Sensor apparatus

A sensor apparatus includes: an element substrate; a detecting section disposed on an upper surface of the element substrate, the detecting section including a reaction section having an immobilization film to detect an analyte; a first IDT electrode configured to generate an acoustic wave which propagates toward the reaction section, and a second IDT electrode configured to receive the acoustic wave which has passed through the reaction section; and a protective film located on the upper surface of the element substrate so as to cover the first IDT electrode, the second IDT electrode, and at least part of the immobilization film, the protective film extending between and contacting with the immobilization film and at least one of the first IDT electrode and the second IDT electrode.

TECHNICAL FIELD

The present invention relates to a sensor apparatus which is capable of measurement on the properties or constituents of an analyte liquid.

BACKGROUND ART

There is known a sensor apparatus which measures the properties or constituents of an analyte liquid by detecting an object to be detected contained in the analyte liquid with use of a detecting element such as a surface acoustic wave device (refer to Patent Literatures 1 to 3, for example).

For example, in a sensor apparatus employing a surface acoustic wave device, a reaction section which undergoes reaction with a component contained in a sample of an analyte liquid, is disposed on a piezoelectric substrate, and the properties or constituents of the analyte liquid are detected by measuring variation in a surface acoustic wave propagating through the reaction section. Such a measurement method using the surface acoustic wave device or the like has the advantage over other measurement methods (for example, enzymatic method) in that it lends itself to simultaneous detection of a plurality of characteristics to be measured.

However, such a conventional sensor apparatus is prone to losses of surface-acoustic-wave energy occurring at a boundary between the piezoelectric substrate and a constituent component disposed on the piezoelectric substrate, which results in difficulties in detecting an object to be detected contained in an analyte with high sensitivity.

CITATION LIST

Patent Literature

SUMMARY OF INVENTION

Technical Problem

Thus, there is a demand for a sensor apparatus which is capable of detecting an object to be detected contained in an analyte liquid with excellent sensitivity.

Solution to Problem

A sensor apparatus according to an embodiment of the invention includes: an element substrate; a detecting section disposed on an upper surface of the element substrate, the detecting section including a reaction section having an immobilization film to detect an analyte; a first IDT electrode configured to generate an acoustic wave which propagates toward the reaction section, and a second IDT electrode configured to receive the acoustic wave which has passed through the reaction section; and a protective film located on the upper surface of the element substrate so as to cover the first IDT electrode, the second IDT electrode, and at least part of the immobilization film, the protective film extending between and contacting with the immobilization film and at least one of the first IDT electrode and the second IDT electrode.

Advantageous Effects of Invention

In accordance with the sensor apparatus according to the embodiment of the invention, in the element substrate, the protective film located on the upper surface of the element substrate covers, in addition to the first IDT electrode and the second IDT electrode, at least part of the immobilization film, the protective film extending between and contacting with the immobilization film and at least one of the first IDT electrode and the second IDT electrode. Accordingly, it is possible to reduce losses of surface-acoustic-wave energy at a boundary between the element substrate and a constituent component disposed on the element substrate, and thereby detect an object to be detected contained in an analyte with high sensitivity.

DESCRIPTION OF EMBODIMENTS

Hereinafter, embodiments of a sensor apparatus according to the invention will be described with reference to drawings. In each drawing to be referred to in the following description, like constituent members are identified with the same reference symbols. Moreover, for example, the size of each member and the distance between the individual members are schematically shown in each drawing and may therefore differ from the actual measurements.

A sensor apparatus100according to an embodiment of the invention will be described with reference toFIGS. 1 to 6.

As shown inFIG. 1, the sensor apparatus100according to the embodiment mainly comprises a first cover member1, an intermediate cover member1A, a second cover member2, and a detecting element3.

Specifically, as shown inFIG. 1(b), the sensor apparatus100has an inlet port14for admission of an analyte liquid, and a flow channel15which is in communication with the inlet port14, is surrounded by the intermediate cover member1A and the second cover member2, and extends at least to a reaction section13. In this embodiment, the intermediate cover member1A and the second cover member2are greater in width than the detecting element3. This allows an analyte liquid to flow so as to cover the entire surface of the detecting element3effectively.

FIG. 1(c)which shows sectional views of the construction shown inFIG. 1(a), wherein there are successively shown, in top-to-bottom order, a section taken along the line a-a, a section taken along the line b-b, and a section taken along the line c-c. The inlet port14is formed so as to pass through the second cover member2in a thickness direction thereof.

As shown inFIGS. 1(a), 1(b)andFIG. 2(a), the first cover member1is shaped like a flat plate. The thickness of the first cover member1falls in the range of 0.1 mm to 1.5 mm, for example. The first cover member1has substantially a rectangular planar configuration. The longitudinal length of the first cover member1falls in the range of 1 cm to 8 cm, for example, and, the widthwise length of the first cover member1falls in the range of 1 cm to 3 cm, for example.

As the material for forming the first cover member1, for example, a glass-epoxy material, paper, plastics, celluloid, ceramics, non-woven fabric, and glass can be used. The use of plastics is desirable from the standpoints of required strength and cost.

Moreover, as shown inFIGS. 1(a) and 2(a), on the upper surface of the first cover member1are formed a terminal6and a wiring line7routed from the terminal6to a position near the detecting element3.

The terminal6is formed on either side of the detecting element3in a width direction on the upper surface of the intermediate cover member1A. Specifically, at least part of the terminals6arranged relative to the detecting element3lies closer to the inlet port14than an inlet port14-side end of the detecting element3. Moreover, in the range of four terminals6placed in an array on one side of the detecting element3with respect to a direction longitudinally of the flow channel15, the wiring lines7connected to two outer terminals6, respectively, have substantially the same length, and, the wiring lines7connected to the other two inner terminals6, respectively, have substantially the same length. This makes it possible to reduce variations in signals obtained by the detecting element3resulting from the difference in length between the wiring lines7. In this case, with a construction in which the wiring lines7are connected so that a potential difference occurs between grounding (earthing) wiring, which is constituted by one pair of the wiring lines7having substantially the same length, and signal wiring, which is constituted by the other pair of the wiring lines7having substantially the same length, for example, upon application of a predetermined voltage from external measurement equipment to a first IDT electrode11as shown inFIG. 4via the wiring line7, a first extraction electrode19, and so forth, it is possible to reduce the signal variations, and thereby achieve an improvement in detection reliability.

When measurement is made on the sensor apparatus100with external measuring equipment (not shown in the drawing), the terminal6and the external measuring equipment are electrically connected to each other. Moreover, the terminal6and the detecting element3are electrically connected to each other via the wiring line7, for example.

A signal issued from the external measuring equipment is inputted to the sensor apparatus100via the terminal6, and, a signal issued from the sensor apparatus100is outputted to the external measuring equipment via the terminal6.

In this embodiment, as shown inFIG. 1(b), the intermediate cover member1A is placed in juxtaposition to the detecting element3on the upper surface of the first cover member1. Moreover, as shown inFIGS. 1(a) and 3(c), the intermediate cover member1A and the detecting element3are arranged with a spacing. Note that the intermediate cover member1A and the detecting element3may be arranged with their sides kept in contact with each other.

As shown inFIGS. 1(b) and 2(b), the intermediate cover member1A has the form of a flat frame constructed of a flat plate having a recess-forming area4, and, the thickness of the intermediate cover member1A falls in the range of 0.1 mm to 0.5 mm, for example.

In this embodiment, as shown inFIG. 1(b), the recess-forming area4is an area located downstream of a first upstream portion1Aa. The intermediate cover member1A is joined to the flat plate-shaped first cover member1, whereupon an element placement section5is defined by the first cover member1and the intermediate cover member1A. That is, the upper surface of the first cover member1located inside the recess-forming area4becomes the bottom surface of the element placement section5, and, the inner wall of the recess-forming area4becomes the inner wall of the element placement section5.

As shown inFIGS. 1 and 3, in a region located downstream of the detecting element3, the intermediate cover member1A does not exist on the first cover member1. This makes it possible to inhibit or reduce generation of bubbles in a part of the intermediate cover member1A located downstream of the first upstream portion1Aa. In consequence, an analyte liquid can be delivered in a bubble-free state onto the detecting element3, thus achieving an improvement in sensitivity or accuracy in detection.

As the material for forming the intermediate cover member1A, for example, resin (including plastics), paper, non-woven fabric, and glass can be used. More specifically, resin materials such as polyester resin, polyethylene resin, acrylic resin, and silicone resin are desirable for use. The first cover member1and the intermediate cover member1A may be formed of either the same material or different materials.

Moreover, in this embodiment, the intermediate cover member1A includes the first upstream portion1Aa. As shown inFIGS. 1(a) and 1(b), when viewed from above, the detecting element3is located on the downstream side relative to the first upstream portion1Aa. In this case, when an analyte liquid flows out over the detecting element3after passing through a part of the flow channel15which corresponds to the first upstream portion1Aa, an excess of the analyte liquid over an amount of the analyte liquid required for measurement flows downstream, wherefore an adequate amount of the analyte liquid can be fed to the detecting element3.

As shown inFIGS. 1(b) and 3(e), the second cover member2covers the detecting element3, and is joined to the first cover member1and the intermediate cover member1A. As shown inFIGS. 1(b) and 1(c), the second cover member2comprises a third substrate2aand a fourth substrate2b.

As the material for forming the second cover member2, for example, resin (including plastics), paper, non-woven fabric, and glass can be used. More specifically, resin materials such as polyester resin, polyethylene resin, acrylic resin, and silicone resin are desirable for use. The first cover member1and the second cover member2may be formed of the same material. In this case, deformation resulting from the difference in thermal expansion coefficient between the first and second cover members can be minimized. The second cover member2may either be joined only to the intermediate cover member1A or be joined to both of the first cover member1and the intermediate cover member1A.

