JP7804489B2 - Detection Device - Google Patents

Description

The present invention relates to a detection device, for example, a detection device to which antibodies can be connected.

One known detection device for detecting antigens, such as viruses, is one that fixes antibodies to the resonance region of a resonator such as an FBAR (Film Bulk Acoustic Resonator) and detects changes in the FBAR's resonance frequency (see, for example, Non-Patent Document 1). Another known detection device is one that fixes antibodies to the propagation path along which elastic waves propagate and detects changes in the velocity of the elastic waves (see, for example, Non-Patent Document 2).

“Biosensor for human IgE detection using shear-mode FBAR devices” Ying-Chung Chen et al., Nanoscale Research Letters 10, Article number 69 (2015) "Development of SH-SAW Biosensor for POCT" by Yatsuda et al., Japan Radio Technical Journal No.64 2013 p41-45

However, if the number of antibodies placed in the resonance region or propagation path differs for each detection device, the test results will vary.

The present invention was developed in consideration of the above issues, and aims to reduce variation in detection results.

The present invention is a detection device comprising a resonator having a resonance region in which elastic waves resonate, and a thin film provided on the resonance region and having a plurality of holes, wherein antibodies can be connected to the resonance region through each of the plurality of holes.

In the above configuration, the planar shape of the resonance region can be rectangular, and a guide having an upper surface higher than the upper surface of the thin film can be provided on the outside of both long sides of the rectangle.

In the above configuration, the resonator may include multiple resonators connected in series.

In the above configuration, the resonator can include a piezoelectric layer and a first electrode and a second electrode sandwiching the piezoelectric layer, and the resonance region can be a region where the first electrode and the second electrode overlap, sandwiching at least a portion of the piezoelectric layer.

In the above configuration, the resonator may include a piezoelectric substrate, a first comb electrode provided on the piezoelectric substrate and having a plurality of first electrode fingers, and a second comb electrode provided on the piezoelectric substrate and having a plurality of second electrode fingers, and the resonance region may be a region in which the plurality of first electrode fingers and the plurality of second electrode fingers are arranged alternately.

In the above configuration, each of the multiple holes can be configured to have an antibody connected to the resonance region.

The present invention is a detection device comprising a propagation path through which elastic waves propagate, and a thin film provided on the propagation path and having a plurality of holes, in which antibodies can be connected to the propagation path through each of the plurality of holes.

In the above configuration, the propagation path may have a rectangular planar shape, and may be configured to include guides on the outside of both long sides of the rectangle, each having an upper surface higher than the upper surface of the thin film.

The above configuration may include a piezoelectric substrate, a pair of first comb electrodes provided on the piezoelectric substrate for transmitting the elastic waves, and a pair of second comb electrodes provided on the piezoelectric substrate for receiving the elastic waves, and the propagation path may include the piezoelectric substrate between the pair of first comb electrodes and the pair of second comb electrodes.

In the above configuration, each of the multiple holes can be configured to have an antibody connected to the propagation path.

In the above configuration, one of the antibodies can be connected to one of the multiple holes.

In the above configuration, the antibody may be configured not to bind to the thin film.

The present invention relates to a detection device comprising: a substrate having a rectangular first region located in the center, and second and third regions located on either side of the long side of the rectangular first region; a lower electrode located on the substrate, extending continuously from the first region to the second region; a piezoelectric layer located on the substrate and the lower electrode, extending continuously from the first region to the second and third regions; an upper electrode located on the piezoelectric layer, extending continuously from the first region to the third region; a rectangular thin film located on the upper electrode corresponding to the first region and corresponding to the first region; antibodies located at the bottoms of multiple holes in the thin film; two guides located along the two long sides of the rectangular shape of the first region, each with an upper surface higher than the upper surface of the thin film; and the multiple holes exposed at the bottom of a first groove between the two guides.

In the above configuration, the lower portions of the two guides can be provided within second grooves provided in the piezoelectric layer, and the upper portions of the two guides can be configured to overlap the thin film outside the second grooves.

The present invention aims to reduce variation in detection results.

FIG. 1(a) is a plan view of a detection device according to Example 1, FIG. 1(b) is a plan view showing a lower electrode, an upper electrode, and a resonance region, and FIG. 1(c) is a cross-sectional view taken along line AA of FIG. 1(a). 2(a) is a cross-sectional view taken along line BB of FIG. 1(a), FIG. 2(b) is an enlarged cross-sectional view of the periphery of the hole, and FIG. 2(c) is another example of the cross-sectional view taken along line BB of FIG. FIG. 3A is a plan view of a detection device according to a first modified example of the first embodiment, and FIG. 3B is a cross-sectional view taken along line AA of FIG. 3A. 4A and 4B are cross-sectional views of detection devices according to second and third modifications of the first embodiment, respectively. FIG. 5A is a plan view of a detection device according to a second embodiment, and FIG. 5B is a cross-sectional view taken along line AA of FIG. 5A. FIG. 6A is a plan view of a detection device according to a first modified example of the second embodiment, and FIG. 6B is a cross-sectional view taken along the line AA in FIG. 6A. FIG. 7A is a plan view of a detection device according to a third embodiment, and FIG. 7B is a cross-sectional view taken along line AA of FIG. 7A. 8A and 8B are block diagrams of detection systems according to a fourth embodiment and a first modification thereof, respectively.

