WO2014045388A1 - Capteur de lumière fluorescente - Google Patents

Capteur de lumière fluorescente Download PDF

Info

Publication number
WO2014045388A1
WO2014045388A1 PCT/JP2012/074179 JP2012074179W WO2014045388A1 WO 2014045388 A1 WO2014045388 A1 WO 2014045388A1 JP 2012074179 W JP2012074179 W JP 2012074179W WO 2014045388 A1 WO2014045388 A1 WO 2014045388A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluorescence
light
emitting element
sensor
substrate
Prior art date
Application number
PCT/JP2012/074179
Other languages
English (en)
Japanese (ja)
Inventor
亮 太田
悦朗 清水
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
Priority to PCT/JP2012/074179 priority Critical patent/WO2014045388A1/fr
Publication of WO2014045388A1 publication Critical patent/WO2014045388A1/fr

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters

Definitions

  • the present invention relates to a fluorescence sensor for measuring the concentration of an analyte in a solution, and more particularly to a fluorescence sensor having an indicator made of an analyte and a hydrogel that generates fluorescence by excitation light.
  • a fluorometer that measures analyte concentration by injecting a solution to be measured containing a fluorescent dye and an analyte into a transparent container, irradiating excitation light, and measuring the fluorescence intensity from the fluorescent dye is known.
  • Fluorescent dyes change in properties due to the presence of an analyte, and generate fluorescence having an intensity corresponding to the analyte concentration when receiving excitation light.
  • a small fluorometer has a light source, a photodetector, and an indicator containing a fluorescent dye. And the excitation light from a light source is irradiated to the indicator which the analyte in a to-be-measured solution can enter / exit, and the photodetector receives the fluorescence which an indicator generate
  • 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 the excitation light E and transmits the fluorescence F. Further, the light emitting element 115 transmits the fluorescence F.
  • the indicator 117 In the fluorescence sensor 104, when the excitation light E generated by the light emitting element 115 enters the indicator 117, the indicator 117 generates fluorescence F corresponding to the analyte concentration.
  • the fluorescent sensor 104 has a simple configuration and can be easily downsized.
  • the present invention has been made in view of the above circumstances, and its object is to provide a fluorescent sensor with high detection sensitivity.
  • the fluorescence sensor of one embodiment of the present invention is disposed in each of two substrate portions and a hollow portion formed in the two substrate portions, receives excitation light, and emits fluorescence having an intensity corresponding to the concentration of the analyte.
  • the two substrate parts comprising two indicators that generate, a light emitting element substrate part provided with a light emitting element that generates the excitation light, and one or more photoelectric conversion elements that convert the fluorescence into an electrical signal. Is formed so that the light emitting element substrate portion is sandwiched between the two indicators, and the light emitting element is disposed between the two indicators.
  • FIG. 5 is an exploded cross-sectional view taken along line VV in FIG. 4 at the distal end portion of the fluorescent sensor.
  • FIG. 5 is a cross-sectional view taken along line VV in FIG. 4 at the distal end portion of the fluorescent sensor.
  • FIG. 11 is a cross-sectional view taken along the line XI-XI in FIG. 10 at the tip of the fluorescent sensor. It is a cross-sectional schematic diagram for demonstrating operation
  • 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. .
  • Fluorescent sensor 4 is a needle-type sensor that can continuously measure the analyte concentration of a solution (body fluid) in a living body after inserting sensor unit 10 into the body for a predetermined period, for example, one week. 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 in the connector unit 8 of the fluorescent sensor 4 or may be disposed in 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 structure of the sensor unit 10 which is a main functional unit of the fluorescence sensor 4 will be described with reference to FIGS.
  • 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.
  • the Z-axis direction shown in the figure is referred to as an upward direction in the fluorescence sensor 4.
  • the X-axis direction indicates the rear in the front-rear direction of the fluorescent sensor 4
  • the Y-axis direction indicates the left direction in the left-right direction.
  • the fluorescence sensor 4 of the first embodiment detects glucose in the body fluid of the subject.
  • the sensor unit 10 includes two frame-shaped substrate portions 40A and 40B having a through-hole 40X and a transparent resin interposed between the two frame-shaped substrate portions 40A and 40B.
  • Two indicators 17A and 17B disposed in a bonding substrate portion 30 to which a wiring substrate portion 20 as a light emitting element substrate portion formed of glass or the like is bonded, and through holes 40X of the frame-like substrate portions 40A and 40B.
