WO2015025946A1 - センサ - Google Patents

センサ Download PDF

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Publication number
WO2015025946A1
WO2015025946A1 PCT/JP2014/071969 JP2014071969W WO2015025946A1 WO 2015025946 A1 WO2015025946 A1 WO 2015025946A1 JP 2014071969 W JP2014071969 W JP 2014071969W WO 2015025946 A1 WO2015025946 A1 WO 2015025946A1
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WO
WIPO (PCT)
Prior art keywords
flow path
path
sensor
inflow
element surface
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2014/071969
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English (en)
French (fr)
Japanese (ja)
Inventor
浩康 田中
秀冶 栗岡
民谷　栄一
真人 齋藤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kyocera Corp
University of Osaka NUC
Original Assignee
Kyocera Corp
Osaka University NUC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kyocera Corp, Osaka University NUC filed Critical Kyocera Corp
Priority to JP2015532909A priority Critical patent/JP6210569B2/ja
Publication of WO2015025946A1 publication Critical patent/WO2015025946A1/ja
Priority to US15/050,220 priority patent/US10295532B2/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • G01N33/5304—Reaction vessels, e.g. agglutination plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/02—Analysing fluids
    • G01N29/022—Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5308—Immunoassay; Biospecific binding assay; Materials therefor for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites

Definitions

  • the present invention relates to a sensor capable of measuring the properties of a liquid or components contained in the liquid.
  • the liquid may be any fluid as long as it has fluidity, and may have a high viscosity.
  • Patent Document 1 As a sensor that outputs a signal corresponding to a detection target included in a sample (sample liquid) located on a detection unit, a sensor that guides the sample liquid onto the detection unit by capillary action is known (for example, Patent Document 1). ).
  • the detection unit is configured by applying a reagent on a substrate that forms the lower surface (bottom surface) of the flow path for guiding the sample liquid, and the flow path lower surface and the detection unit are continuously provided. Yes.
  • a gap may occur between the lower surface of the flow path and the detection unit.
  • a sensor element having a detection unit is accommodated in a package and a flow path is formed in the package, a minute gap is generated between the sensor element and the package, and consequently, the lower surface of the flow path to be continuous and the sensor element A gap is also generated between the element surface (including the detection unit).
  • the flow of the sample liquid due to the capillary phenomenon stops in the gap, and the sample liquid may not reach the element surface (on the detection unit).
  • the sensor which concerns on 1 aspect of this invention has an element surface, The sensor element which outputs the signal according to the detection target contained in the test substance located in the detection part of the said element surface, and the said sensor inside And a package having a flow path including a space located on the element surface, wherein the lower surface of the flow path includes the element surface and an inflow path extending toward the space.
  • a first gap is located between the lower surface of the inflow path and the element surface, and at least a part of the element surface is located above the lower surface of the inflow path. Yes.
  • a sensor has an element surface, and outputs a signal corresponding to a detection target included in a specimen located in a detection portion of the element surface;
  • a third gap is located between the element surface and the lower surface of the outflow path, and the lower surface of the outflow path is at least partially less than the element surface.
  • a sensor includes an element surface, and a sensor element that outputs a signal corresponding to a detection target included in a specimen located in a detection portion of the element surface;
  • the sample liquid that has reached the gap can easily touch the lower surface on the downstream side.
  • the flow due to capillary action tends to exceed the gap.
  • FIG. 1 is a perspective view showing a sensor according to a first embodiment of the present invention. It is a disassembled perspective view of the sensor of FIG. It is a top view which shows the sensor element of the sensor of FIG. 4A is a cross-sectional view taken along the line VIa-VIa of FIG. 1, and FIG. 4B is a cross-sectional view taken along the line VIb-VIb of FIG.
  • FIGS. 5A to 5C are schematic cross-sectional views for explaining the operation of the sensor of FIG.
  • FIGS. 6A and 6B are cross-sectional views showing a sensor according to the second embodiment of the present invention.
