U.S. patent application number 10/871937 was filed with the patent office on 2005-05-19 for biosensor and method of making.
Invention is credited to Bhullar, Raghbir S., Diebold, Eric R., Hill, Brian S., Surridge, Nigel, Walling, Paul Douglas.
Application Number | 20050103624 10/871937 |
Document ID | / |
Family ID | 43385575 |
Filed Date | 2005-05-19 |
United States Patent
Application |
20050103624 |
Kind Code |
A1 |
Bhullar, Raghbir S. ; et
al. |
May 19, 2005 |
Biosensor and method of making
Abstract
An electrochemical biosensor with electrode elements that
possess smooth, high-quality edges. These smooth edges define gaps
between electrodes, electrode traces and contact pads. Due to the
remarkable edge smoothness achieved with the present invention, the
gaps can be quite small, which provides marked advantages in terms
of test accuracy, speed and the number of different functionalities
that can be packed into a single biosensor. Further, the present
invention provides a novel biosensor production method in which
entire electrode patterns for the inventive biosensors can be
formed all at one, in nanoseconds--without regard to the complexity
of the electrode patterns or the amount of conductive material that
must be ablated to form them.
Inventors: |
Bhullar, Raghbir S.;
(Indianapolis, IN) ; Diebold, Eric R.; (Fishers,
IN) ; Hill, Brian S.; (Avon, IN) ; Surridge,
Nigel; (Carmel, IN) ; Walling, Paul Douglas;
(Indianapolis, IN) |
Correspondence
Address: |
WOODARD, EMHARDT, MORIARTY, MCNETT & HENRY LLP
BANK ONE TOWER/CENTER
111 MONUMENT CIRCLE, SUITE 3700
INDIANAPOLIS
IN
46204-5137
US
|
Family ID: |
43385575 |
Appl. No.: |
10/871937 |
Filed: |
June 18, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10871937 |
Jun 18, 2004 |
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10601144 |
Jun 20, 2003 |
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10601144 |
Jun 20, 2003 |
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09411940 |
Oct 4, 1999 |
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6662439 |
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10601144 |
Jun 20, 2003 |
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09684257 |
Oct 6, 2000 |
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6645359 |
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10601144 |
Jun 20, 2003 |
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09840843 |
Apr 24, 2001 |
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6767440 |
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10601144 |
Jun 20, 2003 |
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10264891 |
Oct 4, 2002 |
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Current U.S.
Class: |
204/403.01 ;
427/58 |
Current CPC
Class: |
H05K 1/0393 20130101;
C12Q 1/001 20130101; Y10T 29/49156 20150115; H05K 3/027 20130101;
G01N 27/3272 20130101; Y10T 29/49155 20150115; Y10T 29/49117
20150115; G01N 33/5438 20130101 |
Class at
Publication: |
204/403.01 ;
427/058 |
International
Class: |
G01N 027/26 |
Claims
What is claimed is:
1. A biosensor, comprising: a base substrate having first and
second electrode elements formed thereon; the first and second
electrode elements having first and second respective edges
defining a gap therebetween, the gap having a width and a length;
the first edge being spaced from a first theoretical line by a
first distance that varies along the length of the gap, the first
theoretical line defining a desired shape and placement of the
first edge, wherein the standard deviation of the first distance is
less than about 6 .mu.m over the entire length of the gap; a
reagent at least partially covering the base substrate; and one or
more layers overlying and adhered to the base substrate, the one or
more layers cooperating to form a sample-receiving chamber and a
cover for the biosensor, at least a portion of the reagent and an
electrode being positioned in the chamber.
2. The biosensor of claim 1, wherein the standard deviation of the
first distance is less than about 2 .mu.m.
3. The biosensor of claim 1, wherein the standard deviation of the
first distance is less than about 1 .mu.m.
4. The biosensor of claim 1, wherein the second edge is spaced from
a second theoretical line by a second distance that varies along
the length of the gap, the second theoretical line defining a
desired shape and placement of the second edge, wherein the
standard deviation of the second distance is less than about 6
.mu.m over the entire length of the gap.
5. The biosensor of claim 4, wherein the standard deviation of both
the first distance and the second distance is less than about 2
.mu.m.
6. The biosensor of claim 4, wherein the standard deviation of both
the first distance and the second distance is less than about 1
.mu.m.
7. The biosensor of claim 1, wherein the gap width is about 250
.mu.m or less.
8. The biosensor of claim 1, wherein the gap width is less than
about 50 .mu.m.
9. The biosensor of claim 1, wherein the gap width is less than
about 20 .mu.m.
10. The biosensor of claim 1, wherein the electrode elements are
formed by broad field laser ablation.
11. The biosensor of claim 1, wherein the first and second
electrode elements comprise a first electrode set, one of the
electrodes of the set being the electrode positioned in the sample
receiving chamber.
12. The biosensor of claim 11, further comprising a second
electrode set formed on the base substrate, the second electrode
set having a different feature size than the first electrode
set.
13. The biosensor of claim 1, wherein the first and second
electrode elements comprise first and second electrode traces.
14. The biosensor of claim 1, wherein the first and second
electrode elements comprise first and second contact pads.
15. The biosensor of claim 1, wherein the length of the gap is at
least 0.1 mm.
16. The biosensor of claim 1, wherein the length of the gap is at
least 1 mm.
17. The biosensor of claim 1, wherein the length of the gap is at
least 1 cm.
18. The biosensor of claim 1, wherein the length of the gap is at
least one third the length of the biosensor.
19. The biosensor of claim 1, wherein the length of the gap is at
least one half the length of the biosensor.
20. The biosensor of claim 1, wherein the gap is positioned within
the sample receiving chamber.
21. The biosensor of claim 1, wherein the electrode elements
comprise contact pads and the gap extends between the contact
pads.
22. The biosensor of claim 1, wherein the electrode elements
comprise electrode traces and the gap extends between the electrode
traces.
23. The biosensor of claim 1, wherein the electrode elements
comprise a working electrode and a counter electrode and the gap
extends between the working electrode and the counter
electrode.
24. The biosensor of claim 23, wherein the gap extends across the
sample receiving chamber.
25. A biosensor, comprising: a base substrate having first and
second electrode elements formed thereon; the first and second
electrode elements having first and second respective edges
defining a gap therebetween, the gap having a width and a length;
the first edge being spaced from a first theoretical line by a
first distance that varies along the length of the gap, the first
theoretical line defining a desired shape and placement of the
first edge, wherein the first distance is less than about 6 .mu.m
over the entire length of the gap; a reagent at least partially
covering the base substrate; and one or more layers overlying and
adhered to the base substrate, the one or more layers cooperating
to form a sample-receiving chamber and a cover for the biosensor,
at least a portion of the reagent layer and an electrode being
positioned in the chamber.
26. The biosensor of claim 25, wherein the first distance is less
than about 2 .mu.m.
27. The biosensor of claim 25, wherein the first distance is less
than about 1 .mu.m.
28. The biosensor of claim 25, wherein the second edge is spaced
from a second theoretical line by a second distance that varies
along the length of the gap, the second theoretical line defining a
desired shape and placement of the second edge, wherein the second
distance is less than about 6 .mu.m over the entire length of the
gap.
29. The biosensor of claim 28, wherein the first distance and the
second distance are both less than about 4 .mu.m.
30. The biosensor of claim 28, wherein the first distance and the
second distance are both less than about 2 .mu.m.
31. The biosensor of claim 25, wherein the electrode elements are
formed by broad field laser ablation.
32. The biosensor of claim 25, wherein the first and second
electrode elements comprise an electrode set, one of the electrodes
of the set being the electrode positioned in the sample receiving
chamber.
33. The biosensor of claim 32, further comprising a second
electrode set formed on the base substrate, the second electrode
set having a different feature size than the first electrode
set.
34. The biosensor of claim 25, wherein the first and second
electrode elements comprise first and second electrode traces.
35. The biosensor of claim 25, wherein the first and second
electrode elements comprise first and second contact pads.
36. A method of making a biosensor comprising the following steps:
providing a base substrate having a layer of electrically
conductive material thereon; removing a portion of the conductive
material to form first and second electrode elements on the base
substrate having first and second respective edges defining a gap
therebetween, the gap having a width and a length; the first edge
being spaced from a first theoretical line by a first distance that
varies along the length of the gap, the first theoretical line
defining a desired shape and placement of the first edge, wherein
the standard deviation of the first distance is less than about 6
.mu.m over the entire length of the gap; providing a reagent at
least partially covering the base; and adhering one or more layers
to the base, the one or more layers cooperating to form a
sample-receiving chamber and a cover for the biosensor, at least a
portion of the reagent and an electrode being positioned within the
chamber.
37. The method of claim 36, further comprising removing at least
10% of the conductive material.
38. The method of claim 36, further comprising removing at least
50% of the conductive material.
39. The method of claim 36, further comprising removing at least
90% of the conductive material.
40. The method of claim 36, wherein the electrically conductive
material is removed by broad field laser ablation.
41. The method of claim 36, wherein the first and second electrode
elements comprise a first electrode set.
42. The method of claim 41, further comprising forming a second
electrode set on the base substrate having a feature size different
from the first electrode set, one of the electrodes of the first
electrode set being the electrode positioned within the sample
receiving chamber and one of the electrodes of the second electrode
set being positioned in the sample receiving chamber.
43. The method of claim 36, wherein the standard deviation is less
than about 2 .mu.m.
44. The method of claim 36, wherein the standard deviation is less
than about 1 .mu.m.
45. The method of claim 36, further comprising forming the
electrode elements in less than about 0.25 seconds.
46. The method of claim 36, further comprising forming the
electrode elements in less than about 50 nanoseconds.
47. The method of claim 36, further comprising forming the
electrode elements in less than about 25 nanoseconds.
48. The method of claim 36, wherein the step of adhering the one or
more layers to the base comprises laminating a spacing layer having
a void that defines the perimeter of the sample receiving chamber
over the base substrate and laminating a covering layer over the
spacing layer.
49. The method of claim 48, further comprising forming a vent
opening in the covering layer that communicates with the sample
receiving chamber.
50. A method of forming a biosensor used to measure presence or
concentration of an analyte in a fluid sample, comprising: (a)
providing an electrically conductive material on a base; (b)
removing a portion of the electrically conductive material by broad
field laser ablation to form an electrode set on the base; (c)
providing a reagent at least partially covering the base; and (d)
adhering one or more layers to the base, the one or more layers
cooperating to form a sample-receiving chamber and a cover for the
biosensor, at least a portion of both the reagent layer and the
electrode set being positioned in the chamber.
51. The method of claim 50, wherein the electrode set comprises
first and second electrodes having first and second respective
edges defining a gap therebetween, the gap having a width and a
length, the first edge being spaced from a first theoretical line
by a first distance that varies along the length of the gap, the
first theoretical line defining a desired shape and placement of
the first edge, wherein the standard deviation of the first
distance is less than about 6 .mu.m over the entire length of the
gap.
52. The method of claim 51, wherein the standard deviation of the
first distance is less than about 2 .mu.m.
53. The method of claim 51, wherein the standard deviation of the
first distance is less than about 1 .mu.m.
54. The method of claim 51, wherein the electrode set comprises at
least two electrode sets having different feature sizes.
55. The method of claim 50, wherein the electrode set comprises at
least two electrode sets having different feature sizes.
56. The method of claim 50, wherein step (c) comprises at least
partially covering the electrode set with the reagent.
57. The method of claim 50, further comprising removing at least
10% of the conductive material.
58. The method of claim 50, further comprising removing at least
50% of the conductive material.
59. The method of claim 50, further comprising removing at least
90% of the conductive material.
60. A method of forming a biosensor used to measure concentration
of an analyte in a fluid sample, comprising: (a) providing an
electrically conductive material on a base; (b) removing at least
10% of the electrically conductive material to form at least two
electrode sets on the base, the electrode sets having different
feature sizes; (c) providing a reagent at least partially covering
the base; and (d) adhering one or more layers to the base, the one
or more layers cooperating to form a sample-receiving chamber, at
least a portion of one of the electrode sets being positioned in
the chamber.
61. The method of claim 60, further comprising removing at least
50% of the conductive material.
62. The method of claim 60, further comprising removing at least
90% of the conductive material.
63. The method of claim 60, wherein the electrically conductive
material is removed by broad field laser ablation.
64. The method of claim 60, wherein one of the electrode sets
comprises first and second electrodes having first and second
respective edges defining a gap therebetween, the gap having a
width and a length, the first edge being spaced from a first
theoretical line by a first distance that varies along the length
of the gap, the first theoretical line defining a desired shape and
placement of the first edge, wherein the standard deviation of the
first distance is less than about 6 .mu.m over the entire length of
the gap.
65. The method of claim 64, wherein the standard deviation of the
first distance is less than about 2 .mu.m.
66. The method of claim 64, wherein the standard deviation of the
first distance is less than about 1 .mu.m.
67. The method of claim 60, wherein step (c) comprises at least
partially covering the electrode set with the reagent.
68. A method of manufacturing a plurality of biosensors,
comprising: (a) providing a web of base substrate material having a
metal conductive layer formed thereon; (b) projecting an image of
an electrode pattern onto the metal conductive layer with a laser
apparatus, wherein an electrode pattern that corresponds to the
image is formed by laser ablation on the web of base substrate
material; (c) moving one of the laser apparatus and the web of base
substrate material and repeating step (b) a plurality of times to
produce a plurality of the electrode patterns at spaced intervals
along the web of base substrate material; (d) depositing a reagent
on the web of base substrate material and at least partially
covering each electrode pattern of the plurality of electrode
patterns with the reagent; (e) laminating at least one web of a
covering layer or a spacing layer over the web of base substrate
material, thereby forming a cover and a sample-receiving chamber
for each biosensor; and (f) cutting through the at least one web of
a covering layer or a spacing layer and the web of base substrate
material to form the plurality of biosensors.
69. The method of claim 68, wherein the electrode pattern formed in
step (b) comprises a complete electrode pattern for one of the
biosensors, whereby the complete electrode pattern for each
biosensor is formed in a single step.
70. The method of claim 68, wherein the electrode pattern formed in
step (b) comprises a partial electrode pattern, the image comprises
a plurality of the same or different images, and steps (b) and (c)
are repeated until the plurality of electrode patterns comprises a
plurality of complete electrode patterns, whereby each complete
electrode pattern is formed in multiple steps.
71. The method of claim 68, wherein step (c) comprises continuously
moving the web of base substrate material.
72. The method of claim 68, wherein step (c) comprises moving the
web of base substrate material in discrete increments.
73. The method of claim 68, wherein step (c) comprises moving the
web of base substrate material at a rate of at least 10 meters per
minute.
74. The method of claim 68, wherein the electrode pattern includes
at least two electrode sets having different feature sizes.
75. The method of claim 68, wherein the electrode pattern comprises
first and second electrodes having first and second respective
edges defining a gap therebetween, the gap having a width and a
length, the first edge being spaced from a first theoretical line
by a first distance that varies along the length of the gap, the
first theoretical line defining a desired shape and placement of
the first edge, wherein the standard deviation of the first
distance is less than about 6 .mu.m over the entire length of the
gap.
76. The method of claim 75, wherein the standard deviation is less
than about 2 .mu.m.
77. The method of claim 75, wherein the standard deviation is less
than about 1 .mu.m.
78. The method of claim 68, wherein the metal conductive layer
comprises at least one member selected form the group consisting of
gold, platinum, palladium and iridium.
79. The method of claim 68, wherein step (e) comprises: laminating
the spacing layer over the base substrate material, the spacing
layer having a void that defines the perimeter of the chamber; and
laminating the covering layer over the spacing layer.
80. The method of claim 68, wherein each electrode pattern formed
in step (b) is formed in less than 1 second.
81. The method of claim 68, wherein each electrode pattern formed
in step (b) is formed in less than 0.25 second.
82. The method of claim 68, wherein each electrode pattern formed
in step (b) is formed all at once.
83. The method of claim 68, wherein each electrode pattern formed
in step (b) comprises the entire electrode pattern for one of the
biosensors and each entire electrode pattern is formed all at
once.
84. The method of claim 68, wherein the reagent is applied in a
substantially continuous stripe.
85. The method of claim 68, wherein the electrode pattern is
anisotropic.
86. The method of claim 68, wherein the electrode pattern is
asymmetric.
87. The method of claim 68, wherein the electrode pattern formed in
step (b) comprises a complete electrode pattern for one of the
biosensors, whereby the complete electrode pattern for each
biosensor is formed in a single step, the method further comprising
forming the complete electrical patterns at a rate of at least 100
per minute.
88. The method of claim 87, wherein forming the electrode patterns
comprises removing at least 20% of the metal conductive layer.
89. The method of claim 87, wherein forming the electrode patterns
comprises removing at least 50% of the metal conductive layer.
90. The method of claim 87, wherein forming the electrode patterns
comprises removing at least 90% of the metal conductive layer.
91. The method of claim 68, wherein the electrode pattern formed in
step (b) comprises a complete electrode pattern for one of the
biosensors, whereby the complete electrode pattern for each
biosensor is formed in a single step, the method further comprising
forming the complete electrical patterns at a rate of at least 1000
per minute.
92. The method of claim 91, wherein forming the electrode patterns
comprises removing at least 20% of the metal conductive layer.
93. The method of claim 91, wherein forming the electrode patterns
comprises removing at least 50% of the metal conductive layer.
94. The method of claim 91, wherein forming the electrode patterns
comprises removing at least 90% of the metal conductive layer.
95. The method of claim 68, wherein the electrode pattern formed in
step (b) comprises a complete electrode pattern for one of the
biosensors, whereby the complete electrode pattern for each
biosensor is formed in a single step, the method further comprising
forming the complete electrical patterns at a rate of at least 2000
per minute.
96. The method of claim 95, wherein forming the electrode patterns
comprises removing at least 20% of the metal conductive layer.
97. The method of claim 95, wherein forming the electrode patterns
comprises removing at least 50% of the metal conductive layer.
98. The method of claim 95, wherein forming the electrode patterns
comprises removing at least 90% of the metal conductive layer.
99. The method of claim 68, wherein the electrode pattern formed in
step (b) comprises a complete electrode pattern for one of the
biosensors, whereby the complete electrode pattern for each
biosensor is formed in a single step, the method further comprising
forming the complete electrical patterns at a rate of at least 3000
per minute.
100. The method of claim 99, wherein forming the electrode patterns
comprises removing at least 20% of the metal conductive layer.
101. The method of claim 99, wherein forming the electrode patterns
comprises removing at least 50% of the metal conductive layer.
102. The method of claim 99, wherein forming the electrode patterns
comprises removing at least 90% of the metal conductive layer.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a Continuation in Part of U.S.
patent application Ser. No. 09/840,843, filed Apr. 24, 2001; a
Continuation in Part of U.S. application Ser. No. 10/264,891, filed
Oct. 4, 2002; a Continuation-in-Part of U.S. application Ser. No.
10/601,144, filed Jun. 20, 2003; and claims priority to U.S. patent
application Ser. No. 60/480,397, filed Jun. 20, 2003, each of which
is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to a method of making a
biosensor, more specifically a biosensor having electrode sets
formed by laser ablation.
BACKGROUND
[0003] Electrochemical biosensors are well known and have been used
to determine the concentration of various analytes from biological
samples, particularly from blood. Examples of such electrochemical
biosensors are described in U.S. Pat. Nos. 5,413,690; 5,762,770 and
5,798,031; and 6,129,823 each of which is hereby incorporated by
reference.
[0004] It is desirable for electrochemical biosensors to be able to
analyze analytes using as small a sample as possible, and it is
therefore necessary to minimize the size of their parts, including
the electrodes, as much as possible. As discussed below,
screen-printing, laser scribing, and photolithography techniques
have been used to form miniaturized electrodes.
[0005] Electrodes formed by screen-printing techniques are formed
from compositions that are both electrically conductive and
screen-printable. Furthermore, screen printing is a wet chemical
technique that generally allows reliable formation of structures
and patterns having a gap width or feature size of approximately 75
.mu.m or greater. Such techniques are well known to those of
ordinary skill in the art.
[0006] Laser scribing is a technique that usually uses a high power
excimer laser, such as a krypton-fluoride excimer laser with an
illumination wavelength of 248 nm, to etch or scribe individual
lines in the conductive surface material and to provide insulating
gaps between residual conductive material which forms electrodes
and other desired components. This scribing is accomplished by
moving the laser beam across the surface to be ablated. The
scribing beam generally has a relatively small, focused size and
shape, which is smaller than the features desired for the product,
and the formation of the product therefore requires rastering
techniques. Such a technique can be rather time consuming if a
complex electrode pattern is to be formed on the surface. Further,
the precision of the resulting edge is rather limited. This
scribing technique has been used to ablate metals, polymers, and
biological material. Such systems are well known to those of
ordinary skill in the art, and are described in U.S. Pat. Nos.
5,287,451, 6,004,441, 6,258,229, 6,309,526, WO 00/73785, WO
00/73788, WO 01/36953, WO 01/75438, and EP 1 152 239 each of which
is hereby incorporated by reference. It would be desirable to have
a new method of forming electrodes which allows precise electrode
edges, a variety of feature sizes, and which can be formed in a
high speed/throughput fashion without the use of rastering.
SUMMARY OF THE INVENTION
[0007] The present invention provides an electrochemical biosensor
with electrode elements that possess smooth, high-quality edges.
These smooth edges define gaps between electrodes, electrode traces
and contact pads. Due to the remarkable edge smoothness achieved
with the present invention, the gaps can be quite small, the
advantages of which are described below. Further, the present
invention provides a novel biosensor production method in which
entire electrode patterns for the inventive biosensors can be
formed all at one, in nanoseconds--irrespecti- ve of the complexity
of the electrode patterns or the amount of conductive material that
must be ablated to form them.
[0008] In one form thereof, the present invention provides a
biosensor comprising a base substrate having first and second
electrode elements formed thereon. The first and second electrode
elements have first and second respective edges defining a gap
therebetween. The gap has a width and a length. The first edge is
spaced by a first distance from a first "theoretical line" that
corresponds to the desired or ideal shape and location of the first
edge. This first distance varies along the length of the gap
because the edge actually produced is not as smooth or perfect as
the desired theoretical line. The standard deviation of the first
distance is less than about 6 .mu.m over the entire length of the
gap. The biosensor also includes a reagent at least partially
covering the base substrate and one or more layers overlying and
adhered to the base substrate. The one or more layers cooperate to
form a sample-receiving chamber and a cover for the biosensor, and
at least a portion of both the reagent and an electrode are
positioned in the chamber.
[0009] In a related form of the inventive biosensor described
above, the actual or real deviation of the edge from the
theoretical line is no more than about 6 .mu.m along the entire
length of the gap. Stated another way, the distance between the
edge actually produced and the theoretical line (if the edge were
perfect) is less than 6 .mu.m no matter where along the gap the
distance is measured. More preferably, the real deviation is less
than about 4 .mu.m, most preferably less than about 2 .mu.m. In
this most preferred form, it is possible to space the electrodes as
close as about 5 .mu.m without having the electrical components
touch and thus short. Similarly, the width of the features of the
electrical pattern such as electrode fingers or traces can be as
narrow as about 10 .mu.m. As discussed in detail below, the close
spacing of electrode components allowed by the present invention in
turn allows a greater number of electrode elements and thus greater
functionality in a smaller area.
[0010] The smoothness or quality of the edges is most important in
areas of the biosensor where adjacent edges are positioned close to
one another, e.g., the gap between two electrodes. In a preferred
aspect of the present invention, like the first edge discussed
above, the second edge is spaced from a second theoretical line by
a second distance that varies along the length of the gap. The
first and the second theoretical lines thus define a "theoretical
gap" therebetween. If the production process were perfect, and if
the edges were intended to be straight and parallel to one another,
the theoretical gap width would be constant along its length. In
practice, however, the actual gap width varies from the theoretical
one along the length of the gap. Deviations from theoretical of the
first and second edges can be compounded to produce larger
variations in the actual gap width than are produced in either edge
alone. In a preferred form of the invention, the standard deviation
of the second distance is less than about 6 .mu.m over the entire
length of the gap. More preferably, the standard deviation of both
the first and second distances is less than about 2 .mu.m, even
more preferably, less than about 1 .mu.m.
[0011] In another preferred form of the invention, the method
comprises removing at least 10% of the conductive material, more
preferably at least 50% of the conductive material, and most
preferably at least 90% of the conductive material. The conductive
material is preferably removed by broad field laser ablation, which
allows relatively large percentages of the conductive layer to be
removed from the base substrate very quickly to form electrode
patterns. For example, in preferred forms, the entire electrode
pattern for a biosensor is formed by broad field laser ablation in
less than about 0.25 seconds, more preferably in less than about 50
nanoseconds, and most preferably in less than about 25
nanoseconds.
[0012] As noted above, the inventive method also allows for the
placement of two or more electrode sets having different feature
sizes in the same biosensor. Furthermore, as noted above, the
feature sizes can be quite small and spaced close together.
[0013] In another form, the present invention provides an efficient
and fast method for mass producing biosensors having electrode
patterns with the highly desirable smooth edges discussed above. In
this method, a web of base substrate material having a metal
conductive layer formed thereon is provided. An image of an
electrode pattern is projected onto the metal conductive layer with
a laser apparatus such that an electrode pattern that corresponds
to the image is formed by laser ablation on the web of base
substrate material. Either the laser apparatus or the web of base
substrate material (or both) is moved and this process is repeated
to produce many electrode patterns at spaced intervals along the
web of base substrate material. A reagent is deposited on the web
of base substrate material and at least partially covers each
electrode pattern of the plurality of electrode patterns. At least
one web of a covering layer or a spacing layer is laminated over
the web of base substrate material, thereby forming a cover and a
sample-receiving cavity for each biosensor. The resulting laminated
web of layers is then cut into individual biosensors.