The following describes the examples with reference to the drawings.

[Example 1: Example in which a piezoelectric thin film resonator is used in a detection device]
FIG. 1(a) is a plan view of the detection device 100 according to the first embodiment, FIG. 1(b) is a plan view showing the lower electrode, upper electrode, and resonance region, and FIG. 1(c) is a cross-sectional view taken along the line A-A in FIG. 1(a). FIG. 2(a) is a cross-sectional view taken along the line B-B in FIG. 1(a), and FIG. 2(b) is an enlarged cross-sectional view of the periphery of the hole. The stacking direction of each layer on the substrate 10 is the Z direction, the direction in which the lower electrode 12 is drawn out from the resonance region 28 is the X direction, and the plane direction perpendicular to the X direction is the Y direction. FIG. 1(a) mainly illustrates the thin film 18, the hole 19, the detection unit 22, and the guide 26, with the thin film 18 indicated by a thick dashed line. In FIG. 1(b), the widths Wy in the Y direction of the lower electrode 12 and the upper electrode 16 are approximately the same. However, for ease of understanding, the widths Wy in the X and Y directions of the lower electrode 12 are shown slightly wider than the width of the upper electrode 16 in the Y direction, and the resonance region 28 is indicated by cross-hatching.

As shown in Figures 1(a) to 2(a), the detection device 100 includes a piezoelectric thin-film resonator 20. This piezoelectric thin-film resonator 20 has a substrate 10 with a rectangular (here, rectangular) planar shape and the following laminated film 15 provided on the substrate 10. The laminated film 15 includes an acoustic reflection film 11, a lower electrode 12, a piezoelectric layer 14, an upper electrode 16, a protective film 17, and a connection layer 21 laminated on the substrate 10. The acoustic reflection film 11 is formed by alternating low-acoustic-impedance films 11a and high-acoustic-impedance films 11b. By setting the thickness of each of the films 11a and 11b to approximately 1/4 of the wavelength of the elastic wave, the elastic wave is reflected by the acoustic reflection film 11. Note that in this case, the bottom layer of the acoustic reflection film 11 is the high-impedance film 11b, and the top layer is the low-impedance film 11a.

The substrate 10 and the laminated film 15 are provided with a resonance region 28 (first region), region 29a (second region), and region 29b (third region). The resonance region 28 has a rectangular planar shape with its long sides extending in the X direction and is located in the center of the substrate 10. Regions 29a and 29b are located on both sides of the resonance region 28 in the X direction and serve as pads. The lower electrode 12 has a rectangular planar shape with its long sides extending in the X direction, and extends continuously in the +X direction from the resonance region 28 to region 29a with a predetermined width Wy. The upper electrode 16 has a rectangular planar shape with its long sides extending in the X direction, and extends continuously in the -X direction from the resonance region 28 to region 29b with a predetermined width Wy. The region where the lower electrode 12 and upper electrode 16 overlap, sandwiching at least a portion of the piezoelectric layer 14, is the resonance region 28. The width of the resonance region 28 in the X direction is Wx, and the width of the resonance region 28 in the Y direction is Wy. Elastic waves such as thickness-extensional vibration mode or thickness-shear vibration mode resonate in the laminated film 15 within the resonance region 28. Note that the rectangular shape here does not have to be a geometric rectangle; opposing sides may deviate from parallelism by about 10°. The corners may also be rounded.

The protective film 17 protects the upper electrode 16 and piezoelectric layer 14 from moisture and other contaminants, but is not required. Guides 26 are provided on both sides of the resonance region 28 in the Y direction. As shown in FIG. 2(a), the lower portions of the guides 26 are provided in grooves 27 (second grooves) formed by patterning and removing the laminated film 15. In other words, the guides 26 cover two opposing sidewalls of the patterned laminated film 15, while their upper surfaces are higher than the upper surface of the thin film 18. As shown in FIG. 1(a), the guides 26 extend to the short sides of the substrate 10 in the X direction. As a result, as shown in FIG. 2(a), a groove 27a (first groove) having a width Wy is formed between the two guides 26. As will be described later, a liquid containing an analyte is placed or flows in the groove 27a between the guides 26. Note that because the guides 26 are formed by patterning the patterned laminated film 15, the guides 26 may also cover the surface of the laminated film 15.

A thin film 18 is provided on the protective film 17 in the resonance region 28. The thin film 18 has a plurality of holes 19 penetrating the thin film 18. Detectors 22 are provided within the plurality of holes 19.

As shown in Figure 2(b), a detection unit 22 is provided within the hole 19 of the thin film 18. The detection unit 22 includes a connection unit 23 and an antibody 24. The antibody 24 is an immunoglobulin, such as IgG (Immunoglobulin G) or IgE. The antibody 24 includes an Fc (Fragment Crystallizable) region 24a and a Fab (Fragment Antigen Binding) region 24b. The latter Fab region 24b is a region that binds to an antigen 25. The lower end of the connection unit 23 does not bind to the surface of the thin film 18 but binds to the surface of the connection layer 21, which forms the bottom of the hole 19, and the upper end binds to the Fc region 24a of the antibody 24. In other words, the lower end of the connection unit 23 can be said to bind to the surface of the connection layer 21 via the hole 19. As a result, the antibody 24 is fixed to the connection layer 21 via the connection unit 23. The diameter of the hole 19 is set so that a fixed number of antibodies 24, in this case one antibody 24, can bind to one hole 19.

When the antigen 25 binds to the antibody 24 due to an antigen-antibody reaction, the mass added to the laminated film 15 increases, lowering the resonant frequency of the piezoelectric thin film resonator 20. This change in resonant frequency allows the antigen 25 to be detected. The antigen 25 is a protein in a virus or bacterium, etc., to which the antibody 24 binds, or any other protein itself. By making the Fab region 24b a protein that binds to a specific antigen 25, the specific antigen 25 binds to the antibody 24. For example, a monoclonal antibody can be used as the antibody 24.

Substrate 10 is, for example, a silicon substrate, sapphire substrate, quartz substrate, glass substrate, ceramic substrate, or GaAs substrate. Film 11a is, for example, a silicon oxide film or silicon nitride film, and film 11b is, for example, a tungsten film, tantalum film, molybdenum film, or ruthenium film.

The bottom electrode 12 and top electrode 16 are single layer films of, for example, ruthenium (Ru), chromium (Cr), aluminum (Al), titanium (Ti), copper (Cu), molybdenum (Mo), tungsten (W), tantalum (Ta), platinum (Pt), rhodium (Rh), or iridium (Ir), or stacked films made of multiple types of these films. As an example, the bottom electrode 12 and top electrode 16 are ruthenium films.

The piezoelectric layer 14 may be, for example, an aluminum nitride (AlN) film, a zinc oxide (ZnO) film, a gallium nitride (GaN) film, a lead zirconate titanate (PZT) film, a lead titanate ( _PbTiO3 ) film, a lithium tantalate ( _LiTaO3 ) film, or a lithium niobate ( _LiNbO3 ) film. As an example, the piezoelectric layer 14 is mainly composed of aluminum nitride (AlN) with a principal axis in the (002) direction.

The protective film 17 is an insulating film such as a silicon oxide film, silicon nitride film, or silicon nitride oxide film. The material of the connection layer 21 may be any material that easily bonds the connection portion 23 to its surface and is resistant to corrosion by the liquid containing the sample, such as gold. The connection portion 23 is a protein, such as a self-assembled monolayer or linker protein, with one end binding to a metal layer such as a gold layer and the other end binding to the antibody 24. The thin film 18 is a film, such as a silicon film, in which holes 19 can be easily formed. The material of the thin film 18 is any material that easily bonds the connection portion 23 to its surface and is resistant to corrosion by the liquid containing the sample, such as silicon. If the protective film 17 is made of a material to which the connection portion 23 easily bonds on its upper surface, the connection layer 21 may not be provided.

The planar shapes of the thin film 18 and the connecting layer 21 may be the same as or different from the planar shape of the resonance region 28. The thin film 18 and the connecting layer 21 may be larger or smaller than the resonance region 28.

The thickness of the thin film 18 is, for example, 1 nm to 100 nm, and is, for example, 10 nm. The diameter of the holes 19 is, for example, 1 nm to 100 nm, and is, for example, 20 nm. By appropriately adjusting the diameter of the holes 19, it is possible to bond the connection portions 23 to the connection layer 21 within the holes 19 to the extent that one antibody 24 binds. The diameter of the holes 19 may be increased to bond two or more antibodies 24 to the connection layer 21 within one hole 19. Note that in FIG. 1( a), the holes 19 arranged in the thin film 18 are preferably arranged in a matrix of substantially the same size, so that the number of antibodies 24 can be specified. The density of the holes 19 is, for example, 10 to 10,000/μm ² , and is, for example, 600/μm ^2. By adjusting the density of the holes 19, it is possible to control the number of antibodies 24 that bind to the protective film 17 within the resonance region 28.

The guide 26 is made of a resin such as silicone resin. In Figure 2(a), the side of the groove 27 in the laminate film 15 and the side of the guide 26 are flush with each other, and the guide 26 does not run over the laminate film 15. This guide 26 arrangement is ideal, as it does not take into account pattern misalignment in manufacturing methods such as photolithography. In reality, the side of the groove 27 in the laminate film 15 may separate from the side of the guide 26, or the guide 26 may run over the laminate film 15.

Figure 2(c) is another example of a cross-sectional view taken along line B-B in Figure 1(a), showing an enlarged view of the laminated film 15 and the guide 26. For ease of understanding, the number of holes 19 in the Y direction has been reduced to four from Figures 1(a) and 2(a), and the detection units 22 inside the holes 19 are not shown.

As shown in FIG. 2(c), the upper portion of the guide 26 rides up onto the peripheral edge of the thin film 18. This prevents liquid from seeping into the gap between the side of the groove 27 in the laminated film 15 and the side of the guide 26, or into the interface between the layers of the laminated film 15. The rectangular thin film 18 has a row 19a (see FIG. 2(c)) of holes 19 arranged in the X direction near the long side on the +Y side in FIG. 1(a) (see FIG. 2(c)), and a row B (see FIG. 2(c)) of holes 19 arranged in the X direction near the long side on the -Y side (see FIG. 2(c)). As shown in FIG. 2(c), the upper portion of the guide 26 does not cover the holes 19 in rows 19a and 19b, but covers the peripheral edge of the thin film 18 so as to terminate between the side of the groove 27 and row 19a or 19b. To achieve this, it is preferable to make the distance D1 between the side of the groove 27 and row 19a or 19b greater than the distance D2 between the holes 19 in the Y direction.

By flowing a liquid containing the specimen between the guides 26, the liquid containing the specimen can be efficiently moved onto the thin film 18. If the planar shape of the thin film 18 and connection layer 21 is rectangular and guides 26 are formed along the two long sides of the rectangle on the outside, the specimen (antigen) can be made to act on the antibody 24 more efficiently. Furthermore, when the liquid containing the specimen flows onto the thin film 18 and connection layer 21, the rectangular guides 26 cause the liquid to flow in layers. In this case, if the planar shape of the thin film 18 and connection layer 21 is rectangular, multiple holes 19 will be uniformly arranged at the points where the liquid passes, allowing the specimen to act on the antibody 24 efficiently.

A driving substance may be applied to the thin film 18, and the analyte may be moved onto the thin film 18 by the motor protein. In this case, the guide 26 can also be used to efficiently move the analyte. Because the motor protein moves the analyte in a specific direction, efficient analyte movement is achieved by forming the thin film 18 and connection layer 21 in a rectangular planar shape with the long sides of the rectangle aligned with the direction of analyte movement. Therefore, it is preferable to form the thin film 18 and connection layer 21 in a rectangular planar shape and the guide 26 in a rectangular planar shape along the long sides of the thin film 18 and connection layer 21 on the outside of the two long sides. If the analyte contains an antigen 25, the antigen 25 binds to the antibody 24, increasing the mass of the laminated film 15. This reduces the resonant frequency of the piezoelectric thin film resonator 20. Alternatively, a liquid containing the analyte may be dropped onto the thin film 18. In this case, if the guide 26 is positioned along the four sides of the thin film 18 and surrounds it, the liquid containing the analyte can be retained on the thin film 18, improving detection accuracy.

According to Example 1, a thin film 18 having a plurality of holes 19 is provided on a resonance region 28 where elastic waves resonate. In each of the plurality of holes 19, the antibodies 24 connect to the resonance region 28 without going through the thin film 18. This makes it possible to control the number of antibodies 24 immobilized in the resonance region 28 by adjusting the density of the holes 19. This makes it possible to suppress variation in the number of antibodies 24 immobilized in the resonance region 28 for each detection device 100, thereby suppressing variation in detection results. Note that the thin film 18 only needs to be able to connect the antibodies 24 to the resonance region 28 in each of the plurality of holes 19.

Although multiple antibodies 24 may be provided for one hole 19, it is preferable to adjust the diameter (or area) of the hole 19 so that one antibody 24 is provided for one hole 19. In this way, the number of holes 19 in the resonance region 28 corresponds to the number of antibodies 24.

The multiple holes 19 may be arranged regularly or irregularly. In either case, the number of antibodies 24 within the resonance region 28 can be set by setting the number of holes 19 within the resonance region 28 and the diameter of the holes 19.

It is preferable that the diameter (or area) of the multiple holes 19 is uniform, but the diameter (or area) of the multiple holes 19 may be different. By providing a guide 26, the liquid containing the sample can be efficiently moved over the resonance region 28. The width Wx of the resonance region 28 in the long side direction is preferably 1.5 times or more, and more preferably 2 times or more, the width Wy in the short side direction.

As in Example 1, a piezoelectric thin-film resonator 20 can be used as the resonator. In this case, the resonance region 28 is the region where the lower electrode 12 and upper electrode 16 overlap, sandwiching at least a portion of the piezoelectric layer 14.

[First Modification of First Embodiment: Example of Connecting Bulk Film Resonators in Series]
Modification 1 is an example in which a plurality of piezoelectric thin film resonators are connected in series. Fig. 3(a) is a plan view of detection device 102 according to Modification 1, and Fig. 3(b) is a cross-sectional view taken along line A-A in Fig. 3(a). Fig. 3(a) mainly illustrates thin film 18, hole 19, detection unit 22, and guide 26, with thin film 18 indicated by a thick dashed line.

As shown in Figures 3(a) and 3(b), the detection device 102 has piezoelectric thin-film resonators 20a and 20b mounted on a substrate 10. The resonance region 28a of the piezoelectric thin-film resonator 20a and the resonance region 28b of the piezoelectric thin-film resonator 20b are disposed between guides 26. As shown in Figure 3(b), the lower electrodes 12 of the piezoelectric thin-film resonators 20a and 20b are disposed continuously and integrally from the short side on the -Y side to the short side on the +Y side of the substrate 10 without being separated. On the other hand, the upper electrode 16 is disposed separately in two, on the left and right. Therefore, the piezoelectric thin-film resonators 20a and 20b are formed separated into two, on the -X side and the +X side, with the center of the substrate 10 interposed between them. As a result, the piezoelectric thin-film resonators 20a and 20b are connected in series between the pad connected to the upper electrode 16 on the -X side and the pad connected to the upper electrode 16 on the +X side. The two upper electrodes 16 may be provided integrally and not separated, and the lower electrode 12 may be provided separated into two.

As in Example 1, when one piezoelectric thin film resonator 20 (Example 1) and series-connected piezoelectric thin film resonators 20a and 20b (Variation 1 of Example 1) have the same impedance, the total area of the resonance regions 28a and 28b of the piezoelectric thin film resonators 20a and 20b can be four times the area of the resonance region 28 of the piezoelectric thin film resonator 20. Because the impedance preferable for a detection device is fixed, in Variation 1 of Example 1, the area of the thin film 18 can be four times larger than in Example 1. This improves the sensitivity of the detection device. Three or more piezoelectric thin film resonators may be connected in series.

The planar shape of the resonance regions 28a and 28b is rectangular, and the piezoelectric thin film resonators 20a and 20b are arranged in the direction of the long side of the rectangle (the X direction in Figure 3(a)). Guides 26 are provided on both sides of the resonance regions 28a and 28b, as well as the region between the resonance regions 28a and 28b. This allows the liquid containing the sample to be efficiently moved over the resonance regions 28a and 28b.

[Modification 2 of Example 1]
4A is a cross-sectional view of the detection device 104. The piezoelectric layer 14 shown in FIG. 4A is divided into a lower piezoelectric layer 14a and an upper piezoelectric layer 14b, and an insertion film 13 is provided between the lower piezoelectric layer 14a and the upper piezoelectric layer 14b in the resonance region 28. The insertion film 13 is a temperature compensation film, and the sign of the temperature coefficient of the elastic constant of the insertion film 13 is opposite to the sign of the temperature coefficient of the elastic constant of the piezoelectric layer 14. This makes it possible to suppress the temperature dependence of the resonance frequency and other parameters of the piezoelectric thin-film resonator 20. The insertion film 13 is, for example, a silicon oxide film or a silicon nitride oxide film.

[Modification 3 of Example 1]
Fig. 4(b) is a cross-sectional view of the detection device 105. As shown in Fig. 4(b), the detection device 105 does not include an acoustic reflection film 11, and instead includes a gap 11c in the substrate 10. When viewed from the thickness direction of the substrate 10, the resonance region 28 and the gap 11c overlap.

As in Example 1 and its Modifications 1 and 2, the piezoelectric thin film resonators 20, 20a, and 20b may be SMRs (Solidly Mounted Resonators) having an acoustic reflection film 11. As in Modification 3 of Example 1, the piezoelectric thin film resonators 20, 20a, and 20b may be FBARs (Film Bulk Acoustic Resonators) having an air gap 11c.

[Example 2: Example of using a surface acoustic wave resonator in a detection device]
Fig. 5(a) is a plan view of the detection device 106, and Fig. 5(b) is a cross-sectional view taken along line A-A in Fig. 5(a). The arrangement direction (horizontal direction) of the electrode fingers 34a and 34b is the X direction, the extension direction (vertical direction) of the electrode fingers 34a and 34b is the Y direction, and the normal direction of the piezoelectric substrate 30 is the Z direction. Fig. 5(a) mainly illustrates the reflector 33, IDT 37 (interdigital transducer), pads 39a and 39b, thin film 18, hole 19, detection unit 22, and guide 26, with the thin film 18 indicated by a thick dashed line and the reflector 33, IDT 37, and pads 39a and 39b indicated by cross-hatching.

As shown in Figures 5(a) and 5(b), the detection device 106 has a surface acoustic wave resonator 40 instead of the piezoelectric thin film resonator 20 shown in Figures 1(a) to 2(a). The surface acoustic wave resonator 40 has an IDT 37 and a reflector 33 provided on a piezoelectric substrate 30. The IDT 37 and the reflector 33 are formed from a metal film 31.

The IDT 37 has comb electrodes 36a and 36b. The comb electrode 36a (first comb electrode) has multiple electrode fingers 34a (first electrode fingers) and a bus bar 35a. The +Y side ends of the multiple electrode fingers 34a extending in the Y direction are connected to the bus bar 35a, and the bus bar 35a itself extends in the X direction. The comb electrode 36b (second comb electrode) has multiple electrode fingers 34b (second electrode fingers) and a bus bar 35b. The -Y side ends of the multiple electrode fingers 34b extending in the Y direction are connected to the bus bar 35b, and the bus bar 35b extends in the X direction. The region of the IDT 37 where the electrode fingers 34a and 34b overlap as viewed from the X direction is a resonance region 38 where acoustic waves resonate. In at least a portion of the resonance region 38, the electrode fingers 34a and 34b are arranged alternately.

Reflectors 33 are formed on both sides of the IDT 37 in the X direction. Within the resonance region 38, the acoustic waves excited by the IDT 37 propagate mainly in the X direction, and the reflectors 33 reflect the acoustic waves. The pitch of the electrode fingers 34a and the pitch of the electrode fingers 34b are λ. λ corresponds to the wavelength of the surface acoustic waves excited by the IDT 37. λ is twice the pitch D of the multiple electrode fingers 34a and 34b. Note that λ may be other than twice the pitch D.

A protective film 32 is provided on the piezoelectric substrate 30, covering the metal film 31. A connection layer 21 is provided on the protective film 32 in the resonance region 38. A thin film 18 is provided on the connection layer 21. A plurality of holes 19 are provided through the thin film 18 provided on the electrode fingers 34a and 34b. Antibodies 24 are provided within the plurality of holes 19. Guides 26 are provided on both sides of the surface acoustic wave resonator 40 in the Y direction, so that bus bars 35a and 35b are exposed from the guide 26. Of the two guides 26 extending in the X direction, the guide 26 on the +Y side has a wiring 41a provided below the guide 26, and a pad 39a exposed on the +Y side of the guide 26. The pad 39a is electrically connected to the bus bar 35a via the wiring 41a. The guide 26 on the -Y side has a wiring 41b provided below the guide 26, and a pad 39b exposed on the -Y side of the guide 26. Pad 39b is electrically connected to bus bar 35b via wiring 41b.

The piezoelectric substrate 30 is, for example, a lithium tantalate substrate, a lithium niobate substrate, or a quartz substrate, such as a single-crystal rotated Y-cut X-propagation lithium tantalate substrate or a single-crystal rotated Y-cut X-propagation lithium niobate substrate. The piezoelectric substrate 30 may be bonded directly or via an insulating layer to a support substrate such as a sapphire substrate, silicon substrate, spinel substrate, quartz substrate, or quartz substrate. The metal film 31 is primarily composed of at least one metal selected from the group consisting of aluminum, copper, and molybdenum. The protective film 32 is an insulating film such as a silicon oxide film, silicon nitride film, or silicon nitride oxide film. The materials of the thin film 18, the detection unit 22, and the guide 26 are the same as those in Example 1.

As in Example 2, in the surface acoustic wave resonator, a thin film 18 having multiple holes 19 is provided on a resonance region 38 in which electrode fingers 34a and 34b are alternately arranged. As in FIG. 2(b), in each of the multiple holes 19, the antibody 24 is connected to the resonance region 38 without passing through the thin film 18. As a result, when an antigen 25 binds to the antibody 24, the mass added to the electrode fingers 34a and 34b increases, and the resonance frequency of the surface acoustic wave resonator 40 decreases. This change in resonance frequency enables the antigen 25 to be detected. Furthermore, as in Example 1, variation in the number of antibodies 24 fixed to the resonance region 38 can be suppressed, thereby suppressing variation in detection results.

The resonance region 38 has a rectangular planar shape, and is provided with guides 26 on the outside of both long sides of the rectangle, each with an upper surface higher than the upper surface of the thin film 18. This allows the liquid containing the sample to be efficiently moved onto the resonance region 38.

[Modification 1 of Embodiment 2: Example of connecting multiple surface acoustic wave resonators in series]
Fig. 6(a) is a plan view of the detection device 108, and Fig. 6(b) is a cross-sectional view taken along line A-A in Fig. 6(a). Fig. 5(a) mainly illustrates the reflectors 33, 33a, IDTs 37a, 37b, pads 39a, 39b, thin film 18, hole 19, detection unit 22, and guide 26, with the thin film 18 indicated by a thick dashed line and the reflectors 33, 33a, IDTs 37a, 37b, and pads 39a and 39b indicated by cross-hatching.

As shown in Figures 6(a) and 6(b), two surface acoustic wave resonators 40a and 40b are provided on a piezoelectric substrate 30. Resonance regions 38a and 38b are provided between two guides 26. A reflector 33 is provided on the +X side of surface acoustic wave resonator 40a, and a reflector 33 is provided on the -X side of surface acoustic wave resonator 40b. A reflector 33a is provided between surface acoustic wave resonators 40a and 40b. The reflector 33a is shared by surface acoustic wave resonators 40a and 40b.

The bus bar 35b of the surface acoustic wave resonator 40a and the bus bar 35b of the surface acoustic wave resonator 40b are electrically connected via the reflector 33a. The bus bar 35a of the surface acoustic wave resonator 40a is electrically connected to the pad 39a via the wiring 41a, and the bus bar 35a of the surface acoustic wave resonator 40b is electrically connected to the pad 39b via the wiring 41b. As a result, the surface acoustic wave resonators 40a and 40b are connected in series between the pads 39a and 39b.

In this variant 1, the area of the thin film 18 can be four times larger than in the second embodiment, thereby improving the sensitivity of the detection device. Three or more surface acoustic wave resonators may be connected in series. Furthermore, the planar shape of the resonance regions 38a and 38b is rectangular, and guides 26 are provided on both sides of the resonance regions 38a and 38b. This allows the liquid containing the sample to be efficiently moved over the resonance regions 38a and 38b.

[Example 3: Example in which a propagation path through which elastic waves propagate is adopted in a detection device]
As a third embodiment, an example in which a propagation path through which an elastic wave propagates will be described. Fig. 7(a) is a plan view of the detection device 110, and Fig. 7(b) is a cross-sectional view taken along the line A-A in Fig. 7(a). The propagation direction of the elastic wave is defined as the X direction, the normal direction of the piezoelectric substrate 30 as the Z direction, and the direction parallel to the top surface of the piezoelectric substrate 30 and perpendicular to the X direction as the Y direction. Fig. 7(a) mainly illustrates the IDTs 37a, 37b, pads 39a to 39d, metal film 42, thin film 18, hole 19, detection unit 22, and guide 26, with the thin film 18 indicated by a thick dashed line, and the IDTs 37a, 37b, pads 39a to 39d, and metal film 42 indicated by cross-hatching.

As shown in Figures 7(a) and 7(b), in the detection device 110, IDTs 37a and 37b are provided on a piezoelectric substrate 30. The IDTs 37a and 37b are spaced apart. The region between region 48a in IDT 37a, where electrode fingers 34a and 34b are alternately arranged, and region 48b in IDT 37b, where electrode fingers 34a and 34b are alternately arranged, is propagation path 48 through which elastic waves propagate.

The bus bars 35a and 35b of IDT 37a are electrically connected to pads 39a and 39b, respectively, and the bus bars 35a and 35b of IDT 37b are electrically connected to pads 39c and 39d, respectively.

A metal film 42 is provided on the piezoelectric substrate 30 in the propagation path 48. The metal film 42 may be made of the same material as the metal film 31 that forms the IDTs 37a and 37b, or it may be made of a different material. The metal film 42 is provided for short-circuiting the electric field to suppress electrical sensitivity in the propagation path 48. The metal film 42 does not have to be provided. A protective film 32 is provided on the metal film 42. A thin film 18 is provided on the protective film 32. A plurality of holes 19 are provided through the thin film 18. Antibodies 24 are provided within the plurality of holes 19. Guides 26 are provided on both sides of the propagation path 48 and the IDTs 37a and 37b in the Y direction.

The materials of the piezoelectric substrate 30, metal film 31, protective film 32, thin film 18, detection unit 22, and guide 26 are the same as those in Examples 1 and 2.

When ground potential is supplied to pads 39a and 39c and a high-frequency signal is applied to pad 39d while pad 39c is at ground potential, IDT 37b excites an acoustic wave near the surface of piezoelectric substrate 30. The acoustic wave propagates near the surface of piezoelectric substrate 30 in propagation path 48 and reaches IDT 37a. IDT 37a generates a surface acoustic wave, which outputs a high-frequency signal to pad 39b while pad 39a is at ground potential.

In Example 2, a thin film 18 having multiple holes 19 is provided on a propagation path 48 through which elastic waves propagate. As in Figure 2(b), in each of the multiple holes 19, the antibody 24 is connected to the propagation path 48 without going through the thin film 18. In other words, the propagation path 48 serves as the bottom of the multiple holes 19, and the antibody 24 is connected to the bottom. When an antigen 25 binds to the antibody 24, the mass added to the propagation path 48 increases, and the speed of the elastic wave propagating through the propagation path 48 slows. This change in the speed of the elastic wave allows the antigen 25 to be detected. Furthermore, as in Examples 1 and 2, variation in the number of antibodies 24 fixed to the propagation path 48 can be suppressed, thereby suppressing variability in detection results.

As shown in Figures 7(a) and 7(b), a pair of comb electrodes 36a and 36b (first comb electrodes) of IDT 37b that transmits elastic waves, and a pair of comb electrodes 36a and 36b (second comb electrodes) of IDT 37a that receives elastic waves are provided on piezoelectric substrate 30. Propagation path 48 includes the piezoelectric substrate 30 between IDTs 37b and 37a. As a result, when antigen 25 binds to antibody 24, the mass added to propagation path 48 increases, changing the phase difference between the high-frequency signal input to IDT 37b and the high-frequency signal output to IDT 37a. This change in phase difference allows antigen 25 to be detected.

The propagation path 48 has a rectangular planar shape, and is provided with guides 26 on the outside of both long sides of the rectangle, each with an upper surface higher than the upper surface of the thin film 18. This allows the liquid containing the sample to be efficiently moved along the propagation path 48.

When viewed from the Z direction, the thin film 18 and the connection layer 21 may be the same size as the propagation path 48, or may be larger or smaller than the propagation path 48.

Example 4: Detection system
FIG. 8A is a block diagram of a detection system 112 according to a fourth embodiment. As shown in FIG. 8A, in the detection system 112 according to the fourth embodiment, the oscillation circuit 52 includes a resonator 50. The resonator 50 is the film bulk acoustic resonator 20 or the surface acoustic wave resonator 40 according to the first, second, and modified examples thereof. The oscillation circuit 52 outputs an oscillation signal having an oscillation frequency corresponding to the resonance frequency or anti-resonance frequency of the resonator 50. The detector 54 includes a measuring device 56 and a calculator 58. The measuring device 56 measures the frequency of the oscillation signal output by the oscillation circuit 52. The calculator 58 detects the antigen 25 based on the amount of change in the frequency of the oscillation signal measured by the measuring device 56. The detection system 112 according to the fourth embodiment can detect the antigen 25 as described above.

[Modification 1 of Example 4]
A first modification of the fourth embodiment is an example of a detection system using the third embodiment. FIG. 8B is a block diagram of a detection system 114 according to the first modification of the fourth embodiment. As shown in FIG. 8B, in the detection system 114 according to the first modification of the fourth embodiment, the transmitter 61 transmits a high-frequency signal to the IDT 37b of the detection device 110 according to the third embodiment. The receiver 62 receives the high-frequency signal from the IDT 37a of the detection device 110. The detector 64 includes a measuring device 66 and a calculator 68. The measuring device 66 measures the phase difference between the high-frequency signal transmitted by the transmitter 61 and the high-frequency signal received by the receiver 62. The calculator 68 detects the antigen 25 based on the amount of change in the phase difference measured by the measuring device 66. The detection system 114 according to the first modification of the fourth embodiment can detect the antigen 25 as described above.

Although the present invention has been described in detail above with reference to specific embodiments, the present invention is not limited to these specific embodiments, and various modifications and variations are possible within the scope of the invention as set forth in the claims.

REFERENCE SIGNS LIST 10 Substrate 11 Acoustic reflection film 12 Lower electrode 14 Piezoelectric layer 15 Laminated film 16 Upper electrode 17, 32 Protective film 18 Thin film 19 Hole 20, 20a, 20b Bulk acoustic wave resonator 21 Connection layer 22 Detection section 23 Connection section 24 Antibody 24a Fc region 24b Fab region 25 Antigen 26 Guide 28, 28a, 28b, 38, 38a, 38b Resonance region 30 Piezoelectric substrate 31, 42 Metal film 33, 33a Reflector 34a, 34b Electrode fingers 35a, 35b Bus bar 36a, 36b Comb-shaped electrode 37a, 37b IDT
40, 40a, 40b: surface acoustic wave resonator 48: propagation path

Claims (18)

a resonator having a resonance region in which an elastic wave resonates;
a thin film provided on the resonance region and having a plurality of holes;
Equipped with
A detection device comprising an antibody connected to the resonant region in each of the plurality of holes. The detection device described in claim 1, wherein the planar shape of the resonance region is rectangular, and a guide having an upper surface higher than the upper surface of the thin film is provided on the outside of both long sides of the rectangle. the resonator comprises a plurality of resonators;
one of the upper electrodes and the lower electrodes of the plurality of resonators is provided integrally and continuously, and the other of the upper electrodes and the lower electrodes is provided separately;
3. The detection device according to claim 1, wherein the plurality of resonators are connected in series between two pads connected to the other of the upper electrode and the lower electrode, which are provided separately . the resonator includes a piezoelectric layer and a first electrode and a second electrode sandwiching the piezoelectric layer;
The detection device according to claim 1 or 2, wherein the resonance region is a region where the first electrode and the second electrode overlap with at least a part of the piezoelectric layer sandwiched therebetween. the resonator includes a piezoelectric layer and a first electrode and a second electrode sandwiching the piezoelectric layer;
The detection device according to claim 3 , wherein the resonance region is a region where the first electrode and the second electrode overlap with at least a portion of the piezoelectric layer sandwiched therebetween. the resonator includes a piezoelectric substrate, a first comb electrode provided on the piezoelectric substrate and having a plurality of first electrode fingers, and a second comb electrode provided on the piezoelectric substrate and having a plurality of second electrode fingers;
The detection device according to claim 3 , wherein the resonance region is a region in which the plurality of first electrode fingers and the plurality of second electrode fingers are alternately arranged. the resonator includes a piezoelectric substrate, a first comb electrode provided on the piezoelectric substrate and having a plurality of first electrode fingers, and a second comb electrode provided on the piezoelectric substrate and having a plurality of second electrode fingers;
3. The detection device according to claim 1, wherein the resonance region is a region in which the plurality of first electrode fingers and the plurality of second electrode fingers are alternately arranged. a propagation path along which elastic waves propagate;
a thin film provided on the propagation path and having a plurality of holes;
Equipped with
A detection device comprising an antibody connected to the propagation path in each of the plurality of holes. 9. The detection device according to claim 8 , wherein the propagation path has a rectangular planar shape, and includes guides on the outsides of both long sides of the rectangle, the guides having upper surfaces higher than an upper surface of the thin film. a piezoelectric substrate;
a pair of first comb electrodes provided on the piezoelectric substrate for transmitting the acoustic waves;
a pair of second comb electrodes provided on the piezoelectric substrate and configured to receive the acoustic waves;
Equipped with
10. The detection device according to claim 8 , wherein the propagation path includes the piezoelectric substrate between the pair of first comb electrodes and the pair of second comb electrodes. 9. The detection device according to claim 1, wherein one of the antibodies is connected to one of the plurality of holes. The detection device described in claim 3, wherein one of the antibodies is connected to one of the multiple holes. 10. The detection device of claim 1 or 8 , wherein the antibody does not bind to the thin film. The detection device of claim 11 , wherein the antibody does not bind to the thin film. a substrate having a first region provided in a central portion and having a rectangular shape, and a second region and a third region provided on both sides of the first region in a direction of a long side of the rectangular shape;
the first region, and a lower electrode provided on the substrate continuously from the first region to the second region;
a piezoelectric layer provided on the substrate and the lower electrode continuously from the first region to the second region and the third region;
an upper electrode provided on the piezoelectric layer continuously from the first region to the third region;
a rectangular thin film provided on the upper electrode corresponding to the first region, the rectangular thin film corresponding to the first region;
an antibody provided at the bottom of a plurality of holes provided in the thin film;
two guides provided along two long sides of the rectangular shape of the first region, the upper surfaces of which are higher than the upper surface of the thin film;
A detection device in which the plurality of holes are exposed at the bottom surface of the first groove between the two guides. 16. The detection device according to claim 15, wherein the lower portions of the two guides are provided within second grooves provided in the piezoelectric layer, and the upper portions of the two guides overlap the thin film outside the second grooves. a resonator having a resonance region in which an elastic wave resonates;
a thin film provided on the resonance region and having a plurality of holes;
a connection layer for connecting the antibodies, the connection layer being provided under the plurality of holes so that the antibodies are disposed within the plurality of holes;
A detection device comprising: a propagation path along which elastic waves propagate;
a thin film provided on the propagation path and having a plurality of holes;
a connection layer for connecting the antibodies, the connection layer being provided under the plurality of holes so that the antibodies are disposed within the plurality of holes;
A detection device comprising: