JP2019070630A - Elastic surface wave sensor - Google Patents

Abstract

To provide an elastic surface wave sensor that can dissolve a reactant in the amount of liquid sample necessary for an SAW device and react the reactant with the sample.SOLUTION: The present invention includes: a substance holding unit 8 for holding a secondary antibody (reactant) in a supply passage 5 for flowing a sample dropped from a drop hole 221 to an SAW device 4, the secondary antibody reacting with a liquid sample flowing from the upstream; and a sample supplying unit 9 located below the substance holding unit 8, the sample supplying unit supplying the sample to the SAW device 4 having reacted with the secondary antibody; and a space 10A between the substance holding unit 8 and the sample supplying unit 9, the space being for the secondary antibody to react with the sample.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a surface acoustic wave sensor that supplies a liquid sample to a SAW device to measure its characteristics.

  Conventionally, the lateral flow method is known as a method for detecting a substance in a liquid sample, and immunochromatography (immunochromatographic assay) is widely used as a form of the lateral flow method. In a typical form of immunochromatographic assay, a sandwich assay in which a target substance contained in a sample is sandwiched between two types of antibodies is used.

  For example, when detecting an antigen as a target substance, a test strip using this sandwich assay (see, for example, Patent Document 1) partially overlaps the sample pad to which a liquid sample containing the antigen is dropped, and the sample pad. And a conjugate pad in which the secondary antibody involved in the antigen-antibody reaction with the antigen is attached and retained in a dry state such as freeze-drying, and partially superimposed on the conjugate pad, and the antigen-antibody reaction An antibody-immobilized pad having a primary antibody immobilized thereon, and an absorbent pad partially superposed on the antibody-immobilized pad, which absorbs the analyte and causes the analyte to flow from the sample pad to the antibody-immobilized pad. Prepare. According to this test strip, when the sample dropped onto the sample pad passes through the conjugate pad, the secondary antibody dissolves to cause an antigen and antigen-antibody reaction, and while this sample flows through the antibody-immobilized pad, 1 When an antigen-antibody reaction occurs with the secondary antibody, the primary antibody and the antigen are bound to each other to form a complex of the primary antibody and the antigen as a product of the antigen-antibody reaction. By observing the label of the secondary antibody bound to the antigen in this complex, the substance (antigen) involved in the antigen-antibody reaction can be visually identified.

  In addition, conventionally, there are known surface acoustic wave sensors for detecting characteristics of various substances and measuring properties such as physical property values (see Patent Document 2). The surface acoustic wave sensor includes a surface acoustic wave (SAW) device in which a comb-shaped transmission electrode and a reception electrode are disposed opposite to each other on a piezoelectric substrate with a propagation path of the surface acoustic wave interposed therebetween. By applying a sandwich assay to this surface acoustic wave sensor, substances involved in antigen-antibody reaction can be detected without visual observation.

  More specifically, for example, as described in paragraph [0004] of Patent Document 3, the primary antibody is immobilized in the propagation path of the SAW device, and the dropped sample flows to the propagation path of the SAW device. Place the test strip mentioned above. Then, during the flow of the sample, an antigen-antibody reaction is caused between the antigen and the secondary antibody (reactant), and when the sample reaches the propagation channel, an antigen-antibody reaction occurs between the antigen and the primary antibody. Let In this case, the phase of the surface acoustic wave propagating in the propagation path changes before and after the antigen-antibody reaction, and the characteristic change obtained by receiving this changed surface acoustic wave at the receiving electrode is regarded as the amplification change of the electrical signal. , Antigen-antibody reaction can be detected.

JP 2012-189355 A JP, 2013-096866, A JP, 2017-009492, A

  The surface acoustic wave sensor needs to be wet at substantially the same time on the entire surface of the propagation path when measuring a liquid phase system, so it is necessary to flow several tens of μl of sample toward the propagation path at one time. This fluid volume is equal to the fluid volume of the sample flowing through the conventional test strip. However, since nitrocellulose with a low flow rate is used for the antibody immobilization pad of the test strip, it can not be applied as it is to a surface acoustic wave sensor.

