WO2011108576A1 - 検出デバイス - Google Patents
検出デバイス Download PDFInfo
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- WO2011108576A1 WO2011108576A1 PCT/JP2011/054734 JP2011054734W WO2011108576A1 WO 2011108576 A1 WO2011108576 A1 WO 2011108576A1 JP 2011054734 W JP2011054734 W JP 2011054734W WO 2011108576 A1 WO2011108576 A1 WO 2011108576A1
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- sample
- detection device
- base member
- slide member
- slide
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
- G01N27/3272—Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
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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
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/76—Chemiluminescence; Bioluminescence
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0645—Electrodes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0825—Test strips
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0633—Valves, specific forms thereof with moving parts
- B01L2400/065—Valves, specific forms thereof with moving parts sliding valves
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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
- G01N21/75—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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1016—Control of the volume dispensed or introduced
Definitions
- the present invention relates to a detection device for detecting a substance in a sample.
- 1,5-anhydroglucitol (hereinafter referred to as “1,5-AG”) has attracted attention as a marker for grasping the blood glucose control state of diabetic patients.
- 1,5-AG has advantages such as being less affected by diet and reflecting a relatively short-term blood glucose control state of the past week or so.
- Patent Document 1 describes a biosensor that performs a two-stage reaction for detecting the concentration of glycoprotein in blood. This biosensor has a suction cavity that sucks up a sample by capillary action, an analysis cavity that performs an enzymatic reaction on the sample, and a flow path that connects the suction cavity and the analysis cavity. Reagent is immobilized.
- the present invention has been made in view of the above-described circumstances, and an object thereof is to provide a detection device that can safely perform multi-stage processing with a simple configuration.
- the detection device of the present invention is a detection device for performing detection on a sample, the base member having a sample supply position on the surface to which the sample is supplied, and the sample on the surface of the base member A detection unit formed away from the supply position, a slide body that slides relative to the base member on the surface, and a sample storage that is provided on a part of the slide body and can store the sample And a support member that is fixed to the base member and supports the slide member so as to be slidable relative to the base member.
- the base member and the slide member include the sample It is characterized in that the sliding movement is possible within a range including a superposition position where the storage part is superposed on the detection part and the sample supply position.
- the sample stored in the sample storage unit at the sample supply position moves from the sample supply position to the overlapping position and can be detected by the detection unit.
- the said detection part is formed so that a colorimetric measurement or an electrochemical measurement is possible.
- colorimetric measurement or electrochemical measurement can be performed on the sample moved to the detection unit.
- the base member has an insulating property
- the detection unit has an electrode system including a working electrode, a reference electrode, and a counter electrode formed on the surface of the base member so as to be separated from the sample supply position. Is preferred. In this case, when the sample moves from the sample supply position to the detection unit, the sample comes into contact with each of the working electrode, the reference electrode, and the counter electrode, and electrochemical measurement can be performed on the sample.
- At least one of the facing portions of the sample storage portion and the base member is configured to have at least a portion having hydrophilicity.
- the sample can be easily supplied by spreading the sample in a range having hydrophilicity in the space formed by the sample storage portion and the base member.
- the said support part is provided in two places spaced apart so that the said superimposition position may be located in between on the said base member.
- the slide member can be stably supported on the base member.
- the said support part has a guide part provided in parallel mutually mutually while separating so that the said superimposition position may be located on the said base member.
- the slide member can be freely slid along each of the guide portions provided in parallel with each other.
- the said support part has a coating
- the slide member since the slide member is covered with the covering portion, the slide member can be freely slid relative to the base member, and the slide member is unlikely to fall off the support portion.
- the slide member has a flow stop portion that stops a flow of the sample from the sample storage portion to the electrode system in a part of the slide body, and the flow stop portion is formed by the sample storage portion. It is preferable that it is located between the superimposed position and the sample supply position when in the sample supply position. In this case, since the sample is suppressed from flowing into the electrode system in the flow stopping unit, the sample is detected before the slide member is slid relative to the base member and the sample is moved from the sample supply position to the detection unit. Can be prevented from entering.
- the flow stop part when the sample storage part is at the sample supply position, has at least a part of its edge as viewed in the normal direction of the surface of the base member and the overlap position and the sample. It is preferable to have a hole or a recess positioned between the supply position. In this case, the flow of the sample can be stopped at the edge of the hole or the recess.
- the said flow stop part protrudes in the direction which goes to the said base member from the said slide member when the said slide member is attached to the said base member, and is formed in the said slide member.
- the flow of the sample can be stopped in the flow stop portion by blocking the sample by the flow stop portion.
- the said slide member has a distribution
- circulation suppression part which suppresses the distribution
- the said flow suppression part is formed by cutting off a part of said slide body adjacent to the said sample accommodating part. In this case, it is possible to stop the flow of the sample at the step portion generated by cutting out a part of the slide body.
- At least one of the sample container and the sample supply position is used in pre-processing for removing, capturing, or converting to another substance that does not affect the detection, which interferes with the detection.
- a pretreatment reagent is preferably arranged. In this case, in the state where the sample is stored in the sample storage unit at the sample supply position, the pretreatment is performed by the pretreatment reagent, and the slide member is slid to detect the detection after moving the sample from the sample supply position to the detection unit. It can be carried out.
- At least one of the counter electrode and the reference electrode is a silver-silver chloride electrode using silver and silver chloride. In this case, electrochemical measurement can be performed on the sample with good reproducibility.
- the sample supply position further includes a pair of continuity detection electrodes that are exposed and provided on the surface of the base member, and the pair of continuity detection electrodes are provided by the sample supplied to the sample supply position. May be conducted. In this case, when the sample is supplied to the sample supply position, it can be detected that the sample has been supplied by the pair of conduction detection electrodes becoming conductive.
- the surface of the conduction detection electrode preferably has hydrophilicity. In this case, the conduction detection electrode and the sample are likely to be in close contact.
- the said guide part has hydrophobicity. In this case, the sample can be prevented from entering the gap between the guide portion and the slide member.
- the base member has a long hole formed in a sliding direction of the slide member with respect to the base member, and the slide member is supported by the support portion in the slide member.
- a through hole that overlaps with the elongated hole may be formed when viewed from the thickness direction. In this case, when a rod inserted through the elongated hole and the through hole is used, the sliding direction of the sliding member can be guided in the direction in which the elongated hole extends.
- an oxidoreductase and a redox mediator may be disposed at least on the working electrode of the electrode system.
- the redox mediator includes at least one of ruthenium derivatives, osmium derivatives, ferricyan derivatives, ferrocene derivatives, quinone derivatives, phenothiazine derivatives, phenoxazine derivatives, phenazine derivatives, indophenol derivatives, diphenylamine derivatives, and phenol derivatives. But you can.
- the oxidoreductase is at least one of pyranose oxidase, L-sorbose oxidase, 1,5-anhydroglucitol dehydrogenase, L-sorbose dehydrogenase, and 1,5-anhydroglucitol 6-phosphate dehydrogenase. May be included.
- the pretreatment reagent may include a reagent for removing, capturing, or converting glucose into another substance that does not affect the detection. In these cases, a detection device for 1,5-AG measurement capable of suitably measuring 1,5-AG can be configured.
- the sample can be moved from the sample supply position to the superposition position superimposed on the detection unit by sliding the slide member with respect to the base member. Stage processing is possible.
- FIG. 3B is a cross-sectional view taken along the line CC of FIG. 3A. It is sectional drawing in the DD line
- FIG. 1A is a perspective view showing a detection device 1 of the present embodiment.
- 1B is a cross-sectional view taken along line AA in FIG. 1A.
- 1C is a cross-sectional view taken along line BB in FIG. 1A.
- the detection device 1 includes a base member 10 made of an insulating material, an electrode system (detection unit) 20 formed on the surface of the base member 10, and a surface of the base member 10.
- the slide member 30 is configured to include a slide member 30 that slides relative to the base member 10 and a support portion 40 that supports the slide member 30 so as to be slidable relative to the base member 10.
- the base member 10 includes a substrate 11 formed in a plate shape and a resist layer 12 stacked on the substrate 11.
- One end of the substrate 11 is an insertion portion 11A that is inserted into an inspection device.
- the insulating material for forming the substrate 11 is not particularly limited as long as it is a material having insulating properties and necessary strength.
- a plastic film or the like can be used.
- the plastic film is not particularly limited as long as it is formed on a film containing a polymer compound as a main component.
- Preferred polymer compounds include, for example, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polycarbonate ( PC), polyarylate, polyethersulfone (PES), polyimide, polyamide, polypropylene (PP), polyethylene (PE), cycloolefin polymer (COP), polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), tri Acetyl cellulose (TAC), diacetyl cellulose (DAC), polystyrene (PS), polyurethane, polyvinyl alcohol (PVA), Eval (ethylene-vinyl alcohol copolymer), polyvinyl chloride ( VC), and the like.
- glass or the like can be used as the material of the substrate 11, but among the materials described above, PET is preferable as the material of the substrate 11 because it is easy to handle.
- the resist layer 12 is a layer in which, for example, a thermosetting or ultraviolet curable insulating paint is formed in a thin layer on the surface of the substrate 11 by screen printing or the like.
- the surface exposed to the outside has hydrophobicity.
- the resist layer 12 is formed with an opening through which a counter electrode 21, a working electrode 24, and a reference electrode 27 of the electrode system 20 described later are exposed to the outside.
- the electrode system 20 is formed in a thin film shape on the surface of the substrate 11 of the base member 10, and has a counter electrode 21, a working electrode 24, and a reference electrode 27 formed so as to be exposed in the above-described opening.
- the counter electrode 21 and the working electrode 24 are formed on the substrate 11 by screen printing using conductive carbon ink.
- the counter electrode 21 and the working electrode 24 have wiring portions 22 and 25 provided extending to the insertion portion 11A, and contact electrodes 23 and 26 formed at the position of the insertion portion 11A and conducting to the wiring portions 22 and 25, respectively. Is provided.
- the reference electrode 27 is a silver-silver chloride electrode formed on the substrate 11 by a screen printing method. Like the counter electrode 21 and the working electrode 24, the reference electrode 27 has a wiring portion 28 and a contact electrode 29, and is formed to extend to the insertion portion 11A.
- the contact electrodes 23, 26 and 29 are connected to the inspection device when the insertion portion 11A is inserted into the inspection device.
- the region that overlaps the counter electrode 21, the working electrode 24, and the reference electrode 27 on the surface of the base member 10 is the overlapping position P2 for electrochemical measurement of the sample.
- a measurement reagent (not shown) for reacting with the sample and enabling electrochemical measurement is dipped. Or by a method such as spin coating.
- the overlapping position P2 preferably has a shape that surrounds the counter electrode 21, the working electrode 24, and the reference electrode 27. In the present embodiment, the overlapping position P2 is formed in a substantially rectangular shape.
- the content of the measurement reagent for performing electrochemical measurement on the sample may be appropriately determined by the reaction performed at the overlapping position P2. Only oxidase may be arranged in the measurement or the like for directly detecting the generated hydrogen peroxide. In the case of measurement of sodium ions, potassium ions, etc. that can be measured without requiring a reaction of the substance to be measured, the measurement reagent need not be arranged.
- an oxidoreductase having 1,5-AG oxidizing ability and a redox mediator responsible for mediating the exchange of electrons involved in the redox reaction are arranged in the electrode system 20.
- 1,5-AG oxidoreductase pyranose oxidase, L-sorbose oxidase, 1,5-AG dehydrogenase, L-sorbose dehydrogenase, 1,5-anhydroglucitol 6-phosphate dehydrogenase, etc. should be employed. Can do.
- ruthenium derivatives, osmium derivatives, ferricyan derivatives, ferrocene derivatives, quinone derivatives, phenothiazine derivatives, phenoxazine derivatives, phenazine derivatives, indophenol derivatives, diphenylamine derivatives, phenol derivatives, and the like can be used.
- [osmium (bipyridyl) 2 imidazolyl Cl] Cl 2 [osmium (bipyridyl) 2 Cl] complexed with polyvinylimidazoyl, potassium ferricyanide, sodium ferricyanide, ferrocene, ferrocenemethanol, ferrocene PEG, etc. It can be used.
- phenothiazine derivatives that can be used as redox mediators include thionine acetate, thionine chloride, methylene blue, methylene green, 10- (carboxymethylaminocarbonyl) -3,7'-bis (dimethylamino) -phenothiazine sodium salt, and toluidine blue.
- Azure C Azure A, Azure I, Azure B, new methylene blue, or benzoylleucomethylene blue can be employed.
- methylene blue, thionine acetate, thionine chloride, azure C, azure A, azure I, azure B or toluidine blue O are preferable, and a thionine acetate is more preferable.
- the slide member 30 includes a slide body 32 formed in a plate shape, a sample storage portion 34 provided at a part on one end side of the slide body 32, and a sample storage portion 34 spaced apart so that the sample storage portion 34 is positioned therebetween. It has a pair of spacers 31a and 31b fixed to one surface of the slide body 32 at a location.
- the slide body 32 is formed of a plastic film containing a polymer compound as a main component in the same manner as the substrate 11.
- the material of the slide body 32 is preferably PET.
- a through hole 33 is formed in the vicinity of the center of the slide body 32 so as to penetrate in the thickness direction of the slide body 32.
- the through-hole 33 is formed in a shape in which the slide body 32 is hollowed out into a cylindrical shape with a central axis directed in the plate thickness direction of the slide body 32.
- the sample container 34 is set to a part of the same plastic film as the slide body 32. Further, both sides of the portion where the sample storage portion 34 extends are separated from the slide body 32 by notches (distribution suppressing portions) 32 a and 32 b formed in a plastic film constituting the slide body 32.
- the surface 34a facing the base member 10 has hydrophilicity. Examples of the hydrophilic treatment for hydrophilizing the sample container 34 include a corona treatment, a plasma treatment, a UV / ozone treatment, and a flame treatment.
- examples include a method of applying a hydrophilic compound such as polyvinyl alcohol, hydroxyalkyl cellulose, or agarose to the wall surface of the sample container 34, and a method of forming a silicon oxide film on the wall surface of the sample container 34 by itro treatment.
- a hydrophilic compound such as polyvinyl alcohol, hydroxyalkyl cellulose, or agarose
- examples include a method of applying a hydrophilic compound such as polyvinyl alcohol, hydroxyalkyl cellulose, or agarose to the wall surface of the sample container 34, and a method of forming a silicon oxide film on the wall surface of the sample container 34 by itro treatment.
- the above-described hydrophilic treatment can be appropriately employed.
- the slide body 32 may be formed of a triacetyl cellulose film, and the surface layer of the surface 34a portion of the sample storage portion 34 facing the base member 10 may be made hydrophilic by performing an alkali treatment.
- the spacers 31 a and 31 b are configured by bonding a plastic film having a thickness in the plate thickness direction of the slide body 32 to the slide body 32 with, for example, a double-sided adhesive tape.
- the surfaces of the spacers 31 a and 31 b opposite to the surfaces fixed to the slide body 32 are in contact with the base member 10.
- the sample container 34 and the base member 10 are separated by the thickness of the spacers 31a and 31b. Therefore, the size of the gap created by the spacers 31a and 31b between the sample storage portion 34 and the base member 10 can be set to a different size by changing the thickness of the spacers 31a and 31b. .
- the spacers 31a and 31b may be integrally formed with the slide body 32.
- the slide body 32 can be formed by injection molding or the like so that a groove is formed between the spacer 31a and the spacer 31b.
- the slide member 30 that can accommodate the sample with high accuracy can be easily formed.
- the spacers 31a and 31b are integrally formed with the slide body 32, the manufacturing cost when mass-producing the slide member 30 can be reduced.
- a gap for accommodating a sample by opening a hole in the slide body 32 or cutting the slide body 32 to form a groove, etc. Can also be provided.
- the support portion 40 includes a pair of plate-like guide portions 41 fixed to the resist layer 12 of the base member 10, and a cover member 42 spanned between the guide portions 41.
- board thickness direction of the base member 10 is bonded together by the double-sided adhesive tape, for example.
- the guide part 41 is formed thicker than the plate thickness of the slide member 30 by alternately laminating a plastic film and a double-sided adhesive tape.
- guide surfaces 41 a and 41 b extending in parallel with the direction along the surface of the base member 10 are formed in opposing portions of the pair of guide portions 41.
- the cover member 42 is fixed to the guide portion 41, and has a gap slightly larger than the plate thickness of the slide member 30 in the plate thickness direction of the base member 10, and the counter electrode 21, the working electrode 24, and the like on the base member 10.
- the reference electrode 27 is covered.
- a slide member 30 is inserted into a hollow portion formed by the guide portion 41 and the cover member 42. Therefore, the slide member 30 is guided in the direction in which the guide surfaces 41 a and 41 b extend, and the slide member 30 is slidably moved relative to the base member 10.
- the guide part 41 and the cover member 42 may be integrally formed.
- the support part 40 can be easily mass-produced.
- injection molding, cutting, or the like can be employed as in the case of integrally forming the slide member 30 described above.
- the sample storage portion 34 is covered with the cover.
- the positional relationship is located outside the cavity covered by the member 42.
- the position where the resist layer 12 and the sample storage portion 34 overlap when viewed in the plate thickness direction of the base member 10 is set as a sample supply position P1 for supplying the sample to the sample storage portion 34.
- the edge on the side of the sample storage portion 34 in the through hole 33 is positioned between the overlapping position P2 and the sample supply position P1. For this reason, when the sample storage portion 34 is at the sample supply position P1, the sample stored in the sample storage portion 34 stops at the edge portion on the side of the sample storage portion 34 in the through hole 33 as a boundary, and enters the superposition position P2. Intrusion is suppressed.
- the edge part by the side of the sample accommodating part 34 in the through-hole 33 is a flow stop part which stops the flow of a sample.
- glucose in the sample which is an interfering substance for 1,5-AG measurement
- a pretreatment reagent 13 for a pretreatment reaction is fixedly arranged.
- application drying, screen printing, or the like can be employed.
- the pretreatment reagent 13 of this embodiment contains an enzyme having an activity of degrading or converting glucose.
- oxidizing glucose when oxidizing glucose, it contains glucose oxidase, a mixture of glucose dehydrogenase and coenzyme nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADP), etc.
- NAD nicotinamide adenine dinucleotide
- NADP nicotinamide adenine dinucleotide phosphate
- pretreatment reagent 13 examples include hexokinase and glucokinase.
- the composition of the pretreatment reagent 13 can be appropriately changed according to the required pretreatment reaction when the measurement method for the sample is different or the target substance to be measured is different.
- the content of the pretreatment reaction is not particularly limited, and in addition to various reactions such as decomposition, removal, and conversion, trapping (capturing) such as ion adsorption, affinity adsorption, or adsorption by microbeads using a boric acid complex, etc. Any pretreatment reaction may be performed as long as the reaction is possible on the detection device 1.
- the operation when measuring 1,5-AG using the detection device 1 configured as described above will be described with reference to FIGS. 2A to 2C.
- the user who uses the detection device 1 is a person who measures 1,5-AG with the detection device 1 using a whole blood sample collected from the user.
- the user who uses the detection device 1 is not restricted to this.
- the detection device 1 is prepared in a state where the sample container 34 is located at the sample supply position P1.
- the user sets the detection device 1 to the inspection device by inserting the insertion portion 11A of the detection device 1 into the inspection device. Subsequently, as shown in FIG.
- the user drops a whole blood sample (sample) CS collected from a fingertip or the like onto the sample supply position P1, and a gap between the resist layer 12 of the base member 10 and the sample storage portion 34. Inject. Then, a reaction such as decomposition or conversion of glucose in the whole blood sample CS is started by the pretreatment reagent 13 fixedly arranged at the sample supply position P1.
- glucose in the whole blood sample CS is decomposed, removed, captured, or converted into another substance that does not affect the electrochemical measurement. After completion, the whole blood sample CS becomes a measurement sample (sample) S ready for measurement.
- the user slides the slide member 30 with respect to the base member 10 and moves the sample storage portion 34 to the overlapping position P2. Then, the measurement sample S follows the movement of the slide member 30 and moves on the resist layer 12 of the base member 10, and the measurement sample S reaches the overlapping position P2 to reach the counter electrode 21, the working electrode 24 and the reference of the electrode system 20. In contact with the pole 27.
- the measurement sample S introduced into the superposition position P2 causes a known reaction such as an oxidation-reduction reaction with the measurement reagent arranged at the superposition position P2. Further, a voltage is applied from the inspection device to the electrode system 20 of the detection device 1, and the current value flowing through the electrode system 20 is measured, whereby the concentration of 1,5-AG is measured.
- an electrochemical measurement method an amperometry method (current measurement method), a coulometry method (coulometry method), a potential sweep method, a cyclic voltammetry method, or the like can be appropriately employed.
- the measurement sample (sample) S reaches the overlapping position P2 simply by sliding the slide member 30 relative to the base member 10 after performing the pretreatment reaction at the sample supply position P1.
- a reaction for electrochemical measurement can be performed.
- multi-stage processing can be performed safely with a simple configuration that does not have a complicated flow channel structure.
- the surface of the sample storage unit 34 facing the base member 10 has hydrophilicity, the sample supplied between the sample storage unit 34 and the base member 10 spreads in the sample storage unit 34. Therefore, a certain amount of sample can be easily supplied to the sample storage unit 34. Further, since the sample is slid while the sample is attached to the hydrophilic surface of the sample storage unit 34, it is difficult for the sample to protrude from the sample storage unit 34 when the slide member 30 is slid.
- the support part 40 since the support part 40 is provided in two places spaced apart on the base member 10 so that the overlapping position P2 is located therebetween, the support part 40 can support the slide member 30 at two points away from each other. . For this reason, the support part 40 can support the slide member 30 stably.
- the slide member 30 can be linearly moved along the guide part 41 with high accuracy.
- the support portion 40 is provided with a cover member (covering portion) 42, and has a gap in which the slide member 30 can advance and retract between the base member 10. For this reason, the slide member 30 can be slidably moved and the slide member 30 can be prevented from falling off the support portion 40.
- a flow stop portion is formed by a through hole 33 formed through the slide body 32 of the slide member 30. For this reason, it is suppressed that a sample flows into the electrode system 20 in the through-hole 33, and the whole blood sample CS is prevented from entering the position of the electrode system 20 before the sample is moved from the sample supply position P1 to the overlapping position P2. It is possible to prevent the sample from reaching the electrode system 20 before the pretreatment reaction is completed.
- the notches 32a and 32b are formed between the slide body 32 and the sample storage portion 34, the sample stored in the sample storage portion 34 can be suppressed from flowing into the slide body 32. As a result, a certain amount of sample can be stably stored in the sample storage unit 34.
- the reference electrode 27 is a silver-silver chloride electrode using silver and silver chloride, electrochemical measurement can be performed on the sample with good reproducibility.
- FIG. 3A is a perspective view showing the detection device 2 of the present embodiment.
- 3B is a cross-sectional view taken along the line CC of FIG. 3A.
- 3C is a cross-sectional view taken along the line DD of FIG. 3A.
- the detection device 2 includes a slide member 230 provided in place of the slide member 30, and a support portion 240 provided in place of the support portion 40.
- the slide member 230 has a slide body 232 formed in a substantially plate shape having a distal end 230a and a base end 230b.
- the slide body 232 includes a sample storage portion 234, a flow stop portion 235, a spacer 231, and a stopper.
- a portion 236 and a grip portion 238 are formed in this order from the distal end to the proximal end.
- the sample storage portion 234 is formed in a square shape with a size that overlaps with each of the counter electrode 21, the working electrode 24, and the reference electrode 27 of the electrode system 20, similarly to the sample storage portion 34 described in the first embodiment. .
- the flow stop portion 235 is formed to protrude in the direction toward the base member 10 by a plastic film attached to the slide body 232 with a double-sided adhesive tape on the base end side of the sample storage portion 234. Further, the flow stopping portion 235 is configured such that the surface opposite to the surface attached to the slide body 232 is in contact with the resist layer 12 of the base member 10. At this time, a gap for accommodating the sample is formed between the sample accommodating portion 234 and the resist layer 12.
- the spacer 231 is formed of a plastic film affixed to the slide body 232 with a double-sided adhesive tape, similar to the flow stop portion 235, and is separated from the flow stop portion 235 on the proximal end side with respect to the flow stop portion 235. Is provided.
- the stopper portion 236 is provided adjacent to the base end side of the spacer 231, and is formed so as to protrude from the slide body 232 of the slide member 230 to the base member 10 side.
- the stopper portion 236 is formed so as to be able to come into contact with the edge of the base member 10, and the positional relationship between the slide member 230 and the base member 10 when the stopper portion 236 is in contact with the edge of the base member 10 is slid.
- the overlapping position P ⁇ b> 2 is positioned between the flow stop portion 235 of the member 230 and the spacer 231. Further, the electrode system 20 and the slide member 230 are separated from each other in the thickness direction of the base member 10.
- the grip portion 238 is provided to protrude outward from the edge of the base member 10 when the stopper portion 236 is in a positional relationship where the stopper portion 236 is in contact with the edge of the base member 10.
- the support portion 240 has a pair of guide portions 241 formed so as to extend parallel to each other on the surface of the base member 10 in a direction perpendicular to the direction in which the guide portion 41 described in the first embodiment extends. .
- a cover member 42 is fixed to the guide portion 241.
- a sample supply position P201 is set instead of the sample supply position P1.
- the position of the sample supply position P201 is such that the base member 10 and the sample storage portion 234 overlap each other in the thickness direction of the slide member 230 when the stopper portion 236 is in contact with the edge of the base member 10. It is set on the surface.
- the detection device 2 is prepared in a state where the sample storage unit 234 is positioned at the sample supply position P201. In this state, the user inserts and sets the insertion portion 11A of the detection device 2 into the inspection device.
- the user supplies the whole blood sample CS to the sample supply position P201 by performing the same operation as the operation of supplying the whole blood sample CS to the sample supply position P1 of the detection device 1 described in the first embodiment. Then, the reaction with the pretreatment reagent starts at the sample supply position P201 as in the first embodiment.
- the reaction with the pretreatment reagent is performed for a predetermined time at the sample supply position P201, so that the whole blood sample CS becomes a measurement sample (sample) S ready for measurement as in the detection device 1 of the first embodiment.
- the user grips the grip portion 238 of the slide member 230 and moves the sample storage portion 234 to the overlapping position P2.
- the measurement sample S is in contact with the electrode system 20 when the sample storage portion 234 is at the overlapping position P2.
- a voltage is applied from the inspection device to the electrode system 20 of the detection device 2, and the current value flowing through the electrode system 20 is measured, whereby the concentration of 1,5-AG is measured. Is measured.
- the sample after the pretreatment reaction is performed at the sample supply position P201, the sample reaches the superposition position P2 only by sliding the slide member 30 relative to the base member 10, and electrochemical measurement is performed.
- the reaction for can be performed. For this reason, multi-stage processing can be performed safely with a simple configuration that does not have a complicated flow channel structure.
- the sample storage portion 234 is positioned at the sample supply position P201 in a positional relationship in which the stopper portion 236 and the base member 10 are in contact with each other. For this reason, in order to perform the measurement with respect to the sample using the detection device 2, it is possible to suppress erroneous operation and displacement when the slide member 30 and the base member 10 are combined.
- FIG. 5A is a cross-sectional view showing the detection device 3.
- the detection device 3 is provided in place of the base member 310 provided in place of the base member 10, the optical measurement unit 320 provided in place of the electrode system 20, and the slide member 30.
- the configuration differs from the detection device 1 of the first embodiment in that the slide member 330 is provided.
- the base member 310 is a plate-like member configured to transmit light, and the entire surface is configured to be transparent (including substantially transparent).
- the optical measuring unit 320 is configured to have a color developing substrate layer 321 in a part of the base member 310.
- the chromogenic substrate layer 321 is a film in which a measurement reagent (not shown) described in the first embodiment and a chromogen described later are fixed, and is attached to the base member 310.
- the chromogenic substrate used for absorbance detection is an oxidized chromogenic substrate
- the chromogen used alone is N-carboxymethylaminocarbonyl-4,4′-bis (dimethylamino) diphenylamine sodium salt (DA64), 10 -Carboxymethylaminocarbonyl-3,7-bis (dimethylamino) phenothiazine sodium salt (DA67), bis [3-bis (4-chlorophenyl) -methyl-4-dimethylaminophenyl] amine (BCMA), bis [3- Bis (4-chlorophenyl) -methyl-4-carboxyethylaminophenyl] amine, 10-N-methylcarbamoyl-3,7-dimethylamino-10H-phenothiazine (MCDP), 10-N-carboxymethylcarbamoyl-3,7 -Dimethylamino-10H-phenothiazine (CCAP), 3,3 ′, 5,5
- Examples of coupling chromogens include couplers such as 4-aminoantipyrine (4AA), 3-methyl-2-benzothiazolinone hydrazone (MBTH) and aminodiphenyl compounds (NCP). N-ethyl-N- (3-methylphenyl) -N′-succinylethylenediamine (EMSE), N-ethyl-N- (2-hydroxy-3-sulfopropyl) -3-methoxyaniline (TOOS), etc. Is mentioned.
- couplers such as 4-aminoantipyrine (4AA), 3-methyl-2-benzothiazolinone hydrazone (MBTH) and aminodiphenyl compounds (NCP).
- examples of chromogens include 2- (4-iodophenyl) -3- (4-nitrophenyl) -5-phenyl-2H-tetrazolium chloride (INT), 3- (4 , 5-Dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium bromide (MTT), 3,3 ′-[3,3′-dimethoxy- (1,1′-biphenyl) -4,4 ′ -Diyl] -bis [2- (4-nitrophenyl) -5-phenyl-2H-tetrazolium chloride] (NTB), 2- (4-iodophenyl) -3- (4-nitrophenyl) -5- (2 , 4-Disulfophenyl) -2H-tetrazolium monosodium salt (WST-1), 2- (4-iodophenyl) -3- (2,4-dinitrophenyl) -5
- the region on the base member 310 that overlaps the optical measurement unit 320 is the overlapping position P2 as in the detection device 1 of the first embodiment.
- the slide member 330 includes a slide body 32, a sample storage portion 34 provided at one end of the slide body 32, and a sample supply position P1 and a superposition position P2 when the sample storage portion 34 is at the sample supply position P1. It has the flow stop part 333 provided in the base member 310 side on the slide body 32 so that it may be located.
- the surface on the side facing the base member 310 in the sample storage portion 34 is subjected to a hydrophilic treatment that makes the hydrophilicity relatively higher than that of the flow stop portion 333.
- the flow stopping portion 333 is a region that is hydrophobized on the surface of the slide body 32 and is relatively less hydrophilic than the sample storage portion 34. For this reason, the sample (for example, whole blood sample CS) accommodated in the sample accommodating part 34 flows so that it may spread over the whole sample accommodating part 34, and stops with the part of the flow stop part 333 as a boundary.
- sample for example, whole blood sample CS
- FIG. 5B is a cross-sectional view showing the operation when the detection device 3 is used. As shown in FIG. 5B, also in the detection device 3 of the present embodiment, the whole blood sample CS supplied to the sample supply position P1 does not reach the overlapping position P2 as it is, as in the detection device 1 described above. The slide member 330 is moved to the overlapping position P2 by sliding.
- the optical measurement unit 320 is irradiated with the measurement light L1 by an inspection device (not shown).
- the measurement light is visible light, and it is preferable that the wavelength is long.
- the measurement light L1 is reflected by the optical measurement unit 320, and the reflected light L2 of the measurement light L1 enters a measurement unit (not shown) in the inspection instrument.
- the inspection device performs a colorimetric measurement comparing the colors of the reflected light L2 and the internal standard, and measures the concentration of 1,5-AG.
- 1,5-AG can be measured by colorimetric measurement. Also in the present embodiment, after the pretreatment reaction is performed at the sample supply position P1, the sample reaches the superposition position P2 only by sliding the slide member 330 with respect to the base member 310, and the reaction for colorimetric measurement is performed. be able to. For this reason, multi-stage processing can be performed safely with a simple configuration that does not have a complicated flow channel structure.
- FIGS. 6A and 6B are cross-sectional views showing a detection device of this modification.
- the detection device 3 of this modification has an optical measurement unit 320 a instead of the optical measurement unit 320.
- the base member 310 is configured to be transparent (including substantially transparent) at a portion where the optical measurement unit 320a is located.
- the measurement reagent and the chromogen described in the third embodiment are directly applied and fixed to the position of the detection unit on the surface of the base member 310. Also in this modification, the region on the surface of the base member 310 that overlaps the optical measurement unit 320a is the overlap position P2 as in the detection device 1 of the first embodiment. Even with such a configuration, colorimetric measurement can be performed on the sample as in the third embodiment described above.
- the configuration in which the measurement light L1 is measured by the reflected light L2 reflected by the optical measurement unit 320a is described as an example.
- the slide body 32 is configured to be transparent, the base member 310, the measurement sample S, and the slide Colorimetric measurement may be performed by receiving the transmitted light of the measurement light L1 that has passed through the body 32.
- FIG. 7 is a cross-sectional view showing the configuration of the detection device 4 of this modification.
- a support portion 440 is provided on the resist layer 12 of the base member 10 instead of the support portion 40.
- a slide member 430 is engaged with the support portion 440 in place of the slide member 30.
- the support portion 440 is provided only on one side of the slide member 430.
- the support portion 440 supports the slide member 430 so as to be slidable by step portions 442 and 443 formed in a claw shape and a guide portion 444 formed extending in the depth direction of the paper surface in FIG.
- the slide member 430 does not come off the support portion 440 when the slide member 430 slides on the base member 10 from the sample supply position P1 to the overlapping position P2. For this reason, the sample can be moved from the sample supply position P1 to the overlapping position P2 as in the above-described embodiment.
- the shape for engaging the support portion and the slide member is not limited to the claw shape as described above.
- an edge portion 531a provided in place of the slide member 30 and extending in the slide movement direction.
- the pair of support members 541 may have inclined portions 541a and 541b formed to be inclined at an angle equal to the inclination angle of the edge portion.
- the support portion 540 supports the slide member 530 so as to be slidable with respect to the base member 10. be able to. Further, since the inclined portions 541a and 541b are inclined so that the surface faces the base member 10, the edges 531a and 531b contacting the inclined portions 541a and 541b are prevented from floating in the thickness direction of the base member 10. be able to.
- FIG. 9 is a front view showing a partial configuration of the detection device of the present modification.
- the detection device 6 has an electrode system 620 instead of the electrode system 20.
- the electrode system 620 does not include the counter electrode 21, the wiring portion 22, and the contact electrode 23, but includes the counter / reference electrode 621, the wiring portion 622, and the contact electrode 623 that have both the function of the counter electrode 21 and the function of the reference electrode 27. Have.
- the counter electrode / reference electrode 621 is a silver-silver chloride electrode, that is, the counter electrode and the reference electrode are constituted by one silver-silver chloride electrode. Even with such a configuration, an electrochemical measurement can be performed on a sample in the same manner as the detection devices 1 and 2 described in the first and second embodiments.
- FIG. 10A to 10C are diagrams showing the detection device 7, FIG. 10A is a perspective view showing a part of the configuration of the detection device 7, FIG. 10B is a cross-sectional view showing a part of the configuration of the detection device 7, and FIG. 4 is a perspective view showing a configuration of part of the device 7.
- FIG. 11A and 11B are operation explanatory diagrams for explaining the operation when the detection device 7 is used.
- 12A and 12B are operation explanatory diagrams for explaining the operation when the detection device 7 is used.
- the detection device 7 includes a base member 710 made of an insulating material, a slide member 730 that slides relative to the base member 710 on the surface of the base member 710, and a second embodiment.
- the support portion 740 is configured to support the slide member 730 so as to be slidable relative to the base member 710.
- the base member 710 has the electrode system 20 described in the first embodiment.
- the base member 710 can be formed of the same material as the base member 10 described in the first embodiment, and the base member 710 further includes a resist layer 12.
- a stopper portion 713 that abuts on the slide member 730 and restricts the amount of slide movement of the slide member 730 includes a counter electrode 21, a working electrode 24, a reference electrode 27, and contact electrodes 23, 26, 29.
- a sample supply position P701 for supplying a sample is set on the side opposite to the contact electrodes 23, 26, and 29 with the support portion 740 interposed therebetween.
- the sample supply position P701 is provided at a position protruding outward in the surface direction of the base member 710.
- a protrusion 714 protruding from the surface of the base member 710 is formed on the surface of the base member 710 opposite to the side where the electrode system 20 is located.
- the slide member 730 includes a sample storage portion 734 formed in the same manner as the sample storage portion 234 of the slide member 230 of the second embodiment, and a flow stop portion 235 of the slide member 230 of the second embodiment.
- a flow stop portion 735 formed in the same manner as described above, a contact portion 736 that contacts the stopper portion 713, and a grip portion 738 for gripping the slide member 730 when the slide member 730 is slid on the base member 710.
- the pretreatment reagent 13 described in the above embodiments can be fixed to the sample storage unit 734.
- the pretreatment reagent 13 may be disposed at the sample supply position P701.
- FIGS. 11A to 12B First, a schematic configuration of an inspection apparatus for performing electrochemical measurement of a sample by sliding the slide member 730 with respect to the base member 710 in the detection device 7 of the present embodiment will be described.
- the inspection apparatus 101 contacts the mounting table 110 on which the base member 710 of the detection device 7 is mounted and the contact electrodes 23, 26, and 29 of the base member 710 mounted on the mounting table 110.
- the mounting table 110 includes a mounting surface 111 that comes into contact with the base member 710 and a groove portion 112 into which the protruding portion 714 of the base member 710 fits.
- the groove portion 112 is formed to extend so as to hold a push rod 144 described later so as to be able to advance and retract.
- the contact part 120 is electrically connected to a detection circuit (not shown) that transmits and receives electrical signals via the contact electrodes 23, 26, and 29 of the base member 710.
- the connecting portion 130 is fixed to the frame of the inspection device 101 and has a clamp portion 131 that sandwiches the grip portion 738 of the slide member 730 in the plate thickness direction.
- the advancing / retracting drive unit 140 is connected to the motor 141 that is rotationally driven, the crank unit 142 that is connected to the motor 141 and converts the rotational force of the motor 141 into a swinging motion around the fulcrum O, and the swinging motion of the crank unit 142. It has a link part 143 that converts it into a forward / backward movement in the surface direction of the mounting surface 111, and a push rod 144 that is connected to the link part 143 and moves forward / backward along the groove part 112.
- the motor 141 for example, a stepping motor that rotates by positioning control in synchronization with a pulse signal can be employed.
- the detection device 7 is prepared in a state where the slide member 730 is combined with the base member 710.
- the user attaches the detection device 7 to the inspection apparatus 101 so that the contact electrodes 23, 26, and 29 of the base member 710 are in contact with the contact part 120, and fixes the gripping part 738 of the slide member 730 to the clamp part 131 of the connecting part 130. To do.
- the protrusion 714 formed on the base member 710 is fitted into the groove 112 so that the protrusion 714 is guided by the groove 112, and the base member 710 extends in the direction in which the groove 112 extends with respect to the mounting table 110. Relative movement is possible.
- the slide member 730 is inserted into the support portion 740, and is positioned and attached to the support portion 740 so that the sample storage portion 734 is positioned at the sample supply position P701.
- the user supplies the whole blood sample CS to the sample storage unit 734 at the sample supply position P701.
- the whole blood sample CS stored in the sample storage unit 734 is blocked by the flow stopping unit 735, it does not contact the counter electrode 21, the working electrode 24, and the reference electrode 27 of the electrode system 20.
- a pretreatment reaction is performed on the whole blood sample CS by the pretreatment reagent 13 fixed at the sample supply position 734, and the measurement sample S is obtained as in the first embodiment.
- the motor 141 provided in the advance / retreat drive unit 140 of the inspection device 101 rotates.
- the push rod 144 moves linearly via the crank part 142 and the link part 143, and presses and moves the protruding part 714 of the base member 710.
- the slide member 730 fixed to the inspection apparatus 101 and the base member 710 pressed by the push rod 144 move relative to each other, and the sample storage portion 734 located at the sample supply position P701 is the counter electrode 21 of the electrode system 20,
- the working electrode 24 and the reference electrode 27 move to the overlapping position P2.
- the stopper portion 713 provided on the base member 710 contacts the contact portion 736 of the slide member 730 and further slide movement is restricted.
- the amperometry method current measurement method
- the coulometry method described in the first embodiment
- Electrochemical measurement such as coulometric measurement method), potential sweep method and cyclic voltammetry method is performed.
- the stopper portion 713 is provided on the base member 710, when the slide member 730 is slid on the base member 710, the sample storage portion 734 can be reliably moved to the overlapping position P2.
- FIG. 13 is a plan view showing the detection device 8.
- 14A and 14B are operation explanatory diagrams for explaining the operation when the detection device 8 is used.
- the detection device 8 includes the base member 810 provided in place of the base member 710 and the slide member 830 provided in place of the slide member 730 in the fourth embodiment described above. The configuration is different from that of the detection device 7 in the form.
- the base member 810 is not provided with members corresponding to the stopper portion 713 and the protruding portion 714. Further, the base member 810 has the resist layer 12 described in the first embodiment.
- the base member 810 has a wall portion 814 located between the counter electrode 21, the working electrode 24, and the reference electrode 27 of the electrode system 20 and the contact electrodes 23, 26, and 29.
- the wall portion 814 may be formed by the outer surface of the support portion 740.
- the slide member 830 has a concave portion 838 formed at a position facing the wall portion 814 instead of the grip portion 738 formed on the slide member 730 described above.
- the shape of the recess 838 is not particularly limited, but the recess 838 of the present embodiment is formed with an arcuate contour.
- FIGS. 14A and 14B The operation when the detection device 8 of the present embodiment having the above-described configuration is used will be described with reference to FIGS. 14A and 14B.
- an inspection instrument that performs electrochemical measurement using the detection device 8 extends in the thickness direction of the base member 810 and the slide member 830, and the base member 810 and the slide member 830 A pin 102 formed with a reduced diameter on the near side is provided.
- the pin 102 is attached to the inspection device so that the pin 102 can be advanced and retracted by a drive mechanism (not shown) provided in the inspection device.
- the slide member 830 is inserted into the support portion 840, and the position of the sample storage portion 734 formed on the slide member 830 is aligned with the position of the sample supply position P701.
- the user attaches the detection device 8 to the inspection equipment.
- the contact electrodes 23, 26, and 29 of the base member 810 are fixed and electrically connected to a detection circuit (not shown).
- the user supplies the whole blood sample CS to the sample storage unit 734 of the detection device 8.
- the wall portion 814 of the base member 810 and the slide member 830 are in contact with each other, and a gap is formed in the recess 838.
- the pin 102 is inserted into the gap formed by the recess 838 between the wall 814 of the base member 810 and the slide member 830.
- the pin 102 is linearly moved by the above-described driving mechanism provided in the inspection device, whereby the gap between the wall portion 814 and the concave portion 838 is expanded.
- the base member 810 and the slide member 830 move relative to each other by the gap between the wall portion 814 and the recess 838 being pushed wide, and the sample storage portion 734 located at the sample supply position P701 is overlapped. Move to P2.
- the detection device 8 of the present embodiment also simply slides the slide member 830 relative to the base member 810 after performing the pretreatment reaction at the sample supply position P701.
- the sample reaches the superposition position P2, and a reaction for electrochemical measurement can be performed. For this reason, multi-stage processing can be performed safely with a simple configuration that does not have a complicated flow channel structure.
- FIG. 15A and 15B show the detection device 9, FIG. 15A is a plan view, and FIG. 15B is a side view.
- FIG. 16A and FIG. 16B are operation explanatory diagrams for explaining the operation when the detection device 9 is used.
- the detection device 9 is different in configuration from the detection device 8 of the fifth embodiment in that a slide member 930 is provided instead of the slide member 830.
- the slide member 930 does not have the concave portion 838 of the slide member 830 described in the fifth embodiment, but has a protruding portion 938 extending in the thickness direction of the slide member 930. As shown in FIG. 15B, the protrusion 938 is provided to extend to the opposite side of the base member 810 with the slide member 930 attached to the base member 810.
- the inspection device 101A has an advance / retreat drive unit 150 provided in place of the connecting portion 130 and the advance / retreat drive unit 140, and the contact point 120 is fixed to the frame of the inspection device 101A.
- the configuration is different from the inspection device 101 described in the fourth embodiment.
- the advance / retreat drive unit 150 includes a swinging portion 151 that swings around the fulcrum O2. Engaging wall portions 152 and 153 are formed on the swinging portion 151 so as to engage with the protruding portion 938 when the detection device 9 is set on the inspection apparatus 101A.
- the detection device 9 is prepared in a state where the slide member 930 is combined with the base member 810, and the contact electrodes 23, 26, and 29 of the base member 810 are attached to the contact portion 120. At this time, the protruding portion 938 of the slide member 930 is engaged with the engaging wall portion 152 of the swinging portion 151.
- the slide member 930 is inserted into the support portion 740, and is positioned and attached to the support portion 740 so that the sample storage portion 734 is positioned at the sample supply position P701.
- the user supplies the whole blood sample CS to the sample storage unit 734 at the sample supply position P701.
- the whole blood sample CS stored in the sample storage unit 734 is blocked by the flow stopping unit 735, it does not contact the counter electrode 21, the working electrode 24, and the reference electrode 27 of the electrode system 20.
- a pretreatment reaction is performed on the whole blood sample CS by the pretreatment reagent 13 fixed at the sample supply position 734, and the measurement sample S is obtained as in the first embodiment.
- the swinging part 151 rotates around the fulcrum O2.
- the protrusion 938 of the slide member 930 attached to the inspection device 101A is pushed up.
- the swinging portion 151 moves so that the engaging wall portion 153 closer to the contact portion 120 is separated from the slide member 930.
- the protrusion 938 slides on the surface of the swinging portion 151 by the elasticity of the slide member 930 and contacts the engaging wall portion 153.
- the slide member 930 and the base member 810 move relative to each other, and the sample storage portion 734 located at the sample supply position P701 moves to the overlapping position P2 where the counter electrode 21, the working electrode 24, and the reference electrode 27 of the electrode system 20 are located. And move.
- the present invention is not limited to this, and the surface of the mounting surface 111 of the mounting table 110 by the engaging wall portion 152 of the swinging portion 151.
- a configuration may be adopted in which the protrusion 938 is translated along the axis.
- the inspection device can be provided with a configuration for relatively moving the base member and the slide member of the detection device.
- the base member may be fixed to the inspection device and the slide member may be slid relative to the base member.
- the slide member may be fixed to the inspection device and the base member may be slid relative to the slide member. good.
- the timing and amount of relative movement between the base member and the slide member can be made constant, the reproducibility of the measurement using the detection device can be improved.
- FIG. 17 is a plan view showing the detection device 1001 of the present embodiment.
- FIG. 18 is a cross-sectional view showing the configuration of the detection device 1001.
- FIG. 19 is an operation explanatory diagram for describing an operation when the detection device 1001 is used.
- the detection device 1001 of this embodiment is a pair of conduction detection electrodes 1050 on the sample supply position P701 with respect to the detection device 8 (see FIG. 14A) described in the fifth embodiment.
- the electrode system 620 described in the modification 3 is provided on the base member 1010 provided in place of the base member 810 in place of the electrode system 20 of the fifth embodiment. ing.
- the slide member 830 does not need to be provided with the recess 838.
- the base member 1010 has a base material 1011 and a resist layer 12 made of the same material as the base member 10.
- the base member 1010 is different in shape from the above-described base member 810 in that it does not have the wall portion 814, and is formed in a substantially rectangular plate shape.
- the continuity detection electrode 1050 includes a first electrode 1051 and a second electrode 1054 that are spaced apart from each other on the sample supply position P701, and a wiring 1052 and a wiring 1055 connected to the first electrode 1051 and the second electrode 1054, respectively.
- the contact electrode 1053 and the contact electrode 1056 are connected to the wiring 1052 and the wiring 1055 and spaced apart from each other so as to sandwich the contact electrode 26 and the contact electrode 623 therebetween.
- the first electrode 1051 and the second electrode 1054 of the conduction detecting electrode 1050 are not covered with the resist layer 12 and are exposed to the outside.
- the surfaces of the first electrode 1051 and the second electrode 1054 of the continuity detection electrode 1050 have hydrophilicity, and the pretreatment reagent 13 is fixed thereto.
- the pretreatment reagent 13 is fixed to both the conduction detection electrode 1050 and the sample storage unit 734, and the whole blood sample CS is supplied to the whole blood sample CS when the whole blood sample CS is supplied to the sample supply position P701. It can be quickly dissolved in the sample CS.
- the wiring 1052 and the wiring 1055 are covered with the resist layer 12 and insulated.
- the contact electrode 623 is divided into a contact electrode 623A and a contact electrode 623B in order to detect that the detection device 1001 has been correctly inserted into the inspection apparatus.
- the inspection device can detect that the detection device 1001 has been inserted and can perform a predetermined operation when the detection device 1001 is inserted.
- the predetermined operation for example, when the detection device 1001 is inserted, the power is automatically turned on, the display is turned on, the continuity detection monitoring state is started, or the device is kept warm. An operation such as starting can be given.
- the detection device 1001 can be used by being attached to an inspection apparatus having a detection circuit electrically connected to each of the contact electrodes 26, 623, 1053, and 1056.
- the detection device 1001 When the detection device 1001 is used, the detection device 1001 is connected to the inspection device described above. At this time, the sample storage portion 734 of the slide member 830 of the detection device 1001 is disposed on the sample supply position P701.
- the user of the detection device 1001 slightly bleeds from the fingertip or the like to bring a part of the periphery of the sample supply position P701 into contact with the bleeding site.
- the user's blood is sucked by capillary action between the base member 1010 and the slide member 830 at the sample supply position P ⁇ b> 701 and stored in the sample storage portion 734.
- the blood stored between the base member 1010 and the slide member 830 becomes the whole blood sample CS.
- the whole blood sample CS stored in the sample storage unit 734 is blocked by the flow stopping unit 735 and does not contact the counter / reference electrode 621 and the working electrode 24 of the electrode system 620.
- the whole blood sample CS stored in the sample storage unit 734 dissolves the first electrode 1051, the second electrode 1054, and the pretreatment reagent 13 fixed to the sample storage unit 734, so that The treatment reaction begins.
- the whole blood sample CS contacts both the first electrode 1051 and the second electrode 1054 at the sample supply position P701, the first electrode 1051 and the second electrode 1054 are in a conductive state.
- the fact that the first electrode 1051 and the second electrode 1054 are in a conductive state can be detected as a current from the first electrode 1051 to the second electrode 1054, for example.
- the timing at which the pretreatment reaction starts can be detected by the testing device. Thereby, for example, an appropriate time for performing the pretreatment reaction is measured in the inspection device, the end of the pretreatment reaction is accurately detected, and the inspection device is notified of the timing for sliding the slide member 830. can do.
- the pretreatment reaction is completed, the whole blood sample CS becomes the measurement sample S.
- the slide member 830 When the pretreatment reaction is completed at the sample supply position P701, the slide member 830 is gripped by the inspection device, and the slide member 830 is pulled toward the contact electrodes 26 and 623. As a result, the measurement sample S moves to a position in contact with the counter / reference electrode 621 and the working electrode 24 of the electrode system 620. Then, the electrochemical measurement with respect to the measurement sample S is performed similarly to having demonstrated in each above-mentioned embodiment.
- the pair of continuity detection electrodes 1050 are provided, so that the inspection instrument can detect that the sample is supplied to the sample supply position P701.
- the pretreatment reagent 13 is fixed at the sample supply position P701, the timing at which the sample is supplied to the sample supply position P701 and the timing at which the dissolution of the pretreatment reagent 13 into the sample substantially coincides. For this reason, it is possible to cause the inspection device to detect the timing at which the pretreatment reaction using the pretreatment reagent 13 is started by the pair of conduction detection electrodes 1050.
- the positions of the first electrode 1051 and the second electrode 1054 can be arranged at appropriate positions in the sample supply position P701. Accordingly, for example, the first electrode 1051 and the second electrode 1054 can be electrically connected when a predetermined amount or more of the whole blood sample CS is sucked into the sample storage portion 734. In this case, it is possible to make the inspection device detect whether or not a necessary amount of the whole blood sample CS has been sucked into the sample storage unit 734.
- FIG. 20 is a plan view showing the detection device 1101 of this embodiment.
- FIG. 21 is an operation explanatory diagram for describing an operation when the detection device 1101 is used.
- the detection device 1101 of this embodiment has a contour shape substantially the same as that of the base member 1010 described in the seventh embodiment, in the direction from the sample supply position P701 toward the overlapping position P2.
- the configuration differs from the detection device 1001 described in the seventh embodiment in that it includes a base member 1110 having a long elongated hole 1115 and a slide member 1130 provided instead of the slide member 830. .
- the long hole 1115 formed in the base member 1110 is formed so as to penetrate in the thickness direction of the base member 1110 and is long in the sliding direction of the slide member 1130 relative to the base member 1110.
- the slide member 1130 is a plate member that is rectangular in a plan view and is inserted into the support portion 740 fixed on the surface of the base member 1110. As shown in FIG. A circular through hole 1138 penetrating the sample storage portion 734, the flow stopping portion 735, and the slide member 1130 in the thickness direction is formed.
- the through hole 1138 formed in the slide member 1130 overlaps with the elongated hole 1115 formed in the base member 1110 when viewed from the thickness direction of the slide member 1130 with the slide member 1130 supported by the support portion 740.
- a slide member 1130 is formed along the elongated hole 1115 using a protrusion or a rod (denoted by reference numeral 113 in FIG. 21) that can be inserted into the elongated hole 1115 and the through hole 1138 together. Can be slid. Thereby, the direction in which the slide member 1130 slides is restricted to the direction in which the elongated hole 1115 extends.
- the long hole 1115 formed in the base member 1110 functions as a guide when the slide member 1130 is slid relative to the base member 1110. Thereby, the slide member 1130 can be slid with respect to the base member 1110 with high accuracy.
- Example 1 a spacer having a thickness of 0.31 mm was attached to one side of a PET plate, and the sample accommodating portion having a gap spaced apart by 0.31 mm from the base member was configured as a slide member.
- the spacer is formed by sticking one side of a 0.11 mm thick double-sided adhesive tape to a PET film having a thickness of 0.2 mm, and pasting the other side of the double-sided adhesive tape on one side of a PET plate. Configured.
- 20 ⁇ l of a pseudoserum added with a pretreatment reagent was used.
- the sample container is hydrophobic and the base member is hydrophilic.
- the examination was performed by setting four conditions: a case where the sample storage portion is hydrophilic and the base member is hydrophobic, and a case where the sample storage portion and the base member are both hydrophobic.
- a method of applying agarose to the surface of the resist layer of the sample container or the base member was adopted as a hydrophilic treatment method for hydrophilizing the sample container or the base member.
- a method of hydrophobizing the sample container or base member to make it hydrophobic a method of exposing the PET without particularly treating the base material of the sample container or base member was adopted.
- both the sample container and the base member are hydrophilic, the sample can flow into the gap between the sample container and the base member, and then the slide member is moved relative to the base member. When sliding, the sample slid on the base member following the movement of the slide member.
- the sample storage portion is hydrophobic and the base member is hydrophilic
- the sample can be similarly introduced into the gap between the sample storage portion and the base member, and then the slide member is inserted into the base member.
- the sample was slid, the sample slid on the base member following the movement of the slide member.
- the sample can similarly flow into the gap between the sample storage portion and the base member, and then the slide member is moved to the base member.
- the sample was slid, the sample slid on the base member following the movement of the slide member.
- the sample container and the base member have hydrophobicity
- the sample could be accommodated between the sample container and the base member, but the sample was interposed between the sample container and the base member. In some cases, the sample was repelled when flowing in. In the state where the sample is stored in the sample storage portion, when the slide member is slid with respect to the base member, the sample slides on the base member following the movement of the slide member.
- the sample flows into the sample storage portion, and the sample slides on the base member. It was found preferable to
- Example 2 performed by changing the composition of the sample with respect to Example 1 will be described.
- 20 ⁇ l of human whole blood added with a pretreatment reagent was used as a sample.
- the result that the sample is caused to flow into the sample storage portion and the sample is slid on the base member is the same as that of the first example.
- Example 3 performed by changing the thickness of the spacer in the sample storage portion with respect to Example 1 will be described.
- the spacer was set to a thickness of 1.24 mm, which is four times that of Example 1 described above.
- the spacer is composed of a PET film having a thickness of 0.2 mm and four sets of one side of a double-sided adhesive tape having a thickness of 0.11 mm, which are laminated to form one of the PET plate materials. Pasted on the surface.
- 20 ⁇ l of a sample obtained by adding a pretreatment reagent to pseudoserum was used in the same manner as in Example 1.
- the same result as in Example 1 was obtained.
- the sample when the sample is not attached to the sample storage portion, the sample slides on the base member even if the slide member is slid on the base member. I did not. From these results, it was found that the thickness of the spacer is preferably set so that the sample can be attached to the sample storage portion in view of the amount of the sample used for measurement.
- Example 4 performed by changing the composition of the sample with respect to Example 3 will be described.
- 20 ⁇ l of human whole blood added with a pretreatment reagent was used as a sample.
- the same result as in Example 3 was obtained with respect to the behavior in which the sample was caused to flow into the sample container and the sample was slid on the base member.
- Example 5 an example of measuring human whole blood using the detection device 2 according to the second embodiment of the present invention will be described.
- a pretreatment reagent having the composition shown in Table 1 was fixed to the sample storage portion 234 of the slide member 230.
- the pH of the pretreatment reagent was 7.7.
- a method of fixing the pretreatment reagent to the sample storage unit 234 a method of applying 6 ⁇ l of the pretreatment reagent to the wall surface of the sample storage unit 234 and drying at 50 ° C. for 30 minutes was adopted.
- a measuring reagent having the composition shown in Table 2 was fixed to the electrode system 20 of the base member 10.
- a method for fixing the measurement reagent to the electrode system 20 a method of applying 2 ⁇ l of the measurement reagent to the electrode system 20 and drying at 50 ° C. for 5 minutes was adopted.
- human whole blood sample used in this example was composed of 4 cases of healthy human venous blood collected in a pre-encapsulated blood vessel pre-encapsulated with EDTA-2K (ethylene potassium tetraacetate) (specimens A, B, C, D) Used.
- EDTA-2K ethylene potassium tetraacetate
- the procedure for measuring the human whole blood sample in this example is shown below.
- the slide member 240 was set on the base member 210 so that the sample storage portion 234 was positioned at the sample supply position P1.
- 6 ⁇ l of human whole blood sample CS was supplied to the sample storage unit 234 using a micropipette.
- the human whole blood sample CS was allowed to stand at the sample supply position P1 for 5 minutes, and a pretreatment reaction was performed for 5 minutes with a pretreatment reagent fixed to the sample storage unit 234.
- the base member 210 is moved so that the sample container 234 moves from the sample supply position P1 to the superposition position P2.
- the slide member 240 was slid.
- the human whole blood sample CS became the measurement sample S by the pretreatment reaction, and the measurement sample S moved from the sample supply position 234 to the electrode system 20 by sliding the slide member 240 with respect to the base member 210.
- electrochemical measurement was performed using an amperometry method.
- a potential of 0 V was applied to the reference electrode 27, and a current value was detected after 5 seconds from the start of application.
- the concentration of 1,5-AG in the measurement sample S was calculated.
- the concentration of 1,5-AG was measured using an existing method.
- the procedure for the control experiment is as follows. First, plasma was separated from the above four human whole blood samples by centrifugation. For this plasma, Lana 1,5-AG Auto Liquid (manufactured by Nippon Kayaku Co., Ltd.) and Hitachi 7150 biochemical automatic analyzer are used, and the detection method described in the package insert of the device is used. The concentration of 1,5-AG was measured. Table 3 shows the electrochemical measurement results (Examples) of this example and the measurement results of the control experiment (Comparative Example).
- the electrochemical measurement using the detection device 2 of the present example has a high correlation with the measurement by the existing method.
- the detection device 2 in the present example It was found that the concentration measurement of 1,5-AG using a whole blood sample can be performed with the same accuracy as the existing method.
- pretreatment in the present invention also includes standing the sample at the position, heating or cooling the sample at the sample supply position, and irradiating the sample with electromagnetic waves or light at the sample supply position.
- Electrode system 20 In addition to conductive carbon, gold, platinum, palladium or silver, silver / silver chloride, nickel, copper, titanium, iridium, lead, tin oxide, platinum black or the like is used as a material for forming the electrode system 20. be able to.
- the electrode system 20 may be formed by various vapor deposition methods such as a vacuum method or an electroless method, a sputtering method, a foil attaching method, a plating method, or the like instead of the screen printing method.
- a metal thin film or the like is formed on another base material to form an electrode member, and the electrode member 20 is fixed on the substrate 11 by adhesion or the like.
- a system may be configured.
- the slide body 32 may have a concave portion formed on the surface facing the base member 10 instead of the through hole. Good.
- the pretreatment reagent 13 is fixed to the sample storage unit 34 .
- the present invention is not limited thereto, and the pretreatment reagent is fixed on the resist layer 12 at the sample supply position P1. It doesn't matter.
- the pretreatment reagent 13 is fixed to the sample supply position P1 or the sample container 34 by a method such as dipping or spin coating, or impregnated with the pretreatment reagent 13 and dried.
- the pretreatment reagent 13 may be fixed to the sample supply position P1 or the sample storage part 34 by a method such as adhering filter paper or arranging a carrier such as microbeads into which an active group has been introduced.
- the example in which the operation of sliding the slide members 30 and 230 with respect to the base member 10 is a manual operation by the user.
- the present invention is not limited thereto, and the base member 10 and the slide member are not limited thereto.
- a moving mechanism that holds the members 30 and 230 and slides the slide members 30 and 230 relative to the base member 10 may be provided integrally or separately from the above-described inspection device.
- the operation of sliding the slide member can be automated.
- the configuration for automating the operation of sliding the slide member is illustrated.
- the structure of the moving mechanism which slides a slide member is not restricted to these.
- a configuration for relatively moving the base member and the slide member a configuration using a rack and pinion, a configuration using a worm gear and a worm wheel, or the like may be employed.
- oxidoreductases examples include glucose oxidase, glucose dehydrogenase, lactate oxidase, cholesterol oxidase, cholesterol dehydrogenase, galactose oxidase, uricase, ascorbate oxidase, pyruvate oxidase, and lactate dehydrogenase.
- pretreatment reagent other reagents may be appropriately employed as long as they contain a reagent for removing, supplementing or converting ascorbic acid, uric acid and the like into another substance that does not affect the detection.
- pretreatment reagents include those that adsorb and supplement specific substances as ion adsorption, affinity adsorption, or boric acid complexes, or hormones, receptors, antigens and antibodies. In addition, those that can complement a specific substance such as RNA and DNA in a complementary manner are also included. Furthermore, these pretreatment reagents may be those obtained by immobilizing reagents on a carrier such as microbeads or microspheres.
- the surface of the guide portion described in each of the above embodiments may be made hydrophobic. In this case, it can suppress that a sample flows in between a support part and a slide member.
- the surface of the guide unit is made hydrophobic when the sample stored in the sample storage unit is in contact with the support unit. Thus, the amount of the sample used for the pretreatment reaction and the subsequent detection can be accurately maintained.
- the detection device of the present invention can be used together with an apparatus for performing a medical examination by analyzing a biological sample.
- the detection device of the present invention can be suitably used as a detection device for performing a test requiring a multistage reaction on a liquid biological sample such as blood.
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Abstract
Description
本願は、2010年3月3日に、日本に出願された特願2010-46813号に基づき優先権を主張し、その内容をここに援用する。
試料に対して多段階の処理を行うための検出デバイスとして、例えば特許文献1には血液中の糖タンパク質の濃度を検出するための2段階の反応を行うバイオセンサが記載されている。このバイオセンサは、毛細管現象によって試料を吸い上げる吸引空洞と、試料に対して酵素反応を行う分析空洞と、吸引空洞と分析空洞とを繋ぐ流路とを有しており、吸引空洞には前処理試薬が固定化されている。このバイオセンサでは、毛細管現象によって吸引空洞に試料が吸引されると吸引空洞において前処理が行われ、前処理が終了した試料が遠心力によって吸引空洞から分析空洞へ移動されることで酵素反応が行われる。
本発明の検出デバイスは、試料に対して検出を行うための検出デバイスであって、前記試料が供給される試料供給位置を面上に有するベース部材と、前記ベース部材の前記面上で前記試料供給位置と離間して形成された検出部と、前記ベース部材に対して前記面上で相対的にスライド移動するスライド体、及び前記スライド体の一部に設けられ前記試料を収容可能な試料収容部とを有するスライド部材と、前記ベース部材に固定され、前記ベース部材に対してスライド移動可能に前記スライド部材を支持する支持部と、を備え、前記ベース部材と前記スライド部材とは、前記試料収容部が前記検出部に重畳する重畳位置と前記試料供給位置とを含む範囲で前記スライド移動可能である、ことを特徴とする。
この場合、比色測定又は電気化学的測定を検出部に移動された試料に対して行うことができる。
この場合、試料供給位置から検出部へ試料が移動したときには、作用極、参照極及び対極のそれぞれに試料が接触して、試料に対して電気化学的測定を行うことができる。
この場合、試料収容部とベース部材とによって作られた空間において親水性を有する範囲に試料が広がることで、試料を容易に供給することができる。
この場合、二箇所に設けられた支持部のそれぞれがスライド部材を支持するので、スライド部材をベース部材上で安定して支持することができる。
この場合、互いに平行に設けられた案内部のそれぞれに沿ってスライド部材を自在にスライド移動させることができる。
この場合、被覆部によってスライド部材が覆われているので、スライド部材がベース部材に対して自在にスライド移動できるとともにスライド部材が支持部から脱落しにくい。
この場合、流動停止部において試料が電極系へ流れ込むことが抑制されているので、スライド部材をベース部材に対してスライド移動させて試料供給位置から検出部まで試料を移動させる前に試料が検出部に進入することを抑制できる。
この場合、孔部または凹部の縁部において試料の流動を停止させることができる。
この場合、ベース部材にスライド部材が組み合わせられたときに流動停止部によって試料をせき止めることで、試料の流動を流動停止部において停止させることができる。
この場合、試料収容部に収容された試料がスライド体へ流れ込むことが抑制されているので、試料収容部に一定量の試料を安定して収容することができる。
この場合、スライド体の一部を切り取ることで生じる段差部分において試料の流通を停止させることができる。
この場合、試料供給位置において試料収容部に試料が収容された状態では前処理試薬によって前処理が行われ、スライド部材をスライド移動させて試料供給位置から検出部へ試料を移動させた後に検出を行うことができる。
この場合、試料に対して再現性よく電気化学的測定を行うことができる。
この場合、試料が試料供給位置に供給された場合に、一対の導通検知電極が導通状態となることによって、試料が供給されたことを検知することができる。
この場合、導通検知電極と試料とが密着しやすい。
この場合、案内部とスライド部材との隙間に試料が入り込むのを防止することができる。
この場合、長穴と貫通孔とに挿通される棒などを用いた場合にスライド部材のスライド方向を長穴が延びる方向へガイドすることができる。
また、前記レドックスメディエータは、ルテニウム誘導体、オスミウム誘導体、フェリシアン誘導体、フェロセン誘導体、キノン誘導体、フェノチアジン誘導体、フェノキサジン誘導体、フェナジン誘導体、インドフェノール誘導体、ジフェニルアミン誘導体、フェノール誘導体のうち少なくとも1つを含むものでもよい。
また、前記酸化還元酵素は、ピラノースオキシダーゼ、L-ソルボースオキシダーゼ、1,5-アンヒドログルシトールデヒドロゲナーゼ、L-ソルボースデヒドロゲナーゼ、1,5-アンヒドログルシトール6リン酸デヒドロゲナーゼのうち少なくとも1つを含むものでもよい。
また、前記前処理試薬は、グルコースを除去、捕捉若しくは前記検出に影響しない別の物質に変換するための試薬を含むものでもよい。
これらの場合、1,5-AGの測定を好適に行うことができる1,5-AG測定用検出デバイスを構成することができる。
本発明の第1実施形態の検出デバイスについて、図1から図2を参照して説明する。本実施形態を含む以下の各実施形態における検出デバイスは、1,5-AGを測定するための1,5-AG測定用検出デバイスである。
図1Aは本実施形態の検出デバイス1を示す斜視図である。また、図1Bは、図1AのA-A線における断面図である。また、図1Cは図1AのB-B線における断面図である。
基板11は、一方の端部が検査機器に挿入される挿入部11Aとなっている。基板11を形成する絶縁性材料としては、絶縁性と必要な強度を有する素材であれば特に限定されず、例えば、プラスチックフィルム等を使用することができる。プラスチックフィルムは、高分子化合物を主成分としてフィルム上に成形したものであれば特に制限はないが、好ましい高分子化合物としては、例えば、ポリエチレンテレフタレート(PET)、ポリエチレンナフタレート(PEN)、ポリカーボネート(PC)、ポリアリレート、ポリエーテルサルフォン(PES)、ポリイミド、ポリアミド、ポリプロピレン(PP)、ポリエチレン(PE)、シクロオレフィンポリマー(COP)、ポリメチルメタクリレート(PMMA)、ポリジメチルシロキサン(PDMS)、トリアセチルセルロース(TAC)、ジアセチルセルロース(DAC)、ポリスチレン(PS)、ポリウレタン、ポリビニルアルコール(PVA)、エバール(エチレン-ビニルアルコール共重合体)、ポリ塩化ビニル(PVC)等が挙げられる。この他、基板11の材料としてガラス等を用いることもできるが、上述した材料のうち、PETは扱いが容易なので、基板11の材料として好ましい。
試料収容部34において、ベース部材10に向かう側の面34aは親水性を有する。試料収容部34を親水化する親水化処理は、表面改質処理としては例えばコロナ処理、プラズマ処理、UV/オゾン処理、あるいはフレーム処理などを挙げることができる。また、ポリビニルアルコール、ヒドロキシアルキルセルロース、あるいはアガロースなどの親水性化合物を試料収容部34の壁面に塗布する方法、及びイトロ処理によって試料収容部34の壁面に酸化ケイ素膜を成膜する方法などを挙げることもできる。
なお、上述のベース部材10のレジスト層12の外面を親水化する場合にも上述の親水化処理を適宜採用することができる。また、スライド体32をトリアセチルセルロースフィルムによって形成し、試料収容部34のベース部材10に向かう側の面34a部分の表層を、アルカリ処理を行うことにより親水化して使うこともできる。
スペーサー31a、31bにおいてスライド体32に固定された面と反対側の面はベース部材10に接触するようになっている。試料収容部34とベース部材10とは、スペーサー31a、31bの厚みの分だけ離間している。したがって、試料収容部34とベース部材10との間でスペーサー31a、31bによって作られる隙間の大きさは、スペーサー31a、31bの厚さを変えることで異なる大きさに設定して構成することができる。本実施形態では、試料収容部34とベース部材10とによって作られる空間に一定量の試料が収容されるようになっている。
なお、スペーサー31a、31bは、スライド体32と一体成形されていてもよい。例えば、スペーサ31aとスペーサ31bとの間に溝部が形成されるように射出成形などによってスライド体32を形成することができる。この場合、スペーサー31a、31bがスライド体32と別体である場合と比較して、精度良く試料を収容できるスライド部材30を容易に形成することができる。また、スペーサー31a、31bをスライド体32と一体成形する場合に、スライド部材30を量産するときの製造コストを低減することもできる。
また、スペーサー31a、31bをスライド体32と一体成形する別の方法としては、スライド体32に孔を開けたり、スライド体32を切削して溝を形成するなどして試料を収容するための隙間を設けることもできる。
案内部41は、ベース部材10の板厚方向に厚さを有するプラスチックフィルムが例えば両面粘着テープによって貼り合わせられている。例えば、案内部41はプラスチックフィルムと両面粘着テープが交互に積層されることでスライド部材30の板厚よりも厚く形成されている。また、一対の案内部41において対向する部分には、ベース部材10の面に沿う方向に平行に延びる案内面41a、41bが形成されている。
案内部41及びカバー部材42によって形成された空洞部分には、スライド部材30が挿入されている。このため、スライド部材30は案内面41a、41bが延びる方向に案内され、スライド部材30はベース部材10に対して相対的に自在にスライド移動するようになっている。
このように、本実施形態では、貫通孔33における試料収容部34側の縁部が、試料の流動を停止させる流動停止部になっている。
検出デバイス1は、試料供給位置P1に試料収容部34が位置している状態で用意される。ユーザは、検出デバイス1の挿入部11Aを検査機器に挿入することによって、検出デバイス1を検査機器にセットする。
続いて、図2Aに示すように、ユーザは指先等から採取した全血試料(試料)CSを試料供給位置P1に滴下し、ベース部材10のレジスト層12と試料収容部34との間の隙間に注入する。すると、試料供給位置P1に固定配置された前処理試薬13によって全血試料CS中のグルコースの分解又は変換等の反応が始まる。
さらに、試料収容部34における親水性を有する面に試料が付着しつつ試料がスライド移動されるので、スライド部材30をスライド移動させるときに試料が試料収容部34からはみ出しにくい。
次に、本発明の第2実施形態の検出デバイスについて図3Aないし図4Bを参照して説明する。なお、上述した第1実施形態の検出デバイス1と同様の構成要素には同一符号を付すとともに重複する説明を省略する。
本実施形態の検出デバイス2と上述の検出デバイス1との異なるところは、ベース部材10上に配置されたスライド部材30及び支持部40の形状である。
把持部238は、ストッパ部236がベース部材10の縁に当接している位置関係にあるときに、ベース部材10の縁から外方へ突出して延びて設けられている。
検出デバイス2は、試料供給位置P201に試料収容部234が位置している状態で用意される。この状態で、ユーザは、検出デバイス2の挿入部11Aを検査機器に挿入してセットする。
次に、本発明の第3実施形態の検出デバイスについて図5A及び図5Bを参照して説明する。なお、上述した各実施形態の検出デバイスと同様の構成要素には同一符号を付すとともに重複する説明を省略する。
以下では、上述の第3実施形態の検出デバイス3の変形例について説明する。
図6A及び図6Bは、本変形例の検出デバイスを示す断面図である。本変形例の検出デバイス3は、光学測定部320に代えて光学測定部320aを有している。
ベース部材310は、光学測定部320aが位置する部分において透明(略透明を含む)に構成されている。
このような構成であっても上述の第3実施形態と同様に試料に対して比色測定を行うことができる。
(変形例2)
図7は、本変形例の検出デバイス4の構成を示す断面図である。
本変形例では、ベース部材10のレジスト層12上には、支持部40に代えて支持部440が設けられている。また、支持部440には、スライド部材30に代えてスライド部材430が係合して設けられている。
以下では、電極系20の構成の変形例について説明する。
図9は、本変形例の検出デバイスの一部の構成を示す正面図である。図9に示すように、検出デバイス6は、電極系20に代えて電極系620を有している。
電極系620は、対極21、配線部22及び接点電極23を有しておらず、対極21の機能と参照極27の機能をあわせて有する対極/参照極621、配線部622及び接点電極623を有している。
以下では、本発明の第4実施形態の検出デバイス7について図10Aないし図12Bを参照して説明する。
図10Aないし図10Cは検出デバイス7を示す図で、図10Aは検出デバイス7の一部の構成を示す斜視図、図10Bは検出デバイス7の一部の構成を示す断面図、図10Cは検出デバイス7の一部の構成を示す斜視図である。また、図11A及び図11Bは検出デバイス7の使用時の動作を説明するための動作説明図である。また、図12A及び図12Bは、検出デバイス7の使用時の動作を説明するための動作説明図である。
レジスト層12の面上には、スライド部材730と当接してスライド部材730のスライド移動量を規制するストッパ部713が、対極21、作用極24、及び参照極27と、接点電極23、26、29との間に設けられている。
また、支持部740を挟んで接点電極23、26、29と反対側には、試料を供給するための試料供給位置P701が設定されている。本実施形態では、試料供給位置P701は、ベース部材710の面方向に外方へ突出した位置に設けられている。
試料収容部734には、上述の各実施形態で説明した前処理試薬13を固定することができる。なお、前処理試薬13は試料供給位置P701に配置されていてもよい。
まず、本実施形態の検出デバイス7においてベース部材710に対してスライド部材730をスライドさせて試料の電気化学的測定を行うための検査機器の概略構成について説明する。
連結部130は、検査機器101のフレームに固定されており、スライド部材730の把持部738を板厚方向に挟み込むクランプ部131を有している。
モーター141としては、例えばパルス信号に同期して位置決め制御されて回転動作するステッピングモータなどを採用することができる。
検出デバイス7は、図11Aに示すように、ベース部材710にスライド部材730が組み合わされた状態で用意される。ユーザは、ベース部材710の接点電極23、26、29が接点部120に接触するように検出デバイス7を検査機器101に取り付け、スライド部材730の把持部738を連結部130のクランプ部131に固定する。
また、図11Bに示すように、スライド部材730は支持部740に挿通され、試料収容部734が試料供給位置P701に位置するように位置決めされて支持部740に取り付けられている。
試料供給位置734に固定された前処理試薬13によって、全血試料CSに対する前処理反応が行われ、上述の第1実施形態と同様に測定試料Sとなる。
以下では、本発明の第5実施形態の検出デバイス8について図13、図14A、及び図14Bを参照して説明する。
図13は、検出デバイス8を示す平面図である。また、図14A及び図14Bは、検出デバイス8の使用時の動作を説明する動作説明図である。
図13に示すように、検出デバイス8は、ベース部材710に代えて設けられたベース部材810と、スライド部材730に代えて設けられたスライド部材830とを備えている点で上述の第4実施形態の検出デバイス7と構成が異なっている。
また、ベース部材810は、電極系20の対極21、作用極24及び参照極27と接点電極23、26、29との間に位置する壁部814を有している。なお、壁部814は支持部740の外面によって形成されていてもよい。
図14Aに示すように、本実施形態では、検出デバイス8を用いて電気化学的測定を行う検査機器は、ベース部材810及びスライド部材830の厚さ方向に延び、ベース部材810及びスライド部材830に近い側が縮径されて形成されたピン102を備えている。
ピン102は、検査機器に設けられた図示しない駆動機構によって進退駆動できるように検査機器に取り付けられている。
以下では、本発明の第6実施形態の検出デバイス9について図15Aないし図16Bを参照して説明する。
図15Aおよび図15Bは、検出デバイス9を示す図で、図15Aは平面図、図15Bは側面図である。また、図16A及び図16Bは検出デバイス9の使用時の動作を説明するための動作説明図である。
図15Bに示すように、突起部938は、ベース部材810にスライド部材930が取り付けられた状態で、ベース部材810の反対側へと延びて設けられている。
図16Aに示すように、検査機器101Aは、連結部130及び進退駆動部140に代えて設けられた進退駆動部150を有し、また接点部120は検査機器101Aのフレームに固定されている点で、上述の第4実施形態で説明した検査機器101と構成が異なっている。
検出デバイス9は、図16Aに示すように、ベース部材810にスライド部材930が組み合わされた状態で用意され、ベース部材810の接点電極23、26、29は接点部120に取り付けられる。このとき、スライド部材930の突起部938は揺動部151の係合壁部152に係合している。
試料供給位置734に固定された前処理試薬13によって、全血試料CSに対する前処理反応が行われ、上述の第1実施形態と同様に測定試料Sとなる。
次に、本発明の第7実施形態の検出デバイスについて図17ないし図19を参照して説明する。なお、上述した各実施形態の検出デバイスと同様の構成要素には同一符号を付すとともに重複する説明を省略する。
図17は、本実施形態の検出デバイス1001を示す平面図である。図18は、検出デバイス1001の構成を示す断面図である。図19は、検出デバイス1001の使用時の動作を説明するための動作説明図である。
また、配線1052および配線1055は、レジスト層12に覆われており、絶縁されている。
本実施形態では、接点電極623は、検出デバイス1001が検査機器に正しく挿入されたことを検知するために接点電極623Aと接点電極623Bとに別れている。これにより、検査機器は、検出デバイス1001が挿入されたことを検知して、検出デバイス1001が挿入されたときに所定の動作をすることができる。所定の動作の具体的な例としては、たとえば、検出デバイス1001が挿入されたときに自動的に電源が入ったり、ディスプレイを点灯させたり、導通検知の監視状態を開始させたり、デバイスの保温を開始させたりする等の動作を挙げることができる。
その後、上述の各実施形態で説明したのと同様に測定試料Sに対する電気化学的測定が行われる。
次に、本発明の第8実施形態の検出デバイスについて図20および図21を参照して説明する。なお、上述した各実施形態の検出デバイスと同様の構成要素には同一符号を付すとともに重複する説明を省略する。図20は、本実施形態の検出デバイス1101を示す平面図である。図21は、検出デバイス1101の使用時の動作を説明するための動作説明図である。
(実施例1)
本実施例では、PET製の板材の一方の側に、厚さ0.31mmのスペーサーを貼り付けて、ベース部材から0.31mmだけ離間した隙間を有する試料収容部をスライド部材に構成した。スペーサーは、厚さ0.2mmのPET製フィルムに厚さ0.11mmの両面粘着テープの一方の面を貼り合わせ、両面粘着テープの他方の面をPET製の板材の一方の面に貼り付けて構成した。
試料としては、擬似血清に対して前処理試薬を添加したものを20μl使用した。
本実施例では、試料収容部あるいはベース部材を親水化する親水化処理の方法として、試料収容部あるいはベース部材のレジスト層の表面にアガロースを塗布する方法を採用した。また、試料収容部あるいはベース部材を疎水性にする疎水化処理の方法として、試料収容部あるいはベース部材の基材に対して特に表面処理をせず、PETを露出させる方法を採用した。
次に、実施例1に対して試料の組成を変えて行った実施例2を示す。
本実施例では、試料としてはヒト全血に前処理試薬を添加したものを20μl使用した。本実施例では試料を試料収容部に流入させ、ベース部材上で試料をスライド移動させる挙動については実施例1と同様であるとの結果が得られた。
次に、実施例1に対して試料収容部におけるスペーサーの厚さを変えて行った実施例3を示す。
本実施例では、スペーサーの厚さは上述の実施例1の4倍である厚さ1.24mmに設定して構成した。スペーサーの構成は、厚さ0.2mmのPET製フィルムに厚さ0.11mmの両面粘着テープの一方の面を貼り合わせたものを4組作成し、これらを積層してPET製の板材の一方の面に貼り付けた。
また、試料としては、実施例1と同様に擬似血清に対して前処理試薬を添加したものを20μl使用した。
次に、実施例3に対して試料の組成を変えて行った実施例4を示す。
本実施例では、試料としてはヒト全血に前処理試薬を添加したものを20μl使用した。本実施例では試料を試料収容部に流入させ、ベース部材上で試料をスライド移動させる挙動については実施例3と同様の結果が得られた。
以下では、本発明の第2実施形態の検出デバイス2を用いてヒト全血の測定を行う例を示す。
本実施例では、スライド部材230の試料収容部234に、表1に示す組成の前処理試薬を固定した。前処理試薬のpHは7.7とした。前処理試薬を試料収容部234に固定する方法としては、前処理試薬6μlを試料収容部234の壁面に塗布し、50℃で30分間乾燥させる方法を採用した。
まず、試料収容部234は試料供給位置P1に位置するようにベース部材210にスライド部材240をセットした。続いて、マイクロピペッターを用いてヒト全血試料CSを試料収容部234に6μlだけ供給した。ヒト全血試料CSは試料供給位置P1に5分間静置し、試料収容部234に固定された前処理試薬によって前処理反応を5分間行った。
対照実験の手順は、以下の通りである。まず、上記ヒト全血試料4例に対して、遠心分離法によって血漿を分離した。この血漿に対して、ラナ1,5-AGオートリキッド(日本化薬株式会社製)と日立7150型生化学自動分析装置を用い、装置の添付文書に記載された検出方法を用いて血漿中の1,5-AGの濃度を測定した。
本実施例の電気化学的測定結果(実施例)及び対照実験(比較例)の測定結果を表3に示す。
また、前処理試薬としては、アスコルビン酸、尿酸などを除去、補足もしくは前記検出に影響しない別の物質に変換するための試薬を含むものであれば他の試薬を適宜採用しても良い。
10、310、710、810、1010、1110 ベース部材
20、620 電極系(検出部)
21 対極
24 作用極
27 参照極
30、230、330、430、530、730、830、930、1130 スライド部材
32、232 スライド体
32a、32b 切欠(流通抑制部)
33 貫通孔(流動停止部)
34、234、734 試料収容部
40、240、440、540、740 支持部
41、241、444 案内部
42 カバー部材(被覆部)
235、333、735 流動停止部
320、320a 光学測定部(検出部)
1050 導通検知電極
1115 長穴
1138 貫通孔
P1、P201、P701 試料供給位置
P2 重畳位置
CS 全血試料(試料)
S 測定試料
Claims (22)
- 試料に対して検出を行うための検出デバイスであって、
前記試料が供給される試料供給位置を面上に有するベース部材と、
前記ベース部材の前記面上で前記試料供給位置と離間して形成された検出部と、
前記ベース部材に対して前記面上で相対的にスライド移動するスライド体、及び前記スライド体の一部に設けられ前記試料を収容可能な試料収容部を有するスライド部材と、
前記ベース部材に固定され、前記ベース部材に対して前記スライド移動可能に前記スライド部材を支持する支持部と、
を備え、
前記ベース部材と前記スライド部材とは、前記試料収容部が前記検出部に重畳する重畳位置と前記試料供給位置とを含む範囲で前記スライド移動可能である、
ことを特徴とする検出デバイス。 - 前記検出部は、比色測定、又は電気化学的測定可能に形成されていることを特徴とする請求項1に記載の検出デバイス。
- 前記ベース部材は絶縁性を有し、
前記検出部は、前記ベース部材の前記面上で前記試料供給位置と離間して形成された作用極、参照極及び対極を含む電極系を有する、
ことを特徴とする請求項1に記載の検出デバイス。 - 前記試料収容部と前記ベース部材とにおいて対向する部分の少なくとも一方は、少なくとも一部が親水性を有して構成されていることを特徴とする請求項1から3のいずれか一項に記載の検出デバイス。
- 前記支持部は、前記ベース部材上で前記重畳位置が間に位置するように離間する二箇所に設けられていることを特徴とする請求項1から3のいずれか一項に記載の検出デバイス。
- 前記支持部は、前記ベース部材上で前記重畳位置が間に位置するように離間するとともに互いに平行に設けられた案内部を有することを特徴とする請求項1から3のいずれか一項に記載の検出デバイス。
- 前記支持部は、前記ベース部材との間に前記スライド部材が進退可能な隙間を生じさせて前記重畳位置を被覆する被覆部を有することを特徴とする請求項1から3のいずれか一項に記載の検出デバイス。
- 前記スライド部材は、前記スライド体の一部に、前記試料収容部から前記電極系への前記試料の流れを停止させる流動停止部を有し、
前記流動停止部は、前記試料収容部が前記試料供給位置にあるときに前記重畳位置と前記試料供給位置との間に位置することを特徴とする請求項3に記載の検出デバイス。 - 前記流動停止部は、前記試料収容部が前記試料供給位置にあるときに、前記ベース部材における前記面の法線方向から見て自身の縁部の少なくとも一部が前記重畳位置と前記試料供給位置との間に位置する孔部又は凹部を有することを特徴とする請求項8に記載の検出デバイス。
- 前記流動停止部は、前記ベース部材に前記スライド部材を取り付けたときに前記スライド部材から前記ベース部材に向かう方向へ突出して前記スライド部材に形成されていることを特徴とする請求項8に記載の検出デバイス。
- 前記スライド部材は、前記スライド体と前記試料収容部との間に、前記試料収容部から前記スライド体への前記試料の流通を抑制する流通抑制部を有することを特徴とする請求項1から3のいずれか一項に記載の検出デバイス。
- 前記流通抑制部は、前記試料収容部に隣接した前記スライド体の一部が切り取られて形成されていることを特徴とする請求項11に記載の検出デバイス。
- 前記試料収容部と前記試料供給位置との少なくとも一方には、前記検出の妨げとなる妨害物質を除去、捕捉若しくは前記検出に影響しない別の物質に変換するための前処理において使用される前処理試薬が配置されていることを特徴とする請求項1から3のいずれか一項に記載の検出デバイス。
- 前記対極と前記参照極との少なくとも一方は、銀及び塩化銀を用いた銀‐塩化銀電極である請求項3に記載の検出デバイス。
- 前記試料供給位置において前記ベース部材の前記面上に露出して設けられた互いに離間する一対の導通検知電極をさらに備え、
前記試料供給位置に供給された前記試料によって前記一対の導通検知電極が導通する
ことを特徴とする請求項1から14のいずれか一項に記載の検出デバイス。 - 前記導通検知電極の表面は親水性を有することを特徴とする請求項15に記載の検出デバイス。
- 前記案内部は疎水性を有することを特徴とする請求項6に記載の検出デバイス。
- 前記ベース部材には、前記ベース部材に対する前記スライド部材のスライド方向に長い長穴が形成されており、
前記スライド部材には、前記スライド部材が前記支持部に支持された状態で前記スライド部材の厚さ方向から見たときに前記長穴と重なる貫通孔が形成されている
ことを特徴とする請求項1から17のいずれか一項に記載の検出デバイス。 - 前記電極系の少なくとも前記作用極には、酸化還元酵素及びレドックスメディエータが配置されていることを特徴とする請求項3に記載の検出デバイス。
- 前記レドックスメディエータは、ルテニウム誘導体、オスミウム誘導体、フェリシアン誘導体、フェロセン誘導体、キノン誘導体、フェノチアジン誘導体、フェノキサジン誘導体、フェナジン誘導体、インドフェノール誘導体、ジフェニルアミン誘導体、フェノール誘導体のうち少なくとも1つを含むことを特徴とする請求項19に記載の検出デバイス。
- 前記酸化還元酵素は、ピラノースオキシダーゼ、L-ソルボースオキシダーゼ、1,5-アンヒドログルシトールデヒドロゲナーゼ、L-ソルボースデヒドロゲナーゼ、1,5-アンヒドログルシトール6リン酸デヒドロゲナーゼのうち少なくとも1つを含むことを特徴とする請求項19に記載の1,5-アンヒドログルシトール測定用検出デバイス。
- 前記前処理試薬は、グルコースを除去、捕捉若しくは前記検出に影響しない別の物質に変換するための試薬を含むことを特徴とする請求項13に記載の1,5-アンヒドログルシトール測定用検出デバイス。
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KR102033466B1 (ko) * | 2016-05-04 | 2019-10-17 | 주식회사 디에프아이 | 1,5-안하이드로글루시톨 측정수단 및 그 제조방법 |
KR102033470B1 (ko) * | 2018-04-20 | 2019-10-17 | 주식회사 디에프아이 | 1,5-안하이드로글루시톨 측정수단의 제조방법 |
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