Patent Application
20180024057
The present invention relates to a measurement device, and more specifically, to a measurement device configured to measure an amount of an object to be inspected through use of surface plasmon resonance and an optical waveguide.
A measurement device configured to measure the amount of an object to be inspected through use of a surface plasmon resonance (SPR) phenomenon has been known. Such a measurement device can be used for various chemical analyses and biochemical analyses; for example, measurement of the concentration of a sample and detection of an immune reaction. Examples of the application of those chemical analyses and biochemical analyses include detection of an allergen and/or quantification of the amount of the allergen. In particular, a main allergen in allergy diseases such as infant asthma and atopic dermatitis is considered to be derived from mites contained in indoor dust (house dust). Therefore, it is significantly important for such allergy patients to quantify the amount of the mite allergen in an environment.
As a device configured to measure the amount of the mite allergen through use of the SPR phenomenon, there has been proposed a mite allergen measurement device using prism-type SPR, which is configured to measure a resonance angle (Patent Literature 1). However, in the measurement device disclosed in Patent Literature 1, it is necessary to measure a significantly minute resonance angle change (0.0072° to 0.0000288°), and as a result, a large and precise drive device is required. Therefore, the measurement device disclosed in Patent Literature 1 is used under the premise of being installed in a research facility having a measurement environment controlled precisely. In other words, the measurement device disclosed in Patent Literature 1 is not suitable for simply measuring the amount of the mite allergen in an ordinary environment (for example, a hot and humid state filled with dust) as in a general house and is not assumed to be portable. Further, in the measurement device disclosed in Patent Literature 1, in order to set a sample case (sensor chip), it is necessary to apply matching oil between a prism and the sample case, and hence an operation is significantly complicated. In addition, the amount of the allergen extracted from house dust is extremely small, and the aqueous solution amount thereof is also small. Therefore, in a prism-type measurement device using only one reflection, the sensitivity is liable to be insufficient, and hence high accuracy is required in the fixing amount of an anti-allergen antibody, and a light source and a light receiving element.
The measurement device for the amount of the mite allergen has been described as a typical example of the measurement device using the SPR phenomenon. However, the above-mentioned problems are not limited to the quantification of the amount of the mite allergen and are common to a measurement device configured to measure and/or quantify the amount of an object to be inspected through use of the SPR phenomenon.
The present invention has been made to solve the above-mentioned problems, and an object of the present invention is to provide a measurement device which is compact and portable and is simply operated, and which is capable of quantifying the amount of an object to be inspected with high sensitivity and high accuracy.
A measurement device according to one embodiment of the present invention includes an SPR sensor cell, a light source, and a light receiving element. The SPR sensor cell includes a plurality of optical waveguides, at least one of the plurality of optical waveguides forms a detection unit together with a metal layer onto which a recognition substance for an object to be inspected is fixed, and at least another one of the plurality of optical waveguides forms a reference unit together with a metal layer free of the recognition substance.
In one embodiment, the measurement device further includes a development unit extending across the plurality of optical waveguides. In one embodiment, the development unit includes a porous material.
In one embodiment, the detection unit includes an under-cladding layer, a core layer formed so that at least a part thereof is adjacent to the under-cladding layer, and a metal layer configured to cover the core layer, and the recognition substance is fixed onto the metal layer.
In one embodiment, the SPR sensor cell is removably mounted.
In one embodiment, the recognition substance includes an anti-allergen antibody, and the measurement device is configured to measure an amount of an allergen by an antigen-antibody reaction with the anti-allergen antibody.
According to the embodiment of the present invention, in the measurement device using the SPR phenomenon, the SPR sensor cell includes the plurality of optical waveguides. At least one of the optical waveguides is used as the detection unit onto which the recognition substance for the object to be inspected is fixed, and at least another one of the optical waveguides is used as the reference unit free of the recognition substance. Accordingly, it is possible to realize the measurement device which is compact and portable and is simply operated, and which is capable of quantifying the amount of the object to be inspected with high sensitivity and high accuracy. The measurement device according to the embodiment of the present invention can be easily used by a person (for example, a homemaker) having no expertise, in a home environment.
A measurement device 200 includes an SPR sensor cell 100, a light source 220, and light receiving elements (light measuring instruments) 230. The SPR sensor cell 100 is typically removably mounted on a cell mounting portion 210 to be incorporated into the measurement device 200. The SPR sensor cell 100 is typically inserted into the cell mounting portion 210 in a direction orthogonal to a waveguide direction of an optical waveguide (direction in which a core layer 12 extends) in plan view. In the cell mounting portion 210, in one embodiment, when the SPR sensor cell 100 is mounted at a predetermined position of the cell mounting portion 210, the light source 220, a light source-side optical fiber 240a, the optical waveguide (substantially, the core layer 12) of the SPR sensor cell 100, light receiving element-side optical fibers 240b, and the light receiving elements 230 are arranged so as to be positioned on one axis or on an axis parallel to the one axis. More specifically, in the measurement device 200, in one embodiment, as in the illustrated example, the light source 220, the light source-side optical fiber 240a, and the optical waveguide (substantially, the core layer 12) of the SPR sensor cell 100 are arranged so as to be positioned uniaxially on the light source side, and two branched optical waveguides (substantially, the core layers 12) of the SPR sensor cell 100 and the two light receiving elements 230 are arranged so as to be positioned uniaxially on the light receiving element side, respectively. With such a configuration, the attenuation amount of light in the optical waveguides can be minimized, and hence alight amount sufficient for measurement of SPR can be obtained. As a result, the amount of an object to be inspected (for example, an allergen) can be measured with high sensitivity and high accuracy.
As the light source 220, any suitable light source may be adopted. Specific examples of the light source include a white light source, a monochromatic light source, and a light-emitting diode. The light-emitting diode is preferred. Long lifetime, low cost, and elimination of maintenance can be realized through use of the light-emitting diode as the light source. The light receiving elements (light measuring instruments) 230 are connected to any suitable arithmetic processing device so as to enable accumulation, display, and processing of data. As each of the light receiving elements 230, any suitable light receiving element may be adopted. A photodiode is preferred. Excellent light receiving sensitivity can be realized to enlarge a measurement range through use of the photodiode as the light receiving element.
The light source 220 is connected to the light source-side optical fiber 240a through a light source-side optical connector 221a. The light source-side optical fiber 240a is connected to a light incidence port 12a of the core layer 12 of the SPR sensor cell 100 through a light source-side fiber block 222a. The light receiving element-side optical fibers 240b are connected to light output ports 12b of the core layers 12 through light receiving-element side fiber blocks 222b. The light receiving element-side optical fibers 240b are connected to the light receiving elements 230 through light receiving-element side optical connectors 221b. The light source-side optical fiber 240a is fixed with a light source-side optical fiber fixing device 223a, and the light receiving element-side optical fibers 240b are fixed with light receiving-element side optical fiber fixing devices 223b.
The SPR sensor cell 100 includes an optical waveguide and is configured to detect the state of a sample and/or a change thereof by causing light having a specific wavelength in light introduced into the optical waveguide to generate surface plasmon resonance in a metal layer and attenuating the intensity of the light. In the embodiment of the present invention, the SPR sensor cell 100 includes a plurality of (two in the illustrated example) optical waveguides (substantially, the core layers 12 and 12). At least one of the plurality of optical waveguides forms a detection unit 13a together with a metal layer onto which a recognition substance for the object to be inspected is fixed, and at least another one of the plurality of optical waveguides forms a reference unit 13b together with a metal layer free of the recognition substance. With such a configuration, a light source noise, an environmental noise, and the like can be determined based on a change in light intensity of the reference unit 13b. Therefore, the amount of the object to be inspected can be measured (quantified) more precisely by correcting a change in light intensity of the detection unit 13a with the change in light intensity of the reference unit 13b. The accurate amount of the object to be inspected, having the light source noise, the environmental noise, and the like removed therefrom, can be measured, for example, by previously creating a reference line indicating a relative relationship between the difference of the light intensity in the reference unit 13b and the light intensity in the detection unit 13a, and the amount of the object to be inspected. The recognition substance as used herein refers to a substance that exhibits a specific reaction, binding, adsorption, response, or the like with respect to the object to be inspected. The detailed configuration of the SPR sensor cell is described later in the section B.
The downsizing of the measurement device 200 is realized by adopting the above-mentioned configuration. Specifically, the light-emitting diode and the photodiode can be used as single elements, and the light amount and detection accuracy can also be maintained at sufficient levels. Further, through the above-mentioned uniaxial arrangement, the amount of light propagating through the optical waveguide can be ensured satisfactorily. Thus, both the downsizing and the measurement with high sensitivity and high accuracy can be satisfied. As a result, the measurement device (substantially, a measurement device main body: in which the SPR sensor cell is not mounted) can be installed in a home environment and is portable in one embodiment. The measurement device main body may have a vertical size of, for example, from about 50 mm to about 300 mm, a horizontal size of, for example, from about 50 mm to 250 mm, and a height of, for example, from about 20 mm to about 80 mm.
The measurement device 200 can measure (quantify) the amount of any suitable object to be inspected as long as the SPR phenomenon can be used. As a specific example of the object to be inspected, there is given an allergen (recognition substance: anti-allergen antibody that causes an antigen-antibody reaction with the allergen). In one embodiment, the measurement device 200 is used for quantifying an allergen. In this case, an anti-allergen antibody is fixed (typically, carried) onto the detection unit 13a of the SPR sensor cell 100. As a typical example of the allergen, there is given a mite allergen. When the measurement device 200 is used for quantifying a mite allergen, an anti-mite allergen antibody may be carried onto the detection unit 13a.
The SPR sensor cell 100 includes an optical waveguide main body 10 and a sample mounting portion 20 (hereinafter, the optical waveguide main body 10 and the sample mounting portion 20 are sometimes collectively referred to as “cell main body 110”). For practical purposes, the SPR sensor cell 100 further includes a holder 120 configured to hold and fix the cell main body 110.
Through adoption of the optical waveguide, the SPR sensor cell 100 is downsized to be portable while maintaining the quantification of the amount of the object to be inspected (for example, an allergen) with high sensitivity and high accuracy. The specific description is given below. In a related-art SPR sensor, when light is caused to enter a detection site, it is necessary to cause light to enter the detection site at an appropriate angle. Therefore, an alignment mechanism unit becomes complicated (for example, automatic angle control of incident light with a motor or the like) and requires space, and as a result, it is inevitable that the SPR sensor be enlarged. Meanwhile, in the case of the optical waveguide, propagating light is naturally converged within a desired angle range without considering an incident angle by appropriately designing a refractive index difference between a core layer and a cladding layer forming the optical waveguide. Further, even when light is caused to enter two or more sites, such as the detection unit and the reference unit, as in the embodiment of the present invention, it is only necessary that the optical waveguide (substantially, the core layer) be branched, and the light may be caused to enter only one place. Therefore, the enlargement in size can be avoided. Thus, the SPR sensor cell 100 may have a vertical size of, for example, from about 30 mm to about 100 mm, a horizontal size of, for example, from about 15 mm to about 50 mm, and a thickness of, for example, from about 0.5 mm to about 10 mm. As a result, a person (for example, a homemaker) having no expertise can use the SPR sensor cell 100 easily (that is, without requiring a skill) in a home environment.
The optical waveguide main body 10 includes an under-cladding layer 11, a core layer 12 formed so that at least a part thereof is adjacent to the under-cladding layer 11, a metal layer 13 configured to cover a part of the under-cladding layer and a part of the core layer, and a substrate 14 arranged on a bottom surface side of the under-cladding layer. In the illustrated example, the core layer 12 is buried in the under-cladding layer 11 so that an upper surface thereof is exposed from the under-cladding layer 11. Light having a specific wavelength in light introduced into the core layer 12 causes surface plasmon resonance in the metal layer 13. Based on the attenuation of the intensity of the light caused by a sample on the metal layer (sample including the object to be inspected) and a change in state of the sample, the state of the sample and/or a change therein on the surface of the metal layer can be detected.
As described above, according to the embodiment of the present invention, the SPR sensor cell 100 includes the plurality of optical waveguides. Specifically, the plurality of core layers 12, 12, . . . are formed so as to be surrounded by the under-cladding layer 11 to provide the plurality of optical waveguides, and light propagates through the core layer portion of each of the optical waveguides. In the illustrated example, the two branched core layers 12 and 12 are formed so as to be buried in the under-cladding layer 11 to provide the two optical waveguides. One of the optical waveguides forms the detection unit 13a together with the metal layer 13 which is formed so as to cover apart of the core layer 12 and onto which the recognition substance for the object to be inspected is fixed, and another one of the optical waveguides forms the reference unit 13b together with the metal layer 13 which is formed so as to cover a part of the core layer 12 and onto which the recognition material is not fixed. As described above, the recognition substance refers to a substance that exhibits a specific reaction, binding, adsorption, response, or the like with respect to the object to be inspected. When the object to be inspected is, for example, an allergen, the recognition substance is an anti-allergen antibody that causes an antigen-antibody reaction with the allergen. When the object to be inspected is the allergen, in the detection unit 13a, the allergen in a measurement sample is brought into contact with the anti-allergen antibody fixed onto the metal layer to cause an antigen-antibody reaction, and the amount of the allergen in the sample can be quantified based on a change (typically, attenuation) in light intensity caused by the antigen-antibody reaction. Meanwhile, in the reference unit 13a, as described above, a light source noise, an environmental noise, and the like can be determined based on a change in light intensity. Therefore, the amount of the allergen can be quantified more precisely by correcting the change in light intensity of the detection unit 13a with a change in light intensity of the reference unit 13b. The accurate amount of the allergen, having the light source noise, the environmental noise, and the like removed therefrom, can be measured, for example, by previously creating a reference line indicating a relative relationship between the difference of the light intensity in the reference unit 13b and the light intensity in the detection unit 13a, and the amount of the allergen. In the illustrated example, the embodiment in which the core layer is branched into two layers is illustrated. However, for example, a plurality of core layers extending substantially in parallel to each other may be arranged side by side, or branched core layers and core layers arranged side by side may be combined.
In the illustrated example, description is given of the embodiment in which the two optical waveguides (substantially, the core layers) are arranged. However, three or more (for example, 3 to 8, preferably 3 to 6, more preferably 3 to 5) optical waveguides may be arranged. In this case, a plurality of detection units and/or a plurality of reference units may be used. For example, when five optical waveguides are arranged, four detection units and one reference unit, three detection units and two reference units, two detection units and three reference units, or one detection unit and four reference units may be used. For example, when four detection units and one reference unit are used, the recognition substances to be fixed onto the detection units may be the same in all the four detection units, in the three detection units, or in the two detection units, or may be different from each other in all the four detection units. For example, when five optical waveguides are arranged to measure (quantify) the amounts of mite allergens, the amounts of Derf I, Derf II, Derp I, and Derp II can be all quantified precisely by arranging one optical waveguide as the reference unit and fixing antibodies against Derf I, Derf II, Derp I, and Derp II onto four optical waveguides (detection units). As a result, a relationship between the amount of each of the mite allergens in house dust, and the threshold value of sensitization and/or the threshold value of induction of an asthma attack can be determined.
As necessary, a protective layer (not shown) may be formed on each upper surface of the under-cladding layer 11 and the core layer 12. The protective layer is typically formed so as to cover the entire upper surfaces of the under-cladding layer 11 and the core layer 12.
In one embodiment, a development unit 15 extending across the plurality of optical waveguides (more specifically, the detection unit and the reference unit) is arranged as in the illustrated example.
The under-cladding layer 11 is formed into a shape of a plate having a substantially rectangular shape in plan view, with a predetermined thickness. The thickness of the under-cladding layer (thickness from an upper surface of the core layer) is, for example, from 5 μm to 400 μm.
The under-cladding layer 11 may be formed of any suitable material having a lower refractive index than the core layer described later. Specific examples thereof include a fluorine resin, an epoxy resin, a polyimide resin, a polyamide resin, a silicone resin, an acrylic resin, and modified products thereof (for example, a fluorene-modified product, a deuterium-modified product, and a fluorine-modified product in the case of the resins other than the fluorine resin). Those resins may be used alone or in combination thereof. Those resins can each be used as a photosensitive material preferably by being blended with a photosensitizing agent.
The under-cladding layer 11 may contain particles in addition to the above-mentioned resins. A sufficient S/N ratio can be obtained by dispersing the particles in the under-cladding layer. As the particles, any suitable particles capable of increasing the light reflectance of a surface of the under-cladding layer and/or reducing the light transparency in the under-cladding layer can be used. In the case where the particles are dispersed in the under-cladding layer, the light transmittance of the under-cladding layer at a wavelength of 650 nm may be, for example, 95% or less. When the under-cladding layer contains the particles, the accuracy required in optical coupling to the core layer can be reduced.
As a material for forming the particles, for example, there is given a metal or an inorganic oxide. In addition, an average particle diameter (φ) of the particles is, for example, from 10 nm to 5 μm. A filling ratio of the particles in the under-cladding layer is, for example, from 1% to 50%.
The core layer 12 is formed into a substantially prism shape extending from the light incidence port 12a side in a direction orthogonal to both an insertion and removal direction and a thickness direction of the SPR sensor cell, and in the illustrated example, is branched into two at a predetermined position in the above-mentioned direction. The core layer 12 is buried in the under-cladding layer 11 so that an upper surface thereof is exposed from the under-cladding layer 11. The direction in which the core layer 12 extends is a waveguide direction of the optical waveguide.
The core layer 12 is arranged so that the upper surface thereof is flush with an upper surface of the under-cladding layer 11. The metal layer can be arranged efficiently only on an upper side of the core layer by arranging the core layer so that the upper surface thereof is flush with the upper surface of the under-cladding layer. Further, the core layer is arranged so that both end surfaces thereof in the extending direction are flush with both end surfaces of the under-cladding layer in the extending direction, and the end surfaces function as the light incidence port 12a and the light output port 12b, respectively.
The core layer 12 preferably contains a halogen. When the core layer contains the halogen, the refractive index of the core layer can be decreased. As a result, the detection sensitivity can be enhanced remarkably. The SPR sensor cell according to this embodiment may have detection sensitivity sufficient for quantifying the amount of the object to be inspected (for example, an allergen) while realizing the downsizing that enables the use in a home environment. Examples of the halogen include fluorine, chlorine, bromine, and iodine. Fluorine is preferred. This is because it is easy to adjust the refractive index of the core layer to a desired refractive index. Further, the adhesion of the object to be inspected (for example, an allergen) to the core layer can be suppressed through use of fluorine, and hence measurement accuracy can be increased.
As means for allowing the core layer to contain the halogen, any suitable means can be adopted. Specifically, it is appropriate that the core layer be formed through use of a halogen-containing material. As the halogen-containing material capable of forming a core layer, for example, there are given a halogen atom-containing resin and a halogen compound-containing resin composition. Specific examples of the halogen atom-containing resin include: fluorine atom-containing resins, such as polytetrafluoroethylene, a tetrafluoroethylene-hexafluoropropylene copolymer, a fluorinated epoxy resin, a fluorinated polyimide resin, a fluorinated polyamide resin, a fluorinated acrylic resin, a fluorinated polyurethane resin, and a fluorinated siloxane resin; chlorine atom-containing resins, such as a vinyl chloride resin, a vinyl chloride-ethylene copolymer, and a chlorinated polyolefin resin; and modified products thereof. A fluorine atom-containing resin is preferred. When the fluorine atom-containing resin is used, the refractive index of the core layer can be decreased to enhance sensitivity, and an ensuing decrease in S/N ratio can be suppressed. Further details are as follows. As described above, the refractive index of the core layer can be decreased to enhance sensitivity by using fluorine. On the other hand, when the refractive index of the core layer is decreased to enhance sensitivity, an SPR absorption peak is shifted to a long wavelength side (near-infrared region). In the near-infrared region, C-H vibration absorption is present, and light intensity at an excitation wavelength decreases due to the absorption. As a result, the S/N ratio may decrease or a waveguide mode may exert its influence. The vibration absorption can be shifted to a long wavelength side and a decrease in light intensity can be suppressed by bonding a fluorine atom heavier than a hydrogen atom to carbon, and hence the decrease in S/N ratio can be suppressed. Further, as described above, the adhesion of the object to be inspected (for example, an allergen) to the core layer can be suppressed through use of fluorine, and hence measurement accuracy can be increased. The fluorine atom-containing resin exemplified in the foregoing has a remarkable effect of suppressing the adhesion of the object to be inspected to the core layer. An example of the halogen compound-containing resin composition is a resin composition containing a halogen compound and an epoxy resin, a polyimide resin, a polyamide resin, a silicone resin, an acrylic resin, and/or a urethane resin. Specific examples of the halogen compound include hexabromobenzene, hexachlorobenzene, pentabromobenzene, pentachlorobenzene, pentabromophenol, pentachlorophenol, hexabromobiphenyl, decabromobiphenyl, chlorotetrabromobutane, tetrabromobutane, hexabromocyclododecane, perchloropentacyclodecane, decabromodiphenyl ether, octabromodiphenyl ether, hexabromodiphenyl ether, ethylenebis-tetrabromophthalimide, tetrachlorobisphenol A, tetrabromobisphenol A, brominated polystyrene, halogenated polycarbonate, a halogenated epoxy compound, brominatedpolyphenylene oxide, polychlorostyrene, chlorinated paraffin, tetrabromophthalic anhydride, and tetrachlorophthalic anhydride. The halogen-containing material (material for forming the core layer) may be used as a photosensitive material preferably by being blended with a photosensitizing agent.
The halogen content of the core layer 12 (substantially, the material for forming the core layer) is preferably 35 wt % or more, more preferably 40 wt % or more, still more preferably 50 wt % or more. When the halogen content falls within such a range, a core layer having a desired refractive index is obtained, and as a result, there can be obtained an SPR sensor cell having detection sensitivity capable of realizing the quantification of the amount of an allergen in, for example, a home environment. Further, a core layer having a desired effect of suppressing the adhesion of the object to be inspected is obtained, and hence measurement accuracy can also be increased. On the other hand, the upper limit of the halogen content is preferably 78 wt %. When the upper limit is more than 78 wt %, the core layer may be liquefied or gasified and the shape of the core layer may not be maintained in some cases.
The refractive index of the core layer 12 is preferably 1.43 or less, more preferably 1.41 or less, still more preferably 1.39 or less. When the refractive index of the core layer is set to 1.43 or less, the detection sensitivity can be significantly increased, and the detection sensitivity capable of realizing the quantification of the amount of an allergen, for example, in a home environment can be realized. The lower limit of the refractive index of the core layer 12 is preferably 1.33. When the refractive index of the core layer 12 is 1.33 or more, SPR can be excited even in a sample of an aqueous solution system (refractive index of water: 1.33), and a general-purpose material can be used. The refractive index as used herein refers to a refractive index at a wavelength of 830 nm.
The refractive index of the core layer 12 is higher than that of the under-cladding layer 11. The difference between the refractive index of the core layer and that of the under-cladding layer is preferably 0.010 or more, more preferably 0.020 or more. When the difference between the refractive index of the core layer and that of the under-cladding layer falls within such a range, the optical waveguide of the detection unit can be set to a so-called multimode. Thus, the amount of light transmitted through the optical waveguide can be increased, and as a result, the S/N ratio can be increased. Further, when the optical waveguide is set to a multimode, various light is guided into the detection unit, and attenuation caused by SPR occurs in the various light. Therefore, the sensitivity can be increased.
The thickness of the core layer 12 is, for example, from 5 μm to 200 μm, preferably from 20 μm to 200 μm. In addition, the width of the core layer 12 is, for example, from 5 μm to 200 μm, preferably from 20 μm to 200 μm. When the core layer 12 has such a thickness and/or width, the optical waveguide can be set to the so-called multimode.
As illustrated in
As a material for forming the metal layer 13, there are given gold, silver, platinum, copper, aluminum, and alloys thereof. The metal layer may be a single layer or may have a laminate structure of two or more layers. The thickness (total thickness of all the layers in the case of the laminate structure) of the metal layer is preferably from 20 nm to 70 nm, more preferably from 30 nm to 60 nm.
As described above, in the SPR sensor cell, the development unit 15 extending across the plurality of optical waveguides (substantially, from the detection unit 13a to the reference unit 13b) may be arranged. The development unit 15 may be made of a porous material, for example, paper (for example, filter paper for paper chromatograph) or a porous film (for example, a non-woven fabric, a porous resin film). Through arrangement of the development unit, a liquid sample is enabled to uniformly reach the plurality of optical waveguides (substantially, the detection unit and the reference unit), and in this case, impurities, foreign matter, and the like in the sample can be removed. In the illustrated example, the development unit 15 is arranged across each entire width of the detection unit and the reference unit. However, for example, a trailing edge of the development unit 15 may be arranged in any suitable place of each surface of the detection unit and/or the reference unit within a range in which the above-mentioned effect can be exhibited. Further, unlike the illustrated example, the development unit may be arranged so as to cover each entire surface of the detection unit and the reference unit. The development unit may be arranged, for example, by fixing the above-mentioned material onto a desired place through use of an adhesive or the like.
The porous film has a pore diameter of preferably from 5 nm to 300 μm, more preferably from 10 nm to 100 μm, still more preferably from 25 nm to 50 μm, particularly preferably from 100 nm to 20 μm. When the pore diameter of the porous film is excessively small, there is a risk in that the object to be inspected may not pass or may not be transported through the porous film. When the pore diameter of the porous film is excessively large, there is a risk in that the foreign matter may not be removed. The porous film has a porosity of preferably from 25% to 95%, more preferably from 70% to 90%. Further, it is preferred that the protein adsorption ratio of the porous film be lower, and the protein adsorption ratio is preferably 300 μg/cm2 or less, more preferably 100 μg/cm2 or less, still more preferably 20 μg/cm2 or less, and particularly preferably 5 μg/cm2 or less. When the protein adsorption ratio is excessively large, there is a risk in that the object to be inspected may adsorb to the porous film to make it impossible to perform measurement in the detection unit.
As the porous film, a porous resin film that is easily formed is typically used. Specific examples of a resin that may form the porous film include a fluorine-based resin (e.g., polytetrafluoroethylene: PTFE, or polyvinylidene fluoride: PVDF), an olefin-based resin (e.g., high-molecular-weight polyethylene, high-density polyethylene, low-density polyethylene, or polypropylene), a (meth) acrylic resin (e.g., polymethylmethacrylate), a styrene-based resin (e.g., polystyrene), a vinyl acetate-based resin (e.g., an ethylene-vinyl acetate copolymer), and a cellulose-based material (e.g., a cellulose-mixed ester). In particular, a material having low protein adsorption performance is preferred, and for example, a fluorine-based resin is preferred.
The porous film may be subjected to surface treatment as necessary. As a specific example of the surface treatment, there is given hydrophilic treatment.
The thickness of the development unit 15 is, for example, from 10 μm to 5 mm, preferably from 20 μm to 500 μm, more preferably from 30 μm to 100 μm, still more preferably from 50 μm to 90 μm. With such a thickness, a liquid sample is enabled to satisfactorily reach both the detection unit and the reference unit, and in this case, impurities, foreign matter, and the like in the sample can be satisfactorily removed.
As a material for forming the easy-adhesion layer, there is typically given chromium or titanium. The thickness of the easy-adhesion layer is preferably from 1 nm to 5 nm.
As described above, a protective layer may be formed as necessary. The protective layer may be typically formed as a thin film having the same shape as that of the under-cladding layer in plan view so as to cover the entire upper surfaces of the under-cladding layer 11 and the core layer 12. Through arrangement of the protective layer, when the sample is, for example, a liquid, the sample can be prevented from causing the core layer and/or the cladding layer to swell. As a material for forming the protective layer, there are given, for example, silicon dioxide and aluminum oxide. Those materials may be preferably adjusted so that the refractive index becomes lower than that of the core layer 12. The thickness of the protective layer is preferably from 1 nm to 100 nm, more preferably from 5 nm to 20 nm.
The substrate 14 is a support substrate of the under-cladding layer. The substrate may be omitted as necessary. As a material for forming the substrate, any suitable resin may be used. Specific examples thereof include polyethylene terephthalate, polybutylene terephthalate, polyethylenenaphthalate, polyethylene, polypropylene, polystyrene, and polyimide. The thickness of the substrate is, for example, from 50 μm to 2,000 μm, preferably from 100 μm to 500 μm.
When the measurement device 200 is used for measuring (quantifying) the amount of an allergen, an anti-allergen antibody is fixed (typically, carried) onto the metal layer 13 to form the detection unit 13a in the SPR sensor cell 100. For example, when a mite allergen is quantified, an anti-mite allergen antibody is carried onto the metal layer. The procedure for carrying the anti-mite allergen antibody onto the metal layer is described below.
Through the above-mentioned operations (1) to (6), the anti-mite allergen antibody that performs an antigen-antibody reaction with the mite allergen (antigen) is carried onto the metal layer. In addition to the above-mentioned procedure, for example, a method disclosed in JP 2003-156434 A, JP 2009-216483 A, WO 90/5303 A1, U.S. Pat. No. 5,716,854 A, U.S. Pat. No. 5,922,594 A, or U.S. Pat. No. 8,012,587 B2 may also be used.
The anti-mite allergen antibody is a protein that specifically binds to the mite allergen (antigen) that causes mite allergy. As the mite allergen (antigen), Derf I or Derf II which is an allergy antigenic substance of Dermatophagoides farinae, and Derp I or Derp II which is an allergy antigenic substance of Dermatophagoides pteronyssinus can be targeted. Der I (Derf I and Derp I) is a protein having a molecular weight of about 25K, which has cysteine protease activity and is frequently found in excrements of mites. Therefore, it is considered that Der I may be a gastrointestinal enzyme. Der II (Derf II and Derp II) is a protein having a molecular weight of about 14K and is frequently found in mite bodies. The amino acid sequences of Derf I, Derf II, Derp I, and Derp II are well-known from literatures and the like. Corresponding allergens of Dermatophagoides farinae and Dermatophagoides pteronyssinus have significantly high structural similarity. For example, the amino acid sequences are 78% and 88% identical between Derf I and Derp I and between Derf II and Derp II, respectively. In particular, as an indicator of the amount of mite allergens, a Der I amount (total amount of Derf I and Derp I: amount of group 1 mite allergens) may be used. Specifically, a Der I amount of 2 μg/g in house dust may be defined as a threshold value of sensitization, and a Der I amount of 10 μg/g may be defined as a threshold value of induction of an asthma attack.
The sample mounting portion 20 is defined by an upper surface of the optical waveguide main body 10 and an over-cladding layer 21. Specifically, as illustrated in
As materials for forming the over-cladding layer 21, there are given, for example, the materials for forming the core layer and the under-cladding layer, silicone rubber, a resin film, and an inorganic oxide film. The material for forming the over-cladding layer may be a pressure-sensitive adhesive tape including a base film and a pressure-sensitive adhesive layer. The thickness of the over-cladding layer is preferably from 5 μm to 1,000 μm, more preferably from 25 μm to 200 μm. The refractive index of the over-cladding layer is preferably lower than that of the core layer. In one embodiment, the refractive index of the over-cladding layer is equal to that of the under-cladding layer.
The cell main body 110 can be manufactured by any suitable method. As a specific example of the manufacturing method, there is given a method described in JP 2012-215540 A.
The holder 120 includes an upper plate 30 and a lower plate 40, and the cell main body 110 is held by the upper plate 30 and the lower plate 40.
As illustrated in
In this embodiment, the upper plate 30 and the lower plate 40 include engagement portions capable of being engaged with each other, and the cell main body is strongly held and fixed through engagement of those engagement portions. Specifically, as illustrated in
In the upper plate 30, a first through hole 33 and a second through hole 34, each passing through the upper plate 30 in a vertical direction, are formed on both sides of the two metal layers 13 in plan view, respectively, that is, on the cell insertion side and the measurement device main body side with the two metal layers 13 interposed therebetween. When the upper plate 30 and the lower plate 40 are integrated as the holder 120 so as to hold and fix the cell main body 110, the first through hole 33 and the second through hole 34 each communicate to the sample mounting portion 20. In this configuration, the first through hole 33 is used as a sample introduction portion, and the second through hole 34 serves as a ventilation hole. Therefore, the sample having been introduced into the first through hole 33 flows through the sample mounting portion 20 in the direction of the measurement device main body to be brought into contact with the metal layer 13 through the capillary phenomenon, to thereby enable measurement. The first through hole 33 is formed at a position that is to be placed on an outer side of the measurement device main body when the SPR sensor cell 100 is mounted on the cell mounting portion. With such a configuration, the sample can be introduced after the SPR cell sensor cell is mounted on the cell mounting portion, and hence operability can be enhanced.
The inner diameter of the first through hole 33 is typically from 2 mm to 10 mm, and about 10 μl of the sample can be introduced into the first through hole 33. Further, the inner diameter of the second through hole 34 is typically from 0.1 mm to 2 mm.
As materials for forming the upper plate 30 and the lower plate 40, any suitable materials may be used depending on the purpose and the like. Specific examples of the formation materials include polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polyethylene, polypropylene, polystyrene, and polyimide. The thickness of the upper plate 30 (thickness of a portion in which the push-in portion is not formed) is, for example, from 0.5 mm to 5 mm, preferably from 0.8 mm to 3 mm. The thickness of the lower plate 40 (thickness of a portion in which the cell main body mounting portion is not formed) is, for example, from 0.5 mm to 8 mm, preferably from 0.5 mm to 5 mm.
Each of the upper plate 30 and the lower plate 40 may be manufactured by any suitable method, for example, injection molding or cutting.
Now, as an example of a method of using the measurement device, a quantification method for a mite allergen is described. First, in a room in a house, a building, or the like to be inspected for mite contamination, dust is collected, for example, with a cleaning tool that includes a filter having filter openings capable of collecting the dust. The dust may be collected by wiping the dust with the cleaning tool or by sucking the dust with a vacuum cleaner when the cleaning tool is the vacuum cleaner. For example, when the dust is sucked with the vacuum cleaner, a mite allergen in the room is sucked into the vacuum cleaner through the suction and collected into the filter. The filter is removed from the vacuum cleaner, and a predetermined amount of the dust collected with the filter is dissolved or dispersed in a predetermined amount of a buffer solution (for example, a Tris-buffered solution, TBS, MOPS, a phosphate buffer solution) to prepare a sample liquid. Further, for example, in the case of a cyclone-type vacuum cleaner, a sample liquid may be prepared by pouring a buffer solution into the dust collected into a collecting container or transferring the collected dust to another container and pouring the buffer solution into the dust. Meanwhile, as illustrated in
As described above, the measurement device according to the embodiment of the present invention can be used by a person (for example, a homemaker) having no expertise in a home environment. From such a viewpoint, the measurement device may be provided as a set including predetermined members. Specifically, the measurement device set may include: the measurement device main body having the SPR sensor cell mounted thereon, which can be used continuously by replacing the cell with a new cell; the SPR sensor cell that is used by being replaced for each measurement of the amount of an allergen; and a sample liquid preparation and dropping member capable of preparing a sample liquid from collected house dust and dropping the sample liquid onto the SPR sensor cell. The SPR sensor cell and the measurement device main body are as described above in the sections A and B. The sample liquid preparation and dropping member is configured, for example, as follows. The sample liquid preparation and dropping member is filled with a predetermined amount of the above-mentioned buffer solution and sealed before use. At the time of use, house dust can be supplied to the buffer solution to be dissolved or dispersed therein to prepare a sample liquid. Further, the sample liquid can be dropped from the member onto the sample introduction portion of the SPR sensor cell. Such a sample liquid preparation and dropping member does not need to measure the buffer solution and needs to measure only the house dust. Therefore, the operation of the sample liquid preparation and dropping member is simple, and the concentration of the house dust (as a result, mite allergen) in the sample liquid can be adjusted more accurately. Specifically, as illustrated in
As means for collecting dust, a wiping member may be used. Thus, the above-mentioned set may include the wiping member. In one embodiment, the wiping member is a sheet-like or flat bar-like member including a roughened or porous collecting portion. In this case, a measurer (for example, a homemaker) wipes (or rubs) a test object with the wiping member to collect a sample, and prepares and drops a sample liquid through use of the sample liquid preparation and dropping member, thereby being able to quantify the amount of a mite allergen. Further, in another embodiment, a sheet having a sample collected thereon is immersed in the above-mentioned buffer solution to extract the allergen, to thereby prepare a sample liquid (extraction liquid), and the extraction liquid is dropped onto the sample introduction portion of the SPR sensor cell, with the result that the amount of the mite allergen can be quantified. Further, in another embodiment, the SPR sensor cell can be used for collecting a sample. For example, a sample can be collected through use of the SPR sensor cell by imparting a collecting (typically, wiping) function to the upper plate of the SPR sensor cell. More specifically, the first through hole (sample introduction portion) of the upper plate as illustrated in
When the quantification of the amount of the mite allergen is performed through use of the measurement device according to the embodiment of the present invention in a home environment, it is preferred that the quantification be performed periodically and continuously at a predetermined point (preferably a plurality of points). Through use of such quantification, a more appropriate cleaning method (removal method for the mite allergen) can be clarified, and the amount of the mite allergen can be significantly reduced by periodically and continuously performing the quantification and the appropriate cleaning method in combination. As a result, allergy diseases caused by mites can be significantly effectively prevented.
The present invention is hereinafter described specifically by way of Examples. However, the present invention is not limited to these Examples.
In this Example, the effect of providing a reference unit and a development unit was verified.
First, the SPR sensor cell as illustrated in
Next, dust was collected from a carpet in a room, and a sample liquid was prepared through use of the member as illustrated in
As is apparent from
An SPR sensor cell was manufactured in the same manner as in Example 1 except that the development unit was not provided.
An SPR sensor cell was manufactured in the same manner as in Example 1 except that none of the reference unit and the development unit was provided.
The measurement device of the present invention may be used in general measurement of the amount of an object to be inspected, which may use the SPR phenomenon, and may be used suitably, in particular, for quantification of an allergen (typically a mite allergen).
| Number | Date | Country | Kind |
|---|---|---|---|
| 2015-020936 | Feb 2015 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2016/052646 | 1/29/2016 | WO | 00 |