  Therefore, it is conceivable to use a membrane such as a porous substrate having a flow rate higher than that of nitrocellulose instead of nitrocellulose, but when the flow rate of the sample increases, the antigen-antibody reaction between the sample and the secondary antibody is incomplete. I could have been. This is because in the conventional test strip, the flow rate of nitrocellulose is low, and it takes some time for the secondary antibody to dissolve out of the conjugate pad, so the amount of analyte necessary for the surface acoustic wave sensor is porous. When the material is flushed, the sample passes through the conjugate pad before the secondary antibody dissolves, and an appropriate antigen-antibody reaction can not be obtained between the antigen and the secondary antibody.

  An object of the present invention is to provide a surface acoustic wave sensor capable of dissolving a reaction substance in an amount of a sample necessary for a SAW device and reacting the sample with the sample in order to solve the above-mentioned problems.

  In order to solve the above problems, the invention according to claim 1 is characterized in that a substance holding unit for holding a reactive substance that reacts with a liquid sample flowing from the upstream side, and a downstream side of the substance holding unit A sample supply unit for supplying the sample that has reacted with the reactant to the SAW device; and a gap between the substance holding unit and the sample supply unit for obtaining a time for the reactant to melt and react with the sample Is a surface acoustic wave sensor characterized in that

  According to the first aspect of the present invention, when passing through the substance holding portion, the liquid sample flowing from the upstream side dissolves the reactant in the space on the downstream side thereof, and reacts with the dissolved reactant. The sample that has reacted with the reactant is supplied to the SAW device by the sample supply unit.

  The invention according to claim 2 is the surface acoustic wave sensor according to claim 1, wherein the reaction material is melted on the upstream side of the substance holding portion to obtain time for reacting with the sample. And the air gap of

  The invention according to claim 3 is the surface acoustic wave sensor according to claim 1 or 2, wherein the analyte is the substance by sealing the periphery of the substance holding portion while leaving the passing direction of the analyte. After passing through the inside of the holding portion, it flows into the air gap.

  According to the first aspect of the present invention, since the air gap is provided between the substance holding portion and the sample supply portion, even if the sample of the necessary amount of liquid flows in the SAW device, the reaction material is sufficiently contained in the air gap. It is possible to obtain the time to dissolve it and to react it with the sample. Therefore, since the characteristics of the specimen appropriately reacted to the reactant can be measured by the SAW device, the measurement accuracy of the surface acoustic wave sensor is improved. In addition, since the reactant dissolves in the substance holding portion and the air gap on the downstream side to react with the sample, the amount of the reactant is reduced relative to the amount of liquid required for the sample to reach the SAW device. Can.

  According to the second aspect of the invention, since the second space is provided on the upstream side of the substance holding portion, the state (time) in which the sample remains in the second space to pass through the substance holding portion It is possible to dissolve the reaction substance by using and react with the sample.

  According to the third aspect of the present invention, by sealing the periphery of the substance holding portion while leaving the passing direction of the sample, the sample always flows in the substance holding portion and then flows into the void, for example, It is possible to prevent the sample from flowing above and below the substance holding portion without passing through the inside of the substance holding portion. This makes it possible to improve the efficiency with which the reactant dissolves and reacts with the sample.

(A) is a top view of a surface acoustic wave sensor concerning an embodiment of this invention, (B) is a side view. (A) is the top view which removed the upper surface case of the surface acoustic wave sensor of FIG. 1, (B) is AA sectional drawing of FIG. 1 (A). (A) is BB sectional drawing of the surface acoustic wave sensor of FIG. 1, (B) is CC sectional drawing, (C) is DD sectional drawing. It is an explanatory view showing the state where a sample flows from a sample pad to a sample supply part. It is a photograph which shows the state which the sample flows from a sample pad to a SAW device. It is a photograph which shows the state which the antigen antibody reaction of an antigen and a secondary antibody failed. It is a graph which shows the result of having processed the detection signal of the antigen antibody reaction output from the surface acoustic wave sensor with a signal processing device.

  Hereinafter, the present invention will be described based on the illustrated embodiments.

