Optical sensor, system for detecting detection target substance, and manufacturing method for optical sensor

Abstract

An optical sensor (1) detects a detection target substance. The optical sensor (1) comprises a photonic crystal base material (11) and a resin film (12). The photonic crystal base material (11) has a main surface (13) on which a plurality of minute periodic structures (14) are disposed. The resin film (12) covers at least a portion of the main surface (13) and has a boundary surface (15) having a shape complementary to the plurality of minute periodic structures (14). The resin film (12) includes a host substance (121) that selectively reacts with the detection target substance.

Description

Optical sensor, system for detecting target substance, and method for manufacturing optical sensor

[0001] The present disclosure relates to an optical sensor, a system for detecting a substance to be detected, and a method for manufacturing an optical sensor.

[0002] Optical sensors using photonic crystals have been proposed. For example, Japanese Patent Laid-Open Publication No. 2014-202574 (Patent Document 1) by the present inventors discloses an optical sensor for detecting a target substance. The optical sensor includes a detection site. The detection site has a concave-convex structure that functions as a photonic crystal and includes a recognition element. Japanese Patent Laid-Open Publication No. 2020-85905 (Patent Document 2) and Japanese Patent Laid-Open Publication No. 2017-151033 (Patent Document 3) also disclose optical sensors by the present inventors.

[0003] JP 2014-202574 A JP 2020-85905 A JP 2017-151033 A

[0004] There is a constant demand for user-friendly optical sensors, in other words optical sensors that are easy to handle.

[0005] The present disclosure has been made to solve the above-mentioned problems, and one object of the present disclosure is to provide an optical sensor that is easy to handle. Another object of the present disclosure is to provide a method for easily manufacturing an optical sensor that is easy to handle.

[0006] An optical sensor according to an aspect of the present disclosure detects a substance to be detected. The optical sensor includes a photonic crystal substrate and a resin film. The photonic crystal substrate has a main surface on which a plurality of fine periodic structures are arranged. The resin film covers at least a portion of the main surface and has an interface having a shape complementary to the plurality of fine periodic structures. The resin film contains a host substance that selectively reacts with the substance to be detected.

[0007] A method for manufacturing an optical sensor according to another aspect of the present disclosure includes first and second steps. The first step is a step of preparing a photonic crystal substrate having a main surface on which a plurality of fine periodic structures are arranged. The second step is a step of forming a resin film using a liquid resin containing a host substance that selectively reacts with a substance to be detected. The forming step (second step) is a step of forming the resin film so that the resin film covers at least a portion of the main surface and has an interface having a shape complementary to the plurality of fine periodic structures.

[0008] According to the present disclosure, an optical sensor that is easy to handle can be provided. Furthermore, according to the present disclosure, an optical sensor that is easy to handle can be easily manufactured.

[0009] FIG. 1 is a diagram showing the overall configuration of an ion detection system according to an embodiment of the present disclosure. FIG. 2 is a diagram showing an example of the hardware configuration of a controller. FIG. 3 is a cross-sectional view of an ion sensor according to a comparative example. FIG. 4 is a perspective view of an ion sensor according to the present embodiment. FIG. 5 is a cross-sectional view of an ion sensor and a liquid sample taken along line VV' in FIG. 4. FIG. 6 is another cross-sectional view of an ion sensor and a liquid sample. FIG. 7 is a diagram for explaining an example of the configuration of a liquid sample and an ion sensor. FIG. 8 is a diagram showing the structural formula of KD-M11. FIG. 9 is a diagram showing an example of the hardware configuration of a controller. －１ 15 is a diagram showing the structural formula of. FIG. 15 is a diagram showing the structural formula of valinomycin. FIG. 15 is a diagram showing the structural formula of Bis(12-crown-4). FIG. 15 is a conceptual diagram for explaining the principle of cation detection by an ion sensor. FIG. 15 is a diagram showing an example of the relationship between refractive index difference and reflectance in an ion sensor. FIG. 15 is a flowchart showing the processing procedure for cation detection by an ion sensor according to the present embodiment. FIG. 15 is a diagram showing reflection spectra measured using potassium ion sensors with various dye concentrations. FIG. 15 is a diagram summarizing peak intensities extracted from the reflection spectra shown in FIG. 15. FIG. 15 is a diagram showing evaluation results of the responsiveness of a potassium ion sensor to potassium ions and sodium ions. FIG. 15 is a diagram showing evaluation results of the responsiveness of a sodium ion sensor to potassium ions and sodium ions. FIG. 15 is a flowchart showing an example of the processing procedure for a manufacturing method for an ion sensor according to the present embodiment. ２23 is a diagram showing the relationship between deposition time and reflection peak intensity. FIG. 24 is a diagram for comparing reflection peak intensities when an ion sensor is immersed in hydrochloric acid or potassium hydroxide. FIG. 25 is a diagram summarizing the reflection peak intensities shown in FIG. 21. FIG. 26 is a diagram showing the relationship between spin coating rotation speed and resin film thickness. FIG. 27 is a diagram showing reflection spectra measured in resin films formed at various spin coating rotation speeds. FIG. 28 is a diagram summarizing the reflection peak intensities shown in FIG. 24.

[0010] 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 description thereof will not be repeated.

[0011] <Explanation of Terms> In the present disclosure and its embodiments, "nanometer order" means a range of 1 nm or more and less than 1,000 nm (= 1 μm). "Single-digit nanometer order" means a range of 1 nm or more and less than 10 nm. "Double-digit nanometer order" means a range of 10 nm or more and less than 100 nm. "Triple-digit nanometer order" means a range of 100 nm or more and less than 1,000 nm.

[0012] In the present disclosure and its embodiments, "micrometer order" means a range of 1 μm or more and less than 1,000 mm (= 1 mm). "Single-digit micrometer order" means a range of 1 μm or more and less than 10 μm. "Two-digit nanometer order" means a range of 10 μm or more and less than 100 μm. "Triple-digit micrometer order" means a range of 100 μm or more and less than 1,000 μm (= 1 mm). "Millimeter order" means a range of 1 mm or more and less than 10 mm (= 1 cm).

[0013] In the present disclosure and its embodiments, the term "analyte" refers to a substance that can be detected using the "optical sensor" according to the present disclosure. Examples of the analyte include ions (cations and anions), viruses, microorganisms (bacteria, fungi, etc.), biopolymers (proteins, nucleic acids, substrates, enzymes, lipids, sugar chains, polysaccharides, pollen, etc.), low-molecular-weight compounds (ligands), and antigens (allergens, etc.).

[0014] In the present disclosure and its embodiments, the term "host substance" refers to a substance that selectively (specifically) reacts (reaction includes extraction, attachment, binding, etc.) with a detectable substance. Examples of combinations of a detectable substance and a host substance include ions and ionophores, target molecules and aptamers (nucleic acids, peptides, etc.), antigens and antibodies, substrates and enzymes, 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. The type of detectable substance can be changed by changing the type of host substance. When one of the above combinations is used as a detectable substance, the other can be used as a host substance. In other words, it does not matter which one is the detectable substance and which is the host substance.

[0015] In this disclosure and its embodiments, "visible light" means light in the wavelength range of 360 nm to 830 nm.

[0016] In the following description, the X, Y, and Z directions are perpendicular to one another. The X and Y directions (XY plane directions) are, for example, horizontal directions. The Z direction is, for example, vertical directions. 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."

[0017] In order to facilitate understanding of the structure, the proportions of the structures in the drawings are sometimes altered from the actual proportions.

[0018] [Embodiment] In this embodiment, an example will be described in which the "optical sensor" according to the present disclosure is an ion sensor that detects specific ions (cations) in a liquid sample, and the "detection system for a target substance" according to the present disclosure is an ion detection system. However, the sample to be detected by the "optical sensor" is not limited to a liquid sample. The "optical sensor" may also detect a target substance in a gas sample.

[0019] 1 is a diagram showing the overall configuration of an ion detection system according to an embodiment of the present disclosure. The ion detection system 100 includes an ion sensor 1 (or ion sensor 1A), a holder 2, a light source 3, an optical fiber unit 4, a probe 5, a photodetector 6, and a controller 7. The optical fiber unit 4 includes a first optical fiber 41 and a second optical fiber 42.

[0020] A liquid sample (indicated by SP in the figure) is placed in the ion sensor 1. The ion sensor 1 detects ions (cations in the embodiment described below) that are the target substances contained in the liquid sample. The configuration of the ion sensor 1 will be described in detail with reference to FIGS. 3 to 13.

[0021] The holder 2 is configured to hold the ion sensor 1. In this example, the holder 2 is provided with a through-hole (indicated by a broken line) for light irradiation.

[0022] In response to a command from the controller 7, the light source 3 emits light to irradiate the ion sensor 1. The light irradiated to the ion sensor 1 is referred to as "incident light" and indicated by L1. The incident light is light in a wavelength range in which a spectrum change occurs in the ion sensor 1 between the presence and absence of ions, which are the substance to be detected. In this embodiment, the incident light is visible light.

[0023] Incident light emitted from the light source 3 propagates through the first optical fiber 41 and reaches the probe 5. The probe 5 is disposed near a through-hole provided in the holder 2. The incident light is irradiated upward from the probe 5 toward the ion sensor 1. A portion of the incident light is then absorbed by the ion sensor 1, and a portion of the light not absorbed by the ion sensor 1 is reflected from the ion sensor 1. The light from the ion sensor 1 is referred to as "reflected light" and indicated by L2. The reflected light is generated downward from the ion sensor 1 toward the probe 5 and is taken in by the probe 5. The reflected light taken in by the probe 5 propagates through the second optical fiber 42 and reaches the photodetector 6.

[0024] The photodetector 6 detects the reflected light and outputs a signal indicating the detected intensity to the controller 7. The photodetector 6 includes, for example, a photoreceiver in which a plurality of photoelectric conversion elements capable of detecting light in the wavelength range of the reflected light (visible light in this example) are arranged in an array. Specifically, the photodetector 6 includes an image sensor such as a CCD (Charge Coupled Device) sensor or a CMOS (Complementary Metal Oxide Semiconductor) sensor. The photodetector 6 may include a spectrometer and a single-pixel or multi-pixel photoreceiver.

[0025] The controller 7 controls the components (light source 3 and photodetector 6) of the ion detection system 100. The controller 7 also detects ions, which are the substances to be detected, by performing arithmetic processing on the signal from the photodetector 6. More specifically, the controller 7 generates a reflection spectrum of the ion sensor 1 and detects ions by analyzing peaks in the reflection spectrum.

[0026] 2 is a diagram showing an example of the hardware configuration of the controller 7. The controller 7 includes a processor 71, a memory 72, an input device 73, and an output device 74.

[0027] The processor 71 is a processing circuit such as a central processing unit (CPU) or a microprocessing unit (MPU). The memory 72 is a storage device including a read-only memory (ROM) and a random access memory (RAM). The memory 72 stores a system program including an operating system (OS), a control program including computer-readable code, and various parameters used in the calculations. The processor 71 reads the system program, the control program, and the parameters, expands them into the memory 72, and executes them to perform various calculations for detecting ions. The input device 73 is a keyboard, mouse, touch panel, operation buttons, etc., and accepts operations by a user (a measurer such as a researcher, developer, or student). The output device 74 is a monitor, printer, etc., and outputs the progress and results of the calculations performed by the processor 71 to the user.

[0028] The optical system of the ion detection system 100 is not limited to the configuration shown in FIG. 1 as long as it is possible to irradiate the ion sensor 1 with incident light from the light source 3 and to capture light from the ion sensor 1 (not limited to reflected light, but may also be transmitted light) into the photodetector 6.

[0029] For example, the optical system of the ion detection system 100 may include optical components (not shown) such as mirrors, dichroic mirrors, lenses, and prisms instead of or in addition to the optical fiber section 4 .

[0030] Furthermore, the ion detection system 100 may be configured to irradiate the ion sensor 1 with incident light from above (i.e., through the liquid sample). However, when incident light is irradiated from above the ion sensor 1, the measurement conditions may change depending on the volume (thickness) of the liquid sample, whereas when incident light is irradiated from below the ion sensor 1, the measurement conditions can be consistent without being affected by the volume of the liquid sample.

[0031] <Basic Configuration of Ion Sensor> To facilitate understanding of the features of the ion sensor according to the present embodiment, an ion sensor according to a comparative example will first be briefly described. For details of the ion sensor according to the comparative example, see, for example, Patent Documents 1 and 2.

[0032] 3 is a cross-sectional view schematically showing an ion sensor according to a comparative example. The ion sensor 9 includes a substrate 91 and a photonic crystal 92.

[0033] The substrate 91 is a glass substrate (slide glass), a silicon substrate, a PET (polyethylene terephthalate) film, or the like.

[0034] The photonic crystal 92 is a two-dimensional photonic crystal extending in the XY plane. The photonic crystal 92 has a nano-periodic structure, specifically, a plurality of periodically arranged holes (denoted by h). The photonic crystal 92 includes a resin 921 and metal oxide nanoparticles 922.

[0035] The resin 921 contains, in addition to its main component, polyvinyl chloride (PVC), a material such as an ionophore that selectively reacts with ions. The metal oxide nanoparticles 922 are added to increase the refractive index of the photonic crystal 92 (more specifically, to increase the refractive index difference between the photonic crystal 92 and the liquid sample).

[0036] Here, the resin 921 typically has a thickness of only a few hundred nanometers. To form a nano-periodic structure in such an extremely thin resin film, advanced techniques such as nanoimprinting are used (see Patent Document 2 for details). Furthermore, the mechanical strength of the resin 921 is low. Therefore, special care must be taken in handling the resin 921 to avoid damaging it, for example, when removing the resin 921 from the nanoimprinting mold and fixing it on the substrate 91.

[0037] <<Present Embodiment>> Fig. 4 is a perspective view schematically showing an ion sensor 1 according to this embodiment. The liquid sample is not shown in Fig. 4. Fig. 5 is a cross-sectional view of the ion sensor 1 and the liquid sample taken along line VV' in Fig. 4. Referring to Figs. 4 and 5, the ion sensor 1 includes a photonic crystal substrate 11 and a resin film 12.

[0038] In this embodiment, the shape of the photonic crystal substrate 11 is a flat plate (thin rectangular parallelepiped) that is rectangular when viewed from above. The shape of the photonic crystal substrate 11 is not particularly limited, and may be, for example, a cylindrical shape that is circular when viewed from above. The photonic crystal substrate 11 has a flat main surface 13 that extends in the XY plane.

[0039] The thickness of the photonic crystal substrate 11 is determined to be sufficiently thick so as to ensure the mechanical strength of the ion sensor 1, depending on the material of the photonic crystal substrate 11. The thickness of the photonic crystal substrate 11 is preferably on the order of two digits of micrometers, three digits of micrometers, or millimeters, and more preferably on the order of several tens of micrometers to several millimeters.

[0040] The photonic crystal substrate 11 is configured so that the refractive index changes at a period equal to or shorter than the wavelength of incident light (visible light). More specifically, a plurality of fine periodic structures are arranged on the main surface 13 of the photonic crystal substrate 11. In this example, each fine periodic structure is a pillar 14. The plurality of pillars 14 are periodically arranged at a period equal to or shorter than the wavelength of the incident light. The size (diameter and height) of each of the plurality of pillars 14 is smaller than the wavelength of the incident light.

[0041] Although not shown, the photonic crystal substrate 11 may include a plurality of holes instead of the plurality of pillars 14. The plurality of holes are periodically arranged at a period equal to or less than the wavelength of the incident light. The size (hole diameter and depth) of each of the plurality of holes is smaller than the wavelength of the incident light.

[0042] Resin film 12 is disposed on photonic crystal substrate 11 so as to cover at least a portion of main surface 13 of photonic crystal substrate 11. As will be described later, resin film 12 can be formed by applying a liquid resin (specifically, spin coating, dip coating, or spray coating). Therefore, resin film 12 has, as its lower surface, boundary surface 15 having a shape complementary to the shape of the plurality of pillars 14. As a result, resin film 12 is provided with a plurality of periodically arranged holes complementary to the plurality of pillars 14. Although not shown, if photonic crystal substrate 11 includes a plurality of holes, resin film 12 will be provided with a plurality of pillars.

[0043] The resin film 12 has a sample contact surface 16, which is the upper surface of the resin film 12 and comes into contact with a liquid sample. The resin film 12 has a certain thickness, and the spaces between the pillars 14 are filled with resin. Therefore, unlike the boundary surface 15, the sample contact surface 16 does not have a shape complementary to the shapes of the pillars 14. When the resin film 12 is formed by spin coating a liquid resin or the like, the shape of the sample contact surface 16 is approximately flat (planar).

[0044] If the resin film 12 is too thick, the peak intensity of the reflection spectrum may be low. Conversely, if the resin film 12 is too thin, the difference in peak intensity of the reflection spectrum between the presence and absence of the target substance may be small. In other words, if the resin film 12 is either too thick or too thin, the ion detection sensitivity of the ion sensor 1 may be reduced. Therefore, the thickness of the resin film 12 is determined experimentally so as to achieve the required detection sensitivity. The thickness of the resin film 12 is preferably on the order of three nanometers (= 100 to 1000 nm), and more preferably 500 nm or more and 700 nm or less (see FIG. 23 ).

[0045] 6 is another cross-sectional view of the ion sensor and the liquid sample. The ion sensor 1A further includes a high refractive index layer 17 in addition to the photonic crystal substrate 11 and the resin film 12.

[0046] High-refractive index layer 17 is disposed between the plurality of pillars 14 of photonic crystal substrate 11 and boundary surface 15 of resin film 12. High-refractive index layer 17 can be formed by immersing photonic crystal substrate 11 in a coating solution prior to forming resin film 12 (see FIG. 19 ). Therefore, like resin film 12, high-refractive index layer 17 also has a shape complementary to the shape of the plurality of pillars 14.

[0047] The refractive index of the high refractive index layer 17 is higher than the refractive index of the resin film 12. As will be described in detail later, the provision of the high refractive index layer 17 can improve the ion detection sensitivity. However, ions can be detected even if the high refractive index layer 17 is not provided. Therefore, the high refractive index layer 17 does not have to be provided in the ion sensor 1.

[0048] Note that "the resin film 12 covers at least a portion of the main surface 13 of the photonic crystal substrate 11" is not limited to the case where the resin film 12 is in direct contact with the main surface 13 to cover the main surface 13, but also includes the case where another material (in this example, a high refractive index layer 17) is disposed between the photonic crystal substrate 11 and the resin film 12.

[0049] In the comparative example, even though the resin 921 containing an ionophore that selectively reacts with ions is extremely thin (typically several hundred nanometers thick), a nano-periodic structure of a photonic crystal is formed in the resin 921 itself. In contrast, in the ion sensor 1 or ion sensor 1A according to this embodiment, the resin film 12 containing the ionophore is disposed on the photonic crystal substrate 11. In other words, the configuration that enables the ion sensor 1 to function as a photonic crystal and the configuration that enables the ion sensor 1 to selectively react with ions are separated. This ensures the mechanical strength of the entire ion sensor 1 (1A) thanks to the photonic crystal substrate 11, even if the resin film 12 is thin. Furthermore, unlike the comparative example, the process of removing the resin 921 from the nanoimprint mold and fixing it on the substrate 91 is not required. This eliminates the need for special care to avoid damage to the resin film 12. Therefore, according to this embodiment, an ion sensor 1 (1A) that is easy to handle can be realized.

[0050] 7 is a diagram illustrating an example of the configuration of a liquid sample and an ion sensor 1A. Specific examples will be described using two types of ion sensors 1A used in the examples described below. One is a karyon ion sensor, and the other is a sodium ion sensor.

[0051] The liquid sample contains cations as the substance to be detected. In this example, the cations are potassium ions (K ＋ ) or sodium ions (Na ＋ ) As will be described later, －９ ~10 －１ A number of liquid samples with different cation concentrations within the range of M were prepared and measurements were carried out (see FIGS. 17 and 18).

[0052] The resin film 12 includes, for example, a base material, a plasticizer, a dye, a counter anion, and an ionophore.

[0053] The base material of the resin film 12 is, for example, PVC. In this example, the weight percent concentration of PVC was adjusted to 33 wt %. The base material of the resin film 12 may also be epoxy resin, polyolefin resin (polyethylene, polypropylene, etc.), polystyrene, acrylic resin, polyamide resin (nylon, etc.), polyester, polyvinyl alcohol, polydimethylsiloxane, agarose, polyacrylamide, etc.

[0054] The plasticizer contains dissolved dyes, counter anions, and ionophores. The plasticizer penetrates between the molecules of PVC, the base material of the resin film 12, weakening the intermolecular forces and allowing the PVC molecular chains to move more easily. This allows the substances in the resin film 12 to move more freely. In this example, the plasticizer is nitrophenyl octyl ether (NPOE). In this example, the weight percent concentration of NPOE was adjusted to 66 wt%.

[0055] The plasticizer is not an essential component of the resin film 12. The resin film 12 may contain only the dye, counter anion, and ionophore without adding a plasticizer.

[0056] A dye is a molecule whose color (more specifically, the wavelength of light it absorbs) changes when an ion is extracted by an ionophore. The dye is, for example, a fat-soluble cationic dye, and in this example, it is KD-M11. Figure 8 is a diagram showing the structural formula of KD-M11. In this example, the weight percent concentration of KD-M11 was adjusted to 8 wt%.

[0057] In this example, the change in refractive index of the ion sensor 1A caused by the reaction between the cation and the ionophore is relatively small, so the resin film 12 contains a dye. However, depending on the type of "substance to be detected" according to the present disclosure, the dye is not an essential component. If the change in refractive index of the "optical sensor" caused by the reaction between the "substance to be detected" and the "host substance" is sufficiently large, the resin film 12 does not need to contain a dye.

[0058] The counter anion is a lipid anion, which in this example is tetrakis[3,5-bis(trifluoromethyl)phenyl]borate sodium salt dihydrate (TFPB). －１ In the example, TFPB is －１ The electrolyte concentration (equivalent concentration) was adjusted to 0.8 eq.

[0059] An ionophore is a molecule (ion recognition molecule) capable of recognizing and extracting specific ions. The ionophore corresponds to the "host substance" in this disclosure. In the ion sensor 1A, cations in a liquid sample are optically detected by a change in the reflectance spectrum of the ion sensor 1A due to extraction of the cations by the ionophore. An example of the ionophore in a potassium ion sensor is valinomycin. An example of the ionophore in a sodium ion sensor is Bis(12-crown-4). Figure 10 shows the structural formula of valinomycin. Figure 11 shows the structural formula of Bis(12-crown-4). In the examples, the electrolyte concentration of valinomycin was adjusted to a range of 0.2 to 0.8 eq. Similarly, the electrolyte concentration of Bis(12-crown-4) was adjusted to a range of 0.2 to 0.8 eq.

[0060] 12 is a conceptual diagram for explaining the principle of cation detection by the ion sensor 1 (1A). As shown in FIG. 12, the resin film 12 includes an ionophore 121, a dye 122, and a counter anion 123.

[0061] The ionophore 121 is a cation (M ＋ ), thereby increasing the permeability of the resin film 12 to cations and extracting the cations into the resin film 12. As a result, the dye 122 is deprotonated, releasing protons into the liquid sample. When the dye 122 is deprotonated, the absorption spectrum of the dye 122 changes compared to when the dye 122 is protonated. When the dye 122 is valinomycin, the color of the resin film 12 changes from yellow (peak wavelength: 430 nm) to blue (peak wavelength: 630 nm). Therefore, cations can be detected based on the change in the reflection spectrum of the ion sensor 1 caused by the change in the absorption spectrum of the dye 122. The counter anion 123 is added to balance the charge in the resin film 12 during the protonation / deprotonation of the dye 122.

[0062] The resin film 12 in this embodiment contains a "host substance" (ionophore) that selectively reacts with the target substance (cation). The resin film 12 differs from the block material in Patent Document 3 in that it does not prevent nonspecific adsorption of the target substance to the resin film 12 (see paragraph

[0062] of Patent Document 3).

[0063] 7, the high refractive index layer 17 is preferably a metal oxide layer. In this example, the material of the high refractive index layer 17 is titanium oxide (TiO ２ ). TiO ２ is known to have a high refractive index in the visible range. The material of the high refractive index layer 17 can be other metal oxides, such as silicon dioxide (SiO ２), indium tin oxide (ITO), fluorine-doped tin oxide (FTO), etc. The material of the high refractive index layer 17 may include two or more of these materials. The material of the high refractive index layer 17 is not limited to metal oxides and may be silicon.

[0064] The base material of photonic crystal substrate 11 is preferably a material that can ensure the mechanical strength of ion sensor 1A. In addition, the base material of photonic crystal substrate 11 is preferably a material that is transparent to visible light. In this embodiment, the base material of photonic crystal substrate 11 is glass. The base material of photonic crystal substrate 11 may also be silicon, PET, cycloolefin polymer, or the like.

[0065] <Refractive Index> First, assuming a configuration in which no high refractive index layer 17 is provided between the photonic crystal substrate 11 and the resin film 12, the effects of the difference in refractive index between the photonic crystal substrate 11 and the resin film 12 (refractive index difference) were examined by simulation. The results will be described.

[0066] 13 is a diagram showing an example of the relationship between the refractive index difference and the reflectance in the ion sensor 1A. The horizontal axis represents the refractive index difference between the refractive index of the photonic crystal substrate 11 and the refractive index of the resin film 12. The vertical axis represents the reflectance of the ion sensor 1A.

[0067] 13, the greater the difference in refractive index, the higher the reflectance. In order to sufficiently increase the intensity of the reflected light from the ion sensor 1A and thereby achieve high detection sensitivity, particularly for low-concentration samples, it is preferable that the difference in refractive index be 0.2 or more.

[0068] As a specific example, when the base material of resin film 12 is PVC, the refractive index of PVC is approximately 1.52 to 1.55. When the base material of photonic crystal substrate 11 is glass, the refractive index of glass is approximately 1.4 to 2.0. Therefore, in a configuration in which high refractive index layer 17 is not provided, it is preferable to use, from various types of glass, one with a refractive index of approximately 1.8 to 2.0 as photonic crystal substrate 11 in order to ensure a refractive index difference of 0.2 or more.

[0069] Next, the technical reason for providing the high refractive index layer 17 will be explained. As shown in FIG. 1 , when incident light is irradiated onto the ion sensor 1A from below, a portion of the incident light undergoes fixed-end reflection at the boundary between the air and the lower surface (photonic crystal substrate 11) of the ion sensor 1A. A portion of the light that enters the interior of the ion sensor 1A without undergoing fixed-end reflection undergoes free-end reflection at the boundary between the upper surface (resin film 12) of the ion sensor 1A and the liquid sample. This reflection causes the fixed-end reflected light and the free-end reflected light to constructively interact with each other (thin-film interference) at wavelengths that satisfy the Bragg condition in the ion sensor 1A. Therefore, when the reflection spectrum is measured, a peak appears at a specific wavelength. The peak wavelength of the reflection spectrum depends on the refractive index difference between the ion sensor 1A and the liquid sample.

[0070] The high refractive index layer 17 is TiO ２ When the liquid sample contains cations, the refractive index of the high-refractive-index layer 17 is approximately 2.5. On the other hand, when the liquid sample is mainly composed of water, the refractive index of the liquid sample is approximately 1.3. By providing the high-refractive-index layer 17 in this manner, the refractive index of the ion sensor 1A becomes significantly higher than the refractive index of the liquid sample, thereby increasing the refractive index difference between the ion sensor 1A and the liquid sample. This increases the difference in peak intensity of the reflection spectrum, thereby improving the detection sensitivity (lower detection limit) of cations.

[0071] <Ion Detection Processing Flow> Fig. 14 is a flowchart showing the procedure of the cation detection processing by the ion sensor 1 (1A) according to this embodiment. The processing shown in this flowchart is executed when a predetermined condition is met (for example, when the controller 7 receives an operation by the measurer via the input device 73). Each step is basically realized by software processing by the controller 7 (processor 71), but may also be realized by hardware (electrical circuitry) arranged within the controller 7. Hereinafter, steps are abbreviated as S.

[0072] In S11, the ion sensor 1 containing the liquid sample is placed on the holder 2. This process is typically performed manually by an operator, but can be automated using a feed device (not shown) for the ion sensor 1.

[0073] In S12, the controller 7 controls the light source 3 to irradiate the incident light onto the ion sensor 1 for a predetermined period of time. Then, the controller 7 obtains the detection result of the reflected light from the ion sensor 1 from the photodetector 6. In this way, the reflectance spectrum of the liquid sample is measured.

[0074] In S13, the controller 7 analyzes the reflection spectrum measured in S12 to extract the peak intensity of the reflection spectrum (hereinafter also referred to as "reflection peak intensity").

[0075] In S14, the controller 7 calculates the cation concentration in the liquid sample based on the reflection peak intensities extracted in S13. More specifically, the memory 72 of the controller 7 stores a table (which may be a map, a function, or the like) of correspondence relationships between reflection peak intensities and cation concentrations based on the results of experiments conducted in advance. The controller 7 calculates the cation concentration from the reflection peak intensities by referring to the table.

[0076] In S15, the controller 7 outputs the calculation result in S14 to the output device 74. This completes the series of processes.

[0077] <Example> Hereinafter, the results of measuring the reflection spectrum using the potassium ion sensor and the sodium ion sensor described with reference to FIG. 7 will be described.

[0078] <Effect of Dye Concentration> Figure 15 shows the reflectance spectra measured using potassium ion sensors with various dye concentrations. The horizontal axis represents wavelength, and the vertical axis represents the normalized intensity of reflected light (a value obtained by normalizing the intensity of the reflection spectrum).

[0079] Figure 16 is a diagram summarizing the peak intensities (reflection peak intensities) extracted from the reflection spectrum shown in Figure 15. The horizontal axis represents the weight percent concentration of the dye KDM-11, and the vertical axis represents the normalized intensity of reflected light.

[0080] Four potassium ion sensors were prepared, each with a different weight percent concentration of KDM-11 (2 wt%, 4 wt%, 6 wt%, and 8 wt%). The thin solid line shows the reflectance spectrum when hydrochloric acid (HCl), which does not contain potassium ions (the substance to be detected), was used as the liquid sample. The thick dashed dotted line shows the reflectance spectrum when potassium hydroxide (KOH), which contains potassium ions, was used as the liquid sample.

[0081] 15 and 16 show that the reflection peak intensity is significantly reduced when the liquid sample contains potassium ions, compared to when the liquid sample does not contain potassium ions.

[0082] In addition, it was found that there was a correlation between the weight percent concentration of KDM-11 and the reflection peak intensity. The difference in reflection peak intensity between the liquid sample containing potassium ions and the liquid sample not containing potassium ions was greatest when the weight percent concentration of KDM-11 was 8 wt%. Based on these results, the weight percent concentration of KDM-11 was fixed at 8 wt% in subsequent measurements.

[0083] <<Evaluation of responsiveness to potassium ions>> Figure 17 shows the evaluation results of the responsiveness of the potassium ion sensor to potassium ions and sodium ions. In this example, potassium ions are the substance to be detected, and sodium ions are an interfering substance used as a negative control. The horizontal axis represents the concentration C of potassium ions or sodium ions in the liquid sample on a logarithmic scale. The vertical axis represents the normalized intensity of reflected light. The same applies to Figure 18, which will be described later.

[0084] Three types of potassium ion sensors were prepared, each with different concentrations (0.2 eq, 0.4 eq, 0.8 eq) of valinomycin, an ionophore capable of selectively extracting potassium ions. －９ ~10 －１ The value of M was changed by one digit within the range.

[0085] In all three graphs shown in Figure 17, when the liquid sample contained sodium ions, the reflection peak intensity was approximately constant regardless of the sodium ion concentration. In contrast, when the liquid sample contained potassium ions, the reflection peak intensity changed depending on the potassium ion concentration. This result demonstrates that selective detection of potassium ions was successful.

[0086] When the valinomycin concentration was 0.8 eq, the peak intensity varied significantly depending on whether the liquid sample contained potassium ions or sodium ions, but the peak intensity did not change significantly with changes in potassium ion concentration. On the other hand, when the valinomycin concentration was 0.2 eq or 0.4 eq, the reflection peak intensity changed significantly depending on the potassium ion concentration. Therefore, a valinomycin concentration range of 0.2 to 0.4 eq is considered to be suitable for selective detection of potassium ions.

[0087] <<Evaluation of responsiveness to sodium ions>> Fig. 18 is a diagram showing the evaluation results of the responsiveness of the sodium ion sensor to potassium ions and sodium ions. In this example, contrary to Fig. 17, sodium ions are the target substance and potassium ions are the interfering substance.

[0088] Three types of sodium ion sensors were prepared, each with different concentrations (0.2 eq, 0.4 eq, 0.8 eq) of Bis(12-crown-4), an ionophore capable of selectively extracting sodium ions. －９ ~10 －１ The value of M was changed by one digit within the range.

[0089] When the Bis(12-crown-4) concentration was 0.2 eq or 0.4 eq, there was no difference in the reflection peak intensity depending on whether the liquid sample contained sodium ions or potassium ions. On the other hand, when the Bis(12-crown-4) concentration was 0.8 eq, there was a difference in the reflection peak intensity. From these results, it can be said that the selective detection of sodium ions was also successful.

[0090] <Manufacturing Flow of Ion Sensor> FIG. 19 is a flowchart showing an example of a processing procedure of a manufacturing method of the ion sensor 1 according to this embodiment.

[0091] In S21, a photonic crystal substrate 11 is prepared, having a plurality of pillars 14 arranged on a primary surface 13. The photonic crystal substrate 11 can be fabricated by a known method such as electron beam lithography, dry etching, sputtering, plasma CVD (Chemical Vapor Deposition), focused ion beam (FIB), or nanoimprint lithography.

[0092] In S22, a high refractive index layer 17 is formed on the photonic crystal substrate 11. More specifically, the surface of the photonic crystal substrate 11 is ultrasonically cleaned. Then, the surface of the photonic crystal substrate 11 is cleaned and hydrophilized by atmospheric plasma treatment. The high refractive index layer 17 is formed of TiO ２ In the case of a layer, the surface of the photonic crystal substrate 11 (the main surface 13 on which the plurality of pillars 14 are arranged) is immersed in (contacted with) a coating solution for a predetermined time and left to stand. The coating solution is ammonium hexafluorotitanate ((NH ４ ) ２ TiF ６) in ultrapure water and a mixed solution of boric acid and hydrochloric acid. ２ is precipitated and TiO ２ Then, a TiO ２ The layer is fixed using a photo-curable resin (for example, NOA81). Then, the photonic crystal substrate 11 is immersed in a coating solution to form a TiO ２ The time for precipitating TiO ２ The deposition time is recorded.

[0093] In S23, a liquid resin for forming the resin film 12 is prepared. As described above, the liquid resin may contain a base material, a counter anion, a plasticizer, a dye, and an ionophore. The concentrations of each material (weight percent concentration and equivalent concentration) are set to appropriate values ​​based on prior experiments.

[0094] In S24, conditions for applying the liquid resin prepared in S23 onto the photonic crystal substrate 11 by spin coating are set. Specifically, the spin coating rotation speed and spin coating time (the length of time for which the spin coating rotation speed is maintained) are set. In the above-mentioned example, the spin coating rotation speed was 6,000 rpm, and the spin coating time was 10 seconds. Although not shown, dip coating or spray coating may be used instead of spin coating. In this case, the dip coating conditions or spray coating conditions are set in S24.

[0095] In S25, the liquid resin is dropped onto the high refractive index layer 17, and spin coating is performed according to the spin coating conditions set in S24, thereby forming a resin film 12 on the high refractive index layer 17. The resin film 12 may be formed by dip coating or spray coating. This completes the ion sensor 1, and the series of processes ends.

[0096] <Manufacturing Conditions> Hereinafter, manufacturing conditions for manufacturing a suitable ion sensor 1A will be described.

[0097] <TiO ２ Layer thickness>> Figure 20 shows the TiO ２1 is a graph showing the relationship between deposition time and reflection peak intensity, where the horizontal axis is TiO ２ The vertical axis represents the deposition time, and the vertical axis represents the normalized intensity (reflection peak intensity).

[0098] TiO for forming the high refractive index layer 17 ２ The deposition time was set to four times: 0.5 hours, 1 hour, 1.5 hours, and 2 hours. The thickness of the high refractive index layer 17 was set to TiO ２ It increases in proportion to the deposition time. ２ The deposition times correspond to layer thicknesses of 30 nm, 60 nm, 90 nm and 120 nm.

[0099] From FIG. 20, TiO ２ It can be seen that when the deposition time is 1 hour or more and 1.5 hours or less, the reflection peak intensity exceeds 0.5. Therefore, by setting the layer thickness of the high refractive index layer 17 to 60 nm or more and 90 nm or less, the detection sensitivity of cations can be improved.

[0100] 21 is a graph for comparing the reflection peak intensity when the ion sensor 1A is immersed in hydrochloric acid (concentration 10 mM) or potassium hydroxide (concentration 10 mM). The horizontal axis represents the reflection peak intensity of TiO ２ The vertical axis represents the deposition time. The vertical axis represents the normalized intensity (reflection peak intensity). Figure 22 is a diagram summarizing the reflection peak intensities shown in Figure 21.

[0101] The greater the difference between the reflection peak intensity after immersion in hydrochloric acid and the reflection peak intensity after immersion in potassium hydroxide, the more selectively the detection target cation (sodium ion or potassium ion) can be detected, and the higher the detection sensitivity of the ion sensor 1A. ２ It can be seen that when the deposition time is 1 hour or more and 1.5 hours or less, the difference in reflection peak intensity exceeds 0.5. Therefore, this measurement result also shows that when the layer thickness of the high refractive index layer 17 is 60 nm or more and 90 nm or less, the detection sensitivity of cations is improved.

[0102] <Spin Coating Rotation Speed> Figure 23 is a diagram showing the relationship between the spin coating rotation speed and the thickness (film thickness) of the resin film 12. The horizontal axis represents the spin coating rotation speed, and the vertical axis represents the film thickness. The spin coating time was standardized to 10 seconds. From Figure 23, it can be seen that the film thickness tends to decrease as the spin coating rotation speed increases. By setting the spin coating rotation speed within the range of 2,000 to 6,000 rpm, a film thickness within the range of 500 to 700 nm was obtained.

[0103] Fig. 24 shows the reflection spectra measured for resin films 12 formed at various spin-coating rotation speeds. Fig. 25 summarizes the reflection peak intensities shown in Fig. 24. When the spin-coating rotation speed was within the range of 2,000 to 6,000 rpm (i.e., when the film thickness was within the range of 500 to 700 nm), the difference in peak intensity between when the liquid sample contained potassium ions and when it did not was sufficiently large. This means that potassium ions can be detected with high sensitivity.

[0104] In this way, it is preferable to set the spin coating rotation speed (and spin coating time) so that the film thickness is on the order of three nanometers, and it is preferable to set the spin coating rotation speed (and spin coating time) so that the film thickness is within the range of 500 to 700 nm.

[0105] <Summary> As described above, the ion sensor 1 (1A) according to this embodiment has a structure in which a resin film 12 is disposed on a photonic crystal substrate 11 that serves as an underlying base. The photonic crystal substrate 11 ensures the mechanical strength of the ion sensor 1, making the photonic crystal structure (fine periodic structure) less likely to be damaged. Therefore, this embodiment makes it possible to realize an ion sensor 1 that is easy to handle.

[0106] In this embodiment, TiO ２ , SiO ２ A high refractive index layer 17 containing a high refractive index material such as ITO or FTO is disposed on the photonic crystal substrate 11. This increases the difference between the refractive index of the ion sensor 1A and the refractive index of the liquid sample, thereby improving the ion detection sensitivity.

[0107] In Patent Document 2, metal oxide nanoparticles (zirconium oxide nanoparticles) for increasing the refractive index of resin are difficult to disperse in resin. Consequently, various materials for uniformly dispersing the metal oxide nanoparticles were explored, resulting in the adoption of a specific material (a copolymer of vinyl chloride, vinyl acetate, and vinyl alcohol). In contrast, in this embodiment, the high-refractive index layer 17 can be formed by a simple, well-known method, such as immersion in a coating solution. Furthermore, the resin film 12 can be formed simply by applying a liquid resin onto the high-refractive index layer 17 (by spin coating, dip coating, or spray coating). Therefore, this embodiment allows for the easy-to-handle ion sensor 1A to be easily manufactured.

[0108] [Appendix] Finally, various aspects of the present disclosure are summarized as appendices (clause).

[0109] <Supplementary Note 1> An optical sensor for detecting a substance to be detected, comprising: a photonic crystal substrate having a main surface on which a plurality of fine periodic structures are arranged; and a resin film covering at least a portion of the main surface and having an interface surface with a shape complementary to the plurality of fine periodic structures, wherein the resin film contains a host substance that selectively reacts with the substance to be detected.

[0110] <Supplementary Note 2> The optical sensor according to Supplementary Note 1, further comprising a high refractive index layer disposed between the plurality of fine periodic structures and the boundary surface, the high refractive index layer having a refractive index higher than a refractive index of the resin film.

[0111] <Supplementary Note 3> The optical sensor according to Supplementary Note 2, wherein the high refractive index layer is a metal oxide layer.

[0112] <Supplementary Note 4> The optical sensor according to Supplementary Note 3, wherein the metal oxide layer includes titanium oxide, silicon dioxide, indium tin oxide, or fluorine-doped tin oxide.

[0113] <Supplementary Note 5> The optical sensor according to Supplementary Note 3 or 4, wherein the metal oxide layer has a thickness of 60 nm or more and 90 nm or less.

[0114] <Supplementary Note 6> The optical sensor according to any one of Supplementary Notes 1 to 5, wherein the resin film has a thickness on the order of three digit nanometers.

[0115] <Supplementary Note 7> The optical sensor according to Supplementary Note 6, wherein the resin film has a thickness of 500 nm or more and 700 nm or less.

[0116] <Supplementary Note 8> The optical sensor according to any one of Supplementary Notes 1 to 7, wherein the difference between the refractive index of the photonic crystal substrate and the refractive index of the resin film is 0.2 or more.

[0117] <Supplementary Note 9> The optical sensor according to any one of Supplementary Notes 1 to 8, wherein the material of the photonic crystal substrate is transparent to incident light.

[0118] <Supplementary Note 10> The optical sensor according to any one of Supplementary Notes 1 to 9, wherein the substance to be detected is an ion, the host substance is an ionophore capable of selectively extracting the ion, and the resin film further contains a dye that is deprotonated when the ion is extracted by the ionophore.

[0119] <Supplementary Note 11> The optical sensor according to Supplementary Note 10, wherein the ion is a potassium ion, the ionophore is valinomycin, and the dye is KD-M11.

[0120] <Supplementary Note 12> The optical sensor according to Supplementary Note 10, wherein the ion is a sodium ion, the ionophore is Bis(12-crown-4), and the dye is KD-M11.

[0121] <Supplementary Note 13> The optical sensor according to any one of Supplementary Notes 10 to 12, wherein the resin film further contains a plasticizer.

[0122] <Supplementary Note 14> The optical sensor according to Supplementary Note 13, wherein the plasticizer is NPOE.

[0123] <Supplementary Note 15> A detection system for a substance to be detected, comprising: a holder configured to hold the optical sensor according to any one of Supplementary Notes 1 to 14; a light source that emits incident light to irradiate the optical sensor; a photodetector that detects light from the optical sensor irradiated with the incident light; and a processor that detects the substance to be detected based on a signal from the photodetector.

[0124] <Supplementary Note 16> A method for manufacturing an optical sensor, comprising the steps of: preparing a photonic crystal substrate having a main surface on which a plurality of fine periodic structures are arranged; and forming a resin film using a liquid resin containing a host substance that selectively reacts with a substance to be detected, wherein the forming step is a step of forming the resin film so that the resin film covers at least a part of the main surface and has a contact surface with a shape complementary to the plurality of fine periodic structures.

[0125] <Supplementary Note 17> The method for manufacturing an optical sensor according to Supplementary Note 16, wherein the forming step is a step of forming the resin film having a thickness on the order of three digit nanometers by spin coating, dip coating, or spray coating.

[0126] <Supplementary Note 18> The method for manufacturing an optical sensor according to Supplementary Note 17, wherein the forming step is a step of forming the resin film by spin coating, and a rotation speed of the spin coating is 2,000 rpm or more and 6,000 rpm or less.

[0127] 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.

[0128] 1, 1A Ion sensor, 11 Photonic crystal substrate, 12 Resin film, 121 Ionophore, 122 Dye, 123 Counter anion, 13 Main surface, 14 Pillar, 15 Interface, 16 Sample contact surface, 17 High refractive index layer, 2 Holder, 3 Light source, 4 Optical fiber section, 41 First optical fiber, 42 Second optical fiber, 5 Probe, 6 Photodetector, 7 Controller, 71 Processor, 72 Memory, 73 Input device, 74 Output device, 9 Ion sensor, 91 Substrate, 92 Photonic crystal, 921 Resin, 922 Metal oxide nanoparticles, 100 Ion detection system.

Claims

1. An optical sensor for detecting a substance to be detected, comprising: a photonic crystal substrate having a main surface on which a plurality of fine periodic structures are arranged; and a resin film covering at least a portion of the main surface and having a boundary surface of a shape complementary to the plurality of fine periodic structures, the resin film containing a host material that selectively reacts with the substance to be detected.

2. The optical sensor according to claim 1, further comprising a high refractive index layer disposed between said plurality of fine periodic structures and said boundary surface, said high refractive index layer having a refractive index higher than that of said resin film.

3. The optical sensor according to claim 2, wherein the high refractive index layer is a metal oxide layer.

4. The optical sensor of claim 3, wherein the metal oxide layer comprises titanium oxide, silicon dioxide, indium tin oxide, or fluorine-doped tin oxide.

5. The optical sensor according to claim 3, wherein the thickness of the metal oxide layer is 60 nm or more and 90 nm or less.

6. The optical sensor according to any one of claims 1 to 5, wherein the thickness of the resin film is on the order of three digit nanometers.

7. The optical sensor according to claim 6, wherein the thickness of the resin film is not less than 500 nm and not more than 700 nm.

8. The optical sensor according to any one of claims 1 to 5, wherein the difference between the refractive index of the photonic crystal substrate and the refractive index of the resin film is 0.2 or more.

9. The optical sensor according to any one of claims 1 to 5, wherein the material of the photonic crystal substrate is transparent to incident light.

10. An optical sensor described in any one of claims 1 to 5, wherein the substance to be detected is an ion, the host substance is an ionophore capable of selectively extracting the ion, and the resin film further contains a dye that is deprotonated when the ion is extracted by the ionophore.

11. The optical sensor of claim 10, wherein the ion is a potassium ion, the ionophore is valinomycin, and the dye is KD-M11.

12. The optical sensor of claim 10, wherein the ion is a sodium ion, the ionophore is Bis(12-crown-4), and the dye is KD-M11.

13. The optical sensor according to claim 10, wherein the resin film further contains a plasticizer.

14. The optical sensor of claim 13, wherein the plasticizer is NPOE.

15. A detection system for a target substance comprising: a holder configured to hold an optical sensor according to any one of claims 1 to 5; a light source that emits incident light to irradiate said optical sensor; a photodetector that detects light from said optical sensor irradiated with said incident light; and a processor that detects said target substance based on a signal from said photodetector.

16. A method for manufacturing an optical sensor, comprising: preparing a photonic crystal substrate having a main surface on which a plurality of fine periodic structures are arranged; and forming a resin film using a liquid resin containing a host substance that selectively reacts with a substance to be detected, wherein the forming step is a step of forming the resin film so that the resin film covers at least a portion of the main surface and has a boundary surface having a shape complementary to the plurality of fine periodic structures.

17. The method for manufacturing an optical sensor according to claim 16, wherein the forming step is a step of forming the resin film having a thickness on the order of three digit nanometers by spin coating, dip coating or spray coating.

18. The method for manufacturing an optical sensor according to claim 17, wherein the forming step is a step of forming the resin film by spin coating, and the rotation speed of the spin coating is 2,000 rpm or more and 6,000 rpm or less.