  • FIG. 7A to FIG. 7C are schematic diagrams for explaining a modification.
  • the senor may be set in any direction upward or downward, but in the following, for convenience, the orthogonal coordinate system xyz is defined and the positive side in the z direction is set upward, and the upper surface, the lower surface, etc. The following terms shall be used.
  • FIG. 1 is a perspective view showing a sensor 1 (specimen liquid sensor) according to the first embodiment.
  • the sensor 1 is formed, for example, in a generally rectangular plate shape as a whole.
  • the thickness is, for example, 0.5 mm to 3 mm
  • the length in the x direction is, for example, 1 cm to 5 cm
  • the length in the y direction is, for example, 1 cm to 3 cm.
  • the sensor 1 includes an inlet 3 for taking in the sample liquid, a flow path 5 through which the sample liquid flows from the inlet 3, and an exhaust for exhausting the flow path 5 as the sample liquid flows into the flow path 5.
  • a mouth 7 is formed.
  • the sensor 1 is provided with a plurality of terminals 9 used for input / output of electric signals.
  • the inflow port 3 is opened at one end of the rectangular shape of the sensor 1, for example.
  • the flow path 5 extends in the longitudinal direction of a rectangle.
  • the exhaust port 7 opens, for example, on the upper surface of the sensor 1.
  • the plurality of terminals 9 are located at the other end of the rectangle, for example.
  • Sensor 1 is attached to a reader (not shown) including an oscillation circuit and the like, for example.
  • the mounting is performed, for example, by inserting the end of the sensor 1 on the terminal 9 side into a slot of the reader.
  • the sensor 1 changes the electrical signal input to any one of the plurality of terminals 9 from the reader in accordance with the property or component of the sample liquid taken in from the inflow port 3, and reads the reader from any of the plurality of terminals 9. Output to.
  • the sensor 1 is, for example, a disposable sensor.
  • FIG. 2 is an exploded perspective view of the sensor 1.
  • the sensor 1 has a sensor element 11 and a package 13 that houses the sensor element 11.
  • the sensor element 11 substantially converts an electric signal corresponding to the sample liquid.
  • the package 13 contributes to improvement of the handleability of the sensor element 11 and the like.
  • the sensor element 11 is formed in, for example, a substantially rectangular parallelepiped shape, and the upper surface thereof is an element surface 11a to which a sample liquid is supplied.
  • the sensor element 11 converts an electric signal according to the property or component of the sample liquid on the element surface 11a.
  • the package 13 includes, for example, a layered lower layer member 15, an intermediate layer member 17, and an upper layer member 19 that are sequentially stacked from the lower side.
  • the middle layer member 17 is formed with a notch 17a. Thereby, a space for accommodating the sensor element 11 and the flow path 5 are formed between the lower layer member 15 and the upper layer member 19.
  • the lower layer member 15 has, for example, the same configuration as a printed wiring board.
  • the insulating base 21 is composed mainly of resin or ceramic, for example.
  • the planar shape of the insulating base 21 is the same as the planar shape of the entire sensor 1, for example.
  • the sensor element 11 is disposed on the upper surface of the insulating substrate 21.
  • the sensor element 11 is fixed to the upper surface of the insulating base 21 with an adhesive, for example.
  • the lower layer member 15 has the above-described plurality of terminals 9 and a plurality of wirings 23 that connect the plurality of terminals 9 and the sensor element 11 on the upper surface thereof.
  • the middle layer member 17 is made of an insulating material such as resin or ceramic, for example.
  • the middle layer member 17 is bonded to the lower layer member 15 with an adhesive, for example.
  • the planar shape (schematic shape) of the middle layer member 17 is a rectangle slightly shorter than the lower layer member 15 so that the plurality of terminals 9 are exposed.
  • the upper layer member 19 is made of, for example, a hydrophilic film. Therefore, the upper layer member 19 has higher wettability with respect to the sample liquid than the lower layer member 15 and the middle layer member 17, for example. Note that the wettability (or hydrophilicity) with respect to the sample liquid can be measured by the contact angle with the sample liquid, as is generally known. That is, the higher the wettability, the smaller the contact angle.
  • the upper layer member 19 is bonded to the middle layer member 17 with an adhesive, for example.
  • the planar shape of the upper layer member 19 is a rectangle that is slightly shorter than the lower layer member 15, similarly to the middle layer member 17. Further, the above-described exhaust port 7 is formed in the upper layer member 19.
  • hydrophilic film a commercially available resinous film that has been subjected to hydrophilic treatment (hydrophilic treatment) can be used.
  • a resinous film whose surface is coated with a hydrophilic material may be used.
  • the resin used as the base material is, for example, a polyester type or a polyethylene type.
  • the hydrophilic material is, for example, polyethylene glycol, phosphorylcholine, polyethylene oxide or polyvinyl alcohol.
  • a resinous film made of a hydrophilic material hydrophilic polymer may be used.
  • the senor 1 does not have flexibility, for example.
  • at least one of the lower layer member 15, the middle layer member 17, and the upper layer member 19 does not have flexibility.
  • the thickness of the middle layer member 17 is thicker than the thickness of the sensor element 11. Therefore, the notch 17a forms a space 5b (see FIG. 4) into which the sample liquid flows on the sensor element 11.
  • the flow path 5 constituted by the notch 17a includes this space 5b, an inflow path 5a for allowing the sample liquid to flow into the space 5b, and an outflow path 5c for allowing the sample liquid to flow out of the space 5b.
  • an inflow side lower surface member 25 constituting the lower surface of the inflow passage 5a and an outflow side lower surface member 27 constituting the lower surface of the outflow passage 5c are provided.
  • These members are made of, for example, a hydrophilic film in the same manner as the upper layer member 19. Therefore, the lower surfaces of the inflow channel 5 a and the outflow channel 5 c have a smaller contact angle with the sample liquid than the lower layer member 15 and the middle layer member 17.
  • the inflow side lower surface member 25 is fixed to the lower layer member 15 by, for example, an inflow side adhesive 37 (see FIG. 4).
  • the outflow side lower surface member 27 is fixed to the lower layer member 15 by, for example, an outflow side adhesive 39 (see FIG. 4).
  • the inflow channel 5a extends, for example, in a straight line from the inflow port 3 to the space 5b with a constant width (y direction).
  • the outflow path 5c extends, for example, in a straight line with a constant width from the space 5b to the side opposite to the inlet 3 (in the traveling direction of the sample liquid).
  • the width of the inflow path 5a and the width of the outflow path 5c are, for example, the same as each other and smaller than the width of the space 5b.
  • the channel 5 has a relatively small height in the z direction.
  • the height of the flow path 5 in the z direction is 50 ⁇ m or more and 0.5 mm or less.
  • the height of the flow path 5 is preferably about 50 ⁇ m.
  • the upper surface (the ceiling surface, the lower surface of the upper layer member 19 and the like) of the flow path 5 is hydrophilic, and consequently has a small contact angle with the sample liquid.
  • the height of the flow path 5 in the z direction is small and the contact angle with the sample liquid on the upper surface and the lower surface of the flow path 5 (the inner surface of the flow path 5) is small,
  • the sample fluid flows through the inflow path 5a toward the sensor element 11 by capillary action.
  • the wettability (hydrophilicity) of the inner surface of the flow path 5 may be a height at which the contact angle of the sample liquid (which may be represented by water) is less than 90 °. Further, from the viewpoint of surely causing capillary action, the wettability of the inner surface of the flow path 5 is preferably a height at which the contact angle is less than 60 °. The same applies to the element surface 11a.
  • FIG. 3 is a plan view showing the sensor element 11.
  • the sensor element 11 is composed of, for example, a SAW sensor element using SAW (Surface Acoustic Wave).
  • the sensor element 11 includes, for example, a piezoelectric substrate 29, a metal film 31, a pair of IDT electrodes 33, and a plurality of pads 35 provided on the piezoelectric substrate 29.
  • the piezoelectric substrate 29 is made of, for example, a single crystal substrate having piezoelectricity such as lithium tantalate (LiTaO 3 ) single crystal, lithium niobate (LiNbO 3 ) single crystal, or quartz.
  • the planar shape and various dimensions of the piezoelectric substrate 29 may be set as appropriate.
  • the thickness of the piezoelectric substrate 29 is not less than 0.3 mm and not more than 1.0 mm.
  • the metal film 31 has, for example, a substantially rectangular planar shape, and is provided on the upper surface of the piezoelectric substrate 29 so as to be located at the center in the y direction and to extend over substantially the entire x direction.
  • the metal film 31 has, for example, a two-layer structure of chromium and gold formed on chromium.
  • aptamers made of nucleic acids or peptides are arranged (immobilized) on the surface of the metal film 31.
  • the pair of IDT electrodes 33 is for generating SAW propagating on the upper surface of the piezoelectric substrate 29 and receiving the SAW.
  • the pair of IDT electrodes 33 are arranged with the metal film 31 interposed therebetween. That is, the metal film 31 is located in the SAW propagation path.
  • the arrangement direction of the metal film 31 and the pair of IDT electrodes 33 is, for example, a direction that intersects (more specifically, intersects with) the flow path 5.
  • Each IDT electrode 33 has a pair of comb electrodes.
  • Each comb electrode has a bus bar and a plurality of electrode fingers extending from the bus bar.
  • the pair of comb electrodes are arranged so that the plurality of electrode fingers mesh with each other.
  • the pair of IDT electrodes 33 constitutes a transversal IDT electrode.
  • the frequency characteristics using parameters such as the number of electrode fingers of the IDT electrode 33, the distance between adjacent electrode fingers, and the cross width of the electrode fingers.
  • the SAW excited by the IDT electrode there are Rayleigh waves, Love waves, leaky waves, and the like, and any of them may be used.
  • An elastic member for suppressing SAW reflection may be provided in an outer region of the pair of IDT electrodes 33 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 is practical, and downsizing of the piezoelectric substrate 29 and further downsizing of the sensor element 11 can be realized.
  • the plurality of pads 35 are connected to the IDT electrode 33.
  • the plurality of pads 35 are connected to the wiring 23 of the lower layer member 15 through, for example, bonding wires 36 (see FIG. 4B).
  • a signal input from the terminal 9 is input to the IDT electrode 33 via the pad 35, and a signal output from the IDT electrode 33 is output to the terminal 9 via the pad 35.
  • the IDT electrode 33, the pad 35, and the wiring connecting them are made of, for example, gold, aluminum, an alloy of aluminum and copper, or the like.
  • These conductors may have a multilayer structure.
  • the first layer may be made of titanium or chromium
  • the second layer may be made of aluminum, an aluminum alloy, or gold
  • titanium or chromium may be laminated on the uppermost layer.
  • the thickness of these conductors is, for example, less than 1 ⁇ m, and the influence on the height of the flow path 5 (for example, 50 ⁇ m or more) is small.
  • the sample liquid comes into contact with the metal film 31 on which the aptamer is arranged, a specific target substance in the sample liquid is combined with an aptamer corresponding to the target substance, and the weight of the metal film 31 changes.
  • the phase characteristics of the SAW propagating between the pair of IDT electrodes 33 change. Therefore, the properties or components of the sample liquid can be examined based on the change in the phase characteristics and the like.
  • the element surface 11a described above is a surface including the detection unit 11b, and is configured by the upper surfaces of the piezoelectric substrate 29, the IDT electrode 33, the metal film 31, the pad 35, and the wiring.
  • FIG. 4A is a cross-sectional view taken along the line IVa-IVa in FIG. 1
  • FIG. 4B is a cross-sectional view taken along the line IVb-IVb in FIG.