  • a light emitting element 15 that is disposed on the wiring board portion 20 and emits light in the vertical and horizontal directions, two cover portions 18A and 18B that cover the opening of the upper surface or the lower surface of the through hole 40X, and the cover portions 18A and 18B Two light shielding layers 19A and 19B covering each of them are provided.
  • the first frame substrate portion 40A, the first indicator 17A, 17B, the two cover portions 18A, 18B, and the two light shielding layers 19A, 19B the first frame substrate portion 40A, the first indicator. 17A, the first cover portion 18A and the first light shielding layer 19A are on the upper side, and the second frame-shaped substrate portion 40B, the second indicator 17B, the second cover portion 18B and the second light shielding layer 19B are on the lower side. Are arranged so as to be laminated.
  • the first light shielding layer 19A, the first cover portion 18A, the first frame-like substrate portion 40A provided with the first indicator 17A, and the light emitting element 15 are provided on the upper surface.
  • the wiring board part 20, the second frame-like board part 40B provided with the second indicator 17B, the second cover part 18B, and the second light shielding layer 19B are laminated. That is, the two frame-like substrate portions 40A and 40B are disposed so as to sandwich the wiring substrate portion 20, and the first indicator 17A and the second indicator 17B are stacked so as to sandwich the light emitting element 15.
  • the cover portions 18A and 18B are formed by photodiode elements (hereinafter referred to as “PD elements”) 12A and 12B, which are photoelectric conversion elements that convert the fluorescence F from the light emitting element 15 into an electrical signal.
  • PD elements photodiode elements
  • the upper first cover portion 18A is provided with a first PD element 12A which is a photoelectric conversion element
  • the lower second cover portion 18B is provided with a second PD element 12B. ing.
  • the cover portions 18A and 18B are made of, for example, a silicon substrate having a minute through hole 18X (see FIG. 8), and the light receiving portions 12T of the PD elements 12A and 12B are formed on one side, respectively.
  • the PD elements 12A and 12B have a high conductivity and a low conductivity in which impurities are partially introduced in order to establish electrical connection between the base side of the one-conductivity type light receiving portion and the opposite conductivity type cover portions 18A and 18B.
  • the light receiving portion and the low resistance region may be collectively referred to as PD elements 12A and 12B. That is, the sensor unit 10 of the fluorescent sensor 4 of the present embodiment has a configuration in which two indicators 17A and 17B and PD elements 12A and 12B are provided above and below the light emitting element 15 as a boundary.
  • the minute through holes 18X of the cover portions 18A and 18B are entry paths through which the body fluid including the analyte 9 enters the indicators 17A and 17B. That is, body fluid can pass through the cover portions 18A and 18B.
  • the size, shape, position, and formation density of the minute through holes 18X of the cover portions 18A and 18B are appropriately selected according to the specifications.
  • the minute through holes 18X do not need to be arranged in an orderly manner.
  • the shape of the opening when the minute through hole 18X is observed from the upper surface may be any of a circle, a rectangle, a polygon, and the like.
  • the two cover portions 18A and 18B in which the minute through holes 18X are formed have the same structure as the membrane filter, but are produced by patterning the minute through holes 18X on a silicon plate or a silicon film, for example. .
  • the minute through hole 18X can be formed by dry etching such as ICP-RIE after an etching mask is formed on the surface of a silicon plate or the like by photolithography or a self-assembled film.
  • a machining method using a micro drill or the like may be used to form the minute through hole 18X.
  • a porous semiconductor that can pass a solution containing an analyte may be used for the cover portions 18A and 18B.
  • the porous means a material having voids and pores connected to the outside in the structure. The size, distribution, and shape of the voids / pores need not be regular as long as the solution can pass through.
  • the open porosity of the cover portions 18A and 18B is preferably 5 to 75% by volume, particularly preferably 20 to 50% by volume. If it is more than the said range, a bodily fluid will pass easily, and if it is below the said range, desired mechanical strength will be obtained.
  • the open porosity is a value measured by Archimedes method.
  • the two light shielding layers 19A and 19B provided on the upper and lower sides prevent the excitation light E and the fluorescence F from leaking to the outside, and at the same time, prevent the external light G from entering the indicator 17.
  • the two light shielding layers 19A and 19B have, for example, a submicron pore structure that does not prevent the analyte 9 from passing through the inside and reaching the adjacent indicators 17A and 17B.
  • a resin in which carbon black is mixed into an analyte-permeable polymer such as, or a resin obtained by laminating them is used.
  • a resin material such as silicon, glass or metal having a Young's modulus of several tens to several hundreds of GPa, or polypropylene or polystyrene having a Young's modulus of about 1 GPa to 5 GPa is used. .
  • the same silicon as the material of the cover portion 18A is particularly preferable.
  • the wiring board portion 20 is formed of a transparent resin, glass, or the like so that the excitation light E emitted downward from the light emitting element 15 can be transmitted to the lower indicator 17B side, but the through hole 40X is formed. Only a part may be formed from a transparent member, glass, etc., and may have a light transmittance.
  • the through-hole 40X in which the indicators 17A and 17B and / or the light emitting element 15 are housed is covered with the wiring board portion 20 at the lower surface or the upper surface, and the upper surface or the lower surface is covered with the cover portions 18A and 18B.
  • the side surface constitutes a hollow portion formed by the inner walls of the frame-like substrate portions 40A and 40B.
  • the hollow shape of the through hole 40X here is a rectangular parallelepiped (quadrangular columnar shape), but is not limited to this, and may be a columnar shape, a polygonal columnar shape, or the like. Note that the side surface of the through hole 40X may be inclined with respect to the main surface. Further, a reflective film that reflects the fluorescence F may be disposed on the side surface.
  • the wiring board portion 20 is provided with a wiring 51 that is connected to the external electrode 15T of the light emitting element 15 and supplies a driving signal.
  • wiring 61 for operating the PD elements 12A and 12B of the wiring 60 and transmitting signals is formed in the cover portions 18A and 18B.
  • the wirings 51 and 61 are a part of the plurality of wirings 60.
  • the light emitting element 15 is connected via the through holes 40a and 40b in which the wiring 61 for transmitting the signals of the PD elements 12A and 12B is formed in the frame-like substrate portions 40A and 40B.
  • the detection signal wiring 61 is disposed along with the driving wiring 51 on one main surface (upper surface side) of the wiring substrate section 20 by being guided to the upper surface side of the disposed wiring board section 20.
  • a filter that transmits the fluorescence F and blocks the excitation light E is used as a light receiving surface of the PD elements 12A and 12B, that is, the cover portions 18A and 18B. It is preferable to arrange on the surface facing the indicators 17A and 17B.
  • a filter for example, a light absorption filter that blocks the excitation light E having a wavelength of 375 nm but transmits the fluorescence F having a wavelength of 460 nm is used.
  • a minute through hole through which the analyte can pass is also formed in the filter.
  • the external electrode 15T on the lower surface of the light emitting element 15 is preferably sealed with an insulating resin. Furthermore, the light emitting element 15 may be sealed to the upper surface with a transparent resin or the like. The resin-sealed light emitting element 15 is not easily affected by moisture contained in the indicators 17A and 17B.
  • Indicator 17A, 17B consists of hydrogel which has the fluorescent pigment
  • the indicators 17A and 17B may be the analyte 9 itself in which the fluorescent dye that does not contain the fluorescent dye and the fluorescent dye that generates the fluorescence F exists in the solution.
  • Hydrogel is water such as acrylic hydrogel produced by polymerizing monomers such as polysaccharides such as methylcellulose or dextran, acrylamide, methylolacrylamide, hydroxyethyl acrylate, or urethane hydrogel produced from polyethylene glycol and diisocyanate. It is formed by encapsulating a fluorescent dye in a material that is easy to contain.
  • the hydrogel has a size that does not separate from the sensor through the cover portions 18A and 18B and the light shielding layers 19A and 19B.
  • the hydrogel may have a molecular weight of 1 million or more, or a particle having a diameter larger than the pore diameter of the cover portions 18A and 18B, for example, a particle having a diameter of 50 nm or more, or a form that is crosslinked and does not flow. preferable.
  • phenylboronic acid derivatives having a fluorescent residue are suitable as fluorescent dyes.
  • the fluorescent dye is prevented from detaching from the sensor by using a high molecular weight material or chemically fixing to a hydrogel.
  • the indicator is produced by polymerizing a phosphoric acid buffer containing a fluorescent dye, a gel skeleton-forming material, and a polymerization initiator in a nitrogen atmosphere for 1 hour.
  • a fluorescent dye 9,10-bis [N- [2- (5,5-dimethylborinan-2-yl) benzyl] -N- [6 ′-[(acryloyl polyethylene glycol-3400) carbonylamino ] -N-hexylamino] methyl] -2-acetylanthracene (F-PEG-AAm), acrylamide as the gel skeleton-forming material, sodium peroxodisulfate and N, N, N ′ as the polymerization initiator N'-tetramethylethylenediamine is used.
  • an element that emits light on both the upper and lower sides is selected from light emitting elements that emit desired excitation light E such as an LED element, an organic EL element, an inorganic EL element, or a laser diode element. Further, it is preferable to transmit the fluorescence F.
  • an LED element is used as the light emitting element 15, from the viewpoints of fluorescence transmittance, light generation efficiency, wide wavelength selectivity of the excitation light E, and generation of a light other than a wavelength having an excitation action. preferable.
  • an ultraviolet LED element made of a gallium nitride compound semiconductor formed on a sapphire substrate is particularly preferable.
  • 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 current of the drive signal to the light emitting element 15 is 1 mA to 100 mA
  • the light emission pulse width is 1 ms to 100 ms.
  • the fluorescence F generated from the two indicators 17A and 17B is incident on the PD elements 12A and 12B on the upper surface or the lower surface of the indicators 17A and 17B.
  • the fluorescence F emitted according to the concentration of the analyte 9 is mostly the fluorescence F from the first indicator 17A by the first PD element 12A, and partly by the second PD element 12B.
  • the fluorescence F from the second indicator 17B is mostly detected by the first PD element 12B and partly by the first PD element 12A.
  • the fluorescent sensor 4 can efficiently use the excitation light E from the light emitting element 15 by arranging the indicators 17A and 17B and the PD elements 12A and 12B in the vertical direction with the light emitting element 15 interposed therebetween, so that the conventional fluorescent sensor Higher sensitivity than 104.
  • the fluorescence sensor 4A of the second embodiment will be described. Since the fluorescence sensor 4A is similar to the fluorescence sensor 4, the same components are denoted by the same reference numerals and description thereof is omitted.
  • the fluorescent sensor 4A of the present embodiment is the same in that PD elements 12A and 12B, which are photoelectric conversion elements, are formed in the cover portions 18A and 18B.
  • PD elements 12A and 12B which are photoelectric conversion elements
  • cover portions 18A and 18B are formed in the cover portions 18A and 18B.
  • side opening portions 40S are formed on the side surfaces of the frame-shaped substrate portions 40A and 40B so as to communicate with the through holes 40X of the frame-shaped substrate portions 40A and 40B stacked with the wiring substrate portion 20 interposed therebetween.
  • the cover portions 18A and 18B disposed on the frame-like substrate portions 40A and 40B so as to cover the upper and lower sides of the through holes 40X are the functions of the light shielding layers 19A and 19B, that is, the external light G Has a function of preventing the excitation light E and the fluorescence F from leaking.
  • the two indicators 17A and 17B arranged in the through holes 40X in the frame-shaped substrate portions 40A and 40B are connected to the analytes from the total of the four side surface openings 40S via the light shielding layers 19A and 19B provided on the side surfaces. 9 can enter.
  • the analyte 9 is transmitted from the light shielding layers 19A, 19B provided on the side surfaces to the frame-shaped substrate portions 40A, 40B from the side surface openings 40S of the through holes 40X to the indicators 17A, Enter 17B.
  • the excitation light E emitted from the light emitting element 15 generates the fluorescence F corresponding to the concentration of the analyte 9 from the indicators 17A and 17B, and the fluorescence F1 emitted upward from the first indicator 17A located above is the first.
  • Fluorescence F2 detected by the first PD element 12A of the first cover portion 18A and emitted downward from the second indicator 17B located below is detected by the second PD element 12B of the second cover portion 18B.
  • the fluorescent sensor 4A of the present embodiment has minute through holes in the cover portions 18A and 18B that cover the upper and lower openings of the through holes 40X on the frame-like substrate portions 40A and 40B.
  • 18X does not need to be provided, and as a result, the minute through holes 18X are not formed in the PD elements 12A and 12B.
  • the area of entry of the analyte 9 is increased by the four side surface openings 40S, so that the analyte 9 can easily enter the indicators 17A and 17B, and the response to the concentration change of the analyte 9 is remarkably improved.
  • the side opening 40S communicating with the through-holes 40X of the frame-like substrate portions 40A and 40B is preferably formed on both side surfaces, but is not limited to this, and at least one side surface of the frame-like substrate portions 40A and 40B. It is good also as a structure formed in.
  • the fluorescence sensor 4B of the third embodiment will be described. Since the fluorescence sensor 4B is similar to the fluorescence sensor 4 of the first embodiment, the same components are denoted by the same reference numerals and description thereof is omitted.
  • the fluorescence sensor 4B shown in FIG. 13 has photoelectric conversion elements on the inner side surfaces of the frame-like substrate portions 40A and 40B that form the through holes 40X in which the indicators 17A and 17B are disposed. Are different in that PD elements 12C and 12D are formed.
  • PD elements 12C and 12D as light receiving portions are provided on the side surfaces of the through holes 40X of the frame-like substrate portions 40A and 40B (only the side surfaces in the front-rear direction are shown in FIG. 13).
