WO2014045388A1 - Fluorescent sensor - Google Patents

Fluorescent sensor Download PDF

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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
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WO
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Prior art keywords
light
fluorescence
emitting element
portion
light emitting
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PCT/JP2012/074179
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French (fr)
Japanese (ja)
Inventor
亮 太田
悦朗 清水
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テルモ株式会社
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    • 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 infra-red, visible or ultra-violet 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 infra-red, visible or ultra-violet 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

Abstract

A fluorescent sensor (4) comprising: two substrate sections (40A, 40B); two indicators (17A, 17B) arranged, respectively, in hollow sections formed in the two substrate sections (40A, 40B), said indicators receiving excitation light (E) and generating fluorescent light (F) having an intensity corresponding to the concentration of an analyte (9); a light-emitting element substrate section (20) having provided therein a light-emitting element (15) that emits the excitation light (E); and at least one photoelectric conversion element (12) that converts the fluorescent light (F) to an electric signal. The fluorescent sensor (4) is arranged such that: a joined substrate section (30) is formed by the two substrate sections (40A, 40B) being joined so as to sandwich the light-emitting element substrate section (20); and the light-emitting element (15) is sandwiched between the two indicators (17A, 17B).

Description

Fluorescence sensor

The present invention relates to a fluorescence sensor for measuring the concentration of an analyte in a solution, in particular, it relates to a fluorescent sensor comprising an indicator consisting of hydrogels which generates fluorescence by the analyte and the excitation light.

Various analytical device for measuring an analyte ie, the concentration of the measured substance in solution has been developed. For example, the object to be measured solution was poured into a transparent container containing a fluorescent dye and the analyte, and a fluorometer for measuring the analyte concentration is known by measuring the fluorescence intensity from the irradiated fluorochrome excitation light there. Fluorescent dye generates fluorescence intensities corresponding to analyte concentration when receiving the excitation light properties are altered by the presence of the analyte.

Small fluorometer includes an indicator which contains a light source and a light detector and the fluorescent dye. Then, by irradiating the excitation light from the light source to freely indicator analyte to be measured solution is out, the fluorescent light detector indicator is generated is received. Photodetector is a photoelectric conversion element, and outputs an electric signal corresponding to the received light intensity. Analyte concentration in the solution is calculated based on the electrical signal from the photodetector.

To measure the analyte of trace samples, micro fluorometers have been proposed which is manufactured by using semiconductor manufacturing technology and MEMS technology. Hereinafter, the micro-fluorometer called "fluorescent sensor".

Fluorescence sensor 104 shown in FIGS. 1 and 2 is disclosed in WO 2010/119916 pamphlet. The sensor unit 110 is a main functional unit of the fluorescent sensor 104, the silicon substrate 111 to the photoelectric conversion element 112 is formed, a transparent intermediate layer 113, a filter layer 114, a light emitting element 115, and the transparent protective layer 116, It has an indicator 117, a light-shielding layer 118, a. Analyte 9 passes through the light shielding layer 118, enters the indicator 117. Filter layer of a fluorescent sensor 104 114 is transmitted through the fluorescence F to block the excitation light E. Further, the light emitting element 115 is transmitted through the fluorescence F.

In the fluorescent sensor 104, the pumping light E-emitting element 115 has occurred when incident on indicator 117, the indicator 117 emits fluorescence F in accordance with the analyte concentration.

Some of fluorescence F indicator 117 occurs, passes through the light emitting element 115 and the filter layer 114, and is photoelectrically converted is incident on the photoelectric conversion element 112. Incidentally, the excitation light E-emitting element 115 is emitted in the direction of the photoelectric conversion element 112 (the downward direction) is dimmed by the filter layer 114 to a level no measurement problem as compared to the fluorescence intensity. Fluorescence sensor 104, it is easy to simple compact configuration.

However, the fluorescence sensor 104 for photoelectric conversion elements 112 are in the lower surface of the light emitting element 115, light receiving efficiency of the fluorescence F by the photoelectric conversion element 112 is not a good. Therefore, more detection sensitivity is high fluorescence sensor has been demanded.

The present invention has been made in view of the above circumstances, and its object is that the detection sensitivity is to provide a high fluorescence sensor.