  1 to 5 show an embodiment of the present invention, and FIGS. 1 (A) and 1 (B) are a plan view and a side view of a surface acoustic wave sensor 1 according to this embodiment. The surface acoustic wave sensor 1 combines a primary antibody and a secondary antibody (reactant) by antigen-antibody reaction with an antigen contained in a liquid sample using a sandwich assay method, and the physical property values of the sample, etc. The characteristics of are measured using a SAW device.

  The surface acoustic wave sensor 1 includes a rectangular solid case 2 accommodating a SAW device or the like therein, and a printed circuit board 3 partially projecting from the front of the case 2 and has a length of, for example, about 50 mm. It has become. The surface acoustic wave sensor 1 is a so-called cassette-like sensor device, and is inserted from the printed circuit board 3 side into a cassette insertion port provided in a signal processing device (not shown). The printed circuit board 3 is provided with a pair of contacts 31 electrically connected to the SAW device. These contact points 31 contact the connection terminals in the cassette insertion slot when the surface acoustic wave sensor 1 is inserted into the cassette insertion slot of the signal processing apparatus. Thereby, the SAW device and the signal processing device are electrically connected.

  The case 2 is composed of a bottom case 21 constituting the bottom side of the case 2 and a top case 22 constituting the top side of the case 2. A combination of the bottom case 21 and the top case 22 forms a rectangular shape. Case 2 of A drip hole 221 for dripping a liquid sample into the case 2 is provided on the upper end of the upper surface case 22 at the left end side (the end edge side opposite to the printed circuit board 3). The bottom case 21 and the top case 22 are made of, for example, an insulating material such as plastic.

  FIG. 2A is a plan view showing the surface acoustic wave sensor 1 from which the upper surface case 22 is removed, and FIG. 2B is a cross-sectional view taken along the line A-A of FIG. 1A. . The printed circuit board 3 is fixed to be placed on the bottom case 21, and has a rectangular shape extending from the front side of the case 2 along the longitudinal direction of the case 2 into the case 2. .

  The SAW device 4 is fixed on the printed circuit board 3. The SAW device 4 is, for example, a reflective SAW device, and the piezoelectric substrate 41, the propagation path 42, the interdigital electrode 43, and the sealing member 44 covering the upper side to prevent the sample from adhering to the interdigital electrode 43 Is equipped.

  The piezoelectric substrate 41 is not particularly limited as long as it can propagate surface acoustic waves, and is, for example, a quartz substrate of 36 degrees Y plate 90 degrees X axis propagation, or 36 degrees Y plate X axis propagation tantalum It is lithium oxide (LiTaO3). The surface acoustic wave is a wave that propagates along the surface of the piezoelectric substrate 41, and is, for example, a slip surface acoustic wave on which a shear wave propagates.

  The propagation path 42 is a region on which the sample is placed, and is formed on the surface of the piezoelectric substrate 41 so as to extend from the position adjacent to the comb electrode 43 to one end along the longitudinal direction of the piezoelectric substrate 41. The propagation path 42 is made of, for example, a metal film deposited on the piezoelectric substrate 41, and aluminum (Al), copper (Cu), gold (Au), or the like is used as the material of the metal film. In fact, a material that is chemically stable to the sample is preferable.

  On the upper surface of the propagation path 42, a primary antibody for capturing an antigen in a sample by an antigen-antibody reaction is immobilized. For example, this primary antibody is applied and immobilized on the upper surface of the propagation path 42 and is in a dried state together with the stabilizer. When the analyte is supplied to the propagation path 42, the antigen in the specimen is captured by the antigen-antibody reaction. And change the phase (velocity) of the surface wave transmitted on the propagation path 42.

  The comb electrode 43 is disposed on the other end side of the piezoelectric substrate 41 so as to be adjacent to the propagation path 42. The comb-shaped electrode 43 has a pair of input terminals 431 electrically connected to the contacts 31 of the printed board 3 by the bonding wires 45. When the surface acoustic wave sensor 1 is set in the signal processing device, the comb electrode 43 is electrically connected to the signal processing device via the contact 31 and the bonding wire 45. When a high frequency oscillation signal is applied to the input terminal 431 from the signal processing device, the comb electrode 43 is excited thereby to generate a surface acoustic wave on the piezoelectric substrate 41. The surface acoustic wave generated on the piezoelectric substrate 41 propagates on the propagation path 42 toward one end of the piezoelectric substrate 41, is reflected on one end of the piezoelectric substrate 41, and is received by the comb electrode 43.

