WO2014045762A1 - Fluorescent light sensor and sensor system - Google Patents

Fluorescent light sensor and sensor system Download PDF

Info

Publication number
WO2014045762A1
WO2014045762A1 PCT/JP2013/071793 JP2013071793W WO2014045762A1 WO 2014045762 A1 WO2014045762 A1 WO 2014045762A1 JP 2013071793 W JP2013071793 W JP 2013071793W WO 2014045762 A1 WO2014045762 A1 WO 2014045762A1
Authority
WO
WIPO (PCT)
Prior art keywords
recess
sensor
light
photoelectric conversion
conversion element
Prior art date
Application number
PCT/JP2013/071793
Other languages
French (fr)
Japanese (ja)
Inventor
亮 太田
松本 淳
Original Assignee
テルモ株式会社
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 テルモ株式会社 filed Critical テルモ株式会社
Publication of WO2014045762A1 publication Critical patent/WO2014045762A1/en

Links

Images

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6428Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/645Specially adapted constructive features of fluorimeters
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6428Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks

Definitions

  • the present invention relates to a fluorescence sensor for measuring the concentration of an analyte in a liquid and a sensor system including the fluorescence sensor, and in particular, a fluorescence sensor that is a microfluorometer manufactured using semiconductor manufacturing technology and MEMS technology, and the above-described sensor
  • the present invention relates to a sensor system including a fluorescent sensor.
  • a fluorometer that measures an analyte concentration by injecting a fluorescent dye and a solution to be measured containing an analyte into a transparent container, irradiating excitation light, and measuring the fluorescence intensity from the fluorescent dye is known.
  • Fluorescent dyes change their properties due to the presence of analyte, and when they receive excitation light, they generate fluorescence with an intensity corresponding to the analyte concentration. have.
  • the excitation light from a light source is irradiated to the indicator in which the analyte in a to-be-measured solution can go in and out, and the photodetector receives the fluorescence which an indicator produces.
  • the photodetector is a photoelectric conversion element and outputs an electrical signal corresponding to the received light intensity.
  • the analyte concentration in the solution is calculated based on the electrical signal from the photodetector.
  • microfluorometer manufactured using semiconductor manufacturing technology and MEMS technology.
  • the microfluorometer is referred to as “fluorescence sensor”.
  • the fluorescent sensor 104 shown in FIGS. 1 and 2 is disclosed in International Publication No. 2010/119916.
  • the sensor unit 110 which is a main functional unit of the fluorescence sensor 104 includes a silicon substrate 111 on which a photoelectric conversion element 112 is formed, a transparent intermediate layer 113, a filter layer 114, a light emitting element 115, a transparent protective layer 116, An indicator 117 and a light shielding layer 118 are provided.
  • the analyte 9 passes through the light shielding layer 118 and enters the indicator 117.
  • the filter layer 114 of the fluorescence sensor 104 blocks excitation light and transmits fluorescence. Further, the light emitting element 115 transmits fluorescence.
  • the indicator 117 In the fluorescence sensor 104, when the excitation light generated by the light emitting element 115 enters the indicator 117, the indicator 117 generates fluorescence corresponding to the analyte concentration.
  • the fluorescent sensor 104 has a simple configuration and can be easily downsized.
  • the fluorescent sensor 104 since the fluorescent sensor 104 has the light emitting element 115 and the photoelectric conversion element 112 disposed inside the frame portion that holds the indicator 117, the fluorescent sensor 104 is not easy to manufacture.
  • An object of the embodiment of the present invention is to provide a fluorescent sensor that is easy to manufacture and a sensor system with high detection sensitivity.
  • the fluorescent sensor of one embodiment of the present invention includes an SOI substrate in which an active layer is disposed on a substrate layer via an oxide film, and the active layer constituting the first main surface is a through via. 1 recess is formed, the substrate layer constituting the second main surface is formed with a second recess that is a through via having a size including a region facing the first recess, Furthermore, the substrate part on which a photoelectric conversion element for converting fluorescence into an electric signal is formed, a filter covering the photoelectric conversion element, blocking excitation light, and the second recess, When the excitation light is received, the indicator that generates the fluorescence having an intensity corresponding to the concentration of the analyte and the outside light entering the indicator that covers the opening of the second recess are blocked, but the analyte passes.
  • the light shielding layer to be It covers the region comprises a light-emitting element for generating the excitation light.
  • the sensor system includes an SOI substrate in which an active layer is disposed on a substrate layer via an oxide film, and penetrates through the active layer constituting the first main surface.
  • a first concave portion that is a via is formed, and a second concave portion that is a through via having a size including a region facing the first concave portion is formed in the substrate layer constituting the second main surface.
  • a substrate part on which a photoelectric conversion element for converting fluorescence into an electric signal is formed, a filter covering the photoelectric conversion element and blocking excitation light, and the second recess are provided.
  • the analyte passes through the light-shielding layer, and the first It covers the region immediately below the opening of the part comprises a fluorescent sensor comprising a light emitting element for generating the excitation light, and a main body portion having a computing unit for correcting the electrical signal.
  • a compact fluorescent sensor with high detection sensitivity and a sensor system with high detection sensitivity can be provided.
  • the fluorescence sensor 4 and the sensor system 1 according to the first embodiment of the present invention will be described.
  • the sensor system 1 includes a fluorescent sensor 4, a main body 2, and a receiver 3 that receives and stores a signal from the main body 2. Transmission / reception of signals between the main body 2 and the receiver 3 is performed wirelessly or by wire.
  • the fluorescent sensor 4 includes a needle portion 7 that is punctured by a subject and a connector portion 8 that is joined to the rear end portion of the needle portion 7.
  • the needle part 7 has an elongated needle body part 6 and a needle tip part 5 including a sensor part 10 which is a main function part. Needle tip 5, needle body 6, and connector 8 may be integrally formed of the same material, or may be separately produced and joined.
  • the connector part 8 is detachably fitted to the fitting part 2A of the main body part 2.
  • the plurality of wirings 60 extending from the sensor unit 10 of the fluorescent sensor 4 are electrically connected to the main body unit 2 when the connector unit 8 is mechanically fitted to the fitting unit 2A of the main body unit 2. .
  • the fluorescent sensor 4 is a needle type sensor that can continuously measure the analyte concentration for a predetermined period, for example, one week after the sensor unit 10 is inserted into the body. However, the collected body fluid or the body fluid circulating through the body via the flow path outside the body may be brought into contact with the sensor unit 10 outside the body without inserting the sensor unit 10 into the body.
  • the main body unit 2 includes a control unit 2B that performs driving and control of the sensor unit 10, and a calculation unit 2C that processes a signal output from the sensor unit 10. Note that at least one of the control unit 2B and the calculation unit 2C may be disposed on the connector unit 8 of the fluorescent sensor 4 or the receiver 3.
  • the main body 2 further includes a radio antenna for transmitting and receiving radio signals to and from the receiver 3, a battery, and the like.
  • the main body 2 has a signal line instead of a wireless antenna.
  • the receiver 3 may not be provided when the main body 2 includes a memory unit having a necessary capacity.
  • the fluorescent sensor 4 includes a substrate unit 20, a filter 14, an indicator 17, a light shielding layer 18, and a light emitting element 15 as main functional elements.
  • the substrate unit 20 and the light emitting element 15 are bonded via the bonding layer 13.
  • the substrate unit 20 includes an SOI (Silicon on Insulator) in which an active layer (SOI layer) 21 is disposed on a support substrate layer (substrate layer) 22 via a buried silicon oxide film (Buried Oxide: BOX layer) 23. ) It consists of a substrate.
  • SOI Silicon on Insulator
  • the thickness of the active layer 21 is several ⁇ m to 100 ⁇ m
  • the thickness of the BOX layer 23 having a high light transmittance is 1 ⁇ m to several tens of ⁇ m
  • the thickness of the substrate layer 22 is 10 ⁇ m to several hundreds of ⁇ m.
  • the active layer 21 made of silicon constituting the first main surface 20SA of the substrate part 20 is formed with a recess 24 as a first through via, and the substrate layer made of silicon constituting the second main surface 20SB. 22 is formed with a recess 25 which is a second through via. That is, the recess 24 penetrates the active layer 21, the recess 25 penetrates the substrate layer 22, the bottom surface 24B and the bottom surface 25B are both the BOX layer 23, and the recess 25 and the recess 24 define the BOX layer 23. Is touching through.
  • FIG. 4B is a plan view for explaining an arrangement state of some components of the fluorescence sensor 4.
  • the recesses 24 and 25 are formed in the same region in the XY plane of the substrate unit 20, and the planar view size of the bottom surface 24 ⁇ / b> B of the recess 24 is smaller than the bottom surface 25 ⁇ / b> B of the recess 25. That is, the bottom surface 25B is formed so as to completely cover the bottom surface 24B.
  • the region where the recess 24 is formed includes a region facing the recess 25.
  • a light receiving portion 12T of a photodiode (Photo-Diode: PD) element 12 which is a photoelectric conversion element that converts fluorescence into an electric signal is formed. That is, the PD element 12 is disposed so as to surround the opening of the recess 24 so that the light receiving surface faces the indicator 17 disposed inside the recess 25.
  • the light receiving unit 12T is referred to as a PD element 12.
  • the planar view shape of the concave portion 24 may be a shape obtained by reducing the planar shape of the PD element 12 in order to be arranged inside the PD element 12, but a polygon, a circle, an ellipse, or the like that is different from the shape of the PD element 12. But you can.
  • the filter 14 is disposed so as to cover the wall surface of the PD element 12 and the recess 24 formed on the first main surface 20SA. That is, the filter 14 is not disposed on the bottom surface 24 ⁇ / b> B of the recess 24. Note that a transparent protective film such as silicon oxide may be formed before the filter 14 is formed.
  • the filter 14 blocks excitation light having a wavelength of 375 nm, for example, and blocks the excitation light from entering the active layer 21 including the PD element 12.
  • the filter 14 may be a light shielding layer that blocks light having a wavelength other than the excitation light.
  • the filter in the region covering the PD element 12 on the wall surface of the recess 24 preferably transmits fluorescence from the viewpoint of improving detection sensitivity. Since the PD element 12 has a small signal output due to excitation light that becomes noise, the filter 14 can realize a sensor with a high S / N ratio.
  • a wiring layer 50 including detection signal wirings 51 and 52 and drive signal wirings 53 and 54 is disposed on the first main surface 20SA via the filter 14.
  • the detection signal wirings 51 and 52 output detection signals from the PD element 12.
  • the detection signal wiring 51 is connected to the light receiving portion 12T of the PD element, and the detection signal wiring 52 is connected to the low resistance region 12H of the same semiconductor impurity type as the active layer 21.
  • the drive signal wirings 53 and 54 supply a drive signal to the drive signal electrode 15T of the light emitting element 15. That is, each wiring of the wiring layer 50 is connected to a plurality of wirings 60 that pass through the needle body 6.
  • the bonding layer 13 bonds the substrate unit 20 and the LED and protects the wall surfaces of the PD element 12 and the recess 24.
  • the bonding layer 13 may also be filled in the recess 24. Conversely, the bonding layer 13 may not be formed in the region immediately below the opening of the recess 24.
  • the bonding layer 13 is selected from adhesive materials having characteristics such as electrical insulation, moisture barrier properties, and good transmittance for excitation light.
  • an epoxy resin, a silicone resin, an organic resin such as a transparent amorphous fluororesin, a transparent inorganic material such as a silicon oxide film or a silicon nitride film, or a composite laminated film thereof can be used. .
  • the indicator 17 filled in the recess 25 generates fluorescence due to the interaction with the entering analyte 9 and excitation light.
  • the thickness of the indicator 17 is the same as the depth of the recess 25, that is, the thickness of the substrate layer 22, and is 10 ⁇ m to several hundred ⁇ m.
  • the indicator 17 is made of a base material containing a fluorescent dye that generates fluorescence having an intensity corresponding to the amount of the analyte 9 that has entered the inside, that is, the concentration of the analyte in the solution to be measured.
  • the light shielding layer 18 covering the opening 25A of the recess 25 has a thickness of about several tens of ⁇ m.
  • the light shielding layer 18 prevents excitation light and fluorescence from leaking to the outside, and at the same time, prevents outside light from entering the inside.
  • the light shielding layer 18 also has analyte permeability that does not hinder the passage of the analyte 9.
  • the light leakage prevention layer 19 disposed so as to cover the bottom surface (the surface facing the light emitting surface) and the wall surface of the light emitting element 15 is reflected by the excitation light emitted from the bottom surface and the wall surface and the surface of the active layer 21.
  • the excitation light is prevented from leaking outside. That is, the light leakage prevention layer 19 has a function similar to that of the light shielding layer 18, but does not require analyte permeability.
  • FIGS. 6A to 6F are partial cross-sectional views of the region of the sensor unit 10 of one fluorescent sensor 4.
  • the sensor unit 10 of a large number of fluorescent sensors 4 is collectively included as a wafer process.
  • a sensor substrate is fabricated.
  • the PD element 12 which is a photoelectric conversion element is formed on the active layer 21 of the first main surface 20SA of the SOI wafer 20W using a normal semiconductor process.
  • the planar shape and size of the light receiving portion 12T are preferably elongated, for example, 150 ⁇ m in length and 500 ⁇ m in width because the location where the sensor unit 10 is disposed is the needle tip 5.
  • the light receiving portion 12T is formed by introducing a semiconductor impurity type impurity opposite to that of the active layer 21.
  • the low resistance region 12H is formed by introducing impurities of the same semiconductor impurity type as the active layer 21.
  • the active layer 21 is an N-type semiconductor
  • a P-type semiconductor diffusion layer is formed in the light receiving portion 12T by boron diffusion, and phosphorus, arsenic, or the like is introduced into the low resistance region 12H.
  • the photoelectric conversion element may be a photoconductor (photoconductor) element or a phototransistor element.
  • photo-etching is performed on the active layer 21 of the first main surface 20SA to form a recess 24.
  • Various known methods can be used for etching.
  • the recess 24 is disposed inside the planar region of the PD element 12.
  • the recess 24 is a through via that penetrates the active layer 21, and the BOX layer 23 is exposed on the bottom surface.
  • the filter 14 is formed on the wall surface of the active layer 21 and the recess 24 of the first main surface 20SA.
  • the filter 14 is not formed on the bottom surface 24 ⁇ / b> B of the recess 24 by using film formation by CVD and anisotropic dry etching.
  • a transparent protective film such as a silicon oxide film may be formed before forming the filter 14.
  • the filter 14 may be a multiple interference type such as a dielectric multilayer film, but is preferably an absorption type, for example, a single layer made of silicon, silicon carbide, silicon oxide, silicon nitride, or an organic material, or the single layer. It is a multilayer layer in which layer layers are laminated.
  • the transmittance of the silicon layer and the silicon carbide layer is 10 ⁇ 5 % or less at the excitation light wavelength of 375 nm, whereas the transmittance is 10% or more at the fluorescence wavelength of 460 nm (the transmittance of the excitation light wavelength). (Transmittance of fluorescence wavelength) and the transmittance selectivity of 6 digits or more.
  • detection signal wirings 51 and 52 for outputting a detection signal from the PD element 12 and drive signal wirings 53 and 54 for supplying a driving signal to the light emitting element 15 are formed by sputtering. Alternatively, they are disposed by patterning such as wiring metal film formation and photolithography / etching by vapor deposition or the like.
  • the detection signal wirings 51 and 52 are connected to the light receiving unit 12T and the low resistance region 12H of the PD element through contact holes (not shown) of the filter 14, respectively.
  • the material of the detection signal wirings 51 and 52 and the drive signal wirings 53 and 54 Al, Cu, Au, Pt, W, Mo or the like, which is a metal material, or low resistance polysilicon containing impurities at a high concentration is used. .
  • the detection signal wirings 51 and 52 and the drive signal wirings 53 and 54 are disposed in one wiring layer 50, but a multilayer wiring may be used.
  • a multilayer wiring may be used as the material of the interlayer insulating layer of the multilayer wiring.
  • an inorganic insulating material such as a silicon oxide film or a silicon nitride film, or an organic insulating material such as polyimide is used.
  • At least one of the detection signal wirings 51 and 52 and the drive signal wirings 53 and 54 is widened. You may arrange in.
  • the light emitting element 15 is bonded to the first main surface 20SA of the SOI wafer 20W via the bonding layer 13 so as to cover the opening of the recess 24.
  • the refractive index of the bonding layer 13 filling the concave portion 24 is substantially equal to the refractive index of the BOX layer 23.
  • the light emitting element 15 is selected from a chip on which a light emitting element such as an organic EL element, an inorganic EL element, or a laser diode element is formed.
  • the light-emitting element 15 is a light-emitting diode (LED) from the viewpoints of light generation efficiency, wide wavelength selectivity of excitation light, and generation of light having a wavelength other than excitation light. Is preferred.
  • the bonding layer 13 is manufactured by applying a resin and performing a curing process.
  • a transparent SiO 2 layer or silicon nitride layer or the like may be disposed in advance on the surface to which the resin is applied by a CVD method or the like.
  • a conductive adhesive or flip chip bonding is used for electrical connection between the drive signal electrode 15T of the light emitting element 15 and the drive signal wirings 53 and 54.