Fluorescence sensor of one embodiment of the present invention includes two substrate portion, wherein the respectively arranged in a hollow portion formed in the two substrates portion, the fluorescence intensity corresponding to the concentration of the analyte by receiving excitation light and two indicators that occurs, the light emitting element substrate unit light-emitting element is provided for generating the excitation light, and a one or more photoelectric conversion elements for converting the fluorescence into electrical signals, the two substrates portion the light emitting junction substrate portion bonded to the element to sandwich the substrate portion is formed, the light emitting element is disposed so as to be sandwiched between the two indicators by.

It is an explanatory view showing a sectional structure of a conventional fluorescence sensor. Is an exploded view showing the structure of a conventional fluorescence sensor. It is a configuration diagram of a sensor system according to the first embodiment. Same is a perspective view of the tip of the fluorescence sensor. Same, it is an exploded cross-sectional view taken along line V-V in FIG. 4 at the tip of the fluorescence sensor. Same, it is a cross-sectional view taken along line V-V in FIG. 4 at the tip of the fluorescence sensor. Same cross-sectional schematic view for explaining the operation of the fluorescence sensor. Same is a perspective view of the cover portion of the fluorescent sensor. It is an exploded sectional view of the tip end portion of the fluorescence sensor of the second embodiment. Same is a perspective view of the tip of the fluorescence sensor. Same, it is a cross-sectional view taken along line XI-XI of FIG. 10 at the tip of the fluorescence sensor. Same cross-sectional schematic view for explaining the operation of the fluorescence sensor. It is a schematic cross sectional view for explaining the operation of the fluorescence sensor of the third embodiment. It is a schematic cross sectional view for explaining the operation of the fluorescence sensor of the fourth embodiment. Same cross-sectional schematic view for explaining the operation of the fluorescence sensor variations. It is a schematic cross sectional view for explaining the operation of the fluorescence sensor of the fifth embodiment. Same cross-sectional schematic view for explaining the operation of the fluorescence sensor variations. It shows the distal end portion of the fluorescent sensor is a sectional view showing an example of the wiring board structure. It shows the distal end portion of the fluorescent sensor is a sectional view showing another example of the wiring board structure.

<First Embodiment>
For fluorescence sensor 4 and the sensor system 1 of the first embodiment of the present invention will be described. As shown in FIG. 3, the sensor system 1 includes a fluorescent sensor 4, the main body portion 2, a receiver 3 for storing the received signals from the main unit 2, a. Transmission and reception of signals between the main body portion 2 and receiver 3 is performed in a wireless or wired.

Fluorescence sensor 4, a needle 7 which is punctured on the subject, a connector portion 8 which is joined to the rear end of the needle part 7, made of. Needle 7 has an elongated needle body portion 6, and the needle tip 5 including the sensor unit 10 is a main function unit. Needle tip 5, the needle body 6, the connector portion 8 may be integrally formed of the same material, or may be made separately joined.

Connector portion 8 is fitted detachably fitting portion 2A of the main body portion 2. A plurality of wires 60 extending from the sensor portion 10 of the fluorescence sensor 4 by connectors 8 are fitted portion 2A and mechanically engagement of the main body portion 2 is electrically connected to the main body 2 .

Fluorescence sensor 4, after insertion of the sensor unit 10 in the body, the predetermined time period, e.g., 1 week, a needle-type sensor capable of measuring analyte concentration of the solution (fluid) continued to the body. However, the sensor unit 10 do not inserted into the body, collected body fluid or a body fluid circulated body through the flow path outside the body, it may be contacted with the sensor unit 10 in vitro.

Body 2 has a control unit 2B for performing a driving and control of the sensor unit 10, an operation unit 2C for processing the output signals from the sensor unit 10, a. At least one of the control unit 2B or the arithmetic unit 2C is, may be disposed in the connector portion 8, and the like of the fluorescent sensor 4 may be arranged on the receiver 3.

Although not shown, the main body portion 2 further includes a radio antenna for transmitting and receiving radio signals to and from the receiver 3, and the battery or the like, the. For sending and receiving signals between the receiver 3 via a wire, the body portion 2 has a signal line instead of the radio antenna. It is also the receiver 3 is not the case with a memory portion of the main body portion 2 is required capacity.

