US20100276285A1 - Analysis Tool and Manufacturing Method Thereof - Google Patents
Analysis Tool and Manufacturing Method Thereof Download PDFInfo
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- US20100276285A1 US20100276285A1 US12/740,834 US74083408A US2010276285A1 US 20100276285 A1 US20100276285 A1 US 20100276285A1 US 74083408 A US74083408 A US 74083408A US 2010276285 A1 US2010276285 A1 US 2010276285A1
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- electrode
- reactive
- reactive electrode
- area
- biosensor
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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
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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
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D5/00—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
- B05D5/12—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures to obtain a coating with specific electrical properties
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B38/00—Ancillary operations in connection with laminating processes
- B32B38/04—Punching, slitting or perforating
Definitions
- the present invention relates to a method of manufacturing an analysis tool used to analyze certain components (for example, glucose, cholesterol, or lactic acid) of a specimen (for example, a biochemical specimen such as blood or urine).
- a specimen for example, a biochemical specimen such as blood or urine.
- the analysis tool includes, for example, an electrode-type biosensor 6 shown in FIG. 16 hereto (see, for example, Japanese Patent Application Laid-Open (JP-A) No. 10-318969).
- the biosensor 6 is configured such that a response electric current value necessary to calculate a blood-sugar level is measured using electrodes 61 and 62 provided on a substrate 60 .
- the electrodes 61 and 62 are covered by an insulating film 64 having an opening 64 A, and the portions of the electrodes 61 and 62 exposed by the opening 64 A constitute a reactive electrode 61 A and an counter electrode 62 A.
- the area of the reactive electrode 61 A or the counter electrode 62 A is controlled by the opening 64 A of the insulating film 64 .
- a deviation may be generated in the area of the reactive electrode 61 A due to a deviation in the dimension of the opening 64 A between plural glucose sensors 6 .
- the reactive electrode 61 A facilitates transfer of electrons from/to analysis target components, and a deviation in the area of the reactive electrode 61 A generates a deviation in the sensitivity of the biosensor 6 .
- a narrow-width neck section 71 extends from an electrode main body section 70 , and the electrode main body section 70 is exposed by the opening 73 of the insulating film 72 (see, for example, Japanese Patent Application Laid-Open (JP-A) No. 2007-510902).
- JP-A Japanese Patent Application Laid-Open
- the edge of the opening 73 in the insulating film 72 traverses the neck section 71 . Therefore, even when the dimension of the opening 73 has a deviation, it is possible to suppress a deviation in the area of the electrode main body section 70 .
- the electrode strip 8 shown in FIG. 18 hereto has an reactive electrode 80 and a dummy electrode 81 .
- the electrodes 80 and 81 are exposed by the opening 83 of the insulating film 82 (see, for example, Japanese Patent Application Laid-Open (JP-A) No. 2001-516038).
- JP-A Japanese Patent Application Laid-Open
- the reactive electrode 80 and the dummy electrode 81 have an island shape, it is possible to prevent the deviation in the area of the reactive electrode 80 even when the deviation exists in the dimension of the opening 83 .
- a slit 91 is formed in a metal film of the substrate 90 , and the reactive electrode 93 and the counter electrode 94 are controlled by a pair of covers 92 (see, for example, Japanese Patent Application Laid-Open (JP-A) No. 9-189675).
- JP-A Japanese Patent Application Laid-Open
- the area of the reactive electrode 93 can be controlled without the insulating film, it is possible to advantageously make it easier to perform the manufacturing processes.
- the area of the reactive electrode 93 depends on the accuracy of positioning or the shape of a pair of covers 92 , it is difficult to accurately control the area of the reactive electrode 93 .
- the present invention has been made to control the area of the reactive electrode of the electrode-type analysis tool in a simple, easy, and accurate manner.
- an analysis tool including: a substrate; a first electrode which is formed on the substrate and has an reactive electrode; a second electrode which is formed on the substrate and has an counter electrode; a first control element for controlling a contact area making contact with a specimen in the reactive electrode; and a second control element for controlling an effective area for performing transfer of electrons in at least one of the reactive electrode and the counter electrode.
- the second control element is provided to control the effective area for performing transfer of electrons in the reactive electrode.
- the second control element is at least a slit.
- the slit has a main line extending in a first direction where the reactive electrode and counter electrode are lined up and a subsidiary line extending in a second direction intersecting with the first direction.
- the first control element is arranged such that the edge for controlling the contact area traverses the subsidiary line.
- a method of manufacturing an analysis tool including: a first process for forming plural electrodes on a mother substrate; a second process for forming an element for defining an effective area for performing transfer of electrons in the reactive electrode; and a third process for defining a contact area making contact with a specimen in the reactive electrode.
- the second process is performed by forming a slit in an electrode including the reactive electrode.
- the slit is formed by irradiating laser light onto the electrode.
- the slit is formed to have a main line extending in a first direction where the reactive electrode and the counter electrode are lined up and a subsidiary line extending in a second direction intersecting with the first direction.
- the third process is performed by arranging a control element on the mother substrate.
- the control element is arranged such that an edge for controlling the contact area traverses the subsidiary line.
- the first process is performed by irradiating laser light onto the conductive layer after a conductive layer is formed on the mother substrate.
- FIG. 1 is a perspective diagram illustrating the entire biosensor as an example of the analysis tool according to a first embodiment of the present invention.
- FIG. 2 is a cross-sectional view along the line II-II of FIG. 1 .
- FIG. 3 is an exploded perspective view illustrating the biosensor of FIG. 1 .
- FIG. 4 is a top plan view illustrating the biosensor of FIG. 1 by removing the spacer, the reagent layer, and the cover.
- FIG. 5 is a perspective diagram for describing a method of manufacturing the biosensor of FIG. 1 .
- FIG. 6A is a perspective diagram for describing a method of manufacturing the biosensor of FIG. 1
- FIG. 6B is a top plan view illustrating main components of FIG. 6A .
- FIGS. 7A and 7B are top plan views for describing a method of manufacturing the biosensor of FIG. 1 .
- FIGS. 8A and 8B are top plan views for describing effects of the method of manufacturing the biosensor according to the present invention by enlarging main components of FIG. 7B .
- FIGS. 9A and 9B are perspective diagrams for describing a method of manufacturing the biosensor of FIG. 1 .
- FIG. 10 is a perspective diagram for describing effects of the method of manufacturing the biosensor according to the present invention.
- FIGS. 11A-C are top plan views corresponding to FIG. 4 for describing additional examples of the analysis tool according to the present invention.
- FIG. 12 is a perspective diagram illustrating the entire biosensor as an example of the analysis tool according to the first embodiment of the present invention.
- FIG. 13 is an exploded perspective diagram illustrating the biosensor of FIG. 12 .
- FIG. 14 is a top plan view illustrating the biosensor of FIG. 12 by removing the spacer, the reagent layer, and the cover.
- FIGS. 15A and 15B are graphs illustrating measurement results of the area of the reactive electrode and the response electric current according to the second embodiment.
- FIG. 16 is a top plan view illustrating main components of the biosensor as an example of the analysis tool of the related art.
- FIG. 17 is a top plan view illustrating a chemical sensor electrode as another example of the analysis tool of the related art.
- FIG. 18 is a top plan view illustrating main components of the electrode strip as further another example of the analysis tool of the related art.
- FIG. 19A is a perspective diagram illustrating as still further another example of the analysis tool of the related art by partially exploding the biosensor
- FIG. 19B is a top plan view illustrating the biosensor of FIG. 19A by removing the reagent layer and the cover.
- the biosensor 1 shown in FIGS. 1 to 3 is constructed as a disposable device, and is installed in an analyzer (not shown) such as a concentration measurement apparatus and used to analyze a certain component (for example, glucose, cholesterol, or lactic acid) within a specimen (for example, a biochemical specimen such as blood or urine).
- the biosensor 1 has a configuration obtained by bonding the cover 12 to the substrate 10 having an approximately long rectangular shape by interposing a pair of spacers 11 therebetween.
- a capillary 13 extending in the width direction D 1 of the substrate 10 is defined by each element 10 to 12 .
- the substrate 10 is formed in a shape larger than the cover 12 using an insulation resin material such as PET.
- the substrate 10 has a protrusion in a lateral direction of the cover 12 .
- electrodes 14 and 15 and a reagent layer 16 are provided on the surface of the substrate 10 .
- the electrodes 14 and 15 are formed to have a band shape extending in the longitudinal direction D 2 of the substrate 10 such that, for example, the length L is 2 to 50 mm (refer to FIG. 4 ), and the width W is 0.1 to 5 mm (refer to FIG. 4 ).
- the electrodes 14 and 15 have exposed electrode portions (including the reactive electrode 14 A and the counter electrode 15 A) and terminal portions 14 B and 15 B.
- the reactive electrode 14 A and the counter electrode 15 A are exposed portions inside the capillary 13 and separated from each other by the slit 17 .
- the width of the slit 17 is set to, for example, 10 to 300 ⁇ m.
- the reactive electrode 14 A and the counter electrode 15 A make contact with the specimen introduced into the capillary 13 .
- the reactive electrode 14 A performs transfer of electrons from/to analysis target components within the specimen, and the area of the reactive electrode 14 A influences the measurement accuracy of the biosensor 1 .
- the electrode 14 further includes slits 18 and 19 .
- These slits 18 and 19 are provided to define an effective area, and include main lines 18 A and 19 A, and subsidiary lines 18 B and 19 B.
- the effective area of the reactive electrode 14 A means the area of the portion for performing transfer of electrons from/to the analysis target components within the specimen.
- the reactive electrode 14 A has a smaller effective area which is an area for performing transfer of electrons from/to analysis target components within the specimen by providing slits 18 and 19 in comparison with the area making contact with the specimen inside the capillary 13 .
- the area of the reactive electrode 14 A substantially contributing to such transfer of electrons is referred to as an effective area.
- the main lines 18 A and 19 A extend in a direction of D 1 , and their lengths are set to, for example, 50 to 98% of the widths W of the electrodes 14 and 15 .
- the distance between the main lines 18 A and 19 A is set to, for example, 30% to 98% of the distance between a pair of the spacers 11 .
- the subsidiary lines 18 B and 19 B extend in the direction of D 2 .
- the slit 18 has a U-shape, and the slit 19 has a rectangular shape.
- the terminal portions 14 B and 15 B are provided to make contact with a connector (not shown) of the analyzer when the biosensor 1 is installed in the analyzer.
- the reagent layer 16 is to cover the reactive electrode 14 A and the counter electrode 15 A in series inside the capillary 13 .
- the reagent layer 16 includes, for example, an oxidoreductase and an electron carrier material, and is formed in a solid state readily dissolved in the specimen such as blood.
- the oxidoreductase is selected depending on the type of the analysis target component within the specimen. For example, when glucose is analyzed, glucose oxidase (GOD) or glucose dehydrogenase (GDH) may be used, and typically, PQQGDH is used.
- the electron carrier material may include, for example, a ruthenium complex or an iron complex, and typically [Ru(NH 3 ) 6 ]Cl 3 or K 3 -[Fe(CN) 6 ].
- a pair of spacers 11 are to define the distance from the surface of the substrate 10 to the lower surface of the cover 12 , i.e., the height of the capillary 13 , and are configured of, for example, a double-face adhesive tape or a hot-melt film. These spaces 11 extend in the width direction of the substrate 10 and are also arranged to be separated in a longitudinal direction of the substrate 10 .
- a pair of spacers 11 define the width of the capillary 13 and the area (the contact area making contact with the specimen) of the portion exposed within the capillary 13 (the reactive electrode 14 A and the counter electrode 15 A) in the electrodes 14 and 15 .
- the cover 12 is provided to define the capillary 13 in association with the spacers 11 or the like.
- the cover 12 is formed of the same material as that of the substrate 10 such as PET or thermoplastic resin having a high wettability such as vinylon or high-crystalline PVA.
- the capillary 13 is provided to move the introduced specimen such as blood in the width direction of the substrate 10 using a capillary action and retain the introduced specimen.
- the specimen moves while discharging gas within the capillary 13 .
- the reagent layer 16 is dissolved so as to provide a liquid-phase reaction system including analysis target components such as an oxidoreductase, an electron carrier material, and glucose.
- a conductive layer 20 is formed on the surface of the mother substrate 2 .
- the conductive layer 20 is formed of, for example, gold, platinum, palladium, nickel, or carbon and has a thickness of 0.001 to 100 ⁇ m.
- the formation of the conductive layer 20 is performed by, for example, screen printing, CVD, sputtering, or deposition.
- plural separation slits 21 extending in a direction of D 2 are formed on the conductive layer 20 .
- the conductive layer 20 has plural band-shape electrodes 20 A and 20 B insulated from each other.
- These slits 21 are formed to have a width of 10 to 300 ⁇ m by scanning laser light along a predetermined path, for example, using a laser oscillator 22 .
- the laser oscillator 22 may include, for example, a CO 2 laser oscillator or a YAG laser oscillator, capable of oscillating laser light having a wavelength that can be easily absorbed by the conductive layer 20 and hardly absorbed by the mother substrate 2 .
- a process of forming the conductive layer 20 and a process of forming the slits 21 are not necessarily performed in a separate manner, but may be performed in a collective manner, for example, using a predetermined mask by simultaneously forming the conductive layer 20 and the slits 21 to provide plural band-shape electrodes 20 A and 20 B.
- slits 23 A and 23 B for controlling an effective area of the reactive electrode 14 A are formed.
- Such slits 23 A and 23 B are formed to have main lines 23 Aa and 23 Ba and subsidiary lines 23 Ab and 23 Bb, for example, using a laser oscillator 22 .
- the main lines 23 Aa and 23 Ba extend in a direction of D 1 , and have a length corresponding to, for example, 50 to 98% of the widths of band-shape electrodes 20 A and 20 B.
- the distance between the main lines 23 Aa and 23 Ba is set to, for example, 30 to 98% of the distance between a pair of spacers 24 A and 24 B which will be described below.
- the subsidiary lines 23 Ab and 23 Bb extend in a direction of D 2 , in which the slit 23 A has a U-shape as a whole, and the slit 23 B has a rectangular shape as a whole.
- the shapes of the slits 23 A and 23 B may be variously changed, for example, such that the slit 23 A has a rectangular shape, and the slit 23 B has a U-shape.
- both of the slits 23 A and 23 B may have a U-shape, or both of the slits 23 A and 23 B may have a rectangular shape.
- plural spacers 24 A and 24 B are attached to extend in a direction of D 1 perpendicular to plural separation slits 21 .
- Such spacers 24 A and 24 B may be attached farther than the distance between the main lines 23 Aa and 23 Ba such that the main lines 23 Aa and 23 Ba of the slits 23 A and 23 B for controlling the effective area of the reactive electrode 14 A are exposed.
- the spacers 24 A and 24 B are arranged such that edges of the spacers 24 A and 24 B traverse the subsidiary lines 23 Ab and 23 Bb of the slits 23 A and 23 B.
- the spacers 24 A and 24 B may include, for example, a double-face adhesive tape or a hot-melt film.
- the width and the thickness of each of the spacers 24 A and 24 B are set to, for example, 1 to 20 mm and 20 to 300 ⁇ m, respectively.
- the distance between the spacers 24 A and 24 B is set to, for example, 100 to 3000 ⁇ m.
- a reagent solution includes a liquid-phase or slurry-phase material containing an oxidoreductase and an electron carrier material.
- the oxidoreductase is selected depending on the type of the analysis target component within the specimen. For example, when a biosensor 1 appropriate to analyze glucose is formed, glucose oxidase (GOD) or glucose dehydrogenase (GDH) is used.
- the electron carrier material includes, for example, a ruthenium complex or an iron complex, and typically, [Ru(NH 3 ) 6 ]Cl 3 or K 3 -[Fe(CN) 6 ].
- a sensor assembly 3 is obtained by attaching the cover 26 so as to bridge the spacers 24 A and 24 B.
- the cover 26 may be formed of, for example, the same material as that of the mother substrate 2 such as thermoplastic resin or PET having a high wettability such as vinylon or high-crystalline PVA.
- biosensors 1 can be obtained by cutting the sensor assembly 3 along a predetermined cutting line.
- the cutting of the sensor assembly 3 is performed using, for example, a diamond cutter.
- the effective area of the reactive electrode 14 A is not controlled by the opening of the insulating layer which covers the electrodes 14 and 15 , it is unnecessary to form the insulating layer in order to control the area of the electron transfer surface of the reactive electrode 14 A. Therefore, it is possible to control the area of the electron transfer surface of the reactive electrode 14 A in a simple, easy, and inexpensive manner without complicating the manufacturing processes or equipments.
- the slits 23 A and 23 B, and the laser oscillator 22 are used to control the area of the electron transfer surface of the reactive electrode 14 A when plural separation slits 21 are formed in the conductive layer 20 using the laser oscillator 22 , it unnecessary to prepare special equipment in order to form the slits 23 A and 23 B. Therefore, in this regard, it is possible to improve the measurement accuracy of the biosensor 1 by controlling the area of the electrode transfer surface of the reactive electrode 14 A in a simple, easy, and inexpensive manner.
- the present invention is not limited to the aforementioned embodiments, but may be modified in various manners, for example, as shown in FIGS. 11A to 11C .
- the slits 18 and 19 for controlling the effective area of the reactive electrode 14 A are formed in an L-shape and a U-shape, respectively, by omitting one of the subsidiary lines in the slits 18 and 19 .
- the slit 18 for controlling the effective area of the reactive electrode 14 A is formed in an I-shape by omitting the subsidiary lines, and the slit 19 is formed in a U-shape by omitting one of the subsidiary lines.
- the slits 18 and 19 for controlling the effective area of the reactive electrode 14 A are formed in an L-shape and a U-shape by omitting one of the subsidiary lines and, the slits 18 ′ and 19 ′ are also formed in the counter electrode 15 A.
- the slits 18 and 19 and the slits 18 ′ and 19 ′ are symmetrically arranged with respect to the separation slit 17 .
- the biosensor 4 shown in FIGS. 12 to 14 is formed by stacking the substrate 40 , the spacer 41 , and the cover 42 in a similar way to that of the biosensor 1 described above (refer to FIGS. 1 to 3 ).
- Electrodes 43 and 44 are formed on the substrate 40 .
- the electrodes 43 and 44 have bending portions 43 A and 44 A extending in a direction of D 1 and lead portions 43 B and 44 B extending in a direction of D 2 .
- the bending portions 43 A and 44 A are arranged in parallel in a direction of D 2 , and include an reactive electrode 43 Aa and the counter electrode 44 Aa defined by the spacer 41 .
- slits 45 and 46 are formed in the bending portion 43 A.
- Such slits 45 and 46 are provided to define the area (the effective area) of the electron transfer surface of the reactive electrode 43 Aa. Similar to the slits 18 and 19 of the aforementioned biosensor 1 (refer to FIGS. 3 and 4 ), the slits 45 and 46 include main lines 45 A and 46 A and subsidiary lines 45 B and 46 B.
- the main lines 45 A and 46 A extend in a direction of D 2 , and their lengths are set to, for example, 50 to 98% of the width of the bending portion 43 A.
- the distance between the main lines 45 A and 46 A is set to, for example, 30 to 98% of the width of the slit in the spacer 41 which will be described below.
- the subsidiary lines 45 B and 46 B extend in a direction of D 1 , the slit 45 is formed in a U-shape, and the slit 46 is formed in a rectangular shape.
- the spacer 41 is provided to define the distance from the surface of the substrate 40 to the lower surface of the cover 42 , i.e., the height of the capillary 48 , and has a slit 47 .
- the slit 47 defines the width of the capillary 48 for introducing the specimen and the area of the portion (the reactive electrode 43 Aa and the counter electrode 44 Aa) exposed within the capillary 48 in the electrodes 43 and 44 .
- the spacer 41 is arranged such that the edge of the slit 47 extending in a direction of D 2 traverses the subsidiary lines 45 B and 46 B of the slits 45 and 46 .
- the capillary 48 is provided to move the introduced specimen such as blood in a longitudinal direction D 2 of the substrate 40 using a capillary action and maintain the introduced specimen.
- the reagent layer 48 A is formed to cover at least the reactive electrode 43 Aa.
- Such a spacer 41 is configured of, for example, a double-face adhesive tape or a hot-melt film.
- the cover 42 is provided to define the capillary 13 in association with the spacer 41 or the like, and has a thru-hole 49 .
- the cover 42 is formed of the same material as that of the substrate 40 such as thermoplastic resin or PET having a high wettability such as vinylon or high-crystalline PVA.
- the effective area of the reactive electrode 43 Aa is defined by the slits 45 and 46 , a deviation in the area of the reactive electrode 43 Aa is suppressed. Therefore, it is possible to suppress a deviation in the sensor sensitivity of the biosensor 4 and perform the concentration measurement with excellent accuracy.
- the effective area of the reactive electrode 43 Aa is not controlled by the opening of the insulating layer that covers the electrodes 44 and 45 , it is unnecessary to form the insulating layer in order to control the area of the reactive electrode 43 Aa. Therefore, it is possible to control the area of the reactive electrode 43 Aa in a simple, easy, and inexpensive manner without complicating the manufacturing processes or equipments.
- the shapes of the slits 45 and 46 or the biosensor 4 may be variously modified as described in conjunction with the aforementioned biosensor 1 (refer to FIGS. 3 and 4 ), for example, as shown in FIGS. 11A to 11C .
- the slit for defining the effective area of the reactive electrode is not necessarily formed in a shape combined by straight lines, and, for example, may be formed of a shape having a curve.
- the effective area of the reactive electrode may be defined by other elements than the slit.
- the present invention is also applicable to the biosensor obtained by omitting the covers 12 and 42 .
- the effect obtained when the slit for controlling the effective area of the reactive electrode is provided was evaluated based on a deviation in the area of the reactive electrode.
- the electrode of the biosensor was formed to have a width of 0.85 mm and a length of 30 mm by sputtering nickel as a conductive layer on a PET substrate and forming a separation slit having a width of 150 ⁇ m using a laser oscillator.
- the slit for controlling the effective area of the reactive electrode was formed in a U-shape and a rectangular shape having a width of 150 urn using a laser oscillator in a similar way to the case where the separation slit is formed.
- the length was set to 0.65 mm, and the distance was set to 0.65 mm.
- the shortest distance between the subsidiary line and the cutting slit was set to 0.2 mm.
- the spacer is arranged such that the distance in a longitudinal direction of the substrate becomes 1.4 mm.
- the target effective area of the reactive electrode was set to 0.7 mm 2 .
- the target area of the reactive electrode was set to 1.2 mm 2 .
- the reagent layer containing [Ru(NH 3 )Cl 3 ] of 20 mg as an electron carrier material and glucose oxidase of 1 unit as the oxidoreductase for a single sensor was formed to cover the reactive electrode and the counter electrode.
- the area of the reactive electrode was measured by capturing an image of the reactive electrode using an image-capturing apparatus for the biosensor before the reagent layer and the cover are formed and processing the obtained image using measurement software known in the art.
- the result of the measurement for the area of the reactive electrode is shown in the following Table 1.
- the effect obtained when the slit for controlling the effective area of the reactive electrode is provided was evaluated based on deviations in the sensitivity of the sensor and the area of the reactive electrode.
- Example 1 As the biosensor, an original sensor and a comparison sensor were manufactured in a similar way to Example 1.
- the sensitivity of the biosensor was evaluated based on the response electric current value measured by supplying a specimen having a glucose concentration of 120 mg/dL to the biosensor.
- As the response electric current value a value obtained 5 seconds later after recognizing that the specimen is supplied to the biosensor was employed.
- the measurement results of the response electric current value are shown in the following Table 2 and FIGS. 15A and 15B in association with the measurement results for the area of the reactive electrode.
- both of the S.D. and the C.V. are smaller, and a deviation in the area of the reactive electrode and a deviation in the response electric current value (sensitivity) are smaller in comparison with the comparison sample. Therefore, in the original sample having the slit for controlling the effective area of the reactive electrode, it is possible to form the reactive electrode in a targeted area with excellent accuracy and improve the measurement accuracy by suppressing a deviation in the output (response electric current value) of the sensor.
Abstract
This aims to provide an analyzing tool including a substrate, a first electrode formed on the substrate and having an action pole, a second electrode formed on the substrate and having an opposed pole, and a first regulating element for regulating such a contact area in the action pole as to contact a specimen. The analyzing tool further comprises second regulating elements for regulating the effective area for electron transfers in at least one of the action pole and the opposed pole.
Description
- This application is the National Phase of International Application No. PCT/JP2008/069981, filed 31 Oct. 2008, which claims priority to and the benefit of JP patent application number 2007-282781, filed 31 Oct. 2007, the contents of all which are incorporated by reference herein.
- The present invention relates to a method of manufacturing an analysis tool used to analyze certain components (for example, glucose, cholesterol, or lactic acid) of a specimen (for example, a biochemical specimen such as blood or urine).
- When the glucose concentration in blood is measured, a method of using a disposable analysis tool is being employed as a simple and easy technique. The analysis tool includes, for example, an electrode-type biosensor 6 shown in
FIG. 16 hereto (see, for example, Japanese Patent Application Laid-Open (JP-A) No. 10-318969). The biosensor 6 is configured such that a response electric current value necessary to calculate a blood-sugar level is measured usingelectrodes substrate 60. Theelectrodes insulating film 64 having anopening 64A, and the portions of theelectrodes reactive electrode 61A and ancounter electrode 62A. - In the biosensor 6, the area of the
reactive electrode 61A or thecounter electrode 62A is controlled by the opening 64A of theinsulating film 64. In other words, it is necessary to form theinsulating film 64 using, for example, photolithography in order to control the area of thereactive electrode 61A or thecounter electrode 62A. In addition, a deviation may be generated in the area of thereactive electrode 61A due to a deviation in the dimension of the opening 64A between plural glucose sensors 6. Thereactive electrode 61A facilitates transfer of electrons from/to analysis target components, and a deviation in the area of thereactive electrode 61A generates a deviation in the sensitivity of the biosensor 6. - As a method of controlling an electrode area of the analysis tool, there is the following method as well.
- In the
chemical sensor electrode 7 shown inFIG. 17 hereto, a narrow-width neck section 71 extends from an electrodemain body section 70, and the electrodemain body section 70 is exposed by theopening 73 of the insulating film 72 (see, for example, Japanese Patent Application Laid-Open (JP-A) No. 2007-510902). The edge of theopening 73 in theinsulating film 72 traverses theneck section 71. Therefore, even when the dimension of theopening 73 has a deviation, it is possible to suppress a deviation in the area of the electrodemain body section 70. - The
electrode strip 8 shown inFIG. 18 hereto has anreactive electrode 80 and adummy electrode 81. Theelectrodes electrode strip 8, since thereactive electrode 80 and thedummy electrode 81 have an island shape, it is possible to prevent the deviation in the area of thereactive electrode 80 even when the deviation exists in the dimension of theopening 83. - On the contrary, in the
chemical sensor electrode 7 or theelectrode strip 8 shown inFIGS. 17 and 18 , it is necessary to form theinsulating films main body section 70 or thereactive electrode 80. Therefore, processes or equipments for manufacturing theanalysis tools - In the
biosensor 9 shown inFIGS. 19A and 19B hereto, aslit 91 is formed in a metal film of thesubstrate 90, and thereactive electrode 93 and thecounter electrode 94 are controlled by a pair of covers 92 (see, for example, Japanese Patent Application Laid-Open (JP-A) No. 9-189675). In thisbiosensor 9, since the area of thereactive electrode 93 can be controlled without the insulating film, it is possible to advantageously make it easier to perform the manufacturing processes. On the other hand, since the area of thereactive electrode 93 depends on the accuracy of positioning or the shape of a pair ofcovers 92, it is difficult to accurately control the area of thereactive electrode 93. - The present invention has been made to control the area of the reactive electrode of the electrode-type analysis tool in a simple, easy, and accurate manner.
- According to a first aspect of the present invention, there is provided an analysis tool including: a substrate; a first electrode which is formed on the substrate and has an reactive electrode; a second electrode which is formed on the substrate and has an counter electrode; a first control element for controlling a contact area making contact with a specimen in the reactive electrode; and a second control element for controlling an effective area for performing transfer of electrons in at least one of the reactive electrode and the counter electrode.
- For example, the second control element is provided to control the effective area for performing transfer of electrons in the reactive electrode. For example, the second control element is at least a slit. For example, the slit has a main line extending in a first direction where the reactive electrode and counter electrode are lined up and a subsidiary line extending in a second direction intersecting with the first direction.
- It is preferable that the first control element is arranged such that the edge for controlling the contact area traverses the subsidiary line.
- According to a second aspect of the invention, there is provided a method of manufacturing an analysis tool, the method including: a first process for forming plural electrodes on a mother substrate; a second process for forming an element for defining an effective area for performing transfer of electrons in the reactive electrode; and a third process for defining a contact area making contact with a specimen in the reactive electrode.
- For example, the second process is performed by forming a slit in an electrode including the reactive electrode. For example, the slit is formed by irradiating laser light onto the electrode. For example, the slit is formed to have a main line extending in a first direction where the reactive electrode and the counter electrode are lined up and a subsidiary line extending in a second direction intersecting with the first direction.
- For example, the third process is performed by arranging a control element on the mother substrate. The control element is arranged such that an edge for controlling the contact area traverses the subsidiary line.
- For example, the first process is performed by irradiating laser light onto the conductive layer after a conductive layer is formed on the mother substrate.
-
FIG. 1 is a perspective diagram illustrating the entire biosensor as an example of the analysis tool according to a first embodiment of the present invention. -
FIG. 2 is a cross-sectional view along the line II-II ofFIG. 1 . -
FIG. 3 is an exploded perspective view illustrating the biosensor ofFIG. 1 . -
FIG. 4 is a top plan view illustrating the biosensor ofFIG. 1 by removing the spacer, the reagent layer, and the cover. -
FIG. 5 is a perspective diagram for describing a method of manufacturing the biosensor ofFIG. 1 . -
FIG. 6A is a perspective diagram for describing a method of manufacturing the biosensor ofFIG. 1 , andFIG. 6B is a top plan view illustrating main components ofFIG. 6A . -
FIGS. 7A and 7B are top plan views for describing a method of manufacturing the biosensor ofFIG. 1 . -
FIGS. 8A and 8B are top plan views for describing effects of the method of manufacturing the biosensor according to the present invention by enlarging main components ofFIG. 7B . -
FIGS. 9A and 9B are perspective diagrams for describing a method of manufacturing the biosensor ofFIG. 1 . -
FIG. 10 is a perspective diagram for describing effects of the method of manufacturing the biosensor according to the present invention. -
FIGS. 11A-C are top plan views corresponding toFIG. 4 for describing additional examples of the analysis tool according to the present invention. -
FIG. 12 is a perspective diagram illustrating the entire biosensor as an example of the analysis tool according to the first embodiment of the present invention. -
FIG. 13 is an exploded perspective diagram illustrating the biosensor ofFIG. 12 . -
FIG. 14 is a top plan view illustrating the biosensor ofFIG. 12 by removing the spacer, the reagent layer, and the cover. -
FIGS. 15A and 15B are graphs illustrating measurement results of the area of the reactive electrode and the response electric current according to the second embodiment. -
FIG. 16 is a top plan view illustrating main components of the biosensor as an example of the analysis tool of the related art. -
FIG. 17 is a top plan view illustrating a chemical sensor electrode as another example of the analysis tool of the related art. -
FIG. 18 is a top plan view illustrating main components of the electrode strip as further another example of the analysis tool of the related art. -
FIG. 19A is a perspective diagram illustrating as still further another example of the analysis tool of the related art by partially exploding the biosensor, andFIG. 19B is a top plan view illustrating the biosensor ofFIG. 19A by removing the reagent layer and the cover. - Hereinafter, the analysis tool and the method of manufacturing the same according to the present invention is described below by exemplifying a biosensor with reference to the accompanying drawings.
- First, the first embodiment of the present invention will be described with reference to
FIGS. 1 to 10 . - The
biosensor 1 shown inFIGS. 1 to 3 is constructed as a disposable device, and is installed in an analyzer (not shown) such as a concentration measurement apparatus and used to analyze a certain component (for example, glucose, cholesterol, or lactic acid) within a specimen (for example, a biochemical specimen such as blood or urine). Thebiosensor 1 has a configuration obtained by bonding thecover 12 to thesubstrate 10 having an approximately long rectangular shape by interposing a pair ofspacers 11 therebetween. In thebiosensor 1, a capillary 13 extending in the width direction D1 of thesubstrate 10 is defined by eachelement 10 to 12. - The
substrate 10 is formed in a shape larger than thecover 12 using an insulation resin material such as PET. Thesubstrate 10 has a protrusion in a lateral direction of thecover 12. On the surface of thesubstrate 10,electrodes reagent layer 16 are provided. - The
electrodes substrate 10 such that, for example, the length L is 2 to 50 mm (refer toFIG. 4 ), and the width W is 0.1 to 5 mm (refer toFIG. 4 ). Theelectrodes reactive electrode 14A and thecounter electrode 15A) andterminal portions - The
reactive electrode 14A and thecounter electrode 15A are exposed portions inside the capillary 13 and separated from each other by theslit 17. The width of theslit 17 is set to, for example, 10 to 300 μm. Thereactive electrode 14A and thecounter electrode 15A make contact with the specimen introduced into the capillary 13. Here, thereactive electrode 14A performs transfer of electrons from/to analysis target components within the specimen, and the area of thereactive electrode 14A influences the measurement accuracy of thebiosensor 1. - As shown in
FIGS. 3 and 4 , theelectrode 14 further includesslits slits main lines subsidiary lines reactive electrode 14A means the area of the portion for performing transfer of electrons from/to the analysis target components within the specimen. In other words, thereactive electrode 14A has a smaller effective area which is an area for performing transfer of electrons from/to analysis target components within the specimen by providingslits reactive electrode 14A substantially contributing to such transfer of electrons is referred to as an effective area. - The
main lines electrodes main lines spacers 11. On the other hand, the subsidiary lines 18B and 19B extend in the direction of D2. Theslit 18 has a U-shape, and theslit 19 has a rectangular shape. - As shown in
FIGS. 1 to 3 , theterminal portions biosensor 1 is installed in the analyzer. - The
reagent layer 16 is to cover thereactive electrode 14A and thecounter electrode 15A in series inside the capillary 13. Thereagent layer 16 includes, for example, an oxidoreductase and an electron carrier material, and is formed in a solid state readily dissolved in the specimen such as blood. - The oxidoreductase is selected depending on the type of the analysis target component within the specimen. For example, when glucose is analyzed, glucose oxidase (GOD) or glucose dehydrogenase (GDH) may be used, and typically, PQQGDH is used. The electron carrier material may include, for example, a ruthenium complex or an iron complex, and typically [Ru(NH3)6]Cl3 or K3-[Fe(CN)6].
- A pair of
spacers 11 are to define the distance from the surface of thesubstrate 10 to the lower surface of thecover 12, i.e., the height of the capillary 13, and are configured of, for example, a double-face adhesive tape or a hot-melt film. Thesespaces 11 extend in the width direction of thesubstrate 10 and are also arranged to be separated in a longitudinal direction of thesubstrate 10. In other words, a pair ofspacers 11 define the width of the capillary 13 and the area (the contact area making contact with the specimen) of the portion exposed within the capillary 13 (thereactive electrode 14A and thecounter electrode 15A) in theelectrodes - The
cover 12 is provided to define the capillary 13 in association with thespacers 11 or the like. Thecover 12 is formed of the same material as that of thesubstrate 10 such as PET or thermoplastic resin having a high wettability such as vinylon or high-crystalline PVA. - The capillary 13 is provided to move the introduced specimen such as blood in the width direction of the
substrate 10 using a capillary action and retain the introduced specimen. In other words, in the capillary 13, when the specimen is introduced, the specimen moves while discharging gas within thecapillary 13. In this case, inside the capillary 13, thereagent layer 16 is dissolved so as to provide a liquid-phase reaction system including analysis target components such as an oxidoreductase, an electron carrier material, and glucose. - Next, a method of manufacturing the
biosensor 1 will be described with reference toFIGS. 5 to 10 . - First, as shown in
FIG. 5 , aconductive layer 20 is formed on the surface of themother substrate 2. Theconductive layer 20 is formed of, for example, gold, platinum, palladium, nickel, or carbon and has a thickness of 0.001 to 100 μm. The formation of theconductive layer 20 is performed by, for example, screen printing, CVD, sputtering, or deposition. - Next, as shown in
FIGS. 6A and 6B , plural separation slits 21 extending in a direction of D2 are formed on theconductive layer 20. As a result, theconductive layer 20 has plural band-shape electrodes slits 21 are formed to have a width of 10 to 300 μm by scanning laser light along a predetermined path, for example, using alaser oscillator 22. Thelaser oscillator 22 may include, for example, a CO2 laser oscillator or a YAG laser oscillator, capable of oscillating laser light having a wavelength that can be easily absorbed by theconductive layer 20 and hardly absorbed by themother substrate 2. - Meanwhile, a process of forming the
conductive layer 20 and a process of forming theslits 21 are not necessarily performed in a separate manner, but may be performed in a collective manner, for example, using a predetermined mask by simultaneously forming theconductive layer 20 and theslits 21 to provide plural band-shape electrodes - Next, as shown in
FIG. 6B , slits 23A and 23B for controlling an effective area of thereactive electrode 14A are formed.Such slits laser oscillator 22. The main lines 23Aa and 23Ba extend in a direction of D1, and have a length corresponding to, for example, 50 to 98% of the widths of band-shape electrodes spacers slit 23A has a U-shape as a whole, and theslit 23B has a rectangular shape as a whole. Of course, the shapes of theslits slit 23A has a rectangular shape, and theslit 23B has a U-shape. Alternatively, both of theslits slits - Next, as shown in
FIGS. 7A and 7B ,plural spacers Such spacers slits reactive electrode 14A are exposed. In other words, thespacers spacers slits - The
spacers spacers spacers - As shown in
FIG. 8A , even when the positions where thespacers spacers FIG. 8B , it is possible to suppress a deviation of the effective area of thereactive electrode 14A as long as edges of thespacers slits spacers reactive electrode 14, it is possible to reduce a variation of the (effective) area of the electron transfer surface. Therefore, it is possible to improve the measurement accuracy by reducing a variation of the area of thereactive electrode 14 influencing the measurement accuracy of thebiosensor 1. In addition, even when positions of a pair ofspacers spacers spacer 24A and a variation in the effective area caused by a positional deviation of thespacer 24B. As a result, it is possible to reduce a variation in the area (effective area) of the electron transfer surface, and in this regard, it is possible to improve the measurement accuracy of thebiosensor 1. Next, as shown inFIG. 9A , a reagent solution is applied between thespacers dispenser 25 known in the art. A reagent solution includes a liquid-phase or slurry-phase material containing an oxidoreductase and an electron carrier material. The oxidoreductase is selected depending on the type of the analysis target component within the specimen. For example, when abiosensor 1 appropriate to analyze glucose is formed, glucose oxidase (GOD) or glucose dehydrogenase (GDH) is used. The electron carrier material includes, for example, a ruthenium complex or an iron complex, and typically, [Ru(NH3)6]Cl3 or K3-[Fe(CN)6]. - Next, as shown in
FIG. 9A , asensor assembly 3 is obtained by attaching thecover 26 so as to bridge thespacers cover 26 may be formed of, for example, the same material as that of themother substrate 2 such as thermoplastic resin or PET having a high wettability such as vinylon or high-crystalline PVA. - Finally,
plural biosensors 1 can be obtained by cutting thesensor assembly 3 along a predetermined cutting line. The cutting of thesensor assembly 3 is performed using, for example, a diamond cutter. - In the manufacturing method described above, it is possible to obtain a
biosensor 1 capable of suppressing a deviation in the area (the effective area) of the electron transfer surface of thereactive electrode 14A. Therefore, it is possible to improve measurement accuracy by suppressing a deviation in the measurement result caused by a deviation in the effective area of thereactive electrode 14A of thebiosensor 1. - In addition, since the effective area of the
reactive electrode 14A is not controlled by the opening of the insulating layer which covers theelectrodes reactive electrode 14A. Therefore, it is possible to control the area of the electron transfer surface of thereactive electrode 14A in a simple, easy, and inexpensive manner without complicating the manufacturing processes or equipments. - In addition, if the
slits laser oscillator 22 are used to control the area of the electron transfer surface of thereactive electrode 14A when plural separation slits 21 are formed in theconductive layer 20 using thelaser oscillator 22, it unnecessary to prepare special equipment in order to form theslits biosensor 1 by controlling the area of the electrode transfer surface of thereactive electrode 14A in a simple, easy, and inexpensive manner. - The present invention is not limited to the aforementioned embodiments, but may be modified in various manners, for example, as shown in
FIGS. 11A to 11C . - In the example shown in
FIG. 11A , theslits reactive electrode 14A are formed in an L-shape and a U-shape, respectively, by omitting one of the subsidiary lines in theslits - In the example shown in
FIG. 11B , theslit 18 for controlling the effective area of thereactive electrode 14A is formed in an I-shape by omitting the subsidiary lines, and theslit 19 is formed in a U-shape by omitting one of the subsidiary lines. - In the example shown in
FIG. 11C , theslits reactive electrode 14A are formed in an L-shape and a U-shape by omitting one of the subsidiary lines and, theslits 18′ and 19′ are also formed in thecounter electrode 15A. Theslits slits 18′ and 19′ are symmetrically arranged with respect to the separation slit 17. - Next, the second embodiment of the present invention will be described with reference to
FIGS. 12 to 14 . - The
biosensor 4 shown inFIGS. 12 to 14 is formed by stacking thesubstrate 40, thespacer 41, and thecover 42 in a similar way to that of thebiosensor 1 described above (refer toFIGS. 1 to 3 ). -
Electrodes substrate 40. Theelectrodes portions lead portions portions spacer 41. In addition, slits 45 and 46 are formed in the bendingportion 43A.Such slits slits FIGS. 3 and 4 ), theslits main lines 45A and 46A andsubsidiary lines - The
main lines 45A and 46A extend in a direction of D2, and their lengths are set to, for example, 50 to 98% of the width of the bendingportion 43A. The distance between themain lines 45A and 46A is set to, for example, 30 to 98% of the width of the slit in thespacer 41 which will be described below. On the other hand, the subsidiary lines 45B and 46B extend in a direction of D1, theslit 45 is formed in a U-shape, and theslit 46 is formed in a rectangular shape. - The
spacer 41 is provided to define the distance from the surface of thesubstrate 40 to the lower surface of thecover 42, i.e., the height of the capillary 48, and has aslit 47. Theslit 47 defines the width of the capillary 48 for introducing the specimen and the area of the portion (the reactive electrode 43Aa and the counter electrode 44Aa) exposed within the capillary 48 in theelectrodes spacer 41 is arranged such that the edge of theslit 47 extending in a direction of D2 traverses the subsidiary lines 45B and 46B of theslits - Here, the capillary 48 is provided to move the introduced specimen such as blood in a longitudinal direction D2 of the
substrate 40 using a capillary action and maintain the introduced specimen. In the inner side thereof, thereagent layer 48A is formed to cover at least the reactive electrode 43Aa. Such aspacer 41 is configured of, for example, a double-face adhesive tape or a hot-melt film. - The
cover 42 is provided to define the capillary 13 in association with thespacer 41 or the like, and has a thru-hole 49. Thecover 42 is formed of the same material as that of thesubstrate 40 such as thermoplastic resin or PET having a high wettability such as vinylon or high-crystalline PVA. - In the
biosensor 4, since the effective area of the reactive electrode 43Aa is defined by theslits biosensor 4 and perform the concentration measurement with excellent accuracy. - Since the effective area of the reactive electrode 43Aa is not controlled by the opening of the insulating layer that covers the
electrodes - Meanwhile, the shapes of the
slits biosensor 4 may be variously modified as described in conjunction with the aforementioned biosensor 1 (refer toFIGS. 3 and 4 ), for example, as shown inFIGS. 11A to 11C . - According to the present invention, the slit for defining the effective area of the reactive electrode is not necessarily formed in a shape combined by straight lines, and, for example, may be formed of a shape having a curve. In addition, the effective area of the reactive electrode may be defined by other elements than the slit.
- The present invention is also applicable to the biosensor obtained by omitting the
covers - In this example, the effect obtained when the slit for controlling the effective area of the reactive electrode is provided was evaluated based on a deviation in the area of the reactive electrode.
- (Manufacturing of Biosensor)
- As the biosensor, two kinds of samples were manufactured, including an original sample having the shape shown in
FIGS. 1 to 4 and a comparison sample which does not have the slit for controlling the effective area of the reactive electrode. The electrode of the biosensor was formed to have a width of 0.85 mm and a length of 30 mm by sputtering nickel as a conductive layer on a PET substrate and forming a separation slit having a width of 150 μm using a laser oscillator. The slit for controlling the effective area of the reactive electrode was formed in a U-shape and a rectangular shape having a width of 150 urn using a laser oscillator in a similar way to the case where the separation slit is formed. In the main line of the separation slit, the length was set to 0.65 mm, and the distance was set to 0.65 mm. The shortest distance between the subsidiary line and the cutting slit was set to 0.2 mm. - Meanwhile, the spacer is arranged such that the distance in a longitudinal direction of the substrate becomes 1.4 mm. In the original sample, the target effective area of the reactive electrode was set to 0.7 mm2. In the comparison sample, the target area of the reactive electrode was set to 1.2 mm2.
- The reagent layer containing [Ru(NH3)Cl3] of 20 mg as an electron carrier material and glucose oxidase of 1 unit as the oxidoreductase for a single sensor was formed to cover the reactive electrode and the counter electrode.
- (Measurement of Area of Reactive Electrode)
- The area of the reactive electrode was measured by capturing an image of the reactive electrode using an image-capturing apparatus for the biosensor before the reagent layer and the cover are formed and processing the obtained image using measurement software known in the art. The result of the measurement for the area of the reactive electrode is shown in the following Table 1.
-
TABLE 1 Original Sensor Comparison Sensor No. Area of Reactive Electrode [mm2] Area of Reactive Electrode [mm2] 1 0.684 1.138 2 0.698 1.154 3 0.689 1.146 4 0.702 1.162 5 0.678 1.154 6 0.681 1.174 7 0.675 1.161 8 0.685 1.172 9 0.685 1.151 10 0.683 1.159 11 0.683 1.134 12 0.685 1.152 13 0.681 1.130 14 0.691 1.139 15 0.672 1.111 16 0.682 1.142 17 0.673 1.097 18 0.677 1.121 19 0.669 1.096 20 0.672 1.116 21 0.660 1.123 22 0.672 1.136 23 0.675 1.164 24 0.674 1.191 25 0.675 1.187 26 0.688 1.205 27 0.680 1.204 28 0.684 1.225 29 0.678 1.215 30 0.684 1.229 Ave 0.681 1.156 SD 0.009 0.036 CV % 1.252 3.077 - As recognized from Table 1, in the original sample, both of the S.D. and the C.V. are smaller, and a deviation in the area of the reactive electrode is smaller in comparison with the comparison sample. Therefore, in the original sample having a slit for controlling the effective area of the reactive electrode, it is possible to form the reactive electrode in a targeted area with excellent accuracy.
- In this example, the effect obtained when the slit for controlling the effective area of the reactive electrode is provided was evaluated based on deviations in the sensitivity of the sensor and the area of the reactive electrode.
- As the biosensor, an original sensor and a comparison sensor were manufactured in a similar way to Example 1.
- The sensitivity of the biosensor was evaluated based on the response electric current value measured by supplying a specimen having a glucose concentration of 120 mg/dL to the biosensor. As the response electric current value, a value obtained 5 seconds later after recognizing that the specimen is supplied to the biosensor was employed. The measurement results of the response electric current value are shown in the following Table 2 and
FIGS. 15A and 15B in association with the measurement results for the area of the reactive electrode. -
TABLE 2 Original Sensor Comparison Sensor Area of Area of Reactive Response Reactive Response Electrode Electric Current Electrode Electric Current No. [mm2] Value [μA] [mm2] Value [μA] 1 0.657 2.073 1.195 3.265 2 0.668 2.133 1.220 3.359 3 0.685 2.166 1.214 3.419 4 0.692 2.131 1.199 3.338 5 0.689 2.178 1.207 3.326 6 0.667 2.134 1.201 3.135 7 0.666 2.167 1.180 3.182 8 0.664 2.232 1.150 3.190 9 0.677 2.144 1.131 3.243 10 0.671 2.195 1.095 2.992 11 0.675 2.162 1.082 3.069 12 0.673 2.195 1.069 2.964 13 0.679 2.179 1.075 3.039 14 0.682 2.049 1.046 3.003 15 0.691 2.075 1.080 3.046 Ave 0.676 2.148 1.143 3.171 SD 0.011 0.051 0.063 0.149 CV % 1.563 2.358 5.501 4.701 - As recognized from Table 2, and
FIGS. 15A and 15B , in of the original sample, both of the S.D. and the C.V. are smaller, and a deviation in the area of the reactive electrode and a deviation in the response electric current value (sensitivity) are smaller in comparison with the comparison sample. Therefore, in the original sample having the slit for controlling the effective area of the reactive electrode, it is possible to form the reactive electrode in a targeted area with excellent accuracy and improve the measurement accuracy by suppressing a deviation in the output (response electric current value) of the sensor.
Claims (13)
1. An analysis tool comprising:
a substrate;
a first electrode which is formed on the substrate and which comprises a reactive electrode;
a second electrode which is formed on the substrate and which comprises a counter electrode;
a first control element for controlling a contact area that contacts a specimen at the reactive electrode; and
a second control element for controlling an effective area for performing transfer of electrons at least one of the reactive electrode or the counter electrode.
2. The analysis tool according to claim 1 , wherein the second control element is provided at the first electrode to control the effective area for performing transfer of electrons at the reactive electrode.
3. The analysis tool according to claim 1 , wherein the second control element is at least one slit.
4. The analysis tool according to claim 3 , wherein the at least one slit has a main line extending in a first direction in which the reactive electrode and the counter electrode are aligned and a subsidiary line extending in a second direction that intersects the first direction.
5. The analysis tool according to claim 4 , wherein the first control element is arranged such that an edge for controlling the contact area traverses the subsidiary line.
6. A method of manufacturing an analysis tool, the method comprising:
a first process for forming a plurality of electrodes on a mother substrate;
a second process for forming an element for defining an effective area for performing transfer of electrons at least one of the reactive electrode or the counter electrode; and
a third process for defining a contact area that contacts a specimen at the reactive electrode.
7. The method according to claim 6 , wherein the second process is performed by forming an element for defining the effective area for performing transfer of electrons at the reactive electrode.
8. The method according to claim 6 , wherein the second process is performed by forming a slit in the electrode including the reactive electrode.
9. The method according to claim 8 , wherein the second process is performed by irradiating laser light onto the electrode.
10. The method according to claim 8 , wherein the slit is formed to have a main line extending in a first direction in which the reactive electrode and the counter electrode are aligned and a subsidiary line extending in a second direction that intersects the first direction.
11. The method according to claim 8 , wherein the third process is performed by arranging a control element on the mother substrate.
12. The method according to claim 11 , wherein the control element is arranged such that an edge for controlling the contact area traverses a subsidiary line.
13. The method according to claim 9 , wherein the first process is performed by irradiating laser light onto a conductive layer after the conductive layer is formed on the mother substrate.
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US11073495B2 (en) | 2015-10-15 | 2021-07-27 | Arkray, Inc. | Biosensor and manufacturing method of biosensor |
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- 2008-10-31 WO PCT/JP2008/069981 patent/WO2009057791A1/en active Application Filing
- 2008-10-31 EP EP08845459.0A patent/EP2211172B1/en active Active
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US20030175946A1 (en) * | 2001-04-16 | 2003-09-18 | Hiroyuki Tokunaga | Biosensor |
US20060188395A1 (en) * | 2004-02-04 | 2006-08-24 | Yuko Taniike | Biosensor, and biosensor measuring device and method |
WO2007026683A1 (en) * | 2005-09-02 | 2007-03-08 | Arkray, Inc. | Method for detecting sample supply condition, and analyzer |
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US11073495B2 (en) | 2015-10-15 | 2021-07-27 | Arkray, Inc. | Biosensor and manufacturing method of biosensor |
Also Published As
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EP2211172A4 (en) | 2014-11-26 |
US20140186548A1 (en) | 2014-07-03 |
TW200931012A (en) | 2009-07-16 |
KR101450373B1 (en) | 2014-10-14 |
JPWO2009057791A1 (en) | 2011-03-10 |
TWI460423B (en) | 2014-11-11 |
EP2211172A1 (en) | 2010-07-28 |
CN101842697B (en) | 2016-06-15 |
EP2211172B1 (en) | 2022-03-30 |
US9063077B2 (en) | 2015-06-23 |
JP5290985B2 (en) | 2013-09-18 |
KR20100103481A (en) | 2010-09-27 |
WO2009057791A1 (en) | 2009-05-07 |
CN101842697A (en) | 2010-09-22 |
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