[0014] In a preferred form, the image projected by the laser
apparatus is of the complete electrode pattern for one of the
biosensors, such that the complete electrode pattern for each
biosensor is formed in a single step with a single laser image. In
another preferred form, more than one entire electrode pattern is
formed all at once; i.e., the image includes patterns for two or
more biosensors.
[0015] In another preferred form, the electrode pattern includes at
least two electrode sets having different feature sizes. Examples
of this may include one set of electrodes for measuring analyte
concentration and another set for detecting whether and when the
biosensor has received an adequate dose of sample fluid. The
inventive biosensor may also include electrode elements providing
other features, such as biosensor identification, calibration or
other information associated with the biosensor.
[0016] One advantage of this inventive mass production process is
that it is much faster than prior art processes that require
forming electrode patterns by screen printing, lithography,
rastering and the like. With the laser ablation process employed by
the present invention, the entire electrode pattern for a biosensor
can be formed all at once, in a single step, in only nanoseconds.
This allows a continuous web of material from which the individual
biosensors will ultimately be cut to be processed at speeds of 60
meters per minute or greater.
[0017] Not only is the inventive process much faster than prior art
processes, it provides biosensors with electrode patterns whose
edges have much better edge quality than prior art biosensors. Edge
quality becomes increasingly important as electrode spacing becomes
closer. Close electrode spacing is desirable because it generally
increases the accuracy of the test result, reduces sample size, and
yields a quicker test. Additionally, it allows a greater quantity
of electrode elements and associated functionalities to be packed
into a single biosensor.
[0018] Yet another advantage of the inventive production method is
that it allows a large percentage of the electrically conductive
layer to be removed from the base substrate all at once. By
contrast, prior art rastering processes use a collimated laser beam
that slowly scribes and removes only a thin line of conductive
material, which is a much longer and less versatile process in
comparison with the present invention.
[0019] Another advantage related to the one just noted is that the
manufacturing process of the present invention provides great
freedom in the shape and variation in the electrode pattern
produced in the inventive biosensors. Asymmetric or anisotropic
electrode patterns do not present a problem with the manufacturing
process of the present invention. Further, since the electrode
pattern is preferably projected on the base substrate by a laser
image formed by a mask, limitations as to size, shape, number of
electrode patterns, gap width, etc. that are encountered with prior
art processes are reduced. By comparison, rastering processes are
typically limited to movement of a focused laser beam along axes
that are oriented 90 degrees relative to one another. The resulting
patterns typically are limited to thin lines of the same width
oriented parallel or perpendicular to one another. In addition,
separate but adjacent conductive metal planes used to carry
separate signals in a device can capacitively couple when the
separation distance between the planes becomes very small resulting
in signal degradation and interference between the planes. A method
that allows removal of more conductive material between isolated
traces therefore can be advantageous in minimizing such
interference.
[0020] The following definitions are used throughout the
specification and claims:
[0021] As used herein, the phrase "electrically conductive
material" refers to a layer made of a material that is a conductor
of electricity, non-limiting examples of which include a pure metal
or alloys.
[0022] As used herein, the phrase "electrically insulative
material" refers to a material that is a nonconductor of
electricity.
[0023] As used herein, the term "electrode" means a conductor that
collects or emits electric charge and controls the movement of
electrons. An electrode may include one or more elements attached
to a common electrical trace and/or contact pad.
[0024] As used herein, the term "electrical component" means a
constituent part of the biosensor that has electrical
functionality.
[0025] As used herein, the phrase "electrode system" refers to an
electrical component including at least one electrode, electrical
traces and contacts that connect the element with a measuring
instrument.
[0026] As used herein, the term "electrode element" refers to a
constituent part of an electrode system. Specific non-limiting
examples of electrode elements include electrodes, contact pads and
electrode traces.
[0027] As used herein, the phrase "electrode set" is a grouping of
at least two electrodes that cooperate with one another to measure
the biosensor response.
[0028] As used herein, the term "pattern" means a design of one or
more intentionally formed gaps, a non-limiting example of which is
a single linear gap having a constant width. Not included in the
term "pattern" are natural, unintentional defects.
[0029] As used herein, the phrase "insulative pattern" means a
design of one or more intentionally formed gaps positioned within
or between electrically insulative material(s). It is appreciated
that electrically conductive material may form the one or more
gaps.
[0030] As used herein, the phrase "conductive pattern" means a
design of one or more intentionally formed gaps positioned within
or between electrically conductive material(s). It is appreciated
that exposed electrically insulative material may form the one or
more gaps.
[0031] As used herein, the phrase "microelectrode array" means a
group of microelectrodes having a predominantly spherical
diffusional characteristic.
[0032] As used herein, the phrase "macroelectrode array" means a
group of macroelectrodes having a predominantly radial diffusional
characteristic.
[0033] As used herein, the phrase "electrode pattern" means the
relative configuration of the intentionally formed gaps situated
between the elements of electrodes in an electrode set specifically
or biosensor generally. Non-limiting examples of "electrode
patterns" include any configuration of microelectrode arrays,
macroelectrode arrays or combinations thereof that are used to
measure biosensor response. "Electrode pattern" may also refer to
the shape and configuration of all electrical components that are
formed on the biosensor.
[0034] As used herein, the phrase "feature size" is the smallest
dimension of gaps or spaces found in a pattern. For example, in an
insulative pattern, the feature size is the smallest dimension of
electrically conductive gaps found within or between the
electrically insulative material(s). When, however, the pattern is
a conductive pattern, the feature size is the smallest dimension of
electrically insulative gaps found within or between the
electrically conductive material(s). Therefore, in a conductive
pattern the feature size represents the shortest distance between
the corresponding edges of adjacent elements.
[0035] As used herein, the term "interlaced" means an electrode
pattern wherein the elements of the electrodes are interwoven
relative to one another. In a particular embodiment, interlaced
electrode patterns include electrodes having elements, which are
interdigitated with one another. In the simplest form, interlaced
elements include a first electrode having a pair of elements and a
second electrode having a single element received within the pair
of elements of the first electrode.
[0036] As used herein, the term "ablating" means the removing of
material. The term "ablating" is not intended to encompass and is
distinguished from loosening, weakening or partially removing the
material.
[0037] As used herein, the phrase "broad field laser ablation"
means the removal of material from a substrate using a laser having
a laser beam with a dimension that is greater than the feature size
of the formed pattern. Broad field ablation includes the use of a
mask, pattern or other device intermediate a laser source and a
substrate. The laser is projected through the mask, the latter of
which forms an image of an electrode pattern which is projected
onto and impinges on the substrate to create all or part of the
electrode patterns on the substrate. Broad field laser ablation
simultaneously creates the pattern over a significant area of the
substrate. The use of broad field laser ablation avoids the need
for rastering or other similar techniques that scribe or otherwise
define the pattern by continuous movement of a relatively focused
laser beam relative to the substrate. A non-limiting example of a
process for broad field laser ablation is described below with
reference to biosensor 210.
[0038] As used herein, the term "line" means a geometric figure
formed by a point moving in a first direction along a
pre-determined linear or curved path and in a reverse direction
along the same path. In the present context, an electrode pattern
includes various elements having edges that are defined by lines
forming the perimeters of the conductive material. Such lines
demarcating the edges have desired shapes, and it is a feature of
the present invention that the smoothness of these edges is very
high compared to the desired shape.
[0039] "Theoretical line" as used herein refers to the desired or
ideal shape and location of an edge of an electrode element that
would be obtained if the manufacturing process were perfect. In
most cases, if the edge is straight, the theoretical line will
coincide with the average location of the edge.
[0040] As used herein, the term "point" means a dimensionless
geometric object having no properties except location.
[0041] The smoothness or quality of the edge of an electrode
element can be defined by the distance that the placement of the
edge differs from the theoretical line that represents the perfect
or ideal edge. That is, the edge will be spaced from the
theoretical line by a distance that varies along the length of the
edge. This distance will range from zero to a maximum value. One
useful way to define the quality or smoothness of an edge is to
simply specify the maximum distance that the edge is spaced from
the theoretical line over a specified length of the edge.
[0042] The smoothness or quality of an edge can also be specified
in terms of the "standard deviation" of the distance between the
edge and the theoretical line over a specified length of the edge.
To calculate the standard deviation, the distance must be measured
at discrete intervals along the length, as described in further
detail herein. If the varying distance is denoted "d" and the
number of data points is denoted n, then the standard deviation of
the distance is calculated as
{.SIGMA.(d.sub.i).sup.2/(n-1)}.sup.1/2. So that the equation just
noted accurately approximates the integral equation from which it
is derived, the intervals at which data points are taken should be
spaced closely together. All standard deviations expressed herein
are measured by taking data points that are spaced by no more than
about 20 .mu.m, preferably closer.
[0043] As used herein, the term "smoothness standard deviation,"
when referring to an edge of an electrode element, refers to the
standard deviation of the distance that the edge is spaced from a
theoretical line over a specified length of the edge. The quality
of a gap between electrode elements can be expressed in terms of
the individual deviations or standard deviations of the two edges
forming the gap from the theoretical lines corresponding to the two
edges.
[0044] As used herein, the phrase "biological fluid" includes any
bodily fluid in which the analyte can be measured, for example,
interstitial fluid, dermal fluid, sweat, tears, urine, amniotic
fluid, spinal fluid and blood.
[0045] As used herein, the term "blood" includes whole blood and
its cell-free components, namely plasma and serum.
[0046] As used herein, the term "working electrode" is an electrode
at which analyte, or product, is electrooxidized or electroreduced
with or without the agency of a redox mediator.
[0047] As used herein, the term "counter electrode" refers to an
electrode that is paired with the working electrode and through
which passes an electrochemical current equal in magnitude and
opposite in sign to the current passed through the working
electrode. The term "counter electrode" is meant to include counter
electrodes, which also function as reference electrodes (i.e., a
counter/reference or auxiliary electrode).
[0048] As used herein, the term "electrochemical biosensor" means a
device configured to detect the presence and/or measure the
concentration of an analyte by way of electrochemical oxidation and
reduction reactions within the biosensor. These reactions are
transduced to an electrical signal that can be correlated to an
amount or concentration of the analyte.
[0049] Additional features of the invention will become apparent to
those skilled in the art upon consideration of the following
detailed description of the preferred embodiment exemplifying the
best mode known for carrying out the invention. It should be
understood, however, that the detailed description and the specific
examples, while indicating embodiments of the invention, are given
by way of illustration only, since various changes and
modifications within the spirit and scope of the invention will
become apparent to those skilled in the art from this detailed
description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0050] The following drawings form part of the present
specification and are included to further demonstrate certain
aspects of the present invention. The invention may be better
understood by reference to one or more of these drawings in
combination with the detailed description of specific embodiments
presented herein:
[0051] FIG. 1 is a perspective view of a biosensor of the present
invention;
[0052] FIG. 2 is an exploded assembly view of the biosensor of FIG.
1;
[0053] FIG. 3 is an enlarged plan view of the biosensor of FIG. 1
showing a macroelectrode array and a microelectrode array;
[0054] FIG. 4 is a diagram of the deviation of an edge of an
electrode element from a theoretical or ideal line representing the
desired shape and placement of the edge;
[0055] FIG. 5 is a diagram of the deviation in gap width and
placement resulting from the deviations in the two individual edges
forming the gap;
[0056] FIG. 6 is an enlarged section of the microelectrode array of
FIG. 3;
[0057] FIG. 7 is a diagram of the deviation of an edge of an
electrode element from a theoretical or ideal line representing the
desired shape and placement of the edge;
[0058] FIG. 8 illustrates a cross-section taken along lines 8-8 of
FIG. 1;
[0059] FIG. 9 illustrates a cross-section taken along lines 9-9 of
FIG. 1;
[0060] FIG. 10 is a graph showing the deviation from mean or
theoretical of an electrode edge of the microelectrode array of
FIG. 3;
[0061] FIG. 11 is an exploded assembly view of a biosensor in
accordance with another embodiment of the invention;
[0062] FIG. 12 is an exploded assembly view of a biosensor in
accordance with another embodiment of the invention;
[0063] FIG. 13 is an exploded assembly view of a biosensor in
accordance with another embodiment of the invention;
[0064] FIG. 14 is an exploded assembly view of a biosensor in
accordance with another embodiment of the invention;
[0065] FIG. 15 is an exploded assembly view of a biosensor in
accordance with another embodiment of the invention;
[0066] FIG. 16 is an enlarged perspective view of a biosensor in
accordance with another embodiment of the invention;
[0067] FIG. 17 is a view of an ablation apparatus suitable for use
with the present invention;
[0068] FIG. 18 is a view of the laser ablation apparatus of FIG. 17
showing a second mask;
[0069] FIG. 19 is a view of an ablation apparatus suitable for use
with the present invention;
[0070] FIG. 20 is a schematic of an electrode set ribbon of the
present invention;
[0071] FIG. 21 is a photograph illustrating a biosensor substrate
initially coated with a gold conductive layer from which
approximately 10% of the conductive material has been removed;
[0072] FIG. 22 is a photograph illustrating a biosensor substrate
having an electrical pattern with a gap width of approximately 20
.mu.m and where approximately 20% of the conductive material
initially covering the substrate has been removed to form the
electrical pattern;
[0073] FIG. 23 is a photograph illustrating a biosensor substrate
having an electrical pattern with a gap width of approximately 20
.mu.m and where approximately 50% of the of a conductive material
initially covering the substrate has been removed to form the
electrical pattern; and
[0074] FIG. 24 is a photograph illustrating a biosensor substrate
having an electrical pattern with a gap width of approximately 250
.mu.m and where approximately 90% of the conductive material
initially covering the substrate has been removed to form the
electrical pattern.
DETAILED DESCRIPTION OF THE INVENTION
[0075] For the purposes of promoting an understanding of the
principles of the invention, reference will now be made to the
embodiments illustrated in the drawings, and specific language will
be used to describe the embodiments. It will nevertheless be
understood that no limitation of the scope of the invention is
intended. Alterations and modifications in the illustrated devices,
and further applications of the principles of the invention as
illustrated therein, as would normally occur to one skilled in the
art to which the invention relates are contemplated, are desired to
be protected.
[0076] A biosensor in accordance with the present invention
provides a surface with electrode patterns formed thereon, the
electrode patterns preferably having a smooth edge quality. It is a
particular aspect of the present invention that precise quality is
obtained for the edges of the electrical components located on the
biosensor. Having a smooth or high edge quality of the elements can
contribute to greater precision, accuracy, and reproducibility of
test results. Further, a smooth or high edge quality also allows
for a great number of electrode arrays to be formed on a defined
surface area of the biosensor. By increasing the edge quality of
the elements, it is possible to increase the number of electrode
elements and thus increase the achievable functionality in the
defined surface area. These functions may include, for example:
multiple measurement electrode pairs for simultaneous measurement
of the same or different analytes, including by alternative means;
electrodes used to provide correction factors for the basic
measurement electrodes; electrodes for detecting dose application
or sample sufficiency; multiple electrode traces to monitor
electrode functioning or to provide detection or correction of
defective traces; and multiple contact pads for coupling to the
foregoing functionalities, or for providing additional features
such as identification, calibration, or other information
pertaining to the biosensor. Further, the selected functionalities
for a given biosensor can be provided in a smaller space when the
high edge quality allows closer placement of the electrical
components. It is a feature of the present invention to enable all
of this, and more, in a manner that is relatively fast, reliable
and cost effective.
[0077] Specifically, a biosensor of the present invention has
electrical components with edges that are smooth and are precisely
located. The precise locating of the smooth edge is important,
particularly relative to a corresponding edge of another electrical
component, and especially with respect to a paired element. The
importance and the degree of quality of a component's edge quality
and placement will vary with the nature of the component.
[0078] For macroelectrodes, the edge smoothness and placement are
important for the quality of the electrochemical results obtained
by use of the macroelectrodes. One factor in the accuracy of such a
test is the reproducibility of the area of each macroelectrode.
Obtaining precise edge smoothness and placement will yield an area
which is highly accurate. Another factor in the use of
macroelectrodes is the placement of one of the electrodes relative
to the other, e.g., the position of the counter element(s) in
relationship to the position of the working element(s). Moreover,
since biosensors are generally operated based on calibration
methods that rely on the reproducibility of the sizes and locations
of the measuring electrodes, the ability to consistently produce
lots of such tests trips can enhance the results achieved with the
tests.
[0079] Similarly, the edge smoothness and placement contribute to
the results obtained from microelectrodes. For microelectrodes, the
issues can be magnified because of the number and relatively close
placement of the numerous microelements. Poor edge quality can
greatly affect the operating characteristics of microelectrodes,
and the present invention helps to overcome this potential problem.
Moreover, an advantage of placing microelements in close proximity
is the rapid establishment of steady-state operation. High edge
quality and precise edge placement enables closer placement of the
elements and in turn faster achievement of steady-state operation.
In addition, such closer placement allows for a greater number of
microelements to be placed in a given space.
[0080] In a first aspect, the present invention provides a high
quality edge for the various electrical components on a biosensor.
The quality of the edge relates to the smoothness or uniformity of
the edge relative to a theoretical profile of the edge.
Non-limiting examples of such "smooth" edges formed in accordance
with the present invention are shown in FIGS. 21-24.
[0081] In one respect, the smoothness relates simply to the
deviation of the edge surface relative to the theoretical line
defining the desired shape of the edge. It will be appreciated that
any electrical component on a biosensor has an intended location
and shape that will not be exactly duplicated by the physical
embodiment. The extent to which the actual edge of the component
varies from the theoretical one is a measure of the smoothness of
the edge. As discussed above, this smoothness or quality of the
edge can be expressed in terms of the varying distance that the
edge is spaced from a theoretical line over a specified length.
This distance can be measured at closely spaced intervals, as
discussed in detail below, and the standard deviation of the
distance can be calculated. Further, the maximum value the distance
achieves over a specified length is also a meaningful parameter.
For example, in a design where electrodes are to form a gap having
a desired width of, e.g., 10 .mu.m, the manufacturing process must
be capable of producing edges that will vary by less (preferably
much less) than 5 .mu.m over the length of the gap. Otherwise, the
electrodes may touch and thus short circuit.
[0082] As relates to the various electrical components, the extent
to which a given portion of the component is "smooth" may vary.
Referring in particular to the measuring electrodes, it will be
appreciated that certain edges of the elements are more critical
than others. For example, certain edges of the counter and working
electrodes are adjacent one another and spaced closely together,
while others are not. Also, certain edges are located within the
sample-receiving chamber, and others are not. In a first aspect,
the present invention relates to providing smooth edges for all of
the edges of the measuring electrodes. In another aspect, the
invention provides smooth edges particularly for the edges of the
measuring electrodes located within the sample-receiving chamber,
and more particularly for the edges of the measuring elements that
are adjacent to one another. "Adjacent edges" in this context
refers to the fact that an edge of a counter element is closest to,
i.e., adjacent to, an edge of an element of a working electrode
with which the counter electrode is paired.
[0083] As indicated previously, the present invention relates in
one aspect to providing macroelectrodes having a closely determined
area. The desired accuracy of the provided area can vary based on
the absolute size of the macroelectrode, as determined by the
quality of the edges defining the electrode. Thus, as the
smoothness of the edges improves, the difference between the area
actually occupied by the electrode and the desired area
decreases.
[0084] The spacing of macroelectrodes also can benefit from the
present invention. For example, for macroelectrodes that are spaced
apart by 250 .mu.m, the edges forming the gap preferably have a
smoothness standard deviation of less than about 4 .mu.m over the
entire length of the edges; for elements spaced apart by 100 .mu.m,
the standard deviation is preferably less than about 2 .mu.m.
[0085] For microelectrodes, the desired smoothness can differ. For
example, for microelements that are spaced apart by 50 .mu.m, the
adjacent edges have a smoothness standard deviation of less than
about 6 .mu.m, preferably less than about 2 .mu.m, and most
preferably less than about 1 .mu.m. If the microelements are spaced
apart by about 10 .mu.m, then the smoothness standard deviation is
preferably less than about 1 .mu.m, more preferably less than about
0.5 .mu.m. In general, the smoothness standard deviation for
microelectrodes is preferably less than about 5% of the width of
the gap between adjacent microelements (i.e., feature size), more
preferably less than about 2% of the feature size.
[0086] It is also an aspect of the present invention that the other
electrical components can be provided with smooth edges to
facilitate close placement of such components. Such other
components preferably have a smoothness standard deviation that is
less than about 6 .mu.m, and more preferably less than about 2
.mu.m.
[0087] The present invention also provides for the accurate
placement of the electrical components relative to one another and
to the overall biosensor. The relative placement of components is
achieved, at least in part, by the use of broad field laser
ablation that is performed through a mask or other device that has
a precise pattern for the electrical components. The relative
placement of the components therefore does not depend on the
controlled movement of a rastering laser or of the substrate
relative to the rastering laser. Moreover, this accurate
positioning of adjacent edges is further enhanced by the close
tolerances for the smoothness of the edges.
[0088] Therefore, in a further aspect the invention provides
electrical components that have gaps or features that are precisely
controlled. More specifically, the electrical components will have
designed, theoretical configurations for the gaps between adjacent
edges, whereas the physical embodiments will have variations and
irregularities. The present invention provides gaps between
adjacent edges that are highly uniform. Specifically, the present
invention provides a "uniform gap," which is defined as a gap for
which the smoothness standard deviation for each edge defining the
gap is less than about 6 .mu.m. Preferably, the smoothness standard
deviation of both edges defining the gap is less than about 2
.mu.m, more preferably less than about 1 .mu.m.
[0089] It is appreciated that the biosensor of the present
invention is suitable for use in a system for assessing an analyte
in a sample fluid. In addition to the biosensor, the system
includes a meter (not shown) and provides methods for evaluating
the sample fluid for the target analyte. The evaluation may range
from detecting the presence of the analyte to determining the
concentration of the analyte. The analyte and the sample fluid may
be any for which the test system is appropriate. For purposes of
explanation only, a preferred embodiment is described in which the
analyte is glucose and the sample fluid is blood or interstitial
fluid. However, the present invention clearly is not so limited in
scope.
[0090] Non-limiting examples of meters suitable for use with the
biosensor of the present invention for determination of the analyte
in the sample fluid are disclosed in U.S. Pat. Nos. 4,963,814;
4,999,632; 4,999,582; 5,243,516; 5,352,351; 5,366,609; 5,405,511;
and 5,438,271, the disclosures of each being incorporated herein by
reference. The suitable meter (not shown) will include a connection
with electrodes of the biosensor, and circuitry to evaluate an
electrochemical signal corresponding to the concentration of the
analyte. The meter may also include electrical components that
determine whether the sample fluid has been received by the
biosensor and whether the amount of sample fluid is sufficient for
testing. The meter typically will store and display the results of
the analysis, or may alternatively provide the data to a separate
device.
[0091] The biosensor of the present invention forming part of the
system can provide either a qualitative or quantitative indication
for the analyte. In one embodiment, the biosensor cooperates with
the meter to indicate simply the presence of the analyte in the
sample fluid. The biosensor and meter may also provide a reading of
the quantity or concentration of the analyte in the sample fluid.
In a preferred embodiment, it is a feature of the present invention
that a highly accurate and precise reading of the analyte
concentration is obtained.
[0092] The biosensor is useful for the determination of a wide
variety of analytes. The biosensor, for example, is readily adapted
for use with any suitable chemistry that can be used to assess the
presence of the analyte. Most preferably, the biosensor is
configured and used for the testing of an analyte in a biological
fluid. Commensurate modifications to the system will be apparent to
those skilled in the art. For purposes of explanation, and in a
particularly preferred embodiment, the system is described with
respect to the detection of glucose in a biological fluid.
[0093] The biosensor is also useful with a wide variety of sample
fluids, and is preferably used for the detection of analytes in a
biological fluid. In addition, the biosensor is useful in
connection with reference fluids that are used in conventional
fashion to verify the integrity of the system for testing.
[0094] In a preferred embodiment, the biosensor is employed for the
testing of glucose. The sample fluid in this instance may
specifically include, for example, fresh capillary blood obtained
from the finger tip or approved alternate sites (e.g., forearm,
palm, upper arm, calf and thigh), fresh venous blood, and control
solutions supplied with or for the system. The fluid may be
acquired and delivered to the biosensor in any fashion. For
example, a blood sample may be obtained in conventional fashion by
incising the skin, such as with a lancet, and then contacting the
biosensor with fluid that appears at the skin surface. It is an
aspect of the present invention that the biosensor is useful with
very small fluid samples. It is therefore a desirable feature that
only a slight incising of the skin is necessary to produce the
volume of fluid required for the test, and the pain and other
concerns with such method can be minimized or eliminated.
[0095] Biosensor 210 in accordance with an embodiment of the
present invention has two electrode patterns having different
feature sizes on a common planar surface and thus permits the
accurate measurement of an analyte in a fluid. As shown in FIG. 1,
biosensor 210 comprises a base or base substrate 212, conductive
material 216 positioned on the base 212, a spacer 214, and a cover
218. The cover 218 and spacer 214 cooperate with the base 212 to
define a sample-receiving chamber 220 (FIG. 9) having a sample
inlet opening 221 for the sample fluid, and a reagent 264 for
producing an electrochemical signal in the presence of a test
analyte. The biosensor 210 is formed as a test strip, particularly
one having a laminar construction providing an edge or surface
opening to the sample-receiving chamber 220. The reagent 264, as
shown in FIGS. 2 and 9, is exposed by the sample-receiving chamber
220 to provide the electrochemical signal to a working electrode
also positioned within the chamber 220. In appropriate
circumstances, such as for glucose detection, the reagent may
contain an enzyme and optionally a mediator.
[0096] The base 212 of biosensor 210 includes edges 222 that define
opposite ends 224, 226 and sides 228, 230 extending between the
ends 224, 226. Base 212 also has a top surface 232 supporting the
conductive material 216 and an opposite bottom surface 234 (FIGS. 8
and 9). Illustratively, base 212 has a length of 40 mm and a width
of 10 mm. It is appreciated, however that these values are merely
illustrative and that the dimensions of the base 212 may vary in
accordance with the present disclosure.
[0097] The base 212 is a substrate that is formed from an
insulating material, so that it will not provide an electrical
connection between electrodes formed from the conductive material
216. Non-limiting examples of suitable insulating materials include
glass, ceramics and polymers. Preferably, the base is a flexible
polymer and has a strong absorbance in the UV. Non-limiting
examples of suitable materials include polyethylene terephthalate
(PET), polyethylene naphthalate (PEN), and polyimide films. The
suitable films are commercially available as MELINEX.RTM.,
KALADEX.RTM. and KAPTON.RTM., respectively from E.I. duPont de
Nemours, Wilmington, Del., USA ("duPont") and UPILEX.RTM., a
polyimide film from UBE Industries Ltd, Japan. Preferred materials
are selected from 10 mil thick MELINEX.RTM. 329 or KAPTON.RTM.,
which are coated with 50.+-.4 nm gold within-lot C.V. of <5% by:
Techni-Met Advanced Depositions, Inc., Windsor, Conn., USA. It is
appreciated that the base 212 may be either purchased pre-coated
with conductive material 216 or may be coated by sputtering or
vapor deposition, in accordance with this disclosure. It is further
appreciated that the thickness of the conductive material can vary
in accordance with this disclosure.
[0098] Spacer 214 is illustratively positioned on the top surface
232 of the base 212 adjacent to end 224. Spacer 214 has an upper
surface 236 and a lower surface 238 (FIG. 9) facing the base 212.
Referring now to FIG. 2, the spacer 214 has edges 240, 242, 244,
246. Illustratively, spacer 214 has a length of about 6 mm, a width
of about 10 mm and a height of about 4 mil. It is appreciated,
however that these values are merely illustrative and that the
biosensor may be formed without a spacer and that the dimensions of
the spacer 214 may vary in accordance with the present
disclosure.
[0099] Spacer 214 is formed from an insulating material, so that it
will not provide an electrical connection between electrodes formed
from the conductive material 216. Non-limiting examples of suitable
insulating materials include glass, ceramics, polymers,
photoimageable coverlay materials, and photoresists--non-limiting
examples of which are disclosed in U.S. patent application Ser. No.
10/264,891, filed Oct. 4, 2002, the disclosure of which is
incorporated herein by reference. Illustratively, spacer 214 is
formed of 4 mil MELINEX.RTM. polyester film, which is preferred for
use with whole blood samples. It is appreciated, however, that when
the sample is plasma or serum, 1-2 mil film may be preferred for
use in accordance with this disclosure. It is appreciated, however
that these values are merely illustrative and that the composition
and dimension of the spacer 214 may vary in accordance with the
desired height of the sample-receiving chamber.
[0100] A slit or void 248 is formed in the spacer 214 and extends
from the edge 240 toward the edge 242. The slit 248 defines at
least the length and width of the sample-receiving chamber 220 and
is defined by edges 249. Illustratively, the slit 248 has a length
of 5 mm, a width of 1 mm, and a height of 0.1 mm, but may have a
variety of lengths and widths in accordance with the present
disclosure. It is further appreciated that the edges 249 of the
slit may also be curved or angular in accordance with this
disclosure.
[0101] As shown in FIG. 1, the cover 218 is positioned on the upper
surface 236 of spacer 214. Cover 218 has a first surface 250 and a
second surface 252 (FIG. 9) facing the base 212. Further, the cover
218 has edges 254, 256, 258, 260. As shown in FIG. 1, the cover 218
has a length that is less than the length of the slit 248.
Illustratively, cover 218 has a length of about 4 mm, a width of
about 10 mm and a height of about 0.1 mm. It is appreciated,
however that these values are merely illustrative and that the
biosensor may be formed without a cover and that the dimensions of
the cover 218 may vary in accordance with the present
disclosure.
[0102] The cover 218 is illustratively formed of a clear material
having a hydrophilic adhesive layer in proximity to the spacer.
Non-limiting examples of materials suitable for cover 218 include
polyethylene, polypropylene, polyvinylchloride, polyimide, glass,
or polyester. A preferred material for cover 218 is 100 .mu.m
polyester. A preferred adhesive is ARCare 8586 having a MA-55
hydrophilic coating, commercially available from Adhesives Research
Inc., Glen Rock, Pa. Further, it is appreciated that the cover may
have markings in accordance with this disclosure.
[0103] The slit 248 in the spacer 214, together with the cover 218,
and the base 212, form the sample-receiving chamber 220 (FIG. 9),
which acts to expose reagent 264 to a fluid to be tested from a
user of biosensor 210. This sample-receiving chamber 220 can act as
a capillary channel, drawing the fluid to be tested from the
opening 221 onto a sensing region of the conductive material 216
and toward a vent 262. It is appreciated that the biosensor may be
formed without a spacer in accordance with this disclosure and that
in addition to or instead of the spacer and the cover, a variety of
dielectric materials may cover the base 212 exposing only selected
portions of the conductive material in accordance with this
disclosure. Moreover, it is appreciated that when present, the
dimensions of the channel 220 may vary in accordance with this
disclosure.
[0104] FIG. 2 illustrates the conductive material 216 defining
electrode systems comprising a first electrode set 266 and a second
electrode set 268, and corresponding traces 279, 277 and contact
pads 278, 282, respectively. The conductive material 216 may
contain pure metals or alloys, or other materials, which are
metallic conductors. Preferably, the conductive material is
transparent at the wavelength of the laser used to form the
electrodes and of a thickness amenable to rapid and precise
processing. Non-limiting examples include aluminum, carbon, copper,
chromium, gold, indium tin oxide (ITO), palladium, platinum,
silver, tin oxide/gold, titanium, mixtures thereof, and alloys or
metallic compounds of these elements. Preferably, the conductive
material includes noble metals or alloys or their oxides. Most
preferably, the conductive material includes gold, palladium,
aluminum, titanium, platinum, ITO and chromium. The conductive
material ranges in thickness from about 10 nm to 80 nm, more
preferably, 30 nm to 70 nm. FIGS. 1-3, 6, and 8-9 illustrate the
biosensor 210 with a 50 nm gold film. It is appreciated that the
thickness of the conductive material depends upon the transmissive
property of the material and other factors relating to use of the
biosensor.
[0105] Illustratively, the conductive material 216 is ablated into
two electrode systems that comprise sets 266, 268. In forming these
systems, the conductive material 216 is removed from at least about
5% of the surface area of the base 212, more preferably at least
about 50% of the surface area of the base 212, and most preferably
at least about 90% of the surface area of the base 212. As shown in
FIG. 2, the only conductive material 216 remaining on the base 212
forms at least a portion of an electrode system.
[0106] While not illustrated, it is appreciated that the resulting
patterned conductive material can be coated or plated with
additional metal layers. For example, the conductive material may
be copper, which is then ablated with a laser, into an electrode
pattern; subsequently, the copper may be plated with a
titanium/tungsten layer, and then a gold layer, to form the desired
electrodes. Preferably, a single layer of conductive material is
used, which lies on the base 212. Although not generally necessary,
it is possible to enhance adhesion of the conductive material to
the base, as is well known in the art, by using seed or ancillary
layers such as chromium nickel or titanium. In preferred
embodiments, biosensor 210 has a single layer of gold, palladium,
platinum or ITO.
[0107] As shown in FIGS. 2 and 9, the biosensor 210 includes an
electrode system comprising at least a working electrode and a
counter electrode within the sample-receiving chamber 220. The
sample-receiving chamber 220 is configured such that sample fluid
entering the chamber is placed in electrolytic contact with both
the working electrode and the counter electrode. This allows
electrical current to flow between the electrodes to effect the
electrooxidation or electroreduction of the analyte or its
products.
[0108] Referring now to FIG. 3, the first electrode set 266 of the
electrode system includes two electrodes 270, 272. Illustratively,
electrode 270 is a working electrode and electrode 272 is a counter
electrode. The electrodes 270, 272 each have a single element or
finger 280 that is in communication with a contact pad 278 via a
connecting trace 279 (shown in FIG. 2). The electrode fingers 280
of the electrodes 270, 272 cooperate to define an electrode pattern
formed as a macroelectrode array. It is appreciated, as will be
discussed hereafter, that the electrodes 270, 272 can include more
than one finger each in accordance with this disclosure. It is
further appreciated that the shape, size and relative configuration
of the electrodes or electrode fingers may vary in accordance with
the present disclosure.
[0109] As shown in FIG. 2, the second electrode set 268 includes
two electrodes 274, 276. Illustratively, electrode 274 is a working
electrode and electrode 276 is a counter electrode. Further, the
electrodes 274, 276 each have five electrode elements or fingers
284 that are in communication with a contact pad 282 via a
connecting trace 277. Referring now to FIG. 3, the electrode
fingers 284 cooperate to define an electrode pattern formed as an
interlaced microelectrode array. While five electrode fingers 284
are illustrated, it is appreciated that the elements of electrodes
274, 276 can each be formed with greater or fewer than five
electrode fingers in accordance with this disclosure. It is further
appreciated that the shape, size and relative configuration of the
electrodes may vary in accordance with the present disclosure.
[0110] It is appreciated that the values for the dimensions of the
electrode sets 266, 268 as illustrated in FIG. 2 are for a single
specific embodiment, and these values may be selected as needed for
the specific use. For example, the length of the electrode sets may
be any length up to the length of the base, depending upon the
orientation of the electrode sets on the base. Further, it is
appreciated that the width of the conducting traces in
communication with the electrode sets may vary, a non-limiting
example of which is from about 0.4 mm to about 5 mm. It is further
appreciated that the width of each contact pad may vary, a
non-limiting example of which is from about 1 mm to about 5 mm. The
electrode patterns shown in FIG. 2 are symmetric, however this is
not required, and irregular or asymmetric patterns (or electrode
shapes) are possible in accordance with this disclosure. Further,
the number of electrode sets on the base 212 may vary, and
therefore each base 212 can contain, for example 1 to 1000
electrode sets, preferably 2 to 20 electrode sets, more preferably
2 to 3 electrode sets.
[0111] Referring again to the first electrode set 266 of FIG. 3,
each electrode finger 280 is defined by an inner edge 281, an outer
edge 283, and opposite third and fourth edges 285, 287. Each edge
218, 283, 285, 287 has a smooth edge quality. As discussed earlier,
the edge quality of the electrodes 270, 272 is defined by the
edge's deviation from a theoretical line extending between first
and second points. The following description of deviations can
apply to each edge of electrodes 270, 272 of biosensor 210. For
clarity purposes, however, only the edge 281 of electrode 270 will
be discussed hereafter.
[0112] As shown in FIG. 3, the edge 281 of electrode 270 extends
between points 289, 291 located on the base 212. Points 289, 291
are located at opposite ends of the inner edge 281, which
represents the entire length of the gap 286 between electrodes 280.
It is appreciated that the points 289, 291 may be positioned at a
variety of locations and at a variety of distances relative to one
another depending upon the length of the desired edge in accordance
with this disclosure. However, the length of interest will
typically be the entire length over which a gap extends, since the
smoothness of the adjacent edges is normally most important over
this entire length.
[0113] FIG. 4 illustrates the theoretical line 293 that extends
exactly between points 289, 291. That is, line 293 represents the
ideal or desired edge that would be obtained if the process of
forming the electrodes were perfect. However, at any given point
along the length of line 293, the edge 281 will be spaced in either
direction from theoretical line 293 by a distance "d.sub.i." The
distance d.sub.i varies from zero to a maximum value depending upon
where it happens to be measured, as shown, e.g., with reference to
distances d.sub.1, d.sub.2, d.sub.3 and d.sub.4 in FIG. 4. A
standard deviation of this distance over the length of line 293 is
less than about 6 .mu.m in accordance with this disclosure,
creating an edge with a smooth edge quality. In preferred
embodiments, the standard deviation of the edge 281 from
theoretical line 293 is less than 2 .mu.m, and most preferably less
than 1.0 .mu.m. An example of this deviation from mean or
theoretical is illustrated in FIG. 10.
[0114] The edge quality illustrated in FIG. 10 was measured using
Micro-Measure system commercially available from LPKF Laser
Electronic GmbH, of Garbsen, Germany with Metric 6.21 software. The
Metric software allows the display and measuring of video images on
a PC. Measurements were made by capturing the image and then
allowing the software to place a 10 .mu.m grid over the image. The
grid was aligned with the edge by moving the electrode structure
under the measurement objective. (By physically manipulating the
image, the edge can be vertically aligned to be parallel with the
grid.) Using the software, measurements from the grid line to the
electrode edge were then made at 10 .mu.m intervals along the
length of a line 250 .mu.m long using a point-to-point process. The
effective video magnification to video screen was 575.times..
(Using objective Q750). Video magnification=Actual measured "Scale
length" on the video screen (.mu.m)/Scale value (.mu.m). For
example, 115000 .mu.cm/200 .mu.m=575.times..
[0115] In one analysis of an electrical pattern formed using the
principles of the present invention, the deviation from mean of the
edges was measured using a QVH-606 PRO Vision Measuring System
(computer-controlled non-contact measurement system), commercially
available from Mitutoyo America Corporation, Aurora, Ill. with an
effective magnification to video screen=470.times.. Standard
deviations were calculated from measurements made at an average
interval of 0.69 .mu.m for a length of at least 250 .mu.m. Other
settings: Ring lighting (Intensity 89, Position 60), Edge Detection
(Edge Slope=Falling, Edge Detection TH=169, THS=18.5, THR=0.5 Scan
Interval=1). The standard deviation from the mean value was less
than about 2 .mu.m.
[0116] Referring again to FIG. 4, the line 293 is illustratively a
straight line. It is appreciated, however, that the shape of the
line 293 may be curved or angular, so long as the standard
deviation of the distance of edge 281 from that line 293 over the
length of the edge is less than about 6 .mu.m.
[0117] The electrode fingers 280, as shown in FIG. 3, are separated
from one another by an electrode gap 286, which corresponds to the
feature size of the electrode pattern of the electrode set 266. The
electrode gap 286 shown in FIG. 3 is shown as formed by two
straight edges 281. However, as just noted, the placement of edges
281 varies from theoretical value 293 (FIG. 4) by a distance that
varies along the length of the edge. Illustratively, in biosensor
210, the electrically insulative material of the top surface 232 is
exposed between the electrode fingers 280 along a length 290. It is
appreciated, however, that rather than top surface 232 being
exposed, the base can be coated with materials, or recesses can be
formed between the electrodes as disclosed in U.S. patent
application Ser. No. 09/704,145, filed on Nov. 1, 2000, now U.S.
Pat. No. 6,540,890, the disclosure of which is incorporated herein
by reference.
[0118] As shown in FIGS. 3 and 5, the inner edges 281 of electrode
fingers 280 have an equal length, illustrated by the numeral 290
and are separated from one another by the electrode gap 286, whose
length is also represented by length 290. Because the two edges 281
defining gap 286 are not perfect, gap 286 will in fact vary in
width and placement over its length, as shown with reference to
gaps 292a-292d in FIG. 5. When the deviations of the two edges
defining gap 286 are in the same direction, they tend to cancel
each other as to width deviation, at least in part, and cause a net
shift in placement of the gap, as illustrated with respect to
reference numerals 292c and 292d of FIG. 5. A theoretical gap can
be defined by two theoretical lines 293 associated with edges 281.
The quality of the gap or its deviation from the theoretical gap
can be specified in terms of the quality of the two individual
edges defining it. Preferably, the smoothness standard deviation of
both edges defining gap 286 is less 6 .mu.m, preferably less than
2.0 .mu.m, and most preferably less than 1 .mu.m.
[0119] The electrode fingers 284, which define the elements of
electrodes 274, 276 are illustrated in FIGS. 3 and 6. For clarity
purposes, however, only three of these electrode fingers 284 will
be discussed hereafter as they are illustrated in FIG. 6. Each
electrode finger 284 is defined by a first edge 296 and a second
edge 297. Further, adjacent fingers 284 have spaced-apart third and
fourth edges 298, 299 respectively. These edges 296, 297, 298, 299
of fingers 284 can also have a smooth edge quality. As previously
described with reference to electrodes 270, 272, the edge quality
of the electrodes 274, 276 is defined by the respective edge's
deviation from a line extending between first and second points.
The following description of deviations will apply to each edge of
electrode fingers 284 of biosensor 210. For clarity purposes,
however, only one edge 296 of electrode finger 284 will be
discussed hereafter.
[0120] The edge 296 of electrode finger 284 extends between first
and second points 301, 302 located on the base 212. As shown in
FIG. 7, a theoretical line 300 extends exactly between points 301,
302, which is typically the length of the gap formed by edge 296
and 297. A standard deviation of the varying distance of edge 296
from line 300 is less than about 6 .mu.m, in accordance with this
disclosure, creating an edge with a smooth edge quality. In
preferred embodiments, the standard deviation of the edge 296 from
theoretical line 300 is less than 2 .mu.m, and most preferably less
than 1.0 .mu.m. Illustratively, the line 300 is a straight line. It
is appreciated, however, that the shape of the line 300 may be
curved or angular. It is also appreciated that the specific
positions of first and second locations 300, 301 on the surface 232
may vary in accordance with the disclosure, although the lengths of
most importance are typically the entire length of the gaps between
these closely spaced electrode fingers.
[0121] Referring again to FIG. 3, the electrode fingers 284 are
separated from one another by an electrode gap 288, which
corresponds to the feature size of the electrode pattern of the
electrode set 268. The electrode gap 288 relates to the width
between adjacent edges 296, 297 of fingers 284. Because the two
edges defining gap 288 are not perfect, gap 288 will in fact vary
in position and placement over its length. Illustratively, in
biosensor 210, the electrically insulative material of the base 212
is exposed between the electrode fingers 284 along a length 303. It
is appreciated, however, that rather than top surface 232 being
exposed, the base can be coated with materials, or recesses can be
formed between the electrodes as disclosed in U.S. patent
application Ser. No. 09/704,145, filed on Nov. 1, 2000, now U.S.
Pat. No. 6,540,890, entitled "Biosensor", the disclosure of which
is incorporated herein by reference.
[0122] The electrode gap 288, which corresponds to the feature size
of the electrode pattern of the electrode set 268 is different than
the feature size of the electrode pattern of the electrode set 266.
Illustratively, the feature size, or gap 288 between the electrode
fingers 284 has a width of about 100 .mu.m or less, including about
1 .mu.m to about 100 .mu.m, even more preferably 75 .mu.m or less,
including about 17 .mu.m to about 50 .mu.m.
[0123] It is appreciated that the electrode gap for a
microelectrode array can vary. For example, it is understood that
the electrode gap can be less than 1 .mu.m in accordance with the
present disclosure. The size of the achievable gap is dependent
upon the quality of the optics, the wavelength of the laser, and
the window size of a mask field.
[0124] As illustrated in FIG. 3, the gap 288 has a width along a
length 303 of the opposing edges 296, 297 of the electrode fingers
284. Like gap 286, the quality of gap 286 or its deviation from a
theoretical gap can be specified in terms of the quality of the two
individual edges defining it. Preferably, the smoothness standard
deviation of both edges defining gap 286 is less 6 .mu.m,
preferably less than 2.0 .mu.m, and most preferably less than 1
.mu.m.
[0125] Referring now to FIG. 9, the electrode fingers 284 are
covered with the reagent 264 and may be used to provide
electrochemical probes for specific analytes. The starting reagents
are the reactants or components of the reagent, and are often
compounded together in liquid form before application to the
ribbons or reels, or in capillary channels on sheets of electrodes.
The liquid may then evaporate, leaving the reagent in solid form.
The choice of a specific reagent depends on the specific analyte or
analytes to be measured, and is not critical to the present
invention. Various reagent compositions are well known to those of
ordinary skill in the art. It is also appreciated that the
placement choice for the reagent on the base may vary and depends
on the intended use of the biosensor. Further, it is appreciated
that the techniques for applying the reagent onto the base may
vary. For example, it is within the scope of the present disclosure
to have the reagent screen-printed onto the fingers.
[0126] A non-limiting example of a dispensable reagent for
measurement of glucose in a human blood sample contains 62.2 mg
polyethylene oxide (mean molecular weight of 100-900 kilodaltons),
3.3 mg NATROSOL 250 M, 41.5 mg AVICEL RC-591 F, 89.4 mg monobasic
potassium phosphate, 157.9 mg dibasic potassium phosphate, 437.3 mg
potassium ferricyanide, 46.0 mg sodium succinate, 148.0 mg
trehalose, 2.6 mg TRITON X-100 surfactant, and 2,000 to 9,000 units
of enzyme activity per gram of reagent. The enzyme is prepared as
an enzyme solution from 12.5 mg coenzyme PQQ and 1.21 million units
of the apoenzyme of quinoprotein glucose dehydrogenase, forming a
solution of quinoprotein glucose dehydrogenase. This reagent is
further described in U.S. Pat. No. 5,997,817, the disclosure of
which is expressly incorporated herein by reference.
[0127] A non-limiting example of a dispensable reagent for
measurement of hematocrit in a sample contains oxidized and reduced
forms of a reversible electroactive compound (potassium
hexacyanoferrate (III) ("ferricyanide") and potassium
hexacyanoferrate (II) ("ferrocyanide"), respectively), an
electrolyte (potassium phosphate buffer), and a microcrystalline
material (Avicel RC-591F--a blend of 88% microcrystalline cellulose
and 12% sodium carboxymethyl-cellulose, available from FMC Corp.).
Concentrations of the components within the reagent before drying
are as follows: 400 millimolar (mM) ferricyanide, 55 mM
ferrocyanide, 400 mM potassium phosphate, and 2.0% (weight: volume)
Avicel. A further description of the reagent for a hematocrit assay
is found in U.S. Pat. No. 5,385,846, the disclosure of which is
expressly incorporated herein by reference.
[0128] Non-limiting examples of enzymes and mediators that may be
used in measuring particular analytes in biosensors of the present
invention are listed below in Table 1.
1TABLE 1 Mediator Analyte Enzymes (Oxidized Form) Additional
Mediator Glucose Glucose Dehydrogenase Ferricyanide and Diaphorase
Osmium complexes, nitrosoanaline complexes Glucose
Glucose-Dehydrogenase Ferricyanide (Quinoprotein) Cholesterol
Cholesterol Esterase and Ferricyanide 2,6-Dimethyl-1,4- Cholesterol
Oxidase Benzoquinone 2,5-Dichloro-1,4- Benzoquinone or Phenazine
Ethosulfate HDL Cholesterol Esterase Ferricyanide 2,6-Dimethyl-1,4-
Cholesterol and Cholesterol Oxidase Benzoquinone 2,5-Dichloro-1,4-
Benzoquinone or Phenazine Ethosulfate Triglycerides Lipoprotein
Lipase, Ferricyanide or Phenazine Methosulfate Glycerol Kinase, and
Phenazine Glycerol-3-Phosphate Ethosulfate Oxidase Lactate Lactate
Oxidase Ferricyanide 2,6-Dichloro-1,4- Benzoquinone Lactate Lactate
Dehydrogenase Ferricyanide and Diaphorase Phenazine Ethosulfate, or
Phenazine Methosulfate Lactate Diaphorase Ferricyanide Phenazine
Ethosulfate, or Dehydrogenase Phenazine Methosulfate Pyruvate
Pyruvate Oxidase Ferricyanide Alcohol Alcohol Oxidase
Phenylenediamine Bilirubin Bilirubin Oxidase 1-Methoxy- Phenazine
Methosulfate Uric Acid Uricase Ferricyanide
[0129] In some of the examples shown in Table 1, at least one
additional enzyme is used as a reaction catalyst. Also, some of the
examples shown in Table 1 may utilize an additional mediator, which
facilitates electron transfer to the oxidized form of the mediator.
The additional mediator may be provided to the reagent in lesser
amount than the oxidized form of the mediator. While the above
assays are described, it is contemplated that current, charge,
impedance, conductance, potential, or other electrochemically
indicated property of the sample might be accurately correlated to
the concentration of the analyte in the sample with biosensors in
accordance with this disclosure.
[0130] Another non-limiting example of a suitable dispensable
reagent for use with biosensors of the present invention is
nitrosoanaline reagent, which includes a PQQ-GDH and
para-Nitroso-Aniline mediator. A protocol for the preparation of
the nitrosoanaline reagent is the same in all respects as disclosed
in U.S. patent application Ser. No. 10/688,312, entitled "System
And Method For Analyte Measurement Using AC Phase Angle
Measurement", filed Oct. 17, 2003, the disclosure of which is
incorporated herein by reference. The reagent mass
composition--prior to dispensing and drying is as set forth in
Table 2.
2TABLE 2 Mass for Component % w/w 1 kg solid Polyethylene oxide
(300 KDa) 0.8054% 8.0539 g solid NATROSOL .RTM. 250 M 0.0470%
0.4698 g solid AVICEL .RTM. RC-591F 0.5410% 5.4104 g solid
Monobasic potassium phosphate 1.1437% 11.4371 g (anhydrous) solid
Dibasic potassium phosphate 1.5437% 15.4367 g (anhydrous) solid
Sodium Succinate hexahydrate 0.5876% 5.8761 g solid Potassium
Hydroxide 0.3358% 3.3579 g solid Quinoprotein glucose dehydrogenase
0.1646% 1.6464 g (EncC#: 1.1.99.17) solid PQQ 0.0042% 0.0423 g
solid Trehalose 1.8875% 18.8746 g solid Mediator BM 31.1144 0.6636%
6.6363 g solid TRITON .RTM. X-100 0.0327% 0.3274 g solvent Water
92.2389% 922.3888 g % Solids 0.1352687 Target pH 6.8 Specific
Enzyme Activity Used (U/mg 689 DCIP Dispense Volume per Biosensor
4.6 mg
[0131] A coatable reagent suitable for use with the present
disclosure is as follows in Table 3.
3TABLE 3 Component % w/w Mass for 1 kg Keltrol F, xanthan gum
0.2136% 2.1358 g Sodium Carboxymethylcellulose (CMC) 0.5613% 5.6129
g Polyvinylpyrrolidone, (PVP K25) 1.8952% 18.9524 g PROPIOFAN
.RTM., 2.8566% 28.5657 g GlucDOR 0.3310% 3.3098 g PQQ 0.0092%
0.0922 g Sipernat 320 DS 2.0039% 20.0394 g Na-Succinat .times. 6H2O
0.4803% 4.8027 g Trehalose 0.4808% 4.8081 g KH.sub.2PO.sub.4
0.4814% 4.8136 g K.sub.2HPO.sub.4 1.1166% 11.1658 g Mediator
31.1144 0.6924% 6.9242 g Mega 8 0.2806% 2.8065 g Geropon T 77
0.0298% 0.2980 g KOH 0.1428% 1.4276 g Water 88.4245% 884.2453 g %
Solids 11.5755 Target pH 7.0 Specific Enzyme Activity Used (U/mg
2.23 DCIP Coat Weight 55 g/m.sup.2
[0132] Biosensor 210 is illustratively manufactured using two
apparatuses 10, 10', shown in FIGS. 17-18 and 19, respectively. It
is appreciated that unless otherwise described, the apparatuses 10,
10' operate in a similar manner. Referring first to FIG. 17,
biosensor 210 is manufactured by feeding a roll of ribbon or web 20
having an 80 nm gold laminate, which is about 40 mm in width, into
a custom fit broad field laser ablation apparatus 10. The apparatus
10 comprises a laser source 11 producing a beam of laser light 12,
a chromium-plated quartz mask 14, and optics 16. It is appreciated
that while the illustrated optics 16 is a single lens, optics 16 is
preferably a variety of lenses that cooperate to make the light 12
in a pre-determined shape or image that is then projected onto the
web of base substrate 20.
[0133] A non-limiting example of a suitable ablation apparatus 10
(FIGS. 17-18) is a customized MicrolineLaser 200-4 laser system
commercially available from LPKF Laser Electronic GmbH, of Garbsen,
Germany, which incorporates an LPX-400, LPX-300 or LPX-200 laser
system commercially available from Lambda Physik AG, Gottingen,
Germany and a chromium-plated quartz mask commercially available
from International Phototool Company, Colorado Springs, Co.
[0134] For the MicrolineLaser 200-4 laser system (FIGS. 17-18), the
laser source 11 is a LPX-200 KrF-UV-laser. It is appreciated,
however, that higher wavelength UV lasers can be used in accordance
with this disclosure. The laser source 11 works at 248 nm, with a
pulse energy of 600 mJ, and a pulse repeat frequency of 50 Hz. The
intensity of the laser beam 12 can be infinitely adjusted between
3% and 92% by a dielectric beam attenuator (not shown). The beam
profile is 27.times.15 mm.sup.2 (0.62 sq. inch) and the pulse
duration 25 ns. The layout on the mask 14 is homogeneously
projected by an optical elements beam expander, homogenizer, and
field lens (not shown). The performance of the homogenizer has been
determined by measuring the energy profile. The imaging optics 16
transfer the structures of the mask 14 onto the ribbon 20. The
imaging ratio is 2:1 to allow a large area to be removed on the one
hand, but to keep the energy density below the ablation point of
the applied chromium mask on the other hand. While an imaging of
2:1 is illustrated, it is appreciated that the any number of
alternative ratios are possible in accordance with this disclosure
depending upon the desired design requirements. The ribbon 20 moves
as shown by arrow 25 to allow a number of layout segments to be
ablated in succession.
[0135] The positioning of the mask 14, movement of the ribbon 20,
and laser energy are computer controlled. As shown in FIG. 17, the
laser beam 12 is projected onto the ribbon 20 to be ablated. Light
12 passing through the clear areas or windows 18 of the mask 14
ablates the metal from the ribbon 20. Chromium coated areas 24 of
the mask 14 blocks the laser light 12 and prevent ablation in those
areas, resulting in a metallized structure on the ribbon 20
surface. Referring now to FIG. 18, a complete structure of
electrical components may require additional ablation steps through
a second mask 14'. It is appreciated that depending upon the optics
and the size of the electrical component to be ablated, that only a
single ablation step or greater than two ablation steps may be
necessary in accordance with this disclosure. Further, it is
appreciated that instead of multiple masks, that multiple fields
may be formed on the same mask in accordance with this
disclosure.
[0136] Specifically, a second non-limiting example of a suitable
ablation apparatus 10' (FIG. 19) is a customized laser system
commercially available from LPKF Laser Electronic GmbH, of Garbsen,
Germany, which incorporates a Lambda STEEL (Stable energy eximer
laser) laser system commercially available from Lambda Physik AG,
Gottingen, Germany and a chromium-plated quartz mask commercially
available from International Phototool Company, Colorado Springs,
Co. The laser system features up to 1000 mJ pulse energy at a
wavelength of 308 nm. Further, the laser system has a frequency of
100 Hz. The apparatus 10' may be formed to produce biosensors with
two passes as shown in FIGS. 17 and 18, but preferably its optics
permit the formation of a 10.times.40 mm pattern in a 25 ns single
pass.
[0137] While not wishing to be bound to a specific theory, it is
believed that the laser pulse or beam 12 that passes through the
mask 14, 14', 14" is absorbed within less than 1 .mu.m of the
surface 232 on the ribbon 20. The photons of the beam 12 have an
energy sufficient to cause photo-dissociation and the rapid
breaking of chemical bonds at the metal/polymer interface. It is
believed that this rapid chemical bond breaking causes a sudden
pressure increase within the absorption region and forces material
(metal film 216) to be ejected from the polymer base surface. Since
typical pulse durations are around 20-25 nanoseconds, the
interaction with the material occurs very rapidly and thermal
damage to edges of the conductive material 216 and surrounding
structures is minimized. The resulting edges of the electrical
components have high edge quality and accurate placement as
contemplated by the present invention.
[0138] Fluence energies used to remove or ablate metals from the
ribbon 20 are dependent upon the material from which the ribbon 20
is formed, adhesion of the metal film to the base material, the
thickness of the metal film, and possibly the process used to place
the film on the base material, i.e. supporting and vapor
deposition. Fluence levels for gold on KALADEX.RTM. range from
about 50 to about 90 mJ/cm.sup.2, on polyimide about 100 to about
120 mJ/cm.sup.2, and on MELINEX.RTM. about 60 to about 120
mJ/cm.sup.2. It is understood that fluence levels less than or
greater than the above mentioned can be appropriate for other base
materials in accordance with the disclosure.
[0139] Patterning of areas of the ribbon 20 is achieved by using
the masks 14, 14'. Each mask 14, 14' illustratively includes a mask
field 22 containing a precise two-dimensional illustration of a
pre-determined portion of the electrode component patterns to be
formed. FIG. 17 illustrates the mask field 22 including contact
pads and a portion of traces. As shown in FIG. 18, the second mask
14' contains a second corresponding portion of the traces and the
electrode patterns containing fingers. As previously described, it
is appreciated that depending upon the size of the area to be
ablated, the mask 14 can contain a complete illustration of the
entire electrode pattern for each biosensor (FIG. 19), or partial
patterns different from those illustrated in FIGS. 17 and 18 in
accordance with this disclosure. Preferably, it is contemplated
that in one aspect of the present invention, the entire pattern of
the electrical components on the test strip are laser ablated at
one time, i.e., the broad field encompasses the entire size of the
test strip (FIG. 19), or even encompasses the entire size of two or
more test strips (not shown). In the alternative, and as
illustrated in FIGS. 17 and 18, portions of the entire biosensor
are done successively.
[0140] While mask 14 will be discussed hereafter, it is appreciated
that unless indicated otherwise, the discussion will apply to masks
14', 14" as well. Referring to FIG. 17, areas 24 of the mask field
22 protected by the chrome will block the projection of the laser
beam 12 to the ribbon 20. Clear areas or windows 18 in the mask
field 22 allow the laser beam 12 to pass through the mask 14 and to
impact predetermined areas of the ribbon 20. As shown in FIG. 17,
the clear area 18 of the mask field 22 corresponds to the areas of
the ribbon 20 from which the conductive material 216 is to be
removed.
[0141] Further, the mask field 22 has a length shown by line 30 and
a width as shown by line 32. Given the imaging ratio of 2:1 of the
LPX-200, it is appreciated that the length 30 of the mask is two
times the length of a length 34 of the resulting pattern and the
width 32 of the mask is two times the width of a width 36 of the
resulting pattern on ribbon 20. The optics 16 reduces the size of
laser beam 12 that strikes the ribbon 20. It is appreciated that
the relative dimensions of the mask field 22 and the resulting
pattern can vary in accordance with this disclosure. Mask 14' (FIG.
18) is used to complete the two-dimensional illustration of the
electrical components.
[0142] Continuing to refer to FIG. 17, in the laser ablation
apparatus 10 the excimer laser source 11 emits beam 12, which
passes through the chrome-on-quartz mask 14. The mask field 22
causes parts of the laser beam 12 to be reflected while allowing
other parts of the beam to pass through in the form of an image of
part or all of an electrode pattern. The image or part of laser
beam 12 that passes through mask 14 in turn creates a pattern on
the gold film where impacted by the laser beam 12. It is
appreciated that ribbon or web 20 can be stationary relative to
apparatus 10 or move continuously on a roll through apparatus 10.
Accordingly, non-limiting rates of movement of the ribbon 20 can be
from about 0 m/min to about 100 m/min, more preferably about 30
m/min to about 60 m/min. It is appreciated that the rate of
movement of the ribbon 20 is limited only by the apparatus 10
selected and may well exceed 100 m/min depending upon the pulse
duration of the laser source 11 in accordance with the present
disclosure.
[0143] Once the pattern of the mask 14 is created on the ribbon 20,
the ribbon is rewound and fed through the apparatus 10 again, with
mask 14' (FIG. 18). It is appreciated that laser apparatus 10
could, alternatively, be positioned in series in accordance with
this disclosure. A detailed description of the step and repeat
process is found in U.S. Application Ser. No. 60/480,397, filed
Jun. 20, 2003, entitled "Devices And Methods Relating To Analyte
Sensors", the disclosure of which is incorporated herein by
reference. Thus, by using masks 14, 14', large areas of the web or
ribbon 20 can be patterned using step-and-repeat processes
involving multiple mask fields 22 in the same mask area to enable
the economical creation of intricate electrode patterns and other
electrical components on a substrate of the base, the precise edges
of the electrode components, and the removal of greater amounts of
the metallic film from the base material.
[0144] FIG. 20 is a non-limiting schematic of an electrode set
ribbon 124 formed in accordance with the present disclosure,
although having an electrode pattern different from that
illustrated in FIGS. 17 and 18. The ribbon 124 includes a plurality
of panels 120, each of which includes a plurality of electrode
systems 116. Each system includes two electrodes, both labeled 104
and having a sensing region 110. Also shown is the original
metallic laminate ribbon 122 that is subject to laser ablation to
form the electrode set ribbon 124. The width of the ribbon 122 is
selected to accommodate the laser ablation system 10, 10', and may
be, for example, 40 to 0.4 inches (1.2 m to 10.25 mm). The ribbon
may be any length, and is selected based on the desired number of
electrode sets, and/or the ease of handling and transport of the
ribbons. The size of each individual panel is selected to fit
conveniently on the ribbon, and therefore each panel may contain 1
to 1000 electrode sets, preferably 2 to 20 electrode sets.
[0145] Once the complete electrode patterns are created, it is
appreciated that the ribbon 20 may be coupled to a spacer and a
cover using any number of well-known commercially available
methods. A non-limiting example of a suitable method of
manufacture, is described in detail in U.S. Application Ser. No.
60/480,397, filed Jun. 20, 2003, entitled "Devices And Methods
Relating To Analyte Sensors", the disclosure of which is
incorporated herein by reference. In summary, however, it is
appreciated that a reagent film is placed upon the ribbon and dried
conventionally with an in-line drying system. The rate of
processing is nominally 30-38 meters per minute and depends upon
the rheology of the reagent. Reagents suitable for the biosensor
210 are given above, but a preferable reagent is set out in Table
2.
