U.S. patent application number 11/845860 was filed with the patent office on 2008-04-10 for system and methods for determining an analyte concentration incorporating a hematocrit correction.
Invention is credited to Douglas E. Bell, David Z. Deng, Gary T. Neel, Dennis Slomski.
Application Number | 20080083618 11/845860 |
Document ID | / |
Family ID | 38728889 |
Filed Date | 2008-04-10 |
United States Patent
Application |
20080083618 |
Kind Code |
A1 |
Neel; Gary T. ; et
al. |
April 10, 2008 |
System and Methods for Determining an Analyte Concentration
Incorporating a Hematocrit Correction
Abstract
Methods and devices for determining the concentration of a
constituent in a physiological sample are provided. The blood
sample is introduced into a test strip with portions of the blood
sample being directed to both a first capillary and a second
capillary. The first capillary configured to electrochemically
determine a concentration of a first analyte in a blood sample by
measuring a signal across a set of electrodes. The second capillary
is configured to determine a hematocrit value of the blood sample
by measuring a signal across a second set of electrodes.
Inventors: |
Neel; Gary T.; (Weston,
FL) ; Bell; Douglas E.; (Coral Springs, FL) ;
Slomski; Dennis; (Wellington, FL) ; Deng; David
Z.; (Weston, FL) |
Correspondence
Address: |
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER;LLP
901 NEW YORK AVENUE, NW
WASHINGTON
DC
20001-4413
US
|
Family ID: |
38728889 |
Appl. No.: |
11/845860 |
Filed: |
August 28, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60842032 |
Sep 5, 2006 |
|
|
|
Current U.S.
Class: |
204/403.14 ;
204/400; 205/80; 216/94; 427/58; 427/600; 430/319 |
Current CPC
Class: |
A61B 5/1486 20130101;
G01N 33/66 20130101; A61B 2562/0295 20130101; A61B 5/14546
20130101; C12Q 1/006 20130101; A61B 5/14535 20130101; G01N 27/3272
20130101; Y10T 29/49117 20150115; G01N 27/3274 20130101; A61B
2560/0209 20130101; A61B 2562/085 20130101 |
Class at
Publication: |
204/403.14 ;
204/400; 205/080; 216/094; 427/058; 427/600; 430/319 |
International
Class: |
G01N 27/416 20060101
G01N027/416; B05D 1/00 20060101 B05D001/00; B05D 1/02 20060101
B05D001/02; C12M 1/40 20060101 C12M001/40; G03C 5/00 20060101
G03C005/00; C23F 1/02 20060101 C23F001/02; C25D 5/00 20060101
C25D005/00 |
Claims
1. A biosensor, comprising: a base layer; a first capillary
disposed on the base layer configured to electrochemically
determine a concentration of a first analyte in a blood sample,
wherein the first capillary includes a first set of at least one
electrode; and a second capillary disposed on the base layer
configured to determine a value correlating to the hematocrit level
of the blood sample, wherein the second capillary includes a second
set of at least one electrode.
2. The biosensor of claim 1, wherein an exit port of the first
capillary is fluidly connected to an entry port of the second
capillary.
3. The biosensor of claim 1, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary.
4. The biosensor of claim 1, further including a third capillary
configured to permit determination of a third parameter associated
with the blood sample, wherein the third capillary includes a third
set of electrodes.
5. The biosensor of claim 4, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary and fluidly connected to an entry port of the third
capillary.
6. The biosensor of claim 4, wherein the third parameter is
selected from a group consisting of a temperature, a concentration
of a second analyte, and an on-board control.
7. The biosensor of claim 1, wherein the first capillary further
includes a reagent layer.
8. The biosensor of claim 7, wherein the reagent layer includes at
least one of glucose oxidase, glucose dehydrogenase, potassium
ferricyanide, and ruthenium hexamine.
9. The biosensor of claim 7, wherein the reagent layer is deposited
using a process selected from the group consisting of
screen-printing, spray deposition, piezo, pipetting, and ink jet
printing.
10. The biosensor of claim 1, wherein the first set of electrodes
includes at least one of a working electrode, a proximal electrode,
and a fill-detect electrode.
11. The biosensor of claim 1, wherein the first set of electrodes
and the second set of electrodes share the at least one
electrode.
12. The biosensor of claim 1, further including at least one of an
electrical contact, an auto-on conductor, and a coding region.
13. The biosensor of claim 12, wherein an at least partially
conductive layer at least partially covers at least one of the
electrical contact, the auto-on conductor, and the coding
region.
14. The biosensor of claim 1, wherein the at least one electrode is
at least partially formed from at least one of palladium, gold,
platinum, silver, iridium, carbon, indium tin oxide, indium zinc
oxide, copper, aluminum, gallium, iron, mercury amalgams, tantalum,
titanium, zirconium, nickel, osmium, rhenium, rhodium palladium, an
organometallic, and a metallic alloy.
15. The biosensor of claim 1, wherein the at least one electrode is
at least partially formed using at least one process selected from
the group consisting of sputtering, evaporation, electroplating,
ultrasonic spraying, pressure spraying, direct writing, shadow mask
lithography, lift-off lithography, and laser ablation.
16. The biosensor of claim 1, wherein the biosensor includes a
generally planar base layer.
17. The biosensor of claim 16, wherein the generally planar base
layer includes at least one of an acrylic and a polyester.
18. The biosensor of claim 1, wherein the biosensor further
includes a dielectric spacer layer at least partially deposited on
the at least one electrode.
19. The biosensor of claim 18, wherein the dielectric spacer layer
includes at least one of an acrylic and a polyester.
20. The biosensor of claim 18, wherein the biosensor further
includes an adhesive layer disposed between the dielectric spacer
layer and the at least one electrode.
21. The biosensor of claim 1, further including a second plurality
of electrical contacts that include a code with data relating to
the biosensor.
22. An analyte testing system, comprising: a meter system for
making a measurement of an analyte concentration in a sample,
wherein the meter system is configured to use the biosensor of
claim 1.
23. The analyte testing system of claim 22, wherein the meter
system utilizes the determined hematocrit value to enhance
calculating the concentration of the first analyte.
24. A method for manufacturing a biosensor, comprising: at least
partially forming a plurality of electrodes on a generally planar
base layer; forming a first capillary on the base layer, wherein
the first capillary includes a first set of at least one electrode
selected from the plurality of at least partially formed
electrodes; and forming a second capillary on the base layer,
wherein the second capillary includes a second set of at least one
electrode selected from the plurality of at least partially formed
electrodes.
25. The method of claim 24, wherein an exit port of the first
capillary is fluidly connected to an entry port of the second
capillary.
26. The method of claim 24, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary.
27. The method of claim 24, further including a third capillary
configured to permit determination of a third parameter associated
with the blood sample, wherein the third capillary includes a third
set of electrodes.
28. The method of claim 27, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary and fluidly connected to an entry port of the third
capillary.
29. The method of claim 27, wherein the third parameter is selected
from a group consisting of a temperature, a concentration of a
second analyte, and an on-board control.
30. The method of claim 24, wherein the first capillary further
includes a reagent layer.
31. The method of claim 30, wherein the reagent layer includes at
least one of glucose oxidase, glucose dehydrogenase, potassium
ferricyanide, and ruthenium hexamine.
32. The method of claim 30, wherein the reagent layer is deposited
using a process selected from the group consisting of
screen-printing, spray deposition, piezo, pipetting, and ink jet
printing.
33. The method of claim 24, wherein the first set of electrodes
includes at least one of a working electrode, a proximal electrode,
and a fill-detect electrode.
34. The method of claim 24, wherein the first set of electrodes and
the second set of electrodes share the at least one electrode.
35. The method of claim 24, further including at least one of an
electrical contact, an auto-on conductor, and a coding region.
36. The method of claim 35, wherein an at least partially
conductive layer at least partially covers at least one of the
electrical contact, the auto-on conductor, and the coding
region.
37. The method of claim 24, wherein the at least one electrode is
at least partially formed from at least one of palladium, gold,
platinum, silver, iridium, carbon, indium tin oxide, indium zinc
oxide, copper, aluminum, gallium, iron, mercury amalgams, tantalum,
titanium, zirconium, nickel, osmium, rhenium, rhodium palladium, an
organometallic, and a metallic alloy.
38. The method of claim 24, wherein the at least one electrode is
at least partially formed using at least one process selected from
the group consisting of sputtering, evaporation, electroplating,
ultrasonic spraying, pressure spraying, direct writing, shadow mask
lithography, lift-off lithography, and laser ablation.
39. The method of claim 24, wherein the generally planar base layer
includes at least one of an acrylic and a polyester.
40. The method of claim 24, wherein the biosensor further includes
a dielectric spacer layer at least partially deposited on the at
least one electrode.
41. The method of claim 40, wherein the dielectric spacer layer
includes at least one of an acrylic and a polyester.
42. The method of claim 40, wherein the biosensor further includes
an adhesive layer disposed between the dielectric spacer layer and
the at least one electrode.
43. The method of claim 24, further including a second plurality of
electrical contacts that include a code with data relating to the
biosensor.
44. An analyte testing system comprising a meter system for making
a measurement of an analyte concentration in a sample, the meter
utilizing the biosensor of claim 24.
45. The analyte testing system of claim 44, wherein the meter
system utilizes the determined hematocrit value to enhance
calculating the concentration of the first analyte.
46. A reel for manufacturing biosensors, comprising: a generally
planar base layer including a plurality of at least partially
formed electrodes; a first capillary on the base layer, wherein the
first capillary includes a first set of at least one electrode
selected from the plurality of at least partially formed
electrodes; and a second capillary on the base layer, wherein the
second capillary includes a second set of at least one electrode
selected from the plurality of at least partially formed
electrodes.
47. The reel of claim 46, further including a plurality of
registration points formed on the generally planar base layer.
48. The reel of claim 46, wherein the plurality of registration
points are used to help align the base layer during at least one of
the lamination, punching, etching, scoring, drilling, heating,
compression, molding, printing, laser ablation of conductive
components, reagent deposition, or singulation processes.
