as to form a space on the IDT 11-1 and prevents the IDT 11-1 from coming into contact with the liquid.

Further, the sealing structure 14-2 on the receiving electrode portion side in the SAW sensor 1_1 includes a sealing wall 15-2 and a sealing ceiling 16-2 in the same manner as the sealing structure 14-1, and includes an IDT 11-2. It is a sealing structure that covers the IDT 11-2 so as to form a space on the IDT 11-2 and prevents the IDT 11-2 from coming into contact with the liquid.
Even if there is a change in the atmosphere (for example, humidity) in the detection region, the IDT 11-1 and the IDT 11-2 are less affected by the sealing structure 14-1 and the sealing structure 14-2.
The SAW sensor 1_2, like the SA sensor 1_1, protects the IDT 11_3, so that the sealing structure 14-3 is the same as the sealing structure 14-1, and the sealing structure 14-2 is the same as the sealing structure 14-2 that protects the IDT 11_3. 14-4.

Any one of IDT 11-1 and IDT 11-3 receives a sine wave AC signal via the RF switch 22. One of IDT 11-1 and IDT 11-3 excites SAW corresponding to the input sinusoidal AC signal on the surface of the piezoelectric element substrate. One of IDT 11-2 and IDT 11-4 converts the SAW propagated on the surface of the piezoelectric element substrate 10 into an electrical signal. One of IDT 11-2 and IDT 11-4 outputs the received electrical signal (referred to as a detection signal) to a phase / amplitude detection circuit 23 described later.
When the measurer of the SAW sensor 1 drops a solution onto, for example, the porous substrate on the channel region A and the channel region R, each porous substrate removes the dropped solution by a capillary phenomenon by a capillary phenomenon. It is transported and held inside the material and on the respective surfaces of the channel region A and channel region R.
That is, even if the porous substrate has a portion that does not overlap the detection region in plan view, the porous substrate transfers the solution to the surface of the channel region A and the channel region R and holds the channel. Region A and channel region R can be wetted by the dropped solution.

A sensor circuit 20 shown in FIG. 6 is used for solution measurement using the SAW sensor 1.
The sensor circuit 20 includes a SAW sensor 1, an AC signal source 21, an RF switch 22, a phase / amplitude detection circuit 23, and a PC 24.
The AC signal source 21 generates, for example, a 250 MHz sine wave AC signal. This sine wave AC signal is output by the RF switch 22 to either the IDT 11-1 or IDT 11-3 of the SAW sensor 1 and the phase / amplitude detection circuit 23.
In the case where interference signals such as noise including direct waves other than the main signal included in the signal output from the SAW sensor 1 and other bulk waves are sufficiently small, a sine wave from the AC signal source 21 is used. The AC signal may be a continuous wave. However, when a disturbance signal such as a noise including a direct wave or a bulk wave is large, the sine wave AC signal may be converted into a periodic burst signal and input to the SAW sensor 1. The period of the burst signal is set to be longer than the time required for the SAW to travel between IDT 11-1 and IDT 11-2 on the surface of the piezoelectric element substrate 10, for example. In order to convert to a burst signal, a known burst circuit (not shown) is inserted in series immediately after the AC signal source 21.

The phase / amplitude detection circuit 23 generates a SAW signal based on a detection signal input from one of the IDT 11-2 and IDT 11-4 of the SAW sensor 1 and a sine wave AC signal input from the AC signal source 21. A phase change and an amplitude change according to the propagation time, which is the time required to propagate through the piezoelectric element substrate, are calculated. Specifically, the phase / amplitude detection circuit 23 detects a phase change and an amplitude attenuation amount due to a propagation time required from the input of the sine wave AC signal to the input of the detection signal. The phase / amplitude detection circuit 23 outputs the detected phase change and amplitude attenuation amount to the PC 24.
The PC 24 determines the amount and type of the antigen in the solution that specifically reacts with the surface antibody based on the phase change and amplitude attenuation input from the phase / amplitude detection circuit 23 and displays the determination result. .

Here, the phase change of SAW and the attenuation amount of amplitude will be described. SAW is an acoustic wave that propagates in the vicinity of the surface of the piezoelectric element substrate 10 in a concentrated manner. When a substance is adsorbed on the surface of the piezoelectric element substrate 10, the mass and viscosity per unit volume of the surface change. As a result, the propagation speed and amplitude of the SAW change. Therefore, the propagation time of SAW changes, and the amount of amplitude attenuation changes. In the present embodiment, the antigen contained in the solution is measured using the amount of phase change and the amount of amplitude attenuation.
Specifically, unlike the prior art, the measurer of the SAW sensor 1 includes the antigen in the porous substrate on the channel region A and the channel region R shown in FIG. The solution is dropped, the channel region A and the channel region R are wetted with the solution, and the phase change due to the SAW propagation time is measured for each channel. The difference between the phase change in the channel region A and the phase change in the channel region R is the amount of phase change caused by the antigen-antibody conjugate produced in the channel region A by the antigen-antibody reaction.

  The PC 24 stores the phase change of the channel region A in a memory, and calculates the amount of phase change by calculating the difference between this phase change and the phase change of the channel region R. The PC 24 identifies the antigen contained in the solution based on the phase change amount. The same applies to the attenuation amount of the amplitude, and the antigen contained in the solution is specified based on the change amount of the attenuation amount of the amplitude.

Next, the ratio of the length L2 in the SAW propagation direction of the channel region R to the length L1 of the SAW propagation direction in the channel region A will be described in detail.
In the following description, experimental data described in Non-Patent Document 1 is used as actually measured data.
First, taking the channel region A of the present embodiment as an example, the load is from the state where the load is air (the initial state where the solution is not dripped and the SAW sensor 1 is exposed to air, hereinafter also referred to as air load). Shifts to a state where water is sample water (for example, a state where pure water is dripped onto the SAW sensor 1, hereinafter also referred to as a pure water load), the amount of change in the phase of the output signal with respect to the input signal changes from 20.4 dB to 38.4 dB (See FIG. 3. (a) of Non-Patent Document 1). That is, the amount of change in the phase of the channel region A due to the disturbance is 18 dB (= 38.4 dB-20.4 dB).

In addition, the amount of phase change caused by wetting channel region A with a solution containing HSA (human serum alvin) as an antigen is shown in FIG. 7). It is shown in the calibration curve shown in (b). In this calibration curve, the horizontal axis indicates the concentration of HSA (μg / ml), and the vertical axis indicates the loss Δα / k per unit. For example, when the HSA concentration is 10 μg / ml, the loss Δα / k per unit is 30 ppm. The loss Δα / k per unit can be converted into a loss A [dB] that is a phase change amount in the channel region A by the following equation.
That is,
Δα / k = −Aλ × 10 ⁶ /(L×8.686×2π)
It is.
Here, L is the propagation distance of the dropping surface (ie, L1), λ is the SAW wavelength, and 8.686 is a so-called Napaer constant for unit conversion of energy. These conversions are performed by the phase / amplitude detection circuit 23 shown in FIG.
For example, when the loss Δα / k per unit is 30 ppm, the amount of phase change in the channel region A is 0.5 dB according to the above conversion equation.

Here, a small change (0.5 dB change amount in the above example) due to an antigen-antibody reaction, which is a desired change, is detected in the channel region A, and a large change (18 dB change amount in the above example) due to a disturbance in the channel region R. ) May be detected at a ratio of 1/36 times the length L1.
For example, since the biosensor described in Non-Patent Document 1 has a propagation distance of 6 mm, the length L1 of the channel region A is set to L1 = 6 mm, and the length L2 of the channel region R is set to 6 mm × 1/36 = 0.167 mm. That's fine. In this way, when the measurement limit of the SAW sensor 1 by the sensor circuit 20 shown in FIG. 6 is 0.05 dB / div, the amount of phase change due to the antigen-antibody reaction in the channel region R is 0.5 dB × 1 / 36 = 0.0193 dB, and the phase change amount due to the bio-change (antigen-antibody reaction) in the channel region R can be ignored by the measurement system.

In order to conceptually summarize the above, in sensor 1, the amount of phase change due to disturbance in channel region A (detected value by sensor circuit 20) is CPext, and the amount of phase change due to antigen-antibody reaction in channel region A (sensor circuit) The detection value by 20) is CPrea.
That is, the phase change amount CP_A in the channel region A is
CP_A = CPext + CPrea
It becomes.
On the other hand, the amount of phase change CP_B is:
CP_B = (phase change amount due to disturbance in channel region R) + (phase change amount due to antigen-antibody reaction in channel region R)
= CPext × (L2 / L1) + CPrea × (L2 / L1)
It becomes.

The amount of change in phase due to disturbance in the channel region R is CPext × (L2 / L1), and this value is smaller than the amount of change in phase due to disturbance in the channel region A. Small, detected by the phase / amplitude detection circuit 23 in the sensor circuit 20 and input to the PC 24.
On the other hand, the amount of phase change due to the antigen-antibody reaction in the channel region R is CPrea × (L2 / L1). This value is different from the amount of phase change due to disturbance in the channel region A, and is a value below the measurement limit. Therefore, it is not detected by the phase / amplitude detection circuit 23 in the sensor circuit 20 and is not input to the PC 24.