  Although one end side of the piezoelectric substrate 41 is used for reflection of the surface acoustic wave, a reflector made of a comb electrode or the like may be provided. In addition, a transmission comb electrode and a reception comb electrode may be disposed so as to sandwich the propagation path 42.

  In the case 2, there is provided a sample supply path 5 extended along the longitudinal direction of the case 2 so as to be directed to the SAW device 4 from the position facing the dropping hole 221. The supply path 5 is provided on the bottom case 21 so as to have the same height as the propagation path 42 of the SAW device 4, and the upper supply path 52 facing the upper portion of the lower supply path 51. And

  As shown in FIGS. 3 (A), 3 (B) and 3 (C) showing the B-B cross section, the C-C cross section, and the D-D cross section of FIG. 1A, the lower supply passage 51 has a bottom case 21. And a pair of lower side walls 512 provided so as to project upward along the longitudinal direction at both end edges of the upper surface of the protrusion 511. Further, the upper supply passage 52 is provided at a position facing the lower side wall 512, along the longitudinal direction of the upper surface case 22 and projecting downward toward the lower side wall 512 so as to abut on the lower side wall 512. 521 is provided. As a result, the supply passage 5 becomes a rectangular tubular passage whose upper and lower and both side surfaces are closed.

  A film 6 is disposed on the lower supply passage 51 in the supply passage 5. The film 6 is, for example, a water-repellent plastic film, and makes the sample easily flow in the supply path 5. One end of the film 6 is extended from the supply path 5 onto the piezoelectric substrate 41. This is to prevent the specimen, which has flowed through the supply passage 5, from dripping into the gap between the lower supply passage 51 and the piezoelectric substrate 41.

  A sample pad 7 extended from the position facing the dropping hole 221 toward the SAW device 4 is superimposed on the film 6. The sample pad 7 is a sheet (so-called membrane) made of a porous substrate (for example, a fiber material or the like). The sample dropped from the drop hole 221 is absorbed by the sample pad 7 and flows in the sample pad 7 toward the SAW device 4 side.

  On the downstream side of the sample pad 7, a substance holding portion 8 corresponding to the conjugate pad of the test strip is disposed on the film 6. The substance holding portion 8 is made of a porous base material or a sheet of glass fiber, and a secondary antibody (reactant substance) in a dry state such as freeze-drying is attached and held on the surface or inside thereof.

  The upper supply passage 52 is provided with a narrow passage 522 which protrudes downward so as to abut on the substance holding portion 8. The narrow passage 522 abuts on the upper surface of the substance holding portion 8 to seal the periphery of the substance holding portion 8 leaving the passing direction of the sample. As a result, the sample that has flowed out of the sample pad 7 always passes through the inside of the substance holding unit 8 and then flows downstream, so the contact between the sample and the secondary antibody is increased, and the secondary antibody Can increase the efficiency of antigen binding.

  The sample supply unit 9 is disposed on the film 6 downstream of the substance holding unit 8. The sample supply unit 9 is a sheet made of a porous base material, absorbs the sample having passed through the substance holding unit 8 and supplies (flows) the sample to the propagation path 42 of the SAW device 4. The sample supply unit 9 is extended from the supply path 5 to the upper side of the propagation path 42, and contacts the propagation path 42 by absorbing and expanding the sample, and wets the entire upper surface of the propagation path 42 substantially simultaneously. .

  In the supply path 5, a gap 10 </ b> A is provided between the substance holding unit 8 and the sample supply unit 9. The space 10A is a space formed by arranging the sample supply unit 9 so as not to contact the substance holding unit 8. In the space 10A, the film 6 is exposed in the supply path 5.

  Further, in the supply path 5, an upstream air gap (second air gap) 10 </ b> B is provided between the sample pad 7 and the substance holding portion 8. The upstream side gap 10B is a gap formed by arranging the sample pad 7 so as not to contact the substance holding portion 8, and the film 6 is exposed in the supply path 5 in the upstream side gap 10B.

  FIG. 4 is a schematic view showing a state in which the sample flows from the sample pad 7 to the sample supply unit 9 through the substance holding unit 8. In the figure, the hatched portion is a sample S and the point portion is a secondary antibody. As shown in FIG. 6A, the sample S dropped from the drop hole 221 is absorbed by the sample pad 7 and flows to the downstream side (SAW device 4 side). The sample S that has flowed to the end of the sample pad 7 flows out of the sample pad 7 and stays in the upstream void 10B, as shown in FIG. When the sample S fills the upstream space 10B and comes into contact with the substance holding portion 8, the substance holding portion 8 absorbs the sample S in the upstream space 10B and causes it to flow downstream, as shown in FIG. . At that time, time is obtained for the secondary antibody to dissolve into the sample S and cause an antigen-antigen reaction with the antigen. The specimen S having passed through the substance holding portion 8 flows out from the substance holding portion 8 and stays in the space 10A on the downstream side as shown in FIG. However, time can be obtained for generating an antigen-antibody reaction between the antigen of the sample S and the secondary antibody. The sample in which the secondary antibody is bound to the antigen by the antigen-antibody reaction between the antigen and the secondary antibody is absorbed by the sample supply unit 9 and flowed to the propagation path 42 as shown in FIG.

  As described above, the cavity 10A and the upstream cavity 10B allow the secondary antibody of the substance holding portion 8 to dissolve in the sample S to make time for the antigen and the antigen-antibody reaction by causing the sample S to stay on the film 6. Provided in That is, when the substance holding unit 8 is in contact with the sample pad 7 and the sample supply unit 9, the sample S immediately passes through the substance holding unit 8 due to the absorption power of the sample supply unit 9, and the secondary antibody It becomes insoluble in the sample S and time for producing an antigen-antigen-antibody reaction can not be obtained. However, by providing the upstream air gap 10B and the air gap 10A on the upstream side and the downstream side of the substance holding portion 8, the specimen A stays in the supply passage 5 and the flow velocity decreases, so the specimen S and the substance holding The contact time with the part 8 is prolonged, and the secondary antibody dissolves in the sample to easily cause an antigen-antigen reaction.

  The length in the flow direction of the air gap 10A and the upstream air gap 10B is, for example, about 1 mm to several mm, and the absorbency of the sample S such as the sample pad 7, the substance holding unit 8, the sample supply unit 9, etc. Is set appropriately according to the flow rate of

  FIG. 5 shows the flow state of the sample S photographed using the surface acoustic wave sensor 1 in which the case 2 is formed of translucent plastic so that the inside of the case 2 can be observed from the outside. As shown to the figure (A), in the surface acoustic wave sensor 1 before the test substance S is dripped, the secondary antibody fixed to the substance holding part 8 is reflected in blackishness. In order to be able to confirm the secondary antibody, the secondary antibody is colored.

  When the sample S is dropped from the dropping hole 221, the sample S flows in the sample pad 7 to the substance holding unit 8. As a result, as shown in FIG. 5B, the secondary antibody dissolves in the sample S, and an antigen-antibody reaction between the antigen of the sample S and the secondary antibody occurs. In the state shown in FIG. 5B that the substance holding portion 8 in FIG. 5B looks darker than the substance holding portion 8 in FIG. The irregular reflection due to the unevenness of the upper surface case 22 is suppressed. The sample S in which the secondary antibody is dissolved and bound to the antigen is flowed toward the propagation path 42 by the sample supply unit 9. In FIG. 5C, although the substance holding unit 8 can not be visually recognized, it can be seen that a whitish shadow representing the specimen S in flow appears on the supply path 5 and the SAW device 4. FIG. 5D shows a state where a predetermined time has elapsed after the supply of the sample S is completed, and since the sample S on the supply path 5 is thinner, the sample S is on the propagation path 42 of the SAW device 4. It is understood that it is supplied to

  As a comparison, as shown in FIG. 5D, FIG. 6 shows a state in which a predetermined time has elapsed since the dropping of the sample S, as in the case of FIG. 5D. As can be seen from this figure, in the surface acoustic wave sensor without the air gap 10A and the upstream air gap 10B, the secondary antibody appears blackish because it remains undissolved in the substance holding portion 8.

  FIG. 7 is a graph showing the result of processing the detection signal of the antigen-antibody reaction output from the surface acoustic wave sensor 1 by the signal processing device, the horizontal axis representing time, and the vertical axis representing the phase change of the detection signal. . In addition, lines L1, L2 and L3 in this graph show the phase change when the concentration of the secondary antibody is 0%, 50% and 100% with respect to the predetermined antigen concentration, and L3 in particular The case where the surface acoustic wave sensor 1 of a form is utilized is shown. That is, L1 measures the characteristics of the sample S with the surface acoustic wave sensor without the conventional air gap 10A and the upstream air space 10B, and the time when the secondary antibody dissolves in the sample S and does not react is obtained. L2 represents the case where the secondary antibody was slightly dissolved and reacted with the sample S, but the concentration of the secondary antibody was low. On the other hand, in L3, by measuring the characteristics of the sample S by the surface acoustic wave sensor 1 of the present embodiment, the secondary antibody dissolves sufficiently in the sample S and reacts, and the concentration of the secondary antibody becomes high. Represents the case. As can be seen from this graph, in L1 and L2, since the antigen-antibody reaction between the secondary antibody and the antigen is not sufficiently performed, only a slight phase change showing the antigen-antibody reaction appears. On the other hand, as indicated by L 3, if the surface acoustic wave sensor 1 of the present embodiment is used, the secondary antibody can be sufficiently dissolved in the sample S to cause an antigen-antibody reaction with the antigen. A reaction can be obtained.

  Next, the operation of the above embodiment will be described. The surface acoustic wave sensor 1 is inserted (set) into the cassette insertion slot of the signal processing device from the printed circuit board 3 side. As a result, the pair of contacts 31 of the printed circuit board 3 contact the connection terminals in the cassette insertion slot, and the SAW device 4 signal processing device is electrically connected.

  The signal processing device applies a high frequency oscillation signal to the comb electrode 43 through the contact 31 and the bonding wire 45. As a result, the piezoelectric substrate 41 is excited to generate a surface acoustic wave. This surface acoustic wave is propagated on the propagation path 42 toward one end of the piezoelectric substrate 41 and is reflected by one end of the piezoelectric substrate 41 to form a comb shape. It is received by the electrode 43. The comb electrode 43 converts the surface acoustic wave into an electric signal and transmits the electric signal to the signal processing device. The signal processing device obtains electrical characteristic quantities of the phase change and the amplitude change of the electric signal before the sample S is dropped.

  Next, in a state where the surface acoustic wave sensor 1 is inserted into the signal processing apparatus, the sample S is dropped from the dropping hole 221. The dropped sample S is absorbed by the sample pad 7 and flows downstream. The sample S that has flowed to the end of the sample pad 7 flows out of the sample pad 7 and stays in the upstream void 10B, resulting in a slow flow rate. When the sample S fills the upstream space 10B and contacts the substance holding unit 8, the substance holding unit 8 absorbs the sample S in the upstream space 10B and causes it to flow downstream. At that time, the secondary antibody dissolves in the sample S and causes an antigen-antigen reaction with the antigen.

  The sample S that has passed through the substance holding unit 8 flows out of the substance holding unit 8 and stays in the space 10A on the downstream side, and the flow velocity becomes low again. An antigen-antibody reaction between the antigen of the sample S staying in the space 10A and the secondary antibody occurs. Due to the antigen-antibody reaction between the antigen and the secondary antibody, the sample in which the secondary antibody is bound to the antigen is absorbed by the sample supply unit 9 and flows to the propagation path 42. The sample S that has reached the propagation path 42 is captured by the primary antibody by an antigen-antibody reaction with the primary antibody immobilized on the propagation path 42.

