U.S. patent application number 10/706222 was filed with the patent office on 2004-05-20 for method for making a cell for electrochemical analysis.
This patent application is currently assigned to Roche Diagnostics Corporation. Invention is credited to Bhullar, Raghbir Singh, Hill, Brian.
Application Number | 20040094413 10/706222 |
Document ID | / |
Family ID | 23891864 |
Filed Date | 2004-05-20 |
United States Patent
Application |
20040094413 |
Kind Code |
A1 |
Bhullar, Raghbir Singh ; et
al. |
May 20, 2004 |
Method for making a cell for electrochemical analysis
Abstract
According to an aspect of the invention, a cell for
electrochemical analysis is provided, comprising a body having a
chamber, and a pair of electrodes opposing each other within the
camber comprising a electrically conductive rod extending through
the body transverse to the longitudinal direction and removed
within the capillary channel. According to a preferred embodiment,
at least one reagent is provided within the capillary channel. The
cell may be part of a plurality of such cells connected in
seriatim.
Inventors: |
Bhullar, Raghbir Singh;
(Indianapolis, IN) ; Hill, Brian; (Indianapolis,
IN) |
Correspondence
Address: |
Lawrence A. Steward, Esq.
BRINKS HOFER GILSON & LIONE
Suite 1600
One Indiana Square
Indianapolis
IN
46204
US
|
Assignee: |
Roche Diagnostics
Corporation
|
Family ID: |
23891864 |
Appl. No.: |
10/706222 |
Filed: |
November 12, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10706222 |
Nov 12, 2003 |
|
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09476442 |
Dec 30, 1999 |
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6676815 |
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Current U.S.
Class: |
204/403.01 ;
29/592.1 |
Current CPC
Class: |
G01N 27/3272 20130101;
Y10T 29/49002 20150115 |
Class at
Publication: |
204/403.01 ;
029/592.1 |
International
Class: |
G01N 027/26 |
Claims
What is claimed is:
1. A method of making a cell for electrochemical analysis of a
liquid sample comprising: forming a body of dielectric material
withea rod of electrically conductive material embedded therein;
removing dielectric material and electrically conductive material
to form a chamber within the body; wherein the size and location of
the chamber are such that the rod of electrically conductive
material is divided by a gap.
2. The method of claim 1 wherein multiple chambers are formed in
the body, each chamber dividing the rod of electrically conductive
material.
3. A method of making a cell for electrochemical analysis of a
liquid sample comprising: forming a cylinder of a dielectric
material with a rod of electrically conductive material passing
through the cylinder in a direction perpendicular to the
longitudinal axis of the cylinder; removing dielectric material and
electrically conductive material to form a cylindrical chamber
concentric with the longitudinal axis; wherein the size and
location of the chamber are such that the rod of electrically
conductive material is divided with a gap between a first portion
that terminates at the inner wall of the chamber on one side of the
chamber and a second portion that terminates at the inner wall of
the chamber on an opposite side of the chamber.
4. The method of claim 1 wherein the electrically conductive rod
passes from one side to the other.
5. A cell for electrochemical analysis comprising: a body of a
dielectric material with a rod of electrically conductive material
passing through the body and having a channel perpendicular to the
rod and passing through the rod and dividing it into two opposing
electrodes.
6. The cell of claim 5 further comprising at least one reagent
within the chamber.
7. The cell of claim 5 that is part of a plurality of the cells
connected in seriatim.
8. A cell for electrochemical analysis, comprising: an annular wall
that defines a capillary channel; a pair of opposing electrically
conductive electrodes within the capillary channel that penetrate
the annular wall.
9. The cell of claim 8 further comprising at least one reagent
within the capillary channel.
10. The cell of claim 8 further comprising at least one reagent
deposited on the body within the capillary channel and overlying
the electrodes.
11. The cell of claim 8 that is part of a plurality of the cells
connected in seriatim.
12. A method of making a cell for electrochemical analysis,
comprising: molding a body with an electrically conductive rod;
forming a capillary channel in the body transverse to the
electrically conductive rod; and, removing the electrically
conductive rod from within the capillary channel thereby forming a
pair of opposing electrodes.
13. The method of claim 14 further comprising depositing at least
one reagent within the capillary channel.
