U.S. patent application number 10/976489 was filed with the patent office on 2005-06-23 for electrochemical test strip for reducing the effect of direct interference current.
Invention is credited to Baskeyfield, Damian Edward Haydon, Davies, Oliver William Hardwicke, Leiper, Elaine, Marshall, Robert, Whyte, Lynsey.
Application Number | 20050133368 10/976489 |
Document ID | / |
Family ID | 34577659 |
Filed Date | 2005-06-23 |
United States Patent
Application |
20050133368 |
Kind Code |
A1 |
Davies, Oliver William Hardwicke ;
et al. |
June 23, 2005 |
Electrochemical test strip for reducing the effect of direct
interference current
Abstract
This invention describes an electrochemical sensor which is
adapted to reduce the effects of interfering compounds in bodily
fluids when measuring an analyte in such fluids using an
electrochemical strip. The sensor includes a substrate, a first and
second working electrodes, and a reference electrode. A reagent
layer is disposed on the electrodes such that, in one embodiment it
completely covers all of the first working electrode, but only
partially covers the second working electrode and, in a second
embodiment, it only covers a portion of the first and the second
working electrode. The portion of the working electrodes not
covered by the reagent layer and is used to correct for the
interference effect on the analyte measurement.
Inventors: |
Davies, Oliver William
Hardwicke; (Croy, GB) ; Marshall, Robert;
(Conon Bridge, GB) ; Baskeyfield, Damian Edward
Haydon; (Auldeam, GB) ; Whyte, Lynsey;
(Lochardil, GB) ; Leiper, Elaine; (Dores Road,
GB) |
Correspondence
Address: |
PHILIP S. JOHNSON
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
34577659 |
Appl. No.: |
10/976489 |
Filed: |
October 29, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60516252 |
Oct 31, 2003 |
|
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|
60558424 |
Mar 31, 2004 |
|
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60558728 |
Mar 31, 2004 |
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Current U.S.
Class: |
204/403.01 ;
204/403.06 |
Current CPC
Class: |
A61B 5/150435 20130101;
A61B 5/14532 20130101; Y02A 90/10 20180101; A61B 5/150022 20130101;
C12Q 1/001 20130101; A61B 5/150282 20130101; A61B 5/150358
20130101; A61B 5/1486 20130101; A61B 5/150503 20130101; C12Q 1/006
20130101; G01N 27/3274 20130101 |
Class at
Publication: |
204/403.01 ;
204/403.06 |
International
Class: |
G01N 027/26 |
Claims
1. An electrochemical sensor comprising: a substrate; a first
working electrode disposed on said substrate; a second working
electrode disposed on said substrate; a reference electrode; and a
reagent layer disposed on said first working electrode, wherein
said reagent layer completely covers said first working electrode;
said second working electrode including a covered portion and an
uncovered portion wherein said covered portion of said second
working electrode is covered by said reagent layer.
2. An electrochemical sensor according to claim 1 wherein: said
first working electrode, said second working electrode and said
reference electrode are positioned in a sample receiving chamber;
said sample receiving chamber having a proximal and a distal end,
said distal end including a first opening which is adapted to
receive bodily fluids; and said uncovered portion of said second
working electrode is positioned adjacent said first opening.
3. An electrochemical sensor according to claim 2 wherein said
covered portion of said second working electrode is positioned at a
proximal end of said sample receiving chamber.
4. An electrochemical sensor according to claim 3 wherein said
first working electrode is positioned proximal to said uncovered
portion of said second working electrode and between said reference
electrode and said covered portion of said second working
electrode.
5. An electrochemical sensor according to claim 1 wherein: said
first working electrode, said second working electrode and said
reference electrode are positioned in a sample receiving chamber;
said sample receiving chamber having a proximal and a distal end,
said distal end including a first opening which is adapted to
receive bodily fluids; and said uncovered portion of said second
working electrode comprising two sections, wherein each said
section is positioned adjacent said covered portion of said second
working electrode.
6. An electrochemical sensor according to claim 5, wherein: said
first working electrode is positioned adjacent said distal end of
said sample receiving chamber; said second working electrode is
positioned adjacent said proximal end of said sample receiving
chamber; and said reference electrode is positioned between said
first and said second working electrodes.
7. An electrochemical sensor comprising: a substrate; a first
working electrode disposed on said substrate; a second working
electrode disposed on said substrate; a reference electrode; and a
reagent layer disposed on a portion said first working electrode
and said second working electrode; said first working electrode
having a reagent coated area and an uncoated area; and said second
working electrode having a reagent coated area and an uncoated
area.
8. An electrochemical sensor according to claim 7 wherein: said
first working electrode, said second working electrode and said
reference electrode are positioned in a sample receiving chamber;
said sample receiving chamber has a proximal and a distal end, said
distal end including a first opening which is adapted to receive
bodily fluids; and said uncovered portion of said first working
electrode comprises two sections, wherein each said section is
positioned adjacent said covered portion of said first working
electrode; and said uncovered portion of said second working
electrode comprises two sections, wherein each said section is
positioned adjacent said covered portion of said first working
electrode.
9. An electrochemical sensor according to claim 8, wherein: said
first working electrode is positioned adjacent said distal end of
said sample receiving chamber; said second working electrode is
positioned adjacent said proximal end of said sample receiving
chamber; and said reference electrode is positioned between said
first and said second working electrodes.
10. An electrochemical sensor according to claim 7 wherein said
uncoated area of said first working electrode is not equal to said
uncoated area of said second working electrode.
11. An electrochemical sensor according to claim 7 wherein: said
first working electrode, said second working electrode and said
reference electrode are positioned in a sample receiving chamber;
said sample receiving chamber has a proximal and a distal end, said
distal end including a first opening which is adapted to receive
bodily fluids; said uncovered portion of said second working
electrode is positioned at a proximal end of said sample receiving
chamber; and said uncovered portion of said first working electrode
is positioned proximal to said uncovered portion of said second
working electrode.
12. An electrochemical sensor according to claim 11, wherein: said
covered portion of said first working electrode is positioned
proximal to said uncovered portion of said first working electrode;
and said covered portion of said second working electrode is
positioned proximal to said covered portion of said first working
electrode.
13. An electrochemical sensor according to claim 1, further
including an integrated lance at a distal end of said lance.
14. An electrochemical sensor according to claim 7, further
including an integrated lance at a distal end of said
electrochemical sensor.
Description
PRIORITY
[0001] The present invention claims priority to the following U.S.
Provisional Applications: U.S. Provisional Application Ser. No.
60/516,252 filed on Oct. 31, 2003; U.S. Provisional Application
Ser. No. 60/558,424 filed on Mar. 31, 2004; and U.S. Provisional
Application Ser. No. 60/558,728 filed on Mar. 31, 2004. Which
applications are hereby incorporated herein by reference.