  • the light shielding layers 19A and 19B are arranged so as to cover the openings on the upper surface or the lower surface of the through holes 40X of the frame-shaped substrate portions 40A and 40B.
  • Cover portions 18A and 18B including PD elements 12A and 12B may be provided between the light shielding layers 19A and 19B and the indicators 17A and 17B as in the first embodiment.
  • the analyte 9 enters the indicators 17A and 17B from the upper and lower light shielding layers 19A and 19B.
  • the fluorescent light F corresponding to the concentration of the analyte 9 is generated from the indicators 17A and 17B by the excitation light E from the light emitting element 15, and the fluorescent light F1 emitted laterally from the first indicator 17A located above is first.
  • Fluorescence F2 detected by one PD element 12C and emitted laterally from the second indicator 17B located below is detected by the second PD element 12D.
  • the fluorescence sensor 4B of the present embodiment does not have the PD elements 12B and 12C on the approach path of the analyte 9, so that the PD elements 12B and 12C are slightly penetrated. It is not necessary to provide the hole 18X, and the PD elements 12C and 12D are formed on the front, back, left and right side surfaces of the indicators 17A and 17B.
  • a PD element 12 ⁇ / b> E that is a photoelectric conversion element is provided between the first indicator 17 ⁇ / b> A and the light emitting element 15. That is, in the fluorescent sensor 4C, the light emitting element 15 is disposed between the PD element 12E and the second indicator 17B.
  • a through hole 12X is formed in the approximate center of the PD element 12E. Then, the excitation light E from the light emitting element 15 enters the second indicator 17B on the lower side and enters the first indicator 17A on the upper side through the through hole 12X. A plurality of through holes 12X may be formed in the PD element 12E.
  • the fluorescence F1 emitted downward from the first indicator 17A and the fluorescence F2 emitted upward from the second indicator 17B are both detected by the PD element 12E.
  • the fluorescence sensor 4D is provided with two PD elements 12EA and 12EB each having a through hole 12X, and these PD elements 12EA and 12EB are arranged vertically so as to sandwich the light emitting element 15. May be.
  • the fluorescence F1 emitted downward from the first indicator 17A is emitted from the first PD element 12EA, and the fluorescence F2 emitted upward from the second indicator 17B is emitted from the second PD element 12EB. Detected.
  • the fluorescence sensors 4C and 4D of the present embodiment have high sensitivity because there is no PD element 12 on the entry path of the analyte 9, and therefore it is not necessary to provide the minute through hole 18X in the PD element 12.
  • the fluorescent sensor 4E here has a structure in which the fluorescent sensor 4B shown in FIG. 13 and the fluorescent sensor 4C shown in FIG. 14 are combined.
  • the fluorescence F1 emitted downward from the first indicator 17A on the upper side is detected by the PD element 12E, and the fluorescence F2 emitted in the lateral direction is detected by the PD element 12C. Further, the fluorescence F3 emitted upward from the second indicator 17B on the lower side is detected by the PD element 12E, and the fluorescence F4 emitted in the lateral direction is detected by the PD element 12D.
  • the fluorescence sensor 4F here may have a structure in which the fluorescence sensor 4B shown in FIG. 13 and the fluorescence sensor 4D shown in FIG. 15 are combined.
  • the fluorescence F1 emitted downward from the first indicator 17A on the upper side is detected by the PD element 12EA, and the fluorescence F2 emitted horizontally is detected by the PD element 12C. Further, the fluorescence F3 emitted upward from the second indicator 17B on the lower side is detected by the PD element 12EB, and the fluorescence F4 emitted in the lateral direction is detected by the PD element 12D.
  • the fluorescence sensors 4E and 4F of the present embodiment have high sensitivity because there is no PD element 12 on the approach path of the analyte 9, and therefore it is not necessary to provide the minute through hole 18X in the PD element 12.
  • the shape of the sensor part of the fluorescence sensor demonstrated in the said several embodiment was a right-angled column shape, trapezoid shape, the shape where the side was curved, or a column shape etc. may be sufficient.
  • the wiring board 20 does not have optical transparency, for example, as shown in FIG. 18, two wiring boards 20A and 20B provided with light emitting elements 15A and 15B are bonded in the vertical direction. It is good.
  • FIG. 19 even if a hole 20a is provided in a part of the wiring substrate 20 facing the light emitting element 15 so that the excitation light E from the light emitting element 15 enters the second indicator 17B side. Good. That is, in the configuration of FIG. 19, the excitation light E that has passed through the hole 20 formed in the wiring board 20 is incident on the second indicator 17B.
  • the fluorescence sensor is compatible with various uses such as an enzyme sensor, a pH sensor, an immunosensor, or a microorganism sensor by selecting a fluorescent dye.

