WO2014045385A1 - Fluorescent sensor - Google Patents

Abstract

A fluorescent sensor (4) comprising: a substrate section (20); an indicator (17) arranged upon the substrate section (20), receiving excitation light (E), generating fluorescent light (F) of an intensity corresponding to the concentration of an analyte (9), and having a partially cylindrical exterior; a light-emitting element (15) attached to the substrate section (20) and which generates the excitation light (E); and a photoelectric conversion element (12) that converts the fluorescent light (F) into an electric signal.

Description

Fluorescent sensor

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.

Various analyzers have been developed for measuring the concentration of analytes in solution, that is, analytes. For example, 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. Yes. 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 | occur | 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.

In order to measure an analyte in a very 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”.

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.

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.

Part of the fluorescence F 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 E 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.

However, in the fluorescence sensor 104, since the photoelectric conversion element 112 is on the lower surface of the light emitting element 115, it cannot be said that the light reception efficiency of the fluorescence F by the photoelectric conversion element 112 is good. For this reason, a fluorescence sensor with higher detection sensitivity has been demanded.

Therefore, 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 fluorescent sensor of one embodiment of the present invention is provided on the substrate portion and the substrate portion, receives the excitation light, generates fluorescence having an intensity corresponding to the concentration of the analyte, and has an outer shape of a partial cylindrical shape. An indicator, a light emitting element that is mounted on the substrate portion and generates excitation light, and a photoelectric conversion element that converts the fluorescence into an electric signal are provided.

It is explanatory drawing which showed the cross-section of the conventional fluorescence sensor. It is the exploded view which showed the structure of the conventional fluorescence sensor. It is a block diagram of the sensor system of 1st Embodiment. It is a perspective view of the front-end | tip part of a fluorescence 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. 6 is a cross-sectional view taken along the line VI-VI in FIG. 5 at the tip of the fluorescent sensor. FIG. 4 is a cross-sectional view illustrating a method for manufacturing a fluorescent sensor and showing a mold and a light shielding film. FIG. 4 is a cross-sectional view illustrating a method for manufacturing a fluorescent sensor, in which a light-shielding film is pressed into a recess of a mold. FIG. 5 is a cross-sectional view illustrating a method for manufacturing a fluorescent sensor, in which an indicator is pressed onto a light shielding film in a recess of a mold. FIG. 4 is a cross-sectional view illustrating a method for manufacturing a fluorescent sensor, in which a photoelectric conversion element substrate is arranged on an indicator of a mold. FIG. 5 is a cross-sectional view illustrating a fluorescent sensor that is completed by removing a mold and explaining a method for manufacturing the fluorescent sensor. It is a cross-sectional schematic diagram for demonstrating operation | movement of a fluorescence sensor. It is sectional drawing of the fluorescence sensor of 2nd Embodiment. It is a cross-sectional schematic diagram for demonstrating operation | movement of a fluorescence sensor. It is a perspective view of the front-end | tip part of the fluorescence sensor of 3rd Embodiment. FIG. 16 is a cross-sectional view taken along the line XVI-XVI in FIG. 15 at the tip of the fluorescent sensor. It is a perspective view of the front-end | tip part of the fluorescence sensor of a modification similarly. FIG. 18 is a perspective view of a tip portion of a fluorescent sensor of a modified example different from FIG. It is sectional drawing of the fluorescence sensor of 4th Embodiment. It is sectional drawing of the fluorescence sensor of a modification same as the above. It is sectional drawing which shows an example of a light emitting element shape. It is sectional drawing which shows the other example of a light emitting element shape.

<First Embodiment>
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.

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.

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.

<Structure of sensor part>
Next, 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. 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 in the fluorescence sensor 4. Further, in the drawing, the X-axis direction indicates the rear in the front-rear direction of the fluorescent sensor 4, and 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. As shown in FIG. 4 to FIG. 6, the sensor unit 10 of the present embodiment has a substantially semi-cylindrical outer shape, and a light emitting element 15 that emits light radially upward and leftward and mounted on the upper surface. Detection substrate portion 20, a semi-cylindrical distal end frame 21 fitted to the distal end portion of the detection substrate portion 20, and a semi-cylindrical proximal end frame fitted to the proximal end portion of the detection substrate portion 20. 22 and the outer shape disposed on the detection substrate portion 20 has an arcuate cross section, that is, a partial cylindrical indicator 17 and a light shielding film 19 that covers the indicator 17 in a dome shape. . In addition, the shape of the indicator 17 here is a partial cylindrical shape with the outer shape being a circular arc shape as described above. This partial columnar shape is a shape obtained by cutting a column into approximately half.