  • the drive signal electrode 15T of the light emitting element 15 is electrically connected to the drive signal wirings 53 and 54 at the same time. Since the light emitting element 15 and the substrate portion are electrically bonded simultaneously with the physical bonding, the fluorescent sensor 4 can be easily manufactured.
  • the bonding layer 13 also has a function of a sealing member that seals the electrical connection portion.
  • the light leakage prevention layer 19 is disposed on the lower surface and the wall surface of the light emitting element 15.
  • the light leakage prevention layer 19 may be the same material as the light shielding layer 18, or may be an organic resin mixed with carbon black, a metal, or a multilayer film or a composite film made of these materials. Note that the light emitting element 15 in which the light leakage prevention layer 19 is disposed in advance may be bonded to the substrate unit 20.
  • the excitation light emitted from the bottom surface and the wall surface of the light emitting element 15 is reflected upward, that is, as a reflection film that reflects in the direction of the indicator 17. It is also possible to give this function.
  • the light leakage prevention layer 19 may be disposed on the outer surface of the sensor unit 10 such as the entire lower surface of the substrate unit 20, the wall surface, and the upper surface not covered with the light shielding layer 18.
  • the silicon wafer 20 ⁇ / b> W is turned upside down to form a recess 25 that is a through via in the substrate layer 22 of the second main surface 20 ⁇ / b> SB.
  • a known method can be used for etching the substrate layer 22.
  • the BOX layer 23 is exposed on the bottom surface 25 ⁇ / b> B of the recess 25, and the recess 25 and the recess 24 are in contact with each other via the BOX layer 23.
  • the indicator 17 is filled in the recess 25.
  • the indicator 17 is made of a hydrogel containing a fluorescent dye or a hydrogel combined with a fluorescent dye.
  • the fluorescent dye is selected according to the type of the analyte 9, and any fluorescent dye whose intensity of fluorescence generated according to the amount of the analyte 9 changes reversibly can be used.
  • the fluorescent sensor 4 uses a ruthenium organic complex, a fluorescent phenylboronic acid derivative, a substance that reversibly binds to glucose, such as fluorescein bound to a protein, or the like.
  • Hydrogel components that easily contain water include acrylate hydrogels prepared by polymerizing polysaccharides such as methylcellulose or dextran, monomers such as (meth) acrylamide, methylacrylamide, or hydroxyethyl acrylate, or polyethylene glycol and diisocyanate. Urethane-based hydrogel prepared from the above can be used.
  • the indicator 17 may be bonded to the wall surface of the recess 25, the light shielding layer 18 on the upper surface, the bottom surface 25B of the recess 25, or the like via an adhesive layer such as a silane coupling agent.
  • the indicator 17 may be manufactured by filling the concave portion 25 with an indicator containing a gel skeleton-forming material before polymerization and covering the opening with the light shielding layer 18 and then polymerizing the indicator 17. For example, when a phosphate buffer containing a fluorescent dye, a gel skeleton-forming material, and a polymerization initiator is placed in the recess 24 and left in a nitrogen atmosphere for 1 hour, the indicator 17 is produced.
  • fluorescent dye 9,10-bis [N- [2- (5,5-dimethylborinan-2-yl) benzyl] -N- [6 ′-[(acryloylpolyethyleneglycol-3400) carbonylamino]- n-hexylamino] methyl] -2-acetylanthracene (F-PEG-AAm), acrylamide as the gel skeleton-forming material, sodium peroxodisulfate and N, N, N ′, N as the polymerization initiator '-Tetramethylethylenediamine is used.
  • the light shielding layer 18 is disposed so as to cover the opening of the concave portion 25 of the second main surface 20SB.
  • the light shielding layer 18 has a submicron pore structure, an inorganic thin film such as metal or ceramic, or a composite structure with hydrogels in which carbon black is mixed in a base material of an organic polymer such as polyimide or polyurethane, or Furthermore, a resin in which carbon black is mixed into an analyte-permeable polymer such as celluloses or polyacrylamide, or a resin obtained by laminating them can be used.
  • the sensor substrate 10W having the SOI wafer 20W as a base material is separated into individual pieces, so that a large number of sensor units 10 are manufactured at once.
  • the fluorescence sensor 4 is completed by joining the sensor part 10 with the front-end
  • the manufacturing method of the fluorescent sensor is not limited to this.
  • the silicon wafer 20W in the state shown in FIG. 6C may be separated into pieces, and the light emitting elements 15 and the like may be bonded to the respective substrate portions 20.
  • the silicon wafer 20 ⁇ / b> W may be processed and joined to the connector portion 8 so that the extended portion of the substrate portion 20 constitutes the needle body portion 6 of the needle portion 7.
  • the fluorescent sensor 4 is easy to manufacture and can be mass-produced by a wafer process. For this reason, the fluorescence sensor 4 can provide stable quality at low cost.
  • the light emitting element 15 emits pulsed excitation light having a center wavelength of around 375 nm at an interval of once every 30 seconds, for example.
  • the pulse current to the light emitting element 15 is 1 mA to 100 mA
  • the pulse width of light emission is 1 ms to 100 ms.
  • the excitation light generated by the light emitting element 15 is transmitted through the BOX layer 23 constituting the bottom surface 24 ⁇ / b> B of the recess 24 and enters the indicator 17.
  • the indicator 17 emits fluorescence having an intensity corresponding to the concentration of the analyte 9.
  • the analyte 9 passes through the light shielding layer 18 and enters the indicator 17.
  • the fluorescent dye of the indicator 17 generates fluorescence having a longer wavelength, for example, 460 nm, for example, with respect to excitation light having a wavelength of 375 nm.
  • the fluorescence generated by the indicator 17 passes through the BOX layer 23 and the thin active layer 21 on the BOX layer 23 side of the light receiving unit 12T and enters the light receiving unit 12T of the PD element 12. That is, as already described, the light receiving portion 12T is a diffusion layer in which impurities are introduced from the surface of the active layer 21, and the thin active layer 21 remains on the BOX layer 23 side. Since the fluorescence transmittance of the active layer 21 is not high, the thickness of the active layer 21 remaining on the BOX layer 23 side is preferably 10 ⁇ m or less, particularly preferably 3 ⁇ m or less. The fluorescence is photoelectrically converted by the light receiving unit 12T, and the generated photogenerated charge is output as a detection signal.
  • the calculation unit 2C of the main body unit 2 performs calculation processing based on the detection signal, that is, the current caused by the photogenerated charge from the PD element 12 or the voltage caused by the accumulated photogenerated charge. Calculate the amount of light.
  • the fluorescent sensor 4 Since the fluorescent sensor 4 is manufactured using an SOI substrate, it is easy to manufacture, and further detects the fluorescence from the indicator 17 via the BOX layer 23 having a high transmittance. For this reason, the fluorescence sensor 4 has high detection sensitivity while being small. Similarly, the sensor system 1 including the fluorescent sensor 4 has high detection sensitivity. Furthermore, since a large number of fluorescent sensors can be manufactured at once by processing in a wafer state, the manufacturing process of the fluorescent sensor 4 is easy and the cost is low.
  • the fluorescence sensor 4 there is one concave portion 24 that is a light guide path through which the excitation light from the light emitting element 15 enters the indicator 17.
  • the intensity of the excitation light generated by the light emitting element 15 and incident on the indicator 17 has an in-plane distribution. That is, since the high-intensity excitation light is irradiated to the indicator 17 in the region immediately above the bottom surface 24B of the recess 24, the fluorescence intensity emitted from the indicator 17 in that region is high. However, when high-intensity excitation light is irradiated, deterioration of the indicator 17 may be promoted.
  • the intensity of the excitation light incident on the indicator 17 decreases, and the intensity of the fluorescence emitted by the indicator 17 in that region also decreases. That is, if the intensity of the excitation light incident on the indicator 17 has a large in-plane distribution, the detection sensitivity of the fluorescent sensor may be reduced, or deterioration with time may be accelerated.
  • the active layer 21 has a plurality of recesses 24A.
  • Forming a plurality of recesses 24A in the active layer 21 means forming a plurality of light guides.
  • the indicator 17 in the vicinity of the region immediately above each recess 24A is irradiated with relatively strong excitation light. For this reason, in the fluorescence sensor 4A, the excitation light having a more uniform intensity distribution is incident on the indicator 17, so that there is no possibility that the detection sensitivity is lowered or the deterioration with time is accelerated.
  • the fluorescent sensor 4A has the effect of the fluorescent sensor 4, and further has high detection sensitivity, and the deterioration of the indicator 17 is unlikely to proceed.
  • the planar shape and arrangement of the recesses 24 can take various forms as shown in FIGS. 7A to 7C.
  • the planar shape of the recess 24A is a quadrangle in the fluorescent sensor 4A shown in FIG. 7A, but may be a polygon or an ellipse such as a hexagon as in the fluorescent sensor 4A1 shown in FIG. 7B, or a combination thereof. The shape may be different. Moreover, you may combine the recessed part 24A from which magnitude
  • the size of the planar dimension of the recess 24, for example, the length of the side is 1 ⁇ m to several hundred ⁇ m.
  • the distribution is corrected by the opening area, shape, arrangement, and the like of the plurality of recesses 24, and the intensity distribution of the excitation light incident on the indicator 17 is further increased. Can be averaged.
  • the excitation light distribution suitable for the planar view shape of the indicator 17, that is, the shape of the bottom surface 25 ⁇ / b> B of the recess 25 can be realized by the same method.
  • the fluorescent sensor 4A and the like according to the modified example 1 have the effect of the fluorescent sensor 4, and further, since the intensity distribution of the excitation light incident on the indicator 17 is averaged, the detection is performed while being small. High sensitivity.
  • the sensor system 1A including the fluorescent sensor 4A has high detection sensitivity. Furthermore, the sensitivity reduction phenomenon due to the temporal deterioration peculiar to the fluorescent sensor having the indicator 17 is small.
  • the excitation light is directly incident on the region directly above the recess 24, which is the light guide, so that the intensity of the excitation light is high. However, the intensity of the excitation light decreases with increasing distance from the region directly above.
  • the sensor unit 10B of the fluorescent sensor 4B according to the modified example 2 includes a light scattering layer 26 serving as a light scattering unit on the bottom surface 24B of the recess 24.
  • the light scattering layer 26 is made of, for example, a transparent material in which metal particles are dispersed.
  • metal particles metals with a high particle reflectance such as Al and Ag having a particle size of ⁇ m are suitable, and as transparent materials, resins such as silicone resins or inorganic glasses such as SOG (Spin-On-Glass) are suitable. Is suitable.
  • the light scattering layer 26 is disposed in the recess 24 by a printing method, a photolithography process, or the like. In the fluorescent sensor 4B shown in FIG. 8, the light scattering layer 26 is disposed on the bottom surface 24B of the recess 24, but may be disposed so as to fill the recess 24.
  • the refractive index of the light scattering layer 26 is substantially equal to the refractive index of the BOX layer 23.
  • the excitation light from the light emitting element 15 is scattered by the light scattering layer 26, and the intensity distribution of the excitation light incident on the indicator 17 is averaged. That is, the intensity of the excitation light in the indicator 17 increases in the region away from the bottom surface 24B of the recess 24, the fluorescence intensity emitted from the indicator in that region also increases, and the excitation light in the region immediately below the bottom surface 24B of the recess 24. The strength is weakened.
  • the sensor unit 10B1 of the fluorescence sensor 4B1 of Modification 2 shown in FIG. 9 has a concave lens 26A as light scattering means.
  • the concave lens can be formed by utilizing the meniscus phenomenon due to the surface tension with the wall surface of the recess 24 when the transparent resin such as liquid silicone or the inorganic glass such as SOG is disposed inside the recess 24.
  • a concave surface can be formed in the bonding layer 13 of the recess 24 by performing an etch back process by RIE or the like.
  • a light scattering part 26B which is a light scattering means, is formed in the BOX layer 23.
  • the light scattering portion 26B only needs to be formed on at least one of the bottom surface 24B and the bottom surface 25B.
  • the light scattering portion 26B is a diffraction structure formed with regular irregularities formed in the BOX layer 23, or a light scattering structure with irregular irregularities.
  • the structure is processed on the BOX layer 23 of the Si wafer on which the BOX layer 23 is formed, and then the active layer 21 is formed on the BOX layer 23, whereby the light scattering portion 26B. Is formed.
  • a metal scattering film 26C as a light scattering means is disposed on the BOX layer 23 on the bottom surface of the recess 25.
  • the metal scattering film 26C is formed by lift-off of a fine metal pattern or photolithography.
  • a light scattering layer 26D in which metal particles as light scattering means are dispersed is disposed in the BOX layer 23 on the bottom surface 25B of the recess 25.
  • the metal scattering film 26 ⁇ / b> C and the light scattering layer 26 ⁇ / b> D may be disposed on the entire bottom surface 25 ⁇ / b> B of the recess 25.
  • Fluorescence sensor 4B equipped with a light scattering means that averages the in-plane distribution of the excitation light intensity has higher detection sensitivity and less sensitivity reduction due to deterioration with time, in addition to the effects of fluorescence sensor 4 and the like.
  • the sensor system 1C and the fluorescence sensor 4C of the second embodiment will be described. Since the fluorescent sensor 4C and the like are similar to the fluorescent sensor 4 and the like, the same components are denoted by the same reference numerals and description thereof is omitted.
  • the light emitting element 15 is generated in addition to the PD element 12 which is the first photoelectric conversion element for detecting the fluorescence generated by the indicator 17.
  • a PD element 12B which is a second photoelectric conversion element that detects excitation light to be emitted, is formed.
  • the PD element 12 and the PD element 12B are PD elements having the same semiconductor structure, and the PD element 12B is disposed in a region outside the PD element 12.
  • the light emitting element 15L covers not only the area directly under the opening of the recess 24 but also the area directly under the second PD element 12B. That is, the dimension in plan view of the light emitting element 15 is a size that covers a region immediately below the opening of the recess 24 and also covers a region directly below the PD element 12B.
  • the filter 14 is not disposed on the surface of the PD element 12B. Therefore, the PD element 12B outputs an electrical signal (detection signal) corresponding to the intensity of the excitation light generated by the light emitting element 15L.
  • the manufacturing method of the fluorescent sensor 4C is similar to the manufacturing method of the fluorescent sensor 4.
  • the PD element (light receiving part) 12B is formed simultaneously with the formation of the light receiving part 12T and the low resistance region 12H of the PD element by the impurity implantation process.
  • the diffusion layer (light receiving portion) of the PD element 12B that detects the excitation light of the LED may be a diffusion layer having the same structure (concentration and diffusion depth) as the PD element 12T, but it matches the excitation light wavelength and the fluorescence wavelength.
  • the structure of the diffusion layer may be different.
  • the first main surface 20SA of the substrate unit 20 is also provided with a detection signal wiring (not shown) that transmits a detection signal output from the PD element 12B.
  • the detection signal wiring 52 connected to the low resistance region 12H serves as a common wiring for the PD element 12 and the PD element 12B.
  • the intensity of the fluorescence generated by the indicator 17 increases or decreases depending on not only the amount of analyte but also the intensity of excitation light.
  • the calculation unit 2C that processes the electrical signal (detection signal) output from the fluorescence sensor 4C converts the electrical signal (detection signal) from the first PD element 12 to the second PD element 12B. Correct based on the electrical signal.
  • the fluorescence sensor 4C and the sensor system 1C have the effects of the fluorescence sensor 4 and the sensor system 1 and the like, and the intensity of excitation light changes due to variations in the light emission efficiency of the light emitting element 15L or excitation light amount drift during operation. However, highly accurate measurement is possible.
  • the PD element 12 ⁇ / b> T is formed in the active layer 21 similarly to the sensor unit 10 of the fluorescence sensor 4, and the second recess 25 of the substrate layer 22 is further formed.
  • a PD element 12D is also formed on the wall surface.
  • the PD element 12D covered with the filter 14D may be formed on at least one of the four wall surfaces.
  • the PD elements 12D and 12 (12T) are connected to the respective wiring layers 50 through the through wiring 58, and the low resistance regions 12HD1 and 12HD2 through the through wiring 59.
  • the substrate portion 20 is an SOI substrate, the recesses 24 and 25 can be easily formed. Furthermore, since the PD element 12D is formed on the wall surface surrounding the indicator 17, the sensitivity is high.
  • PD elements may be formed on the active layer 21 in addition to the wall surface and bottom surface of the second recess 25 of the substrate layer 22. That is, in the fluorescence sensor in which the fluorescence sensor 4 and the fluorescence sensor 4D are combined, photoelectric conversion elements are formed on the area surrounding the first recess 24 of the active layer 21 and the wall surface of the second recess 25 of the substrate layer 22. Yes.
  • the fluorescent sensor has high sensitivity because it has a large light receiving area.
  • a plurality of concave portions 24 may be formed as in the fluorescence sensor 4A, or a light diffusion portion may be provided as in the fluorescence sensor 4B.
  • the fluorescent sensor 4 that detects saccharides such as glucose has been described as an example.
  • the fluorescent dye corresponds to various uses such as an enzyme sensor, a pH sensor, an immune sensor, or a microorganism sensor. be able to.
  • an enzyme sensor e.g., a hydroxypyrenetrisulfonic acid derivative or the like
  • a phenylboronic acid derivative having a fluorescent residue is used when measuring a saccharide.
  • a potassium ion e.g., a crown ether derivative having a fluorescent residue is used.