14. The method of claim 14 further comprising depositing at least
one reagent within the capillary channel in liquid form through
capillary action.
15. The method of claim 14 further comprising forming a plurality
of parallel capillary channels in the body and removing the
electrically conductive rod from within each capillary channel.
16. The method of claim 14 comprising partially forming the
capillary channel while molding the body.
17. A cell made by the method of claim 14.
18. A method of making a cell for electrochemical analysis,
comprising: molding a body as a parallel row of cell bodies with an
electrically conductive rod transverse to the row of cell bodies;
forming a plurality of parallel capillary channels in the body
transverse to the electrically conductive rod, one capillary
channel for each cell body; and, removing the electrically
conductive rod from within each capillary channel.
19. The method of claim 18 further comprising separating the cell
bodies.
20. A cell made by the method of claim 18.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates to test cells for
electrochemical analysis.
[0002] Test cells for electrochemical analysis are well known. They
have been used to determine the concentration of various analytes
from biological samples, particularly from blood. Cells for
electrochemical analysis are described in U.S. Pat. Nos. 5,413,690;
5,762,770 and 5,798,031; as well as in International Publication
No. WO99/13101, each of which are hereby incorporated by
reference.
[0003] An electrochemical biosensor typically includes a sensor
strip. The sensor strip includes a space that holds the sample to
be analyzed, may include reagents to be released into the sample,
and includes an electrode set. The electrode set normally includes
an insulating substrate, and electrodes that contact the sample,
which have contact pads for electrically connecting the electrodes
to the electronics of an analysis apparatus.
SUMMARY OF THE INVENTION
[0004] According to an aspect of the invention, a cell for
electrochemical analysis is provided, comprising a body having a
chamber, and a pair of electrodes opposing each other within the
chamber comprising a metal rod extending through the body
transverse to the longitudinal direction and removed within the
capillary channel. According to a preferred embodiment, at least
one reagent is provided within the capillary channel. The cell may
be part of a plurality of such cells connected in seriatim.
[0005] According to a further aspect of the invention, a method of
making a cell for electrochemical analysis is provided, comprising
molding a body with a metal rod, forming a capillary channel
transverse to the metal rod, and removing the metal rod from within
the capillary channel thereby forming a pair of opposing
electrodes. According to a preferred embodiment, the method further
comprises depositing at least one reagent within the capillary
channel. According to a further aspect of the invention, the method
comprises molding a body as a parallel row of cell bodies with a
metal rod transverse to the row of cell bodies.
[0006] According to a further aspect of the invention, a method of
electrochemically analyzing a sample is provided, comprising
drawing the sample within a cell for electrochemical analysis of
the type described above, and applying a difference in electrical
potential across the electrodes.
[0007] Many fluid samples may be analyzed according to the numerous
aspects of the invention. For example, human body fluids such as
whole blood, blood serum, urine, and cerebrospinal fluid may be
measured. Also fermentation products and in environmental
substances, which potentially contain environmental contaminants,
may be measured.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 presents a perspective view of an cell for
electrochemical analysis according to an aspect of the
invention.
[0009] FIG. 2 presents a top plan view of the FIG. 1 cell.
[0010] FIG. 3 presents a side cross-sectional view taken along line
3-3 of FIG. 2.
[0011] FIG. 4 presents a side cross-section view taken along line
4-4 of FIG. 2.
[0012] FIG. 5 presents a perspective view of a body comprising a
plurality of cell bodies, according to a further aspect of the
invention.
[0013] FIG. 6 presents a perspective cross-sectional view taken
along line 6-6 of FIG. 5.
[0014] FIG. 7 presents the perspective cross-sectional view of FIG.
6 with a reagent deposited within the cells.
[0015] FIG. 8 presents a perspective of a cell for electrochemical
analysis according to a further aspect of the invention.
[0016] FIG. 9 presents a perspective view of a body comprising a
plurality of cell bodies, according to a further aspect of the
invention.
[0017] FIG. 10 presents a schematic view of a sample analysis
method and apparatus.
[0018] FIG. 11 presents a top plan view of a rotary clip for use
with the cell of the invention.
[0019] FIG. 12 presents a side plan view of a linear clip for use
with the cell of the invention.
[0020] FIG. 13 presents an end view of a cell according to an
aspect of the invention.
[0021] FIG. 14 presents an end view of a cell having a chamber with
an oblong cross-section, according to a further aspect of the
invention.
[0022] FIG. 15 is a side cross-sectional view of a cell having a
chamber that is enlarged at one end, according to a further aspect
of the invention.
[0023] FIG. 16 is a side cross-sectional view of a cell having a
chamber that is enlarged at one end, according to a further aspect
of the invention.
[0024] FIG. 17 is an end view of a cell according to a further
aspect of the invention.
[0025] FIG. 18 is a side cross-sectional view of the FIG. 17 cell
taken along line 18-18 of FIG. 17.
[0026] FIG. 19 is an enlarged top pan view of a rod according to an
aspect of the invention.
[0027] FIG. 20 is a side view of the FIG. 19 rod.
[0028] FIG. 21 is an end view of a cell according to a further
aspect of the invention.
[0029] FIG. 22 is a side cross-sectional view of the FIG. 21 cell
taken along line 22-22 of FIG. 21.
DETAILED DESCRIPTION
[0030] Various aspects of the invention are presented in FIGS.
1-22, which are not drawn to scale and wherein like components are
numbered alike. Referring now to FIG. 14, numerous views of a cell
10 for electrochemical analysis are presented according to an
aspect of the invention. FIG. 1 presents a perspective view of the
cell 10, FIG. 2 presents a top plan view, FIG. 3 presents a side
cross-sectional view taken along line 3-3 of FIG. 2, and FIG. 4
presents a side cross-sectional view taken along line 4-4 of FIG.
2.
[0031] The cell 10 comprises a cell body 12 of dielectric material
having a chamber 14 extending in a longitudinal direction 16. In
the example presented in FIGS. 1-4, the cell body 12 is an annular
wall that defines the chamber 14. A pair of electrodes 18 and 19
opposing each other within the chamber comprise a rod of
electrically conductive material extending through the cell body 12
transverse to the longitudinal direction 16 and removed within the
chamber 14. The chamber 14 divides the rod of electrically
conductive material, thereby forming the pair of opposing
electrodes 18 and 19. The rod of electrically conductive material
preferably extends in a direction perpendicular to the longitudinal
axis 16 of the cell body 12 (particularly if cylindrical) or the
chamber 14. As used herein, the term "perpendicular" is intended to
indicate an angle on the order of 90.degree., and is intended to
include moderate deviations from exactly 90.degree. to the extent
that functionality of the electrochemical cell is not adversely
effected. Some variation is inevitable in a manufacturing
process.
[0032] The pair of electrodes 18 and 19 penetrate the annular wall
of the cell body 12 within the chamber 14. The metal rod, and hence
the electrodes 18 and 19, may be circular in cross section (as
shown), or square, rectangular, triangular, polygonal, or any other
shape suitable for an electrode. According to a preferred
embodiment, the chamber 14 is a capillary channel and extends all
the way through the cell body 12.
[0033] As best shown in FIG. 4, the size and location of the
chamber 14 are such that the rod of electrically conductive
material is divided with a dielectric gap 40 between a first
portion 42 that terminates at the inner wall of the chamber 14 on
one side of the chamber 14 and a second portion 44 that terminates
at the inner wall of the chamber 14 on an opposite side of the
chamber 14. The rod of electrically conductive material passes from
one side to the other, but is divided. The gap 40 is presented from
another view in FIG. 13 as seen looking into one of the ends of
cell 10. Another view of the gap 40 is presented in FIG. 14 wherein
the chamber 14 is oblong transverse to the axis of the rod.
According to a preferred embodiment, the gap 40 is within the
range, inclusive, of 1 micrometer to 3000 micrometers. According to
a more preferred embodiment, the gap 40 is within the range,
inclusive, of 5-1000 micrometers. According to a particularly
preferred embodiment, the gap 40 is on the order 25
micrometers.
[0034] Referring again to FIG. 14, the cell body 12 is preferably
injection molded around the rod, thus embedding the rod in the cell
body 12, and the rod is removed from within the chamber 14 by, for
example, mechanical or laser drilling using machining methods known
in the art thereby reducing the rod to individual electrodes 18 and
19. The diameter of the hole drilled is preferably slightly larger
than the diameter of the rod so that the two electrodes are
separated and electrically insulated from each other, as shown in
FIG. 4. The hole drilled may be circular in cross-section. The
chamber 14 may be partially molded, and the chamber 14 may be fully
or partially formed by removing the dielectric material forming the
body 12.
[0035] Examples of metals that may be implemented in forming the
electrodes 18 and 19 include aluminum, carbon (such as graphite),
cobalt, copper, gallium, gold, indium, iridium, iron, lead,
magnesium, mercury (as an amalgam), nickel, niobium, osmium,
palladium, platinum, rhenium, rhodium, selenium, silicon (such as
highly doped polycrystalline silicon), silver, tantalum, tin,
titanium, tungsten, uranium, vanadium, zinc, zirconium, mixtures
thereof, and alloys or metallic compounds of these elements.
Preferably, the electrode set is constructed of gold, platinum,
palladium, iridium, or alloys of these metals, since such noble
metals and their alloys are unreactive in biological systems. The
rod may be a material or a metal other than a noble metal, for
example graphite or copper. In such case, the surface of the
electrodes 18 and 19 within the chamber may be plated with a noble
metal after the metal rod is removed from within the chamber 14,
for example by immersion or electroless plating.
[0036] The volume of chamber 14 within the electrochemical cell may
be relatively small, such as 5 microliters or less. Volumes as
small as 1 microliter or less are envisioned in the practice of the
invention. Volume of the chamber 14 may be reduced by reducing the
height of the cell 10 in the longitudinal direction 16, by reducing
the diameter of the chamber 14, and/or by making the chamber
oblong, as presented in FIG. 14.
[0037] Referring now to FIGS. 15 and 16, the chamber 14 need not
have a constant cross-section section. For example, it may have a
smaller diameter at one end of the body than the other. Referring
now specifically to FIG. 15, a cell 100 having a body 112 and a
chamber 114 is presented wherein the chamber 114 is enlarged on one
end by a plurality of concentric circular sections 102, each
section 102 closer to the end of the cell 100 having a larger
diameter than the previous one. Referring now specifically to FIG.
16, a cell 200 having a body 212 and a chamber 214 is presented
wherein the chamber 214 is enlarged on one end and reduces in
diameter with curvilinear sloping sides to the reduced diameter on
the other end. Enlarging the chamber on one end facilitates
applying the sample to the cell particularly if done manually.
[0038] Referring now to FIG. 5, a perspective view of an embodiment
is presented wherein the cell 10 is part of a plurality of cells 10
connected in seriatim. FIG. 6 presents a cross-sectional view of
the cells 10 of FIG. 5 taken along line 6-6 of FIG. 5. Each chamber
14 divides the rod of electrically conductive material. FIG. 7
presents a view identical to FIG. 6, except the cells 10 further
comprise at least one reagent 20 within the chamber 14. In the
example presented, the at least one reagent 20 is deposited on the
cell body 12 within the chamber 14 and overlying the electrodes 18
and 19. The cells 10 connected in seriatim as shown in FIGS. 5-7
may be used in that form, or may be separated into individual cells
10, as shown in FIGS. 1-4.
[0039] The reagent may be deposited, for example, by dipping the
cell into the reagent in liquid form to a depth that deposits the
reagent at the desired level within the chamber 14. For a capillary
chamber 14, the reagent may be drawn into the cell body 12 via
capillary action. The reagent may reach an equilibrium level that
may correspond to the desired level within the chamber 14. If the
desired level is less than the equilibrium level, then the cell 10
is dipped for a period of time that is less than the time it takes
for the reagent to reach the equilibrium level with the chamber 14.
If the desired level is greater than the equilibrium level, then
the cell 10 is dipped a greater distance into the reagent.
[0040] According to a further aspect of the invention, with
reference to FIGS. 1-4, a method of making a cell 10 for
electrochemical analysis is provided, comprising molding a cell
body 12 with a metal rod, forming a chamber 14 transverse to the
metal rod, removing the metal rod from within the chamber 14
thereby forming a pair of opposing electrodes 18 and 19. The method
may further comprise depositing at least one reagent within the
chamber 14, for example, by drawing the reagent into the chamber 14
in liquid form via chamber action. As presented in FIGS. 5-7, the
method may further comprise forming a plurality of parallel
chambers 14 in the cell body 12 and removing the metal rod from
within each chamber 14. The chamber 14 may be at least partially
formed while molding the cell body 12.
[0041] According to a further aspect of the invention, with
reference to FIGS. 5-7, a method of making a cell 10 for
electrochemical analysis is provided, comprising molding a body 22
as a parallel row of cell bodies 12 with a metal rod transverse to
the row of cell bodies 12, forming a plurality of parallel chambers
14 in the body 22 transverse to the metal rod, one chamber 14 for
each the cell body 12, and removing the metal rod from within each
chamber 14. The method may further comprise separating the cell
bodies 12, thereby forming individual cells 10.
[0042] The cell body 12 of FIGS. 1-4 is cylindrical with a pair of
opposing planar sides 24 and 25 aligned with the electrodes 18 and
19 and extending in the longitudinal direction 16, and the body 22
of FIGS. 5-7 is molded as a row of discrete cell bodies 12
interconnected by the metal rod that forms the electrodes 18 and
19. Referring now to FIG. 8 (first drawing sheet), a cell 10 is
presented having cylindrical cell body 12 without the planar sides
24 and 25. The cross-sectional shape of cell body 12 may also be
square, rectangular, polygonal, or any other shape suitable for use
in a cell 10. Referring now to FIG. 9 (third drawing sheet), the
body 22 may comprise a parallel row of cell bodies having a
cylindrical cross-section. In the example presented, the body 22 is
monolithic. It may be implemented in the monolithic form, or planar
sides 24 and 25 (FIGS. 1-7) may be formed by machining the body 22,
or the cell bodies 12 may be otherwise rendered discrete and
interconnected by the metal rod.
[0043] Referring now to FIG. 10, a method of electrochemically
analyzing a sample 26, comprising drawing the sample into a cell 10
for electrochemical analysis and applying a difference in
electrical potential, indicated as V, across the electrodes 18 and
19. An electrochemical reaction commences, particularly where the
electrodes 18 and 19 are closest together, that is indicative of a
chemical property of the sample. The indication may be in the form
of a current, an impedance, or other measurement, as is known in
the art. The method may further comprise suspending at least one
reagent in the sample, preferably by depositing the at least one
reagent being deposited on the cell body 12 within the chamber 14
before drawing the sample 26 into the chamber.
[0044] Placing the electrodes 18 and 19 close together is
advantageous as closer proximity tends to decrease the time it
takes to make a measurement. The novel manufacturing method of the
invention creates a pair of opposing fingers in the side wall of
the cell 12 that are in very close proximity, as best shown in
FIGS. 4 and 6. The center of the chamber and the center of the
metal rod are preferably aligned, and the diameter of the hole
drilled through the metal rod while forming the electrodes 18 and
19 is preferably slightly larger than the diameter of the rod so
that the two electrodes are separated and electrically insulated
from each other, but preferably not larger than needed to reliably
and repeatedly separate the electrodes, taking manufacturing
tolerances and other manufacturing process variations into
account.
[0045] An analysis device 28 (shown in phantom) is typically
provided to measure current, impedance, or other property. The
analysis device may be provided with an electrical connector, and
the electrochemical cell 10 is inserted into the electrical
connector in contact with the electrodes 18 and 19, manually or by
an automatic feeding mechanism. The electrochemical cell 10 may be
used in individual form, as presented in FIGS. 14 and 8, and/or as
an interconnected row as presented in FIGS. 5-7 and 9 with an
appropriate electrical connector that contacts each set of
electrodes 18 and 19. Examples of measuring apparatus that may be
adapted for use with the cells of the present invention are
disclosed in U.S. Pat. Nos. 4,963,814; 4,999,632; 4,999,582; and
5,243,516, and U.S. patent application Ser. No. 08/996,280, filed
Dec. 22, 1997 to Beaty et al.
[0046] Referring now to FIGS. 11 and 12, a rotary clip 30 and a
linear clip 32 are presented, according to a further aspect of the
invention, for product packaging of the electrochemical cell 10.
The cells 10 may be stacked horizontally, vertically, and/or
helically within the clips 30 and 32. The bodies may also be
oriented radially or circumferentially in the rotary clip 30. The
rotary clip 30 may be configured as a carousel. The cells may or
may not be connected in seriatim within the clips 30 and 32. The
clips 30 and 32 are particularly desirable for use with an
automatic analysis device 28.
[0047] Referring now to FIGS. 17 and 18, a cell 300 is presented
according to a further aspect of the invention. FIG. 18 is a
cross-sectional view taken along line 18-18 of FIG. 17. Cell 300
has a body 312, a chamber 314, and electrodes 318 and 319. The
chamber 314 is oblong transverse to the axis of the rod that forms
the electrodes 318 and 319, and the rod is removed from within the
chamber 314, as previously described herein. Referring now to FIGS.
19 and 20, a top plan view and a side elevational view of a rod 320
is presented of the type used to form the electrodes 318 and 319.
The rod 320 comprises a disk 322 with fingers 324 extending
therefrom on opposite sides of the disk 322. The rod 320 may be
formed, by example, by periodically stamping disks 322 in a rod of
constant cross-section.
[0048] Referring now to FIGS. 21 and 22, a cell 400 is presented
according to a further aspect of the invention. Cell 400 has a body
412, a chamber 414, and the electrodes 318 and 319. The chamber 414
is oblong transverse to the axis of the rod that forms the
electrodes 318 and 319, and the rod is removed from within the
chamber 414, as previously described herein. The chamber 414 is
enlarged on one end thereby forming a funnel shape. The various
features of the numerous embodiments presented herein may be used
alone, or in combination with one or more other features, thus
creating innumerable variations all according to aspects of the
invention.
[0049] The reagent 20 provides electrochemical probes for specific
analytes. The choice of specific reagent 20 depends on the specific
analyte or analytes to be measured, and are well known to those of
ordinary skill in the art. An example of a reagent that may be used
in cell 10 of the present invention is a reagent for measuring
glucose from a whole blood sample. A non-limiting example of a
reagent for measurement of glucose in a human blood sample contains
62.2 mg polyethylene oxide (mean molecular weight of 100-900
kilodaltons), 3.3 mg NATROSOL 250M, 41.5 mg AVICEL RC-591 F, 89.4
mg monobasic potassium phosphate, 157.9 mg dibasic potassium
phosphate, 437.3 mg potassium ferricyanide, 46.0 mg sodium
succinate, 148.0 mg trehalose, 2.6 mg TRITON X-100 surfactant, and
2,000 to 9,000 units of enzyme activity per gram of reagent. The
enzyme is prepared as an enzyme solution from 12.5 mg coenzyme PQQ
and 1.21 million units of the apoenzyme of quinoprotein glucose
dehydrogenase. This reagent is further described in WO 99/30152,
the disclosure of which is incorporated herein by reference.
[0050] When hematocrit is to be determined, the reagent includes
oxidized and reduced forms of a reversible electroactive compound
(potassium hexacyanoferrate (III) ("ferricyanide") and potassium
hexacyanoferrate (II) ("ferrocyanide"), respectively), an
electrolyte (potassium phosphate butter), and a microcrystalline
material (Avicel RC-591 F-a blend of 88% microcrystalline cellulose
and 12% sodium carboxymethyl-cellulose, available from FMC Corp.).
Concentrations of the components within the reagent before drying
are as follows: 400 millimolar (mM) ferricyanide, 55 mM
ferrocyanide, 400 mM potassium phosphate, and 2.0% (weight: volume)
Avicel. A further description of the reagent for a hematocrit assay
is found in U.S. Pat. No. 5,385,846, the disclosure of which is
incorporated herein by reference. A hematocrit reagent is
preferably not deposited on the surface of the electrodes 18 and
19. It may be deposited within the chamber 14 at an end opposite to
the electrodes 18 and 19.
[0051] Other non-limiting examples of enzymes and mediators that
may be used in measuring particular analytes in sensor 20 of the
present invention are listed below in Table 1. The electrochemical
cell of the invention may have a plurality of reagents deposited on
the cell body within the chamber.
1TABLE 1 Mediator Additional Analyte Enzymes (Oxidized Form)
Mediator Glucose Glucose Ferricyanide Dehydrogenase and Dia phorase
Glucose Glucose- Ferricyanide Dehydrogenase (Quinoprotein)
Cholesterol Cholesterol Ferricyanide 2,6-Dimethyl-1,4- Esterase and
Benzoquinone Cholesterol 2,5-Dichloro-1,4- Oxidase Benzoquinone or
Phenazine Ethosulfate HDL Cholesterol Ferricyanide
2,6-Dimethyl-1,4- Cholesterol Esterase and Benzoquinone Cholesterol
2,5-Dichloro-1,4- Oxidase Benzoquinone or Phenazine Ethosulfate
Triglycerides Lipoprotein Ferricyanide or Phenazine Lipase,
Glycerol Phenazine Methosulfate Kinase, and Ethosulfate Glycerol-3-
Phosphate Oxidase Lactate Lactate Oxidase Ferricyanide
2,6-Dichloro-1,4- Benzoquinone Lactate Lactate Ferricyanide
Dehydrogenase Phenazine and Diaphorase Ethosulfate, or Phenazine
Methosulfate Lactate Diaphorase Ferricyanide Phenazine Dehydro-
Ethosulfate, genase or Phenazine Methosulfate Pyruvate Pyruvate
Oxidase Ferricyanide Alcohol Alcohol Oxidase Phenylene- diamine
Bilirubin Bilirubin Oxidase 1-Methoxy- Phenazine Methosulfate Uric
Acid Uricase Ferricyanide
[0052] In some of the examples shown in Table 1, at least one
additional enzyme is used as a reaction catalyst. Also, some of the
examples shown in Table 1 may utilize an additional mediator, which
facilitates electron transfer to the oxidized form of the mediator.
The additional mediator may be provided to the reagent in lesser
amount than the oxidized form of the mediator. While the above
assays are described, it is appreciated that a variety of
electrochemical assays may be conducted with sensor 10 in
accordance with this disclosure.
[0053] According to a preferred embodiment, the reagents are
applied in liquid form and dried. As used herein, the term "dry" or
"dried" is intended to mean removing water from the reagent to the
point where it is immobile, chemically stable, and reactive when it
comes in contact with the sample. The cell of the present invention
may also include microspheres, as described in pending patent
application entitled "MICROSPHERE CONTAINING SENSOR", attorney
docket no. 9793/31, inventors Raghbir Singh Bhullar and Brian S.
Hill, filed Deceber 23, 1999, hereby incorporated by reference. The
microspheres decrease sample size and improve flow of the sample
within the cell. A reagent may be deposited on the
microspheres.
[0054] Referring again to FIGS. 5-7, in one embodiment, the body 12
cells 10 are formed by injection molding polycarbonate around a
solid gold rod on the order 500 micrometers in diameter. A suitable
rod is available from ENGELHARD-CLAL LP, of New Jersey, U.S.A. The
chamber 14 is mechanically drilled having a diameter on the order
of 500 micrometers. The central axis of the drilling operation is
aligned with the central axis of the rod, and perpendicular
thereto. The actual diameter of the rod is typically slightly less
than the nominal diameter of 500 micrometers. Conversely, the
actual diameter of the chamber drilled is typically slightly larger
than the nominal diameter of 500 micrometers. The result is that
the rod is divided into to electrodes separated by dielectric gap
40 having a desirable width. The cell 10 according to this
embodiment has a length in the longitudinal direction on the order
of 36 millimeters and an outside diameter on the order of 16
millimeters. The flat faces 24 and 25 are on the order of 14
millimeters apart.
[0055] Products made by the methods disclosed herein are also
represent further aspects of the invention. Although the invention
has been described and illustrated with reference to specific
illustrative embodiments thereof, it is not intended that the
invention be limited to those illustrative embodiments. Those
skilled in the art will recognize that variations and modifications
can be made without departing from the true scope and spirit of the
invention as defined by the claims that follow. It is therefore
intended to include within the invention all such variations and
modifications as fall within the scope of the appended claims and
equivalents thereof.
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