The fluorescent sensor 4 here is provided with a light shielding film 19, an indicator 17, and a detection substrate 20 in order from the top. That is, in the fluorescent sensor 4, the indicator 17 is disposed on the detection substrate unit 20 having the light emitting element 15, and the indicator 17 is covered with the light shielding film 19. The light shielding film 19 is bonded to the edge portion (both end portions) of the detection substrate unit 20.

The detection substrate 20 here has a photodiode element (hereinafter referred to as “PD element”) 12 that is a photoelectric conversion element that converts the fluorescence F from the indicator 17 into an electrical signal on the upper surface side on which the light emitting element 15 is mounted. Is formed. That is, the fluorescent sensor 4 of the present embodiment has a configuration in which the indicator 17 is disposed on the detection substrate unit 20 on which the light emitting element 15 and the PD element 12 are provided, and the indicator 17 is covered with the light shielding film 19. .

The light-shielding property is necessary for the detection substrate unit 20. Therefore, it is preferable to use a silicon substrate, and the PD element 12 formed on the silicon substrate is preferable as the photoelectric conversion element. For example, the PD element 12 has a structure in which a p-type diffusion region is formed in an n-type silicon semiconductor.

Here, it is preferable that a filter that transmits the fluorescence F and blocks the excitation light E is formed on the surface of the PD element 12 in order to prevent the excitation light E from entering (not shown). As the filter, for example, it is preferable to use a light absorption filter that blocks excitation light E having a wavelength of 375 nm but transmits fluorescence F having a wavelength of 460 nm.

The detection substrate unit 20 may be a composite material in which a light-shielding cover layer is laminated on a flexible sheet, for example, a polyimide sheet on which aluminum or gold is vapor-deposited. Alternatively, a composite material in which a light-shielding metal foil such as stainless steel and a flexible sheet are bonded together may be used.

As the flexible sheet, various flexible materials other than polyimide, for example, plastic materials such as PET (polyethylene terephthalate), or rubber materials such as PDMS (polydimethylsiloxane) can be used.

Alternatively, a thin metal plate having a light shielding property may be used.

When a composite material or a metal plate is used as the detection substrate unit 20, the photoelectric conversion element is manufactured by forming an organic semiconductor such as pentacene by vapor deposition or coating, and then partially doping impurities. The

For example, organic semiconductors include polycyclic aromatic hydrocarbons such as pentacene, anthracene, or rubrene, low-molecular compounds such as tetracyanoquinodimethane (TCNQ), polyacetylene, poly-3-hexylthiophene (P3HT), or poly A polymer such as paraphenylene vinylene (PPV) can be used.

The photoelectric conversion element is not limited to the PD element 12 and is selected from various photoelectric conversion elements such as a photoconductor or a phototransistor.

In addition, here, the detection substrate unit 20 on which the PD element 12 is mainly provided is used, but it is needless to say that the light emitting element substrate on which the light emitting element is mainly mounted may be used.

The detection substrate unit 20 includes the wiring 60 shown in FIG. 3, and a wiring that is connected to the external electrode of the light emitting element 15 and supplies a driving signal and a wiring that transmits the signal of the PD element 12 are formed (whichever (Not shown).

The light shielding film 19 covers the indicator 17 to prevent the excitation light E and the fluorescence F from leaking to the outside, and at the same time, prevents the external light G (see FIG. 12) from entering the indicator 17. Further, the light shielding film 19 has a pore structure of, for example, a submicron size that does not prevent the analyte 9 from passing through the inside and reaching the adjacent indicator 17. The light-shielding film 19 is made of an inorganic material such as metal or ceramic, a composite composition with a hydrogel in which carbon black is mixed in a base material of an organic polymer such as polyimide or polyurethane, or a cellulose or polyacrylamide. A resin in which carbon black is mixed into an analyte-permeable polymer or a resin in which these are laminated is used. The light shielding film 19 here constitutes an entry path through which the body fluid containing the analyte 9 enters the indicator 17.

The light emitting element 15 provided on the detection substrate unit 20 is an element that transmits fluorescence F among 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. Is selected.

In addition, as the light emitting element 15, an LED element is used 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. Furthermore, among LED elements, 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. For example, the current of the drive signal to the light emitting element 15 is 1 mA to 100 mA, and the light emission pulse width is 1 ms to 100 ms.

The indicator 17 is made of a hydrogel having a fluorescent dye that generates fluorescence F having a wavelength longer than that of the excitation light E by the analyte 9 and the excitation light E. That is, the indicator 17 is composed of a hydrogel that contains the fluorescent dye that generates the fluorescent light F with a light amount corresponding to the analyte concentration in the sample and that allows the excitation light E and the fluorescent light F to pass therethrough satisfactorily. The indicator 17 may be the analyte 9 itself in which the fluorescent dye that does not include the fluorescent dye and 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.

It is preferable that the hydrogel has a size that does not leave the sensor through the light shielding film 19. For this reason, it is preferable that the hydrogel has a molecular weight of 1 million or more, or a form in which the hydrogel is crosslinked and does not flow.

On the other hand, when measuring sugars such as glucose, 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 17 is produced by polymerizing a phosphate buffer containing a fluorescent dye, a gel skeleton-forming material, and a polymerization initiator in a nitrogen atmosphere for 1 hour. For example, as 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.

In addition, the external electrode of the light emitting element 15 is preferably sealed with an insulating resin. Furthermore, the light emitting element 15 may be sealed with a transparent intermediate layer up to the upper surface. The resin-sealed light emitting element 15 is not easily affected by the moisture of the indicator 17.

The distal end frame 21 and the proximal end frame 22 fitted before and after the detection substrate unit 20 are made of silicon, glass, metal, or the like, or a resin material such as polypropylene or polystyrene. Further, the distal end frame 21 and the base end frame 22 may be provided with a plurality of openings that communicate with the indicator 17, and the light shielding film 19 may be provided so as to cover these openings. Thereby, the analyte 9 can enter the indicator 17 from the front-rear direction, and the entry area of the analyte 9 to the indicator 17 can be increased.

Here, the manufacturing method of the fluorescence sensor 4 will be briefly described with reference to FIGS.
First, as shown in FIGS. 7 and 8, the light shielding film 19 is embossed on the mold 200 in which the arc-shaped recess 201 is formed.

Next, as shown in FIG. 9, a predetermined amount of the indicator 17 is embossed on the light shielding film 19 of the mold 200. The indicator 17 at this time is in a dry state so that it can be easily manufactured. The set amount of the indicator 17 is an amount such that the expanded state containing moisture is substantially the same as the capacity of the recess 201 provided with the light shielding film 19. Note that the liquid indicator 17 may be injected onto the light shielding film 19 of the mold 200. Thus, the indicator 17 covered with the light shielding film 19 is completed.

Subsequently, as shown in FIG. 10, the detection substrate unit 20 on which the light emitting element 15 and the PD element 12 are mounted on the indicator 17 is placed so that the surface of the detection substrate unit 20 faces the indicator 17. And the end of the light shielding film 19 are bonded.

Thus, as shown in FIG. 11, by removing the mold frame 200, the detection substrate portion 20 is covered with the light-shielding film 19 having a semicircular cross section (arc shape), and the partial columnar indicator 17 is provided. A part of the fluorescence sensor 4 is completed.

Then, the distal end portion of the detection substrate portion 20 and the distal end frame 21 are fitted and adhered, and the peripheral end portion of the distal end frame 21 and the arc-shaped distal end portion of the light shielding film 19 are adhered. Further, the base end portion of the detection substrate unit 20 and the base end frame 22 are fitted and bonded, and the peripheral end portion of the base end frame 22 and the arcuate base end portion of the light shielding film 19 are bonded. Thus, the fluorescence sensor 4 is produced.

In the fluorescence sensor 4 of the present embodiment, as shown in FIG. 12, the excitation light E from the light emitting element 15 provided at the approximate center of the flat portion of the indicator 17 is received and the indicator 17 responds to the concentration of the analyte 9. The generated fluorescence F enters the PD element 12. At this time, the fluorescence F emitted according to the concentration of the analyte 9 is detected from the indicator 17 by the upper surface of the PD element 12. Therefore, in the fluorescence sensor 4, the excitation light E from the light emitting element 15 is evenly applied to the partial cylindrical indicator 17, and the sensitivity becomes higher than that of the conventional fluorescence sensor 104. That is, the fluorescence sensor 4 has high sensitivity because it can efficiently use the excitation light E from the light emitting element 15.

Further, the fluorescent sensor 4 has a substantially semi-cylindrical shape, and has a partial cylindrical shape (a cross-sectional arc shape) in which the surface of the indicator 17 is formed in an arc shape, and the surface of the indicator 17 is covered with a light shielding film 19. Yes. For this reason, the fluorescent sensor 4 can take a large area for the analyte 9 to enter the indicator 17 through the light shielding film 19, so that the analyte 9 can easily enter the indicator 17. The response to is greatly improved.

In addition, the shape of the indicator 17 is not limited to the partial columnar shape, and may be a polygonal cross-sectional shape such as a dome shape.

Second Embodiment
Next, 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.

Compared with the fluorescent sensor 4 of the first embodiment, the fluorescent sensor 4A of the present embodiment is the same in that the indicator 17 is provided on the detection substrate unit 20, but as shown in FIG. The difference is that the PD element 12 is mounted on the portion 20.

Specifically, in the detection substrate unit 20, the PD element 12 is formed at a position avoiding the light emitting element 15 mounted on the upper surface.

In the fluorescence sensor 4A here, as shown in FIG. 14, the analyte 9 enters the indicator 17 from the light shielding film 19 as in the first embodiment. The fluorescent light F corresponding to the concentration of the analyte 9 is generated from the indicator 17 by the excitation light E emitted from the light emitting element 15 in the upper and left radial directions, and the fluorescent light F emitted downward from the indicator 17 is generated on the detection substrate unit 20. It is detected by the PD element 12 mounted on the upper surface.

From the above, the fluorescence sensor 4A of the present embodiment has the same effect as the fluorescence sensor 4 of the first embodiment, and is more sensitive.

<Third Embodiment>
Next, 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 fluorescent sensor 4B of this embodiment shown in FIGS. 15 and 16 has a frame portion 18 that has a partial cylindrical shape (a cross-sectional arc shape) so as to cover the indicator 17 as compared with the fluorescent sensor 4 of the first embodiment. Different points are provided.

Specifically, the fluorescence sensor 4B here is provided with a frame portion 18 formed in an arc shape so as to cover the indicator 17, and a light shielding film 19 is provided so as to cover the frame portion 18. The frame portion 18 is formed of stainless steel, a flexible material, or the like having a thickness of 10 μm, and a plurality of slits 18 a are formed so that the analyte 9 can enter the indicator 17 along the longitudinal axis direction of the fluorescent sensor 4 </ b> B.

The frame portion 18 is deformed so that the indicator 17 has a partial cylindrical shape (circular arc shape). In addition, the side edge part of the frame part 18 is adhere | attached on the upper surface of 20 A of light emitting element board | substrate parts formed from the non-transparent member in which the light emitting element 15 was mounted. Further, the frame portion 18 may be a rigid substrate formed in an arc shape in advance.

From the above, in addition to the effect of the fluorescence sensor 4 of the first embodiment, the fluorescence sensor 4B of the present embodiment has a remarkable strength by providing the frame portion 18 as compared with the configuration in which the indicator 17 is covered only by the light shielding film 19. improves.

The frame portion 18 is not limited to the plurality of slits 18a in the direction along the longitudinal axis direction in the fluorescence sensor 4B, and, for example, as shown in FIG. 17, the frame portion 18 extends along the short axis direction in the fluorescence sensor 4B. It is good also as the slit 18b. The plurality of slits formed in the frame portion 18 may have any shape such as a spiral shape or a lattice shape. Further, the frame portion 18 may have a mesh structure formed of metal or the like as shown in FIG.

<Fourth embodiment>
Next, the fluorescence sensors 4C and 4D of the fourth embodiment will be described. Since the fluorescence sensor 4C is similar to the fluorescence sensors 4 and 4B of the first embodiment and the third embodiment, the same components are denoted by the same reference numerals and description thereof is omitted.

19 is different from the fluorescent sensors 4 and 4B of the first embodiment and the third embodiment in that the PD element 12 is provided in the frame portion 18 as shown in FIG.

Specifically, a plurality of PD elements 12 are formed on the inner surface side of the frame portion 18 that faces the indicator 17 and contacts. That is, the fluorescence emitted radially from the indicator 17 by the plurality of PD elements 12 formed in the frame portion 18 is detected.

As shown in FIG. 20, the frame portion 18 </ b> A in the fluorescence sensor 4 </ b> D here connects a plurality of substrate portions 31 in which PD elements 12 are formed on a rigid substrate or a flexible substrate made of silicon or the like by a flexible substrate 32. Thus, the dome shape is formed in a circular arc shape (semicircular shape) in cross section. That is, 18 A of frame parts are arrange | positioned so that the indicator 17 may be covered so that the indicator 17 may become a partial cylinder shape (section circular arc shape).

Note that the frame portion 18 </ b> A here has a micro through hole (not shown) so that the substrate portion 31, the PD element 12, and the flexible substrate 32 can enter the body fluid containing the analyte 9 into the indicator 17. That is, body fluid can pass through the frame portion 18A. Further, a light shielding film 19 that covers the frame portion 18A may be provided.

The size, shape, position, and formation density of the minute through holes of the frame portion 18A are appropriately selected according to the specifications. For example, the minute through holes do not need to be arranged in an orderly manner. Moreover, the shape of the opening when the minute through hole is observed from the upper surface may be any of a circle, a rectangle, a polygon, and the like.

The frame portion 18A in which the minute through holes are formed in this way has the same structure as the membrane filter, but is produced by patterning the minute through holes on a silicon plate or a silicon film, for example. Specifically, the minute through hole 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. For forming the minute through hole, a machining method using a micro drill or the like may be used.

Further, a porous semiconductor through which a solution containing an analyte can pass may be used for the frame portion 18A. 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 frame portion 18A 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.

As described above, the fluorescence sensors 4C and 4D of the present embodiment have a plurality of PD elements that individually receive the fluorescence F from the indicator 17 in addition to the effects of the fluorescence sensors 4 and 4B of the first embodiment and the third embodiment. By forming 12 on the frame portions 18 and 18A, higher sensitivity is obtained. The above configuration can also be applied to the frame portion 18 of the rigid substrate previously formed in an arc shape described in the third embodiment.

The light emitting element 15 is optimized in shape so that the excitation light E is uniformly irradiated to the indicator 17 by using a lens, a sealing resin, or the like according to the partial cylindrical shape of the indicator 17, for example, FIG. It is preferable to use a dome shape such as a shell shape or a partial cylindrical shape as shown in FIG.

In the above description, a sensor that detects saccharides such as glucose has been described as an example. However, a fluorescent sensor can be used for various applications such as an enzyme sensor, a pH sensor, an immunosensor, or a microorganism sensor by selecting a fluorescent dye. ing.

That is, the present invention is not limited to the above-described embodiments and modifications, and various changes and modifications can be made without departing from the scope of the present invention.

Claims (7)

1. A substrate section;
   An indicator that is disposed on the substrate portion, receives excitation light, generates fluorescence having an intensity according to the concentration of the analyte, and has an outer shape of a partial cylindrical shape;
   A light emitting element mounted on the substrate unit for generating excitation light;
   A photoelectric conversion element for converting the fluorescence into an electrical signal;
   A fluorescent sensor comprising:
2. 2. The fluorescent sensor according to claim 1, wherein the indicator is covered with a light-shielding film through which the analyte bonded to the substrate portion passes and exhibits the partial cylindrical shape.
3. 3. The fluorescent sensor according to claim 1, wherein the indicator is covered with a frame portion through which the analyte bonded to the substrate portion can pass and has the partial cylindrical shape.
4. The fluorescent sensor according to claim 3, wherein a slit is formed in the frame portion.
5. 4. The fluorescent sensor according to claim 3, wherein the frame portion has a mesh shape.
6. The fluorescent sensor according to claim 1, wherein the photoelectric conversion element is formed on the substrate portion.
7. 6. The fluorescent sensor according to claim 1, wherein the photoelectric conversion element is formed in the frame portion.

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