U.S. patent application number 12/740834 was filed with the patent office on 2010-11-04 for analysis tool and manufacturing method thereof.
This patent application is currently assigned to ARKRAY, INC.. Invention is credited to Tomohiro Fujii, Yasuhide Kusaka.
Application Number | 20100276285 12/740834 |
Document ID | / |
Family ID | 40591170 |
Filed Date | 2010-11-04 |
United States Patent
Application |
20100276285 |
Kind Code |
A1 |
Fujii; Tomohiro ; et
al. |
November 4, 2010 |
Analysis Tool and Manufacturing Method Thereof
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.
Inventors: |
Fujii; Tomohiro; (Kyoto,
JP) ; Kusaka; Yasuhide; (Kyoto, JP) |
Correspondence
Address: |
THOMAS, KAYDEN, HORSTEMEYER & RISLEY, LLP
600 GALLERIA PARKWAY, S.E., STE 1500
ATLANTA
GA
30339-5994
US
|
Assignee: |
ARKRAY, INC.
Kyoto
JP
|
Family ID: |
40591170 |
Appl. No.: |
12/740834 |
Filed: |
October 31, 2008 |
PCT Filed: |
October 31, 2008 |
PCT NO: |
PCT/JP2008/069981 |
371 Date: |
July 14, 2010 |
Current U.S.
Class: |
204/400 ;
427/554; 427/77 |
Current CPC
Class: |
G01N 27/3272 20130101;
B05D 5/12 20130101; G01N 27/3271 20130101; B32B 38/04 20130101 |
Class at
Publication: |
204/400 ; 427/77;
427/554 |
International
Class: |
G01N 27/26 20060101
G01N027/26; B05D 5/12 20060101 B05D005/12 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 31, 2007 |
JP |
2007-282781 |
Claims
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.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] 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.
TECHNICAL FIELD
[0002] 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).
BACKGROUND ART
[0003] 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 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 64A, and the portions of the electrodes 61 and 62
exposed by the opening 64A constitute a reactive electrode 61A and
an counter electrode 62A.
[0004] In the biosensor 6, the area of the reactive electrode 61A
or the counter electrode 62A is controlled by the opening 64A of
the insulating film 64. In other words, it is necessary to form the
insulating film 64 using, for example, photolithography in order to
control the area of the reactive electrode 61A or the counter
electrode 62A. In addition, a deviation may be generated in the
area of the reactive electrode 61A due to a deviation in the
dimension of the opening 64A between plural glucose sensors 6. The
reactive electrode 61A facilitates transfer of electrons from/to
analysis target components, and a deviation in the area of the
reactive electrode 61A generates a deviation in the sensitivity of
the biosensor 6.
[0005] As a method of controlling an electrode area of the analysis
tool, there is the following method as well.
[0006] In the chemical sensor electrode 7 shown in FIG. 17 hereto,
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). 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.
[0007] 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). In such an electrode strip 8, since 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.
[0008] On the contrary, in the chemical sensor electrode 7 or the
electrode strip 8 shown in FIGS. 17 and 18, it is necessary to form
the insulating films 72 and 82 using, for example, photolithography
or the like in order to control the area of the electrode main body
section 70 or the reactive electrode 80. Therefore, processes or
equipments for manufacturing the analysis tools 7 and 8 become
complicated, and manufacturing cost increases.
[0009] In the biosensor 9 shown in FIGS. 19A and 19B hereto, 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). In this biosensor 9, since 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. On the other hand, since 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.
DISCLOSURE OF THE INVENTION
Problems to be Solved by the Invention
[0010] 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.
Means of Solving the Problems
[0011] 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.
[0012] 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.
[0013] It is preferable that the first control element is arranged
such that the edge for controlling the contact area traverses the
subsidiary line.
[0014] 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.
[0015] 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.
[0016] 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.
[0017] 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.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] 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.
[0019] FIG. 2 is a cross-sectional view along the line II-II of
FIG. 1.
[0020] FIG. 3 is an exploded perspective view illustrating the
biosensor of FIG. 1.
[0021] FIG. 4 is a top plan view illustrating the biosensor of FIG.
1 by removing the spacer, the reagent layer, and the cover.
[0022] FIG. 5 is a perspective diagram for describing a method of
manufacturing the biosensor of FIG. 1.
[0023] FIG. 6A is a perspective diagram for describing a method of
manufacturing the biosensor of FIG. 1, and FIG. 6B is a top plan
view illustrating main components of FIG. 6A.
[0024] FIGS. 7A and 7B are top plan views for describing a method
of manufacturing the biosensor of FIG. 1.
[0025] 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.
[0026] FIGS. 9A and 9B are perspective diagrams for describing a
method of manufacturing the biosensor of FIG. 1.
[0027] FIG. 10 is a perspective diagram for describing effects of
the method of manufacturing the biosensor according to the present
invention.
[0028] FIGS. 11A-C are top plan views corresponding to FIG. 4 for
describing additional examples of the analysis tool according to
the present invention.
[0029] 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.
[0030] FIG. 13 is an exploded perspective diagram illustrating the
biosensor of FIG. 12.
[0031] FIG. 14 is a top plan view illustrating the biosensor of
FIG. 12 by removing the spacer, the reagent layer, and the
cover.
[0032] 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.
[0033] FIG. 16 is a top plan view illustrating main components of
the biosensor as an example of the analysis tool of the related
art.
[0034] FIG. 17 is a top plan view illustrating a chemical sensor
electrode as another example of the analysis tool of the related
art.
[0035] 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.
[0036] 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, and FIG. 19B is a top plan view
illustrating the biosensor of FIG. 19A by removing the reagent
layer and the cover.
BEST MODE FOR CARRYING OUT THE INVENTION
[0037] 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.
[0038] First, the first embodiment of the present invention will be
described with reference to FIGS. 1 to 10.
[0039] 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. In the biosensor 1, a capillary 13 extending in the
width direction D1 of the substrate 10 is defined by each element
10 to 12.
[0040] 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. On the
surface of the substrate 10, electrodes 14 and 15 and a reagent
layer 16 are provided.
[0041] The electrodes 14 and 15 are formed to have a band shape
extending in the longitudinal direction D2 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 14A and the counter electrode 15A) and terminal portions
14B and 15B.
[0042] The reactive electrode 14A and the counter electrode 15A 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 .mu.m. The reactive electrode 14A and the
counter electrode 15A make contact with the specimen introduced
into the capillary 13. Here, the reactive electrode 14A performs
transfer of electrons from/to analysis target components within the
specimen, and the area of the reactive electrode 14A influences the
measurement accuracy of the biosensor 1.
[0043] As shown in FIGS. 3 and 4, 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 18A and 19A, and subsidiary
lines 18B and 19B. Here, the effective area of the 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, the reactive 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
providing slits 18 and 19 in comparison with the area making
contact with the specimen inside the capillary 13. Here, the area
of the reactive electrode 14A substantially contributing to such
transfer of electrons is referred to as an effective area.
[0044] The main lines 18A and 19A extend in a direction of D1, 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 18A
and 19A is set to, for example, 30% to 98% of the distance between
a pair of the spacers 11. On the other hand, the subsidiary lines
18B and 19B extend in the direction of D2. The slit 18 has a
U-shape, and the slit 19 has a rectangular shape.
[0045] As shown in FIGS. 1 to 3, the terminal portions 14B and 15B
are provided to make contact with a connector (not shown) of the
analyzer when the biosensor 1 is installed in the analyzer.
[0046] The reagent layer 16 is to cover the reactive electrode 14A
and the counter electrode 15A 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.
[0047] 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.sub.3).sub.6]Cl.sub.3 or
K.sub.3-[Fe(CN).sub.6].
[0048] 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. In other words, 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 14A and the counter electrode 15A) in the
electrodes 14 and 15.
[0049] 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.
[0050] 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 the capillary 13. In
this case, inside 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.
[0051] Next, a method of manufacturing the biosensor 1 will be
described with reference to FIGS. 5 to 10.
[0052] First, as shown in FIG. 5, 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 .mu.m. The formation of
the conductive layer 20 is performed by, for example, screen
printing, CVD, sputtering, or deposition.
[0053] Next, as shown in FIGS. 6A and 6B, plural separation slits
21 extending in a direction of D2 are formed on the conductive
layer 20. As a result, the conductive layer 20 has plural
band-shape electrodes 20A and 20B insulated from each other. These
slits 21 are formed to have a width of 10 to 300 .mu.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.sub.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.
[0054] Meanwhile, 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 20A and 20B.
[0055] Next, as shown in FIG. 6B, slits 23A and 23B for controlling
an effective area of the reactive electrode 14A are formed. Such
slits 23A and 23B are formed to have main lines 23Aa and 23Ba and
subsidiary lines 23Ab and 23Bb, for example, using a 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 20A and 20B. The distance
between the main lines 23Aa and 23Ba is set to, for example, 30 to
98% of the distance between a pair of spacers 24A and 24B which
will be described below. On the other hand, the subsidiary lines
23Ab and 23Bb extend in a direction of D2, in which the slit 23A
has a U-shape as a whole, and the slit 23B has a rectangular shape
as a whole. Of course, the shapes of the slits 23A and 23B may be
variously changed, for example, such that the slit 23A has a
rectangular shape, and the slit 23B has a U-shape. Alternatively,
both of the slits 23A and 23B may have a U-shape, or both of the
slits 23A and 23B may have a rectangular shape.
[0056] Next, as shown in FIGS. 7A and 7B, plural spacers 24A and
24B are attached to extend in a direction of D1 perpendicular to
plural separation slits 21. Such spacers 24A and 24B may be
attached farther than the distance between the main lines 23Aa and
23Ba such that the main lines 23Aa and 23Ba of the slits 23A and
23B for controlling the effective area of the reactive electrode
14A are exposed. In other words, the spacers 24A and 24B are
arranged such that edges of the spacers 24A and 24B traverse the
subsidiary lines 23Ab and 23Bb of the slits 23A and 23B.
[0057] The spacers 24A and 24B may include, for example, a
double-face adhesive tape or a hot-melt film. The width and the
thickness of each of the spacers 24A and 24B are set to, for
example, 1 to 20 mm and 20 to 300 .mu.m, respectively. The distance
between the spacers 24A and 24B is set to, for example, 100 to 3000
.mu.m.
[0058] As shown in FIG. 8A, even when the positions where the
spacers 24A and 24B are attached are deviated from the target
positions in a direction of D2, or the spacers 24A and 24B are
attached with an inclination as shown in FIG. 8B, it is possible to
suppress a deviation of the effective area of the reactive
electrode 14A as long as edges of the spacers 24A and 24B are
arranged to traverse the subsidiary lines 23Ab and 23Bb of the
slits 23A and 23B. In other words, even when the edges of the
spacers 24A and 24B are deviated from predetermined positions in a
portion having a narrow width on the electron transfer surface
contributing to transfer of electrons in the 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 the
reactive electrode 14 influencing the measurement accuracy of the
biosensor 1. In addition, even when positions of a pair of spacers
24A and 24B are deviated from predetermined positions, if the
distance between a pair of spacers 24A and 24B is within an
allowable range, it is possible to compensate for a variation in
the effective area caused by a positional deviation of the spacer
24A and a variation in the effective area caused by a positional
deviation of the spacer 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 the biosensor 1. Next, as shown in FIG. 9A,
a reagent solution is applied between the spacers 24A and 24B, for
example, using a 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 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.sub.3).sub.6]Cl.sub.3 or
K.sub.3-[Fe(CN).sub.6].
[0059] Next, as shown in FIG. 9A, a sensor assembly 3 is obtained
by attaching the cover 26 so as to bridge the spacers 24A and 24B.
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.
[0060] Finally, plural 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.
[0061] 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 the
reactive 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 the reactive
electrode 14A of the biosensor 1.
[0062] In addition, since the effective area of the reactive
electrode 14A 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 14A. Therefore,
it is possible to control the area of the electron transfer surface
of the reactive electrode 14A in a simple, easy, and inexpensive
manner without complicating the manufacturing processes or
equipments.
[0063] In addition, if the slits 23A and 23B, and the laser
oscillator 22 are used to control the area of the electron transfer
surface of the reactive electrode 14A 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 23A and 23B. 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 14A in a simple, easy, and inexpensive manner.
[0064] 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.
[0065] In the example shown in FIG. 11A, the slits 18 and 19 for
controlling the effective area of the reactive electrode 14A are
formed in an L-shape and a U-shape, respectively, by omitting one
of the subsidiary lines in the slits 18 and 19.
[0066] In the example shown in FIG. 11B, the slit 18 for
controlling the effective area of the reactive electrode 14A 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.
[0067] In the example shown in FIG. 11C, the slits 18 and 19 for
controlling the effective area of the reactive electrode 14A 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 15A. The slits 18 and 19 and the slits 18' and
19' are symmetrically arranged with respect to the separation slit
17.
[0068] Next, the second embodiment of the present invention will be
described with reference to FIGS. 12 to 14.
[0069] 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).
[0070] Electrodes 43 and 44 are formed on the substrate 40. The
electrodes 43 and 44 have bending portions 43A and 44A extending in
a direction of D1 and lead portions 43B and 44B extending in a
direction of D2. The bending portions 43A and 44A are arranged in
parallel in a direction of D2, and include an reactive electrode
43Aa and the counter electrode 44Aa defined by the spacer 41. In
addition, slits 45 and 46 are formed in the bending portion 43A.
Such slits 45 and 46 are provided to define the area (the effective
area) of the electron transfer surface of the reactive electrode
43Aa. 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 45A and 46A and subsidiary lines 45B and 46B.
[0071] 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 bending portion 43A. The distance between the main lines 45A
and 46A is set to, for example, 30 to 98% of the width of the slit
in the spacer 41 which will be described below. On the other hand,
the subsidiary lines 45B and 46B extend in a direction of D1, the
slit 45 is formed in a U-shape, and the slit 46 is formed in a
rectangular shape.
[0072] 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 43Aa
and the counter electrode 44Aa) 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 D2 traverses the
subsidiary lines 45B and 46B of the slits 45 and 46.
[0073] 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, the reagent layer 48A is
formed to cover at least the reactive electrode 43Aa. Such a spacer
41 is configured of, for example, a double-face adhesive tape or a
hot-melt film.
[0074] 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.
[0075] In the biosensor 4, since the effective area of the reactive
electrode 43Aa is defined by the slits 45 and 46, a deviation in
the area of the reactive electrode 43Aa 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.
[0076] Since the effective area of the reactive electrode 43Aa 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 43Aa.
Therefore, it is possible to control the area of the reactive
electrode 43Aa in a simple, easy, and inexpensive manner without
complicating the manufacturing processes or equipments.
[0077] Meanwhile, 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.
[0078] 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.
[0079] The present invention is also applicable to the biosensor
obtained by omitting the covers 12 and 42.
Example 1
[0080] 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.
[0081] (Manufacturing of Biosensor)
[0082] 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
.mu.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. 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.
[0083] 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 mm.sup.2. In the comparison sample, the
target area of the reactive electrode was set to 1.2 mm.sup.2.
[0084] The reagent layer containing [Ru(NH.sub.3)Cl.sub.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.
[0085] (Measurement of Area of Reactive Electrode)
[0086] 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-US-00001 TABLE 1 Original Sensor Comparison Sensor No. Area
of Reactive Electrode [mm.sup.2] Area of Reactive Electrode
[mm.sup.2] 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
[0087] 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.
Example 2
[0088] 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.
[0089] As the biosensor, an original sensor and a comparison sensor
were manufactured in a similar way to Example 1.
[0090] 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-US-00002 TABLE 2 Original Sensor Comparison Sensor Area of
Area of Reactive Response Reactive Response Electrode Electric
Current Electrode Electric Current No. [mm.sup.2] Value [.mu.A]
[mm.sup.2] Value [.mu.A] 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
[0091] 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.
* * * * *