The present invention relates to a sensor element and a sensor device.
There is a heretofore known surface acoustic wave sensor element for measuring properties or constituents of an analyte liquid by detecting a detection target contained in the analyte liquid via an antibody bound to the surface of the element using an acoustic wave (refer to Patent Literature 1, for example). A sensor device which incorporates the sensor element is required to be constructed as a structurally simplified system of compact design capable of withstanding service under various environmental conditions.
Patent Literature 1: WO 2013/108608
A sensor element in accordance with one embodiment of the invention is a sensor for detecting a detection target contained in a sample. The sensor element comprises: a quartz substrate having the following Euler angles, φ=0°, 97.2°≤θ≤128.9°, and 85°≤ψ≤95°; a detection section located on an upper surface of the quartz substrate; and a protective film. The detection section includes a reaction portion which reacts with the detection target, a first IDT electrode which generates a surface acoustic wave which propagates toward the reaction portion, and a second IDT electrode which receives a surface acoustic wave which has passed through the reaction portion. The protective film covers at least the first IDT electrode and the second IDT electrode. An expression 0<tc≤0.17λ is satisfied, in which tc denotes a thickness of a part of the protective film covering the first IDT electrode and the second IDT electrode, namely denotes a thickness standardized by a wavelength λ (μm) of the surface acoustic wave.
A sensor device in accordance with one embodiment of the invention comprises: the above-described sensor element in which the reactant is bound, via an immobilization film, to the quartz substrate; a supply section which delivers the sample containing the detection target to the detection section of the sensor element; and a signal processing section which detects the detection target based on an electrical signal outputted from the sensor element.
The objects, features, and advantages of the invention will become more apparent by reference to the following detailed description in conjunction with the accompanying drawings.
Practical realization of easy and speedy medical examination such as a blood test at an other-than-hospital location such as at home or at pharmacy is conducive to early detection of a disease and early medical treatment for the disease. Testing equipment for use in such a case is preferably designed as a system which is compact and simple in structure, and yet withstands service under various environmental conditions. However, for example, a sensor element of conventional design undergoes characteristic variation with changes in ambient temperature, which leads to difficulties in attaining high measurement accuracy.
In accordance with a sensor element according to the embodiment of the invention, by providing a quartz substrate having specific Euler angles; and a protective film having a specific thickness, it is possible to reduce phase variation in surface acoustic waves caused by changes in temperature.
Moreover, in accordance with a sensor device according to the embodiment of the invention, by providing the sensor element described above, highly accurate measurement can be performed with a compact and simple configuration.
The following describes the details of a sensor element and a sensor device according to the embodiment of the invention with reference to the drawings. In each of the drawings to be referred to in the following description, like constituent members are identified with the same reference symbols. Moreover, the size of each member and the distance between the individual members are schematically represented in each drawing and may therefore differ from the actual measurements.
A sensor device according to the embodiment of the invention comprises: a sensor element; a supply section which delivers a sample containing a detection target to the sensor element; and a signal processing section which detects the detection target based on an electrical signal outputted from the sensor element.
The signal generator SG generates a signal having a frequency of f, and outputs the generated signal to the sensor element 3. As will hereafter be described in detail, the sensor element 3 has a detection section 30 for detecting a detection target and a reference section 30R, and, the signal outputted from the signal generator SG is inputted to each of the detection section 30 and the reference section 30R.
With the supply of a sample containing a detection target received by the sensor element 3, upon input of the signal outputted from the signal generator SG to each of the detection section 30 and the reference section 30R, then a detection signal corresponding to the detection target is outputted from each of the detection section 30 and the reference section 30R.
Based on the detection signal outputted from the sensor element 3, the calculation section 140 determines a detection voltage by calculation using a predetermined calculating method such for example as a heterodyne method. Based on the detection voltage calculated by the calculation section 140, the measurement section 150 detects the presence or absence of the detection target contained in the sample or the content of the detection target contained in the sample.
In the present embodiment, the calculation section 140 and the measurement section 150 constitute the signal processing section. Note that the constituent components of the signal processing section are not limited to the calculation section 140 and the measurement section 150, and the signal processing section may thus be configured in any form that enables detection of a detection target based on an electrical signal outputted from the sensor element.
Next, the sensor device main body 101 will be described with reference to
As shown in
More specifically, as shown in
In
(First Cover Member)
As shown in
As the material for forming the first cover member 1, it is possible to use, for example, a glass-epoxy material, paper, plastics, celluloid, ceramic, non-woven fabric, or glass. The use of plastics is desirable from the standpoint of required strength, as well as from a cost standpoint.
Moreover, as shown in
The terminal 6 is formed on the upper surface of the first cover member 1 so as to be located on each side of the sensor element 3 in the width direction. More specifically, at least part of the terminals 6 facing the sensor element 3 lies closer to the inlet 14 than the inlet 14-side end of the sensor element 3. Moreover, in an arrangement of four terminals 6 located on one side of the sensor element 3 with respect to a longitudinal direction of the flow channel 15, the wiring lines 7 each connected to corresponding one of the outer two terminals 6 are substantially equal in length, and also the wiring lines 7 each connected to corresponding one of the inner two terminals 6 are substantially equal in length. This makes it possible to reduce variation in signals obtained by the sensor element 3 due to the difference in length between the wiring lines 7. In this case, for example, when inputting an electrical signal from the signal generator SG to a first IDT electrode 11 as shown in
The sensor element 3 of the sensor device main body 101 can be connected to the calculation section 140 by providing electrical connection between the calculation section 140 and the terminal 6 located opposite to the terminal 6 connected to the signal generator SG, with the sensor element 3 lying between the opposed terminals 6. Moreover, the terminal 6 and the sensor element 3 are electrically connected to each other via the wiring line 7, etc.
In sample measurement operation, a signal from the signal generator SG is inputted, via the terminal 6, to the sensor element 3 of the sensor device main body 101, and, a signal from the sensor element 3 is outputted, via the terminal 6, to the calculation section 140.
(Intermediate Cover Member 1A)
In the present embodiment, as shown in
As shown in
In the present embodiment, as shown in
As shown in
As the material for forming the intermediate cover member 1A, it is possible to use, for example, resin (including plastics), paper, non-woven fabric, and glass. More specifically, resin materials such as polyester resin, polyethylene resin, acrylic resin, and silicone resin can be used. The first cover member 1 and the intermediate cover member 1A may be formed either of the same material or of different materials.
Moreover, in the present embodiment, the intermediate cover member 1A comprises the first upstream portion 1Aa, and, as shown in
(Second Cover Member 2)
As shown in
As the material for forming the second cover member 2, it is possible to use, for example, resin (including plastics), paper, non-woven fabric, and glass. More specifically, resin materials such as polyester resin, polyethylene resin, acrylic resin, and silicone resin can be used. It is advisable that the second cover member 2 and the first cover member 1 are formed of the same material. This makes it possible to reduce deformation resulting from the difference in thermal expansion coefficient between these cover members. The second cover member 2 may either be joined only to the intermediate cover member 1A or be joined to both of the first cover member 1 and the intermediate cover member 1A.
As shown in
In the present embodiment, as shown in
The first cover member 1, the intermediate cover member 1A, and the second cover member 2 may be formed of the same material. This makes it possible to render the individual members substantially uniform in thermal expansion coefficient, and thereby protect the sensor device main body 101 from deformation resulting from the difference in thermal expansion coefficient among these members. Moreover, there may be a case where a biological material is applied to the reaction portion 13. In this regard, among biological materials, some are susceptible to quality degradation under exposure to external light such as ultraviolet radiation. It is thus advisable to use an opaque material having light-blocking capability for the first cover member 1, the intermediate cover member 1A, and the second cover member 2. On the other hand, for a case where external light-caused quality degradation hardly occurs in the reaction portion 13, the second cover member 2 defining the flow channel 15 may be formed of a nearly transparent material. This permits visual observation of the condition of the analyte liquid flowing through the interior of the flow channel 15, wherefore an optical detection method can be used in combination.
(Sensor Element 3)
The sensor element 3 according to the present embodiment will be described with reference to
The sensor element 3 is mainly composed of an element substrate 10 located on the upper surface of the first cover member 1; and at least one detection section 30 which is located on an upper surface 10a of the element substrate 10 which is located opposite to the first cover member 1, and detects a detection target contained in an analyte liquid. Note that “a component located on the upper surface 10a” is not limited to one placed so as to directly contact with the upper surface 10a, but is construed as subsuming a component placed indirectly on the upper surface 10a, with other member lying in between. Similar conditions hold true throughout the following description.
More specifically, the sensor element 3 in the present embodiment comprises: the element substrate 10; the detection section 30 located on the upper surface 10a of the element substrate 10, the detection section 30 including a reaction portion 13 which reacts with a detection target, a first IDT (Inter Digital Transducer) electrode 11 which generates a surface acoustic wave which propagates toward the reaction portion 13, and a second IDT electrode 12 which receives a surface acoustic wave which has passed through the reaction portion 13; and a protective film 28 which covers at least the first IDT electrode 11 and the second IDT electrode 12. The sensor element 3 may be further provided with a reference section 30R. The reference section 30R may be composed of a metallic film 13R, a first IDT electrode 11 which generates a surface acoustic wave which propagates toward the metallic film 13R, and a second IDT electrode 12 which receives a surface acoustic wave which has passed through the metallic film 13R. In this case, the protective film 28 also covers at least the first IDT electrode 11 and the second IDT electrode 12 of the reference section 30R. Note that the metallic film 13R does not necessarily have to be provided in the reference section 30R.
On the upper surface 10a of the element substrate 10, in addition to the first IDT electrode 11, the reaction portion 13, the metallic film 13R, and the second IDT electrode 12, a first extraction electrode 19 and a second extraction electrode 20 are provided.
(Element Substrate 10)
The element substrate 10 is a quartz substrate having the following Euler angles, φ=0°, 97.2°≤θ≤128.9σ, and 85°≤ψ≤95°, or more specifically having the following Euler angles, φ=0°, 110.0°≤θ≤128.9°, and 85°≤ψ≤95°. The plan configuration and dimensions of the element substrate 10 are suitably determined. For example, the element substrate 10 has a thickness tb which satisfies 0.3 mm≤tb≤1 mm, or more specifically satisfies 0.35 mm≤tb≤0.55 mm.
In the present embodiment, the surface roughness of that part of the element substrate 10 provided with an immobilization film 13a is smaller than the surface roughness of the upper surface of the immobilization film 13a. Thus, for example, with respect to the case where an aptamer or an antibody as will hereafter be described is immobilized on the surface of the element substrate 10, the bindability and adherability of the aptamer or antibody to the surface of the immobilization film 13a can be enhanced, thus enabling immobilization with higher density. This makes it possible to increase the detection sensitivity of the detection target.
(IDT Electrodes 11 and 12)
As shown in
The first IDT electrode 11 generates a surface acoustic wave (SAW) in response to an input signal from the signal generator SG, and the second IDT electrode 12 receives the SAW generated in the first IDT electrode 11, and outputs a signal based on the received SAW to the calculation section 140. The first IDT electrode 11 and the second IDT electrode 12 are arranged in line with each other so that the SAW generated in the first IDT electrode 11 can be received by the second IDT electrode 12. The design of frequency response characteristics of SAW can be made on the basis of the number of the electrode fingers of the first IDT electrode 11 and the second IDT electrode 12, the distance between the adjacent electrode fingers, the intersection width of the electrode fingers, etc., used as parameters.
Among various existing modes of vibration for SAW to be excited by the IDT electrode, for example, a vibration mode of transversal waves called SH waves is utilized in the sensor element 3 according to the present embodiment. For example, the frequency of SAW may be adjusted to fall within a range of several megahertz (MHz) to several gigahertz (GHz). By setting the SAW frequency within a range of several hundred MHz to 2 GHz in particular, it is possible to provide suitability for practical use, as well as to achieve a reduction in size of the sensor element 3 and hence miniaturization of the sensor device main body 101 as a whole. The thicknesses and lengths of predetermined constituent elements in the present embodiment will be described with respect to the case where the center frequency of SAW is set to a several hundred MHz.
The first IDT electrode 11 and the second IDT electrode 12 may be either of a single-layer structure composed of, for example, a gold thin layer, or of a multilayer structure such as a three-layer structure obtained by successively laminating a titanium layer, a gold layer, and a titanium layer in the order named, or a chromium layer, a gold layer, and a chromium layer in the order named, from the element substrate 10 side.
A thickness of each of the first IDT electrode 11 and the second IDT electrode 12 is set in a range of 0.005λ to 0.015λ, for example. Note that a thickness expressed in λ refers to a thickness standardized by the wavelength λ (μm) of a surface acoustic wave. In the following description, each and every thickness expressed in λ refers to a standardized thickness.
For the purpose of reducing SAW reflection, an elastic member may be disposed externally of the first IDT electrode 11 and the second IDT electrode 12 in the direction of SAW propagation (width direction).
(Protective Film 28)
In the present embodiment, the protective film 28 is located on the upper surface 10a of the element substrate 10 so as to cover at least the first IDT electrode 11 and the second IDT electrode 12, or equivalently part of the upper surface 10a of the element substrate 10. In the present embodiment, as shown in
The thickness of the protective film 28, or equivalently a thickness tc of a part of the protective film 28 covering the first IDT electrode 11 and the second IDT electrode 12 satisfies 0<tc≤0.17λ, or more specifically satisfies 0<tc≤0.05λ. In the present embodiment, a part of the protective film 28 covering the first IDT electrode 11 and the second IDT electrode 12 and a part of the protective film 28 covering the region between the first IDT electrode 11 and the second IDT electrode 12 have the same thickness. In measuring the thickness of the protective film 28, a part thereof which does not cover the first IDT electrode 11 and the second IDT electrode 12 may be subjected to the measurement, and yet, the execution of measurement on other location than the above-described part shall not be ruled out.
As shown in
As shown in
The protective film 28 may be made smaller in thickness than the first IDT electrode 11 and the second IDT electrode 12. This makes it possible to reduce the influence of the protective film 28 upon SAW propagating between the first IDT electrode 11 and the second IDT electrode 12, and thereby reduce losses of SAW energy. In this case, the protective film 28 may be configured so that at least part of an upper surface thereof is positioned at a level lower than the upper surface of the first IDT electrode 11 and the upper surface of the second IDT electrode 12.
Moreover, in the present embodiment, the protective film 28 may be made to have a compressive stress. For example, the compressive stress is measured using a warp gauge or in accordance with Raman spectrometry. When using the warp gauge, the compressive stress of the protective film 28 is measured on the basis of the amount of warpage of each of the protective film 28-bearing element substrate 10 and the protective film 28-free element substrate 10 (the element substrate 10 with the protective film 28 removed). When adopting the Raman spectrometry, the compressive stress of the protective film 28 is measured on the basis of Raman spectra in each of the protective film 28-bearing part of the element substrate 10 and the protective film 28-free part (the part with the protective film 28 removed) of the element substrate 10. For example, by adjusting the protective film 28 to be greater than or equal to 50 Mpa in compressive stress, it is possible to reduce losses due to the placement of a liquid (for example, analyte liquid) on the reaction portion, and thereby achieve measurement with greater accuracy. Alternatively, the compressive stress of the protective film 28 may be measured using an X-ray on the basis of the lattice conditions of the protective film 28 in itself.
(Reaction Portion 13)
The reaction portion 13 is disposed in the region between the first IDT electrode 11 and the second IDT electrode 12. In the present embodiment, as described above, the protective film 28 covers the first IDT electrode 11 and the second IDT electrode 12, and, as shown in
In the present embodiment, the reaction portion 13 comprises: the immobilization film 13a (for example, a metallic film) located on the upper surface 10a of the element substrate 10; and a reactant bound to the upper surface of the immobilization film 13a, the reactant reacting with a detection target. For example, the immobilization film 13a and the reactant may be either chemically bound together or bound together via an intermediary substance, or, they may be brought into physical adhering contact with each other. The selection of the reactant is suitably made in accordance with the detection target. For example, when a specific cell or living tissue in an analyte liquid is detected as a detection target, a nucleic acid- or peptide-made aptamer may be used as the reactant, or, when a specific antigen in an analyte liquid is detected as a detection target, an antibody can be used. In the present embodiment, as a reaction between the reactant and the detection target, for example, the reactant and the detection target are bound together under a chemical reaction or an antigen-antibody reaction. Alternatively, the detection target may be adsorbed on the reactant under detection target-reactant interaction. The reaction is not limited thereto, and hence, as the reactant of the present embodiment for use in the reaction portion 13, it is possible to use a reactant which causes, by its presence, variation in SAW characteristics upon contact of the detection target with the reaction portion 13, depending on the type or content of the detection target. The reaction portion 13 serves to react with a detection target contained in an analyte liquid, and more specifically, upon contact of the analyte liquid with the reaction portion 13, a specific detection target contained in the analyte liquid is bound to an aptamer adapted to a reaction with the detection target.
In the present embodiment, the reaction portion 13 is situated on the upper surface 10a of the element substrate 10 via the protective film 28, so as to lie between the first IDT electrode 11 and the second IDT electrode 12. That is, the immobilization film 13a is spaced away from the upper surface 10a of the element substrate 10 by a distance corresponding to the thickness of the protective film 28. Since the reaction portion 13 is not covered with the protective film 28, the reaction portion 13 can contact with the analyte liquid.
The immobilization film 13a may be either of a single-layer structure composed of, for example, a gold layer, or of a multilayer structure such as a two-layer structure composed of a titanium layer and a gold layer lying on the titanium layer or a two-layer structure composed of a chromium layer and a gold layer lying on the chromium layer. Moreover, the immobilization film 13a may be formed of the same material as that used for the first IDT electrode 11 and the second IDT electrode 12. In this case, the immobilization film 13a and the first and second IDT electrodes 11 and 12 can be formed in one process step. Instead of the above-mentioned metallic film, for example, an oxide film such as a SiO2 film or TiO2 film may be used as the material for forming the immobilization film 13a.
In the example shown in
(Extraction Electrodes 19 and 20)
As shown in
The first extraction electrode 19 and the second extraction electrode 20 may be formed of the similar material to that used for the first IDT electrode 11 and the second IDT electrode 12 and may have the similar structure to the first IDT electrode 11 and the second IDT electrode 12, and hence, for example, the first and second extraction electrodes may be either of a single-layer structure composed of, for example, a gold thin layer, or of a multilayer structure such as a three-layer structure obtained by successively laminating a titanium layer, a gold layer, and a titanium layer in the order named, or a chromium layer, a gold layer, and a chromium layer in the order named, from the element substrate 10 side.
In the present embodiment, the quartz-made element substrate 10 has the following Euler angles, φ=0°, 97.2°≤θ≤128.9°, and 85°≤ψ≤95°, and, an expression 0<tc≤0.17λ is satisfied, in which tc denotes a thickness of a part of the protective film 28 covering the first IDT electrode 11 and the second IDT electrode 12. The fulfillment of such a prescribed range of Euler angles in the element substrate 10 and the thickness of the protective film 28 allows improvement in temperature characteristics.
In the present embodiment, the temperature characteristics of the sensor element can be determined as TCF (Temperature Coefficients of Frequency) by leaving the sensor element to stand in a thermostatic chamber under different internal temperature conditions, namely 10° C., 25° C., and 40° C., respectively, measuring the frequency response characteristics of the sensor element under each temperature condition, and calculating a frequency change per unit temperature variation. It can be judged that the sensor element exhibits increasingly higher level of temperature characteristics as the TCF is decreased. That is, the lower the TCF is, the higher the level of temperature characteristics is, which means that a decline in measurement accuracy resulting from a change in temperature can be reduced. In a conventional sensor element, for example, temperature characteristics TCF thereof is about 75 ppm/° C. or greater in terms of absolute value (TCF≤−75 ppm, and, 75 ppm TCF). When incorporated in medical equipment required to afford high measurement accuracy, this sensor element may suffer a decline in measurement accuracy under the influence of temperature changes. In this regard, the sensor element 3 in the present embodiment fulfills the above-described range of Euler angles in the element substrate 10 and the thickness of the protective film 28, and hence achieves improvement in temperature characteristics up to a level where TCF falls within a range of ±5 ppm/° C. (TCF satisfies −5 ppm≤TCF≤5 ppm). With the improvement of the temperature characteristics, for example, even if the sensor device 100 is placed in service under various environmental conditions, such as outdoors and indoors, measurement can be accomplished with high accuracy regardless of temperatures. In the present embodiment, for example, the attainment of high measurement accuracy is ascertained with use of the coefficient of variation (CV) of a measured value obtained by detection of a detection target by the sensor element with consideration given only to the influence of temperature changes. In the present embodiment, the range of the temperature characteristics TCF is not limited to ±5 ppm/° C., and hence TCF may take on any values that would achieve greater measurement accuracy than has hitherto been obtainable. For example, the temperature characteristics TCF may be adjusted to fall within a range of ±15 ppm/° C.
(Detection of Detection Target by Sensor Element 3)
In the process of detecting a detection target contained in an analyte liquid by the sensor element 3 which utilizes SAW thus far described, a signal from the signal generator SG is first inputted to the first IDT electrode 11 via the wiring line 7, the first extraction electrode 19, etc.
Upon inputting the signal, in the detection section 30, a region of the surface of the element substrate 10 in which the first IDT electrode 11 is formed is excited, thus producing SAW having a predetermined frequency. Part of the SAW generated propagates toward the reaction portion 13, passes through the reaction portion 13, and reaches the second IDT electrode 12. In the reaction portion 13, an aptamer at the reaction portion 13 is bound to a specific detection target contained in the analyte liquid, and the weight (mass) of the reaction portion 13 changes by an amount corresponding to the binding, with consequent variation in the characteristics, such as the phase, of the SAW passing through the reaction portion 13. In response to the arrival of the SAW having varied characteristics at the second IDT electrode 12, a corresponding detection voltage is developed in the second IDT electrode 12. In the case of providing the reference section 30R, in a like manner, following the propagation and passage of SAW through metallic film 13R, a reference voltage is developed.
The thus developed voltage is outputted, through the second extraction electrode 20, the wiring line 70, etc., to the calculation section 140 and the measurement section 150 to examine properties and constituents of the analyte liquid.
In the sensor device main body 101, capillarity is utilized to direct the analyte liquid to the reaction portion 13.
More specifically, as described above, upon joining the second cover member 2 to the intermediate cover member 1A, as shown in
With such a pipe-like channel capable of causing capillarity defined by the cover members including the intermediate cover member 1A and the second cover member 2, upon contact of the analyte liquid with the inlet 14, the analyte liquid is drawn into the interior of the sensor device main body 101 while passing through the flow channel 15. Thus, the sensor device main body 101 is capable of directing the analyte liquid to the reaction portion 13 by means of an analyte liquid suction mechanism of its own without the necessity of using an instrument such as a pipette.
(Positional Relationship Between Flow Channel 15 and Sensor Element 3)
In the present embodiment, the flow channel 15 for analyte liquid has a depth of about 0.3 mm, whereas the sensor element 3 has a thickness of about 0.3 mm, that is; as shown in
The sensor element 3 is secured to the bottom surface of the element receiving portion 5 by a die-bonding material composed predominantly of resin such as epoxy resin, polyimide resin, or silicone resin, for example.
The end 19e of the first extraction electrode 19 and the wiring line 7 are electrically connected to each other by a metallic narrow wire 27 formed of Au, for example. The connection between the end 20e of the second extraction electrode 20 and the wiring line 7 is made in a similar manner. Means for connecting each of the first extraction electrode 19 and the second extraction electrode 20 to the wiring line 7 is not limited to the metallic narrow wire 27, but may be an electrically-conductive adhesive such as a Ag paste, for example. With a clearance left in the part of connection between the wiring line 7 and each of the first extraction electrode 19 and the second extraction electrode 20, damage of the metallic narrow wire 27 can be suppressed when bonding the second cover member 2 to the first cover member 1. Moreover, the first extraction electrode 19, the second extraction electrode 20, the metallic narrow wire 27 and the wiring line 7 may be covered with the protective film 28. Since the first extraction electrode 19, the second extraction electrode 20, the metallic narrow wire 27 and the wiring line 7 are covered with the protective film 28, it is possible to suppress corrosion of these electrodes or the like.
As described heretofore, in accordance with the sensor device main body 101 according to the present embodiment, by placing the sensor element 3 in the element receiving portion 5 of the first cover member 1, it is possible to provide the flow channel 15 for analyte liquid extending from the inlet 14 to the reaction portion 13, and thereby allow the analyte liquid sucked from the inlet 14 under capillarity or by other means to flow to the reaction portion 13. That is, there is provided the sensor device main body 101 in which, even with use of the sensor element 3 having a certain thickness, an analyte liquid can be efficiently directed to the sensor element 3 by virtue of the analyte liquid suction mechanism of the device's own.
A sensor element 3A according to the second embodiment of the invention comprises, in addition to the constituent components of the above-described sensor element 3 according to the first embodiment, a first reflector and a second reflector, and the protective film 28 covers the first reflector and the second reflector. For example, a thickness tr of a part of the protective film 28 covering the first reflector and the second reflector satisfies 0<tr≤0.05λ.
(First Reflector 11A and Second Reflector 12A)
In the present embodiment, the detection section 30 further includes the first reflector 11A and the second reflector 12A. The first reflector 11A is a reflector located opposite to the reaction portion 13 with respect to the first IDT electrode 11, and, the second reflector 12A is a reflector located opposite to the reaction portion 13 with respect to the second IDT electrode 12. Like the detection section 30, the reference section 30R may also include the first reflector 11A and the second reflector 12A.
Among the SAW propagating over the element substrate 10, SAW propagating outward from the first IDT electrode 11 and the second IDT electrode 12 is not used for measurement, with consequent energy losses. With the first reflector 11A and the second reflector 12A, SAW propagating outward from the first IDT electrode 11 and the second IDT electrode 12 can be reflected by the first reflector 11A and the second reflector 12A so as to be used for measurement. This makes it possible to reduce energy losses, and thereby attain higher noise immunity and hence higher measurement accuracy.
Moreover, in the present embodiment, like the first IDT electrode 11 and the second IDT electrode 12, the first reflector 11A and the second reflector 12A are covered with the protective film 28, and, the thickness tr of a part of the protective film 28 covering the first reflector 11A and the second reflector 12A satisfies 0<tr≤0.05λ. By covering the first reflector 11A and the second reflector 12A with the protective film 28, it is possible to suppress contact of an analyte liquid with the first reflector 11A and the second reflector 12A, and thereby reduce corrosion of the reflectors caused by oxidation, for example.
A sensor element 3B according to the third embodiment of the invention differs from the foregoing embodiment in an area covered with a protective film 28A.
In the present embodiment, as shown in
The SAW generated in the first IDT electrode 11, while propagating through the protective film 28A-bearing part of the upper surface 10a of the element substrate 10 under the influence of the protective film 28A, propagates through the protective film 28A-free part thereof without incurring the influence of the protective film 28A. In the present embodiment, the reaction portion 13 is placed so as to directly contact with the upper surface 10a of the element substrate 10, wherefore SAW is allowed to propagate while acting more effectively on the reaction portion 13 lying on the upper surface 10a of the element substrate 10. This makes it possible to achieve further reduction in energy losses, and thereby attain higher noise immunity and hence higher measurement accuracy.
Moreover, the center-side end of the protective film 28A and the IDT electrode-side end of the reaction portion 13 may either contact with each other or be spaced apart without contact. By contacting the ends with each other, it is possible to reduce acoustical boundaries in the SAW propagation path, and thereby achieve efficient transmission of vibration energy generated in the IDT electrode 11 to the reaction portion 13, with consequent loss reduction. On the other hand, by spacing the ends apart without contact, it is possible to maintain the exposed length of the reaction portion 13 invariant even if the end of the protective film 28A is displaced from its normal position due to manufacturing variation, and thereby reduce variation in sensitivity.
<Sensor Element Manufacturing Process>
The following describes a procedure in the manufacturing of the sensor element 3 provided in the sensor device main body 101 according to the embodiment of the invention.
First, a quartz-made element substrate 10 is washed. After that, on an as needed basis, an Al film 50 is formed on the lower surface of the element substrate 10 by RF sputtering (
Next, an electrode pattern is formed on the upper surface 10a of the element substrate 10. In this process, a photoresist pattern 51 of image reversal type for electrode pattern formation is formed by photolithography technique (
Next, a metallic layer 52 having a three-layer (Ti/Au/Ti) structure is formed on each of a photoresist pattern 51-bearing part and a photoresist pattern 51-free part of the upper surface 10a of the element substrate 10 by an electron beam evaporation apparatus (
Next, a Ti/Au/Ti electrode pattern 53 is formed by lifting off the photoresist pattern 51 with use of a solvent, and thereafter performing oxygen-plasma ashing treatment (
Next, the protective film 28 is formed on the upper surface 10a of the element substrate 10 so as to cover the Ti/Au/Ti electrode pattern 53 by TEOS (Tetra Ethyl Ortho Silicate)-plasma CVD technique, for example (
Next, a pattern of the protective film 28 is formed by forming a positive photoresist 54 on the upper surface of the protective film 28, and thereafter etching the protective film 28 by RIE equipment (
The immobilization film 13a is formed on the upper surface of the protective film 28. Herein, a photoresist pattern 54 of image reversal type for the formation of the immobilization film 13a is formed by photolithography technique, and then a metallic layer having a three-layer (Ti/Au/Ti) structure is formed on each of a photoresist pattern 54-bearing part and a photoresist pattern 54-free part of the upper surface 10a of the protective film 28 by an electron beam evaporation apparatus (
Next, a Ti/Au/Ti immobilization film 13a is formed by lifting off the photoresist pattern 54 with use of a solvent, and thereafter performing oxygen-plasma ashing treatment (
After that, the Al film 50 formed on the lower surface of the element substrate 10 is removed with use of fluoronitric acid. A nucleic acid- or peptide-made aptamer is immobilized on the upper surface of the immobilization film 13a to form the reaction portion 13.
The sensor element 3 is formed in the manner thus far described.
Next, the element substrate 10 is divided into pieces of predetermined size by dicing (
With subsequent installation of the intermediate cover member 1A, the second cover member 2, etc. being accomplished, the sensor device main body 101 according to the embodiment of the invention is formed.
Meanwhile, a substrate installed with each of the signal generator SG, the calculation section 140, and the measurement section 150 constructed of, for example, a semiconductor element is prepared independently of the sensor device main body 101, and, with subsequent electrical connection between the sensor device main body 101 thus obtained and each semiconductor element being established, the sensor device 100 is formed.
The invention may be carried into effect in various forms without being limited to the embodiments thus far described. For example, although the reaction portion 13 in the above-described embodiments has been illustrated as comprising the immobilization film 13a and the aptamer immobilized on the upper surface of the immobilization film 13a, a substance to be immobilized on the upper surface of the immobilization film 13a is not limited to the aptamer, but may be any of reactants that react with a detection target contained in an analyte liquid with consequent changes in SAW characteristics before and after the passage of the sample through the reaction portion 13. Moreover, for example, where the immobilization film 13a is capable of reaction with the detection target in the analyte liquid, the reaction portion 13 may be composed solely of the immobilization film 13a without using a reactant such as the aptamer. In addition, as the immobilization film 13a, instead of the metallic film, it is possible to use a non-conductive film, on the upper surface of which is immobilized an aptamer.
Moreover, the sensor element 3 may be constructed by co-arranging a plurality of different elements on a single substrate. For example, an enzyme electrode for use with an enzyme electrode method may be disposed next to a SAW element. In this case, in addition to measurement based on an immunization method using an antibody or aptamer, enzymatic method-based measurement can also be conducted, wherefore increasing numbers of measurement points can be checked at one time.
Moreover, although the foregoing embodiments have been described with respect to the case where there is provided a single sensor element 3, a plurality of the sensor elements 3 may be arranged. In this case, the element receiving portion 5 may be provided for each sensor element 3 on an individual basis, or, the element receiving portion 5 may be configured to have a length or width large enough to receive all the sensor elements 3.
Moreover, although the foregoing embodiments have been described with respect to the case where the first cover member 1, the intermediate cover member 1A, and the second cover member 2 are provided as separate components, this is not intended to be limiting of the invention, and hence 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.
Moreover, the described constituent components of the embodiments may be used in combination. For example, the first reflector and the second reflector of the sensor element 3A as the second embodiment may be applied to the sensor element 3B as the third embodiment.
(Study in Simulation)
With use of the values of Euler angles (φ, θ, ψ) of the quartz substrate serving as the element substrate 10 and the thickness tc of a part of the protective film 28 covering the first IDT electrode 11 and the second IDT electrode 12 as parameters, the above-described temperature coefficients of frequency (TCF) were calculated by simulation. In this simulation, TCF was determined by calculation using software employing a finite-element method (FEM) (MATLAB manufactured by The MathWorks, Inc.).
In the simulation, Euler angles φ, θ, and ψ were set to satisfy φ=0°, 0°≤θ≤180°, and 0°≤ψ≤90°, and a protective film thickness tc was adjusted to satisfy the expression 0≤tc≤0.2λ. TCF corresponding to each condition was calculated, and then a mathematical expression representing the relationship between TCF [ppm/° C.], tc [μm] and θ [°] was derived. The derived relational expression is as follows:
TCF=−11.1θtc+3.1θ+1615.1tc−390 (where φ=0°, and ψ=90°) (1).
The range of Euler angles and the range of protective film thickness tc with which TCF falls within a ±5 ppm/° C. range were determined in accordance with the expression (1).
It has been found that TCF fell within a range of ±5 ppm/° C. when the Euler angles of the element substrate had φ=0°, 97.2°≤θ≤128.9°, and 85°≤ψ≤95°, and the thickness of the protective film satisfied 0<tc≤0.17λ.
(Verification with Measured Values)
The adequacy of the range of Euler angles and the range of protective film thickness obtained by the described study in simulation was verified on the basis of measured values.
Example of Verification 1
TCF (Temperature Coefficients of Frequency) measurement was made on a sensor element produced in conformity with the design of the above-described embodiment in a manner whereby the Euler angles of the element substrate were such that φ, θ, and ψ were equal to 0°, 128°, and 90°, respectively, and the protective film thickness tc was equal to 0.026λ. The result showed that TCF stood at 4.9 ppm/° C., from which it followed that TCF could fall within a range of ±5 ppm/° C. when the Euler angles and the protective film thickness fulfilled their respective ranges set in the simulation.
Example of Verification 2
TCF measurement was made on a sensor element produced in conformity with the design of the above-described embodiment in a manner whereby the Euler angles of the element substrate were such that φ, θ, and ψ were equal to 0°, 127°, and 90°, respectively, and the protective film thickness tc was equal to 0.026λ. The result showed that TCF stood at 0.9 ppm/° C., from which it followed that TCF could fall within a range of ±5 ppm/° C. when the Euler angles and the protective film thickness fulfilled their respective ranges set in the simulation.
Example of Verification 3
TCF measurement was made on a sensor element produced in conformity with the design of the above-described embodiment in a manner whereby the Euler angles of the element substrate were such that φ, θ, and ψ were equal to 0°, 126°, and 90°, respectively, and the protective film thickness tc was equal to 0.026λ. The result showed that TCF stood at −4.8 ppm/° C., from which it followed that TCF could fall within a range of ±5 ppm/° C. when the Euler angles and the protective film thickness fulfilled their respective ranges set in the simulation.
Example of Verification 4
TCF measurement was made on a sensor element produced in conformity with the design of the above-described embodiment in a manner whereby the Euler angles of the element substrate were such that φ, θ, and ψ were equal to 0°, 127°, and 90°, respectively, and the protective film thickness tc was equal to 0.026λ. The result showed that TCF stood at −2.5 ppm/° C., from which it followed that TCF could fall within a range of ±5 ppm/° C. when the Euler angles and the protective film thickness fulfilled their respective ranges set in the simulation.
Example of Verification 5
TCF measurement was made on a sensor element produced similarly to those produced for the above-described verification examples in a manner whereby the Euler angles of the element substrate were such that φ, θ, and ψ were equal to 0°, 132.9°, and 90°, respectively, and the protective film thickness tc was equal to 0.026λ. The result showed that TCF stood at 31.9 ppm/° C., from which it followed that TCF could not fall within a range of ±5 ppm/° C. when the Euler angles and the protective film thickness fell outside their respective ranges set in the simulation.
The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description and all changes which come within the meaning and the range of equivalency of the claims are therefore intended to be embraced therein.
Number | Date | Country | Kind |
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2016-038436 | Feb 2016 | JP | national |
Filing Document | Filing Date | Country | Kind |
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PCT/JP2017/008015 | 2/28/2017 | WO | 00 |