As shown inFIGS. 1(c), 3(c), and 3(d), the third substrate2ais bonded to the upper surface of the intermediate cover member1A. The third substrate2ais shaped like a flat plate having a thickness of 0.1 mm to 0.5 mm, for example. The fourth substrate2bis bonded to the upper surface of the third substrate2a. The fourth substrate2bis shaped like a flat plate having a thickness of 0.1 mm to 0.5 mm, for example. By joining the fourth substrate2bto the third substrate2a, as shown inFIG. 1(b), the flow channel15is formed on the lower surface of the second cover member2. The flow channel15extends from the inlet port14to at least a region immediately above the reaction section13, and has a rectangular sectional profile, for example. The third substrate2aand the fourth substrate2bmay be formed of the same material, or, an unitary construction of the combined third and fourth substrates2aand2bmay be used.

In this embodiment, as shown inFIG. 1(b), neither the intermediate cover member1A nor the third substrate2aexists at an end of the flow channel15, and, a gap left between the fourth substrate2band the first cover member1serves as an air release hole18. The air release hole18is provided to let air and so forth present in the flow channel15go out. The opening of the air release hole18may be given any shape which is capable of release of air present in the flow channel15, and thus, for example, a circular shape or a rectangular shape may be adopted. For example, in the case of an air release hole18having a circular opening, the opening is designed to have a diameter of less than or equal to 2 mm, and, in the case of an air release hole18having a rectangular shape, the air release hole18is designed so that each side of the rectangle has a length of less than or equal to 2 mm.

The first cover member1, the intermediate cover member1A, and the second cover member2may be formed of the same material. In this case, since these members are substantially uniform in thermal expansion coefficient, it is possible to reduce deformation of the sensor apparatus100caused by the difference in thermal expansion coefficient among the members. Moreover, in the case of application of a biomaterial to the reaction section13, some biomaterials are prone to quality degradation under external light such as ultraviolet rays. In this regard, it is advisable to use an opaque material having light-blocking capability as the material for forming the first cover member1, the intermediate cover member1A, and the second cover member2. On the other hand, when the reaction section13is substantially free of external light-induced quality degradation, the second cover member2constituting the flow channel15may be formed of a nearly transparent material. In this case, the condition of an analyte liquid flowing through the interior of the flow channel15can be visually checked, thus permitting the combined use of an optical detection system.

The detecting element3in the present embodiment will be described with reference toFIGS. 1 to 6, in particular,FIGS. 4 to 6.

FIG. 6is an enlarged sectional view showing part of the sensor apparatus shown inFIG. 5, and more specificallyFIG. 6(a)is an enlarged view of the principal portion of the detecting element shown inFIG. 5(b), andFIG. 6(b)is an enlarged view of part of the principal portion shown inFIG. 6(a).

As shown inFIG. 6, the detecting element3generally comprises an element substrate10adisposed on the upper surface of the first cover member1, and at least one detecting section10b, disposed on the upper surface of the element substrate10a, for detecting an object to be detected (detection target) contained in an analyte liquid.

Specifically, as shown inFIG. 6, the detecting element3in this embodiment comprises: the element substrate10a; the detecting section10bdisposed on the upper surface of the element substrate10a, the detecting section10bincluding the reaction section13having an immobilization film13ato detect an object to be detected, a first IDT (InterDigital Transducer) electrode11configured to generate an acoustic wave which propagates toward the reaction section13, and a second IDT electrode12configured to receive the acoustic wave which has passed through the reaction section13; and a protective film28located on the upper surface of the element substrate10aso as to cover the first IDT electrode11, the second IDT electrode12, and at least part of the immobilization film13a, the protective film28extending between and contacting with the immobilization film13aand at least one of the first IDT electrode11and the second IDT electrode12.

The detecting section10bincludes, in addition to the first IDT electrode11, the reaction section13, and the second IDT electrode12, the protective film28, a first extraction electrode19, a second extraction electrode20, and so forth.

The element substrate10ais constructed of a substrate of single crystal having piezoelectric properties such for example as quartz, lithium tantalate (LiTaO3) single crystal, or lithium niobate (LiNbO3) single crystal. The planar configuration and dimensions of the element substrate10aare suitably determined. The element substrate10ahas a thickness of 0.3 mm to 1 mm, for example.

In this embodiment, a surface roughness of the upper surface of the immobilization film13ais greater than a surface roughness of a region where the immobilization film13ais located in the element substrate10a. In this case, for example, in immobilizing aptamers and antibodies, which will hereafter be described, onto the surface of the element substrate10a, it is possible to increase bindability of the aptamers and antibodies to the surface of the immobilization film13a, thus enabling high-density immobilization. This makes it possible to improve detection sensitivity of the object to be detected.

As shown inFIGS. 4 and 6, the first IDT electrode11comprises a pair of comb electrodes. Each comb electrode includes two bus bars opposed to each other and a plurality of electrode fingers11ato11e(11a,11b,11c,11d, and11e) each extending from corresponding one of the bus bars toward the other. A pair of the comb electrodes is disposed so that the plurality of electrode fingers11ato11eare arranged in an interdigitated pattern. The second IDT electrode12is similar in configuration to the first IDT electrode11. The first IDT electrode11and the second IDT electrode12constitute a transversal IDT electrode.