RELATED APPLICATIONS
[0002] The present invention is related to the following co-pending
U.S. applications: U.S. patent application Ser. No. ______
[Attorney Docket Number DDI-5027 USNP], filed on Oct. 29, 2004;
U.S. patent application Ser. No. ______ [Attorney Docket Number
DDI-5042 USNP], filed on Oct. 29, 2004; U.S. patent application
Ser. No. ______ [Attorney Docket Number DDI-5065], filed on Oct.
29, 2004; U.S. patent application Ser. No. ______ [Attorney Docket
Number DDI-5066], filed on Oct. 29, 2004; and U.S. patent
application Ser. No. ______ [Attorney Docket Number DDI-5067],
filed on Oct. 29, 2004.
FIELD OF THE INVENTION
[0003] The present invention is related, in general to
electrochemical strips and systems which are designed to reduce the
effect of interfering compounds on measurements taken by such
analyte measurement systems and, more particularly, to an improved
electrochemical strip for reducing the effects of direct
interference currents in a glucose monitoring system wherein the
electrochemical strip has electrodes with uncoated regions.
BACKGROUND OF INVENTION
[0004] In many cases, an electrochemical glucose measuring system
may have an elevated oxidation current due to the oxidation of
interfering compounds commonly found in physiological fluids such
as, for example, acetaminophen, ascorbic acid, bilirubin, dopamine,
gentisic acid, glutathione, levodopa, methyldopa, tolazimide,
tolbutamide, and uric acid. The accuracy of glucose meters may,
therefore, be improved by reducing or eliminating the portion of
the oxidation current generated by interfering compounds. Ideally,
there should be no oxidation current generated from any of the
interfering compounds so that the entire oxidation current would
depend only on the glucose concentration.
[0005] It is, therefore, desirable to improve the accuracy of
electrochemical sensors in the presence of potentially interfering
compounds such as, for example, ascorbate, urate, and,
acetaminophen, commonly found in physiological fluids. Examples of
analytes for such electrochemical sensors may include glucose,
lactate, and fructosamine. Although glucose will be the main
analyte discussed, it will be obvious to one skilled in the art
that the invention set forth herein may also be used with other
analytes.
[0006] Oxidation current may be generated in several ways. In
particular, desirable oxidation current results from the
interaction of the mediator with the analyte of interest (e.g.,
glucose) while undesirable oxidation current is generally comprised
of interfering compounds being oxidized at the electrode surface
and by interaction with the mediator. For example, some interfering
compounds (e.g., acetominophen) are oxidized at the electrode
surface. Other interfering compounds (e.g., ascorbic acid), are
oxidized by chemical reaction with the mediator. This oxidation of
the interfering compound in a glucose measuring system causes the
measured oxidation current to be dependent on the concentration of
both the glucose and any interfering compound. Therefore, in the
situation where the concentration of interfering compound oxidizes
as efficiently as glucose and the interferent concentration is high
relative to the glucose concentration, the measurement of the
glucose concentration would be improved by reducing or eliminating
the contribution of the interfering compounds to the total
oxidation current.
[0007] One known strategy that can be used to decrease the effects
of interfering compounds is to use a negatively charged membrane to
cover the working electrode. As an example, a sulfonated
fluoropolymer such as NAFION.TM. may be used to repel all
negatively charged chemicals. In general, most interfering
compounds such as ascorbate and urate have a negative charge, thus,
the negatively charged membrane prevents the negatively charged
interfering compounds from reaching the electrode surface and being
oxidized at that surface. However, this technique is not always
successful since some interfering compounds such as acetaminophen
do not have a net negative charge, and thus, can pass through a
negatively charged membrane. Nor would this technique reduce the
oxidation current resulting from the interaction of interfering
compounds with some mediators. The use of a negatively charged
membrane on the working electrode could also prevent some commonly
used mediators, such as ferricyanide, from passing through the
negatively charged membrane to exchange electrons with the
electrode.
[0008] Another known strategy that can be used to decrease the
effects of interfering compounds is to use a size selective
membrane on top of the working electrode. As an example, a 100
Dalton exclusion membrane such as cellulose acetate may be used to
cover the working electrode to exclude all chemicals with a
molecular weight greater than 100 Daltons. In general, most
interfering compounds have a molecular weight greater than 100
Daltons, and thus, are excluded from being oxidized at the
electrode surface. However, such selective membranes typically make
the test strip more complicated to manufacture and increase the
test time because the oxidized glucose must diffuse through the
selective membrane to get to the electrode.
[0009] Another strategy that can be used to decrease the effects of
interfering compounds is to use a mediator with a low redox
potential, for example, between about -300 mV and +100 mV (when
measured with respect to a saturated calomel electrode). Because
the mediator has a low redox potential, the voltage applied to the
working electrode may also be relatively low which, in turn,
decreases the rate at which interfering compounds are oxidized by
the working electrode. Examples of mediators having a relatively
low redox potential include osmium bipyridyl complexes, ferrocene
derivatives, and quinone derivatives. A disadvantage of this
strategy is that mediators having a relatively low potential are
often difficult to synthesize, unstable and have a low water
solubility.
[0010] Another known strategy that can be used to decrease the
effects of interfering compounds is to use a dummy electrode which
is coated with a mediator. In some instances the dummy electrode
may also be coated with an inert protein or deactivated redox
enzyme. The purpose of the dummy electrode is to oxidize the
interfering compound at the electrode surface and/or to oxidize the
mediator reduced by the interfering compound. In this strategy, the
current measured at the dummy electrode is subtracted from the
total oxidizing current measured at the working electrode to remove
the interference effect. A disadvantage of this strategy is that it
requires that the test strip include an additional electrode and
electrical connection (i.e., the dummy electrode) which cannot be
used to measure glucose. The inclusion of dummy electrode is an
inefficient use of an electrode in a glucose measuring system.
SUMMARY OF INVENTION
[0011] The invention described herein is directed to an
electrochemical sensor which reduces the effects of interferences.
An electrochemical sensor according to the present invention
includes a substrate, at least first and second working electrodes
and a reference electrode. In one embodiment of an electrochemical
sensor according to the present invention, a reagent layer is
disposed on the electrodes such that it completely covers all of
the first working electrode and only partially covers the second
working electrode. In a method according to the present invention,
the oxidation current generated at the portion of the second
working electrode not covered by the reagent layer is used to
correct for the effect of interfering substances on the glucose
measurement.
[0012] In one embodiment of the present invention, the
electrochemical glucose test strip includes a first and second
working electrodes, where the first working electrode is completely
covered with a reagent layer and the second working electrode is
only partially covered with the reagent layer. Thus, the second
working electrode has a reagent coated area and an uncoated area.
The reagent layer may include, for example, a redox enzyme such as
glucose oxidase and a mediator such as, for example, ferricyanide.
