U.S. patent application number 09/834000 was filed with the patent office on 2001-10-25 for material for establishing solid state contact for ion selective electrodes.
This patent application is currently assigned to Bayer Corporation. Invention is credited to Chan, Andy D.C..
Application Number | 20010032784 09/834000 |
Document ID | / |
Family ID | 22399026 |
Filed Date | 2001-10-25 |
United States Patent
Application |
20010032784 |
Kind Code |
A1 |
Chan, Andy D.C. |
October 25, 2001 |
Material for establishing solid state contact for ion selective
electrodes
Abstract
A polymeric material which to form a stable, reproducible
interface between the ionic and electronic domains of an ion
selective sensor, or an ion selective field effect transistor, or
the like is provided. When employed in an ion selective sensor, the
polymeric material is advantageously provided over a solid internal
reference electrode and an ion selective material is provided
thereover. According to one embodiment, the polymeric material of
the invention includes less than about
1.63.times.10.sup.<immobilized charged sites per gram (less than
about 2.72 millaequivalents/gram). According to another embodiment,
the polymeric material includes immobilized sites of charge
opposite that of mobile ions involved in the redox couple. A
preferred polymeric material comprises a copolymer of
methacrylamidopropyltrimethylammoniumchloride and
methylmethacrylate.
Inventors: |
Chan, Andy D.C.; (Franklin,
CA) |
Correspondence
Address: |
BAYER CORPORATION
Legal Department
63 North Street
Medfield
MA
02052
US
|
Assignee: |
Bayer Corporation
|
Family ID: |
22399026 |
Appl. No.: |
09/834000 |
Filed: |
April 12, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09834000 |
Apr 12, 2001 |
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09031491 |
Feb 26, 1998 |
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6251246 |
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09031491 |
Feb 26, 1998 |
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08121822 |
Sep 15, 1993 |
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5804049 |
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Current U.S.
Class: |
204/418 |
Current CPC
Class: |
G01N 27/3335 20130101;
G01N 27/414 20130101 |
Class at
Publication: |
204/418 |
International
Class: |
G01N 027/414 |
Claims
What is claimed is:
1. An ion selective sensor comprising: an electrically conductive
material providing a reference redox couple; a polymeric material
having immobilized charged sites provided on said electrically
conductive material, said polymeric material having immobilized
charged sites; and an ion selective material covering said
polymeric material.
2. The ion selective sensor as recited in claim 1, wherein said
polymeric material includes less than 1.63.times.10.sup.21
immobilized charge sites per gram.
3. The ion selective sensor as recited in claim 1, wherein said
polymeric material includes from about 5.5.times.10.sup.19 to about
1.4.times.10.sup.21 immobilized charged sites per gram.
4. The ion selective sensor as recited in claim 3, wherein said
polymeric material includes from about 4.1.times.10.sup.20 to about
1.1.times.10.sup.21 immobilized charged sites per gram.
5. The ion selective sensor as recited in claim 4, wherein said
polymeric material includes from about 5.5.times.10.sup.20 to about
8.2.times.10.sup.20 immobilized charged sites per gram.
6. The ion selective sensor as recited in claim 1, wherein said
polymeric material includes immobilized charged sites selected from
the group consisting of those having a positive charge, those
having a negative charge and those having both positive and
negative charge.
7. The ion selective sensor as recited in claim 1, wherein said
polymeric material includes immobilized positively-charged sites
and immobilized negatively-charged sites.
8. The ion selective sensor as recited in claim 1, and further
comprising a non-electrically conducting substrate, wherein said
redox couple is provided on said substrate, and said polymeric
material is provided so as to cover said redox couple and to extend
onto said substrate.
9. The ion selective sensor as recited in claim 1, wherein said
polymeric material swells to a weight of not more than 5 times its
dry weight when contacted with water.
10. The ion selective sensor as recited in claim 9, wherein said
polymeric material swells to a weight of from about 1.5 to about 3
times its dry weight when contacted with water.
11. The ion selective sensor as recited in claim 10, wherein said
polymeric material swells to a weight of about 2 times its dry
weight when contacted with water.
12. The ion selective sensor as recited in claim 1, wherein said
polymeric material comprises the copolymerization product of at
least one charged monomer and at least one member selected from the
group consisting of neutral monomers and polymers.
13. The ion selective sensor as recited in claim 12, wherein said
polymeric material comprises the copolymerization product of at
least one charged acrylic monomer and at least one neutral acrylic
monomer.
14. The ion selective sensor as recited in claim 13, wherein said
at least one neutral acrylic monomer comprises at least one
component of the formula CH.sub.2.dbd.C(R.sub.1)(COOR.sub.2), where
R.sub.1 and R.sub.2 are each selected from the group consisting of
hydrogen, hydrocarbons, and alcohols, and can be the same or
different.
15. The ion selective sensor as recited in claim 14, where R.sub.1
is selected from the group consisting of hydrogen and lower alkyl
groups, and R.sub.2 is selected from the group consisting of
linear, branched and cyclic hydrocarbons and alcohols of from 1 to
20 carbon atoms.
16. The ion selective sensor as recited in claim 15, wherein said
neutral acrylic monomer comprises methylmethacrylate.
17. The ion selective sensor as recited in claim 13, wherein said
at least one charged acrylic monomer has the formula: 3where
R.sub.1 is selected from the group consisting of hydrogen,
hydrocarbons groups, and alcohol groups, and Y has the formula:
4where R.sub.2 is selected from the group consisting of straight or
branched saturated hydrocarbon chains, straight or branched
unsaturated hydrocarbon chains and straight or branched saturated
or unsaturated hydrocarbon chains having hydroxy functionalities,
R.sub.3, R.sub.4, and R.sub.5 are each selected from the group
consisting of hydrogen, hydrocarbon groups, and alcohol groups, and
can be the same or different, and Z.sup.- is selected from the
group consisting of halides, acetate, and methylsulfate ion.
18. The ion selective sensor as recited in claim 17, where: R.sub.1
is selected from the group consisting of H and CH.sub.3, R.sub.2 is
selected from the group consisting of straight and branched
saturated hydrocarbon chains, R.sub.3, R.sub.4, and R.sub.5 are
each selected from the group consisting of H and CH.sub.3 and can
be the same or different, and Z.sup.- is a halide.
19. The ion selective sensor as recited in claim 18, where R.sub.3,
R.sub.4, and R.sub.5 each comprise CH.sub.3, and Z.sup.- is
chloride.
20. The ion selective sensor as recited in claim 19, wherein said
at least one charged acrylic monomer comprises
methacrylamidopropyltrimethylammoni- umchloride.
21. A method of providing a stable and reproducible electrical
interface between a solid contact reference providing a redox
couple and an ion selective material of an ion selective sensor or
the like, comprising: contacting both said solid contact reference
and said ion selective material with a polymeric material having
immobilized charged sites, said polymeric material carrying
immobilized charged sites.
22. The method as recited in claim 21, wherein said polymeric
material includes less than 1.63.times.10.sup.21 immobilized charge
sites per gram.
23. The method as recited in claim 22, wherein said polymeric
material includes from about 5.5.times.10.sup.19 to about
1.4.times.10.sup.21 immobilized charged sites per gram.
24. The method as recited in claim 23, wherein said polymeric
material includes from about 4.1.times.10.sup.20 to about
1.1.times.10.sup.21 immobilized charged sites per gram.
25. The method as recited in claim 24, wherein said polymeric
material includes from about 5.5.times.10.sup.20 to about
8.2.times.10.sup.20 immobilized charged sites per gram.
26. The method as recited in claim 21, wherein said polymeric
material includes immobilized charged sites selected from the group
consisting of those having a positive charge and those having a
negative charge, and those having both positive and negative
charges.
27. The method as recited in claim 21, wherein said polymeric
material includes immobilized positively-charged sites and
immobilized negatively-charged sites.
28. The method as recited in claim 21, wherein said solid contact
reference is provided on a substrate, and said polymeric material
covers said solid contact reference and extends to cover a portion
of said substrate, and said polymeric material is selected so as to
firmly adhere to said substrate.
29. The method as recited in claim 21, wherein said polymeric
material swells to a weight of not more than 5 times its dry weight
when contacted with water.
30. The method as recited in claim 29, wherein said polymeric
material swells to a weight of from about 1.5 to about 3 times its
dry weight when contacted with water.
31. The method as recited in claim 30, wherein said polymeric
material swells to a weight of about 2 times its dry weight when
contacted with water.
32. The method as recited in claim 21, wherein said polymeric
material comprises the copolymerization product of at least one
charged monomer and at least one member selected from the group
consisting of neutral monomers and polymers.
33. The method as recited in claim 32, wherein said polymeric
material comprises the copolymerization product of at least one
charged acrylic monomer and at least one neutral acrylic
monomer.
34. A method of forming an ion selective sensor comprising the
steps of. providing an electrically conductive material; creating a
redox couple including a portion of said electrically conductive
material; coating said redox couple with a polymeric material
having immobilized charged sites, said polymeric material carrying
immobilized charged sites; and covering said polymeric material
with an ion selective material.
35. The method as recited in claim 34, wherein said coating step
comprises casting a reaction mixture, dissolved in an organic
solvent, including the polymerization product of: (A) a compound
having the formula CH.sub.2.dbd.C(R.sub.1)(COOR.sub.2), where
R.sub.1 and R.sub.2 are each selected from the group consisting of
hydrogen, hydrocarbons, and alcohols, and can be the same or
different; and (B) a species having the formula: 5where R.sub.1 is
selected from the group consisting of hydrogen, hydrocarbons
groups, and alcohol groups, and Y has the formula: 6where R.sub.2
is selected from the group consisting of straight or branched
saturated hydrocarbon chains, straight or branched unsaturated
hydrocarbon chains and straight or branched saturated or
unsaturated hydrocarbon chains having hydroxy functionalities,
R.sub.3, R.sub.4, and R.sub.5 are each selected from the group
consisting of hydrogen, hydrocarbon groups, and alcohol groups, and
can be the same or different, and Z.sup.- is selected from the
group consisting of halides, acetate, and methylsulfate ion, onto
said salt layer so as to completely cover said layer with said
mixture; and drying said mixture of said organic solvent.
36. An ion selective sensor comprising: an electrically conductive
material providing a reference redox couple; a polymeric material
provided on said electrically conductive material, said polymeric
material having immobilized sites of charge opposite that of mobile
ions involved in said redox couple; and an ion selective material
covering said polymeric material.
37. A method of providing a stable and reproducible electrical
interface between a solid contact reference providing a redox
couple and an ion selective material of an ion selective sensor or
the like, comprising: contacting both said solid contact reference
and said ion selective material with a polymeric material having
immobilized sites of charge opposite that of mobile ions involved
in said redox couple.
38. A method of forming an ion selective sensor comprising the
steps of: providing an electrically conductive material; creating a
redox couple including a portion of said electrically conductive
material; coating said redox couple with a polymeric material
having immobilized sites of charge opposite that of mobile ions
involved in said redox couple; and covering said polymeric material
with an ion selective material.
39. The ion selective sensor as recited in claim 8, wherein said
polymeric material is selected so as to firmly adhere to said
substrate and to said ion selective material and to form bonds
thereto which are stronger than the force required to rupture said
ion selective material or said polymeric material.
40. The ion selective sensor as recited in claim 1, wherein said
electrically conductive reference electrode material providing a
redox couple comprises a conductive metal and a salt of said
conductive metal in contact therewith.
41. The ion selective sensor as recited in claim 40, wherein said
electrically conductive reference electrode material providing a
redox couple comprises s silver/silver chloride.
42. The method as recited in claim 21, wherein said solid contact
reference comprises a conductive metal and a salt of said
conductive metal in contact therewith.
43. The method as recited in claim 42, wherein said solid contact
reference comprises silver/silver chloride.
44. The ion selective electrode as recited in claim 1, and further
comprising a salt added to said polymeric material.
45. The ion selective electrode as recited in claim 1, wherein said
polymeric material has a ratio of anionic to cationic or cationic
to anionic transference numbers of less than about 6.0.
46. The ion selective electrode as recited in claim 45, wherein
said ratio is less than about 2.6.
47. The ion selective electrode as recited in claim 46, wherein
said ratio is less than about 1.9.
48. The method as recited in claim 34, and further comprising the
steps of selecting an electrically non-conductive substrate; and
depositing said electrically conductive material onto a portion of
said substrate.
49. The method as recited in claim 38, and further comprising the
step of: selecting an electrically non-conductive substrate; and
depositing said electrically conductive material onto a portion of
said substrate.
50. A chemical responsive field effect transducer comprising: a
layer of semiconductor material having a surface; a pair of first
diffusion regions of a first doping characteristic at said surface;
a second diffusion region of a second doping characteristic at said
surface between said pair of first diffusion regions; an
electrically insulating material provided on said surface; a
polymeric material having immobilized charged sites provided on
said electrically conductive material, said polymeric material
carrying less than about 1.63.times.10.sup.21 immobilized charged
sites per gram, said polymeric material separated from said
diffusion regions by said insulating material; an ion selective
material provided on said polymeric material; and an electrically
insulating encapsulant sealing said transducer from a sample region
while leaving exposed a region of said ion selective material for
exposure to a sample.
51. The transducer as recited in claim 50, and further comprising
an ion barrier material separating said insulating material from
said polymeric material.
52. The transducer as recited in claim 51, wherein said ion barrier
material is selected from the group consisting of Si.sub.3N.sub.4,
Al.sub.2O.sub.3, and Ta.sub.2O.sub.5.
53. The transducer as recited in claim 50, and further comprising a
non-electrically conducting substrate, wherein said semiconductor
material layer is provided on said substrate.
54. The transducer as recited in claim 50, wherein said polymeric
material swells to a weight of not more than 5 times its dry weight
when contacted with water.
55. The transducer as recited in claim 50, wherein said polymeric
material comprises the copolymerization product of at least one
charged monomer and at least one member selected from the group
consisting of neutral monomers and polymers.
56. The transducer as recited in claim 55, wherein said polymeric
material comprises the copolymerization product of at least one
charged acrylic monomer and at least one neutral acrylic
monomer.
57. The transducer as recited in claim 50, and further comprising a
salt added to said polymeric material.
58. The transducer as recited in claim 50, wherein the ratio of
anionic to cationic or cationic to anionic transference numbers is
less than about 6.0.
59. The transducer as recited in claim 50, wherein said first
doping characteristic of said pair of first diffusion regions
comprises a heavily doped characteristic of a first polarity, and
said second doping characteristic of said second diffusion region
comprises a lightly doped characteristic of said first
polarity.
60. The transducer as recited in claim 50, wherein said first
doping characteristic of said pair of first diffusion regions
comprises a first doping polarity, and said second doping
characteristic of said second diffusion region comprises a doping
characteristic of a second polarity opposite said first
polarity.
61. A method of making a chemical responsive field effect
transducer comprising: (a) providing a layer of semiconductor
material having a surface; (b) doping a pair of first regions at
said surface to provide a first doping characteristic therein; (c)
doping a second region of said surface between said pair of first
regions so as to provide a second doping characteristic therein;
(d) covering said diffusion regions with an electrically insulating
material; (e) providing a polymeric material adjacent said
electrically insulating material, said polymeric material having
immobilized charged sites and carrying less than about
1.63.times.10.sup.21 immobilized charged sites per gram; (f)
covering said polymeric material with an ion selective material;
and (g) encapsulating said transducer with an electrically
insulating encapsulant so as to separate said transducer from a
sample region while leaving exposed a region of said ion selective
material for exposure to a sample.
62. The method as recited in claim 61, and further comprising,
between steps (d) and (e), the step of: depositing an ion barrier
material on said insulating material, such that said ion barrier
material is disposed between said insulating material and said
polymeric material.
Description
FIELD OF THE INVENTION
[0001] The present invention relates generally to ion selective
electrodes, ion selective sensors, and ion selective field effect
transducers, and more specifically to a solid contact material for
use in such devices.
TECHNICAL REVIEW
[0002] In many settings, for example the clinical laboratory or the
analytical or industrial chemical laboratory, the need for rapid
analysis of the concentration of a variety of ionic species or
analytes in solution exists. Conventionally, in such analyses, an
ion selective electrode is brought into contact with a test
solution into which a reference electrode is also immersed. The ion
selective electrode and the reference electrode are connected via a
voltmeter and a potentiometric determination of the activity of a
particular analyte in solution is made. The activity measurement
may be correlated to the concentration of the analyte in solution
using reference solutions or standard solutions of known
concentration.
[0003] Typically, ion selective electrodes have been fabricated
according to the following designs. One conventional design
consists of an internal redox couple reference electrode, an
ion-selective membrane, and an internal liquid electrolyte
contacting the reference electrode and the membrane. The ion
selective membrane is advantageously fabricated so as to include
therein a particular molecule selectively complexing the ion to be
analyzed, and the electrolyte advantageously includes a relatively
high concentration of the ion to be analyzed and the anion of the
redox couple, for example chloride in a silver/silver chloride
reference. The potentiometric determination is based upon the
principle that the electromotive force detected by the voltmeter is
proportional to the logarithmic concentration of analyte in
solution. Standard solutions of known analyte concentrations are
typically used and a calibration curve is established in such
analyses, and the concentration of analyte in the test sample is
determined by comparison with the calibration curve. However, such
a system requires maintenance of the electrode in an environment in
which the electrode is not permitted to dry out, and is not
amenable to electrode significant miniaturization, for example in
the fabrication of planar electrodes.
[0004] Hydrogels, that is, neutral polymeric matrices incorporating
salts, have been employed in ion selective electrodes in a manner
similar to that of the above-described liquid electrolyte. However,
hydrogels tend to swell unacceptably during use. Such swelling may
have several detrimental effects, one of which is physical
disruption, ultimately rupture, of the overlaying ion selective
membrane, and another of which is unstable concentration of the
analyte ion within the hydrogel as the swell value changes,
resulting in imprecision and inaccuracy in analysis.
[0005] Another ion selective electrode design involves a reference
redox couple, for example a silver/silver chloride electrode,
covered with a conventional ion selective membrane, and is known as
a "coated wire electrode". Such a design would appear to be
amenable to miniaturization and to planar electrode fabrication.
However, in an ion analysis system, it is important that junction
potentials at material and phase interfaces of the overall
voltametric determination circuit be as stable and reproducible as
possible, so as to assure precision and accuracy in analysis.
Instability in interface junction potential of the ion selective
membrane/reference redox couple interface is observed in coated
wire electrodes, at which a border between a domain of electronic
conductivity and ionic conductivity exists, which border is void of
chemical or electronic equilibria thereacross due to the lack of an
internal contacting solution. Such a border is known in the art as
a "blocked" interface.
[0006] One method of stabilizing such a junction potential is
described in pending U.S. patent application Ser. No. 07/650,347,
assigned to the assignee of this application, and corresponding
European Patent Publication No. 0498572 A2, published Aug. 12,
1992, both of which are incorporated herein by reference. Described
is a redox couple reference contacted by an ion selective membrane
including a fortiophore designed to complex an ionic species of the
redox couple.
[0007] U.S. Pat. No. 4,434,249 describes the preparation of
ion-transfer membranes and methods of preparing such membranes from
acrylic monomers and, particularly, of copolymers of at least two
acrylic monomers. Specifically described is a membrane composition
having a monomeric component (>88 mol %) of a non-ionic
hydrophobic material such as methyl methacrylate (MMA) and a
monomeric component (3-12% mol %) of an acrylic monomer containing
ionogenous groups such as methacrylamidopropyltrimethylammonium
chloride (MAPTAC). The patent describes an optimum concentration
level of the ionogenous monomer for transfer of ions across this
bulk material, departures from which will decrease transference. No
teaching is made of utilizing the material as an interface between
two different conducting domains, for example, electronic and ionic
domains.
[0008] European Patent Publication No. 0325562 A2, incorporated
herein by reference, describes an ion selective electrode in which
an ion exchange resin is incorporated between an electrochemical
redox couple and an ion selective membrane, the ion exchange resin
being selected so as to have ions counter to those to be analyzed
chemically linked to the polymer defining the resin. The
publication teaches the use of standard, commercially-available ion
exchange resins, for example, Amberlite, Dowex, and Nafion, which
typically have a capacity on the order of 4.3 milliequivalents per
gram, that is, about 2.5.times.10.sup.21 charged sites per gram of
material. While neither aqueous swell values nor adherence
characteristics of this approach are documented in the publication,
ion exchange resins typically swell unacceptably in such
circumstances, even to the point of dissolving, and adherence
between an ion exchange resin and an inert substrate is generally
thought to be poor. Indeed, adhesion between many polymeric
materials incorporating charged groups and other polymeric layers
or substrates must often be augmented by an intermediate, inert,
mesh-like layer such as, for example, silated
polyvinylchloride.
[0009] Ion selective membranes have also been used as gate
materials in ion selective field effect transistors. An
electronic/ionic domain boundary complication exists in that
technology as well.
[0010] Therefore, it remains a challenge in the art to formulate a
solid state material to serve as an interface between the
electronic and ionic domains of ion selective sensors, ion
selective field effect transducers, and the like, such material
having a rapidly equilibrating, reproducible swell value below that
at which physical disruption of any device in which it is employed
occurs, which is easy to prepare and use, and which adheres well to
typical substrates and to adjacent layers in devices in which it is
employed.
[0011] Accordingly, it is a general purpose of the present
invention to provide a means and method of establishing or
maintaining a more stable equilibria between electronic and ionic
domains, which equilibria facilitate stable and reproducible
junction potentials in electrochemical devices, using a material
which is easy to prepare and use, which adheres well to typical
substrates and adjacent materials in electrochemical devices in
which it is employed, and which has a stable and reproducible swell
value.
SUMMARY OF THE INVENTION
[0012] The foregoing and other objects and advantages of the
present invention are achieved by providing an ion selective sensor
comprising an electrically conductive material providing a
reference redox couple, a polymeric material having immobilized
charged sites provided on the electrically conductive material, and
an ion selective material covering the polymeric material.
Preferably, the polymeric material carries less than about
1.63.times.10.sup.21 immobilized charge sites per gram. The ion
selective electrode may additionally comprise a substrate onto
which the electrically conductive reference electrode material is
deposited.
[0013] It is another object of the present invention to provide an
ion selective sensor comprising an electrically conductive material
providing a reference redox couple, a polymeric material provided
on the electrically conductive material, the polymeric material
having immobilized sites of charge opposite that of mobile ions
involved in the redox couple, and an ion selective material
covering the polymeric material.
[0014] It is another object of the present invention to provide a
method of providing a stable and reproducible electrical interface
between a solid contact reference providing a redox couple and an
ion selective material of an ion selective sensor or the like,
comprising contacting both the solid contact reference and the ion
selective material with a polymeric material having immobilized
charged sites, the polymeric material carrying less than about
1.63.times.10.sup.21 immobilized charged sites per gram.
[0015] It is another object of the present invention to provide a
method of forming an ion selective sensor comprising the steps of
providing an electrically conductive material creating a redox
couple including a portion of the electrically conductive material,
coating the redox couple with a polymeric material having
immobilized charged sites, and covering the polymeric material with
an ion selective material.
[0016] It is another object of the present invention to provide a
method of providing a stable and reproducible electrical interface
between a solid contact reference providing a redox couple and an
ion selective material of an ion selective sensor or the like,
comprising contacting both the solid contact reference and the ion
selective material with a polymeric material having immobilized
sites of charge opposite that of mobile ions involved in the redox
couple.
[0017] It is another object of the present invention to provide a
method of forming an ion selective sensor comprising the steps of
providing an electrically conductive material, creating a redox
couple including a portion of the electrically conductive material,
coating the redox couple with a polymeric material having
immobilized sites of charge opposite that of mobile ions involved
in the redox couple, and covering the polymeric material with an
ion selective material.
[0018] It is another object of the present invention to provide a
chemical responsive field effect transducer comprising a layer of
semiconductor material having a surface, a pair of first diffusion
regions of a first doping characteristic at the surface, a second
diffusion region of a second doping characteristic at the surface
between the pair of first diffusion regions, an electrically
insulating material provided on the surface, a polymeric material
having immobilized charged sites provided on the electrically
conductive material, the polymeric material carrying less than
about 1.63.times.10.sub.21 immobilized charged sites per gram, the
polymeric material separated from the diffusion regions by the
insulating material, an ion selective material provided on the
polymeric material, and an electrically insulating encapsulant
sealing the transducer from a sample region while leaving exposed a
region of the ion selective material for exposure to a sample.
[0019] It is still another object of the present invention to
provide a method of making a chemical responsive field effect
transducer comprising the steps of providing a layer of
semiconductor material having a surface, doping a pair of first
regions at the surface to provide a first doping characteristic
therein, doping a second region of said surface between the pair of
first regions so as to provide a second doping characteristic
therein, covering the diffusion regions with an electrically
insulating material, providing a polymeric material adjacent the
electrically insulating material, the polymeric material having
immobilized charged sites and carrying less than about
1.63.times.10.sub.21 immobilized charged sites per gram, covering
the polymeric material with an ion selective material, and
encapsulating the transducer with an electrically insulating
encapsulant so as to separate the transducer from a sample region
while leaving exposed a region of the ion selective material for
exposure to a sample.
[0020] These and other objects in view, as will be apparent to
those skilled in the art, the invention resides in the combination
of elements set forth in the specification and covered by the
claims appended hereto.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] The above and other features, objects and advantages of the
present invention will be better understood from the following
specification when read in conjunction with the accompanying
drawings, in which:
[0022] FIG. 1 is a cross-sectional, schematic view of an ion
selective electrode according to the prior art;
[0023] FIG. 2 is a cross-sectional, schematic view of an ion
selective electrode according to one embodiment of the present
invention;
[0024] FIG. 3 is a cross-sectional, schematic view of an ion
selective field effect transistor according to one embodiment of
the present invention; and
[0025] FIG. 4 is a cross-sectional, schematic view of an ion
selective field effect transistor according to another embodiment
of the present invention.
DESCRIPTION OF PREFERRED EMBODIMENTS
[0026] A prior art coated wire ion selective sensor 10 is
illustrated in cross-section in FIG. 1, and includes a
substantially planar non-conducting substrate 12, and redox couple
14 fabricated thereon. Redox couple 14 typically comprises a metal
16 such as silver, onto which a salt of the metal 18 such as silver
chloride is deposited. Ion selective membrane 20 is
electrochemically generated thereover, typically covering redox
couple 14 and contacting portions of substrate 12 in areas 13
surrounding redox couple 14 which redox couple 14 does not cover.
Membrane 20 typically comprises a polymeric membrane incorporating
an ion selective species which imparts ion selectivity to the
membrane. Such ion selective species may take the form of, for
example, a non-dissociable ion-specific ligand, i.e. an ionophore,
or an electrically charged liquid ion-exchanger.
[0027] Lead 22, typically formed of a conductive material such as
the metal which comprises metal 16, may pass through substrate 12
just under metal 16 to make contact therewith, as illustrated in
FIG. 1, or may be deposited upon substrate 12 so as to make contact
with metal 16. According to the latter arrangement (not
illustrated), lead 22 would typically be covered by an electrically
insulating material at portions which would otherwise make contact
with membrane 20. Both of these arrangements are well-known in the
art.
[0028] The scheme at the right of FIG. 1 represents, approximately,
the chemical and electrochemical equilibria associated with ion
selective electrode 10. In the scheme of FIG. 1, level I represents
electronic contact between reference redox couple 14 and lead 22 of
circuitry defining analytical apparatus. Level II represents the
electrochemical equilibrium associated with typical reference redox
couples, for example, one in which M represents a metal such as
silver and MX represents the salt of the metal, X being an ion such
as chloride. In level III, P.sub.1A.sup.+ represents the
association between the material of ion selective membrane 20,
P.sub.1, typically polymeric material including an ionophore, and
analyte species analyte A.sup.+, a cation according to this
exemplary scheme. Level IV represents the analyte medium, typically
an aqueous solution containing analyte A.sup.+. From the scheme of
FIG. 1, it can be seen that equilibria exist between levels I and
II in the form of electron transport and between levels III and IV
in the form of ionic transport, but that no equilibrium exists
between levels II and III, representing the interface of reference
redox couple 14 and ion selective membrane 20, and resulting in a
"blocked" interface. As described above, such a "blocked" junction
potential is typically unstable and irreproducible, resulting in
imprecision and inaccuracy in electrochemical analysis.
[0029] An ion selective sensor 30 in accordance with one embodiment
of the present invention is schematically illustrated in
cross-section in FIG. 2, typically fabricated atop substantially
planar non-conducting substrate 32, and comprises reference redox
couple 34, polymeric material 40 in contact therewith, and ion
selective material 42 in contact with polymeric material 40.
[0030] Substrate 32 may comprise any electrically insulating
material such as glass, ceramic, silicon wafer, plastic, polymer
resin or the like, the particular substrate material or its
configuration not being critical to the present invention.
[0031] Redox couple 34 is typically deposited atop a portion of
substrate 32 and may comprise any standard redox reference couple,
for example a metal 36 and a salt of the metal 38. In a preferred
embodiment, redox couple 34 comprises a layer of silver 36 with a
layer of silver chloride 38 in contact therewith, typically created
or deposited thereover. Silver chloride layer 38 may be made
according to any known method, for example by printing using
standard microfabrication techniques, or by plating from solution,
for example from a concentrated solution of potassium chloride or
sodium chloride.
[0032] Lead 39 provides electrical contact for couple 34, and may
pass through substrate 32 (as illustrated) or may be deposited upon
substrate 32 (not shown). Lead 39 may be made from any conductive
material such as silver, copper, nickel, gold, platinum, zinc,
etc., and typically comprises silver, platinum, or gold according
to preferred embodiments of the present invention.
[0033] Contacting redox couple 34, and completely covering redox
couple 34 and extending onto portions 35 of substrate 32 according
to preferred embodiments of the present invention is polymeric
material 40. Material 40 may be provided upon redox couple 34 and
substrate 32 according to any of the well-known methods for
depositing polymeric materials onto other materials, for example by
casting from solution as a dissolved polymer or copolymer,
polymerizing or copolymerizing the material directly upon the redox
couple and substrate, or fabricating a sheet of material 40 and
pressing it onto redox couple 34 and substrate 32. According to
preferred embodiments of the present invention, polymeric material
40 is cast from solution, either by spin casting or drop-casting
onto redox couple 34 and substrate 32. The solution employed may be
any solution in which polymeric material 40 is soluble, typically
an organic solvent.
[0034] Polymeric material 40 may comprise any material having
sufficient molecular weight to form a film or coating on redox
couple 34 and substrate 32, yet have a molecular weight low enough
to be non-crystalline in character, typically in the range of 2,000
to 250,000 Daltons, more typically in the range of 5,000 to 150,000
Daltons.
[0035] Preferably, polymeric material 40, when contacted with
water, relatively quickly and reproducibly equilibrates to a stable
swell value. Material 40 should swell so as to comprise a weight
not more than 5 times its dry weight when contacted with water,
preferably from about 1.5 to about 3 times its dry weight, and more
preferably does not swell to more than about 2 times its dry weight
when contacted with water. As noted above, rapid and stable
equilibration of the swell value of a material involved in
electronic or ionic conductivity of an ion selective sensor or
other electrochemical device results in rapid and stable
equilibration of the overall electrode in terms of precision and
accuracy in readout.
[0036] According to one embodiment of the present invention,
polymeric material 40 comprises less than about
1.63.times.10.sup.21 immobilized charged sites per gram
(corresponding to less than about 2.72 milliequivalents/gram
(meq/g)). As used herein, charged sites per gram and meg/g refer to
dry weight of polymeric material 40. Preferably, material 40
comprises from about 5.5.times.10.sup.19 to about
1.4.times.10.sup.21 immobilized charged sites per gram (from about
0.09 to about 2.26 meq/g), more preferably from about
4.1.times.10.sup.20 to about 1.1.times.10.sup.21 immobilized
charged sites per gram (from about 0.68 to about 1.81 meq/g), and
most preferably from about 5.5.times.10.sup.21 to about
8.2.times.10.sup.20 immobilized charged sites per gram (from about
0.91 to about 1.36 meq/g). Employment of material 40 including
these preferred ranges of the number of immobilized charged
sites/gram advantageously affects the overall performance of ion
selective sensor 30, especially in terms of swell, adherence,
longevity, and precision and accuracy.
[0037] According to another embodiment of the present invention,
polymeric material 40 has immobilized sites of charge opposite that
of mobile ions involved in redox couple 34. That is, if a typical
silver/silver chloride redox couple is employed as a reference 34,
polymeric material 40 advantageously includes immobilized
positively charged sites, counter to the chloride ions involved in
the redox couple. Such a choice of charged polymeric material
results in stable equilibrium between reference redox couple 34 and
polymeric material 40, as will be further described below.
[0038] Polymeric material 40 may comprise the polymerization or
copolymerization product of at least one monomer carrying at least
one charged site, and at least one inert monomer. Preferably,
material 40 comprises the polymerization product of anionic,
cationic, or zwitterionic species, and typically at least one other
non-ionic species. A non-limiting exemplary list of charged sites
which may be associated with species polymerized to form material
40 includes sulfonate, carboxylate, phosphonate, ammonium groups,
quaternary ammonium groups, phosphonium groups, quaternary
phosphonium groups, etc. A wide range of counter ions to balance
these charged groups may be employed, and ions to be analyzed by
the electrode of the invention and/or ions participating in the
reference redox couple may be advantageously selected as counter
ions.
[0039] An exemplary list of polymers suitable for use as material
40 includes polystyrene having fixed charged sites, perfluorinated
ionomers, sulfonated styrene-divinyl benzene resins, divinyl
naphthalene acid polymers, vinyl pyridinium salts, quaternized
vinyl benzyl halides, acrylate polymers such as those described in
copending, commonly-owned U.S. patent application Ser. No.
08/045,847, filed Apr. 9, 1993, and incorporated herein by
reference, nitrile-containing polymers, amide-containing polymers,
and the like.
[0040] A particularly preferred class of monomers suitable for
polymerization or copolymerization to form polymeric material 40 of
the present invention is described in U.S. Pat. No. 4,434,249, and
an article entitled "Acrylic Ion-Transfer Polymers", issued Feb.
28, 1984, by C. L. Ballestrasse and T. R. Beck, Journal of the
Electrochemical Society, 134, 11, 2745-2749 (1987), both of which
are incorporated herein by reference.
[0041] According to one preferred embodiment, polymeric material 40
comprises the copolymerization product of at least one charged
acrylic monomer and at least one neutral acrylic monomer.
Preferably, the charged acrylic monomer or monomers employed has
the formula: 1
[0042] where R.sub.1 is selected from the group consisting of
hydrogen, hydrocarbons groups, and alcohol groups, and Y has the
formula: 2
[0043] where R.sub.2 is selected from the group consisting of
straight or branched saturated hydrocarbon chains, straight or
branched unsaturated hydrocarbon chains and straight or branched
saturated or unsaturated hydrocarbon chains having hydroxy
functionalities, R.sub.3, R.sub.4, and R.sub.5 are each selected
from the group consisting of hydrogen, hydrocarbon groups, and
alcohol groups, and can be the same or different, and Z.sup.- is
selected from the group consisting of halides, acetate, and
methylsulfate ion.
[0044] More preferably, R.sub.1 is selected from the group
consisting of H and CH.sub.3, R.sub.2 is selected from the group
consisting of straight and branched saturated hydrocarbon chains,
R.sub.3, R.sub.4, and R.sub.5 are each selected from the group
consisting of H and CH.sub.3 and can be the same or different, and
Z is a halide. According to a particularly preferred embodiment,
RI, R.sub.3, R.sub.4 and R.sub.5 each comprise CH.sub.3, R.sub.2 is
(CH.sub.2).sub.3, and Z is chloride.
[0045] The neutral acrylic monomer or monomers employed, according
to this embodiment, may comprise at least one component of the
formula CH.sub.2.dbd.C(R.sub.1)(COOR.sub.2), where R.sub.1 and
R.sub.2 are each selected from the group consisting of hydrogen,
hydrocarbons, and alcohols, and can be the same or different.
Preferably, R.sub.1 is selected from the group consisting of
hydrogen and lower alkyl groups, and R.sub.2 is selected from the
group consisting of linear, branched and cyclic hydrocarbons and
alcohols of from 1 to 20 carbon atoms. According to the above
description, hydrocarbon groups such as hydrogen, alkyl, alkenyl,
alkynyl, cycloalkyl, aryl, alkaryl, aralkyl, and the like may be
selected.
[0046] As used herein, the terms "hydrocarbon", "alkyl",
"cycloalkyl" and similar hydrocarbon terminology is meant to
include alcohols and hydrogen, although specific reference to the
inclusion of hydrogen and/or alcohols is frequently made herein.
Examples of such groups are methyl, propenyl, ethynyl, cyclohexyl,
phenyl, tolyl, benzyl, hydroxyethyl and the like.
[0047] Copolymerization of material 40 may be effected by
conventional means including anionic, cationic, or free-radical
polymerization initiators.
[0048] In a particularly preferred embodiment, polymeric material
40 comprises a copolymer of
methacrylamidopropyltrimethylammoniumchloride (MAPTAC) and
methylmethacrylate (MMA). A random copolymer may be employed, for
example made from the polymerization reaction of a mixture of these
monomers in a predetermined ratio, or a block copolymer comprising
blocks of from about 1 to 500 monomer units of each of the
above-noted monomers may be fabricated. A block copolymer may be a
random mixture of blocks of a variety of molecular weights, or may
be a mixture of blocks of relatively narrow molecular weights,
depending upon the application. Preferably, a mixture of MAPTAC and
MMA monomers are polymerized in solution.
[0049] According to one of the embodiments of the invention
described above, the ratio of relative amounts of MAPTAC and MMA
monomers are selected so as to provide the above-described
preferred ranges of charged sites/gram (meq/g). To formulate a
polymeric material carrying less than about 1.63.times.10.sup.21
immobilized charged sites per gram, a mixture would be polymerized
comprising a weight ratio of MAPTAC to MMA of less than about
60/40. To formulate a polymeric material including from about
5.5.times.10.sup.19 to 1.4.times.10.sup.21 immobilized charged
sites per gram, a MAPTAC/MMA weight ratio of from about 2/98 to
about 50/50 would be copolymerized. To formulate a polymeric
material including from about 4.1.times.10.sup.20 to about
1.1.times.10.sup.21 immobilized charged sites per gram, a
MAPTAC/MMA weight ratio of from about 15/85 to about 40/60 would be
employed. To formulate a polymeric material including from about
5.5.times.10.sup.20 to about 8.2.times.10.sup.20 immobilized
charged sites per gram, a MAPTAC/MMA weight ratio of from about
20/80 to about 30/70 would be employed.
[0050] According to embodiments hereinabove described, polymeric
material 40 may include immobilized positively charged sites,
negatively-charged sites, or both positively and negatively charged
sites. According to embodiments in which only negatively charged or
positively-charged immobilized sites exist in polymeric material
40, addition of salts to material 40 may be particularly
advantageous and is within the scope of the present invention. As
noted above, the counterions of the immobilized charged sites
associated with material 40 may be advantageously selected so as to
be the same as either analyte ions in a solution or ions involved
in reference redox couple 34. Salts selected for addition to
polymeric material 40 may also be advantageously selected so as to
include analyte ions and/or ions involved in reference redox couple
34. For example, when a silver/silver chloride redox couple 34 is
employed, ion selective membrane is selective for a particular
cation, and polymeric material 40 includes immobilized positively
charged sites, a salt including the cation to be analyzed and
chloride may advantageously be added to polymeric material 40.
[0051] Addition of such salts to polymeric material 40 typically
advantageously affects the transference characteristic of material
40. The principle transference is described in U.S. Pat. No.
4,434,249, referenced above. It is advantageous according to the
present invention to fabricate ion selective sensor 30 to have an
overall transference approaching an ideal value of 1.0 for the ion
to be sensed, while having a transference approaching an ideal
value of zero for ions of charged opposite that of the ion to be
sensed. However, within polymeric material 40 itself, it is
desirable that transference numbers for both cationic and anionic
species be greater than zero, preferably between about 0.1 and
about 1.0.
[0052] Addition of salts to polymeric material 40 may be carried
out according to several methods. According to one method,
polymeric material 40 may be cast as a free-standing polymer, cut
to size, and soaked in an aqueous solution comprising the salt to
be added. Typically, such an aqueous solution has a concentration
of about 0.1-0.2 M. Alternatively, material 40 may be polymerized
or copolymerized in the presence of such salts, or may be drop cast
or spin cast from a solution including the selected salt during the
fabrication of ion sensitive sensor 30 or ion selective field
effect transistors 40 or 80, described below. According to another
method, salts may be screen-printed onto redox couple 34 prior to
application of polymeric material 40.
[0053] According to this embodiment, a particular salt is added
preferably such that the cationic and anionic transference numbers
of polymeric material 40 are both within about two orders of
magnitude. More preferably, a particular salt is added such that
the ratio of cationic to anionic or anionic to cationic
transference is not more than about 6.0, still more preferably not
more than about 2.6, and most preferably not more than about 1.9.
According to preferred embodiments, polymeric material 40 is
selected such that such salts may be added without affecting the
specificity of cationic or anionic transport within the
material.
[0054] Contacting, and completely covering polymeric material 40
according to preferred embodiments of the present invention is ion
selective material 42. The choice of material 42 is not critical to
the present invention, thus selection may be made from any of a
wide variety of known materials incorporating a variety of known
ionophores or ion exchangers to impart ion selectivity to the
material. Ion selective material 42 may be a commercially-available
or pre-fabricated membrane cut to size and placed atop polymeric
material 40, may be fabricated and dissolved in a suitable solvent
and cast onto polymeric material 40, or may be formulated and
polymerized in solution atop polymeric material 40. Preferably, ion
selective material 42 is a membrane cast from solution atop
material 40. Additionally, it is within the scope of the present
invention to use other ion selective materials such as ion
selective glasses or the like as ion selective material 42.
[0055] A non-limiting exemplary list of materials suitable for
formation of ion selective material 42 includes polyvinylchloride,
polystyrene, polyacrylate, polycarbonates, silicone rubber,
polyesters, polyamides, vinylidene chloride, acrylonitrile,
polyurethanes, polyvinylidene chloride, polyvinylidene chloride
copolymerized with polyvinylchloride, polyvinyl butyryl, polyvinyl
formal, polyvinyl acetate, polyvinyl alcohol, cellulose esters, and
copolymers of the above materials, as well as glasses. Plasticizers
may be used in the preparation of a membrane comprising ion
selective material 42, such as o-nitrophenyl-octylether,
dimethylphthalate, dioctylphenyl-phosphonate, dibutylphthalate,
hexamethylphosphoramide, dibutyladipate, dioctylphthalate,
diundecylphthalate, dioctyladipate, dioctyl sebacate, and other
conventional plasticizers.
[0056] As noted, to impart ion selectivity to material 42, a
suitable ionophore or ion exchanger is typically employed. Any
known ionophore selective to the ion to be analyzed may be
employed. A non-limiting exemplary list of ionophores includes: for
potassium, valinomycin, dicyclohexano-18-crown-6,
dibenzo-18-crown-6, tetraphenyl borate, tetrakis (chlorophenyl)
borate; for calcium, bis(didecylphosphate),
bis(4-octylphenylphosphate),
bis(4-(1,1,3,3-tetramethylbutyl)phenylphosph- ate
tetracosamethylcyclododecasiloxane, N, N'-di(11-ethoxycarbonyl)
undecyl)-N, N',4, 5-tetramethyl-3,6-dioxaoctane diamide; for
hydrogen, tridodecylamine, N-methyl N-octadecyl (1-methyl,
2-hydroxy, 2-phenyl) ethylamine, N-octadecyl 3-hydroxy
n-propylamine, N, N' bis (octadecyl ethylene amine),
p-octadecyloxy-m-chlorophenylhydrazonemeso oxalonitrile; for
sodium, monensin, N,N',N"-triheptyl-N, N', N"-trimethyl-4,4',
4"-propylidintris-(3-oxabutyramide), N,N,N',N'-tetracyclohexyl-
1,2-phenylenedioxydiacetamide,
4-octadecanoyloxymethyl-N,N,N',N',-tetracy- clohexyl-1
,2-phenylenedioxydiacetamide, bis[(12-crown-4)methyl]dodecylmet-
hylmalonate; for lithium, N, N'-diheptyl-N, N',
5,5-tetramethyl-3,7-dioxon- onanediamide), 12-crown-4,
6,6-dibenzyl-14 crown-4; for chloride, quaternary ammonium
chloride, tributyl tin chloride.
[0057] A variety of components and methods for fabrication of ion
selective materials, in particular membranes, in accordance with
the present invention are known in the art and may be found, for
example, in International Patent Publication No. WO 91/11710,
published Aug. 8, 1991, and U.S. Pat. Nos. 4,214,968, 3,562,129,
3,753,887, and 3,856,649, all of which are incorporated herein by
reference, as well as commonly-owned pending U.S. patent
application Ser. No. 07/650,347 and European Patent Publication No.
0325562 A2, both of which are referenced above.
[0058] Referring now to the scheme of FIG. 2, an approximation of
the advantageous chemical equilibria associated with the ion
selective sensor of the present invention is represented. Level V
represents electronic flow to and from redox couple 34 through lead
39. Level VI represents the electrochemical equilibrium associated
with redox couple 34 such as, for example, silver/silver chloride.
Level VII illustrates the association of the ion X.sup.- of redox
couple 34, for example chloride ion, with portions of polymeric
material 40 represented by P.sub.2, and the incorporation of an ion
to be analyzed, for example, a cation represented as A.sup.+,
associated with portions of polymeric material 40 as represented by
P.sub.3. If immobilized positively-charged sites are associated
with polymeric material 40, the association represented by
P.sub.2X.sup.- is enhanced when silver/silver halide is selected as
redox couple 34, as well as association with any anion to be
analyzed. If polymeric material 40 includes immobilized
negatively-charged sites, association with any positive ion
included in an electrochemical equilibrium associated with redox
couple 34 and/or association with a positively charged ion to be
analyzed, represented in FIG. 2 as cation A.sup.+, is enhanced. If
polymeric material 40 is selected so as to comprise only
positively-charged or negatively-charged immobilized sites, it is
preferably also selected so as to be able to incorporate to some
extent ions of a charge the same as that of the immobilized sites,
so that equilibrium both with anions associated with redox couple
34 and cations associated with the analyte species may exist (as
described above), and this may ensue according to the preferred
ranges of immobilized charged sites per gram of polymeric material
40 according to the present invention. Level VIII of the scheme of
FIG. 2 represents portions of ion selective material 42,
represented as P.sub.1, associated with the ion to be analyzed,
cation A.sup.+ in this scheme. Level IX represents the analyte
medium containing exemplary analyte A.sup.+, which may comprise an
aqueous or organic solution, blood or plasma, skin, or the like, a
wide variety of analyte media being measurable with ion selective
sensors fabricated in accordance with the present invention.
[0059] As can be seen from the scheme of FIG. 2, equilibria exist
between each of the levels V-IX. Between levels V and VI,
electronic transport exists, similarly to the state of the prior
art represented by levels I and II of FIG. 1. Between levels VIII
and IX, ionic transport exists, similarly to the state of transport
between levels III and IV in the representation of the prior art in
FIG. 1 However, according to the present invention, between levels
VI and VII, ionic transport exists, aided by association between
portions P.sub.2 of polymeric material 40 and an ion associated
with the equilibrium of redox couple 34 (X.sup.-).
[0060] Additionally, ionic transport between levels VII and VIII
exists, in the form of exemplary analyte ion (A.sup.+) transport
between portion P, of ion selective material 42 (level VIII) and
polymeric material 40 (level VII). The result is thus "unblocked"
junction potential across ion selective sensor 30, resulting in
improved precision and accuracy in analysis of ionic species.
[0061] As noted above, one problem commonly associated with
fabrication of planar electrochemical devices is poor adherence
between layers. Often delamination is a determining factor in the
lifetime of a particular device, or in the feasibility of device
production. The ion selective sensor of the present invention is
commonly mounted in a sampling device comprising a sample chamber
which is mounted so as to cover ion selective material 42 above
redox couple 34, the sample chamber allowing a sample solution to
contact material 42 above redox couple 34. An exemplary sample
chamber is described in commonly-owned, copending U.S. patent
application Ser. No. 08/045,847, referenced above. In such a
sampling device, with reference to FIG. 2, a gasket or other
apparatus generally applies pressure atop ion selective material 42
in the direction of substrate 32, which may alleviate some
delamination problems once device fabrication is complete. However,
typical microfabrication of such sensors involves fabrication of a
plurality of devices on a single chip, followed by singulation
(dicing) of the chip to provide a plurality of sensors, and then
installation of each sensor device into an encasing sample device.
Such singulation and separation may result in delamination if
adherence between the various layers is not good.
[0062] It has surprisingly been found that polymeric material 40,
according to preferred embodiments of the present invention,
adheres well to a variety of insulating substrate materials and to
a variety of ion selective materials, such that auxiliary binding
layers are not needed between polymeric material 40 and substrate
32 or between material 40 and material 42.
[0063] Mechanical adhesion of layers can be characterized by
methods including the tape, blister, scratch/scrape, ultrasonic
bath and peel tests. A simple yet effective semi-quantitative test
for adherence is the tape test. In a typical procedure, a sensor
fabricated in accordance with the present invention, schematically
represented in FIG. 2, is fabricated on a chip along with a
plurality of such electrodes. A piece of commercially available
(3M) adhesive tape is pressed atop a chip including a plurality of
such electrodes, typically a chip of about 2 inches by 2 inches in
dimension, and the tape is removed by slowly pulling upwards at an
angle approximately perpendicular to the surface of the chip. Tape
is advantageously selected to have an adhesive strength such that
if mechanical adhesion between the layers is good the tape will
peel off without disrupting the layers, but if adhesion is poor
delamination will occur. Alternatively, pieces of tape with
increasing adhesive properties may be used in such a test until
delamination of one layer from another layer occurs, or rupture of
any layers occurs. A goal in fabrication of ion selective sensors
such as those of the present invention is that, when tape of
sufficient adhesive quality is used, rupture of ion selective
material 42, especially when material 42 comprises a membrane,
and/or polymeric material 40 will occur rather than delamination of
ion selective material 42 from polymeric material 40, or
delamination of polymeric material 40 from substrate 32. Stated
another way, the polymeric material 40 is selected so as to bond
sufficiently to substrate 32 and to ion selective material 42 such
that adhesion between polymeric material 40 and substrate 32 and
between polymeric material 40 and ion selective material 42 is
stronger than force needed to rupture either material 42 or
material 40. Material selected as polymeric material 40 in
accordance with the present invention surprisingly shows good
adhesive properties. The result is surprising in that, as noted
above, immobilized charged sites associated with polymeric material
are thought to be inconsistent with good adhesion of such polymeric
material to an insulating substrate or to adjacent layers in
typical planar electrochemical devices.
[0064] Referring now to FIG. 3, a chemical-responsive transducer,
and specifically an ion selective field effect transistor (ISFET)
incorporating the polymeric material 40 of the present invention is
schematically illustrated in cross-section. Such transducers, and
particularly ISFETs, are described in "Ion Selective Electrodes And
Analytical Chemistry" vol. 2, Freiser, H., Plenum Press, New York
(1979), incorporated herein by reference, in U.S. patent
application Ser. No. 07/650,347, referenced above, and in U.S. Pat.
No. 4,502,938, incorporated herein by reference. As used herein,
electrochemical transducer is meant to define a field effect device
for use in the separate or simultaneous detection and/or
measurement of various chemical properties including ion activity
and concentration, presence and concentration of enzymes,
substrates, antibodies, antigens, hormones, reducible gases,
glucose, lactate, pyruvates, creatinine, urea, and the like. Such
devices may be advantageously used for signal amplification and/or
processing involved in the measurement of the above-noted species
and others during flow-injection-analysis, flow-through cuvette
apparatus suitable for the continuous or intermittent on-line
monitoring of blood in the clinical or laboratory environment, and
the like. Suitable devices which may be advantageously modified by
incorporation of the polymeric material 40 of the present invention
include any electrochemically-based transducer that employs an
ion-selective material such as a membrane and in which conductivity
across a boundary between an electrical and a chemical domain is
advantageously stabilized.
[0065] An ISFET will be used to descriptively exemplify such a
transducer, but it is to be understood that the electrochemical
transducer of the present invention is not limited to a transistor
embodiment. Such transistors are fabricated by replacing or
augmenting a metal gate with an ion selective material such as
membrane or glass, an electrolyte (or analyte) solution contacting
the membrane, and a reference electrode contacting the electrolyte
solution, the reference electrode being in electrical contact with
the gate circuit of the ISFET.
[0066] Referring to FIG. 3, ISFET 41 is illustrated and comprises
substantially planar electrically insulating substrate 44;
semiconductor 46 which may be an n-doped or p-doped material, and
comprising p-type silicon according to a preferred embodiment
deposited atop substrate 44; diffusion regions including source 48
and drain 50 separately formed in semiconductor 46 having a first
doping polarity and comprising, for example, n-type silicon
according to a preferred embodiment; leads 52 and 54 contacting
source 48 and drain 50, respectively, formed from any conductive
material such as metal; insulating layer 56 coating semiconductor
46 (and source and drain 48 and 50 formed therein) at all places
except where leads 52 and 54 contact source and drain 48 and 50,
insulating layer 56 comprising SiO.sub.2 according to a preferred
embodiment; polymeric material 40 in accordance with the present
invention formed atop insulating layer 56 above diffusion region,
or channel 51 of semiconductor 46 between source 48 and drain 50,
formed in well 57 according to one embodiment; ion selective
material 42 formed atop polymeric material 40; and encapsulant 58
sealing portions of ISFET 41, and especially contacts 52 and 54,
but leaving exposed a portion of ion selective material 42. Region
51 of semiconductor 46 between source 48 and drain 50 has a doping
polarity that is either different from that of source 48 and drain
50 or of a different magnitude. For example, source 48 and drain 50
may comprise n-type silicon while region 51 may comprise p-type
silicon. Alternately, source 48 and drain 50 may be relatively
heavily doped to a particular polarity, region 51 being lightly
doped to the same polarity.
[0067] Sample 60, which may or may not include an analyte or ion,
is provided in contact with material 42, and reference electrode 62
is provided in contact with electrolyte or analyte solution 60.
Illustrated in FIG. 3 is a liquid electrolyte 60 contacting
material 42 and encapsulant 58 and being contained within boundary
59, such as a beaker or the like. Contact 64 contacts lead 52, and
contact 68 contacts lead 54, thus the drain circuit of ISFET 41
contains lead 52, contact 64, conductor 70, contact 68, lead 54,
drain 50, region 51, source 48 and a potential source 71. The drain
circuit is in electrical contact with reference electrode 62, thus
electrode 62, electrolyte 60, ion selective material 42, polymeric
material 40, and potential source 73 complete the gate circuit of
ISFET 41. Contact 72, in electrical connection with conductor 70,
may contact semiconductor 46 to provide a stable reference for the
gate and drain circuits of ISFET 41.
[0068] FIG. 4 illustrates a second embodiment of the present
invention in which an ISFET incorporates polymeric material 40.
Components and features common to FIGS. 3 and 4 are represented by
common numerical designations. In FIG. 4, as in FIG. 3, the metal
gate of a field effect transistor is replaced by ion selective
material 42, polymeric material 40, electrolyte or analyte solution
60, and reference electrode 62. The embodiment illustrated in FIG.
4 additionally comprises ion-barrier layer 74 between polymeric
material 40 and insulator 56. Layer 74 may comprise a conducting
metal such as gold, silver, platinum, copper, brass, zinc, etc., or
their oxides or alloys. Particularly preferred materials suitable
for use as layer 74 are Al.sub.2O.sub.3, Ta.sub.2O.sub.5, and
Si.sub.3N.sub.4. Exemplary materials suitable for components of
ISFET 41 according to the present invention, and exemplary
dimensional specifications for the components may be found in U.S.
Pat. No. 4,502,938, referenced above.
[0069] The "unblocked" junction potential as described above with
reference to FIG. 2, is realized according to the embodiment of the
present invention defining the transducer of FIG. 3 and FIG. 4.
[0070] The dimensions of ion selective sensor 30 and ISFET 40 are
not critical to the present invention. Dimensions typically found
in planar electrochemical devices fabricated according to
conventional thin-film or thick-film techniques are acceptable.
Additionally, although substrate 32 is illustrated in FIG. 2, upon
which ion selective sensor 30 is fabricated, sensor 30 may be
fabricated without a substrate, in the form of the well-known
"dipped" electrode. Such an embodiment will be clearly understood
by referring to U.S. Pat. No. 3,714,015, and incorporated herein by
reference.
[0071] In the following examples, a preliminary procedure was used
to evaluate the sensors of the present invention. This preliminary
procedure described is not meant to constitute a final, rigorous
evaluation.
[0072] The following examples are intended to illustrate the
benefits of the present invention, but do not exemplify the full
scope of the invention. For example, although the thick-film
technique is exclusively exemplified, it is to be understood that
the thin-film technique may be selected; although only a
one-electrode device is fabricated, a device including a plurality
of electrodes on a single chip could be fabricated, as well as a
plurality of transducers on a single chip. Additionally, the
specific shape and arrangement of the components of the electrode
of the present invention may be significantly altered, such
alteration being within the scope of the invention. These and other
modifications and their equivalents are understood to be within the
scope of the present invention.
EXAMPLE 1
[0073] In this and the following examples, ion selective sensors
were fabricated by screen printing a plurality of individual
electrodes on a laser scored ceramic wafer, and following the
deposition of an ion selective membrane, the wafer was singulated
on the laser score lines so as to create a plurality of individual
sensor chips. For the purpose of simplicity in this and the
following examples, procedures will be described as if a single
chip were fabricated.
[0074] An ion selective sensor base chip was fabricated on a 0.457
cm.times.1.143 cm electrically insulating composite substrate
compromising approximately 96% Al.sub.2O.sub.3 and approximately 4%
binder, available from Coors Ceramic Company, Grand Junction, Colo.
The laser score process needed for wafer singulation is available
from Lasereliance Technologies, Altamonte Springs, Fla. Using the
thick-film deposition technique, a conductive strip was fabricated
by screen printing, using a framed, stainless 325 mesh/0.1 mm
emulsion-coated screen available from Affiliated Manufacturers,
Inc., North Branch, New Jersey. The silver conductive paste is
available as part no. 3571 UF, from Metech Company of Elverson, Pa.
The conductive strip was fabricated so as to create an oval
electrode with the approximate dimensions of 1.52 mm.times.0.762
mm. The paste was fired using a Fast Fire, 7 zone belt furnace with
an attached 3 zone dryer available from BTU of Billerica, Mass. in
accordance with manufacturer's recommendations. Subsequently, a
gold conductor and contact pad was screen printed so as to overlap
and make contact to the silver conductor. The contact pad extends
approximately 2.03 mm from the Dielectric coating edge and has a
contact area of approximately 1.66 mm. The gold paste is available
as part no. MTPC10391 from Metech Company, Elverson, Pa. Firing was
carried out according to manufacturer's recommendations. A
dielectric (glass) passivation was then printed over both
conductors with openings so as to define the active electrode area
and the contact pads. The dielectric paste, part no. 9615, is
available from E.I. Dupont, Wilmington, Del., and was fired
according to manufacturer's recommendations.
[0075] The gold contact pads were masked with 0.250" skived TFE
film tape with a silicon adhesive available from Green Rubber,
Cambridge, Mass. The silver electrodes were then galvanostatically
plated with silver chloride from 0.1 M KCl for 10 minutes -2.00 mA.
The tape was removed and the chip was rinsed in deionized water and
air dried.
EXAMPLE 2
[0076] A copolymer of MAPTAC and MMA was synthesized according to
the following method. MAPTAC was purchased as a 50 weight percent
aqueous solution inhibited with 600 ppm MEHQ from Aldrich of
Milwaukee, Wis., and was used as received. MMA was purchased from
Aldrich of Milwaukee, Wis., and was distilled prior to use.
Isopropyl alcohol (IPA) was HPLC grade from Fisher of Pittsburgh,
Pa., and was used as received. Anhydrous ethanol was from Quantum
Chemical of Cincinnati, Ohio, and was used-as received.
Azobisisobutyronitrile (AIBN) was from Kodak Chemical of Rochester,
N.Y., and was recrystallized in acetone prior to use. Anhydrous
diethyl ether was from Fisher, and was used as received. A
copolymer having a weight ratio of 25 parts MAPTAC to 75 parts MMA
was synthesized as follows. 10 mL of IPA, 5 g of a 50 weight
percent aqueous solution of MAPTAC and 7.5 g of MMA were added to a
test tube which was then covered with a septum. A needle connected
to a nitrogen line was inserted into the septum and the reaction
mixture was mixed with nitrogen bubbles for about 5 minutes. 0.11 g
of AIBN was next added to the reaction mixture and this was mixed
for an additional 20 minutes with nitrogen bubbles. The needle was
removed and the test tube was placed in a 70.degree. C. water bath
for 2.5 hours. The water bath was then removed and the test tube
sat capped overnight at room temperature. The polymer was removed
from the test tube by breaking the glass. Pieces of polymer were
dissolved in a 10% solution of anhydrous ethanol, precipitated into
anhydrous diethyl ether, filtered, and then dried 30 minutes with
vacuum.
EXAMPLE 3
[0077] Silated PVC was synthesized in house, according to
commonly-owned, pending U.S. patent application Ser. No.
07/817,721, filed Jan. 7, 1992. A 25/75 weight ratio of MAPTAC/MMA,
prepared according to Example 2, was dissolved as a 5% weight
solution in ethanol. A chip fabricated according to Example 1 was
prepared as described in Example 1, and the ethanol solution
containing MAPTAC/MMA was drop cast thereover using a Pasteur
pipette. The ethanol was driven off by drying at room temperature
followed by drying at 80.degree. C. for 30 minutes. The resultant
MAPTAC/MMA layer had a thickness of about 10 mm. The chip was then
spun cast with a 1% weight solution of silated PVC in
tetrahydrofuran at 4,000 RPM for 30 seconds and cured for 2 hours
at 80.degree. C. The resultant silated PVC layer had a thickness of
about 1 mm.
EXAMPLE 4
[0078] A chip including a membrane selective for hydrogen ion (a pH
sensor) was fabricated as follows The pH sensor was prepared by
depositing a hydrogen ion selective membrane atop the sensor
fabricated in accordance with Example 3 according to the following
method. Tetrahydrofuran (THF) was purchased from Aldrich, of
Milwaukee, Wis. Tridodecylamine (TDDA) was purchased from Fluka, of
Buchs, Switzerland. Potassium tetrakis (p-chlorophenyl) borate
(KTpClPB) was purchased from Fluka. Dioctylphthalate (DOP) was
purchased from Fluka. PVC was purchased from Fluka. A 10% by weight
membrane solution was prepared in THF containing 2 weight percent
TDDA, 0.1 weight percent KTpClPB, 65 weight percent DOP, and 33
weight percent PVC. A volume of 3.6 ml of membrane solution was
solvent cast onto a chip fabricated in accordance with Example 3.
The layer was dried at room temperature in a THF environment for
about 24 hours. Final membrane thickness was approximately 120
mm.
EXAMPLE 5
[0079] A chip including a membrane selective for the potassium ion
was fabricated as follows. Valinomycin (VAL) was purchased from
Fluka. Diundecylphthalate (DUP) was purchased from Scientific
Polymer Products of Ontario, N.Y. A 10% by weight membrane solution
was formulated in THF containing 1 weight percent VAL, 33 weight
percent PVC, 66 weight percent DUP, and 0.2 weight percent KTpClPB.
A membrane layer was cast atop a chip fabricated in accordance with
Example 3 in the manner described in Exhibit 4.
EXAMPLE 6
[0080] A chip including a membrane selective for the sodium ion was
fabricated as follows. Methyl monensin ester (MMO) was purchased
from Calbiochem of LaJolla, Calif. o-nitrophenol octyl ether (NPOE)
was purchased from Fluka.
[0081] A 10% by weight membrane solution was formulated in THF
containing 2 weight percent MMO, 30 weight percent PVC, 67.6 weight
percent o-NPOE, and 0.4 weight percent KTpClPB. A membrane layer
was cast atop a chip fabricated in accordance with Example 3 in the
manner described in Example 4.
EXAMPLE 7
[0082] A chip including a membrane selective for the calcium ion
was fabricated as follows: (R,R)-N,N'-[BIS(11
-ethoxycarbonyl)undecyl]-N,N'-4- ,5-tetramethyl-3,6doxaoctane
diamide (ETH1001) was purchased from Fluka. A 10 percent by weight
solution in THF was prepared by adding 3.3 weight percent ETH1001,
1.2 weight percent KTpClPB, 30 weight percent PVC, and 6.5.5 weight
percent NPOE. The solution was solvent cast onto a chip prepared in
accordance with Example 3 in the manner described in Example 4.
EXAMPLE 8
[0083] Five day whole blood and serum studies were conducted for pH
sensors using chips fabricated in accordance with Example 4. Sample
chambers were constructed so as to expose all sample solutions to
an area of the ion selective membrane immediately above the
reference redox couple. A conventional silver/silver chloride
reference electrode and the gold contact pad of the pH chip were
connected to a high impedance voltmeter, the reference electrode
also being exposed to sample solutions.
[0084] Seven sensors were tested. The sensors were first wetup in
pH 7 buffer and initial slopes were determined. The sensors were
then soaked for approximately 48 hours in the buffer solution.
[0085] On day one, potentiometric selectivity coefficients were
determined using the fixed interference method. Buffer solutions
were: 1) 10 mM NaOH, 130 mM NaCl, 10 mM TRIS, 2) 190 mM KCl, 10 mM
KOH, 10 mM TRIS, 3) 60 mM LiOH, 6.6 mM citric acid, 11.4 mM boric
acid, 4) 130 mM CaCl.sub.2, 20 mM Ca(OH).sub.2, 10 mM TRIS, and 5)
130 mM MgCl.sub.2, 20 mM Mg(OH).sub.2, 10 mM TRIS. The pH of each
solution was adjusted by dropwise addition of 1 N HCl. Slope was
determined at the end of the day.
[0086] On days 2-4, the following test sequence was carried out:
(A) aqueous test (slope determination and triplicate measurements
of a variety of pH standard solutions); (B) the pH of 20 samples of
human serum was measured; (C) aqueous test, as in (A); (D) pH
measurement of 10 human whole blood samples, followed by a slope
determination (WB 1); (E) a repeat of step (D) for a second blood
sample (WB 2); (F) a repeat of step (D) for a third blood sample
(WB 3); (G) a repeat of the aqueous test of step (A).
[0087] The results of this test are given in Table 1. The average
readings of each of the seven sensors are displayed along with
standard deviation and % cv, measured against the results of a
control pH test run on the same samples using a commercially
available pH sensor (Ciba Corning Diagnostics Corp., 200 series
glass pH electrode). The results show good precision and accuracy
of pH measurement carried out in accordance with the ion selective
pH sensor of the present invention. Selectivity of the pH sensor of
the present invention, with respect to lithium, sodium, potassium,
magnesium, and calcium were determined using the fixed interference
method. Selectivity, slope, and linearity of the sensor was
good.
EXAMPLE 9
[0088] The five (5) day whole blood and serum study of Example 8
was carried out using potassium sensors using chips fabricated in
accordance with Example 5. Four potassium sensors were fabricated.
On day 1, potentiometric selectivity coefficients were determined
using the separate solution method. Results were similar to
conventional K.sup.+ electrodes. On days 24, the test sequence
described in Example 8 was carried out, with the exception that
step A was carried out using 644 Cal and 644 Slope solutions,
commercially available from Ciba Corning Diagnostics of Medfield,
Mass. and potassium was measured rather than pH. The results of
this test are given in Tables 2 and 3. The average readings of each
of the four sensors are displayed along with standard deviation and
% CV, measured against the results of a control potassium test run
on the same samples using a commercially available potassium sensor
(Ciba Coming Diagnostics Corp. 200 series potassium electrode). The
accuracy and precision of the blood and serum feasibility test was
very good. Slope, linearity, and selectivity coefficients were also
good.
EXAMPLE 10
[0089] The five day whole blood and serum study described in
Example 8 was conducted for sodium sensors using chips fabricated
in accordance with Example 6. Sample chambers were constructed as
in Example 8. The slope and calibration solutions described in
Example 9 were used. The control sensor was a commercially
available sodium sensor (Ciba Corning Diagnostics Corp. 200 series
glass sodium sensor). Table 4 gives average precision values for 5
sensors fabricated according to this example. The results are very
good. Slope, linearity, and selectivity were also good.
EXAMPLE 11
[0090] The five day whole blood and serum study described in
Example 8 was conducted for calcium sensors including chips
fabricated in accordance with Example 7. Five sensors were
fabricated. Sample chambers were constructed in accordance with
Example 8. The slope and calibration solutions were 634 cal and 634
slope solutions, commercially available from Ciba Corning
Diagnostics Corp. Table 5 lists average precision values. Precision
and accuracy are very good. Linearity, slope and selectivity were
also good.
EXAMPLE 12
[0091] Transference number determinations in the MAPTAC/MMA
membrane material fabricated in accordance with Example 2, were
carried out. Free-standing MAPTAC/MMA was formed by drop casting
from a 5 weight percent solution in ethanol, similar to the drop
casting method described in Example 3. The free-standing membranes,
after air-drying, had a thickness of approximately 82 mm. The
membranes were soaked in 160 mM solution of NaCl for about 30
minutes, and swelled to about 2.1 times their dry weight as a
result. Circular sections were cut out of the free-standing
membranes and mounted in the well-known Phillips bodies. The fill
solution was the same as the soak solution and a silver/silver
chloride internal reference was used. EMF measurements were made in
beakers with a saturated KCl calomel reference electrode.
Transference numbers were determined by the EMF method whereby
membrane potentials are measured using electrolyte concentrations
C1 and C2 on either side of the membrane. The concentration of NaCl
on one side was kept constant at 160 mM and the concentration C2 of
NaCl or KNO.sub.3 on the other side was varied. Reference to this
well-known method may be found in "Transport Phenomena in
Membranes", by N. Lakshminarayanaiah, New York, Academic Press,
(1969). Results are tabulated in Table 6. Appreciable cationic as
well as anionic transport in the films tested was observed. Ionic
transport was also observed to be a non-selective phenomenon, as
evidenced by the similarity in the results when NaCl is replaced by
KNO.sub.3.
EXAMPLE 13
[0092] A pH sensor was prepared in accordance with Example 4. A
25/75 weight ratio of MAPTAC/MMA in ethanol was spun cast on the
chip for 30 seconds at 750 RPM. The chip was air dried. A pH
membrane was cast atop the chip in accordance with Example 4. Using
6200C Permanent Mending Tape from 3M Corporation of St. Paul,
Minn., the tape was pressed atop the chip and slowly removed by
pulling upwards at an angle approximately perpendicular to the
surface of the chip. Adhesion was observed to be good. Aqueous
performance was tested over 40 days and was very good.
[0093] The preceding examples are set forth to illustrate specific
embodiments of the invention and are not intended to limit the
scope of the invention. Additional embodiments and advantages
within the scope of the claimed invention, for example measuring
electoactive species other than simple inorganic ions, will be
apparent to those of ordinary skill in the art.
1TABLE 1 pH: WHOLE BLOOD AND SERUM SENSOR NO. 1 2 3 4 5 6 7 CONTROL
Day 2: serum avg 8.061587 8.056022 8.072486 8.079076 8.098774
8.071817 8.057097 8.005298 SD 0.012465 0.010118 0.014113 0.015777
0.013251 0.015623 0.013466 0.011889 % cv 0.154619 0.125592 0.174827
0.195283 0.163619 0.193556 0.167135 0.148515 WB 1 avg 7.706525
7.695725 7.701741 7.68968 7.693139 7.698948 7.694457 7.603658 SD
0.009755 0.007797 0.008811 0.019299 0.016945 0.018739 0.015882
0.016429 % cv 0.126575 0.101321 0.114402 0.250968 0.220263 0.243398
0.206411 0.216065 WB 2 avg 7.699835 7.684835 7.692228 7.684354
7.68996 7.694301 7.688545 7.574038 SD 0.00237 0.002147 0.001877
0.002363 0.003676 0.002652 0.002929 0.002591 % cv 0.030786 0.027932
0.024396 0.030755 0.047802 0.034466 0.03809 0.034212 WB 3 avg
7.705122 7.688145 7.696397 7.688071 7.696104 7.698188 7.693823
7.5846 SD 0.001594 0.001889 0.001267 0.001848 0.002384 0.001471
0.002554 0.002283 % cv 0.020687 0.024572 0.016461 0.024042 0.030972
0.019111 0.033201 0.030099 Day 3: serum avg 8.049192 8.040586
8.043998 8.050155 8.054434 8.051513 8.042659 7.989721 SD 0.01013
0.00927 0.009733 0.009183 0.012032 0.011378 0.011184 0.009878 % cv
0.125846 0.115294 0.121002 0.11407 0.149383 0.141316 0.139062
0.123637 WB 1 avg 7.671816 7.64788 7.666324 7.661085 7.67144
7.66472 7.665776 7.566504 SD 0.015767 0.012876 0.012965 0.014039
0.019848 0.018604 0.017862 0.00688 % cv 0.205513 0.16836 0.16911
0.183256 0.258727 0.242718 0.233013 0.090932 WB 2 avg 7.710719
7.684293 7.704729 7.700617 7.710989 7.699919 7.698856 7.589368 SD
0.009972 0.007915 0.009009 0.010334 0.014195 0.011513 0.011141
0.007044 % cv 0.129324 0.103 0.116927 0.134196 0.184085 0.149524
0.144712 0.092816 WB 3 avg 7.725511 7.701296 7.721992 7.714652
7.724535 7.714606 7.714507 1.603402 SD 0.006266 0.00385 0.005618
0.006141 0.008245 0.006667 0.00799 0.007351 % cv 0.081109 0.049998
0.072753 0.079605 0.106733 0.086421 0.103568 0.096676 Day 4 serum
avg 8.054572 8.05256 8.056934 8.062627 8.068998 8.101428 8.056291
8.000674 SD 0.009893 0.008643 0.009516 0.010136 0.01189 0.016209
0.010325 0.010781 % cv 0.12282 0.107328 0.118104 0.125717 0.147359
0.200076 0.128158 0.134749 WB 1 avg 7.653196 7.629177 7.65007
7.646547 7.653276 7.667271 7.648862 7.547893 SD 0.011171 0.006606
0.00967 0.009947 0.012524 0.013148 0.009121 0.002723 % cv 0.145962
0.086595 0.126408 0.130086 0.163642 0.171479 0.119242 0.036075 WB 2
avg 7.656357 7.623297 7.645822 7.64422 7.655154 7.700881 7.649585
7.508605 SD 0.011384 0.008108 0.007122 0.010447 0.013335 0.011147
0.013093 0.002409 % cv 0.148684 0.106358 0.093153 0.13666 0.174192
0.144755 0.171163 0.032079 WB 3 avg 7.726021 7.691833 7.7155495
7.714141 7.711244 7.772353 7.712899 7.584241 SD 0.011128 0.008903
0.011885 0.011111 0.019226 0.014096 0.013054 0.008243 % cv 0.144038
0.115751 0.154041 0.144034 0.249318 0.181362 0.169251 0.108689 avg
7.670686 7.655651 7.667248 7.663609 7.667841 7.666509 7.659115
7.584853 SD 0.011073 0.008864 0.011907 0.011031 0.01978 0.013553
0.013017 0.008274 % cv 0.144355 0.115789 0.155293 0.143942 0.257959
0.176779 0.169954 0.109082
[0094]
2TABLE 2 K+, SERUM SERUM mM CONCENTRATION PRECISION % CV SENSOR #
DAY 2 DAY 3 DAY 4 DAY 2 DAY 3 DAY 4 1 4.45 4.34 4.29 1.80 0.22 0.27
2 4.58 4.33 4.34 0.83 0.26 0.30 3 4.58 4.36 4.31 0.97 0.20 0.18 4
4.43 4.35 4.34 0.87 0.14 0.10 CONTROL 4.38 4.33 4.33 0.52 0.40
0.34
[0095]
3TABLE 3 K+, WHOLE BLOOD SENSOR NO. 1 2 3 4 CONTROL DAY 2 4.40 4.34
4.36 4.34 4.33 0.03 0.04 0.03 0.03 0.01 0.77 0.81 0.80 0.68 0.28
4.29 4.20 4.23 4.21 4.23 0.03 0.04 0.03 0.03 0.02 0.69 0.85 0.62
0.62 0.46 4.24 4.17 4.20 4.21 4.16 0.02 0.02 0.03 0.02 0.02 0.53
0.47 0.61 0.46 0.42 DAY 3 4.15 4.04 4.09 4.10 4.01 0.03 0.04 0.04
0.04 0.01 0.74 1.00 0.94 0.88 0.31 4.15 4.06 4.12 4.10 4.11 0.03
0.03 0.03 0.03 0.02 0.67 0.69 0.68 0.67 0.45 3.72 3.65 3.68 3.68
3.57 0.03 0.03 0.03 0.03 0.01 0.70 0.85 0.81 0.87 0.26 DAY 4 4.18
4.11 4.26 4.16 4.12 0.05 0.04 0.06 0.04 0.00 1.11 1.08 1.39 0.96
0.08 4.03 4.01 4.00 4.03 4.00 0.03 0.03 0.08 0.03 0.00 0.65 0.65
1.88 0.75 0.10 3.82 3.79 3.83 3.80 3.81 0.03 0.02 0.03 0.02 0.01
0.76 0.60 0.77 0.61 0.38
[0096]
4TABLE 4 Na+ SENSOR PRECISION WHOLE BLOOD SERUM +/- 1.4% +/- 0.45%
1.6 0.40 1.3 0.95 1.1 0.58 1.5 0.38
[0097]
5TABLE 5 Ca++ SENSOR PRECISION WHOLE BLOOD SERUM +/- 3.6% +/- 1.6%
1.7 2.1 1.9 0.8 1.9 2.3 2.7 1.3
[0098]
6TABLE 6 TRANSFERENCE NUMBER MEASUREMENTS C.sub.2 range slope
r.sup.2 t.sub.+ t.sub.- 0.12-0.20M 41.9 0.984 0.35 0.65 NaCl
0.12-0.20M 27.0 0.940 0.23 0.77 KNO.sub.3 10.sup.-5-1M 33.5 0.983
0.28 0.72 NaCl slope = Slope of Cell EMF r.sup.2 = Correlation
Coefficient t.sub.+ = Cation Transference Number t.sub.31 = Anion
Transference Number
* * * * *