US20150346144A1 - Ph meter - Google Patents

Ph meter Download PDF

Info

Publication number
US20150346144A1
US20150346144A1 US14/758,491 US201314758491A US2015346144A1 US 20150346144 A1 US20150346144 A1 US 20150346144A1 US 201314758491 A US201314758491 A US 201314758491A US 2015346144 A1 US2015346144 A1 US 2015346144A1
Authority
US
United States
Prior art keywords
analyte
sample
anvils
electrode
sensor
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.)
Abandoned
Application number
US14/758,491
Other languages
English (en)
Inventor
Eric Lee
Steve Roth
Thang Huy Vu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Parker Hannifin Corp
Original Assignee
Senova Systems Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Senova Systems Inc filed Critical Senova Systems Inc
Priority to US14/758,491 priority Critical patent/US20150346144A1/en
Assigned to SENOVA SYSTEMS, INC. reassignment SENOVA SYSTEMS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ROTH, STEVE, VU, Thang Huy, LEE, ERIC
Publication of US20150346144A1 publication Critical patent/US20150346144A1/en
Assigned to PARKER-HANNIFIN CORPORATION reassignment PARKER-HANNIFIN CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SENOVA SYSTEMS, INC.
Abandoned legal-status Critical Current

Links

Images

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
    • G01N27/416—Systems
    • G01N27/4166—Systems measuring a particular property of an electrolyte
    • G01N27/4167—Systems measuring a particular property of an electrolyte pH
    • 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
    • G01N27/301—Reference electrodes
    • 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
    • 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
    • G01N27/4163—Systems checking the operation of, or calibrating, the measuring apparatus
    • G01N27/4165—Systems checking the operation of, or calibrating, the measuring apparatus for pH meters
    • 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
    • G01N27/36—Glass electrodes

Definitions

  • the present invention provides improved analyte sensors that enable precise measurement of analyte concentrations, including but not limited to hydronium ion concentration or pH.
  • the invention relates generally to the field of analytical chemistry and specifically to pH measurement technology.
  • Measurement of analyte concentration, such as pH, in samples is constrained by available sample volume. Most commercially available pH electrodes require at least milliliter volume samples. Very few specialized glass probes containing a working electrode (the “sensor”), reference electrode, and counter electrodes are available that are advertised as capable of measuring pH in sample volumes as low as 0.5 microliter, and those are very expensive (e.g. Thermo Scientific Orion 9810 BN). However, glass probes designed for small sample volumes present many challenges.
  • One challenge is positioning of the probe in the sample. Proper probe placement requires ensuring adequate contact between the glass membrane and the reference junction of the probe and the sample. The bulbous shape of glass probes makes this challenge especially difficult. Similarly, semi-solid samples, such as from a tissue biopsy, may require larger volumes, relative to that for liquid samples, when using glass electrodes, as the shape of the probe again may lead to inadequate sample contact for semi-solid samples of small volume.
  • Another challenge is the potential for contamination of samples due to transfer of salts or other materials (“mass”) from the electrodes in the probe into the sample. As sample volume decreases, the effect of such mass transfer increases for any probe.
  • Another challenge is sample evaporation, as evaporation is relatively greater in low volume samples, and evaporative effects may be difficult to monitor. Loss of sample volume can lead to erroneous results.
  • glass probes can only measure one sample at a time.
  • To increase throughput in a system requiring analyte concentration measurement using a glass probe one must either increase the number of probes used or decrease the average time required for each measurement.
  • pH measurement using a glass electrode requires that a potentiometric signal reach steady state (as may be defined by algorithms for a given system)
  • decreasing measurement time is inherently a limited approach.
  • Glass probes are relatively expensive to manufacture, however, and, for repeat use, they must be rinsed between samples to reduce the chances for cross contamination, further impeding high sample throughput in pH measurement. Fouling, a source of drift and error, is also particularly problematic with glass probes, because samples containing protein, sugar, or other constituents that interact with the glass can foul the probe. Glass probes require frequent maintenance to eliminate or reduce fouling and ensure accuracy, and frequent re-calibration is also required. These operations increase the risk of damage, which only increases in the small confines necessitated by small volume samples.
  • pH electrodes feature a glass membrane in the form of an essentially spherical bulb.
  • a reference junction is also provided in the body of the electrode located near the glass membrane. In all cases, all combination electrodes must be immersed to a depth sufficient to cover the reference junction, which cannot be located co-planar to the glass membrane except in complex designs.
  • a further limitation arises from the liquid junction of the reference electrode. Proper functioning of the reference electrode depends on fluid communication between the analyte and the internal reference solution through a porous junction such as a frit. Under typical use conditions a small quantity of the internal reference solution is allowed to pass through the porous junction into the analyte.
  • the traditional glass pH probe has a working electrode (WE) that is an ion-selective electrode made of a fragile, doped glass membrane sensitive to hydrogen ions.
  • WE working electrode
  • the pH-responsive glass membrane is the primary analyte sensing element in this type of probe and so is referred to as the “working” electrode.
  • Hydrogen ions within the sample solution bind to the outside of the glass membrane, thereby causing a change in potential on the interior surface of the membrane.
  • This change in potential is measured against the constant potential of a conventional reference electrode (RE), such as an electrode based on silver/silver chloride.
  • RE conventional reference electrode
  • the difference in potential is then correlated to a pH value by plotting the difference on a calibration curve.
  • the calibration curve is created through a multistep process whereby the user plots changes in potential for various known buffer standards.
  • Traditional pH meters are based on this principle.
  • the RE plays a critical role in the accuracy of the measurement.
  • a highly stable electrode potential is necessary. This is commonly achieved using redox systems in which all active components are maintained at constant concentration.
  • a chloridized silver wire is immersed in concentrated potassium chloride (KCl) solution.
  • KCl concentrated potassium chloride
  • the KCl solution is in fluid and electric communication with the analyte through a porous frit. This liquid junction gives rise to possible contamination of the internal KCl solution, which would change the electrode potential, resulting in drift of the measurement.
  • Other disadvantages include the propensity to leakage of the internal electrolyte, and clogging due to drying or precipitation inside the liquid junction.
  • the present invention provides sensors, sensor components, and methods for their fabrication and use, particularly voltammetric or amperometric methods for detecting analyte concentration that not only enable the measurement of analyte concentration in small volume samples but also provide improved performance with all sample volumes.
  • the present invention provides sensors with substantially flat sensing surfaces on which all sensing elements are located co-planar to one another. These configurations allow even small volumes of sample to contact all sensing elements, for example in the form of a liquid film captured between the sensing surface and another solid surface.
  • the sensing elements may be located on opposite surfaces capturing the liquid.
  • the sample is held by capillary action within the gap formed by the sensor without the use of a sample container. In this way the sample size is no longer dependent on the size of the sensor, but rather by the dimension of the gap formed by the sensor and a complementary surface.
  • a uniform liquid film can be formed with a volume of 10 microliters or less.
  • the sensitivity of measurement is not reduced as the sample volume decreases, because sensitivity is primarily a function of the surface area of the sensor and not of the sample volume. Indeed, sensor surface areas substantially larger than that possible with conventional glass probes can be made to allow detection of low analyte concentrations.
  • some implementations of the current invention provide systems that enable precise containment of small sample volumes, as well as sensors with planar geometries that facilitate formation of small gaps with a complementary solid surface, including arrangements where the sensing elements are located on one or both sides of that defined space.
  • the present invention provides devices and methods for measuring the concentration of an analyte in microliter-scale liquid samples (e.g. about 10 ⁇ L or less) in which the sample is held by surface tension between two anvils, each comprising a containment area where the sample is deposited (or contacted).
  • One or both anvils have embedded in them one or more electrodes of the analyte sensor in conductive contact with a surface of the anvil having a containment area wetted by the sample.
  • the containment area is defined by a surface wetted by the analyte surrounded by a surface not wetted by the analyte, wherein the surface wetted by the analyte comprises the sensing elements.
  • one or more electrodes of the sensor are fabricated by coating or printing the electrode components on a suitable substrate, such substrates including solids, porous, and/or flexible materials.
  • the present invention provides devices that enable multi-channel analyte concentration measurements on a plurality of microliter samples, each held by surface tension between two anvil surfaces that form a sensor, wherein a single voltammetric scan is performed across an array of such sensors.
  • the device for making analyte concentration measurements on a plurality of microliter liquid samples contained by surface tension comprises: means for containing a plurality of microliter samples by surface tension between opposing, proximal-ends of a plurality of sets of anvils, wherein each set of anvils provides a functional sensor, said anvils optionally in a substantially parallel, spaced-apart relationship; means for supplying current to the anvils; means for holding the anvils in an array; means for performing voltammetric scanning of the sensors; and means connected to the sensors for accepting signals transmitted through them and making analyte concentration measurements thereon, wherein analyte concentration measurements are made at more than one sensor simultaneously using the more than one sensors and more than one means for accepting signals and making analyte concentration measurements thereon.
  • the present invention provides an analyte sensor for measuring analyte concentration in a sample comprising: a first anvil and a second anvil that together form the analyte sensor, wherein said anvils are mechanically coupled to one another by a means that enables adjustment of the separation between the anvils such that a liquid sample placed on a surface of one of said anvils can be contacted with a surface the other anvil, thereby establishing conductive contact between the two anvils through the analyte, and retained in such position for a sufficient period of time for an analyte measurement to be made using voltammetric scanning.
  • the present invention provides methods and materials for preparing components of electrodes useful in the sensors of the invention.
  • the materials of the present invention are redox-active analyte-sensitive materials (RAMs) useful, e.g., in a working electrode.
  • the materials are polymers comprising such RAMS covalently attached thereto.
  • these materials are RAMS suitable for incorporation in printing inks that can be used in print-based fabrication methods.
  • the materials are composites formed by an ionic liquid, a conductive material, including but not limited to carbon, and a polymer, including but not limited to polyvinylidene fluoride (PVDF), that are useful in forming junctions between an electrode, such as a reference electrode, and the sample in which analyte concentration is to be measured.
  • PVDF polyvinylidene fluoride
  • the methods of the invention include methods for making and purifying the RAMS, polymers, and composites of the invention.
  • the present invention provides electrodes and electrode components and methods for their manufacture and use. These electrodes and electrode components can, in accordance with various embodiments of the invention, be employed in miniaturized sensors for measuring analyte concentrations in microliter-scale samples. In some embodiments, the electrodes and electrode components are useful as replacement parts for sensors in general use to provide better performance and/or to reduce maintenance costs.
  • the methods of the invention include methods for making miniaturized sensors and miniaturized electrodes by depositing sensing materials on suitable substrates by means of various coating, printing, microfabrication, and photolithography methods.
  • the present invention provides reference electrodes that employ composites comprising at least one room temperature ionic liquid (RTIL), a carbon allotrope, and a polymeric material that combines the RTIL and the carbon allotrope into a conductive solid matrix.
  • RTIL room temperature ionic liquid
  • the resultant solid matrix is useful as a component of an RE that contains an internal reference system such as Ag/AgCl immersed in a KCl solution, where the conductive solid matrix separates the KCl solution from the analyte.
  • the conductive solid matrix is useful as a component of an RE that contains no internal solution.
  • the RE can be used in conjunction with various combinations of WE and counter electrode (CE) in voltammetric analysis.
  • the conductive solid matrix acts as a barrier between a constant chemical environment with a characteristic electrode potential and the analyte.
  • the solid matrix is electrically conductive and substantially impermeable to the analyte except protons therein.
  • the conductive solid matrix is referred to as a conductive analyte barrier (CAB).
  • a distinguishing feature of the CAB is its proton permeability through the RTIL component and electrical conductivity through the carbon component.
  • the CAB is used in conjunction with a conventional Ag/AgCl redox couple in contact with concentrated KCl solution.
  • the CAB contacts the solid Ag/AgCl redox couple directly.
  • Alternative reference electrode systems such as saturated calomel or copper/copper sulfate systems also produce viable REs in accordance with this invention.
  • the CAB comprises an RTIL, a polymer miscible or partially miscible with the RTIL, and a finely divided carbon allotrope such as graphite powder or carbon nanotubes.
  • these ingredients are made into a composite by blending with a melt or solution of the polymer, and then solidified by cooling or by removing the solvent by evaporation. The resulting solid is shaped to fit the opening of a tube, for example, followed by filling the tube with the Ag/AgCl/KCl components.
  • the melt or solution is used to fill a porous structure such as glass, ceramic, or an inert microporous material such as cellulose. After solidification the porous matrix is shaped and assembled as described above.
  • RTIL and carbon allotrope are incorporated into one or more precursors of a multi-part reactive polymer system such as epoxy or polyurethane. Combining the reactive precursors initiates polymerization. Upon reaction completion, a substantially homogeneous polymer matrix is obtained that is rendered conductive by both the RTIL and carbon components.
  • an RTIL containing a reactive functional group is used to enable attachment onto a host polymer, or is polymerized or copolymerized to form conductive macromolecular analogs.
  • RTIL derivative and its macromolecular equivalent the techniques described in the previous embodiments is used to form the CAB.
  • a macromolecular RTIL or its copolymer with good mechanical strength can be used to form the CAB in the shape required, but in other embodiments, a soft or fragile macromolecular RTIL with good electrochemical qualities is reinforced by a porous matrix.
  • the advantage of using a macromolecular RTIL is to reduce loss of RTIL moieties to the analyte, which is undesirable both because of a possible change in local RTIL concentration in the CAB, affecting its stability, and possible contamination of the analyte especially for small analyte volumes.
  • the CAB comprises an RTIL, a miscible or partially miscible polymer, and a carbon allotrope or carbonaceous porous support.
  • An additional component in the CAB is a saturated or supersaturated concentration of AgCl, obtained by adding AgCl to the RTIL prior to blending with other components. This CAB is then brought into contact with Ag/AgCl in the form of a chloridized silver surface. The concentration of AgCl dissolved in the RTIL component and, in turn, the CAB, ensures that the electrode potential at the chloridized silver is kept constant.
  • the RTIL is a single RTIL or a combination of RTILs.
  • the CAB comprises an ionic solid based on polycationic congeners of RTILs.
  • the CAB comprises a blend of polycations and polyanions.
  • FIG. 1 shows a schematic view of an illustrative voltammetric sensor device in accordance with a representative embodiment of the present invention.
  • FIG. 2 shows a schematic view of a reference electrode construct in accordance with a representative embodiment of the present invention.
  • FIG. 3 shows a graph demonstrating the stability of three reference electrodes in accordance with representative embodiments of the present invention.
  • FIG. 4 shows a graph demonstrating the average potential of each electrode after it has undergone pH 2-12 staircase testing in accordance with a representative embodiment of the present invention.
  • FIG. 5 shows a schematic view of a reference electrode construct in accordance with a representative embodiment of the present invention.
  • FIG. 6 shows a graph demonstrating stable potential by directly embedding the Ag/AgCl wire directly into the composite plug reference junction in accordance with a representative embodiment of the present invention.
  • FIG. 7 shows a schematic view of a working electrode construct in accordance with a representative embodiment of the present invention.
  • FIG. 8 shows schematic views of a pH-sensing electrode in accordance with a representative embodiment of the present invention.
  • FIG. 9 shows schematic views of a pH sensor assembly in accordance with a representative embodiment of the present invention.
  • FIG. 10 shows schematic views of counter and reference electrodes positioned opposite a working electrode in accordance with representative embodiments of the present invention.
  • FIG. 11 shows a graph demonstrating square wave voltammetry plots for calibration data that was generated using electrode assemblies of the present invention with BDH Brand standards for pH 2, 4, 7, and 10.
  • FIG. 12 shows a graph demonstrating peak data from FIG. 11 that was plotted versus pH buffer.
  • FIG. 13 shows a graph demonstrating the comparison of pH as measured by a pH sensor device of the instant invention and a commercially available pH meter.
  • FIGS. 14-18 show graphs demonstrating overlaid plots of square wave voltammetry analysis for each buffer in FIG. 13 .
  • FIG. 19 shows a graph demonstrating peak data from FIGS. 14-18 .
  • FIG. 20 shows a schematic view of a single well pH sensing device in accordance with a representative embodiment of the present invention.
  • FIG. 21 shows a schematic view of a pH sensing device in accordance with a representative embodiment of the present invention.
  • the present invention provides compounds, compositions, methods, electrodes, electrode components, and sensors, including solid state analyte sensors, superior to those currently known in the art. To facilitate appreciation of the benefits of the invention, the following definitions are provided for the convenience of the reader.
  • a binder includes a composition of only a single binder and compositions that are mixtures of binders.
  • Alkanyl refers to a saturated branched, straight-chain or cyclic alkyl group. Typical alkanyl groups include, but are not limited to, methanyl; ethanyl; propanyls such as propan-1-yl, propan-2-yl(isopropyl), cyclopropan-1-yl, etc.; butyanyls such as butan-1-yl, butan-2-yl(sec-butyl), 2-methyl-propan-1-yl(isobutyl), 2-methyl-propan-2-yl(t-butyl), cyclobutan-1-yl, and the like.
  • Alkenyl refers to an unsaturated branched, straight-chain or cyclic alkyl group having at least one carbon-carbon double bond derived by the removal of one hydrogen atom from a single carbon atom of a parent alkene.
  • the group may be in either the cis or trans conformation about the double bond(s).
  • Typical alkenyl groups include, but are not limited to, ethenyl; propenyls such as prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl(allyl), prop-2-en-2-yl, cycloprop-1-en-1-yl; cycloprop-2-en-1-yl; butenyls such as but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl, but-2-en-1-yl, but-2-en-2-yl, buta-1,3-dien-1-yl, buta-1,3-dien-2-yl, cyclobut-1-en-1-yl, cyclobut-1-en-3-yl, cyclobuta-1,3-dien-1-yl, and the like.
  • Alkoxy by itself or as part of another substituent refers to a radical —OR 100 where R 100 represents an alkyl group as defined herein. Representative examples include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, and the like.
  • Alkyl refers to a saturated or unsaturated, branched, straight-chain or cyclic monovalent hydrocarbon group derived by the removal of one hydrogen atom from a single carbon atom of a parent alkane, alkene or alkyne.
  • Typical alkyl groups include, but are not limited to, methyl; ethyls such as ethanyl, ethenyl, ethynyl; propyls such as propan-1-yl, propan-2-yl, cyclopropan-1-yl, prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl(allyl), cycloprop-1-en-1-yl; cycloprop-2-en-1-yl, prop-1-yn-1-yl, prop-2-yn-1-yl, etc.; butyls such as butan-1-yl, butan-2-yl, 2-methyl-propan-1-yl, 2-methyl-propan-2-yl, cyclobutan-1-yl, but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-2-yl, buta-1,
  • alkyl is specifically intended to include groups having any degree or level of saturation, i.e., groups having exclusively single carbon-carbon bonds, groups having one or more double carbon-carbon bonds, groups having one or more triple carbon-carbon bonds and groups having mixtures of single, double and triple carbon-carbon bonds. Where a specific level of saturation is intended, the expressions “alkanyl,” “alkenyl,” and “alkynyl” are used. The expression “lower alkyl” refers to alkyl groups comprising from 1 to 8 carbon atoms.
  • Alkynyl refers to an unsaturated branched, straight-chain or cyclic alkyl group having at least one carbon-carbon triple bond derived by the removal of one hydrogen atom from a single carbon atom of a parent alkyne.
  • Typical alkynyl groups include, but are not limited to, ethynyl; propynyls such as prop-1-yn-1-yl, prop-2-yn-1-yl, butynyls such as but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, and the like.
  • Aryl refers to a monovalent aromatic hydrocarbon group derived by the removal of one hydrogen atom from a single carbon atom of a parent aromatic ring system.
  • Typical aryl groups include, but are not limited to, groups derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexalene, as-indacene, s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene,
  • the aryl group may be, for example, (C 5 -C 14 ) aryl, including but not limited to (C 5 -C 10 ).
  • Illustrative aryls include cyclopentadienyl, phenyl and naphthyl.
  • Arylalkyl refers to an acyclic alkyl group in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp 3 carbon atom, is replaced with an aryl group.
  • Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethan-1-yl, 2-phenylethen-1-yl, naphthylmethyl, 2-naphthylethan-1-yl, 2-naphthylethen-1-yl, naphthobenzyl, 2-naphthophenylethan-1-yl and the like.
  • arylalkyl group is (C 6 -C 20 ) arylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkyl group is (C 1 -C 6 ) and the aryl moiety is (C 5 -C 14 ).
  • Illustrative embodiments include the arylalkyl group (C 6 -C 13 ), e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkyl group is (C 1 -C 3 ) and the aryl moiety is (C 5 -C 10 ).
  • an “analyte” is a chemical species of interest present in a sample, the presence of which is detectable or the concentration of which is measurable using an analyte sensor system that incorporates a working electrode.
  • an “analyte-sensitive material” or “ASM” is a redox-active material that is sensitive or substantially sensitive to the presence or concentration of an analyte in a sample within those user-defined application-specific tolerances. “Substantially sensitive” to an analyte is used to mean sensitive within the tolerances required for a given application, as those tolerances are defined by an end user.
  • an “analyte-insensitive material” or “AIM” is a redox-active material that is insensitive or substantially insensitive to the presence or the concentration of an analyte in a sample. “Substantially insensitive” to an analyte is used to mean insensitive within the tolerances required for a given application, as those tolerances are defined by an end user.
  • An “analyte insensitive electrode” is a special case of a reference electrode where the current flow depends in part on redox processes that are independent of the presence or concentration of species (apart from a minimum threshold of supporting electrolyte) in the sample composition including but not limited to the analyte.
  • the AIE serves to provide a response that does not vary across time or sample composition and therefore can be used as an internal standard or ‘zero point’ to which the WE response may be compared. See PCT Pub. No. 2010/104962, incorporated herein by reference.
  • An AIE contains one or more RAMs in electrical contact with a conductive substrate, a pseudo reference electrode (PRE, as defined below), and a means to place the RAM and often the PRE in a constant chemical environment isolated from, but in electrical and fluid communication with, an analyte solution.
  • the conductive substrate and RAM of an AIE may be referred to herein as an “internal working electrode” or “IWE”.
  • IWE internal working electrode
  • AIE can, depending on context, refer to the integrated functional unit (IWE, constant chemical environment, and PRE) or to the IWE or only to the matrix material component of the IWE.
  • a constant chemical environment is a buffer material that resists change in hydronium ion or hydroxide ion, i.e.
  • Buffer solutions are the simplest form of constant chemical environment.
  • ASMs of the current invention respond precisely to the formulation of buffer solutions. This characteristic leads to the deliberate use of a buffer solution to produce a signal even more stable than conventional reference electrodes such as Ag/AgCl/KCl.
  • the design and implementation of materials to create constant chemical environments are detailed below.
  • a constant chemical environment used in conjunction with an AIM such as ferrocene overcomes two shortcoming of that compound, namely: 1) its propensity to respond slightly to changes in analyte pH despite expectations to the contrary; and 2) the limited pH range (ca. 4 or above) for which ferrocene responds with a usable voltammetric signal.
  • an “analyte sensing device” is a sensor, a means to measure the signal from the sensor, and optionally a means to display that signal.
  • a pH meter is a type of analyte sensing device.
  • an analyte sensing device includes a controller/processor unit, associated programs and algorithms, and a probe.
  • the CE serves as a source or sink of electrons and allows current to flow through the WE to effect the redox reaction.
  • CEs are typically made using relatively chemically inert materials, commonly platinum (Pt), but carbon allotropes are also commonly employed. Certain other metals may also be used, especially those exhibiting stability in harsh environments. Examples include, but are not limited to, gold, stainless steel, titanium, and specialty alloys.
  • Coaxial refers to a common axis about which various components, for example, electrodes, are positioned. In some embodiments, “coaxial” refers to a radial symmetry of concentrically or approximately concentrically positioned components. In some embodiments, the term “coaxial” refers to one or more electrodes being concentrically positioned within an outer or externally positioned electrode component; for example and without limitation, a WE, CE, and RE are coaxially positioned when the CE is the outer ring of a sensor tip that is immersed in the analyte solution, the WE is in the middle of the tip, and the RE is interposed between CE and the WE. See PCT Pub. No. 2010/111531, incorporated herein by reference.
  • Dispersed or “associated” in reference to a material, means that it is dissolved in a solution or suspended as a colloid, in a gas, liquid or solid.
  • the term also encompasses embodiments in which the material is covalently bound to the surface of a solid or to a component of the solid.
  • the term also encompasses embodiments in which the material is incorporated as a dopant in a crystal lattice.
  • the term also encompasses materials intercalated within a solid.
  • Electrode is a component of a probe.
  • a “pseudo-reference electrode” or “PRE” is a type of electrode in the category of electrodes whose potentials vary predictably in accordance with the conditions of their environments. Once established, such correlation may be used to calculate an electrode potential for known conditions even if those conditions go beyond the relatively narrow range in which conventional reference electrodes are applicable, for example non-aqueous solutions or temperatures far from ambient. In those situations they provide a reasonably constant potential over the timescale of an electrochemical experiment, and the absolute potential of the PRE can be back-calibrated to a RE if required.
  • Pseudo-reference electrodes typically do not comprise both halves of a redox couple.
  • One example of a PRE is a silver wire (used commonly in non-aqueous electrochemistry). More recently, PREs have been used as a component of an AIE.
  • a “redox-active material” is a compound or composition that may be oxidized and reduced. “Redox activity” refers to either or both of those processes.
  • a “reference electrode” is an electrode used to establish the potential difference applied to the WE.
  • REs have a certain fixed chemical composition and therefore a fixed electrochemical potential, thus allowing measurement of the potential difference applied to the WE in a known, controlled manner.
  • An RE typically comprises two halves of a redox couple in contact with an electrolyte of fixed chemical composition and ionic strength. Because both halves of the redox couple are present and the composition of all the species involved is fixed, the system is maintained at equilibrium, and the potential drop (i.e., the measured voltage) across the electrode-electrolyte interface of the RE is then thermodynamically fixed and constant.
  • a commonly used RE system is the Ag
  • the two half-cell reactions are therefore: Ag + +e ⁇ ⁇ Ag; and AgCl+e ⁇ ⁇ Ag+Cl ⁇ .
  • the standard hydrogen electrode with all species at unit activity by convention the standard hydrogen electrode is defined as having a potential of 0.0V; and R, T, and F are the universal gas constant, temperature, and Faraday constant, respectively, in appropriate units.
  • the potential of this system depends only on the concentration (more strictly speaking the activity) of Cl ⁇ ion present, which, if this is fixed, provides a stable, fixed potential.
  • RE systems are known in the art. It is imperative that the composition of the RE remains constant, and hence almost no current should be passed through the RE (otherwise electrolysis will occur and the composition of the RE will change), which necessitates the use of a third electrode, the counter electrode (CE), to complete the circuit.
  • two-electrode configurations can be used in the special case where the WE is a microelectrode, having at least one dimension typically smaller than 100 micrometers. In this case, the currents passed at the WE are small, and therefore a two-electrode cell can be used with a RE, but without the need for a CE.
  • a “probe” refers to a sensor that contains multiple electrodes.
  • a probe can include, for example, a working electrode, a counter-electrode and a reference electrode (either a conventional reference electrode or a pseudo reference electrode).
  • a probe can include, for example, a working electrode, a counter electrode and an analyte-insensitive electrode (an IWE and PRE).
  • a “sensor” is an electrode or collection of electrodes that generate a signal in response to the presence of an analyte.
  • a “surface” of an electrode refers to the functional surface, i.e., that portion of the surface that is in contact with the analyte sample and serves an electrical or electrochemical purpose. It would not, for example, include an insulating WE housing through which no current or voltage passes.
  • the surface of a WE is the portion of the electrode surface in contact with the sample that detects current or electrical potential relative to the RE.
  • the surface of a CE refers to the portion in contact with the sample that serves to deliver or accept current to or from the WE.
  • a “working electrode” or “WE” is the electrode at which the electrochemical process for detecting the analyte of interest occurs.
  • the working electrode may be sensitive to one or more analyte(s) in the test sample, or it may be chemically modified with analyte sensitive species/materials.
  • the electrochemical response of the working electrode is measured after some perturbation to the system under study has been applied.
  • the perturbation may be the application of a potential difference to the WE that induces electron transfer to occur, and the resulting current at the WE is then recorded as a function of the applied potential (voltammetric mode). This example of mode of operation is illustrative and not exhaustive, as many other modes are known in the art.
  • the WEs of the invention contain an ASM that can undergo a reversible electrochemical redox reaction dependent upon the concentration of analyte (hydrogen ions for a pH meter; other analytes for other analyte sensing devices) in a sample solution and an applied electrical potential. For example, where there is a high concentration of hydrogen ions present in a sample solution, the redox reaction occurs at a lower potential. Conversely, where there is a low concentration of hydrogen ions present in a sample solution, the redox reaction occurs at a higher potential.
  • the relationship between these characteristic potentials and the sample solution pH is a function of the chemical identity of the ASM.
  • An algorithm converts electrical potential to pH value to provide a means of determining the pH of an unknown sample.
  • the present invention provides miniaturized analyte sensors that enable measurement of analyte concentration in small sample volumes of about ten or fewer microliters, using voltammetric sensor technology.
  • the invention provides sensor technology for measurement of electrolyte in solutions, including, most notably, but not limited to, hydronium ion concentration or pH.
  • Other voltammetric sensor technologies provided by this invention include sensors designed for specific analytes presently detected with sensors in various form factors and sample containment arrangements.
  • the present invention also provides analyte concentration measurement devices in which the reference, sensor, and counter electrodes are spatially oriented in means advantageous to measuring analyte concentration in small sample volumes.
  • various sensor components are placed in a pair of “anvils” on which the sample is placed (or otherwise contacted) in performing the measurement.
  • the sample is held in place by surface tension between the two anvils, each comprising a surface having a containment area where the sample is deposited (or otherwise contacted) for measurement.
  • One or typically both anvils have embedded in them one or more electrodes of the analyte sensor in conductive contact with a surface of the anvil having a containment area wetted by the sample.
  • the containment area is defined by a hydrophilic coating that facilitates spreading of the sample on the surface of the sensing elements.
  • one or more electrodes of the sensor are fabricated by printing the electrode components on suitable conductive substrates including, but not limited to, carbon allotropes, noble metals, and conductive polymers.
  • these devices enable multi-channel analyte concentration measurements on a plurality of microliter-scale liquid samples, each held by surface tension between two anvils that together form a sensor, wherein a single voltammetric analysis is performed across an array of such sensors.
  • the device for making analyte concentration measurements on a plurality of liquid samples contained by surface tension comprises: means for containing a plurality of liquid samples by surface tension between opposing, proximal-ends of a plurality of sets of anvils, wherein each set of anvils provides a functional sensor, said anvils optionally in a substantially parallel, spaced-apart relationship; means for supplying current to the anvils; means for holding the anvil pairs in an array; means for performing voltammetric analysis with the sensors; and means connected to the sensors for accepting signals transmitted through them and making analyte concentration measurements thereon, wherein analyte concentration measurements are made at more than one sensors simultaneously using the more than one electrode and more than one means for accepting signals and making analyte concentration measurements thereon.
  • the invention provides an analyte sensor for measuring analyte concentration in a sample comprising: a first anvil and a second anvil that together form the analyte sensor, wherein said anvils are mechanically coupled to one another by a means that enables adjustment of the separation between the anvils such that a liquid sample placed on a surface of one of said anvils can be contacted with a surface the other anvil, thereby placing the two anvils in conductive contact, and retained in such position for a sufficient period of time for an analyte measurement to be made using voltammetric scanning.
  • the devices of the invention can take the form and optionally include the functions of devices currently marketed for making optical absorbance measurements on microliter-scale samples generally described in U.S. Pat. Nos. 7,397,036; 7,872,749; and 8,189,199 (see also U.S. Pat. Nos. 7,623,225 and 8,223,338), each of which is incorporated herein by reference.
  • Those of skill in the art will recognize the significant benefit of combining the pH measurement technology of the present invention with the optical absorbance measurement technology described in these patents.
  • a voltammetric sensor device The mechanism of action in a voltammetric sensor device is uniquely different from that of glass pH probes, which generate a potentiometric signal.
  • a redox reaction that occurs upon exposure of a sample to the working electrode gives rise to peak voltage in square wave voltammetry analysis that is highly dependent on sample pH (or other analyte concentration).
  • a linear relationship of pH to peak voltage exists that is highly reproducible.
  • Voltammetric sensor devices for measurement of pH (and other analyte concentrations) are described in PCT Pub. Nos. WO 2010/111531; WO 2010/118156; and 2012/018632, each of which is incorporated herein by reference.
  • the microsensors of the invention are particularly effective at measuring analyte concentration in low sample volumes, because for voltammetric sensor devices, decreasing sample volume increases the ratio of sensor surface area in contact with the sample to sample volume. Increasing this ratio results in a larger portion of the available analyte in contact with the sensor surface. When a greater portion of the sample interacts with the sensor surface, more signal is generated; this benefits detection and analysis of dilute analyte samples.
  • Voltammetric sensor devices of the invention can be entirely solid state and have reversible chemistry surfaces. They are more resistant to fouling and do not require re-calibration. Hence the device can be assembled with factory calibrated sensors in a ready state for sample measurement.
  • a voltammetric sensor device has three main components, the sensor or working electrode, the reference electrode, and the counter electrode. In the voltammetric microsensor devices of the invention, these three components can be spatially oriented in a manner that facilitates accurate analyte concentration measurement very small volume samples.
  • the electrodes of a voltammetric sensor are generally described below, together with the improvements to them provided by the present invention.
  • the reference electrode may be solid state, liquid filled, or gel filled.
  • the reference electrode is used for normalization of measurements of electrolyte (analyte) in solution.
  • a typical reference electrode is a silver/silver chloride reference electrode.
  • the silver/silver chloride reference electrode can be constructed, as shown in FIG. 1 .
  • the methods and materials of the present invention include embodiments that can be used to avoid many common problems observed with conventional reference electrodes. More specifically, the invention solves problems that result in drifting, clogging, and salt leakage, problems currently encountered with all types of reference electrodes today, by providing a new type of reference electrode junction.
  • the reference electrode needs to maintain a stable potential that does not vary or drift over time.
  • the cause of drift observed in conventional pH meters and other analyte sensors is mostly due to the reference junction.
  • Another issue with existing reference electrode junction technology is cross contamination of the internal solution of the reference electrode with the external analyte or other components in the sample. This can be detrimental in many applications that require absolute control of the measured sample.
  • the present invention provides a solid composite material that provides all the performance of a traditional junction, but does not foul, clog, or leak.
  • the present invention provides a sensor comprising a voltammetric WE in combination with a RE fabricated substantially as described in U.S. Pat. No. 7,628,901, incorporated herein by reference.
  • the invention provides a sensor comprising a voltammetric WE in combination with a RE having a reference junction that is a composite material comprising of an ionic liquid (IL), including but not limited to an RTIL, a conductive material, and a polymer.
  • IL ionic liquid
  • the present invention provides a reference electrode with an analyte contact surface that exhibits a highly stable potential; is wet-dry reversible, that is, does not significantly change its physical or electrochemical characteristics even if the electrode is allowed to dry under typical room conditions; is resistant to a wide range of chemicals; and requires no tedious maintenance procedures typical of conventional liquid-junction reference electrodes.
  • the present invention provides reference electrodes suitable for voltammetric pH measurements comprising an RTIL in a matrix material that exhibits structural integrity, electrical conductivity, and selective passage of protons.
  • suitable ILs include room temperature ionic liquids (RTILs) are organic salts that exist in liquid state at ambient temperatures. Typically they consist of bulky, asymmetric organic cations such as 1-alkyl-3-methylimidazolium, 1-alkylpyridinium, N-methyl-N-alkylpyrrolidinium and ammonium ions. Typical anions include tetrafluoroborate and hexafluorophosphate. A large variety of compositions have been produced with common attributes of being powerful solvents and electrolytes. Both attributes are important in producing stable CABs in the RE.
  • RTILs room temperature ionic liquids
  • the IL is 1-Methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide. In an alternate embodiment, the IL is 1-Methyl-1-propylpiperidinium bis(trifluoromethylsulfonyl)imide. Both ILs are available commercially from Iolitec (Cat. No. IL-0099 and IL-0045, respectively).
  • Various conductive materials can be used as a component of the CAB, including but not limited to carbon, copper, and gold.
  • the conductive material is a graphite powder of 45 micron particle size (commercially available from Sigma Aldrich, Cat. No. 496596).
  • Various hydrophobic polymers can be used a component of the CAB.
  • the polymer is polyvinylidene flouride (PVDF, commercially available from Sigma Aldrich, Cat. No. 427152).
  • the present invention provides solid composite materials comprising such mixtures of IL, conductive material, and polymer.
  • the composite material is a mixture of PVDF, carbon, and an IL.
  • PVDF polyvinylidene fluoride
  • Kynar 721, Arkema polyvinylidene fluoride
  • graphite powder 250 mg
  • 1.5 g of 1-Methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide was then added to the PVDF/graphite mixture and mixed thoroughly. After 15 min the mixture was heated to 200° C. for 1 hour to form a melt. The melt was allowed to cool for 15 minutes and then removed from the vial. A plug was punched out of the composite disc and used as a reference junction.
  • a reference electrode comprising a reference junction of the invention.
  • Each reference electrode was tested to determine the reference potential using pH 2, 4, 7, 10, and 12 standard buffer solutions and the results compared to those obtained using a Cole Parmer standard calomel electrode (SCE) with an Agilent multimeter.
  • SCE Cole Parmer standard calomel electrode
  • the composite plug was installed into one end of a housing comprising a polysulfone tube having an internal diameter (ID) of 0.122′′.
  • the other end of the polysulfone tube opens up to an ID of 0.250′′ and was filled with a reference solution composed of 3M KCl solution saturated with AgNO 3 and thickened with 2% hydroxyethyl cellulose.
  • a chloridized silver wire was embedded into the reference solution and suspended in place with a polytetrafluoroethylene (PTFE) plug.
  • the PTFE plug was sealed with an epoxy adhesive.
  • FIG. 2 A schematic of a non-limiting, representative construct is shown in FIG. 2 .
  • Each reference electrode was tested using a “pH staircase” at pH 2, 4, 7, 10, 12. The potential was measured with an Agilent multimeter.
  • the graph provided in FIG. 3 demonstrates the stability of three reference electrodes across a broad pH range and demonstrates that the composite plug allows ionic communication between the Ag/AgCl redox system and the external analyte. A small deviation was observed when the RE was tested in phthalate buffer (pH 4).
  • a second reference electrode of the invention was constructed to illustrate how the invention eliminates the need of an internal filling solution, thereby providing a completely solid state reference electrode. This was accomplished by embedding a Ag/AgCl wire directly into the composite plug reference junction prepared as described above. A Ag/AgCl disc was also demonstrated to work well. In both versions, the back end can be sealed with a suitable material, such as an epoxy. FIG. 5 illustrates the construct containing the wire embedded directly into the reference junction.
  • reference electrodes can be made in any size, including a size small enough to permit locating them in one of the anvils that forms a sensor in the miniaturized sensors of the invention. Moreover, one can make the reference electrodes using microfabrication techniques standard in the art.
  • the working electrode of the voltammetric sensors of the invention can be constructed of a suitable electrically conductive substrate, such as carbon or certain metals, or certain semiconductors.
  • This substrate is coated with an analyte-sensing material attached to the substrate covalently, by polymeric entrapment, by adhesion or adsorption, or by other means.
  • the redox active analyte sensing material is covalently attached to the substrate surface.
  • the analyte sensing material is not attached directly to the substrate surface but is instead either covalently attached to or physically entrapped within a polymeric or composite material that is in turn attached to the substrate surface (covalently or by adhesion or adsorption).
  • the electrode is simply prepared from a polymeric material that contains such sensing chemistry (i.e., a RAM) attached to the polymer matrix covalently, by polymeric entrapment, by adhesion or adsorption, or by other means to form a conductive material.
  • a polymeric material that contains such sensing chemistry (i.e., a RAM) attached to the polymer matrix covalently, by polymeric entrapment, by adhesion or adsorption, or by other means to form a conductive material.
  • the polymeric material can be any material described in PCT Publication WO 2012/018632.
  • the present invention also provides new polymeric materials suitable for use in the working electrodes of the invention.
  • the polymeric material is a hybrid silica-polyvinyl alcohol (PVA), which can be prepared as described in Pirzada et al., 2012, Langmuir 28: 5834-5844, incorporated herein by reference, and the RAM is covalently attached to either the PVA, the silica, or both, or the RAM is physically entrapped within nanofibers composed of such material.
  • PVA silica-polyvinyl alcohol
  • a polymeric cyclodextrin with RAM molecules entrapped in the individual cyclodextrin molecules is used, either alone or in admixture with another polymer or material.
  • the working electrode substrate (if present, and if not present, then the material comprising the analyte sensing chemistry) has electrical contact point(s) for applying electrical current.
  • a working electrode in accordance with the present invention is shown in FIG. 7 .
  • the counter electrode supplies current to complete the circuit between the sample and device and must be conductive.
  • the spatial arrangement of the working, reference, and counter electrodes can be designed in any fashion that provides simultaneous contact of these components with the sample, and immersion into the sample is not required.
  • a microliter-level analyte sample appropriately held by capillarity and spread into a thin film is sufficient to span the active surfaces of the sensing elements.
  • the voltammetric sensor technology of the present invention is useful in many applications where glass electrodes provide only limited utility or simply cannot be used.
  • the present invention provides methods for high throughput pH (or other analyte concentration) measurement of samples, including biological samples such as serum, urine, plasma, cell lysates, and like liquids.
  • robotics are employed using disposable or re-useable multi-well format sensor devices provided by the invention and described below.
  • practice of the present invention allows in-line monitoring of pH (or other analyte concentration) using extremely small sensors.
  • the ability to detect changes at microliter-scale aliquots directly improves the resolution of the measurement.
  • This is of enormous benefit for use in, for example and without limitation, HPLC, LCMS, and other chromatography systems.
  • In-line pH monitoring is of limited utility with glass electrodes due to size restrictions, re-calibration requirements, and drift related error.
  • glass electrodes require a much larger sample volume to envelop the sensing membrane and reference junction contemporaneously with the same analyte composition. Resolution is inherently poor due to uncertain mixing patterns in the vicinity of the electrode even if the remainder of the flow path has been designed to enable high resolution separation.
  • the voltammetric sensors of the invention particularly those that are entirely solid state, are not limited by these restrictions.
  • the miniaturized sensors of the invention are also of significant benefit in diagnostic applications.
  • the invention provides devices that can be used to measure pH (or other analyte concentration) at the point of care with high mobility and reliability.
  • the invention also provides disposable, one-time use sensors that can provide accurate results reliably and with minimal maintenance.
  • monitoring of pH in cell culture or electrolytes in commercially available sterile culture bags or other containers is enabled by installing single-use voltammetric sensor devices of the invention into such containers.
  • the devices of the invention are not susceptible to breakage, nor do they require periodic re-calibration necessitated by drift due to fouling or contamination of the reference electrode.
  • Another advantage is that these devices can be flat and/or flexible and so easily secured to an inside wall of the bag or other container. Electrical connections can be made across the wall of the bag or other container maintaining wall integrity, so the devices can be connected to the required electronics.
  • the present invention provides a multi-position microliter-scale voltammetric sensor device capable of delivering accurate results with sample volumes less than 10 microliters, for pH, electrolytes, or other sample constituents.
  • samples applied to the device are spatially contained in the absence of a vessel by means of capillary affect, hydrophobic containment, or micro-wells.
  • the sensor devices of the present invention exploit the fact that only surface contact of the sensor components to the analyte sample is required to obtain a measurement.
  • the analyte sample volume is governed primarily by the space between two planar surfaces incorporating the sensing elements.
  • devices are provided where the gap between the planar surfaces is precisely and reproducibly regulated by mechanical or electromechanical means, using a variety of mechanisms, including but not limited to rack-and-pinion, screw-driven positioners, and servo motors and associated circuitry, optionally with optical or mechanical monitoring and feedback control.
  • Capillary forces hold the liquid sample in place without requiring a sample container. In general the smaller the gap the easier the liquid is retained between two wetted surfaces; this particularly favors retention and measurement of microliter-scale analyte samples.
  • samples are spatially constrained with two opposing parts, in the form of anvils, of a voltammetric sensor device.
  • the amount of the sample subject to capillary capture is dependent on the sample surface tension relative to the opposing planar surfaces.
  • the analyte is presumed to wet all of the sensing elements: working electrode, reference electrode, and counter electrode.
  • the area wetted by the analyte is optionally confined by surrounding the sensing elements with a surface not wetted by the analyte.
  • the analyte sample is confined by the area, shape, and the arrangement of hydrophobic and hydrophilic portions of opposing anvil surfaces.
  • the present invention provides, in some embodiments, for use of a hydrophobic material such as polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), other fluorinated polymers, polysulfone, polyethersulfone, polyphenylenesulfide, and other polymers or copolymers that exhibit good chemical resistance and are inherently hydrophobic, to increase surface tension with aqueous analyte samples.
  • PVDF polyvinylidene fluoride
  • PTFE polytetrafluoroethylene
  • other fluorinated polymers polysulfone, polyethersulfone, polyphenylenesulfide, and other polymers or copolymers that exhibit good chemical resistance and are inherently hydrophobic
  • a hydrophobic coating may be applied to the surface of an electrode to define the area wetted by the aqueous analyte sample.
  • the hydrophobic polymer material is also used as support for one or more sensing elements in the construction of the anvil-like structures that form the capillary space for analyte retention.
  • FIG. 8 illustrates schematically a pH-sensing electrode of the present invention.
  • the sensing elements comprise cylindrical or annular-shaped electrodes embedded in an insulation made from a hydrophobic polymer material from the preceding list. Each electrode is wired with signal leads for capturing the signal generated.
  • the overall cylindrical shape of this sensor assembly is preferred for capturing and spreading a liquid droplet across all of the sensing elements uniformly.
  • a sensor assembly is located opposite a cylinder of similar dimensions to form two opposing, parallel planar surfaces, as shown FIG. 9 .
  • the sensor assembly In part (a) of FIG. 9 , the sensor assembly is located in an open position. A droplet of analyte sample is placed on the lower cylinder as shown in part (b). Then the sensor assembly is lowered to a precisely regulated distance from the lower cylinder such that the analyte sample contacts both planar surfaces and fills the gap thus formed, as shown in (c). The size of the gap determines the liquid volume needed to fill the space and to ensure wetting of the sensing elements. Using a cylindrical sensor assembly of about 1 cm in diameter, no more than 10 microliters of analyte is sufficient to generate a pH measurement reliably.
  • the lower limit of the analyte volume is determined not only by the mechanical precision of controlling the capillary space, but also by the nature of the analyte sample and the characteristics of the sensing elements, especially of the working electrode.
  • the amount of hydronium ions in the analyte should be above a certain level such that in the course of voltammetric measurement the concentration of that ion should not be significantly affected due to redox reaction with the analyte sensing molecule.
  • Such changes are minimal in typical pH measurements where the ratio between analyte volume and working electrode surface is so large that redox reactions at the electrode surfaces have virtually no effect on the composition of the analyte.
  • FIG. 10 show (a) the counter and reference electrodes located opposite the working electrode; and (b) the counter electrode located opposite the working and reference electrodes.
  • the analyte sample is placed on the lower planar surface, and then the upper planar surface is lowered to form the capillary space, thereby establishing a predetermined analyte volume, wetting of all sensing elements, and thus electrical communication enabling pH measurement.
  • FIG. 10 A series of experiments was conducted to illustrate the features of this invention using configuration (a) depicted in FIG. 10 .
  • Two electrode assemblies were constructed, wherein the upper assembly comprised a working electrode, and the lower assembly comprised the reference and counter electrodes.
  • Analyte samples of 10 microliters were dispensed on the lower electrode assembly, and the upper assembly was lowered using a modified microscope stage until it contacted the analyte sample.
  • a video camera was used to verify liquid contact on both planar surfaces.
  • Calibration data was generated using BDH Brand standards for pH 2, pH 4, pH 7, and pH 10. Square wave voltammetry plots for each buffer are overlaid in FIG. 11 (10 microliter sample sizes).
  • the peak data from FIG. 11 was plotted versus pH buffer to provide the results shown in FIG. 12 .
  • the plot demonstrates a linear relationship between pH and peak voltages from square wave voltammetry with 10 ⁇ L volume samples.
  • FIGS. 14-18 show overlaid plots of square wave voltammetry analysis for each buffer.
  • sample volume requirements are determined by the size of each well.
  • the sensor is shaped to conform to the walls of a well; the surface of these walls incorporates the redox active material that provides the sensor chemistry.
  • the bottom of the well is formed, at least in part, by the reference electrode.
  • a hydrophobic barrier is employed in some embodiments to facilitate containment of the sample in the well.
  • the counter electrode is positioned in the well to complete the circuit (when sample is present).
  • the device is provided in a multi-well plate, enabling high throughput pH measurements optionally aided by robotics.
  • FIG. 20 illustrates a single well embodiment of this device, in accordance with a representative embodiment of the invention.
  • a third embodiment of the miniaturized analyte sensors of the invention is produced by “printing” one or more of the reference, counter, and working electrodes onto a suitable substrate surface.
  • the substrate may be in any shape.
  • the substrate is an electrically conductive thin polymeric material or flexible substrate.
  • hydrophobic coating materials are utilized to delineate the sample application area.
  • Thin flat circuits are constructed in a manner similar to that employed to make a electronic circuit boards.
  • a composite composed of polyvinylidene fluoride (PVDF), a room temperature ionic fluid (RTIL), and a conductive material such as carbon is used in some embodiments to print or coat over a silver/silver chloride or other electrode material previously printed on the substrate to form the reference electrode.
  • a conductive polymer or coating solution containing analyte-specific redox active material is printed onto the substrate in close proximity to the printed reference electrode to create the sensor surface.
  • a third printed or otherwise attached electrode in close proximity serves as the counter electrode.
  • the figure below shows some embodiments of this device.
  • the size of the sensor (including the optional hydrophobic barrier) may be, for example and without limitation, about 2.5 millimeters in diameter.
  • the design can be constructed with multiple sensors on the same substrate, including, but not limited to, a pattern that matches the multi-well layout of commercially available multi-well plates. An exemplary configuration of the sensor elements is shown in FIG. 21 .
  • Fabrication methods for making other types of sensors can be readily adapted in view of the present disclosure to manufacture the electrodes and sensors of this invention. See, e.g., U.S. Pat. Nos. 5,676,820; 5,942,103; 6,063,259; 6,468,785; 6,878,255; and 6,893,552; PCT Publication WO 2011/031463; Windmiller et al., 2012, Chem. Comm. 48: 6794; Kagie et al., 2008, Electroanalysis 20: 1610; Chuang et al., 2010, Analyst 135: 1230; and Wang et al., 2005, Lab on a Chip 5: 226, each of which is incorporated herein by reference.
  • the present invention provides a variety of RAMs suitable for use in printing inks and coating formulations for sensor fabrication.
  • the following examples describe the syntheses of such RAMS.
  • a RAM suitable for use in printing inks and coating formulations for sensor fabrication was synthesized according to the equation provided in Formula I, as follows:
  • 1,5-dichloroanthraquinone (20 gm, 0.072 moles) was stirred in ethylene glycol (300 mL). To this mixture was added potassium hydroxide pellets (11.8 gm, 85%, 0.179 moles). This reaction was stirred at 120° C. and after approximately 2 hours a dark red solution had formed. Heating was continued for an additional 16 hours. After cooling, the reaction mixture was added to water (800 mL) and this was left at room temperature overnight. The solid which had separated was isolated by filtration and dried. The dried solid was stirred overnight in diethyl ether (500 mL) which dissolved most of the un-reacted starting quinone. The insoluble material was isolated by filtration and dried to give 11.1 gm of crude product.
  • a RAM suitable for use in printing inks and coating formulations for sensor fabrication was synthesized according to the equation provided in Formula II, as follows:
  • a RAM suitable for use in printing inks and coating formulations for sensor fabrication was synthesized according to the equation provided in Formula III, as follows:
  • a RAM suitable for use in printing inks and coating formulations for sensor fabrication was synthesized according to the equation provided in Formula IV, as follows:
  • a RAM suitable for use in printing inks and coating formulations for sensor fabrication was synthesized according to the equation provided in Formula V, as follows:
  • a RAM suitable for use in printing inks and coating formulations for sensor fabrication was synthesized according to the equation provided in Formula VI, as follows:
  • a RAM suitable for use in printing inks and coating formulations for sensor fabrication was synthesized according to the equation provided in Formula VII, as follows:
  • a RAM suitable for use in printing inks and coating formulations for sensor fabrication was synthesized according to the equation provided in Formula VIII, as follows:
  • a RAM suitable for use in printing inks and coating formulations for sensor fabrication was synthesized according to the equation provided in Formula IX, as follows:
  • Each of the RAMs in the above examples is used in conjunction with a coating material, such as a conductive ink, which contains functional groups reactive to the RAM.
  • a coating material such as a conductive ink, which contains functional groups reactive to the RAM.
  • the coating material is combined with the RAM to achieve covalent attachment, and then the coating material is applied to a substrate with suitable electrical connections to deliver the signal generated by the RAM.
  • the conductive material is first coated onto the substrate and then reacted with the RAM.
  • Other procedural combinations are used to achieve a variety of surface properties. In all cases the surface of the finished coating contains a concentration of the RAM determined by formulation, reaction conditions, and method of coating application.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
US14/758,491 2012-12-27 2013-12-27 Ph meter Abandoned US20150346144A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US14/758,491 US20150346144A1 (en) 2012-12-27 2013-12-27 Ph meter

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261746479P 2012-12-27 2012-12-27
PCT/US2013/078018 WO2014106066A1 (en) 2012-12-27 2013-12-27 Ph meter
US14/758,491 US20150346144A1 (en) 2012-12-27 2013-12-27 Ph meter

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2013/078018 A-371-Of-International WO2014106066A1 (en) 2012-12-27 2013-12-27 Ph meter

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US16/667,693 Continuation US11378546B2 (en) 2012-12-27 2019-10-29 PH Meter

Publications (1)

Publication Number Publication Date
US20150346144A1 true US20150346144A1 (en) 2015-12-03

Family

ID=51022085

Family Applications (2)

Application Number Title Priority Date Filing Date
US14/758,491 Abandoned US20150346144A1 (en) 2012-12-27 2013-12-27 Ph meter
US16/667,693 Active US11378546B2 (en) 2012-12-27 2019-10-29 PH Meter

Family Applications After (1)

Application Number Title Priority Date Filing Date
US16/667,693 Active US11378546B2 (en) 2012-12-27 2019-10-29 PH Meter

Country Status (6)

Country Link
US (2) US20150346144A1 (de)
EP (2) EP3734264A1 (de)
JP (2) JP2016502116A (de)
KR (1) KR102263528B1 (de)
CN (1) CN105122047A (de)
WO (1) WO2014106066A1 (de)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10830725B2 (en) 2018-11-12 2020-11-10 International Business Machines Corporation Electronic chemical sensor
WO2020237204A1 (en) * 2019-05-22 2020-11-26 The Board Of Trustees Of The Leland Stanford Junior University Voltammetric sensor platforms, systems, methods, and structures
US11467124B2 (en) * 2017-05-02 2022-10-11 The University Of British Columbia Apparatus, systems and methods for in situ measurement of an oxidation / reduction potential and pH of a solution

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016109329A2 (en) * 2014-12-30 2016-07-07 Water Lens, LLC Compositions, apparatus and methods for determining ph of an analyte solution
EP3329266A4 (de) 2015-07-29 2019-07-10 Parker-Hannifin Corporation Festkörperelektroden und sensoren mit redoxaktiven oberflächenbereichen
US11079350B2 (en) * 2016-03-25 2021-08-03 Parker-Hannifin Corporation Solid state pH sensing continuous flow system
CN108148176B (zh) * 2018-01-09 2020-12-29 安徽艾佩科电子材料有限公司 一种用于电阻型存储材料的聚氨酯
EP3742158A1 (de) * 2019-05-21 2020-11-25 ABB Schweiz AG Referenzelektrode für einen ph-sensor und ph-sensor
CN111398376B (zh) * 2020-05-07 2022-03-25 中国核动力研究设计院 一种耐高压三电极电化学传感器
JP2023007958A (ja) * 2021-07-02 2023-01-19 シスメックス株式会社 イオンセンサ、イオンセンサの製造方法及びイオンの測定方法
US11846598B2 (en) 2021-12-31 2023-12-19 Analog Devices International Unlimited Company Reference electrode

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030047451A1 (en) * 2000-07-20 2003-03-13 Bhullar Raghbir Singh Recloseable biosensor
US20040132220A1 (en) * 2001-01-08 2004-07-08 Leonard Fish Diagnostic instruments and methods for detecting analytes
US20040251131A1 (en) * 2002-07-02 2004-12-16 Hiroya Ueno Biosensor, biosensor chip, and biosensor device
US20080000771A1 (en) * 2005-08-03 2008-01-03 Takashi Kakiuchi Reference electrode, salt bridge and ionic concentration measuring device by the use of reference electrode and salt bridge

Family Cites Families (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LU50233A1 (de) * 1966-01-10 1967-07-10
DE3568874D1 (en) * 1984-06-13 1989-04-20 Ares Serono Inc Photometric instruments, their use in methods of optical analysis, and ancillary devices therefor
US5141868A (en) * 1984-06-13 1992-08-25 Internationale Octrooi Maatschappij "Octropa" Bv Device for use in chemical test procedures
JPS62112046A (ja) * 1985-11-11 1987-05-23 Shimadzu Corp イオン濃度測定装置
US4871442A (en) * 1986-05-01 1989-10-03 Terumo Corporation Ion sensor
JPH0750067B2 (ja) * 1987-07-04 1995-05-31 株式会社堀場製作所 極薄液体膜形成方式による物性測定方法
JPH01263550A (ja) * 1988-04-14 1989-10-20 Terumo Corp イオンセンサ
JPH05119012A (ja) * 1991-10-30 1993-05-14 Kanzaki Paper Mfg Co Ltd 電気化学測定用セル
US5362812A (en) * 1993-04-23 1994-11-08 Minnesota Mining And Manufacturing Company Reactive polymeric dyes
US5676820A (en) 1995-02-03 1997-10-14 New Mexico State University Technology Transfer Corp. Remote electrochemical sensor
US5942103A (en) 1995-02-03 1999-08-24 New Mexico State University Technology Transfer Corporation Renewable-reagent electrochemical sensor
JP3643863B2 (ja) * 1995-08-09 2005-04-27 アークレイ株式会社 液体保持具とその製造方法
JPH09127039A (ja) * 1995-11-06 1997-05-16 Nippon Telegr & Teleph Corp <Ntt> 電気化学検出器及びその製造方法
US6063259A (en) 1996-06-11 2000-05-16 New Mexico State University Technology Transfer Corporation Microfabricated thick-film electrochemical sensor for nucleic acid determination
AU6157898A (en) * 1997-02-06 1998-08-26 E. Heller & Company Small volume (in vitro) analyte sensor
JPH10325821A (ja) * 1997-05-26 1998-12-08 Nec Corp 電気化学測定装置
US20020144905A1 (en) * 1997-12-17 2002-10-10 Christian Schmidt Sample positioning and analysis system
US6893552B1 (en) 1997-12-29 2005-05-17 Arrowhead Center, Inc. Microsensors for glucose and insulin monitoring
US6587705B1 (en) 1998-03-13 2003-07-01 Lynn Kim Biosensor, iontophoretic sampling system, and methods of use thereof
JPH11304666A (ja) * 1998-04-24 1999-11-05 Hitachi Ltd 試料ハンドリングツールおよびその使用方法
US6468785B1 (en) 1999-02-19 2002-10-22 New Mexico State University Technology Transfer Corporation Doped conducting polymers applications and methods
DE19916921A1 (de) 1999-04-14 2000-10-19 Fraunhofer Ges Forschung Elektrisches Sensorarray
US6878255B1 (en) 1999-11-05 2005-04-12 Arrowhead Center, Inc. Microfluidic devices with thick-film electrochemical detection
AUPR393701A0 (en) * 2001-03-23 2001-04-26 Commonwealth Scientific And Industrial Research Organisation Self-reducing anthraquinone compounds
US6960287B2 (en) * 2001-06-11 2005-11-01 Bayer Corporation Underfill detection system for a test sensor
JP2003104930A (ja) * 2001-09-28 2003-04-09 Kawasaki Kasei Chem Ltd ９，１０−アントラキノニルエーテルの製造方法
US6630521B2 (en) * 2001-11-13 2003-10-07 Eastman Chemical Company Anthraquinone colorants containing copolymerizable vinyl groups
US6939450B2 (en) 2002-10-08 2005-09-06 Abbott Laboratories Device having a flow channel
AT413766B8 (de) * 2003-05-15 2006-06-15 Hoffmann La Roche Potentiometrische, ionenselektive elektrode
EP1861653B1 (de) 2005-02-11 2014-05-21 NanoDrop Technologies LLC Vorrichtung und verfahren zum messen des signals eines durch oberflächenspannung zusammengehaltenen fluoreszenten nanotropfens
JP3930517B2 (ja) * 2005-03-23 2007-06-13 株式会社東芝 生体分子の定量分析チップ、及び、定量分析方法、定量分析装置及びシステム
GB0526051D0 (en) 2005-12-21 2006-02-01 Oxford Biosensors Ltd Cholesterol sensor
JP2009530642A (ja) 2006-03-23 2009-08-27 ナノドロップ・テクノロジーズ・インコーポレイテッド 表面張力によって保持された多数のサンプルの光学的測定を行うための測定器
JP5018777B2 (ja) * 2006-07-05 2012-09-05 パナソニック株式会社 液体試料測定方法および装置
US7348783B1 (en) * 2006-08-18 2008-03-25 Chung Yuan Christian University Multi-functional pH meter and fabrication thereof
CN101523201B (zh) 2006-09-13 2016-08-24 株式会社堀场制作所 离子液体覆盖参比电极及使用其的电化学测定装置
EP2062037A2 (de) * 2006-09-14 2009-05-27 Agency for Science, Technology And Research Elektrochemischer sensor mit ineinandergreifenden mikroelektroden und leitfähigem polymer
EP1983592A1 (de) 2007-04-17 2008-10-22 Nederlandse Organisatie voor Toegepast-Natuuurwetenschappelijk Onderzoek TNO Verfahren zur Herstellung einer Elektrode
US8197650B2 (en) * 2007-06-07 2012-06-12 Sensor Innovations, Inc. Silicon electrochemical sensors
JP2009085797A (ja) * 2007-09-28 2009-04-23 Fujifilm Corp バイオチップを用いた検査方法及び装置
CA2702523A1 (en) 2007-10-23 2009-04-30 Nanodrop Technologies Llc Photometer with modular light emitter
DE102007050477A1 (de) 2007-10-23 2009-04-30 Kurt-Schwabe-Institut für Mess- und Sensortechnik e.V. Meinsberg Miniaturisierte planare Indikatorelektrode und Verfahren zu ihrer Herstellung
WO2009060849A1 (ja) * 2007-11-05 2009-05-14 Nippon Kayaku Kabushiki Kaisha バイオセンサ
WO2009146396A1 (en) 2008-05-30 2009-12-03 Craig Whitehouse Single and multiple operating mode ion sources with atmospheric pressure chemical ionization
CN102232182B (zh) 2008-10-03 2015-01-14 纳诺多普科技有限责任公司 用于最佳吸光度测量的光程长度传感器和方法
WO2010039975A1 (en) 2008-10-03 2010-04-08 Nanodrop Technologies Llc Dual sample mode spectrophotometer
TWI502195B (zh) * 2009-03-10 2015-10-01 Senova Systems Inc 在用於測量樣品中之分析物的電化學感測裝置中所用的多相分析物非敏感性電極、包含此電極的電化學感測裝置，與使用此感測裝置測量樣品中之分析物的方法
WO2010111531A2 (en) 2009-03-25 2010-09-30 Senova Systems, Inc. Device for detecting an analyte
EP2417442A4 (de) 2009-04-07 2013-06-26 Senova Systems Inc Vorrichtung für den nachweis eines analyten in einer fliessfähigen probe
WO2011031463A2 (en) 2009-08-25 2011-03-17 The Regents Of The University Of California Nanomotor-based patterning of surface microstructures
JP5937592B2 (ja) * 2010-07-26 2016-06-22 セノバ システムズ インコーポレイテッド 分析物センサー
GB2490117B (en) * 2011-04-18 2014-04-09 Schlumberger Holdings Electrochemical pH sensor
WO2012083258A2 (en) * 2010-12-16 2012-06-21 Sensor Innovations, Inc. Electrochemical sensors
JP5899885B2 (ja) * 2011-01-31 2016-04-06 ソニー株式会社 燃料電池、燃料電池の製造方法、電子機器、ニコチンアミドアデニンジヌクレオチド固定化電極、ニコチンアミドアデニンジヌクレオチド固定化担体、酵素反応利用装置、タンパク質固定化電極およびタンパク質固定化担体
GB2497791B (en) * 2011-12-21 2021-01-20 Schlumberger Holdings Derivatization of carbon
WO2013093899A1 (en) * 2011-12-23 2013-06-27 Schlumberger Technology B.V. Electrochemical sensor for ph measurement
EP2807477B1 (de) * 2012-01-25 2019-01-02 Parker-Hannifin Corporation Analytsensor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030047451A1 (en) * 2000-07-20 2003-03-13 Bhullar Raghbir Singh Recloseable biosensor
US20040132220A1 (en) * 2001-01-08 2004-07-08 Leonard Fish Diagnostic instruments and methods for detecting analytes
US20040251131A1 (en) * 2002-07-02 2004-12-16 Hiroya Ueno Biosensor, biosensor chip, and biosensor device
US20080000771A1 (en) * 2005-08-03 2008-01-03 Takashi Kakiuchi Reference electrode, salt bridge and ionic concentration measuring device by the use of reference electrode and salt bridge

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Cicmil et al. (D. Cicmil, S. Anastasova, A. Kavanagh, D. Diamond, U. Mattinen, J. Bobacka, A. Lewenstam, A. Radu, Ionic liquid-based, liquid-junction-free reference electrode, Electroanalysis, 23(8) (2011) 1881-1890). *
Cicmil et al. (Dimitrije Cicmil, Salzitsa Anastasova, Andrew Kavanagh, Dermot Diamond, Ulriika Mattinen, Johan Bobacka, Andrzej Lewenstam, Aleksandar Radu, Ionic Liquid-Based, Liquid-Junction-Free Reference Electrode, Electroanalysis, 23 (8) (2011) 1881-1890 *
Zuo et al. (Shaohua Zuo, Yuanjie Teng, Huihui Yuan, Minbo Lan, Direct electrochemistry of glucose oxidase on screen-printed electrodes through one-step enzyme immobilization process with silica sol–gel/polyvinyl alcohol hybrid film, Sensors and Actuators B: Chemical, 133 (2008) 555-560) *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11467124B2 (en) * 2017-05-02 2022-10-11 The University Of British Columbia Apparatus, systems and methods for in situ measurement of an oxidation / reduction potential and pH of a solution
US10830725B2 (en) 2018-11-12 2020-11-10 International Business Machines Corporation Electronic chemical sensor
WO2020237204A1 (en) * 2019-05-22 2020-11-26 The Board Of Trustees Of The Leland Stanford Junior University Voltammetric sensor platforms, systems, methods, and structures

Also Published As

Publication number Publication date
JP6883068B2 (ja) 2021-06-09
CN105122047A (zh) 2015-12-02
US11378546B2 (en) 2022-07-05
JP2019194618A (ja) 2019-11-07
KR102263528B1 (ko) 2021-06-09
US20200064307A1 (en) 2020-02-27
EP3734264A1 (de) 2020-11-04
EP2939011A1 (de) 2015-11-04
KR20150102103A (ko) 2015-09-04
JP2016502116A (ja) 2016-01-21
EP2939011A4 (de) 2016-11-23
WO2014106066A1 (en) 2014-07-03

Similar Documents

Publication Publication Date Title
US11378546B2 (en) PH Meter
EP3486645B1 (de) Analytsensor
US10261043B2 (en) Analyte sensor
EP2406620B1 (de) Vorrichtung zur bereitstellung einer vorrichtung zur internen kalibrierung bei einem elektrochemischen sensor
JP2003525450A (ja) 固体状態参照系を持つ電極デバイス
CN112179964B (zh) 一种基于聚苯乙烯/金传感材料的自校准电极阵列及应用
CN109211989B (zh) 一种用于检测阿特拉津的电化学适配体传感器及其制备和检测方法
Mugo et al. An integrated carbon entrapped molecularly imprinted polymer (MIP) electrode for voltammetric detection of resveratrol in wine
Gyetvai et al. Solid contact micropipette ion selective electrode for potentiometric SECM
Taei et al. A voltammetric sensor based on multiwalled carbon nanotubes and a new azoferrocene derivative for determination of glutathione
Zarei et al. Electrochemical determination of riboflavin by an ionic liquid modified carbon paste electrode as a sensitive sensor
González-López et al. Electrochemical micropipette-tip for low-cost environmental applications: Determination of anionic surfactants through their interaction with methylene blue
Nagy et al. Electrochemical sensors developed for gathering microscale chemical information
Li et al. Sensitive determination of urapidil at an electrochemically pretreated glassy carbon electrode by linear sweep voltammetry
Zhang et al. Sensitive determination of adenine on poly (amidosulfonic acid)-modified glassy carbon electrode
Ramadan et al. Electrochemical sensing of antipyrine and its interaction with ds-DNA modified electrode.
Varga et al. Electrochemical time of flight method for determination of diffusion coefficients of glucose in solutions and gels
CN112198213A (zh) 一种用于检测谷氨酸浓度的非酶电化学传感器及采用其的检测方法
CN110672683A (zh) 一种自由氯微电极的制备装置
Souto et al. Development of solid contact micropipette Zn-ion selective electrode for corrosion studies
Abd-Elkader et al. Electrochemical Sensing of Antipyrine and its Interaction with ds-DNA Modified Electrode
Alemayehu Innovative Drug Discovery

Legal Events

Date Code Title Description
AS Assignment

Owner name: SENOVA SYSTEMS, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:LEE, ERIC;ROTH, STEVE;VU, THANG HUY;SIGNING DATES FROM 20150624 TO 20150629;REEL/FRAME:035971/0864

AS Assignment

Owner name: PARKER-HANNIFIN CORPORATION, OHIO

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SENOVA SYSTEMS, INC.;REEL/FRAME:040940/0299

Effective date: 20160920

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

STPP Information on status: patent application and granting procedure in general

Free format text: AWAITING RESPONSE FOR INFORMALITY, FEE DEFICIENCY OR CRF ACTION

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

STPP Information on status: patent application and granting procedure in general

Free format text: AWAITING RESPONSE FOR INFORMALITY, FEE DEFICIENCY OR CRF ACTION

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION