Detection kit, detection system and detection method for target substance

Abstract

To stably detect a detection target substance that might be contained in a gaseous sample, by a simple structure.SOLUTION: A sheet sensor 1 includes a photonic crystal 12, an antibody 13, and a hydrogel 14. The photonic crystal 12 includes a minute structure (a plurality of small holes) formed so that the index of refraction changes at cycles of not larger than the wavelength of an incident light L1. The antibody 13 is fixed to the photonic crystal 12 and can make a detection target substance (a virus, for example) specifically attach to the antibody. The hydrogel 14 is arranged on the photonic crystal 12 to cover the antibody 13. The hydrogen 14 holds an aqueous liquid to be a place of reaction to make the detection target substance specifically attach to the antibody 13.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The present disclosure relates to a detection kit, a detection system, and a detection method for a target substance, and more particularly to a detection technique for a target substance that may be contained in a gas sample. [Background technology]

[0002] Techniques for detecting target substances using photonic crystals have been proposed. For example, an optical sensor disclosed in International Publication No. 2010 / 044274 (Patent Document 1) includes a concave-convex structure that functions as a photonic crystal in which predetermined shapes are periodically arranged two-dimensionally, and a metal layer that is formed on the surface of the concave-convex structure and is capable of exciting localized surface plasmon resonance. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2010 / 044274 [Patent Document 2] Japanese Patent Application Laid-Open No. 2005-180928 [Non-patent literature]

[0004] [Non-Patent Document 1] Nao Kobayashi, Tomoya Shimizu, Hiroki Kawasaki, Hirozora Yamada, Hideaki Hisamoto, Takeshi Sueyoshi, Tatsuro Endo, "Fabrication of TiO2 Hydrogel Hybrid Photonic Crystals Aimed at Highly Sensitive Fluorescence-Enhanced Biosensing," 39th Workshop of the Society of Chemistry and Micro-Nano Systems, May 27-28, 2019 Summary of the Invention [Problem to be solved by the invention]

[0005] There is a demand for detecting and identifying the types of target substances (e.g., viruses, microorganisms, pollen, etc. floating in the air) that may be contained in a gas sample. In particular, it is desirable to be able to stably detect target substances with as simple a configuration as possible.

[0006] The present disclosure has been made to solve the above-mentioned problems, and an object of the present disclosure is to stably detect a target substance that may be contained in a gas sample using a simple configuration. [Means for solving the problem]

[0007] (1) A detection kit for a target substance according to one aspect of the present disclosure detects a target substance that may be contained in a gas sample by irradiating it with incident light. The detection kit includes a photonic crystal, a host material, and a water-retaining layer. The photonic crystal includes a periodically arranged microstructure. The host material is fixed to the microstructure and is capable of specifically adhering the target substance. The water-retaining layer is disposed on the photonic crystal so as to cover the host material. The water-retaining layer retains an aqueous liquid that provides a reaction site for specifically adhering the target substance to the host material.

[0008] (2) The water-retaining layer contains a hydrogel.

[0009] (3) The hydrogel includes at least one of polyethylene glycol diacrylate, polyacrylamide, collagen, elastin, polyvinyl alcohol, polyvinylpyrrolidone, and sodium polyacrylate.

[0010] (4) The water-retaining layer includes urethane foam.

[0011] (5) The thickness of the water-retaining layer is on the order of submillimeters or less, which allows the target substance taken in from the surface of the water-retaining layer to diffuse through the water-retaining layer and reach the host substance.

[0012] (6) The detection kit further comprises a packaging material that covers the photonic crystal, the host material, and the water-retaining layer, the packaging material including a barrier layer that prevents water vapor from passing through the water-retaining layer.

[0013] (7) A detection system for a substance to be detected according to another aspect of the present disclosure includes the above-described detection kit, a light source that emits incident light, a photodetector that detects detection light that is light that is reflected or diffracted from the incident light by the detection kit, and a processor that performs arithmetic processing to detect the substance to be detected based on features extracted from the detection light.

[0014] (8) The processor calculates the concentration of the substance to be detected contained in the gas sample from the intensity at a specific wavelength by referring to the correspondence between the intensity of the detection light at a specific wavelength and the concentration of the substance to be detected.

[0015] (9) A method for detecting an analyte substance according to yet another aspect of the present disclosure uses a detection kit to detect an analyte substance that may be contained in a gas sample. The detection kit includes a photonic crystal, a host substance, and a water-retaining layer. The photonic crystal includes a periodically arranged microstructure. The host substance is fixed to the microstructure and is capable of specifically adhering to the analyte substance. The water-retaining layer is disposed on the photonic crystal so as to cover the host substance. The detection method includes first to third steps. The first step is a step of leaving the detection kit in the gas sample and allowing the analyte substance to specifically adsorb to the host substance in the water-retaining layer. The second step is a step of irradiating incident light onto the detection kit after leaving it therein and acquiring detection light, which is light that is reflected or diffracted by the detection kit from the incident light. The third step is a step of performing arithmetic processing to detect the analyte substance based on feature quantities extracted from the detection light.

[0016] (10) The step of performing calculation processing (third step) includes a step of calculating the concentration of the substance to be detected contained in the gas sample from the intensity at a specific wavelength by referring to the correspondence relationship that exists between the intensity at a specific wavelength of the detection light and the concentration of the substance to be detected.

[0017] (11) The method for detecting a substance to be detected further includes the step of removing the water-retaining layer from the photonic crystal prior to irradiation with incident light.

[0018] (12) A method for detecting an analyte substance according to yet another aspect of the present disclosure uses a detection kit to detect an analyte substance that may be contained in a gas sample. The method includes a photonic crystal and a host substance. The photonic crystal includes a periodically arranged microstructure. The host substance is fixed to the microstructure and is capable of specifically attaching the analyte substance. The detection method includes first to third steps. The first step is a step of introducing at least a portion of the gas sample into an aqueous liquid. The second step is a step of arranging a liquid so as to cover the host substance, and allowing the analyte substance to specifically attach to the host substance in the liquid. The third step is a step of irradiating incident light onto the detection kit in which the liquid is arranged, and acquiring detection light, which is light that is reflected or diffracted from the incident light by the detection kit. The fourth step is a step of performing arithmetic processing to detect the analyte substance based on feature quantities extracted from the detection light.

[0019] (13) The introducing step (first step) includes introducing a wipe of the solid surface that has been in contact with the gas sample as the liquid. [Effects of the Invention]

[0020] According to the present disclosure, a target substance that may be contained in a gas sample can be stably detected with a simple configuration. [Brief explanation of the drawings]

[0021] [Figure 1] 1 is a diagram showing an outline of the overall configuration of a detection system for a target substance according to a first embodiment. [Figure 2] FIG. 2 is a block diagram showing a typical hardware configuration of a controller. [Figure 3] 1 is a perspective view schematically illustrating a configuration of a sheet sensor according to a first embodiment. [Figure 4]4 is a cross-sectional view of the sheet sensor taken along line IV-IV' in FIG. 3. [Figure 5] FIG. 10 is a diagram showing an image of a sheet sensor. [Figure 6] FIG. 10 is a diagram showing an enlarged image of the center portion of the sheet sensor. [Figure 7] FIG. 1 is a diagram for explaining the role of a hydrogel. [Figure 8] FIG. 2 is a conceptual diagram for qualitatively explaining the principle of optical detection of a target substance in the first embodiment. [Figure 9] 3 is a flowchart showing a method for producing a kit for detecting a target substance in the first embodiment. [Figure 10] FIG. 1 is a schematic process diagram of a method for producing a kit for detecting a target substance. [Figure 11] 4 is a flowchart showing the processing procedure for detecting a target substance in the first embodiment. [Figure 12] FIG. 2 is a conceptual diagram for explaining the correspondence between a feature amount extracted from a reflectance spectrum and the concentration of a substance to be detected. [Figure 13] FIG. 10 is a diagram showing an example of a measurement result of a reflection spectrum of a sheet sensor in a state where a target substance is not detected. [Figure 14] FIG. 10 is a diagram showing an example of the results of evaluating the influence of the thickness of the hydrogel based on the shift amount of the peak wavelength. [Figure 15] FIG. 10 is a diagram showing an example of the results of evaluating the effect of the thickness of the hydrogel based on the amount of change in peak intensity. [Figure 16] FIG. 10 is a cross-sectional view of a sheet sensor according to a second embodiment. [Figure 17] 10 is a flowchart showing the processing procedure for detecting a target substance in the second embodiment. [Figure 18] FIG. 1 shows an example of the measurement results of the reflectance spectrum when the spike protein of the novel coronavirus is used as the substance to be detected. [Figure 19] FIG. 19 is a diagram showing the correspondence between virus concentration and the amount of change in peak intensity, determined from the measurement results of FIG. 18. DETAILED DESCRIPTION OF THE INVENTION

[0022] <Terminology> In the present disclosure and its embodiments, the term "nanometer order" includes a range of 1 nm to 1000 nm (=1 μm), and the term "submillimeter order" includes a range of 100 μm to 1 mm.

[0023] In the present disclosure and its embodiments, the term "gaseous sample" refers to a gaseous substance containing a target substance or a gaseous substance that may contain a target substance. Examples of gaseous samples include, but are not limited to, atmospheric air (indoor or outdoor air). A gaseous sample may be, for example, air collected in a container, or a gas other than air collected in a container.

[0024] In the present disclosure and its embodiments, the term "substance to be detected" refers to a substance that can be detected using a detection kit according to the present disclosure. Examples of the substance to be detected include viruses, microorganisms (bacteria, fungi, etc.), biopolymers (proteins, nucleic acids, lipids, polysaccharides, pollen, etc.), and antigens (allergens, etc.).

[0025] The substance to be detected is not limited to biological substances, but may also be metal nanoparticles, metal nanoparticle aggregates, metal nanoparticle assembly structures, semiconductor nanoparticles, organic nanoparticles, resin beads, etc. "Metal nanoparticles" are metal particles having a size on the order of nanometers. "Metal nanoparticle aggregates" are aggregates formed by the aggregation of multiple metal nanoparticles. "Metal nanoparticle assembly structures" are structures in which, for example, multiple metal nanoparticles are fixed to the surface of beads via interaction sites, with gaps between them and spaced apart at intervals equal to or less than the diameter of the metal nanoparticles. "Semiconductor nanoparticles" are semiconductor particles having a size on the order of nanometers. "Organic nanoparticles" are particles made of organic compounds having a size on the order of nanometers. "Resin beads" are particles made of resin having a size on the order of nanometers.

[0026] In the present disclosure and its embodiments, the term "host substance" refers to a substance to which a detectable substance can specifically adhere. Examples of combinations of a host substance and a detectable substance to which a detectable substance can specifically adhere include antigens and antibodies, sugar chains and proteins, lipids and proteins, low-molecular-weight compounds (ligands) and proteins, proteins and proteins, and single-stranded DNA and single-stranded DNA. When one of two substances with specific affinity is a detectable substance, the other can be used as a host substance. When an antigen is a detectable substance, an antibody can be used as a host substance. Conversely, when an antibody is a detectable substance, the antigen can be used as a host substance. In the present disclosure and its embodiments, the type of detectable antigen (virus, allergen, etc.) can be changed by changing the type of antibody. Therefore, the type of antigen detectable by the present disclosure and its embodiments is not particularly limited.

[0027] In this disclosure and its embodiments, "visible light" or light in the "visible range" refers to light in the wavelength range of 360 nm to 830 nm. "Infrared light" or light in the "infrared range" refers to light in the wavelength range of 830 nm to 2,500 nm. "White light" refers to light having a wavelength range spanning at least a portion of the visible range and at least a portion of the infrared range.

[0028] [Embodiment 1] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. In the drawings, the same or corresponding parts are designated by the same reference numerals, and their description will not be repeated. In the drawings, the proportions are sometimes changed from the actual proportions to facilitate understanding of the structure.

[0029] In this embodiment, viruses floating in the air are detected using a virus detection system, which is an example of a "detection system for a substance to be detected" according to the present disclosure. The X and Y directions represent horizontal directions. The X and Y directions are perpendicular to each other. The Z direction represents the vertical direction. The direction of gravity is downward in the Z direction. The upward Z direction may be abbreviated as "upward," and the downward Z direction may be abbreviated as "downward."

[0030] <Overall system configuration> 1 is a diagram showing a schematic diagram of the overall configuration of a virus detection system according to embodiment 1. The virus detection system 100 includes a sheet sensor 1, an XYZ axis stage 2, a light source 3, a photodetector 4, and a controller 5.

[0031] The sheet sensor 1 is a sheet-like optical sensor capable of detecting viruses. The sheet sensor 1 is the main body of a virus detection kit 10 (see FIG. 10(G)), which corresponds to the "detection kit" according to the present disclosure. There are no particular limitations on the type of virus that the sheet sensor 1 detects. Various sheet sensors 1 can be used depending on the type of virus to be detected. The configuration of the sheet sensor 1 will be described in detail with reference to FIGS. 3 to 6.

[0032] The XYZ-axis stage 2 is configured so that the sheet sensor 1 can be installed thereon. The XYZ-axis stage 2 is provided with an adjustment mechanism (not shown in this example). The adjustment mechanism is a drive mechanism such as a servo motor or a focusing handle. The adjustment mechanism adjusts the relative positional relationship between the irradiation position of the incident light L1 and the XYZ-axis stage 2 in response to a command from the controller 5. The virus detection system 100 may be provided with a stage whose position is fixed, instead of the XYZ-axis stage 2.

[0033] The light source 3 emits incident light L1 to irradiate the sheet sensor 1 in response to a command from the controller 5. The incident light L1 in the first embodiment is white light. Specifically, the light source 3 is, for example, a xenon lamp, a tungsten halogen lamp, a white LED (Light Emitting Diode), or a white laser. When the incident light L1 irradiates the sheet sensor 1, a portion of the incident light L1 is reflected (more specifically, Fresnel reflection) by the sheet sensor 1. This reflected light L2 reaches the photodetector 4.

[0034] The photodetector 4 has optical characteristics that enable it to detect light (white light in this embodiment) in the wavelength range of the reflected light L2 from the sheet sensor 1. The photodetector 4 detects the reflected light L2 in response to a command from the controller 5, and outputs the detection result to the controller 5.

[0035] The photodetector 4 is, for example, a multi-pixel photodetector including a plurality of pixels (photoelectric conversion elements) arranged in a two-dimensional array. Specifically, the photodetector 4 includes a CCD (Charged-Coupled Device) image sensor, a CMOS (Complementary Metal-Oxide-Semiconductor) image sensor, or the like. The photodetector 4 may further include a spectroscope having a dispersive optical element (typically a diffraction grating or a prism).

[0036] The photodetector 4 may be a single-pixel photodetector. Specifically, the photodetector 4 may be a photodiode such as a PIN photodiode or an avalanche photodiode (APD), a phototube, or a photomultiplier. As will be described later, it is not essential that the photodetector 4 have a spectroscopic function.

[0037] The controller 5 controls each device (XYZ axis stage 2, light source 3, and photodetector 4) in the virus detection system 100. The controller 5 also generates a reflection spectrum of the sheet sensor 1 based on the detection result by the photodetector 4, and analyzes the reflection spectrum.

[0038] 2 is a block diagram showing a typical hardware configuration of the controller 5. The controller 5 includes a processor 51, a memory 52, an input device 53, a display 54, and a communication interface (IF) 55. The memory 52 includes a read only memory (ROM) 521, a random access memory (RAM) 522, and a hard disk drive (HDD) 523.

[0039] The processor 51 is communicatively connected to the memory 52, the input device 53, the display 54, and the communication IF 55 via a bus or the like. The processor 51 controls the overall operation of the controller 5. The memory 52 stores an operating system and application programs executed by the processor 51. The input device 53 accepts user input. The input device 53 is typically a keyboard or a mouse. The display 54 displays various types of information. The communication IF 55 is an interface for communicating with external devices (not shown).

[0040] 1, as long as it is possible to irradiate incident light L1 from the light source 3 onto the sheet sensor 1 and to capture reflected light L2 from the sheet sensor 1 into the photodetector 4. For example, the optical system of the virus detection system 100 may further include optical components (not shown) such as mirrors, dichroic mirrors, lenses, prisms, and optical fibers.

[0041] 1 also shows an example in which the reflected light L2 of the incident light L1 by the sheet sensor 1 is detected by the photodetector 4. However, the photodetector 4 may detect the diffracted light of the incident light L1 by the sheet sensor 1 instead of the reflected light L2. The reflected light L2 or the diffracted light corresponds to the "detection light" according to the present disclosure.

[0042] <Sensor configuration> Fig. 3 is a perspective view schematically showing the configuration of the sheet sensor 1 according to the first embodiment. Fig. 4 is a cross-sectional view of the sheet sensor 1 taken along line IV-IV' in Fig. 3. Fig. 5 is a view showing an image of the sheet sensor 1. Fig. 6 is a view showing an SEM (Scanning Electron Microscope) image of the central portion of the sheet sensor 1. With reference to Figs. 3 to 6, the sheet sensor 1 includes a substrate 11, a photonic crystal 12, an antibody 13, and a hydrogel 14.

[0043] The substrate 11 provides mechanical strength to the sheet sensor 1. The material of the substrate 11 is not particularly limited, and may be, for example, glass, quartz, silicon, or a PET (polyethylene terephthalate) film. The shape of the substrate 11 is not particularly limited, but in this embodiment, it has a planar shape (a rectangular parallelepiped shape) that is rectangular when viewed from above.

[0044] Photonic crystal 12 is disposed on substrate 11 and is configured so that its refractive index changes at a period roughly equivalent to the wavelength of incident light L1. In this embodiment, photonic crystal 12 is made of a polymer. Specifically, the material of photonic crystal 12 is, for example, an epoxy resin-based photocurable resin, polyolefin resin (polyethylene, polypropylene, etc.), polystyrene, polyvinyl chloride, acrylic resin, polyamide resin (nylon, etc.), or polyester.

[0045] In this embodiment, a plurality of pores are periodically arranged two-dimensionally in the photonic crystal 12. The diameter φ of the pore opening, the distance between adjacent pores (spacing I), and the depth D of the pores are all equal to or less than the wavelength of the incident light L1. In the example described below, the diameter φ is 230 nm, the spacing I is 230 nm, and the depth D is 200 nm.

[0046] The multiple pores correspond to the "microstructure" according to the present disclosure. In this example, each pore is a non-through hole with a hollow interior. However, the pores may also be through holes. The interior of the pores may also be filled with a metal, a liquid, or the like. The "microstructure" is not limited to pores, and may also be, for example, protrusions.

[0047] The antibody 13 is fixed to the pores of the photonic crystal 12. The antibody 13 is a specific antibody capable of specifically binding to a virus, which is the substance to be detected. The antibody 13 is an example of a "host substance" according to the present disclosure. "Binding" is one aspect of "attachment."

[0048] The hydrogel 14 is disposed on the photonic crystal 12 so as to cover the antibody 13. The hydrogel 14 contains a hydrophilic polymer that is insoluble in water and has a three-dimensional network structure in which polymer chains are cross-linked. The hydrogel 14 holds an aqueous liquid.

[0049] FIG. 7 is a diagram illustrating the role of the hydrogel 14. FIG. 7 schematically illustrates the process by which virus V binds to antibody 13. More specifically, virus V in the atmosphere is first taken up into the hydrogel 14 from the surface of the hydrogel 14 (see FIG. 7(A)). The virus V taken up into the hydrogel 14 diffuses in the aqueous liquid held in the hydrogel 14 (see FIG. 7(B)). The virus V then reaches antibody 13 and specifically binds to antibody 13 (see FIG. 7(C)).

[0050] For virus V to bind to antibody 13, an aqueous liquid is required around antibody 13, and hydrogel 14 holds an aqueous liquid (for example, pure water or an acetone / water mixed solvent). In other words, a water content of 0% means dryness, but the water content of hydrogel 14 is higher than 0%. This allows hydrogel 14 to function as a so-called "liquid reservoir," providing a site for the antigen-antibody reaction between virus V and antibody 13.

[0051] If the thickness (gel thickness) TH of the hydrogel 14 is too thin, the hydrogel 14 may not be able to retain an adequate amount of aqueous liquid, possibly causing the area around the antibody 13 to dry out. This may prevent the antigen-antibody reaction between the virus V and the antibody 13, making the virus V undetectable. On the other hand, if the gel thickness TH is too thick, the amount of virus V that diffuses through the aqueous liquid and reaches the antibody 13 is reduced, resulting in a smaller change in the refractive index around the photonic crystal 12 (described later). This reduces the likelihood of changes in the reflection spectrum, making highly accurate detection of the virus V difficult. Furthermore, the longer the diffusion time, the longer the detection time (the time from when the virus V is taken into the hydrogel 14 until the antigen-antibody reaction occurs) may be. Therefore, there is an appropriate range for the gel thickness TH. Under typical operating conditions (appropriate temperature and humidity conditions), it is desirable to prioritize improved detection accuracy and / or shorter detection time over a lack of liquid, and to make the gel thickness TH as thin as possible within the appropriate range. More specifically, the gel thickness TH is preferably on the order of submillimeters or less, and is 20 μm in the example described below.

[0052] The hydrogel 14 is an example of a "water retention layer" according to the present disclosure. The "water retention layer" according to the present disclosure is not limited to this and may be, for example, urethane foam (sponge) as long as it is a material that can retain an aqueous liquid.

[0053] Fig. 8 is a conceptual diagram for qualitatively explaining the principle of optical detection of virus V in embodiment 1. Fig. 8 shows the reflection spectrum of sheet sensor 1 acquired using photodetector 4.

[0054] The refractive index around the photonic crystal 12 changes as the antigen-antibody reaction between the virus V and the antibody 13 occurs. This causes a decrease in the intensity of the reflection spectrum, as shown in Figure 8. The amount of decrease in the reflection spectrum intensity (decrease in peak intensity) depends on the frequency of the antigen-antibody reaction, i.e., the amount of virus detected. Therefore, the amount of virus detected can be quantitatively determined by calculating the decrease in the peak intensity of the reflection spectrum.

[0055] The antigen-antibody reaction between the virus V and the antibody 13 can also cause a shift in the reflection spectrum. Therefore, the amount of virus detected can be quantitatively determined from the amount of shift in the reflection spectrum (the amount of shift in the peak wavelength). However, if the amount of decrease in peak intensity is used, a single-pixel photodetector 4 without spectroscopic capabilities can be used, which simplifies the configuration of the virus detection system 100.

[0056] <Virus detection kit manufacturing flow> Next, a method for manufacturing a virus detection kit including the sheet sensor 1 will be described. It is conceivable to use precision processing techniques such as lithography or electron beam lithography to form the photonic crystal 12. However, these techniques require expensive exposure equipment, and mass-producing sheet sensors requires preparing a number of exposure equipment corresponding to the production volume, which may increase manufacturing costs. In contrast, in this embodiment, the sheet sensor 1 is manufactured using imprint (transfer) technology. This allows the manufacturing cost of the sheet sensor 1 to be reduced.

[0057] Fig. 9 is a flowchart showing a method for manufacturing a virus detection kit according to the first embodiment. Fig. 10 is a schematic diagram showing the steps of the method for manufacturing a virus detection kit. This manufacturing method can be achieved using a commercially available nanoimprinting apparatus (for example, X-300 manufactured by SCIVAX Corporation). Hereinafter, steps will be abbreviated as S.

[0058] 9 and 10(A), in S11, a transfer molding material 12A made of a polymer is formed on a substrate 11. In S12, a mold 9 to be used in imprint technology is prepared (see FIG. 10(B)). In S13, the mold 9 is pressed against the transfer molding material 12A to form a photonic crystal 12 (see FIG. 10(C)). The transfer method may be a thermal method (heating + pressure + cooling), a photocuring method (pressure + ultraviolet irradiation), or a room temperature method (pressure retention). Thereafter, in S14, the mold 9 is peeled off (removed) from the photonic crystal 12 (see FIG. 10(D)).

[0059] In S15, the antibody 13 is immobilized on the photonic crystal 12 (see FIG. 10(E)). Various known techniques can be used for the process of immobilizing the antibody 13. For example, the steps may be performed in the following order: cleaning the photonic crystal 12, molecular modification to the surface of the photonic crystal 12, and dripping of the antibody solution.

[0060] In S16, a hydrogel 14A is formed on the photonic crystal 12 to which the antibody 13 is immobilized (see FIG. 10(F)). More specifically, a coating liquid containing a composition for forming the hydrogel 14A and a medium is applied to the photonic crystal 12, and the medium is removed from the coating film thus formed, thereby forming the hydrogel 14A. Methods for removing the medium include evaporating and removing the medium from the coating film by heating or the like.

[0061] The composition for forming the hydrogel 14A includes a hydrophilic polymer. The hydrophilic polymer is a resin having hydrophilic groups such as hydroxyl groups or ion-exchange groups. The hydrophilic polymer preferably includes a cross-linked hydrophilic resin, which exhibits high water retention due to a network structure formed by cross-linking of molecular chains of the hydrophilic resin. Specifically, the hydrophilic polymer may include at least one of polyethylene glycol, polyacrylamide, collagen, elastin, polyvinyl alcohol, polyvinylpyrrolidone, and sodium polyacrylate. The composition may further include, for example, an amino acid, an aminosulfonic acid, and / or an aminophosphonic acid. These substances can improve the water retention of the hydrogel 14. The medium contained in the coating liquid may be, for example, water, methanol, ethanol, 1-propanol, or 2-propanol. One of these may be used alone, or two or more may be used in combination as long as they are compatible.

[0062] In S17, an aqueous liquid is introduced into the hydrogel 14. The type of aqueous liquid is appropriately selected depending on the combination of the virus V (detection target substance) and the antibody 13 (host substance). Then, the sheet sensor 1 carrying the hydrogel 14 in a water-retaining state is sealed in a packaging material 15 (see FIG. 10(G)). The packaging material 15 is, for example, an aluminum laminate film (aluminum pouch) and includes an inner layer (such as polypropylene) 151, a barrier layer (such as aluminum foil) 152 that prevents the transmission of water vapor, and an outer layer (such as PET) 153. This completes the virus detection kit 10, and the series of processes is completed.

[0063] <Detection flow for target substance> 11 is a flowchart showing the processing procedure for detecting a target substance in embodiment 1. This flowchart is executed, for example, when a predetermined condition is met. Each step is basically realized by software processing by controller 5, but may also be realized by hardware (electrical circuitry) arranged within controller 5. The same applies to the flowchart in FIG. 17, which will be described later.

[0064] Referring to FIG. 11, in S21, the sheet sensor 1 is exposed to the atmosphere to be inspected. Since it takes a certain amount of time for viruses V in the atmosphere to be taken into the hydrogel 14 and cause an antigen-antibody reaction, the sheet sensor 1 is left until a specified time has elapsed (S22). The specified time is set by experiment or simulation depending on the type of virus V, the expected concentration of virus V in the atmosphere, etc., but is typically several tens of minutes (for example, about 20 to 30 minutes). Once the specified time has elapsed (YES in S22), the sheet sensor 1 is collected and placed on the XYZ axis stage 2 (S23). Note that these processes are performed manually by an operator, but may also be automated using industrial machinery (not shown), such as a belt conveyor or a robot arm.

[0065] In S24, the hydrogel 14 is removed from the sheet sensor 1. For example, the hydrogel 14 can be physically peeled off. As will be described later with reference to FIG. 15, removing the hydrogel 14 enables more accurate reflection spectrum measurement (especially peak intensity measurement). However, S24 may be skipped and the reflection spectrum may be measured with the hydrogel 14 still supported.

[0066] In S25, the controller 5 controls the light source 3 to emit incident light L1. Then, the controller 5 acquires the reflection spectrum of the sheet sensor 1 from the photodetector 4. After acquiring the reflection spectrum, the controller 5 controls the light source 3 to stop emitting the incident light L1.

[0067] In S26, the controller 5 analyzes the reflection spectrum acquired in S25 and extracts feature quantities. The controller 5 can extract feature quantities by comparing the reflection spectrum acquired in S25 with a reference spectrum predetermined in the memory 52. ​​More specifically, the controller 5 calculates the difference in intensity at the peak wavelength between the two reflection spectra as the "amount of change in peak intensity." Alternatively, the controller 5 may calculate the difference in peak wavelength between the two reflection spectra as the "amount of shift in peak wavelength."

[0068] FIG. 12 is a conceptual diagram illustrating the correspondence between the feature amount extracted from the reflectance spectrum and the concentration of the target substance. With reference to FIGS. 11 and 12, in S27, the controller 5 calculates the concentration of the target substance in the atmosphere based on the feature amount extracted in S26. More specifically, the memory 52 of the controller 5 stores the correspondence as shown in FIG. 12 as a data table (which may be a map, a function, or the like) based on the results of an experiment conducted in advance. The controller 5 can calculate the concentration of the target substance from the feature amount by referring to the data table. If the concentration of the target substance is below a predetermined value (for example, the detection limit), the controller 5 can determine that the target substance in the atmosphere has not been detected.

[0069] In S28, the controller 5 displays the calculation result of S27 on the display 54. The controller 5 may transmit the calculation result to an external device (such as a database not shown) via the communication IF 55. This completes the series of processes.

[0070] <Example> <Presence or absence of hydrogel> The sheet sensor 1 according to the first embodiment was actually fabricated and evaluated, and the results are described below. For comparison, a sheet sensor without the hydrogel 14 was also fabricated and evaluated. The notation "without gel" indicates the evaluation result of the sheet sensor without the hydrogel 14, and the notation "with gel" indicates the evaluation result of the sheet sensor 1 according to the first embodiment.

[0071] 13 shows an example of the measurement results of the reflection spectrum of the sheet sensor when the target substance is not being detected (before exposure to the atmosphere). It was confirmed that the provision of the hydrogel 14 caused a peak shift (red shift) of about 20 nm to the longer wavelength side.

[0072] <Effect of hydrogel thickness> Next, we will explain the results of evaluating the effect of the thickness of the hydrogel 14 (gel thickness TH) on the reflection spectrum. In this evaluation test, the sheet sensor was immersed in a mixed solvent of acetone and water. Acetone is known to shrink hydrogels. The reflection spectrum was measured when the acetone concentration (volume concentration of acetone in the above mixed solvent) was set to various values, and feature quantities (shift in peak wavelength, change in peak intensity) were extracted from the reflection spectrum.

[0073] Fig. 14 shows an example of the results of evaluating the effect of the thickness of the hydrogel 14 based on the shift in peak wavelength. Fig. 15 shows an example of the results of evaluating the effect of the thickness of the hydrogel 14 based on the change in peak intensity. The horizontal axes of Figs. 14 and 15 represent acetone concentration. The vertical axis of Fig. 14 represents the shift in peak wavelength relative to the case where the solvent is water (acetone concentration = 0). The vertical axis of Fig. 15 represents the change in peak intensity relative to the case where the solvent is water.

[0074] 14, the amount of shift in the peak wavelength in the sheet sensor 1 provided with the hydrogel 14 was almost the same as that in the case where no hydrogel was provided, even when the acetone concentration was high and the amount of contraction of the hydrogel 14 was large. In other words, the effect of contraction of the hydrogel 14 on the peak shift was limited.

[0075] On the other hand, as shown in Figure 15, when no hydrogel was provided, the peak intensity was almost constant regardless of the acetone concentration, whereas when the acetone concentration was high and the amount of contraction of the hydrogel 14 was large, the peak intensity decreased significantly. This indicates that the contraction of the hydrogel 14 (i.e., the thickness of the hydrogel 14) has a certain degree of influence on the peak intensity. Therefore, it is desirable to measure the peak intensity after removing the hydrogel 14 (see S24 in Figure 11).

[0076] As described above, in the first embodiment, the hydrogel 14 provided on the photonic crystal 12 exhibits a moisture-retaining function around the antibody 13. This prevents the area around the antibody 13 from drying out, and allows for a stable antigen-antibody reaction between the virus, which is the substance to be detected, and the antibody 13. The hydrogel 14 is easy to form and is also suitable for mass production. Therefore, according to the first embodiment, a substance to be detected that may be contained in a gas sample can be stably detected with a simple configuration. Furthermore, by determining in advance the correspondence between the substance to be detected and the feature amount of the reflection spectrum, the substance to be detected that may be contained in the gas sample can be quantitatively detected.

[0077] [Embodiment 2] In the second embodiment, a configuration will be described in which no hydrogel 14 is provided. The overall configuration of the virus detection system is the same as that of virus detection system 100 shown in Fig. 1, and therefore description thereof will not be repeated.

[0078] 16 is a cross-sectional view of the sheet sensor according to embodiment 2. The sheet sensor 1A differs from the sheet sensor 1 according to embodiment 1 (see FIG. 4) in that it does not include hydrogel 14 and the antibody 13 is exposed.

[0079] 17 is a flowchart showing the processing steps of the detection process for a target substance in the second embodiment. In S31, the target substance that may be contained in the gas sample is collected in an aqueous liquid. More specifically, by passing the gas sample through the aqueous liquid, the components contained in the gas sample can be replaced by the aqueous liquid. Alternatively, a swab may be used to collect a sample of a wipe of a solid surface (e.g., a table surface) that has come into contact with the gas sample (e.g., air in which droplets may be suspended).

[0080] In S32, the aqueous liquid prepared in S31 is dropped onto sheet sensor 1A (photonic crystal 12). The process from S33 onwards is similar to the process from S25 onwards in the first embodiment (see FIG. 11), and therefore detailed description thereof will not be repeated.

[0081] <Example> <Virus concentration dependency> This section describes the measurement results of the reflectance spectrum at various concentrations of the target substance, the spike protein of the novel coronavirus (SARS-CoV-2).

[0082] Figure 18 shows an example of the measurement results of the reflectance spectrum when the spike protein of the novel coronavirus is used as the detection target substance. The horizontal axis represents wavelength, and the vertical axis represents reflection intensity. The spike protein concentration (hereinafter referred to as "virus concentration") was set to seven values ​​in the range of 0 to 100 ng / mL. As shown in Figure 18, it was confirmed that the peak intensity of the reflectance spectrum decreased as the virus concentration increased. It was also confirmed that the peak wavelength of the reflectance spectrum shifted slightly toward longer wavelengths as the virus concentration increased.

[0083] Figure 19 shows the correspondence between virus concentration and change in peak intensity, determined from the measurement results in Figure 18. The horizontal axis represents virus concentration on a logarithmic scale, and the vertical axis represents change in peak intensity relative to a virus concentration of 0.

[0084] As shown in Figure 19, the correlation between the virus concentration and the change in peak intensity was expressed as a straight line on a semi-logarithmic graph. The error bars at each virus concentration represent the standard deviation of the measurement results for three samples (N = 3). The coefficient of determination, R 2 The peak intensity was 0.9931. The detection limit was 1.2 pg / mL. In the second embodiment as well, by obtaining such a correspondence relationship in advance and storing it in memory 52, the virus concentration can be quantitatively determined from the amount of change in peak intensity.

[0085] As described above, in the second embodiment, an aqueous liquid containing a target substance that may be contained in a gas sample is dropped onto the sheet sensor 1A. This also enables stable detection of a target substance that may be contained in a gas sample with a simple configuration. Also, in the second embodiment, as in the first embodiment, by determining in advance the correspondence (see FIG. 19) between the target substance and a feature amount of the reflection spectrum (in this example, the amount of change in peak intensity), the target substance that may be contained in the gas sample can be quantitatively detected.

[0086] The embodiments disclosed herein should be considered to be illustrative in all respects and not restrictive. The scope of the present disclosure is defined by the claims, not by the description of the above embodiments, and is intended to include all modifications within the meaning and scope of the claims. [Explanation of symbols]

[0087] 1,1A sheet sensor, 2 XYZ axis stage, 3 light source, 4 photodetector, 5 controller, 51 processor, 52 memory, 53 input device, 54 display, 55 communication IF, 9 mold, 10 virus detection kit, 11 substrate, 12 photonic crystal, 13 antibody, 14,14A hydrogel, 15 packaging material, 151 inner layer, 152 barrier film, 153 outer layer, 100 virus detection system.

Claims

1. A detection kit for a target substance, which detects a target substance that may be contained in a gas sample by irradiating the target substance with incident light, comprising: a photonic crystal including periodically arranged microstructures; a host substance immobilized on the microstructure and capable of specifically attaching the analyte; a water-retaining layer including a hydrogel or a urethane foam and disposed on the photonic crystal so as to cover the host material; A kit for detecting a substance to be detected, wherein the water-retaining layer retains an aqueous liquid that provides a reaction site for specifically attaching the substance to be detected to the host substance.

2. The water-retaining layer contains the hydrogel, 2. The kit for detecting a target substance according to claim 1, wherein the hydrogel contains at least one of polyethylene glycol diacrylate, polyacrylamide, collagen, elastin, polyvinyl alcohol, polyvinylpyrrolidone, and sodium polyacrylate.

3. 3. The detection kit for a target substance according to claim 1, wherein the thickness of the water-retaining layer is on the order of submillimeters or less, so that the target substance taken up through the surface of the water-retaining layer can diffuse through the water-retaining layer and reach the host substance.

4. a packaging material that covers the photonic crystal, the host material, and the water retention layer; 4. The kit for detecting a target substance according to claim 1, wherein the packaging material includes a barrier layer that prevents water vapor from passing through the water retaining layer.

5. The detection kit according to any one of claims 1 to 3, a light source that emits the incident light; a photodetector for detecting detection light, which is the incident light reflected or diffracted by the detection kit; a processor that performs calculations for quantitatively detecting the target substance based on the feature amount extracted from the detection light.

6. 6. The detection system for a detectable substance according to claim 5, wherein the processor calculates the concentration of the detectable substance contained in the gas sample from the intensity at a specific wavelength by referring to a correspondence relationship that exists between the intensity at the specific wavelength of the detection light and the concentration of the detectable substance.

7. A method for detecting a target substance, which may be contained in a gas sample, using a detection kit, comprising: The detection kit comprises: a photonic crystal including periodically arranged microstructures; a host substance immobilized on the microstructure and capable of specifically attaching the analyte; a water-retaining layer disposed on the photonic crystal so as to cover the host material; The detection method includes: leaving the detection kit in the gas sample to allow the target substance to specifically adhere to the host substance in the water retaining layer; a step of irradiating incident light onto the detection kit after being left standing, and acquiring detection light which is light reflected or diffracted by the detection kit from the incident light; and performing a calculation process for quantitatively detecting the target substance based on the feature amount extracted from the detection light.

8. 8. The method for detecting a substance to be detected according to claim 7, wherein the step of performing the arithmetic processing includes a step of calculating the concentration of the substance to be detected contained in the gas sample from the intensity of the detection light at a specific wavelength by referring to a correspondence relationship that holds between the intensity of the detection light at the specific wavelength and the concentration of the substance to be detected.

9. 9. The method for detecting a target substance according to claim 7, further comprising the step of removing the water-retaining layer from the photonic crystal prior to the irradiation with the incident light.

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