JP6128764B2 - Biosensor, detection method, detection system, and detection apparatus - Google Patents

Description

  The present invention relates to a biosensor, a detection method, a detection system, and a detection apparatus.

  Conventionally, there is a detection method for detecting a change in the state of the substrate surface. For example, there is a biosensor that measures the properties or components of an analyte solution using surface acoustic waves. Further, for example, there is an SPR (Surface Plasmon Resonance) measuring device. There is a technique related to detection of clinical markers for diseases or medical events using a plurality of antibodies having different specificities for clinical markers.

JP-A-6-133759 JP-T-2005-534907

  However, in the conventional detection method for detecting the change in the state of the substrate surface, the substance to be detected is not detected when the substance to be detected is not on the substrate surface.

  The disclosed technology has been made in view of the above, and an object thereof is to provide a biosensor, a detection method, a detection system, and a detection device that can improve detection sensitivity.

  In one embodiment, the disclosed biosensor includes a substrate and a detection unit provided on the substrate. In one embodiment, the biosensor is provided with at least one of an upper part and a lower part of the substrate, and includes a flow inlet into which the analyte solution flows and a groove extending from the flow inlet to at least the detection part. It has a member. Further, in one embodiment, the biosensor includes a pair of electrodes that are arranged at intervals from each other and generate an electric field that passes through the detection unit in a space formed on the detection unit by the groove.

  According to one embodiment of the disclosed biosensor, detection method, detection system, and detection apparatus, the detection sensitivity can be improved.

FIG. 1 is a perspective view of a biosensor according to an embodiment. FIG. 2 is an exploded perspective view of the first cover member and the second cover member. FIG. 3 is a perspective view of the biosensor shown in FIG. 1 with the fourth substrate removed. 4A is a cross-sectional view taken along the line IVa-IVa 'of FIG. 4B is a cross-sectional view taken along line IVb-IVb ′ of FIG. FIG. 5 is a perspective view of a detection element used in the biosensor shown in FIG. FIG. 6 is a plan view of the detection element shown in FIG. 5 with the first and second hollow members removed. FIG. 7 is a cross-sectional view showing a modification of the biosensor according to the embodiment. FIG. 8 is a cross-sectional view showing another modification of the biosensor according to the embodiment. FIG. 9 is a plan view illustrating an example in which a cover member is bonded to a substrate. FIG. 10 is a cross-sectional view illustrating an example of a case where a cover member is bonded to a substrate.

  Hereinafter, embodiments of the disclosed biosensor will be described in detail with reference to the drawings as appropriate. As described in detail below, the disclosed biosensor has a substrate and a detection unit provided on the substrate. In addition, the disclosed biosensor has a cover member that is provided on at least one of the upper part and the lower part of the substrate, and that has an inlet into which the sample solution flows and a groove extending from the inlet to at least the detection part. In addition, the disclosed biosensor has a pair of electrodes that are arranged at a distance from each other and generate an electric field that passes through the detection unit in a space formed on the detection unit by the groove. As a result, the detection sensitivity can be improved. For example, when an electric field is generated in which the substance to be detected moves to the detection surface (refers to the surface of the detection unit) according to the charge of the substance to be detected, the substance to be detected and the detection are detected. The probability of contact with the surface can be increased, and detection sensitivity can be improved. In other words, the substance in the sample solution floating between the electrodes can be drawn to the detection unit side, and the detection sensitivity can be improved. Further, as a result of generating an electric field that moves the substance to be detected to the detection surface in accordance with the charge of the substance to be detected, the measurement time can be shortened.

  In addition, below, when a numerical range is shown using "-", unless there is particular notice, a numerical value of a minimum and an upper limit shall be included, respectively. For example, in the numerical range “300 to 500”, unless otherwise specified, the lower limit indicates “300” and the upper limit indicates “500”.

[Example of biosensor structure]
The disclosed biosensor is used in a detection technique for detecting a change in the state of the substrate surface. For example, the disclosed biosensor includes a measurement cell used for measurement by an SPR (Surface Plasmon Resonance) device, a SAW (Surface Acoustic Wave) sensor, a QCM (Quartz Crystal Microbalance). Method) Crystal sensor. The disclosed biosensor is preferably a SAW sensor. By realizing a biosensor as a SAW sensor, the biosensor can be easily realized in a small size.

  Hereinafter, an example of the structure of the disclosed biosensor will be described in detail using a case where the disclosed biosensor is a SAW sensor. In one example of the embodiment, the biosensor 100 as the SAW sensor has a first cover member on which the substrate is disposed on the upper surface. Biosensor 100 has a second cover member joined to the first cover member. That is, the biosensor 100 includes a first cover member on which the substrate is disposed on the upper surface, and a second cover member joined to the first cover member with the substrate interposed therebetween.

  Further, in the biosensor 100 as the SAW sensor, at least one of the first cover member and the second cover member has an inflow port into which the sample solution flows and a groove portion extending from the inflow port to at least the surface of the substrate. For example, in the biosensor 100 as the SAW sensor, in an example of the embodiment, the first cover member has a concave portion on the upper surface, the concave portion accommodates the substrate, and the second cover member has a groove portion.

  Further, the biosensor 100 as the SAW sensor has a pair of electrodes. The pair of electrodes are arranged at a distance from each other, and generate an electric field passing through the detection unit in a space formed on the detection unit by the groove. For example, the pair of electrodes generates an electric field having a component in the thickness direction of the detection unit. For example, the pair of electrodes are provided in the thickness direction of the detection unit with the space between the space formed on the detection unit by the groove and the detection unit interposed therebetween. The first electrode that is one of the pair of electrodes is provided on a substrate, for example. Moreover, the 2nd electrode which is another electrode of a pair of electrodes is provided in the position facing the inner 1st electrode of the inner wall of a groove part, for example. In addition, the detection unit is provided on the first electrode, for example.

  In the following description, a case where the first electrode is provided over the substrate will be described unless otherwise specified, but the present invention is not limited thereto. Hereinafter, the case where the second electrode is provided on the inner surface of the groove portion will be described. However, the present invention is not limited to this. That is, the pair of electrodes may be arranged at any position as long as the electric field passing through the detection unit can be generated in the space formed on the detection unit by the groove. For example, the first electrode may be provided on the lower surface of the substrate, and the second electrode may be provided on the upper surface of the cover member. For example, the first electrode and the second electrode may be arranged side by side on the substrate. Hereinafter, the case where the second electrode is provided at a position facing the first electrode will be described, but the present invention is not limited to this.

  Further, in the following example, a third electrode made of a material that is exposed to the space formed by the groove and is less reactive with the specimen solution is provided on the substrate at a distance from the first electrode. The third electrode functions as a reference electrode by being electrically connected to the first electrode via a potentiometer. A voltage can be stably applied between the first electrode and the second electrode by the third electrode. In addition, if the third electrode is, for example, a first silver chloride electrode or a calomel electrode, the reactivity with respect to the specimen solution can be lowered.

  In addition, the biosensor 100 as the SAW sensor is provided on the surface of the substrate in an example of the embodiment, and includes a first IDT (Inter Digital Transducer) electrode that generates an elastic wave propagating toward the detection unit. The biosensor 100 includes a second IDT electrode that is provided on the substrate surface and receives an elastic wave that has passed through the detection unit. In addition, the biosensor 100 includes a first hollow member that is provided with a first vibration space on the first IDT electrode and bonded to the upper surface of the substrate, and that seals the first IDT electrode in the first vibration space. In addition, the biosensor 100 includes a second hollow member that provides a second vibration space on the second IDT electrode and is bonded to the upper surface of the substrate, and seals the second IDT electrode in the second vibration space.

