GB2501245A - Solid state ion detection system - Google Patents

Solid state ion detection system Download PDF

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Publication number
GB2501245A
GB2501245A GB1205636.2A GB201205636A GB2501245A GB 2501245 A GB2501245 A GB 2501245A GB 201205636 A GB201205636 A GB 201205636A GB 2501245 A GB2501245 A GB 2501245A
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Prior art keywords
ion
electrode
working
detection system
conductive layer
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GB201205636D0 (en
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Tatyana Korochkina
David GETHIN
Sridhar Govindarajan
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Swansea University
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Swansea University
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28Electrolytic cell components
    • G01N27/30Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3271Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
    • G01N27/3272Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/403Cells and electrode assemblies
    • G01N27/4035Combination of a single ion-sensing electrode and a single reference electrode

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Electrochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Biophysics (AREA)
  • Hematology (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
  • Testing Resistance To Weather, Investigating Materials By Mechanical Methods (AREA)

Abstract

The present invention discloses an ion detection system for measuring target ion concentration and a method for fabricating the same. The system generally shown as 100 in Figure 1 includes a pair of electrodes which are a working electrode 1 and a reference electrode 2. Each electrode includes a substrate 3; an electrically conductive layer 4 supported on a surface of the substrate; and an intermediate electrically and ionically conductive layer 5 in contact with the electrically conductive layer. The working electrode includes an ion-selective membrane layer 7 within a boundary formed by a barrier layer 6a and the reference electrode includes a non-selective membrane 8 within a boundary formed by a barrier layer 6b. The conductive layer may include metal/metal salts or may be silver/silver chloride and there may be no salt bridge between the working and reference electrodes.

Description

Ion Detection System
Field of the Invention
The present invention relates to an ion detection system and in particular to solid state ion detection system for use in medical devices to determine ion concentrations.
Background of the Invention
Electrochernical methods such as potentiometrV1 amperometrY and voltammetrY have been applied in the analytical laboratories to determine specific chemical components contained in clinical, :.. environmental and industrial samples. PotentiometriC measurements using ion-selective (or working) electrode coupled with a reference electrode are widely used in clinical chemistry to measure * concentration (or activity) of ions such as sodium, potassium, chloride and calcium in body fluids such as blood, serum, plasma, urine, and cerebrospiflal fluid.
Known systems are expensive and sometimes complicated to operate and so there is an increasing demand for simple portable medical devices for use at remote sites such as point of care testing and oh spot monitoring. Although numerous schemes have been proposed to develop miniaturised working * electrodes, reference electrodes have not been extensively developed for miniaturisation and for mass production. Lack of suitable reference electrodes has led to development of ion detection systems that do not require a reference electrode and hence are less accurate.
US 7373195 describes an implantable electrode pair having a potassium ion-selective electrode as the working electrode and a sodium ion-selective electrode as the reference electrode. This arrangement allows for determining a potassium ion coticentration at least in part as a function of the sodium ion concentration and the potential difference. To measure a potassium ion concentration an additional step such as determining a sodium ion concentration near the sodium ion-selective electrode is required.
1JS2008/0149501 describes a set of at least two ion-selective solid-contact electrodes. The electrodes are selective to a different ion of an analysis solution. One of the electrodes is used as a reference electrode. This arrangement can only be used if the activity of a reference ion is kept constant and therefore not suitable for most clinical ion activity measurements.
In "Disposable blood potassium sensors based on screen-printed thick film electrodes" by H. Xu et al., Measurement Science and Technology 21, pages 1-5 (2010), the authors describe a screen-printed, solid state, planar, disposable sensor, consisting of a potassium ion-selective electrode and a reference : electrode for the clinic potassium tests. However, this approach is specific to the potassium ion and therefore is not suitable for a broad field of use.
A Kisiel et al. (cf. The Analyst 130, 2005, pages 1655 to 1662) described several attempts to construct all-solid-state reference electrodes with conducting polymers. All layers of conducting polymers such as polypyrrole (PPy) and 0ly(3,4ethylenedioxytoPThe) (PEDOT) with different doping anions were trocheniically deposited Ofl glassy carbon. The reference electrode was covered by a PVC based membrane containing both cation and anion lipophilic components as well as dispersed AgCI with traces of metallic Ag and KCl to assure constant electrode potential. Fabrication of these reference electrodes includes several different time consuming steps. Therefore, they are not suitable for mass production.
Accordingly, it is an object of the present invention to provide a stable, compact ion detection system for physiologically relevant ions, including both a working and a reference electrode, with a working electrode having reproducible electrochemical responses relative to a reference electrode for different target ion concentrations suitable for mass production using mercially available materials.
Another object of the invention is to provide a stable, compact ion detection system having no salt bridge.
Still another object of the present invention is to provide a stable, compaction detection system having no internal electrolyte solutions in both the working and reference electrodes.
Yet another object of the invention is to provide a stable, compact ion detection system which does not require calibration and which has a rapid solution equilibration time.
Summary ofthe Invention
* * According to a first aspect of the invention there is provided an ion detection system including a solid-state ion-selective working electrode4 a solid-state and liquid junction-free reference electrode each of said electrodes having a substrate, an electrically conductive layer overlaying said substrate and an lctronically and ionically conductive layer overlaying at least part of the electrically conductive layer, wherein an ion selective membrane layer is overlaid on the electrically and ionically conductive layer on * the working electrode within a boundary formed by a first insulating barrier layer and a non-selective ** membrane layer is overlaid over the electrically and ionically conductive layer of the reference electrode within a boundary formed by a second insulating barrier layer.
Preferably the substrate is a water impermeable substrate.
It is envisaged that the water impermeable substrate is non-conductive.
preferably the substrate is planar. Because the substrate is planar and the other layers are laid over the substrate as layers, it means that the electrodes themselves can be made to be planar which means that the ion detection system can be very compact.
it is preferred that the conductive layer is between 10 im and 30 tIm in thickness and more preferably between is and 25 firm it is envisaged that the conductive layer employs any one of various conductive materials. For example, the conductive layer may include metal/metal salts or carbon.
It is envisaged that the conductive layer is a silver/silver chloride or carbon. Individual parts of the conductive layer may be formed by a silver based material or a carbon layer.
It is preferred that an electrically and ionically conductive layer is overlaid on the conductive layer such that an intermediate layer is formed between the conductive layer and the membrane layers.
It is preferred that a barrier layer is overlaid on the conductive layer such that a portion of the : conductive layer is uncovered so forming a receptacle for the membrane layers.
It is envisaged that the ion-selective membrane layer is a membrane through which only a * predetermined ion can pass while the non-selective membrane layer is a membrane that is not specific to any ion with the result that a potential difference between the working and reference electrode is generated corresponding to ionic activity or concentration of the predetermined ion in a sample solution that the working and reference electrodes are contacted with preferably the working electrode includes anion specific ligand.
It is envisaged that the Iigand is positioned within a boundary formed by the water impermeable barrier.
It is preferred that the reference electrode includes a salt solution contained within a boundary formed by the water impermeable barrier.
preferably there is no salt bridge between the working and reference electrode.
According to a second aspect of the invention there is provided a method of making an ion detection system comprising a working and a reference electrode, where for both the electrodes the method involves the steps of providing a substrate, printing an electrically conductive layer on the surface of the substrate; printing an intermediate electrically and ionically conductive layer on a portion of the electrically conductive layer; and then depending on whether the electrode is a working or a reference electrode, in the case of the working electrode, forming an ion-selective membrane layer that is in contact with the intermediate electrically and ionically conductive layer or for the reference electrode forming a non-selective membrane layer in contact with the intermediate electrically and ionically conductive layer.
Preferably a water-impermeable barrier layer is overlaid on the conductive layer such that a portion of the conductive layer is uncovered and forms a boundary for the membrane layer.
Preferably the printing process is a screen printing process.
It is envisaged that the layers, which are typically printed layers are cured by heating. * * . * . .
preferably the printed layers, and the ion-selective and non-selective membranes are polymerized in situ.
According to a further aspect of the invention there is provided a method for measuring the ion activity in an analysis solution, comprising the steps of immersing an ion detection system comprising at least * one set of working and reference electrodes according to a first aspect of the invention in an analysis solution and recording a rest potential across the working and reference electrodes.
According to yet a further aspect of the invention there is prth'ided laboratory apparatus having a set comprising at least two solid-contact electrodes according to claim 1, one of the solid-contact electrodes serving as a reference electrode.
The present invention seeks to overcome the problems of the prior art by providing an easy to manufacture ion detection systems for use in medical devices that is stable, compact and accurate and which allows for a range of electrolytes to be detected. Furthermore the invention provides for a working electrode having reproducible electrochemical responses relative to a reference electrode for different target ion concentrations suitable for mass production using commercially available materials.
Benefits and advantages of the present invention include, but are not limited to a stable, compact, inexpensive, salt-bridge free, all-solid-state, planar, disposable ion detection system which does not require internal water-based electrolytes and calibration.
Brief Description of the Drawings
An embodiment of the invention will now be described. The accompanying drawings, which are incorporated in and form a part of the specification, illustrate an embodiment of the present invention and, together with the description, serve to explain the principles of the invention-In the drawings: FIGURE lisa schematic representation of a top view of the ion detection system including the working * . and reference electrodes.
FIGURE 2 is a schematic representation of a side view of the assembled working or reference electrode illustrated in FIGURE 1 hereof.
FIGURE 3 is a typical ion detection system comprising silver/silver chloride working and reference electrodes.
Detailed Description of the Invention
The ion detection system generally shown as 100 in Figure 1 is formed of a working, electrode (1), and reference electrode, (2). The ion detection system may be manufactured by screen printing. An example is the use of a DEK 248 screen printing press for printing the planar, all-solid-state ion detection system including working (potassium sensor) and reference electrodes. An ink formulation for printing functional materials such as biological, conducting, iconducting, and insulating materials has two purposes, firstly to act as a vehicle to apply the functional material to a substrate and secondly to allow the formation of good quality ink film after drying while retaining material functionality. There are competing properties that the ink needs to have, i.e. to provide the appropriate rheological properties for the printing process while not compromising the functionality of the material An electrically conductive layer, (4), is screen printed on one surface of the substrate. commercially available silver/silver chloride ink with 40:60 ratio of silver/silver chloride (C61003P7, GEM, UK) as well as carbon graphite ink (C2000S02P2. GEM, UK) were found to be suitable for this layer in terms of functionality and print quality. They formed a relatively rough surface finish increasing the effective surface area of the electrode which is important for a rapid electrode response as well as provided sufficient conductivity. It is preferred that the thickness of this layer is between 10 lAm and 30 im and more preferably between 15 and 25 1Am. Silver/silver chloride was found in preliminary experiments to be suitable for both the reference and the working electrode. Carbon graphite ink was also found to be suitable for both the working and pseudo reference electrode, The working and reference electrodes consisted of a number of layers, typically four layers, consecutively printed on PET flexible substrate: 1) AgJAgCI and carbon conductor materials were printed to produce all silver, all carbon or combined : silver/carbon electrode arrays, 2) two layers of conducting polymer PEDOT:PSS ink was printed over the electrodes and 3) the insulator was printed over the electrodes. The number of layers can vary depending on the sensitivity and low detection limit required. Substrate, (3), includes a nonconductive, water impermeable material to which electrode layers may adhere. In the ion detection systems tested, *:** thin (100 p.m to 330 p.m), substantially planar, flexible substrates of optically clear and white polyester both with adhesion promoting coating (PMX729 and PMX749 respectively, Hi-Fi Industrial films Ltd. UK), * *.
as examples, were successfully employed.
An electrically conductive layer, (4), is screen printed on one surface of the substrate.
The intermediate electrically and ionically conductive polymer layer, (5), is printed over a portion of the electrically conductive layer, (4). This layer has two purposes, firstly to act as an ion-to.electrOfl transducer and secondly to improve potential stability of the electrode pair. Commercially available solvent based standard PEDOT:PSS ink (Orgacon ELP 3000 series, Agfa-Gevaert UK) was found in preliminary experiments to be suitable for this layer. Both ELF' 3040 premium and ELP 3145 grade PEDOT:PSS inks permitted good print quality. It is preferred that two layers are printed to ensure good conductivity. The first layer is dried before the second layer is printed.
If the sensor is used for monitoring potassium levels, the working electrode is a potassium sensor in combination with a reference electrode. A VMP3 potentiostat was set-up as an open circuit and the potential was recorded across screen printed working (potassium sensor) and reference electrodes in a given solution. The working and reference electrodes of the ion detection system were connected to the VMP3 potentiostat via a 1 mm, 16 ways connector and 14 ways ribbon cable, referred to as a S-I connector. The basis of the open circuit voltage technique is the measurement of potential difference across two electrodes. The open circuit voltage experiment consists of a period during which no potential or current is applied to the working electrode. The cell is disconnected from the power :. amplifier. The evolution of the rest potential is recorded over desired period of time. The set-up was left r: for about 5-15 mm per solution. All measurements were performed under ambient conditions. Before and after each measurement all electrodes were rinsed in Dl water. It was found that the voltage level 4**ê 4.: was largely stable after 5 minutes, and readings of voltage were therefore taken at this time point for each solution.
*., For the working electrode the membrane cocktail composition is 1%-3%(wt) Potassium ionophore I, Valmnomicvn (60403, Sigma-Aldrich, UK); 0.S%-1.5%(wt) KTChP Potassium tetrakis(4-chlorophenyl)borate (KTChP) (60591, Sigma-Aldrich, UK), 31%-33%(Wt) PVC (Polyvinyl chloride) (81392, Sigma-Aldrich UK) and 63%-65.5%(Wt) Bis(2ethylheXYl)SebaCate (DOS) (84818, Sigma-Aldrich, UK) in a solvent of 1 mL THE (Tetrahydrofuran) (401757, Sigma.Aldrich, UK) per 100mg of cocktail.
To make the ion-selective membrane the following steps are taken: * Calculate weight of cocktail components based on desired total volume.
The membrane cocktail components are weighed exactly in a glass bottle with an extra wide screw neck provided with a lid (BTF-630-OSOL Fisher scientific, UK).
Make sure the molar ratio of potassium ionophore I and lipophilic salt KTChP is 1:1 as a slight excess in the amount of lipophilic anionic sites in the membrane may drastically change the electrode characteristics (cation exchange properties).
* 1 mL of THF is added per 100mg of cocktail.
* In orderto dissolve PVC easily the mixture must be shaken vigorously immediately after adding THF for 2-4 mm, for example, using a vortex agitator.
* The clear solution is applied manually into the working electrode well using a pipette.
* The electrode must be protected from dust.
* Allow the solvent to evaporate overnight or dry the membrane in a conveyer belt dryer for S mm at 50C.
* The working electrode is ready for testing. *. *t * . . * * * *
For a non-selective membrane the cocktail composition is typically 0.9-2%% KTChP Potassium tetrakis(4-chlorophenyl)borate (KTChP) (60591, Sigma-AldriCh UK), 1.1%-2.5% MTDDACI MethyltridodecYlammoh1m chloride (molar ratio KTChP: MTDDA-Cl is 1:1) (91661, sigma-Aldrich, UK), 65%-68% DOS and 30%-33% PVC. The solvent is 1 m1 THE per 100mg of cocktail flee *:. To make the membrane the following stages are taken: * Calculate weight of cocktail components based on desired total volume.
* The membrane cocktail components are weighed exactly in a glass bottle with an extra wide screw neck provided with a lid (BTF-630-OSOL Fisher Scientific, UK)- * Make sure the molar ratio of lipophilic salts MTDDA-CI and KTCbP is 1:1 as a slight excess in the amount of lipophilic sites in the membrane may drastically change the reference electrode characteristics (cation and anion exchange properties)- 1 mL of THE is added per 100 mg of cocktail.
* In order to dissolve PVC easily the mixture must be shaken vigorously immediately after adding THF for 2-4 mm, for example, using a vortex agitator.
* Add O.12g to O.lGg of ground KCI and 0.045g to O.06g of powdered AgCI in molar ratio KCI: AgCI equal to S 1.
* Mix thoroughly for about 2 mm using, for example, a vortex agitator to yield a suspension.
* The greyish solution is applied manually into the reference electrode well using a pipette.
* The reference electrode must be protected from dust.
* Allow the solvent to evaporate overnight or dry the membrane in a conveyer belt dryer for S mm at 50C.
* The reference electrode is ready for testing.
Several conventional reference electrodes such as Lithium Acetate, Hg/Hg2SO4, Ag/AgO and SCE were characterised in KCI and NaCI solutions against a platinum electrode to identify the one with most stable and constant potential prior to using it in printed ion detection system characterization. The electrochemical interface, VMP3 was set up as an open circuit, and the potential was recorded across *. the 2 mm platinum disk electrode, (working electrode (WE)) and the conventional 8 mm Lithium Acetate reference electrode, in five (1O1M -105M) standard solutions. Also, the potential was recorded across the conventional reference electrode such as SCE, Hg2504 and Ag/AgCl as WE and conventional Lithium Acetate reference electrode as reference electrode (Re12). The set-up was left for about 5 -15 mm per *** :. solution. All potentiometric measurements were performed under ambient conditions. Before and after each measurement all electrodes were rinsed in distilled water. The responses of different conventional reference electrodes were evaluated through a five point calibration curve. The response of conventional Lithium Acetate reference electrode measured against platinum WE showed some dependency of potential versus electrolyte concentrations. It is characterized by a slope of -10.3 mV deC in KCI and NaCI solutions. There was no change in the potential difference versus electrolyte nature.
The response of two (Ag/AgCI and Hg2SO4) conventional reference electrodes used as WEs against Lithium Acetate reference electrode showed some dependency of potential versus electrolyte concentrations. The concentration dependency of the Hg2SO4 reference electrode was characterized by a slope of 14.7 mV deC1 in KCl and NaCI solutions. But, there was no change in the potential difference for conventional SCE versus the conventional Lithium Acetate reference electrode. This suggests that the conventional SCE is suitable for the printed sensor and reference electrode characterisation.
The response of the printed reference electrodes showed excellent independence of potential versus electrolyte nature and concentration. Dependences are characterized by slope of 0.4 mV dec' and 1.4 mV dec in KCI and NaCI respectively.
Initial calibration experiments (the printed sensor vs. conventional SCE reference electrode and printed reference electrode vs. conventional SCE reference electrode) showed the AgfAgCl printed sensors as well as Ag/AgO printed reference electrodes from batch 1 and batch 2 to be working well. Further calibration experiments of the printed potassium detection systems (the printed sensor vs. printed reference electrode) showed the printed potassium detection system also to be working well. The potassium detection system exhibits a near Nernstian response (average = 60.2 mV/dee) over a given * * range of activity (or concentration). All calibration curves were very similar, indicating good ion * detection system reproducibility with the ratio of Stdev/Average less than 5%. The conductor material * *. * ** has an impact on the potassium detection system response. Carbon ink decreases the system potential * by about 180 mV. ***
Typical lower limit of detection of the printed potassium detection system is around 10 lAM which is consistent with that of the printed potassium sensor vs. conventional SCE reference electrode. This is *** sufficient for accurate measurements of potassium for physiologically relevant concentrations in the region of 3.5 -5.3 mM.
Preliminary results showed that the sensitivity of the printed potassium detection system was maintained for up to 15 days storage An important requirement for working electrodes is insensitivity of the potential to possible interfereflts. From the point of view of sensor application the most severe one is -Na' The potentiometric selectivity coefficient defines the ability of the potassium-selective electrode to distinguish the potassium ion from others. The selectivity coefficient, KKN3POt, was evaluated by means of the emf response of the potassium detection system in mixed solutions of the primary ion, K', and interfering ion, Na' using the fixed interference method. The potential difference was measured in solutions of constant level of about 150 mM of interfering ion, 0Na, and varying activity of the primary ion, tT (10 -10.1 M). The potential difference values obtained were plotted vs. the activity of the primary ion 0K The value of 0K at the intersection of the extrapolated linear portions of this plot was used to calculate KKNÔ°' from the Nikolsky.Eisenman equation: TTpOI -____ K,Na -:frn. a Na *
* Where ZK and 1Na are integers with sign and magnitude corresponding to the charge of the primary and * interfering ions respectively. The potentiometric log selectivity coefficient of the potassium sensor was - 4.21. This is superior to those that are known. ****
The stability of the Ag/AgCI potassium detection system was examined by performing an initial calibration curve, followed by a second calibration 24 hours later. Both calibration curves are very similar, indicating good stability and repeatability of the sensor response over a 24 hour period. a a *e.
It was found that the resistance of all conductive materials increases with a decrease in nominal line width from 2 to 0.5 mm: from 3 to ii ohms for silver/silver chloride ink, from 0.7 to 3.7 kOhms for carbon ink, from 4 to 22 kohms for std PEDOT:PSS ink, from 2.5 to 11 kohms for premium grade PEPOT:PSS ink and from 2.8 to 11.6 kohms for R &D type UV-stable PEDOT:PSS ink. The silver/silver chloride displayed the smallest line resistance followed by carbon, premium grade PEDOT:P5S, R &D type IJV-stable PEDOT:PSS, and standard PIDOT:PSS. Both the premium grade PEDOT:PSS and the R&D type tiV-stable PEDOT:PSS displayed reduced line resistance as opposed to standard PEDOT:PSS, as expected. Measurements of line resistance of 0.5, 1 and 2 mm nominal line widths were repeated to investigate the effect of time. It was found that the line resistance of all conductive materials is maintained after 40 days storage. The correlation between resistance and cros-sectiOn area of printed lines (tracks) was examined by comparing Ag/ACCI results for batch 1 and 2. It was found that a slight increase in the cross section area for batch 2 lines was reflected in a slight reduction in the line resistance as expected. This is indicative of good correlation between resistance and cross-section area of printed lines. Overall, this confirms the stability of the screen printing process and its suitability for volume nufacturing of the ion detection system.
Although the invention discusses individual embodiments, the invention is intended to cover combinations of those embodiments. * . * *
S *fl*
GB1205636.2A 2012-03-29 2012-03-29 Solid state ion detection system Withdrawn GB2501245A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050191428A1 (en) * 2004-03-01 2005-09-01 Buck Michael D. Ion-selective electrodes
US7373195B2 (en) * 2004-07-30 2008-05-13 Medtronic, Inc. Ion sensor for long term use in complex medium

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050191428A1 (en) * 2004-03-01 2005-09-01 Buck Michael D. Ion-selective electrodes
US7373195B2 (en) * 2004-07-30 2008-05-13 Medtronic, Inc. Ion sensor for long term use in complex medium

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Measurement Science and Technology, 21, 13 April 2010, H Xu, "Disposable blood potassium sensors based on screen-printed thick film electrodes", pages 1-5 *

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