  • the inflow path 5a for allowing the sample liquid to flow into the space 5b on the detection unit 11b and the outflow path 5c for allowing the sample liquid to flow out of the space 5b are formed inside the package 13.
  • the upper surfaces of the inflow path 5a, the space 5b, and the outflow path 5c are all constituted by an upper layer member 19 made of a hydrophilic film. Accordingly, these upper surfaces are continuous with each other to form a continuous surface 5e.
  • the term “continuous” means that there is no gap or step in the side view of the flow path.
  • the continuous surface 5e extends in a straight line shape or a curve shape close to a straight line in a side view of the flow path.
  • the lower surface of the inflow path 5a is constituted by the inflow side lower surface member 25, while the lower surface of the space 5b is constituted by the element surface 11a. Accordingly, a gap G1 is generated between the two.
  • the lower surface of the space 5b is configured by the element surface 11a
  • the lower surface of the outflow path 5c is configured by the outflow side lower surface member 27, and a gap G2 is generated between them.
  • the element surface 11a is made higher than the lower surface of the inflow path 5a.
  • the lower surface of the outflow path 5c is made higher than the element surface 11a.
  • Such height adjustment is performed by adjusting the thicknesses of the inflow side adhesive 37 and the outflow side adhesive 39, for example.
  • the height may be adjusted by adjusting the thicknesses of the inflow side lower surface member 25 and the outflow side lower surface member 27.
  • the upper surface of the piezoelectric substrate 29 is higher than the lower surface of the inflow path 5a.
  • the detection part 11b (and element surface 11a containing the detection part 11b) located on the piezoelectric substrate 29 is higher than the lower surface of the inflow path 5a.
  • 5 (a) to 5 (c) are diagrams for explaining the operation of the sensor 1, and are schematic cross-sectional views near the gap G1.
  • the sample liquid L taken in from the inflow port 3 tries to wet the upper surface and the lower surface of the inflow channel 5a and eventually flows through the inflow channel 5a toward the space 5b by capillary action. . Then, the sample liquid L reaches the gap G1.
  • the sample liquid L proceeds on the upper surface side so as to further wet the continuous surface 5e.
  • the progress of the sample liquid L stops when the lower surface to be wetted is interrupted.
  • the side surface of the inflow side lower surface member 25 is a cut surface of a hydrophilic film and generally has low wettability.
  • the sample liquid L advances on the upper surface side, the sample liquid L becomes a part of the element surface 11a (in this embodiment, a gap). G1 side edge). Then, the specimen liquid L resumes progressing to wet the element surface 11a.
  • the sample liquid flows through the space 5b by capillary action.
  • the effect that the sample liquid exceeds the gap G1 is more likely to occur because the element surface 11a is more likely to touch the sample liquid as the element surface 11a is higher than the lower surface of the inflow path 5a.
  • the action of the sample liquid exceeding the gap G1 is likely to occur because the smaller the contact angle with the sample liquid on the continuous surface 5e, the more the sample liquid proceeds on the continuous surface 5e in an attempt to wet the continuous surface 5e.
  • the right triangle T can be approximated by the hypotenuse of the right triangle T.
  • the height of the element surface 11a can be set appropriately.
  • a right triangle first right angle
  • the hypotenuse of the first right triangle is approximate to the surface of the sample liquid L that is in contact with the continuous surface 5e at a predetermined contact angle that should touch the element surface 11a.
  • the height may be set so as to abut.
  • the gap G1 of the element surface 11a if the element surface 11a is higher than the lower surface of the inflow channel 5a by a difference larger than the product of the length of the gap G1 in the flow path direction and the tangent of the contact angle, the gap G1 of the element surface 11a The side edge abuts against the hypotenuse of the first right triangle.
  • the right triangle T is used as the right side of the lower surface of the inflow passage 5a.
  • the vertical line of the continuous surface 5e drawn from the edge of the continuous surface 5e is one adjacent side
  • the line along the continuous surface 5e is the other adjacent side
  • the element surface from the edge on the gap G1 side of the lower surface of the inflow channel 5a Assume a right triangle (second right triangle) having a hypotenuse as a line abutting a part of 11a (the edge on the gap G1 side in this embodiment).
  • the angle formed by the other adjacent side (continuous surface 5e) and the oblique side in the second right triangle approximates the maximum contact angle at which the sample liquid L can touch the element surface 11a.
  • the angle may be smaller than the angle formed by the other adjacent side (continuous surface 5e) and the hypotenuse.
  • the contact angle should be smaller than the angle formed by the continuous surface 5e and the line (slanted side) extending from the edge of the lower surface of the inflow passage 5a on the gap G1 side so as to be in contact with a part of the element surface 11a. That's fine.
  • Some hydrophilic films and the like can have a contact angle with water of less than 10 °. Note that it is difficult to measure the contact angle in a range of less than 10 °, and specifying that the contact angle is less than 10 ° is substantially the same as specifying that the wettability is maximally high.
  • the continuous surface 5e (and the lower surfaces of various channels) preferably have a contact angle with the sample liquid of less than 10 °.
  • the lower surface (element surface 11a) on the downstream side with respect to the gap G1 (the whole in the present embodiment) is a lower surface on the upstream side with respect to the gap G1 (inflow path 5a). Higher than the lower surface). Therefore, the specimen liquid that has progressed on the upper surface side so as to wet the continuous surface 5e is allowed to touch a part (edge) of the element surface 11a beyond the gap G1, and the flow due to the capillary phenomenon is continued to the element surface 11a side. Can do.
  • FIGS. 6A and 6B are sectional views corresponding to FIGS. 4A and 4B, showing a sensor 201 according to the second embodiment of the present invention.
  • the sensor 201 is different from the first embodiment in that the sensor element 211 has a short-circuit electrode 241 and a protective film 243 and that a convex portion 245 is provided on the continuous surface 205e in a front view of the flow path. Specifically, it is as follows.
  • the short-circuit electrode 241 is provided between the pair of IDT electrodes 33 on the upper surface of the piezoelectric substrate 29.
  • the protective film 243 covers the upper surface of the piezoelectric substrate 29 from above the pair of IDT electrodes 33 and the short-circuit electrode 241.
  • the metal film 31 is provided on the protective film 243.
  • the short-circuit electrode 241 is for electrically short-circuiting the SAW propagation path on the upper surface of the piezoelectric substrate 29.
  • the SAW loss can be reduced depending on the type of SAW.
  • the loss suppression effect by the short circuit electrode 241 is high when a leaky wave is used as SAW.
  • the short-circuit electrode 241 is formed over a range equivalent to the range of the detection unit 11b indicated by a dotted line in FIG.
  • the short-circuit electrode 241 may be in an electrically floating state or may be given a ground potential.
  • the protective film 243 covers substantially the whole of the piezoelectric substrate 29 except for the arrangement region of the pads 35, and contributes to preventing oxidation of conductors such as the pair of IDT electrodes 33 and the short-circuit electrodes 241.
  • the protective film 243 is made of an inorganic insulating material, for example.
  • the inorganic insulating material is, for example, silicon oxide (for example, SiO 2 ), aluminum oxide, zinc oxide, titanium oxide, silicon nitride, or silicon.
  • the thickness of the protective film 243 (height from the upper surface of the piezoelectric substrate 29) is larger than the thickness of the conductor such as the IDT electrode 33, for example.
  • the thickness of the protective film 243 is, for example, not less than 200 nm and not more than 10 ⁇ m.
  • the convex portion 245 is configured, for example, by attaching a hydrophilic film to the lower surface of the upper layer member 19.
  • the contact angle with the sample liquid on the lower surface of the convex portion 245 is preferably equal to or smaller than the contact angle with the sample liquid on the lower surface of the upper layer member 19.
  • the convex portion 245 has, for example, the same width as the metal film 31 and extends over the inflow path 5a, the space 5b, and the outflow path 5c.
  • the element surface 211a (including the detection unit 211b) is set higher than the lower surface of the inflow path 5a, and the gap is the same as in the first embodiment.
  • the sample liquid can be caused to flow so as to exceed G1.
  • the protective film 243 contributes to making the element surface 211a higher than the lower surface of the inflow path 5a depending on the thickness. Since the thickness of the protective film 243 can be adjusted relatively easily in the formation of a thin film such as CVD, the height of the element surface 211a can be easily adjusted.
  • the convex portion 245 Since the convex portion 245 has a short distance from the element surface 211a, a capillary phenomenon easily occurs. Therefore, for example, it is possible to preferentially flow the sample liquid on the detection unit 211b over the side of the space 5b, and to suppress the formation of bubbles on the detection unit 211b. This effect is remarkable when the contact angle with the sample liquid on the lower surface of the convex portion 245 is smaller than the contact angle with the sample liquid on the surface adjacent to the side.
  • FIG. 7A to FIG. 7C are schematic cross-sectional views showing modifications of the channel shape and the like.
  • FIG. 7 (a) shows a cross-sectional view of the flow channel as seen from the side, as in FIG.
  • the continuous surface 5e is inclined. Specifically, it is inclined so that the height of the space 5b is lower than the height of the inflow channel 5a.
  • Such an inclination can be realized by appropriately adjusting the thickness of the middle layer member 17 or by bending the upper layer member 19 in the space 5b having a larger area than the inflow path 5a.
  • the continuous surface 5e is inclined as described above, for example, the sample liquid L is expected to more easily exceed the gap G1.
  • FIG. 7 (b) shows a cross-sectional view of the flow channel as seen from the side, as in FIG.
  • the entire element surface 311a is not higher than the lower surface of the inflow passage 5a, but only a part of the element surface 311a is formed on the lower surface of the inflow passage 5a by forming the convex portion 311c on the element surface 311a.
  • the convex portion 311c is formed, for example, by placing a metal or resin on the piezoelectric substrate 29. Also in such an aspect, when the sample liquid touches the convex portion 311c, the sample liquid tries to wet the convex portion 311c, thereby restarting the flow of the sample liquid on the lower surface side.
  • FIG. 7C shows a cross-sectional view of the flow path 5 as viewed from the front.
  • This cross-sectional view may be a cross section at any position of the inflow path 5a, the space 5b, and the outflow path 5c.
  • the channel 5 is chamfered by a curved surface at the side corners of the upper surface.
  • Such chamfering is realized, for example, by forming an inclined surface on the side surface of the notch 17a when the notch 17a is formed in the middle layer member 17.
  • the height of the flow path is low at the chamfered portion, and the sample liquid tends to exceed the gap at this position.
  • the present invention is not limited to the above embodiment, and may be implemented in various modes.
  • Sensor is not limited to those using SAW.
  • surface plasmon resonance may be used, or vibration of a crystal resonator may be used.
  • the sensor is not limited to a biosensor.
  • a detection part is not limited to what an aptamer is arrange
  • the detection unit may be configured by an electrode for measuring pH (pH) based on a change in potential.
  • a plurality of pairs of IDT electrodes may be arranged in the flow direction.
  • the type of aptamer arranged between each IDT electrode pair is changed and a plurality of types of measurements are performed, or the IDT electrode pair in which the aptamer is arranged is compared with the IDT electrode pair in which the aptamer is not arranged. Measurements can be made.
  • the senor may be used for any purpose.
  • any kind of sample sample liquid
  • the type of specimen may be a body fluid (for example, blood), a beverage, a chemical solution, or water that is not pure water (for example, seawater, lake water, groundwater). Also good.
  • the type of specimen may include water or oil.
  • the type of specimen may be a solution or a sol.
  • each specimen has uncertainties in its components.
  • the type of specimen is blood
  • the amount of components contained in the blood varies from person to person (depending on the individual specimen), so that blood is the measurement target of the sensor. Therefore, strictly speaking, the contact angle with the specimen on the inner surface of the flow path is different for each specimen.
  • the difference is a slight difference.
  • the sensor using a capillary phenomenon is comprised so that such a difference may not become a problem. Therefore, for example, the contact angle with the specimen on the inner surface of the flow channel of the product may be determined by the contact angle with each specimen, or may be judged by the contact angle with the specimen having a standard component configuration. Good. In the case where a specific specimen can exist, the latter is preferable.
  • the contact angle with the specimen is often judged by the contact angle with water.
  • the flow path through which the sample liquid flows may be appropriately configured in addition to those exemplified in the embodiment.
  • the inlet 3 is opened at the end surface of the package 13, but may be opened at the upper surface of the package 13.
  • the exhaust port 7 is opened on the upper surface of the package 13, but may be opened on the end surface of the package 13.
  • the width of the inflow path 5a and the outflow path 5c is narrower than the width of the space 5b, but may be equal to the width of the space 5b.
  • the flow path need not include both the inflow path and the outflow path.
  • the outflow path is not essential.
  • an exhaust port may be formed adjacent to the space on the element surface.
  • the configuration in which the lower surface on the downstream side with respect to the gap (concave portion) is higher than the lower surface on the upstream side with respect to the gap is the inflow path and the outflow path. It is not necessary to be applied to both, and it may be applied to only one of them.
  • the flow path may be formed by an appropriate member.
  • the middle layer member is composed of two layers, and the first layer arranged on the lower layer member has a shape in which a hole for arranging the sensor element is formed, and the second layer arranged thereon is a sensor.
  • a shape for forming a hole and a notch corresponding to the inflow path may be formed, and the inflow side lower surface member 25 of the embodiment may be omitted.
  • the method of increasing the wettability of the inner surface of the flow path is not limited to the method of disposing a hydrophilic film.
  • you may perform a hydrophilic process with respect to a base material.
  • the hydrophilic treatment include a method of arranging (fixing) a coating agent. More specifically, for example, ashing with oxygen plasma may be performed on the substrate, a silane coupling agent may be applied, and polyethylene glycol as a coating agent may be applied. Further, for example, the substrate may be surface-treated using a treatment agent having phosphorylcholine to fix phosphorylcholine as a coating agent.
  • the region where the contact angle with the sample liquid is small does not necessarily have to be the surface of the convex portion.
  • the lower surface of the upper layer member is subjected to hydrophilic treatment (or hydrophobization treatment), and an area having a small contact angle with the sample liquid is appropriately positioned ( For example, it may be formed at a position facing the detector.
  • the upper surface of the piezoelectric substrate is higher than the lower surface of the inflow path, and the upper surface of the element surface is higher than the lower surface of the inflow path. It is also effective.
  • the surface when a predetermined configuration is added to the upper surface of the piezoelectric substrate is the element surface. Additional configurations include a detection unit, IDT, protective layer (SiO 2 ), and the like.
  • the entire upper surface of the piezoelectric substrate does not necessarily have to be higher than the lower surface of the inflow path, and only a part of the upper surface may be higher.
  • the gap (recess) on the lower surface of the flow path is not limited to the gap between the sensor element and the package.
  • the configuration in which the lower surface of the downstream side with respect to the gap is made higher than the lower surface of the upstream side with respect to the gap includes the combination of the lower surface of the inflow path and the element surface, and the element surface and the outflow. It is not limited to the combination of the lower surface of the road.
  • the above-described features may be applied to the lower surfaces before and after any gap caused by constituting a package from a plurality of members. Even in such a case, there is an effect that the sample liquid exceeds the gap.

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PCT/JP2014/071969 2013-08-23 2014-08-22 センサ Ceased WO2015025946A1 (ja)

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JP6479117B2 (ja) 2019-03-06
US20160169874A1 (en) 2016-06-16

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