<Structure of the sensor section>
Next, with reference to FIGS. 4 to 8, a description will be given of the structure of the sensor portion 10 which is the main functional part of the fluorescence sensor 4. Note that FIG. Are all schematic views for explaining the dimensional ratio and the like of the vertical and horizontal is different from the actual, it may not be shown some components. Further, the Z-axis direction shown in FIG referred upward in fluorescence sensor 4. Moreover, in the drawings, X-axis direction indicates the longitudinal direction of the rear of the fluorescence sensor 4, Y-axis direction indicates a leftward direction of the left and right directions.

Fluorescence sensor 4 of the first embodiment detects the glucose in the subject fluid. As shown in FIGS. 4 and 5, the sensor unit 10 includes two frame-like substrate portion 40A with the through hole 40X, 40B and the two frame-like substrate portion 40A, the transparent resin to be interposed between 40B, a bonding substrate portion 30 and the wiring board 20 are respectively joined as a light emitting element substrate part formed like a glass, two indicators 17A which are arranged frame-like substrate portion 40A, and 40B of the through hole 40X, 17B When is disposed on the wiring substrate 20, a light-emitting element 15 that emits light in the vertical and horizontal directions, the two cover portions 18A covering the upper surface or lower surface of the opening of the through hole 40X, and 18B, these cover portions 18A, 18B of having two light shielding layers 19A respectively covering, and 19B, the.

Incidentally, the two frame-like substrate portion 40A, 40B, two indicators 17A, 17B, two cover portions 18A, 18B and two light shielding layers 19A, among 19B, the first frame-like substrate portion 40A, a first indicator 17A, the first cover portion 18A and the first light-shielding layer 19A is the upper side, the second frame-shaped board portion 40B, a second indicator 17B, a second cover portion 18B and the second light-shielding layer 19B is the lower side each are arranged so as laminating.

Specifically, from the top in order, the first light-shielding layer 19A, the first cover portion 18A, a first frame-shaped substrate portion 40A in which the first indicator 17A is provided, the light emitting element 15 is disposed on the upper surface wiring board unit 20, the second frame-shaped board portion 40B of the second indicator 17B is provided, the second cover portion 18B and the second light-shielding layer 19B are laminated. That is, the two frame-like substrate portion 40A, 40B is disposed so as to sandwich the wiring substrate 20, the first indicator 17A and a second indicator 17B are stacked so as to sandwich the light-emitting element 15.

Fluorescence sensor 4 here, the cover unit 18A, 18B is a photoelectric conversion element for converting the fluorescence F into an electric signal from the light emitting element 15 Photo Zehnder diode element (hereinafter referred to as "PD device") 12A, 12B are formed have been made of a semiconductor material analytes 9 passes. Note that the first cover portion 18A of the upper side, the first PD element 12A is provided a photoelectric conversion element, the second cover portion 18B of the lower side, the second PD element 12B is provided ing.

Cover section 18A, 18B is a micro through hole 18X (see FIG. 8), for example, a silicon substrate, respectively PD element 12A on one side, the 12B of the light receiving portion 12T is formed. Incidentally, PD elements 12A, 12B includes a one conductivity type of the light receiving portion, opposite conductivity type of the cover portion 18A, partially high conductivity by introducing an impurity low to make electrical connections 18B base side of it is composed of a resistor region, the following, together with the light receiving unit low-resistance region, PD elements 12A, sometimes referred to 12B. That is, the sensor section 10 of the fluorescence sensor 4 of this embodiment has two indicators 17A vertically bordering the light-emitting element 15, 17B and PD elements 12A, configured to 12B are provided.

Cover section 18A, 18B minute through hole 18X of a approach path body fluids containing analytes 9 enters the indicator 17A, the 17B. That is, the cover section 18A, 18B is, fluid can pass through.

Cover section 18A, 18B minute through hole 18X of the size, shape, location, and the formation density as appropriate depending on the specifications chosen. For example, (see FIG. 8) minute through holes 18X are not required to be orderly arranged. The shape of the opening when observing a minute through hole 18X from above can be circular, rectangular or may be any of polygonal,.

Two cover portions 18A of minute through holes 18X are formed, 18B is the same structure as a membrane filter, e.g., a silicon plate or a silicon film or the like, it is manufactured by patterning a minute through hole 18X . Specifically, minute through holes 18X are on the surface of the silicon plate or the like, after forming an etching mask by photolithography or self-assembled film etc. can be produced by dry etching such as ICP-RIE. The formation of the minute through holes 18X, may be used machining method by a micro drill or the like.

The cover portion 18A, the 18B, a solution containing the analyte may be used can pass through the porous semiconductor. Note that the porous means a material having a void and the pore connected to an external to the structure. Void / pore size, distribution and shape, the solution is passed if, need not have a regularity.

Cover section 18A, an open porosity of 18B is preferably 5 to 75 vol%, particularly preferably 20 to 50 vol%. If the range of, body fluid tends to pass through, desired mechanical strength can be obtained if less than the range. Incidentally, the open porosity is a value measured by the Archimedes method.

Two light-shielding layer 19A provided on the upper and lower, 19B, the excitation light E and fluorescence F is at the same time to prevent the light leakage to the outside, to prevent the external light G enters the indicator 17.

Two light shielding layers 19A, 19B is the analyte 9, indicators 17A to close through the interior, not prevented from reaching the 17B, for example, a pore structure of submicron size. Shielding layer 19A, the 19B, a metal, an inorganic material such as ceramics or composite composition of the hydrogel such that the carbon black is mixed in the base material of organic polymer such as polyimide or polyurethane, or, celluloses or polyacrylamides analyte permeable polymer resin mixed with carbon black etc., or using them was laminated resin or the like.

Two frame-like substrate portion 40A, the 40B, several hundred GPa silicon Young's modulus from several tens of GPa, glass or metal, or a Young's modulus of a resin material polypropylene or polystyrene degree of 1 GPa ~ 5 GPa . The same silicon as the material of the cover portion 18A is particularly preferred. The wiring board unit 20, the lower surface side of the indicator 17B side to the transparent resin as the emitted excitation light E can be transmitted from the light emitting element 15 to the lower side, it is formed of glass or the like, to form the through hole 40X portion only transparent member, it may be those formed of glass or the like and has a light transmitting property.

Indicator 17A, 17B and / or through hole 40X of the light emitting element 15 is housed inside the lower surface or upper surface is covered with the wiring board 20 is covered top or bottom cover portion 18A, and 18B , side constitutes a hollow portion formed by the inner wall of the frame-shaped substrate portion 40A, 40B. Hollow here the through hole 40X is a rectangular parallelepiped (square pillar), without being limited thereto, may be cylindrical, or polygonal shape. Incidentally, the side surface of the through hole 40X may be inclined with respect to the principal surface. Furthermore, it may be arranged that the reflection film for reflecting the fluorescence F on the side face.

The wiring board 20, wiring 51 for supplying the external electrode 15T connected to the drive signal of the light emitting element 15 is disposed. Cover section 18A, the 18B, PD elements 12A of the wiring 60, 12B is operated, wires 61 for transmitting a signal is formed. The wiring 51 and 61 is part of a plurality of wires 60. Incidentally, as shown in FIG. 6, PD elements 12A of the wiring 60, 12B of the signal line 61 is frame-shaped substrate portion 40A for transmitting, through holes 40a formed in 40B, via 40b, the light emitting element 15 is It is led to the upper surface side of the wiring board portion 20 which is arranged, together with the wiring 51 for driving at one main surface (upper surface) of the wiring board 20, the wiring 61 of the detection signal is assigned.

Incidentally, PD element 12A, to the excitation light E is prevented from entering the 12B, a filter which blocks the transmitted excitation light E and fluorescence F, PD element 12A, the light receiving surface of 12B, i.e., the cover unit 18A, 18B indicator 17A, preferably arranged on the surface facing the 17B. Such a filter, for example, but blocks the excitation light E of wavelength 375 nm, fluorescence F wavelength of 460nm using a light absorbing filter which transmits. When disposing the filter, the analyte to filter fine holes can pass is formed. The external electrode 15T of the lower surface of the light emitting element 15 is preferably sealed with an insulating resin. Further, the light emitting element 15 may be sealed with a transparent resin or the like to the top surface. Emitting element 15 that is sealed with resin, the indicator 17A, 17B is less susceptible to moisture contained.

Indicator 17A, 17B is the analyte 9 and the excitation light E, consisting of hydrogels with a fluorescent dye than the excitation light E generates a fluorescence F having a long wavelength. That two indicators 17A, 17B comprises a fluorescent dye that emits fluorescence F in an amount corresponding to the analyte concentration in the sample, the excitation light E and fluorescence F is composed of hydrogel satisfactorily transmitted. Incidentally, the indicator 17A, 17B does not contain a fluorescent dye, a fluorescent dye that emits fluorescence F may be the analyte 9 itself in solution.

Hydrogel include polysaccharides such as cellulose or dextran, acrylamide, methylol acrylamide, water urethane hydrogel like to produce acrylic hydrogel or polyethylene glycol with a diisocyanate to prepare by polymerizing a monomer such as hydroxyethyl acrylate It is formed by containing the fluorescent dye to easily comprise material.

Hydrogels cover section 18A, 18B and the light-shielding layer 19A, it is preferable via 19B is that there is no size to leave out the sensor. Therefore, the hydrogel, it molecules constituting Do a molecular weight of 1,000,000 or more, or cover portion 18A, or 18B is of the hole diameter or less on the example the diameter 50nm or more particulate or crosslinked in a form not flow preferable.

On the other hand, as the fluorescent dye, in the case of measuring the sugar such as glucose is phenylboronic acid derivatives having a fluorescent residues are suitable. Fluorescent dye, or a high molecular weight material, or by or chemically fixed to hydrogel, and is prevented from being detached out of the sensor.

A fluorescent dye, and a gel scaffolds, a polymerization initiator, a phosphate buffer solution containing, for 1 hour in a nitrogen atmosphere, by polymerizing, the indicator is produced. For example, as the fluorescent dye, 9,10-bis [N- [2- (5,5- dimethyl-Helsingborg nan-2-yl) benzyl] -N- [6 '- [(acryloyl polyethylene glycol -3400) carbonylamino ] the -n- hexylamino] methyl] -2-acetylanthracene (F-PEG-AAm), as the gel-scaffolds, acrylamide, as the polymerization initiator, sodium peroxodisulfate and N, N, N ' , using N'- tetramethylethylenediamine.

The light emitting element 15, LED elements, organic EL elements, inorganic EL elements or from among the light emitting elements that emit light of the desired excitation light E such as a laser diode element, an element that emits light on both upper and lower surfaces are selected. Further, it is preferable to transmit the fluorescence F.

Note that the light-emitting element 15, a fluorescent transmittance, light generation efficiency, the wavelength selectivity of the breadth of the excitation light E, and from the viewpoint of not only the light of the other wavelengths slightly occurs with excitation effect, LED elements preferable. Further among the LED elements, ultraviolet LED element consisting of the formed gallium nitride-based compound semiconductor on a sapphire substrate is particularly preferred.

Emitting element 15, the center wavelength in a single interval to pulse emission of the excitation light of about 375nm, for example 30 seconds. For example, the current of the drive signal to the light emitting element 15 is 1 mA ~ 100 mA, the pulse width of the emission is 1 ms ~ 100 ms.

In fluorescence sensor 4 of this embodiment, as shown in FIG. 7, two indicators 17A, the fluorescence F generated from 17B indicator 17A, the upper surface or lower surface of the PD element 12A of 17B, incident on 12B. At this time, the fluorescence F which emits light in accordance with the concentration of the analyte. 9, the fluorescence F is mostly from the first indicator 17A in the first PD element 12A, in part by the second PD element 12B, the fluorescence F from 2 indicator 17B is the most first PD element 12B, a portion is detected by the first PD element 12A. Therefore, the fluorescence sensor 4, the vertical direction in the indicator 17A sandwich the light-emitting element 15, 17B and the PD element 12A, by disposing the 12B, a conventional fluorescence sensor for the excitation light E can be efficiently utilized from the light emitting element 15 the more sensitive 104.

<Second Embodiment>
It will now be described fluorescence sensor 4A of the second embodiment. Since fluorescence sensor 4A is similar to the fluorescence sensor 4, and the same elements are denoted by the same reference numerals, and a description thereof will be omitted.