The first IDT electrode11is intended for generation of predetermined surface acoustic wave (SAW), and the second IDT electrode12is intended for reception of the SAW generated in the first IDT electrode11. The first IDT electrode11and the second IDT electrode12are positioned on the same straight line so that the SAW generated in the first IDT electrode11can be received by the second IDT electrode12. Frequency response characteristics can be designed on the basis of the number of the electrode fingers of the first IDT electrode11and the second IDT electrode12, the distance between the adjacent electrode fingers, the crossing width of the electrode fingers, etc., used as parameters.

There are various modes of vibration for SAW to be excited by the IDT electrode. In the detecting element3according to the embodiment, for example, a vibration mode of transversal waves called SH waves is utilized. The frequency of SAW may be set within the range of several megahertz (MHz) to several gigahertz (GHz), for example. It is advisable to set the SAW frequency within the range of several hundred MHz to 2 GHz from the practicality standpoint, and also in the interest of miniaturization of the detecting element3that will eventually be conducive to miniaturization of the sensor apparatus100. The thicknesses and lengths of predetermined constituent elements in the embodiment will be described with respect to the case where the center frequency of SAW falls in a several hundred MHz range.

The first IDT electrode11and the second IDT electrode12may be of a single-layer structure composed of, for example, a gold thin layer, or may be of a multilayer structure such as a three-layer structure composed of a titanium layer, a gold layer, and a titanium layer, or a three-layer structure composed of a chromium layer, a gold layer, and a chromium layer, in the order, named, from the element-substrate10aside.

A thickness of the first IDT electrode11and the second IDT electrode12may be set to fall within the range of 0.005λ to 0.015λ, for example.

An elastic member may be disposed externally of the first IDT electrode11and the second IDT electrode12in a SAW propagation direction (width direction) to reduce SAW reflection.

As shown inFIGS. 4 and 6, the reaction section13is disposed between the first IDT electrode11and the second IDT electrode12.

In this embodiment, the reaction section13comprises the immobilization film13a(for example, a metallic film) formed on the upper surface of the element substrate10a, and a reactant immobilized on the upper surface of the immobilization film13afor reaction with an object to be detected. The reactant is suitably selected depending on an object to be detected which is a detection target. For example, when the object to be detected is a specific cell or living tissue present in an analyte liquid, an aptamer composed of a nucleic acid or a peptide can be used as the reactant. For example, in this embodiment, while a reaction between the reactant and the object to be detected may be a binding reaction of the object to be detected and the reactant such as a chemical reaction or an antigen-antibody reaction, the reaction is not so limited, but may be a binding reaction of the object to be detected and the reactant under the interaction of the object to be detected with the reactant, or an adsorption reaction of the object to be detected to the reactant. Exemplary of a reactant which can be used for the reaction section13in the embodiment is one which causes, by its presence, variation in surface-acoustic-wave characteristics according to the type or content of the object to be detected when an analyte is brought into contact with the reaction section13. The reaction section13is intended for causing reaction with an object to be detected contained in an analyte liquid, and, more specifically, upon contact of an analyte liquid with the reaction section13, a specific object to be detected contained in the analyte liquid is bound to an aptamer adapted to the object to be detected.

The immobilization film13a(metallic film) may be of a single-layer structure composed of, for example, a gold layer, or may be of a multilayer structure such as a two-layer structure composed of a titanium layer and a gold layer situated on the titanium layer or a two-layer structure composed of a chromium layer and a gold layer situated on the chromium layer. Moreover, the immobilization film13amay be formed of the same material as a material used for the first IDT electrode11and the second IDT electrode12. In this case, the immobilization film13aand the first and second IDT electrodes11and12can be formed in the same process step. Instead of the above-mentioned metallic film, for example, an oxide film such as a SiO2film or TiO2film may be used as the material of construction of the immobilization film13a.

Given that the first IDT electrode11, the second IDT electrode12, and the reaction section13arranged in the width direction of the flow channel are grouped into a set, then, as shown inFIG. 4, two sets are provided in the sensor apparatus100according to the embodiment. In this case, by designing the reaction section13of one of the sets and the reaction section13of the other to undergo reaction with different detection targets, it is possible to detect two different objects to be detected by a single sensor apparatus.

In this embodiment, as shown inFIG. 6, the upper surface of the immobilization film13acomprises regions13a1which are covered with the protective film28and are at ends of the side of the first IDT electrode11and the side of the second IDT electrode12, respectively, and a region13a2of a center part which is not covered with the protective film28. An upper surface of the region13a1which is covered with the protective film28is at a higher level than an upper surface of the region13a2which is not covered with the protective film28. In this case, in the reaction section13, energy of SAW propagating between the first IDT electrode11and the second IDT electrode12tends to be further concentrated on the upper surface of the region13a2which is not covered with the protective film28in the upper surface of the immobilization film13a, wherefore an object to be detected can be detected with high sensitivity. As a specific example, as shown inFIG. 6(b), the upper surface of the immobilization film13amay be so inclined that a level of the upper surface becomes lower as approaching from the region13a1which is covered with the protective film28to the region13a2which is not covered with the protective film28.