  An example of the configuration of the biosensor 100 as the SAW sensor will be described in detail with reference to the drawings as appropriate. In addition, in each drawing demonstrated below, the same code shall be attached | subjected to the same structural member. Further, the size of each member, the distance between members, and the like are schematically illustrated, and may differ from actual ones. In addition, the biosensor 100 may be set in any direction upward or downward. However, for the sake of convenience, the biosensor 100 is defined as an orthogonal coordinate system xyz and the upper side with the positive side in the z-axis direction as the upper side. , Terms such as underside are used.

  As shown in FIGS. 1 to 6, the biosensor 100 includes a first cover member 1, a second cover member 2, and a detection element 3. The first cover member 1 includes a first substrate 1a and a second substrate 1b stacked on the first substrate 1a. The second cover member 2 includes a third substrate 2a stacked on the second substrate 1b and a fourth substrate 2b stacked on the third substrate 2a, and includes a second electrode 62. The detection element 3, which is a surface acoustic wave element, includes a substrate 10, a first IDT electrode 11, a second IDT electrode 12, a detection unit 13, and a first electrode 61.

  The first cover member 1 and the second cover member 2 are bonded together, and the detection element 3 is housed inside the bonded first cover member 1 and second cover member 2. As shown in the cross-sectional view of FIG. 4, the first cover member 1 has a recess 5 on the upper surface, and the detection element 3 is disposed in the recess 5.

  As shown in FIG. 1, the second cover member 2 has an inflow port 14 that is an inlet of the sample solution at an end in the longitudinal direction (x-axis direction), and is directed from the inflow port 14 to a portion directly above the detection element 3. It has the groove part 15 extended. In FIG. 1, the groove portion 15 is indicated by a broken line in order to indicate the position of the groove portion 15. Further, the second cover member 2 has a second electrode 62 at a position facing the inner first electrode 61 on the inner wall of the groove portion 15.

  FIG. 2 shows an exploded perspective view of the first cover member 1 and the second cover member 2.

  The 1st board | substrate 1a which comprises the 1st cover member 1 is flat form, The thickness is 0.1 mm-0.5 mm, for example. The planar shape of the first substrate 1a is generally rectangular, but one end in the longitudinal direction has an arc shape protruding outward. The length of the first substrate 1a in the x-axis direction is, for example, 1 cm to 5 cm, and the length in the y-axis direction is, for example, 1 cm to 3 cm.

  The second substrate 1b is bonded to the upper surface of the first substrate 1a. The 2nd board | substrate 1b is made into the flat frame shape which provided the through-hole 4 for recessed part formation in the flat plate, The thickness is 0.1 mm-0.5 mm, for example. The outer shape when viewed in plan is substantially the same as that of the first substrate 1a, and the length in the x-axis direction and the length in the y-axis direction are also substantially the same as those of the first substrate 1a.

  The concave portion 5 is formed in the first cover member 1 by joining the second substrate 1b provided with the through hole 4 for forming the concave portion to the flat first substrate 1a. That is, the upper surface of the first substrate 1 a located inside the through hole 4 for forming recesses is the bottom surface of the recess 5, and the inner wall of the through hole 4 for forming recesses is the inner wall of the recess 5.

  On the upper surface of the second substrate 1b, a terminal 6 and a wiring 7 routed from the terminal 6 to the recess forming through hole 4 are formed. The terminal 6 is formed at the other end of the upper surface of the second substrate 1b in the x-axis direction. The portion where the terminal 6 is formed is a portion that is actually inserted when the biosensor 100 is inserted into an external measuring instrument (not shown), and is electrically connected to the external measuring instrument via the terminal 6. Will be connected. Further, the terminal 6 and the detection element 3 are electrically connected through a wiring 7 or the like. Then, a signal from an external measuring device is input to the biosensor 100 via the terminal 6, and a signal from the biosensor 100 is output to the external measuring device via the terminal 6.

  A second cover member 2 is bonded to the upper surface of the first cover member 1 composed of the first substrate 1a and the second substrate 1b. The second cover member 2 has a third substrate 2a and a fourth substrate 2b.

  The third substrate 2a is bonded to the upper surface of the second substrate 1b. The 3rd board | substrate 2a is flat form, The thickness is 0.1 mm-0.5 mm, for example. The planar shape of the third substrate 2a is generally rectangular, but, like the first substrate 1a and the second substrate 1b, one end in the longitudinal direction has an arc shape protruding outward. The length of the third substrate 2a in the x-axis direction is slightly shorter than the length of the second substrate 1b in the x-axis direction so that the terminals 6 formed on the second substrate 1b are exposed. It is 8 mm to 4.8 cm. The length in the y-axis direction is, for example, 1 cm to 3 cm like the first substrate 1a and the second substrate 1b.

  A cutout 8 is formed in the third substrate 2a. The cutout 8 is a portion in which the third substrate 2a is cut out from the apex portion of the one end in the arc shape of the third substrate 2a toward the other end in the x-axis direction. The notch 8 is for forming the groove 15. A first through hole 16 and a second through hole 17 that penetrate the third substrate 2a in the thickness direction are formed on both sides of the notch 8 of the third substrate 2a. When the third substrate 2 a is laminated on the second substrate 1 b, the connection portion between the detection element 3 and the wiring 7 is positioned inside the first through hole 16 and the second through hole 17. A portion between the first through hole 16 and the notch 8 of the third substrate 2a serves as a first partition 25 that partitions the groove 15 and a space formed by the first through hole 16 as described later. Further, a portion between the second through hole 17 and the notch 8 of the third substrate 2 a becomes a second partition portion 26 that partitions the groove 15 and the space formed by the second through hole 17.

  The fourth substrate 2b is bonded to the upper surface of the third substrate 2a. The 4th board | substrate 2b is flat form, The thickness is 0.1 mm-0.5 mm, for example. The outer shape when viewed in plan is substantially the same as that of the third substrate 2a, and the length in the x-axis direction and the length in the y-axis direction are also substantially the same as those of the third substrate 2a. The fourth substrate 2b is joined to the third substrate 2a in which the notch 8 is formed, so that the groove portion 15 is formed on the lower surface of the second cover member 2. That is, the lower surface of the fourth substrate 2 b located inside the notch 8 becomes the bottom surface of the groove portion 15, and the inner wall of the notch 8 becomes the inner wall of the groove portion 15. The groove 15 extends from the inflow port 14 to at least a region directly above the detection unit 13, and the cross-sectional shape is, for example, a rectangular shape.

  The fourth substrate 2b is formed with a third through hole 18 that penetrates the fourth substrate 2b in the thickness direction. The third through hole 18 is located on the end of the notch 8 when the fourth substrate 2b is stacked on the third substrate 2a. Therefore, the end portion of the groove portion 15 is connected to the third through hole 18. The third through hole 18 is for releasing the air in the groove 15 to the outside.

  A second electrode 62 is formed on a portion of the lower surface of the fourth substrate 2b facing the detection unit 13. Note that the portion of the lower surface of the fourth substrate 2 b that faces the detection unit 13 is a part of the inner wall of the groove 15. In addition, a lead electrode 63 (not shown) of the second electrode 62 is also formed on the lower surface of at least one of the third substrate 2a and the fourth substrate 2b. The second electrode 62 and the extraction electrode 63 are formed by using a thin film forming method such as a sputtering method, a vapor deposition method, or a CVD (Chemical Vapor Deposition) method. A detailed example will be described. After the metal layer is formed on the lower surface of the fourth substrate 2b, patterning is performed by a photolithography method using a reduction projection exposure machine (stepper) and a RIE (Reactive Ion Etching) apparatus. By executing, the second electrode 62 and the extraction electrode 63 are formed.

  The first substrate 1a, the second substrate 1b, the third substrate 2a, and the fourth substrate 2b are made of, for example, paper, plastic, celluloid, ceramics, or the like. These substrates can all be formed of the same material. By forming all of these substrates with the same material, the thermal expansion coefficients of the respective substrates can be made substantially uniform, so that deformation due to the difference in the thermal expansion coefficients of the respective substrates is suppressed. The detection unit 13 may be coated with a biomaterial, but some of the detection unit 13 is easily deteriorated by external light such as ultraviolet rays. In that case, an opaque material having a light shielding property may be used as the material of the first cover member 1 and the second cover member 2. On the other hand, when almost no alteration due to light outside the detection unit 13 occurs, the second cover member 2 in which the groove 15 is formed may be formed of a material that is nearly transparent. In this case, the state of the sample solution flowing in the flow channel can be visually confirmed.

  Next, the detection element 3 will be described. 5 is a perspective view of the detection element 3, and FIG. 6 is a plan view of the detection element 3 with the first hollow member 21 and the second hollow member 22 removed.

  The detection element 3 includes a substrate 10, a first electrode 61 disposed on the upper surface of the substrate 10, a detection unit 13 provided on the first electrode 61, a first IDT electrode 11, a second IDT electrode 12, a first extraction electrode 19, and A second extraction electrode 20 and a third electrode 64 are provided.

  The substrate 10 is made of a single crystal substrate having piezoelectricity such as a lithium tantalate (LiTaO 3) single crystal, a lithium niobate (LiNbO 3) single crystal, or a crystal. The planar shape and various dimensions of the substrate 10 may be set as appropriate. As an example, the thickness of the substrate 10 is 0.3 mm to 1.0 mm.

  The first IDT electrode 11 has a pair of comb electrodes as shown in FIG. Each comb electrode has two bus bars facing each other and a plurality of electrode fingers extending from each bus bar to the other bus bar side. The pair of comb electrodes are arranged so that a plurality of electrode fingers mesh with each other. The second IDT electrode 12 is configured similarly to the first IDT electrode 11. The first IDT electrode 11 and the second IDT electrode 12 constitute a transversal IDT electrode.

  The first IDT electrode 11 is for generating a predetermined surface acoustic wave, and the second IDT electrode 12 is for receiving the SAW generated by the first IDT electrode 11. The first IDT electrode 11 and the second IDT electrode 12 are arranged in the same straight line so that the second IDT electrode 12 can receive the SAW generated in the first IDT electrode 11. The frequency characteristics can be designed using parameters such as the number of electrode fingers of the first IDT electrode 11 and the second IDT electrode 12, the distance between adjacent electrode fingers, the width of intersection of the electrode fingers, and the like. As SAWs excited by the IDT electrodes, there are various vibration modes. For example, the detection element 3 uses a vibration mode of a transverse wave called an SH wave.

  Further, an elastic member for suppressing SAW reflection may be provided outside the first IDT electrode 11 and the second IDT electrode 12 in the SAW propagation direction (y-axis direction). The SAW frequency can be set, for example, within a range of several megahertz (MHz) to several gigahertz (GHz). Especially, if it is set to several hundred MHz to 2 GHz, it is practical, and downsizing of the detection element 3 and thus downsizing of the biosensor 100 can be realized.

  The first IDT electrode 11 is connected to the first extraction electrode 19. The first extraction electrode 19 is extracted from the first IDT electrode 11 to the side opposite to the detection unit 13, and the end 19 e of the first extraction electrode 19 is electrically connected to the wiring 7 provided on the first cover member 1. Yes. The second IDT electrode 12 is connected to the second extraction electrode 20. The second extraction electrode 20 is extracted from the second IDT electrode 12 to the side opposite to the detection unit 13, and the end 20 e of the second extraction electrode 20 is electrically connected to the wiring 7.

  The first IDT electrode 11, the second IDT electrode 12, the first extraction electrode 19 and the second extraction electrode 20 are made of, for example, aluminum, an alloy of aluminum and copper, or the like. These electrodes may have a multilayer structure. In the case of a multilayer structure, for example, the first layer is made of titanium or chromium, and the second layer is made of aluminum or an aluminum alloy.

  The first IDT electrode 11 and the second IDT electrode 12 are covered with a protective film (not shown). The protective film contributes to preventing oxidation of the first IDT electrode 11 and the second IDT electrode 12. The protective film is made of, for example, silicon oxide, aluminum oxide, zinc oxide, titanium oxide, silicon nitride, or silicon. The thickness of the protective film is, for example, about 1/10 (10 to 30 nm) of the thickness of the first IDT electrode 11 and the second IDT electrode 12. The protective film may be formed over the entire top surface of the substrate 10 so as to expose the end 19e of the first extraction electrode 19 and the end 20e of the second extraction electrode 20.

  Between the first IDT electrode 11 and the second IDT electrode 12, the first electrode 61 and the detection unit 13 are provided. The first electrode 61 has, for example, chromium and a gold two-layer structure formed on the chromium. The detection unit 13 is provided on the surface of the first electrode 61 or the surface of the substrate 10, and an aptamer made of a nucleic acid or a peptide is fixed thereon. The nucleic acid is, for example, DNA (Deoxyribo Nucleic Acid), RNA (Ribo Nucleic Acid), PNA (Peptide Nucleic Acid) and the like. In the case where the target substance is contained in the sample solution, when the sample solution comes into contact with the detection unit 13, the target substance in the sample solution is combined with the aptamer fixed to the detection unit 13, and the state of the substrate surface changes. It will be.

  In the example shown in FIGS. 4B to 6, assuming that the first IDT electrode 11, the second IDT electrode 12, and the detection unit 13 arranged along the y-axis direction are one set, the biosensor 100 is provided with two sets. ing. For example, a detection unit 13-1 and a detection unit 13-2 are provided. Thereby, it becomes possible to perform two types of detection by one biosensor by making the aptamer fixed to one detection part 13 different. Further, one of the two detection units 13 may be used as a reference by not fixing an aptamer fixed to the other. In the example illustrated in FIGS. 4B to 6, the case where the detection unit 13-2 is used as a reference is illustrated.

  Moreover, in the example shown in FIGS. 4B to 6, the case where the detection unit 13 is provided on the entire surface of the first electrode 61 is shown as an example, but the present invention is not limited to this. For example, the detection unit 13 may be provided only on a part of the surface of the first electrode 61, or may be provided across both the surface of the first electrode 61 and the surface of the substrate 10. In addition, the detection unit 13 may be provided at a place different from the place where the first electrode 61 is provided.

  The first electrode 61 is connected to the extraction electrode. In the example shown in FIGS. 5 and 6, the case where the first electrode 61 and the third electrode 64 are connected to the second extraction electrode 20 is shown as an example. However, the present invention is not limited to this, Depending on the arrangement, it may be connected to the first extraction electrode 19 or may be connected to another extraction electrode. Note that the first electrode 61 may be formed on the substrate 10 using any method, and is formed using the same method as the second electrode 62, for example.

  Thus, the first electrode 61, the second electrode 62, and the third electrode 64 are each connected to the extraction electrode. As a result, an electric field is generated between the first electrode 61 and the second electrode 62 by applying a voltage to the extraction electrode connected to the first electrode 61 and the extraction electrode connected to the second electrode 62. It becomes possible. The voltage applied to the first electrode 61 and the second electrode 62 is determined in consideration of the charge of the target substance, the oxidation-reduction potential of the substance contained in the sample solution, the hydrogen overvoltage, the oxygen overvoltage, and the like. Further, by connecting a measuring instrument for measuring a high-impedance potential difference (voltage difference) between the extraction electrode connected to the third electrode 64 and the extraction electrode connected to the first electrode 61, the third The electrode can be used as a reference electrode. Thereby, the voltage applied to the first electrode 61 and the second electrode 62 can be stabilized.

  Here, the direction of the electric field generated between the first electrode 61 and the second electrode 62 is set to the direction in which the substance to be detected moves to the detection unit 13 according to the charge of the substance to be detected. Sometimes, the detection sensitivity of the biosensor can be improved.

  In the example illustrated in FIGS. 4B to 6, the case where the first electrode 61 is provided only on one of the two detection units 13 is illustrated. Specifically, the two detection units 13 are both provided on the metal, while only the metal provided at the lower part of the detection unit 13-1 is connected to the second extraction electrode 20 and functions as the first electrode 61. The case of doing is shown as an example. However, the present invention is not limited to this, and the first electrode 61 may be provided in both of the detection units 13. In addition, when the 1st electrode 61 is provided in one of the two detection parts 13, the 1st electrode 61 is provided in the lower part of the detection part 13 which is not a reference.

  The first IDT electrode 11 is covered with a first hollow member 21 as shown in FIG. The 1st hollow member 21 is located in the upper surface of the board | substrate 10, and the inside is hollow. A hollow portion of the first hollow member 21 in a state where the first hollow member 21 is placed on the upper surface of the substrate 10 is the first vibration space 23. The first IDT electrode 11 is sealed in the first vibration space 23. Thus, the first IDT electrode 11 is isolated from the outside air and the sample solution, and the first IDT electrode 11 can be protected. In addition, since the first vibration space 23 is secured, it is possible to suppress the deterioration of the characteristics of the SAW excited in the first IDT electrode 11.

  Similarly, the second IDT electrode 12 is covered with the second hollow member 22. Similarly to the first hollow member 21, the second hollow member 22 is located on the upper surface of the substrate 10, and the inside is hollow as shown in FIG. 4A. A hollow portion of the second hollow member 22 in a state where the second hollow member 22 is placed on the upper surface of the substrate 10 is the second vibration space 24. The second IDT electrode 12 is sealed in the second vibration space 24. Thereby, the second IDT electrode 12 is isolated from the outside air and the sample solution, and the second IDT electrode 12 can be protected. In addition, since the second vibration space 24 is secured, it is possible to suppress deterioration of the characteristics of the SAW received at the second IDT electrode 12.

  The shape of the vibration space may be a rectangular parallelepiped shape, may be a dome shape when viewed in cross section, may be an ellipse shape when viewed in plan, and the shape and arrangement of the IDT electrode. In combination, any shape may be used.

  The first hollow member 21 includes an annular frame fixed to the upper surface of the substrate 10 so as to surround the two first IDT electrodes 11 arranged along the x-axis direction, and a frame so as to close the opening of the frame. It consists of a lid fixed to the body. Such a structure can be formed, for example, by forming a resin film using a photosensitive resin material and patterning the resin film by a photolithography method or the like. The second hollow member 22 can be formed in the same manner.

  In the biosensor 100, the two first IDT electrodes 11 are covered with one first hollow member 21, but the two first IDT electrodes 11 may be covered with separate first hollow members 21. Alternatively, the two first IDT electrodes 11 may be covered with one first hollow member 21 and a partition may be provided between the two first IDT electrodes 11. Similarly, for the second IDT electrode 12, the two second IDT electrodes 12 may be covered with separate second hollow members 22, and a partition is formed between the two second IDT electrodes 12 using one second hollow member 22. May be provided.

  In order to detect the sample solution in the detection element 3 using SAW, first, an AC voltage of a predetermined frequency is applied to the first IDT electrode 11 from an external measuring instrument via the wiring 7 or the first extraction electrode 19. To do. Then, the surface of the substrate 10 is excited in the region where the first IDT electrode 11 is formed, and SAW having a predetermined frequency is generated. Part of the generated SAW propagates toward the detection unit 13, passes through the detection unit 13, and then reaches the second IDT electrode 12. Here, in the detection unit 13, when the target substance is contained in the sample solution, a change caused by a reaction with the target substance or the like occurs on the substrate surface. As a result, characteristics such as the phase of the SAW passing under the detection unit 13 change. When the SAW whose characteristics have changed in this way reaches the second IDT electrode 12, a signal corresponding to the SAW is output from the second IDT electrode 12. This signal is output to the outside through the second extraction electrode 20 and the wiring 7 and the sample solution is read by an external measuring device through a signal processing circuit that outputs a voltage corresponding to a characteristic change such as a phase. The properties and ingredients can be investigated.

  In order to guide the sample solution to the detection unit 13, the biosensor 100 uses a capillary phenomenon. Specifically, since the second cover member 2 is joined to the first cover member 1, the groove portion 15 formed on the lower surface of the second cover member 2 becomes an elongated tube. Taking into account the material of the first cover member 1 and the second cover member 2 and the like, by setting the width or diameter of the groove portion 15 to a predetermined value, a capillary phenomenon is caused in the elongated tube formed by the groove portion 15. it can. The width (dimension in the y-axis direction) of the groove portion 15 is, for example, 0.5 mm to 3 mm, and the depth (dimension in the z-axis direction) is, for example, 0.1 mm to 0.5 mm. In addition, the groove part 15 has the extension part 15e which is a part extended beyond the detection part 13, and the 3rd through-hole 18 connected with the extension part 15e is formed in the 2nd cover member 2. As shown in FIG. When the sample solution enters the flow path, the air present in the flow path is released to the outside from the third through hole 18.

  By forming a tube that generates such a capillary phenomenon in the cover member including the first cover member 1 and the second cover member 2, the sample solution flows through the groove 15 when the sample solution is brought into contact with the inlet 14. It is sucked into the cover member as a path. Therefore, according to the biosensor 100, since the sample sensor itself has a sample solution suction mechanism, the sample solution can be sucked without using an instrument such as a pipette. Moreover, since the part with the inflow port 14 is roundish and the inflow port 14 is formed at the apex, the inflow port 14 is easily discriminated.

  By the way, the channel of the sample solution formed by the groove 15 has a depth of about 0.3 mm, whereas the detection element 3 has a thickness of about 0.3 mm. The depth of the channel and the thickness of the detection element 3 Are almost equal. Therefore, if the detection element 3 is placed on the flow channel as it is, the flow channel is blocked. Therefore, in the biosensor 100, as shown in FIG. 4, a recess 5 is provided in the first cover member 1 on which the detection element 3 is mounted, and the detection element 3 is accommodated in the recess 5, thereby allowing the flow of the sample solution. The road is not blocked. That is, by setting the depth of the concave portion 5 to be approximately the same as the thickness of the detection element 3 and mounting the detection element 3 in the concave portion 5, the flow path formed by the groove portion 15 can be secured.

  FIG. 3 is a perspective view of the second cover member 2 in a state where the fourth substrate 2b is removed. Since the flow path of the sample solution is secured, the sample solution flowing into the flow path due to capillary action is detected. It is possible to guide smoothly to the portion 13.

  From the viewpoint of sufficiently securing the flow path for the sample solution, as shown in FIG. And good. For example, if the height from the bottom surface of the recess 5 on the upper surface of the substrate 10 is made the same as the depth of the recess 5, the bottom surface of the flow path and the detection unit 13 are almost aligned when the inside of the groove portion 15 is viewed from the inlet 14. Can be the same height. In the biosensor 100, the thickness of the substrate 10 is made smaller than the depth of the recess 5, and the height of the first hollow member 21 and the second hollow member 22 from the bottom surface of the recess 5 is substantially the same as the depth of the recess 5. I am doing so. When the height from the bottom surface of the concave portion 5 of the first hollow member 21 and the second hollow member 22 is made larger than the depth of the concave portion 5, the first partition portion 25 and the second partition portion 26 of the third substrate 2a are made more than other portions. Although it is necessary to process thinly, by making the height from the bottom face of the recessed part 5 of the 1st hollow member 21 and the 2nd hollow member 22 substantially the same as the depth of the recessed part 5, the need for such a process becomes unnecessary. Production efficiency is good.

  The planar shape of the recess 5 is, for example, similar to the planar shape of the substrate 10, and the recess 5 is slightly larger than the substrate 10. More specifically, the recess 5 is sized such that a gap of about 100 μm is formed between the side surface of the substrate 10 and the inner wall of the recess 5 when the substrate 10 is mounted in the recess 5.

  The detection element 3 is fixed to the bottom surface of the recess 5 with a die bond material mainly composed of epoxy resin, polyimide resin, silicon resin, or the like. The end 19e of the first extraction electrode 19 and the wiring 7 are electrically connected by a thin metal wire 27 made of, for example, Au. The connection between the end 20e of the second extraction electrode 20 and the wiring 7 is the same. The connection between the first lead electrode 19 and the second lead electrode 20 and the wiring 7 is not limited to the metal thin wire 27 but may be a conductive adhesive such as Ag paste, for example. The connection between the end of the extraction electrode 63 formed on the lower surface of the fourth substrate 2b and the wiring 7 is the same. In this case, it connects with a conductive adhesive instead of a thin metal wire.

  Since a gap is provided in the connection portion between the first extraction electrode 19, the second extraction electrode 20, the extraction electrode 63 and the wiring 7, the metal is formed when the second cover member 2 is bonded to the first cover member 1. Breakage of the thin wire 27 is suppressed. This gap can be easily formed by providing the first through hole 16 and the second through hole 17 in the third substrate 2a. In addition, the presence of the first partition portion 25 between the first through hole 16 and the groove portion 15 prevents the sample solution flowing through the groove portion 15 from flowing into the gap formed by the first through hole 16. it can. Thereby, it is possible to suppress occurrence of a short circuit due to the sample solution between the plurality of first extraction electrodes 19. Similarly, the presence of the second partition portion 26 between the second through hole 17 and the groove portion 15 suppresses the sample solution flowing through the groove portion 15 from flowing into the gap formed by the second through hole 17. Can do. Thereby, it is possible to suppress occurrence of a short circuit due to the sample solution between the plurality of second extraction electrodes 20.

  The first partition portion 25 is located on the first hollow member 21, and the second partition portion 26 is located on the second hollow member 22. Therefore, more strictly speaking, the flow path of the sample solution is defined not only by the groove portion 15 but also by the side wall on the groove portion side of the first hollow member 21 and the side wall on the groove portion side of the second hollow member 22. From the viewpoint of preventing leakage of the sample solution into the gap formed by the first through hole 16 and the second through hole 17, the first partition portion 25 is on the upper surface of the first hollow member 21, and the second partition portion 26 is In the biosensor 100, it is better to contact with the upper surface of the second hollow member 22, but between the lower surface of the first partition member 25 and the upper surface of the first hollow member 21, and the lower surface of the second partition member 26. And a gap between the upper surface of the second hollow member 22. This gap is, for example, 10 μm to 60 μm. By providing such a gap, for example, even when pressure is applied to this portion when the biosensor 100 is pinched with a finger, the pressure is absorbed by the gap, and the first hollow member 21 and the second hollow member 21 are absorbed. It is possible to suppress the pressure from directly acting on the member 22. As a result, the first vibration space 23 and the second vibration space 24 can be prevented from being greatly distorted. In addition, since the sample solution usually has a certain degree of viscoelasticity, it is difficult for the sample solution to enter the gap by setting the gap to 10 μm to 60 μm, and the sample solution is formed by the first through hole 16 and the second through hole 17. It is also possible to suppress leakage into the gap.

  The width of the first partition portion 25 is wider than the width of the first vibration space 23. In other words, the side wall of the first partition portion 25 is positioned on the frame of the first hollow member 21. Thereby, even when the 1st partition part 25 contacts the 1st hollow member 21 with the pressure from the outside, since the 1st partition part 25 is supported by the frame part, it can suppress a deformation | transformation of the 1st hollow member 21. it can. For the same reason, it is preferable that the width of the second partition portion 26 is wider than the width of the second vibration space 24.

  The first extraction electrode 19, the second extraction electrode 20, the extraction electrode 63, the metal thin wire 27, and the wiring 7 located in the gap formed by the first through hole 16 and the second through hole 17 are covered with an insulating member 28. ing. Since the first extraction electrode 19, the second extraction electrode 20, the extraction electrode 63, the thin metal wire 27, and the wiring 7 are covered with the insulating member 28, these electrodes can be prevented from corroding. Further, by providing the insulating member 28, the sample solution enters the gap between the first partition part 25 and the first hollow member 21 or the gap between the second partition part 26 and the second hollow member 22. Even in this case, the sample solution is blocked by the insulating member 28. Therefore, a short circuit between the extraction electrodes due to leakage of the sample solution can be suppressed. In addition, although the insulating member 28 was demonstrated using the example with which all the insides of the space | gap were filled, the space which is not partially filled may remain | survive.

  As described above, according to the biosensor 100 described above, the detection element 3 is accommodated in the recess 5 of the first cover member 1, thereby securing a flow path for the sample solution from the inlet 14 to the detection unit 13. Thus, the sample solution aspirated from the inlet by capillary action or the like can flow to the detection unit 13. That is, it is possible to provide the biosensor 100 having the suction mechanism itself while using the thick detection element 3.

  In addition, according to the biosensor 100 described above, a pair of electrodes is provided in the thickness direction of the detection unit 13, and an electric field can be generated in the space formed on the detection unit by the groove. As a result, the detection sensitivity can be improved. Specifically, when an electric field is generated such that the substance to be detected moves to the detection surface according to the charge of the substance to be detected, the probability that the substance to be detected and the detection surface are in contact with each other is increased. And detection sensitivity can be improved.

  For example, proteins have a positive or negative charge from the isoelectric point depending on the pH. Based on this, by generating an electric field from a pair of electrodes in accordance with the charge of the protein to be detected, the protein to be detected can be brought closer to the surface of the detection unit 13. As a result, the probability that the detection target substance and the detection surface come into contact with each other can be increased, and the detection sensitivity can be improved.

  Conversely, substances other than the detection target can be moved away from the surface of the detection unit 13 by generating an electric field. That is, an electric field may be generated so that a substance other than the detection target moves away from the detection surface in accordance with the charge of the substance other than the detection target. In that case, it is possible to prevent substances other than the detection target from adhering to the detection surface non-specifically and affecting the change in the state of the detection surface. As a result, the SN ratio is improved and the detection sensitivity can be improved.

  Furthermore, the above-described two types of electric field application may be sequentially performed in a predetermined procedure. Specifically, a voltage is applied between the first electrode and the second electrode so that the substance to be detected approaches the detection surface after detecting that the sample solution has flowed in based on a change in the state of the detection surface. Next, the detection target that non-specifically adheres to the detection surface between the first electrode and the second electrode when the change in the output signal due to the binding of the substance to be detected to the detection surface becomes a specific state What is necessary is just to apply the voltage which a substance other than moves away from a detection surface.

  Such voltage application state control (a series of sequence control) can be automatically controlled on the detector body side that connects the biosensor 100 and reads a signal.

  Further, an example in which an electric field corresponding to the charge of a substance other than the detection target is generated will be described below. First, latex particles or gold (nano) particles whose surface is positively or negatively charged are contained in the sample solution. These latex particles and gold particles can specifically capture the substance to be detected. However, it is different from the structure for capturing the substance to be detected arranged on the detection surface. As a result, when latex particles or gold particles are applied to the detection target substance captured on the detection surface, the latex particles or gold particles adhere only to the detection target substance on the detection surface. For this reason, even when the concentration of the substance to be detected is very small, the signal intensity accompanying the detection increases, and the detection sensitivity is improved. Here, by applying an electric field in such a direction that the latex particles and gold (nano) particles move away from the detection surface by the first electrode and the second electrode, surplus latex particles and gold particles that do not adhere to the substance to be detected. Can be removed. That is, latex particles and gold (nano) particles that do not adhere to the detection target substance can be easily removed without additionally performing a B / F separation operation performed in a so-called ELISA or the like.

  Latex particles and gold particles may be introduced into the biosensor 100 after being mixed in the sample solution in advance, or may be introduced into the biosensor 100 by being attached to the flow path in a detachable state. It may be included in the sample solution by contacting with the sample solution.

  FIG. 7 is a cross-sectional view showing a modification of the biosensor 100. The cross-sectional view of FIG. 7 corresponds to the cross section shown in FIG. 4A.

  In this modification, the position where the terminal 6 is formed is changed. In the embodiment described above, the terminal 6 is formed at the other end portion in the longitudinal direction of the second substrate 1b. However, in this modification, it is formed on the upper surface of the fourth substrate 2b. The terminal 6 and the wiring 7 are electrically connected by a through conductor 29 that penetrates the second cover member 2. The through conductor 29 is made of, for example, Ag paste or plating. The terminal 6 can also be formed on the lower surface side of the first cover member 1. Therefore, the terminal 6 can be formed at an arbitrary position on the surface of the first cover member 1 and the second cover member 2, and the position thereof can be determined according to the measuring instrument to be used.

  FIG. 8 is a cross-sectional view showing another modification of biosensor 100. This cross-sectional view corresponds to the cross section shown in FIG. 4B.

  In this modification, an absorbing material 30 that absorbs the sample solution at a predetermined speed is provided at the end of the flow path formed by the groove 15. By providing such an absorbing material 30, it is possible to absorb the excess sample solution and make the amount of the sample solution flowing on the detection unit 13 constant to perform stable measurement. The absorbent material 30 is made of, for example, a porous material that can absorb a liquid such as a sponge.

  In addition, the structure of the biosensor 100 described above is an example, and the present invention is not limited to this, and any biosensor 100 may be used. For example, a region between the first IDT electrode 11 and the second IDT electrode 12 on the surface of the substrate 10 that is a piezoelectric substrate without using a metal film may be used as the detection unit 13. In this case, the physical property such as the viscosity of the sample solution is detected by directly attaching the sample solution to the surface of the substrate 10. More specifically, the SAW phase change due to a change in the viscosity of the sample solution on the detection unit 13 is read.

  For example, in the above-described embodiment, the detection element 3 is composed of a surface acoustic wave element. However, the detection element 3 is not limited to this, and an optical waveguide or the like is formed so that surface plasmon resonance occurs, for example. The detected element 3 may be used. In this case, for example, a change in the refractive index of light in the detection unit is read. In addition, the detection element 3 in which a vibrator is formed on a piezoelectric substrate such as quartz can be used. In this case, for example, a change in the oscillation frequency of the vibrator is read.

  Further, for example, as the detection element 3, a plurality of types of devices may be mixed on the same substrate. For example, an enzyme electrode method enzyme electrode may be provided next to the SAW element. In this case, in addition to the immunization method using an antibody or an aptamer, measurement by an enzyme method is possible, and the number of items that can be examined at a time can be increased.

  Further, for example, in the above-described embodiment, the first cover member 1 is formed by the first substrate 1a and the second substrate 1b, and the second cover member 2 is formed by the third substrate 2a and the fourth substrate 2b. Although an example is shown, the present invention is not limited to this, and one in which any of the substrates is integrated, for example, the first cover member 1 in which the first substrate 1a and the second substrate 1b are integrated may be used.

  In the above example, the third electrode is provided as a reference electrode. However, the function of the third electrode may be provided to the second electrode. In that case, the material constituting the second electrode is assumed to be less reactive to the sample solution.

  For example, in the above-described embodiment, an example in which one detection element 3 is provided has been described. However, a plurality of detection elements 3 may be provided. In this case, the recess 5 may be provided for each detection element 3 or a long recess 5 that can accommodate all the detection elements 3 may be formed.

  Moreover, the groove part 15 may be provided in any of the 1st cover member 1 and the 2nd cover member 2, and may be provided in both. For example, the flow path may be formed by providing a groove in both the first cover member 1 and the second cover member 2, and one of the first cover member 1 and the second cover member 2 may be formed. The channel may be formed by providing a groove.

  For example, in the above-described embodiment, the case where the substrate 10 is provided on the first cover member 1 and the first cover member 1 and the second cover member 2 are joined is described as an example. However, the present invention is not limited to this. For example, the flow path may be formed by bonding a cover member directly to the substrate 10.

  The case where the cover member 52 is joined to the board | substrate 10 is demonstrated using FIGS. 9-10. FIG. 9 is a plan view illustrating an example in which a cover member is bonded to a substrate. The plan view of FIG. 9 is a plan view showing the xy plane. In the case of explaining using FIG. 9 to FIG. 10, the case where the flow path is formed by arranging the cover member 52 at an interval from the surface of the substrate 10 by the frame body 51 bonded to the substrate 10 is used. Although explained, it is not limited to this. For example, a groove may be provided in the cover member itself, and the cover member may be provided directly on the upper surface of the substrate 10, or a flow path may be provided by providing grooves in both the cover member and the substrate 10 provided on the upper surface of the substrate 10. It may be formed, or a channel may be formed by providing a groove in the substrate 10.

  As shown in FIG. 9, the substrate 10 includes a first electrode 61, a third electrode 64, and two detection units 13-1 and 13-2, and convex portions 51-1 to 51-1 extending in the x-axis direction. Part 51-4. In the example shown in FIG. 9, the first IDT electrode 11 and the second IDT electrode 12 are provided below the portion 54 and the portion 55 in the substrate surface of the substrate 10. In the example shown in FIG. 9, there are four convex portions 51, which are arranged in parallel to each other, so that the portion of the substrate surface where the detection portion 13 is provided and the portion where the portion 54 or 55 is provided. The case where and are separated is shown. However, the present invention is not limited to this, and the four convex portions 51 may not be arranged in parallel, and the convex portion 51-1 and the convex portion 51-4 may not be provided in the example illustrated in FIG. good.

  Here, the convex portions 51-1 to 51-4 are formed by, for example, photolithography. As a more detailed example, after covering the substrate surface of the substrate 10 with an arbitrary resist, by removing unnecessary resist so that the convex portions 51-1 to 51-4 are formed, the convex portions 51-1 to convex portion 51-4 are formed. The length of the convex portions 51-1 to 51-4 in the z-axis direction may be any length, and is preferably 30 μm to 100 μm.

  FIG. 10 is a cross-sectional view illustrating an example of a case where a cover member is bonded to a substrate. The cross-sectional view shown in FIG. 10 is a cross-sectional view in the yz plane. In the example shown in (1) of FIG. 10, the substrate 10 has a first IDT electrode 11 and a second IDT electrode 12 on the substrate surface. The substrate surface of the substrate 10 is covered with a protective film 50 that contributes to preventing oxidation of each electrode and wiring.

  The protective film 50 contributes to preventing oxidation of each electrode and wiring. The protective film 50 is made of, for example, silicon oxide, aluminum oxide, zinc oxide, titanium oxide, silicon nitride, or silicon. For example, the protective film 50 is silicon dioxide (SiO2).

  The protective film 50 is formed over the entire top surface of the substrate 10 so as to expose the extraction electrode. Since the first IDT electrode 11 and the second IDT electrode 12 are covered with the protective film 50, the IDT electrode can be prevented from corroding.

  The thickness of the protective film 50 is, for example, 100 nm to 10 μm. Note that the protective film 50 does not necessarily have to be formed over the entire top surface of the substrate 10. For example, the protective film 50 covers only the vicinity of the center of the top surface of the substrate 10 so that the region along the outer periphery of the top surface of the substrate 10 including the extraction electrode is exposed. You may form as follows. Further, in the examples shown in FIGS. 9 and 10, the case where the protective film 50 is used is shown as an example, but the present invention is not limited to this, and the protective film 50 may not be used.

  The short-circuit electrode 42 is for electrically short-circuiting the portion of the upper surface of the substrate 10 that becomes the SAW propagation path. By providing the short-circuit electrode 42, the loss of SAW can be reduced depending on the type of SAW. Note that, particularly when a leaky wave is used as the SAW, it is considered that the loss suppression effect by the short-circuit electrode 42 is high.

  The short-circuit electrode 42 has, for example, a rectangular shape extending along the SAW propagation path from the first IDT electrode 11 to the second IDT electrode 12. The width of the short-circuit electrode 42 in the direction orthogonal to the SAW propagation direction (x-axis direction) is, for example, the same as the intersection width of the electrode fingers of the first IDT electrode 11. The end of the short-circuit electrode 42 on the first IDT electrode side in the direction parallel to the SAW propagation direction (y-axis direction) is the SAW half wavelength from the center of the electrode finger located at the end of the first IDT electrode 11. Located in a remote location. Similarly, the end of the short-circuit electrode 42 on the second IDT electrode 12 side in the y-axis direction is located away from the center of the electrode finger located at the end of the second IDT electrode 12 by a half wavelength of SAW.

  Here, it is possible to design the frequency characteristics using parameters such as the number of electrode fingers of the first IDT electrode 11 and the second IDT electrode 12, the distance between adjacent electrode fingers, and the intersection width of the electrode fingers. Examples of the SAW excited by the IDT electrode include a Rayleigh wave, a love wave, and a leaky wave. An elastic member for suppressing SAW reflection may be provided in a region outside the first IDT electrode 11 in the SAW propagation direction. The SAW frequency can be set, for example, within a range of several megahertz (MHz) to several gigahertz (GHz). Especially, if it is several hundred MHz to 2 GHz, it will be practical, and it will be possible to reduce the size of the substrate 10 and thus the size of the biosensor 100A.

  The short-circuit electrode 42 may be in an electrically floating state, or may be provided with a ground potential lead electrode and connected to this to be a ground potential. When the short-circuit electrode 42 is set to the ground potential, propagation of a direct wave due to electromagnetic coupling between the first IDT electrode 11 and the second IDT electrode 12 can be suppressed.

  The short-circuit electrode 42 is made of, for example, aluminum or an alloy of aluminum and copper. These electrodes may have a multilayer structure. In the case of a multilayer structure, for example, the first layer is made of titanium or chromium, and the second layer is made of aluminum or an aluminum alloy.

  In addition, the substrate 10 has a convex portion 51− after a conductive line for connecting to the first electrode 61, the detection portion 13, and the end portion 20e of the second extraction electrode 20 is formed on the protective film 50 covering the substrate surface. 1 to convex portions 51-4 are formed. That is, the substrate 10 is formed on the protective film 50 covering the substrate surface, the conductive wire for connecting to the first electrode 61, the detection unit 13, and the end 20e of the second extraction electrode 20, and the projections 51-1 to 51-1. Part 51-4.

  Here, as shown in (2) of FIG. 10, the flow path and the vibration space are formed by joining the cover member 52 on the substrate 10 having the detection unit 13. Specifically, the convex portions 51-1 to 51-4 provided on the substrate 10 and the cover member 52 are joined. As a result, a groove for guiding the sample solution to the detection unit 13 is formed, and a vibration space is formed on the IDT electrode.

  Arbitrary methods may be used for joining the convex portions 51-1 to 51-4 and the cover member 52, for example, an ultraviolet adhesive may be used. The cover member 52 may be formed using an arbitrary material, preferably a hydrophilic material, and more preferably a hydrophilic film. Alternatively, the surface facing the flow path may be hydrophilized using a material that does not have hydrophilicity as the cover member 52.

  A second electrode 62 and a lead electrode 63 are formed in advance on the surface of the cover member 52 facing the flow path. When the cover member 52 is connected to the convex portion 51, the lead electrode 63 formed on the cover member 52 and the lead electrode 63 formed from the upper surface of the convex portion 51-4 to the surface of the substrate 10 are electrically connected. By connecting, it is possible to connect to the external electrode.

  For example, an arbitrary process may be performed on the detection unit 13. For example, a process for preventing the substance from adhering to the detection unit 13 may be performed. For example, based on the fact that nucleic acids such as DNA are negatively charged, the nucleic acid such as DNA can be prevented from adhering by charging the metal film of the detection unit 13 negatively by an arbitrary method. Also good. Similarly, a metal film formed of a metal other than gold may be used as the metal film of the detection unit 13 used as a reference in view of the tendency that nucleic acids such as DNA adhere to gold. In the example illustrated in FIG. 10, the extraction electrode 63 is provided on both the substrate 10 and the cover member 52. However, the embodiment is not limited thereto, and the cover member 52 is not limited thereto. It may be provided only for.

  In the example shown in FIGS. 9 and 10, the second electrode 62 is formed on the main surface of the cover member 52 on the side facing the flow path, but may be provided on the main surface on the opposite side. In this case, the second electrode 62 may be formed before the cover member 52 is connected to the convex portion 51, or may be formed after joining.

  Furthermore, in the example shown in FIGS. 9 and 10, the example in which the first electrode 61 and the second electrode 62 are disposed so as to face the inside of the flow path has been described. However, the first electrode 61 is provided below the protective film 50. The second electrode 62 may be formed on the main surface opposite to the main surface facing the flow path of the cover member 52.

  Moreover, it replaces with the convex parts 51-1 to 51-4 of FIG. 9, 10, and has a through-hole which exposes the part 55, and the convex part 51-2 is from the area | region where the convex part 51-1 is arrange | positioned. From the area where the convex part 51-3 is arranged to the area where the convex part 51-4 is arranged, having a wide convex part continuously covering up to the arranged area and a through hole exposing the portion 54 You may use the wide convex part which covers continuously. With such a configuration, a large number of planar regions can be provided on the upper surface of the convex portion, so that connection electrodes and the like can be routed.

  Moreover, although the example shown in FIGS. 9 and 10 has been described using an example in which a short-circuit electrode is provided, the short-circuit electrode is not essential and may be omitted.

  The biosensor described above can be used for general purposes such as maintenance of beauty and youth, such as fatigue and anti-aging markers, in addition to conventional medical uses such as cancer markers. Here, by embedding a SAW chip as a high-sensitivity transducer as a disposable sensor, a hydrogen peroxide source can be easily detected, and a light, thin and small sensor suitable for disposable can be obtained.

  In addition, for example, the SAW propagation path that is an action part with a biological substance and the IDT electrode that is a conversion part to an electric signal can be finely formed on one substrate. As a result, the biosensor itself can be made very small, can be mass-produced by a wafer process, etc., and a disposable sensor chip can be easily realized.

  In addition, for example, the detection circuit of SAW is the same as the circuit configuration adopted in many wireless terminals and communication devices in tablet terminals, and the above-described detection circuit of biosensor is an electronic device such as a wireless terminal or tablet terminal. It is also possible to easily connect to.

Embodiment of detection method
In one embodiment, the disclosed detection method includes a contact step of bringing the specimen solution into contact with the detection unit 13 of the biosensor 100 described above. For example, the specimen solution is directly introduced into the flow path from the inlet 14, and the specimen solution is guided from the inlet 14 to the detector 13 via the groove 15, thereby being brought into contact with the detector 13.

  In addition, the disclosed detection method includes a detection step in which a detection process is performed by detecting a change in the state of the surface of the detection unit 13 in contact with the sample solution in the contact step.

  Here, the change in the state of the substrate surface means a change in mass, a change in dielectric constant, a change in viscoelasticity, a change in propagation characteristics, a change in resonance frequency, and the like caused by the substance to be detected being bonded to or adhering to the detection unit 13. Etc. For example, when measurement is performed using an SPR device, when a substance to be detected is combined with the detection unit 13, the mass and dielectric constant of the substrate surface change, and an SPR angle change due to this change occurs. In this case, the change in the state of the substrate surface is a change in mass or a change in dielectric constant due to the adhesion of the substance to be detected, and the change in the state of the substrate surface is detected by detecting the SPR angle change. In addition, when the SAW sensor is used, a propagation characteristic change caused by a mass change or a viscoelastic change on the substrate surface occurs. In this case, the change in the state of the substrate surface is a change in mass or a change in viscoelasticity caused by adhesion of a substance to be detected, and a change in the state of the substrate surface is detected by detecting a change in propagation characteristics. In addition, when the QCM measuring apparatus is used, a resonance frequency change caused by a mass change on the substrate surface occurs. In this case, the change in the state of the substrate surface is a change in mass due to the adhesion of the substance to be detected, and the change in the state of the substrate surface is detected by detecting the change in resonance frequency.

[Embodiments of Detection System and Detection Device]
In one embodiment, the disclosed detection system performs detection processing by detecting a change in the state of the surface of the detection unit 13 due to the biosensor described above and the specimen solution contacting the surface of the detection unit 13 of the biosensor. And a detection device to be executed.

  The detection device is a device that executes an arbitrary detection process using the above-described biosensor. Examples of the detection device include an SPR device, a SAW sensor control device, and a QCM measurement device. The detection device is preferably a SAW sensor control device. The SPR device, the SAW sensor control device, and the QCM measurement device as the disclosed detection device may be any device as long as measurement can be performed using the above-described biosensor, and a known device may be used as it is. It may be used after remodeling.

DESCRIPTION OF SYMBOLS 1 1st cover member 2 2nd cover member 3 Detection element 4 Through-hole 5 for recessed part formation Recess 8 Notch 10 Board | substrate 11 1st IDT electrode 12 2nd IDT electrode 13 Detection part 14 Inflow port 15 Groove part 61 1st electrode 62 2nd electrode 100 biosensor

Claims (10)

A substrate,
A detector provided on the substrate;
A cover member provided on at least one of an upper part and a lower part of the substrate, and having an inflow port into which a sample solution flows and a groove extending from the inflow port to at least the detection unit;
An electric field passing through the detection unit is generated in a space formed on the detection unit by the groove unit on the inner wall of the flow path into which the analyte solution flows formed by the groove unit. A pair of electrodes ;
A first IDT (InterDIgital Transducer) electrode that is provided on the surface of the substrate and generates an elastic wave propagating toward the detection unit on the surface of the substrate;
A second IDT electrode that is provided on the surface of the substrate and receives the elastic wave that has passed through the detection unit;
And the detection unit is arranged between the pair of electrodes in one direction and between the first IDT electrode and the second IDT electrode in another direction different from the one direction .   The biosensor according to claim 1, wherein the cover member is bonded onto the substrate. The cover member includes a first cover member on which the substrate is disposed on an upper surface, and a second cover member joined to the first cover member with the substrate interposed therebetween,
The biosensor according to claim 1, wherein at least one of the first cover member and the second cover member includes the inflow port and the groove portion. A first electrode that is one electrode of the pair of electrodes is provided in the flow path and on the substrate, and a second electrode that is the other electrode of the pair of electrodes is the first electrode of the groove portion. Provided in a position facing the first electrode in the inner wall of the flow path;
The biosensor according to claim 1, wherein the detection unit is provided on the first electrode. Is bonded to the upper surface of the substrate a first vibration space provided before SL on the 1IDT electrode, a first hollow member for sealing the first 1IDT electrode to said first oscillation space,
2. A second hollow member provided with a second vibration space on the second IDT electrode and bonded to the upper surface of the substrate, and further comprising a second hollow member for sealing the second IDT electrode in the second vibration space. 5. The biosensor according to any one of 4 above.   The biosensor according to any one of claims 1 to 5, wherein latex particles or gold particles whose surfaces are positively or negatively charged are attached to the inner wall of the flow path. The substrate is a piezoelectric substrate;
The biosensor according to claim 1, wherein the detection unit is a surface of the substrate to which the specimen solution is directly attached. A substrate, a detection unit provided on the substrate, an inlet provided at least one of an upper part and a lower part of the substrate, and a groove extending from the inlet to at least the detection unit; The detection unit is disposed in a space formed on the detection unit by the groove part and spaced from each other on the inner wall of the flow path into which the sample solution flows formed by the cover part and the groove part. A pair of electrodes that generate an electric field that passes through, a first IDT electrode that is provided on the surface of the substrate, generates an elastic wave that propagates toward the detection unit on the surface of the substrate, and a surface that is provided on the surface of the substrate. and, and a second 2IDT electrode for receiving the acoustic wave that has passed through the detector, the detector is, between the pair of electrodes in one direction and the other direction different from the direction A contacting step of contacting the sample solution to the detecting section of the arrangement biosensor between Oite the first 1IDT electrode and the second 2IDT electrode,
And a detection step of executing a detection process by detecting a change in the state of the surface of the detection unit in contact with the sample solution in the contact step. A substrate, a detection unit provided on the substrate, an inlet provided in at least one of an upper part and a lower part of the substrate, and a groove extending from the inlet to at least the detection unit. The detection unit is arranged in a space formed on the detection unit by the groove part, spaced from each other on the inner wall of the flow path into which the sample solution formed by the groove part flows. A pair of electrodes that generate an electric field passing through the first IDT electrode that is provided on the surface of the substrate and generates an elastic wave that propagates toward the detection unit on the surface of the substrate; and a surface that is provided on the surface of the substrate is and, and a second 2IDT electrode for receiving the acoustic wave that has passed through the detector, the detector is, between the pair of electrodes in one direction, and the other that is different from the one direction A biosensor is disposed between the first 1IDT electrode and the second 2IDT electrode in,
A detection system comprising: a detection device that performs a detection process by detecting a change in the state of the surface of the detection unit caused by the sample solution coming into contact with the surface of the detection unit of the biosensor. A substrate, a detection unit provided on the substrate, an inlet provided in at least one of an upper part and a lower part of the substrate, and a groove extending from the inlet to at least the detection unit. The detection unit is arranged in a space formed on the detection unit by the groove part, spaced from each other on the inner wall of the flow path into which the sample solution formed by the groove part flows. A pair of electrodes that generate an electric field passing through the first IDT electrode that is provided on the surface of the substrate and generates an elastic wave that propagates toward the detection unit on the surface of the substrate; and a surface that is provided on the surface of the substrate is and, and a second 2IDT electrode for receiving the acoustic wave that has passed through the detector, the detector is, between the pair of electrodes in one direction, and the other that is different from the one direction Detection process by detecting the change of state of the on the surface of the detector arrangement biosensor between the first 1IDT electrode and the second 2IDT electrode, the detection portion of the surface due to the sample solution is contacted in The detection apparatus provided with the detection control part which performs.

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