  The signal processing apparatus applies a high frequency oscillation signal to the comb-shaped electrode 43 to generate a surface acoustic wave after a predetermined time has elapsed since the dropping of the sample S. The surface acoustic wave reflected on one end side of the piezoelectric substrate 41 is received by the comb electrode 43, converted into an electric signal, and transmitted to the signal processing device. The signal processing device obtains electrical characteristic quantities of the phase change and the amplitude change of the electric signal after the antigen-antibody reaction of the sample S. The signal processing apparatus calculates the characteristics of the sample S by comparing the timing when the sample S is flowed to the propagation path 42, that is, the signal when the SAW device 4 is in the liquid phase and the signal after a predetermined time has elapsed. Do. Alternatively, the signal processing device calculates the characteristics of the sample S from the slope in the antigen-antibody reaction. The measurement by the signal processing device is continuously performed from before dropping the sample S until after a predetermined time has elapsed.

  As described above, according to the surface acoustic wave sensor 1 according to this embodiment, since the air gap 10A is provided between the substance holding portion 8 and the sample supply portion 9, a sample of the liquid amount necessary for the SAW device 4 is obtained. Even when S flows, the secondary antibody (reactant) can be sufficiently dissolved in the space 10A to cause an antigen-antibody reaction with the antigen of the sample S. Therefore, since the characteristics of the sample S appropriately reacted with the secondary antibody can be measured by the SAW device 4, the measurement accuracy of the surface acoustic wave sensor 1 is improved. In addition, since the secondary antibody is melted in the substance holding portion 8 and the air gap 10A on the downstream side to cause an antigen-antibody reaction with the sample S, the amount of liquid necessary for causing the sample S to reach the SAW device 4 is The amount of secondary antibody can be reduced.

  Further, since the upstream side void (second void) 10B is provided on the upstream side of the substance holding portion 8, the sample S remains in the upstream side void (second void) 10B in order to pass through the substance holding portion 8. It is possible to dissolve the secondary antibody using the above conditions and cause an antigen-antibody reaction with the sample S.

  Further, by sealing the periphery of the substance holding portion 8 leaving the passing direction of the sample S, the sample S always flows in the substance holding portion 8 and then flows into the air gap 10A. It can prevent flowing up and down the substance holding part 8 without passing through the inside of the substance holding part 8. Thereby, it is possible to melt the secondary antibody and improve the efficiency of the antigen-antibody reaction with the sample S.

  The embodiment of the present invention has been described above, but the specific configuration is not limited to the above embodiment, and even if there is a change in design or the like within the scope of the present invention, Included in the invention. For example, in the above embodiment, the upstream air gap 10B is provided on the upstream side of the substance holding portion 8, but at least only the air gap 10A on the downstream side may be provided. In addition, the sample S is made to flow to the substance holding unit 8 by the sample pad 7. However, for example, the supply path 5 on the upstream side of the substance holding unit 8 is inclined to allow the sample S to flow to the substance holding unit 8. May be

DESCRIPTION OF SYMBOLS 1 surface acoustic wave sensor 2 case 3 printed circuit board 4 SAW device 41 piezoelectric substrate 42 propagation path 43 comb-shaped electrode 5 supply path 6 film 7 sample pad 8 substance holding part 9 specimen supply part 10A void 10B upstream void S analyte

Claims (3)

A substance holding unit for holding a reaction substance that reacts with a liquid sample that has flowed from the upstream side; a sample supply unit that is disposed downstream of the substance holding unit and supplies the sample that has reacted with the reaction substance to the SAW device And a gap is provided between the substance holding unit and the sample supply unit for obtaining a time for the reaction substance to melt and react with the sample.
Surface acoustic wave sensor characterized by On the upstream side of the substance holding unit, a second void is provided to obtain time for the reactant to melt and react with the sample.
The surface acoustic wave sensor according to claim 1, characterized in that By sealing the periphery of the substance holding portion while leaving the passing direction of the sample, the sample is allowed to flow into the void after passing through the substance holding portion.
The surface acoustic wave sensor according to claim 1 or 2, characterized in that