The first working electrode will have a superposition of two
oxidation current sources, one from glucose and a second from
interferents. Similarly, the second working electrode will have a
superposition of three oxidation current sources from glucose,
interferents at the reagent coated portion, and interferents at the
uncoated portion. The uncoated portion of the second working
electrode will only oxidize interferents and not oxidize glucose
because there is no reagent is in this area. The oxidation current
measured at the uncoated portion of the second working electrode
may then be used to estimate the total interferent oxidation
current and calculate a corrected oxidation current which removes
the effects of interferences.
[0013] In an alternative strip embodiment according to the present
invention, the electrochemical glucose test strip includes a first
and second working electrodes, where the first and second working
electrode are only partially covered with the reagent layer. Thus,
in this embodiment both the first and second working electrode have
a reagent coated portion and an uncoated portion. The first
uncovered area of the first working electrode and the second
uncovered area of the second working electrode are different. The
oxidation current measured at the uncoated portion of the first and
second working electrodes are used to estimate the interferent
oxidation current for the uncoated portion and to calculate a
corrected glucose current.
BRIEF DESCRIPTION OF DRAWINGS
[0014] A better understanding of the features and advantages of the
present invention will be obtained by reference to the following
detailed description that sets forth illustrative embodiments, in
which the principles of the invention are utilized, and the
accompanying drawings, of which:
[0015] FIG. 1 is an exploded perspective view of a test strip
according to an embodiment of the present invention;
[0016] FIG. 2 is a simplified plane view of a distal portion of a
test strip according to the embodiment of the present invention
illustrated in FIG. 1 including a conductive layer and an
insulation layer;
[0017] FIG. 3 is a simplified plane view of a distal portion of a
test strip according to the embodiment of the present invention
illustrated in FIG. 1 wherein the position of a reagent layer is
illustrated with the conductive layer and the insulation layer;
[0018] FIG. 4 is an exploded perspective view of a test strip
according to a further embodiment of the present invention;
[0019] FIG. 5 is a simplified plane view of a distal portion of a
test strip according to the embodiment of the present invention
illustrated in FIG. 4 including of a conductive layer and an
insulation layer; and
[0020] FIG. 6 is a simplified plane view of a distal portion of a
test strip according to the embodiment of the present invention
illustrated in FIG. 4 wherein a reagent layer is illustrated with
the conductive layer and the insulation layer.
[0021] FIG. 7 is a simplified plane view of a distal portion of a
test strip according to the embodiment of the present invention
illustrated in FIG. 4 wherein a reagent layer is illustrated with
the conductive layer.
[0022] FIG. 8 is a simplified plane view of a distal portion of a
test strip according to another embodiment of the present invention
wherein a reagent layer is illustrated with the conductive layer
that helps reduce an IR drop effect.
[0023] FIG. 9 is a simplified plane view of a distal portion of a
test strip according to yet another embodiment of the present
invention wherein a reagent layer is illustrated with the
conductive layer and the insulation layer such there are two
working electrodes that have an uncoated portion.
[0024] FIG. 10 is a simplified plane view of a distal portion of a
test strip according to still yet another embodiment of the present
invention wherein a reagent layer is illustrated with the
conductive layer and the insulation layer such there are two
working electrodes that have an uncoated portion.
[0025] FIG. 11 is a graph showing the current at a first working
electrode of a strip designed in accordance with the present
invention tested with 70 mg/dL glucose samples in blood spiked with
varying levels of uric acid.
[0026] FIG. 12 is a graph showing the current at a first working
electrode at a strip designed in accordance with the present
invention tested with 240 mg/dL glucose samples in blood spiked
with varying levels of uric acid.
[0027] FIG. 13 is an exploded perspective view of a test strip that
has an integrated lance.
[0028] FIG. 14 is a simplified schematic showing a meter
interfacing with a test strip that has a first contact, second
contact, and reference contact disposed on a substrate.
DETAILED DESCRIPTION OF THE INVENTION
[0029] This invention described herein includes a test strip and
method for improving the selectivity of an electrochemical glucose
measuring system.
[0030] FIG. 1 is an exploded perspective view of a test strip
according to a first embodiment of the present invention. In the
embodiment of the present invention illustrated in FIG. 1, an
electrochemical test strip 62, which may be used for measuring
glucose concentration in bodily fluids such as blood or
interstitial fluid, includes a first working electrode 10 and a
second working electrode 12, where first working electrode 10 is
completely covered with a reagent layer 22 and second working
electrode 12 is only partially covered with reagent layer 22. Thus,
the second working electrode has a reagent coated portion and an
uncoated portion. Reagent layer 22 may include, for example, a
redox enzyme such as, for example, glucose oxidase and a mediator
such as, for example, ferricyanide. Because ferricyanide has a
redox potential of approximately 400 mV (when measured with respect
to a saturated calomel electrode) at a carbon electrode, the
introduction of a bodily fluid e.g., blood may generate a
significant oxidation of interferents by the mediator and/or the
working electrode. Therefore, the oxidation current measured at
first working electrode 10 will be a superposition of oxidation
current sources: a first, desirable, oxidation current generated by
the oxidation of glucose and a second, undesirable, oxidation
current generated by the interferents. The oxidation current
measured at second working electrode 12 will also be a
superposition of oxidation current sources: a first, desirable
oxidation current generated by the oxidation of glucose, a second,
undesirable oxidation current generated by interferents at the
covered portion of working electrode 12 and a third oxidation
current generated by interferents at the uncovered portion of
working electrode 12. The uncoated portion of second working
electrode 12 will only oxidize interferents and not oxidize glucose
because there is no reagent on the uncoated portion of second
working electrode 12. Because the oxidation current measured at the
uncoated portion of second working electrode 12 does not depend on
glucose and the uncoated area of second working electrode 12 is
known, it is possible to calculate the interferent oxidation
current for the uncoated portion of the second working electrode
12. In turn, using the interferent oxidation current calculated for
the uncoated portion of second working electrode 12 and knowing the
area of first working electrode 10 and the area of the coated
portion of second working electrode 12, it is possible to calculate
a corrected glucose current which accounts for the effects of
interfering compounds oxidized at the electrode.
[0031] FIG. 1 is an exploded perspective view of a test strip 62
according to a first embodiment of the present invention. Test
strip 62, as illustrated in FIG. 1, may be manufactured by a series
of 6 consecutive printing steps which lay down six layers of
material on substrate 50. The six layers may be deposited by, for
example, screen printing on substrate 50. In an embodiment of this
invention, the 6 layers may include a conductive layer 64, an
insulation layer 16, a reagent layer 22, an adhesive layer 66, a
hydrophilic layer 68, and a top layer 40. Conductive layer 64 may
further includes first working electrode 10, second working
electrode 12, reference electrode 14, first contact 11, second
contact 13, reference contact 15, and strip detection bar 17.
Insulation layer 16 may further include cutout 18. Adhesive layer
66 may further include first adhesive pad 24, second adhesive pad
26, and third adhesive pads 28. Hydrophilic layer 68 may further
include first hydrophilic film 32, and second hydrophilic film 34.
Top layer 40 may further includes a clear portion 36 and opaque
portion 38. Test strip 62 has a first side 54 and second side 56, a
distal electrode side 58, and a proximal electrode side 60 as
illustrated in FIG. 1. The following sections will describe the
respective layers of test strip 62 in more detail.
[0032] In one embodiment of the present invention, substrate 50 is
an electrically insulating material such as plastic, glass,
ceramic, and the like. In a preferred embodiment of this invention,
substrate 50 may be a plastic such as, for example, nylon,
polycarbonate, polyimide, polyvinylchloride, polyethylene,
polypropylene, PETG, or polyester. More particularly the polyester
may be, for example Melinex.RTM. ST328 which is manufactured by
DuPont Teijin Films. Substrate 50 may also include an acrylic
coating which is applied to one or both sides to improve ink
adhesion.
[0033] The first layer deposited on substrate 50 is conductive
layer 64 which includes first working electrode 10, second working
electrode 12, reference electrode 14, and strip detection bar 17.
In accordance with the present invention, a screen mesh with an
emulsion pattern may be used to deposit a material such as, for
example, a conductive carbon ink in a defined geometry as
illustrated in FIG. 1. Reference electrode 14 may also be a counter
electrode, a reference/counter electrode, or a quasi-reference
electrode. Conductive layer 64 may be disposed on substrate 50 by
using screen printing, rotogravure printing, sputtering,
evaporation, electroless plating, ink jetting, sublimation,
chemical vapor deposition, and the like. Suitable materials which
may be used for conductive layer 64 are Au, Pd, Ir, Pt, Rh,
stainless steel, doped tin oxide, carbon, and the like. In an
embodiment of this invention, the carbon ink layer may have a
height between 1 and 100 microns, more particularly between 5 and
25 microns, and yet even more particularly at approximately 13
microns. The height of the conductive layer can vary depending on
the desired resistance of the conductive layer and the conductivity
of the material used for printing the conductive layer.
[0034] First contact 11, second contact 13, and reference contact
15 may be used to electrically interface with a meter. This allows
the meter to electrically communicate to first working electrode
10, second working electrode 12, and reference electrode 14 via,
respective, first contact 11, second contact 13, and reference
contact 15.
[0035] The second layer deposited on substrate 50 is insulation
layer 16. Insulation layer 16 is disposed on at least a portion of
conductive layer 64 as shown in FIG. 1. FIG. 2 is a simplified
plane view of a distal portion of test strip 62 which highlights
the position of first working electrode 10, second working
electrode 12, and reference electrode 14 with respect to insulation
layer 16. Insulation layer 16 further includes a cutout 18 which
may have a T-shaped structure as shown in FIGS. 1 and 2. Cutout 18
exposes a portions of first working electrode 10, second working
electrode 12, and reference electrode 14 which can be wetted with
liquid. Cutout 18 further includes a distal cutout width W1,
proximal cutout width W2, a distal cutout length L4 and a proximal
cutout length L5. Distal cutout width W1 corresponds to the width
of first working electrode 10 and reference electrode 14 as
illustrated in FIG. 2. Distal cutout length L4 corresponds to a
length which is greater than both first working electrode 10 and
reference electrode 14 together. Proximal cutout width W2 and
proximal cutout length LS form a rectangular section which exposes
the width and length of second working electrode 12. In accordance
with the present invention, distal cutout width W1, proximal cutout
width W2, distal cutout length L4 and proximal cutout length L5 may
have a respective dimension of approximately 0.7, 1.9, 3.2, and
0.43 mm. In one embodiment of the present invention, first working
electrode 10, reference electrode 14, and second working electrode
12 have a respective length of L1, L2, and L3 which may be about
0.8, 1.6, and 0.4 mm. In accordance with the present invention,
electrode spacing S1 is a distance between first working electrode
10 and reference electrode 14; and between reference electrode 14
and second working electrode 12 which may be about 0.4 mm.
[0036] The third layer deposited on substrate 50 is a reagent layer
22. Reagent layer 22 is disposed on at least a portion of
conductive layer 64 and insulation layer 16 as shown in FIGS. 1.
FIG. 3 is a simplified plane view of a distal portion of test strip
62 according to the first embodiment of the present invention which
highlights the position of reagent layer 22 with respect to first
working electrode 10, second working electrode 12, reference
electrode 14, and insulation layer 16. Reagent layer 22 may be in
the shape of a rectangle having a reagent width W3 and a reagent
length L6 as illustrated in FIGS. 1 and 3. In one embodiment of the
invention, reagent width W3 may be about 1.3 mm and reagent length
L6 may be about 4.7 mm. In a further embodiment of the present
invention, reagent layer 22 has a sufficiently large width W3 and
length L6 such that reagent layer 22 completely covers first
working electrode 10 and reference electrode 14. However, reagent
layer 22 has an appropriately sized width W3 and length L6 such
that second working electrode is not completely covered with
reagent layer 22. In such a scenario, second working electrode 12
has a coated portion 12c and an uncoated portions 12u as
illustrated in FIG. 3. Uncoated portions 12u may be in the shape of
two rectangles where uncoated portions 12u has a wing width W4 and
a length that corresponds to second working electrode length L3. As
a non-limiting example, wing width W4 may be about 0.3 mm. In one
embodiment of the present invention, reagent layer 22 may include a
redox enzyme such as, for example, glucose oxidase or PQQ-glucose
dehydrogenase (where PQQ is an acronym for
pyrrolo-quinoline-quinone) and a mediator such as, for example,
ferricyanide.
[0037] The fourth layer deposited on substrate 50 is an adhesive
layer 66 which includes a first adhesive pad 24, a second adhesive
pad 26, and a third adhesive pad 28. First adhesive pad 24 and
second adhesive pad 26 form the walls of a sample receiving
chamber. In one embodiment of the present invention, first adhesive
pad 24 and second adhesive pad 26 may be disposed on substrate 50
such that neither of the adhesive pads touches reagent layer 22. In
another embodiments of the present invention where the strip volume
needs to be reduced, first adhesive pad 24 and/or second adhesive
pad 26 may be disposed on substrate 50 such there is overlap with
reagent layer 22. In an embodiment of the present invention,
adhesive layer 66 has a height of about 70 to 110 microns. Adhesive
layer 66 may include a double sided pressure sensitive adhesive, a
UV cured adhesive, heat activated adhesive, thermosetting plastic,
or other adhesive known to those skilled in the art. As a
non-limiting example, adhesive layer 66 may be formed by screen
printing a pressure sensitive adhesive such as, for example, a
water based acrylic copolymer pressure sensitive adhesive which is
commercially available from Tape Specialties LTD in Tring, Herts,
United Kingdom (part#A6435).
[0038] The fifth layer deposited on substrate 50 is a hydrophilic
layer 68 which includes a first hydrophilic film 32 and second
hydrophilic film 34 as illustrated in FIG. 1. Hydrophilic layer 68
forms the "roof" of the sample receiving chamber. The "side walls"
and "floor" of the sample receiving chamber are formed by a portion
of adhesive layer 66 and substrate 50, respectively. As a
non-limiting example, hydrophilic layer 68 may be an optically
transparent polyester with a hydrophilic anti-fog coating such as
those commercially obtained from 3M. The hydrophilic nature of the
coating is used in the design of strip 62 because it facilitates
filling of liquid into the sample receiving chamber.
[0039] The sixth and final layer deposited on substrate 50 is a top
layer 40 which includes a clear portion 36 and opaque portion 38 as
illustrated in FIG. 1. In accordance with the present invention,
top layer 40 includes a polyester which is coated on one side with
a pressure sensitive adhesive. Top layer 40 has an opaque portion
38 which helps the user observe a high degree of contrast when
blood is underneath clear portion 36. This allows a user to
visually confirm that the sample receiving chamber is sufficiently
filled. After strip 62 is fully laminated, it is cut along incision
line A-A' and in the process creates sample inlet 52 as illustrated
in FIG. 3.
[0040] The first test strip embodiment as illustrated in FIGS. 1-3
may have a possible drawback in that reagent layer 22 may dissolve
in a liquid sample and move a portion of the dissolved reagent
layer over the uncoated portions 12u of second working electrode
12. If such a scenario were to occur, uncoated portions 12u would
also measure an oxidation current that is also proportional to the
glucose concentration. This would degrade the ability to use
mathematical algorithms for removing the effect of interferent
oxidation. In an alternative embodiment of the present invention,
reagent layer 22 should be designed to dissolve in such a way that
it does not migrate to uncoated portions 12u. For example, reagent
layer 22 may be chemically bound to the first working electrode 10,
second working electrode 12, and reference electrode 14 or may have
a thickening agent that minimizes the migration of dissolved
reagent layer 22.
[0041] A further embodiment of the present invention as illustrated
in FIG. 4, the embodiment illustrated in FIG. 4 reduces, and in
certain circumstances minimizes, the immigration of dissolved
reagent to an uncoated portion of the second working electrode. In
this embodiment, second working electrode 102 has a C-shaped
geometry where 2 discrete portions of second working electrode 102
are exposed by cutout 108 as illustrated in FIG. 4. In accordance
with the present invention, reagent layer 110 is disposed on only a
portion of second working electrode 102 to form an uncoated portion
102u and coated portion 102c as illustrated in FIG. 6. Uncoated
portion 102u is adjacent to sample inlet 52. Coated portion 102c is
adjacent to first working electrode 100. When applying liquid to
sample inlet 52 of an assembled test strip 162, the liquid will
flow from sample inlet 52 to coated portion 102c until all
electrodes are covered with liquid. By positioning uncoated portion
102u upstream of the liquid flow, this almost entirely prevents
reagent layer 110 from dissolving and migrating to uncoated portion
102u. This enables the mathematical algorithm to accurately remove
the effects of interferents from the measured oxidation
current.
[0042] FIG. 4 is an exploded perspective view of a test strip 162.
Test strip 162 is manufactured in a manner similar to test strip 62
except that there are geometric or positional changes to a
conductive layer 164, an insulation layer 106, and a reagent layer
110. For the second embodiment of this invention, substrate 50,
adhesive layer 66, hydrophilic layer 68, and top layer 40 are the
same as the first strip embodiment. Test strip 162 has a first side
54 and second side 56, a distal electrode side 58, and a proximal
electrode side 60. It should also be noted that the first and
second test strip embodiment of the present invention may have
elements with similar structure which are denoted with the same
element number and name. If analogous elements between the
respective test strip embodiments are different in structure, the
elements may have the same name, but be denoted with a different
element number. The following sections will describe the respective
layers of test strip 162 in more detail.
[0043] For the strip embodiment illustrated in FIG. 4, the first
layer deposited on substrate 50 is conductive layer 164 which
includes first working electrode 100, second working electrode 102,
reference electrode 104, first contact 101, second contact 103, and
reference contact 105, and strip detection bar 17. In accordance
with the present invention, a screen mesh with an emulsion pattern
may be used to deposit a material such as, for example, a
conductive carbon ink in a defined geometry as illustrated in FIG.
4. First contact 101, second contact 103, and reference contact 105
may be used to electrically interface with a meter. This allows the
meter to electrically communicate to first working electrode 100,
second working electrode 102, and reference electrode 104 via,
respective, first contact 101, second contact 103, and reference
contact 105.
[0044] The second layer deposited on substrate 50 in FIG. 4 is
insulation layer 106. Insulation layer 106 is disposed on at least
a portion of conductive layer 164 as shown in FIG. 4. FIG. 5 is a
simplified plane view of a distal portion of test strip 162 which
highlights the position of first working electrode 100, second
working electrode 102, and reference electrode 104 with respect to
insulation layer 106.
[0045] The third layer deposited on substrate 50 in FIG. 4 is a
reagent layer 110 such that reagent layer 110 is disposed on at
least a portion of conductive layer 164 and insulation layer 106 as
shown in FIG. 6. FIG. 6 is a simplified plane view of a distal
portion of test strip 162 according to the second embodiment of the
present invention which highlights the position of reagent layer
110 with respect to first working electrode 100, second working
electrode 102, reference electrode 104, and insulation layer 106.
Reagent layer 110 may be in the shape of a rectangle having a
reagent width W13 and a reagent length L16. In one embodiment of
this invention, reagent width W13 may be about 1.3 mm and reagent
length L16 may be about 3.2 mm. In a preferred embodiment of the
present invention, reagent layer 110 has a sufficient width W13 and
length L16 such that reagent layer 110 completely covers first
working electrode 100, coated portion 102c, and reference electrode
104, but does not cover uncoated portion 102u.
[0046] FIG. 7 is a simplified plane view of a distal portion of a
test strip according to the embodiment of the present invention
illustrated in FIG. 4 wherein a reagent layer is illustrated with
the conductive layer. In contrast to FIG. 6, FIG. 7 does not show
insulation layer 106. This helps demonstrate the conductive
relationship between uncoated portion 102u and coated portion 102c
which was hidden underneath the opaque character of insulation
layer 106.
[0047] For the strip embodiment illustrated in FIG. 4, insulation
layer 106 is used to define the width of the first working
electrode 100, second working electrode 102, and reference
electrode 104. Insulation layer 106 further includes a cutout 108
which may have a T-shaped structure as shown in FIG. 4 to 6. Cutout
108 exposes a portion of first working electrode 100, second
working electrode 102, and reference electrode 104 which can be
wetted with liquid. Cutout 108 further includes a distal cutout
width W11, proximal cutout width W12, a distal cutout length L14
and a proximal cutout length L15 as illustrated in FIG. 5 and 6.
