WO2017169715A1 - Inspection device, inspection apparatus and inspection method - Google Patents
Inspection device, inspection apparatus and inspection method Download PDFInfo
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- WO2017169715A1 WO2017169715A1 PCT/JP2017/010093 JP2017010093W WO2017169715A1 WO 2017169715 A1 WO2017169715 A1 WO 2017169715A1 JP 2017010093 W JP2017010093 W JP 2017010093W WO 2017169715 A1 WO2017169715 A1 WO 2017169715A1
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- inspection device
- inspection
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
Definitions
- the present invention relates to a test device for detecting an antigen, antibody, deoxyribonucleic acid, or the like, which is a test substance, a test apparatus equipped with the test device, and a test method.
- the binding phenomenon between a test substance and a capture substance is optically determined.
- a method of detecting is known. In this method, a test substance is bound to a capture substance fixed at a predetermined position, and a label that emits fluorescence upon receiving excitation light, or a label that catalyzes a substrate reaction to generate color, fluorescence, or chemiluminescence. Or the like is applied to the test substance, and light generated due to the label is detected.
- a method of detecting a fluorescence generated from a fluorescent label by attaching a fluorescent label to a binding substance such as an antibody that specifically binds to the test substance, a binding of an antibody that specifically binds to the test substance
- a binding substance such as an antibody that specifically binds to the test substance
- a binding of an antibody that specifically binds to the test substance There are known methods for detecting color development, fluorescence, chemiluminescence, etc. generated from a chromogenic substrate, fluorescent substrate, or chemiluminescent substrate that reacts with this enzyme as a catalyst. Identification becomes possible.
- a multi-item simultaneous detection chip in which biologically related molecules are regularly arranged on a two-dimensional substrate has been conventionally used.
- a device made of a porous substrate in which a large number of through-holes (pores) are arranged on a support has been studied.
- a porous silicon (Si) base material As a porous substrate, a porous silicon (Si) base material is known, but silicon has low reflectivity, and the light generated in the pores is reflected multiple times in the pores. Since the signal intensity is greatly attenuated, there is a problem that the light extraction efficiency of the optical signal generated in the pore is very low.
- Patent Document 1 As a means for solving the above problem, porous silicon is thermally oxidized to be locally transparent silicon oxide (SiO 2 ), and the oxidized region is surrounded by a frame (wall) made of silicon.
- a configuration has been proposed in which the light output aperture is substantially widened to improve the light extraction efficiency.
- the amount of extracted light is increased by making the diameter of the pores of the porous substrate larger than the inside in the diameter of the opening portions on the front and back sides.
- Patent Document 3 proposes a device having tapered pores whose diameter gradually increases toward the light extraction surface of the substrate.
- Patent Document 1 Although it is possible to improve the light extraction efficiency with an increase in the light aperture ratio, the light incident on the silicon wall is attenuated because the reflectance of silicon used as the frame wall is low. The extraction efficiency of light incident on the frame wall is not improved.
- Patent Document 2 since the opening diameter on both surfaces of one side and the other surface of porous silicon is larger than the inner opening diameter, the light traveling toward one surface or the other surface side The light extraction efficiency is increased because the light aperture ratio is improved. However, since light that travels to one surface or the other surface is not directed to the opposite surface, a light detector is disposed only on one surface or only on the other surface. When used in a measuring apparatus that performs detection, it is not possible to achieve a sufficient improvement in extraction efficiency.
- Patent Document 3 a portion of light that has occurred in the pores and that has progressed toward the surface opposite to the light extraction surface is formed by tapered pores whose diameter gradually increases toward the light extraction surface of the substrate. Although it can be reflected by the inner wall surface and directed toward the light extraction surface side, it is expressed by the ratio of the length of the pore to the diameter of the pore due to the demand for higher performance of the chip as described above. When the aspect ratio becomes large, a sufficient taper angle cannot be set, so that the light extraction efficiency cannot be sufficiently improved.
- the inspection device of the present invention is an inspection device having a plurality of pores penetrating from one surface of the plate-like substrate to the other surface,
- the pore is continuous with the columnar hollow portion extending with the same opening diameter and the inner wall surface forming the columnar hollow portion formed on the other surface side of the columnar hollow portion, and the pore is larger than the opening diameter in the columnar hollow portion.
- Having a reflective surface to reduce the opening diameter of This is an inspection device in which the angle formed by the reflection surface and the other surface is 0 ° or more and 45 ° or less.
- a trapping substance that specifically binds to a specific substance is fixed on the inner wall surface of the hollow columnar portion of the present invention.
- the capture substance is preferably an antigen, an antibody, or deoxyribonucleic acid (DNA).
- the reflective surface is preferably a metal surface.
- the pore has a tapered portion that gradually decreases the opening diameter of the pore from one surface toward the columnar hollow portion.
- the plate-like substrate may be made of one or more materials of Si, SiO 2 , Al, Al 2 O 3 and a resin material.
- the material constituting the reflecting surface may be different from the material constituting the columnar hollow portion.
- the opening diameter in the columnar hollow portion of the pore is preferably 1 ⁇ m to 100 ⁇ m.
- the opening diameter is defined by the equivalent circle diameter of the opening region in a cross section parallel to one surface.
- the equivalent circle diameter refers to the diameter of a circle having the same area as the area of the opening region.
- the thickness of the plate-like substrate is preferably 100 ⁇ m to 2000 ⁇ m.
- the inspection apparatus of the present invention includes the inspection device of the present invention, A solution supply unit for supplying an inspection solution into the pores of the inspection device;
- the inspection apparatus includes a photodetector that is disposed on one surface side of the inspection device and detects light emitted from the inspection device.
- the inspection method of the present invention fixes a capture substance that specifically binds to a specific substance on the inner wall surface of the columnar hollow portion of the at least some pores of the inspection device of the present invention, Supply the sample liquid containing the specific substance, and bind the specific substance to the capture substance.
- a labeling substance that specifically binds to a specific substance is bound to the specific substance, This is an inspection method for detecting light emitted from the one surface of the inspection device in a state in which the inspection solution is supplied to the pores and the inspection solution is retained in the pores.
- an enzyme label is used as the label
- the light produced when the substrate is catalyzed by the enzyme label may be detected.
- the substrate include a chromogenic substrate, a fluorescent substrate, and a chemiluminescent substrate, and these substrates are appropriately selected depending on the type of enzyme label.
- the light emitted from the inspection device differs depending on the substrate, and the detected light is light absorption (coloration), fluorescence, or chemiluminescence.
- a substance containing a fluorescent label is used as a labeling substance, excitation light that excites the fluorescent label is irradiated to the inspection device, and the labeling substance is irradiated by excitation light as light emitted from the inspection device. Fluorescence resulting from may be detected.
- the inspection device of the present invention is an inspection device having a plurality of pores penetrating from one surface of a plate-like substrate to the other surface, and the columnar hollow portion in which the pores extend with the same opening diameter, and the columnar shape
- the reflective surface formed on the other surface side of the hollow portion is continuous with the inner wall surface of the columnar hollow portion and has a smaller opening diameter than the pores of the columnar hollow portion. Since the formed angle is 0 ° or more and 45 ° or less, it is possible to improve the extraction efficiency of light generated in the pores to the one surface side of the inspection device.
- FIG. 1 It is a perspective view of the inspection device concerning the embodiment of the present invention. It is a top view of the inspection device shown in FIG. It is sectional drawing of the test
- FIG. 1 is a perspective view of an inspection device according to a first embodiment of the present invention
- FIG. 2 is a plan view of the inspection device of FIG. 1
- FIG. 3 is a sectional view taken along line III-III of the inspection device of FIG. 4 is a bottom view of the inspection device of FIG.
- the inspection device 1 of the present embodiment includes a plate-like base material 10 having a plurality of pores 14 penetrating from one surface 11 to the other surface 12, and the pores 14 extend in the same opening diameter.
- 40 and a reflecting surface that is formed on the other surface 12 side of the columnar hollow portion 40 and that is continuous with the inner wall surface 41 constituting the columnar hollow portion 40 and that makes the opening diameter ⁇ of the pore 14 smaller than that of the columnar hollow portion 40. 42.
- the reflection surface 42 has an angle ⁇ with the other surface 12 of 0 ° or more and 45 ° or less.
- the inner wall surface 14 a of the pore 14 includes at least an inner wall surface 41 and a reflecting surface 42 that constitute the columnar hollow portion 40.
- a trapping substance 30 that specifically binds to a specific substance is fixed to the inner wall surface 14 a of the pore 14.
- acquisition substance 30 should just be provided in the inner wall surface 41 which comprises a columnar hollow part among the inner wall surfaces 14a.
- the plan view shown in FIG. 2 is a view of the inspection device 1 as viewed from one surface 11, and the bottom view of FIG. 4 is a view of the inspection device 1 as viewed from the other surface 12.
- the external shape of the inspection device 1 is configured by the external shape of the plate-like base material 10 as shown in FIG. 1, in the following, one surface 11 and the other surface 12 of the plate-like base material 10 are Sometimes referred to as one surface and the other surface of the inspection device 1.
- the plate-like substrate 10 is made of one or more materials of Si (silicon), SiO 2 (silicon oxide), Al (aluminum), Al 2 O 3 (alumina), and a resin material. Preferably it is.
- the plate-like substrate 10 may be opaque made of Si or Al, or may be transparent made of SiO 2 or Al 2 O 3 .
- the plate-like substrate 10 may be composed of any single material, or may include, for example, a Si portion and a SiO 2 portion by partially oxidizing the Si substrate,
- the Al base material may be partially oxidized to include an Al portion and an Al 2 O 3 portion.
- the plate-like substrate 10 may be composed of a main body member made of Si, SiO 2 , Al, or Al 2 O 3 and a surface member made of a resin material.
- the thickness t (see FIG. 3) of the plate-like substrate 10 is not particularly limited, but is preferably about 100 ⁇ m to 2000 ⁇ m.
- the length (thickness) t 1 of the columnar hollow portion 40 and the length t 2 in the pore length direction of the portion where the reflecting surface 42 is arranged in a tapered shape hereinafter, “ The total of the thickness t 2 of the reflecting surface 42 is called the thickness t 2 of the plate-like substrate 10.
- the pores 14 provided in the plate-like substrate 10 are preferably arranged as shown in the present embodiment, but may be arranged randomly. In the present embodiment, 9 pores of 3 rows ⁇ 3 columns are provided for easy visual recognition, but the inspection device 1 includes, for example, 100 pores of 10 rows ⁇ 10 columns. There is no limit to the number of pores provided in the case. In addition, for example, an inspection device including a plurality of inspection regions may be provided with 100 pore regions of 10 rows ⁇ 10 columns as one inspection region.
- the cross-sectional shape (opening shape) parallel to the one surface 11 of the pore 14 is a square shape, but the opening shape is not limited to a rectangle such as a square or a rectangle, but a circle, an ellipse, a triangle, It may be a pentagon or more polygon. Note that the corners of the polygon may be rounded due to manufacturing reasons.
- the opening diameter ⁇ of the pore 14 is a circle-equivalent diameter in a cross-sectional shape (opening region) parallel to one surface 11 of the pore 14.
- the opening diameter ⁇ of the pore 14 is the same in the columnar hollow portion 40, and is configured to become smaller as it approaches the other surface 12 by the reflecting surface 42.
- the opening diameter in the columnar hollow portion 40 of the pores 14 is preferably about 1 ⁇ m to 100 ⁇ m. More preferably, it is 3 ⁇ m to 50 ⁇ m, and particularly preferably 5 ⁇ m to 30 ⁇ m.
- the aspect ratio (t / ⁇ ) represented by the thickness of the plate-like substrate with respect to the opening diameter in the columnar hollow portion 40 is preferably 5 or more and 100 or less. When the aspect ratio is within this range, the effect of providing the reflecting surface 42 is particularly remarkable.
- the aspect ratio with respect to the opening diameter of the thickness from the one surface 11 side with respect to the opening diameter in the columnar hollow part 40 to the portion including the reflecting surface 42 is 5 or more and 100 or less. It is preferable that
- the reflection surface 42 only needs to be reflective to light generated due to a sign described later.
- having the reflectivity means that the reflectance with respect to the light to be reflected is 50% or more.
- the reflectance at least for the wavelength of 550 nm may be 50% or more.
- a reflectance of 50% or more with respect to the entire visible light (wavelength 400 nm to 700 nm) is preferable because it can be applied regardless of the type of label.
- the reflective surface 42 may be a metal surface made of a metal such as steel, stainless steel, aluminum, gold, platinum, silver, copper, titanium, nickel, cobalt, tin, tungsten, molybdenum, or niobium.
- high resin reflectance such as white resin, for example, may be composed of pigments or fillers such as TiO 2, Al 2 O 3.
- the angle ⁇ between the reflecting surface 42 and the other surface 12 is 0 ° to 45 °.
- ⁇ is 0 °
- the reflecting surface 42 and the other surface 12 are parallel.
- the reflecting surface 42 is provided as a tapered portion that gradually decreases the opening diameter of the pore from the columnar hollow portion 40 toward the other surface 12.
- FIG. 5 is a schematic view showing a part of the cross section of the inspection device 1.
- This test device 1 binds a test substance to a capture substance (not shown in FIG. 5) fixed to the inner wall surface 14a of the pore 14, and further receives a secondary antibody labeled with an enzyme. Used in a test method for detecting the presence or absence of the test substance and / or the amount of the test substance by detecting an optical signal that is chemiluminescent using the enzyme (label F) as a catalyst by binding to the test substance. It is done.
- the light generated in one pore 14 is repeatedly reflected by the inner wall surface 14a of the pore 14 and emitted from the surface.
- the reflecting surface 42 by providing the reflecting surface 42, the light generated by the sign F and radiated to the other surface 12 side is reflected directly or by the inner wall surface 14a and incident on the reflecting surface 42 is reflected.
- the light is reflected by the surface 42 and guided to the one surface 11 side. As a result, the amount of light emitted from the one surface 11 of the light generated in the pores 14 can be effectively increased.
- the reflecting surface 42 having an angle ⁇ formed with the other surface 12 of 45 ° or less is continuously provided on the inner wall surface 41 constituting the columnar hollow portion 40, the inner wall surface 14 a of the pore 14, in particular, Of the light generated on the inner wall surface 41 of the columnar hollow portion 40, the light incident on the reflecting surface 42 can be efficiently reflected. If the angle ⁇ is 45 ° or less, the proportion of the light incident on the reflective surface 42 that is reflected toward one surface is set to be equal to or greater than the proportion of the light reflected toward the other surface. Therefore, the effect of improving the light extraction amount on the one surface 11 side is high. As the angle ⁇ approaches 0 °, it is possible to increase the proportion of light reflected toward one surface of the light incident on the reflecting surface 42. However, when the angle ⁇ is small, the opening diameter on the other surface 12 is relatively small, and it may be difficult to suck the test solution from the other surface 12 into the pores. What is necessary is just to determine suitably in the range of -45 degrees.
- the light extracted from the one surface 11 side is significantly increased by reflecting the light generated from the pores 14 by the reflection surface 42 provided on the other surface 12 side. Can be made.
- the test substance (target molecule) to be tested in this testing device 1 is mainly a biological molecule, such as proteins such as antigens and antibodies, saccharides, peptides, DNA, ribonucleic acid (RNA), peptides Examples thereof include nucleic acids (peptide nucleic acid: PNA).
- acquisition substance 30 specifically couple
- the test device 1 is suitable for an allergy test provided with an allergen that is a kind of antigen as a capture substance.
- different trapping substances can be fixed between the plurality of pores 14. Accordingly, it is possible to simultaneously inspect a plurality of test substances with one inspection device 1. Note that there may be two or more pores containing the same type of trapping substance between the plurality of pores 14. If an inspection device in which pores 14 in which different capture substances are fixed are alternately arranged and pores in which the same kind of capture substance is fixed is used is used, a test result with reduced variation is obtained. It becomes possible.
- a plurality of allergens can be provided in one test device by providing pores to which different types of allergens are fixed. It becomes possible to test the response to
- a capture substance may be bound (fixed), and different capture substances may be fixed between a plurality of examination regions. Since a plurality of pores are provided in one inspection region, it is possible to simultaneously inspect a plurality of test substances while improving the sensitivity to one kind of test substance. Note that there may be two or more regions containing the same type of capture substance between a plurality of inspection regions.
- FIGS. 6 to 10 are sectional views of a part of the inspection device of the design change example.
- a plurality of pores 14 shown in each figure are arranged two-dimensionally.
- the reflection surface 43 is parallel to the other surface 12 of the plate-like substrate 10, that is, the angle formed with the other surface is 0 °.
- the pore 14 has an inner wall surface 14 a composed of an inner wall surface 41 of the columnar hollow portion 40, a reflecting surface 43, and an inner wall surface 48 constituting a small-diameter hollow portion having an opening diameter smaller than that of the columnar hollow portion 40.
- the total of the thickness t 1 of the columnar hollow portion 40 and the thickness t 3 of the small-diameter hollow portion whose opening diameter is narrowed by the reflecting surface 43 is the thickness t of the plate-like substrate 10.
- the reflection surface 44 is a curved surface.
- the pore 14 has an inner wall surface 14 a composed of an inner wall surface 41 of the columnar hollow portion 40 and a reflecting surface 44 formed of a curved surface.
- the sum of the thickness t 1 of the columnar hollow portion 40 and the thickness t 4 in the pore length direction of the portion where the curved reflecting surface 44 is formed is the thickness t of the plate-like substrate 10. is there.
- the reflecting surface 44 is a curved surface
- the angle formed between the tangent at the position on the most surface 12 side of the reflecting surface 44 and the other surface 12 is ⁇ , and this angle ⁇ should be 0 ° to 45 °. That's fine. Also in this case, the same effect as the above embodiment can be obtained.
- the inspection device of the third modification shown in FIG. 8 includes the same reflective surface 42 as that of the above-described embodiment. Furthermore, a tapered surface 45 whose opening diameter gradually increases from one columnar hollow portion 40 is provided in the pore opening portion on the one surface 11 side of the plate-like substrate 10.
- the pore 14 has an inner wall surface 14 a composed of the inner wall surface 41, the reflecting surface 42, and the tapered surface 45 of the columnar hollow portion 40.
- the sum of the thickness t 1 of the columnar hollow portion 40, the thickness t 2 occupied by the reflecting surface 42, and the thickness t 5 in the pore length direction of the portion where the tapered surface 45 is formed is a plate shape. It is the thickness t of the base material 10.
- Increasing the opening diameter of the opening of one surface 11 as in this example can increase the amount of light extracted from the one surface 11 side of the light generated in the pores 14, which is preferable.
- the inspection device of the design modification example 4 shown in FIG. 9 includes a reflective surface 42 on the other surface 12 side in succession to the inner wall surface 41 of the columnar hollow portion 40, as in the above-described embodiment.
- a tapered surface 49 is provided on the other surface 12 side of 42 to increase the opening diameter again.
- the pore 14 has an inner wall surface 14 a composed of the inner wall surface 41, the reflecting surface 42, and the tapered surface 49 of the columnar hollow portion 40.
- the total of the thickness t 1 of the columnar hollow portion 40, the thickness t 2 occupied by the reflecting surface 42, and the thickness t 6 occupied by the tapered surface 49 is the thickness t of the plate-like substrate 10. In this way, by providing a portion having a larger opening diameter on the other surface 12 side than the reflecting surface 42, the inspection solution into the pores 14 from the other surface 12 side in the inspection method described later. The structure is easy to suck up.
- the thickness of the columnar hollow 40 It is desirable that the ratio of t 1 to the opening diameter of the columnar hollow portion is 5 to 100.
- the thickness t 1 of the columnar hollow portion 40 and the reflection are excluded except for the thickness t 6 occupied by the tapered surface 49. It is desirable that the ratio of the total t 1 + t 2 of the thickness t 2 occupied by the surface 42 to the opening diameter of the columnar hollow portion is 5 to 100.
- the plate-like substrate 10 may be made of a single material, or may be made of a plurality of materials that differ depending on the part.
- FIG. 10 shows a configuration example of an inspection device having portions made of different materials.
- FIG. 10 is a cross-sectional view of a part of the inspection device.
- the inspection device shown in FIG. 10 has pores 14 having the same shape as that of the inspection device of design modification example 3 shown in FIG.
- the plate-like base material 10 includes a main body member 17 constituting the columnar hollow portion 40, and a first surface member 18 a constituting the tapered surface 45 and one surface 11 made of a material different from that of the main body member 17.
- the second surface member 18b that constitutes the reflecting surface 42 and the other surface 12.
- a plate-like main body member 17 made of Si, SiO 2 , Al, or Al 2 O 3 having a plurality of columnar pores is produced.
- a main body member made of Si having a plurality of columnar pores can use a microporous Si manufacturing process known in MEMS (Micro Electro Mechanical System) technology.
- the main body member made of SiO 2 having a plurality of columnar pores can be obtained by performing a thermal oxidation process on the main body member made of Si.
- a plate-like body member made of Al having a plurality of columnar pores can be produced by forming pores in an Al plate-like substrate by a mechanical method such as a drill, or by etching or the like.
- the production method of the main body member 17 is not limited to these, and various known techniques for forming a porous substrate can be used.
- the opening diameter on one surface 11 of the plate-like base material 10 and the one surface 11 is made larger than that of the columnar hollow portion 40.
- the first surface member 18a constituting the tapered surface 45 and the second surface member 18b constituting the reflecting surface 42 and the other surface 12 for reducing the opening diameter on the other surface 12 side of the columnar hollow portion 40 are: For example, it can be manufactured using a 3D printer.
- a 3D printer is preferably a modeling method (powder sintering layered modeling method) in which a high-power laser beam is applied to a powdered material and sintered. In particular, the material powder and the laser are simultaneously irradiated to melt any part. If it is the thing of the modeling system made to make it laminate, the freedom degree of a foundation
- the first material having a desired shape is formed by a metal material that can constitute a reflective surface, such as steel, stainless steel, aluminum, gold, platinum, silver, titanium, copper, nickel, cobalt, tin, tungsten, molybdenum, or niobium. And the 2nd surface member 18a, 18b can be produced easily.
- the first and second surface members 18a and 18b made of a photocurable resin are produced by an optical modeling method in which a liquid photocurable resin composition is cured and laminated one by one with an ultraviolet laser. May be.
- a reflective material may be selected as the photocurable resin.
- UV (Ultraviolet) cured epoxy resin, UV cured acrylic resin, and the like can be given.
- the capture substance which is a specific binding substance that specifically binds to the test substance is bound (immobilized) to the inner wall surface 14a of the pore 14 of the plate-like substrate 10 manufactured as described above.
- the inspection device 1 to be used for inspection can be manufactured.
- a known method can be applied without any particular limitation.
- the method disclosed in the above-described Patent Document 1 can be used.
- FIG. 11 is a diagram schematically showing the configuration of the inspection apparatus 50 according to an embodiment of the present invention.
- the inspection apparatus 50 according to the present embodiment is disposed on the inspection device 1, the solution supply unit 60 that supplies the inspection solution into the pores 14 of the inspection device 1, and the one surface 11 side of the inspection device 1.
- a photodetector 70 a photodetector 70.
- the light detector 70 detects light emitted from the inspection device 1.
- FIG. 12 is a diagram illustrating a schematic configuration of the solution supply unit 60.
- the solution supply unit 60 stores the inspection solution 61 installed on the other surface 12 side of the inspection device 1, and the inspection installed in the upper part of the storage unit 62 and stored in the storage unit 62.
- the pipette part 64 for sucking the solution 61 for use, and the pressure of the depressurizing space part 66 and the depressurizing space part 66 arranged on the one surface 11 side of the inspection device 1 installed on the pipette part 64 are reduced.
- a pump 68 for pressurization is provided.
- the reduced pressure space 66 is decompressed by the pump 68, whereby the inspection solution 61 passes through the pipette part 64 and the pore 14 of the inspection device 1. Supplied in. Note that the inspection solution 61 is supplied to the pores 14 of the inspection device 1 and the inspection solution 61 is discharged from the pores 14 by depressurization and pressurization of the reduced pressure space 66 by the pump 68. it can.
- the test solution 61 is a solution supplied into the pores 14 at the time of light detection, but the solution supply unit 60 includes a sample solution, a label solution, a cleaning solution, and the like to be supplied into the pores 14 in the test process. It is also used for supply. That is, the solution supply unit 60 supplies a necessary solution to the pores 14 for each inspection process.
- the light emitted from the inspection device and detected by the photodetector is, for example, fluorescence generated when the label attached to the test substance is excited, or luminescence generated by the label acting as a catalyst of the reaction solution It is an optical signal resulting from a label, such as fluorescence or chemiluminescence.
- a label such as fluorescence or chemiluminescence.
- the optical signal includes absorbance (colorimetric) in addition to fluorescence and chemiluminescence light.
- FIG. 13 is a diagram schematically showing the inspection process.
- a capturing substance 30 such as an allergen is fixed to the inner wall surface 14a of the pore 14 of the inspection device 1 (S1).
- a specimen liquid containing a test substance (for example, a specific IgE antibody that specifically binds to the allergen) is supplied to the pores 14 of the test device 1, and the test substance 32 is bound to the capture substance 30 (S2). ).
- the above-described solution supply unit 60 is used for supplying the sample liquid.
- the sample liquid is efficiently brought into contact with the capture substance 30 in the pores 14 by repeatedly pumping and discharging the sample liquid by the pipette unit 64 while the sample liquid is stored in the storage unit 62. Can do.
- a labeled solution containing a labeled substance 35 in which a label F is added to a substance 33 (for example, a secondary antibody) that specifically binds to the test substance 32 is supplied to the pores 14.
- a substance 33 for example, a secondary antibody
- the labeling substance 35 is bound to the test substance 32 (S3).
- the label solution is supplied to the pores 14 by the solution supply unit 60 in the same manner as the sample solution.
- the labeling substance 35 is bound to the test substance 32 after the test substance 32 is bound to the capture substance 30. It is also possible to combine the test substance 32 and the labeling substance 35 by mixing and supply the mixed liquid into the pores 14. In this case, by supplying the mixed liquid to the pores 14, the test substance 32 to which the labeling substance 35 is bound can be bound to the capture substance 30 fixed in the pores 14.
- the cleaning solution is supplied to the pores 14 using the solution supply unit 60 in the same manner as the supply of the sample solution, and nonspecific adsorption is performed in the pores 14.
- the test substance 32 and the labeling substance 35 are removed.
- the cleaning solution is discharged, and light generated from a luminescence reaction that acts using the label F as a substrate is detected by the photodetector 70 in a state where the inspection solution such as a buffer solution is filled in the pores 14 (S4). ).
- the inspection device 1 when the light emitted from the inspection device 1 is detected by the photodetector 70, the inspection device 1 includes the reflection surface 42, thereby reflecting the light generated in the pore 14 and emitted to the other surface 12 side. Since the light can be reflected to the one surface 11 side by the surface 42, light detection can be performed efficiently on the one surface 11 side.
- the buffer solution is supplied into the pore 14 as a test solution, and the fluorescence measurement is performed with the pore 14 filled with the buffer solution. .
- the inspection device is irradiated with light having a wavelength that excites the fluorescent label as excitation light, and fluorescence from the label excited by the excitation light is detected.
- the photodetector 70 used for detecting the fluorescent label is provided with an excitation light irradiation unit.
- the label F is an enzyme label that catalyzes a chemiluminescent substrate such as luminol
- a reaction solution containing a chemiluminescent substrate that promotes a chemical reaction using the enzyme label as a catalyst after the washing treatment is used as a test solution.
- the enzyme label imparted to the test substance 32 captured by the capture material 30 in the pores 14 becomes the substance in the reaction solution.
- Luminescence generated by catalyzing a chemical reaction is detected. In this case, luminescence detection is performed in a state where the pores 14 are filled with the reaction solution.
- enzyme labels that produce chemiluminescence include enzymes that react with chemiluminescent substrates such as luminol, lophine, lucigenin and oxalate.
- HRP horseradish peroxidase
- a reaction liquid luminol reaction liquid
- HRP functions as a catalyst an enzyme for reacting a luminol-based chemiluminescent substrate.
- ALP alkaline phosphatase
- the luminol reaction solution contains at least a luminol substrate and a hydrogen peroxide solution.
- the enzyme label catalyzes the oxidation of luminol in the presence of hydrogen peroxide.
- the reaction solution preferably contains a sensitizer that sensitizes chemiluminescence.
- chemiluminescent substrate described above but also a reaction solution containing a luminescent substrate or a fluorescent substrate may be used to detect a color (absorption) reaction or fluorescence. it can.
- the inspection device of the present invention by using the inspection device of the present invention, the light generated in the pores is efficiently emitted from the surface of the inspection device, and the light extraction efficiency is high. Is possible.
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Abstract
[Problem] To provide an inspection device with which it is possible to improve light extraction efficiency, in addition to an inspection apparatus equipped with the inspection device, and an inspection method. [Solution] This inspection device (1) comprises a plurality of pores (14) that pass through a plate-shaped substrate (10) from a first surface (11) to a second surface (12). Each of the pores (14) has a columnar cavity (40) that extends in the same opening diameter, and a reflective surface (42) that is formed on the second surface (12) side of the columnar cavity (40), that is contiguous with the inner wall surface of the columnar cavity (40), and that reduces the opening diameter of the pores to smaller than the opening diameter in the columnar cavity (40). The angle formed by the reflective surface (42) and the second surface (12) is from 0° to 45°.
Description
本発明は、被検物質である抗原、抗体もしくはデオキシリボ核酸などを検出するための検査デバイス、その検査デバイスを備えた検査装置および検査方法に関する。
The present invention relates to a test device for detecting an antigen, antibody, deoxyribonucleic acid, or the like, which is a test substance, a test apparatus equipped with the test device, and a test method.
生化学的な反応、例えば、酵素反応、核酸ハイブリダイゼーション、抗原－抗体反応などの特異的結合反応を検査する方法の一つとして、被検物質と捕捉物質との間の結合現象を光学的に検出する方法が知られている。この方法は、所定位置に固定されている捕捉物質に被検物質を結合させ、励起光を受けて蛍光を発する標識、あるいは、基質の反応を触媒して発色、蛍光もしくは化学発光を生じさせる標識などをその被検物質に付与し、かかる標識に起因して生じる光を検出するものである。より具体的には、被検物質に特異的に結合する抗体などの結合物質に蛍光標識を付与し、蛍光標識から生じる蛍光を検出する方法、被検物質に特異的に結合する抗体などの結合物質に酵素を標識し、この酵素を触媒として反応する発色基質、蛍光基質、あるいは化学発光基質から生じる発色や蛍光、化学発光を検出する方法等が知られており、これらにより、被検物質の特定が可能となる。
As one of the methods for examining biochemical reactions, for example, specific binding reactions such as enzyme reactions, nucleic acid hybridizations, and antigen-antibody reactions, the binding phenomenon between a test substance and a capture substance is optically determined. A method of detecting is known. In this method, a test substance is bound to a capture substance fixed at a predetermined position, and a label that emits fluorescence upon receiving excitation light, or a label that catalyzes a substrate reaction to generate color, fluorescence, or chemiluminescence. Or the like is applied to the test substance, and light generated due to the label is detected. More specifically, a method of detecting a fluorescence generated from a fluorescent label by attaching a fluorescent label to a binding substance such as an antibody that specifically binds to the test substance, a binding of an antibody that specifically binds to the test substance There are known methods for detecting color development, fluorescence, chemiluminescence, etc. generated from a chromogenic substrate, fluorescent substrate, or chemiluminescent substrate that reacts with this enzyme as a catalyst. Identification becomes possible.
このような検査に用いられるバイオチップとしては、二次元基板上に生体関連分子が規則的に配列された多項目同時検出のためのチップが従来用いられている。近年では、支持体に多数の貫通孔（細孔）が整列配置されてなる多孔性基板からなるデバイスの検討が進められている。細孔内に捕捉物質を固定化し、被検物質を含有する検体液を多孔性基板の裏面側から表面へと貫通孔を介してポンプで汲み上げ、循環させることにより、検体液が捕捉物質に効率的に接触されて、被検物質を捕捉物質に結合させることができ、測定時間の大幅な短縮化を図ることができる。
As a biochip used for such an inspection, a multi-item simultaneous detection chip in which biologically related molecules are regularly arranged on a two-dimensional substrate has been conventionally used. In recent years, a device made of a porous substrate in which a large number of through-holes (pores) are arranged on a support has been studied. By immobilizing the capture substance in the pores, pumping the sample liquid containing the test substance from the back side to the surface of the porous substrate through the through-hole and circulating it, the sample liquid becomes efficient as the capture substance The test substance can be bonded to the capture substance and the measurement time can be greatly shortened.
多孔性を有する基板としては、多孔性のシリコン（Ｓｉ）基材が知られているが、シリコンは反射率が低く、細孔内で生じた光は細孔内で多重反射するうちに、その信号強度が大幅に減衰してしまうため、細孔内で生じた光信号の光取り出し効率が非常に低いという問題がある。
As a porous substrate, a porous silicon (Si) base material is known, but silicon has low reflectivity, and the light generated in the pores is reflected multiple times in the pores. Since the signal intensity is greatly attenuated, there is a problem that the light extraction efficiency of the optical signal generated in the pore is very low.
特許文献１では、上記問題を解決する手段として、多孔性シリコンを熱酸化処理して局部的に透明な酸化シリコン（ＳｉＯ２）化し、その酸化された領域をシリコンからなる枠（壁）によって取り囲むことにより、光の出射開口を実質的に広げて光取り出し効率を向上させた構成が提案されている。
In Patent Document 1, as a means for solving the above problem, porous silicon is thermally oxidized to be locally transparent silicon oxide (SiO 2 ), and the oxidized region is surrounded by a frame (wall) made of silicon. Thus, a configuration has been proposed in which the light output aperture is substantially widened to improve the light extraction efficiency.
特許文献２では、多孔性基材の細孔の径が表裏の開口部分の径において内部よりも大きくすることにより、取り出し光量を増加させている。
In Patent Document 2, the amount of extracted light is increased by making the diameter of the pores of the porous substrate larger than the inside in the diameter of the opening portions on the front and back sides.
特許文献３では、基材の光取り出し面に向かって徐々に径が拡がるテーパ状の細孔を備えたデバイスが提案されている。
Patent Document 3 proposes a device having tapered pores whose diameter gradually increases toward the light extraction surface of the substrate.
特許文献１では、光開口率の増加に伴う光取り出し効率の向上は可能であるが、枠壁として用いられているシリコンの反射率が低いため、シリコンの壁に入射する光は減衰されてしまい枠壁に入射する光の取り出し効率は向上しない。特に、チップの高性能化を図るためには、チップを厚くして、検出領域を広げたり、細孔を高密度化したりする必要が生じると考えられ、細孔の長さ（基板厚み）と開口径とのアスペクト比を大きくする必要性が生じる。細孔のアスペクト比が大きくなると、シリコン枠で囲まれた領域のアスペクト比も追従して大きくなるために、シリコン枠で囲まれた領域の光出射開口が実質的に狭くなり、シリコン枠での多重反射による光信号減衰の影響が大きくなる。
In Patent Document 1, although it is possible to improve the light extraction efficiency with an increase in the light aperture ratio, the light incident on the silicon wall is attenuated because the reflectance of silicon used as the frame wall is low. The extraction efficiency of light incident on the frame wall is not improved. In particular, in order to improve the performance of the chip, it is considered necessary to increase the thickness of the chip, expand the detection area, or increase the density of the pores. There is a need to increase the aspect ratio with the opening diameter. As the aspect ratio of the pores increases, the aspect ratio of the region surrounded by the silicon frame also increases accordingly, so the light exit aperture of the region surrounded by the silicon frame becomes substantially narrow, The influence of optical signal attenuation due to multiple reflection is increased.
特許文献２の構成によれば、多孔性シリコンの一方の面および他方の面の両面における開口径が内部の開口径よりも大きいことから、一方の面あるいは他方の面側に向かって進行する光に対する光開口率が向上するため光取り出し効率が上昇する。しかし、一方の面にあるいは、他方の面側に進む光を反対の面側に向けるものではないために、一方の面側にのみ、もしくは他方の面側にのみ光検出器を配置して光検出を実施する測定装置に用いられる場合には、十分な取り出し効率の向上を達成することはできない。
According to the configuration of Patent Document 2, since the opening diameter on both surfaces of one side and the other surface of porous silicon is larger than the inner opening diameter, the light traveling toward one surface or the other surface side The light extraction efficiency is increased because the light aperture ratio is improved. However, since light that travels to one surface or the other surface is not directed to the opposite surface, a light detector is disposed only on one surface or only on the other surface. When used in a measuring apparatus that performs detection, it is not possible to achieve a sufficient improvement in extraction efficiency.
特許文献３では、基材の光取り出し面に向かって徐々に径が拡がるテーパ状の細孔により、細孔内で生じ、光取り出し面とは反対の面に向かって進行した光の一部を内壁面で反射させて光取り出し面側へと向かわせることができるが、既述のような、チップの高性能化の要請により、細孔の長さの細孔の直径に対する比で表されるアスペクト比が大きくなると、十分なテーパ角度をつけることができないため、光取り出し効率を十分に向上させることはできない。
In Patent Document 3, a portion of light that has occurred in the pores and that has progressed toward the surface opposite to the light extraction surface is formed by tapered pores whose diameter gradually increases toward the light extraction surface of the substrate. Although it can be reflected by the inner wall surface and directed toward the light extraction surface side, it is expressed by the ratio of the length of the pore to the diameter of the pore due to the demand for higher performance of the chip as described above. When the aspect ratio becomes large, a sufficient taper angle cannot be set, so that the light extraction efficiency cannot be sufficiently improved.
本発明は、上記事情に鑑み、従来のデバイスよりも光取り出し効率を向上させることができる検査デバイスを提供することを目的とする。また、本発明は高い光取り出し効率を実現した検査デバイスを備えた検査装置および検査方法を提供することを目的とする。
In view of the above circumstances, an object of the present invention is to provide an inspection device capable of improving the light extraction efficiency as compared with a conventional device. Another object of the present invention is to provide an inspection apparatus and an inspection method provided with an inspection device that realizes high light extraction efficiency.
本発明の検査デバイスは、板状基材の一方の面から他方の面に貫通する複数の細孔を備えた検査デバイスであって、
細孔が、同一開口径で延びる柱状中空部と、柱状中空部の他方の面側に形成された、柱状中空部を構成する内壁面に連続し、柱状中空部における開口径よりもその細孔の開口径を小さくする反射面を有し、
反射面と他方の面とのなす角度が０°以上４５°以下である検査デバイスである。 The inspection device of the present invention is an inspection device having a plurality of pores penetrating from one surface of the plate-like substrate to the other surface,
The pore is continuous with the columnar hollow portion extending with the same opening diameter and the inner wall surface forming the columnar hollow portion formed on the other surface side of the columnar hollow portion, and the pore is larger than the opening diameter in the columnar hollow portion. Having a reflective surface to reduce the opening diameter of
This is an inspection device in which the angle formed by the reflection surface and the other surface is 0 ° or more and 45 ° or less.
細孔が、同一開口径で延びる柱状中空部と、柱状中空部の他方の面側に形成された、柱状中空部を構成する内壁面に連続し、柱状中空部における開口径よりもその細孔の開口径を小さくする反射面を有し、
反射面と他方の面とのなす角度が０°以上４５°以下である検査デバイスである。 The inspection device of the present invention is an inspection device having a plurality of pores penetrating from one surface of the plate-like substrate to the other surface,
The pore is continuous with the columnar hollow portion extending with the same opening diameter and the inner wall surface forming the columnar hollow portion formed on the other surface side of the columnar hollow portion, and the pore is larger than the opening diameter in the columnar hollow portion. Having a reflective surface to reduce the opening diameter of
This is an inspection device in which the angle formed by the reflection surface and the other surface is 0 ° or more and 45 ° or less.
本発明の細孔の柱状中空部の内壁面に特定の物質と特異的に結合する捕捉物質が固定されていることが好ましい。
It is preferable that a trapping substance that specifically binds to a specific substance is fixed on the inner wall surface of the hollow columnar portion of the present invention.
上記捕捉物質としては、抗原、抗体またはデオキシリボ核酸（deoxyribonucleic acid：ＤＮＡ）が好ましい。
The capture substance is preferably an antigen, an antibody, or deoxyribonucleic acid (DNA).
本発明の検査デバイスは、反射面が金属面であることが好ましい。
In the inspection device of the present invention, the reflective surface is preferably a metal surface.
本発明の検査デバイスは、細孔が、一方の面から柱状中空部に向かって細孔の開口径を徐々に小さくするテーパ部を有することが好ましい。
In the inspection device of the present invention, it is preferable that the pore has a tapered portion that gradually decreases the opening diameter of the pore from one surface toward the columnar hollow portion.
本発明の検査デバイスにおいて、板状基材は、Ｓｉ、ＳｉＯ２、Ａｌ、Ａｌ２Ｏ３および樹脂材料のうちの１つまたは２つ以上の材料からなるものとすることができる。
In the inspection device of the present invention, the plate-like substrate may be made of one or more materials of Si, SiO 2 , Al, Al 2 O 3 and a resin material.
本発明の検査デバイスにおいて、反射面を構成する材料は、柱状中空部を構成する材料と異なるものであってもよい。
In the inspection device of the present invention, the material constituting the reflecting surface may be different from the material constituting the columnar hollow portion.
本発明の検査デバイスは、細孔の上記柱状中空部における開口径は１μｍ～１００μｍであることが好ましい。ここで、開口径は一方の面に平行な断面における開口領域の円相当直径で定義する。円相当直径とはその開口領域の面積と同一の面積の円の直径をいう。
In the inspection device of the present invention, the opening diameter in the columnar hollow portion of the pore is preferably 1 μm to 100 μm. Here, the opening diameter is defined by the equivalent circle diameter of the opening region in a cross section parallel to one surface. The equivalent circle diameter refers to the diameter of a circle having the same area as the area of the opening region.
本発明の検査デバイスは、板状基材の厚さが１００μｍ～２０００μｍであることが好ましい。
In the inspection device of the present invention, the thickness of the plate-like substrate is preferably 100 μm to 2000 μm.
本発明の検査装置は、本発明の検査デバイスと、
検査デバイスの細孔中に検査用溶液を供給する溶液供給部と、
検査デバイスの一方の面側に配置され、検査デバイスから出射される光を検出する光検出器とを備えた検査装置である。 The inspection apparatus of the present invention includes the inspection device of the present invention,
A solution supply unit for supplying an inspection solution into the pores of the inspection device;
The inspection apparatus includes a photodetector that is disposed on one surface side of the inspection device and detects light emitted from the inspection device.
検査デバイスの細孔中に検査用溶液を供給する溶液供給部と、
検査デバイスの一方の面側に配置され、検査デバイスから出射される光を検出する光検出器とを備えた検査装置である。 The inspection apparatus of the present invention includes the inspection device of the present invention,
A solution supply unit for supplying an inspection solution into the pores of the inspection device;
The inspection apparatus includes a photodetector that is disposed on one surface side of the inspection device and detects light emitted from the inspection device.
本発明の検査方法は、本発明の検査デバイスの上記少なくとも一部の細孔の柱状中空部の内壁面に特定の物質と特異的に結合する捕捉物質を固定し、
上記特定の物質を含有する検体液を供給して、特定の物質を捕捉物質に結合させ、
特定の物質と特異的に結合する標識物質を特定の物質に結合させ、
細孔に検査用溶液を供給して細孔に検査用溶液を留めた状態で、検査デバイスの上記一方の面から出射される光を検出する検査方法である。 The inspection method of the present invention fixes a capture substance that specifically binds to a specific substance on the inner wall surface of the columnar hollow portion of the at least some pores of the inspection device of the present invention,
Supply the sample liquid containing the specific substance, and bind the specific substance to the capture substance.
A labeling substance that specifically binds to a specific substance is bound to the specific substance,
This is an inspection method for detecting light emitted from the one surface of the inspection device in a state in which the inspection solution is supplied to the pores and the inspection solution is retained in the pores.
上記特定の物質を含有する検体液を供給して、特定の物質を捕捉物質に結合させ、
特定の物質と特異的に結合する標識物質を特定の物質に結合させ、
細孔に検査用溶液を供給して細孔に検査用溶液を留めた状態で、検査デバイスの上記一方の面から出射される光を検出する検査方法である。 The inspection method of the present invention fixes a capture substance that specifically binds to a specific substance on the inner wall surface of the columnar hollow portion of the at least some pores of the inspection device of the present invention,
Supply the sample liquid containing the specific substance, and bind the specific substance to the capture substance.
A labeling substance that specifically binds to a specific substance is bound to the specific substance,
This is an inspection method for detecting light emitted from the one surface of the inspection device in a state in which the inspection solution is supplied to the pores and the inspection solution is retained in the pores.
本発明の検査方法においては、上記標識として酵素標識を用い、上記検査用溶液として酵素標識により触媒されて反応する基質を含む反応液を用い、上記検査デバイスから出射される光として、反応液中の基質が酵素標識により触媒されて生じる光を検出してもよい。
なお、基質としては、発色基質、蛍光基質および化学発光基質などが挙げられ、これらの基質は酵素標識の種類に応じて適宜選択される。また、この基質に応じて、検査デバイスから出射される光は異なり、検出される光は、吸光（呈色）、蛍光または化学発光である。 In the test method of the present invention, an enzyme label is used as the label, a reaction solution containing a substrate that is catalyzed by the enzyme label and reacts as the test solution, and light emitted from the test device is used in the reaction solution. The light produced when the substrate is catalyzed by the enzyme label may be detected.
Examples of the substrate include a chromogenic substrate, a fluorescent substrate, and a chemiluminescent substrate, and these substrates are appropriately selected depending on the type of enzyme label. Moreover, the light emitted from the inspection device differs depending on the substrate, and the detected light is light absorption (coloration), fluorescence, or chemiluminescence.
なお、基質としては、発色基質、蛍光基質および化学発光基質などが挙げられ、これらの基質は酵素標識の種類に応じて適宜選択される。また、この基質に応じて、検査デバイスから出射される光は異なり、検出される光は、吸光（呈色）、蛍光または化学発光である。 In the test method of the present invention, an enzyme label is used as the label, a reaction solution containing a substrate that is catalyzed by the enzyme label and reacts as the test solution, and light emitted from the test device is used in the reaction solution. The light produced when the substrate is catalyzed by the enzyme label may be detected.
Examples of the substrate include a chromogenic substrate, a fluorescent substrate, and a chemiluminescent substrate, and these substrates are appropriately selected depending on the type of enzyme label. Moreover, the light emitted from the inspection device differs depending on the substrate, and the detected light is light absorption (coloration), fluorescence, or chemiluminescence.
本発明の検査方法においては、標識物質として蛍光標識を含む物質を用い、蛍光標識を励起させる励起光を検査デバイスに照射し、上記検査デバイスから出射される光として、励起光の照射により標識物質から生じる蛍光を検出してもよい。
In the inspection method of the present invention, a substance containing a fluorescent label is used as a labeling substance, excitation light that excites the fluorescent label is irradiated to the inspection device, and the labeling substance is irradiated by excitation light as light emitted from the inspection device. Fluorescence resulting from may be detected.
本発明の検査デバイスは、板状基材の一方の面から他方の面に貫通する複数の細孔を備えた検査デバイスであって、細孔が、同一開口径で延びる柱状中空部と、柱状中空部の他方の面側に形成された、柱状中空部の内壁面に連続し、柱状中空部の細孔よりも開口径を小さくする反射面を有し、その反射面と他方の面とのなす角度が０°以上４５°以下であるので、細孔内において生じる光の検査デバイスの一方の面側への取り出し効率を向上させることができる。
The inspection device of the present invention is an inspection device having a plurality of pores penetrating from one surface of a plate-like substrate to the other surface, and the columnar hollow portion in which the pores extend with the same opening diameter, and the columnar shape The reflective surface formed on the other surface side of the hollow portion is continuous with the inner wall surface of the columnar hollow portion and has a smaller opening diameter than the pores of the columnar hollow portion. Since the formed angle is 0 ° or more and 45 ° or less, it is possible to improve the extraction efficiency of light generated in the pores to the one surface side of the inspection device.
以下、図面を参照して本発明の実施形態を詳細に説明する。なお、本明細書において「～」とは、その前後に記載される数値を下限値および上限値として含む意味で使用される。
Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In the present specification, “to” is used to mean that the numerical values described before and after it are included as a lower limit value and an upper limit value.
図１は本発明の第１の実施形態にかかる検査デバイスの斜視図であり、図２は図１の検査デバイスの平面図、図３は図２の検査デバイスのIII-III線断面図、図４は図１の検査デバイスの下面図である。
1 is a perspective view of an inspection device according to a first embodiment of the present invention, FIG. 2 is a plan view of the inspection device of FIG. 1, and FIG. 3 is a sectional view taken along line III-III of the inspection device of FIG. 4 is a bottom view of the inspection device of FIG.
本実施形態の検査デバイス１は、一方の面１１から他方の面１２に貫通する複数の細孔１４を備えた板状基材１０を備え、細孔１４が、同一開口径で延びる柱状中空部４０と、柱状中空部４０の他方の面１２側に形成された、柱状中空部４０を構成する内壁面４１に連続し、柱状中空部４０よりも細孔１４の開口径φを小さくする反射面４２とを有してなる。なお、この反射面４２は、他方の面１２とのなす角度θが０°以上４５°以下である。細孔１４の内壁面１４ａは、柱状中空部４０を構成する内壁面４１と反射面４２とを少なくとも含む。そして、細孔１４の内壁面１４ａには特定の物質と特異的に結合する捕捉物質３０が固定されている。なお、捕捉物質３０は内壁面１４ａのうち、少なくとも柱状中空部を構成する内壁面４１に備えられていればよい。
The inspection device 1 of the present embodiment includes a plate-like base material 10 having a plurality of pores 14 penetrating from one surface 11 to the other surface 12, and the pores 14 extend in the same opening diameter. 40 and a reflecting surface that is formed on the other surface 12 side of the columnar hollow portion 40 and that is continuous with the inner wall surface 41 constituting the columnar hollow portion 40 and that makes the opening diameter φ of the pore 14 smaller than that of the columnar hollow portion 40. 42. The reflection surface 42 has an angle θ with the other surface 12 of 0 ° or more and 45 ° or less. The inner wall surface 14 a of the pore 14 includes at least an inner wall surface 41 and a reflecting surface 42 that constitute the columnar hollow portion 40. A trapping substance 30 that specifically binds to a specific substance is fixed to the inner wall surface 14 a of the pore 14. In addition, the capture | acquisition substance 30 should just be provided in the inner wall surface 41 which comprises a columnar hollow part among the inner wall surfaces 14a.
図２に示す平面図は、検査デバイス１を一方の面１１から見た図であり、図４に示す下面図は、検査デバイス１を他方の面１２から見た図である。なお、図１に示す通り、検査デバイス１の外形は板状基材１０の外形により構成されるものであるため、以下において、板状基材１０の一方の面１１および他方の面１２を、検査デバイス１の一方の面および他方の面と称する場合がある。
The plan view shown in FIG. 2 is a view of the inspection device 1 as viewed from one surface 11, and the bottom view of FIG. 4 is a view of the inspection device 1 as viewed from the other surface 12. In addition, since the external shape of the inspection device 1 is configured by the external shape of the plate-like base material 10 as shown in FIG. 1, in the following, one surface 11 and the other surface 12 of the plate-like base material 10 are Sometimes referred to as one surface and the other surface of the inspection device 1.
板状基材１０は、Ｓｉ（シリコン）、ＳｉＯ２（シリコン酸化物）、Ａｌ（アルミニウム）、Ａｌ２Ｏ３（アルミナ）および樹脂材料のいずれか１つもしくは２つ以上の材料から構成されていることが好ましい。板状基材１０は、ＳｉあるいはＡｌなどからなる不透明なものであってもよいし、ＳｉＯ２あるいはＡｌ２Ｏ３などからなる透明なものであってもよい。板状基材１０は、いずれか単体の材料で構成されていてもよいし、例えば、Ｓｉ基材を一部酸化することによりＳｉ部分とＳｉＯ２部分とを含むものであってもよいし、Ａｌ基材を一部酸化して、Ａｌ部分とＡｌ２Ｏ３部分とを含むものであってもよい。また、板状基材１０は、Ｓｉ、ＳｉＯ２、ＡｌもしくはＡｌ２Ｏ３の本体部材と樹脂材料からなる表面部材とからなるものであってもよい。
The plate-like substrate 10 is made of one or more materials of Si (silicon), SiO 2 (silicon oxide), Al (aluminum), Al 2 O 3 (alumina), and a resin material. Preferably it is. The plate-like substrate 10 may be opaque made of Si or Al, or may be transparent made of SiO 2 or Al 2 O 3 . The plate-like substrate 10 may be composed of any single material, or may include, for example, a Si portion and a SiO 2 portion by partially oxidizing the Si substrate, The Al base material may be partially oxidized to include an Al portion and an Al 2 O 3 portion. Further, the plate-like substrate 10 may be composed of a main body member made of Si, SiO 2 , Al, or Al 2 O 3 and a surface member made of a resin material.
板状基材１０の厚さｔ（図３参照）には、特に制限はないが、１００μｍ～２０００μｍ程度が好ましい。本実施形態の検査デバイス１においては、柱状中空部４０の長さ（厚み）ｔ１と反射面４２がテーパ状に配置された部分の細孔長さ方向における長さｔ２（以下において、「反射面４２が占める厚みｔ２」という。）との合計が板状基材１０の厚みｔである。
The thickness t (see FIG. 3) of the plate-like substrate 10 is not particularly limited, but is preferably about 100 μm to 2000 μm. In the inspection device 1 of the present embodiment, the length (thickness) t 1 of the columnar hollow portion 40 and the length t 2 in the pore length direction of the portion where the reflecting surface 42 is arranged in a tapered shape (hereinafter, “ The total of the thickness t 2 of the reflecting surface 42 is called the thickness t 2 of the plate-like substrate 10.
板状基材１０に設けられる細孔１４は、本実施形態に示すように、整列配置されていることが好ましいが、ランダムに配置されていてもよい。本実施形態においては、視認容易のために３行×３列の９本の細孔を有するものとしたが、例えば、１０行×１０列の１００本の細孔を含むなど、検査デバイス１中に備えられる細孔の数に制限はない。また、例えば、１０行×１０列の１００本の細孔領域を１つ検査領域とし、複数の検査領域を備えた検査デバイスを備えていてもよい。
The pores 14 provided in the plate-like substrate 10 are preferably arranged as shown in the present embodiment, but may be arranged randomly. In the present embodiment, 9 pores of 3 rows × 3 columns are provided for easy visual recognition, but the inspection device 1 includes, for example, 100 pores of 10 rows × 10 columns. There is no limit to the number of pores provided in the case. In addition, for example, an inspection device including a plurality of inspection regions may be provided with 100 pore regions of 10 rows × 10 columns as one inspection region.
本実施形態における細孔１４の一方の面１１に平行な断面形状（開口形状）は、正方形状であるが、開口形状は、正方形、長方形などの矩形に限らず、円形、楕円形、三角形あるいは五角形以上の多角形であってもよい。なお、作製上の都合により多角形状の角部には丸みがつく場合がある。細孔１４の開口径φは、細孔１４の一方の面１１に平行な断面の形状（開口領域）における円相当直径である。
In the present embodiment, the cross-sectional shape (opening shape) parallel to the one surface 11 of the pore 14 is a square shape, but the opening shape is not limited to a rectangle such as a square or a rectangle, but a circle, an ellipse, a triangle, It may be a pentagon or more polygon. Note that the corners of the polygon may be rounded due to manufacturing reasons. The opening diameter φ of the pore 14 is a circle-equivalent diameter in a cross-sectional shape (opening region) parallel to one surface 11 of the pore 14.
図３に示すように、細孔１４の開口径φは、柱状中空部４０においては同一であり、反射面４２により他方の面１２に近づくにつれ小さくなるように構成されている。
なお、細孔１４の柱状中空部４０における開口径（上述の断面の開口領域における円相当直径）が１μｍ～１００μｍ程度であることが好ましい。より好ましくは３μｍ～５０μｍであり、特に好ましくは５μｍ～３０μｍである。 As shown in FIG. 3, the opening diameter φ of thepore 14 is the same in the columnar hollow portion 40, and is configured to become smaller as it approaches the other surface 12 by the reflecting surface 42.
The opening diameter in the columnarhollow portion 40 of the pores 14 (equivalent circle diameter in the opening region of the above-mentioned cross section) is preferably about 1 μm to 100 μm. More preferably, it is 3 μm to 50 μm, and particularly preferably 5 μm to 30 μm.
なお、細孔１４の柱状中空部４０における開口径（上述の断面の開口領域における円相当直径）が１μｍ～１００μｍ程度であることが好ましい。より好ましくは３μｍ～５０μｍであり、特に好ましくは５μｍ～３０μｍである。 As shown in FIG. 3, the opening diameter φ of the
The opening diameter in the columnar
柱状中空部４０における開口径に対する板状基材の厚みで表されるアスペクト比（ｔ／φ）は５以上、１００以下であることが好ましい。アスペクト比がこの範囲にあるとき、上記の反射面４２を備えることによる効果が特に顕著である。なお、柱状中空部４０における開口径に対する一方の面１１側から反射面４２を含む部分までの厚み（本実施形態においては厚みｔと同一）の、開口径に対するアスペクト比が、５以上、１００以下であることが好ましい。
The aspect ratio (t / φ) represented by the thickness of the plate-like substrate with respect to the opening diameter in the columnar hollow portion 40 is preferably 5 or more and 100 or less. When the aspect ratio is within this range, the effect of providing the reflecting surface 42 is particularly remarkable. In addition, the aspect ratio with respect to the opening diameter of the thickness from the one surface 11 side with respect to the opening diameter in the columnar hollow part 40 to the portion including the reflecting surface 42 (same as the thickness t in this embodiment) is 5 or more and 100 or less. It is preferable that
反射面４２は後述する標識に起因して生じる光に対して反射性を有するものであればよい。ここで、反射性を有するとは、反射すべき光に対する反射率が５０％以上であることをいう。例えば、標識に起因して生じる光の波長が５５０ｎｍである場合には、少なくとも波長５５０ｎｍに対する反射率が５０％以上であればよい。なお、可視光（波長４００ｎｍ～７００ｎｍ）の全域に対して反射率が５０％以上であれば、標識の種類に関わらず適用可能となるため、好ましい。
The reflection surface 42 only needs to be reflective to light generated due to a sign described later. Here, having the reflectivity means that the reflectance with respect to the light to be reflected is 50% or more. For example, when the wavelength of light generated due to the label is 550 nm, the reflectance at least for the wavelength of 550 nm may be 50% or more. A reflectance of 50% or more with respect to the entire visible light (wavelength 400 nm to 700 nm) is preferable because it can be applied regardless of the type of label.
反射面４２は例えば、鋼、ステンレス、アルミニウム、金、白金、銀、銅、チタン、ニッケル、コバルト、錫、タングステン、モリブデンあるいはニオブなどの金属から構成された金属面とすることができる。あるいは白色樹脂などの反射率の高い樹脂、例えば、顔料もしくはＴｉＯ２、Ａｌ２Ｏ３等のフィラーから構成されていてもよい。
The reflective surface 42 may be a metal surface made of a metal such as steel, stainless steel, aluminum, gold, platinum, silver, copper, titanium, nickel, cobalt, tin, tungsten, molybdenum, or niobium. Alternatively high resin reflectance such as white resin, for example, may be composed of pigments or fillers such as TiO 2, Al 2 O 3.
反射面４２は、他方の面１２となす角度θが０°～４５°である。θが０°のとき、反射面４２と他方の面１２とは平行となる。本実施形態において、反射面４２は、細孔の開口径を柱状中空部４０から他方の面１２に向けて徐々に小さくするテーパ部として備えられている。
The angle θ between the reflecting surface 42 and the other surface 12 is 0 ° to 45 °. When θ is 0 °, the reflecting surface 42 and the other surface 12 are parallel. In the present embodiment, the reflecting surface 42 is provided as a tapered portion that gradually decreases the opening diameter of the pore from the columnar hollow portion 40 toward the other surface 12.
上記実施形態の検査デバイス１の上記反射面４２を備えたことによる効果について図５を参照して説明する。
図５は検査デバイス１の断面の一部を示した模式図である。本検査デバイス１は、細孔１４の内壁面１４ａに固定された捕捉物質（図５中では省略している。）に被検物質を結合させ、更に、酵素で標識された２次抗体を被検物質に結合させ、この酵素(標識Ｆ)を触媒とした化学発光である光信号を検出することにより被検物質の有無および被検物質の量、またはそのいずれかを検出する検査方法に用いられる。 The effect by having provided the saidreflective surface 42 of the test | inspection device 1 of the said embodiment is demonstrated with reference to FIG.
FIG. 5 is a schematic view showing a part of the cross section of theinspection device 1. This test device 1 binds a test substance to a capture substance (not shown in FIG. 5) fixed to the inner wall surface 14a of the pore 14, and further receives a secondary antibody labeled with an enzyme. Used in a test method for detecting the presence or absence of the test substance and / or the amount of the test substance by detecting an optical signal that is chemiluminescent using the enzyme (label F) as a catalyst by binding to the test substance. It is done.
図５は検査デバイス１の断面の一部を示した模式図である。本検査デバイス１は、細孔１４の内壁面１４ａに固定された捕捉物質（図５中では省略している。）に被検物質を結合させ、更に、酵素で標識された２次抗体を被検物質に結合させ、この酵素(標識Ｆ)を触媒とした化学発光である光信号を検出することにより被検物質の有無および被検物質の量、またはそのいずれかを検出する検査方法に用いられる。 The effect by having provided the said
FIG. 5 is a schematic view showing a part of the cross section of the
１つの細孔１４内で発生した光はその細孔１４の内壁面１４ａで反射を繰り返して表面から出射される。このとき、反射面４２を備えていることにより、標識Ｆによって生じ、他方の面１２側に放射された光のうち、直接もしくは内壁面１４ａで反射されて反射面４２に入射した光が、反射面４２で反射され、一方の面１１側へと導光される。その結果として、細孔１４内で発生した光の一方の面１１から出射する光量を効果的に増加させることができる。
The light generated in one pore 14 is repeatedly reflected by the inner wall surface 14a of the pore 14 and emitted from the surface. At this time, by providing the reflecting surface 42, the light generated by the sign F and radiated to the other surface 12 side is reflected directly or by the inner wall surface 14a and incident on the reflecting surface 42 is reflected. The light is reflected by the surface 42 and guided to the one surface 11 side. As a result, the amount of light emitted from the one surface 11 of the light generated in the pores 14 can be effectively increased.
他方の面１２とのなす角度θが４５°以下である反射面４２が柱状中空部４０を構成する内壁面４１に連続して備えられていることにより、細孔１４の内壁面１４ａ、特には、この柱状中空部４０の内壁面４１で発生した光のうち反射面４２に入射した光を効率よく反射することができる。上記角度θが４５°以下であれば、反射面４２に入射する光のうち一方の面側に向けて反射させる光の割合を他方の面側に向けて反射される光の割合以上とすることができるので、一方の面１１側における光取り出し光量を向上させる効果が高い。角度θが０°に近づくほど、反射面４２に入射した光のうち一方の面側に向けて反射させる光の割合を大きくすることができる。但し、角度θが小さくなると、相対的に、他方の面１２における開口径が小さくなり、他方の面１２から検査用溶液を細孔内へ吸引させにくくなる場合があるため、角度θは０°～４５°の範囲で適宜定めればよい。
Since the reflecting surface 42 having an angle θ formed with the other surface 12 of 45 ° or less is continuously provided on the inner wall surface 41 constituting the columnar hollow portion 40, the inner wall surface 14 a of the pore 14, in particular, Of the light generated on the inner wall surface 41 of the columnar hollow portion 40, the light incident on the reflecting surface 42 can be efficiently reflected. If the angle θ is 45 ° or less, the proportion of the light incident on the reflective surface 42 that is reflected toward one surface is set to be equal to or greater than the proportion of the light reflected toward the other surface. Therefore, the effect of improving the light extraction amount on the one surface 11 side is high. As the angle θ approaches 0 °, it is possible to increase the proportion of light reflected toward one surface of the light incident on the reflecting surface 42. However, when the angle θ is small, the opening diameter on the other surface 12 is relatively small, and it may be difficult to suck the test solution from the other surface 12 into the pores. What is necessary is just to determine suitably in the range of -45 degrees.
以上の通り、本検査デバイス１では、細孔１４から生じた光を他方の面１２側に備えられた反射面４２で反射することにより、一方の面１１側からの光取り出し光量を大幅に増加させることができる。
As described above, in the present inspection device 1, the light extracted from the one surface 11 side is significantly increased by reflecting the light generated from the pores 14 by the reflection surface 42 provided on the other surface 12 side. Can be made.
本検査デバイス１において検査対象とされる被検物質（標的分子）は、主として、生体由来分子であり、抗原および抗体などのタンパク質、糖類、ペプチド、ＤＮＡ、リボ核酸（ribonucleic acid：ＲＮＡ）、ペプチド核酸（peptide nucleic acid：ＰＮＡ）などである。そして、細孔１４の内壁面１４ａに固定されている、特定の物質と特異的に結合する捕捉物質３０としては、特定の物質であるこれらの被検物質と特異的に結合する物質である。特に、本検査デバイス１は、抗原の一種であるアレルゲンを捕捉物質として備えたアレルギー検査に好適である。
The test substance (target molecule) to be tested in this testing device 1 is mainly a biological molecule, such as proteins such as antigens and antibodies, saccharides, peptides, DNA, ribonucleic acid (RNA), peptides Examples thereof include nucleic acids (peptide nucleic acid: PNA). And as the capture | acquisition substance 30 specifically couple | bonded with the specific substance fixed to the inner wall face 14a of the pore 14, it is a substance couple | bonded specifically with these test substances which are specific substances. In particular, the test device 1 is suitable for an allergy test provided with an allergen that is a kind of antigen as a capture substance.
なお、複数の細孔１４間では、異なる捕捉物質を固定させておくこともできる。これにより、１つの検査デバイス１で、複数の被検物質についての検査を同時に行うことが可能となる。なお、複数の細孔１４間では、同一種の捕捉物質を含む細孔が２以上あってもよい。互いに異なる捕捉物質が固定されている細孔１４が交互に配置されて周期的に同一種の捕捉物質が固定された細孔が配置された検査デバイスを用いれば、ばらつきを抑制した検査結果を得ることが可能となる。
It should be noted that different trapping substances can be fixed between the plurality of pores 14. Accordingly, it is possible to simultaneously inspect a plurality of test substances with one inspection device 1. Note that there may be two or more pores containing the same type of trapping substance between the plurality of pores 14. If an inspection device in which pores 14 in which different capture substances are fixed are alternately arranged and pores in which the same kind of capture substance is fixed is used is used, a test result with reduced variation is obtained. It becomes possible.
例えば、１つもしくは複数の細孔１４に捕捉物質である同一種のアレルゲンを固定することとして、互いに異なる種類のアレルゲンが固定された細孔を備えることにより、１つの検査デバイスに複数種のアレルゲンに対する反応を同時に検査することが可能となる。
For example, by fixing the same type of allergen as a capture substance to one or a plurality of pores 14, a plurality of allergens can be provided in one test device by providing pores to which different types of allergens are fixed. It becomes possible to test the response to
また、複数の細孔１４を含む検査領域を複数備えたデバイスにおいては、１つの検査領域中の細孔には同一種のアレルゲンを固定し、１つの検査領域中の細孔には同一種の捕捉物質を結合（固定）し、複数の検査領域間では、異なる捕捉物質を固定させるようにしてもよい。１つの検査領域内に複数の細孔を備えているので、一種の被検物質に対する感度を向上させつつ、複数の被検物質についての検査を同時に行うことが可能となる。なお、複数の検査領域間では、同一種の捕捉物質を含む領域が２以上あってもよい。互いに異なる捕捉物質が固定されている検査領域が交互に配置されて周期的に同一種の捕捉物質が固定された検査領域が配置された検査デバイスを用いれば、ばらつきを抑制した検査結果を得ることが可能となる。
In a device having a plurality of inspection regions including a plurality of pores 14, the same type of allergen is fixed to the pores in one inspection region, and the same type of allergen is fixed to the pores in one inspection region. A capture substance may be bound (fixed), and different capture substances may be fixed between a plurality of examination regions. Since a plurality of pores are provided in one inspection region, it is possible to simultaneously inspect a plurality of test substances while improving the sensitivity to one kind of test substance. Note that there may be two or more regions containing the same type of capture substance between a plurality of inspection regions. By using an inspection device in which inspection areas to which different capture substances are fixed are alternately arranged and inspection areas to which the same kind of capture substances are periodically fixed are used, it is possible to obtain inspection results with reduced variation. Is possible.
上記実施形態の検査デバイスの設計変更例を図６～図１０に示す。図６～図１０には、設計変更例の検査デバイスの一部の断面図を示す。実際の検査デバイスにおいては、各図に示す細孔１４が二次元状に複数配列されてなることが好ましい。
Examples of design changes of the inspection device of the above embodiment are shown in FIGS. 6 to 10 are sectional views of a part of the inspection device of the design change example. In an actual inspection device, it is preferable that a plurality of pores 14 shown in each figure are arranged two-dimensionally.
図６に示す設計変更例１の検査デバイスは、反射面４３が板状基材１０の他方の面１２と平行である、すなわち他方の面とのなす角度が０°である。細孔１４は柱状中空部４０の内壁面４１、反射面４３および、柱状中空部４０よりも開口径が小さい小径中空部を構成する内壁面４８からなる内壁面１４ａを有する。本設計変更例１においては、柱状中空部４０の厚みｔ１と反射面４３により開口径が狭められた小径中空部の厚みｔ３との合計が板状基材１０の厚みｔである。
反射面４３が他方の面１２と平行であるとき、柱状中空部４０で生じて反射面４３に入射した光を全て一方の面１１側に向けて反射させることができ、好ましい。 In the inspection device of the first modification shown in FIG. 6, thereflection surface 43 is parallel to the other surface 12 of the plate-like substrate 10, that is, the angle formed with the other surface is 0 °. The pore 14 has an inner wall surface 14 a composed of an inner wall surface 41 of the columnar hollow portion 40, a reflecting surface 43, and an inner wall surface 48 constituting a small-diameter hollow portion having an opening diameter smaller than that of the columnar hollow portion 40. In the present design change example 1, the total of the thickness t 1 of the columnar hollow portion 40 and the thickness t 3 of the small-diameter hollow portion whose opening diameter is narrowed by the reflecting surface 43 is the thickness t of the plate-like substrate 10.
When the reflectingsurface 43 is parallel to the other surface 12, all the light generated in the columnar hollow portion 40 and incident on the reflecting surface 43 can be reflected toward the one surface 11 side, which is preferable.
反射面４３が他方の面１２と平行であるとき、柱状中空部４０で生じて反射面４３に入射した光を全て一方の面１１側に向けて反射させることができ、好ましい。 In the inspection device of the first modification shown in FIG. 6, the
When the reflecting
図７に示す設計変更例２の検査デバイスは、反射面４４が曲面である。本例において細孔１４は、柱状中空部４０の内壁面４１および曲面からなる反射面４４からなる内壁面１４ａを有する。本設計変更例２においては、柱状中空部４０の厚みｔ１と曲面の反射面４４が形成された部分の細孔長さ方向における厚みｔ４との合計が板状基材１０の厚みｔである。反射面４４が曲面である場合には、反射面４４の最も他方の面１２側の位置における接線と、他方の面１２とのなす角度をθとし、この角度θが０°～４５°であればよい。この場合にも、上記実施形態と同様の効果を得ることができる。
In the inspection device according to the second modification shown in FIG. 7, the reflection surface 44 is a curved surface. In the present example, the pore 14 has an inner wall surface 14 a composed of an inner wall surface 41 of the columnar hollow portion 40 and a reflecting surface 44 formed of a curved surface. In the present design change example 2, the sum of the thickness t 1 of the columnar hollow portion 40 and the thickness t 4 in the pore length direction of the portion where the curved reflecting surface 44 is formed is the thickness t of the plate-like substrate 10. is there. When the reflecting surface 44 is a curved surface, the angle formed between the tangent at the position on the most surface 12 side of the reflecting surface 44 and the other surface 12 is θ, and this angle θ should be 0 ° to 45 °. That's fine. Also in this case, the same effect as the above embodiment can be obtained.
図８に示す設計変更例３の検査デバイスは、上述の実施形態と同一の反射面４２を備えている。さらに、板状基材１０の一方の面１１側の細孔開口部に一方の柱状中空部４０から徐々に開口径が広がるテーパ面４５を備えている。本例において細孔１４は、柱状中空部４０の内壁面４１、反射面４２およびテーパ面４５からなる内壁面１４ａを有する。本設計変更例３においては、柱状中空部４０の厚みｔ１、反射面４２が占める厚みｔ２、およびテーパ面４５が形成された部分の細孔長さ方向における厚みｔ５の合計が板状基材１０の厚みｔである。本例のように一方の面１１の開口部の開口径を大きくすることにより、細孔１４中で生じた光の一方の面１１側における光取り出し光量を増加させることが可能であり、好ましい。
The inspection device of the third modification shown in FIG. 8 includes the same reflective surface 42 as that of the above-described embodiment. Furthermore, a tapered surface 45 whose opening diameter gradually increases from one columnar hollow portion 40 is provided in the pore opening portion on the one surface 11 side of the plate-like substrate 10. In this example, the pore 14 has an inner wall surface 14 a composed of the inner wall surface 41, the reflecting surface 42, and the tapered surface 45 of the columnar hollow portion 40. In the present design change example 3, the sum of the thickness t 1 of the columnar hollow portion 40, the thickness t 2 occupied by the reflecting surface 42, and the thickness t 5 in the pore length direction of the portion where the tapered surface 45 is formed is a plate shape. It is the thickness t of the base material 10. Increasing the opening diameter of the opening of one surface 11 as in this example can increase the amount of light extracted from the one surface 11 side of the light generated in the pores 14, which is preferable.
図９に示す設計変更例４の検査デバイスは、上述の実施形態と同様に、柱状中空部４０の内壁面４１に連続して他方の面１２側に反射面４２を備えており、その反射面４２のさらに他方の面１２側に再び開口径を大きくするテーパ面４９を備えている。本例において細孔１４は、柱状中空部４０の内壁面４１、反射面４２およびテーパ面４９からなる内壁面１４ａを有する。本設計変更例４においては、柱状中空部４０の厚みｔ１、反射面４２が占める厚みｔ２、およびテーパ面４９が占める厚みｔ６の合計が板状基材１０の厚みｔである。このように、反射面４２よりも他方の面１２側にさらに開口径の大きくなる部分を備えることにより、後述の検査方法において、この他方の面１２側からの細孔１４内への検査用溶液の吸い上げやすい構造となる。
The inspection device of the design modification example 4 shown in FIG. 9 includes a reflective surface 42 on the other surface 12 side in succession to the inner wall surface 41 of the columnar hollow portion 40, as in the above-described embodiment. A tapered surface 49 is provided on the other surface 12 side of 42 to increase the opening diameter again. In the present example, the pore 14 has an inner wall surface 14 a composed of the inner wall surface 41, the reflecting surface 42, and the tapered surface 49 of the columnar hollow portion 40. In the present design modification example 4, the total of the thickness t 1 of the columnar hollow portion 40, the thickness t 2 occupied by the reflecting surface 42, and the thickness t 6 occupied by the tapered surface 49 is the thickness t of the plate-like substrate 10. In this way, by providing a portion having a larger opening diameter on the other surface 12 side than the reflecting surface 42, the inspection solution into the pores 14 from the other surface 12 side in the inspection method described later. The structure is easy to suck up.
なお、図６のような反射面４３の他方の面１２側にさらに小径中空部を備える構成の場合には、他方の面１２側の中空部の厚みｔ３を除く、柱状中空部４０の厚みｔ１の柱状中空部の開口径に対する比が５～１００であることが望ましい。同様に、図９のような反射面４２の他方の面１２側にテーパ面４９を備える構成の場合にも、テーパ面４９が占める厚みｔ６を除く、柱状中空部４０の厚みｔ１と反射面４２が占める厚みｔ２の合計ｔ１＋ｔ２の柱状中空部の開口径に対する比が５～１００であることが望ましい。
In the case of construction with a further small diameter hollow portion on the other surface 12 side of the reflecting surface 43 as shown in FIG. 6, except for the thickness t 3 of the hollow portion of the other surface 12 side, the thickness of the columnar hollow 40 It is desirable that the ratio of t 1 to the opening diameter of the columnar hollow portion is 5 to 100. Similarly, in the case of the configuration having the tapered surface 49 on the other surface 12 side of the reflecting surface 42 as shown in FIG. 9, the thickness t 1 of the columnar hollow portion 40 and the reflection are excluded except for the thickness t 6 occupied by the tapered surface 49. It is desirable that the ratio of the total t 1 + t 2 of the thickness t 2 occupied by the surface 42 to the opening diameter of the columnar hollow portion is 5 to 100.
上記各例において、板状基材１０は単一の材料により構成されていてもよいし、部分によって異なる複数の材料により構成されていてもよい。図１０に異なる材料で構成された部分を有する検査デバイスの構成例を示す。図１０は、検査デバイスの一部の断面図である。
In each of the above examples, the plate-like substrate 10 may be made of a single material, or may be made of a plurality of materials that differ depending on the part. FIG. 10 shows a configuration example of an inspection device having portions made of different materials. FIG. 10 is a cross-sectional view of a part of the inspection device.
図１０に示す検査デバイスは、図８に示した設計変更例３の検査デバイスと同様の形状の細孔１４を有する。ここで、板状基材１０は、柱状中空部４０を構成する本体部材１７と、本体部材１７とは異なる材料からなる、テーパ面４５および一方の面１１を構成する第１の表面部材１８ａと、反射面４２および他方の面１２を構成する第２の表面部材１８ｂとから構成される。
The inspection device shown in FIG. 10 has pores 14 having the same shape as that of the inspection device of design modification example 3 shown in FIG. Here, the plate-like base material 10 includes a main body member 17 constituting the columnar hollow portion 40, and a first surface member 18 a constituting the tapered surface 45 and one surface 11 made of a material different from that of the main body member 17. The second surface member 18b that constitutes the reflecting surface 42 and the other surface 12.
本検査デバイスの作製方法について説明する。
まず、複数の柱状の細孔を有するＳｉ、ＳｉＯ２、ＡｌもしくはＡｌ２Ｏ３からなる板状の本体部材１７を作製する。例えば、複数の柱状の細孔を有するＳｉからなる本体部材は、ＭＥＭＳ（Micro Electro Mechanical System）技術において公知のマイクロポーラスＳｉの製造プロセスを用いることができる。さらに、Ｓｉからなる本体部材に対して熱酸化処理を行うことにより、複数の柱状の細孔を有するＳｉＯ２からなる本体部材を得ることができる。複数の柱状の細孔を有するＡｌからなる板状の本体部材は、Ａｌの板状基材にドリルなどの機械的な手法で細孔を形成して作製することもできるし、エッチング等により細孔を形成して作製することもできる。また、Ａｌからなる本体部材に対して陽極酸化処理を施すことにより、複数の柱状の細孔を有するＡｌ２Ｏ３からなる本体部材を得ることができる。なお、本体部材１７の作製方法は、これらに限らず、多孔性基板を形成する種々の公知の手法を用いることができる。 A method for manufacturing this inspection device will be described.
First, a plate-likemain body member 17 made of Si, SiO 2 , Al, or Al 2 O 3 having a plurality of columnar pores is produced. For example, a main body member made of Si having a plurality of columnar pores can use a microporous Si manufacturing process known in MEMS (Micro Electro Mechanical System) technology. Furthermore, the main body member made of SiO 2 having a plurality of columnar pores can be obtained by performing a thermal oxidation process on the main body member made of Si. A plate-like body member made of Al having a plurality of columnar pores can be produced by forming pores in an Al plate-like substrate by a mechanical method such as a drill, or by etching or the like. It can also be produced by forming holes. Further, by performing the anodic oxidation process with respect to the body member made of Al, it is possible to obtain a body member made of Al 2 O 3 having a plurality of pores of columnar. The production method of the main body member 17 is not limited to these, and various known techniques for forming a porous substrate can be used.
まず、複数の柱状の細孔を有するＳｉ、ＳｉＯ２、ＡｌもしくはＡｌ２Ｏ３からなる板状の本体部材１７を作製する。例えば、複数の柱状の細孔を有するＳｉからなる本体部材は、ＭＥＭＳ（Micro Electro Mechanical System）技術において公知のマイクロポーラスＳｉの製造プロセスを用いることができる。さらに、Ｓｉからなる本体部材に対して熱酸化処理を行うことにより、複数の柱状の細孔を有するＳｉＯ２からなる本体部材を得ることができる。複数の柱状の細孔を有するＡｌからなる板状の本体部材は、Ａｌの板状基材にドリルなどの機械的な手法で細孔を形成して作製することもできるし、エッチング等により細孔を形成して作製することもできる。また、Ａｌからなる本体部材に対して陽極酸化処理を施すことにより、複数の柱状の細孔を有するＡｌ２Ｏ３からなる本体部材を得ることができる。なお、本体部材１７の作製方法は、これらに限らず、多孔性基板を形成する種々の公知の手法を用いることができる。 A method for manufacturing this inspection device will be described.
First, a plate-like
上記で作製した板状の本体部材１７の細孔の開口を有する一方の面において、板状基材１０の一方の面１１および、一方の面１１における開口径を柱状中空部４０よりも大きくするテーパ面４５を構成する第１の表面部材１８ａと、柱状中空部４０の他方の面１２側において開口径を小さくさせる反射面４２および他方の面１２を構成する第２の表面部材１８ｂとは、例えば、３Ｄプリンタを用いて作製することができる。
On one surface of the plate-shaped main body member 17 having the opening of the pores, the opening diameter on one surface 11 of the plate-like base material 10 and the one surface 11 is made larger than that of the columnar hollow portion 40. The first surface member 18a constituting the tapered surface 45 and the second surface member 18b constituting the reflecting surface 42 and the other surface 12 for reducing the opening diameter on the other surface 12 side of the columnar hollow portion 40 are: For example, it can be manufactured using a 3D printer.
３Ｄプリンタとしては、粉末状の材料に高出力のレーザー光線をあて焼結させる造形方式（粉末焼結積層造形方式）のものが好ましく、特には、材料粉末とレーザーを同時に照射し任意の部分を溶融させ、積層させる造形方式のものであれば、下地の自由度が高くより好ましい。この手法を用いれば、鋼、ステンレス、アルミニウム、金、白金、銀、チタン、銅、ニッケル、コバルト、錫、タングステン、モリブデンあるいはニオブなど反射面を構成しうる金属材料により、所望の形状の第１および第２の表面部材１８ａ、１８ｂを容易に作製することができる。あるいは、液体状の光硬化性樹脂組成物を、紫外線レーザーで一層ずつ硬化させて積層していく光造形方式により、光硬化性樹脂からなる第１および第２の表面部材１８ａ、１８ｂを作製してもよい。この場合、光硬化性樹脂として、反射性を有する材料を選択すればよい。例えば、ＵＶ（Ultraviolet）硬化エポキシ樹脂、ＵＶ硬化アクリル樹脂、などがあげられる。
A 3D printer is preferably a modeling method (powder sintering layered modeling method) in which a high-power laser beam is applied to a powdered material and sintered. In particular, the material powder and the laser are simultaneously irradiated to melt any part. If it is the thing of the modeling system made to make it laminate, the freedom degree of a foundation | substrate is high and more preferable. By using this method, the first material having a desired shape is formed by a metal material that can constitute a reflective surface, such as steel, stainless steel, aluminum, gold, platinum, silver, titanium, copper, nickel, cobalt, tin, tungsten, molybdenum, or niobium. And the 2nd surface member 18a, 18b can be produced easily. Alternatively, the first and second surface members 18a and 18b made of a photocurable resin are produced by an optical modeling method in which a liquid photocurable resin composition is cured and laminated one by one with an ultraviolet laser. May be. In this case, a reflective material may be selected as the photocurable resin. For example, UV (Ultraviolet) cured epoxy resin, UV cured acrylic resin, and the like can be given.
なお、以上のようにして作製された板状基材１０の細孔１４の内壁面１４ａに被検物質と特異的に結合する特異的結合物質である捕捉物質を結合させる（固定化する）ことにより、検査に供する検査デバイス１を作製することができる。
細孔１４の内壁面１４ａへの捕捉物質の固定方法は公知の方法を特に制限なく適用することができる。例えば、既述の特許文献１等に開示されている方法を用いることができる。 In addition, the capture substance which is a specific binding substance that specifically binds to the test substance is bound (immobilized) to theinner wall surface 14a of the pore 14 of the plate-like substrate 10 manufactured as described above. Thus, the inspection device 1 to be used for inspection can be manufactured.
As a method for fixing the trapping substance to theinner wall surface 14a of the pore 14, a known method can be applied without any particular limitation. For example, the method disclosed in the above-described Patent Document 1 can be used.
細孔１４の内壁面１４ａへの捕捉物質の固定方法は公知の方法を特に制限なく適用することができる。例えば、既述の特許文献１等に開示されている方法を用いることができる。 In addition, the capture substance which is a specific binding substance that specifically binds to the test substance is bound (immobilized) to the
As a method for fixing the trapping substance to the
次に、本発明の検査デバイスを備えた検査装置および本発明の検査デバイスを用いた検査方法を説明する。
Next, an inspection apparatus provided with the inspection device of the present invention and an inspection method using the inspection device of the present invention will be described.
図１１は、本発明の一実施形態の検査装置５０の構成を模式的に示す図である。本実施形態の検査装置５０は、上記検査デバイス１と、この検査デバイス１の細孔１４中に検査用溶液を供給する溶液供給部６０と、検査デバイス１の一方の面１１側に配置された光検出器７０とを備えている。光検出器７０は、検査デバイス１から出射される光を検出するものである。
FIG. 11 is a diagram schematically showing the configuration of the inspection apparatus 50 according to an embodiment of the present invention. The inspection apparatus 50 according to the present embodiment is disposed on the inspection device 1, the solution supply unit 60 that supplies the inspection solution into the pores 14 of the inspection device 1, and the one surface 11 side of the inspection device 1. And a photodetector 70. The light detector 70 detects light emitted from the inspection device 1.
図１２は溶液供給部６０の概略構成を示す図である。
溶液供給部６０は、検査デバイス１の他方の面１２側に設置される検査用溶液６１を貯留する貯留部６２と、貯留部６２の上部に設置されて、貯留部６２に貯留されている検査用溶液６１を吸引するピペット部６４と、このピペット部６４上に設置される検査デバイス１の一方の面１１側に配置される減加圧空間部６６および減加圧空間部６６の圧力を減圧もしくは加圧するためのポンプ６８を備えている。 FIG. 12 is a diagram illustrating a schematic configuration of thesolution supply unit 60.
Thesolution supply unit 60 stores the inspection solution 61 installed on the other surface 12 side of the inspection device 1, and the inspection installed in the upper part of the storage unit 62 and stored in the storage unit 62. The pipette part 64 for sucking the solution 61 for use, and the pressure of the depressurizing space part 66 and the depressurizing space part 66 arranged on the one surface 11 side of the inspection device 1 installed on the pipette part 64 are reduced. Alternatively, a pump 68 for pressurization is provided.
溶液供給部６０は、検査デバイス１の他方の面１２側に設置される検査用溶液６１を貯留する貯留部６２と、貯留部６２の上部に設置されて、貯留部６２に貯留されている検査用溶液６１を吸引するピペット部６４と、このピペット部６４上に設置される検査デバイス１の一方の面１１側に配置される減加圧空間部６６および減加圧空間部６６の圧力を減圧もしくは加圧するためのポンプ６８を備えている。 FIG. 12 is a diagram illustrating a schematic configuration of the
The
ピペット部６４の先端が検査用溶液６１中に浸漬された状態で、ポンプ６８により減加圧空間部６６を減圧することにより検査用溶液６１がピペット部６４を介して検査デバイス１の細孔１４内に供給される。なお、ポンプ６８による減加圧空間部６６の減圧および加圧により、検査デバイス１の細孔１４への検査用溶液６１の供給および、細孔１４からの検査用溶液６１の排出を行うことができる。
In a state where the tip of the pipette part 64 is immersed in the inspection solution 61, the reduced pressure space 66 is decompressed by the pump 68, whereby the inspection solution 61 passes through the pipette part 64 and the pore 14 of the inspection device 1. Supplied in. Note that the inspection solution 61 is supplied to the pores 14 of the inspection device 1 and the inspection solution 61 is discharged from the pores 14 by depressurization and pressurization of the reduced pressure space 66 by the pump 68. it can.
ここで、検査用溶液６１は、光検出時に細孔１４中に供給される溶液であるが、溶液供給部６０は、検査工程において細孔１４中に供給すべき検体液、標識溶液、洗浄液等の供給にも用いられる。すなわち、溶液供給部６０は検査の工程毎に必要な溶液を細孔１４に供給するものである。
Here, the test solution 61 is a solution supplied into the pores 14 at the time of light detection, but the solution supply unit 60 includes a sample solution, a label solution, a cleaning solution, and the like to be supplied into the pores 14 in the test process. It is also used for supply. That is, the solution supply unit 60 supplies a necessary solution to the pores 14 for each inspection process.
以下、上記検査装置５０を用いた本発明の検査方法について説明する。
本発明において検査デバイスから出射され、光検出器により検出される光は、例えば、被検物質に付与された標識が励起されて生じる蛍光、もしくは標識が反応液の触媒として作用することで生じる発光、蛍光、化学発光など、標識に起因する光信号である。なお、被検物質が自家蛍光を生じるものであれば、標識は不要であり、自家蛍光を検出すればよい。また、ここで光信号とは、蛍光、化学発光光のほか、吸光度（比色）を含むものとする。 Hereinafter, the inspection method of the present invention using theinspection apparatus 50 will be described.
In the present invention, the light emitted from the inspection device and detected by the photodetector is, for example, fluorescence generated when the label attached to the test substance is excited, or luminescence generated by the label acting as a catalyst of the reaction solution It is an optical signal resulting from a label, such as fluorescence or chemiluminescence. In addition, if the test substance generates autofluorescence, no label is necessary, and autofluorescence may be detected. Here, the optical signal includes absorbance (colorimetric) in addition to fluorescence and chemiluminescence light.
本発明において検査デバイスから出射され、光検出器により検出される光は、例えば、被検物質に付与された標識が励起されて生じる蛍光、もしくは標識が反応液の触媒として作用することで生じる発光、蛍光、化学発光など、標識に起因する光信号である。なお、被検物質が自家蛍光を生じるものであれば、標識は不要であり、自家蛍光を検出すればよい。また、ここで光信号とは、蛍光、化学発光光のほか、吸光度（比色）を含むものとする。 Hereinafter, the inspection method of the present invention using the
In the present invention, the light emitted from the inspection device and detected by the photodetector is, for example, fluorescence generated when the label attached to the test substance is excited, or luminescence generated by the label acting as a catalyst of the reaction solution It is an optical signal resulting from a label, such as fluorescence or chemiluminescence. In addition, if the test substance generates autofluorescence, no label is necessary, and autofluorescence may be detected. Here, the optical signal includes absorbance (colorimetric) in addition to fluorescence and chemiluminescence light.
図１３は検査工程を模式的に示す図である。
検査デバイス１の細孔１４の内壁面１４ａにはアレルゲンなどの捕捉物質３０が固定されている（Ｓ１）。この検査デバイス１の細孔１４に被検物質（例えば、上記アレルゲンと特異的に結合する特異的ＩｇＥ抗体）を含む検体液を供給して、被検物質３２を捕捉物質３０に結合させる（Ｓ２）。検体液の供給には、上述の溶液供給部６０を用いる。貯留部６２に検体液を貯留させた状態で、ポンプを動作させてピペット部６４による検体液の吸引および排出を繰り返すことにより、検体液を細孔１４内の捕捉物質３０に効率よく接触させることができる。 FIG. 13 is a diagram schematically showing the inspection process.
A capturingsubstance 30 such as an allergen is fixed to the inner wall surface 14a of the pore 14 of the inspection device 1 (S1). A specimen liquid containing a test substance (for example, a specific IgE antibody that specifically binds to the allergen) is supplied to the pores 14 of the test device 1, and the test substance 32 is bound to the capture substance 30 (S2). ). The above-described solution supply unit 60 is used for supplying the sample liquid. The sample liquid is efficiently brought into contact with the capture substance 30 in the pores 14 by repeatedly pumping and discharging the sample liquid by the pipette unit 64 while the sample liquid is stored in the storage unit 62. Can do.
検査デバイス１の細孔１４の内壁面１４ａにはアレルゲンなどの捕捉物質３０が固定されている（Ｓ１）。この検査デバイス１の細孔１４に被検物質（例えば、上記アレルゲンと特異的に結合する特異的ＩｇＥ抗体）を含む検体液を供給して、被検物質３２を捕捉物質３０に結合させる（Ｓ２）。検体液の供給には、上述の溶液供給部６０を用いる。貯留部６２に検体液を貯留させた状態で、ポンプを動作させてピペット部６４による検体液の吸引および排出を繰り返すことにより、検体液を細孔１４内の捕捉物質３０に効率よく接触させることができる。 FIG. 13 is a diagram schematically showing the inspection process.
A capturing
次に、検体液を排出した後、被検物質３２と特異的に結合する物質３３（例えば、二次抗体）に標識Ｆが付与されてなる標識物質３５を含む標識溶液を細孔１４に供給して、被検物質３２に標識物質３５を結合させる（Ｓ３）。標識溶液の細孔１４へ供給は上記検体液の供給と同様に溶液供給部６０により行う。
Next, after discharging the sample liquid, a labeled solution containing a labeled substance 35 in which a label F is added to a substance 33 (for example, a secondary antibody) that specifically binds to the test substance 32 is supplied to the pores 14. Then, the labeling substance 35 is bound to the test substance 32 (S3). The label solution is supplied to the pores 14 by the solution supply unit 60 in the same manner as the sample solution.
なお、上記測定方法においては、被検物質３２の捕捉物質３０への結合の後に、標識物質３５を被検物質３２に結合させているが、検査装置５０外において、あらかじめ検体液と標識溶液を混合して被検物質３２と標識物質３５を結合させ、その混合液を細孔１４内に供給するようにしてもよい。この場合、混合液の細孔１４への供給により、細孔１４内に固定された捕捉物質３０に、標識物質３５が結合された被検物質３２を結合させることができる。
In the measurement method described above, the labeling substance 35 is bound to the test substance 32 after the test substance 32 is bound to the capture substance 30. It is also possible to combine the test substance 32 and the labeling substance 35 by mixing and supply the mixed liquid into the pores 14. In this case, by supplying the mixed liquid to the pores 14, the test substance 32 to which the labeling substance 35 is bound can be bound to the capture substance 30 fixed in the pores 14.
そして、標識溶液もしくは混合液を排出した後、検体液の供給と同様の方法で、溶液供給部６０を用いて細孔１４に洗浄液を供給して、細孔１４中に非特異吸着している被検物質３２や標識物質３５を除去する。
Then, after discharging the labeling solution or the mixed solution, the cleaning solution is supplied to the pores 14 using the solution supply unit 60 in the same manner as the supply of the sample solution, and nonspecific adsorption is performed in the pores 14. The test substance 32 and the labeling substance 35 are removed.
最後に、洗浄液を排出して、細孔１４内にバッファ溶液等の検査用溶液を充填させた状態で、標識Ｆを基質として作用する発光反応から生じる光を光検出器７０により検出する（Ｓ４）。なお、光検出器７０による検査デバイス１からの出射光の検出時、検査デバイス１が反射面４２を備えたことにより、細孔１４内において生じ、他方の面１２側に放射された光を反射面４２により一方の面１１側へ反射させることができるので、一方の面１１側において光取り出し効率よく光検出を行うことができる。
Finally, the cleaning solution is discharged, and light generated from a luminescence reaction that acts using the label F as a substrate is detected by the photodetector 70 in a state where the inspection solution such as a buffer solution is filled in the pores 14 (S4). ). In addition, when the light emitted from the inspection device 1 is detected by the photodetector 70, the inspection device 1 includes the reflection surface 42, thereby reflecting the light generated in the pore 14 and emitted to the other surface 12 side. Since the light can be reflected to the one surface 11 side by the surface 42, light detection can be performed efficiently on the one surface 11 side.
標識Ｆが蛍光色素、量子ドットなどの蛍光標識である場合には、バッファ溶液を検査用溶液として細孔１４内に供給し、細孔１４内をバッファ溶液で満たした状態で、蛍光測定を行う。具体的には、蛍光標識を励起する波長の光を励起光として検査デバイスに照射し、その励起光により励起された標識からの蛍光を検出する。なお、蛍光標識の検出の際に用いられる光検出器７０には、励起光照射部が備えられている。
When the label F is a fluorescent label such as a fluorescent dye or a quantum dot, the buffer solution is supplied into the pore 14 as a test solution, and the fluorescence measurement is performed with the pore 14 filled with the buffer solution. . Specifically, the inspection device is irradiated with light having a wavelength that excites the fluorescent label as excitation light, and fluorescence from the label excited by the excitation light is detected. The photodetector 70 used for detecting the fluorescent label is provided with an excitation light irradiation unit.
一方、標識Ｆがルミノールなどの化学発光基質を触媒する酵素標識である場合には、上記洗浄処理の後、酵素標識を触媒として化学反応が促進される化学発光基質を含む反応液を検査用溶液として細孔１４中に供給する。そして、光検出器７０では、細孔１４にこの反応液を供給にすることにより、細孔１４の捕捉物質３０に捕捉された被検物質３２に付与された酵素標識が反応液中の物質の化学反応を触媒して生じる発光を検出する。この場合、反応液により細孔１４が満たされた状態で発光検出を行う。
On the other hand, when the label F is an enzyme label that catalyzes a chemiluminescent substrate such as luminol, a reaction solution containing a chemiluminescent substrate that promotes a chemical reaction using the enzyme label as a catalyst after the washing treatment is used as a test solution. To be fed into the pores 14. Then, in the photodetector 70, by supplying this reaction solution to the pores 14, the enzyme label imparted to the test substance 32 captured by the capture material 30 in the pores 14 becomes the substance in the reaction solution. Luminescence generated by catalyzing a chemical reaction is detected. In this case, luminescence detection is performed in a state where the pores 14 are filled with the reaction solution.
化学発光を生じる酵素標識しては、ルミノール、ロフィン、ルシゲニンおよびシュウ酸エステルなどの化学発光基質と反応する酵素などが挙げられる。ＨＲＰ（西洋わさびペルオキシダーゼ）酵素が標識として用いられる場合には、ＨＲＰが触媒として機能するルミノール系の化学発光基質を含有する反応液（ルミノール反応液）を、ＡＬＰ（アルカリホスファターゼ）酵素が用いられる場合にはジオキセタン系化学発光基質を含有する反応液を用いることが好ましい。
Examples of enzyme labels that produce chemiluminescence include enzymes that react with chemiluminescent substrates such as luminol, lophine, lucigenin and oxalate. When HRP (horseradish peroxidase) enzyme is used as a label, a reaction liquid (luminol reaction liquid) containing a luminol-based chemiluminescent substrate in which HRP functions as a catalyst is used, and an ALP (alkaline phosphatase) enzyme is used. It is preferable to use a reaction solution containing a dioxetane chemiluminescent substrate.
ルミノール反応液には、少なくともルミノール基質と過酸化水素水が含まれる。酵素標識は、過酸化水素水存在下において、ルミノールの酸化を触媒するものである。反応液中には、化学発光を増感する増感剤を含むことが好ましい。
The luminol reaction solution contains at least a luminol substrate and a hydrogen peroxide solution. The enzyme label catalyzes the oxidation of luminol in the presence of hydrogen peroxide. The reaction solution preferably contains a sensitizer that sensitizes chemiluminescence.
なお、酵素標識を用いた光検出においては、上記の化学発光基質のみならず、発光基質あるいは蛍光基質を含む反応液を用い、呈色（吸光）反応や、蛍光を検出するものとすることもできる。
In light detection using an enzyme label, not only the chemiluminescent substrate described above but also a reaction solution containing a luminescent substrate or a fluorescent substrate may be used to detect a color (absorption) reaction or fluorescence. it can.
いずれの検出方法であっても、本発明の検査デバイスを用いることにより、細孔中で生じた光は検査デバイスの表面から効率よく出射され、光の取り出し効率が高いので、高精度な光検出が可能である。
Regardless of the detection method, by using the inspection device of the present invention, the light generated in the pores is efficiently emitted from the surface of the inspection device, and the light extraction efficiency is high. Is possible.
１ 検査デバイス
１０ 板状基材
１１ 板状基材（検査デバイス）の一方の面
１２ 板状基材（検査デバイス）の他方の面
１４ 細孔
１４ａ 細孔の内壁面
１７ 本体部材
１８ａ、１８ｂ 表面部材
３０ 捕捉物質
３２ 被検物質
３３ 被検物質に特異的に結合する物質
３５ 標識物質
４０ 柱状中空部
４１ 柱状中空部を構成する内壁面
４２、４３、４４ 反射面
４５、４９ テーパ面
４８ 小径中空部の内壁面
５０ 検査装置
６０ 溶液供給部
６１ 検査用溶液
６２ 貯留部
６４ ピペット部
６６ 減加圧空間部
６８ ポンプ
７０ 光検出器
Ｆ 標識 DESCRIPTION OFSYMBOLS 1 Inspection device 10 Plate-like base material 11 One side of plate-like base material (inspection device) 12 Other side of plate-like base material (inspection device) 14 Pore 14a Inner wall surface of pore 17 Main body members 18a, 18b Surface Member 30 Capturing substance 32 Test substance 33 Substance specifically binding to the test substance 35 Labeling substance 40 Columnar hollow part 41 Inner wall surface constituting the columnar hollow part 42, 43, 44 Reflecting surface 45, 49 Tapered surface 48 Small-diameter hollow Inner wall surface 50 Inspection device 60 Solution supply unit 61 Solution for inspection 62 Storage unit 64 Pipette unit 66 Depressurized space 68 Pump 70 Photodetector F Label
１０ 板状基材
１１ 板状基材（検査デバイス）の一方の面
１２ 板状基材（検査デバイス）の他方の面
１４ 細孔
１４ａ 細孔の内壁面
１７ 本体部材
１８ａ、１８ｂ 表面部材
３０ 捕捉物質
３２ 被検物質
３３ 被検物質に特異的に結合する物質
３５ 標識物質
４０ 柱状中空部
４１ 柱状中空部を構成する内壁面
４２、４３、４４ 反射面
４５、４９ テーパ面
４８ 小径中空部の内壁面
５０ 検査装置
６０ 溶液供給部
６１ 検査用溶液
６２ 貯留部
６４ ピペット部
６６ 減加圧空間部
６８ ポンプ
７０ 光検出器
Ｆ 標識 DESCRIPTION OF
Claims (13)
- 板状基材の一方の面から他方の面に貫通する複数の細孔を備えた検査デバイスであって、
前記細孔が、同一開口径で延びる柱状中空部と、該柱状中空部の前記他方の面側に形成された、前記柱状中空部を構成する内壁面に連続し、前記柱状中空部における開口径よりも該細孔の開口径を小さくする反射面を有し、
該反射面と前記他方の面とのなす角度が０°以上４５°以下である検査デバイス。 An inspection device having a plurality of pores penetrating from one surface of a plate-like substrate to the other surface,
The pores are continuous with the columnar hollow portion extending with the same opening diameter, and the inner wall surface of the columnar hollow portion formed on the other surface side of the columnar hollow portion, and the opening diameter in the columnar hollow portion Having a reflecting surface that reduces the aperture diameter of the pores,
An inspection device in which an angle formed by the reflecting surface and the other surface is 0 ° or more and 45 ° or less. - 前記細孔の前記柱状中空部の内壁面に特定の物質と特異的に結合する捕捉物質が固定されている請求項１記載の検査デバイス。 The inspection device according to claim 1, wherein a trapping substance that specifically binds to a specific substance is fixed to an inner wall surface of the columnar hollow portion of the pore.
- 前記捕捉物質が、抗原、抗体またはデオキシリボ核酸である請求項２に記載の検査デバイス。 3. The inspection device according to claim 2, wherein the capture substance is an antigen, an antibody, or deoxyribonucleic acid.
- 前記反射面が金属面である請求項１から３のいずれか１項に記載の検査デバイス。 The inspection device according to any one of claims 1 to 3, wherein the reflecting surface is a metal surface.
- 前記細孔が、前記一方の面から前記柱状中空部に向かって、該細孔の開口径を徐々に小さくするテーパ部を有する請求項１から４のいずれか1項に記載の検査デバイス。 The inspection device according to any one of claims 1 to 4, wherein the pore has a tapered portion that gradually decreases an opening diameter of the pore from the one surface toward the columnar hollow portion.
- 前記板状基材がＳｉ、ＳｉＯ２、Ａｌ、Ａｌ２Ｏ３および樹脂材料のうちの１つまたは２つ以上の材料からなる請求項１から５のいずれか１項に記載の検査デバイス。 One or more inspection device according to claims 1 consisting of a material in any one of 5 of said plate-like substrate is Si, SiO 2, Al, Al 2 O 3 and the resin material.
- 前記反射面を構成する材料が前記柱状中空部を構成する材料と異なる請求項１から６のいずれか１項に記載の検査デバイス。 The inspection device according to any one of claims 1 to 6, wherein a material constituting the reflecting surface is different from a material constituting the columnar hollow portion.
- 前記細孔の前記柱状中空部における開口径は１μｍ～１００μｍである請求項１から７のいずれか１項に記載の検査デバイス。 The inspection device according to any one of claims 1 to 7, wherein an opening diameter of the pores in the columnar hollow portion is 1 µm to 100 µm.
- 前記板状基材の厚さは１００μｍ～２０００μｍである請求項１から８いずれか１項に記載の検査デバイス。 The inspection device according to any one of claims 1 to 8, wherein the thickness of the plate-like substrate is 100 µm to 2000 µm.
- 請求項１から９のいずれか１項に記載の検査デバイスと、
前記検査デバイスの前記細孔中に検査用溶液を供給する溶液供給部と、
前記検査デバイスの前記一方の面側に配置され、前記検査デバイスから出射される光を検出する光検出器とを備えた検査装置。 The inspection device according to any one of claims 1 to 9,
A solution supply unit for supplying a test solution into the pores of the test device;
An inspection apparatus including a photodetector that is disposed on the one surface side of the inspection device and detects light emitted from the inspection device. - 請求項１から９のいずれか１項に記載の検査デバイスの前記細孔の前記柱状中空部の内壁面に特定の物質と特異的に結合する捕捉物質を固定し、
前記特定の物質を含有する検体液を供給して、前記特定の物質を前記捕捉物質に結合させ、
前記特定の物質と特異的に結合する標識物質を前記特定の物質に結合させ、
前記細孔に検査用溶液を供給して該細孔に前記検査用溶液を留めた状態で、前記検査デバイスの前記一方の面から出射される光を検出する検査方法。 A capture substance that specifically binds to a specific substance is fixed to the inner wall surface of the columnar hollow portion of the pore of the inspection device according to any one of claims 1 to 9,
Supplying a sample liquid containing the specific substance to bind the specific substance to the capture substance;
Binding a labeling substance that specifically binds to the specific substance to the specific substance;
An inspection method for detecting light emitted from the one surface of the inspection device in a state in which the inspection solution is supplied to the pores and the inspection solution is retained in the pores. - 前記標識物質として酵素標識を用い、
前記検査用溶液として、前記酵素標識により触媒されて反応する基質を含む反応液を用い、
前記出射される光として、前記反応液中の前記基質が前記酵素標識により触媒されて生じる光を検出する請求項１１記載の検査方法。 Using an enzyme label as the labeling substance,
As the test solution, a reaction solution containing a substrate that is catalyzed by the enzyme label and reacts,
The inspection method according to claim 11, wherein as the emitted light, light generated when the substrate in the reaction solution is catalyzed by the enzyme label is detected. - 前記標識物質として蛍光標識を含む物質を用い、
該蛍光標識を励起させる励起光を前記検査デバイスに照射し、
前記出射される光として、前記励起光の照射により前記標識物質から生じる蛍光を検出する請求項１１記載の検査方法。 Using a substance containing a fluorescent label as the labeling substance,
Irradiating the inspection device with excitation light for exciting the fluorescent label;
The inspection method according to claim 11, wherein fluorescence emitted from the labeling substance by irradiation with the excitation light is detected as the emitted light.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003066042A (en) * | 2001-08-27 | 2003-03-05 | Nippon Shokubai Co Ltd | Biochip |
| JP2004012206A (en) * | 2002-06-05 | 2004-01-15 | Fuji Photo Film Co Ltd | Measuring chip |
| JP2004191127A (en) * | 2002-12-10 | 2004-07-08 | Nippon Sheet Glass Co Ltd | Biochemical vessel |
| JP2004286579A (en) * | 2003-03-20 | 2004-10-14 | Kanagawa Acad Of Sci & Technol | DNA analysis array, DNA analysis system and analysis method using the same |
| JP2005113136A (en) * | 2003-09-19 | 2005-04-28 | Foundation For The Promotion Of Industrial Science | Method and apparatus for patterning fluid dispersible substance on substrate, perforated sheet material therefor, and method for producing the same |
| JP4125244B2 (en) * | 2002-04-19 | 2008-07-30 | インフィネオン テクノロジーズ アクチエンゲゼルシャフト | Apparatus comprising locally oxidized porous silicon and method for producing the same |
| JP2009008672A (en) * | 2007-05-31 | 2009-01-15 | Canon Inc | Detection element, detection device and method for producing detection element |
-
2017
- 2017-03-14 WO PCT/JP2017/010093 patent/WO2017169715A1/en active Application Filing
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003066042A (en) * | 2001-08-27 | 2003-03-05 | Nippon Shokubai Co Ltd | Biochip |
| JP4125244B2 (en) * | 2002-04-19 | 2008-07-30 | インフィネオン テクノロジーズ アクチエンゲゼルシャフト | Apparatus comprising locally oxidized porous silicon and method for producing the same |
| JP2004012206A (en) * | 2002-06-05 | 2004-01-15 | Fuji Photo Film Co Ltd | Measuring chip |
| JP2004191127A (en) * | 2002-12-10 | 2004-07-08 | Nippon Sheet Glass Co Ltd | Biochemical vessel |
| JP2004286579A (en) * | 2003-03-20 | 2004-10-14 | Kanagawa Acad Of Sci & Technol | DNA analysis array, DNA analysis system and analysis method using the same |
| JP2005113136A (en) * | 2003-09-19 | 2005-04-28 | Foundation For The Promotion Of Industrial Science | Method and apparatus for patterning fluid dispersible substance on substrate, perforated sheet material therefor, and method for producing the same |
| JP2009008672A (en) * | 2007-05-31 | 2009-01-15 | Canon Inc | Detection element, detection device and method for producing detection element |
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