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Optics & Photonics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

Cette invention concerne un capteur de lumière fluorescente (4) comprenant : deux parties substrats (40A, 40B) ; deux indicateurs (17A, 17B) placés, respectivement, dans des parties creuses formées dans les deux parties substrats (40A, 40B), lesdits indicateurs recevant la lumière d'excitation (E) et générant une lumière fluorescente (F) d'une intensité correspondant à la concentration d'un analyte (9) ; une partie substrat (20) pour élément électroluminescent comportant un élément électroluminescent (15) qui génère la lumière d'excitation (E) ; et au moins un élément de conversion photoélectrique (12) qui convertit la lumière fluorescente (F) en signal électrique. Le capteur de lumière fluorescente (4) est agencé comme suit : une partie substrats joints (30) est formée par les deux parties substrats (40A, 40B) jointes de façon à prendre en sandwich la partie substrat (20) pour élément électroluminescent ; et l'élément électroluminescent (15) est pris en sandwich entre les deux indicateurs (17A, 17B).
PCT/JP2012/074179 2012-09-21 2012-09-21 Capteur de lumière fluorescente WO2014045388A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/JP2012/074179 WO2014045388A1 (fr) 2012-09-21 2012-09-21 Capteur de lumière fluorescente

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP2012/074179 WO2014045388A1 (fr) 2012-09-21 2012-09-21 Capteur de lumière fluorescente

Publications (1)

Publication Number Publication Date
WO2014045388A1 true WO2014045388A1 (fr) 2014-03-27

Family

ID=50340742

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2012/074179 WO2014045388A1 (fr) 2012-09-21 2012-09-21 Capteur de lumière fluorescente

Country Status (1)

Country Link
WO (1) WO2014045388A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5910661A (en) * 1997-05-13 1999-06-08 Colvin, Jr.; Arthur E. Flourescence sensing device
JP2001525930A (ja) * 1997-05-13 2001-12-11 コルビン，アーサー・イー・ジュニア 改良された蛍光検出デバイス
JP2002523774A (ja) * 1998-08-26 2002-07-30 センサーズ・フォー・メデセン・アンド・サイエンス・インコーポレーテッド 光学式検知装置
JP2003515163A (ja) * 1999-11-24 2003-04-22 アイオワ ステイト ユニヴァーシティ リサーチ ファウンデーション インコーポレイテッド 光センサ及びアレイ含有薄膜電界発光素子
WO2004071291A2 (fr) * 2003-02-13 2004-08-26 Medtronic, Inc. Detecteur chimique implantable
JP2012093128A (ja) * 2010-10-25 2012-05-17 Olympus Corp 蛍光センサ

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5910661A (en) * 1997-05-13 1999-06-08 Colvin, Jr.; Arthur E. Flourescence sensing device
JP2001525930A (ja) * 1997-05-13 2001-12-11 コルビン，アーサー・イー・ジュニア 改良された蛍光検出デバイス
JP2002523774A (ja) * 1998-08-26 2002-07-30 センサーズ・フォー・メデセン・アンド・サイエンス・インコーポレーテッド 光学式検知装置
JP2003515163A (ja) * 1999-11-24 2003-04-22 アイオワ ステイト ユニヴァーシティ リサーチ ファウンデーション インコーポレイテッド 光センサ及びアレイ含有薄膜電界発光素子
WO2004071291A2 (fr) * 2003-02-13 2004-08-26 Medtronic, Inc. Detecteur chimique implantable
JP2012093128A (ja) * 2010-10-25 2012-05-17 Olympus Corp 蛍光センサ

Similar Documents

Publication Publication Date Title
JP5638343B2 (ja) 蛍光センサ
JP5307901B2 (ja) 蛍光センサ、針型蛍光センサ、およびアナライトの計測方法
EP1596712B1 (fr) Detecteur chimique
US5517313A (en) Fluorescent optical sensor
EP2557415A1 (fr) Capteur de fluorescence
KR102491854B1 (ko) 분광기
JPS62261036A (ja) 物質濃度を測定するためのセンサ素子
US9541503B2 (en) Compact systems, compact devices, and methods for sensing luminescent activity
US20180164263A1 (en) Optochemical sensor
CN102353659B (zh) 生物芯片荧光微光谱检测装置及制作方法
WO2008105435A1 (fr) Système de détection de fluorescence
CN105378461A (zh) 采用荧光标记的测定装置
WO2014045388A1 (fr) Capteur de lumière fluorescente
JP7308209B2 (ja) 光検出モジュールおよび光検出装置
WO2014045387A1 (fr) Capteur fluorescent
WO2014045384A1 (fr) Capteur de lumière fluorescente
WO2014045761A1 (fr) Capteur de lumière fluorescente
WO2013161990A1 (fr) Capteur de lumière fluorescente
JP2012075750A (ja) 生体成分測定装置
WO2014045385A1 (fr) Capteur de lumière fluorescente
WO2014045386A1 (fr) Capteur de lumière fluorescente
WO2013161989A1 (fr) Capteur de fluorescence
WO2014045762A1 (fr) Capteur de lumière fluorescente et système de détection
WO2013094562A1 (fr) Capteur de fluorescence, système de capteur et procédé de correction de capteur de fluorescence
JP2012247260A (ja) 蛍光センサ

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: 12885010

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: 12885010

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP