JP2015059869A - Fluorescence sensor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a fluorescence sensor 10 having high measuring accuracy.SOLUTION: A fluorescence sensor 10 includes: a light shield layer 21; an indicator 22; a substrate section 31; a transparent layer 32 covering a lower surface of the substrate section 31; a semiconductor layer 33 provided below the transparent layer 32, a through-hole 33H penetrating a first principal surface 33SA and a second principal surface 33SB, a PD element 41 detecting fluorescent light generated by the indicator 22 being formed on the second principal surface 33SB, and a PD element 42 detecting excitation light being formed on a wall surface 33HW of the through-hole 33H; and an LED element 23 generating the excitation light received by the indicator 22 via the through-hole 33H.

Description

  The present invention relates to a fluorescent sensor that measures the concentration of an analyte in a liquid, and more particularly to a fluorescent sensor that is a microfluorometer manufactured using semiconductor manufacturing technology and MEMS technology.

  Various analyzers for measuring the concentration of an analyte in a liquid, that is, a substance to be measured have been developed. For example, a fluorometer that measures an analyte concentration by injecting a fluorescent dye and a solution to be measured containing an analyte into a transparent container, irradiating excitation light, and measuring the fluorescence intensity from the fluorescent dye is known. . Fluorescent dyes generate fluorescence with intensity corresponding to the analyte concentration when receiving excitation light

  A small-sized 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 in which the analyte in a to-be-measured solution can go in and out, and the photodetector receives the fluorescence which an indicator produces. The photodetector is a photoelectric conversion element and outputs an electrical signal corresponding to the received light intensity. The analyte concentration in the solution is calculated based on the electrical signal from the photodetector.

  In recent years, in order to measure an analyte in a very small amount of sample, a microfluorometer manufactured using a semiconductor manufacturing technique and a MEMS technique has been proposed. Hereinafter, the microfluorometer is referred to as “fluorescence sensor”.

  For example, the fluorescence sensor 110 shown in FIGS. 1 and 2 is disclosed in International Publication No. 2010/119916. The sensor unit 120 which is a main functional unit of the fluorescence sensor 110 includes a silicon substrate 133 on which a photoelectric conversion element 141 is formed, a transparent intermediate layer 132, a filter layer 151, a light emitting element 123, a transparent protective layer 132A, An indicator 122 and a light shielding layer 121 are included. The analyte 9 passes through the light shielding layer 121 and enters and exits the indicator 122. The filter layer 151 blocks excitation light and transmits fluorescence. The light emitting element 123 transmits fluorescence.

  In the fluorescence sensor 110, when the excitation light generated by the light emitting element 123 enters the indicator 122, the indicator 122 generates fluorescence having an intensity corresponding to the analyte concentration.

  Part of the fluorescence generated by the indicator 122 passes through the light emitting element 123 and the filter layer 151, enters the photoelectric conversion element 141, and is photoelectrically converted. Note that the excitation light emitted from the light emitting element 123 in the direction of the photoelectric conversion element 141 (downward) is attenuated by the filter layer 151 to a level causing no problem in measurement as compared with the fluorescence intensity. The fluorescent sensor 110 has a simple configuration and can be easily downsized.

  However, the fluorescent sensor 110 is not easy to manufacture because the light emitting element 115 is mounted between the indicator 122 and the photoelectric conversion element 141.

  Furthermore, since the fluorescence intensity depends on the excitation light intensity, if the fluorescence intensity generated by the light emitting element 115 changes, there is a possibility that accurate measurement may not be easy.

International Publication No. 2010/119916 Pamphlet

  An object of an embodiment of the present invention is to provide a fluorescent sensor with high measurement accuracy.

  The fluorescence sensor of one embodiment of the present invention includes a light-blocking layer that blocks excitation light and fluorescence, through which the analyte passes, an indicator that generates fluorescence with intensity corresponding to the concentration of the analyte when the excitation light is received, An opening on the upper surface is covered with the light-shielding layer, and a substrate portion having a first through hole in which the indicator is disposed, a transparent layer covering the lower surface of the first through hole, and under the transparent layer There is a second through-hole penetrating the first main surface and the second main surface, and a first light receiving portion for detecting the fluorescence generated by the indicator is formed on one main surface. A semiconductor layer in which a second light receiving portion for detecting the excitation light is formed on at least one of the other main surface and the wall surface of the second through hole, and disposed below the second through hole. Received by the indicator through the second through hole. Comprising a light emitting element for generating the excitation light.

  According to the embodiment of the present invention, a fluorescent sensor with high measurement accuracy can be provided.

It is sectional drawing of the sensor part of the conventional fluorescence sensor. It is an exploded view of the sensor part of the conventional fluorescence sensor. It is a perspective view of a sensor system which has a fluorescence sensor of a 1st embodiment. It is an exploded view of the sensor part of the fluorescence sensor of a 1st embodiment. It is a perspective view of the SOI substrate of the fluorescence sensor of 1st Embodiment. It is sectional drawing along the VI-VI line of FIG. 5 of the SOI substrate of the fluorescence sensor of 1st Embodiment. It is sectional drawing for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. It is sectional drawing for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. It is sectional drawing for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. It is sectional drawing for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. It is sectional drawing for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. It is sectional drawing for demonstrating the manufacturing method of the fluorescence sensor of 1st Embodiment. It is sectional drawing of the fluorescence sensor of 2nd Embodiment. It is sectional drawing of the fluorescence sensor of 3rd Embodiment.

<First Embodiment>
First, the sensor system 1 including the fluorescent sensor 10 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 10, 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 fluorescence sensor 10 includes a needle portion 12 that is punctured by a subject, and a connector portion 11 that is joined to a rear end portion of the needle portion 12. Needle portion 12 and connector portion 11 may be integrally formed of the same material, or may be separately manufactured and joined.

  The connector part 11 is detachably fitted to the fitting part 2A of the main body part 2. A plurality of wires (not shown) extending from the sensor unit 20, which is a main function unit disposed at the distal end of the needle unit 12 of the fluorescent sensor 10, have a connector unit 11 and a fitting unit 2 </ b> A of the main unit 2. By mechanically fitting, the main body 2 is electrically connected. The main body unit 2 includes a control unit 2B that performs driving and control of the sensor unit 20, and a calculation unit 2C that processes a signal output from the sensor unit 20. Note that at least one of the control unit 2B and the calculation unit 2C may be disposed in the connector unit 11 or the like of the fluorescent sensor 10, or may be disposed in the receiver 3.

  The fluorescence sensor 10 is a needle-type sensor capable of continuously measuring the analyte concentration for a predetermined period, for example, one week after the sensor unit 20 is inserted into the body. However, the collected body fluid or the body fluid circulating through the body via the flow path outside the body may be brought into contact with the sensor unit 20 outside the body without inserting the sensor unit 20 into the body.

Although not shown, the main body 2 further includes a wireless antenna for transmitting and receiving a wireless signal 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 20 which is a main functional unit of the fluorescence sensor 10 will be described with reference to FIG. 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.

  The fluorescent sensor 10 includes an SOI (Silicon on Insulator) substrate 30 as a main component. In the SOI substrate 30, an active layer (SOI layer) is disposed on a semiconductor substrate via a buried silicon oxide film (Buried Oxide: BOX layer). Hereinafter, the active layer of the SOI substrate 30 is referred to as a semiconductor layer 33, the BOX layer is referred to as a transparent layer 32, and the semiconductor substrate is referred to as a substrate portion 31. The thickness of the semiconductor layer 33 made of silicon is several μm to 100 μm, the thickness of the transparent layer 32 made of silicon oxide having a high light transmittance is 1 μm to several tens of μm, and the thickness of the substrate portion 31 made of single crystal silicon. The thickness is 10 μm to several hundred μm.

  The sensor unit 20 of the fluorescent sensor 10 includes a light shielding layer 21, an indicator 22, an SOI substrate 30, an LED element 23 that is a light emitting element, and a light leakage prevention layer 24. The SOI substrate 30 includes a substrate portion 31, a transparent layer 32, and a semiconductor layer 33 having a second through hole 33H.

The light shielding layer 21 allows the analyte 9 to pass freely, but blocks excitation light and fluorescence. When the indicator 22 receives the excitation light, the indicator 22 generates fluorescence having an intensity corresponding to the concentration of the analyte. The substrate unit 31 includes
There is a first through hole 31H in which the opening on the upper surface is covered with the light shielding layer 21 and the indicator 22 is disposed inside. The transparent layer 32 through which the excitation light and the fluorescence pass covers the lower surface of the first through hole 31H of the substrate portion 31. The second through hole 33H of the semiconductor layer 33 disposed under the transparent layer 32 passes through the first main surface and the second main surface. And the 1st light-receiving part which detects the fluorescence which the indicator 22 generate | occur | produces in one main surface is formed, and the 2nd light-receiving part which detects excitation light on the other main surface or the wall surface of the 2nd through-hole 33H Is formed. The LED 23 disposed below the second through hole 33H generates excitation light received by the indicator 22 through the second through hole 33H.

  The light shielding layer 21 has a thickness of about several tens of μm. The light shielding layer 21 prevents excitation light and fluorescence from leaking to the outside, and at the same time, prevents outside light from entering the inside. The light shielding layer 21 also has analyte permeability that does not prevent the passage of the analyte 9.

  A first through hole 31 </ b> H is formed in the substrate portion 31 of the SOI substrate 30, and a second through hole 33 </ b> H is formed in the semiconductor layer 33. That is, the through hole 31H penetrates the substrate portion 31 and the through hole 33H penetrates the semiconductor layer 33, but both bottom surfaces are concave portions (vias) of the transparent layer 32. The through holes 33 </ b> H and 31 </ b> H are formed in the same region in the XY plane of the substrate portion 31, and both are in contact with each other through the transparent layer 32.

  The indicator 22 filled in the through hole 31H of the SOI substrate 30 generates fluorescence when receiving excitation light by the interaction with the analyte 9 that has entered. The thickness of the indicator 22 is the same as the depth of the through hole 31H, that is, the thickness of the substrate portion 31, and is 10 μm to several hundred μm. The indicator 22 is made of a base material containing a fluorescent dye that generates fluorescence having an intensity corresponding to the amount of the analyte 9 that has entered the inside, that is, the concentration of the analyte in the solution to be measured.

  If the light emitting surface covers the opening of the through hole 33H of the semiconductor layer 33, the LED element 23 uses the through hole 33H as a light guide path to the indicator 22 disposed in the through hole 31H via the transparent layer 32. Is irradiated. Although not shown, the electrode 23T of the LED element 23 is connected to a wiring disposed on the second main surface 33SB of the semiconductor layer 33 via an insulating layer, and the wiring extends to the connector portion 11. Has been.

  The light leakage prevention layer 24 disposed so as to cover the bottom surface (the surface facing the light emitting surface) and the wall surface of the LED element 23 is reflected by the excitation light emitted from the bottom surface and the wall surface and the surface of the semiconductor layer 33. The excitation light is prevented from leaking outside. That is, the light leakage prevention layer 24 has a function similar to that of the light shielding layer 21, but does not require analyte permeability.

  As will be described later, the SOI substrate 30 and the LED element 23 are bonded by a bonding layer 25 (see FIG. 12). The bonding layer 25 also has a function of protecting the PD elements 41 and 42. The bonding layer 25 may be filled in the through hole 33H. Conversely, the bonding layer 25 may not be formed in the region immediately below the opening of the through hole 33H.

  The bonding layer 25 is selected from adhesive materials having characteristics such as electrical insulation, moisture barrier properties, and good transmittance for excitation light. As the bonding layer 25, an epoxy resin, a silicone resin, an organic resin such as a transparent amorphous fluororesin, a transparent inorganic material such as a silicon oxide film or a silicon nitride film, or a composite laminated film thereof can be used. .

  As shown in FIGS. 5 and 6, the semiconductor layer 33 of the SOI substrate 30 of the fluorescence sensor 10 includes photodiodes (Photo Diode: PD) elements 41 and 42 that are light receiving units that convert light into electric signals. Is formed.

  That is, the PD element 41 that is the first light receiving portion is formed around the through hole 33H of the second main surface 33SB of the semiconductor layer 33, and the second light receiving portion is formed on the wall surface 33HW of the through hole 33H. The PD element 42 is formed. The PD element 41 is a first light receiving unit for detecting fluorescence, while the PD element 42 is a second light receiving unit for detecting excitation light.

  Although not shown, the PD elements 41 and 42 are connected to the wiring arranged on the second main surface 33SB via an insulating layer, and the wiring extends to the connector portion 11.

  The PD element 41 is preferably covered with a filter (not shown) that blocks excitation light. Note that the filter is not an essential component, but is preferably disposed to improve detection sensitivity.

  In the fluorescence sensor 10, the analyte concentration is calculated from the signal from the PD element 41 and the signal from the PD element 42. That is, the signal of the PD element 41 indicating the fluorescence intensity is corrected by the signal of the PD element 42 indicating the excitation light intensity. The relationship between the excitation light intensity, the fluorescence intensity, and the analyte concentration is stored in advance in the computing unit 2C, for example.

  The fluorescence sensor 10 can measure with high accuracy even if the excitation light intensity changes.

  Further, the PD element 42 is formed on the wall surface 33HW of the through hole 33H, which is a surface different from the second main surface 33SB on which the PD element 41 is formed. For this reason, it is not necessary to reduce the light receiving area of the PD element 41 in order to form the PD element 42. For this reason, the fluorescence sensor 10 is highly sensitive.

  Further, since the PD element 42 converts surplus carriers generated by the light entering the semiconductor layer 33 from the wall surface 33HW into an electric signal, it also has an effect of improving the S / N ratio of the PD element 41. That is, the PD element 42 also has a function of preventing carriers generated by the excitation light from diffusing inside.

  Furthermore, since the fluorescence sensor 10 uses the SOI substrate 30, it is easy to manufacture. Moreover, since the moisture-containing indicator 22 is sealed inside the through hole 31H, the electric wirings such as the PD elements 41 and 42 and the LED element 23 are not easily adversely affected.

<Method for manufacturing fluorescent sensor>
Next, a method for manufacturing the fluorescence sensor 10 will be described with reference to FIGS. 7 to 12 are partial cross-sectional views of the region of the sensor unit 20 of one fluorescent sensor 10, but in an actual process, after a large number of fluorescent sensors 10 are manufactured collectively as a wafer process. Are separated into individual fluorescent sensors.

  First, as shown in FIG. 7, a mask 30 </ b> M <b> 1 having an opening for forming a through hole 33 </ b> H is disposed on the second main surface 33 </ b> SB of the semiconductor layer 33 of the SOI substrate 30.

  Then, the second main surface 33SB of the semiconductor layer 33 is etched to form the through hole 33H. Various known methods can be used for etching. In particular, a selective etching method in which the etching rate of the transparent layer 32 is very slow as compared with the etching rate of the semiconductor layer 33 is preferable. The transparent layer 32 becomes a so-called etching stop layer, and the through hole 33H penetrates the semiconductor layer 33 and the bottom surface becomes a through via of the transparent layer 32.

  As shown in FIG. 8, a mask 30M2 for forming the PD elements 41 and 42 in a predetermined region is provided. Then, as shown in FIG. 9, PD elements 41 and 42 are formed using a normal semiconductor process. When the semiconductor layer 33 is an N-type semiconductor, the PD elements 41 and 42 form a P-type semiconductor diffusion layer by boron diffusion. Although not shown, phosphorus, arsenic, or the like is introduced into the low resistance region of the semiconductor layer 33 paired with the light receiving portion.

  The photoelectric conversion element may be a photoconductor (photoconductor) element or a phototransistor element.

  The PD element 42 shown in FIG. 5 is formed on the four wall surfaces of the through hole 33H. For this reason, the PD element 41 formed so as to surround the through hole 33H is not adversely affected by the light incident from the wall surface.

  Although not shown, a filter is formed so as to cover the PD element 41. A transparent protective film such as a silicon oxide film may be formed before forming the filter.

  Next, as illustrated in FIG. 10, the through hole 31 </ b> H is formed in the substrate portion 31 by the same formation method as the through hole 33 </ b> H.

  Then, as shown in FIG. 11, the indicator 22 is filled in the through hole 31 </ b> H, and the opening is sealed with the light shielding layer 21.

  The indicator 22 is made of a hydrogel containing a fluorescent dye or a hydrogel combined with a fluorescent dye. The fluorescent dye is selected according to the type of the analyte 9, and any fluorescent dye whose intensity of fluorescence generated according to the amount of the analyte 9 changes reversibly can be used. In order to measure saccharides such as glucose, the fluorescent sensor 10 uses a ruthenium organic complex, a fluorescent phenylboronic acid derivative, or a substance that reversibly binds to glucose such as fluorescein bound to protein.

  Hydrogel components that easily contain water include acrylate hydrogels prepared by polymerizing polysaccharides such as methylcellulose or dextran, monomers such as (meth) acrylamide, methylacrylamide, or hydroxyethyl acrylate, or polyethylene glycol and diisocyanate. Urethane-based hydrogel prepared from the above can be used.

  The indicator 22 may be bonded to the wall surface of the through hole 31H, the light shielding layer 21 on the top surface, the bottom surface 25B of the through hole 31H, or the like via an adhesive layer such as a silane coupling agent.

  Alternatively, the indicator 22 may be manufactured by filling the through hole 31H with an indicator containing a gel skeleton-forming material before polymerization and covering the opening with the light shielding layer 21, followed by polymerization. For example, when a phosphate buffer containing a fluorescent dye, a gel skeleton-forming material, and a polymerization initiator is placed in the through hole 31H and left for 1 hour in a nitrogen atmosphere, the indicator 22 is produced. As the fluorescent dye, 9,10-bis [N- [2- (5,5-dimethylborinan-2-yl) benzyl] -N- [6 ′-[(acryloylpolyethyleneglycol-3400) carbonylamino]- n-hexylamino] methyl] -2-acetylanthracene (F-PEG-AAm), acrylamide as the gel skeleton-forming material, sodium peroxodisulfate and N, N, N ′, N as the polymerization initiator '-Tetramethylethylenediamine is used.

  The light shielding layer 21 has a submicron pore structure, an inorganic thin film such as metal or ceramic, or a composite structure with hydrogels in which carbon black is mixed in a base material of organic polymer such as polyimide or polyurethane, or Furthermore, a resin in which carbon black is mixed into an analyte-permeable polymer such as celluloses or polyacrylamide, or a resin obtained by laminating them can be used.

  In order to prevent reflection of excitation light on the surface of the transparent layer 32, it is preferable that the refractive index of the bonding layer 25 filling the through-hole 33 </ b> H is substantially equal to the refractive index of the transparent layer 32.

  Then, as shown in FIG. 12, the LED element 23 is bonded to the SOI substrate 30 through the bonding layer 25.

  The LED element 23 is selected from a chip on which a light emitting element such as an organic EL element, an inorganic EL element, or a laser diode element is formed. The LED element 23 is a light emitting diode (LED) from the viewpoints of light generation efficiency, wide wavelength selectivity of excitation light, and generation of light having a wavelength other than excitation light. Is preferred.

The bonding layer 25 is produced, for example, by applying a resin and performing a curing process. A transparent SiO ₂ layer or silicon nitride layer or the like may be disposed in advance on the surface to which the resin is applied by a CVD method or the like.

  When the LED element 23 is bonded to the SOI substrate 30, the electrode 23T for the drive signal of the LED element 23 is electrically connected to a wiring (not shown). Since the LED element 23 and the SOI substrate 30 are electrically bonded simultaneously with the physical bonding, the fluorescent sensor 10 can be easily manufactured. The bonding layer 25 also has a function of a sealing member that seals the electrical connection portion.

  Next, the light leakage prevention layer 24 is disposed on the lower surface and the wall surface of the LED element 23. The light leakage prevention layer 24 may be the same material as the light shielding layer 21, or may be an organic resin mixed with carbon black, a metal, or a multilayer film or a composite film made of these materials. Note that the LED element 23 in which the light leakage prevention layer 24 is disposed in advance may be bonded to the SOI substrate 30.

  In addition, when a highly reflective metal film such as aluminum or silver is used as the light leakage prevention layer 24, the reflection light that reflects the excitation light emitted from the bottom surface and the wall surface of the LED element 23 upward, that is, toward the indicator 22 is used. It is also possible to give this function.

  The light leakage prevention layer 24 may also be disposed on the outer surface of the sensor unit 20 such as the entire lower surface of the SOI substrate 30, the wall surface, and the upper surface not covered with the light shielding layer 21.

  As described above, since the fluorescence sensor 10 uses the SOI substrate 30, it can be manufactured easily and can be mass-produced by a wafer process. For this reason, the fluorescence sensor 10 can provide stable quality at low cost.

<Operation of fluorescent sensor>
Next, the operation of the fluorescence sensor 10 will be described.

  The LED element 23 emits pulsed excitation light having a center wavelength of around 375 nm at intervals of, for example, once every 30 seconds. For example, the pulse current to the LED element 23 is 1 mA to 100 mA, and the pulse width of light emission is 1 ms to 100 ms.

  The excitation light generated by the LED element 23 passes through the transparent layer 32 that forms the bottom surface of the through hole 33H and enters the indicator 22. The indicator 22 emits fluorescence having an intensity corresponding to the concentration of the analyte 9. The analyte 9 passes through the light shielding layer 21 and enters the indicator 22. For example, the fluorescent dye of the indicator 22 generates fluorescence having a longer wavelength, for example, 460 nm with respect to excitation light having a wavelength of 375 nm.

  The fluorescence generated by the indicator 22 passes through the transparent layer 32 and the thin semiconductor layer 33 on the transparent layer 32 side of the PD element 41 and enters the PD element 41. That is, as already described, the PD element 41 is a diffusion layer in which impurities are introduced from the surface of the semiconductor layer 33, and the thin semiconductor layer 33 remains on the transparent layer 32 side. Since the fluorescence transmittance of the semiconductor layer 33 is not high, the thickness of the semiconductor layer 33 remaining on the transparent layer 32 side is preferably 10 μm or less, particularly preferably 3 μm or less. The fluorescence is photoelectrically converted by the PD element 41, and the generated photogenerated charge is output as a detection signal.

  On the other hand, a part of the excitation light generated by the LED element 23 enters the PD element 42 formed on the wall surface 33HW of the through hole 33H, and a detection signal is output.

  Since the photo-generated charges due to the excitation light incident on the wall surface 33HW become detection signals by the PD element 42, the PD element 41 is not adversely affected.

  In the fluorescent sensor 10, the calculation unit 2C of the main body unit 2 calculates based on the detection signal, that is, the current caused by the photogenerated charges from the PD elements 41 and 42 or the voltage caused by the accumulated photogenerated charges. Processing is performed to calculate the amount of analyte.

Second Embodiment
Next, a sensor system 1A having the fluorescence sensor 10A and the fluorescence sensor 10A of the second embodiment will be described. Since the fluorescent sensor 10A and the like are similar to the fluorescent sensor 10 and the like, the same components are denoted by the same reference numerals and description thereof is omitted.

  As shown in FIG. 13, in the fluorescence sensor 10A, a PD element 43, which is a third light receiving portion for detecting fluorescence, is formed on the wall surface of the through hole 31H of the substrate portion 31 made of silicon. The PD element 43 is preferably covered with a filter (not shown) that blocks excitation light and transmits fluorescence.

The filter may be a multiple interference type such as a dielectric multilayer film, but is preferably an absorption type, for example, a single layer made of silicon, silicon carbide, silicon oxide, silicon nitride, or an organic material, or the single layer It is a multilayer layer in which layers are stacked. For example, the transmittance of the silicon layer and the silicon carbide layer is 10 ⁻⁵ % or less at the excitation light wavelength of 375 nm, whereas the transmittance is 10% or more at the fluorescence wavelength of 460 nm (the transmittance of the excitation light wavelength). (Transmittance of fluorescence wavelength) and the transmittance selectivity of 6 digits or more.

  The PD element 43 is formed by the same method as the PD element 42 and the like after the through hole 31H is formed. In addition, the PD element 43 should just be formed in at least one part of the wall surface of the through-hole 31H.

  The fluorescence sensor 10A and the like have the effect of the fluorescence sensor 10 and can convert fluorescence into an electric signal more efficiently, and thus have higher accuracy.

<Third Embodiment>
Next, the fluorescence sensor 10B of 3rd Embodiment and the sensor system 1B which has the fluorescence sensor 10B are demonstrated. Since the fluorescent sensor 10B and the like are similar to the fluorescent sensor 10 and the like, the same components are denoted by the same reference numerals and description thereof is omitted.

  As shown in FIG. 14, in the fluorescence sensor 10 </ b> B, the PD element 41 </ b> B that is a first light receiving unit that detects fluorescence is formed on the first main surface 33 </ b> SA of the semiconductor layer 33, and the second light receiving unit that detects excitation light. The PD element 42 </ b> B as a part is formed on the second main surface 33 </ b> SB of the semiconductor layer 33.

  In the fluorescent sensor 10B, the PD element 41B is first formed when the SOI substrate 30B is manufactured. That is, after the transparent layer 32 is disposed on the substrate portion 31, a silicon layer having a predetermined thickness is disposed. Impurities are doped by the same method as already described to form a PD element 41B having a predetermined thickness. Then, a silicon layer is further disposed on the PD element 41B to form the PD element 42B.

  The PD element 42B may be formed after the through hole 33H is formed. At this time, the PD element 42B which is an excitation light illuminance monitor may be formed up to the wall surface of the through hole 33H.

  The fluorescence generated by the indicator 22 enters the PD element 41 </ b> B through the transparent layer 32. On the other hand, the excitation light generated by the LED element 23 enters the PD element 42 </ b> B through the bonding layer 25. Since the carrier generated in each PD element becomes a signal in each PD element, it does not adversely affect another PD element. In addition, the signal according to the wavelength of the light to detect can be efficiently output by changing the bias voltage applied to PD element 41B and PD element 42B.

  The fluorescence sensor 10B and the like have the same effects as the fluorescence sensor 10.

  In the fluorescent sensor 10B, the third PD element may be formed on the wall surface of the through hole 31H, as in the fluorescent sensor 10A.

  In the above description, the fluorescent sensor 10 that detects saccharides such as glucose has been described as an example. However, by selecting a fluorescent dye, various applications such as an enzyme sensor, a pH sensor, an immunosensor, or a microorganism sensor can be supported. . For example, when measuring the concentration of hydrogen ions or carbon dioxide in a living body, a hydroxypyrenetrisulfonic acid derivative or the like is used as a fluorescent dye, and a phenylboronic acid derivative having a fluorescent residue is used when measuring a saccharide. When a potassium ion is used, a crown ether derivative having a fluorescent residue is used.

  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.

DESCRIPTION OF SYMBOLS 1, 1A, 1B ... Sensor system 2 ... Main-body part 3 ... Receiver 9 ... Analyte 10, 10A, 10B ... Fluorescence sensor 20 ... Sensor part 21 ... Light shielding layer 22 ... Indicator 23 ... LED element 24 ... Light leakage prevention layer 25 ... Bonding Layer 30 ... SOI substrate 31 ... Substrate portion 31H ... Through hole 32 ... Transparent layer 33 ... Semiconductor layer 33H ... Through hole 41-43 ... PD element

Claims (4)

A light-shielding layer that blocks excitation light and fluorescence through which the analyte passes;
An indicator that generates fluorescence having an intensity corresponding to the concentration of the analyte when receiving the excitation light;
A substrate portion having a first through hole in which an opening on an upper surface is covered with the light shielding layer and the indicator is disposed inside;
A transparent layer covering the lower surface of the first through hole;
There is a second through hole disposed under the transparent layer and penetrating the first main surface and the second main surface, and the first fluorescent light generated by the indicator is detected on one main surface. A semiconductor layer in which a light receiving part is formed and a second light receiving part for detecting the excitation light is formed on at least one of the other main surface and the wall surface of the second through hole;
And a light emitting element for generating the excitation light received by the indicator through the second through hole, which is disposed below the second through hole. The semiconductor layer is the active layer of an SOI substrate in which an active layer is disposed on a support substrate via an oxide film;
The substrate unit is the support substrate of the SOI substrate;
The fluorescent sensor according to claim 1, wherein the transparent layer is the oxide film of the SOI substrate.   The fluorescence sensor according to claim 2, wherein the analyte concentration is calculated from a signal from the first light receiving unit and a signal from the second light receiving unit. A third light receiving portion for detecting the fluorescence is formed on a wall surface of the first through hole of the substrate portion;
4. The fluorescence sensor according to claim 3, wherein the analyte concentration is calculated from a signal from the first light receiving unit, a signal from the second light receiving unit, and a signal from the third light receiving unit.

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