WO2017210465A1 - Prussian blue screen-printed electrode for determining cation concentration in physiological samples - Google Patents
Prussian blue screen-printed electrode for determining cation concentration in physiological samples Download PDFInfo
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- WO2017210465A1 WO2017210465A1 PCT/US2017/035509 US2017035509W WO2017210465A1 WO 2017210465 A1 WO2017210465 A1 WO 2017210465A1 US 2017035509 W US2017035509 W US 2017035509W WO 2017210465 A1 WO2017210465 A1 WO 2017210465A1
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- DCYOBGZUOMKFPA-UHFFFAOYSA-N iron(2+);iron(3+);octadecacyanide Chemical compound [Fe+2].[Fe+2].[Fe+2].[Fe+3].[Fe+3].[Fe+3].[Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] DCYOBGZUOMKFPA-UHFFFAOYSA-N 0.000 title claims abstract description 71
- 229960003351 prussian blue Drugs 0.000 title claims abstract description 71
- 239000013225 prussian blue Substances 0.000 title claims abstract description 71
- 150000001768 cations Chemical class 0.000 title claims description 22
- 229910001414 potassium ion Inorganic materials 0.000 claims description 66
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 60
- 229910001415 sodium ion Inorganic materials 0.000 claims description 59
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 claims description 57
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 20
- 210000002966 serum Anatomy 0.000 claims description 13
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 12
- 229910052709 silver Inorganic materials 0.000 claims description 12
- 239000004332 silver Substances 0.000 claims description 12
- 229910001416 lithium ion Inorganic materials 0.000 claims description 10
- 229910001419 rubidium ion Inorganic materials 0.000 claims description 8
- 210000004243 sweat Anatomy 0.000 claims description 8
- 210000001138 tear Anatomy 0.000 claims description 8
- 210000002700 urine Anatomy 0.000 claims description 8
- HBBGRARXTFLTSG-UHFFFAOYSA-N Lithium ion Chemical compound [Li+] HBBGRARXTFLTSG-UHFFFAOYSA-N 0.000 claims description 7
- NCMHKCKGHRPLCM-UHFFFAOYSA-N caesium(1+) Chemical compound [Cs+] NCMHKCKGHRPLCM-UHFFFAOYSA-N 0.000 claims description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
- 239000011591 potassium Substances 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
- 239000012530 fluid Substances 0.000 abstract description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 46
- 239000012091 fetal bovine serum Substances 0.000 description 46
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 14
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 12
- FGDZQCVHDSGLHJ-UHFFFAOYSA-M rubidium chloride Chemical compound [Cl-].[Rb+] FGDZQCVHDSGLHJ-UHFFFAOYSA-M 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 230000006870 function Effects 0.000 description 8
- 238000002484 cyclic voltammetry Methods 0.000 description 7
- 150000001340 alkali metals Chemical group 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 229910003202 NH4 Inorganic materials 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052716 thallium Inorganic materials 0.000 description 4
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229910052792 caesium Inorganic materials 0.000 description 3
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052730 francium Inorganic materials 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010027439 Metal poisoning Diseases 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 150000003818 basic metals Chemical group 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000001055 blue pigment Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 238000007675 cardiac surgery Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- KLMCZVJOEAUDNE-UHFFFAOYSA-N francium atom Chemical compound [Fr] KLMCZVJOEAUDNE-UHFFFAOYSA-N 0.000 description 1
- 208000010501 heavy metal poisoning Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000004220 muscle function Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- NCCSSGKUIKYAJD-UHFFFAOYSA-N rubidium(1+) Chemical compound [Rb+] NCCSSGKUIKYAJD-UHFFFAOYSA-N 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01M—PROCESSES OR MEANS, e.g. BATTERIES, FOR THE DIRECT CONVERSION OF CHEMICAL ENERGY INTO ELECTRICAL ENERGY
- H01M4/00—Electrodes
- H01M4/02—Electrodes composed of, or comprising, active material
- H01M4/36—Selection of substances as active materials, active masses, active liquids
- H01M4/38—Selection of substances as active materials, active masses, active liquids of elements or alloys
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/333—Ion-selective electrodes or membranes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/48—Systems using polarography, i.e. measuring changes in current under a slowly-varying voltage
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01M—PROCESSES OR MEANS, e.g. BATTERIES, FOR THE DIRECT CONVERSION OF CHEMICAL ENERGY INTO ELECTRICAL ENERGY
- H01M4/00—Electrodes
- H01M4/02—Electrodes composed of, or comprising, active material
- H01M4/04—Processes of manufacture in general
- H01M4/0402—Methods of deposition of the material
- H01M4/0414—Methods of deposition of the material by screen printing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E60/00—Enabling technologies; Technologies with a potential or indirect contribution to GHG emissions mitigation
- Y02E60/10—Energy storage using batteries
Definitions
- the alkali metal group includes lithium, sodium, potassium, rubidium, cesium, and francium (Li, Na, K, Rib, Cs, and Fr).
- Thallium (TI) though belonging to the basic metal group, also exhibits alkali metal monocation properties.
- Physiologically important alkali metals include sodium and potassium. Potassium ion (K + ) is the major intracellular cation and sodium ion (Na + ) is the major extracellular cation. The concentration differences of these cations generate the membrane potential needed for normal cellular functions, especially muscle function. Thus, it is important to be able to monitor extracellular potassium ion concentrations in human fluids, especially prior to or during cardiac surgery.
- the present invention provides a method for detecting cations using a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode).
- a Prussian blue electrode e.g., a Prussian blue screen-printed electrode
- the invention provides a method for electrochemical determination of the concentration of cations in a sample.
- the method comprises contacting a sample containing one or more cations with an electrochemical cell comprising a Prussian blue electrode (e.g., Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to provide a voltamagram; and determining the concentration of one or more monocations from the voltamagram.
- a Prussian blue electrode e.g., Prussian blue screen-printed electrode
- the Prussian blue electrode (e.g., a Prussian blue screen- printed electrode) is a carbon electrode.
- the counter electrode is the base material of the Prussian blue electrode and can be a carbon electrode.
- the reference electrode comprises a conducting metal (e.g., silver).
- the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
- Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
- the concentration of the monocation is determined continuously.
- determining the concentration of the monocation comprises determining the concentration of a specific monocation in the presence of a plurality of other monocations.
- Representative detectable and quantitatable monocations include lithium ion, sodium ion, potassium ion, rubidium ion, cesium ion, and ammonium ion.
- the monocation is sodium ion or potassium ion.
- the monocation is cesium ion, rubidium ion, or lithium ion.
- the monocation is sodium ion.
- the monocation is potassium ion.
- the concentration of potassium ion is determined in the presence of sodium ion.
- the invention provides a method for electrochemical determination of the concentrations of sodium ion and potassium ion in a sample.
- the method comprises contacting a sample containing sodium ion and potassium ion with an electrochemical cell comprising a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to obtain a voltamagram; and determining the concentration of sodium ion and potassium ion from the voltamagram.
- a Prussian blue electrode e.g., a Prussian blue screen-printed electrode
- the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
- Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
- physiological samples such as human plasma, serum, blood urine, sweat, or tears.
- concentration of the sodium ion and potassium ion is determined continuously.
- the concentration of sodium ion determined and quantitated is from about 1 mM to about 500 mM.
- the concentration of potassium ion determined and quantitated is from about 1 mM to about 100 mM, and in presence of physiological sodium ion (about 100 mM).
- the invention provides a method for selective electrochemical determination of the concentrations of potassium ion in a sample containing sodium ion.
- the method comprises contacting a sample containing potassium and sodium ions with an electrochemical cell comprising a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to obtain a voltamagram; and determining the concentration of sodium ion and potassium ion from the voltamagram.
- a Prussian blue electrode e.g., a Prussian blue screen-printed electrode
- the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
- Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
- the concentration of potassium ion is determined continuously.
- the concentration of potassium ion determined and quantitated is from about 1 mM to about 100 mM, and in the presence of physiological concentrations of sodium ion (about 100 mM).
- FIGURE 1 compares square-wave voltamagram (SWV) results for 0.1 M solutions of LiCl, NaCl, KC1, RbCl, CsCl, and NH 4 C1, respectively, in FBS (fetal bovine serum) obtained using a Prussian blue screen-printed electrode (SPE) (frequency 1 Hz, amplitude 50 mV, deposition potential -1 V, end potential 1 V, deposition time 300 s).
- FIGURES 1A to IF are the normalized SWV for 0.1 M solutions of LiCl, NaCl, KCl, RbCl, CsCl, and NH 4 Cl in FBS, respectively.
- FIGURES 2A-2F compare square-wave voltamagram (SWV) results for diluted solutions of LiCl, NaCl, KCl, RbCl, CsCl, and NH 4 C1, respectively, in FBS obtained using a Prussian blue screen-printed electrode (SPE) (solid line 0.1 M cation; dashed line 0.01 M; dotted line 0.001 M; solid line, FBS only).
- SPE Prussian blue screen-printed electrode
- FIGURE 3 compares square-wave voltamagram (SWV) results for dilutions of potassium ion solutions in FBS obtained using a Prussian blue screen-printed electrode (SPE): 0.1 M, 0.05 M, 0.025 M, 0.0125 M, 0.00625 M, 0.003125 M, 0.0015625 M KCl, FBS only.
- SPE Prussian blue screen-printed electrode
- FIGURES 4A-4E compare three-dimensional (3D) plots of square-wave voltamagram (SWV) results (current (A) v. voltage (V) v. potassium ion concentration (M) in FBS) obtained using a Prussian blue screen-printed electrode (SPE).
- SWV square-wave voltamagram
- FIGURE 5 is a contour plot of voltage (V) as a function of potassium ion concentration (M) (0.00 to 0.10 M in FBS).
- V voltage
- M potassium ion concentration
- FIGURES 6A-6C compare peak voltage (6 A), peak width at half height (6B), and normalized parameters (ratio to FBS) (6C) as a function of potassium ion concentration (0.001 to 0.1 M in FBS).
- FIGURES 7A and 7B show data analysis for potassium ion dilutions in FBS.
- FIGURE 7 A illustrates normalized parameters: ratio to FBS control as a function of potassium ion concentration (0.001 to 0.1 M in FBS) and current at 0 V, 0.15 V, 0.1 V, 0.158157 V (peak position of FBS), 0.2 V, and 0.3 V.
- Ratio to FBS control (Current at X voltage) / Current at X voltage of FBS).
- 0.1 M KCl in FBS (Current at green dot) / (Current at dot) in FIGURE 7B.
- FIGURE 8 compares square-wave voltamagram (SWV) results for dilutions of potassium ion solutions in 0.1 M aqueous sodium chloride obtained using a Prussian blue screen-printed electrode (SPE): 0.1 M, 0.05 M, 0.025 M, 0.0125 M, 0.00625 M, 0.003125 M, 0.0015625 M KCl, no potassium ion, 0.1 M NaCl only.
- SWV square-wave voltamagram
- FIGURES 9A-9C compare absolute current (9 A) at specified voltage peak voltage (current at 0 V, 0.15 V, 0.1 V, 0.158157 V, 0.2 V, 0.3 V) (9 A), peak voltage (9B), and peak width at half height (9C) as a function of potassium ion concentration (0.001 to 0.1 M in 0.1 M NaCl).
- the present invention provides a method for detecting cations using a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode).
- a Prussian blue electrode e.g., a Prussian blue screen-printed electrode.
- the electrode, electrochemical cell, and methods of the invention are useful for electrochemically detecting monocations in the presence of other monocations.
- the electrode and methods of the invention advantageously provide quantitation of monocations in physiological fluids.
- Screen-printed Prussian blue electrodes have been used for the determination of hydrogen peroxide at a low detection potential. These electrodes are useful for the development of enzymatic biosensors based on oxidases, for working with microvolumes, and for decentralized assays.
- the configuration of one representative screen-printed Prussian blue electrode is as follow: Ceramic substrate: L33 x W10 x HO.5 mm/Electric contacts: Silver.
- the electrochemical cell consists of (1) working electrode: Prussian blue/carbon (4 mm diameter); (2) counter electrode: carbon; and (3) reference electrode: silver. This electrode can be fabricated or purchased from Dropsens, Parque Tecnologico de Asturias - Edif. CEEI. 33428 LLanera (Asturias) Spain.
- Prussian blue is a dark blue pigment with the idealized chemical formula Fe 7 (CN)i g.
- Therapeutically, Prussian blue is used as a sequestering agent useful in treating certain kinds of heavy metal poisoning (e.g., by thallium and radioactive isotopes of cesium).
- the therapeutic activity of Prussian blue exploits its ion exchange properties and high affinity for certain "soft" metal cations.
- Prussian blue incorporates monocations belonging to the alkali metal group. Affinity to Prussian blue increases as the ionic radius of the cation increases. Consequently, Prussian blue preferentially binds to cesium (ionic radius 0.169 nm) and thallium (0.147 nm) over potassium (0.133 nm) and sodium (0.116 nm).
- the relevant physiological ions are potassium ion and sodium ion, the others alkali metal ions are only present in trace quantity in physiological fluid.
- a Prussian blue electrode e.g., a Prussian blue screen-printed electrode that is a carbon electrode modified with Prussian blue
- Prussian blue electrode refers to an electrode, such as a carbon electrode, that has been modified to include Prussian blue (i.e., idealized chemical formula Fe 7 (CN) 18 ).
- Prussian blue screen-printed electrode refers to a screen- printed electrode, such as a carbon electrode, that has been modified to include Prussian blue.
- the invention provides a method for electrochemical determination of the concentration of cations in a sample.
- the method comprises contacting a sample containing one or more cations with an electrochemical cell comprising a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to provide a voltamagram; and determining the concentration of one or more monocations from the voltamagram.
- a Prussian blue electrode e.g., a Prussian blue screen-printed electrode
- the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
- Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
- the concentration of the monocation is determined continuously.
- determining the concentration of the monocation comprises determining the concentration of a specific monocation in the presence of a plurality of other monocations.
- Representative detectable and quantitatable monocations include lithium ion, sodium ion, potassium ion, rubidium ion, cesium ion, and ammonium ion.
- the monocation is sodium ion or potassium ion.
- the monocation is cesium ion, rubidium ion, or lithium ion.
- the monocation is sodium ion.
- the monocation is potassium ion.
- the concentration of potassium ion is determined in the presence of sodium ion.
- the invention provides a method for electrochemical determination of the concentrations of sodium ion and potassium ion in a sample.
- the method comprises contacting a sample containing sodium ion and potassium ion with an electrochemical cell comprising a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to obtain a voltamagram; and determining the concentration of sodium ion and potassium ion from the voltamagram.
- a Prussian blue electrode e.g., a Prussian blue screen-printed electrode
- the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
- Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
- the concentration of the sodium ion and potassium ion is determined continuously.
- the concentration of sodium ion determined and quantitated is from about 1 mM to about 500 mM.
- the concentration of potassium ion determined and quantitated is from about 1 mM to about 100 mM in presence of physiological sodium ion (about 100 mM).
- the Prussian blue electrode (e.g., a Prussian blue screen-printed electrode, such as a Prussian blue modified-carbon screen-printed electrode) useful in the invention requires only a small volume of sample (50 uL or less), which is advantageous in the biomedical field if patient blood or serum is to be tested.
- the present invention provides for the differential detection of K + and Na + by a Prussian blue electrode.
- Measurements were conducted with the Autolab PGSATA128N potentiostat using cyclic voltammetry.
- the electrodes were purchased from DropSens and consisted of a Prussian blue screen-printed electrode (carbon working electrode), a carbon counter electrode, and a silver reference electrode.
- the circuit was completed by using a 50 ⁇ droplet of LiCl, NaCl KC1, MgCl2, or CaCl2 solution.
- the cyclic voltammetry scans were performed from -0.6 to 0.8 V at 100 mV/s.
- the Prussian blue screen-printed electrode exhibits distinct cyclic voltammetry scans when exposed to either Na + or K + , while the bivalent cation (Mg 2+ ) or smaller alkali metal (Li + ) do not.
- the Na + cyclic voltammetry scan was characterized by oxidation/reduction peaks at -0.10V/-0.12V and broad shoulders 0.0-0.1V/-0.1 to 0.1V.
- the K + cyclic voltammetry scan was characterized by oxidation/reduction peaks at 0.20V/0.05V with no shoulders.
- the performance of the Prussian blue screen-printed electrode was evaluated in phosphate buffered saline (PBS and FBS), mimicking physiological conditions.
- FIGURES 1-9 The performance of the Prussian blue screen-printed electrode in the detection and quantitation of cations (e.g., potassium ion) is demonstrated in FIGURES 1-9.
- cations e.g., potassium ion
- FIGURES 1-7 show that potassium ion can be detected in presence of plasma/serum in the form of FBS, which has high level of sodium ion and low physiological level of potassium ion.
- FBS the large peak (signal) due to sodium ion was not detected due the presence of low level of potassium ion.
- FIGURE 1 compares square-wave voltamagram (SWV) results for 0.1 M solutions of LiCl, NaCl, KCl, RbCl, CsCl, and H 4 C1, respectively, in FBS (fetal bovine serum) obtained using a Prussian blue screen-printed electrode (SPE) (frequency 1 Hz, amplitude 50 mV, deposition potential -1 V, end potential 1 V, deposition time 300 s).
- FIGURES 1A to IF are the normalized SWV for 0.1 M solutions of LiCl, NaCl, KCl, RbCl, CsCl, and NH 4 C1 in FBS, respectively. Each ion is exhibiting different SWV profiles despite the fact that FBS contains ions including Na + and K + . This is same as FIGURE 1 with each ion plot separated to further demonstrate the differences in SWV profiles.
- SWV square-wave voltamagram
- FIGURES 2A-2F compare square-wave voltamagram (SWV) results for diluted solutions of LiCl, NaCl, KCl, RbCl, CsCl, and NH 4 C1, respectively, in FBS obtained using a Prussian blue screen-printed electrode (SPE) (solid line 0.1 M cation; dashed line
- the electrode was not able to differentiate Li + and Na + from ions in the FBS - most likely Na + . However, the electrode was able to detect K + as shift in the peak and Rb + , Cs + , and NH 4 + as reduction in the Na + peak endogenous to FBS.
- FIGURE 3 compares square-wave voltamagram (SWV) results for dilutions of potassium ion solutions in FBS obtained using a Prussian blue screen-printed electrode (SPE): 0.1 M, 0.05 M, 0.025 M, 0.0125 M, 0.00625 M, 0.003125 M, 0.0015625 M KCl, FBS only. Dose dependent shift in peak with increasing amount of K + is indicative that quantitation of K + in FBS or serum is possible.
- FIGURES 4A-4E compare three-dimensional (3D) plots of square-wave voltamagram (SWV) results (current (A) v. voltage (V) v. potassium ion concentration (M) in FBS) obtained using a Prussian blue screen-printed electrode (SPE).
- FIGURE 5 is a contour plot of voltage (V) as a function of potassium ion concentration (M) (0.00 to 0.10 M in FBS).
- V voltage
- M potassium ion concentration
- FIGURES 6A-6C compare peak voltage (6 A), peak width at half height (6B), and normalized parameters (ratio to FBS) (6C) as a function of potassium ion concentration (0.001 to 0.1 M in FBS). This demonstrates that quantitation of K + can be done using peak voltage, peak width at half height unnormalized or normalized versus FBS (serum) alone.
- FIGURES 7A and 7B show data analysis for potassium ion dilutions in FBS.
- FIGURE 7 A illustrates normalized parameters: ratio to FBS control as a function of potassium ion concentration (0.001 to 0.1 M in FBS) and current at 0 V, 0.15 V, 0.1 V, 0.158157 V (peak position of FBS), 0.2 V, and 0.3 V.
- Ratio to FBS control (Current at X voltage) / Current at X voltage of FBS).
- 0.1 M KC1 in FBS (Current at green dot) / (Current at dot) in FIGURE 7B. This shows that normalized parameters at various voltage can be used to further refine the most desirable parameter for quantitation of K+.
- FIGURES 8 and 9 show that potassium ion can be detected in presence of physiological concentration of sodium chloride (0.1 M in water).
- FIGURE 8 compares square-wave voltamagram (SWV) results for dilutions of potassium ion solutions in 0.1 M aqueous sodium chloride obtained using a Prussian blue screen-printed electrode (SPE): 0.1 M, 0.05 M, 0.025 M, 0.0125 M, 0.00625 M, 0.003125 M, 0.0015625 M KC1, no potassium ion, 0.1 M NaCl only.
- SWV square-wave voltamagram
- FIGURES 9A-9C compare absolute current (9 A) at specified voltage peak voltage (current at 0 V, 0.15 V, 0.1 V, 0.158157 V, 0.2 V, 0.3 V) (9 A), peak voltage (9B), and peak width at half height (9C) as a function of potassium ion concentration (0.001 to 0.1 M in 0.1 M NaCl).
- the methods of the invention advantageously provide for the determination of these monocations in fluids that contain other ions for which Prussian blue is not selective.
- the methods of the invention are effectively for determining the concentrations of lithium ion, potassium ion, rubidium ion, and cesium ion in presence of sodium ion.
- the Prussian blue electrode (e.g., the Prussian blue screen-printed electrode) shows specific detection for K + and Na + .
- the increasing presence of K + in physiological buffer, which contains primarily Na + resulted in concentration dependent shift in the cyclic voltammetry scan. This property was used to quantitate both Na + and K + in physiological fluid and, in turn, the membrane potential.
- the biosensor offers the potential to be implanted for the continuous monitoring of K+/Na+.
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Abstract
Determination of monocation concentration in physiological fluids using an electrochemical cell having a Prussian blue electrode as a working electrode.
Description
PRUSSIAN BLUE SCREEN-PRINTED ELECTRODE FOR DETERMINING CATION CONCENTRATION IN PHYSIOLOGICAL SAMPLES
CROSS REFERENCE TO RELATED APPLICATION
This application claims the benefit of US Application No. 62/344,257, filed June 1, 2016, expressly incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
The alkali metal group includes lithium, sodium, potassium, rubidium, cesium, and francium (Li, Na, K, Rib, Cs, and Fr). Thallium (TI), though belonging to the basic metal group, also exhibits alkali metal monocation properties. Physiologically important alkali metals include sodium and potassium. Potassium ion (K+) is the major intracellular cation and sodium ion (Na+) is the major extracellular cation. The concentration differences of these cations generate the membrane potential needed for normal cellular functions, especially muscle function. Thus, it is important to be able to monitor extracellular potassium ion concentrations in human fluids, especially prior to or during cardiac surgery.
Despite advances in analytical devices and methods for detecting cations, such as potassium ion and sodium ion, a need exists for improved devices and methods that advantageously selectively detect desired cations in the presence of others. The present invention seeks to fulfill this need and provides further related advantages.
SUMMARY OF THE INVENTION
The present invention provides a method for detecting cations using a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode).
In one aspect, the invention provides a method for electrochemical determination of the concentration of cations in a sample. In one embodiment, the method comprises contacting a sample containing one or more cations with an electrochemical cell comprising a Prussian blue electrode (e.g., Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to provide a voltamagram; and determining the concentration of one or more monocations from the voltamagram.
In certain embodiments, the Prussian blue electrode (e.g., a Prussian blue screen- printed electrode) is a carbon electrode.
In certain embodiments, the counter electrode is the base material of the Prussian blue electrode and can be a carbon electrode.
In certain embodiments, the reference electrode comprises a conducting metal (e.g., silver).
In certain embodiments, the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
In certain embodiments, the concentration of the monocation is determined continuously.
In certain embodiments, determining the concentration of the monocation comprises determining the concentration of a specific monocation in the presence of a plurality of other monocations.
Representative detectable and quantitatable monocations include lithium ion, sodium ion, potassium ion, rubidium ion, cesium ion, and ammonium ion. In certain embodiments, the monocation is sodium ion or potassium ion. In certain embodiments, the monocation is cesium ion, rubidium ion, or lithium ion. In certain embodiments, the monocation is sodium ion. In certain embodiments, the monocation is potassium ion. In certain embodiments, the concentration of potassium ion is determined in the presence of sodium ion.
In another aspect, the invention provides a method for electrochemical determination of the concentrations of sodium ion and potassium ion in a sample. In one embodiment, the method comprises contacting a sample containing sodium ion and potassium ion with an electrochemical cell comprising a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to obtain a voltamagram; and determining the concentration of sodium ion and potassium ion from the voltamagram.
In certain embodiments, the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
In certain embodiments, the concentration of the sodium ion and potassium ion is determined continuously.
In certain embodiments, the concentration of sodium ion determined and quantitated is from about 1 mM to about 500 mM.
In certain embodiments, the concentration of potassium ion determined and quantitated is from about 1 mM to about 100 mM, and in presence of physiological sodium ion (about 100 mM).
In a further aspect, the invention provides a method for selective electrochemical determination of the concentrations of potassium ion in a sample containing sodium ion. In one embodiment, the method comprises contacting a sample containing potassium and sodium ions with an electrochemical cell comprising a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to obtain a voltamagram; and determining the concentration of sodium ion and potassium ion from the voltamagram.
In certain embodiments, the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
In certain embodiments, the concentration of potassium ion is determined continuously.
In certain embodiments, the concentration of potassium ion determined and quantitated is from about 1 mM to about 100 mM, and in the presence of physiological concentrations of sodium ion (about 100 mM).
DESCRIPTION OF THE DRAWINGS
The foregoing aspects and many of the attendant advantages of this invention will become more readily appreciated as the same become better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings.
FIGURE 1 compares square-wave voltamagram (SWV) results for 0.1 M solutions of LiCl, NaCl, KC1, RbCl, CsCl, and NH4C1, respectively, in FBS (fetal bovine serum) obtained using a Prussian blue screen-printed electrode (SPE) (frequency 1 Hz, amplitude 50 mV, deposition potential -1 V, end potential 1 V, deposition time 300 s).
FIGURES 1A to IF are the normalized SWV for 0.1 M solutions of LiCl, NaCl, KCl, RbCl, CsCl, and NH4Cl in FBS, respectively.
FIGURES 2A-2F compare square-wave voltamagram (SWV) results for diluted solutions of LiCl, NaCl, KCl, RbCl, CsCl, and NH4C1, respectively, in FBS obtained using a Prussian blue screen-printed electrode (SPE) (solid line 0.1 M cation; dashed line 0.01 M; dotted line 0.001 M; solid line, FBS only).
FIGURE 3 compares square-wave voltamagram (SWV) results for dilutions of potassium ion solutions in FBS obtained using a Prussian blue screen-printed electrode (SPE): 0.1 M, 0.05 M, 0.025 M, 0.0125 M, 0.00625 M, 0.003125 M, 0.0015625 M KCl, FBS only.
FIGURES 4A-4E compare three-dimensional (3D) plots of square-wave voltamagram (SWV) results (current (A) v. voltage (V) v. potassium ion concentration (M) in FBS) obtained using a Prussian blue screen-printed electrode (SPE).
FIGURE 5 is a contour plot of voltage (V) as a function of potassium ion concentration (M) (0.00 to 0.10 M in FBS). The peak current shifts slightly to a more positive voltage as K+ concentration increases. The mid-level current around the peak decreases as K+ concentration increases, denoting the peak becoming sharper.
FIGURES 6A-6C compare peak voltage (6 A), peak width at half height (6B), and normalized parameters (ratio to FBS) (6C) as a function of potassium ion concentration (0.001 to 0.1 M in FBS).
FIGURES 7A and 7B show data analysis for potassium ion dilutions in FBS. FIGURE 7 A illustrates normalized parameters: ratio to FBS control as a function of potassium ion concentration (0.001 to 0.1 M in FBS) and current at 0 V, 0.15 V, 0.1 V, 0.158157 V (peak position of FBS), 0.2 V, and 0.3 V. Ratio to FBS control = (Current at X voltage) / Current at X voltage of FBS). For example, 0.1 M KCl in FBS: (Current at green dot) / (Current at dot) in FIGURE 7B.
FIGURE 8 compares square-wave voltamagram (SWV) results for dilutions of potassium ion solutions in 0.1 M aqueous sodium chloride obtained using a Prussian blue screen-printed electrode (SPE): 0.1 M, 0.05 M, 0.025 M, 0.0125 M, 0.00625 M, 0.003125 M, 0.0015625 M KCl, no potassium ion, 0.1 M NaCl only.
FIGURES 9A-9C compare absolute current (9 A) at specified voltage peak voltage (current at 0 V, 0.15 V, 0.1 V, 0.158157 V, 0.2 V, 0.3 V) (9 A), peak voltage (9B), and
peak width at half height (9C) as a function of potassium ion concentration (0.001 to 0.1 M in 0.1 M NaCl).
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a method for detecting cations using a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode). The electrode, electrochemical cell, and methods of the invention are useful for electrochemically detecting monocations in the presence of other monocations. The electrode and methods of the invention advantageously provide quantitation of monocations in physiological fluids.
Screen-printed Prussian blue electrodes (e.g., disposable electrodes) have been used for the determination of hydrogen peroxide at a low detection potential. These electrodes are useful for the development of enzymatic biosensors based on oxidases, for working with microvolumes, and for decentralized assays. The configuration of one representative screen-printed Prussian blue electrode is as follow: Ceramic substrate: L33 x W10 x HO.5 mm/Electric contacts: Silver. The electrochemical cell consists of (1) working electrode: Prussian blue/carbon (4 mm diameter); (2) counter electrode: carbon; and (3) reference electrode: silver. This electrode can be fabricated or purchased from Dropsens, Parque Tecnologico de Asturias - Edif. CEEI. 33428 LLanera (Asturias) Spain.
Prussian blue is a dark blue pigment with the idealized chemical formula Fe7(CN)i g. Therapeutically, Prussian blue is used as a sequestering agent useful in treating certain kinds of heavy metal poisoning (e.g., by thallium and radioactive isotopes of cesium). The therapeutic activity of Prussian blue exploits its ion exchange properties and high affinity for certain "soft" metal cations.
Prussian blue incorporates monocations belonging to the alkali metal group. Affinity to Prussian blue increases as the ionic radius of the cation increases. Consequently, Prussian blue preferentially binds to cesium (ionic radius 0.169 nm) and thallium (0.147 nm) over potassium (0.133 nm) and sodium (0.116 nm). However, the relevant physiological ions are potassium ion and sodium ion, the others alkali metal ions are only present in trace quantity in physiological fluid.
In the practice of the method of the invention, a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode that is a carbon electrode modified with Prussian blue) was employed as the working electrode in an electrochemical cell. As used herein,
the term "Prussian blue electrode" refers to an electrode, such as a carbon electrode, that has been modified to include Prussian blue (i.e., idealized chemical formula Fe7(CN)18).
As used herein, the term "Prussian blue screen-printed electrode" refers to a screen- printed electrode, such as a carbon electrode, that has been modified to include Prussian blue.
In one aspect, the invention provides a method for electrochemical determination of the concentration of cations in a sample. In one embodiment, the method comprises contacting a sample containing one or more cations with an electrochemical cell comprising a Prussian blue electrode (e.g., a Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to provide a voltamagram; and determining the concentration of one or more monocations from the voltamagram.
In certain embodiments, the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
In certain embodiments, the concentration of the monocation is determined continuously.
In certain embodiments, determining the concentration of the monocation comprises determining the concentration of a specific monocation in the presence of a plurality of other monocations.
Representative detectable and quantitatable monocations include lithium ion, sodium ion, potassium ion, rubidium ion, cesium ion, and ammonium ion. In certain embodiments, the monocation is sodium ion or potassium ion. In certain embodiments, the monocation is cesium ion, rubidium ion, or lithium ion. In certain embodiments, the monocation is sodium ion. In certain embodiments, the monocation is potassium ion. In certain embodiments, the concentration of potassium ion is determined in the presence of sodium ion.
In another aspect, the invention provides a method for electrochemical determination of the concentrations of sodium ion and potassium ion in a sample. In one embodiment, the method comprises contacting a sample containing sodium ion and potassium ion with an electrochemical cell comprising a Prussian blue electrode (e.g., a
Prussian blue screen-printed electrode) (working electrode), a counter electrode, and a reference electrode; using the electrochemical cell to vary potential applied to the sample and to measure current to obtain a voltamagram; and determining the concentration of sodium ion and potassium ion from the voltamagram.
In certain embodiments, the counter electrode is a carbon electrode and the reference electrode is a silver electrode.
Suitable samples for applicable to the method include physiological samples, such as human plasma, serum, blood urine, sweat, or tears.
In certain embodiments, the concentration of the sodium ion and potassium ion is determined continuously.
In certain embodiments, the concentration of sodium ion determined and quantitated is from about 1 mM to about 500 mM.
In certain embodiments, the concentration of potassium ion determined and quantitated is from about 1 mM to about 100 mM in presence of physiological sodium ion (about 100 mM).
The Prussian blue electrode (e.g., a Prussian blue screen-printed electrode, such as a Prussian blue modified-carbon screen-printed electrode) useful in the invention requires only a small volume of sample (50 uL or less), which is advantageous in the biomedical field if patient blood or serum is to be tested. The present invention provides for the differential detection of K+ and Na+ by a Prussian blue electrode.
Measurements were conducted with the Autolab PGSATA128N potentiostat using cyclic voltammetry. The electrodes were purchased from DropSens and consisted of a Prussian blue screen-printed electrode (carbon working electrode), a carbon counter electrode, and a silver reference electrode. The circuit was completed by using a 50 μΐ droplet of LiCl, NaCl KC1, MgCl2, or CaCl2 solution. The cyclic voltammetry scans were performed from -0.6 to 0.8 V at 100 mV/s.
The Prussian blue screen-printed electrode exhibits distinct cyclic voltammetry scans when exposed to either Na+ or K+, while the bivalent cation (Mg2+) or smaller alkali metal (Li+) do not. The Na+ cyclic voltammetry scan was characterized by oxidation/reduction peaks at -0.10V/-0.12V and broad shoulders 0.0-0.1V/-0.1 to 0.1V. The K+ cyclic voltammetry scan was characterized by oxidation/reduction peaks at 0.20V/0.05V with no shoulders.
The performance of the Prussian blue screen-printed electrode was evaluated in phosphate buffered saline (PBS and FBS), mimicking physiological conditions. The presence of bivalent cation (Mg2+) or smaller alkali metal (Li+) did not affect the PBS or FBS cyclic voltammetry scan. Increasing concentration of K+ caused a concentration dependent shift from Na+ to that of K+.
The performance of the Prussian blue screen-printed electrode in the detection and quantitation of cations (e.g., potassium ion) is demonstrated in FIGURES 1-9.
FIGURES 1-7 show that potassium ion can be detected in presence of plasma/serum in the form of FBS, which has high level of sodium ion and low physiological level of potassium ion. In FBS, the large peak (signal) due to sodium ion was not detected due the presence of low level of potassium ion.
FIGURE 1 compares square-wave voltamagram (SWV) results for 0.1 M solutions of LiCl, NaCl, KCl, RbCl, CsCl, and H4C1, respectively, in FBS (fetal bovine serum) obtained using a Prussian blue screen-printed electrode (SPE) (frequency 1 Hz, amplitude 50 mV, deposition potential -1 V, end potential 1 V, deposition time 300 s). FIGURES 1A to IF are the normalized SWV for 0.1 M solutions of LiCl, NaCl, KCl, RbCl, CsCl, and NH4C1 in FBS, respectively. Each ion is exhibiting different SWV profiles despite the fact that FBS contains ions including Na+ and K+. This is same as FIGURE 1 with each ion plot separated to further demonstrate the differences in SWV profiles.
FIGURES 2A-2F compare square-wave voltamagram (SWV) results for diluted solutions of LiCl, NaCl, KCl, RbCl, CsCl, and NH4C1, respectively, in FBS obtained using a Prussian blue screen-printed electrode (SPE) (solid line 0.1 M cation; dashed line
0.01 M; dotted line 0.001 M; solid black, FBS only). The electrode was not able to differentiate Li+ and Na+ from ions in the FBS - most likely Na+. However, the electrode was able to detect K+ as shift in the peak and Rb+, Cs+, and NH4 + as reduction in the Na+ peak endogenous to FBS.
FIGURE 3 compares square-wave voltamagram (SWV) results for dilutions of potassium ion solutions in FBS obtained using a Prussian blue screen-printed electrode (SPE): 0.1 M, 0.05 M, 0.025 M, 0.0125 M, 0.00625 M, 0.003125 M, 0.0015625 M KCl, FBS only. Dose dependent shift in peak with increasing amount of K+ is indicative that quantitation of K+ in FBS or serum is possible.
FIGURES 4A-4E compare three-dimensional (3D) plots of square-wave voltamagram (SWV) results (current (A) v. voltage (V) v. potassium ion concentration (M) in FBS) obtained using a Prussian blue screen-printed electrode (SPE).
FIGURE 5 is a contour plot of voltage (V) as a function of potassium ion concentration (M) (0.00 to 0.10 M in FBS). The peak current (red on contour plot) shifts slightly to a more positive voltage as K+ concentration increases. The amount of green (mid-level current) around the peak decreases as K+ concentration increases, denoting the peak becoming sharper. The contour plot clearly demonstrates the dose dependent shift in the Na+ peak with increasing amount of K+, as well as a sharpening of the peak.
FIGURES 6A-6C compare peak voltage (6 A), peak width at half height (6B), and normalized parameters (ratio to FBS) (6C) as a function of potassium ion concentration (0.001 to 0.1 M in FBS). This demonstrates that quantitation of K+ can be done using peak voltage, peak width at half height unnormalized or normalized versus FBS (serum) alone.
FIGURES 7A and 7B show data analysis for potassium ion dilutions in FBS.
FIGURE 7 A illustrates normalized parameters: ratio to FBS control as a function of potassium ion concentration (0.001 to 0.1 M in FBS) and current at 0 V, 0.15 V, 0.1 V, 0.158157 V (peak position of FBS), 0.2 V, and 0.3 V. Ratio to FBS control = (Current at X voltage) / Current at X voltage of FBS). For example, 0.1 M KC1 in FBS: (Current at green dot) / (Current at dot) in FIGURE 7B. This shows that normalized parameters at various voltage can be used to further refine the most desirable parameter for quantitation of K+.
FIGURES 8 and 9 show that potassium ion can be detected in presence of physiological concentration of sodium chloride (0.1 M in water). These data clearly demonstrate that the effect observed in FBS or serum was due to the effect of K+ on Na+ profile; most likely through displacement of Na+ from the electrode and replacing with K+.
FIGURE 8 compares square-wave voltamagram (SWV) results for dilutions of potassium ion solutions in 0.1 M aqueous sodium chloride obtained using a Prussian blue screen-printed electrode (SPE): 0.1 M, 0.05 M, 0.025 M, 0.0125 M, 0.00625 M, 0.003125 M, 0.0015625 M KC1, no potassium ion, 0.1 M NaCl only.
FIGURES 9A-9C compare absolute current (9 A) at specified voltage peak voltage (current at 0 V, 0.15 V, 0.1 V, 0.158157 V, 0.2 V, 0.3 V) (9 A), peak voltage (9B), and
peak width at half height (9C) as a function of potassium ion concentration (0.001 to 0.1 M in 0.1 M NaCl).
Due to the selectivity of Prussian blue toward certain monocations, the methods of the invention advantageously provide for the determination of these monocations in fluids that contain other ions for which Prussian blue is not selective. For example, the methods of the invention are effectively for determining the concentrations of lithium ion, potassium ion, rubidium ion, and cesium ion in presence of sodium ion.
The Prussian blue electrode (e.g., the Prussian blue screen-printed electrode) shows specific detection for K+ and Na+. The increasing presence of K+ in physiological buffer, which contains primarily Na+, resulted in concentration dependent shift in the cyclic voltammetry scan. This property was used to quantitate both Na+ and K+ in physiological fluid and, in turn, the membrane potential. As Prussian blue is nontoxic in vivo, the biosensor offers the potential to be implanted for the continuous monitoring of K+/Na+.
While the preferred embodiment of the invention has been illustrated and described, it will be appreciated that various changes can be made therein without departing from the spirit and scope of the invention.
Claims
1. A method for electrochemical determination of the concentration of cations in a sample, comprising
contacting a sample containing one or more cations with an electrochemical cell comprising a Prussian blue electrode as the working electrode, a counter electrode, and a reference electrode;
using the electrochemical cell to vary potential applied to the sample and to measure current to provide a voltamagram; and
determining the concentration of a monocation from the voltamagram.
2. The method of Claim 1, wherein the Prussian blue electrode is a Prussian blue screen-printed electrode.
3. The method of Claim 1, wherein the Prussian blue electrode is a carbon electrode.
4. The method of Claim 1, wherein the counter electrode is a carbon electrode.
5. The method of Claim 1, wherein the reference electrode is a silver electrode.
6. The method of Claim 1, wherein the sample is a physiological sample.
7. The method of Claim 1, wherein the sample is human plasma, serum, blood urine, sweat, or tears.
8. The method of Claim 1, wherein the concentration of the monocation is determined continuously.
9. The method of Claim 1, wherein determining the concentration of the monocation comprises determining the concentration of a specific monocation in the presence of a plurality of other monocations.
10. The method of Claim 1, wherein the monocation is selected from the group consisting of lithium ion, sodium ion, potassium ion, rubidium ion, cesium ion, and ammonium ion.
11. The method of Claim 1, wherein the monocation is sodium ion or potassium ion.
12. The method of Claim 1, wherein the monocation is cesium ion, rubidium ion, or lithium ion.
13. The method of Claim 1, wherein the monocation is sodium ion.
14. The method of Claim 1, wherein the monocation is potassium ion.
15. The method of Claim 1, wherein the concentration of potassium ion is determined in the presence of sodium ion.
16. A method for electrochemical determination of the concentrations of sodium ion and potassium ion in a sample, comprising
contacting a sample containing sodium ion and potassium ion with an electrochemical cell comprising a Prussian blue electrode as a working electrode, a counter electrode, and a reference electrode;
using the electrochemical cell to vary potential applied to the sample and to measure current to obtain a voltamagram; and
determining the concentration of sodium ion and potassium ion from the voltamagram.
17. The method of Claim 16, wherein the Prussian blue electrode is a Prussian blue screen-printed electrode.
18. The method of Claim 16, wherein the Prussian blue electrode is a carbon electrode.
19. The method of Claim 16, wherein the counter electrode is a carbon electrode.
20. The method of Claim 16, wherein the reference electrode is a silver electrode.
21. The method of Claim 16, wherein the sample is a physiological sample.
22. The method of Claim 16, wherein the sample is human plasma, serum, blood urine, sweat, or tears.
23. The method of Claim 16, wherein the concentrations of sodium ion and potassium ion are determined continuously.
24. The method of Claim 16, wherein the concentration of sodium ion determined is from about 1 mM to about 500 mM.
25. The method of Claim 16, wherein the concentration of potassium ion determined is from about 1 mM to about 100 mM.
26. The method of Claim 25, wherein the concentration of potassium ion is determined in presence of physiological concentrations of sodium ion.
27. A method for selective electrochemical determination of the concentration of potassium ion in a sample containing sodium ion, comprising
contacting a sample containing potassium and sodium ions with an electrochemical cell comprising a Prussian blue electrode as a working electrode, a counter electrode, and a reference electrode;
using the electrochemical cell to vary potential applied to the sample and to measure current to obtain a voltamagram; and
determining the concentration of potassium ion from the voltamagram.
28. The method of Claim 27, wherein the concentration of potassium ion determined is from about 1 mM to about 100 mM.
29. The method of Claim 27, wherein the concentration of potassium ion is determined in presence of physiological concentrations of sodium ion.
30. The method of Claim 27, wherein the Prussian blue electrode is a Prussian blue screen-printed electrode.
31. The method of Claim 27, wherein the Prussian blue electrode is a carbon electrode.
32. The method of Claim 27, wherein the counter electrode is a carbon electrode.
33. The method of Claim 27, wherein the reference electrode is a silver electrode.
34. The method of Claim 27, wherein the sample is a physiological sample.
35. The method of Claim 27, wherein the sample is human plasma, serum, blood urine, sweat, or tears.
36. The method of Claim 27, wherein the concentration of potassium ion is determined continuously.
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US11331020B2 (en) | 2020-02-06 | 2022-05-17 | Trustees Of Boston University | Enzyme-based electrochemical nicotine biosensor |
US11536685B2 (en) | 2020-02-06 | 2022-12-27 | Trustees Of Boston University | High throughput assay for identifying microbial redox enzymes |
US11801000B2 (en) | 2021-04-30 | 2023-10-31 | Trustees Of Boston University | Hormone electrochemical biosensor |
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US4214968A (en) * | 1978-04-05 | 1980-07-29 | Eastman Kodak Company | Ion-selective electrode |
US4487679A (en) * | 1984-03-15 | 1984-12-11 | Eastman Kodak Company | Potassium ion-selective electrode |
EP0833149A1 (en) * | 1996-09-25 | 1998-04-01 | Kyoto Daiichi Kagaku Co., Ltd. | Method for measuring ion concentration |
US20080223732A1 (en) * | 2003-01-20 | 2008-09-18 | Universal Biosensors Pty Ltd. | Electrochemical detection method |
US20070042450A1 (en) * | 2005-04-15 | 2007-02-22 | Worcester Polytechnic Institute | Multi-transduction mechanism based microfluidic analyte sensors |
US20130001102A1 (en) * | 2006-12-13 | 2013-01-03 | Giuseppe Palleschi | Process for the preparation of modified electrodes, electrodes prepared with said process, and enzymatic biosensors comprising said electrodes |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US11331020B2 (en) | 2020-02-06 | 2022-05-17 | Trustees Of Boston University | Enzyme-based electrochemical nicotine biosensor |
US11536685B2 (en) | 2020-02-06 | 2022-12-27 | Trustees Of Boston University | High throughput assay for identifying microbial redox enzymes |
US11801000B2 (en) | 2021-04-30 | 2023-10-31 | Trustees Of Boston University | Hormone electrochemical biosensor |
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