Distal cutout width W11 corresponds to the width of uncoated
portion 102u. Distal cutout length L14 is greater than the length
uncoated portion 102u. Proximal cutout width W12 and proximal
cutout length L15 forms a rectangular section which approximately
exposes the width and length of first working electrode 100,
reference electrode 104, and coated portion 102c.
[0048] In accordance with the present invention, distal cutout
width W11, proximal cutout width W12, distal cutout length L14 and
proximal cutout length L15 may have a respective dimension of
approximately 1.1, 0.7, 2.5, and 2.6 mm.
[0049] In the embodiment of FIG. 4, uncoated portion 102u,
reference electrode 104, first working electrode 100, and coated
portion 102c have a respective length of L10, L12, L11, and L13
which may be about 0.7, 0.7, 0.4, and 0.4 mm. Electrode spacing S11
is a distance between uncoated portion 102u and reference electrode
104 which may be between about 0.2 to 0.75 mm, and more preferably
between 0.6 to 0.75 mm. Electrode spacing S10 is a distance between
reference electrode 104 and first working electrode 100; and
between coated portion 102c and first working electrode 100 which
may be about 0.2 mm. It should be noted that electrode spacing S11
is greater than S10 to decrease the possibility of reagent
dissolving and migrating to uncoated portion 102u. Additionally,
electrode spacing S11 is greater than S10 to decrease the
possibility of reagent layer 110 being disposed on uncoated portion
102u because of variations in the printing process. The fourth
through sixth layer which is successively disposed on strip 162 in
the same manner as the first strip embodiment. The relative
position and shape of the adhesive layer 66, hydrophilic layer 68,
and top layer 40 are illustrated in FIG. 4.
[0050] In the embodiment of the invention illustrated in FIG. 8,
the C-shape of second working electrode 102 may be partially
altered so that the order in which liquid would wet the electrodes
would be uncoated portion 102u, first working electrode 100,
reference electrode 104, and then coated portion 102c. In the
alternative format, first working electrode 100 and coated portion
102c would be equidistant from reference electrode 104 which is
desirable from an IR drop perspective. In the second strip
embodiment (i.e. test strip 162) illustrated in FIG. 7, the
electrodes are arranged so that the order in which liquid would wet
the electrodes would be uncoated portion 102u, reference electrode
104, first working electrode 100, and then coated portion 102c. For
test strip 162, coated portion 102c is farther away from reference
electrode 104 than the distance between first working electrode 100
and reference electrode 104.
[0051] An algorithm may, therefore be used to calculate a corrected
glucose current that is independent of interferences. After dosing
a sample onto a test strip, a constant potential is applied to the
first and second working electrodes and a current is measured for
both electrodes. At the first working electrode where reagent
covers the entire electrode area, the following equation can be
used to describe the components contributing to the oxidation
current,
WE.sub.1=G+I.sub.cov (Eq 1)
[0052] where WE.sub.1 is a current density at the first working
electrode, G is a current density due to glucose which is
independent of interferences, and I.sub.cov is a current density
due to interferences at the portion of a working electrode covered
with reagent.
[0053] At the second working electrode which is partially covered
with reagent, the following equation can be used to describe the
components contributing to the oxidation current,
WE.sub.2=G+I.sub.cov+I.sub.unc (Eq 2)
[0054] where WE.sub.2 is a current density at the second working
electrode and I.sub.unc is a current density due to interferences
at the portion of a working electrode not covered with reagent.
[0055] To reduce the effects of interferences, an equation is
formulated which describes the relationship between the interferent
current at the coated portion of the second working electrode and
the uncoated portion of the second working electrode. It is
approximated that the interferent oxidation current density
measured at the coated portion is the same as the current density
measured at the uncoated portion. This relationship is further
described by the following equation, 1 I cov = A cov A unc .times.
I unc ( Eq 3 a )
[0056] where A.sub.cov is an area of second working electrode
covered with reagent and A.sub.unc is an area of second working
electrode not covered with reagent.
[0057] Uncoated portions 12u can oxidize interferents, but not
glucose because it is not coated with reagent layer 22. In
contrast, coated portion 12c can oxidize glucose and interferents.
Because it was experimentally found that uncoated portions 12u
oxidizes interferents in a manner proportional to the area of
coated portion 12c, it is possible to predict the proportion of
interferent current measured overall at second working electrode
12. This allows the overall current measured at second working
electrode 12 to be corrected by subtracting the contribution of the
interferent current. In an embodiment of the present invention the
ratio of A.sub.unc:A.sub.cov may be between about 0.5:1 to 5:1, and
is preferably about 3:1. More details describing this mathematical
algorithm for current correction will be described in a later
section.
[0058] In an alternative embodiment of the present invention, the
interferent oxidation current density measured at the coated
portion may be different than the current density measured at the
uncoated portion. This may be ascribed to a more efficient or less
efficient oxidation of interferents at the coated portion. In one
scenario, the presence of a mediators may enhance the oxidation of
interferences relative to the uncoated portion. In another
scenario, the presence of viscosity increasing substances such as
hydroxyethyl cellulose may decrease the oxidation of interferences
relative to the uncoated portion. Depending on the components
included in the reagent layer which partially coats the second
working electrode, it is possible that the interferent oxidation
current density measured at the coated portion may be more or less
than the uncoated portion. This behavior may be phenomenologically
modeled by re-writing Equation 3a to the following form,
I.sub.cov=f.times.I.sub.unc (Eq 3b)
[0059] where f is a correction factor which incorporates the
effects of the interferent oxidation efficiency of the coated to
uncoated portion.
[0060] In an embodiment of the present invention, Equation 1, 2,
and 3a may be manipulated to derive an equation that outputs a
corrected glucose current density independent of interferences. It
should be noted that the three equations (Equation 1, 2, and 3a)
collectively have 3 unknowns which are G, I.sub.cov, and I.sub.unc.
Equation 1 can be rearranged to the following form.
G=WE.sub.1-I.sub.cov (Eq 4)
[0061] Next, I.sub.cov from Equation 3a can be substituted into
Equation 4 to yield Equation 5. 2 G = WE 1 - [ A cov A unc .times.
I unc ] ( Eq 5 )
[0062] Next, Equation 1 and Equation 2 can be combined to yield
Equation 6.
I.sub.unc=WE.sub.2-WE.sub.1 (Eq 6)
[0063] Next, I.sub.unc from Equation 6 can be substituted into
Equation 5 to yield Equation 7a. 3 G = WE 1 - { ( A cov A unc ) X (
WE 2 - WE 1 ) } ( Eq 7 a )
[0064] Equation 7a outputs a corrected glucose current density G
which removes the effects of interferences requiring only the
current density output of the first and second working electrode,
and a proportion of the coated to uncoated area of the second
working electrode. In one embodiment of the present invention the
proportion 4 A cov A unc
[0065] may be programmed into a glucose meter, in, for example, a
read only memory. In another embodiment of the present invention,
the proportion 5 A cov A unc
[0066] may be transferred to the meter via a calibration code chip
which would may account for manufacturing variations in A.sub.cov
or A.sub.unc.
[0067] In an alternative embodiment to the present invention
Equation 1, 2, and 3b may be used when the interferent oxidation
current density for the coated portion is different from the
interferent oxidation current density of the uncoated portion. In
such a case, an alternative correction Equation 7b is derived as
shown below.
G=WE.sub.1-{f.times.(WE.sub.2.times.WE.sub.1)} (Eq 7b)
[0068] In another embodiment of the present invention, the
corrected glucose current Equation 7a or 7b may be used by the
meter only when a certain threshold is exceeded. For example, if
WE.sub.2 is about 10% or greater than WE.sub.1, then the meter
would use Equation 7a or 7b to correct for the current output.
However, if WE.sub.2 is about 10% or less than WE.sub.1, the meter
would simple take an average current value between WE.sub.1 and
WE.sub.2 to improve the accuracy and precision of the measurement.
The strategy of using Equation 7a or 7b only under certain
situations where it is likely that a significant level of
interferences are in the sample mitigates the risk of
overcorrecting the measured glucose current. It should be noted
that when WE.sub.2 is sufficiently greater than WE.sub.1 (e.g.
about 20% or more), this is an indicator of having a sufficiently
high concentration of interferents. In such a case, it may be
desirable to output an error message instead of a glucose value
because a very high level of interferents may cause a breakdown in
the accuracy of Equation 7a or 7b.
[0069] In the embodiment of the present invention illustrated in
FIGS. 9 and 10, the first and second working electrodes are
partially covered with the reagent layer in such a way that that
the uncoated portions of the first and second working electrodes
are different. This contrasts the previously described first and
second test strip embodiments where the first working electrode is
completely covered with the reagent layer.
[0070] FIG. 9 is a simplified plane view of a distal portion of a
test strip 2000 according to yet another embodiment of the present
invention wherein a reagent layer 22 is illustrated with the
conductive layer and insulation layer 2002 such there are two
working electrodes which have an uncoated portion. Test strip 2002
is manufactured in a manner similar to test strip 62 except that
there is a geometric change to cutout 18 as shown in FIG. 1. Test
strip 2002 has the same substrate 50, conductive layer 64, reagent
layer 22, adhesive layer 66, hydrophilic layer 68, and top layer 40
as test strip 62. Test strip 2002 was modified to have a cutout
2004 which has a dumbbell like shape as illustrated in FIG. 9. The
modified shape for cutout 2004 allows first working electrode 2008
to include a first coated portion 2008c and an first uncoated
portion 2008u; and second working electrode 2006 to include a
second coated portion 2006c and second uncoated portion 2006u. In
order for test strip 2000 to effectively reduce the effects of
interferents, the two first uncoated portions 2008u must have a
different total area than the two second uncoated portions
2006u.
[0071] FIG. 10 is a simplified plane view of a distal portion of a
test strip 5000 according to still yet another embodiment of the
present invention wherein a reagent layer 820 is illustrated with
the conductive layer such there are two working electrodes which
have an uncoated portion. Test strip 5000 is manufactured in a
manner similar to test strip 162 except that there is a geometric
change to conductive layer 164 such that both a first working
electrode 4002 and a second working electrode 4004 have a C-shape.
Test strip 5000 has the same substrate 50, insulation layer 106,
reagent layer 110, adhesive layer 66, hydrophilic layer 68, and top
layer 40 as test strip 162. The modified geometry allows first
working electrode 4002 to include a first coated portion 4002c and
an first uncoated portion 4002u; and second working electrode 4004
to include a second coated portion 4004c and second uncoated
portion 4004u. In order for test strip 2000 to effectively reduce
the effects of interferents, first uncoated portion 4002u must have
a different area than second uncoated portion 4004u.
[0072] Test strips 2000 and 5000 have an advantage in that they may
be easier to manufacture in regards to depositing the reagent layer
with the required registration and also any subsequently deposited
layers. Furthermore, both the first and second working electrodes
will have to some extent the same chemical and electrochemical
interactions with any interfering substances thus ensuring greater
accuracy in the correction process. With both working electrodes
having some level of uncoated area the same reactions will occur on
both electrodes but to a different extent. Using a simple
modification to Equation 7a, the following Equation 7c can be used
as the correction equation for glucose, 6 G = WE 1 - { ( f 1 + f 2
f 2 - 1 ) .times. ( WE 2 - WE 1 ) } ( Eq 7 c )
[0073] where 7 f 1 = A cov1 A unc1 , f 2 = A cov1 A unc2 ,
[0074] A.sub.unc1=is an uncoated area of the first working
electrode, A.sub.unc2=is an uncoated area of the second working
electrode, A.sub.cov1=is a coated area of the first working
electrode, and A.sub.cov2=is a coated area of the second working
electrode.
[0075] One advantage of the present invention is the ability to use
the first and second working electrode to determine that the sample
receiving chamber has been sufficiently filled with liquid. It is
an advantage of this invention in that the second working electrode
not only corrects the interferent effect, but can also measure.
glucose. This allows for a more accurate results because 2 glucose
measurements can be averaged together while using only one test
strip.
EXAMPLE 1
[0076] Test strips were prepared according to the first embodiment
of the present invention as illustrated in FIG. 1 to 3. These test
strips were tested in blood having various concentrations of
interferents. To test these strips, they were electrically
connected to a potentiostat which has the means to apply a constant
potential of 0.4 volts between the first working electrode and the
reference electrode; and the second working electrode and the
reference electrode. A sample of blood is applied to the sample
inlet allowing the blood to wick into the sample receiving chamber
and to wet first working electrode, second working electrode, and
reference electrode. The reagent layer becomes hydrated with blood
and then generates ferrocyanide which may be proportional to the
amount of glucose and/or interferent concentration present in the
sample. After about 5 seconds from the sample application to the
test strip, an oxidation of ferrocyanide is measured as a current
for both the first and second working electrode.
[0077] FIG. 11 shows the current responses of the first working
electrode tested with 70 mg/dL glucose samples in blood spiked with
varying levels of uric acid. The uncorrected current at the first
working electrode (depicted by squares) shows an increase in
current that is proportional to the uric acid concentration.
However, the corrected current (depicted by triangles) which is
processed by Equation 7a shows no effect from the increasing uric
acid concentration.
[0078] FIG. 12 shows the current responses of the first working
electrode tested with 240 mg/dL glucose samples in blood spiked
with varying levels of uric acid. The purpose of testing strips at
240 mg/dL glucose is to show that the correction algorithm of
Equation 7a is also valid over a range of glucose concentrations.
Similar to FIG. 11, the uncorrected current at the first working
electrode (depicted by squares) shows an increase in current that
is proportional to the uric acid concentration. However, the
corrected current (depicted by triangles) shows no effect from the
increasing uric acid concentration.
EXAMPLE 2
[0079] To show that the method of correcting the current for
interferents applies to a wide variety of interferents, strips
built according to the embodiment of FIG. 1 were also tested with
acetaminophen and gentisic acid at various concentration levels, in
addition to uric acid. For purposes of quantitating the magnitude
of this effect, a change in glucose output of greater than 10% (for
glucose level >70 mg/dL) or 7 mg/dL (for glucose level <=70
mg/dL) was defined as a significant interference. Table 1 shows
that the uncorrected current at the first working electrode shows a
significant interferent effect at a lower interferent concentration
than strips tested with a corrected current response using Equation
7a. This shows that the method of correcting the current output of
the first working electrode using Equation 7a is effective in
correcting for interferences. Table 1 shows that the current
correction in Equation 7a is effective for interferences with
respect to acetaminophen, gentisic acid, and uric acid. Table 1
also shows the concentration range of the interferent which is
normally found in blood. In addition, Table 1 also shows that the
current correction in Equation 7a is effective at 240 mg/dL glucose
concentration level.
[0080] FIG. 13 shows an exploded perspective view of a test strip
800 that is designed to lance a user's skin layer so as cause
physiological fluid to be expressed and collected into test strip
800 in a seamless manner. Test strip 800 includes a substrate 50, a
conductive layer 802, an insulation layer 804, a reagent layer 820,
an adhesive layer 830, and a top layer 824. Test strip 800 further
includes a distal end 58 and a proximal end 60.
[0081] In test strip 800, conductive layer 802 is the first layer
disposed on substrate 50. Conductive layer 802 includes a second
working electrode 806, a first working electrode 808, a reference
electrode 810, a second contact 812, a first contact 814, a
reference contact 816, a strip detection bar 17, as shown in FIG.
13. The material used for conductive layer 802 and the process for
printing conductive layer 802 is the same for both test strip 62
and test strip 800.
[0082] Insulation layer 804 is the second layer disposed on
substrate 50. Insulation layer 16 includes a cutout 18 which may
have a rectangular shaped structure. Cutout 18 exposes a portion of
second working electrode 806, first working electrode 808, and
reference electrode 810 which can be wetted with a liquid. The
material used for insulation layer 804 and the process for printing
insulation layer 804 is the same for both test strip 62 and test
strip 800.
[0083] Reagent layer 820 is the third layer disposed on substrate
50, first working electrode 808 and reference electrode 810. The
material used for reagent layer 820 and the process for printing
reagent layer 820 is the same for both test strip 62 and test strip
800.
[0084] Adhesive layer 830 is the fourth layer disposed on substrate
50. The material used for adhesive layer 830 and the process for
printing adhesive layer 830 is the same for both test strip 62 and
test strip 800. The purpose of adhesive layer 830 is to secure top
layer 824 to test strip 800. In an embodiment of this invention,
top layer 824 may be in the form of an integrated lance as shown in
FIG. 13. In such an embodiment, top layer 824 may include a lance
826 which is located at distal end 58.
[0085] Lance 826, which may also be referred to as a penetration
member, may be adapted to pierce a user's skin and draw blood into
test strip 800 such that second working electrode 806, first
working electrode 808, and reference electrode 810 are wetted.
Lance 826 includes a lancet base 832 that terminates at distal end
58 of the assembled test strip. Lance 826 may be made with either
an insulating material such as plastic, glass, and silicon, or a
conducting material such as stainless steel and gold. Further
descriptions of integrated medical devices that use an integrated
lance can be found in International Application No. PCT/GB01/05634
and U.S. patent application Ser. No. 10/143,399. In addition, lance
826 can be fabricated, for example, by a progressive die-stamping
technique, as disclosed in the aforementioned International
Application No. PCT/GBO1/05634 and U.S. patent application Ser. No.
10/143,399.
[0086] FIG. 14 is a simplified schematic showing a meter 900
interfacing with a test strip. In an embodiment of this invention
the following test strips may be suitable for use with meter 900
which are test strip 62, test strip 162, test strip 800, test strip
2000, test strip 3000, or test strip 5000. Meter 900 has at least
three electrical contacts that form an electrical connection to the
second working electrode, the first working electrode, and the
reference electrode. In particular second contact (13, 103, or 812)
and reference contact (15, 105, or 816) connect to a first voltage
source 910; first contact (11, 101, or 814) and the reference
contact (15, 105, or 816) connect to a second voltage source
920.
[0087] When performing a test, first voltage source 910 applies a
first potential E1 between the second working electrode and the
reference electrode; and second voltage source 920 applies a second
potential E2 between the first working electrode and the reference
electrode. In one embodiment of this invention, first potential E1
and second potential E2 may be the same such as for example about
+0.4 V. In another embodiment of this invention, first potential El
and second potential E2 may be different. A sample of blood is
applied such that the second working electrode, the first working
electrode, and the reference electrode are covered with blood. This
allows the second working electrode and the first working electrode
to measure a current which is proportional to glucose and/or
non-enzyme specific sources. After about 5 seconds from the sample
application, meter 900 measures an oxidation current for both the
second working electrode and the first working electrode.
1TABLE 1 Summary of Interference Performance Using Uncorrected and
Corrected Current Output Glucose Inteferent Normal Concen-
Concentration Concentration tration where effect is range of Mode
Interferent (mg/dL) signficant interferent Un- Acetaminophen 70 11
1-2 corrected Un- Gentisic Acid 70 10 0.05-0.5 corrected Un- Uric
Acid 70 5 2.6-7.2 corrected Un- Acetaminophen 240 16 1-2 corrected
Un- Gentisic Acid 240 12 0.05-0.5 corrected Un- Uric Acid 240 8
2.6-7.2 corrected Corrected Acetaminophen 70 120 1-2 Corrected
Gentisic Acid 70 47 0.05-0.5 Corrected Uric Acid 70 33 2.6-7.2
Corrected Acetaminophen 240 59 1-2 Corrected Gentisic Acid 240 178
0.05-0.5 Corrected Uric Acid 240 29 2.6-7.2
[0088] It will be recognized that equivalent structures may be
substituted for the structures illustrated and described herein and
that the described embodiment of the invention is not the only
structure which may be employed to implement the claimed invention.
In addition, it should be understood that every structure described
above has a function and such structure can be referred to as a
means for performing that function. While preferred embodiments of
the present invention have been shown and described herein, it will
be obvious to those skilled in the art that such embodiments are
provided by way of example only. Numerous variations, changes, and
substitutions will now occur to hose skilled in the art without
departing from the invention. It should be understood that various
alternatives to the embodiments of the invention described herein
may be employed in practicing the invention. It is intended that
the following claims define the scope of the invention and that
methods and structures within the scope of these claims and their
equivalents be covered thereby.
* * * * *