Fluorescence sensor 4A of the present embodiment is different from the fluorescence sensor 4 in the first embodiment, the cover portion 18A, PD element 12A, which is a photoelectric conversion element 18B, but is in that 12B is formed of the same, FIG. as shown in 9, forming a frame-like substrate portion 40A to be laminated across the wiring board 20, the side openings 40S to communicate with the 40B of the through hole 40X frame-like substrate portion 40A, the side surface of the 40B, FIG. 10 and FIG. 11 is different two light shielding layers 19A so as to cover the side openings 40S, a 19B in that arranged on the side surface. Then, the fluorescence sensor 4A herein, cover portion 18A which is disposed to cover the upper and lower through holes 40X frame-like substrate portion 40A, the 40B, 18B is the light-shielding layer 19A, 19B functions, i.e., external light G to prevent the ingress, it has a function, of preventing the light leakage of the excitation light E and fluorescence F.

That is, two indicators 17A which are arranged frame-like substrate portion 40A, and 40B in the through hole 40X, the 17B, the light blocking layer 19A provided on the side surface, through 19B, the analyte from a total of four side openings 40S 9 it is possible to enter.

Specifically, shown in FIG. 12, the fluorescent sensors 4A, the light-shielding layer 19A provided on the side surface, the analyte 9 19B are frame-like substrate portion 40A, 40B in the through hole 40X of the side openings 40S from the indicator 17A, entering the 17B. Then, by the excitation light E for emitting the light emitting element 15, the indicator 17A, the fluorescence F is generated in accordance with the concentration of the analyte 9 17B, the fluorescence F1 emitted from the first indicator 17A positioned above upward first detected by the first PD element 12A of the first cover portion 18A, the fluorescence F2 emitted downward from the second indicator 17B positioned below is detected by the second PD device 12B of the second cover portion 18B that.

Fluorescence sensor 4A of the present embodiment from the above, in addition to the effect of the fluorescent sensor 4 in the first embodiment, the cover portion 18A which covers the opening of the upper and lower through holes 40X frame-like substrate portion 40A, the 40B, minute through holes 18B may not be provided 18X, as a result, the PD element 12A, is a minute through hole 18X to 12B are not formed, further, a high sensitivity. Further, by four side openings 40S, it enters the area of ​​the analyte 9 that increases the indicator 17A, the analyte 9 is liable to enter the 17B, the response to changes in the concentration of the analyte 9 is remarkably improved.

Incidentally, the side opening 40S that communicates with the frame-shaped substrate portion 40A, and 40B of the through hole 40X is preferably more formed on both sides, without being limited thereto, the frame-shaped substrate portion 40A, at least one side of the 40B it may be configured to be formed.

<Third Embodiment>
It will now be described fluorescence sensor 4B according to the third embodiment. Fluorosensor 4B, since similar to the fluorescence sensor 4 in the first embodiment, and the same elements are denoted by the same reference numerals, and a description thereof will be omitted.

Fluorosensor 4B shown in FIG. 13, when compared with the fluorescence sensor 4 in the first embodiment, the indicator 17A, the frame-shaped substrate portion 40A which forms a through hole 40X to 17B are disposed, the photoelectric conversion element to the inner surface of the 40B PD element 12C as in that a 12D are formed differently.

Specifically, the fluorescence sensor 4B is frame-like substrate portion 40A, PD elements 12C as a light receiving portion on each side of the through hole 40X of 40B, 12D are provided (It should be noted that only the side in the longitudinal direction in FIG. 13 shown ). Further, here, the frame-shaped substrate portion 40A, 40B of the through hole 40X of the upper or lower surface of the opening shielding layer 19A so as to cover the, 19B are disposed. In addition, these light-shielding layers 19A, 19B and indicators 17A, also between the 17B, similarly to the first embodiment, PD elements 12A, the cover section 18A having a 12B, may be provided 18B.

The fluorescence sensor 4B configured as described above, the upper and lower light blocking layer 19A, the analyte 9 19B enters the indicator 17A, the 17B. Then, by the excitation light E from the light emitting element 15, the indicator 17A, the fluorescence F is generated in accordance with the concentration of the analyte 9 17B, the fluorescence F1 emitted from the first indicator 17A located above the lateral first detected by the first PD element 12C, the fluorescence F2 emitted laterally from the second indicator 17B positioned below is detected by the second PD elements 12D.

Fluorescence sensor 4B of this embodiment from the above, in addition to the effect of the fluorescent sensor 4 in the first embodiment, since on the approach path of the analyte 9 PD elements 12B, 12C are not, these PD element 12B, minute through the 12C It may not be provided a hole 18X, further indicator 17A, since the PD element 12C around the left and right sides of 17B, 12D are formed, the more sensitive.

<Fourth Embodiment>
Then, the fluorescence sensor 4C according to the fourth embodiment, 4D will be described. Incidentally, the fluorescence sensor 4C, 4D, since similar to the fluorescence sensor 4 in the first embodiment, and the same elements are denoted by the same reference numerals, and description thereof is omitted.

As shown in FIG. 14, the fluorescence sensor 4C here, PD element 12E is provided a photoelectric conversion element between the light emitting element 15 and the first indicator 17A. That is, the fluorescence sensor 4C, the light emitting element 15 is disposed between the PD elements 12E and the second indicator 17B.

The approximate center of the PD element 12E, the through hole 12X is formed. Then, the excitation light E from the light emitting element 15 is adapted to enter the second indicator 17B on the lower side, incident on the first indicator 17A of the upper side through the through hole 12X. The plurality of through holes 12X may be formed in the PD device 12E.

In fluorosensor 4C herein, a fluorescence F1 emitted downward from the first indicator 17A, a fluorescent F2 emitted upward from the second indicator 17B are both detected by the PD element 12E.

Incidentally, as shown in FIG. 15, the fluorescence sensor 4D is a through hole 12X is formed of two PD elements 12Ea, provided 12Eb, these PD elements 12Ea, arranged vertically so 12Eb sandwich the light emitting element 15 it may be.

In fluorosensor 4D herein, the fluorescence F1 emitted downward from the first indicator 17A is a first PD element 12Ea, by fluorescence F2 emitted upward from the second indicator 17B is a second PD element 12EB It is detected.

Fluorosensor 4C, 4D of this embodiment from above, both because there is no PD element 12 on approach path of the analyte 9, a high sensitivity since it is not necessary to provide a fine through hole 18X to PD element 12.

<Fifth Embodiment>
Then, the fluorescence sensor 4E according to the fifth embodiment, 4F will be described. Incidentally, the fluorescence sensor 4E, 4F, since similar to the fluorescence sensor 4 in the first embodiment, and the same elements are denoted by the same reference numerals, and description thereof is omitted.

As shown in FIG. 16, the fluorescence sensor 4E here is a fluorescent sensor 4B shown in FIG. 13, a structure combining a fluorescence sensor 4C shown in FIG. 14.

That is, in the fluorescence sensor 4E herein, fluorescence F1 emitted downward from the first indicator 17A of the upper side is detected by the PD element 12E, the fluorescence F2 emitted laterally is detected by the PD elements 12C. The fluorescent F3 emitted upward from the second indicator 17B of the lower side is detected by the PD element 12E, fluorescent F4 emitted in the lateral direction is detected by the PD elements 12D.

Furthermore, as shown in FIG. 17, the fluorescence sensor 4F here is a fluorescent sensor 4B shown in FIG. 13, a fluorescence sensor 4D shown in FIG. 15, or may be a combination of the structure.

That is, in the fluorescence sensor 4F herein, fluorescence F1 emitted downward from the first indicator 17A of the upper side is detected by the PD element 12Ea, fluorescence F2 emitted laterally is detected by the PD elements 12C. The fluorescent F3 emitted upward from the second indicator 17B of the lower side is detected by the PD element 12Eb, fluorescent F4 emitted laterally is detected by the PD elements 12D.

Fluorosensor 4E of this embodiment from above, 4F are all because there is no PD element 12 on approach path of the analyte 9, a high sensitivity since it is not necessary to provide a fine through hole 18X to PD element 12.

Although the shape of the sensor portion of the fluorescence sensor described in more of the above embodiments was right prism shape, trapezoidal shape, or a shape side is curved or cylindrical shape or the like.

Further, the wiring substrate 20, need not have a light transmitting property, for example, as shown in FIG. 18 were bonded light emitting element 15A, 2 single wiring board 20A which 15B is provided, and 20B in the vertical direction configuration it may be. Incidentally, as shown in FIG. 19, also the excitation light E from the light emitting element 15 is provided with a facing portion in the hole 20a emitting element 15 is provided in the wiring substrate 20 so as to be incident on the second indicator 17B side good. That is, in the configuration of FIG. 19, the pumping light E which passes through a hole 20 formed in the wiring substrate 20 is incident on the second indicator 17B.

Also has been described a sensor for detecting a saccharide such as glucose as an example, fluorescent sensors, by selection of a fluorescent dye, an enzyme sensor, pH sensor, and corresponds to the various applications, such as an immunosensor or a microorganism sensor.

That is, the present invention is not limited to the embodiments and modifications described above, in a range not changing the gist of the present invention, various changes can modifications thereof.

Claims (10)

  1. And two of the base plate portion,
    Are respectively disposed in the hollow portion formed in the two substrate portion, and the two indicators for generating the fluorescence intensity corresponding to the concentration of the analyte by receiving excitation light,
    A light emitting element substrate unit light-emitting element is provided for generating the excitation light,
    One or more photoelectric conversion elements for converting the fluorescence into an electric signal,
    Equipped with a,
    Fluorescence, wherein the bonding substrate portion joined so as to sandwich the light emitting element substrate section by the two substrates portion is formed, the light emitting element between the two indicators are arranged to be interposed between sensor.
  2. Claims wherein the one or more photoelectric conversion elements are arranged in an opening of the hollow portion formed on the upper surface and the lower surface of the bonding substrate portion, and being provided so as to face the two indicators fluorescence sensor according to 1.
  3. Is disposed so as to cover the opening of the hollow portion, claim 1 or claim, wherein a through-hole and the photoelectric conversion element is provided with a cover portion made of a semiconductor material provided the analyte passes fluorescence sensor according to claim 2.
  4. The upper and lower surfaces of the bonded substrate portion, the fluorescence sensor according to any of claims 1 to 3, characterized in that the light-shielding layer in which the analyte passes is provided.
  5. Wherein the two sides of the base plate, the side opening communicating with the hollow portion is formed,
    Fluorescence sensor according to any of claims 1 to 4, wherein a light shielding layer in which the analyte passes is provided so as to cover the side opening.
  6. Fluorescence sensor according to any of claims 1 to 4, wherein the one or more photoelectric conversion elements are arranged on the inner surface of the two substrates portion forming the hollow portion.
  7. Fluorescence sensor according to any of claims 1 to 6 in which at least one is characterized by being disposed between the indicator and the light emitting element of the one or more photoelectric conversion elements.
  8. Fluorescence sensor according to claim 7, wherein the one or more photoelectric conversion elements are disposed between the two indicators and the light emitting element.
  9. The light emitting element substrate unit, fluorescence sensor according to any of claims 1 to 8, characterized in that it has a light transmission property.
  10. The light emitting element substrate unit, fluorescence claimed in any of claims 8, characterized in that the excitation light to a portion of the light emitting element is provided has a hole for passing sensor.
PCT/JP2012/074179 2012-09-21 2012-09-21 Fluorescent sensor WO2014045388A1 (en)

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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 (en) * 1997-05-13 2001-12-11 コルビン,アーサー・イー・ジュニア Improved fluorescence detection device
JP2002523774A (en) * 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 Optical detection device
JP2003515163A (en) * 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 Light sensors and arrays containing thin electroluminescent device
WO2004071291A2 (en) * 2003-02-13 2004-08-26 Medtronic, Inc. Implantable chemical sensor
JP2012093128A (en) * 2010-10-25 2012-05-17 Olympus Corp Fluorescence sensor

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 (en) * 1997-05-13 2001-12-11 コルビン,アーサー・イー・ジュニア Improved fluorescence detection device
JP2002523774A (en) * 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 Optical detection device
JP2003515163A (en) * 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 Light sensors and arrays containing thin electroluminescent device
WO2004071291A2 (en) * 2003-02-13 2004-08-26 Medtronic, Inc. Implantable chemical sensor
JP2012093128A (en) * 2010-10-25 2012-05-17 Olympus Corp Fluorescence sensor

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