Abstract

A fluorescent light sensor (4) comprising: a substrate section (20) comprising an SOI substrate having an active layer (21) arranged upon a substrate layer (22) via a BOX layer (23) and having a PD element (12) formed therein, said substrate section having a first recessed section (24), being a through-hole via, formed on the active layer (21) and a second recessed section (25), being a through-hole via of a size that includes an area facing the first recessed section (24), formed in the substrate layer (22); a filter (14) that shields excitation light covering the PD element (12); an indicator (17) arranged in the second recessed section (25); a light-shielding layer (18) covering the opening of the second recessed section (25); and a light-emitting element (15) generating the excitation light.

Description

蛍光センサ及びセンサシステムFluorescence sensor and sensor system
 本発明は、液体中のアナライトの濃度を計測する蛍光センサ及び前記蛍光センサを具備するセンサシステムに関し、特に半導体製造技術及びMEMS技術を用いて作製された微小蛍光光度計である蛍光センサ及び前記蛍光センサを具備するセンサシステムに関する。 The present invention relates to a fluorescence sensor for measuring the concentration of an analyte in a liquid and a sensor system including the fluorescence sensor, and in particular, a fluorescence sensor that is a microfluorometer manufactured using semiconductor manufacturing technology and MEMS technology, and the above-described sensor The present invention relates to a sensor system including a fluorescent sensor.
 液体中のアナライトすなわち被計測物質の濃度を測定するための様々な分析装置が開発されている。例えば、蛍光色素とアナライトを含む被計測溶液とを透明容器に注入し、励起光を照射し蛍光色素からの蛍光強度を計測することによりアナライト濃度を計測する蛍光光度計が知られている。蛍光色素は、アナライトの存在によって性質が変化し励起光を受光するとアナライト濃度に対応した強度の蛍光を発生する
 小型の蛍光光度計は、光源と光検出器と蛍光色素を含有したインジケータとを有している。そして、被計測溶液中のアナライトが出入り自在なインジケータに光源からの励起光を照射し、インジケータが発生する蛍光を光検出器が受光する。光検出器は光電変換素子であり、受光強度に応じた電気信号を出力する。光検出器からの電気信号をもとに溶液中のアナライト濃度が算出される。
Various analyzers for measuring the concentration of an analyte in a liquid, that is, a substance to be measured have been developed. For example, a fluorometer that measures an analyte concentration by injecting a fluorescent dye and a solution to be measured containing an analyte into a transparent container, irradiating excitation light, and measuring the fluorescence intensity from the fluorescent dye is known. . Fluorescent dyes change their properties due to the presence of analyte, and when they receive excitation light, they generate fluorescence with an intensity corresponding to the analyte concentration. have. And the excitation light from a light source is irradiated to the indicator in which the analyte in a to-be-measured solution can go in and out, and the photodetector receives the fluorescence which an indicator produces. The photodetector is a photoelectric conversion element and outputs an electrical signal corresponding to the received light intensity. The analyte concentration in the solution is calculated based on the electrical signal from the photodetector.
 近年、微量試料中のアナライトを計測するために、半導体製造技術及びMEMS技術を用いて作製される微小蛍光光度計が提案されている。以下、微小蛍光光度計のことを「蛍光センサ」と呼ぶ。 In recent years, in order to measure an analyte in a small amount of sample, a microfluorometer manufactured using semiconductor manufacturing technology and MEMS technology has been proposed. Hereinafter, the microfluorometer is referred to as “fluorescence sensor”.
 例えば、図1及び図2に示す蛍光センサ104が国際公開第2010/119916号パンフレットに開示されている。蛍光センサ104の主機能部であるセンサ部110は、光電変換素子112が形成されているシリコン基板111と、透明中間層113と、フィルタ層114と、発光素子115と、透明保護層116と、インジケータ117と、遮光層118と、を有する。アナライト9は、遮光層118を通過して、インジケータ117に進入する。蛍光センサ104のフィルタ層114は励起光を遮断し蛍光を透過する。さらに、発光素子115は蛍光を透過する。 For example, the fluorescent sensor 104 shown in FIGS. 1 and 2 is disclosed in International Publication No. 2010/119916. The sensor unit 110 which is a main functional unit of the fluorescence sensor 104 includes a silicon substrate 111 on which a photoelectric conversion element 112 is formed, a transparent intermediate layer 113, a filter layer 114, a light emitting element 115, a transparent protective layer 116, An indicator 117 and a light shielding layer 118 are provided. The analyte 9 passes through the light shielding layer 118 and enters the indicator 117. The filter layer 114 of the fluorescence sensor 104 blocks excitation light and transmits fluorescence. Further, the light emitting element 115 transmits fluorescence.
 蛍光センサ104では、発光素子115が発生した励起光がインジケータ117に入射すると、インジケータ117はアナライト濃度に応じた蛍光を発生する。 In the fluorescence sensor 104, when the excitation light generated by the light emitting element 115 enters the indicator 117, the indicator 117 generates fluorescence corresponding to the analyte concentration.
 インジケータ117が発生した蛍光の一部は、発光素子115とフィルタ層114とを通過し、光電変換素子112に入射し光電変換される。なお、発光素子115が光電変換素子112の方向(下方向)出射した励起光は、フィルタ層114により蛍光強度と比較して計測上問題ないレベルまで減光される。蛍光センサ104は、構成が単純で小型化が容易である。 Part of the fluorescence generated by the indicator 117 passes through the light emitting element 115 and the filter layer 114, enters the photoelectric conversion element 112, and is photoelectrically converted. The excitation light emitted from the light emitting element 115 in the direction of the photoelectric conversion element 112 (downward) is attenuated by the filter layer 114 to a level that causes no problem in measurement as compared with the fluorescence intensity. The fluorescent sensor 104 has a simple configuration and can be easily downsized.
 しかし、蛍光センサ104は、インジケータ117を保持する枠部の内部に発光素子115及び光電変換素子112を配設するため、蛍光センサ104は、製造が容易ではなかった。 However, since the fluorescent sensor 104 has the light emitting element 115 and the photoelectric conversion element 112 disposed inside the frame portion that holds the indicator 117, the fluorescent sensor 104 is not easy to manufacture.
 本発明の実施形態は、製造が容易な蛍光センサ及び検出感度が高いセンサシステムを提供することを目的とする。 An object of the embodiment of the present invention is to provide a fluorescent sensor that is easy to manufacture and a sensor system with high detection sensitivity.
 本発明の一態様の蛍光センサは、活性層が酸化膜を介して基板層上に配設されているSOI基板からなり、第1の主面を構成する前記活性層には貫通ビアである第1の凹部が形成されており、第2の主面を構成する前記基板層には前記第1の凹部と対向する領域を含む大きさの貫通ビアである第2の凹部が形成されており、さらに、蛍光を電気信号に変換する光電変換素子が形成されている基板部と前記光電変換素子を覆っている、励起光を遮断するフィルタと、前記第2の凹部に配設されている、前記励起光を受光するとアナライトの濃度に応じた強度の前記蛍光を発生するインジケータと、前記第2の凹部の開口を覆っている、前記インジケータへの外光進入を遮断するが、アナライトは通過する遮光層と、前記第1の凹部の開口の直下領域を覆っている、前記励起光を発生する発光素子と、を具備する。 The fluorescent sensor of one embodiment of the present invention includes an SOI substrate in which an active layer is disposed on a substrate layer via an oxide film, and the active layer constituting the first main surface is a through via. 1 recess is formed, the substrate layer constituting the second main surface is formed with a second recess that is a through via having a size including a region facing the first recess, Furthermore, the substrate part on which a photoelectric conversion element for converting fluorescence into an electric signal is formed, a filter covering the photoelectric conversion element, blocking excitation light, and the second recess, When the excitation light is received, the indicator that generates the fluorescence having an intensity corresponding to the concentration of the analyte and the outside light entering the indicator that covers the opening of the second recess are blocked, but the analyte passes. The light shielding layer to be It covers the region comprises a light-emitting element for generating the excitation light.
 また、本発明の別の一態様のセンサシステムは、活性層が酸化膜を介して基板層上に配設されているSOI基板からなり、第1の主面を構成する前記活性層には貫通ビアである第1の凹部が形成されており、第2の主面を構成する前記基板層には前記第1の凹部と対向する領域を含む大きさの貫通ビアである第2の凹部が形成されており、さらに、蛍光を電気信号に変換する光電変換素子が形成されている基板部と前記光電変換素子を覆っている、励起光を遮断するフィルタと、前記第2の凹部に配設されている、前記励起光を受光するとアナライトの濃度に応じた強度の前記蛍光を発生するインジケータと、前記第2の凹部の開口を覆っている、前記インジケータへの外光進入を遮断するが、アナライトは通過する遮光層と、前記第1の凹部の開口の直下領域を覆っている、前記励起光を発生する発光素子と、を具備する蛍光センサと、前記電気信号を補正する演算部を有する本体部と、を具備する。 The sensor system according to another aspect of the present invention includes an SOI substrate in which an active layer is disposed on a substrate layer via an oxide film, and penetrates through the active layer constituting the first main surface. A first concave portion that is a via is formed, and a second concave portion that is a through via having a size including a region facing the first concave portion is formed in the substrate layer constituting the second main surface. Furthermore, a substrate part on which a photoelectric conversion element for converting fluorescence into an electric signal is formed, a filter covering the photoelectric conversion element and blocking excitation light, and the second recess are provided. An indicator that generates the fluorescence having an intensity according to the concentration of the analyte when receiving the excitation light, and covers the opening of the second recess, blocking external light from entering the indicator, The analyte passes through the light-shielding layer, and the first It covers the region immediately below the opening of the part comprises a fluorescent sensor comprising a light emitting element for generating the excitation light, and a main body portion having a computing unit for correcting the electrical signal.
 本発明の実施形態によれば、小型で検出感度が高い蛍光センサ及び検出感度が高いセンサシステムを提供できる。 According to the embodiment of the present invention, a compact fluorescent sensor with high detection sensitivity and a sensor system with high detection sensitivity can be provided.
従来の蛍光センサのセンサ部の断面構造を示した説明図である。It is explanatory drawing which showed the cross-section of the sensor part of the conventional fluorescence sensor. 従来の蛍光センサのセンサ部の構造を説明するための分解図である。It is an exploded view for demonstrating the structure of the sensor part of the conventional fluorescence sensor. 第1実施形態の蛍光センサを有するセンサシステムを説明するための斜視図である。It is a perspective view for demonstrating the sensor system which has the fluorescence sensor of 1st Embodiment. 第1実施形態の蛍光センサのセンサ部の構造を示す断面図である。It is sectional drawing which shows the structure of the sensor part of the fluorescence sensor of 1st Embodiment. 第1実施形態の蛍光センサのセンサ部の配置を示す上面図である。It is a top view which shows arrangement | positioning of the sensor part of the fluorescence sensor of 1st Embodiment. 第1実施形態の蛍光センサの構造を説明するためのセンサ部の分解図である。It is an exploded view of the sensor part for demonstrating the structure of the fluorescence sensor of 1st Embodiment. 第1実施形態の蛍光センサの製造方法を説明するためのセンサ部の断面構造を示す模式図である。It is a schematic diagram which shows the cross-section of the sensor part for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. 第1実施形態の蛍光センサの製造方法を説明するためのセンサ部の断面構造を示す模式図である。It is a schematic diagram which shows the cross-section of the sensor part for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. 第1実施形態の蛍光センサの製造方法を説明するためのセンサ部の断面構造を示す模式図である。It is a schematic diagram which shows the cross-section of the sensor part for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. 第1実施形態の蛍光センサの製造方法を説明するためのセンサ部の断面構造を示す模式図である。It is a schematic diagram which shows the cross-section of the sensor part for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. 第1実施形態の蛍光センサの製造方法を説明するためのセンサ部の断面構造を示す模式図である。It is a schematic diagram which shows the cross-section of the sensor part for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. 第1実施形態の蛍光センサの製造方法を説明するためのセンサ部の断面構造を示す模式図である。It is a schematic diagram which shows the cross-section of the sensor part for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. 第1実施形態の変形例1の蛍光センサのセンサ部の凹部を示す上面図である。It is a top view which shows the recessed part of the sensor part of the fluorescence sensor of the modification 1 of 1st Embodiment. 第1実施形態の変形例1の蛍光センサのセンサ部の凹部を示す上面図である。It is a top view which shows the recessed part of the sensor part of the fluorescence sensor of the modification 1 of 1st Embodiment. 第1実施形態の変形例1の蛍光センサのセンサ部の凹部を示す上面図である。It is a top view which shows the recessed part of the sensor part of the fluorescence sensor of the modification 1 of 1st Embodiment. 第1実施形態の変形例2の蛍光センサのセンサ部の構造を示す断面図である。It is sectional drawing which shows the structure of the sensor part of the fluorescence sensor of the modification 2 of 1st Embodiment. 第1実施形態の変形例2の蛍光センサのセンサ部の構造を示す断面図である。It is sectional drawing which shows the structure of the sensor part of the fluorescence sensor of the modification 2 of 1st Embodiment. 第1実施形態の変形例2の蛍光センサのセンサ部の構造を示す断面図である。It is sectional drawing which shows the structure of the sensor part of the fluorescence sensor of the modification 2 of 1st Embodiment. 第1実施形態の変形例2の蛍光センサのセンサ部の構造を示す断面図である。It is sectional drawing which shows the structure of the sensor part of the fluorescence sensor of the modification 2 of 1st Embodiment. 第1実施形態の変形例2の蛍光センサのセンサ部の構造を示す断面図である。It is sectional drawing which shows the structure of the sensor part of the fluorescence sensor of the modification 2 of 1st Embodiment. 第2実施形態の蛍光センサのセンサ部の構造を示す断面図である。It is sectional drawing which shows the structure of the sensor part of the fluorescence sensor of 2nd Embodiment. 第3実施形態の蛍光センサのセンサ部の構造を示す断面図である。It is sectional drawing which shows the structure of the sensor part of the fluorescence sensor of 3rd Embodiment.
 <第1実施形態>
 最初に、本発明の第1実施形態の蛍光センサ4及びセンサシステム1について説明する。図3に示すように、センサシステム1は、蛍光センサ4と、本体部2と、本体部2からの信号を受信し記憶するレシーバー3と、を有する。本体部2とレシーバー3との間の信号の送受信は無線又は有線で行われる。
<First Embodiment>
First, the fluorescence sensor 4 and the sensor system 1 according to the first embodiment of the present invention will be described. As shown in FIG. 3, the sensor system 1 includes a fluorescent sensor 4, a main body 2, and a receiver 3 that receives and stores a signal from the main body 2. Transmission / reception of signals between the main body 2 and the receiver 3 is performed wirelessly or by wire.
 蛍光センサ4は、被検体に穿刺される針部7と、針部7の後端部と接合されたコネクタ部8と、からなる。針部7は、細長い針本体部6と、主要機能部であるセンサ部10を含む針先端部5と、を有する。針先端部5、針本体部6、コネクタ部8は、同一材料により一体形成されていてもよいし、別々に作製され接合されていてもよい。 The fluorescent sensor 4 includes a needle portion 7 that is punctured by a subject and a connector portion 8 that is joined to the rear end portion of the needle portion 7. The needle part 7 has an elongated needle body part 6 and a needle tip part 5 including a sensor part 10 which is a main function part. Needle tip 5, needle body 6, and connector 8 may be integrally formed of the same material, or may be separately produced and joined.
 コネクタ部8は、本体部2の嵌合部2Aと着脱自在に嵌合する。蛍光センサ4のセンサ部10から延設された複数の配線60は、コネクタ部8が本体部2の嵌合部2Aと機械的に嵌合することにより、本体部2と電気的に接続される。 The connector part 8 is detachably fitted to the fitting part 2A of the main body part 2. The plurality of wirings 60 extending from the sensor unit 10 of the fluorescent sensor 4 are electrically connected to the main body unit 2 when the connector unit 8 is mechanically fitted to the fitting unit 2A of the main body unit 2. .
 蛍光センサ4は、センサ部10を体内に挿入後、所定期間、例えば、1週間、継続してアナライト濃度を測定可能な針型センサである。しかし、センサ部10を体内に挿入しないで、採取した体液、又は体外の流路を介して体内と循環する体液を、体外においてセンサ部10と接触させてもよい。 The fluorescent sensor 4 is a needle type sensor that can continuously measure the analyte concentration for a predetermined period, for example, one week after the sensor unit 10 is inserted into the body. However, the collected body fluid or the body fluid circulating through the body via the flow path outside the body may be brought into contact with the sensor unit 10 outside the body without inserting the sensor unit 10 into the body.
 本体部2は、センサ部10の駆動及び制御などを行う制御部2Bと、センサ部10から出力された信号を処理する演算部2Cと、を有する。なお、制御部2B又は演算部2Cの少なくともいずれかが、蛍光センサ4のコネクタ部8等に配設されていてもよいし、レシーバー3に配設されていてもよい。 The main body unit 2 includes a control unit 2B that performs driving and control of the sensor unit 10, and a calculation unit 2C that processes a signal output from the sensor unit 10. Note that at least one of the control unit 2B and the calculation unit 2C may be disposed on the connector unit 8 of the fluorescent sensor 4 or the receiver 3.
 図示しないが、本体部2は、レシーバー3との間で無線信号を送受信するための無線アンテナと、電池等と、をさらに有する。レシーバー3との間の信号を有線にて送受信する場合には、本体部2は無線アンテナに代えて信号線を有する。なお、本体部2が必要な容量のメモリ部を有する場合にはレシーバー3はなくてもよい。 Although not shown, the main body 2 further includes a radio antenna for transmitting and receiving radio signals to and from the receiver 3, a battery, and the like. When transmitting / receiving a signal to / from the receiver 3 by wire, the main body 2 has a signal line instead of a wireless antenna. Note that the receiver 3 may not be provided when the main body 2 includes a memory unit having a necessary capacity.
<センサ部の構造>
 次に、図4A、図4B及び図5を用いて、蛍光センサ4の主要機能部であるセンサ部10の構造について説明する。なお、図は、いずれも説明のための模式図であり、縦横の寸法比等は実際とは異なっており、一部の構成要素を図示しない場合もある。また、図に示すZ軸方向を上方向という。
<Structure of sensor part>
