DETECTEUR D'ESPECE A ACTIVITE REDOX ET METHODE D'UTILISATION CONNEXE

REDOX-ACTIVE SPECIES SENSOR AND METHOD OF USE THEREOF

Abrégé anglais

An amperometric membrane sensor that utilizes redox-carriers to transfer the
redox potential of an oxidizing or reducing species to an electrode. The
sensor consists
of a membrane containing a first redox carrier, and a second redox carrier in
the internal
electrolyte of a membrane amperometric sensor. One implementation of this
sensor
utilizes a quinone carrier in a liquid membrane, and a vanadate carrier in the
electrolyte to
produce a sensor that responds to chlorine and chloroamine containing aqueous
solutions.
This strategy for the construction of an amperometric sensor allows the
detection and
quantification of redox-active membrane impermeant species.

Revendications

Claims:
1. A redox relay membrane system for use with an electrode to transfer a
redox potential from a redox-active species to an electrode by redox
reactions, said redox
relay membrane system comprising:
a redox relay membrane comprising a first redox carrier and a membrane, said
membrane being impermeant to redox-active species; and
an internal electrolyte solution comprising an electrolyte and a second redox
carrier.
2. The redox relay membrane system of claim 1 wherein said first redox
carrier is selected from the group consisting of
quinone and hydroquinones including benzo-, naphtho, and anthro-quinones,
thiols and disulfides,
flavins,
metal complexes of porphyrins,
metal complexes of phthalocyanins,
ferrocene and other neutral transition complexes of cyclopentadiene
derivatives,
and metal complexes of dithiolenes.
3. The redox relay membrane system of claim 2 wherein said first redox
carrier comprises a quinone.
4. The redox relay membrane system of claim 2 wherein said second redox
carrier comprises an inorganic species, said inorganic species characterized
as being
oxidized or reduced by said first redox carrier and being oxidized or reduced
by an
electrode.
22

5. The redox relay membrane system of claim 3 wherein said second redox
carrier is selected from the group consisting of
transition metal cations including, chromium(3+), manganese (2+), iron (2+ and
3+), cobalt (2+ and 3+), nickel (2+), copper (2+), or zinc(2+); oxo, hydroxo,
chloro,
bromo, amine, azido, thiocyanato, and
cyano complex ions of vanadium, chromium, molybdenum, manganese, rhenium,
iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium,
platinum, copper;
silver, gold and
oxyanions of sulfur, arsenic, antimony, chlorine, and bromine.
6. The redox relay membrane system of claim 5 wherein said second redox
carrier is ferrocyanide anion or trivalent vanadium oxyanion.
7. The redox relay membrane system of claim 4 wherein said membrane
comprises a supported liquid membrane.
8. The redox relay membrane system of claim 6 wherein said membrane
comprises a supported liquid membrane.
9. The redox relay membrane system of claim 7, wherein the supported
liquid membrane comprises a porous support polymer comprising a solvent.
10. The redox relay membrane system of claim 8, wherein the supported
liquid membrane comprises a porous support polymer comprising a solvent.
11. The redox relay membrane system of claim 9, wherein the porous support
polymer comprises a microporous polycarbonate membrane and the solvent is
selected
from the group consisting of o-nitrophenyl octyl ether, dioctyl adipate,
adipate esters,
sebacate esters, phthalate esters, glycol esters, low volatility ethers, low
volatility
aromatic and aliphatic hydrocarbons, trimellitic acid esters, phosphate
triesters,
chlorinated paraffins and mixtures thereof.
23

12. The redox relay membrane system of claim 10, wherein the porous
support polymer comprises a microporous polycarbonate membrane and the solvent
is
selected from the group consisting of o-nitrophenyl octyl ether, dioctyl
adipate, adipate
esters, sebacate esters, phthalate esters, glycol esters, low volatility
ethers, low volatility
aromatic and aliphatic hydrocarbons, trimellitic acid esters, phosphate
triesters,
chlorinated paraffins, and mixtures thereof.
13. The redox relay membrane system of claim 7, wherein the supported
liquid membrane comprises a plasticized polymer.
14. The redox relay membrane system of claim 8, wherein the supported
liquid membrane comprises a plasticized polymer.
15. The redox relay membrane system of claim 13, wherein the plasticized
polymer comprises poly(vinyl chloride).
16. The redox relay membrane system of claim 14, wherein the plasticized
polymer comprises poly(vinyl chloride).
17. The redox relay membrane system of claim 15, wherein the plasticized
polymer comprises a high molecular weight poly(vinyl chloride) plasticized
with a
solvent selected from the group consisting of o-nitrophenyl octyl ether,
dioctyl adipate,
adipate esters, sebacate esters, phthalate esters, glycol esters, low
volatility ethers,
trimellitic acid esters, phosphate triesters, chlorinated paraffins, and
mixtures thereof.
18. The redox relay membrane system of claim 16, wherein the plasticized
polymer comprises a high molecular weight poly(vinyl chloride) plasticized
with a
solvent selected from the group consisting of o-nitrophenyl octyl ether,
dioctyl adipate,
adipate esters, sebacate esters, phthalate esters, glycol esters, low
volatility ethers,
trimellitic acid esters, phosphate triesters, chlorinated paraffins, and
mixtures thereof.
24

19. The redox relay membrane system of claim 17, wherein the electrolyte
comprises a Group I metal halide, nitrate, or perchlorate.
20. The redox relay membrane system of claim 18, wherein the electrolyte
comprises a Group I metal halide, nitrate, or perchlorate.
21. The redox relay membrane system of claim 19, wherein the Group I metal
halide, nitrate, or perchlorate comprises KCl, NaCl, KNO3, NaNO3, KClO4,
NaClO4 or a
mixture thereof.
22. The redox relay membrane system of claim 20, wherein the Group I metal
halide comprises KCl, NaCl, KNO3, NaNO3, KClO4, NaClO4 or a mixture thereof.
23. The redox relay membrane system of claim 21 wherein said membrane is
comprising from 0.1% to 10% by weight of a guanidinium salt.
24. The redox relay membrane system of claim 22 wherein said membrane is
comprising from 0.1% to 10% by weight of a guanidinium salt.
25. The redox relay membrane system of claim 23, wherein the guanidinium
salt comprises 1% to 5% by weight of the membrane.
26. The redox relay membrane system of claim 24, wherein the guanidinium
salt comprises 1% to 5% by weight of the membrane.

27. The redox relay membrane system of claim 25, wherein the guanidinium
salt has the formula:
<IMG>
wherein R1, R2, R3, R4, R5 and R6 are independently selected from the group
consisting of substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl,
substituted
alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted aryl,
heteroaryl and
substituted heteroaryl such that the salt has an affinity for the membrane and
X- is an
anion.
28. The redox relay membrane system of claim 26, wherein the guanidinium
salt has the formula:
<IMG>
wherein R1, R2, R3, R4, R5 and R6 are independently selected from the group
consisting of substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl,
substituted
alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted aryl,
heteroaryl and
substituted heteroaryl such that the salt has an affinity for the membrane and
X- is an
anion.
29. The redox relay membrane system of claim 27, wherein X- is selected
from the group consisting of chloride, bromide, fluoride, iodide, hydroxide,
acetate,
carbonate, sulfate and nitrate and combinations thereof.
30. The redox relay membrane system of claim 28, wherein X- is selected
from the group consisting of chloride, bromide, fluoride, iodide, hydroxide,
acetate,
carbonate, sulfate and nitrate and combinations thereof.
26

31. The redox relay membrane system of claim 29, wherein R1, R2, R3, R4,
R5 and R6 are independently selected from the group consisting of hydrogen, C1-
30
alkyl, and aryl.
32. The redox relay membrane system of claim 30, wherein R1, R2, R3, R4,
R5 and R6 are independently selected from the group consisting of hydrogen, C1-
30
alkyl, and aryl.
33. The redox relay membrane system of claim 31, wherein the guanidinium
salt is not covalently bonded to the membrane.
34. The redox relay membrane system of claim 32, wherein the guanidinium
salt is not covalently bonded to the membrane.
35. The redox relay membrane system of any one of claims 1 to 34 wherein
said first redox carrier and said second redox carrier are selected such that
said first redox
carrier is oxidized and said second redox carrier is oxidized to permit
measurement of an
oxidizing species.
36. The redox relay membrane system of any one of claims 1 to 34 wherein
said first redox carrier and said second redox carrier are selected such that
said first redox
carrier is reduced and said second redox carrier is reduced to permit
measurement of a
reducing species.
37. An amperometric sensor combination comprising:
a redox relay membrane comprising a first redox carrier and a membrane, said
membrane being impermeant to redox-active species;
an internal electrolyte solution comprising an electrolyte and a second redox
carrier; and
an electrode.
27

38. The amperometric sensor combination of claim 37, wherein said electrode
comprises:
an inert cathode; and
a reversible anode.
39. The amperometric sensor combination of claim 38, wherein the inert
cathode is selected from the group consisting of silver, palladium, iridium,
rhodium,
ruthenium, and osmium and alloys thereof and the reversible anode is selected
from the
group consisting of lead/lead sulfate, silver/silver oxide-hydroxide,
silver/silver chloride
and lead/lead oxide-hydroxide.
40. The amperometric sensor combination of claim 39, wherein the inert
cathode is selected from the group consisting of silver, palladium, and
iridium, and alloys
thereof and the reversible anode is selected from the group consisting of
lead/lead sulfate,
silver/silver oxide-hydroxide, silver/silver chloride and lead/lead oxide-
hydroxide.
41. The combination of claim 38, wherein the inert cathode comprises gold or
platinum and the reversible anode is an Ag/AgCl electrode.
42. The combination of claim 41 wherein said first redox carrier is selected
from the group consisting of
quinone and hydroquinones including benzo-, naphtho, and anthro-quinones,
thiols and disulfides,
flavins,
metal complexes of porphyrins,
metal complexes of phthalocyanins,
ferrocene and other neutral transition complexes of cyclopentadiene
derivatives,
and metal complexes of dithiolenes.
43. The combination of claim 42 wherein said first redox carrier comprises a
quinone.
28

44. The combination of claim 42 wherein said second redox carrier comprises
an inorganic species, said inorganic species characterized as being oxidized
or reduced by
said first redox carrier and being oxidized or reduced by the electrode.
45. The combination of claim 43 wherein said second redox carrier is selected
from the group consisting of
transition metal cations including, chromium(3+), manganese (2+), iron (2+ and
3+), cobalt (2+ and 3+), nickel (2+), copper (2+), or zinc(2+); oxo, hydroxo,
chloro,
bromo, amine, azido, thiocyanato, and
cyano complex ions of vanadium, chromium, molybdenum, manganese, rhenium,
iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium,
platinum, copper,
silver, gold and
oxyanions of sulfur, arsenic, antimony, chlorine, and bromine.
46. The combination of claim 45 wherein said second redox carrier is
ferrocyanide or trivalent vanadium oxyanion.
47. The combination of claim 44 wherein said membrane comprises a
supported liquid membrane.
48. The combination of claim 46 wherein said membrane comprises a
supported liquid membrane.
49. The sensor of claim 47, wherein the supported liquid membrane comprises
a porous support polymer comprising a solvent.
50. The combination of claim 48, wherein the supported liquid membrane
comprises a porous support polymer comprising a solvent.
29

51. The combination of claim 49, wherein the porous support polymer
comprises a microporous polycarbonate membrane and the solvent is selected
from the
group consisting of o-nitrophenyl octyl ether, dioctyl adipate, adipate
esters, sebacate
esters, phthalate esters, glycol esters, low volatility ethers, low volatility
aromatic and
aliphatic hydrocarbons, trimellitic acid esters, phosphate triesters,
chlorinated paraffins,
and mixtures thereof.
52. The combination of claim 50, wherein the porous support polymer
comprises a microporous polycarbonate membrane and the solvent is selected
from the
group consisting of o-nitrophenyl octyl ether, dioctyl adipate, adipate
esters, sebacate
esters, phthalate esters, glycol esters, low volatility ethers, low volatility
aromatic and
aliphatic hydrocarbons, trimellitic acid esters, phosphate triesters,
chlorinated paraffins,
and mixtures thereof.
53. The combination of claim 47, wherein the supported liquid membrane
comprises a plasticized polymer.
54. The combination of claim 48, wherein the supported liquid membrane
comprises a plasticized polymer.
55. The combination of claim 53, wherein the plasticized polymer comprises
poly(vinyl chloride).
56. The combination of claim 54, wherein the plasticized polymer comprises
poly(vinyl chloride).
57. The combination of claim 55, wherein the plasticized polymer comprises a
high molecular weight poly(vinyl chloride) plasticized with a solvent selected
from the
group consisting of o-nitrophenyl octyl ether, dioctyl adipate, adipate
esters, sebacate
esters, phthalate esters, glycol esters, low volatility ethers, trimellitic
acid esters,
phosphate triesters, chlorinated paraffins, and mixtures thereof.

58. The combination of claim 56, wherein the plasticized polymer comprises a
high molecular weight poly(vinyl chloride) plasticized with a solvent selected
from the
group consisting of o-nitrophenyl octyl ether, dioctyl adipate, adipate
esters, sebacate
esters, phthalate esters, glycol esters, low volatility ethers, trimellitic
acid esters,
phosphate triesters, chlorinated paraffins, and mixtures thereof.
59. The combination of claim 57, wherein the electrolyte comprises a Group I
metal halide, nitrate, or perchlorate.
60. The combination of claim 58, wherein the electrolyte comprises a Group I
metal halide, nitrate, or perchlorate.
61. The combination of claim 59, wherein the Group I metal halide, nitrate, or
perchlorate comprise KCl, NaCl, KNO3, NaNO3, KClO4, NaClO4 or a mixture
thereof.
62. The combination of claim 60, wherein the Group I metal halide, nitrate, or
perchlorate comprise KCl, NaCl, KNO3, NaNO3, KClO4, NaClO4 or a mixture
thereof.
63. The combination of claim 61 wherein said membrane is comprising from
0.1% to 10% by weight of a guanidinium salt.
64. The combination of claim 62 wherein said membrane is comprising from
0.1% to 10% by weight of a guanidinium salt.
65. The combination of claim 63, wherein the guanidinium salt comprises 1%
to 5% by weight of the membrane.
66. The combination of claim 64, wherein the guanidinium salt comprises 1
to 5% by weight of the membrane.
31

67. The combination of claim 65, wherein the guanidinium salt has the
formula:
<IMG>
wherein R1, R2, R3, R4, R5 and R6 are independently selected from the group
consisting of substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl,
substituted
alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted aryl,
heteroaryl and
substituted heteroaryl such that the salt has an affinity for the membrane and
X- is an
anion.
68. The combination of claim 66, wherein the guanidinium salt has the
formula:
<IMG>
wherein R1, R2, R3, R4, R5 and R6 are independently selected from the group
consisting of substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl,
substituted
alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted aryl,
heteroaryl and
substituted heteroaryl such that the salt has an affinity for the membrane and
X- is an
anion.
69. The combination of claim 67, wherein X- is selected from the group
consisting of chloride, bromide, fluoride, iodide, hydroxide, acetate,
carbonate, sulfate
and nitrate and combinations thereof.
70. The combination of claim 68, wherein X- is selected from the group
consisting of chloride, bromide, fluoride, iodide, hydroxide, acetate,
carbonate, sulfate
and nitrate and combinations thereof.
32

71. The combination of claim 69, wherein R1, R2, R3, R4, R5 and R6 are
independently selected from the group consisting of hydrogen, C1-30 alkyl, and
aryl.
72. The combination of claim 70, wherein R1, R2, R3, R4, R5 and R6 are
independently selected from the group consisting of hydrogen, C1-30 alkyl, and
aryl.
73. The combination of claim 71, wherein the guanidinium salt is not
covalently bonded to the membrane.
74. The combination of claim 72, wherein the guanidinium salt is not
covalently bonded to the membrane.
75. The combination of claim 73, wherein said combination is formed on a
printed circuit board, wherein the membrane is sealed at its outer edges to
prevent
communication between the electrolyte and a medium in which said redox-active
species
is sensed except through the membrane.
76. The combination of claim 74, wherein said combination is formed on a
printed circuit board and said membrane is sealed at its outer edges to
prevent
communication between the electrolyte and a medium in which said redox-active
species
is sensed except through the membrane.
77. The combination of any one of claims 41 to 76 wherein said first redox
carrier and said second redox carrier are selected such that said first redox
carrier is
oxidized and said second redox carrier is oxidized to permit measurement of an
oxidizing
species.
78. The combination of any one of claims 41 to 76 wherein said first redox
carrier and said second redox carrier are selected such that said first redox
carrier is
reduced and said second redox carrier is reduced to permit measurement of a
reducing
species.
33

79. An amperometric sensor combination, comprising:
an inert cathode and a reversible anode printed on a gas-impervious circuit
board
substrate;
a well surrounding the cathode and the anode;
a redox relay membrane covering the well, said redox-relay membrane
comprising a first redox carrier and a membrane, said membrane being
impermeant to
redox-active species; and
a hydrogel in the well, wherein the hydrogel comprises an electrolyte and a
second redox carrier.
80. The combination of claim 79 wherein said first redox carrier is selected
from the group consisting of
quinone and hydroquinones including benzo-, naphtho, and anthro-quinones,
thiols and disulfides,
flavins,
metal complexes of porphyrins,
metal complexes of phthalocyanins,
ferrocene and other neutral transition complexes of cyclopentadiene
derivatives,
and metal complexes of dithiolenes.
81. The combination of claim 79 wherein said first redox carrier comprises a
quinone.
82. The combination of claim 81 wherein said second redox carrier comprises
an inorganic species, said inorganic species characterized as being oxidized
or reduced by
said first redox carrier and being oxidized or reduced by the electrode.
34

83. The combination of claim 81 wherein said second redox carrier is selected
from the group consisting of
transition metal cations including, chromium(3+), manganese (2+), iron (2+ and
3+), cobalt (2+ and 3+), nickel (2+), copper (2+), or zinc(2+); oxo, hydroxo,
chloro,
bromo, amine, azido, thiocyanato, and
cyano complex ions of vanadium, chromium, molybdenum, manganese, rhenium,
iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium,
platinum, copper,
silver, gold and
oxyanions of sulfur, arsenic, antimony, chlorine, and bromine.
84. The combination of claim 83 wherein said second redox carrier is
ferrocyanide or trivalent vanadium.
85. The combination of claim 84, wherein the well defining the electrolyte
volume comprises a laminate material having a hole, wherein the hole is placed
over the
anode and the cathode.
86. The combination of claim 85, further comprising a guard ring deposited on
the gas-impervious substrate, wherein the redox-active species impermeant
membrane
also covers the guard ring.
87. The combination of claim 86, wherein the hydrogel is selected from the
group consisting of cross-linked acrylates, methyl methacrylates,
methacrylates,
hydryxalkyl acrylates, hydroxyalkyl(meth)acrylates, acrylamides, silicone
hydrogels,
gelatin, cellulose nitrate, cellulose, agar, and agarose and combinations
thereof.
88. The method of preparing an amperometric sensor comprising:
impregnating a redox impermeant membrane with a first redox carrier to produce
a redox relay membrane;
dissolving an electrolyte and a second redox carrier in a solvent to prepare
an
internal electrolyte solution; and

placing said internal electrolyte solution on an electrode and covering said
internal electrolyte solution with said redox-relay membrane.
89. The method of claim 88, wherein said electrode comprises:
an inert cathode; and
a reversible anode.
90. The method of claim 89, further comprising selecting the inert cathode
from the group consisting of silver, palladium, iridium, rhodium, ruthenium,
and osmium
and alloys thereof and the reversible anode is selected from the group
consisting of
lead/lead sulfate, silver/silver oxide-hydroxide, silver/silver chloride and
lead/lead oxide-
hydroxide.
91. The method of claim 90, wherein the inert cathode selected from the group
consisting of silver, palladium, and iridium, and alloys thereof and the
reversible anode is
selected from the group consisting of lead/lead sulfate, silver/silver oxide-
hydroxide,
silver/silver chloride and lead/lead oxide-hydroxide.
92. The method of claim 89, further comprising selecting gold or platinum for
the inert cathode and employing a reversible anode that is an Ag/AgCl
electrode.
93. The method of claim 92 further comprising selecting said first redox
carrier from the group consisting of
quinone and hydroquinones including benzo-, naphtho, and anthro-quinones,
thiols and disulfides,
flavins,
metal complexes of porphyrins,
metal complexes of phthalocyanins,
ferrocene and other neutral transition complexes of cyclopentadiene
derivatives,
and metal complexes of dithiolenes.
36

94. The method of claim 92 wherein said second redox carrier comprises an
inorganic species, said inorganic species characterized as being oxidized or
reduced by
said first redox carrier and being oxidized or reduced by the electrode.
95. The method of claim 94 further comprising selecting said second redox
from the group consisting of
transition metal cations including chromium(3+), manganese (2+), iron (2+ and
3+), cobalt (2+ and 3+), nickel (2+), copper (2+), or zinc(2+),
oxo, hydroxo, chloro, bromo, amine, azido, thiocyanato, and cyano complex ions
of vanadium, chromium, molybdenum, manganese, rhenium, iron, ruthenium,
osmium,
cobalt, rhodium, iridium, nickel, palladium, platinum, copper, silver, gold
and
oxyanions of sulfur, arsenic, antimony, chlorine, bromine.
96. The method of claim 93, further comprising depositing said amperometric
sensor on a printed circuit board, and sealing said membrane is sealed at its
outer edges to
prevent communication between the electrolyte and a medium in which said redox-
active
species is sensed except through the membrane.
97. The method of claim 96, wherein depositing comprises printing the anode
and cathode onto the substrate using a method for printing circuit boards.
98. The method of claim 96 further comprising depositing a guard ring onto
the substrate.
99. The method of claim 96 further comprising forming a well around the
anode and the cathode and covering the well with the membrane to define an
electrolyte
volume.
100. The method of claim 99, wherein placing an electrolyte solution
comprising an electrolyte and a second redox carrier between the anode and the
cathode
comprises adding the electrolyte to the well.
37

101. The method of claim 100, wherein adding the electrolyte solution to the
well comprises adding the electrolyte to the well as a solution.
102. The method of claim 101, wherein the solution is allowed to dry.
103. The method of claim 100, wherein adding the electrolyte solution to the
well comprises forming a hydrogel in the well.
104. The method of claim 103, wherein the hydrogel is selected from the group
consisting of cross-linked acrylates, methyl methacrylates, methacrylates,
hydryxalkyl
acrylates, hydroxyalkyl(meth)acrylates, acrylamides, silicone hydrogels,
gelatin,
cellulose nitrate, cellulose, agar, and agarose and methods thereof.
105. The method of claim 99, wherein forming a well around the anode and the
cathode comprises placing a laminating material comprising a hole onto the
substrate
such that the hole is disposed over the anode and cathode.
106. The method of claim 99, wherein covering the well with the membrane
comprises depositing a plasticized PVC membrane material dissolved in a
volatile
solvent over the well.
107. The method of claim 106, further comprising first covering the well with
a
layer of microporous cellulose acetate and then depositing the PVC membrane
material
onto the microporous cellulose acetate.
108. A method of preparing an amperometric sensor, the method comprising
selecting a guanidinium salt, preparing a solvent containing the guanidinium
salt,
imbibing a first redox-active species impermeant membrane with the solvent,
forming a
reversible anode and an inert cathode, applying an electrolyte solution
comprising an
electrolyte and a second redox carrier over the anode and the cathode,
allowing the
38

solution to evaporate and covering both electrodes with the redox-active
species
impermeant membrane, such that the membrane prevents communication between the
electrolyte and an ambient environment except through the membrane.
109. The method of claim 108, wherein the electrolyte layer is a hydrogel.
110. The method of claim 109, wherein the hydrogel is selected from the group
consisting of gelatin, cellulose nitrate, cellulose, agar and agarose.
111. The method of claim 109 wherein the hydrogel is selected from the group
consisting of cross-linked acrylates, methyl methacrylates, methacrylates,
hyroxyalkyl
acrylates, hydroxyalkyl(meth)acrylates and acrylamides.
112. A method of measuring a redox-active species in a liquid sample, said
method comprising relaying a redox potential from said sample through a redox
relay
membrane, relaying said redox potential through an electrolyte solution, said
electrolyte
solution comprising an electrolyte and a second redox carrier and applying an
electrical
potential to an electrode.
113. The method of claim 112 further comprising removing an ionic product of
an electrode reaction from said electrolyte solution using a guanidinium salt.
114. The method of claim 113 wherein the redox active species comprise
chlorine, hypochlorous acid, hypochlorite ion, other chlorine oxyacids and
their
conjugate bases, other halogens, oxyhaloacids and their conjugate bases,
monochloroamine, dichloramine, trichloroamine, other chloroamines derived from
organic amines, other haloamine species, hydrogen peroxide, hydroperoxyl
anion,
peroxide dianion, sulfur dioxide, bisulfite anion, sulfite dianion, thiosufate
dianion,
hydrogen sulfide, hydrosulfide anion, sulfide dianion, mercaptans and their
conjugate
bases, or organic disulfides.
39

115. The method of claim 113 wherein said first redox carrier and said second
redox carrier are selected such that said first redox carrier is oxidized and
said second
redox carrier is oxidized to permit measurement of an oxidizing species.
116. The method of claim 113 wherein said first redox carrier and said second
redox carrier are selected such that said first redox carrier is reduced and
said second
redox carrier is reduced to permit measurement of a reducing species.
117. A sensor for aqueous chlorine and chlorine-ammonia mixtures comprised
of a supported liquid membrane consisting of a microporous polycarbonate
support
membrane containing 2-methylnaphthoquinone dissolved in ortho-nitrophenyl
octyl ether
at a concentration between 0.1 and 5% (wt/wt), in contact with an agar (0.1-
2.0 wt%)
hydrogel electrolyte containing sodium meta-vanadate (5-50 millimolar) and
potassium
chloride (0.1-1.0 molar), in separate contact with a silver/silver chloride
anode and a
gold cathode.

Description

CA 02495534 2005-02-04
SCS/seh 7293-70302-Ol 01/14/05 EXPRESS MAIL LABEL NO. EV514607032US
DATE OF DEPOSIT: January 14, 2005
REDOX-ACTIVE SPECIES SENSOR AND METHOD OF USE THEREOF
FIELD
The present invention relates to a redox-carrier membrane system for detecting
and quantifying redox-active membrane-impermeant species by means of an
amperometric membrane sensor based on the redox-Garner membrane system.
Additionally, a method of detecting and quantifying redox-active impermeant
species is
provided.
BACKGROUND
Amperometric membrane sensors are well known. For example, a Clark cell can
be used to detect dissolved oxygen or other oxidizing small molecules [see,
for example,
Janata, J., Principles of Chemical Sensors, Plenum Publishing, 1991 and
Polarographic
Oxygen Sensors, Chapter 4,Gnaiger, E. and Forstner, H. (Eds.), Springer-
Verlag, 1983].
Such sensors consist of a membrane, an internal electrolyte and an electrode.
The species
detected diffuses through the membrane and the internal electrolyte and is
reduced or
oxidized at the electrode to generate a current that is proportional to the
concentration of
the species in the external solution. The specificity of these sensors is
determined by the
selectivity of the diffusion through the membrane layer. In an oxygen
electrode, the
oxygen molecule can diffuse to the electrode to generate the current due to
reduction at
the electrode. At the same time, ionic species are repelled by the membrane
and
therefore cannot contribute to the current generated.
Chlorine sensors are known to operate on the same principle [Janata, op cit.].
In
these sensors, the membrane must allow the free diffusion of chlorine. Since
chlorine in
water forms an equilibrium mixture of dissolved chlorine and hypochlorous
acid, some
chlorine sensors also detect the hypochlorous acid that diffuses through the
membrane.
Hypochlorous acid is a weak acid (pKa = 7.49; Pourbaix, Atlas of
Electrochemical
Equilibria in Aqueous Solutions, Section 20.2, Pergamon Press, 1966) and
therefore the
concentration of this species depends on the pH. The conjugate base,
hypochlorite anion,
is ionic and is therefore repelled by the membrane of conventional chlorine
sensors. The
result is that conventional amperometric chlorine sensors do not function in
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solution. In fact, the sensitivity of the sensors falls off rapidly as the pH
increases above
pH 7. Such amperometric chlorine sensors are also insensitive to other
chlorine species.
For example, in a mixture of chlorine and ammonia, mono-, di-, and tri-
chloroamines are
formed [Soulard, M.; Bloc, F. Hatterer J. Chem. soc. Dalton 1981, 2300-2310].
These
species are similarly repelled by the membrane of a conventional chlorine
sensor and do
not produce a signal.
Chlorination and chloramination of domestic drinking water supplies is widely
practiced as part of a disinfection process to produce potable water
(Alternative
Disinfectants and Oxidants Guidance Manual, United States Environmental
Protection
Agency,1999, EPA 815-R-99-014]. Determination of the levels of chloroamines in
disinfection processes is currently done using colorimetric or titrimetric
methods because
the currently available chlorine sensors do not detect chloroamines. This is
tedious and
cannot be done in a continuous fashion.
Amperometric biosensors have also been developed for the measurement of
biological species such as glucose. These so-called biosensors have
immobilized enzyme
membranes. Some of the drawbacks of the current amperometric biosensors have
been
noted and analyzed. For example, direct electron transfer between enzymes and
electrode
surfaces is rarely encountered because the active site of redox enzymes is
generally
buried within the body of the protein. Hence, electron transfer is usually
performed
according to a 'shuttle' mechanism involving free-diffusing electron-
transferring redox
species. These redox mediators must diffuse freely between the active sites of
the
enzymes and the electrode surface through a predominantly aqueous layer as
required for
the stability and reactivity of the enzyme. Hence, these electrodes show a
limited long-
term stability as a consequence of the unavoidable leaking of the mediator
from the
sensor surface.
These amperometric enzyme electrodes are very different from amperometric
membrane sensors of the type we describe, with the exception that they also
use redox
relays. The rationale for these biosensors is to use enzymatic specificity
based on
specific molecular recognition of a biological substrate. On a fundamental
level,
therefore, these enzyme electrodes require enzymatic catalysis in order to
function. Of
course, the sensors must also be robust. Clearly, naturally occurring enzymes
are not
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robust enough to have utility in sensors, as their functionality depends
entirely upon their
three dimensional structure and this is dependent upon factors including
temperature, pH
and salt concentration.
In a related application, redox relay membranes have been described as
biomimetic models of reaction coupling between two aqueous compartments
[Anderson,
S.S.; Lyle, LG.; Petrson, R. Nature,1976, 259, 147-148; Grimaldi, J.J.;
Bioleau, S.;
Lehn, J.-M. Nature 1977, 265, 229-230]. As the name suggests, the redox relays
mimic
redox relays that are known to occur in biological systems, such as electron
transfer
during respiration. In both the natural system and the biomimetic models, the
electron
transfer is actually a cascade; with a drop of energy occurring along the
relay.
Accordingly, the systems have to be set up in such as fashion that they drive
the process
toward the product. An electron acceptor terminates the systems. In the
biomimetic
models electron transfer is detected using the W spectrum of the ferri-
ferrocyanide pair.
Neither paper describes what happens as the driving force falls off, but
presumably, the
reduction of the product ceases and hence a constant level of product is
maintained. In
sensors, it is the drop in driving force that is measured. Hence, while these
redox relay
models are useful for studying biological electron transfer systems, they lack
utility as
sensors for redox-active species.
It is an object of the present invention to overcome the deficiencies in the
prior
art.
SUMMARY
A redox relay membrane system for use with an electrode to transfer a redox
potential from a redox-active species to an electrode by redox reactions is
provided in one
embodiment of the invention. The redox relay membrane system comprises:
a redox relay membrane comprises a first redox carrier and a membrane, the
membrane being impermeant to redox-active species; and
an internal electrolyte solution comprises an electrolyte and a second redox
carrier.
In another aspect of the redox relay membrane system the first redox Garner is
selected from the group consisting of
3

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quinone and hydroquinones including benzo-, naphtho, and anthro-quinones,
thiols and disulfides,
flavins,
metal complexes of porphyrins,
metal complexes of phthalocyanins,
ferrocene and other neutral transition complexes of cyclopentadiene
derivatives,
and metal complexes of dithiolenes.
In another aspect of the redox relay membrane system the first redox carrier
comprises a quinone.
In another aspect of the redox relay membrane system the second redox carrier
comprises an inorganic species, the inorganic species characterized as being
oxidized or
reduced by the first redox carrier and being oxidized or reduced by an
electrode.
In another aspect of the redox relay membrane system the second redox carrier
is
selected from the group consisting of
transition metal cations including, chromium(3+), manganese (2+), iron (2+ and
3+), cobalt (2+ and 3+), nickel (2+), copper (2+), or zinc(2+); oxo, hydroxo,
chloro,
bromo, amine, azido, thiocyanato, and
cyano complex ions of vanadium, chromium, molybdenum, manganese, rhenium,
iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium,
platinum, copper,
silver, gold and
oxyanions of sulfur, arsenic, antimony, chlorine, and bromine.
In another aspect of the redox relay membrane system the second redox carrier
is
ferrocyanide anion or trivalent vanadium oxyanion.
In another aspect of the redox relay membrane system the membrane comprises a
supported liquid membrane.
In another aspect of the redox relay membrane system the supported liquid
membrane comprises a porous support polymer comprises a solvent.
In another aspect of the redox relay membrane system the porous support
polymer
comprises a microporous polycarbonate membrane and the solvent is selected
from the
group consisting of o-nitrophenyl octyl ether, dioctyl adipate, adipate
esters, sebacate
esters, phthalate esters, glycol esters, low volatility ethers, low volatility
aromatic and
4

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aliphatic hydrocarbons, trimellitic acid esters, phosphate triesters,
chlorinated paraffins
and mixtures thereof.
In another aspect of the redox relay membrane system the supported liquid
membrane comprises a plasticized polymer.
In another aspect of the redox relay membrane system the plasticized polymer
comprises polyvinyl chloride).
In another aspect of the redox relay membrane system the plasticized polymer
comprises a high molecular weight polyvinyl chloride) plasticized with a
solvent
selected from the group consisting of o-nitrophenyl octyl ether, dioctyl
adipate, adipate
esters, sebacate esters, phthalate esters, glycol esters, low volatility
ethers, trimellitic acid
esters, phosphate triesters, chlorinated paraffins, and mixtures thereof.
In another aspect of the redox relay membrane system the electrolyte comprises
a
Group I metal halide, nitrate, or perchlorate.
In another aspect of the redox relay membrane system the Group I metal halide,
nitrate, or perchlorate comprise KCI, NaCI, KN03, NaN03, KC104, NaC104 or a
mixture
thereof.
In another aspect of the redox relay membrane system the membrane comprises
from 0.1 % to 10% by weight of a guanidinium salt.
In another aspect of the redox relay membrane system the guanidinium salt
comprises 1% to 5% by weight of the membrane.
In another aspect of the redox relay membrane system the guanidinium salt has
the formula:
~~o-RS ~
R~.N~N-R4
i i
R2 R3
wherein R1, R2, R3, R4, RS and R6 are independently selected from the group
consisting of substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl,
substituted
alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted aryl,
heteroaryl and
substituted heteroaryl such that the salt has an affinity for the membrane and
X- is an
anion.

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In another aspect of the redox relay membrane system X- is selected from the
group consisting of chloride, bromide, fluoride, iodide, hydroxide, acetate,
carbonate,
sulfate and nitrate and combinations thereof.
In another aspect of the redox relay membrane system R1, R2, R3, R4, R5 and R6
are independently selected from the group consisting of hydrogen, C1-30 alkyl,
and aryl.
In another aspect of the redox relay membrane system the guanidinium salt is
not
covalently bonded to the membrane.
In another aspect of the redox relay membrane system the first redox carrier
and
the second redox carrier are selected such that the first redox carrier is
oxidized and the
second redox earner is oxidized to permit measurement of an oxidizing species.
In another aspect of the redox relay membrane system the first redox carrier
and
the second redox carrier are selected such that the first redox carrier is
reduced and the
second redox carrier is reduced to permit measurement of a reducing species.
In another embodiment of the invention, an amperometric sensor combination is
provided that comprises:
a redox relay membrane comprises a first redox earner and a membrane, the
membrane being impermeant to redox-active species;
an internal electrolyte solution comprises an electrolyte and a second redox
carrier; and
an electrode.
In another aspect of the combination the electrode comprises:
an inert cathode; and
a reversible anode.
In another aspect of the combination the inert cathode is selected from the
group
consisting of silver, palladium, iridium, rhodium, ruthenium, and osmium and
alloys
thereof and the reversible anode is selected from the group consisting of
lead/lead sulfate,
silver/silver oxide-hydroxide, silver/silver chloride and leadllead oxide-
hydroxide.
In another aspect of the combination the inert cathode is selected from the
group
consisting of silver, palladium, and iridium, and alloys thereof and the
reversible anode is
selected from the group consisting of lead/lead sulfate, silver/silver oxide-
hydroxide,
silver/silver chloride and lead/lead oxide-hydroxide.
6

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In another aspect of the combination the inert cathode comprises gold or
platinum
and the reversible anode is an Ag/AgCI electrode.
In another aspect of the combination the first redox Garner is selected from
the
group consisting of
quinone and hydroquinones including benzo-, naphtho, and anthro-quinones,
thiols and disulfides,
flavins,
metal complexes of porphyrins,
metal complexes of phthalocyanins,
ferrocene and other neutral transition complexes of cyclopentadiene
derivatives,
and metal complexes of dithiolenes.
In another aspect of the combination the first redox Garner comprises a
quinone.
In another aspect of the combination the second redox Garner comprises an
inorganic species, the inorganic species characterized as being oxidized or
reduced by the
first redox Garner and being oxidized or reduced by the electrode.
In another aspect of the combination the second redox carrier is selected from
the
group consisting of
transition metal cations including, chromium(3+), manganese (2+), iron (2+ and
3+), cobalt (2+ and 3+), nickel (2+), copper (2+), or zinc(2+); oxo, hydroxo,
chloro,
bromo, amine, azido, thiocyanato, and
cyano complex ions of vanadium, chromium, molybdenum, manganese, rhenium,
iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium,
platinum, copper,
silver, gold and
oxyanions of sulfi.w, arsenic, antimony, chlorine, and bromine.
In another aspect of the combination the second redox carrier is ferrocyanide
or
trivalent vanadium oxyanion.
In another aspect of the combination the membrane comprises a supported liquid
membrane.
In another aspect of the combination the supported liquid membrane comprises a
porous support polymer comprises a solvent.
7

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In another aspect of the combination the porous support polymer comprises a
microporous polycarbonate membrane and the solvent is selected from the group
consisting of o-nitrophenyl octyl ether, dioctyl adipate, adipate esters,
sebacate esters,
phthalate esters, glycol esters, low volatility ethers, low volatility
aromatic and aliphatic
hydrocarbons, trimellitic acid esters, phosphate triesters, chlorinated
paraffins, and
mixtures thereof.
In another aspect of the combination the supported liquid membrane comprises a
plasticized polymer.
In another aspect of the combination the plasticized polymer comprises
polyvinyl
chloride).
In another aspect of the combination the plasticized polymer comprises a high
molecular weight polyvinyl chloride) plasticized with a solvent selected from
the group
consisting of o-nitrophenyl octyl ether, dioctyl adipate, adipate esters,
sebacate esters,
phthalate esters, glycol esters, low volatility ethers, trimellitic acid
esters, phosphate
triesters, chlorinated paraffins, and mixtures thereof.
In another aspect of the combination the electrolyte comprises a Group I metal
halide, nitrate, or perchlorate:
In another aspect of the combination the Group I metal halide, nitrate, or
perchlorate comprise KCl, NaCl, KN03, NaN03, KC104, NaC104 or a mixture
thereof.
In another aspect of the combination the membrane comprises from 0.1% to 10%
by weight of a guanidinium salt.
In another aspect of the combination the guanidinium salt comprises 1 % to 5%
by
weight of the membrane.
In another aspect of the combination the guanidinium salt has the formula:
t~.0+N-RS x0
R~.,N~N.R4
i i
R2 R3
wherein R1, R2, R3, R4, RS and R6 are independently selected from the group
consisting of substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl,
substituted
alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted aryl,
heteroaryl and
8

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substituted heteroaryl such that the salt has an affinity for the membrane and
X- is an
anion.
In another aspect of the combination X- is selected from the group consisting
of
chloride, bromide, fluoride, iodide, hydroxide, acetate, carbonate, sulfate
and nitrate and
combinations thereof.
In another aspect of the combination R1, R2, R3, R4, RS and R6 are
independently selected from the group consisting of hydrogen, C1-30 alkyl, and
aryl.
In another aspect of the combination the guanidinium salt is not covalently
bonded to the membrane.
In another aspect the combination is formed on a printed circuit board,
wherein
the membrane is sealed at its outer edges to prevent communication between the
electrolyte and a medium in which the redox-active species is sensed except
through the
membrane.
In another aspect of the combination the first redox carrier and the second
redox
carrier are selected such that the first redox carrier is oxidized and the
second redox
carrier is oxidized to permit measurement of an oxidizing species.
In another aspect of the combination the first redox Garner and the second
redox
carrier are selected such that the first redox carrier is reduced and the
second redox
Garner is reduced to permit measurement of a reducing species.
In another embodiment of the invention an amperometric sensor combination is
provided that comprises:
an inert cathode and a reversible anode printed on a gas-impervious circuit
board
substrate;
a well surrounding the cathode and the anode;
a redox relay membrane covering the well, the redox-relay membrane comprises a
first redox carrier and a membrane, the membrane being impermeant to redox-
active
species; and
a hydrogel in the well, wherein the hydrogel comprises an electrolyte and a
second redox Garner.
In another aspect of the combination the first redox Garner is selected from
the
group consisting of
9

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quinone and hydroquinones including benzo-, naphtho, and anthro-quinones,
thiols and disulfides,
flavins,
metal complexes of porphyrins,
metal complexes of phthalocyanins,
ferrocene and other neutral transition complexes of cyclopentadiene
derivatives,
and metal complexes of dithiolenes.
In another aspect of the combination the first redox carrier comprises a
quinone.
In another aspect of the combination the second redox Garner comprises an
inorganic species, the inorganic species characterized as being oxidized or
reduced by the
first redox carrier and being oxidized or reduced by the electrode.
In another aspect of the combination the second redox carrier is selected from
the
group consisting of
transition metal cations including, chromium(3+), manganese (2+), iron (2+ and
3+), cobalt (2+ and 3+), nickel (2+), copper (2+), or zinc(2+); 0x0, hydroxo,
chloro,
bromo, amine, azido, thiocyanato, and
cyano complex ions of vanadium, chromium, molybdenum, manganese, rhenium,
iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium,
platinum, copper,
silver, gold and
oxyanions of sulfur, arsenic, antimony, chlorine, and bromine.
In another aspect of the combination the second redox Garner is ferrocyanide
or
trivalent vanadium.
In another aspect of the combination the well defining the electrolyte volume
comprises a laminate material having a hole, wherein the hole is placed over
the anode
and the cathode.
In another aspect the combination further comprises a guard ring deposited on
the
gas-impervious substrate, wherein the redox-active species impermeant membrane
also
covers the guard ring.
In another aspect of the combination the hydrogel is selected from the group
consisting of cross-linked acrylates, methyl methacrylates, methacrylates,
hydryxalkyl

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acrylates, hydroxyalkyl(meth)acrylates, acrylamides, silicone hydrogels,
gelatin,
cellulose nitrate, cellulose, agar, and agarose and combinations thereof.
In yet another embodiment of the invention, a method of preparing an
amperometric sensor comprises:
impregnating a redox impermeant membrane with a first redox carrier to produce
a redox relay membrane;
dissolving an electrolyte and a second redox carrier in a solvent to prepare
an
internal electrolyte solution; and
placing the internal electrolyte solution on an electrode and covering the
internal
electrolyte solution with the redox-relay membrane.
In another aspect of the method, the electrode comprises:
an inert cathode; and
a reversible anode.
In another aspect the method further comprises selecting the inert cathode
from
the group consisting of silver, palladium, iridium, rhodium, ruthenium, and
osmium and
alloys thereof and the reversible anode is selected from the group consisting
of lead/lead
sulfate, silver/silver oxide-hydroxide, silver/silver chloride and lead/lead
oxide-
hydroxide.
In another aspect of the method, the inert cathode is selected from the group
consisting of silver, palladium, and iridium, and alloys thereof and the
reversible anode is
selected from the group consisting of lead/lead sulfate, silver/silver oxide-
hydroxide,
silver/silver chloride and lead/lead oxide-hydroxide.
In another aspect the method further comprises selecting gold or platinum for
the
inert cathode and employing a reversible anode that is an Ag/AgCI electrode.
In another aspect the method further comprises selecting the first redox
carrier
from the group consisting of
quinone and hydroquinones including benzo-, naphtho, and anthro-quinones,
thiols and disulfides,
flavins,
metal complexes of poiphyrins,
metal complexes of phthalocyanins,
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ferrocene and other neutral transition complexes of cyclopentadiene
derivatives,
and metal complexes of dithiolenes.
In another aspect of the method, the second redox carrier comprises an
inorganic
species, the inorganic species characterized as being oxidized or reduced by
the first
redox carrier and being oxidized or reduced by the electrode.
In another aspect, the method further comprises selecting the second redox
from
the group consisting of
transition metal cations including chromium(3+), manganese (2+), iron (2+ and
3+), cobalt (2+ and 3+), nickel (2+), copper (2+), or zinc(2+),
oxo, hydroxo, chloro, bromo, amine, azido, thiocyanato, and cyano complex ions
of vanadium, chromium, molybdenum, manganese, rhenium, iron, ruthenium,
osmium,
cobalt, rhodium, iridium, nickel, palladium, platinum, copper, silver, gold
and
oxyanions of sulfur, arsenic, antimony, chlorine, bromine.
In another aspect, the method further comprises depositing the amperometric
sensor on a printed circuit board, and sealing the membrane is sealed at its
outer edges to
prevent communication between the electrolyte and a medium in which the redox-
active
species is sensed except through the membrane.
In another aspect of the method, depositing comprises printing the anode and
cathode onto the substrate using a method for printing circuit boards.
In another aspect the method further comprises depositing a guard ring onto
the
substrate.
In another aspect the method further comprises forming a well around the anode
and the cathode and covering the well with the membrane to define an
electrolyte
volume.
In another aspect of the method, placing an electrolyte solution comprises an
electrolyte and a second redox carrier between the anode and the cathode
comprises
adding the electrolyte to the well.
In another aspect of the method, adding the electrolyte solution to the well
comprises adding the electrolyte to the well as a solution.
In another aspect of the method, the solution is allowed to dry.
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In another aspect of the method, adding the electrolyte solution to the well
comprises forming a hydrogel in the well.
In another aspect of the method, the hydrogel is selected from the group
consisting of cross-linked acrylates, methyl methacrylates, methacrylates,
hydryxalkyl
acrylates, hydroxyalkyl(meth)acrylates, acrylamides, silicone hydrogels,
gelatin,
cellulose nitrate, cellulose, agar, and agarose and methods thereof.
In another aspect of the method, forming a well around the anode and the
cathode
comprises placing a laminating material comprises a hole onto the substrate
such that the
hole is disposed over the anode and cathode.
In another aspect of the method, covering the well with the membrane comprises
depositing a plasticized PVC membrane material dissolved in a volatile solvent
over the
well.
In another aspect the method further comprises first covering the well with a
layer
of microporous cellulose acetate and then depositing the PVC membrane material
onto
the microporous cellulose acetate.
In yet another embodiment of the invention, a method of preparing an
amperometric sensor is provided. The method comprises selecting a guanidinium
salt,
preparing a solvent containing the guanidinium salt, imbibing a first redox-
active species
impermeant membrane with the solvent, forming a reversible anode and an inert
cathode,
applying an electrolyte solution comprises an electrolyte and a second redox
earner over
the anode and the cathode, allowing the solution to evaporate and covering
both
electrodes with the redox-active species impermeant membrane, such that the
membrane
prevents communication between the electrolyte and an ambient environment
except
thmugh the membrane.
In another aspect of the method, the electrolyte layer is a hydrogel.
In another aspect of the method, the hydrogel is selected from the group
consisting of gelatin, cellulose nitrate, cellulose, agar and agarose.
In another aspect of the method, the hydrogel is selected from the group
consisting of cross-linked acrylates, methyl methacrylates, methacrylates,
hyroxyalkyl
acrylates, hydroxyalkyl(meth)acrylates and acrylamides.
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In yet another embodiment of the invention, a method of measuring a redox-
active species in a liquid sample is provided. The method comprises relaying a
redox
potential from the sample through a redox relay membrane, relaying the redox
potential
through an electrolyte solution, the electrolyte solution comprises an
electrolyte and a
second redox carrier and applying an electrical potential to an electrode.
In another aspect the method further comprises removing an ionic product of an
electrode reaction from the electrolyte solution using a guanidinium salt.
In another aspect of the method, the redox active species comprise chlorine,
hypochlorous acid, hypochlorite ion, other chlorine oxyacids and their
conjugate bases,
other halogens, oxyhaloacids and their conjugate bases, monochloroamine,
dichloramine,
trichloroamine, other chloroamines derived from organic amines, other
haloamine
species, hydrogen peroxide, hydroperoxyl anion, peroxide dianion, sulfur
dioxide,
bisulfate anion, sulfite dianion, thiosufate dianion, hydrogen sulfide,
hydrosulfide anion,
sulfide dianion, mercaptans and their conjugate bases, or organic disulfides.
In another aspect of the method, the first redox carrier and the second redox
Garner are selected such that the first redox Garner is oxidized and the
second redox
carrier is oxidized to permit measurement of an oxidizing species.
In another aspect of the method, the first redox carrier and the second redox
carrier are selected such that the first redox carrier is reduced and the
second redox
Garner is reduced to permit measurement of a reducing species.
In yet another embodiment of the invention, a sensor for aqueous chlorine and
chlorine-ammonia mixtures is provided that comprises a supported liquid
membrane
consisting of a microporous polycarbonate support membrane containing 2-
methylnaphthoquinone dissolved in ortho-nitrophenyl octyl ether at a
concentration
between 0.1 and 5 % (wt/wt), in contact with an agar (0.1- 2.0 wt%) hydrogel
electrolyte
containing sodium meta-vanadate (5 - 50 millimolar) and potassium chloride
(0.1-1.0
molar), in separate contact with a silver/silver chloride anode and a gold
cathode.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a redox carrier membrane amperometric sensor for an oxidizing
analyte
in the external solution in accordance with an embodiment of the invention.
14

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FIG. 2 shows the sensor of an embodiment of the invention's response to
hypochlorite (left) and monochloroamine (right). [pH 6.0, 50 ppm bicarbonate
buffer, 25
°C, concentrations in ppm).
DETAILED DESCRIPTION
The strategy for construction of a redox carrier membrane amperometric sensor
is
illustrated in FIG. 1 for an oxidizing analyte in the external solution.
Detection of
membrane-impermeant oxidizing or reducing species is achieved via a redox
relay in
which the species of interest oxidizes or reduces a redox carrier in the
membrane, the
oxidized or reduced earner diffuses to the inner interface of the sensor where
it in turn
oxidizes or reduces an aqueous redox carrier in the internal electrolyte. The
discharge of
this second carrier at a polarized electrode then generates a current in
proportion to the
concentration of the initial oxidant or reductant concentration in the sample.
FIG. 1
External Membrane Internal
solution electrolyte Electrode
OX ~ Cmred . CaqoX ne
i i
i i
RED ~ CmoX ~ Caqred
In FIG. 1, OX is the oxidizing species to be detected by the sensor, for
example,
but not limited to hypochlorite or monochloroamine. This species is present in
the
external solution at some concentration. At the membrane-external solution
interface, the
species OX oxidizes the redox carrier in the membrane (Cm) from its reduced
form
(Cm,.~) to its oxidized form (Cm°X). As a result the species OX is
itself reduced to a
reduced form RED. The oxidized membrane carrier (Cm°x) diffuses down
its
concentration gradient towards the internal electrolyte solution. At the
internal solution-
membrane interface, the oxidized membrane carrier oxidizes a redox carrier in
the
aqueous internal electrolyte from its reduced form (Caq,~) to its oxidized
form (Caq°X).
At the same time this reaction regenerates the reduced form of the membrane
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carrier (Cmred). The oxidized aqueous redox carrier in the internal
electrolyte then
diffuses down its concentration to the electrode where it is reduced. This
consumes
electrons from the external circuit which can be measured as the analytical
signal. The
reaction regenerates the reduced form of the aqueous redox Garner.
It is obvious that this strategy is potentially reversible and would equally
apply to
the detection of the species RED in the external solution. In this case RED
would reduce
CmoX to Cn,,~ which in turn would reduce CaqoX to Caq~ that would then be
oxidized at
the electrode to produce electrons in the external circuit.
In either the oxidizing or reducing form of the sensor; a number of conditions
must apply to produce an effective sensor. The principal driving force for the
sensor is
the potential of the electrode, either cathodic or anodic, relative to a
reference and/or
counter electrode within the internal electrolyte. The applied potential of
the electrode
must be chosen to provide a spontaneous conversion between CaqaX and Caq,~
such that
the required carrier species is discharged at the electrode. This will create
the
concentration gradient to move the aqueous carrier from the membrane interface
to the
electrode. Furthermore, at the internal electrolyte/membrane interface the
redox reaction
between the membrane redox carrier and the aqueous redox carrier must be
spontaneous
towards the required products of the reaction (CaqoX + Cmna for a sensor of
OX; Caq,.~ +
CmoX for a sensor for RED). This in tum will create the required concentration
gradient
in the membrane redox carrier across the membrane. Finally, at the external
solution/membrane interface the redox reaction between the membrane redox
carrier and
the detected species in the external solution is spontaneous towards the
required products
of the reaction (CxnoX + RED for a sensor of OX; Cm,.~ + OX for a sensor of
RED).
In addition to the thermodynamic considerations, there are kinetic
considerations
that will govern the utility of a sensor designed according to FIG. 1. The
membrane
redox carrier should diffuse across the membrane at a sufficient rate to
produce a
detectible current. T'he diffusion through the membrane will depend on the
nature of the
carrier, the thickness of the membrane and the viscosity of the membrane.
Diffusion of
the aqueous redox carrier within the internal aqueous electrolyte should also
be
acceptably fast. This too is determined by the nature of the carrier, the
thickness of the
aqueous internal electrolyte layer, and the viscosity of the electrolyte. At
the same time,
16

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the interfacial reaction rates at the external solution/membrane interface and
the internal
solution/membrane interface should also be sufficiently rapid to provide a
detectible
current.
Finally, all real redox systems will involve counter ions and other reactants
and
products of the redox reactions. These additional species play a role in the
thermodynamic and kinetic factors noted above. For example, the membrane will
typically have a low dielectric constant that will not support charge
separation. Thus the
oxidation of Cm,.~a to CtnaX will typically be accompanied by the transfer of
a counter
cation to the membrane phase for each electron transferred from OX to Cm.
Similar
transfers also apply in a sensor for RED. Some provision should be made to
accommodate the counterion within the membrane phase, either, for example, but
not
limited to, through association with the membrane redox carrier itself or with
a second
carrier specifically for the counterion [for example as reported by Grimaldi,
J.J.; Lehn, J.-
M. J. Am. Chem. Soc. 1979,101, 1333-1334]. Similar considerations apply to all
other
redox couples in the system. In a global sense, the overall reaction from the
external
solution to the discharge at the electrode involves the transfer of a
counterion from the
external solution to the internal electrolyte or in the other direction to
provide for charge
neutralization of the electrons) transferred from OX (or to RED) to (or from)
the
polarized electrode. In either case, the continued stable fiW ction of the
sensor requires
these additional fluxes to be balanced using an appropriate reaction at the
internal counter
electrode, or via a mechanism to equilibrate composition such as providing an
additional
carrier in the membrane [for example, but not to be limiting, as in U.S.
Patent No.
6,391,174]
These general considerations could be applied to the detection of a number of
different oxidizing and reducing species. For example, OX could be chlorine,
hypochlorous acid, hypochlorite ion, other chlorine oxyacids and their
conjugate bases,
other halogens, oxyhaloacids and their conjugate bases, monochloroamine,
dichloramine,
trichloroamine, other chloroamines derived from organic amines, other
haloamine
species, hydrogen peroxide, hydroperoxyl anion, peroxide dianion, etc.
Examples for
RED include sulfi~r dioxide, bisulfite anion, sulfite dianion, thiosufate
dianion, hydrogen
sulfide, hydrosulfide anion, sulfide dianion, mercaptans and their conjugate
bases;
17

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organic disulfides, etc. These lists are not exhaustive as many additional
species will
fulfill the thermodynamic constraints upon the species OX and RED as described
above,
as would be known to one skilled in the art.
Example 1
As a practical implementation of the general strategy we considered a sensor
for
aqueous chlorine and aqueous chlorine/ammonia mixtures - a sensor for the
total of
oxidizing chlorine species in an aqueous solution. All these chlorine species
(free
chlorine, hypochlorous acid, hypochlorite, mono-, di- and tri-chloroamines)
are strong
oxidizing agents. For example the standard reduction potential for
hypochlorous acid is
+1.715 V vs NHE [Pourbaix, op cit.] while the standard reduction potential of
monochloroamine is +1.527 V vs NHE [Soulard et al op cit.]]. These species are
therefore capable of oxidizing hydroquinones (H2Q) to quinones (Q) (standard
reduction
potential = +0.44V vs NHE [Clark, W.M. Oxidation-Reduction Potentials of
Organic
Systems, Williams and Wilkins, 1960]). Thus the reaction:
HZQ + HOCI --> Q + HCl + HZO
fulfills the requirement of spontaneity for the reaction at the external
solution/membrane interface.
At the membrane/internal electrolyte interface, a quinone is capable of
oxidizing a
variety of inorganic species such as ferrocyanide (standard reduction
potential for
ferricyanide = +0.36 V [Clark, op cit. ] ) or trivalent vanadium (reduction
potential for
H2V04 ~ 0-+0.2V near pH 7 [ Pourbaix, op cit. section 9.1 ] ). Thus a reaction
such as:
2 Fe(CI~6a' + Q -> H2Q + 2 Fe(C1~63' + 2H+
or
HV205 + Q + 3H20 -~ 2HZV04 + HZQ (pH > 4)
fulfills the requirement of spontaneity for the reaction at the internal
electrolyte/membrane interface. The product ferricyanide or ortho-vanadate
ions can be
discharged at an electrode potential more negative than -0.3 V relative to
AgJAgCI. This
fulfills all the thermodynamic requirements for a sensor for the oxidizing
chlorine species
noted above.
18

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The kinetic requirements for the sensor require a sufficiently rapid diffusion
of the
membrane redox carriers Q and H2Q. This can be achieved in solvent-polymer
membranes with a large solvent fraction, or in supported liquid membrane such
as those
formed by imbibing a non-polar solvent into the pores of a microporous
membrane. The
diffusion flux will be enhanced as the thickness of the membrane decreases.
The
diffusion will be enhanced by quinones of relatively low molecular weight such
as
menadione (Vitamin K).
The overall process for the proposed embodiment of the redox relay carrier
membrane system for a chlorine species sensor involves the transfer of two
electrons
from the external solution to the internal electrolyte solution with the
concomitant
transfer of two protons from the internal electrolyte to the external
solution. The internal
electrolyte solution will thus become basic as the sensor functions. This is
similar to the
build-up of hydroxide ions in a conventional Clark cell for dissolved oxygen
and could be
equilibrated through the use of an additional ion exchange carver as
previously disclosed
[for example as in U.S. Patent No. 6,391,174]. In this approach external
chloride would
be exchanged for the internal hydroxide, and would ultimately be incorporated
in a silver
chloride counter electrode to result in an overall neutral process.
Example 2
A functioning sensor was constructed on a printed circuit board (PCB) on which
a
gold cathode of 1 mm diameter was formed within a concentric silver-silver
chloride
anode of 6 mm diameter. The PCB was cleaned with ethanol and a layer of two
sided
tape (3M) with a 6 mm diameter hole punched was placed over the anode. The
backing
of the two sided tape provided a shallow reservoir into which a warm solution
of agar in
O.1M potassium chloride containing 5 x 10'3 M sodium meta-vanadate was placed.
The
excess agar was screened to flush with the tape backing, allowed to cool, and
the backing
was removed to produce a thin layer of the agar hydrogel covering the anode
and cathode
completely.
The membrane was formed in a l3mm diameter NucleoporeTM membrane filter
with a nominal pore diameter of 0.4 microns. A solution of menadione (2-
methylnaphthoquinone; 12 mg) in ortho-nitrophenyl octyl ether (0.1 ml) was
imbibed in
19

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the pores of the filter on a glass plate, allowed to soak for 20 minutes, and
the excess
solution was removed onto KimWipeTM tissues. The membrane was placed above the
agar layer on the PCB and secured in placed by pressing the edges of the
membrane to
the two-sided tape layer on the PCB. The PCB was mounted in a connector that
supplied
a potential of -O.SV to the cathode relative to the anode, and the current of
the sensor was
monitored.
Example 3
The electrode was placed in a 50 ppm bicarbonate buffer at pH 6. The electrode
showed no response to dissolved oxygen levels in this solution, but gave
positive current
response to both 10 ppm hypochlorite solution and 10 ppm monochloroamine
solution in
the same buffer at pH 6Ø
Nbnod~lorc~an;ne
21.0 21.0
16.0 ~ ~ 16.0
0.
12.0
0.t0 ~ 0.~
6.4
1.6 ~ ~ ~ ~ ~ ~ ~ ~ 1.6
taoo 2000 3000 ~ooo soon o soo tooo tsao aooo ~soo 3000 asoo .am
time (sera Hme (set
FIG. 2: Sensor response to hypochlorite (left) and monochloroamine (right).
[pH
6.0, 50 ppm bicarbonate buffer, 25 °C, concentrations in ppm]
FIG. 2 shows the response of the sensor to an increasing series of
concentrations
of hypochlorite (left) and monochloroamine (right). In both cases the
calibration was
linear with slopes that were equal within experimental error.

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It should be recognized that the illustrated embodiments are only particular
examples of the inventions and should not be taken as a limitation on the
scope of the
inventions. As would be known to one skilled in the art, the invention can
take many
forms. For example, other hydrogels may include but are not restricted to
cross-linked
acrylates, methacrylates, hydroxyalkyl(meth)acrylates and acrylamides,
silicone
hydrogels, gelatin, cellulose nitrate, cellulose, and agarose. Similarly,
redox carriers
other than quinones can be employed, and would be readily determined from the
foregoing description by one skilled in the art. Also, other membrane types
would be
applicable as well. For example, but not to be limiting, supported membranes
based on
microporous Teflon and plasticized membranes such as plasticized poly
vinylchloride,
silicone rubber, and polyurethanes can also be employed.. Further the PCB or
printed
circuit board mentioned in the above example can take many forms and methods
of
construction. For example but not to be limiting the substrate can be a
fiberglass
material, TeflonTM, polyimide or other commercially available materials for
the
construction of printed circuit boards. There are also ceramic substrates
available. Some
of these systems may be on flexible substrate materials. The process that is
used to
deposit the sensor electrodes also varies. The most basic printed circuit
board uses a
copper etching process followed by electroplating or immersion plating
techniques to
achieve the desired gold and silver/silver chloride electrodes. It is also
possible to use
metallic pastes which are "screened" onto the substrate and subsequently cured
by
heating.
21