In this embodiment, as shown inFIG. 6(b), the upper surface of the region13a1which is covered with the protective film28in the upper surface of the immobilization film13ais at substantially the same level as at least one of the upper surface of the first IDT electrode11and the upper surface of the second IDT electrode12. This makes it possible to reduce losses of energy when SAW propagating through the element substrate10ais transmitted from the first IDT electrode11via the immobilization film13ato the second IDT electrode12.

Moreover, the upper surface of the region13a2which is not covered with the protective film28in the upper surface of the immobilization film13ais at a lower level than at least one of the upper surface of the first IDT electrode11and the upper surface of the second IDT electrode12. In this case, in the reaction section13, energy of SAW propagating between the first IDT electrode11and the second IDT electrode12tends to be concentrated on the upper surface of the immobilization film13a, wherefore an object to be detected can be detected with even higher sensitivity.

In this embodiment, as shown inFIG. 6(b), a thickness of the region13a1which is covered with the protective film28of the immobilization film13ais greater than a thickness of the region13a2which is not covered with the protective film28thereof. In the immobilization film13a, given that the wavelength of SAW propagating between the first IDT electrode11and the second IDT electrode12is λ, then a thickness of the region13a1which is covered with the protective film28may be set to fall within, for example, the range of 0.005λ to 0.015λ, and, for example, and a thickness of the region13a2which is not covered with the protective film28may be set to be 0.01λ or below smaller than the thickness of the region13a1which is covered with the protective film28, and may thus be set to fall within the range of 0.004λ to 0.014λ. In this case, even if the region13a2which is not covered with the protective film28of the immobilization film13ahas a relatively small thickness, in the reaction section13, losses of energy of SAW propagating between the first IDT electrode11and the second IDT electrode12can be reduced. In addition to that, since the SAW energy tends to be concentrated on the upper surface of the region13a2which is not covered with the protective film28of the immobilization film13a, it is possible to detect an object to be detected with even higher sensitivity. As a specific example, as shown inFIG. 6(b), the immobilization film13amay be so shaped that its thickness becomes smaller as approaching from the region13a1which is covered with the protective film28to the region13a2which is not covered with the protective film28.

In this embodiment, the surface roughness of the upper surface of the region13a2which is not covered with the protective film28in the upper surface of the immobilization film13ais greater than the surface roughness of the upper surface of the first IDT electrode11and the surface roughness of the upper surface of the second IDT electrode12. In this case, since the surface area of the immobilization film13acan be increased, it is possible to immobilize reactants such as aptamers and antibodies onto the immobilization film13aat high densities, and thereby improve detection sensitivity of the object to be detected. a surface roughness of the upper surface of the region13a2which is not covered with the protective film28in the upper surface of the immobilization film13amay be set to fall within the range of 2.0 to 10.0 nm, for example, in terms of arithmetic average roughness Ra. The surface roughness of each constituent element may be determined by measurement using arithmetic average roughness Ra. In the case where a film or the like is disposed on a measurement target, for example, graphic analyses of the sectional profile of the measurement target are performed on the basis of a photograph of the section obtained by means of SEM (Scanning Electron Microscopy), TEM (Transmission Electron Microscopy), or otherwise, for surface roughness measurement. Moreover, when direct measurement of the measurement target is possible, the measurement may be effected with use of a commonly-used surface-roughness meter of contact type or non-contact type.

Moreover, it is advisable that the surface roughness of the upper surface of the region13a1which is covered with the protective film28in the upper surface of the immobilization film13ais substantially equal to the surface roughness of the upper surface of the first IDT electrode11and the surface roughness of the upper surface of the second IDT electrode12. This makes it possible to render the immobilization film13a, the first IDT electrode11, and the second IDT electrode12uniform in bondability to the protective film28.

As shown inFIG. 6, the protective film28is located on the upper surface of the element substrate10aso as to cover the first IDT electrode11and the second IDT electrode12. This makes it possible to inhibit an analyte liquid from contact with the first IDT electrode11and the second IDT electrode12, and thereby retard corrosion of the IDT electrodes caused by oxidation, for example. Examples of materials used for the protective film28include silicon oxide, aluminum oxide, zinc oxide, titanium oxide, silicon nitride, and silicon. Such a material is properly used as a major constituent, namely a component constituting the greatest proportion in mass, of a material for forming the protective film28, and is therefore not defined as the constituent material when mixed merely as impurities in very small amounts, for example.

Moreover, in this embodiment, as shown inFIG. 6, the protective film28also covers at least part of the immobilization film13a, and extends between and contacts with the immobilization film13aand at least one of the first IDT electrode11and the second IDT electrode12. This makes it possible to reduce losses of SAW energy at an interface between the element substrate10aand a constituent component disposed on the element substrate10a, and thereby detect an object to be detected contained in an analyte with high sensitivity. As a specific example, as shown inFIG. 6(b), the protective film28covers the ends of the immobilization film13alocated on the side of the first IDT electrode11and the side of the second IDT electrode12. This makes it possible to inhibit an analyte liquid from contact with the end of the immobilization film13aand thereby retard corrosion caused for example by oxidation, as well as to immobilize reactants such as aptamers and antibodies onto the central region13a2of the immobilization film13awhich is not covered with the protective film28and thereby ensure detection sensitivity of the object to be detected.

In this embodiment, as shown inFIG. 6(b), the protective film28extends between and contact with the immobilization film13aand at least one of the first IDT electrode11and the second IDT electrode12. As a specific example, as shown inFIG. 6(b), the protective film28is disposed so as to thoroughly fill the gap between the immobilization film13aand the first, second IDT electrode11,12disposed on the element substrate10a. In this case, the interposition of the protective film28between the immobilization film13aand the first, second IDT electrode11,12makes it possible to suppress acoustic impedance variation, and thereby minimize the influence of reflected waves entailed by the placement of other member, with consequent reduction in SAW energy losses.

As shown inFIGS. 4 and 6, the first IDT electrode11and the second IDT electrode12include a plurality of electrode fingers11ato11eand the plurality of electrode fingers12ato12e(12a,12b,12c,12d, and12e) which are spaced apart from each other, respectively, and, as shown inFIG. 6(b), the protective film28is made in continuous (connected) form so as to11eover, out of the plurality of electrode fingers11ato11e, as well as12ato12e, two adjacent electrode fingers, for example, the electrode fingers11aand11b, as well as12aand12b, and also over that part of the element substrate10alocated between the two electrode fingers11aand11b, as well as12aand12b. This makes it possible to inhibit occurrence of short-circuiting between the plurality of electrode fingers of the IDT electrode caused by an analyte liquid.

Moreover, as shown inFIG. 6(b), an end of the protective film28located on a side of the reaction section13(the immobilization film13a) comprises a lower end part and an upper end part, the lower end part being closer to a center part of the reaction section13(the immobilization film13a) than the upper end part when viewed in a lateral section. As used herein, the language “lateral section” means, as will be seen fromFIG. 1(b)for example, a section taken along the line a-a ofFIG. 1(a)or a line perpendicular to the line a-a, looking from the side of the sensor apparatus. Moreover, the language “end located on a side of the reaction section13” means an end of the protective film28opposite the end located toward at least one of the first IDT electrode11and the second IDT electrode12under the condition where, for example, as described above, the protective film28lies also in between the reaction section13and at least one of the first IDT electrode11and the second IDT electrode12, and does not cover the entire area of the reaction section13. Furthermore, as shown inFIG. 6(b), an end of the protective film28located on the side of the reaction section13(the immobilization film13a) comprises a lower end part and an upper end part, the end being inclined so that the distance between the end and a center part of the reaction section13(the immobilization film13a) becomes shorter as the end going from the upper end part to the lower end part when viewed in a lateral section. This makes it possible to inhibit an analyte liquid from contact with the first IDT electrode11and the second IDT electrode12more effectively. Moreover, by forming the protective film28so as to cover the upper surface of the element substrate10a, it is possible to enhance stability of connection with the element substrate10a.

In this embodiment, a thickness of the protective film28may be set to fall within the range of 0.001λ to 0.05λ, for example. While the thickness of the protective film28may be measured in a part of the protective film28which covers neither the first IDT electrode11nor the second IDT electrode12, the measurement in other part will not be excluded herein.

As an alternative to the configuration as shown inFIG. 6just described, a thickness of the protective film28may be smaller than the thickness of the first IDT electrode11and the thickness of the second IDT electrode12. This makes it possible to reduce the influence of the protective film28upon SAW propagating between the first IDT electrode11and the second IDT electrode12, and thereby reduce losses of SAW energy. In this case, the upper surface of the protective film28may be, at least partly, positioned at a level lower than the upper surface of the first IDT electrode11and the upper surface of the second IDT electrode12.

As shown inFIG. 4, the first extraction electrode19is connected to the first IDT electrode11, and the second extraction electrode20is connected to the second IDT electrode12. The first extraction electrode19is extracted from the first IDT electrode11in the opposite direction to the reaction section13, and, an end19eof the first extraction electrode19is electrically connected to the wiring line7disposed in the first cover member1. The second extraction electrode20is extracted drawn from the second IDT electrode12in the opposite direction to the reaction section13, and, an end20eof the second extraction electrode20is electrically connected to the wiring line7.

The first extraction electrode19and the second extraction electrode20may be made similar in material and configuration to the first IDT electrode11and the second IDT electrode12, and may thus be of a single-layer structure composed of, for example, a gold thin layer, or may be of a multilayer structure such as a three-layer structure composed of a titanium layer, a gold layer, and a titanium layer, or a three-layer structure composed of a chromium layer, a gold layer, and a chromium layer, in the order named, from the element-substrate10aside.

(Detection of Detection Target Using Detecting Element3)

In the process of detection of an object to be detected contained in an analyte liquid by the detecting element3that utilizes SAW as above described, the first step is to apply a predetermined voltage from external measuring equipment to the first IDT electrode11via the wiring line7, the first extraction electrode19, and so forth.

Upon the voltage application, on the surface of the element substrate10a, the first IDT electrode11-forming region is excited, thus producing SAW having a predetermined frequency. Part of the SAW so generated propagates toward the reaction section13, passes through the reaction section13, and reaches the second IDT electrode12. In the reaction section13, the aptamer on the reaction section13is bound to a specific object to be detected contained in the analyte liquid, and the weight (mass) of the reaction section13changes correspondingly, which results in variation in the characteristics, such as a phase, of the SAW passing through the reaction section13. In response to the arrival of the SAW having varied characteristics at the second IDT electrode12, a corresponding voltage is developed in the second IDT electrode12.

The thereby developed voltage is outputted through the second extraction electrode20, the wiring line70, and so forth. By reading the output with external measuring equipment, it is possible to examine the properties and constituents of the analyte liquid.

In the sensor apparatus100, capillarity is utilized to direct the analyte liquid to the reaction section13.

Specifically, as described earlier, when the second cover member2is joined to the intermediate cover member1A, as shown inFIG. 1, the flow channel15is defined, in the form of a narrow elongate pipe, on the lower surface of the second cover member2. Thus, by setting, for example, the width or the diameter of the flow channel15at a predetermined value with consideration given to the type of the analyte liquid, the materials of construction of the intermediate cover member1A and the second cover member2, and so forth, it is possible to cause capillarity in the flow channel15in the form of a narrow elongate pipe. For example, the flow channel15has a width of 0.5 mm to 3 mm, and a depth of 0.1 mm to 0.5 mm. As shown inFIG. 1(b), the flow channel15has a downstream portion (extension)15bwhich is a portion extending beyond the reaction section13, and, the second cover member2is formed with the air release hole18which is in communication with the extension15b. Upon admission of the analyte liquid into the flow channel15, air present in the flow channel15is expelled out of the air release hole18.

With such a pipe form capable of causing capillarity defined by the cover members including the intermediate cover member1A and the second cover member2, upon contact with the inlet port14, the analyte liquid is drawn into the interior of the sensor apparatus100while passing through the flow channel15. Thus, the sensor apparatus100has an analyte liquid suction mechanism built in itself, and is therefore capable of analyte liquid suction without using an instrument such as a pipette.

In this embodiment, while the analyte-liquid flow channel15has a depth of about 0.3 mm, the detecting element3has a thickness of about 0.3 mm, that is; as shown inFIG. 1(b), the depth of the flow channel15and the thickness of the detecting element3are substantially equal. Therefore, if the detecting element3is placed as it is on the upper surface of the first cover member1, the flow channel15will be blocked. In this regard, in the sensor apparatus100, as shown inFIGS. 1(b)and5, the element placement section5is defined by the first cover member1on which the detecting element3is mounted, and the intermediate cover member1A joined onto the first cover member1. The detecting element3is housed in this element placement section5so that the analyte-liquid flow channel15will not be blocked. That is, the depth of the element placement section5is adjusted to be substantially equal to the thickness of the detecting element3, and, the detecting element3is mounted inside the element placement section5. Thereby, the flow channel15can be provided.

The detecting element3is secured to the bottom surface of the element placement section5by, for example, a die-bonding material composed predominantly of resin such as epoxy resin, polyimide resin, or silicone resin.

The end19eof the first extraction electrode19and the wiring line7are electrically connected to each other by a metallic narrow wire27formed of, for example, Au. The connection between the end20eof the second extraction electrode20and the wiring line7is made in a similar way. Means for connecting the wiring line7with the first and second extraction electrodes19and20is not limited to the metallic narrow wire27, but may be of an electrically-conductive adhesive such as a Ag paste. Since a gap is left in the part where the wiring line7makes connection with each of the first and second extraction electrodes19and20, it is possible to suppress damage of the metallic narrow wire27when bonding the second cover member2to the first cover member1. Moreover, the first extraction electrode19, the second extraction electrode20, the metallic narrow wire27, and the wiring line7are covered with the protective film28. By covering the first extraction electrode19, the second extraction electrode20, the metallic narrow wire27, and the wiring line7with the protective film28, it is possible to suppress corrosion of these electrodes and the like.

As described heretofore, according to the sensor apparatus100in the embodiment, by placing the detecting element3in the element placement section5of the first cover member1, it is possible to provide the analyte-liquid flow channel15extending from the inlet port14to the reaction section13, and thereby allow the analyte liquid, which has been drawn into the apparatus through the inlet port14under capillarity for example, to flow to the reaction section13. That is, even with use of the detecting element3having a certain thickness, since the sensor apparatus100has an analyte liquid suction mechanism built in itself, it is possible to provide a sensor apparatus100capable of directing an analyte liquid to the detecting element3efficiently.

<Manufacturing Process of Detecting Element>

The following describes a procedure in the making of the detecting element3provided in the sensor apparatus100according to the embodiment of the invention.FIG. 7is a schematic view showing procedural steps for manufacturing the detecting element3.

First, a quartz-made element substrate10ais washed. After that, on an as needed basis, an Al film is formed on the lower surface of the element substrate10aby RF sputtering technique (FIG. 7(a)).

Next, an electrode pattern is formed on the upper surface of the element substrate10a. In this step, a photoresist pattern51of image reversal type for electrode-pattern formation is formed by photolithography technique (FIG. 7(b)).

Next, a metallic layer52having a three-layer structure composed of Ti/Au/Ti layers is formed on each of a photoresist pattern51-bearing part and a photoresist pattern51-free part of the upper surface of the element substrate10aby electron-beam vapor deposition equipment (FIG. 7(c)).

Next, a Ti/Au/Ti electrode pattern53is formed by lifting off the photoresist pattern51using a solvent, followed by oxygen-plasma asking treatment (FIG. 7(d)). In this embodiment, the Ti/Au/Ti electrode pattern53constitutes, in addition to a pair of IDT electrodes11and12, immobilization film13a, a reflector and mounting extraction electrodes19and20. The pair of IDT electrodes11and12are disposed so as to face each other, and, one of them serves as a transmitter, whereas the other serves as a receiver.

Next, a protective film28is formed on the upper surface of the element substrate10aso as to cover the Ti/Au/Ti electrode pattern53by, for example, TEOS (Tetra Ethyl Ortho Silicate)-plasma CVD technique (FIG. 7(e)).

Next, a protective film28pattern is defined by first forming a positive photoresist54on the upper surface of the protective film28, followed by etching of the protective film28using RIE equipment (FIG. 7(f)). Specifically, the positive photoresist54is formed on a part of the protective film28which covers the IDT electrodes11and12and part of the immobilization film13a, and, following the completion of etching of other part free of the photoresist54using the RIE equipment, the photoresist54is lifted off with use of a solvent, whereupon the protective film28pattern for covering the IDT electrodes11and12and part of the immobilization film13ais formed. Note that, by removing the protective film28from a photoresist54-free part of the Ti/Au/Ti electrode pattern53by etching using the RIE equipment, and subsequently etching the outermost Ti layer of the electrode pattern, a part of the immobilization film13awhich is not covered with the protective film28may be given a two-layer structure composed of Au/Ti layers. In consequence, the immobilization film13ahaving a two-layer structure composed of Au/Ti layers is located between the paired IDT electrodes11and12. Given that the pair of IDT electrodes11and12and the immobilization film13aof Au/Ti two-layer structure are grouped into a set, then there are provided two sets on a single sensor, and, one of the two sets is used as a set for detection, whereas the other is used as a set for reference.

After that, the Al film50formed on the lower surface of the element substrate10ais removed with use of fluonitric acid.

An aptamer composed of a nucleic acid or a peptide is immobilized on the upper surface of the immobilization film13ato form the reaction section13(FIG. 7(g)).

In the manner as described heretofore, the detecting element3is formed.

Next, the element substrate10ais cut in a predetermined size by dicing (FIG. 7(h)). After that, separate detecting elements3obtained by cutting process are fixedly attached, at their back sides, onto a wiring-equipped glass epoxy mounting substrate (hereafter referred to as “mounting substrate”) corresponding to the first cover member1with use of an epoxy adhesive. Then, a Au narrow wire used as the lead wire27is set to provide electrical connection between the wiring line7connected to the terminal6disposed on the mounting substrate and the end19e,20eof the extraction electrode disposed on the detecting element3(FIG. 7(i)).

Following the completion of placement of the intermediate cover member1A, the second cover member2, and so forth, the sensor apparatus100according to an embodiment of the invention is formed.

The manufacturing process of the detecting element3, as well as the manufacturing process of the sensor apparatus100, is not limited to the aforestated procedure shown inFIG. 7, and it is thus possible to adopt any other manufacturing process that enables production of the element substrate10awhose upper surface is configured so that the region10a2where the reaction section13is located is lower than the regions10a1where the first IDT electrode11and the second IDT electrode12are located.

The invention is not limited to the embodiment thus far described, and may therefore be carried into effect in various forms.

Although the reaction section13in the aforestated embodiment has been illustrated as comprising the immobilization film13aand the aptamer immobilized on the upper surface of the immobilization film13a, the invention is not limited to the aptamer, and thus, as an alternative, a reactant which undergoes reaction with an object to be detected contained in an analyte liquid and causes variation in SAW characteristics before and after analyte passage through the reaction section13may be immobilized on the upper surface of the immobilization film13a. Moreover, for example, in the case where the object to be detected in the analyte liquid reacts with the immobilization film13a, the reaction section13may be composed solely of the immobilization film13awithout using a reactant such as the aptamer. Moreover, a non-conductive film may be used as the immobilization film13ainstead of a metallic film, and the aptamer may be immobilized on the upper surface of the non-conductive film.

Moreover, the detecting element3may be constructed of a single substrate on which a variety of devices are disposed. For example, an enzyme electrode for use with enzyme electrode method may be disposed next to a SAW device. In this case, in addition to measurement based on the immuno method using an antibody or aptamer, measurement based on the enzymatic method can also be conducted, thus increasing the number of measurement points that can be checked at one time.

Moreover, while the embodiment has been described with respect to the case of providing a single detecting element3, a plurality of detecting elements3may be provided. In this case, the element placement section5is formed for each detecting element3on an individual basis, or, the element placement section5is configured to have a length or width large enough to receive all of the detecting elements3.

Moreover, while the embodiment has been described with respect to the case where the first cover member1, the intermediate cover member1A, and the second cover member2are provided as separate components, this does not constitute any limitation, and thus either a combination of some of these members in an unitary structure or a combination of all the members in an unitary structure may be adopted.

REFERENCE SIGNS LIST