U.S. patent application number 11/888859 was filed with the patent office on 2009-12-03 for strip electrode with conductive nano tube printing.
This patent application is currently assigned to MysticMD Inc.. Invention is credited to Joel S. Douglas.
Application Number | 20090297836 11/888859 |
Document ID | / |
Family ID | 35394770 |
Filed Date | 2009-12-03 |
United States Patent
Application |
20090297836 |
Kind Code |
A1 |
Douglas; Joel S. |
December 3, 2009 |
Strip electrode with conductive nano tube printing
Abstract
A sensor system that detects a current representative of a
compound in a liquid mixture features a multi or three electrode
strip adapted for releasable attachment to signal readout
circuitry. The strip comprises an elongated support which is
preferably flat adapted for releasable attachment to the readout
circuitry; a first conductor and a second and a third conductor
each extend along the support and comprise means for connection to
the circuitry. The circuit is formed with single-walled or multi
walled nanotubes conductive traces and may be formed from multiple
layers or dispersions containing, carbon nanotubes, carbon
nanotubes/antimony tin oxide, carbon nanotubes/platinum, or carbon
nanotubes/silver or carbon nanotubes/silver-chloride. An active
electrode formed from a separate conductive carbon nanotubes layer
or suitable dispersion, positioned to contact the liquid mixture
and the first conductor, comprises a deposit of an enzyme capable
of catalyzing a reaction involving the compound and preferably an
electron mediator, capable of transferring electrons between the
enzyme-catalyzed reaction and the first conductor. A reference
electrode also formed from a conductive carbon nanotube layer or
suitable dispersion is positioned to contact the mixture and the
second conductor. The system includes circuitry adapted to provide
an electrical signal representative of the current which is formed
from printing conductive inks made with nano size particles such as
conductive carbon or carbon/platinum or carbon/silver, or carbon
nanotubes/antimony tin oxide to form a conductive carbon nanotube
layers. The multiple-electrode strip is manufactured, by then
applying the enzyme and preferably the mediator onto the electrode.
Alternatively the electrode can have a carbon nanotubes/antimony
tin oxide, carbon nanotubes/platinum, or carbon nanotubes/silver or
carbon nanotubes/silver-chloride surface and or a conductive carbon
or silver ink surface connecting leg. The carbon nanotube solution
is first coated and patterned into electro shapes and the
conductive carbon nanotubes, carbon or silver ink can be attached
by printing the ink to interface with the carbon nanotube electro
surface. A platinum electrode test strip is also disclosed that is
formed from either nano platinum distributed in the carbon nanotube
layer or by application or incorporation of platinum to the carbon
nanotube conductive ink.
Inventors: |
Douglas; Joel S.; (Groton,
CT) |
Correspondence
Address: |
MICHAUD-DUFFY GROUP LLP
306 INDUSTRIAL PARK ROAD, SUITE 206
MIDDLETOWN
CT
06457
US
|
Assignee: |
MysticMD Inc.
Groton
CT
|
Family ID: |
35394770 |
Appl. No.: |
11/888859 |
Filed: |
August 2, 2007 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11063504 |
Feb 23, 2005 |
7285198 |
|
|
11888859 |
|
|
|
|
60546762 |
Feb 23, 2004 |
|
|
|
Current U.S.
Class: |
428/336 ;
252/500; 252/502; 252/512; 252/513; 252/514; 252/518.1; 252/519.5;
252/520.1; 252/520.2; 252/520.3; 252/521.2; 427/58; 977/750;
977/752 |
Current CPC
Class: |
C12Q 1/002 20130101;
B82Y 30/00 20130101; Y10T 428/265 20150115; C12Q 1/001
20130101 |
Class at
Publication: |
428/336 ;
252/500; 252/502; 252/512; 252/513; 252/514; 252/518.1; 252/519.5;
252/520.1; 252/520.2; 252/520.3; 252/521.2; 427/58; 977/750;
977/752 |
International
Class: |
B32B 5/22 20060101
B32B005/22; H01B 1/12 20060101 H01B001/12; H01B 1/04 20060101
H01B001/04; H01B 1/22 20060101 H01B001/22; H01B 1/02 20060101
H01B001/02; B05D 5/12 20060101 B05D005/12 |
Claims
1. A method for making an electrochemical reaction surface from a
conductive film, comprising: providing a plurality of nanotubes
with an outer diameter of less than 10 nm; and forming a film of
said nanotubes on a surface of a substrate.
2. The method of claim 1, wherein the step of forming the film
comprises a method selected from the group consisting of spray
painting, dip coating, spin coating, knife coating, kiss coating,
gravure coating, screen printing, ink jet printing, and pad
printing.
3. A multi-layered structure for making an electrochemical reaction
surface comprising: an electrically conductive film comprising a
plurality of nanotubes with an outer diameter of less than 10 nm;
and a polymeric layer disposed on at least a portion of said
electrically conductive film.
4. The multi-layered structure of claim 3, wherein said nanotubes
are selected from the group consisting of single-walled nanotubes
(SWNTs), double-walled nanotubes (DWNTs), multi-walled nanotubes
(MWNTs), and mixtures thereof.
5. The multi-layered structure of claim 3, wherein said nanotubes
are substantially single-walled nanotubes (SWNTs).
6. The multi-layered structure of claim 3, wherein said nanotubes
are present in said film at about 0.001 to about 10% based on
weight.
7. The multi-layered structure of claim 3, wherein the film has a
volume resistance in the range of about 100 ohms/cm 2 to about
50,000 ohms/cm 2.
8. The multi-layered structure of claim 3, wherein the film is in
the form of a solid film, a foam, or a fluid.
9. The multi-layered structure of claim 3, further comprising a
polymeric material, wherein the polymeric material comprises a
material selected from the group consisting of thermoplastics,
thermosetting polymers, elastomers, conducting polymers and
combinations thereof.
10. The multi-layered structure of claim 3, further comprising a
polymeric material, wherein the polymeric material comprises a
material selected from the group consisting of ceramic hybrid
polymers, phosphine oxides and chalcogenides.
11. The multi-layered structure of claim 3, further comprising a
polymeric material wherein the nanotubes are dispersed
substantially homogenously throughout the polymeric material.
12. The multi-layered structure of claim 3, further comprising a
polymeric material wherein the nanotubes are present in a gradient
fashion.
13. The multi-layered structure of claim 3, further comprising a
polymeric material wherein the nanotubes are present on a surface
of said polymeric material.
14. The multi-layered structure of claim 3, further comprising a
polymeric material wherein the nanotubes are formed in an internal
layer of said polymeric material.
15. The multi-layered structure of claim 3, further comprising an
opaque substrate, wherein the nanotubes are present on a surface of
said opaque substrate.
16. The multi-layered structure of claim 3, further comprising an
additive selected from the group consisting of a dispersing agent,
a binder, a cross-linking agent, a stabilizer agent, a coloring
agent, a UV absorbent agent, and a charge adjusting agent.
17. The multi-layered structure of claim 3, wherein the film has a
total transmittance of at least about 60%.
18. The multi-layered structure of claim 3, wherein said film has a
thickness between about 0.005 to about 1,000 microns.
19. The multi-layered structure of claim 3, wherein the nanotubes
are oriented.
20. The multi-layered structure of claim 3, wherein the nanotubes
are oriented in the plane of the film.
21. An electrochemical reactive surface formed from a dispersion of
nanotubes comprising a plurality of nanotubes with an outer
diameter of less than 10 nm and having a surface morphology of less
than 33 microns RMS.
22. The dispersion of claim 21, wherein said nanotubes have an
outer diameter of about 0.5 to 10 nm.
23. The dispersion of claim 21, wherein said nanotubes are selected
from the group consisting of single-walled nanotubes (SWNTs),
double-walled nanotubes (DWNTs), multi-walled nanotubes (MWNTs),
and mixtures thereof.
24. The dispersion of claim 21, wherein said nanotubes are
substantially single-walled nanotubes (SWNTs).
25. The dispersion of claim 21, further comprising a polymeric
material, wherein the polymeric material comprises a material
selected from the group consisting of thermoplastics, thermosetting
polymers, elastomers, conducting polymers and combinations
thereof.
26. The dispersion of claim 21, further comprising a polymeric
material, wherein the polymeric material comprises a material
selected from the group consisting of ceramic hybrid polymers, and
phosphine oxides chalcogenides.
27. The dispersion of claim 21, further comprising a plasticizer,
softening agent, filler, reinforcing agent, processing aid,
stabilizer, antioxidant, dispersing agent, binder, a cross-linking
agent, a coloring agent, a UV absorbent agent, or a charge
adjusting agent.
28. The dispersion of claim 21, further comprising conductive
organic materials, inorganic materials, or combinations or mixtures
thereof.
29. The dispersion of claim 21, wherein the conductive organic
materials are selected from the group consisting of buckeyballs,
carbon black, fullerenes, nanotubes with an outer diameter of
greater than about 0.5 nm, and combinations and mixtures
thereof.
30. The dispersion of claim 21, wherein the conductive inorganic
materials are selected from the group consisting of aluminum,
antimony, beryllium, cadmium, chromium, cobalt, copper, doped metal
oxides, iron, gold, lead, manganese, magnesium, mercury, metal
oxides, nickel, platinum, silver, steel, titanium, zinc, and
combinations and mixtures thereof.
31. The dispersion of claim 21, further comprising a conductive
material selected from the group consisting of tin-indium mixed
oxide, antimony-tin mixed oxide, fluorine-doped tin oxide,
aluminum-doped zinc oxide and combinations and mixtures
thereof.
32. The dispersion of claim 21, further comprising conductors,
fluids, gelatins, ionic compounds, semiconductors, solids,
surfactants, or combinations or mixtures thereof.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional application of U.S. patent
application Ser. No. 11/063,504 filed Feb. 23, 2005, which claims
priority to U.S. Provisional Application No. 60/546,762 entitled
Strip electrode with conductive nano tube printing and methods,
filed on Feb. 23, 2004 which is entirely and specifically
incorporated by reference.
FIELD OF THE INVENTION
[0002] The invention relates to a carbon nanotube electrode with a
modified surface, to a method of production of such an electrode,
and to the use of such an electrode in bioelectrochemistry. The
electrode can be connected by a conductive carbon, silver ink or
conductive carbon nanotube trace that is capable of conducting the
electrons from the bioelectrochemistry reaction to a meter that
reads the bioelectrochemistry result.
BACKGROUND OF THE INVENTION
[0003] Various electrochemical sensors are known which employ
enzymes to sense the presence of a compound that serves as an
enzyme substrate. As just one example, Nakamura U.S. Pat. No.
4,224,125 discloses an enzyme electrode system in which an enzyme,
such as glucose oxidase, is used to sense glucose. A redox compound
is used to accept electrons from the enzyme. For example, Nakamura
discloses press molding to the electrode a mixture of glucose
oxidase cross-linked by gluteraldehyde and a fluorocarbon polymer
powder together with a cation exchange resin containing potassium
ferricyanide. Nakamura's electrode system consists of three
electrodes: an enzyme electrode, a reference electrode, and a
counter electrode.
[0004] In another example, U.S. Pat. No. 4,225,410 to Pace
discloses a multi-layer enzyme sensor; for example a sensor that
measures levels of lactate dehydrogenase. NAD.sup.+ is generated at
a fourth electrode, and the enzymatic reaction converts it to NADH
which is sensed at the monitoring electrode by undisclosed means. A
barrier/counter electrode and a reference electrode are used in
conjunction with the monitoring electrode. However, the surface
roughness of the electrodes and the difficulty in forming a well
defined electrode causes the electro chemical reaction differences
between strips. A means is needed to minimize this surface
variation so that the strips manufactured give more repeatable
results between strips and that the calibration effort is
reduced.
[0005] Each of the above references is incorporated herein by
reference in its entirety.
SUMMARY OF THE INVENTION
[0006] This invention relates to enzymatic sensor electrodes and
their combination with reference electrodes to detect a compound in
a liquid mixture. The electrodes are formed from a conductive layer
made of carbon nanotubes and alloyed with other conductive and non
conductive material such as carbon nanotubes, carbon
nanotubes/antimony tin oxide, carbon nanotubes/platinum, or carbon
nanotubes/silver or carbon nanotubes/silver-chloride and
communicate electrically with conductive ink or conductive carbon
nanotubes, carbon nanotubes/antimony tin oxide, carbon
nanotubes/platinum, or carbon nanotubes/silver or carbon
nanotubes/silver-chloride traces on the substrate.
[0007] The invention uses thin electrodes that have a very smooth
surface morphology which permits the formation of surface texture
less than 0.33 microns and nano size particles to produce well
defined and smooth electrodes. The coating is formed from a
conductive carbon nanotube coating which includes as part of the
formulation carbon nanotubes, carbon nanotubes/antimony tin oxide,
carbon nanotubes/platinum, or carbon nanotubes/silver or carbon
nanotubes/silver-chloride. It can also be modified to use a
platinum electrode by either integrating the platinum into the
conductive carbon nanotube formulation or by applying it to the
electrode surface. Either nano size platinum or aqueous platinum
can be used for this purpose. These coatings when applied to a non
conductive surface allow the production of an electrode that has
very repeatable surface areas between different electrodes which
improves consistency of biosensors made by the invention.
[0008] In addition, conductive coatings such as described in U.S.
patent application Ser. No. 2002/0143094, Polymer Nanocomposites
and Methods of Preparation, to Conroy et al.; U.S. patent
application Ser. No. 2002/0035170, Electromagnetic Shielding
Composite Comprising Nanotubes, to Glatkowski et al.; U.S. patent
application Ser. No. 2002/0180077, Carbon Nanotube Fiber-Reinforced
Composite Structures for EM and Lightning Strike Protection, to
Glatkowski et al.; U.S. patent application Ser. No. 2003/0008123,
Nanocomposite Dielectrics, to Glatkowski et al.; U.S. patent
application Ser. No. 2003/0164427, ESD Coatings for Use with
Spacecraft, to Glatkowski et al; and U.S. patent application Ser.
No. 2003/0122111, Coatings Comprising Carbon Nanotubes and Methods
for Forming Same, to Glatkowski et al all included herein by
reference. The coatings made from the referenced patents and
applications can be made from single wall or multi wall carbon
nanotubes preferably sized to be less than 3.5 nm and greater than
0.1 nm in outer dimension size. Additionally conductive dispersions
such as Acheson Electrodag 427 Antimony Tin Oxide (ATO) ink can be
alloyed with either single wall or multi wall carbon nanotubes
preferably sized to be greater than 3.5 nm and less than 10 nm in
outer dimension size. The carbon nano tubes are mixed uniformly
into the Acheson Electrodag 427 such that the percent by weight is
between 0.5 to 10%. Preferably the carbon nano tubes are added such
that they make up 3% by weight of the mixture. Additionally
platinum nano particles can be added and mixed uniformly to the
coating such that the percent by weight is between 0.5 to 10%.
Preferably the nano size platinum particles are added such that
they make up 4% by weight of the mixture. Each of the above
references is incorporated herein by reference in its entirety. The
resulting coating thicknesses are between about 0.5 nm to about
1000 microns
[0009] Any of the aforementioned coatings result in improved
electrode repeatability, total light transmittance of greater than
70% and reduced haze value less than 2.0%, and the film has a
surface resistance in the range of less than about 50,000
ohms/square.
[0010] One aspect of the invention generally features a
multi-electrode strip for releasable attachment to signal readout
circuitry, forming a sensor system that detects a current
representative of a compound in a liquid mixture. The strip
comprises an elongated support (preferably flat) adapted for
releasable attachment to the readout circuitry. A first
conductorand a second conductor each extend along the support and
comprise a means for connection to the circuitry. An active
electrode, positioned to contact the liquid mixture and the first
conductor, comprises a deposit of an enzyme capable of catalyzing a
reaction involving the compound. Electrons are transferred between
the enzyme-catalyzed reaction and the first conductor to create the
current. A reference electrode is positioned to contact the mixture
and the second conductor.
[0011] The preferred embodiment of the strip includes the following
features: a conductive carbon nanotube electrode formed by coating
the substrate with a conductive carbon nanotube solution similar to
that found in U.S. patent application Ser. No. 2003/0122111, to
Glatkowski, or U.S. Pat. No. 6,265,466 to Glatkowski et al. and
U.S. Pat. No. 6,493,208 to Piche et al. Each of the above
referenced patents is incorporated herein by reference in its
entirety.
[0012] In addition conductive coatings such as described in U.S.
patent application Ser. No. 2002/0143094, Polymer Nanocomposites
and Methods of Preparation, to Conroy et al., U.S. patent
application Ser. No. 2002/0035170, Electromagnetic Shielding
Composite Comprising Nanotubes, to Glatkowski et al., U.S. patent
application Ser. No. 2002/0180077, Carbon Nanotube Fiber-Reinforced
Composite Structures for EM and Lightning Strike Protection, to
Glatkowski et al., U.S. patent application Ser. No. 2003/0008123,
Nanocomposite Dielectrics, to Glatkowski et al., U.S. patent
application Ser. No. 2003/0164427, ESD Coatings for Use with
Spacecraft, to Glatkowski et al., and U.S. patent application Ser.
No. 2003/0122111, Coatings Comprising Carbon Nanotubes and Methods
for Forming Same, to Glatkowski et al., all included herein by
reference. The coatings made from the referenced patents and
applications can be made from single wall or multi wall carbon
nanotubes preferably sized to be less than 3.5 nm and greater than
0.1 nm in outer dimension size. Additionally conductive dispersions
such as Acheson Electrodag 427 Antimony Tin Oxide (ATO) ink can be
alloyed with either single wall or multi wall carbon nanotubes
preferably sized to be greater than 3.5 nm and less than 10 nm in
size to achieve a coating that allows for improved surface which
permits the formation of surface texture less than 0.33 microns and
improved repeatability of the edges of the electrode shape. The
carbon nano tubes are mixed uniformly into the Acheson Electrodag
427 such that the percent by weight is between 0.5 to 10%.
Preferably the carbon nano tubes are added such that they make up
3% by weight of the mixture. Additionally platinum nano particles
can be added and mixed uniformly to the coating such that the
percent by weight is between 0.5 to 10%. Preferably the nano size
platinum particles are added such that they make up 4% by weight of
the mixture. Each of the above referenced patents is incorporated
herein by reference in its entirety.
[0013] Additionally the electrodes are formed such that they
provide well defined areas as well as having smooth surface
morphology. The improved surface morphology is attained by the
carbon nanotubes, carbon nanotubes/antimony tin oxide, carbon
nanotubes/platinum, or carbon nanotubes/silver or carbon
nanotubes/silver-chloride dispersion or coating. The small size
permits the formation of surface texture less than 0.33 microns.
These conductive coatings knit together to form a conductive trace
and the overlaying of the polymer binder or dispersion within a
polymer binder provides a porous layer that allows the passage of
the electrons formed from the electrochemical reaction. The well
defined electrode shapes can be accomplished by different methods.
The first being inkjet printing where an inkjet printer applies the
image of the electrode with an ink containing conductive carbon
nanotube material. Then a binder polymer is applied leaving behind
well defined electrodes with a smooth surface morphology. The
polymer binder is not conductive therefore the electrodes laid down
in the first step are the only conductive paths. The ink jetting
can be accomplished by using precision components from the Lee
Company of Westbrook, Conn., such as the VHS-S/P 10+ Nanoliter
Dispensing Valves.
[0014] The polymeric material is selected from the group consisting
of thermoplastics, thermosetting polymers, elastomers, conducting
polymers and combinations thereof, or the polymeric material
comprises a material selected from the group consisting of
polyethylene, polypropylene, polyvinyl chloride, styrenic,
polyurethane, polyimide, polycarbonate, polyethylene terephthalate,
cellulose, gelatin, chitin, polypeptides, polysaccharides,
polynucleotides and mixtures thereof, or ceramic hybrid polymers,
Ethylene Glycol Monobuti Ether Acetate, phosphine oxides and
chalcogenides. Alternatively a polymeric material wherein the
conductive elements are dispersed substantially homogenously or in
a gradient throughout the polymeric material can be used such as
the Acheson Electrodag PF 427.
[0015] The second most preferred means of forming a well defined
film electrode is to apply the conductive carbon nanotube layer
uniformly to the substrate and then screen print the polymer binder
to protect only the electrode regions. The unprotected carbon
nanotube material is removed leaving only the finished
electrodes.
[0016] The third most preferred means is to print the conductive
carbon nanotube layer in the required pattern using a template or
mask. Then the polymer binder is applied to the entire surface. The
polymer binder is not conductive therefore the electrodes laid down
in the first step are the only conductive paths.
[0017] The fourth most preferred means of forming a well-defined
electrode is to apply the conductive carbon nanotube ink either in
a two pass system or one pass system. In the one pass system the
binder and nanotubes and other conductive components of the ink are
in the same dip. In the two pass system the nanotubes are applied
first by either printing, spraying coating, or dip coating and the
polymer binder is applied second after the first pass is dried.
U.S. Pat. No. 6,121,011 issued to Douglas et al., Methods for
applying a reagent to an analytical test device describes various
nozzle based and brush based coating means useful in applying the
conductive carbon nanotube ink. However, one skilled in the art can
reverse this order and achieve excellent results. The coating is
then formed into electrodes by laser cutting or etching the
electrodes.
[0018] The fifth most preferred means is to apply the one pass
system where the binder and nanotubes are in the same dip and then
using standard photoliograph, screen printing or ink jetting
methods to form the electrodes. Photo definable electrode
manufacturing is described in U.S. Pat. No. 6,245,215 issued to
Douglas et al., Membrane based electrochemical test device and
related methods and U.S. Pat. No. 6,582,573 issued to Douglas et
al., Membrane based electrochemical test device, their disclosure
is included by in there entirety by reference.
[0019] Once the electrodes have been suitably formed an electron
mediator (most preferably a ferrocene or Imidozole Osmium mediator
is applied to the active electrode. The osmium mediator allows the
reaction to occur with a very low potential or voltage between the
electrodes. It is included in the active electrode deposit to
affect the electron transfer. The compound being detected is
glucose, and the enzyme is glucose oxidase or glucose
dehydrogenase. The active electrode and the reference electrode are
carbon nanotube based coatings applied to the elongated support,
e.g. the active electrode is formed by printing (e.g., screen
printing, ink jetting, or other printing means) the conductive
carbon nanotube mixture, the enzyme and the mediator, and the
reference electrode is also formed by printing the conductive
carbon nanotube mixture. The means for connecting to the readout
circuit are formed from an ink comprising a conductive compound
positioned toward one end of the elongated support, and the
conductive carbon nanotube electrodes are positioned remote from
that end.
[0020] The requirement for the use of a mediated chemistry can be
eliminated by forming one or more of the electrodes with platinum
nano particles or by adding or applying aqueous platinum to the
electrode. This then forms a traditional platinum electro chemical
sensor system.
[0021] In another aspect, the invention features screen printing
the enzyme onto a substrate to form an enzymatic sensing electrode.
The conductive carbon nanotube mixture is comprised of solutions
formed from either carbon nanotubes, carbon nanotubes/antimony tin
oxide, carbon nanotubes/platinum, or carbon nanotubes/silver or
carbon nanotubes/silver-chloride used for printing the electrode
and includes a second coat of a liquid polymer, or a suspension of
conductive material such as carbon nanotubes, carbon
nanotubes/antimony tin oxide, carbon nanotubes/platinum, or carbon
nanotubes/silver or carbon nanotubes/silver-chloride suspended in a
suitable polymer. The enzyme is applied as a second step and
preferably, it also includes a mediator capable of transferring
electrons between the enzymatic reaction and a conductor on the
substrate when used with a non platinized sensor configuration.
Also preferably, the substrate is a flexible, high-dielectric
polymeric substance, such as polyvinyl chloride, polyester, or
polycarbonate.
[0022] The invention enables a very small, inexpensively
manufactured, disposable electrode strip that provides an accurate
electronic readout of the target compound. In particular, the
active electrode is sized to be covered by a small amount of body
fluid produced from a drop of blood or interstitial fluid (ISF)
generated from a needle-prick, laser cut, or microporation
technique on the body, and the reference electrode is sized and
spaced from the active electrode a distance such that the reference
electrode is covered by the same small amount of body fluid.
Additionally the very repeatable surface formed by the conductive
mixtures or dispersions of carbon nanotubes, carbon
nanotubes/antimony tin oxide, carbon nanotubes/platinum, or carbon
nanotubes/silver or carbon nanotubes/silver-chloride and the well
defined area formed by the deposition methods of the invention form
a consistent surface morphology. The electrode formed by the
invention results in a more consistent surface area thereby
minimizing strip to strip variation in manufacturing due to the
improved surface morphology and the improved electrode
definition.
[0023] The use of the transparent conductive carbon nanotubes,
carbon nanotubes/antimony tin oxide, carbon nanotubes/platinum, or
carbon nanotubes/silver or carbon nanotubes/silver-chloride
coatings also permits the manufacturer from having alternative
brand test strips used in their meters. This allows inferior or
poorly manufactured product to be detected and prevented from being
used in the test device. The transparent nature of the conductor
when used with an appropriately configured LED and detector system
can prevent the utilization of non branded product being used in
the test device.
[0024] The ability to form well formed boundaries and smooth
surface morphology (the coatings of this invention permits the
formation of surface texture less than 0.33 microns) permits the
electrodes formed by the use of this invention to be more
repeatable and therefore more consistent from electrode to
electrode when manufacturing large numbers of electrodes. Electro
chemical detection using enzymatic means is sensitive to the
surface area of the electrode. Therefore variation in surface area
results in different response from electrode to electrode. The
consistent boundary and smooth surface morphology makes the
electrode surface area more consistent between test strips
manufactured from existing processes that use large particle carbon
and conductive inks. The large size of the current carbon particles
require that the screen mesh be large enough to allow the
conductive particles to pass. The larger mesh further increases the
surface area consistency between strips by the rough edges of the
electrode. Both variables of rough surface and electrode rough edge
profile make consistency between test strips difficult and
therefore requires the manufacturer to spend considerable time and
effort to sort and calibrate the electrodes.
[0025] The small size of the nano particles and the high
conductivity of nano size particles allow the electrodes made with
this invention to be more consistent and repeatable. Nano tubes and
dispersions made from nano tubes that are at least less than 20 nm
in diameter form a very consistent electrical conductive path. In
addition the ability to form the electrode shapes in a highly
repeatable and accurate form allows the electrodes to be positioned
closer together than the current materials and processes allow.
This has an added advantage of permitting the sample size used to
be smaller because the sample must cover the electrodes for the
system to work. An electrode set that is positioned closer together
requires less sample size to get an electrochemical result.
Furthermore this high electrical conductivity coupled with small
size and improved surface morphology results in a bio sensor that
is consistently better than current carbon and silver screen
printed electrodes. The resulting film has a surface resistance in
the range of less than about 50,000 ohms/square and total light
transmittance of greater than 70% as well as reduced haze value
less than 2.0%. The resulting coating thicknesses are between about
0.5 nm to about 1000 microns
[0026] Other features and advantages of the invention will be
apparent from the following description of the preferred
embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] FIG. 1 is a front of a strip-supported electrode
configuration.
[0028] FIG. 2 is a front of an alternate strip-supported electrode
configuration.
[0029] FIG. 3 is a schematic of using a transparent conductor
coating as a means of preventing off brand test strip use.
[0030] FIG. 4 shows CNT inks or dispersion coated on Polyester.
[0031] FIG. 5 is a two part CNT ink or dispersion formed by inkjet
printing.
[0032] FIG. 6 shows a screen printed polymer binder method.
[0033] FIG. 7 shows a CNT printed coating method.
[0034] FIG. 8 shows a laser removal method.
[0035] FIG. 9 is the photolithography method.
[0036] FIG. 10 is a one part ink printed by conventional
processes.
DESCRIPTION OF THE INVENTION
Electrode Structure
[0037] In general, the strip electrode of the invention comprises a
conductive electrode coated with a mixture of conductive carbon
nanotubes or dispersion made from carbon nanotubes/antimony tin
oxide, carbon nanotubes/platinum, or carbon nanotubes/silver or
carbon nanotubes/silver-chloride, formed by coating the substrate
with a conductive carbon nanotube solution similar to that found in
conductive coatings such as described in U.S. patent application
Ser. No. 2002/0143094, Polymer Nanocomposites and Methods of
Preparation, to Conroy et al., U.S. patent application Ser. No.
2002/0035170, Electromagnetic Shielding Composite Comprising
Nanotubes, to Glatkowski et al., U.S. patent application Ser. No.
2002/0180077, Carbon Nanotube Fiber-Reinforced Composite Structures
for EM and Lightning Strike Protection, to Glatkowski et al., U.S.
patent application Ser. No. 2003/0008123, Nanocomposite
Dielectrics, to Glatkowski et al., U.S. patent application Ser. No.
2003/0164427, ESD Coatings for Use with Spacecraft, to Glatkowski
et al., and U.S. patent application Ser. No. 2003/0122111, Coatings
Comprising Carbon Nanotubes and Methods for Forming Same, to
Glatkowski or made from coatings as described in U.S. Pat. No.
6,265,466 to Glatkowski et al. and U.S. Pat. No. 6,493,208 to Piche
et al., all included herein by reference or made from dispersions
of carbon nanotubes, carbon nanotubes/antimony tin oxide, carbon
nanotubes/platinum, or carbon nanotubes/silver or carbon
nanotubes/silver-chloride, and a catalytically active enzyme and an
optional mediator compound. The resulting film has a surface
resistance in the range of less than about 50,000 ohms/square,
total light transmittance of greater than 70% as well as reduced
haze value less than 2.0% prior to application of the catalytically
active enzyme and the resulting coating thicknesses are between
about 0.5 nm to about 1000 microns. When such a coated electrode is
contacted with a substrate containing an analyte for which the
enzyme exerts a catalytic effect, the mediator compound transfers a
charge to the electrode and this can be used to give a readout
signal, against a standard electrode, correlated with the
concentration of the said analyte, even in the presence of other
analytes since enzymes are typically highly selective in their
catalytic action. U.S. Pat. No. 5,849,174 generally describes
methods of coating a conductive electrode with enzyme and mediator;
that application is hereby incorporated herein by reference. The
mediator compounds described in U.S. Pat. No. 5,849,174 include
polyviologens, fluoranil and chloranil. However, the preferred
mediator compounds are metallocene compounds, and in particular the
ferrocenes (biscyclopentadienyl iron and its derivatives) or
Imidozole Osmium mediator. Osmium mediator allows the reaction to
occur with a very low potential or voltage between the electrodes.
Each of the above referenced patents is incorporated herein by
reference in its entirety.
[0038] The particular enzyme employed may be selected from a range
of enzymes including the following:
TABLE-US-00001 Enzyme Substrate Pyruvate Oxidase Pyruvate L-Amino
Acid Oxidase L-Amino Acids Aldehyde Oxidase Aldehydes Xanthine
Oxidase Xanthines Glucose Oxidase Glucose Glycollate Oxidase
Glycollate Sarcosine Oxidase Sarcosine Lactate Oxidase Lactate
Glutathione Reductase NAD(P)H Lipoamide Dehydrogenase NADH PQQ
Enzymes Glucose Dehydrogenase Glucose Methanol Dehydrogenase
Methanol and Other Alkanols Methylamine Dehydrogenase Methylamine
Haem-Containing Enzymes Lactate Dehydrogenase Lactate(Yeast
Cytochrome b2) Horse-Radish Peroxidase Hydrogen Peroxide Peroxidase
Hydrogen Peroxide Galactose Oxidase Galactose
[0039] The strip electrode has the following design criteria. The
electrodes on the strip should be as small as possible and the
strip should preferably be disposable. The strip should be elongate
for ready handling as an electrode for ready assembly to equipment
on the one hand and contact with the sample on the other. It must
be sensitively manipulable. It may carry, prior to assembly or in
the assembled structure, the reference electrode as well as the
`sensitive` electrode in spaced non-contiguous relationship.
[0040] The invention is particularly useful for selective
detection, measurement or monitoring of a given dissolved analyte
in a mixture of dissolved analytes.
[0041] The elongate support could be any shape, but conveniently it
comprises a flat strip. A flat strip has been found to help achieve
the smoothest surface morphology (this permits the formation of
surface texture less than 0.33 microns) and the least variation in
edge profile.
[0042] By way of example only, conductive carbon nanotube
electrodes of the invention can be formed on the strip; Imidozole
Osmium mediator can be deposited on the surface of the conductive
carbon nanotube electrode by evaporation of a toluene solution; and
enzyme can be bonded to the surface by the use of
1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluene
sulphonate (referred to below as "carbodiimide").
[0043] The reference electrode can be any convenient reference
electrode. We have found it useful to provide adjacent but not
contiguous to the first electrode, a flat layer of silver and to
convert the surface thereof to silver chloride so as to give an
Ag/AgCl reference electrode. This can be accomplished by alloying
the conductive carbon nanotube material with nano size AG/AGCL
material or by applying a colloidal AG/AGCL mixture into or onto
the conductive carbon nanotube electrode. This method can also be
used to form a platinum electrode which is desirable in some
instances because it eliminates the need for the mediator and it
also increases the electrode's sensitivity to the oxidase
reaction.
[0044] Typically, the electrical connections can be metal contacts
which extend down, and preferably contact the strip electrodes, and
make electrical contact each with its respective electrode.
[0045] The readout means is preferably a digital indicator suitably
connected to a dedicated potentiostat which poises the electrode
potential at e.g. +150 mV vs. Ag/AgCl for a glucose system. The
current flowing is then proportional to glucose concentration.
[0046] In a particular version of this type of sensor that has only
two electrodes but is consistent with three electrode embodiments,
it comprises: [0047] (a) a flat first electrode area of known area
small enough to be completely coverable by the small amount of body
fluid produced from lancing or laser hole, etc. The body fluid
generated is applied to the active electrode which is treated with
the appropriate reagent formulation to produce a consistent electro
chemical result. When the active electrode known area is formed
from the conductive carbon nanotube materials of the invention by
one of the preferred methods then the surface morphology which is
less than 0.33 microns and the repeatable boundary forms an
excellent and repeatable first electrode. [0048] (b) (b) a
reference electrode area on the same surface separate from but
sufficiently close to the sensitive electrode area that the said
body fluid also reaches the reference electrode to establish
electrical communication; and [0049] (c) (c) conductive elements
extending separately along the same surface of, and thus insulated
from the elongate support member, communicating one with each
electrode for connection to a signal readout means attachable to
one end of the member.
[0050] The ability to form well formed boundaries and smooth
surface morphology permits the electrodes formed by the use of this
invention to be more repeatable and therefore more consistent from
electrode to electrode when manufacturing large numbers of
electrodes. The small size of the conductive particles allows the
surface morphology to be less than 0.33 microns. Electro chemical
detection using enzymatic means is sensitive to the surface area of
the electrode. Therefore variation in surface area results in a
different response from electrode to electrode. The boundary and
smooth surface morphology makes the electrode surface area more
consistent between test strips manufactured from existing processes
that use large particle carbon and conductive inks. The large size
of the carbon particles require that the screen mesh be large
enough to allow the conductive particles to pass. The larger mesh
further increases the surface area consistency between strips by
the rough edges of the electrode. Both variables of smooth surface
and electrode rough edge profile make consistency between test
strips difficult and therefore requires the manufacturer to spend
considerable time and effort to sort and calibrate the electrodes.
In addition the ability to form the electrode shapes in a highly
repeatable and accurate form allows the electrodes to be positioned
closer together than the current materials and processes allow. The
repeatable and consistent formation of electrodes is an advantage
because it permits the sample size used to be smaller because the
sample must cover the electrodes for the system to work. An
electrode set that is positioned closer together requires less
sample size to get an electrochemical result. Furthermore the high
electrical conductivity of these coatings coupled with small size
and improved surface morphology results in a bio sensor that is
consistently better than current carbon and silver screen printed
electrodes.
[0051] As an example, the area of the first (i.e. sensitive or
active) electrode is generally substantially square; although it
may be rectangular or otherwise shaped, but in any case usually
will correspond in area to a square of 5 mm edge length, or below
e.g., from about 2 to about 4 mm.
[0052] For convenience, this document will refer hereinafter to
body fluid-glucose-measuring equipment as being typical but not
limitative of equipment with which the present invention is
concerned.
[0053] An example reagent formulation suitable for use in the
present invention is described below. This reagent may be used to
determine the presence or concentration of glucose in an aqueous
fluid sample. Preferably, this reagent formulation is used with an
electrochemical sensor having an opposing electrode 3, working
electrode 2 and reference electrode 5.
TABLE-US-00002 Reagent Formulation Material Amount/Concentration
2-(N-morpholino)ethane- 100 millimolar (mM) (MES buffer) sulfonic
acid Triton X-100 0.08% wt/wt Polyvinyl alcohol (PVA) 1.00% wt/wt
mol. wt. 10K 88% hydrolized Imidazole osmium mediator, .sup. 6.2 mM
reduced, as defined in U.S. Pat. No. 5,437,999 Glucose Oxidase 6000
units/mL
[0054] The above reagent formulation may be prepared using the
following procedures: [0055] (a) 1.952 grams of MES buffer is added
to 85 mL of water. The mixture is stirred until the components
dissolve. The pH of the solution is adjusted to 5.5 with NaOH. The
volume of the solution is then brought to 100 mL of final buffer
solution. [0056] (b) 0.08 grams of Triton X-100 and 1 gram of PVA
is added to a beaker capable of holding all the components (e.g., a
200 mL beaker). The buffer solution is added to bring the total
solution weight to 100 grams. The mixture is heated to boiling and
stirred to dissolve the PVA. [0057] (c) 4.0 mg of the reduced
osmium mediator is added to 1 mL of the solution from step (b)
above. The mixture is stirred to dissolve the mediator. [0058] (d)
The mixture is left to cool to room temperature. [0059] (e) 6000
units of glucose oxidase are added and the mixture is mixed until
the enzyme is dissolved.
[0060] The above reagent formulation may be used to determine the
presence or concentration of glucose in an aqueous fluid sample. As
will be apparent to those skilled in the art, other reagent
formulations may be employed to assay different analytes. Such
reagent formulations are well known in the art. Typically, such
reagent formulations are designed to react specifically with the
desired analyte to form a measurable electrochemical signal.
[0061] Without being limited to theory, it is believed that in the
example reagent formulation described above, glucose is
anaerobically oxidized or reduced with the involvement of the
enzyme and the redox mediator. Such a system is sometimes referred
to as an amperometric biosensor. Amperometry refers to a current
measurement at constant applied voltage on the working electrode.
In such a system, the current flowing is limited by mass transport.
Therefore, the current is proportional to the bulk glucose
concentration. The analyte, enzyme and mediator participate in a
reaction where the mediator is either reduced (receives at least
one electron) or oxidized (donates at least one electron). The
glucose reaction ends when glucose oxidase is oxidized and the
mediator is reduced. The mediator is then oxidized at the surface
of the working electrode by the applied potential difference.
Changes in the system amperage result from changes in the ratio of
oxidized/reduced form of the redox mediator. The amperage change
directly correlates to the detection or measurement of glucose in
the test sample. However, the carbon nanotube conductive coating
works equally as well when used in a test strip based on coulometry
measurements. Coulometry measures virtually all the analyte in a
sample which enables the use of very small samples.
[0062] Various enzymes may be used in the reagent formulations
employed in this invention. The particular enzyme employed will
vary depending on the analyte to be detected or measured. Preferred
enzymes include glucose oxidase, glucose dehydrogenase, cholesterol
esterase and alcohol oxidase. The amount of enzyme employed will
generally range from about 0.5 to about 3.0 million units of enzyme
per liter of reagent formulation.
[0063] The reagent formulation will also typically contain a redox
mediator. The redox mediator will generally be chosen to be
compatible with the enzyme employed and combinations of redox
mediators and enzymes are well known in the art. Suitable redox
mediators include, by way of example, imidazole osmium mediator,
potassium ferricyanide and ferrocene derivatives, such as
1,1.cent.-dimethyl ferrocene, or Imidozole Osmium. The amount of
redox mediator employed in the reagent formulation will typically
range from about 0.15M to about 0.7M. Additional mediators suitable
for use in this invention include methylene blue, p-benzoquinone,
thionine, 2,6-dichloroindophenol, gallocyanine, indophenol,
polyviologen, osmium bis (2,2.cent.-bipyridine) dihydrochloride,
and riboflavin-5.cent.-phosphate ester. Optionally, these mediators
can be chemically bound or entrapped in a matrix, such as a
polymer, using procedures well known in the art.
[0064] Examples of enzyme/mediator combinations suitable for use in
this invention include, but are not limited to, the following:
TABLE-US-00003 Analyte Enzyme Mediator glucose glucose
dehydrogenase ferricyanide glucose glucose oxidase
tetracyanoquinodimethane cholesterol cholesterol esterase
ferricyanide alcohol alcohol oxidase phenylenediamine glucose
glucose oxidase imidazole osmium mediator
[0065] A preferred reagent chemistry uses imidazole osmium mediator
as a mediator or 1,1' dimethyl ferrocene.
[0066] In addition to an enzyme and a redox mediator, the reagent
layer on the electrode preferably further comprises a buffer, a
stabilizer, a dispersant, a thickener or a surfactant. These
materials are typically employed in amounts which optimize the
reaction of the reagents with the analyte. The concentration ranges
for these components referred to below are for the reagent
formulation before it has dried on the electrode surface.
[0067] A buffer is preferably employed in the reagent formulation
to provide a satisfactory pH for enzyme function. The buffer used
must have a higher oxidation potential than the reduced form of the
redox mediator. A preferred buffer for use in this invention is a
phosphate buffer having a concentration ranging from about 0.1M to
about 0.5M. Other suitable buffers include BES, BICINE, CAPS, EPPS,
HEPES, MES, MOPS, PIPES, TAPS, TES and TRICINE buffers
(collectively known as `GOOD` buffers), citrate, TRIS buffer, and
the like. The `GOOD` and TRIS buffers are commercially available
from Sigma-Aldrich, Inc. (St. Louis, Mo., U.S.A.).
[0068] A stabilizer may also be employed in the reagent formulation
to stabilize the enzyme. When the enzyme used is glucose oxidase, a
preferred stabilizer is potassium glutamate at a concentration
ranging from about 0.01 to 4.0% weight. Other suitable stabilizers
include succinate, aspartate, blue dextran and the like.
[0069] Additionally, dispersants may be used in the reagent
formulation to enhance the dispersion of the redox mediator and to
inhibit its recrystallisation. Suitable dispersants include
microcrystalline cellulose, dextran, chitin and the like.
Typically, the dispersant is used in the reagent formulation in an
amount ranging from about 1.0 to about 4.5% weight. Preferred
dispersants include, but are not limited to, AVICEL RC-591 (a
microcrystalline cellulose available from FMC Corp.) and
NATROSOL-250 M (a microcrystalline hydroxyethylcellulose available
from Aqualon).
[0070] A thickener may also be employed in the reagent formulation
to hold the reagent to the electrode surface. Suitable thickeners
include water-soluble polymers, such as polyvinylpyrrolidone.
[0071] Additionally, a surfactant may be added to the reagent
formulation to facilitate rapid and total wetting of the electrode
surface. Preferably, the reagent formulation contains a nonionic
surfactant in an amount ranging from about 0.01 to 0.3% by weight.
A preferred surfactant is TRITON X-100, available from
Sigma-Aldrich, Inc.
[0072] The working electrode can be made by different ways.
[0073] FIG. 1 shows a front view of a strip electrode where the
strip 1 and electrodes 244 and 265 are formed from the same
conductive material of this invention. The material formed from
single-walled or multi walled nanotubes and may be formed from
multiple layers or dispersions containing, carbon nanotubes, carbon
nanotubes/antimony tin oxide, carbon nanotubes/platinum, or carbon
nanotubes/silver or carbon nanotubes/silver-chloride.
[0074] FIG. 2 shows the strip (1) is formed by applying a small
section of uniformly coated CNT and binder material (10). Then
traditional conductive ink leads (15) are sandwiched together with
the uniformly coated CNT and binder material piece to form the
completed electrodes (20). The material formed from single-walled
or multi walled nanotubes and may be formed from multiple layers or
dispersions containing, carbon nanotubes, carbon nanotubes/antimony
tin oxide, carbon nanotubes/platinum, or carbon nanotubes/silver or
carbon nanotubes/silver-chloride. Alternatively the strip could be
made by first screen printing the electrodes leads and then screen
printing the CNT and binder material (10) so that it overlaps the
distal ends of the electrodes (20) leads.
[0075] The process of forming the strip (1) in FIG. 2 is as
follows: [0076] a) A piece of thin plastic film is coated with CNT
and polymer binder forming (5). [0077] b) The coated thin plastic
film (55) is cut into a small well defined strip forming (10).
[0078] c) A plastic film is cut to form a handle (30). [0079] d)
Adhesive (35) is applied to the handle (30) forming handle (40).
[0080] e) The small section of coated thin plastic film (10) is
applied to the handle (40) defining the active electrode (44) of
the strip. [0081] f) A small notch (45) is punched into the coated
thin plastic film (10) applied to the handle (30) further defining
the active electrode (44) of the strip (1) which is new sub part
(50). [0082] g) A plastic film (55) is cut to form a mirror image
of the first handle (30). [0083] h) Conductive carbon ink (60) is
applied to the second handle (55) using conventional screen
printing means and dried to conductive lead for active electrode
(44), working electrode (65) and the reference electrode (66). This
forms new sub part (70). [0084] i) The AG/CL electrode is formed by
spraying the colloidal AG/CL to a specific electrode while
positioning a mask to hide the areas where the AG/CL is not
desired. [0085] j) A glucose oxidase based reagent mixture is
applied to the active electrode (44). [0086] k) The first sub part
(50) and second sub part (70) are positioned and the conductive
traces are brought into contact to form a complete electrode system
(80) of the strip.
[0087] Another embodiment of the invention uses test strips made
from the aforementioned forming means. However, the final step of
the manufacturing process prior to applying the glucose oxidase
reagent mixture, which is formulated without the associated
mediator, is to apply a mixture of platinum to one or more of the
electrodes. The platinum is a concentration of 40% by weight in
aqueous type solution of platinum nanoparticles similar to that
sold by Pred Materials International, Inc., 60 East 42nd Street,
Suite 1456, New York, N.Y. 10165 is used. The platinum solution can
be applied by ink jetting which can be accomplished by using
precision components from the Lee Company of Westbrook, Conn., such
as the VHS-S/P 10+ Nanoliter Dispensing Valves. Additionally, the
platinum can be added to the carbon nanotube ink by introducing the
desired amount of nano size particles (similar in size to the
carbon) into the carbon nanotube ink. The nano size platinum
material can be obtained from Sigma-Aldrich company item 483966,
platinum nanosize activated powder, which can be added to the
dispersion to achieve a percent weight of between 0.5% and 10%. The
glucose oxidase reagent mixture, which is formulated without the
associated mediator, is then applied to the working electrode
(44).
[0088] The next preferred method of the invention to form a strip
is mechanical formation of the electrodes in FIG. 1. The electrodes
are formed mechanically after coating the conductive ink (199) on a
flexible film (200). The ink can be formed from single-walled or
multi walled nanotubes and may be formed from multiple layers or
dispersions containing, carbon nanotubes, carbon nanotubes/antimony
tin oxide, carbon nanotubes/platinum, or carbon nanotubes/silver or
carbon nanotubes/silver-chloride. This forms conductive material
(201) when cured properly. The strip (1) electrodes are formed from
CNT material (201) by mechanically removing the CNT material (201)
to form the active electrode (244), working electrode (265) and the
reference electrode (266). The CNT material (201) can be removed by
various means as shown in FIG. 5 through FIG. 10. After forming the
electrodes the AG/CL electrode is formed by spraying the colloidal
AG/CL to a specific electrode while positioning a mask to hide the
areas where the AG/CL is not desired.
[0089] FIG. 4 shows conductive material of the invention coated
(1005 and 1010) on Polyester (2).
[0090] FIG. 5 is two part CNT ink with inkjet printing means of
forming the electrodes in FIG. 1. The ink jet prints the image
(1001) of the electrode to be formed with the Carbon Nanotube
material (CNT) (1005) bearing ink. The non conductive polymer
binder is applied over the entire area coating both the inkjet
printing and non printed areas. The polymer binder (1010) can then
be removed leaving behind CNT formed electrodes. The polymer binder
(1010) can be removed by either chemical or mechanical means such
as a Universal Laser Systems of Phoenix Ariz., VersaLaser product
to form (1011). Alternatively the polymer binder (1010) can also be
left on the entire surface because the conductive CNT material
(1005) is the electrode and the polymer binder is non conductive.
The polymer binder (1010) is porous and is selected to provide wear
resistance and is not in itself conductive. A polyurethane base
binder is used to cover the carbon nanotubes. The area coated with
the CNT ink (1005) is conductive and forms the electrodes.
[0091] FIG. 6 shows a screen printed polymer binder method of
application means for forming the electrodes in FIG. 1. In this
embodiment the ink (1005) is applied uniformly over the entire
surface of the strip. The polymer binder (1010) is then screen
printed onto the strip (1) defining the electrodes. The ink (1005)
is then removed from the unprotected areas mechanically or by use
of a laser such as a Universal Laser Systems of Phoenix Ariz.,
VersaLaser product to form (1011).
[0092] FIG. 7 shows a printed coating method for forming the
electrodes in FIG. 1. For a one part ink the CNT ink (1005) is
printed on the flexible substrate to define the electrodes. The
polymer binder (1010) is then applied to the whole surface of the
strip, and the CNT coated areas define the electrodes (1009). The
printing can be accomplished by screen printing, ink jet printing,
gravure, flexo, pad printing or other printing means.
[0093] FIG. 8 shows a laser removal method for forming the
electrodes in FIG. 1. The CNT ink (1005) is applied either as a two
part coating or a one part coating with the polymer binder (1010).
A laser such as the Universal laser Systems Versalaser is used to
remove the CNT (1005) and polymer binder (1010) to form the
conductive areas of the strip (1012).
[0094] FIG. 9 is the photolithography method using a CNT ink (1005)
for forming the electrodes in FIG. 14. The CNT ink (1005) and
polymer binder (1010) coating is applied then a photolithography
definable mask (2000) is applied. The strip (1) is exposed,
developed and the undeveloped areas are removed using an etching
process. The photolithography definable mask is then removed to
expose the formed electrodes (244), (265, (266).
[0095] FIG. 10 is a one part ink (1005) printed electrodes formed
by conventional processes such as screen printing, ink jet
printing, gravure, flexo, pad printing or other printing means. The
one part ink (1005) can be formed from single-walled or multi
walled nanotubes and may be formed from multiple layers or
dispersions containing, carbon nanotubes, carbon nanotubes/antimony
tin oxide, carbon nanotubes/platinum, or carbon nanotubes/silver or
carbon nanotubes/silver-chloride. The formed electrodes (244),
(265, (266) are printed images resulting from the printing
process.
[0096] The FIG. 3 is a schematic of using a transparent conductor
coating as a means of preventing off brand test strip use. The use
of the transparent conductive carbon nanotube coatings (1200) also
permits the manufacturer from having alternative brand test strips
used in their meters. The use of the transparent conductor prevents
inferior or poorly manufactured product to be detected and
prevented from being used in the test device designed for use with
a strip of the invention. The transparent nature of the conductor
when used with an appropriately configured LED (1205) and photo
detector system (1210) can prevent the utilization of non branded
product being used in the test device. The test strip (1215) is
inserted in test meter (1220) not shown. The LED (1205 and photo
detector (1210) are positioned within test meter (1220) such that
when the test strip (1200) is in meter (1220) the test strip (1200)
is positioned between LED (1205) and photo detector (1210) so that
at least one of the electrode leads (1250) is in a direct path of
LED light (1240). The electronics (1230) not shown in test meter
(1220) only enables the sensing circuits (1240) not shown in test
meter (1220) to test the strip (1) if the LED (1205) light (1240)
and photo detector (1210) can receive light (1240). This requires
that the electrode leads (1250) are transparent and able to
transmit the LED light (1240).
[0097] Use of the Electrochemical Test Device
[0098] To illustrate the use of an electrochemical test device of
this invention, the following glucose assay is described. It will
be understood, however, that by selecting the proper reagent, other
analytes may be determined using these procedures.
[0099] Reagents
[0100] Various types of analytical or electrochemical sensor
reagents may be applied to the electrodes. To create a functional
electrochemical test device, a reagent chemistry must be selected
based on the analyte to be tested and the desired detection limits.
Preferably, the reagent is deposited on the specific electrodes
such that a uniform amount is applied from sensor to sensor and the
reagent is applied uniformly over the appropriate electrodes. The
reagent may be applied using any conventional procedure, such as
screen printing, inkjet printing, or discrete application using
IVEK pumps or any other drop on demand system capable of delivering
consistent and uniform volume of reagent.
[0101] The specific electrodes coated will depend on the specific
reagent(s) employed. Typically, the reagent is applied to the
working electrode, but may in some cases also be applied to the
other electrodes. After the reagent has been placed on the
appropriate electrodes, it is typically dried. Subsequently, when
the test device is used, the test sample of aqueous fluid, such as
blood, rehydrates the reagent and a potential [is applied to the
electrodes from which a current measurement may be taken by a
meter.
[0102] An example reagent formulation suitable for use in the
present invention is described below. This reagent may be used to
determine the presence or concentration of glucose in an aqueous
fluid sample. Preferably, this reagent formulation is used with an
electrochemical sensor having a counter electrode, working
electrode and reference electrode.
TABLE-US-00004 Reagent Formulation Material Amount/Concentration
2-(N-morpholino)ethane- (MES 100 millimolar (mM) buffer) sulfonic
acid Triton X-100 0.08% wt/wt Polyvinyl alcohol (PVA) 1.00% wt/wt
mol. wt. 10K 88% hydrolized Imidazole osmium mediator, .sup. 6.2 mM
reduced, as defined in U.S. Pat. No. 5,437,999 Glucose Oxidase 6000
units/mL
[0103] The above patent disclosure is incorporated herein by
reference in its entirety.
[0104] The above reagent formulation may be prepared using the
following procedures: [0105] (a) 1.952 grams of MES buffer is added
to 85 mL of nanograde water. The mixture is stirred until the
components dissolve. The pH of the solution is adjusted to 5.5 with
NaOH. The volume of the solution is then brought to 100 mL of final
buffer solution. [0106] (b) 0.08 grams of Triton X-100 and 1 gram
of PVA is added to a beaker capable of holding all the components
(e.g., a 200 mL beaker). The buffer solution is added to bring the
total solution weight to 100 grams. The mixture is heated to
boiling and stirred to dissolve the PVA. [0107] (c) 4.0 mg of the
reduced osmium mediator is added to 1 mL of the solution from step
(b) above. The mixture is stirred to dissolve the mediator. [0108]
(d) The mixture is left to cool to room temperature. [0109] (e)
6000 units of glucose oxidase are added and the mixture is mixed
until the enzyme is dissolved.
[0110] The above reagent formulation may be used to determine the
presence or concentration of glucose in an aqueous fluid sample. As
will be apparent to those skilled in the art, other reagent
formulations may be employed to assay different analytes. Such
reagent formulations are well known in the art. Typically, such
reagent formulations are designed to react specifically with the
desired analyte to form a measurable electrochemical signal.
[0111] Without being limited to theory, it is believed that in the
example reagent formulation described above, glucose is
anaerobically oxidized or reduced with the involvement of the
enzyme and the redox mediator. Such a system is sometimes referred
to as an amperometric biosensor. Amperometry refers to a current
measurement at constant applied voltage on the working electrode.
In such a system, the current flowing is limited by mass transport.
Therefore, the current is proportional to the bulk glucose
concentration. The analyte, enzyme and mediator participate in a
reaction where the mediator is either reduced (receives at least
one electron) or oxidized (donates at least one electron). The
glucose reaction ends when glucose oxidase is oxidized and the
mediator is reduced. The mediator is then oxidized at the surface
of the working electrode by the applied potential difference.
Changes in the system amperage result from changes in the ratio of
oxidized/reduced forms of the redox mediator. The amperage change
directly correlates to the detection or measurement of glucose in
the test sample.
[0112] Various enzymes may be used in the reagent formulations
employed in this invention. The particular enzyme employed will
vary depending on the analyte to be detected or measured. Preferred
enzymes include glucose oxidase, glucose dehydrogenase, cholesterol
esterase and alcohol oxidase. The amount of enzyme employed will
generally range from about 0.5 to about 3.0 million units of enzyme
per liter of reagent formulation.
[0113] The electrodes of the electrochemical test device are
prepared as described above and the electrode is coated with 1.0
.mu.L (micro liter) of the above-described reagent formulation and
dried.
[0114] The electrochemical test device is then inserted in a meter
before the test sequence is initiated. Any suitable meter device
which has contacts that interface with the test device contacts may
be employed. Such metering devices are well known in the art. The
meter will generally contain a measuring circuit and be adapted to
apply an algorithm to the current measurement whereby the analyte
level is provided and visually displayed. Examples of suitable
power sources and meters may be found, for example, in U.S. Pat.
Nos. 4,963,814; 4,999,632; and 4,999,582 to Parks et al., U.S. Pat.
No. 5,243,516 to White et al., and European Patent Application No.
89116797.5, to Hill et al. The disclosures of these patents are
incorporated by herein by reference in their entirety.
[0115] A small sample of body fluid or other aqueous fluid is then
applied to the test device. The current is measured about 10 to
about 30 seconds after applying the sample. The current is read by
the meter between the working and counter electrode and,
optionally, is compared to the reference electrode, if it is
present. The meter then applies the algorithm to the current
measurement and converts the measurement to an analyte
concentration. This analyte level is visually displayed on the
meter.
[0116] From the foregoing description, various modifications and
changes in the electrochemical test devices, processes and methods
of this invention will occur to those skilled in the art. All such
modifications coming within the scope of the appended claims are
intended to be included therein.
[0117] Alternatively in an alternate embodiment a clear or
transparent electrode coating can be used to prevent off brand
utilization of test strips by using an LED and detector to transmit
and receive light through the conductor which cannot be done with
existing conductive materials because they are not transparent.
This is done by first selecting a clear handle material such as
polyester and then using a suitable LED and detector circuit as
part of the test meter and positioning it such that the LED
transmits through the clear handle material and the electrode from
the transparent carbon nanotube conductive material. If the
corresponding LED does not detect the LED then the electrodes can
not be made of the transparent carbon nanotube conductive material
and the test is aborted by programming contained in the meter.
[0118] Additionally the strip (1) electrode can be coated both as
one part or two part inks such that the electrodes are formed with
well defined edges and smooth surface morphology to produce a
consistent surface area with minimal surface area variation from
strip to strip.
[0119] Additionally as shown in FIG. 4 CNT ink can be coated on
Polyester handle which forms a transparent handle that is capable
of permitting light to transmit through the test strip. When used
with the appropriate light detection means FIG. 4 incorporated on
the meter, the strip can prevent the use of unlicensed product in
the meter
[0120] Additionally as shown in FIG. 5 is two part CNT ink with
inkjet printing means of forming the electrodes in FIG. 1. The ink
jet prints the image (1001) of the electrode to be formed with the
Carbon Nanotube material (CNT) (1005) bearing ink. The non
conductive polymer binder is applied over the entire area coating
both the inkjet printing and non printed areas. The polymer binder
(1010) can then be removed leaving behind CNT formed electrodes.
The polymer binder (1010) can be removed by either chemical or
mechanical means such as a Universal Laser Systems of Phoenix
Ariz., VersaLaser product to form (1011). Alternatively the polymer
binder (1010) can also be left on the entire surface because the
conductive CNT material (1005) is the electrode and the polymer
binder is not conductive. The polymer binder (1010) is porous and
is selected to provide wear resistance and is not in itself
conductive. A polyurethane base binder is used to cover the carbon
nanotubes. The area coated with the CNT ink (1005) is conductive
and forms the electrodes.
[0121] Additionally FIG. 6 shows a screen printed polymer binder
method of application means for forming the electrodes in FIG. 1.
In this embodiment the ink (1005) is applied uniformly over the
entire surface of the strip. The polymer binder (1010) is then
screen printed onto the strip (1) defining the electrodes. The ink
(1005) is then removed from the unprotected areas mechanically or
by use of a laser such as a Universal Laser Systems of Phoenix
Ariz., VersaLaser product to form (1011).
[0122] Additionally FIG. 7 shows a printed coating method for
forming the electrodes in FIG. 1. The CNT ink (1005) is printed on
the flexible substrate to define the electrodes. The polymer binder
(1010) is then applied to the whole surface of the strip, and the
CNT coated areas define the electrodes (1009). The printing can be
accomplished by screen printing, ink jet printing, gravure, flexo,
pad printing or other printing means.
[0123] Additionally FIG. 8 shows a laser removal method for forming
the electrodes in FIG. 1. The CNT ink (1005) is applied either as a
two part coating or a one part coating with the polymer binder
(1010). The polymer binder (1010 used can also be conductive such
as Acheson Electrodag 427 Antimony Tin Oxide (ATO) ink. A laser
such as the Universal laser Systems Versalaser is used to remove
the CNT (1005) and polymer binder (1010) to form the conductive
areas of the strip (1012).
[0124] Additionally FIG. 9 shows the photolithography method using
a one part CNT ink (1005) for forming the electrodes in FIG. 14.
The CNT ink (1005) and polymer binder (1010) coating is applied,
then a photolithography definable mask (2000) is applied. The strip
(1) is exposed, developed and the undeveloped areas are removed
using an etching process. The photolithography definable mask is
then removed to expose the formed electrodes (244), (265, (266).
The photolithography technique can be extended to a two part ink
system if it is desired. To do so may require two photolithography
steps for the conductive CNT ink and one for the polymer binder
however one step has been found to be acceptable. The polymer
binder (1010 used can also be conductive such as Acheson Electrodag
427 Antimony Tin Oxide (ATO) ink.
[0125] Conventional photolithography techniques or other electronic
circuit fabrication technologies are used to form the electrodes.
In the first step of a typical process, a photoresist material is
applied to the conductive layer and dried. Any suitable photoresist
material may be employed, including both negative and positive
photoresist materials. A preferred material is the negative
semi-aqueous resist available from Dupont under the tradename
"Resiston".
[0126] A developer mask is then positioned over the photoresist
layer. The mask can be either a contact or non-contact type. The
patterning and masking methods that can be employed to form the
electrode shapes, conductive lines, contact pads, etc., according
to this invention can include mechanical masks, contact masks and
the like, as well as other methods useful herein. For example,
Chapter 14 of the above mentioned Harper, Handbook of Materials and
Processes for Electronics, can be referred to for such methods. The
developer mask, which has cutout portions in the shape of the
electrodes, only covers a portion of the photoresist layer leaving
a portion of photoresist layer exposed. The uncovered or exposed
photoresist layer is then irradiated with ultraviolet (UV) light.
Upon exposure to ultraviolet light, the photoresist material
becomes insoluble in the developer solvent. The UV-exposed,
insoluble photoresist material is termed "patterned photoresist".
The developer mask is then removed and the photoresist layer is
contacted with developer to remove the photoresist material
previously covered by the developer mask. The developer used in
this step will vary depending on the particular photoresist
material employed. Typically, the proper developer for use with a
particular photoresist will be specified by the manufacturer of the
resist material. When "Resiston" is used as the photoresist, the
developer/solvent recommended by Dupont should be employed and
careful attention paid to recommended procedures. If an alternate
photoresist is selected, such as Shipley "AZ-11", then an alternate
developer would be used to remove the unexposed photoresist.
[0127] A chemical etchant is then used to remove the conductive
layer no longer protected by the photoresist material. The chemical
etchant does not remove the conductive material still protected by
the remaining exposed, insoluble photoresist layer. Suitable
chemical etchants include hydrofluoric acid or ammonium
fluoride/hydrofluoric acid mixtures. A solvent is then applied to
the patterned photoresist areas defining the electrodes to remove
the patterned photoresist layer. Suitable solvents for removing the
photoresist layer include, by way of example, sulfuric
acid/dichromate or ammonia/hydrogen peroxide. Treatment with the
solvent exposes the surface of the electrodes. Each electrode
comprises three areas: a contact pad, a lead and an electrode area.
Preferably, after exposure of the electrodes, the leads of each
electrode are insulated by applying an epoxy resin material to the
leads.
[0128] Optionally, the third electrode, if present, is then
converted into a reference electrode by applying a suitable
reference material. Suitable reference materials include
silver/silver chloride, a mercury/mercury chloride and
platinum/hydrogen materials. Such materials can be applied to the
third electrode area of the reference electrode by any deposition
method.
[0129] The electrochemical test device is then completed by
applying an appropriate reagent to the working electrode. Suitable
reagents for determining the presence or concentration of various
analytes are well known in the art and are described in further
detail herein below.
[0130] Additionally FIG. 10 shows a one part ink printed by
conventional processes such as screen printing, ink jet printing,
gravure, flexo, pad printing or other printing means. The one part
ink (1005) can be formed from single-walled or multi walled
nanotubes and may be formed from multiple layers or dispersions
containing, carbon nanotubes, carbon nanotubes/antimony tin oxide,
carbon nanotubes/platinum, or carbon nanotubes/silver or carbon
nanotubes/silver-chloride. The formed electrodes (244), (265),
(266) are the result of the printing method.
[0131] Additionally as shown in FIG. 3 is a schematic of using a
transparent conductor coating as a means of preventing off brand
test strip use. The use of the transparent conductive carbon
nanotube coatings (1200) also permits the manufacturer from having
alternative brand test strips used in their meters. This prevents
inferior or poorly manufactured product to be detected and
prevented from being used in the test device designed for use with
a strip of the invention. The transparent nature of the conductor
when used with an appropriately configured LED (1205) and photo
detector system (1210) can prevent the utilization of non-branded
product being used in the test device. The test strip (1215) is
inserted in test meter (1220) not shown. The LED (1205) and photo
detector (1210) are positioned within test meter (1220) such that
when the test strip (1200) is in meter (1220) the test strip (1200)
is positioned between LED (1205) and photo detector (1210) so that
at least one of the electrode leads (1250) is in a direct path of
LED light (1240). The electronics (1230) not shown in test meter
(1220) only enables the sensing circuits (1240) not shown in test
meter (1220) to test the strip (1) if the LED (1205) light (1240)
and photo detector (1210) can receive light (1240). This requires
that the electrode leads (1250) are transparent and able to
transmit the led light (1240).
[0132] Additionally as shown in FIG. 2 the combination layer method
can be used to form the electrodes in FIG. 1. The strip (1) is
formed by applying a small section of uniformly coated CNT and
binder material (10). Then traditional conductive ink leads (15)
are sandwiched together with the uniformly coated CNT and binder
material piece to form the completed electrodes (20). The process
of forming the strip (1) is as follows: [0133] a) A piece of thin
plastic film is coated with CNT and polymer binder forming (5).
[0134] b) The coated thin plastic film (55) is cut into a small
well defined strip forming (10). [0135] c) A plastic film is cut to
form a handle (30). [0136] d) Adhesive (35) is applied to the
handle (30) forming handle (40). [0137] e) The small section of
coated thin plastic film (10) is applied to the handle (40)
defining the active electrode (44) of the strip. [0138] f) A small
notch (45) is punched into the coated thin plastic film (10)
applied to the handle (30) further defining the active electrode
(44) of the strip (1) which is new sub part (50). [0139] g) A
plastic film (55) is cut to form a mirror image of the first handle
(30). [0140] h) Conductive carbon ink (60) is applied to the second
handle (55) using conventional screen printing means and dried to
conductive lead for active electrode (44), working electrode (65)
and the reference electrode (66). This forms new sub part (70).
[0141] i) The AG/CL electrode is formed by spraying the colloidal
AG/CL to a specific electrode while positioning a mask to hide the
areas where the AG/CL is not desired. [0142] j) The first sub part
(50) and second sub part (70) are positioned and the conductive
traces are brought into contact form a complete electrode system
(80) of the strip. [0143] k) A glucose oxidase reagent mixture is
applied to the active electrode (44).
[0144] Another embodiment of the invention uses test strips made
from the aforementioned forming means. However, the final step of
the manufacturing process prior to applying the glucose oxidase
reagent mixture, which is formulated without the associated
mediator, is to apply a mixture of platinum to one or more of the
electrodes. The mixture of the platinum used is a concentration of
40% by weight in aqueous type solution of platinum nanoparticles
similar to that sold by Pred Materials International, Inc., 60 East
42nd Street, Suite 1456, New York, N.Y. 10165. Additionally, the
platinum can be added to the carbon nanotube ink by introducing the
desired amount of nano size particles (similar in size to the
carbon) into the carbon nanotube ink. The nano size platinum
material can be obtained from Sigma-Aldrich company item 483966,
Platinum Nanosize activated powder. The glucose oxidase reagent
mixture which is formulated without the associated mediator is then
applied to the working electrode (44).
[0145] The next preferred method of the invention to form a strip
is mechanical formation of the electrodes in FIG. 1. The electrodes
are formed mechanically after coating the CNT ink (199) on a
flexible film (200). The ink can be formed from single-walled or
multi walled nanotubes and may be formed from multiple layers or
dispersions containing, carbon nanotubes, carbon nanotubes/antimony
tin oxide, carbon nanotubes/platinum, or carbon nanotubes/silver or
carbon nanotubes/silver-chloride. This forms CNT material (201)
when cured properly. The strip (1) electrodes (244), (265), (266)
are formed from CNT material (201) by mechanically removing the CNT
material (201) to form the active electrode (244), working
electrode (265) and the reference electrode (266). The CNT material
(201) can be removed by various means as shown in FIG. 5 through
FIG. 10. After forming the electrodes the AG/CL electrode is formed
by spraying the colloidal AG/CL to a specific electrode while
positioning a mask to hide the areas where the AG/CL is not
desired.
[0146] Another embodiment uses a transparent conductor coating as a
means of preventing off brand test strip use. The use of the
transparent conductive carbon nanotube coatings (1200) also permits
the manufacturer from having alternative brand test strips used in
their meters. This prevents inferior or poorly manufactured product
to be detected and prevented from being used in the test device
design for use with a test strip of the invention. The transparent
nature of the conductor when used with an appropriately configured
LED (1205) and photo detector system (1210) can prevent the
utilization of non branded product being used in the test device.
The test strip (1215) is inserted in test meter (1220) not shown.
The LED (1205) and photo detector (1210) are positioned within test
meter (1220) such that when the test strip (1200) is in meter
(1220) the test strip (1200) is positioned between LED (1205) and
photo detector (1210) so that at least one of the electrode leads
(1250) is in a direct path of LED light (1240) The electronics
(1230) not shown in test meter (1220) only enables the sensing
circuits (1240) not shown in test meter (1220) to test the strip
(1) if the LED (1205) light (1240) and photo detector (1210) can
receive light (1240). This requires that the electrode leads (1250)
are transparent and able to transmit the LED light (1240).
[0147] Another embodiment of the invention uses test strips made
from the aforementioned forming means. However, the final step of
the manufacturing process prior to applying the glucose oxidase is
to apply a mixture of platinum and water to one or more of the
electrodes. The platinum can be applied by ink jetting which can be
accomplished by using precision components from the Lee Company of
Westbrook, Conn., such as the VHS-S/P 10+ Nanoliter Dispensing
Valves A concentration of 40% by weight in aqueous type solution of
platinum nanoparticles similar to that sold by Pred Materials
International, Inc., 60 East 42nd Street, Suite 1456, New York,
N.Y. 10165 is used.
[0148] Alternatively, the platinum can be added to the dispersion.
A typical platinum can be acquired from Sigma-Aldrich company item
483966, Platinum Nanosize activated powder. To achieve the
necessary platinum loading of the dispersion the platinum is added
to the dispersion from approximately 0.5 to 10% of the weight of
the dispersion and mixed thoroughly.
[0149] Other methods of applying or incorporating the platinum into
the strip are envisioned such as incorporating it into the polymer
binder as well as into the Carbon nanotube ink.
[0150] Although only a few exemplary embodiments of the present
invention have been described in detail in this disclosure, those
skilled in the art who review this disclosure will readily
appreciate that many modifications are possible in the exemplary
embodiments (such as variations in sizes, structures, shapes and
proportions of the various elements, values of parameters, or use
of materials) without materially departing from the novel teachings
and advantages of the invention. Accordingly, all such
modifications are intended to be included within the scope of the
invention as defined in the appended claims.
[0151] Other substitutions, modifications, changes and omissions
may be made in the design, operating conditions and arrangement of
the preferred embodiments without departing from the spirit of the
invention as expressed in the appended claims.
[0152] Additional advantages, features and modifications will
readily occur to those skilled in the art. Therefore, the invention
in its broader aspects is not limited to the specific details, and
representative devices, shown and described herein. Accordingly,
various modifications may be made without departing from the spirit
or scope of the general inventive concept as defined by the
appended claims and their equivalents.
[0153] All references cited herein, including all U.S. and foreign
patents and patent applications, all priority documents, all
publications, and all citations to government and other information
sources, are specifically and entirely hereby incorporated herein
by reference. It is intended that the specification and examples be
considered exemplary only, with the true scope and spirit of the
invention indicated by the following claims. As used herein and in
the following claims, articles such as "the", "a" and "an" can
connote the singular or plural.
* * * * *