49. The reel of claim 46, wherein the plurality of registration
points are separated by less than 500 mm.
50. The reel of claim 46, wherein at least one of the plurality of
registration points is less than 10 mm wide.
51. The reel of claim 46, wherein an exit port of the first
capillary is fluidly connected to an entry port of the second
capillary.
52. The reel of claim 46, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary.
53. The reel of claim 46, further including a third capillary
configured to permit determination of a third parameter associated
with the blood sample, wherein the third capillary includes a third
set of electrodes.
54. The reel of claim 53, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary and fluidly connected to an entry port of the third
capillar.
55. The reel of claim 53, wherein the third parameter is selected
from a group consisting of a temperature, a concentration of a
second analyte, and an on-board control.
56. The reel of claim 46, wherein the first capillary further
includes a reagent layer.
57. The reel of claim 56, wherein the reagent layer includes at
least one of glucose oxidase, glucose dehydrogenase, potassium
ferricyanide, and ruthenium hexamine.
58. The reel of claim 56, wherein the reagent layer is deposited
using a process selected from the group consisting of
screen-printing, spray deposition, piezo, pipetting, and ink jet
printing.
59. The reel of claim 46, wherein the first set of electrodes
includes at least one of a working electrode, a proximal electrode,
and a fill-detect electrode.
60. The reel of claim 46, wherein the first set of electrodes and
the second set of electrodes share the at least one electrode.
61. The reel of claim 46, further including at least one of an
electrical contact, an auto-on conductor, and a coding region.
62. The reel of claim 61, wherein an at least partially conductive
layer at least partially covers at least one of the electrical
contact, the auto-on conductor, and the coding region.
63. The reel of claim 46, wherein the at least one electrode is at
least partially formed from at least one of palladium, gold,
platinum, silver, iridium, carbon, indium tin oxide, indium zinc
oxide, copper, aluminum, gallium, iron, mercury amalgams, tantalum,
titanium, zirconium, nickel, osmium, rhenium, rhodium palladium, an
organometallic, and a metallic alloy.
64. The reel of claim 46, wherein the at least one electrode is at
least partially formed using at least one process selected from the
group consisting of sputtering, evaporation, electroplating,
ultrasonic spraying, pressure spraying, direct writing, shadow mask
lithography, lift-off lithography, and laser ablation.
65. The reel of claim 46, wherein the generally planar base layer
includes at least one of an acrylic and a polyester.
66. The reel of claim 46, wherein the biosensor further includes a
dielectric spacer layer at least partially deposited on the at
least one electrode.
67. The reel of claim 66, wherein the dielectric spacer layer
includes at least one of an acrylic and a polyester.
68. The reel of claim 66, wherein the biosensor further includes an
adhesive layer disposed between the dielectric spacer layer and the
at least one electrode.
69. The reel of claim 46, further including a second plurality of
electrical contacts that include a code with data relating to the
reel.
70. An analyte testing system comprising a meter system for making
a measurement of an analyte concentration in a sample, the meter
utilizing the biosensors of claim 46.
71. The analyte testing system of claim 70, wherein the meter
system utilizes the determined hematocrit value to enhance
calculating the concentration of the first analyte.
72. A method of manufacturing a plurality of test strips for a
biosensor, comprising: forming a reel containing a base layer;
forming a plurality of electrodes on the base layer; and partially
forming a test strip, wherein the test strip includes a first
capillary on the base layer including at least one of the plurality
of electrodes and the test strip further includes a second
capillary on the base layer including at least one of the plurality
of electrode.
73. The method of claim 72, wherein the reel includes a plurality
of registration points.
74. The method of claim 72, wherein an exit port of the first
capillary is fluidly connected to an entry port of the second
capillary.
75. The method of claim 72, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary.
76. The method of claim 72, further including a third capillary
configured to permit determination of a third parameter associated
with the blood sample, wherein the third capillary includes a third
set of electrodes.
77. The method of claim 76, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary and fluidly connected to an entry port of the third
capillary.
78. The method of claim 76, wherein the third parameter is selected
from a group consisting of a temperature, a concentration of a
second analyte, and an on-board control.
79. The method of claim 72, wherein the first capillary further
includes a reagent layer.
80. The method of claim 79, wherein the reagent layer includes at
least one of glucose oxidase, glucose dehydrogenase, potassium
ferricyanide, and ruthenium hexamine.
81. The method of claim 79, wherein the reagent layer is deposited
using a process selected from the group consisting of
screen-printing, spray deposition, piezo, pipetting, and ink jet
printing.
82. The method of claim 72, wherein the first set of electrodes
includes at least one of a working electrode, a proximal electrode,
and a fill-detect electrode.
83. The method of claim 72, wherein the first set of electrodes and
the second set of electrodes share the at least one electrode.
84. The method of claim 72, further including at least one of an
electrical contact, an auto-on conductor, and a coding region.
85. The method of claim 84, wherein an at least partially
conductive layer at least partially covers at least one of the
electrical contact, the auto-on conductor, and the coding
region.
86. The method of claim 72, wherein the at least one electrode is
at least partially formed from at least one of palladium, gold,
platinum, silver, iridium, carbon, indium tin oxide, indium zinc
oxide, copper, aluminum, gallium, iron, mercury amalgams, tantalum,
titanium, zirconium, nickel, osmium, rhenium, rhodium palladium, an
organometallic, and a metallic alloy.
87. The method of claim 72, wherein the at least one electrode is
at least partially formed using at least one process selected from
the group consisting of sputtering, evaporation, electroplating,
ultrasonic spraying, pressure spraying, direct writing, shadow mask
lithography, lift-off lithography, and laser ablatio.
88. The method of claim 72, wherein the biosensor includes a
generally planar base layer.
89. The method of claim 88, wherein the generally planar base layer
includes at least one of an acrylic and a polyester.
90. The method of claim 72, wherein the biosensor further includes
a dielectric spacer layer at least partially deposited on the at
least one electrode.
91. The method of claim 90, wherein the dielectric spacer layer
includes at least one of an acrylic and a polyester.
92. The method of claim 90, wherein the biosensor further includes
an adhesive layer disposed between the dielectric spacer layer and
the at least one electrode.
93. The method of claim 72, further including a second plurality of
electrical contacts that include a code with data relating to the
plurality of test strips.
94. An analyte testing system comprising a meter system for making
a measurement of an analyte concentration in a sample, the meter
utilizing the biosensor of claim 72.
95. The analyte testing system of claim 94, wherein the meter
system utilizes the determined hematocrit value to enhance
calculating the concentration of the first analyte.
96. A test card for quality control analysis of biosensors,
comprising: a base layer, wherein the base layer includes a
plurality of electrodes; a plurality of partially formed test
strips, wherein each test strip includes a first capillary on the
base layer including at least one of the plurality of electrodes
and each test strip further includes a second capillary on the base
layer including at least one of the plurality of electrodes.
97. The test card of claim 96, wherein an exit port of the first
capillary is fluidly connected to an entry port of the second
capillary.
98. The test card of claim 96, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary.
99. The test card of claim 96, further including a third capillary
configured to permit determination of a third parameter associated
with the blood sample, wherein the third capillary includes a third
set of electrodes.
100. The test card of claim 99, wherein an entry port of the first
capillary is fluidly connected to an entry port of the second
capillary and fluidly connected to an entry port of the third
capillary.
101. The test card of claim 99, wherein the third parameter is
selected from a group consisting of a temperature, a concentration
of a second analyte, and an on-board control.
102. The test card of claim 96, wherein the first capillary further
includes a reagent layer.
103. The test card of claim 102, wherein the reagent layer includes
at least one of glucose oxidase, glucose dehydrogenase, potassium
ferricyanide, and ruthenium hexamine.
104. The test card of claim 102, wherein the reagent layer is
deposited using a process selected from the group consisting of
screen-printing, spray deposition, piezo, pipetting, and ink jet
printing.
105. The test card of claim 96, wherein the first set of electrodes
includes at least one of a working electrode, a proximal electrode,
and a fill-detect electrode.
106. The test card of claim 96, wherein the first set of electrodes
and the second set of electrodes share the at least one
electrode.
107. The test card of claim 96, further including at least one of
an electrical contact, an auto-on conductor, and a coding
region.
108. The test card of claim 107, wherein an at least partially
conductive layer at least partially covers at least one of the
electrical contact, the auto-on conductor, and the coding
region.
109. The test card of claim 96, wherein the at least one electrode
is at least partially formed from at least one of palladium, gold,
platinum, silver, iridium, carbon, indium tin oxide, indium zinc
oxide, copper, aluminum, gallium, iron, mercury amalgams, tantalum,
titanium, zirconium, nickel, osmium, rhenium, rhodium palladium, an
organometallic, and a metallic alloy.
110. The test card of claim 96, wherein the at least one electrode
is at least partially formed using at least one process selected
from the group consisting of sputtering, evaporation,
electroplating, ultrasonic spraying, pressure spraying, direct
writing, shadow mask lithography, lift-off lithography, and laser
ablation.
111. The test card of claim 96, wherein the biosensor includes a
generally planar base layer.
112. The test card of claim 111, wherein the generally planar base
layer includes at least one of an acrylic and a polyester.
113. The test card of claim 96, wherein the biosensor further
includes a dielectric spacer layer at least partially deposited on
the at least one electrode.
114. The test card of claim 113, wherein the dielectric spacer
layer includes at least one of an acrylic and a polyester.
115. The test card of claim 113, wherein the biosensor further
includes an adhesive layer disposed between the dielectric spacer
layer and the at least one electrode.
116. The test card of claim 96, further including a second
plurality of electrical contacts that include a code with data
relating to the biosensor.
117. An analyte testing system comprising; a meter system for
making a measurement of an analyte concentration in a sample,
wherein the meter system is configured to use at least one of the
plurality of partially formed test strips of claim 96.
118. The analyte testing system of claim 117, wherein the meter
system utilizes the determined hematocrit value to enhance
calculating the concentration of the first analyte.