  The phase change amount CPext × (L2 / L1) due to the disturbance in the channel region R having a small variation is input to the PC 24 as the phase change amount of the channel region R. The amount of phase change CPrea × (L2 / L1) due to the antigen-antibody reaction is not input. The PC 24 multiplies the phase change amount CPext × (L2 / L1), which is input in this way due to disturbance with small variation, to return to the original amount of disturbance with little variation. This is subtracted from the phase change amount CP_A in the channel region A. Thereby, the PC 24 can specify the antigen from the amount of phase change (detected value by the sensor circuit 20) due to the antigen-antibody reaction in the channel region A.

  As described above, in the SAW sensor 1 of the present embodiment, the reference signal is input, the SA1 sensor 1_1 that outputs the first measurement signal when the antigen-antibody reaction occurs, the reference signal is input, and the first elastic surface And a second surface acoustic wave element that outputs a second measurement signal when the same antigen-antibody reaction as that of the wave element occurs. The SAW sensor 1 is a surface acoustic wave sensor that identifies an antigen by detecting a change amount in an antigen-antibody reaction from a phase difference and an amplitude ratio between a first measurement signal and a second measurement signal. The ratio between the length L1 in the direction in which the reference signal 1_1 is propagated and the length L2 in the direction in which the reference signal of the SA1 sensor 1_2 is propagated is a target change amount in the antigen-antibody reaction in the SA1 sensor 1_1, and the SA1 sensor 1_1. It is set according to the ratio of the amount of change between the state in which the load is air and the state in which the load is sample water.

  For example, in the above example, a value of 5 times the measurement limit value (a value determined according to the detection limit value of the surface acoustic wave sensor) is set as a loss range that is easy to measure. If the value is equal to or less than / 18 dB, the bio-change in the channel region B can be ignored as described above. That is, (length L1 / length L2) is equal to or less than the value (ratio) of the value determined according to the detection limit value of the surface acoustic wave sensor with respect to the amount of change between the air load and the pure water load in the channel region A. Then, the antigen can be identified in the channel region A as described above.

According to the SAW sensor 1 of the present embodiment, variation in the amount of change due to disturbance in the channel region R can be suppressed, so that the amount of change in the antigen-antibody reaction in the channel region A can be easily detected, and the target antigen can be detected. It becomes possible to easily detect the amount of change for identification.
Further, in the above-described differential detection, the channel region A and the channel region R can have the same surface structure, so that the measurement can be simplified. That is, in both the channel regions A and B, since the solution containing the antigen only needs to be dropped onto the porous material on the channel region, the measurement can be easily performed.
Further, the amount of change in the channel region R may be multiplied by (length L1 / length L2) without canceling the conversion amount caused by the substantially same amount of disturbance, so that the channel region R is smaller in area than the channel region A. Therefore, the occupation rate of the detection area of the SAW sensor 1 can be reduced.
As described above, according to the present invention, it is possible to provide a surface acoustic wave sensor that can improve measurement accuracy, can be easily measured, and has a small detection region.

(Second Embodiment)
The second embodiment of the present invention will be described below with reference to the drawings.
In the following description of each embodiment, the same components as those described above are denoted by the same reference numerals in the drawings, and description thereof is omitted.
In the present embodiment, a configuration in which an input electrode is shared between the SAW sensor 2_1 having the channel region A and the SAW sensor 2_2 having the channel region R will be described.

FIG. 3 is a schematic diagram showing the configuration of the SAW sensor 2 according to the second embodiment of the present invention.
As shown in FIG. 3, the SAW sensor 2 includes a SAW sensor 2_1 and a SAW sensor 2_2.
In the SAW sensor 2 shown in FIG. 3, compared to the SAW sensor 1 shown in FIG. 1, the IDT 11-1 (transmission electrode 11-1a and transmission electrode 11-1b) of the SAW sensor 1_1 and the IDT 11-3 of the SAW sensor 1_2 ( The transmission electrode 11-3a and the transmission electrode 11-3b) are made common and are IDT11-1. Further, the channel region A and the channel region R are arranged on opposite sides with the common IDT 11-1 interposed therebetween.
The measurement method is the same as the measurement method described in the first embodiment, and measurement is performed using the sensor circuit 20 shown in FIG.
Since the SAW sensor 2 can reduce the number of input electrodes, a surface acoustic wave sensor with a small size can be provided.

(Third embodiment)
The third embodiment of the present invention will be described below with reference to the drawings.
In the present embodiment, a configuration in which the SAW sensor 3_1 and the SAW sensor 3_2 have a common input electrode and a common channel region will be described.
FIG. 4 is a schematic diagram showing the configuration of the SAW sensor 3 according to the third embodiment of the present invention.
As shown in FIG. 4, the SAW sensor 3 includes a SAW sensor 3_1 and a SAW sensor 3_2.
In the SAW sensor 3 shown in FIG. 4, compared to the SAW sensor 1 shown in FIG. 1, the IDT 11-1 (transmission electrode 11-1a and transmission electrode 11-1b) of the SAW sensor 1_1 and the IDT 11-3 of the SAW sensor 1_2 ( The transmission electrode 11-3a and the transmission electrode 11-3b) are made common and are IDT11-1. Also, the common IDT 11-1, the IDT 11-2 (receiving electrode 11-2a and receiving electrode 11-2b) of the SAW sensor 3_1, and the IDT 11-4 (receiving electrode 11-4a and receiving) of the SAW sensor 3_2 are received. Between the electrode 11-4b), a channel region C in which the channel region A and the channel region R are shared is provided.

The height of IDT 11-2 and IDT 11-4 (the length in the direction perpendicular to the SAW propagation direction) is set to approximately half that of IDT 11-1, and the height of SAW sensor 3 is set to IDT 11-1. It is set to be the height of.
The measurement method is the same as the measurement method described in the first embodiment, and measurement is performed using the sensor circuit 20 shown in FIG.
In the SAW sensor 2, since the input electrode can be omitted and the channel region can be shared, a surface acoustic wave sensor having a smaller size can be provided. In addition, when a solution containing an antigen is dropped on the porous substrate on the channel region C, an antigen-antibody reaction occurs in the channel region of the SAW sensor 3_1 and the channel region of the SAW sensor 3_2. It is not necessary to repeat the operation of dropping the solution, and simple measurement can be performed.

  The embodiments of the present invention have been described in detail above with reference to the drawings. However, the specific configuration is not limited to the above-described one, and various design changes and the like can be made without departing from the scope of the present invention. Is possible. For example, in each of the above embodiments, an example using the transmission electrode and the reception electrode has been shown. However, a SAW reflector (reflector) is provided instead of the reception electrode so that the transmission electrode also functions as the reception electrode. It doesn't matter.

  In the description of the embodiment, the change of the measurement target is an antigen-antibody reaction, and the disturbance is air and water. However, the change in the measurement target is not limited to the antigen-antibody reaction. The disturbance is not limited to air and water, but may be other characteristic changes due to temperature, non-specific changes due to antigens other than the target, and the like. In other words, the present invention is applicable when the target change amount in the measurement target is smaller than the change amount due to the disturbance.

  Moreover, in description of embodiment, although the porous base material 13 is installed as shown in FIG. 2, this is not necessarily required. It is possible to drop the solution onto the surface of the reaction region thin film 12 without providing the porous substrate 13.

  1, 2, 3, 100 ... SAW sensor, 10 ... piezoelectric element substrate, 11 ... electrode, 12 ... reaction region thin film, 13 ... porous substrate, 20 ... sensor circuit, 21 ... AC signal source, 22 ... RF switch, 23 ... Phase / amplitude detection circuit, 24 ... PC

Claims (5)

When the target change amount in the measurement target is small compared to the change amount due to disturbance,
In order to perform differential detection, a first surface acoustic wave element and a second surface acoustic wave element are included.
The propagation distance of the second surface acoustic wave element is set to be smaller than the detection limit of the surface acoustic wave sensor with respect to the propagation distance of the first surface acoustic wave element. To
A surface acoustic wave sensor. When the target change amount in the measurement target is small compared to the change amount due to disturbance,
In order to perform differential detection, a first surface acoustic wave element and a second surface acoustic wave element are included.
The propagation distance of the second surface acoustic wave element with respect to the propagation distance of the first surface acoustic wave element, the ratio of the disturbance and the amount of change of the measurement object, and the amount of change of the measurement object in the second surface acoustic wave element Is set smaller than the detection limit of the surface acoustic wave sensor,
A surface acoustic wave sensor. Consists of one input electrode and two output electrodes,
The surface acoustic wave sensor according to claim 1 , wherein the surface acoustic wave sensor is provided. Consists of one input / output electrode and a reflector.
The surface acoustic wave sensor according to claim 1 , wherein the surface acoustic wave sensor is provided. The target change amount in the measurement target is the change due to the antigen-antibody reaction,
The amount of change due to disturbance is a change between a state where the load is air and a state where the load is sample water.
The surface acoustic wave sensor according to any one of claims 1 to 4 , wherein the surface acoustic wave sensor is provided.