Optical sensor and detection device

JPWO2023238705A5Active Publication Date: 2025-02-04MURATA MFG CO LTD
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Patent Information

Application Number
JP2024526372
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-05-26
Filing Date
2023-05-26
Publication Date
2025-02-04
Estimated Expiration
2043-05-26

AI Technical Summary

Technical Problem

Existing biosensors can only detect one type of substance at a time, limiting their ability to accurately detect multiple items simultaneously.

Method used

An optical sensor incorporating multiple types of quantum dots, enzymes, and quenchers within a hydrogel, where the enzyme reactions and energy transfer between quantum dots and quenchers allow for the detection of various substances by adjusting the energy levels and band gaps of the quantum dots, enabling the separation of fluorescence peaks for accurate detection of multiple items.

Benefits of technology

Enables the high-accuracy detection of multiple substances using a single sensor by preventing wavelength overlap and ensuring that each quencher reacts with only one type of quantum dot, allowing for precise identification of different substances.

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Abstract

An optical sensor 1 includes a fluorescent part (for example, a fluorescent layer 10) that contains a plurality of types of quantum dots 50, enzymes 60, and quenchers 70 in a hydrogel 15.
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Description

Optical sensors and detection devices

[0001] The present invention relates to optical sensors and detection devices.

[0002] Non-Patent Document 1 discloses a biosensor using quantum dots and an enzyme. In the biosensor described in Non-Patent Document 1, quantum dot-enzyme conjugates are confined in a hydrogel.

[0003] Biosensors and Bioelectronics 31 (2012) 529-536

[0004] In the example of Non-Patent Document 1, a biosensor is constructed by arranging a glucose sensor using glucose oxidase (GOX) as an enzyme and an alcohol sensor using alcohol oxidase (AOX) as an enzyme in the middle of a microchannel.

[0005] However, the biosensor described in Non-Patent Document 1 can only detect either glucose or alcohol using one sensor, so it is desirable to be able to detect multiple items using one sensor.

[0006] An object of the present invention is to provide an optical sensor capable of detecting a plurality of items with high accuracy, and a detection device including the optical sensor.

[0007] The optical sensor of the present invention comprises a fluorescent part containing multiple types of quantum dots, enzymes, and quenchers in a hydrogel.

[0008] The detection device of the present invention comprises a light-transmitting container, a sensor unit arranged inside the container, and a light-emitting element and a light-receiving element arranged outside the container so as to face the sensor unit, and the sensor unit is an optical sensor of the present invention.

[0009] According to the present invention, it is possible to provide an optical sensor capable of detecting a plurality of items with high accuracy. Furthermore, according to the present invention, it is possible to provide a detection device including the optical sensor.

[0010] FIG. 1 is a schematic diagram illustrating the principle of quantum dot luminescence. FIG. 2 is a schematic diagram illustrating the principle of quantum dot quenching by a quencher. FIG. 3 is a schematic diagram illustrating an example of a combination of quantum dots and a quencher. FIG. 4 is a schematic diagram illustrating another example of a combination of quantum dots and a quencher. FIG. 5 is a schematic diagram illustrating an optical sensor according to an embodiment of the present invention. FIG. 6A is a schematic diagram illustrating an example of red quantum dots contained in a hydrogel. FIG. 6B is a schematic diagram illustrating an example of green quantum dots contained in a hydrogel. FIG. 7 is a graph showing the relationship between glucose concentration and lactic acid concentration and green fluorescence peak intensity. FIG. 8 is a graph showing the relationship between glucose concentration and lactic acid concentration and red fluorescence peak intensity. FIG. 9 is a schematic diagram illustrating an example of a quantum dot and an enzyme complexed together. FIG. 10 is a schematic diagram illustrating a detection device according to an embodiment of the present invention. FIG. 11 is a schematic diagram illustrating an enlarged portion of the detection device shown in FIG. 10. FIG. 12 is a schematic diagram illustrating a detection device according to another embodiment of the present invention.

[0011] The optical sensor and detection device of the present invention will be described below. Note that the present invention is not limited to the following configurations and may be modified as appropriate within the scope of the present invention. Furthermore, a combination of multiple individual preferred configurations described below also constitutes the present invention.

[0012] The drawings shown below are schematic diagrams, and the dimensions, aspect ratio, scale, etc. may differ from those of the actual product.

[0013] [Optical Sensor] The optical sensor of the present invention comprises a fluorescent part containing multiple types of quantum dots, enzymes, and quenchers in a hydrogel.

[0014] The optical sensor of the present invention utilizes an enzyme reaction in which an enzyme reacts with a substance to be detected. This method allows for the detection of various substances by changing the enzyme.

[0015] Furthermore, the optical sensor of the present invention utilizes the phenomenon in which electrons excited in quantum dots are transferred to a quencher. As will be described later, the quencher includes those generated by enzyme reactions (H 2 O 2Coenzymes that help enzymes function can also function as quenchers.

[0016] FIG. 1 is a schematic diagram for explaining the light emission principle of quantum dots.

[0017] As shown in Figure 1, when a quantum dot is excited, the excited electrons emit fluorescence when they return to the ground state. Specifically, electrons in the valence band VB are excited to the conduction band CB by excitation light, and fluorescence is emitted when the electrons return from the conduction band CB to the valence band VB. The band gap shown in Figure 1 corresponds to the color (emission wavelength) of the quantum dot. In some cases, a defect level exists below the conduction band CB, and fluorescence is emitted when the electrons return from the defect level to the valence band VB.

[0018] FIG. 2 is a schematic diagram for explaining the principle of quenching of quantum dots by a quencher.

[0019] As shown in Figure 2, when electrons excited to the conduction band CB move from the quantum dot to the quencher, the quantum dot stops emitting fluorescence. It is believed that an optimal value exists for the energy difference ΔE between the quantum dot and the quencher in order for electrons to move (Marcus theory). In Figure 2, LUMO represents the lowest unoccupied molecular orbital, and HOMO represents the highest occupied molecular orbital. While Figure 2 shows an example in which electrons move to the LUMO, electron transfer to other molecular orbitals may also be used. The same applies to Figures 3 and 4, which will be described later.

[0020] In the optical sensor of the present invention, multiple types of quantum dots, enzymes, and quenchers are confined within the hydrogel. This allows a single sensor to detect multiple items. However, if the quencher reacts with multiple types of quantum dots, the detection accuracy may be reduced.

[0021] However, quantum dots used as phosphors have small wavelength dispersion and can adjust the center wavelength by changing the size, composition, etc., so that the wavelength bands of multiple colors for each quantum dot do not overlap. Thus, in the optical sensor of the present invention, the use of quantum dots as phosphors makes it easy to adjust the color, allowing a color that easily transfers electrons to the quencher to be selected. Therefore, the quencher can be prevented from reacting with multiple types of quantum dots, allowing for accurate detection of multiple items.

[0022] Furthermore, if at least one quencher has a relationship in which it reacts with only one quantum dot, even if another quencher reacts with multiple quantum dots, the peaks of both can be separated, allowing each item to be detected with high accuracy. Therefore, in the optical sensor of the present invention, it is sufficient that at least one quencher has a relationship in which it reacts with only one quantum dot, but it is preferable that all quenchers have a relationship in which they react with multiple types of quantum dots in a one-to-one relationship.

[0023] FIG. 3 is a schematic diagram for explaining an example of a combination of quantum dots and a quencher.

[0024] As shown in Fig. 3, as a combination of a certain type of quantum dot and a quencher that quenches the fluorescence of that quantum dot, it is preferable to combine a quantum dot with a low energy level at the bottom of the conduction band CB (quantum dot 1 in Fig. 3) with a quencher with a low LUMO energy level (quencher 1 in Fig. 3), and to combine a quantum dot with a high energy level at the bottom of the conduction band CB (quantum dot 2 in Fig. 3) with a quencher with a high LUMO energy level (quencher 2 in Fig. 3). The same applies to combinations of quantum dots and quenchers when there are three or more types.

[0025] Alternatively, as a combination of a certain type of quantum dot and a quencher that quenches the fluorescence of the quantum dot, it is preferable to combine a quantum dot with a small band gap (quantum dot 1 in FIG. 3) with a quencher with a low LUMO energy level (quencher 1 in FIG. 3), and to combine a quantum dot with a large band gap (quantum dot 2 in FIG. 3) with a quencher with a high LUMO energy level (quencher 2 in FIG. 3). The same applies to combinations of quantum dots and quenchers when there are three or more types.

[0026] FIG. 4 is a schematic diagram for explaining another example of a combination of quantum dots and a quencher.

[0027] As shown in FIG. 4 , a combination of a certain type of quantum dot and a quencher that quenches the fluorescence of that quantum dot may be such that a quantum dot having a high energy level at the bottom of the conduction band CB (quantum dot 1 in FIG. 4 ) is combined with a quencher having a high LUMO energy level (quencher 1 in FIG. 4 ), and a quantum dot having a low energy level at the bottom of the conduction band CB (quantum dot 2 in FIG. 4 ) is combined with a quencher having a low LUMO energy level (quencher 2 in FIG. 4 ). Unlike the example shown in FIG. 3 , the example shown in FIG. 4 combines a quantum dot having a small band gap (quantum dot 1 in FIG. 4 ) with a quencher having a high LUMO energy level (quencher 1 in FIG. 4 ), and a quantum dot having a large band gap (quantum dot 2 in FIG. 4 ) with a quencher having a low LUMO energy level (quencher 2 in FIG. 4 ). When the materials constituting the quantum dots are different, the positions of the energy bands are different, and therefore, such a combination of quenchers can be achieved by using quantum dots 1 and 2 made of different materials. The same applies to combinations of quantum dots and quenchers when there are three or more types.

[0028] The energy level of the quencher is related to the oxidation-reduction potential, and can therefore be measured by electrochemical measurement.

[0029] For example, a working electrode (e.g., platinum), a reference electrode (e.g., silver / silver chloride), and a counter electrode (e.g., platinum) are placed in a solution containing a substance to be detected (e.g., glucose), and cyclic voltammetry measurement is performed using a potentiostat. 2 O 2 A hydrogel containing the quencher (which is not necessary when produced by an enzymatic reaction, as in the case of ) is formed, and the redox reaction of the quencher occurs in conjunction with the enzymatic reaction. When the current is measured while sweeping the voltage, a current peak is observed at the redox potential of the quencher. The energy level of the quencher can be determined from the level of the redox potential.

[0030] On the other hand, the energy level of quantum dots can be measured by methods such as photoelectron spectroscopy, optical absorption spectroscopy, etc. In particular, in the case of quantum dots of the same material but with different composition ratios (such as ZAIS, which will be described later), the energy level can also be determined from the size of the band gap (short wavelength emission: large band gap, long wavelength emission: small band gap), as in the example shown in Figure 3.

[0031] In the optical sensor of the present invention, the quantum dots are, for example, ZnS-AgInS 2 Examples of quantum dots include solid solutions (ZAIS). By changing the composition ratio of ZAIS, it is possible to prepare multiple types of quantum dots with different band gaps. Furthermore, using ZAIS as quantum dots can reduce toxicity compared to quantum dots containing elements such as Cd.

[0032] The optical sensor of the present invention may further include reference quantum dots in the hydrogel. The reference quantum dots are quantum dots that are unlikely to react with the substance to be detected and emit a constant light as a reference. The reference quantum dots are confined in a protective film such as glass beads.

[0033] In the optical sensor of the present invention, the quencher may be one that has been added to the hydrogel in advance, or one that has been produced by an enzymatic reaction. 2 O 2 is dissolved O 2On the other hand, when a quencher is added, the presence or absence of the quencher affects the dissolved O 2 It is not affected by concentration and the choice of enzymes is expanded.

[0034] In the optical sensor of the present invention, the hydrogel is preferably non-ionic. By using a non-ionic hydrogel, even if a quencher having a charge is used, the quencher is not trapped by the charge of the hydrogel, and the quencher can move freely and quench the quantum dots. This allows for a wider range of quencher options.

[0035] The optical sensor of the present invention may include a fluorescent layer as the fluorescent portion.

[0036] The optical sensor of the present invention preferably further comprises a light-transmitting support member on one main surface side of the fluorescent layer, which can support the fluorescent layer.

[0037] The support member may be made of an inorganic material or an organic material. Examples of support members made of inorganic materials include glass substrates. Examples of support members made of organic materials include resin films such as polyethylene terephthalate (PET) films.

[0038] The optical sensor of the present invention preferably further comprises a light-shielding layer on the other main surface side of the fluorescent layer, and in this case, the optical sensor of the present invention may further comprise a reflective layer between the fluorescent layer and the light-shielding layer.

[0039] FIG. 5 is a schematic diagram showing an optical sensor according to one embodiment of the present invention.

[0040] 5 includes a fluorescent layer 10 as a fluorescent portion. A support member 20 is provided on one main surface of the fluorescent layer 10, and a light-shielding layer 30 is provided on the other main surface of the fluorescent layer 10. Furthermore, a reflective layer 40 is provided between the fluorescent layer 10 and the light-shielding layer 30.

[0041] For example, the optical sensor 1 is fabricated by using a PET film as the support member 20 and coating the fluorescent layer 10, the reflective layer 40, and the light-shielding layer 30 on the support member 20 in this order.

[0042] The fluorescent layer 10 contains multiple types of quantum dots 50 , enzymes 60 , and quenchers 70 in a hydrogel 15 .

[0043] The light-shielding layer 30 is made of polyethylene glycol (PEG) hydrogel mixed with carbon black.

[0044] The reflective layer 40 is made of polyethylene glycol (PEG) hydrogel with TiO 2 The particles are mixed.

[0045] As an example specifically illustrating the optical sensor of the present invention, an optical sensor was fabricated by the following method: It should be noted that the present invention is not limited to the following example.

[0046] A 0.8 mL solution of a mixture of acrylamide:N,N'-methylenebisacrylamide = 29:1 4 w / v%, red quantum dots ZAIS-QD 0.17 μM, green quantum dots ZAIS-QD 4.7 μM, glucose dehydrogenase (GDH) 44 unit / mL, lactate oxidase (LOx) 2.9 unit / mL, β-nicotinamide adenine dinucleotide (NAD) 1.8 mM, ammonium peroxodisulfate 0.1 w / v%, and N,N,N',N'-tetramethylethylenediamine 0.04 v / v% in phosphate buffered saline (PBS) was dropped onto the support member and allowed to harden in an airtight environment.

[0047] GDH and LOx are enzymes, and NAD serves as both a quencher and a coenzyme for GDH. Ammonium peroxodisulfate and N,N,N',N'-tetramethylethylenediamine are polymerization initiators. M stands for mol / L.

[0048] FIG. 6A is a schematic diagram showing an example of red quantum dots contained in a hydrogel.

[0049] The red quantum dot 51 is, for example, a core-shell quantum dot composed of a core 51A and a shell 51B that covers the core 51A.

[0050] FIG. 6B is a schematic diagram showing an example of green quantum dots contained in a hydrogel.

[0051] The green quantum dot 52 is, for example, a core-shell quantum dot composed of a core 52A and a shell 52B that covers the core 52A.

[0052] Among the enzymes contained in the fluorescent layer 10, lactate oxidase (LOx) undergoes an enzymatic reaction with lactic acid (Lac), which is one of the substances to be detected. 2 O 2 is generated, selectively reducing the emission of the red quantum dots 51.

[0053] Among the enzymes contained in the fluorescent layer 10, glucose dehydrogenase (GDH) undergoes an enzymatic reaction with glucose (Glu), which is one of the substances to be detected, and at the same time, reduces the quencher NAD, thereby eliminating the quenching function and increasing the luminescence of the red quantum dots 51 and the green quantum dots 52.

[0054] The fluorescence spectrum of the optical sensor 1 placed in the PBS solution was measured using a plate reader.

[0055] First, the sensor fluorescence was measured using a plate reader by exciting at a wavelength of 450 nm, and a spectrum with overlapping green and red was obtained. A Gaussian function was used to separate the spectrum into a first peak (green) and a second peak (red). The respective peak values ​​for green and red were used as the measured values.

[0056] The relationship between the glucose concentration and the lactic acid concentration and the green fluorescence peak intensity is shown in Table 1, and the relationship between the glucose concentration and the lactic acid concentration and the red fluorescence peak intensity is shown in Table 2. The fluorescence peak intensity is a normalized value, with 1 being the value when the elapsed time is 0 minutes.

[0057]

[0058]

[0059] Fig. 7 is a graph showing the relationship between the glucose concentration and lactic acid concentration and the green fluorescent peak intensity. Fig. 8 is a graph showing the relationship between the glucose concentration and lactic acid concentration and the red fluorescent peak intensity.

[0060] As can be seen from FIG. 7, the green fluorescence peak increased when glucose (Glu) was added, but the change was small when lactic acid (Lac) was added.

[0061] As can be seen from FIG. 8, the red fluorescence peak increased when glucose (Glu) was added, and decreased when lactic acid (Lac) was added.

[0062] From the above results, after determining the glucose concentration using the green signal, the lactate concentration can also be determined by subtracting the contribution of glucose from the red signal. Therefore, both glucose and lactate concentrations can be detected using a single sensor.

[0063] In the optical sensor of the present invention, the fluorescent portion (fluorescent layer) may include reference quantum dots. In this case, the reference quantum dots may be, for example, core-shell quantum dots composed of a core and a shell covering the core, and may be surrounded by a protective film such as glass beads. Because the reference quantum dots are confined in a protective film such as glass beads, they do not react to the detection target and emit a constant amount of light as a reference. Therefore, by using the reference light emission as a reference and observing the ratio of, for example, red light emission to green light emission, the sensor response can be detected without being affected by the state of the intermediate path.

[0064] In the optical sensor of the present invention, at least one type of quantum dot may be conjugated with an enzyme, in which case one type of quantum dot may be conjugated with an enzyme, two or more types of quantum dots may be conjugated with an enzyme, or all types of quantum dots may be conjugated with an enzyme.

[0065] When quantum dots are conjugated with enzymes, the enzyme reaction occurs near the quantum dots, improving the sensor response, and thus increasing the sensor's sensitivity and shortening the response time.

[0066] FIG. 9 is a schematic diagram showing an example of a state in which quantum dots and an enzyme are combined.

[0067] In the example shown in FIG. 9, a quantum dot 50 is conjugated with four enzymes 60 .

[0068] The quantum dots 50 are, for example, ZnS-AgInS 2 It is a solid solution (ZAIS).

[0069] The quantum dots 50 may be coordinated with a ligand such as mercaptopropionic acid.

[0070] The enzyme 60 is, for example, glucose oxidase (GOx, GOD) or glucose dehydrogenase (GDH).

[0071] [Detection device] The detection device of the present invention comprises a light-transmitting container, a sensor unit arranged inside the container, and a light-emitting element and a light-receiving element arranged outside the container so as to face the sensor unit, and the sensor unit is the optical sensor of the present invention.

[0072] In the detection device of the present invention, data acquired from a sensor unit placed inside a container can be read outside the container. In this way, data acquisition and reading are separated between the inside and outside of the container, which makes it possible to prevent bacteria and other contaminants from entering the container.

[0073] The detection device of the present invention can flexibly accommodate various container shapes. In addition, by arranging multiple optical sensors of the present invention in one container, it can also accommodate multi-point measurements.

[0074] The detection device of the present invention can be used, for example, to monitor cellular metabolism.

[0075] The detection device of the present invention preferably further includes a communication unit on the outside of the container that transmits data acquired from the sensor unit to an external device. In particular, it is preferable that the communication unit wirelessly transmits the data acquired from the sensor unit to the external device.

[0076] Fig. 10 is a schematic diagram showing a detection device according to one embodiment of the present invention, and Fig. 11 is a schematic enlarged view of the detection device shown in Fig. 10.

[0077] 10 and 11 is applied to a container 110 for small-scale culture, such as a petri dish, a flask, etc. In the example shown in Fig. 10, the container 110 is placed in an incubator.

[0078] In the detection device 100, a sensor unit 120 is disposed inside a container 110, and a light-emitting element 130 and a light-receiving element 140 are disposed outside the container 110 so as to face the sensor unit 120. The sensor unit 120 is, for example, the optical sensor 1 shown in FIG.

[0079] The detection device 100 preferably further includes a communication unit 150 outside the container 110, which transmits data acquired from the sensor unit 120 to an external device. In the example shown in Fig. 10, the communication unit 150 wirelessly transmits the data acquired from the sensor unit 120 to a computer PC, which is an example of an external device. The computer PC, which is an example of an external device, receives data compliant with a standard such as BLE (Bluetooth (registered trademark) Low Energy) via an antenna ANT.

[0080] FIG. 12 is a schematic diagram showing a detection device according to another embodiment of the present invention.

[0081] A detection device 100A shown in FIG. 12 is applied to a vessel 110A for mass culture such as a bioreactor.

[0082] In the detection device 100A, a plurality of sensor units 120 are arranged inside a container 110A, and a light-emitting element 130 and a light-receiving element 140 are arranged outside the container 110A so as to face each of the sensor units 120. The sensor units 120 are, for example, the optical sensor 1 shown in FIG.

[0083] The detection device 100A preferably further includes a communication unit 150 outside the container 110A that transmits data acquired from the sensor unit 120 to an external device (not shown).

[0084] In yet another embodiment of the present invention, the container (not shown) constituting the detection device may be a single-use bag (disposable bag). In this case, the sensor unit may be attached to the single-use bag or may be crimped and incorporated therein.

[0085] The optical sensor of the present invention is not limited to the above embodiment, as long as it includes a fluorescent portion containing multiple types of quantum dots, enzymes, and quenchers in a hydrogel. Similarly, the detection device of the present invention is not limited to the above embodiment, as long as it includes a sensor portion disposed inside a light-transmitting container, a light-emitting element and a light-receiving element disposed outside the container so as to face the sensor portion, and the sensor portion is the optical sensor of the present invention. Therefore, various applications and modifications can be made within the scope of the present invention regarding the configuration, manufacturing conditions, etc. of the optical sensor and detection device.

[0086] The present specification discloses the following:

[0087] <1> An optical sensor having a fluorescent part containing multiple types of quantum dots, enzymes, and quenchers in a hydrogel.

[0088] <2> The optical sensor according to <1>, wherein a combination of a certain type of quantum dot and a quencher that quenches fluorescence from the quantum dot is such that a quantum dot having a high energy level at the bottom of the conduction band is combined with a quencher having a high LUMO energy level, and a quantum dot having a low energy level at the bottom of the conduction band is combined with a quencher having a low LUMO energy level.

[0089] <3> The optical sensor according to <1> or <2>, wherein a combination of a certain type of quantum dot and a quencher that quenches fluorescence from the quantum dot is such that a quencher having a low LUMO energy level is combined with a quantum dot having a small band gap, and a quencher having a high LUMO energy level is combined with a quantum dot having a large band gap.

[0090] <4> The optical sensor according to any one of <1> to <3>, further comprising reference quantum dots in the hydrogel.

[0091] <5> The optical sensor according to any one of <1> to <4>, further comprising: a fluorescent layer as the fluorescent portion; and a light-transmitting support member on one main surface side of the fluorescent layer.

[0092] <6> The optical sensor according to <5>, further comprising a light-shielding layer on the other main surface side of the fluorescent layer.

[0093] <7> The optical sensor according to <6>, further comprising a reflective layer between the fluorescent layer and the light-shielding layer.

[0094] <8> The optical sensor according to any one of <1> to <7>, wherein at least one type of quantum dot and the enzyme are conjugated.

[0095] <9> The optical sensor according to any one of <1> to <8>, wherein the hydrogel is nonionic.

[0096] <10> A detection device comprising: a light-transmitting container; a sensor unit disposed inside the container; and a light-emitting element and a light-receiving element disposed outside the container so as to face the sensor unit, wherein the sensor unit is the optical sensor according to any one of <1> to <9>.

[0097] <11> The detection device according to <10>, further comprising a communication unit on the outside of the container that transmits data acquired from the sensor unit to an external device.

[0098] REFERENCE SIGNS LIST 1 Optical sensor 10 Fluorescent layer (fluorescent portion) 15 Hydrogel 20 Support member 30 Light-shielding layer 40 Reflective layer 50 Quantum dot 51 Red quantum dot 51A Red quantum dot core 51B Red quantum dot shell 52 Green quantum dot 52A Green quantum dot core 52B Green quantum dot shell 60 Enzyme 70 Quencher 100, 100A Detector 110, 110A Container 120 Sensor portion 130 Light-emitting element 140 Light-receiving element 150 Communication portion

Claims

1. An optical sensor comprising a fluorescent portion containing multiple types of quantum dots, enzymes, and quenchers in a hydrogel.

2. A combination of a certain type of quantum dot and a quencher that quenches the fluorescence of the quantum dot is Quantum dots with a high energy level at the bottom of the conduction band are combined with a quencher with a high LUMO energy level.

2. The optical sensor according to claim 1, wherein a quantum dot having a low energy level at the bottom of the conduction band is combined with a quencher having a low LUMO energy level.

3. A combination of a certain type of quantum dot and a quencher that quenches the fluorescence of the quantum dot is Quantum dots with small band gaps are combined with quenchers with low LUMO energy levels, 3. The optical sensor according to claim 1, wherein a quantum dot having a large band gap is combined with a quencher having a high LUMO energy level.

4. The optical sensor according to claim 1 or 2, further comprising reference quantum dots in the hydrogel.

5. The fluorescent portion includes a fluorescent layer, The optical sensor according to claim 1 , further comprising a light-transmitting support member on one main surface side of the fluorescent layer.

6. The optical sensor according to claim 5 , further comprising a light-shielding layer on the other main surface side of the fluorescent layer.

7. The optical sensor of claim 6 , further comprising a reflective layer between the fluorescent layer and the light-shielding layer.

8. 3. The optical sensor according to claim 1, wherein at least one type of said quantum dot and said enzyme are conjugated.

9. The optical sensor of claim 1 or 2, wherein the hydrogel is non-ionic.

10. A light-transmitting container; A sensor unit disposed inside the container; a light emitting element and a light receiving element that are arranged on the outside of the container so as to face the sensor unit, A detection device, wherein the sensor portion is the optical sensor according to claim 1 or 2.

11. The detection device according to claim 10 , further comprising a communication unit on the outside of the container, the communication unit transmitting data acquired from the sensor unit to an external device.