Description
[0001] This application claims priority to U.S. Provisional Patent
Application No. 60/842,032, filed Sep. 5, 2006, the content of
which is incorporated herein by reference.
DESCRIPTION OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to the field of diagnostic
testing systems for measuring the concentration of an analyte in a
blood sample and, more particularly, to methods for measuring an
analyte concentration that incorporates a hematocrit
correction.
[0004] 2. Background of the Invention
[0005] The present disclosure relates to a biosensor system for
measuring an analyte in a bodily fluid, such as blood, wherein the
system comprises a unique process and system for correcting
inaccuracies in sample concentration measurements. For example, the
present disclosure provides methods of correcting analyte
concentration measurements of bodily fluids.
[0006] Electrochemical sensors have long been used to detect and/or
measure the presence of substances in a fluid sample. In the most
basic sense, electrochemical sensors comprise a reagent mixture
containing at least an electron transfer agent (also referred to as
an "electron mediator") and an analyte specific bio-catalytic
protein (e.g. a particular enzyme), and one or more electrodes.
Such sensors rely on electron transfer between the electron
mediator and the electrode surfaces and function by measuring
electrochemical redox reactions. When used in an electrochemical
biosensor system or device, the electron transfer reactions are
transformed into an electrical signal that correlates to the
concentration of the analyte being measured in the fluid
sample.
[0007] The use of such electrochemical sensors to detect analytes
in bodily fluids, such as blood or blood derived products, tears,
urine, and saliva, has become important, and in some cases, vital
to maintain the health of certain individuals. In the health care
field, people such as diabetics, for example, have a need to
monitor a particular constituent within their bodily fluids. A
number of systems are available that allow people to test a body
fluid, such as, blood, urine, or saliva, to conveniently monitor
the level of a particular fluid constituent, such as, for example,
cholesterol, proteins, and glucose. Patients suffering from
diabetes, a disorder of the pancreas where insufficient insulin
production prevents the proper digestion and utilization of sugar,
have a need to carefully monitor their blood glucose levels on a
daily basis. Routine testing and controlling blood glucose for
people with diabetes can reduce their risk of serious damage to the
eyes, nerves, and kidneys.
[0008] A number of systems permit people to conveniently monitor
their blood glucose levels, and such systems typically include a
test strip where the user applies a blood sample and a meter that
"reads" the test strip to determine the glucose level in the blood
sample. An exemplary electrochemical biosensor is described in U.S.
Pat. No. 6,743,635 ('635 patent) which is incorporated by reference
herein in its entirety, The 635 patent describes an electrochemical
biosensor used to measure glucose level in a blood sample. The
electrochemical biosensor system is comprised of a test strip and a
meter. The test strip includes a sample chamber, a working
electrode, a counter electrode, and fill-detect electrodes. A
reagent layer is disposed in the sample chamber. The reagent layer
contains an enzyme specific for glucose, such as, glucose oxidase,
and a mediator, such as, potassium ferricyanide or ruthenium
hexaamine. When a user applies a blood sample to the sample chamber
on the test strip, the reagents react with the glucose in the blood
sample and the meter applies a voltage to the electrodes to cause
redox reactions. The meter measures the resulting current that
flows between the working and counter electrodes and calculates the
glucose level based on the current measurements.
[0009] Biosensors configured to measure a blood constituent may be
affected by the presence of certain blood components that may
undesirably affect the measurement and lead to inaccuracies in the
detected signal. This inaccuracy may result in an inaccurate
glucose reading, leaving the patient unaware of a potentially
dangerous blood sugar level, for example. As one example, the
particular blood hematocrit level (i.e., the percentage of the
amount of blood that is occupied by red blood cells) can
erroneously affect a resulting analyte concentration
measurement.
[0010] Variations in a volume of red blood cells within blood can
cause variations in glucose readings measured with disposable
electrochemical test strips. Typically, a negative bias (i.e.,
lower calculated analyte concentration) is observed at high
hematocrits, while a positive bias (i.e., higher calculated analyte
concentration) is observed at low hematocrits. At high hematocrits,
for example, the red blood cells may impede the reaction of enzymes
and electrochemical mediators, reduce the rate of chemistry
dissolution since there less plasma volume to solvate the chemical
reactants, and slow diffusion of the mediator. These factors can
result in a lower than expected glucose reading as less current is
produced during the electrochemical process. Conversely, at low
hematocrits, less red blood cells may affect the electrochemical
reaction than expected, and a higher measured current can result.
In addition, the blood sample resistance is also hematocrit
dependent, which can affect voltage and/or current
measurements.
[0011] Several strategies have been used to reduce or avoid
hematocrit based variations on blood glucose readings as described
in U.S. patent application Ser. No. 11/401,458 which is
incorporated by reference herein in its entirety. For example, test
strips have been designed to incorporate meshes to remove red blood
cells from the samples, or have included various compounds or
formulations designed to increase the viscosity of red blood cell
and attenuate the effect of low hematocrit on concentration
determinations. Further, biosensors have been configured to measure
hematocrit by measuring optical variations after irradiating the
blood sample with light, or measuring hematocrit based on a
function of sample chamber fill time. These methods have the
disadvantages of increasing the cost and complexity of test strips
and may undesirably increase the time required to determine an
accurate glucose measurement.
[0012] In addition, alternating current (AC) impedance methods have
also been developed to measure electrochemical signals at
frequencies independent of a hematocrit effect. Such methods suffer
from the increased cost and complexity of advanced meters required
for signal filtering and analysis.
[0013] An additional prior hematocrit correction scheme is
described in U.S. Pat. No. 6,475,372. In that method, a two
potential pulse sequence is employed to estimate an initial glucose
concentration and determine a multiplicative hematocrit correction
factor. A hematocrit correction factor is a particular numerical
value or equation that is used to correct an initial concentration
measurement, and may include determining the product of the initial
measurement and the determined hematocrit correction factor. Data
processing using this technique, however, is complicated because
both a hematocrit correction factor and an estimated glucose
concentration must be determined to establish the corrected glucose
value. In addition, the time duration of the first step greatly
increases the overall test time of the biosensor, which is
undesirable from the user's perspective.
[0014] Accordingly, novel systems and methods for providing
corrected analyte concentration measurements are desired that
overcome the drawbacks of current biosensors and improve upon
existing electrochemical biosensor technologies so that
measurements are more accurate.
SUMMARY OF THE INVENTION
[0015] One embodiment is directed to a biosensor having a base
layer including a first capillary disposed on the base layer
configured to electrochemically determine a concentration of a
first analyte in a blood sample, and wherein the first capillary
includes a first set of at least one electrode. The biosensor also
includes a second capillary disposed on the base layer configured
to determine a value correlating to the hematocrit level of the
blood sample, and wherein the second capillary includes a second
set of at least one electrode.
[0016] Another embodiment of the invention is directed to a method
for manufacturing a biosensor comprising at least partially forming
a plurality of electrodes on a generally planar base layer. The
method also includes forming a first capillary disposed on the base
layer, and wherein the first capillary includes a first set of at
least one electrode selected from the plurality of at least
partially formed electrodes. Further, the method includes forming a
second capillary on the base layer, and wherein the second
capillary includes a second set of at least one electrode selected
from the plurality of at least partially formed electrodes.
[0017] Another embodiment of the invention is directed to a reel
for manufacturing biosensors comprising a generally planar base
layer including a plurality of at least partially formed
electrodes. Additionally, the reel includes a first capillary
disposed on the base layer, and wherein the first capillary
includes a first set of at least one electrode selected from the
plurality of at least partially formed electrodes. The reel also
includes forming a second capillary on the base layer, and wherein
the second capillary includes a second set of at least one
electrode selected from the plurality of at least partially formed
electrodes.
[0018] Another embodiment of the invention is directed to a method
of manufacturing a plurality of test strips for a biosensor
comprising forming a reel containing a base layer. Moreover, the
method includes forming a plurality of electrodes on the base
layer, and partially forming a test strip, wherein the test strip
includes a first capillary on the base layer including at least one
of the plurality of electrodes and the test strip further includes
a second capillary on the base layer including at least one of the
plurality of electrodes.
[0019] Another embodiment of the invention is directed to a test
card for quality control analysis of biosensors comprising a base
layer, wherein the base layer includes a plurality of electrodes.
Further, a plurality of partially formed test strips, wherein each
test strip includes a first capillary on the base layer including
at least one of the plurality of electrodes and each test strip
further includes a second capillary on the base layer including at
least one of the plurality of electrodes.
[0020] Additional objects and advantages of the invention will be
set forth in part in the description which follows, and in part
will be obvious from the description, or may be learned by practice
of the invention. The objects and advantages of the invention will
be realized and attained by means of the elements and combinations
particularly pointed out in the appended claims.
[0021] It is to be understood that both the foregoing general
description and the following detailed description are exemplary
and explanatory only and are not restrictive of the invention, as
claimed.
[0022] The accompanying drawings, which are incorporated in and
constitute a part of this specification, illustrate several
embodiments of the invention and together with the description,
serve to explain the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] The accompanying drawings, which are incorporated in and
constitute a part of this specification, illustrate several
embodiments of the invention and together with the description,
serve to explain the principles of the invention.
[0024] FIG. 1A illustrates test media that can be produced using
the methods of the present disclosure.
[0025] FIG. 1B illustrates a test meter that can be used with test
media produced according to the methods of the present
disclosure.
[0026] FIG. 1C illustrates a test meter that can be used with test
media produced according to the methods of the present
disclosure.
[0027] FIG. 2A is a top plan view of a test strip according to an
exemplary embodiment of the invention.
[0028] FIG. 2B is a cross-sectional view of the test strip of FIG.
2A, taken along line 2B-2B.
[0029] FIG. 3A shows a configuration of sample chambers on test
strip 10 according to the methods of the present disclosure.
[0030] FIG. 3B shows a configuration of sample chambers on test
strip 10 according to the methods of the present disclosure.
[0031] FIG. 3C shows a configuration of sample chambers on test
strip 10 according to the methods of the present disclosure.
[0032] FIG. 4A is a top view of a reel according to an exemplary
disclosed embodiment of the invention.
[0033] FIG. 4B is an enlarged tip view of a feature set on the reel
of FIG. 4A.
[0034] FIG. 5 is a top view of a test card according to a further
illustrative embodiment of the invention.
[0035] FIG. 6 is a diagram of the manufacturing process before
production testing according to a further illustrative embodiment
of the invention.
DESCRIPTION OF THE EMBODIMENTS
[0036] Reference will now be made in detail to the exemplary
embodiments of the invention, examples of which are illustrated in
the accompanying drawings. Wherever possible, the same reference
numbers will be used throughout the drawings to refer to the same
or like parts.
[0037] In accordance with an exemplary embodiment, a biosensor
manufacturing method is described. Many industries have a
commercial need to monitor the concentration of particular
constituents in a fluid. The oil refining industry, wineries, and
the dairy industry are examples of industries where fluid testing
is routine. In the health care field, people such as diabetics, for
example, need to monitor various constituents within their bodily
fluids using biosensors. A number of systems are available that
allow people to test a body fluid (e.g., blood, urine, or saliva),
to conveniently monitor the level of a particular fluid
constituent, such as, for example, cholesterol, proteins or
glucose.
[0038] For purposes of this disclosure, "distal" refers to the
portion of a test strip further from the fluid source (i.e., closer
to the meter) during normal use, and "proximal" refers to the
portion closer to the fluid source (e.g., a finger tip with a drop
of blood for a glucose test strip) during normal use. The test
strip may include a plurality of sample chambers for receiving a
user's fluid sample, such as, for example, a blood sample. The
sample chambers and test strip of the present specification can be
formed using materials and methods described in commonly owned U.S.
Pat. No. 6,743,635, which is hereby incorporated by reference in
its entirety. Accordingly, a sample chamber may include a first
opening in the proximal end of the test strip and a second opening
for venting the sample chamber. Each sample chamber may be
dimensioned so as to be able to draw the blood sample in through
the first opening and to hold the blood sample in the sample
chamber by capillary action. The test strip can include a tapered
section that is narrowest at the proximal end, or can include other
indicia in order to make it easier for the user to locate the first
opening and apply the blood sample.
[0039] A first set of electrodes, such as a working electrode and a
counter (or in an exemplary embodiment, proximal) electrode, can be
disposed in a first sample chamber optionally along with one or
more fill-detect electrodes. A reagent layer is disposed in the
first sample chamber and preferably contacts at least the working
electrode. The reagent layer may include an enzyme, such as glucose
oxidase or glucose dehydrogenase, and a mediator, such as potassium
ferricyanide or ruthenium hexamine. The first sample chamber may be
configured to permit determination of one or more analytes in a
blood sample, such as, for example, glucose. A second set of
electrodes may be disposed in a second sample chamber, such as, for
example, a proximal electrode and a distal electrode. The
electrodes may be spaced at a predetermined distance such that
hematocrit may be determined by measurement of electrical impedance
between the two electrodes in the second sample chamber.
[0040] The test strip has, near its distal end, a plurality of
electrical contacts that are electrically connected to the
electrodes via conductive traces. In addition, the test strip may
also include a second plurality of electrical strip contacts near
the distal end of the strip. The second plurality of electrical
contacts can be arranged such that they provide, when the strip is
inserted into the meter, a distinctly discernable lot code readable
by the meter. In some embodiments, the electrical contacts may be
at least partially covered with an at least partially conductive
material to improve the wear properties of the electrical
contacts.
[0041] An individual test strip may also include an embedded code
relating to data associated with a lot of test strips, or data
particular to that individual strip. The embedded information
presents data readable by the meter signaling the meter's
microprocessor to access and utilize a specific set of stored
calibration parameters particular to test strips from a
manufacturing lot to which the individual strip belongs, or to an
individual test strip. The system may also include a check strip
that the user may insert into the meter to check that the
instrument is electrically calibrated and functioning properly. The
readable code can be read as a signal to access data, such as
calibration coefficients, from an on-board memory unit in the
meter.
[0042] In order to save power, the meter may be battery powered and
may stay in a low-power sleep mode when not in use. When the test
strip is inserted into the meter, one or more electrical contacts
on the test strip form electrical connections with one or more
corresponding electrical contacts in the meter. The second
plurality of electrical contacts may bridge a pair of electrical
contacts in the meter, causing a current to flow through a portion
of the second plurality of electrical contacts. The current flow
through the second plurality of electrical contacts causes the
meter to wake up and enter an active mode. The meter also reads the
code information provided by the second plurality and can then
identify, for example, the particular test to be performed or a
confirmation of proper operating status. Calibration data
pertaining to the strip lot, for either the analyte test or the
hematocrit test, discussed below, can also be encoded or otherwise
represented. In addition, based on the particular code information,
the meter can also identify the inserted strip as either a test
strip or a check strip. If the meter detects a check strip, it
performs a check strip sequence. If the meter detects a test strip,
it performs a test strip sequence. In the test strip sequence, the
meter validates the working electrode, counter electrode, and, if
included, the fill-detect electrodes, by confirming that there are
no low-impedance paths between any of these electrodes. If the
electrodes are valid, the meter indicates to the user that a sample
may be applied to the test strip. The meter then applies a
drop-detect voltage between any two suitable electrodes and detects
a fluid sample, such as, a blood sample, by detecting a current
flow between the working and proximal electrodes (i.e., a current
flow through the blood sample as it bridges the working and
proximal electrodes). To detect that an adequate sample is present
in the sample chamber and that the blood sample has traversed the
reagent layer and mixed with the chemical constituents in the
reagent layer, the meter may apply a fill-detect voltage to the one
or more fill-detect electrodes and measure any resulting current
flow. If a resulting electrical property reaches a sufficient level
within a predetermined period of time, the meter indicates to the
user that adequate sample is present and has mixed with the reagent
layer.
[0043] The meter can be programmed to wait for a predetermined
period of time after initially detecting the blood sample to allow
the blood sample to react with the reagent layer. Alternatively,
the meter may be configured to immediately begin taking readings in
sequence. During an exemplary fluid measurement sequence using
amperometry, the meter applies an assay voltage between the working
and proximal electrodes and takes one or more measurements of the
resulting current flowing between the working and counter
electrodes. The assay voltage is near the redox potential of the
chemistry in the reagent layer, and the resulting current is
related to the concentration of the particular constituent
measured, such as, for example, the glucose level in a blood
sample. Voltammetry and coulometry approaches, as known in the art,
could also be employed.
[0044] In one example, the reagent layer may react with glucose in
the blood sample in order to determine the particular glucose
concentration. In one example, glucose oxidase or glucose
dehydrogenase is used in the reagent layer. During a sample test,
the glucose oxidase initiates a reaction that oxidizes the glucose
to gluconic acid and reduces a mediator such as ferricyanide or
ruthenium hexamine. When an appropriate voltage is applied to a
working electrode relative to a counter electrode, the ferrocyanide
is oxidized to ferricyanide, thereby generating a current that is
related to the glucose concentration in the blood sample.
[0045] The test strip may also include a second sample chamber
configured to permit determination of hematocrit. The meter can
determine hematocrit by measuring the impedance of the blood sample
in the second sample chamber by applying an appropriate voltage
and/or current and reading suitable measurements to calculate an
impedance value. The calculated impedance value correlates with
hematocrit, which can vary and can affect glucose
determination.
[0046] The meter can calculate the glucose level based on the
measured current from the first sample chamber and, optionally,
enhance that calculation based on the impedance value determined
using the second sample chamber. This data along with other
calibration data contained within the test strip may permit the
meter to determine a glucose level and display the calculated
glucose level to the user.
[0047] Electrodes positioned within the sample chamber may include
a working electrode, a counter electrode, a fill-detect electrode,
a proximal electrode, and a distal electrode. A reagent layer can
be disposed in the first sample chamber and may cover at least a
portion of the working electrode, which can also be disposed at
least partially in the sample chamber. The reagent layer can
include, for example, an enzyme, such as glucose oxidase or glucose
dehydrogenase, and a mediator, such as potassium ferricyanide or
ruthenium hexamine, to facilitate the detection of glucose in
blood. It is contemplated that other reagents and/or other
mediators can be used to facilitate detection of glucose and other
constituents in blood and other body fluids. The reagent layer can
also include other components, such as buffering materials (e.g.,
potassium phosphate), polymeric binders (e.g.,
hydroxypropyl-methyl-cellulose, sodium alginate, microcrystalline
cellulose, polyethylene oxide, hydroxyethylcellulose, and/or
polyvinyl alcohol), and surfactants (e.g., Triton X-100 or Surfynol
485).
[0048] As mentioned previously, biosensors may inaccurately measure
a particular constituent level in blood due to unwanted effects of
certain blood components on the method of measurement. For example,
the hematocrit level (i.e., the percentage of blood occupied by red
blood cells) in blood can erroneously affect a resulting analyte
concentration measurement. Thus, it may be desirable to apply
chemical additives and/or signal processing techniques as
previously described, to reduce the sensitivity of the blood sample
to hematocrit. Further, it may be desirable to separately measure
hematocrit of a blood sample such that any analyte measurement can
be adjusted to correct for hematocrit variations. In accordance
with an exemplary embodiment of the present invention, a blood
sample may be divided into at least two different regions on a
biosensor and tested separately. For example, a blood sample may be
diverted into a first sample chamber to undergo an electrochemical
test, as described above, to determine, for example, the
concentration of glucose within the sample. The blood sample may
also be diverted into a second sample chamber to undergo a separate
test, as discussed in detail below, to determine the hematocrit
level of the blood sample. It is also contemplated that a third
sample chamber may be used to perform another determination, such
as, for example, a determination of blood sample temperature, a
concentration of a second analyte, a second measurement of the
first analyte concentration, and/or an on board control to perform
a calibration step. In some embodiments, the second sample chamber
may be configured to perform one or more determinations as
described for the third sample chamber, as outlined in detail
below.
[0049] In some embodiments, first and second sample chambers can be
dimensioned and configured to draw a blood sample into the sample
chambers via capillary action. Each sample chamber may also include
one or more electrodes positioned within the sample chambers and
configured to contact the blood sample. The first sample chamber
may include reagents and electrodes configured to determine a blood
glucose concentration. Hematocrit may be measured using the second
sample chamber. For example, the second chamber may include a set
of electrodes spaced apart at a predetermined distance, and
hematocrit may be determined by measuring an impedance of the blood
sample between the electrodes. The distance between the electrodes
in the second sample chamber can be optimized for measuring
hematocrit while the electrodes of the first sample chamber may be
configured for glucose determination.
[0050] Hematocrit may be determined using any methods known in the
art. For example, hematocrit may use electrical, optical, chemical,
or any other suitable method. Optical methods may include
reflective or transmission techniques. Electrical methods may
include amperometric, voltametric, or coulometric. In some
embodiments, hematocrit may be determined using an AC excitation,
wherein an impedance measurement may be obtained using digital
signal processing, analog processing, or a similar suitable
technique.
[0051] To determine impedance, an AC signal can be applied across a
set of electrodes in the second sample chamber. Impedance may
include real or complex values, wherein effective, reactive,
capacitive and/or resistive parameters may be associated with
hematocrit. As explained by the Coulter principle, blood hematocrit
can be derived from an impedance measurement obtained by applying
an AC signal to the blood sample. More specifically, impedance
Z.sub.R can be measured from the blood sample by dividing the
phasor voltage V.sub.r applied across the electrodes and dividing
this value by the phasor current I.sub.r passing through the
electrodes and the blood sample. Thus, the impedance of the blood
sample is: Z R = V r I r ##EQU1##
[0052] Following impedance measurement, hematocrit can be
determined by applying the measured impedance value or multiple
values at several different frequencies of excitation to an
equation, an algorithm, a look-up chart, or any other suitable
method. For example, an algorithm may correlate a glucose level
with an electrical measurement value up to a threshold value, and
above that threshold, a correction value correlated with hematocrit
may be applied to any glucose determination. Once the value
correlated to the hematocrit level within the blood sample is
determined, the value may be used to modify the calculated glucose
concentration such that an enhanced or corrected value of the
concentration of glucose of the blood sample can be determined.
Determining a glucose measurement and/or a hematocrit value may
also require incorporating of one or more correction values, such
as, for example, for variations in a temperature of a blood
sample.
[0053] In accordance with another exemplary embodiment of the
present invention, a test strip may further comprise a third sample
chamber configured to permit determination of a third parameter
associated with a blood sample. The third parameter to be measured
may be selected from a group consisting of a temperature, a
concentration of a second analyte, and an on-board control, as
described in detail below.
[0054] In some embodiments, one or more sample chambers may be
configured to receive a control solution. The control solution may
be used to periodically test one or more functions of a meter. For
example, a control solution may include a solution of known
electrical properties and an electrical measurement of the solution
may be performed by the meter. When the meter detects the use of a
control solution, it can provide an operational check of both
sample chambers functionality to verify the systems measurement
integrity. The meter read-out may then be compared to the known
glucose value of the solution to confirm that the meter is
functioning to an appropriate accuracy. Any measurement of a
control solution may be performed using one or more electrodes of
the second sample chamber. In addition, data associated with a
measurement of a control solution may be processed, stored and/or
displayed using a meter differently to any data associated with a
glucose measurement. Such different treatment of data associated
with the control solution may permit a meter, or user, to
distinguish a glucose measurement, or may permit exclusion of any
control measurements when conducting any statistical analysis of
glucose measurements.
[0055] The present disclosure provides a method for producing a
diagnostic test strip 10, as shown in FIG. 1A. Test strip 10 of the
present disclosure may be used with a suitable test meter 400, 408,
as shown in FIGS. 1B and 1C, to detect or measure the concentration
of one or more analytes. As shown in FIG. 1A, test strip 10 are
planar and elongated in design. However, test strip 10 may be
provided in any suitable form including, for example, ribbons,
tubes, tabs, discs, or any other suitable form. Furthermore, test
strip 10 can be configured for use with a variety of suitable
testing modalities, including electrochemical tests, photochemical
tests, electro-chemiluminescent tests, and/or any other suitable
testing modality.
[0056] Test meter 400, 408 may be selected from a variety of
suitable test meter types. For example, as shown in FIG. 1B, test
meter 400 includes a vial 402 configured to store one or more test
strips 10. The operative components of test meter 400 may be
contained in a meter cap 404. Meter cap 404 may contain electrical
meter components, can be packaged with test meter 400, and can be
configured to close and/or seal vial 402. Alternatively, a test
meter 408 can include a monitor unit separated from storage vial,
as shown in FIG. 1C. Any suitable test meter may be selected to
provide a diagnostic test using test strip 10 produced according to
the disclosed methods.
Test Strip Configuration
[0057] With reference to the drawings, FIGS. 2A and 2B show a test
strip 10, in accordance with an exemplary embodiment of the present
invention. Test strip 10 preferably takes the form of a generally
flat strip that extends from a proximal end 12 to a distal end 14.
Preferably, test strip 10 is sized for easy handling. For example,
test strip 10 can measure approximately 35 mm long (i.e., from
proximal end 12 to distal end 14) and approximately 9 mm wide. The
strip, however, can be any convenient length and width. For
example, a meter with automated test strip handling may utilize a
test strip smaller than 9 mm wide. Additionally, proximal end 12
can be narrower than distal end 14 in order to provide facile
visual recognition of the distal end. Thus, test strip 10 can
include a tapered section 16, in which the full width of test strip
10 tapers down to proximal end 12, making proximal end 12 narrower
than distal end 14. As described in more detail below, the user
applies the blood sample to an opening in proximal end 12 of test
strip 10. Thus, providing tapered section 16 in test strip 10, and
making proximal end 12 narrower than distal end 14, assists the
user in locating the opening where the blood sample is to be
applied. Further, other visual means, such as indicia, notches,
contours or the like are possible.
[0058] As shown in FIG. 2B, test strip 10 can have a generally
layered construction. Working upwardly from the bottom layer, test
strip 10 can include a base layer 18 extending along the entire
length of test strip 10. Base layer 18 can be formed from an
electrically insulating material and have a thickness sufficient to
provide structural support to test strip 10. For example, base
layer 18 can be formed from a polyester (e.g., PET), acrylic,
and/or other plastic material and be about 0.35 mm thick.
[0059] According to the illustrative embodiment, a conductive layer
20 is disposed on base layer 18. Conductive layer 20 includes a
plurality of electrodes disposed on base layer 18 near proximal end
12, a plurality of electrical contacts disposed on base layer 18
near distal end 14, and a plurality of conductive regions
electrically connecting the electrodes to the electrical contacts.
In the illustrative embodiment depicted in FIG. 2A, the plurality
of electrodes includes a working electrode 22, a proximal electrode
(or counting electrode) 24, a distal electrode (or fill
detect-anode) 28, and a fill-detect electrode (or fill-detect
cathode) 30. Defined between proximal electrode 24 and distal
electrode 28 is an electrically isolated region 26, wherein the
distance between electrodes 24 and 28 may be about 1 mm. The
electrical contacts can correspondingly include a working electrode
contact 32, a proximal electrode contact 34, a distal electrode
contact 36, and a fill-detect electrode contact 38, The conductive
regions can include a working electrode conductive region 40,
electrically connecting working electrode 22 to working electrode
contact 32, a proximal electrode conductive region 42, electrically
connecting proximal electrode 24 to proximal electrode contact 36,
a distal electrode conductive region 44 electrically connecting
distal electrode 28 to distal electrode contact 36, and a
fill-detect electrode conductive region 46 electrically connecting
fill-detect electrode 30 to fill-detect contact 38. Further, the
illustrative embodiment is depicted with conductive layer 20
including an auto-on conductor 48 disposed on base layer 18 near
distal end 14.
[0060] In addition, the present disclosure provides test strips 10
that include electrical contacts that are resistant to scratching
or abrasion. Such test strips 10 can include conductive electrical
contacts formed of two or more layers of conductive and/or
semi-conductive material. Referring to FIG. 2B, A first lower
conductive layer 20 can include a conductive metal, ink, or paste.
A second upper layer (not illustrated) can include a conductive ink
or paste. Further, in some embodiments, the upper layer can have a
resistance to abrasion that is greater than the lower layer. In
addition, the second upper layer may have a thickness such that,
even when scratched or abraded, the entire thickness of the
conductive layer will not be removed, and the electrical contact
will continue to function properly. Thus, such test strips 10 can
include electrical contacts having material properties and
dimensions such that, even when scratched or abraded, test strips
10 will continue to function properly. Further information relating
to electrical contacts that are resistant to scratching or abrasion
are described in U.S. patent application Ser. No. 11/458,298 which
is incorporated by reference herein in its entirety.
[0061] The next layer in the illustrative test strip 10 is a
dielectric spacer layer 64 disposed on conductive layer 20.
Dielectric spacer layer 64 is composed of an electrically
insulating material, such as polyester (e.g., PET), acrylic, and/or
other plastic material. Dielectric spacer layer 64 can be about
0.100 mm thick and covers portions of working electrode 22,
proximal electrode 24, distal electrode 28, fill-detect electrode
30, and conductive regions 40-46, but in the illustrative
embodiment does not cover electrical contacts 32-38 or auto-on
conductor 48. For example, dielectric spacer layer 64 can cover
substantially all of conductive layer 20 thereon, from a line just
proximal of contacts 32 and 34 all the way to proximal end 12,
except for a first sample chamber 52 and a second sample chamber 58
extending from proximal end 12. In this way, first sample chamber
52 can define an exposed portion 54 of working electrode 22, an
exposed portion 56 of proximal electrode 24, and an exposed portion
62 of fill-detect electrode 30. Second sample chamber 58 can define
an exposed portion 59 of proximal electrode 24 and an exposed
portion 60 of distal electrode 28. In some embodiments, first
sample chamber 52 may be configured to detect an analyte
concentration in a blood sample and second sample chamber 58 may be
configured to determine a hematocrit of the blood sample. The shape
of sample chambers 52 and 58 may be achieved prior to application
on the base layer. Alternatively sample chambers 52 and 58 may be
formed subsequently, which may allow for tighter tolerances to be
achieved in the formation of the sample chambers 52 and 58.
[0062] A cover 72, having a proximal end 74 and a distal end 76,
can be attached to dielectric spacer layer 64 via an adhesive layer
78. Cover 72 can be composed of an electrically insulating
material, such as polyester, and can have a thickness of about 0.1
mm. Additionally, cover 72 can be transparent.
[0063] Adhesive layer 78 can include a polyacrylic or other
adhesive and have a thickness of about 0.013 mm. Adhesive layer 78
can consist of sections disposed on spacer layer 64 on opposite
sides of first sample chamber 52. A break 84 in adhesive layer 78
extends from a distal end 70 of first sample chamber 52 to an
opening 86. Cover 72 can be disposed on adhesive layer 78 such that
its proximal end 74 is aligned with proximal end 12 and its distal
end 76 is aligned with opening 86. In this way, cover 72 covers
first sample chamber 52 and break 84. It is also contemplated that
cover 72 may similarly cover second sample chamber 58.
[0064] Proximal end 74 of cover 72 can extend from distal end 70
beyond proximal end 12 to create an overhang, as shown in FIG. 2B.
The overhang may be formed by extending cover 72 beyond proximal
end 12 and/or by removing at least part of base layer 18 or other
appropriate material under cover 72 to create a notch or similar
structure. This overhang/notch configuration can aid in forming a
hanging reservoir for a blood sample, via surface tension, to aid
in providing a sufficient sample into first sample chamber 52 and
second sample chamber 58. It is also contemplated that various
materials, surface coatings (e.g., hydrophilic and/or hydrophobic),
or other structure protrusions and/or indentations at proximal end
12 may be used to form a suitable blood sample reservoir.
[0065] First sample chamber 52 and second sample chamber 58 may be
configured to receive separate portions of a blood sample applied
to test strip 10. A proximal end 68 of first sample chamber 52 may
define a first opening in first sample chamber 52, through which
the blood sample is introduced into first sample chamber 52. At
distal end 70 of first sample chamber 52, break 84 may define a
second opening in first sample chamber 52, for venting first sample
chamber 52 as a fluid sample enters first sample chamber 52. First
sample chamber 52 may be dimensioned such that a blood sample
applied to its proximal end 68 may be drawn into first sample
chamber 52 by capillary action, with break 84 venting first sample
chamber 52 through opening 86, as the blood sample enters.
Moreover, first sample chamber 52 can advantageously be dimensioned
so that the blood sample that enters first sample chamber 52 by
capillary action is about 1 micro-liter or less. For example, first
sample chamber 52 can have a length (i.e., from proximal end 12 to
distal end 70) of about 0.140 inches, a width of about 0.060
inches, and a height (which can be substantially defined by the
thickness of dielectric spacer layer 64) of about 0.005 inches.
Other dimensions could be used, however.
[0066] Proximal end 12 of second sample chamber 58 may define a
first opening in second sample chamber 58, through which the blood
sample is introduced into second sample chamber 58. Second sample
chamber 58 may be dimensioned such that a blood sample applied to
its proximal end may be drawn into second sample chamber 58 by
capillary action. Additionally, second sample chamber 58 can
advantageously be dimensioned so that the blood sample that enters
second sample chamber 58 by capillary action is about 0.5
micro-liters or less.
[0067] In some embodiments, a secondary sample chamber may be
configured for operation with a continuous glucose monitoring
system (not shown). Such a system may include systems and/or
devices configured to automatically monitor a patient's glucose
level. Such systems may periodically sample body fluid containing
cellular or biological matter that may affect a glucose
determination. Such systems may also benefit by using a secondary
sample chamber configured to determine hematocrit, or a similar
measurement, using one of more of the methods described here.
[0068] FIGS. 3A, 3B and 3C show various illustrative embodiments of
test strip 10. Specifically, first sample chamber 52 and second
sample chamber 58 may be variously configured in test strip 10. As
shown in FIG. 3A, first sample chamber 52 and second sample chamber
58 may be arranged in a bifurcated configuration on test strip 10,
wherein first sample chamber 52 may be fluidly connected to a blood
reservoir 63 and second sample chamber 58 may be fluidly connected
to blood reservoir 63. Such a configuration may permit fluid to
flow from blood reservoir 63 into first sample chamber 52 (via an
inlet) and second sample chamber 58 (via a second inlet) at
appropriate flow rates. It is contemplated that first sample
chamber 52 and second sample chamber 58 may also share a common
inlet.
[0069] FIG. 3B shows test strip 10 according to another
illustrative embodiment. Test strip 10 may include first sample
chamber 52 fluidly connected to second sample chamber 58 such that
a blood sample may flow from one sample chamber into another sample
chamber. For example, test strip 10 may be configured such that a
blood sample applied to proximal end 12 flows into an inlet of
second sample chamber 58. The sample may, through capillary action,
flow through second sample chamber 58 to an outlet of second sample
chamber 58, which may be fluidly connected to an inlet of first
sample chamber 52. Again, through capillary action, the blood
sample may flow through first sample chamber 52. Such a
configuration may permit a blood sample to flow into second sample
chamber 58 wherein hematocrit may be determined, and flow into
first sample chamber 52 wherein a glucose concentration may be
determined. It is also contemplated that sample chambers 52, 58 may
be configured such that blood flows from the blood sample into
first sample chamber 52, and from first sample chamber 52 into
second sample chamber 58.
[0070] FIG. 3C shows test strip 10 according to another
illustrative embodiment, wherein test strip 10 may include a third
sample chamber 61. Third sample chamber 61 may be configured to
permit determination of a third parameter associated with the blood
sample, such as, for example, a blood sample temperature, a
concentration of a second analyte within the blood sample, a second
measurement associated with the first analyte, or any suitable
measurement. Third sample chamber 61 may include one or more
different or shared components associated with first sample chamber
52 and second sample chamber 58, such as, for example, one or more
electrodes, or reagent layers.
[0071] In some embodiments, third sample chamber 61 may be
configured to provide an on-board control, wherein a function
and/or calibration of test strip 10 may be conducted to at least
partially confirm the accuracy of a measurement associated with
test strip 10. The third sample chamber 61 may be fluidly connected
to first and/or second sample chambers 52, 58. These and other
configurations of multiple sample chambers within test strip 10 are
contemplated within the scope of the present invention.
[0072] As shown in FIG. 2B, a reagent layer 90 is disposed in first
sample chamber 52, wherein reagent layer 90 may include one or more
chemical constituents to enable the level of glucose in the blood
sample to be determined electrochemically. Thus, reagent layer 90
may include an enzyme specific for glucose and a mediator, as
described above. In addition, reagent layer 90 may also include
other components, buffering materials (e.g., potassium phosphate),
polymeric binders (e.g., hydroxypropyl-methyl-cellulose, sodium
alginate, microcrystalline cellulose, polyethylene oxide,
hydroxyethylcellulose, and/or polyvinyl alcohol), and surfactants
(e.g., Triton X-100 or Surfynol 485).
[0073] As depicted in FIG. 2B, the arrangement of the various
layers in illustrative test strip 10 can result in test strip 10
having different thicknesses in different sections. In particular,
among the layers above base layer 18, much of the thickness of test
strip 10 can come from the thickness of spacer layer 64. Thus, the
edge of spacer layer 64 that is closest to distal end 14 can define
a shoulder 92 in test strip 10. Shoulder 92 can define a thin
section 94 of test strip 10, extending between shoulder 92 and
distal end 14, and a thick section 96, extending between shoulder
92 and proximal end 12. The elements of test strip 10 used to
electrically connect it to the meter, namely, electrical contacts
32-38 and auto-on conductor 48, can all be located in thin section
94. Accordingly, the connector in the meter can be sized and
configured to receive thin section 94 but not thick section 96, as
described in more detail below. This can beneficially cue the user
to insert the correct end, i.e., distal end 14 in thin section 94,
and can prevent the user from inserting the wrong end, i.e.,
proximal end 12 in thick section 96, into the meter. Although FIGS.
2A and 2B illustrate an illustrative embodiment of test strip 10,
other configurations, chemical compositions and electrode
arrangements could be used.
[0074] As depicted in FIG. 2A fill-detect electrode 30 can function
with working electrode 22 to perform a fill-detect feature, as
previously described. Further, working electrode 22 may operate in
conjunction with proximal electrode 24 to detection of a
constituent of a sample in first sample chamber 52, as described
above. Other configurations of electrodes on test strip 10 are
possible, such as, for example, multiple fill-detect electrodes and
multiple working electrodes.
[0075] As depicted in the FIG. 2B, fill-detect electrode 30 is
advantageously located on the distal side of reagent layer 90. In
this arrangement, the sample introduced into first sample chamber
52 will have traversed reagent layer 90 before reaching fill-detect
electrode 30. This arrangement beneficially allows the fill-detect
electrode 30 to indicate not only whether sufficient blood sample
is present in first sample chamber 52, but also when,
concomitantly, the blood sample has sufficiently mixed with the
chemical constituents of reagent layer 90.
Test Strip Array Configuration
[0076] Test strips can be manufactured by forming a plurality of
strips in an array along a reel or web of substrate material. The
term "reel" or "web" as used herein applies to continuous webs of
indeterminate length, or to sheets of determinate length. The
individual strips, after being formed, can be separated during
later stages of manufacturing. An illustrative embodiment of a
batch process of this type is described below. First, an
illustrative test strip array configuration is described.
[0077] FIG. 4A shows a series of traces 80 formed in a substrate
material coated with a conductive layer. Traces 80, formed in the
exemplary embodiment by laser ablation, partially form the
conductive layers of two rows of ten test strips as shown. In the
exemplary embodiment depicted, proximal ends 12 of the two rows of
test strips are in juxtaposition in the center of a reel 100.
Distal ends 14 of test strips 10 are arranged at the periphery of
reel 100. It is also contemplated that the proximal ends 12 and
distal ends 14 of test strips 10 can be arranged in the center of
reel 100. Alternatively, the two distal ends 14 of test strips 10
can be arranged in the center of reel 100. The lateral spacing of
test strips 10 may be designed to allow a single cut to separate
two adjacent test strips. The separation of test strip 10 from reel
100 can electrically isolate one or more conductive components of
the separated test strip 10.
[0078] As depicted in FIG. 4A, trace 80 for an individual test
strip forms a plurality of conductive components; e.g., electrodes,
conduction regions and electrode contacts. Trace 80 is comprised of
individual cuts made by a laser following a specific trajectory, or
vector. A vector can be linear or curvilinear, and define spaces
between conductive components that are electrically isolating.
Generally a vector is a continuous cut made by the laser beam.
[0079] The conductive components can be partially or entirely
defined by ablated regions, or laser vectors, formed in the
conductive layer. The vectors may only partially electrically
isolate the conductive component, as the component can remain
electrically connected to other components following laser
ablation. The electrical isolation of the conductive components can
be achieved following "singulation," when individual test strips
are separated from reel or web 100. It is also contemplated that
other conductive components may be electrically isolated during the
laser ablation process. For example, fill detect electrodes may be
isolated with the addition of one or more vectors.
[0080] FIG. 4A also includes registration points 102 at the distal
end 14 of each test strip on reel 100. Registration points 102
assist the alignment of the layers during lamination, punching,
etching, scoring, drilling, heating, compression, molding,
printing, and/or other manufacturing processes. It is further
contemplated that registration points 102 may be located at
locations other than the distal end 14 of each test strip trace 80
on reel 100. High quality manufacturing may require additional
registration points 102 to ensure adequate alignment of laminate
layers and/or other manufacturing processes, such as, for example,
laser ablation of conductive components, reagent deposition,
singulation, etc. It is contemplated that registration points 102
may be separated by less than 500 mm and may be less than 10 mm
wide.
[0081] FIG. 5 shows a "test card" 104 separated from reel 100. Test
card 104 can contain a plurality of test strips 10 or traces 80,
and a plurality of conductive components. In the preferred
embodiment test card 104 can contain between 6 and 12 test strips
10 or traces 80. In other embodiments, test card 104 can contain a
plurality of test strips 10 or traces 80. In the illustrated
embodiment, test card 104 can include a lateral array of test
strips 10 or traces 80. In other embodiments, test card 104 can
include an array or arrays of test strips 10 or traces 80 in
longitudinal and/or lateral configurations. It is further
contemplated that test strips 10 or traces 80 may be in any
arrangement on reel 100 suitable for manufacturing.
[0082] Test card 104 contains a plurality of conductive components.
Some conductive components can be electrically isolated when test
card 104 is removed from reel 100. As shown in FIG. 5, working
electrode 22 is electrically isolated. Other embodiments could
include additional electrically isolated conductive components not
shown in FIG. 5. It may be possible to analyze properties of the
electrically isolated conductive components to assess the quality
of the manufacturing process. The efficiency of the quality
assessment process can be increased by testing at least one of the
plurality of electrically isolated conductive components.
Batch Manufacturing of Test Strips
[0083] Test strip 10 may be manufactured using any suitable
manufacturing methods. For example, one or more conductive
components may be manufactured using laser ablation employing
projected masks or raster scanning methods, screen printing, insert
injection molding, and any other suitable techniques. One or more
sample chambers, or capillaries, may be formed using a spacer,
dielectric build-up, injection molded, laser ablation, or other
suitable method. One illustrative embodiment for manufacturing test
strip 10 will now be described in detail.
[0084] FIGS. 4A through 6 illustrate an exemplary method of
manufacturing test strips. Although these figures shows steps for
manufacturing test strip 10, as shown in FIGS. 4A through 6, it is
to be understood that similar steps can be used to manufacture test
strips having other configurations.
[0085] With reference to FIG. 5, a plurality of test strips 10 can
be produced by forming a structure 120 that includes a plurality of
test strip traces 122 on reel 100. Test strip traces 122 include a
plurality of traces 80, and can be arranged in an array that
includes a plurality of rows. Each row 124 can include a plurality
of test strip traces 122.
[0086] The separation process can also be used to electrically
isolate conductive components of test strip 10. Laser ablation of
the conductive layer may not electrically isolate certain
conductive components. The non-isolated conductive components may
be isolated by the separation process whereby test strips are
separated from reel 100. The separation process may sever the
electrical connection, isolating the conductive component.
Separating test strip 10 can electrically isolate the counting
electrode 24, fill detect-anode 28 and fill-detect cathode 30. The
separation process can complete the electrical isolation of
conductive components by selectively separating conductive
components.
[0087] Further, the separation process can provide some or all of
the shape of the perimeter of test strips 10. For example, the
tapered shape of tapered sections 16 of test strips 10 can be
formed during this punching process. Next, a slitting process can
be used to separate test strip traces 122 in each row 124 into
individual test strips 10. The separation process may include
stamping, slitting, scoring and breaking, or any suitable method to
separate test strip 10 and/or card 104 from reel 100.
[0088] FIGS. 4A and 4B show only one test strip trace 122 (either
partially or completely fabricated), in order to illustrate various
steps in a preferred method for forming test strip traces 122. In
this exemplary approach, test strip traces 122 in integrated
structure 120 are all formed on a sheet of material that serves as
base layer 18 in the finished test strips 10. The other components
in the finished test strips 10 are then built up layer-by-layer on
top of base layer 18 to form test strip traces 122. In each of
FIGS. 4A and 4B, the outer shape of test strip 10 that would be
formed in the overall manufacturing process is shown as a dotted
line.
[0089] The exemplary manufacturing process employs base layer 18
covered by conductive layer 20. Conductive layer 20 and base layer
18 can be in the form of a reel, ribbon, continuous web, sheet, or
other similar structure. Conductive layer 20 can include any
suitable conductive or semi-conductor material, such as palladium,
gold, platinum, silver, iridium, carbon, indium tin oxide, indium
zinc oxide, copper, aluminum, gallium, iron, mercury amalgams,
tantalum, titanium, zirconium, nickel, osmium, rhenium, rhodium
palladium, an organometalic, and/or other conductive or
semi-conductor materials known in the art. Conductive layer 20 can
be formed by sputtering, vapor deposition, screen printing or any
suitable manufacturing method. For example, one or more electrodes
may be at least partially formed by sputtering, evaporation,
electroplating, ultrasonic spraying, pressure spraying, direct
writing, shadow mask lithography, lift-off lithography, or laser
ablation. Also, the conductive material can be any suitable
thickness and can be bonded to base layer 18 by any suitable
means.
[0090] As shown in FIG. 2A, conductive layer 20 can include working
electrode 22, proximal electrode 24, distal electrode 28, and
fill-detect cathode 30. Trace 80 can be formed by laser ablation
where laser ablation can include any device suitable for removal of
the conductive layer in appropriate time and with appropriate
precision and accuracy. Various types of lasers can be used for
sensor fabrication, such as, for example, solid-state lasers (e.g.
Nd:YAG and titanium sapphire), copper vapor lasers, diode lasers,
carbon dioxide lasers and excimer lasers. Such lasers may be
capable of generating a variety of wavelengths in the ultraviolet,
visible and infrared regions. For example, excimer laser provides
wavelength of 248 nm, a fundamental Nd:YAG laser gives 1064 nm, a
frequency tripled Nd:YAG wavelength is at 355 nm and a Ti:sapphire
laser is at approximately 800 nm. The power output of these lasers
may vary and is usually in range 10-100 watts.
[0091] The laser ablation process can include a laser system. The
laser system can include a laser source. The laser system can
further include means to define trace 80, such as, for example, a
focused beam, projected mask or other suitable technique. The use
of a focused laser beam can include a device capable of rapid and
accurate controlled movement to move the focused laser beam
relative to conductive layer 20. The use of a mask can involve a
laser beam passing through the mask to selectively ablate specific
regions of conductive layer 20. A single mask can define test strip
trace 80, or multiple masks may be required to form test strip
trace 80. To form trace 80, the laser system can move relative to
conductive layer 20. Specifically, the laser system, conductive
layer 20, or both the laser system and conductive layer 20 may move
to allow formation trace 80 by laser ablation. Exemplary devices
available for such ablation techniques include Microline Laser
system available from LPKF Laser Electronic GmbH (Garbsen, Germany)
and laser micro machining systems from Exitech, Ltd (Oxford, United
Kingdom).
[0092] In the next step, dielectric spacer layer 64 can be applied
to conductive layer 20) as illustrated in FIG. 2B. Spacer layer 64
can be applied to conductive layer 20 in a number of different
ways. In an exemplary approach, spacer layer 64 is provided as a
sheet or web large enough and appropriately shaped to cover
multiple test strip traces 80. In this approach, the underside of
spacer layer 64 can be coated with an adhesive to facilitate
attachment to conductive layer 20. Portions of the upper surface of
spacer layer 64 can also be coated with an adhesive in order to
provide adhesive layer 78 in each of test strips 10. Various sample
chambers can be cut, formed or punched out of spacer layer 64 to
shape it before, during or after the application of spacer layer 64
to conductive layer 20. In addition, spacer layer 64 can include
adhesive sections and can include a break for each test strip
trace. Spacer layer 64 is then positioned over conductive layer 20,
as shown in FIG. 2B, and laminated to conductive layer 20. When
spacer layer 64 is appropriately positioned on conductive layer 20,
exposed electrode portions 54-62 are accessible through sample
chambers 52 and 58. Similarly, spacer layer 64 leaves contacts
32-38 and auto-on conductor 48 exposed after lamination.
[0093] Alternatively, spacer layer 64 could be applied in other
ways. For example, spacer layer 64 can be injection molded onto
base layer 18 and a substrate. Spacer layer 64 could also be built
up on dielectric layer 50 by screen-printing successive layers of a
dielectric material to an appropriate thickness, e.g., about 0.005
inches. A preferred dielectric material comprises a mixture of
silicone and acrylic compounds, such as the "Membrane Switch
Composition 5018" available from E.I. DuPont de Nemours & Co.,
Wilmington, Del. Other materials could be used, however.
[0094] Additionally, sample chambers can be formed after
application of spacer layer 64 on top of base layer 18 and
conductive layer 20 via the aforementioned laser ablation process.
This process allows for the removal of the conductive layer within
sample chambers.
[0095] Reagent layer 90 can then be applied to each test strip
structure. In an illustrative approach, reagent layer 90 is applied
by dispensing a formulation onto exposed portion 54 of working
electrode 22 and letting it dry to form reagent layer 90.
Alternatively, other methods, such as screen-printing, spray
deposition, piezo and ink jet printing, can be used to apply the
composition used to form reagent layer 90.
[0096] An exemplary formulation contains 250 mM potassium phosphate
at pH 6.75, 175-190 mM ruthenium hexamine, 5000 U/mL glucose
dehydrogenase, 0.5-2.0% polyethylene oxide, 0.025-0.20% NATROSOL
250M (hydroxyethylcellulose), 0.675-2.5% Avicel (microcrystalline
cellulose), 0.05-0.20% Triton-X surfactant and 2.5-5.0% trehalose.
In some embodiments, various constituents may be added to reagent
layer 90 to at least partially reduce a hematocrit bias of any
measurement. For example, various polymers, molecules, and/or
compounds may be added to reagent layer 90 to reduce cell migration
and hence may increase the accuracy of a measurement based on an
electrochemical reaction. Also, one or more conductive components
may be coated with a surface layer (not shown) to at least
partially restrict cell migration onto the one or more conductive
components. These and other techniques known in the art may be used
to reduce hematocrit bias from any measurement.
[0097] Cover 72 can then be attached to adhesive layer 78. Cover 72
may be large enough to cover multiple test strip traces 122.
Attaching cover 72 can complete the formation of the plurality of
test strip traces 122. The plurality of test strip traces 122 can
then be separated from each other to form a plurality of test
strips 10, as described above.
Quality Control Testing of Test Strips
[0098] FIG. 6 shows a further illustrative embodiment of a test
strip manufacturing method. The manufacturing method utilizes a web
200 containing conductive layer 20 and base layer 18. Conductive
layer 20 and base layer 18 can be any suitable material. Web 200
can be any dimension suitable for production of test strips 10. Web
200 is passed through any suitable device and ablated by process
300.
[0099] Ablation 300 can include any suitable ablation process
capable of forming conductive components in conductive layer 20. In
the illustrative embodiment, ablation 300 is achieved by laser
ablation. The ablation process may not electrically isolate all
conductive components. For example, counting electrode 24 may not
be isolated by laser ablation but can be isolated by subsequent
separation from web 200. In the illustrative embodiment, working
electrode 22 is electrically isolated during ablation process 300.
The proximal electrode 24, distal electrode 28 and fill-detect
cathode 30 may not be electrically isolated during ablation process
300. Specifically, subsequent separation process can electrically
isolate the proximal electrode 24, distal electrode 28 and
fill-detect cathode 30.
[0100] Web 200 can be passed through any suitable ablation device
at speeds sufficient to produce an appropriate rate of test strip
production. The ablation process can be sufficiently rapid to allow
the continuous movement of web 200 through the laser ablation
device. Alternatively, web 200 can be passed through the ablation
device in a non-continuous (i.e., start-and-stop) manner.
[0101] The properties of the conductive components formed by
ablation process 300 can be analyzed during or following ablation
process 300. Analysis of ablation process 300 can include optical,
chemical, electrical or any other suitable analysis means. The
analysis can monitor the entire ablation process, or part of the
ablation process. For example, the analysis can include monitoring
vector formation to ensure the dimensions of the formed vector are
within predetermined tolerance ranges.
[0102] Quality control analysis, which can be performed during or
upon completion of the manufacturing process, can also include
monitoring the effectiveness and/or efficiency of the vector
formation process. In particular, the width of the resulting
vectors can be monitored to ensure acceptable accuracy and
precision of the cuts in conductive layer 20. For example, the
quality of the laser ablation process can be analyzed by monitoring
the surface of conductive layer 20 and/or base layer 18 following
ablation. Partial ablation of base layer 18 can indicate that the
laser power is set too high or the beam is traveling too slowly. By
contrast, a partially ablated conductive layer may indicate
insufficient laser power or that the beam is traveling too quickly.
Incomplete ablation of gaps may result in the formation of vectors
that are not electrically isolating between conductive
components.
[0103] In the illustrative embodiment, the dimensions of working
electrode 22 can be analyzed to determine the quality of the
manufacturing process. For example optical analysis (not shown) can
monitor the width of working electrode 22 to ensure sufficient
accuracy of ablation process 300. Further, the alignment of working
electrode 22 relative to registration points 102 can be monitored.
Optical analysis can be performed by using VisionPro system from
Cognex Vision Systems (Natick, Massachusetts).
[0104] As described above, the ablation process produces an array
of test strips 202 on web 200. Following formation of test strip
array 202 and corresponding conductive components, dielectric
spacer layer 64 is laminated to conductive layer 20. A spacer
lamination process 302 can include registration points 102 to
correctly align spacer layer 64 with conductive layer 20. Spacer
layer 64 may contain registration points 102 corresponding to
registration points 102 of test strip array 202. Spacer lamination
process may output a three layer laminate 204.
[0105] A test card 206 may be separated from three layer laminate
204. The separation may be achieved using punching, slitting,
cutting, or any other appropriate process. Test card 206 can be
analyzed by a test card analysis process 306 to test the quality of
any previous manufacturing process. Test card analysis process 306
can include optical, electrical, chemical or any other suitable
means for testing test card 206. In an illustrative embodiment, the
electrical properties of working electrode 22 can be tested. At
least one of the plurality of working electrodes 22 of test card
206 can be analyzed for electrochemical and surface properties. For
example, chronoamperometry can be used to test working electrode
22. Chronoamperometry is an electrochemical technique that uses a
voltage signal for excitation and measures current generated as a
result of the excitation as a function of time.
[0106] Further, test card analysis process 306 may include
measuring the width of space 26 between proximal electrode 24 and
distal electrode 28 for accuracy. Additionally, a test card 104 may
comprise test strips 10 in which sample chambers 52 and 58 have
been formed, as discussed above. Under such circumstances test card
analysis process 306 may include testing at least one of sample
chambers 52 and 58 to determine if they have the dimensions that
fit within predetermined tolerances, for example.
[0107] The results of test card analysis process 306 can be
compared to previous manufacturing process. Alternatively, the
results of test card analysis process 306 may be compared to
modeled or simulated results using computational methods. The
results can be used to ensure high-quality manufacturing processes.
Deviation from acceptable or expected results may require altering
upstream manufacturing processes, or altering downstream
manufacturing processes to address the deviations. Following
acceptance of the results of test card analysis process 306, the
quality of upstream manufacturing processes can be confirmed.
[0108] Following a satisfactory feedback 308 from test card
analysis process 306, the chemistry can be applied to three-layer
laminate 204 by a chemistry application process 310. A resulting
laminate 208 can contain any appropriate reagent suitable for the
specific test strip. A reagent application process 310 can include
any appropriate process. In the preferred embodiment, quality
control testing is not performed following reagent application
process 310. In other embodiments, quality control analysis can be
conducted following reagent application process 310. For example,
quality control analysis can monitor the effectiveness of the
chemistry application. Specifically, optical analysis may be
required to determine the extent of reagent covering working
electrode 22 and/or counter electrode 24. Alternatively, any
previous or upstream manufacturing process can be tested following
formation of laminate 208.
[0109] Following reagent application process 310, cover 72 can be
applied to laminate 208 using any appropriate cover application
process 312. Cover 72 may be centered on laminate 208. The
resulting laminate 210 can be tested to ensure the quality of the
cover application process 312. For example, optical means can be
used to monitor the alignment of cover 72 to laminate 210.
Alternatively, laminate 210 can be tested to ensure the quality of
any upstream manufacturing process as described previously.
Following cover application process 312, laminate 210 can be moved
to a production testing 314.
[0110] The manufacturing process can be halted at any stage based
upon the results of the quality control testing during
manufacturing or production. Alternatively, one or more
manufacturing processes can be adjusted based on the results of the
quality control analysis. Quality control tests can be conducted in
real time, and/or may include analysis of test cards removed from
the production line. If the quality control testing is performed on
test cards taken out of the production line, any production of the
same lot or batch can be intercepted in the manufacturing process
downstream of the quality control testing. Test card 206 can
contain addressable information, identifying where the test card
was removed from the production line. Consequently any deviations
from appropriate manufacturing quality can be isolated to specific
regions of the production line.
CONCLUSION
[0111] In summary, determining hematocrit levels by measuring the
impedance of a blood sample in a separate sample chamber has a
number of advantages. It can be applied to many biosensors, not
just oxidation-based glucose sensors. It has a high degree of
accuracy and precision in regards to measuring and correcting for
hematocrit since the presence of a separate chamber allows for
optimizing the distance between the proximal and distal electrode
specifically for measuring impedance of a blood sample. Further,
since the impedance measurement can occur concurrently with the
electrochemical measurement in another sample chamber, the amount
of test time can be kept to a minimum.
[0112] While various test strip structures and manufacturing
methods are described as possible candidates for use to measure
HCT, they are not intended to be limiting of the claimed invention.
Unless expressly noted, the particular test strip structures and
manufacturing methods are listed merely as examples and are not
intended to be limiting of the invention as claimed. Other
embodiments of the invention will be apparent to those skilled in
the art from consideration of the specification and practice of the
invention disclosed herein. It is intended that the specification
and examples be considered as exemplary only, with a true scope and
spirit of the invention being indicated by the following
claims.
* * * * *