[0146] The materials are processed in continuous reels such that
the electrode pattern is orthogonal to the length of the reel, in
the case of the base. Once the base has been coated, the spacer
material is laminated onto the coated ribbon 20. Prior to
laminating the spacer material, however, a portion of the spacer
material is removed, thereby forming a slit. A punching process is
used to remove the unneeded portion of the spacer. The die set
governs the shape of the slit. The resulting slit-spacer is placed
in a reel-to-reel process onto the base. A cover is then laminated
onto the spacer using a reel-to reel process. The biosensors can
then be produced from the resulting reels of material by means of
slitting and cutting.
[0147] The slit in the spacer preferably forms a capillary fill
space between the base and the cover. A hydrophobic adhesive on the
spacer prevents the test sample from flowing into the reagent under
the spacer and therefore the fill space defines the test chamber
volume. It is appreciated that the chamber volume can vary in
accordance with this disclosure depending upon the application of
the biosensor. A non-limiting detailed description of suitable fill
volumes is found in U.S. Application Ser. No. 60/480,397, noted
above.
[0148] As discussed above, biosensor 210 has two electrode patterns
having different feature sizes on a common planar surface and thus
achieves multiple functionalities on that surface. Preferably,
electrode set 266 has an electrode pattern formed as a macro
electrode array with a first pre-defined feature size. A
non-limiting example of a suitable functionality of the
macroelectrode array is hematocrit level correction, which is
described in U.S. patent application Ser. No. 10/688,312, entitled
"System And Method For Analyte Measurement Using AC Phase Angle
Measurement", filed Oct. 17, 2003, the disclosure of which is
incorporated herein by reference. Further, it is appreciated that
during use, a test meter (not shown) applies a voltage to one
electrode and measures the current response at the other electrode
to obtain a signal as described in U.S. patent application Ser. No.
10/688,312 just noted.
[0149] Electrode set 268 has an electrode pattern formed as an
interlaced microelectrode array with a second pre-defined feature
size. A non-limiting example of a suitable functionality of the
microelectrode array is glucose estimation, which is also described
in U.S. patent application Ser. No. 10/688,312. Further, it is
appreciated that during use, a test meter (not shown) applies a
voltage to one electrode and measures the current response at the
other electrode to obtain a signal as described in U.S. patent
application Ser. No. 10/688,312.
[0150] In operation, a user places his or her lanced finger at
opening 221 of biosensor 210. A liquid sample (whole blood) flows
from the finger into the opening 221. The liquid sample is
transported via capillary action through the sample-receiving
chamber 220 and across the fingers 280 of the element of the
electrode set 266. Subsequently, the liquid sample flows through
the sample-receiving chamber 220 toward vent 262 and into
engagement with the reagent 264 situated upon the fingers 284 of
the element of the electrode set 268. As discussed above,
hematocrit correction values are determined from the interaction of
the liquid sample with the fingers 280 and a glucose determination
from the interaction of the liquid sample/reagent mixture with the
fingers 284. While hematocrit and glucose determination
functionalities are described with reference to biosensor 210, it
is appreciated that the electrode patterns, may be used for a
variety of functionalities in accordance with the present
disclosure.
[0151] The processes and products described include disposable
biosensors, especially for use in diagnostic devices. However, also
included are electrochemical biosensors for non-diagnostic uses,
such as measuring an analyte in any biological, environmental, or
other, sample. In addition, it is appreciated that various uses and
available functions of the biosensor may stand alone or be combined
with one another in accordance with this disclosure.
[0152] As discussed below with reference to FIGS. 11-16, each of
the disclosed biosensors operates from the standpoint of a user in
a manner similar to that described above with reference from 210.
In addition, like components of the biosensors are numbered
alike.
[0153] Referring now to FIG. 11, a biosensor 310 is formed and
manufactured in a manner similar to biosensor 210 except for the
pattern of the conductive material 216 positioned on the base 212.
The conductive material 216 of biosensor 310 defines a first
electrode system 366 and a second electrode system 368. The
electrode systems 366, 368 are similar to the systems of biosensor
210 except for the resulting pattern of the connecting traces 377,
379 and contact pads 378, 383 on the base 212. It is submitted that
the traces 377, 379 and pads 378, 383 may take on a variety of
shapes and sizes in accordance with this disclosure.
[0154] As shown in FIG. 12, a biosensor 510 is formed in a manner
similar to biosensor 210 except for the pattern of the conductive
material 216 positioned on the base 212. In addition to electrode
set 268, the conductive material 216 of biosensor 510 defines a
first electrode set 566. The electrode set 566 is similar to set
366 except for the configuration of the interlacing electrode
pattern formed by the elements of the electrodes.
[0155] Specifically, the first electrode set 566 includes a working
electrode having an element with one electrode finger 581 and a
counter electrode having an element with two electrode fingers 580.
The fingers 580, 581 cooperate with one another to create an
interlaced electrode pattern configured as a macroelectrode array
having a feature size or gap width of about 250 .mu.m. The
electrodes 580, 581 each have an electrode width of about 250
.mu.m. As discussed above with set 266, the electrode and gap
widths may vary in accordance with this disclosure.
[0156] As described above with reference to biosensor 210, the
first and second electrode sets 566, 268 have different feature
sizes and are used to create different functionalities on biosensor
510. A non-limiting example of a suitable functionality of the
first electrode set 566 is for determining correction factors for
hematocrit levels. The measurement methods are as discussed above
with reference to biosensor 210.
[0157] Referring now to FIG. 13, a biosensor 610 is formed in a
manner similar to biosensor 210 except for the pattern of the
conductive material 216 positioned on the base 212. In addition to
the first electrode set 566 as discussed above, the conductive
material 216 of biosensor 610 defines a second electrode set 668
spaced-apart from set 566.
[0158] The electrode set 668 is similar to set 268 except for the
pattern of interlacing electrode pattern in the element of the
electrodes. Specifically, the second electrode set 668 includes a
working electrode and a counter electrode, each having an element
with three electrode fingers 661. The fingers 661 cooperate with
one another to define an interlaced electrode pattern configured as
a microelectrode array having a feature size or gap width of about
50 .mu.m, which is less than the feature size of the electrode
pattern of the set 566. The electrodes 661 each have an electrode
width of about 50 .mu.m. As discussed above with set 268, the
electrode and gap widths may vary in accordance with this
disclosure.
[0159] In addition, biosensor 610 includes a reagent 664. Reagent
664 is similar to reagent 264, and only differs in its width as it
is applied onto the base 212. Specifically, the reagent 664 extends
across electrode fingers 661. A non-limiting example of a suitable
functionality of the second electrode set 668 is a glucose
determination functionality. The measurement methods are as
discussed above with reference to biosensor 210.
[0160] As shown in FIG. 14, a biosensor 710 is formed in a manner
similar to biosensor 210 except for the pattern of the conductive
material 216 positioned on the base 212. The conductive material
216 of biosensor 710 defines the first electrode set 366 as
discussed above and a second electrode set 768. The electrode set
768 is similar to set 268 except for the pattern of an interlacing
electrode pattern formed by the element of the electrodes.
Specifically, the second electrode set 768 includes a working
electrode and a counter electrode, each having element with five
electrode fingers 770. The fingers 770 cooperate with one another
to define an interlaced electrode pattern configured as a
microelectrode array having a feature size or gap width of about 30
.mu.m, which is less than the feature size of electrode pattern of
set 366. The electrode fingers 770 each have an electrode width of
about 50 .mu.m. As discussed above with set 266, the electrode and
gap widths may vary in accordance with this disclosure. A
non-limiting example of a suitable functionality of the second
electrode set 668 is a glucose determination functionality. The
measurement methods are as discussed above with reference to
biosensor 210.
[0161] In addition, biosensor 710 includes a reagent 364 that is
dispensed upon the fingers 770 by any of a variety of dispensing
methods that are well known to those skilled in the art. Reagent
364 is preferably the reagent set forth in Table 3. Moreover, it is
appreciated that a variety of reagents, non-limiting examples of
which have been discussed above, may be used in accordance with
this disclosure.
[0162] FIG. 15 illustrates a biosensor 1310 in accordance with this
disclosure. Biosensor 1310 is formed in a manner similar to
biosensor 210 except for the configuration of the conductive
material 216 positioned on the base 212, the cover 1118, and the
spacer 1114. The cover 1118 and spacer 1114 are similar to cover
218 and spacer 214 except for their dimensions relative to the base
212 as shown in FIG. 15. The conductive material 216 of biosensor
1310 defines a first electrode set 1366 and a second electrode set
1368. The first electrode set 1366 includes a working electrode and
a counter electrode, each having five electrode fingers 1370. The
fingers 1370 cooperate with one another to define an interlaced
electrode pattern formed as a microelectrode array having a feature
size or gap width of about 17 .mu.m. The electrode fingers 1370
each have an electrode width of about 20 .mu.m.
[0163] The second electrode set 1368 includes a working electrode
and a counter electrode, each having three electrode fingers 1371.
The electrode fingers 1371 cooperate with one another to define an
interlaced electrode pattern formed as a microelectrode array
having a feature size or gap width of about 10 .mu.m. The electrode
fingers 1371 each have an electrode width of about 20 .mu.m. As
discussed above with set 266, the electrode and gap widths of
fingers 1370 and 1371 may vary in accordance with this
disclosure.
[0164] The reagent 264 extends across the electrode fingers 1371 of
the electrode set 1368. A non-limiting example of a suitable
functionality of the first electrode set 1366 includes hematocrit
correction as described above with reference to biosensor 210.
Likewise, a non-limiting example of a suitable functionality of the
second electrode set 1368 is used for determining a glucose
estimate as described above with reference to biosensor 210. The
method of measurement for the electrode sets, 1366 and 1368 is also
as described above with reference to biosensor 210.
[0165] FIG. 16 illustrates biosensor 1510. Biosensor 1510 is
identical to biosensor 210, except for the reagent 1564. Reagent
364 is dispensed onto the electrode fingers 284 as discussed above
with reference to biosensor 710 of FIG. 14.
[0166] FIGS. 21-24 are photographs of electrical patterns formed
using the principles of the present invention. FIG. 21 is a
photograph of a base substrate having an electrical pattern formed
thereon by removing 10% of the conductive material initially
covering the base substrate. In this embodiment the conductive
material is gold. The pattern was formed with a single pulse of a
laser.
[0167] FIG. 22 is a photograph of a base substrate having an
electrical pattern formed thereon by removing 20% of the conductive
material initially covering the base substrate. In this embodiment
the conductive material is gold and the gap widths are
approximately 20 .mu.m as indicated. The pattern was formed with a
single pulse of a laser.
[0168] FIG. 23 is a photograph of a base substrate having an
electrical pattern formed thereon by removing 50% of the conductive
material initially covering the base substrate. In this embodiment
the conductive material is gold and the gap widths are
approximately 20 .mu.m as indicated. The pattern was formed with a
single pulse of a laser.
[0169] FIG. 24 is a photograph of a base substrate having an
electrical pattern formed thereon by removing 90% of the conductive
material initially covering the base substrate. In this embodiment
the conductive material is gold and the gap widths are
approximately 250 .mu.m as indicated. The pattern was formed with a
single pulse of a laser.
[0170] Several production runs were made which demonstrate the very
fast speed in which the electrical patterns of the biosensors in
accordance with the present invention can be produced. Many of the
runs included electrode patterns with two different feature sizes,
as indicated in Table 4. FIGS. 21-24 are photos taken of selected
ones of the electrode structures, as also indicated in Table 4. The
masks used to make the patterns included both "Structure 1" and
"Structure 2" listed in Table 4. A single laser pulse of about 25
nanoseconds was used to form the patterns. As indicated, long webs
(about 450 m or more) of material were passed under the laser
ablation apparatus at a controlled speed as the electrical patterns
were formed. The pitch or distance between the electrical patterns
was 9.015 mm for all runs, which corresponds to a preferred width
of a biosensor made in accordance with the present invention.
4TABLE 4 Roll Structure 1 Structure 2 Run time Patterns Length Run
# Finger/Gap (.mu.m) Finger/Gap (.mu.m) (min) per min. Figure (m) 1
20/20 250/200 20 2585 466 2 250/50 -- 40 1256 453 3 20/250 250/20
13 3873 24 454 (Structure 1) 4 20/20 250/20 22 2284 453 (Structure
2) 5 50/50 100/100 22 2289 454 6 100/50 -- 20 2518 454 7 20/20
100/20 23 2363 FIG. 23 - 490 Structure 1; FIG. 22 - Structure 2 8
50/100 -- 19 2755 472 9 20/20 50/20 19 2860 490
[0171] The "patterns per minute" column reflects the speed at which
substrates for individual biosensors can be formed. For example, in
Run No. 1, 2585 base substrates each corresponding to a single
biosensor, and each having two (2) electrode feature sizes, are
formed in a single minute. As can be seen from the above table 4,
the method embodied by the present invention is well suited to fast
mass production.
[0172] Although the invention has been described in detail with
reference to a preferred embodiment, variations and modifications
exist within the scope and spirit of the invention, on as described
and defined in the following claims.
* * * * *