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WO2015127354A1 - Capteur potentiométrique, kit et procédé d'utilisation - Google Patents

Capteur potentiométrique, kit et procédé d'utilisation Download PDF

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Publication number
WO2015127354A1
WO2015127354A1 PCT/US2015/017075 US2015017075W WO2015127354A1 WO 2015127354 A1 WO2015127354 A1 WO 2015127354A1 US 2015017075 W US2015017075 W US 2015017075W WO 2015127354 A1 WO2015127354 A1 WO 2015127354A1
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WIPO (PCT)
Prior art keywords
magnesium
sensing membrane
electrode
well
porphyrin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2015/017075
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English (en)
Inventor
Todd ANDRADE
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Siemens Healthcare Diagnostics Inc
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Siemens Healthcare Diagnostics Inc
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Filing date
Publication date
Application filed by Siemens Healthcare Diagnostics Inc filed Critical Siemens Healthcare Diagnostics Inc
Publication of WO2015127354A1 publication Critical patent/WO2015127354A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes
    • C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
    • 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
    • G01N27/27—Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
    • 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
    • G01N27/302—Electrodes, e.g. test electrodes; Half-cells pH sensitive, e.g. quinhydron, antimony or hydrogen electrodes

Definitions

  • Magnesium assays are being increasingly requested in hospitals and clinical research institutions.
  • a robust magnesium sensor capable of detecting a biological active portion ionized form may aid in the clinical diagnosis of patients.
  • an optical signal may result from an analyte linkage wherein chromophore molecules have adapted to a magnesium ion. This optical signal may be identified, and then during post-processing, magnesium concentrations may be determined.
  • FIG. 1 illustrates a schematic diagram of an exemplary embodiment of a potentiometnc sensor in accordance with the present disclosure.
  • FIG. 2 illustrates a partial cross sectional view of the exemplary embodiment of the potentiometnc sensor taken along lines 2-2 in FIG. 1 showing a pH electrode, a pH-analyte electrode and a reference electrode positioned within wells.
  • FIG. 3 illustrates a partial cross sectional view of the exemplary embodiment of the potentiometric sensor taken along the lines 3-3 in FIG. 1 showing a pH electrode, a pH-analyte electrode and a reference electrode illustrated in FIG. 1 .
  • FIG. 4 illustrates a block diagram of an exemplary embodiment of a potentiometric kit in accordance with the present disclosure.
  • FIG. 5 illustrates a structural formula for the chemical compound Protoporphyrin IX.
  • FIG. 6 illustrates a flow chart of an exemplary method for determining a concentration of Mg 2+ within a sample using a potentiometric sensor.
  • FIG. 7 illustrates a partial cross sectional view of an exemplary embodiment of a potentiometric sensor showing a reference electrode positioned within a flow channel in accordance with the present disclosure.
  • any reference to “one embodiment,” “an embodiment,” “some embodiments,” “one example,” “for example,” or “an example” means that a particular element, feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment.
  • the appearance of the phrase “in some embodiments” or “one example” in various places in the specification is not necessarily all referring to the same embodiment, for example.
  • Circuitry may be analog and/or digital components, or one or more suitably programmed processors (e.g., microprocessors) and associated hardware and software, or hardwired logic. Also, “components” may perform one or more functions. The term “component,” may include hardware, such as a processor (e.g., microprocessor), an application specific integrated circuit (ASIC), field programmable gate array (FPGA), a combination of hardware and software, and/or the like.
  • processors e.g., microprocessor
  • ASIC application specific integrated circuit
  • FPGA field programmable gate array
  • Software may include one or more computer readable instructions that when executed by one or more components cause the component to perform a specified function. It should be understood that the algorithms described herein may be stored on one or more non-transient memory. Exemplary non-transient memory may include random access memory, read only memory, flash memory, and/or the like. Such non-transient memory may be electrically based, optically based, and/or the like.
  • the term user is not limited to a human being, and may comprise, a computer, a server, a website, a processor, a network interface, a human, a user terminal, a virtual computer, combinations thereof, and the like, for example.
  • the potentiometric sensor 10 is generally a membrane- based magnesium sensor capable of quantitatively measuring a concentration of ionized magnesium species within a sample solution.
  • the potentiometric sensor 10 may include a housing 12 supporting and/or encompassing one or more working pH electrodes 14, one or more working pH-analyte electrodes 16, and one or more reference electrodes 18. Additionally, the housing 12 may house one or more additional electrodes for sensing other species within a sample solution. For example, the housing 12 may house electrodes sensing other species including, but not limited to, creatinine, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, urea nitrogen, lactase dehydrogenase (LD), cholesterol, bilirubin, choline esterase, neutral lipid, glucose, hematocrit, and/or the like.
  • LD lactase dehydrogenase
  • a sample may be provided to one or more sample inlets 20 of the housing 12 and pass through a flow channel 22 of the housing 12 to one or more wells 24 of the housing 12.
  • one or more reference electrodes 18 may be positioned in one or more flow channels 22 and/or the one or more wells 24 of the housing 12.
  • one or more reference electrode 18 may be positioned in one or more well 24 of the housing 12 as shown in FIG. 3.
  • one or more reference electrode 18 may be positioned in the one or more flow channel 22, but not disposed within any of the well(s) 24.
  • the sample may be any fluidic sample and/or sample capable of being fluidic (e.g., a biological sample mixed with a fluidic substrate).
  • the sample may include tissue, fluid, and/or other material derived from a patient.
  • the sample may include, but is not limited to, serum, heparinized plasma, throat swabs, sputum, urine, blood, surgical drain fluids, tissue biopsies, and/or the like. It should be noted that although the present disclosure is directed towards a biological sample, one skilled in art will appreciate that the concepts disclosed herein may be applied to any sample wherein a concentration of magnesium may be determined, and as such, the present disclosure is not limited to biological samples.
  • the sample may flow through the flow channel 22 by a driving force.
  • the driving force may include, but is not limited to, capillary force, pressure, gravity, vacuum, electrokinesis, and/or the like.
  • solvent may be used as a solution to deliver the sample to the one or more working pH electrodes 14, the one or more working pH- analyte electrodes 16, and/or the one or more reference electrodes 18.
  • the solvent may deliver the sample to the one or more working pH electrodes 14, the one or more working pH-analyte electrodes 16, and/or the one or more reference electrodes 18, and then the solvent may evaporate. Evaporation of the solvent may cure one or more membranes on the surface of the particular electrode 14, 16 and/or 18.
  • the flow channel 22 may be a hollow channel.
  • a portion and/or the entire flow channel 22 may be filled with a carrier material.
  • a portion and/or the entire flow channel 22 may be filled with filter paper, gel, and/or beads.
  • the housing 12 is formed of a multi-layer stack including a fluid card layer 26.
  • the flow channel 22 may be formed within the fluid card layer 26.
  • the fluid card layer 26 may be formed of material including, but not limited to, plastic, ceramic, glass, and/or the like, for example.
  • the flow channel 22 may be formed through removal of a portion of the fluid card layer 26.
  • the flow channel 22 may be formed via a mold having the flow channel 22 shaped therein.
  • the shape of the flow channel 22 may be rectangular, circular, and/or any fanciful shape.
  • the flow channel 22 may deliver the sample to one or more wells 24, three of which are labeled in FIG. 3 as 24a, 24b and 24c.
  • Each well 24 may intersect with the one or more working pH electrodes 14, the one or more working pH-analyte electrodes 16, or the one or more reference electrodes 18.
  • the wells 24 may intersect with two or more of the electrodes from the group of the working pH electrodes 14, the working pH-analyte electrodes 16 and/or the reference electrodes 18.
  • two or more working pH electrodes 14 may be positioned within a single well 24.
  • FIG. 7 shows an example of a potentiometric sensor 10a that is constructed in a similar manner as the potentiometric sensor 10 discussed herein, with the exception that one or more reference electrode 18 may be positioned within the flow channel 22 as illustrated in FIG. 7. In some embodiments of the potentiometric sensor 10a, one or more reference electrode 18 may solely be positioned within the flow channel 22 and not within the well(s) 24.
  • Each well 24 may have a first end 31 and a second end 33, and may be shaped to house at least one type of electrode 14, 16 or 18.
  • the electrode may be positioned at the second end 33 of the well 24, for example.
  • the sample may flow through the flow channel 22 into the first end 31 of the well 24 and may then contact the electrode positioned on the second end 33 of the well 24.
  • the sample may flow through the flow channel 22 and into the first end 31 a of the well 24a.
  • the sample may then flow through the well 24a to the working pH electrode 14 positioned on the second end 33a of the well 24a.
  • the height h and the diameter d of each well may be determined based on the desired flow of the sample through the well. For example, in some embodiments, the height h and the diameter d of each well may be determined to increase turbulent flow of the sample through the well 24 if mixing of the sample with a reagent is desired.
  • each well 24 may be formed based on effects of an electroactive area for each conductive electrode, effects of deposition volume for membrane dispensing, and/or containment of membrane components. For example, size and shape of wells 24 may be determined such that the migration and/or interference of membrane components discussed herein may be minimized.
  • the one or more wells 24 may be a hollow channel. Alternatively, a portion and/or the entire well 24 may be filled with a carrier material. For example, in some embodiments, a portion and/or the entire well 24 may be filled with filter paper, gel, and/or beads. In some embodiments, the same material(s) may be used to fill the well 24 and the flow channel 22. Alternatively, different material(s) may be used to fill the well 24 and the flow channel 22.
  • the housing 12 may include a laminate layer 34.
  • One or more wells 24 may be formed within the laminate layer 34.
  • the laminate layer 34 may be formed of a dielectric material, including, but not limited to, plastic, ceramic, glass, and/or the like.
  • the laminate layer 34 may be patterned to form a part of well 24 intersecting the reference electrode 18 and may be formed through removal of portions of the laminate layer 34.
  • the wells 24 may be formed via a mold having each well 24 shaped therein, or deposition of a material onto a substrate around each well 24.
  • Each electrode 14, 16 and 18 may include one or more conductive layers 36.
  • the one or more conductive layer 36 may be formed of any suitable conductive material including, but not limited to, carbon, silver, silver chloride, gold, platinum, palladium, and/or the like.
  • the one or more conductive layers 36 may be sputtered, electroplated, screen printed, inkjet printed, and/or any other technique capable of applying conductive material to the housing 12 associated with fabrication of a sensor array.
  • the conductive layer 36 may be formed by laser ablation of a gold sputtered metal film on a backing with the laminate layer 34 defining wells 24 wherein the electrodes 14, 16, and 18 will be placed.
  • the conductive layer 36 may be formed of localized positioning of a carbon within the housing 12.
  • electrodes 14, 16 and 18 may also include leads 38 for connection to voltmeters 40 and/or a computer system 42 for measurement.
  • the housing 12 may also include a substrate 44 which may be physically configured to receive electrodes 14, 16 and 18 upon a surface 46 of the substrate.
  • the substrate 44 may be formed of a rigid material.
  • the substrate 44, or a portion of the substrate 44 may be formed of flexible material.
  • the materiality of the substrate 44 may serve as the physical and electronic domain for measuring potential between the one or more working pH electrodes 14, the one or more working pH-analyte electrodes 16, and/or the one or more reference electrodes 18.
  • the substrate 44 may be formed of materials including, but not limited to, plastic, ceramic, glass, and/or any material capable of containing electrodes.
  • the substrate 44 may be formed of polyethylene terephthalate (PET).
  • the one or more working pH electrodes 14 may include one or more pH sensing membranes 48.
  • the working pH electrode 14 illustrated in FIG. 3 includes pH sensing membrane 48a and the working pH-analyte electrode 16 includes a pH sensing membrane 48b.
  • the one or more pH sensing membranes 48a may be deposited on the conductive layer 36 such that the pH sensing membrane 48a may be exposed to the environment (e.g., sample) having an unknown Mg 2+ concentration.
  • the pH sensing membrane 48a may be formed of material including, but not limited to, ionophore(s), ionic salt(s), a polymer backbone, plasticizer(s), and/or solvent.
  • the pH sensing membrane 48 may include: an ionophore (2 wt% tridodecylamine (TDDA), ionic salt (21 mole% potassium tetrakis (4- chlorophenyl) borate) (KTpCIPB)), a polymer backbone (33 wt% polyvinyl chloride (PVC)), a plasticizer (65% Di-n-octyl phthalate (DOP)), and a solvent (10w/v% tetrahydrofuran (THF)).
  • TDDA tridodecylamine
  • KTpCIPB ionic salt
  • PVC polymer backbone
  • DOP Di-n-octyl phthalate
  • THF Di-n-octyl phthalate
  • lonophores of the pH sensing membrane 48a may include, but are not limited to, triaurylammonium chloride, 4-nonadecylpyridine, N,N- Dioctadecylmethylamine, and/or the like.
  • membranes formed of pH sensitive dyes may be used to measure changes in pH in addition to, or in lieu of ionophore(s).
  • the pH sensitive dyes may measure proton changes, hydrogen concentration and/or the like.
  • pH sensitive dyes such as polyaniline and/or polypyrrole films may be used to form the pH sensing membrane 48a.
  • optically active molecular indicators may additionally be used to monitor changes in pH.
  • optically active molecular indicators may include, but are not limited to, 6-carboxyfluorescein, 2', 7'- bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, 1 ,4-dihydroxyphthalonitrile, 8- hydroxypyrene-1 ,3,6-trisulfonic acid (HPTS)1 , seminaphthorhodafluor (SNARF)/seminaphthofluorescein (SNAFL) dyes, boron-dipyrromethene (KBH-01 ), and/or the like.
  • Ionic salts of the pH sensing membrane 48a may include, but are not limited to, sodium tetraphenylborate, sodium tetrakis (4-fluorophenyl)borate dehydrate, and/or the like.
  • Polymers of the pH sensing membrane 48a may include, but are not limited to, polyurethane (hydrophilic), silicone rubber, and/or the like.
  • Plasticizers of the pH sensing membrane 48a may include, but are not limited to, dibutyl sebacate, Bis(1 -butylpentyl)decan-1 ,10-diyl diglutarate, bis(l- butylpentyl)adipate, bis(2-ethylhexyl)sebacate, 2-nitrophenyl octyl ether, and/or the like.
  • the magnesium sensing membrane 52 may be formed of one or more enzymes and one or more porphyrins.
  • the porphyrin(s) is specific for magnesium, while the enzyme(s) catalyzes insertion of a magnesium ion into the porphyrin.
  • the one or more working pH-analyte electrodes 16 may include the pH sensing membrane 48b and a magnesium sensing membrane 52.
  • the pH sensing membrane 48b may be formed of materials similar to pH sensing membrane 48a as described herein.
  • the ionophore(s) senses protons alleviated from porphyrin upon insertion of the magnesium ion.
  • the pH sensing membrane 48b may be deposited and/or formed on the magnesium sensing membrane 52 such that the pH sensing membrane 48b is exposed to the environment (e.g., sample) having an unknown Mg 2+ concentration.
  • the pH sensing membrane 48b may be deposited and/or formed on the conductive layer 36 with the magnesium sensing membrane 52 deposited and/or formed on the pH sensing membrane 48b.
  • the magnesium sensing membrane 52 may be formed of the enzyme, magnesium protoporphyrin chelatase (6.6.1 .1 .), and the porphyrin, protoporphyrin IX (Mg).
  • the enzyme magnesium protoporphyrin chelatase may include three subunits, Chi I , ChID, and ChlH. This enzyme may be isolated/reconstituted (e.g., soybean) from plants and/or cloned/expressed through gene encoding.
  • active and stable enzymes for the magnesium sensing membrane 52 may be found using methods and techniques as described in at least Ribo Guo, Meizhong Luo, and Jon D. Weinstein. "Magnesium-Chelatase from Developing Pea Leaves.” Plant Physiology, 1 16(2). (1998): 605-615, and/or L.C. Gibson, P.E. Jensen, C.N. Hunter, "Magnesium chelatase from Rhodobacter sphaeroides: initial characterization of the enzyme using purified subunits and evidence for a Bchl-BchD complex.” Journal of Biochemistry, 337(Pt. 2). (1999): 243-251 , which are hereby incorporated by reference in their entirety.
  • the enzyme may be obtained from a commercial source and/or synthesized within a lab. In other embodiments, the enzyme may be extracted and isolated from any source that natively and/or recombinantly produces the enzyme. That is, the enzyme may be natively produced by the source from which it is obtained, or the source may be genetically engineered to recombinantly produce the enzyme.
  • the enzyme of the magnesium sensing membrane 52 may be immobilized on and/or within the membrane. Immobilization of the enzyme on and/or within the magnesium sensing membrane 52 may be through adsorption, covalent binding, cross-linking of the enzyme, entrapment within gels, entrapment within polymer matrices, and/or the like.
  • porphyrin of the magnesium sensing membrane 52 may be obtained from a commercial source.
  • the porphyrin may be obtained as Protoporphyrin IX (SKU-P8293-1 G) shown in FIG. 5.
  • Protoporphyrin IX is manufactured and distributed by the Sigma-Aldrich Corporation, having a corporate office location in St. Louis, MO.
  • Protoporphyrin IX is generally a biochemically used carrier molecule for divalent cations such as iron, magnesium and zinc.
  • porphyrin may be extracted and isolated.
  • porphyrin may be extracted and isolated using techniques as described in Michelle L. Dean, Tyson A. Miller, and Christian Bruckner. "Egg-Citing! Isolation of Protoporphyrin IX from Brown Eggshells and Its Detection by Optical Spectroscopy and Chemiluminescence.” J. Chem. Edu., 88(6). (201 1 ): 788-792, which is hereby incorporated by reference in its entirety.
  • ATP adenosine triphosphate
  • ATP may be included within the magnesium sensing membrane 52.
  • ATP may be immobilized on and/or within the magnesium sensing membrane 52.
  • ATP may be within the sample.
  • ATP concentrations of approximately 1 mM and greater may enable design of the potentiometric sensor 10 without the inclusion of ATP within the magnesium sensing membrane 52.
  • a polymer may be used to immobilize the enzyme, ATP, and/or porphyrin on and/or within the magnesium sensing membrane 52.
  • polymers such as polyvinyl alcohol (PVA), mesoporous silica, hydrogels, sol-gel precursor mixtures of 3- glycidoxypropyltrimethoxysilane with methyltrimethoxysilane or tetraethoxysilane, ionic liquid methylimidazolium hexafluophosphate, photopolymerization of poly(ethylene glycol) diacrylate (PEG- DA) with 2-hydroxy-2-methyl phenyl-propanone as photoinitiator protoporphyrin IX, and/or the like, may be used to immobilize components into the magnesium sensing membrane 52.
  • PVA polyvinyl alcohol
  • mesoporous silica such as hydrogels, sol-gel precursor mixtures of 3- glycidoxypropyltrimethoxysilane with
  • the one or more working pH electrodes 14, the one or more working pH-analyte electrodes 16, and the one or more reference electrodes 18 may be connected to one or more voltmeters 40.
  • working pH electrode 14 and reference electrodes 18 are connected to voltmeter 40a
  • working pH-analyte electrode 16 and reference electrode 18 are connected to voltmeter 40b.
  • Voltmeters 40a and 40b may measure changes in electrical potential between the reference electrode 18 and the working pH electrode 14, and the reference electrode 18 and the working pH-analyte electrode 16, respectively.
  • the voltmeters 40 may be in communication with one or more computer systems 42.
  • the one or more computer systems 42 may be a system or systems that are able to embody and/or execute the logic of the processes described herein.
  • Logic embodied in the form of software instructions and/or firmware may be executed on any appropriate hardware.
  • logic embodied in the form of software instructions and/or firmware may be executed on dedicated system or systems, on a personal computer system, on a distributed processing computer system, and/or the like.
  • logic may be implemented in a stand-alone environment operating on a single computer system and/or logic may be implemented in a networked environment such as a distributed system using multiple computers and/or processors.
  • the computer system 42 may include one or more processors 54 working together, or independently to, execute processor executable code, one or more memories 56 capable of storing processor executable code, one or more input devices 58, and one or more output devices 60.
  • Each element of the computer system 42 may be partially or completely network-based or cloud based, and may or may not be located in a single physical location.
  • the one or more processors 54 may communicate with the voltmeters 40 via a network.
  • the terms "network-based”, “cloud-based”, and any variations thereof, are intended to include the provision of configurable computational resources on demand via interfacing with a computer and/or computer network, with software and/or data at least partially located on the computer and/or computer network.
  • the network may permit bidirectional communication of information and/or data between the one or more processors 54 and/or the voltmeters 40.
  • the network may interface with the one or more processors 54 and the voltmeters 40, in a variety of ways.
  • the network may interface by optical and/or electronic interfaces, and/or may use a plurality of network topographies and/or protocols including, but not limited to, Ethernet, TCP/IP, circuit switched paths, combinations thereof, and/or the like.
  • the network may be implemented as the World Wide Web (or Internet), a local area network (LAN), a wide area network (WAN), a metropolitan network, a wireless network, a cellular network, a GSM-network, a CDMA network, a 3G network, a 4G network, a satellite network, a radio network, an optical network, a cable network, a public switch telephone network, an Ethernet network, combinations thereof, and/or the like.
  • the network may use a variety of protocols to permit bi-directional interface and/or communication of data and/or information between the one or more processors 54 and the voltmeters 40.
  • the network may be the Internet and/or other network.
  • a primary user interface of the computer system 42 may be delivered through a series of web pages (e.g., pH and/or Mg 2+ concentration determination webpages). It should be noted that the primary user interface of the computer system 42 may also be another type of interface including, but not limited to, Windows-based application.
  • the one or more processors 54 may be implemented as a single processor or multiple processors working together, or independently, to execute the logic as described herein. It is to be understood, that in certain embodiments using more than one processor 54, the processors 54 may be located remotely from one another, located in the same location, or comprising a unitary multi-core processor. The processors 54 may be capable of reading and/or executing processor executable code and/or capable of creating, manipulating, retrieving, altering and/or storing data structure into the one or more memories 56.
  • Exemplary embodiments of the one or more processors 54 may include, but are not limited to, a digital signal processor (DSP), a central processing unit (CPU), a field programmable gate array (FPGA), a microprocessor, a multi-core processor, combinations thereof, and/or the like, for example.
  • DSP digital signal processor
  • CPU central processing unit
  • FPGA field programmable gate array
  • microprocessor a microprocessor
  • multi-core processor combinations thereof, and/or the like, for example.
  • additional processors 54 may include, but are not limited to implementation as a personal computer, a cellular telephone, a smart phone, network-capable television set, a television set-top box, a tablet, an e-book reader, a laptop computer, a desktop computer, a network-capable handheld device, a video game console, a server, a digital video recorder, a DVD-player, a Blu-Ray player, and/or combinations thereof, for example.
  • the one or more processors 54 may be capable of communicating with the one or more memories 56 via a path (e.g., data bus).
  • the one or more processors 54 may also be capable of communicating with the input devices 58 and/or the output devices 60.
  • the one or more processors 54 may be capable of interfacing and/or communicating with the voltmeters 40.
  • the one or more processors 54 may be capable of communicating by exchanging signals (e.g., analog, digital, optical, and/or the like) using a network protocol.
  • the one or more memories 56 may be capable of storing processor executable code. Additionally, the one or more memories 56 may be implemented as a conventional non-transient memory, such as, for example, random access memory (RAM), a CD-ROM, a hard drive, a solid state drive, a flash drive, a memory card, a DVD-ROM, a floppy disk, an optical drive, combinations thereof, and/or the like.
  • RAM random access memory
  • one or more memories 56 may be located in the same physical location as the processor 54, and/or one or more memories 56 may be located remotely from the processor 54.
  • one or more memories 56 may be located remotely from the processor 54 and communicate with other processors via the network.
  • a first memory may be located in the same physical location as the processor 54, and additional memories 56 may be located in a remote physical location from the processor 54.
  • one or more memories 56 may be implemented as a "cloud memory" (i.e., one or more memories 56 may be partially or completely based on or accessed using the network).
  • the one or more input devices 58 may be capable of receiving information input from a user and/or processor(s), and may be capable of transmitting such information to the one or more processors 54, network, and/or voltmeters 40.
  • the one or more input devices 58 may include, but are not limited to, implementation as a keyboard, touchscreen, mouse, trackball, microphone, fingerprint reader, infrared port, slide-out keyboard, flip-out keyboard, cell phone, PDA, video game controller, remote control, fax machine, network interface, combinations thereof, and the like, for example.
  • the one or more output devices 60 may be capable of outputting information in a form perceivable by a user and/or processors(s).
  • the one or more output devices may include, but are not limited to, implementation as a computer monitor, a screen, a touchscreen, a speaker, a website, a television set, a smart phone, a PDA, a cell phone, a fax machine, a printer, a laptop computer, combinations thereof, and/or the like, for example.
  • the one or more input devices 58 and the one or more output devices 60 may be implemented as a single device, such as, for example, a touchscreen or a tablet.
  • the term user is not limited to a human being, and may comprise, a computer, a server, a website, a processor, a network interface, a human, a user terminal, a virtual computer, combinations thereof, and/or the like, for example.
  • the one or more memories 56 may store processor executable code and/or information comprising one or more database 64 and program logic 66.
  • the processor executable code may be stored as a data structure, such as a database and/or a data table, for example.
  • outputs of one or more voltmeters 40 may be stored in one or more databases and/or data tables 64 within the one or more memories 56.
  • FIG. 6 illustrates a flow chart 70 of an exemplary method for determining Mg 2+ concentration within a sample using the potentiometric sensor 10.
  • the sample (e.g., blood) may be provided into the sample inlet 20 of the potentiometric sensor 10.
  • the sample may flow through the flow channel(s) 22. Flow through the flow channels 22 may be by any force such as capillary, pressure, and/or the like.
  • the sample may flow through the flow channels 22 to one or more wells 24, and come into contact with one or more working pH electrodes 14, one or more working pH-analyte electrodes 16, and one or more reference electrodes 18.
  • the enzyme within the magnesium sensing membrane 52 may catalyze the insertion of magnesium into the porphyrin of the magnesium sensing membrane 52.
  • magnesium protoporphyrin chelatase (6.6.1 .1 ) may catalyze the insertion of magnesium into protoporphyrin IX.
  • the enzyme-catalyzed insertion of magnesium may include the use of hydrolyzable adenosine triphosphate (ATP), the sample may react with the enzyme such that:
  • the protons produced in the reaction may be detected by the use of the pH sensing membranes 48a and 48b via electrical potential measurements of electrodes 14, 16 and 18, obtained by voltmeters 40a and 40b.
  • the potential difference between the working pH electrode 14 and the reference electrode 18 may be obtained by the voltmeter 40a.
  • the potential difference between the working pH-analyte electrode 16 and the reference electrode 18 may be obtained by the voltmeter 40b.
  • the potential difference measurements may be communicated to and/or stored in one or more data tables 64 within the computer system 42.
  • the processor 54 may analyze the potential difference measurements and determine an indirect measurement of magnesium within the sample using the differential potentiometric measurements. For example, based on the kinetics of the reaction, the concentration of components may be selected for an expected analyte range within the sample and as such, an increase of H + production may be directly dependent on an increase in Mg 2+ concentration, and vice versa.
  • the expected analyte range may be between approximately 0.1 mmol/L to 10 mmol/L, for example. In other embodiments, the expected analyte range may be between approximately 0.45 mmol/L to 0.66 mmol/L.
  • Variations in proton concentration may change the potential of the pH sensing membrane layers 48a and 48b, and as such, the electrical potential measurements of electrodes 14 and 16, obtained by voltmeters 40a and 40b may change accordingly.
  • the electrical potential measured through the voltmeter 40a and the electrical potential measured through the voltmeter 40b may be substantially similar (e.g., 200 mV). If there is an increase in pH about the working pH electrode 14 and the working pH- analyte electrode 16, the electrical potential measured through the voltmeter 40a may still be substantially similar to the electrical potential measured through the voltmeter 40b.
  • the reaction of the Mg 2+ on and/or within the magnesium sensing membrane 52 of the working pH- analyte electrode 16 may provide additional H + production about the working pH- analyte electrode 16.
  • This additional H + production may decrease the pH about the working pH-analyte electrode 16, and thus may decrease the electrical potential measured through the voltmeter 40b as compared to voltmeter 40a.
  • the resulting decrease in electrical potential measured by voltmeter 40b as compared to voltmeter 40a may be analyzed to determine the amount of Mg 2+ within the sample.
  • inventive concept(s) disclosed herein are well adapted to carry out the objects and to attain the advantages mentioned herein, as well as those inherent in the inventive concept(s) disclosed herein. While the embodiments of the inventive concept(s) disclosed herein have been described for purposes of this disclosure, it will be understood that numerous changes may be made and readily suggested to those skilled in the art which are accomplished within the scope and spirit of the inventive concept(s) disclosed herein.

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Abstract

La présente invention concerne un capteur potentiométrique pour déterminer une concentration de magnésium dans un échantillon qui comprend une électrode de référence, une électrode pH et une électrode pH-analyte. L'électrode pH-analyte comprend une membrane de détection de magnésium ayant une porphyrine spécifique pour le magnésium et une enzyme qui catalyse l'insertion d'un ion magnésium dans la porphyrine. La membrane de détection de pH comprend un ionophore qui détecte des protons extraits de la porphyrine lors de l'insertion de l'ion magnésium.
PCT/US2015/017075 2014-02-24 2015-02-23 Capteur potentiométrique, kit et procédé d'utilisation Ceased WO2015127354A1 (fr)

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US61/943,538 2014-02-24

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11113511B2 (en) 2017-02-01 2021-09-07 Lg Household & Health Care Ltd. Makeup evaluation system and operating method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4927516A (en) * 1986-06-27 1990-05-22 Terumo Kabushiki Kaisha Enzyme sensor
US20090020423A1 (en) * 2007-07-17 2009-01-22 Chung Yuan Christian University Potentiometric Mg2+ Sensor and Method thereof
WO2013019982A2 (fr) * 2011-08-02 2013-02-07 Colorado State University Research Foundation Système de biocaptage avec durée de vie prolongée via un recyclage de cofacteur

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4927516A (en) * 1986-06-27 1990-05-22 Terumo Kabushiki Kaisha Enzyme sensor
US20090020423A1 (en) * 2007-07-17 2009-01-22 Chung Yuan Christian University Potentiometric Mg2+ Sensor and Method thereof
WO2013019982A2 (fr) * 2011-08-02 2013-02-07 Colorado State University Research Foundation Système de biocaptage avec durée de vie prolongée via un recyclage de cofacteur

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11113511B2 (en) 2017-02-01 2021-09-07 Lg Household & Health Care Ltd. Makeup evaluation system and operating method thereof

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