Next, the structure of the sensor unit 10 that is a main functional unit of the fluorescence sensor 4 will be described with reference to FIGS. 4A, 4B, and 5. In addition, all the figures are schematic diagrams for explanation, and the vertical and horizontal dimensional ratios and the like are different from actual ones, and some components may not be shown. Further, the Z-axis direction shown in the figure is referred to as an upward direction.
 蛍光センサ4は、基板部20と、フィルタ14と、インジケータ17と、遮光層18と、発光素子15と、を主機能要素として具備する。基板部20と発光素子15とは、接合層13を介して接合されている。 The fluorescent sensor 4 includes a substrate unit 20, a filter 14, an indicator 17, a light shielding layer 18, and a light emitting element 15 as main functional elements. The substrate unit 20 and the light emitting element 15 are bonded via the bonding layer 13.
 基板部20は、活性層(SOI層)21が、埋め込みシリコン酸化膜(Buried Oxide:BOX層)23を介して、支持基板層(基板層)22上に配設されているSOI(Silicon on Insulator)基板からなる。活性層21の厚さは数μm~100μmであり、光透過率の高いBOX層23の厚さは1μm~数10μmであり、基板層22の厚さは10μm~数百μmである。 The substrate unit 20 includes an SOI (Silicon on Insulator) in which an active layer (SOI layer) 21 is disposed on a support substrate layer (substrate layer) 22 via a buried silicon oxide film (Buried Oxide: BOX layer) 23. ) It consists of a substrate. The thickness of the active layer 21 is several μm to 100 μm, the thickness of the BOX layer 23 having a high light transmittance is 1 μm to several tens of μm, and the thickness of the substrate layer 22 is 10 μm to several hundreds of μm.
 基板部20の第1の主面20SAを構成するシリコンからなる活性層21には第1の貫通ビアである凹部24が形成されており、第2の主面20SBを構成するシリコンからなる基板層22には第2の貫通ビアである凹部25が形成されている。すなわち、凹部24は活性層21を貫通しており、凹部25は基板層22を貫通しており、底面24B及び底面25BはともにBOX層23であり、凹部25と凹部24とはBOX層23を介して接している。 The active layer 21 made of silicon constituting the first main surface 20SA of the substrate part 20 is formed with a recess 24 as a first through via, and the substrate layer made of silicon constituting the second main surface 20SB. 22 is formed with a recess 25 which is a second through via. That is, the recess 24 penetrates the active layer 21, the recess 25 penetrates the substrate layer 22, the bottom surface 24B and the bottom surface 25B are both the BOX layer 23, and the recess 25 and the recess 24 define the BOX layer 23. Is touching through.
 ここで、図4Bは、蛍光センサ4の一部の構成要素の配置状態を説明するための平面図である。図4Bに示すように、凹部24、25は基板部20のXY平面内の同一領域内に形成され、かつ凹部24の底面24Bの平面視寸法は凹部25の底面25Bよりも小さい。すなわち底面25Bは底面24Bを完全に覆うように形成されている。言い換えれば、凹部24が形成されている領域は凹部25と対向する領域を含む。 Here, FIG. 4B is a plan view for explaining an arrangement state of some components of the fluorescence sensor 4. As shown in FIG. 4B, the recesses 24 and 25 are formed in the same region in the XY plane of the substrate unit 20, and the planar view size of the bottom surface 24 </ b> B of the recess 24 is smaller than the bottom surface 25 </ b> B of the recess 25. That is, the bottom surface 25B is formed so as to completely cover the bottom surface 24B. In other words, the region where the recess 24 is formed includes a region facing the recess 25.
 発光素子15は、光出射面が活性層21の凹部24の開口を覆っていれば、凹部24を導光路としてBOX層23を介して凹部24に配設されたインジケータ17に励起光が照射される。 In the light emitting element 15, if the light emitting surface covers the opening of the recess 24 of the active layer 21, excitation light is irradiated to the indicator 17 disposed in the recess 24 through the BOX layer 23 with the recess 24 as a light guide. The
 活性層21の主面の凹部24を取り囲む領域には、蛍光を電気信号に変換する光電変換素子であるフォトダイオード(Photo Diode:PD)素子12の受光部12Tが形成されている。すなわち、PD素子12は、凹部25の内部に配設されたインジケータ17に対して、受光面が向くように凹部24の開口を囲むように配置されている。なお、以下、受光部12Tを、PD素子12という。凹部24の平面視形状は、PD素子12の内側に配置するため、PD素子12の平面形状を縮小化した形状でもよいが、PD素子12の形状と異なっている多角形、円形、楕円形等でもよい。 In a region surrounding the recess 24 on the main surface of the active layer 21, a light receiving portion 12T of a photodiode (Photo-Diode: PD) element 12 which is a photoelectric conversion element that converts fluorescence into an electric signal is formed. That is, the PD element 12 is disposed so as to surround the opening of the recess 24 so that the light receiving surface faces the indicator 17 disposed inside the recess 25. Hereinafter, the light receiving unit 12T is referred to as a PD element 12. The planar view shape of the concave portion 24 may be a shape obtained by reducing the planar shape of the PD element 12 in order to be arranged inside the PD element 12, but a polygon, a circle, an ellipse, or the like that is different from the shape of the PD element 12. But you can.
 さらに、第1の主面20SAに形成されたPD素子12及び凹部24の壁面を覆うように、フィルタ14が配設されている。すなわち、フィルタ14は、凹部24の底面24Bには配設されていない。なお、フィルタ14を形成前に、酸化シリコン等の透明保護膜を形成してもよい。 Furthermore, the filter 14 is disposed so as to cover the wall surface of the PD element 12 and the recess 24 formed on the first main surface 20SA. That is, the filter 14 is not disposed on the bottom surface 24 </ b> B of the recess 24. Note that a transparent protective film such as silicon oxide may be formed before the filter 14 is formed.
 フィルタ14は、例えば波長375nmの励起光を遮断し、励起光が、PD素子12を含む活性層21に入射するのを遮断する。フィルタ14は励起光以外の波長の光も遮断する遮光層であってもよい。ただし、凹部24の壁面のPD素子12を覆っている領域のフィルタは、検出感度向上の観点から蛍光を透過することが好ましい。フィルタ14により、PD素子12はノイズとなる励起光による信号出力が少ないため、SN比の高いセンサが実現できる。 The filter 14 blocks excitation light having a wavelength of 375 nm, for example, and blocks the excitation light from entering the active layer 21 including the PD element 12. The filter 14 may be a light shielding layer that blocks light having a wavelength other than the excitation light. However, the filter in the region covering the PD element 12 on the wall surface of the recess 24 preferably transmits fluorescence from the viewpoint of improving detection sensitivity. Since the PD element 12 has a small signal output due to excitation light that becomes noise, the filter 14 can realize a sensor with a high S / N ratio.
 さらに、第1の主面20SAには、フィルタ14を介して、検出信号配線51、52及び駆動信号配線53、54からなる配線層50が配設されている。検出信号配線51、52はPD素子12からの検出信号を出力する。検出信号配線51はPD素子の受光部12Tに接続されており、検出信号配線52は活性層21と同じ半導体不純物タイプの低抵抗領域12Hと接続されている。駆動信号配線53、54は、発光素子15の駆動信号電極15Tに駆動信号を供給する。すなわち配線層50の各配線は、針本体部6を挿通する複数の配線60と接続されている。 Further, a wiring layer 50 including detection signal wirings 51 and 52 and drive signal wirings 53 and 54 is disposed on the first main surface 20SA via the filter 14. The detection signal wirings 51 and 52 output detection signals from the PD element 12. The detection signal wiring 51 is connected to the light receiving portion 12T of the PD element, and the detection signal wiring 52 is connected to the low resistance region 12H of the same semiconductor impurity type as the active layer 21. The drive signal wirings 53 and 54 supply a drive signal to the drive signal electrode 15T of the light emitting element 15. That is, each wiring of the wiring layer 50 is connected to a plurality of wirings 60 that pass through the needle body 6.
 接合層13は、基板部20とLEDとを接合するとともに、PD素子12及び凹部24の壁面を保護する。接合層13は凹部24の内部にも充填されていてもよい。逆に、接合層13を凹部24の開口の直下領域に形成しなくてもよい。 The bonding layer 13 bonds the substrate unit 20 and the LED and protects the wall surfaces of the PD element 12 and the recess 24. The bonding layer 13 may also be filled in the recess 24. Conversely, the bonding layer 13 may not be formed in the region immediately below the opening of the recess 24.
 接合層13は、電気的絶縁性を有すること、水分遮断性を有すること、励起光に対して良好な透過率を有すること、などの特性を有する接着材料から選択される。接合層13としては、エポキシ樹脂、シリコーン樹脂、透明な非晶性フッ素樹脂等の有機樹脂、あるいはシリコン酸化膜やシリコン窒化膜などの透明無機材料、さらにはこれらの複合積層膜が使用可能である。 The bonding layer 13 is selected from adhesive materials having characteristics such as electrical insulation, moisture barrier properties, and good transmittance for excitation light. As the bonding layer 13, an epoxy resin, a silicone resin, an organic resin such as a transparent amorphous fluororesin, a transparent inorganic material such as a silicon oxide film or a silicon nitride film, or a composite laminated film thereof can be used. .
 凹部25の内部に充填されたインジケータ17は、進入してきたアナライト9との相互作用及び励起光により蛍光を発生する。インジケータ17の厚さは、凹部25の深さ、すなわち、基板層22の厚さと同じで、10μm~数百μmである。インジケータ17は、内部に進入したアナライト9の量、すなわち被計測溶液中のアナライト濃度に応じた強度の蛍光を発生する蛍光色素が含まれたベース材料から構成されている。 The indicator 17 filled in the recess 25 generates fluorescence due to the interaction with the entering analyte 9 and excitation light. The thickness of the indicator 17 is the same as the depth of the recess 25, that is, the thickness of the substrate layer 22, and is 10 μm to several hundred μm. The indicator 17 is made of a base material containing a fluorescent dye that generates fluorescence having an intensity corresponding to the amount of the analyte 9 that has entered the inside, that is, the concentration of the analyte in the solution to be measured.
 凹部25の開口25Aを覆っている遮光層18は、厚さが数10μm程度である。遮光層18は、励起光及び蛍光が外部へ漏光するのを防止すると同時に、外光が内部に進入するのを防止する。また、遮光層18はアナライト9の通過を妨げないアナライト透過性も有している。 The light shielding layer 18 covering the opening 25A of the recess 25 has a thickness of about several tens of μm. The light shielding layer 18 prevents excitation light and fluorescence from leaking to the outside, and at the same time, prevents outside light from entering the inside. The light shielding layer 18 also has analyte permeability that does not hinder the passage of the analyte 9.
 発光素子15の底面(光出射面と対向する面)及び壁面を覆うように配設された漏光防止層19は、底面及び壁面から出射される励起光、及び、活性層21の表面で反射した励起光が外部に漏光するのを防止する。すなわち、漏光防止層19は遮光層18と類似した機能を有するが、アナライト透過性は必要ない。 The light leakage prevention layer 19 disposed so as to cover the bottom surface (the surface facing the light emitting surface) and the wall surface of the light emitting element 15 is reflected by the excitation light emitted from the bottom surface and the wall surface and the surface of the active layer 21. The excitation light is prevented from leaking outside. That is, the light leakage prevention layer 19 has a function similar to that of the light shielding layer 18, but does not require analyte permeability.
<蛍光センサの製造方法>
 次に、図6A~図6Fを用いて、蛍光センサ4の製造方法について説明する。なお、図6A~図6Fは1個の蛍光センサ4のセンサ部10の領域の部分断面図であるが、実際の工程では、ウエハプロセスとして一括して多数の蛍光センサ4のセンサ部10を有するセンサ基板が作製される。
<Method for manufacturing fluorescent sensor>
Next, a method for manufacturing the fluorescence sensor 4 will be described with reference to FIGS. 6A to 6F. 6A to 6F are partial cross-sectional views of the region of the sensor unit 10 of one fluorescent sensor 4. However, in the actual process, the sensor unit 10 of a large number of fluorescent sensors 4 is collectively included as a wafer process. A sensor substrate is fabricated.
 最初に、図6Aに示すように、SOIウエハ20Wの第1の主面20SAの活性層21に、通常の半導体プロセスを用いて、光電変換素子であるPD素子12が形成される。受光部12Tの平面形状及び大きさは、センサ部10の配設箇所が針先端部5であるために、例えば、縦150μm、横500μmのように細長い形状であることが好ましい。 First, as shown in FIG. 6A, the PD element 12 which is a photoelectric conversion element is formed on the active layer 21 of the first main surface 20SA of the SOI wafer 20W using a normal semiconductor process. The planar shape and size of the light receiving portion 12T are preferably elongated, for example, 150 μm in length and 500 μm in width because the location where the sensor unit 10 is disposed is the needle tip 5.
 受光部12Tは、活性層21とは逆の半導体不純物タイプの不純物を導入して形成される。一方、低抵抗領域12Hは、活性層21と同じ半導体不純物タイプの不純物を導入して形成される。例えば活性層21がN型半導体の場合、受光部12Tはボロン拡散によりP型半導体の拡散層が形成され、低抵抗領域12Hには、リン又はヒ素等が導入され形成される。 The light receiving portion 12T is formed by introducing a semiconductor impurity type impurity opposite to that of the active layer 21. On the other hand, the low resistance region 12H is formed by introducing impurities of the same semiconductor impurity type as the active layer 21. For example, when the active layer 21 is an N-type semiconductor, a P-type semiconductor diffusion layer is formed in the light receiving portion 12T by boron diffusion, and phosphorus, arsenic, or the like is introduced into the low resistance region 12H.
 光電変換素子としては、フォトコンダクタ(光導電体)素子、又はフォトトランジスタ(Photo Transistor)素子などでもよい。 The photoelectric conversion element may be a photoconductor (photoconductor) element or a phototransistor element.
 次に、図6Bに示すように、第1の主面20SAの活性層21にフォトエッチングが行われ、凹部24が形成される。エッチングには公知の各種の方法を用いることができる。凹部24は、PD素子12の平面領域より内側に配置される。凹部24は活性層21を貫通する貫通ビアであり、底面にはBOX層23が露出している。 Next, as shown in FIG. 6B, photo-etching is performed on the active layer 21 of the first main surface 20SA to form a recess 24. Various known methods can be used for etching. The recess 24 is disposed inside the planar region of the PD element 12. The recess 24 is a through via that penetrates the active layer 21, and the BOX layer 23 is exposed on the bottom surface.
 続いて、第1の主面20SAの活性層21及び凹部24の壁面にフィルタ14が形成される。ここで、フィルタ14は、CVD法による成膜及び異方性ドライエッチングを用いることにより、凹部24の底面24Bには形成されない。なお、フィルタ14形成前に、シリコン酸化膜等の透明保護膜を形成しておいてもよい。 Subsequently, the filter 14 is formed on the wall surface of the active layer 21 and the recess 24 of the first main surface 20SA. Here, the filter 14 is not formed on the bottom surface 24 </ b> B of the recess 24 by using film formation by CVD and anisotropic dry etching. A transparent protective film such as a silicon oxide film may be formed before forming the filter 14.
 フィルタ14は、誘電体多層膜等の多重干渉型でもよいが、好ましくは、吸収型であり、例えばシリコン、炭化シリコン、酸化シリコン、窒化シリコン、もしくは有機材料等からなる単層層、又は前記単層層を積層した多層層である。例えば、シリコン層及び炭化シリコン層は、励起光波長の375nmでは透過率は10-5%以下であるのに対して、蛍光波長の460nmでは透過率10%以上と、(励起光波長の透過率/蛍光波長の透過率)の比として6桁以上の透過率選択性を有する。 The filter 14 may be a multiple interference type such as a dielectric multilayer film, but is preferably an absorption type, for example, a single layer made of silicon, silicon carbide, silicon oxide, silicon nitride, or an organic material, or the single layer. It is a multilayer layer in which layer layers are laminated. For example, the transmittance of the silicon layer and the silicon carbide layer is 10 −5 % or less at the excitation light wavelength of 375 nm, whereas the transmittance is 10% or more at the fluorescence wavelength of 460 nm (the transmittance of the excitation light wavelength). (Transmittance of fluorescence wavelength) and the transmittance selectivity of 6 digits or more.
 次に、図6Cに示すように、PD素子12からの検出信号を出力するための検出信号配線51、52及び発光素子15に駆動信号を供給するための駆動信号配線53、54が、スパッタ法又は蒸着法等により配線金属成膜及びフォトリソ・エッチング等のパターニング加工等により配設される。検出信号配線51、52は、それぞれ、PD素子の受光部12T、低抵抗領域12Hと、フィルタ14のコンタクトホール(不図示)を介して接続される。 Next, as shown in FIG. 6C, detection signal wirings 51 and 52 for outputting a detection signal from the PD element 12 and drive signal wirings 53 and 54 for supplying a driving signal to the light emitting element 15 are formed by sputtering. Alternatively, they are disposed by patterning such as wiring metal film formation and photolithography / etching by vapor deposition or the like. The detection signal wirings 51 and 52 are connected to the light receiving unit 12T and the low resistance region 12H of the PD element through contact holes (not shown) of the filter 14, respectively.
 検出信号配線51、52及び駆動信号配線53、54の材料は、金属材料であるAl、Cu、Au、Pt、W、Mo等、又は、不純物を高濃度に含んだ低抵抗ポリシリコン等を用いる。 As the material of the detection signal wirings 51 and 52 and the drive signal wirings 53 and 54, Al, Cu, Au, Pt, W, Mo or the like, which is a metal material, or low resistance polysilicon containing impurities at a high concentration is used. .
 蛍光センサ4では、1層の配線層50に検出信号配線51、52及び駆動信号配線53、54が配設されているが、多層配線にすることも可能である。多層配線の層間絶縁層の材料は、シリコン酸化膜もしくはシリコン窒化膜等の無機絶縁材料、又は、ポリイミド等の有機絶縁材料を用いる。 In the fluorescent sensor 4, the detection signal wirings 51 and 52 and the drive signal wirings 53 and 54 are disposed in one wiring layer 50, but a multilayer wiring may be used. As the material of the interlayer insulating layer of the multilayer wiring, an inorganic insulating material such as a silicon oxide film or a silicon nitride film, or an organic insulating material such as polyimide is used.
 なお、発光素子15が発生する励起光が基板部20に入射しないように、フィルタ14の機能を補完するために、検出信号配線51、52及び駆動信号配線53、54の少なくともいずれかを、幅広に配設してもよい。 In order to supplement the function of the filter 14 so that the excitation light generated by the light emitting element 15 does not enter the substrate portion 20, at least one of the detection signal wirings 51 and 52 and the drive signal wirings 53 and 54 is widened. You may arrange in.
 次に、図6Dに示すように発光素子15が、SOIウエハ20Wの第1の主面20SAに凹部24の開口を覆うように接合層13を介して接合される。なお、励起光のBOX層23の表面での反射を防止するためには、凹部24に充填する接合層13の屈折率を、BOX層23の屈折率と略同等にすることが好ましい。 Next, as shown in FIG. 6D, the light emitting element 15 is bonded to the first main surface 20SA of the SOI wafer 20W via the bonding layer 13 so as to cover the opening of the recess 24. In order to prevent reflection of excitation light on the surface of the BOX layer 23, it is preferable that the refractive index of the bonding layer 13 filling the concave portion 24 is substantially equal to the refractive index of the BOX layer 23.
 発光素子15は、有機EL素子、無機EL素子、又はレーザダイオード素子などの発光素子が形成されたチップの中から選択される。そして、発光素子15は、光発生効率、励起光の波長選択性の広さ、及び励起光以外の波長の光を僅かしか発生しないことなどの観点からは、発光ダイオード(Light Emitting Diode:LED)が好ましい。 The light emitting element 15 is selected from a chip on which a light emitting element such as an organic EL element, an inorganic EL element, or a laser diode element is formed. The light-emitting element 15 is a light-emitting diode (LED) from the viewpoints of light generation efficiency, wide wavelength selectivity of excitation light, and generation of light having a wavelength other than excitation light. Is preferred.
 接合層13は、例えば樹脂を塗布し硬化処理を行うことで作製される。なお樹脂を塗布する表面にCVD法等により、予め透明なSiO層又はシリコン窒化層等を配設しておいてもよい。発光素子15の駆動信号電極15Tと駆動信号配線53、54との電気的接続には導電性接着剤、又は、フリップチップボンディングなどを用いる。 For example, the bonding layer 13 is manufactured by applying a resin and performing a curing process. A transparent SiO 2 layer or silicon nitride layer or the like may be disposed in advance on the surface to which the resin is applied by a CVD method or the like. A conductive adhesive or flip chip bonding is used for electrical connection between the drive signal electrode 15T of the light emitting element 15 and the drive signal wirings 53 and 54.
 発光素子15が第1の主面20SAに接合されるときに、同時に、発光素子15の駆動信号電極15Tは、駆動信号配線53、54と電気的に接続される。発光素子15と基板部とは物理的接合と同時に、電気的接合も行われるため、蛍光センサ4は作製が容易である。そして、接合層13は電気的接続部を封止する封止部材の機能も有している。 When the light emitting element 15 is bonded to the first main surface 20SA, the drive signal electrode 15T of the light emitting element 15 is electrically connected to the drive signal wirings 53 and 54 at the same time. Since the light emitting element 15 and the substrate portion are electrically bonded simultaneously with the physical bonding, the fluorescent sensor 4 can be easily manufactured. The bonding layer 13 also has a function of a sealing member that seals the electrical connection portion.
 次に、発光素子15の下面及び壁面に、漏光防止層19が配設される。漏光防止層19は、遮光層18と同じ材料でもよいし、カーボンブラックを配合した有機樹脂、金属、又は、これらの材料からなる多層膜又は複合膜でもよい。なお、漏光防止層19が予め配設された発光素子15を、基板部20に接合してもよい。 Next, the light leakage prevention layer 19 is disposed on the lower surface and the wall surface of the light emitting element 15. The light leakage prevention layer 19 may be the same material as the light shielding layer 18, or may be an organic resin mixed with carbon black, a metal, or a multilayer film or a composite film made of these materials. Note that the light emitting element 15 in which the light leakage prevention layer 19 is disposed in advance may be bonded to the substrate unit 20.
 なお、漏光防止層19として、アルミニウム又は銀等の反射率の高い金属膜を用いると、発光素子15の底面及び壁面から放射される励起光を、上方すなわちインジケータ17の方向に反射する反射膜としての機能を付与することもできる。 In addition, when a highly reflective metal film such as aluminum or silver is used as the light leakage prevention layer 19, the excitation light emitted from the bottom surface and the wall surface of the light emitting element 15 is reflected upward, that is, as a reflection film that reflects in the direction of the indicator 17. It is also possible to give this function.
 また、漏光防止層19を、基板部20の下面全体、壁面及び遮光層18に覆われていない上面等のセンサ部10の外面にも配設してもよい。 Further, the light leakage prevention layer 19 may be disposed on the outer surface of the sensor unit 10 such as the entire lower surface of the substrate unit 20, the wall surface, and the upper surface not covered with the light shielding layer 18.
 次に、図6Eに示すように、シリコンウエハ20Wは、上下反転され、第2の主面20SBの基板層22に貫通ビアである凹部25が形成される。基板層22のエッチングには公知の方法を用いることができる。凹部25の底面25BにはBOX層23が露出し、凹部25と凹部24とはBOX層23を介して接する。 Next, as shown in FIG. 6E, the silicon wafer 20 </ b> W is turned upside down to form a recess 25 that is a through via in the substrate layer 22 of the second main surface 20 </ b> SB. A known method can be used for etching the substrate layer 22. The BOX layer 23 is exposed on the bottom surface 25 </ b> B of the recess 25, and the recess 25 and the recess 24 are in contact with each other via the BOX layer 23.
 次に、図6Fに示すように、凹部25の内部にインジケータ17が充填される。インジケータ17は蛍光色素を含有したハイドロゲル、又は、蛍光色素が結合されたハイドロゲルからなる。蛍光色素は、アナライト9の種類に応じて選択され、アナライト9の量に応じて発生する蛍光の強度が可逆的に変化する蛍光色素ならば、どのようなものにも使用できる。蛍光センサ4は、グルコースのような糖類を測定するために、蛍光色素には、ルテニウム有機錯体、蛍光フェニルボロン酸誘導体、又は蛋白と結合したフルオレセイン等のグルコースと可逆結合する物質等を用いる。 Next, as shown in FIG. 6F, the indicator 17 is filled in the recess 25. The indicator 17 is made of a hydrogel containing a fluorescent dye or a hydrogel combined with a fluorescent dye. The fluorescent dye is selected according to the type of the analyte 9, and any fluorescent dye whose intensity of fluorescence generated according to the amount of the analyte 9 changes reversibly can be used. In order to measure saccharides such as glucose, the fluorescent sensor 4 uses a ruthenium organic complex, a fluorescent phenylboronic acid derivative, a substance that reversibly binds to glucose, such as fluorescein bound to a protein, or the like.
 含水し易いハイドロゲルの成分としてはメチルセルロースもしくはデキストランなどの多糖類、(メタ)アクリルアミド、メチルアクリルアミド、もしくはヒドルキシエチルアクリレート等のモノマーを重合して作製するアクリレート系ハイドロゲル、又はポリエチレングリコールとジイソシアネートから作製するウレタン系ハイドロゲルなどを用いることができる。 Hydrogel components that easily contain water include acrylate hydrogels prepared by polymerizing polysaccharides such as methylcellulose or dextran, monomers such as (meth) acrylamide, methylacrylamide, or hydroxyethyl acrylate, or polyethylene glycol and diisocyanate. Urethane-based hydrogel prepared from the above can be used.
 インジケータ17は、シランカップリング剤などの接着層を介して、凹部25の壁面、上面の遮光層18又は凹部25の底面25B等と接合されていてもよい。 The indicator 17 may be bonded to the wall surface of the recess 25, the light shielding layer 18 on the upper surface, the bottom surface 25B of the recess 25, or the like via an adhesive layer such as a silane coupling agent.
 なお、凹部25に重合前のゲル骨格形成材を含むインジケータを充填し、遮光層18で開口を覆った後に、重合させてインジケータ17を作製してもよい。例えば、蛍光色素と、ゲル骨格形成材と、重合開始剤と、を含むリン酸緩衝液を、凹部24の内部に入れ、窒素雰囲気下で1時間放置すると、インジケータ17が作製される。蛍光色素としては、9、10-ビス[N-[2-(5,5-ジメチルボリナン-2-イル)ベンジル]-N-[6‘-[(アクリロイルポリエチレングリコール-3400)カルボニルアミノ]-n-ヘキシルアミノ]メチル]-2-アセチルアントラセン(F-PEG-AAm)を、ゲル骨格形成材としては、アクリルアミドを、重合開始剤としては、ペルオキソ二硫酸ナトリウム及びN、N、N’、N‘-テトラメチルエチレンジアミンを用いる。 Note that the indicator 17 may be manufactured by filling the concave portion 25 with an indicator containing a gel skeleton-forming material before polymerization and covering the opening with the light shielding layer 18 and then polymerizing the indicator 17. For example, when a phosphate buffer containing a fluorescent dye, a gel skeleton-forming material, and a polymerization initiator is placed in the recess 24 and left in a nitrogen atmosphere for 1 hour, the indicator 17 is produced. As the fluorescent dye, 9,10-bis [N- [2- (5,5-dimethylborinan-2-yl) benzyl] -N- [6 ′-[(acryloylpolyethyleneglycol-3400) carbonylamino]- n-hexylamino] methyl] -2-acetylanthracene (F-PEG-AAm), acrylamide as the gel skeleton-forming material, sodium peroxodisulfate and N, N, N ′, N as the polymerization initiator '-Tetramethylethylenediamine is used.
 最後に、遮光層18が、第2の主面20SBの凹部25の開口を覆うように配設される。遮光層18には、サブミクロンサイズのポア構造からなる、金属、セラミック等の無機薄膜又は、ポリイミドもしくはポリウレタン等の有機ポリマーの基材にカーボンブラックが混入されたハイドロゲル類とのコンポジット構造、又は、セルロース類もしくはポリアクリルアミド等のアナライト透過性ポリマーにカーボンブラックを混入した樹脂、又は、それらを積層化した樹脂等を用いることができる。 Finally, the light shielding layer 18 is disposed so as to cover the opening of the concave portion 25 of the second main surface 20SB. The light shielding layer 18 has a submicron pore structure, an inorganic thin film such as metal or ceramic, or a composite structure with hydrogels in which carbon black is mixed in a base material of an organic polymer such as polyimide or polyurethane, or Furthermore, a resin in which carbon black is mixed into an analyte-permeable polymer such as celluloses or polyacrylamide, or a resin obtained by laminating them can be used.
 そして、SOIウエハ20Wを母材とするセンサ基板10Wが個片化されることにより、多数のセンサ部10が一括して作製される。そして、センサ部10が、別途作製された、コネクタ部8から延設された針本体部6の先端部と接合されることで、蛍光センサ4が完成する。 Then, the sensor substrate 10W having the SOI wafer 20W as a base material is separated into individual pieces, so that a large number of sensor units 10 are manufactured at once. And the fluorescence sensor 4 is completed by joining the sensor part 10 with the front-end | tip part of the needle | hook main-body part 6 extended from the connector part 8 produced separately.
 蛍光センサの製造方法としては、これに限られるものではなく、例えば、図6Cに示す状態のシリコンウエハ20Wを個片化し、それぞれの基板部20に、発光素子15等を接合してもよい。 The manufacturing method of the fluorescent sensor is not limited to this. For example, the silicon wafer 20W in the state shown in FIG. 6C may be separated into pieces, and the light emitting elements 15 and the like may be bonded to the respective substrate portions 20.
 また、基板部20の延設部が針部7の針本体部6を構成するようにシリコンウエハ20Wを加工し、コネクタ部8と接合してもよい。 Alternatively, the silicon wafer 20 </ b> W may be processed and joined to the connector portion 8 so that the extended portion of the substrate portion 20 constitutes the needle body portion 6 of the needle portion 7.
 以上の説明のように、蛍光センサ4は、製造が容易であり、かつ、ウエハプロセスにより一括大量生産が可能である。このため、蛍光センサ4は、安価に安定した品質を提供できる。 As described above, the fluorescent sensor 4 is easy to manufacture and can be mass-produced by a wafer process. For this reason, the fluorescence sensor 4 can provide stable quality at low cost.
<蛍光センサの動作>
 次に、蛍光センサ4の動作を説明する。
<Operation of fluorescent sensor>
Next, the operation of the fluorescence sensor 4 will be described.
 発光素子15は、例えば30秒に1回の間隔で中心波長が375nm前後の励起光をパルス発光する。例えば、発光素子15へのパルス電流は1mA~100mAであり、発光のパルス幅は1ms~100msである。 The light emitting element 15 emits pulsed excitation light having a center wavelength of around 375 nm at an interval of once every 30 seconds, for example. For example, the pulse current to the light emitting element 15 is 1 mA to 100 mA, and the pulse width of light emission is 1 ms to 100 ms.
 発光素子15が発生した励起光は、凹部24の底面24Bを構成するBOX層23を透過してインジケータ17に入射する。インジケータ17は、アナライト9の濃度に対応した強度の蛍光を発する。なお、アナライト9は遮光層18を通過して、インジケータ17に進入する。インジケータ17の蛍光色素は、例えば、波長375nmの励起光に対して、より長波長の例えば波長460nmの蛍光を発生する。 The excitation light generated by the light emitting element 15 is transmitted through the BOX layer 23 constituting the bottom surface 24 </ b> B of the recess 24 and enters the indicator 17. The indicator 17 emits fluorescence having an intensity corresponding to the concentration of the analyte 9. The analyte 9 passes through the light shielding layer 18 and enters the indicator 17. The fluorescent dye of the indicator 17 generates fluorescence having a longer wavelength, for example, 460 nm, for example, with respect to excitation light having a wavelength of 375 nm.
 インジケータ17が発生した蛍光は、BOX層23と受光部12TのBOX層23側の薄い活性層21とを通過して、PD素子12の受光部12Tに入射する。すなわち、すでに説明したように、受光部12Tは活性層21の表面から不純物が導入された拡散層であり、BOX層23側に薄い活性層21が残っている。活性層21の蛍光透過率は高くはないため、BOX層23側に残った活性層21の厚さは、10μm以下であることが好ましく、特に好ましくは3μm以下である。蛍光は受光部12Tで光電変換され、生じた光発生電荷は検出信号として出力される。 The fluorescence generated by the indicator 17 passes through the BOX layer 23 and the thin active layer 21 on the BOX layer 23 side of the light receiving unit 12T and enters the light receiving unit 12T of the PD element 12. That is, as already described, the light receiving portion 12T is a diffusion layer in which impurities are introduced from the surface of the active layer 21, and the thin active layer 21 remains on the BOX layer 23 side. Since the fluorescence transmittance of the active layer 21 is not high, the thickness of the active layer 21 remaining on the BOX layer 23 side is preferably 10 μm or less, particularly preferably 3 μm or less. The fluorescence is photoelectrically converted by the light receiving unit 12T, and the generated photogenerated charge is output as a detection signal.
 蛍光センサ4では、本体部2の演算部2Cが検出信号、すなわち、PD素子12からの光発生電荷に起因する電流又は蓄積した光発生電荷に起因する電圧をもとに演算処理を行い、アナライト量を算出する。 In the fluorescent sensor 4, the calculation unit 2C of the main body unit 2 performs calculation processing based on the detection signal, that is, the current caused by the photogenerated charge from the PD element 12 or the voltage caused by the accumulated photogenerated charge. Calculate the amount of light.
 蛍光センサ4は、SOI基板を用いて製造されるため、製造が容易であり、さらに、インジケータ17からの蛍光を、透過率の高いBOX層23を介して検出する。このため蛍光センサ4は、小型でありながら検出感度が高い。同様に蛍光センサ4を具備するセンサシステム1は検出感度が高い。さらに、ウエハ状態で加工することにより、一括して多数の蛍光センサが製造できるので、蛍光センサ4は製造工程が容易であり、コストが安い。 Since the fluorescent sensor 4 is manufactured using an SOI substrate, it is easy to manufacture, and further detects the fluorescence from the indicator 17 via the BOX layer 23 having a high transmittance. For this reason, the fluorescence sensor 4 has high detection sensitivity while being small. Similarly, the sensor system 1 including the fluorescent sensor 4 has high detection sensitivity. Furthermore, since a large number of fluorescent sensors can be manufactured at once by processing in a wafer state, the manufacturing process of the fluorescent sensor 4 is easy and the cost is low.
<第1実施形態の変形例1>
 次に、変形例1のセンサシステム1A及び蛍光センサ4Aについて説明する。蛍光センサ4A等は蛍光センサ4等と類似しているので同じ構成要素には同じ符号を付し説明は省略する。
<Variation 1 of the first embodiment>
Next, a sensor system 1A and a fluorescence sensor 4A according to Modification 1 will be described. Since the fluorescence sensor 4A and the like are similar to the fluorescence sensor 4 and the like, the same components are denoted by the same reference numerals and description thereof is omitted.
 図4Bに示したように、蛍光センサ4では、発光素子15からの励起光がインジケータ17に入射する導光路である凹部24は1個である。発光素子15が発生し、インジケータ17に入射する励起光の強度は、面内分布がある。すなわち、凹部24の底面24Bの直上領域のインジケータ17には高強度の励起光が照射されるため、その領域のインジケータ17が発光する蛍光強度は高い。しかし、高強度の励起光が照射されると、インジケータ17の劣化が促進されるおそれがある。これに対して、凹部24の底面24Bの直上領域から離れるに従い、インジケータ17に入射する励起光の強度は低くなり、その領域のインジケータ17が発光する蛍光強度も低くなる。すなわち、インジケータ17に入射する励起光の強度に大きな面内分布があると、蛍光センサの検出感度が低下したり、経時劣化が加速したりするおそれがある。 As shown in FIG. 4B, in the fluorescence sensor 4, there is one concave portion 24 that is a light guide path through which the excitation light from the light emitting element 15 enters the indicator 17. The intensity of the excitation light generated by the light emitting element 15 and incident on the indicator 17 has an in-plane distribution. That is, since the high-intensity excitation light is irradiated to the indicator 17 in the region immediately above the bottom surface 24B of the recess 24, the fluorescence intensity emitted from the indicator 17 in that region is high. However, when high-intensity excitation light is irradiated, deterioration of the indicator 17 may be promoted. In contrast, as the distance from the region immediately above the bottom surface 24B of the recess 24 increases, the intensity of the excitation light incident on the indicator 17 decreases, and the intensity of the fluorescence emitted by the indicator 17 in that region also decreases. That is, if the intensity of the excitation light incident on the indicator 17 has a large in-plane distribution, the detection sensitivity of the fluorescent sensor may be reduced, or deterioration with time may be accelerated.
 これに対して、図7A~図7Cに示すように、変形例1の蛍光センサ4Aでは、活性層21に、複数の凹部24Aが形成されている。活性層21に複数の凹部24Aを形成することは、複数の導光路を形成することである。そして、それぞれの凹部24Aの直上領域の近傍のインジケータ17には比較的強い励起光が照射される。このため、蛍光センサ4Aは、より均一な強度分布の励起光がインジケータ17に入射するため、検出感度が低下したり、経時劣化が加速したりするおそれがない。 On the other hand, as shown in FIGS. 7A to 7C, in the fluorescent sensor 4A of the first modification, the active layer 21 has a plurality of recesses 24A. Forming a plurality of recesses 24A in the active layer 21 means forming a plurality of light guides. The indicator 17 in the vicinity of the region immediately above each recess 24A is irradiated with relatively strong excitation light. For this reason, in the fluorescence sensor 4A, the excitation light having a more uniform intensity distribution is incident on the indicator 17, so that there is no possibility that the detection sensitivity is lowered or the deterioration with time is accelerated.
 蛍光センサ4Aは、蛍光センサ4の効果を有し、さらに、検出感度が高いだけでなく、インジケータ17の劣化が進行しにくい。 The fluorescent sensor 4A has the effect of the fluorescent sensor 4, and further has high detection sensitivity, and the deterioration of the indicator 17 is unlikely to proceed.
 凹部24の平面形状及び配置は、図7A~図7Cに示すように様々な形態が可能である。凹部24Aの平面形状は、図7Aに示す蛍光センサ4Aでは、四角形であるが、図7Bに示す蛍光センサ4A1のように、6角形等の多角形もしくは楕円形でもよいし、又は、それらを組み合わせたような形状等でもよい。また図7Cに示す蛍光センサ4A2のように大きさが異なる凹部24Aを組み合わせてもよい。凹部24の平面寸法の大きさ、例えば、辺の長さは、1μmから数百μmである。 The planar shape and arrangement of the recesses 24 can take various forms as shown in FIGS. 7A to 7C. The planar shape of the recess 24A is a quadrangle in the fluorescent sensor 4A shown in FIG. 7A, but may be a polygon or an ellipse such as a hexagon as in the fluorescent sensor 4A1 shown in FIG. 7B, or a combination thereof. The shape may be different. Moreover, you may combine the recessed part 24A from which magnitude | sizes differ like the fluorescence sensor 4A2 shown to FIG. 7C. The size of the planar dimension of the recess 24, for example, the length of the side is 1 μm to several hundred μm.
 また、発光素子15に発光強度の面内分布がある場合には、複数の凹部24の開口面積、形状及び配置等により分布を補正して、インジケータ17に入射する励起光の強度分布を、さらに平均化できる。また、同様の方法で、インジケータ17の平面視形状すなわち凹部25の底面25Bの形状に適した励起光分布を実現することもできる。 In addition, when the light emitting element 15 has an in-plane distribution of the emission intensity, the distribution is corrected by the opening area, shape, arrangement, and the like of the plurality of recesses 24, and the intensity distribution of the excitation light incident on the indicator 17 is further increased. Can be averaged. Moreover, the excitation light distribution suitable for the planar view shape of the indicator 17, that is, the shape of the bottom surface 25 </ b> B of the recess 25 can be realized by the same method.
 以上の説明のように、変形例1の蛍光センサ4A等は、蛍光センサ4の効果を有し、さらにインジケータ17に入射する励起光の強度分布が平均化されているため、小型でありながら検出感度が高い。同様に蛍光センサ4A等を具備するセンサシステム1Aは検出感度が高い。さらに、インジケータ17を有する蛍光センサ特有の経時劣化による感度低下現象が小さい。 As described above, the fluorescent sensor 4A and the like according to the modified example 1 have the effect of the fluorescent sensor 4, and further, since the intensity distribution of the excitation light incident on the indicator 17 is averaged, the detection is performed while being small. High sensitivity. Similarly, the sensor system 1A including the fluorescent sensor 4A has high detection sensitivity. Furthermore, the sensitivity reduction phenomenon due to the temporal deterioration peculiar to the fluorescent sensor having the indicator 17 is small.
<第1実施形態の変形例2>
 次に、変形例2のセンサシステム1B及び蛍光センサ4Bについて説明する。蛍光センサ4B等は蛍光センサ4等と類似しているので同じ構成要素には同じ符号を付し説明は省略する。
<Modification 2 of the first embodiment>
Next, the sensor system 1B and the fluorescence sensor 4B of Modification 2 will be described. Since the fluorescence sensor 4B and the like are similar to the fluorescence sensor 4 and the like, the same components are denoted by the same reference numerals and description thereof is omitted.
 導光路である凹部24の直上領域には励起光が直接、入射するため励起光の強度が高いが、直上領域から離れるにしたがって励起光の強度は低下する。 The excitation light is directly incident on the region directly above the recess 24, which is the light guide, so that the intensity of the excitation light is high. However, the intensity of the excitation light decreases with increasing distance from the region directly above.
 これに対して、図8に示すように、変形例2の蛍光センサ4Bのセンサ部10Bは、凹部24の底面24Bに光散乱手段である光散乱層26を具備する。光散乱層26は、例えば、金属粒子が分散された透明材料からなる。金属粒子としては、粒径がμmサイズのAl、Ag等の反射率の高い金属が適しており、透明材料としてはシリコーン系樹脂等の樹脂又はSOG(Spin-On-Glass)等の無機ガラスが適している。光散乱層26は、印刷法又はフォトリソ加工法等により、凹部24に配置される。なお、図8に示す蛍光センサ4Bでは、光散乱層26は凹部24の底面24Bに配設されているが、凹部24を充填するように配設してもよい。 On the other hand, as shown in FIG. 8, the sensor unit 10B of the fluorescent sensor 4B according to the modified example 2 includes a light scattering layer 26 serving as a light scattering unit on the bottom surface 24B of the recess 24. The light scattering layer 26 is made of, for example, a transparent material in which metal particles are dispersed. As metal particles, metals with a high particle reflectance such as Al and Ag having a particle size of μm are suitable, and as transparent materials, resins such as silicone resins or inorganic glasses such as SOG (Spin-On-Glass) are suitable. Is suitable. The light scattering layer 26 is disposed in the recess 24 by a printing method, a photolithography process, or the like. In the fluorescent sensor 4B shown in FIG. 8, the light scattering layer 26 is disposed on the bottom surface 24B of the recess 24, but may be disposed so as to fill the recess 24.
 なお、励起光のBOX層23の表面での反射を防止するためには、光散乱層26の屈折率を、BOX層23の屈折率と略同等にすることが好ましい。 In order to prevent reflection of excitation light on the surface of the BOX layer 23, it is preferable that the refractive index of the light scattering layer 26 is substantially equal to the refractive index of the BOX layer 23.
 発光素子15からの励起光は、光散乱層26により散乱され、インジケータ17に入射する励起光は強度分布が平均化する。すなわち、インジケータ17内における励起光の強度は、凹部24の底面24Bから離れた領域も強くなり、その領域のインジケータが発光する蛍光強度も高くなるとともに、凹部24の底面24Bの直下領域の励起光強度は弱くなる。 The excitation light from the light emitting element 15 is scattered by the light scattering layer 26, and the intensity distribution of the excitation light incident on the indicator 17 is averaged. That is, the intensity of the excitation light in the indicator 17 increases in the region away from the bottom surface 24B of the recess 24, the fluorescence intensity emitted from the indicator in that region also increases, and the excitation light in the region immediately below the bottom surface 24B of the recess 24. The strength is weakened.
 次に、図9に示す変形例2の蛍光センサ4B1のセンサ部10B1では、光散乱手段である凹レンズ26Aを有する。凹レンズは、液状のシリコーン等の透明樹脂又はSOG等の無機ガラスを凹部24の内部に配置する際の凹部24の壁面との表面張力によるメニスカス現象を利用して形成できる。又は凹部24を含む活性層21に接合層13を形成した後、RIE等によるエッチバック加工することにより、凹部24の接合層13に凹面を形成することもできる。 Next, the sensor unit 10B1 of the fluorescence sensor 4B1 of Modification 2 shown in FIG. 9 has a concave lens 26A as light scattering means. The concave lens can be formed by utilizing the meniscus phenomenon due to the surface tension with the wall surface of the recess 24 when the transparent resin such as liquid silicone or the inorganic glass such as SOG is disposed inside the recess 24. Alternatively, after forming the bonding layer 13 on the active layer 21 including the recess 24, a concave surface can be formed in the bonding layer 13 of the recess 24 by performing an etch back process by RIE or the like.
 図10に示す変形例2の蛍光センサ4B2のセンサ部10B2では、光散乱手段である光散乱部26BがBOX層23に形成されている。光散乱部26Bは、底面24B又は底面25Bの少なくともいずれかに形成されていればよい。 In the sensor part 10B2 of the fluorescence sensor 4B2 of the modification 2 shown in FIG. 10, a light scattering part 26B, which is a light scattering means, is formed in the BOX layer 23. The light scattering portion 26B only needs to be formed on at least one of the bottom surface 24B and the bottom surface 25B.
 光散乱部26Bは、BOX層23に形成された規則的な凹凸を形成された回折構造又は不規則な凹凸による光散乱構造等である。例えば、SOIウエハ20Wの製造時において、BOX層23が形成されたSiウエハのBOX層23に前記構造を加工した後、BOX層23のうえに活性層21を形成することで、光散乱部26Bが形成される。 The light scattering portion 26B is a diffraction structure formed with regular irregularities formed in the BOX layer 23, or a light scattering structure with irregular irregularities. For example, when the SOI wafer 20W is manufactured, the structure is processed on the BOX layer 23 of the Si wafer on which the BOX layer 23 is formed, and then the active layer 21 is formed on the BOX layer 23, whereby the light scattering portion 26B. Is formed.
 図11に示す変形例2の蛍光センサ4B3のセンサ部10B3では、凹部25の底面のBOX層23に光散乱手段である金属散乱膜26Cが配設されている。金属散乱膜26Cは、微細な金属パターンのリフトオフ又はフォトリソ等により形成される。又は図12に示す変形例2の蛍光センサ4B4では、凹部25の底面25BのBOX層23に光散乱手段である金属粒子を分散させた光散乱層26Dが配設されている。金属散乱膜26C及び光散乱層26Dは、凹部25の底面25B全体に配設されてもよい。 In the sensor unit 10B3 of the fluorescence sensor 4B3 of the modified example 2 shown in FIG. 11, a metal scattering film 26C as a light scattering means is disposed on the BOX layer 23 on the bottom surface of the recess 25. The metal scattering film 26C is formed by lift-off of a fine metal pattern or photolithography. Alternatively, in the fluorescence sensor 4B4 of Modification 2 shown in FIG. 12, a light scattering layer 26D in which metal particles as light scattering means are dispersed is disposed in the BOX layer 23 on the bottom surface 25B of the recess 25. The metal scattering film 26 </ b> C and the light scattering layer 26 </ b> D may be disposed on the entire bottom surface 25 </ b> B of the recess 25.
 励起光強度の面内分布を平均化する光散乱手段を具備する蛍光センサ4B等は、蛍光センサ4等が有する効果に加えて、より検出感度が高く、かつ経時劣化による感度低下現象が小さい。 Fluorescence sensor 4B equipped with a light scattering means that averages the in-plane distribution of the excitation light intensity has higher detection sensitivity and less sensitivity reduction due to deterioration with time, in addition to the effects of fluorescence sensor 4 and the like.
<第2実施形態>
 次に、第2実施形態のセンサシステム1C及び蛍光センサ4Cについて説明する。蛍光センサ4C等は蛍光センサ4等と類似しているので同じ構成要素には同じ符号を付し説明は省略する。
Second Embodiment
Next, the sensor system 1C and the fluorescence sensor 4C of the second embodiment will be described. Since the fluorescent sensor 4C and the like are similar to the fluorescent sensor 4 and the like, the same components are denoted by the same reference numerals and description thereof is omitted.
 図13に示すように、蛍光センサ4Cのセンサ部10Cの活性層21には、インジケータ17が発生する蛍光を検出する第1の光電変換素子であるPD素子12に加えて、発光素子15が発生する励起光を検出する第2の光電変換素子であるPD素子12Bが形成されている。PD素子12とPD素子12Bとは同じ半導体構造のPD素子であり、PD素子12Bは、PD素子12の外側の領域に配置される。 As shown in FIG. 13, in the active layer 21 of the sensor unit 10C of the fluorescence sensor 4C, the light emitting element 15 is generated in addition to the PD element 12 which is the first photoelectric conversion element for detecting the fluorescence generated by the indicator 17. A PD element 12B, which is a second photoelectric conversion element that detects excitation light to be emitted, is formed. The PD element 12 and the PD element 12B are PD elements having the same semiconductor structure, and the PD element 12B is disposed in a region outside the PD element 12.
 発光素子15Lは、凹部24の開口の直下領域だけでなく、第2のPD素子12Bの直下領域も覆っている。すなわち、発光素子15の平面視寸法は、凹部24の開口の直下領域を覆い、かつ、PD素子12Bの直下領域も覆う大きさである。 The light emitting element 15L covers not only the area directly under the opening of the recess 24 but also the area directly under the second PD element 12B. That is, the dimension in plan view of the light emitting element 15 is a size that covers a region immediately below the opening of the recess 24 and also covers a region directly below the PD element 12B.
 なお、PD素子12Bの表面には、フィルタ14は配設されていない。このため、PD素子12Bは、発光素子15Lが発生する励起光の強度に応じた電気信号(検出信号)を出力する。 Note that the filter 14 is not disposed on the surface of the PD element 12B. Therefore, the PD element 12B outputs an electrical signal (detection signal) corresponding to the intensity of the excitation light generated by the light emitting element 15L.
 蛍光センサ4Cの製造方法は、蛍光センサ4の製造方法と類似している。図6Aで示した工程において、不純物注入処理によるPD素子の受光部12T及び低抵抗領域12Hの形成と同時に、PD素子(受光部)12Bが形成される。このとき、LEDの励起光を検出するPD素子12Bの拡散層(受光部)は、PD素子12Tと同じ構造(濃度及び拡散深さ)の拡散層でも良いが、励起光波長と蛍光波長に合わせて、拡散層の構造が異なっても良い。 The manufacturing method of the fluorescent sensor 4C is similar to the manufacturing method of the fluorescent sensor 4. In the process shown in FIG. 6A, the PD element (light receiving part) 12B is formed simultaneously with the formation of the light receiving part 12T and the low resistance region 12H of the PD element by the impurity implantation process. At this time, the diffusion layer (light receiving portion) of the PD element 12B that detects the excitation light of the LED may be a diffusion layer having the same structure (concentration and diffusion depth) as the PD element 12T, but it matches the excitation light wavelength and the fluorescence wavelength. Thus, the structure of the diffusion layer may be different.
 基板部20の第1の主面20SAには、PD素子12Bから出力される検出信号を伝達する検出信号配線(不図示)も配設されている。なお、低抵抗領域12Hと接続された検出信号配線52は、PD素子12とPD素子12Bとの共通配線となる。 The first main surface 20SA of the substrate unit 20 is also provided with a detection signal wiring (not shown) that transmits a detection signal output from the PD element 12B. Note that the detection signal wiring 52 connected to the low resistance region 12H serves as a common wiring for the PD element 12 and the PD element 12B.
 インジケータ17が発生する蛍光の強度は、アナライト量だけでなく励起光強度により増減する。センサシステム1Cでは、蛍光センサ4Cから出力された電気信号(検出信号)を処理する演算部2Cが、第1のPD素子12からの電気信号(検出信号)を、第2のPD素子12Bからの電気信号をもとに補正する。 The intensity of the fluorescence generated by the indicator 17 increases or decreases depending on not only the amount of analyte but also the intensity of excitation light. In the sensor system 1C, the calculation unit 2C that processes the electrical signal (detection signal) output from the fluorescence sensor 4C converts the electrical signal (detection signal) from the first PD element 12 to the second PD element 12B. Correct based on the electrical signal.
 蛍光センサ4C及びセンサシステム1Cは、蛍光センサ4及びセンサシステム1等が有する効果を有し、さらに、励起光の強度が、発光素子15Lの発光効率バラツキ又は動作時の励起光量ドリフト等により変化しても、高精度の測定が可能である。 The fluorescence sensor 4C and the sensor system 1C have the effects of the fluorescence sensor 4 and the sensor system 1 and the like, and the intensity of excitation light changes due to variations in the light emission efficiency of the light emitting element 15L or excitation light amount drift during operation. However, highly accurate measurement is possible.
<第3実施形態>
 次に、第3実施形態のセンサシステム1D及び蛍光センサ4Dについて説明する。蛍光センサ4D等は蛍光センサ4等と類似しているので同じ構成要素には同じ符号を付し説明は省略する。
<Third Embodiment>
Next, the sensor system 1D and the fluorescence sensor 4D of the third embodiment will be described. Since the fluorescence sensor 4D and the like are similar to the fluorescence sensor 4 and the like, the same components are denoted by the same reference numerals and description thereof is omitted.
 図14に示すように、蛍光センサ4Dのセンサ部10Dでは、蛍光センサ4のセンサ部10と同様に活性層21にPD素子12Tが形成されており、さらに基板層22の第2の凹部25の壁面にも、PD素子12Dが形成されている。フィルタ14Dで覆われたPD素子12DはPD素子12Dは、四面ある壁面の少なくとも一の壁面に形成されていてもよい。 As shown in FIG. 14, in the sensor unit 10 </ b> D of the fluorescence sensor 4 </ b> D, the PD element 12 </ b> T is formed in the active layer 21 similarly to the sensor unit 10 of the fluorescence sensor 4, and the second recess 25 of the substrate layer 22 is further formed. A PD element 12D is also formed on the wall surface. The PD element 12D covered with the filter 14D may be formed on at least one of the four wall surfaces.
 PD素子12D、12(12T)は、貫通配線58を介して、低抵抗領域12HD1、12HD2は貫通配線59を介して、それぞれの配線層50と接続されている。 The PD elements 12D and 12 (12T) are connected to the respective wiring layers 50 through the through wiring 58, and the low resistance regions 12HD1 and 12HD2 through the through wiring 59.
 蛍光センサ4Dは、基板部20がSOI基板であるため、凹部24、25の形成が容易である。さらに、PD素子12Dがインジケータ17を取り囲む壁面に形成されているため高感度である。 In the fluorescent sensor 4D, since the substrate portion 20 is an SOI substrate, the recesses 24 and 25 can be easily formed. Furthermore, since the PD element 12D is formed on the wall surface surrounding the indicator 17, the sensitivity is high.
 また、蛍光センサ4Dにおいて、基板層22の第2の凹部25の壁面及び底面に加えて、活性層21にもPD素子を形成してもよい。すなわち、蛍光センサ4と蛍光センサ4Dとを組み合わせた蛍光センサでは、活性層21の第1の凹部24を取り囲む領域、及び基板層22の第2の凹部25の壁面に光電変換素子が形成されている。前記蛍光センサは、受光面積が広いので高感度である。さらに、蛍光センサ4Dにおいても、蛍光センサ4Aのように複数の凹部24を形成してもよいし、蛍光センサ4Bのように光拡散部を具備していてもよい。 In the fluorescent sensor 4D, PD elements may be formed on the active layer 21 in addition to the wall surface and bottom surface of the second recess 25 of the substrate layer 22. That is, in the fluorescence sensor in which the fluorescence sensor 4 and the fluorescence sensor 4D are combined, photoelectric conversion elements are formed on the area surrounding the first recess 24 of the active layer 21 and the wall surface of the second recess 25 of the substrate layer 22. Yes. The fluorescent sensor has high sensitivity because it has a large light receiving area. Further, also in the fluorescence sensor 4D, a plurality of concave portions 24 may be formed as in the fluorescence sensor 4A, or a light diffusion portion may be provided as in the fluorescence sensor 4B.
 また、上記説明では、グルコース等の糖類を検出する蛍光センサ4等を例に説明したが、蛍光色素の選択によって、酵素センサ、pHセンサ、免疫センサ、又は微生物センサ等の多様な用途に対応することができる。例えば、蛍光色素に、生体内の水素イオン濃度又は二酸化炭素を測定する場合には、ヒドロキシピレントリスルホン酸誘導体などを用い、糖類を測定する場合には蛍光残基を有するフェニルボロン酸誘導体などを用い、カリウムイオンを測定する場合には蛍光残基を有するクラウンエーテル誘導体などを用いる。 In the above description, the fluorescent sensor 4 that detects saccharides such as glucose has been described as an example. However, depending on the selection of the fluorescent dye, it corresponds to various uses such as an enzyme sensor, a pH sensor, an immune sensor, or a microorganism sensor. be able to. For example, when measuring the concentration of hydrogen ions or carbon dioxide in a living body, a hydroxypyrenetrisulfonic acid derivative or the like is used as a fluorescent dye, and a phenylboronic acid derivative having a fluorescent residue is used when measuring a saccharide. When a potassium ion is used, a crown ether derivative having a fluorescent residue is used.
 すなわち、本発明は上述した実施形態等に限定されるものではなく、本発明の要旨を変えない範囲において、種々の変更、改変、組み合わせ等ができる。 That is, the present invention is not limited to the above-described embodiment and the like, and various changes, modifications, combinations, and the like can be made without departing from the scope of the present invention.
 本出願は、2012年9月21日に日本国に出願された特願2012-207771号を優先権主張の基礎として出願するものであり、上記の開示内容は、本願明細書、請求の範囲、図面に引用されたものとする。 This application is filed on the basis of a priority claim based on Japanese Patent Application No. 2012-207771 filed in Japan on September 21, 2012, and the above disclosure includes the present specification, claims, It shall be cited in the drawing.

Claims (17)

  1.  活性層が酸化膜を介して基板層上に配設されているSOI基板からなり、第1の主面を構成する前記活性層には貫通ビアである第1の凹部が形成されており、第2の主面を構成する前記基板層には前記第1の凹部と対向する領域を含む大きさの貫通ビアである第2の凹部が形成されており、さらに、蛍光を電気信号に変換する光電変換素子が形成されている基板部と
     前記光電変換素子を覆っている、励起光を遮断するフィルタと、
     前記第2の凹部に配設されている、前記励起光を受光するとアナライトの濃度に応じた強度の前記蛍光を発生するインジケータと、
     前記第2の凹部の開口を覆っている、前記インジケータへの外光進入を遮断するが、アナライトは通過する遮光層と、
     前記第1の凹部の開口の直下領域を覆っている、前記励起光を発生する発光素子と、を具備することを特徴とする蛍光センサ。
    The active layer is formed of an SOI substrate disposed on the substrate layer with an oxide film interposed therebetween, and the active layer constituting the first main surface has a first recess as a through via, and The substrate layer constituting the main surface 2 is formed with a second recess, which is a through via having a size including a region facing the first recess, and further, a photoelectric conversion device that converts fluorescence into an electric signal. A substrate portion on which a conversion element is formed, a filter covering the photoelectric conversion element and blocking excitation light;
    An indicator that is disposed in the second recess and generates the fluorescence having an intensity corresponding to the concentration of the analyte when receiving the excitation light;
    A light-shielding layer covering the opening of the second recess and blocking outside light entering the indicator, but through which the analyte passes;
    A fluorescence sensor comprising: a light emitting element that generates the excitation light and covers a region immediately below the opening of the first recess.
  2.  前記活性層の前記第1の凹部を取り囲む領域、又は、前記基板層の前記第2の凹部の壁面の少なくともいずれかに前記光電変換素子が形成されていることを特徴とする請求項1に記載の蛍光センサ。 The photoelectric conversion element is formed in at least one of a region surrounding the first recess of the active layer and a wall surface of the second recess of the substrate layer. Fluorescent sensor.
  3.  前記基板部、前記フィルタ、前記インジケータ、前記遮光層及び前記発光素子を含むセンサ部を有する針先端部と、体外に配置される本体部の嵌合部と嵌合するコネクタ部と、を具備する、体内のアナライトを計測する針型センサであることを特徴とする請求項2に記載の蛍光センサ。 A needle tip portion having a sensor portion including the substrate portion, the filter, the indicator, the light shielding layer, and the light emitting element; and a connector portion fitted to a fitting portion of a main body portion arranged outside the body. The fluorescent sensor according to claim 2, wherein the fluorescent sensor is a needle-type sensor that measures an analyte in the body.
  4.  前記第1の主面に、前記光電変換素子と接続された検出信号配線と、前記発光素子と接続された駆動信号配線と、が配設されていることを特徴とする請求項3に記載の蛍光センサ。 The detection signal wiring connected to the photoelectric conversion element and the drive signal wiring connected to the light emitting element are disposed on the first main surface. Fluorescent sensor.
  5.  前記活性層に複数の前記第1の凹部が形成されていることを特徴とする請求項4に記載の蛍光センサ。 The fluorescent sensor according to claim 4, wherein a plurality of the first recesses are formed in the active layer.
  6.  前記第1の凹部を導光路として前記インジケータに入射する前記励起光を拡散する光拡散部を具備することを特徴とする請求項4又は請求項5に記載の蛍光センサ。 The fluorescence sensor according to claim 4 or 5, further comprising a light diffusing portion for diffusing the excitation light incident on the indicator with the first concave portion as a light guide path.
  7.  前記活性層の前記第2の凹部と対向しない領域に第2の光電変換素子が形成されており、
     前記発光素子が、前記第1の凹部の開口の直下領域及び前記第2の光電変換素子の直下領域を覆っていることを特徴とする請求項6に記載の蛍光センサ。
    A second photoelectric conversion element is formed in a region of the active layer that does not face the second recess,
    The fluorescence sensor according to claim 6, wherein the light emitting element covers a region immediately below the opening of the first recess and a region directly below the second photoelectric conversion element.
  8.  前記光電変換素子からの電気信号が、前記第2の光電変換素子からの電気信号を用いて、補正されることを特徴とする請求項7に記載の蛍光センサ。 The fluorescence sensor according to claim 7, wherein an electrical signal from the photoelectric conversion element is corrected using an electrical signal from the second photoelectric conversion element.
  9.  活性層が酸化膜を介して基板層上に配設されているSOI基板からなり、第1の主面を構成する前記活性層には貫通ビアである第1の凹部が形成されており、第2の主面を構成する前記基板層には前記第1の凹部と対向する領域を含む大きさの貫通ビアである第2の凹部が形成されており、さらに、蛍光を電気信号に変換する光電変換素子が形成されている基板部と
     前記光電変換素子を覆っている、励起光を遮断するフィルタと、
     前記第2の凹部に配設されている、前記励起光を受光するとアナライトの濃度に応じた強度の前記蛍光を発生するインジケータと、
     前記第2の凹部の開口を覆っている、前記インジケータへの外光進入を遮断するが、アナライトは通過する遮光層と、
     前記第1の凹部の開口の直下領域を覆っている、前記励起光を発生する発光素子と、を具備する蛍光センサと、
     前記光電変換素子からの前記電気信号を補正する演算部を有する本体部と、を具備することを特徴とするセンサシステム。
    The active layer is formed of an SOI substrate disposed on the substrate layer with an oxide film interposed therebetween, and the active layer constituting the first main surface has a first recess as a through via, and The substrate layer constituting the main surface 2 is formed with a second recess, which is a through via having a size including a region facing the first recess, and further, a photoelectric conversion device that converts fluorescence into an electric signal. A substrate portion on which a conversion element is formed, a filter covering the photoelectric conversion element and blocking excitation light;
    An indicator that is disposed in the second recess and generates the fluorescence having an intensity corresponding to the concentration of the analyte when receiving the excitation light;
    A light-shielding layer covering the opening of the second recess and blocking external light entering the indicator, but through which the analyte passes;
    A fluorescence sensor comprising: a light emitting element that generates the excitation light, covering a region immediately below the opening of the first recess;
    And a main body having an arithmetic unit for correcting the electric signal from the photoelectric conversion element.
  10.  前記活性層の前記第1の凹部を取り囲む領域、又は、前記基板層の前記第2の凹部の壁面の少なくともいずれかに前記光電変換素子が形成されていることを特徴とする請求項9に記載のセンサシステム。 The photoelectric conversion element is formed in at least one of a region surrounding the first recess of the active layer or a wall surface of the second recess of the substrate layer. Sensor system.
  11.  前記基板部、前記フィルタ、前記インジケータ、前記遮光層及び前記発光素子を含むセンサ部を有する針先端部と、体外に配置される本体部の嵌合部と嵌合するコネクタ部と、を具備する、体内のアナライトを計測する針型センサであることを特徴とする請求項10に記載のセンサシステム。 A needle tip portion having a sensor portion including the substrate portion, the filter, the indicator, the light shielding layer, and the light emitting element; and a connector portion fitted to a fitting portion of a main body portion arranged outside the body. The sensor system according to claim 10, wherein the sensor system is a needle-type sensor that measures an analyte in the body.
  12.  前記第1の主面に、前記光電変換素子と接続された検出信号配線と、前記発光素子と接続された駆動信号配線と、が配設されていることを特徴とする請求項11に記載のセンサシステム。 The detection signal wiring connected to the photoelectric conversion element and the drive signal wiring connected to the light emitting element are disposed on the first main surface. Sensor system.
  13.  前記活性層に複数の前記第1の凹部が形成されていることを特徴とする請求項12に記載のセンサシステム。 The sensor system according to claim 12, wherein a plurality of the first recesses are formed in the active layer.
  14.  前記第1の凹部を導光路として前記インジケータに入射する前記励起光を拡散する光拡散部を具備することを特徴とする請求項12又は請求項13に記載のセンサシステム。 14. The sensor system according to claim 12, further comprising: a light diffusing unit that diffuses the excitation light incident on the indicator using the first concave portion as a light guide path.
  15.  前記活性層の前記第2の凹部と対向しない領域に第2の光電変換素子が形成されており、
     前記発光素子が、前記第1の凹部の開口の直下領域及び前記第2の光電変換素子の直下領域を覆っていることを特徴とする請求項14に記載のセンサシステム。
    A second photoelectric conversion element is formed in a region of the active layer that does not face the second recess,
    The sensor system according to claim 14, wherein the light emitting element covers a region immediately below the opening of the first recess and a region directly below the second photoelectric conversion element.
  16.  前記光電変換素子からの電気信号が、前記第2の光電変換素子からの電気信号を用いて、補正されることを特徴とする請求項15に記載のセンサシステム。 The sensor system according to claim 15, wherein an electric signal from the photoelectric conversion element is corrected by using an electric signal from the second photoelectric conversion element.
  17.  前記活性層の前記第2の凹部と対向しない領域に第2の光電変換素子が形成されており、
     前記発光素子が、前記第1の凹部の開口の直下領域及び前記第2の光電変換素子の直下領域を覆っており、
     前記光電変換素子からの電気信号が、前記第2の光電変換素子からの電気信号を用いて、補正されることを特徴とする請求項9に記載のセンサシステム。
    A second photoelectric conversion element is formed in a region of the active layer that does not face the second recess,
    The light emitting element covers a region immediately below the opening of the first recess and a region directly below the second photoelectric conversion element;
    The sensor system according to claim 9, wherein an electrical signal from the photoelectric conversion element is corrected using an electrical signal from the second photoelectric conversion element.
PCT/JP2013/071793 2012-09-21 2013-08-12 Fluorescent light sensor and sensor system WO2014045762A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2012207771 2012-09-21
JP2012-207771 2012-09-21

Publications (1)

Publication Number Publication Date
WO2014045762A1 true WO2014045762A1 (en) 2014-03-27

Family

ID=50341086

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2013/071793 WO2014045762A1 (en) 2012-09-21 2013-08-12 Fluorescent light sensor and sensor system

Country Status (1)

Country Link
WO (1) WO2014045762A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62261036A (en) * 1986-04-23 1987-11-13 ア−・フアウ・エル ア−・ゲ− Sensor element for measuring concentration of substance
JP2003525432A (en) * 2000-03-02 2003-08-26 マイクロチップス・インコーポレーテッド Microfabricated devices for storing and selectively exposing chemicals and devices
JP2012093128A (en) * 2010-10-25 2012-05-17 Olympus Corp Fluorescence sensor
JP2012520087A (en) * 2009-04-13 2012-09-06 オリンパス株式会社 Fluorescence sensor, needle-type fluorescence sensor, and analyte measurement method

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62261036A (en) * 1986-04-23 1987-11-13 ア−・フアウ・エル ア−・ゲ− Sensor element for measuring concentration of substance
JP2003525432A (en) * 2000-03-02 2003-08-26 マイクロチップス・インコーポレーテッド Microfabricated devices for storing and selectively exposing chemicals and devices
JP2012520087A (en) * 2009-04-13 2012-09-06 オリンパス株式会社 Fluorescence sensor, needle-type fluorescence sensor, and analyte measurement method
JP2012093128A (en) * 2010-10-25 2012-05-17 Olympus Corp Fluorescence sensor

Similar Documents

Publication Publication Date Title
JP5638343B2 (en) Fluorescent sensor
JP5307901B2 (en) Fluorescence sensor, needle-type fluorescence sensor, and analyte measurement method
JP6087337B2 (en) Fluorescence sensor and sensor system
US8976357B2 (en) Optical sensor and electronic apparatus utilizing an angle limiting filter
US5894351A (en) Fluorescence sensing device
US20040161853A1 (en) Implantable chemical sensor with rugged optical coupler
JPS6398548A (en) Sensor element for measuring substance concentration
JPS62261036A (en) Sensor element for measuring concentration of substance
JP2013040797A (en) Fluorescence sensor
CA2680194A1 (en) Light emitting diode for harsh environments
JP2002502495A (en) Improved fluorescence detection device
US8710606B2 (en) Optical sensor and electronic apparatus
WO2014045762A1 (en) Fluorescent light sensor and sensor system
JP2015059869A (en) Fluorescence sensor
KR20230004694A (en) Integrated Particulate Matter Sensor with Cavity
WO2013161989A1 (en) Fluorescence sensor
WO2014045387A1 (en) Fluorescent sensor
WO2014045386A1 (en) Fluorescent sensor
WO2013161990A1 (en) Fluorescent light sensor
KR101240294B1 (en) Biosensor module using silicon nano-wire
WO2013161991A1 (en) Fluorescence sensor
WO2014045761A1 (en) Fluorescent light sensor
JP2012247260A (en) Fluorescence sensor
WO2014045388A1 (en) Fluorescent sensor
WO2013094562A1 (en) Fluorescence sensor, sensor system, and fluorescence sensor correction method

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13838606

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13838606

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP