WO1991008474A1 - Improvements in and relating to microelectrodes and amperometric assays - Google Patents

Improvements in and relating to microelectrodes and amperometric assays Download PDF

Info

Publication number
WO1991008474A1
WO1991008474A1 PCT/GB1990/001874 GB9001874W WO9108474A1 WO 1991008474 A1 WO1991008474 A1 WO 1991008474A1 GB 9001874 W GB9001874 W GB 9001874W WO 9108474 A1 WO9108474 A1 WO 9108474A1
Authority
WO
WIPO (PCT)
Prior art keywords
electrodes
apertures
microelectrode
electrode
species
Prior art date
Application number
PCT/GB1990/001874
Other languages
French (fr)
Inventor
Hubert Hugues Jacques Girault
Brian Jeffrey Seddon
Original Assignee
Ecossensors Limited
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 Ecossensors Limited filed Critical Ecossensors Limited
Priority to EP91900041A priority Critical patent/EP0504196B1/en
Priority to US07/852,223 priority patent/US5512489A/en
Priority to DE69021888T priority patent/DE69021888T2/en
Publication of WO1991008474A1 publication Critical patent/WO1991008474A1/en
Priority to US08/399,176 priority patent/US5635054A/en

Links

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
    • G01N27/403—Cells and electrode assemblies
    • 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
    • G01N27/42—Measuring deposition or liberation of materials from an electrolyte; Coulometry, i.e. measuring coulomb-equivalent of material in an electrolyte
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/18—Water
    • G01N33/1813—Water specific cations in water, e.g. heavy metals

Definitions

  • This invention relates to an improved methoo of ma ⁇ ng an electrode (in particular a microelectrode), an electrode made by the method, an assay method for the determi ation of -che presence of a redox species (e.g. a heavy metal _ in liquid carrier media using the electrode and re ⁇ ox species detection equipment designed to utilise the assay metnod.
  • a redox species e.g. a heavy metal _ in liquid carrier media using the electrode and re ⁇ ox species detection equipment designed to utilise the assay metnod.
  • Microelectrcdes provide many advantages in electro ⁇ chemistry and electroanalysis (some of which are discussed in Wightman, R.M., Anal. Chem. , 1982, 54, 2522) in par ⁇ ticular the possibility of electrolysis in resistive media or dilute solutions, and of microanalysis with improved sensitivity and precision. For these reasons a great deal of effort has been dedicated to establish a way of fabri ⁇ cating a regular microscopic disc array electrode. Any proposed method of fabrication must ensure that all the distinctive features of individual microelectrodes are retained, and in addition circumvent the problems assoc ⁇ iated with the measurement of extremely small currents (pA- nA), observed for single microdisc electrodes.
  • pA- nA extremely small currents
  • the former approach failed because of adhesion problems between the insulating photoresist layer and the metal substrate.
  • the latter method of fabrication was self defeating because, although the size of the pore is well characterised, the pore density and distribution were undefined and the electrode ultimately irreproducible.
  • a method of making a microelectrode comprising a layer of electrically insulating material having an array of aper ⁇ tures formed therein and electrically conducting material visible through the apertures, is characterised in that the apertures are formed by photo-ablation.
  • the layer is a sheet of flexible plastics material (suitably a polyester or other polymer film) and the apertures are formed by photo-ablation.
  • a particularly preferred form of electrode made by the method of this invention is a microdisc array electrode in which the apertures are of the same size and shape and are distri ⁇ ubbed over the sheet in a regular array.
  • the sheet can be of a thickness in the range 2 microns to 500 microns and the apertures are suitably of diameter (or transverse dimension if not circular) of between 5 microns and 100 microns.
  • a hexagon ⁇ al array cf 10 micron diameter apertures with edge/edge separations of 100 microns between the apertures in the array has been found to be one convenient arrangement offering many useful commercial applications.
  • An alternative method of making the electrode involves supporting a layer of electrode material on a substrate, laying a thin polymer film onto the electrode material (e.g. by vapour polymerisation) and then drilling apertures by photo-ablation through the polymer film.
  • the layer of electrode material is conveniently thick-film printed (to any desired pattern) on the substrate.
  • a microband array electrode comprising a set of spaced-aoart slot-shaped apertures exposing narrow strips (e.g. parallel strips) of a common electrode material .
  • the formation of the array of apertures by a photo- ablation technique has proved to be particularly convenient and typically involves photographically creating spaced- apart ablatable areas on the sheet interspersed by more resistant non-ablatable regions, and then removing the sheet material only over the ablatable areas using a nigh power source of radiation (e.g. from an excimer laser).
  • a nigh power source of radiation e.g. from an excimer laser.
  • the conducting material is suitably a thixotropic paste based on carbon or metallic particles (e.g. platinum or gold) applied sufficiently thickly so that where the paste is applied to a pre-drilled sheet of plastics mater ⁇ ial each aperture formed in the non-conducting sheet is substantially filled with conducting particles.
  • a thixotropic paste based on carbon or metallic particles (e.g. platinum or gold) applied sufficiently thickly so that where the paste is applied to a pre-drilled sheet of plastics mater ⁇ ial each aperture formed in the non-conducting sheet is substantially filled with conducting particles.
  • a pre-drilled coated sheet can be bonded, conducting side down, on a substrate of sufficient thickness to give the required rigidity to the sandwich thus produced.
  • the alternative thick film method which drills apertures through to the electrode material already has a suitable support substrate.
  • the substrate can be of electrically conducting or non-conducting material, and can incorporate suitable electrical conductors for applying potentials to and/or leading currents to/from the one or more conducting areas exposed in the apertures.
  • the fabri- cation method proposed in tms first aspect of the inven ⁇ tion is essentially a three dimensional thick film process.
  • the procedure circumvents all the past difficul ⁇ ties including the aforementioned, and is based on p ⁇ n- ciples of photo-machining of polymer films by laser pnoto- ablation to produce matrices of well defined aperture size, distribution, density anc geometry.
  • the process can fabricate array patterns in support matrices of thickness 2 ⁇ m to 500 ⁇ m, and the apertures can be filled with the required conducting particles.
  • the filled sheet can then be mounted by encapsulation on an inert substrate e.g. by a heat sealing process.
  • a microelectrode made oy tne method of the invention represents a further aspect of this invention.
  • Initial trials have suggesteo that such electrodes have useful applications in electroanalysis, high resolution electro ⁇ chemistry, pathogen testing techniques, antibody or enzyme reactions, and bioelectrochemical assay methods.
  • Arrays may be patterned: e.g. hexagonal, square etc.
  • the spacing between conducting areas can be varied at will.
  • the ability to set the aperture separation is a very advantageous feature.
  • the separation can be made very small (a few microns) for the mom or- ing of catalytic current.
  • Arrays of electrodes can be made from different con ⁇ uct- ing materials (e.g. platinum, gold, carbon etc).
  • composition of electrode material can be varied (e.g.ligand ⁇ and complexing agents can be incorpcrated in the conducting material to add chemical selectivity to an electroanalysis to be performed with the electrode array) .
  • Apertures or groups of apertures within an array can be individually addressed to a set electric potential and therefore the electrode array could be used in multicom- ponent determination simultaneously.
  • the electrode design is ideally suited to chemical immobilisation of reactants (enzyme or antibody) onto the insulating area by covalent bonding hence allowing direct application to biosensor and biochemical assay technology.
  • a particularly promising application involves the use of an electrode made by the method of this invention for redox species analysis using Voltam etry.
  • redox species such as pesticides or heavy metals in water is important to tne monitoring ana control of environmental pollution.
  • the type of information required for comprehensive environment studies not only includes a single sampled measurement cf a specific redox species (e.g. metal j at a given place and time, but should include extensive distriDution anG fluc ⁇ tuation data on major pollutants in order to ascertain origin.
  • the device is a multi-heavy metal ion detector directed essentially at in-the-fielc measurement which may be used as a portable hand-held device or form part of a remote sensing network.
  • An analytical method based en this aspect of the invention is electrochemically based and relies on the properties of a microelectrode according to this invention.
  • an assay method for a target redox species analysis in a liquid carrier comprises moistening an absorbent medium containing a dry reactant for the species with the liquid carrier, the absorbent medium being sandwiched between two electrodes, one of which is a microelectrode according to this inven ⁇ tion, the moistening process being monitored by measuring the conductance between the two electrodes and the con ⁇ centration of the target redox species being determined by measuring the current flowing between the two electrodes when applying a varying potential therebetween.
  • a programmed voltage scan ramp or step formed is used for the concentration measurement.
  • the target redox species could be, inter alia, a crug, a bioproduct or a heavy metal ion.
  • an assay method for a trace redox species analysis in a liquid carrier comprises moistening an absorbent medium containing a dry reactant for tne species with the liquid carrier, the absorbent medium being sandwiched between two electrodes, one of which is a microelectrode according to this invention, applying a first potential across the electrodes to cause any species drawn into the medium and reacted with the reactant therein to migrate ions onto the conductive areas of the micro ⁇ electrode, applying a second potential of opposite polar ⁇ ity across the electrodes to strip the said ions from the microelectrode and determining the nature of the "stripped" ion from a knowledge of the redox potential requirec tc effect stripping.
  • a particularly useful application of the assay method of this invention for trace redox species is in the determination of which heavy metal ions are present in a sample of water, the dry reactant in the absorbent medium being a mercury salt.
  • the method of analysis in this case is an adaption of anodic stripping voltammetry.
  • the invention comprises an assay unit which includes a pad of dry absorbent material incorporating the required dry form redox reagent sand- wiched between a microelectrode according to this invention and a counter electrode, the sandwich being mounted on a support means that includes a contact to at least one of the electrodes.
  • the support means is a non-conducting .e.g. glass) plate having two contacts, one leading to eacn of the different electrodes.
  • the redox reagent can oe a mercury salt and where testing on waters with very low electrical conductivity is in mind, a readily lonisable salt (such as sodium chloride).
  • An assay device in accordance with this aspect of the invention can be used as a disposable component whicn is connected to (e.g. plugged into) a suitable potentiostat.
  • a fully portable testing equipment is available in this manner, with testing simply requiring a wetting of the absorbent pad of a fresh device and subsequent application of the appropriate potentials to the electrodes using the potentiostat to carry out the required Voltammetry or Anodic Stripping Voltammetry.
  • Figure 1 is a much enlarged sectional view cf part of a microdisc array electrode according to the invention
  • Figure 2 is a plan view from above of the part shown in Figure 1 ,
  • Figure 3 is a much enlarged sectional side view of part of a microband array electrode according to the invention.
  • Figure 4 is a plan view from above of the part shown in Figure 3,
  • Figure 5 is a schematic view of laser equipment for forming an array of apertures in a component of a micro ⁇ electrode
  • Figure 6 is a si ⁇ e elevational view of an assay device in accordance with a further aspect of the invention.
  • Figure 7 is a schematic sectional view througn part of the device of Figure 6 with the vertical scale exaggeratec for ease of viewing, and
  • Figure 8 is a graph showing the applied potential for a trace element detected with a device such as that snown in Figures 6 and 7 by stripping analysis.
  • the microdisc array electrode partially shown in Figures 1 and 2 comprises a substrate 1 on which a pet— forated sheet 2 of non-conducting material coated on one side with a layer 3 of conducting material is applied.
  • the perforations are regularly spaced equally sized apertures A drilled by photo-ablation and forming an array over the entire effective area of the micro ⁇ isc array electrode.
  • the substrate 1 would be a sheet of polyvinylchloride of a thickness of 500 microns, the sheet 2 a polyester sheet of a thickness of 100 microns and the layer 3 a cured carbon paste of a cured thickness of 500 microns.
  • the array shown in Figure 2 has circular discs of 10 micron diameter in a 100 micron spaced hexagon pattern. Other geometries such as those leading to microband elec ⁇ trodes are also envisaged. Since each aperture is filled with the conducting paste, each filled aperture forms a conducting area surrounded by a non-conducting region.
  • All exposed conducting areas can be connected to the same layer 3 but it will be appreciated that where end uses re ⁇ uire different potentials to be aDcliec tc cifferent discs or cifferent grouDs of discs.
  • the layer 2 car. oe appropriately ⁇ ivideo and connectec tc its own suppl l ⁇ a ⁇ . Tne supply ea ⁇ has not been snown in Figures 1 and 2 out sucr, a leac can oe seen at 11 in Figure 5.
  • FIGS 3 anc 4 correspond tc Figures 1 an ⁇ 2 but snow a microband electrode the apertures 4 now peing narrow slits.
  • Tne micro-array electrode shown m Figure 3 was made by tmck-film printing con ⁇ uctmc electrode material 2 onto an electrically insulating substrate 1 n the required pattern.
  • a layer 2 of polymer film is tnen vapour polymerised over the printed material 2 anc suose- ⁇ uent.y Grilled using laser photo-ab ation tc oro ⁇ uce tne apertures 4. With carbon in the material 2 vitrified carbon is formed in tne apertures 4 giving the electrode high durability and good electrical properties.
  • Photo-ablation of the required aperture pattern is schematically illustrated in Figure 5 where 30 indicates a high power laser source (e.g. a Lambda Physih LPX 2051 unit), 21 a reducing lens and 2 the plastics film requiring to be drilled.
  • the film 2 can have an apertured mask printed thereon wnereby only the film exposed througn tne apertures in the mask is available for ablation or a mask 32 (e.g. of metal) can be located in the optical path anywhere between the laser source 31 and the film 2.
  • a metal mask contacting the film 2 can also be used.
  • the minimum size of the apertures 4 that can be produced in a plastics film are expected to be 1 to 2 microns but they can be as large as desired.
  • the film 2 could be poly-para-xylylene (Parylene N) or other CH materials (such as polystyrene or polyethylene for example) .
  • Parylene N poly-para-xylylene
  • CH materials such as polystyrene or polyethylene for example
  • suitable laser sources may be mentione ⁇ a KrF laser (wavelength 248 nm) of fluence in the range
  • a KrF laser of 300 mJ output (a Questek 2440 unit) can be used generat ⁇ ing a fluence at the mask of 0.3 J/cm" over an area cf 1 cm'".
  • an array cf 15 micron diameter apertures 4 on 100 micron hole centres was accurately formed in the film 2.
  • a metal mask 32 with an array of 45 micron diameter holes on 300 micron hole centres was located in the beam from a 600 mJ KrF laser and projected down onto a 2 micron thick Parylene N film with a three times reduction of image in the lens 31.
  • the fluence at the mask was 0.044 J/cm 2 and at the film it was 0.4 J/cm2.
  • the device shown in Figures 6 and 7 comprises a rectangular substrate 10 of non-conducting material on which a microelectrode 12 has been provided. Adhered over the electrode 12 is a pad 13 of absorbent material and overlying the pad 13 is a counter electrode 14.
  • the electrode 14 can be applied by printing and will have an area larger than the sum of the apertures of the electrode 13. Conducting leads 11 and 15 connect contact areas 16 and 17 to the two electrodes 12 and 14.
  • the areas 16 and 17 are positioned so that slipping the substrate 10 into a holder (shown dotted at 20) which is connected to an electronic unit 21 by a cable 22, automatically places the device in circuit with the electronic equipment in the unit 21.
  • the unit 21 can comprise a miniatured microprocessor witn control poten ⁇ tiostat incorporating a sensitive ⁇ croammeter.
  • the pad 13 will include some par- tides of common salt and mercurous chloride (say 105& w/w of NaCl and 5% w/w of Hg ⁇ Cl ⁇ ) or other ⁇ ried reactants necessary to provide conductivity and oxidised mercury for an electroplating operation.
  • the micro-conducting areas of the electrode 12 will be carbon and the electrode 14 will be of si 1 er/si1ver chloride. Dipping the pad 13 into a sample of the water to be tested, will draw water into the pad 13 by capillarity action where it will dissolve the salt and redox reagent forming a conductive solution between the electrodes 12 and 14.
  • Electrode 12 For voltammetric analysis, current is passes ⁇ with electrode 12 as working electrode and electrode 14 as a controlled voltage secondary electrode.
  • elec ⁇ trode 14 For stripping analysis, current is passed with elec ⁇ trode 14 as anode to plate mercury and any heavy metal present onto the micro-conductive areas of the electrode 12. Plating current is maintained by hemispherical mass transport inherent to the micro-array geometry for long enough (typically 2 or 3 minutes) to plate a detectable amount of the heavy metal onto the conducting areas.
  • microelectrodes are cheap enough to be disposed of after a single use, "memory" problems, such as can occur with laboratory-based equip ⁇ ment, will be avoided since after use for one analysis, the electrode will be discarded.
  • the invention makes possible an assay device which comes in two sections; a sensing unit consisting of a disposable or reusable film cartridge driven by a pocket size computerised potentiostat which comprises the control and signal handling unit.
  • the output of the instrument is a current which is proportional to the concentration of the trace metal ion at a potential specific to the ion itself.
  • electroanal sis method described hereabove can be easily adapted to enzyme chemistry or/and immunochemistry for use as a biosensor.
  • enzymes or/and antibodies can be covalently immobilized on the perforated polymer sheet 2 in Figure 1 and electron carrier species cften called mediators can be detected on the microelectrode array in a very efficient manner due to the close proximity between the electrode and the immobilised species leading to feedback diffusion enhancement.

Abstract

A photo-ablation technique is used to create apertures (4) in a layer (2) of electrically insulating material and allow electrically conducting material (3) exposed through the apertures to create a microelectrode. The microelectrode can be used for assay methods and in an assay unit.

Description

IMPROVEMENTS IN AND RELATING TO MICROELECTRODES AND AMPEROMETRIC ASSAYS
Technical Fie c
This invention relates to an improved methoo of maκιng an electrode (in particular a microelectrode), an electrode made by the method, an assay method for the determi ation of -che presence of a redox species (e.g. a heavy metal _ in liquid carrier media using the electrode and reαox species detection equipment designed to utilise the assay metnod.
Background Art
Microelectrcdes provide many advantages in electro¬ chemistry and electroanalysis (some of which are discussed in Wightman, R.M., Anal. Chem. , 1982, 54, 2522) in par¬ ticular the possibility of electrolysis in resistive media or dilute solutions, and of microanalysis with improved sensitivity and precision. For these reasons a great deal of effort has been dedicated to establish a way of fabri¬ cating a regular microscopic disc array electrode. Any proposed method of fabrication must ensure that all the distinctive features of individual microelectrodes are retained, and in addition circumvent the problems assoc¬ iated with the measurement of extremely small currents (pA- nA), observed for single microdisc electrodes.
Many approaches have been proposed for the construc- tion of a microdisc array electrode including photolitho¬ graphic methods (see e.g. Osteryoung, J. and He pel , T., J. Electroch'em. Soc. , 1986, 133, 757-760 and W. Siu and R.S.C. Cobbold, Med. & Biol . Eng., 1976, 14, 109), as well as the use of icropore membrane matrices (see e.g. Wang, J., J. Electrochem. Soc, 1988, 249, 339-345, and Cheng, F., Anal. Chem., 198S, 61, 762-766). The former approach failed because of adhesion problems between the insulating photoresist layer and the metal substrate. The latter method of fabrication was self defeating because, although the size of the pore is well characterised, the pore density and distribution were undefined and the electrode ultimately irreproducible.
Summary cf the Invention According to the first aspect of this invention a method of making a microelectrode comprising a layer of electrically insulating material having an array of aper¬ tures formed therein and electrically conducting material visible through the apertures, is characterised in that the apertures are formed by photo-ablation.
Suitably the layer is a sheet of flexible plastics material (suitably a polyester or other polymer film) and the apertures are formed by photo-ablation. A particularly preferred form of electrode made by the method of this invention is a microdisc array electrode in which the apertures are of the same size and shape and are distri¬ buted over the sheet in a regular array. In the field of microdisc electrodes the sheet can be of a thickness in the range 2 microns to 500 microns and the apertures are suitably of diameter (or transverse dimension if not circular) of between 5 microns and 100 microns. A hexagon¬ al array cf 10 micron diameter apertures with edge/edge separations of 100 microns between the apertures in the array has been found to be one convenient arrangement offering many useful commercial applications.
An alternative method of making the electrode involves supporting a layer of electrode material on a substrate, laying a thin polymer film onto the electrode material (e.g. by vapour polymerisation) and then drilling apertures by photo-ablation through the polymer film. The layer of electrode material is conveniently thick-film printed (to any desired pattern) on the substrate. This alternative method has a particular advantage when the electrode material includes carbon, since the photo-ablation used to form the apertures can vitrify the carbon in the areas of electrode material exposed by the photo-ablation.
As well as microαisc arrays the invention extenαs to icroband arrays, a microband array electrode comprising a set of spaced-aoart slot-shaped apertures exposing narrow strips (e.g. parallel strips) of a common electrode material .
The formation of the array of apertures by a photo- ablation technique has proved to be particularly convenient and typically involves photographically creating spaced- apart ablatable areas on the sheet interspersed by more resistant non-ablatable regions, and then removing the sheet material only over the ablatable areas using a nigh power source of radiation (e.g. from an excimer laser). Using photo-ablation, means that an exceedingly accurate array of apertures of any required size can be produced using well established techniques.
The conducting material is suitably a thixotropic paste based on carbon or metallic particles (e.g. platinum or gold) applied sufficiently thickly so that where the paste is applied to a pre-drilled sheet of plastics mater¬ ial each aperture formed in the non-conducting sheet is substantially filled with conducting particles.
A pre-drilled coated sheet can be bonded, conducting side down, on a substrate of sufficient thickness to give the required rigidity to the sandwich thus produced. The alternative thick film method which drills apertures through to the electrode material already has a suitable support substrate. The substrate can be of electrically conducting or non-conducting material, and can incorporate suitable electrical conductors for applying potentials to and/or leading currents to/from the one or more conducting areas exposed in the apertures.
From the above, it will be appreciated that the fabri- cation method proposed in tms first aspect of the inven¬ tion is essentially a three dimensional thick film process. The procedure circumvents all the past difficul¬ ties including the aforementioned, and is based on pπn- ciples of photo-machining of polymer films by laser pnoto- ablation to produce matrices of well defined aperture size, distribution, density anc geometry. The process can fabricate array patterns in support matrices of thickness 2μm to 500μm, and the apertures can be filled with the required conducting particles. The filled sheet can then be mounted by encapsulation on an inert substrate e.g. by a heat sealing process.
A microelectrode made oy tne method of the invention represents a further aspect of this invention. Initial trials have suggesteo that such electrodes have useful applications in electroanalysis, high resolution electro¬ chemistry, pathogen testing techniques, antibody or enzyme reactions, and bioelectrochemical assay methods.
The following list details the important characteris- tics of an electrode made by the method of the invention which underline its use in electroanalysis and application to chemical sensors. It should be appreciated that the method of fabrication here discussed is uniquely controll¬ able in terms of device specification and this has not been found to be true for earlier attempts at fabrication.
1. Uniformity of electrode shapes within an array, size may range from 5 μm to 50 μm in diameter. A reproducible manufacturing method produces identical array electrodes and is essential for reliable analytical application. The small aperture size produces an amperometric signal with improved analytical properties such as detectabil- ity, sensitivity and precision even in the presence of dissolved oxygen in the analyte.
2. Variable array size, from a few apertures (say six) to many thousands. The number of apertures within tne array will αepend on application: current amp ification increases linearly with the number of isolated electrodes.
3. Arrays may be patterned: e.g. hexagonal, square etc.
4. The spacing between conducting areas can be varied at will. The ability to set the aperture separation is a very advantageous feature. For example, the separation can be made very small (a few microns) for the mom or- ing of catalytic current.
5. Arrays of electrodes can be made from different conσuct- ing materials (e.g. platinum, gold, carbon etc).
6. The composition of electrode material can be varied (e.g.ligandε and complexing agents can be incorpcrated in the conducting material to add chemical selectivity to an electroanalysis to be performed with the electrode array) .
7. Apertures or groups of apertures within an array can be individually addressed to a set electric potential and therefore the electrode array could be used in multicom- ponent determination simultaneously.
8. The electrode design is ideally suited to chemical immobilisation of reactants (enzyme or antibody) onto the insulating area by covalent bonding hence allowing direct application to biosensor and biochemical assay technology.
A particularly promising application involves the use of an electrode made by the method of this invention for redox species analysis using Voltam etry.
Accurate determination of redox species such as pesticides or heavy metals in water is important to tne monitoring ana control of environmental pollution. The type of information required for comprehensive environment studies not only includes a single sampled measurement cf a specific redox species (e.g. metal j at a given place and time, but should include extensive distriDution anG fluc¬ tuation data on major pollutants in order to ascertain origin.
The techniques presently employed by consultant analysts for tne determination of heavy metals in water samples include the laboratory based techniques. Atomic Spectroscopy (Absorption and Emission) and Polarσgrapny (Pulse and Derivative). These conventional analytical methods are by nature timely and consequently expensive, relying on sampling procedures of a given water supply.
This invention also relates to an analytical method and device which need not be laooratory bound. In one embodiment, the device is a multi-heavy metal ion detector directed essentially at in-the-fielc measurement which may be used as a portable hand-held device or form part of a remote sensing network.
An analytical method based en this aspect of the invention is electrochemically based and relies on the properties of a microelectrode according to this invention.
According to this aspect of the invention an assay method for a target redox species analysis in a liquid carrier comprises moistening an absorbent medium containing a dry reactant for the species with the liquid carrier, the absorbent medium being sandwiched between two electrodes, one of which is a microelectrode according to this inven¬ tion, the moistening process being monitored by measuring the conductance between the two electrodes and the con¬ centration of the target redox species being determined by measuring the current flowing between the two electrodes when applying a varying potential therebetween.
Suitably a programmed voltage scan ramp or step formed) is used for the concentration measurement.
The target redox species could be, inter alia, a crug, a bioproduct or a heavy metal ion.
According to a further aspect of the analytical method aspect of the invention an assay method for a trace redox species analysis in a liquid carrier comprises moistening an absorbent medium containing a dry reactant for tne species with the liquid carrier, the absorbent medium being sandwiched between two electrodes, one of which is a microelectrode according to this invention, applying a first potential across the electrodes to cause any species drawn into the medium and reacted with the reactant therein to migrate ions onto the conductive areas of the micro¬ electrode, applying a second potential of opposite polar¬ ity across the electrodes to strip the said ions from the microelectrode and determining the nature of the "stripped" ion from a knowledge of the redox potential requirec tc effect stripping.
A particularly useful application of the assay method of this invention for trace redox species is in the determination of which heavy metal ions are present in a sample of water, the dry reactant in the absorbent medium being a mercury salt. The method of analysis in this case is an adaption of anodic stripping voltammetry.
In its equipment aspect the invention comprises an assay unit which includes a pad of dry absorbent material incorporating the required dry form redox reagent sand- wiched between a microelectrode according to this invention and a counter electrode, the sandwich being mounted on a support means that includes a contact to at least one of the electrodes. Suitably the support means is a non-conducting .e.g. glass) plate having two contacts, one leading to eacn of the different electrodes. In the case of an assay αevice for heavy metal detection, the redox reagent can oe a mercury salt and where testing on waters with very low electrical conductivity is in mind, a readily lonisable salt (such as sodium chloride).
An assay device in accordance with this aspect of the invention can be used as a disposable component whicn is connected to (e.g. plugged into) a suitable potentiostat. A fully portable testing equipment is available in this manner, with testing simply requiring a wetting of the absorbent pad of a fresh device and subsequent application of the appropriate potentials to the electrodes using the potentiostat to carry out the required Voltammetry or Anodic Stripping Voltammetry.
Brief Description of Drawings
The various aspects of this invention will now be further described, by way of example, with reference tc the accompanying drawings, in which:
Figure 1 is a much enlarged sectional view cf part of a microdisc array electrode according to the invention,
Figure 2 is a plan view from above of the part shown in Figure 1 ,
Figure 3 is a much enlarged sectional side view of part of a microband array electrode according to the invention,
Figure 4 is a plan view from above of the part shown in Figure 3,
Figure 5 is a schematic view of laser equipment for forming an array of apertures in a component of a micro¬ electrode,
Figure 6 is a siαe elevational view of an assay device in accordance with a further aspect of the invention.
Figure 7 is a schematic sectional view througn part of the device of Figure 6 with the vertical scale exaggeratec for ease of viewing, and
Figure 8 is a graph showing the applied potential for a trace element detected with a device such as that snown in Figures 6 and 7 by stripping analysis.
Description of Preferred Embodiments
The microdisc array electrode partially shown in Figures 1 and 2 comprises a substrate 1 on which a pet— forated sheet 2 of non-conducting material coated on one side with a layer 3 of conducting material is applied.
The perforations are regularly spaced equally sized apertures A drilled by photo-ablation and forming an array over the entire effective area of the microσisc array electrode.
In a typical case the substrate 1 would be a sheet of polyvinylchloride of a thickness of 500 microns, the sheet 2 a polyester sheet of a thickness of 100 microns and the layer 3 a cured carbon paste of a cured thickness of 500 microns. The array shown in Figure 2 has circular discs of 10 micron diameter in a 100 micron spaced hexagon pattern. Other geometries such as those leading to microband elec¬ trodes are also envisaged. Since each aperture is filled with the conducting paste, each filled aperture forms a conducting area surrounded by a non-conducting region. All exposed conducting areas (or discs) can be connected to the same layer 3 but it will be appreciated that where end uses reαuire different potentials to be aDcliec tc cifferent discs or cifferent grouDs of discs. the layer 2 car. oe appropriately σivideo and connectec tc its own suppl lεaα. Tne supply eaα has not been snown in Figures 1 and 2 out sucr, a leac can oe seen at 11 in Figure 5.
Figures 3 anc 4 correspond tc Figures 1 anσ 2 but snow a microband
Figure imgf000012_0001
electrode the apertures 4 now peing narrow slits. Tne micro-array electrode shown m Figure 3 was made by tmck-film printing conαuctmc electrode material 2 onto an electrically insulating substrate 1 n the required pattern. A layer 2 of polymer film is tnen vapour polymerised over the printed material 2 anc suose- αuent.y Grilled using laser photo-ab ation tc oroαuce tne apertures 4. With carbon in the material 2 vitrified carbon is formed in tne apertures 4 giving the electrode high durability and good electrical properties.
Photo-ablation of the required aperture pattern is schematically illustrated in Figure 5 where 30 indicates a high power laser source (e.g. a Lambda Physih LPX 2051 unit), 21 a reducing lens and 2 the plastics film requiring to be drilled. The film 2 can have an apertured mask printed thereon wnereby only the film exposed througn tne apertures in the mask is available for ablation or a mask 32 (e.g. of metal) can be located in the optical path anywhere between the laser source 31 and the film 2. A metal mask contacting the film 2 can also be used.
The minimum size of the apertures 4 that can be produced in a plastics film are expected to be 1 to 2 microns but they can be as large as desired.
The film 2 could be poly-para-xylylene (Parylene N) or other CH materials (such as polystyrene or polyethylene for example) . As examples of suitable laser sources may be mentioneα a KrF laser (wavelength 248 nm) of fluence in the range
0.2 to 0.4 J/cm" and (depending on the polymer film 2 being used) ArF (wavelength 1S3 nm) and XeC (wavelength 208 nm) lasers of fluences in the range 0.1 to 1.0 J/cm .
For contact imaging using a metal mask 32 in contact with a Parylene N film of 2 microns thickness, a KrF laser of 300 mJ output (a Questek 2440 unit) can be used generat¬ ing a fluence at the mask of 0.3 J/cm" over an area cf 1 cm'". Using 25 shots of the source 3C, an array cf 15 micron diameter apertures 4 on 100 micron hole centres was accurately formed in the film 2.
For projection imaging, a metal mask 32 with an array of 45 micron diameter holes on 300 micron hole centres was located in the beam from a 600 mJ KrF laser and projected down onto a 2 micron thick Parylene N film with a three times reduction of image in the lens 31. The fluence at the mask was 0.044 J/cm 2 and at the film it was 0.4 J/cm2.
Again 25 shots of the source 30 were required to dril the accurate array of apertures 4 in the film 2.
The device shown in Figures 6 and 7 comprises a rectangular substrate 10 of non-conducting material on which a microelectrode 12 has been provided. Adhered over the electrode 12 is a pad 13 of absorbent material and overlying the pad 13 is a counter electrode 14. The electrode 14 can be applied by printing and will have an area larger than the sum of the apertures of the electrode 13. Conducting leads 11 and 15 connect contact areas 16 and 17 to the two electrodes 12 and 14.
Conveniently, the areas 16 and 17 are positioned so that slipping the substrate 10 into a holder (shown dotted at 20) which is connected to an electronic unit 21 by a cable 22, automatically places the device in circuit with the electronic equipment in the unit 21. The unit 21 can comprise a miniatured microprocessor witn control poten¬ tiostat incorporating a sensitive ππcroammeter.
For testing for the presence of heavy metals .e.g. Pb, Cd, Fe, Zn) in water, the pad 13 will include some par- tides of common salt and mercurous chloride (say 105& w/w of NaCl and 5% w/w of Hg^Cl^) or other αried reactants necessary to provide conductivity and oxidised mercury for an electroplating operation. The micro-conducting areas of the electrode 12 will be carbon and the electrode 14 will be of si 1 er/si1ver chloride. Dipping the pad 13 into a sample of the water to be tested, will draw water into the pad 13 by capillarity action where it will dissolve the salt and redox reagent forming a conductive solution between the electrodes 12 and 14.
For voltammetric analysis, current is passeα with electrode 12 as working electrode and electrode 14 as a controlled voltage secondary electrode. The electrochemi¬ cal reaction on electrode 12, i.e. oxidation or reduction of the target redox species is followed by classical microelectrode electroanalytical methodology.
For stripping analysis, current is passed with elec¬ trode 14 as anode to plate mercury and any heavy metal present onto the micro-conductive areas of the electrode 12. Plating current is maintained by hemispherical mass transport inherent to the micro-array geometry for long enough (typically 2 or 3 minutes) to plate a detectable amount of the heavy metal onto the conducting areas.
By virtue of the fact that the microelectrodes are cheap enough to be disposed of after a single use, "memory" problems, such as can occur with laboratory-based equip¬ ment, will be avoided since after use for one analysis, the electrode will be discarded.
The polarity of the applied potential is now reversed so that electrode 12 serves as anode and the polarity is increased as a plot is taken of current against voltage. One example of such a plot is shown in Figure 8 which snows the stripping of lead cations from mercury coated ππcrc- conductive areas.
It will be appreciated, therefore, that the invention makes possible an assay device which comes in two sections; a sensing unit consisting of a disposable or reusable film cartridge driven by a pocket size computerised potentiostat which comprises the control and signal handling unit. The output of the instrument is a current which is proportional to the concentration of the trace metal ion at a potential specific to the ion itself.
The electroanal sis method described hereabove can be easily adapted to enzyme chemistry or/and immunochemistry for use as a biosensor. Indeed, enzymes or/and antibodies can be covalently immobilized on the perforated polymer sheet 2 in Figure 1 and electron carrier species cften called mediators can be detected on the microelectrode array in a very efficient manner due to the close proximity between the electrode and the immobilised species leading to feedback diffusion enhancement.
It should be stressed that the sensitivity and ac¬ curacy of the method and apparatus described herein, are at least comparable to the equivalent laboratory-based methods and equipment.

Claims

1. A method of making a microelectrode comprising a layer of electrically insulating material having an array of apertures formed therein and electrically conducting material visible through the apertures, characterised m that the apertures are formed by photo-ablation.
2. A method according to claim 1, characterised in that the insulating layer is a plastics film and the conducting material is applied to one side of the film after the apertures have been formed therein.
3. A method according to claim 1, characterised in that the insulating layer is applied over conducting material supported on an electrically insulating substrate and the apertures are then formed in the insulating layer to expose the conducting material.
4. A microelectrode made by the method of claim 1, characterised in that the layer of insulating material has a thickness in the range of 2 to 500 microns and each aperture has a maximum transverse dimension of between 5 and 100 microns.
5. A method for a target redox species analysis in a liquid carrier comprising moistening an absorbent medium containing a dry reactant for the species with the liquid carrier, the absorbent medium being sandwiched between two electrodes, characterised in that one of the electrodes is a microelectrode according to claim 1, the moistening process being monitored by measuring the conductance between the two electrodes and the concentration of the target redox species being determined by measuring the current flowing between the two electrodes when applying a varying potential therebetween.
6. A method according to claim 5, characterised in that a programmed voltage scan is used for the concentra¬ tion measurement.
7. An assay method for a trace redox species analysis in a liquid carrier comprising moistening an absorbent medium containing a dry reactant for the species with the liquid carrier, the absorbent medium being sandwiched between two electrodes, characterised in that one of the electrodes is a microelectrode according to claim 1, and in that a first potential is applied across the electrodes to cause any species drawn into the medium and reacted with the reactant therein to migrate ions onto the conductive areas of the microelectrode, applying a second potential of opposite polarity across the electrodes to strip the said ions from the microelectrode and determining the nature of the stripped ion from a knowledge of the redox potential required to effect stripping.
8. An assay unit, characterised in that it includes a pad of dry absorbent material sandwiched between a micro- electrode as claimed in claim 1 and a counter electrode, the absorbent material incorporating a dry-form redox reagent and the sandwich being mounted on a support means that includes a contact to at least one of the electrodes.
9. An assay unit as claimed in claim 8, characterised in that the support means is a non-conducting plate having two contacts, one leading to each of the different electrodes.
10. An assay unit as claimed in claim 9, charac¬ terised in that the redox reagent is a mercury salt.
PCT/GB1990/001874 1989-12-04 1990-12-03 Improvements in and relating to microelectrodes and amperometric assays WO1991008474A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP91900041A EP0504196B1 (en) 1989-12-04 1990-12-03 Improvements in and relating to microelectrodes and amperometric assays
US07/852,223 US5512489A (en) 1989-12-04 1990-12-03 Microelectrodes and amperometric assays
DE69021888T DE69021888T2 (en) 1989-12-04 1990-12-03 MICROELECTRODES AND AMPEROMETRIC TESTS.
US08/399,176 US5635054A (en) 1989-12-04 1995-03-06 Microelectrodes and amperometric assays

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB898927377A GB8927377D0 (en) 1989-12-04 1989-12-04 Improvements in and relating to amperometric assays
GB8927377.5 1989-12-04

Publications (1)

Publication Number Publication Date
WO1991008474A1 true WO1991008474A1 (en) 1991-06-13

Family

ID=10667393

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1990/001874 WO1991008474A1 (en) 1989-12-04 1990-12-03 Improvements in and relating to microelectrodes and amperometric assays

Country Status (9)

Country Link
US (3) US5512489A (en)
EP (2) EP0504196B1 (en)
AT (1) ATE126888T1 (en)
AU (1) AU6880091A (en)
DE (1) DE69021888T2 (en)
DK (1) DK0504196T3 (en)
ES (1) ES2077213T3 (en)
GB (1) GB8927377D0 (en)
WO (1) WO1991008474A1 (en)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0494382A1 (en) * 1990-12-10 1992-07-15 Ppg Industries, Inc. Cathode in a layered circuit and electrochemical cell for measurement of oxygen in fluids
WO1994008236A1 (en) * 1992-10-07 1994-04-14 Ecossensors Limited Gas permeable membranes for amperometric gas electrodes and uses thereof
WO1995022052A1 (en) * 1994-02-11 1995-08-17 Ecossensors Limited Detection of lead in blood
EP0685735A1 (en) * 1994-06-03 1995-12-06 Metrohm Ag Voltammetric apparaus, indicating electrode arrangement for such apparatus, especially as a part of a tape cassette, and voltammetric method for serial analysis
WO1996000385A1 (en) * 1994-06-24 1996-01-04 Environmental Sensors Ltd. The production of electrodes for electrochemical sensing
WO1996001993A1 (en) * 1994-07-11 1996-01-25 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Electrochemical analysis process
WO1996010174A1 (en) * 1994-09-28 1996-04-04 Cranfield Biotechnology Ltd. Electrochemical oxygen sensor
WO1996024840A1 (en) * 1995-02-10 1996-08-15 Ecossensors Limited Measuring metal ions in a solution
US5554268A (en) * 1995-02-22 1996-09-10 Priddy; Richard V. Disposable sensor for metal analysis
WO1996033403A1 (en) * 1995-04-19 1996-10-24 The Manchester Metropolitan University Sensor
GB2291714B (en) * 1993-04-07 1997-03-05 Ecossensors Ltd Biological species detection method and biosensor therefor
US5646863A (en) * 1994-03-22 1997-07-08 Morton; Stephen G. Method and apparatus for detecting and classifying contaminants in water
AU682188B2 (en) * 1989-12-30 1997-09-25 Rowett Research Institute, The Method to detect bone and other connective tissue disorders in humans and animals
US5676820A (en) * 1995-02-03 1997-10-14 New Mexico State University Technology Transfer Corp. Remote electrochemical sensor
WO1998023957A1 (en) * 1996-11-27 1998-06-04 Ecole Polytechnique Federale De Lausanne (Laboratoire D'electrochimie) Surface patterning of affinity reagents using photoablation
EP0908725A1 (en) * 1997-09-30 1999-04-14 Seiko Epson Corporation Manufacture of a microsensor device
US5942103A (en) * 1995-02-03 1999-08-24 New Mexico State University Technology Transfer Corporation Renewable-reagent electrochemical sensor
US7073246B2 (en) 1999-10-04 2006-07-11 Roche Diagnostics Operations, Inc. Method of making a biosensor
US8105478B2 (en) 2004-01-29 2012-01-31 Siemens Aktiengesellschaft Method for measuring the concentration or change in concentration of a redox-active substance and corresponding device

Families Citing this family (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8927377D0 (en) * 1989-12-04 1990-01-31 Univ Edinburgh Improvements in and relating to amperometric assays
US5292423A (en) 1991-04-09 1994-03-08 New Mexico State University Technology Transfer Corp. Method and apparatus for trace metal testing
US6770179B1 (en) * 1993-05-10 2004-08-03 Universite De Montreal Biosensors comprising a covalently attached monomolecular biological conjugate layer and a transducing device
GB9311035D0 (en) * 1993-05-28 1993-07-14 Environmental Med Prod Electrochemical metal analysis
DE69528387T2 (en) * 1995-06-06 2003-02-13 Orchid Biosciences Inc MANUFACTURE OF ELECTRICAL CABLES THROUGH HOLES
WO1997008544A1 (en) * 1995-08-22 1997-03-06 Andcare, Inc. Handheld electromonitor device
CA2173932A1 (en) * 1996-04-11 1997-10-12 Gilles Y. Champagne Method for manufacturing an array of microelectrodes
EP0961932A1 (en) * 1996-05-16 1999-12-08 Sendx Medical, Inc. Sensors with subminiature through holes, and method for fabricating such sensors
US6146510A (en) * 1996-05-16 2000-11-14 Sendx Medical, Inc. Sensor cartridge for a fluid analyte analyzer
US6022463A (en) * 1996-05-16 2000-02-08 Sendx Medical, Inc. Sensors with subminiature through holes
US5858452A (en) * 1996-05-16 1999-01-12 Sendx Medical, Inc. Method for fabricating wiring substrate with subminiature thru-holes
US6063259A (en) * 1996-06-11 2000-05-16 New Mexico State University Technology Transfer Corporation Microfabricated thick-film electrochemical sensor for nucleic acid determination
EP0950184A1 (en) * 1996-06-27 1999-10-20 Cellstat Technologies, Inc. High-throughput screening method and apparatus
WO1998058249A1 (en) * 1997-06-19 1998-12-23 Jongman Park HgO-MODIFIED ELECTRODE FOR ANODIC STRIPPING ANALYSIS
AU9786798A (en) * 1997-10-10 1999-05-03 Biosepra Inc. Aligned multiwell multiplate stack and method for processing biological/chemicalsamples using the same
US20020144905A1 (en) * 1997-12-17 2002-10-10 Christian Schmidt Sample positioning and analysis system
US7244349B2 (en) * 1997-12-17 2007-07-17 Molecular Devices Corporation Multiaperture sample positioning and analysis system
JP3486171B2 (en) * 1997-12-17 2004-01-13 エコル・ポリテクニック・フェデラル・ドゥ・ロザンヌ（エ・ペー・エフ・エル） Positioning and electrophysiological characterization of single cell and reconstituted membrane systems on microstructured carriers
US8974386B2 (en) 1998-04-30 2015-03-10 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8346337B2 (en) 1998-04-30 2013-01-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9066695B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8688188B2 (en) 1998-04-30 2014-04-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8465425B2 (en) 1998-04-30 2013-06-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6175752B1 (en) 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
US6949816B2 (en) 2003-04-21 2005-09-27 Motorola, Inc. Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same
US8480580B2 (en) 1998-04-30 2013-07-09 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
GB9809918D0 (en) 1998-05-08 1998-07-08 Isis Innovation Microelectrode biosensor and method therefor
DE19831529C2 (en) * 1998-07-14 2002-04-11 Micronas Gmbh Method of making an electrode
DE19930104C1 (en) * 1999-07-01 2001-02-15 Fraunhofer Ges Forschung Method of making an electrode assembly
US6645359B1 (en) * 2000-10-06 2003-11-11 Roche Diagnostics Corporation Biosensor
US6662439B1 (en) * 1999-10-04 2003-12-16 Roche Diagnostics Corporation Laser defined features for patterned laminates and electrodes
US6682647B1 (en) 2000-05-10 2004-01-27 New Mexico State University Technology Transfer Corporation Bismuth-based electrochemical stripping analysis
US7067046B2 (en) * 2000-08-04 2006-06-27 Essen Instruments, Inc. System for rapid chemical activation in high-throughput electrophysiological measurements
US7270730B2 (en) 2000-08-04 2007-09-18 Essen Instruments, Inc. High-throughput electrophysiological measurement system
US6540890B1 (en) * 2000-11-01 2003-04-01 Roche Diagnostics Corporation Biosensor
US6560471B1 (en) 2001-01-02 2003-05-06 Therasense, Inc. Analyte monitoring device and methods of use
CH697478B1 (en) * 2001-05-22 2008-11-14 Adamant Technologies Sa electrode for electrochemical sensor system and method for determining the pH of a chlorinated water.
US6814844B2 (en) 2001-08-29 2004-11-09 Roche Diagnostics Corporation Biosensor with code pattern
US7018843B2 (en) 2001-11-07 2006-03-28 Roche Diagnostics Operations, Inc. Instrument
WO2003043945A1 (en) * 2001-11-16 2003-05-30 North Carolina State University Biomedical electrochemical sensor array and method of fabrication
GB0130684D0 (en) * 2001-12-21 2002-02-06 Oxford Biosensors Ltd Micro-band electrode
US6866758B2 (en) * 2002-03-21 2005-03-15 Roche Diagnostics Corporation Biosensor
US6830668B2 (en) * 2002-04-30 2004-12-14 Conductive Technologies, Inc. Small volume electrochemical sensor
GB0211449D0 (en) * 2002-05-17 2002-06-26 Oxford Biosensors Ltd Analyte measurement
EP1406085A1 (en) * 2002-10-01 2004-04-07 Metrohm Ag Electrode, electrode element, methods of their fabrication and use of said electrode
US7200538B2 (en) * 2003-01-15 2007-04-03 General Electric Company Methods and apparatus for modeling gas turbine engines
KR100785670B1 (en) 2003-06-20 2007-12-14 에프. 호프만-라 로슈 아게 Method and reagent for producing narrow, homogenous reagent strips
GB2404738B (en) * 2003-08-04 2005-09-28 Schlumberger Holdings System and method for sensing using diamond based microelectrodes
US9012232B2 (en) * 2005-07-15 2015-04-21 Nipro Diagnostics, Inc. Diagnostic strip coding system and related methods of use
EP1557665A1 (en) * 2004-01-21 2005-07-27 CSEM Centre Suisse d'Electronique et de Microtechnique SA Electrode system for an electrochemical sensor
US8308922B2 (en) 2004-01-29 2012-11-13 Siemens Aktiengesellschaft Electrochemical transducer array and use thereof
US20050221473A1 (en) * 2004-03-30 2005-10-06 Intel Corporation Sensor array integrated circuits
GB0409809D0 (en) * 2004-05-01 2004-06-09 Univ Cranfield Sensor devices
US20050274849A1 (en) * 2004-06-10 2005-12-15 Klosner Mark A Highly-integrated low-mass solar sail
GB0414546D0 (en) * 2004-06-29 2004-08-04 Oxford Biosensors Ltd Electrode for electrochemical sensor
US20060008581A1 (en) * 2004-07-09 2006-01-12 Mark Hyland Method of manufacturing an electrochemical sensor
FR2878621B1 (en) * 2004-12-01 2007-03-09 Rech S Geol Et Minieres Brgmet DEVICE FOR IN SITU MEASUREMENT OF THE METAL ION CONTENT OF WATER
US20060256599A1 (en) * 2005-03-22 2006-11-16 Malin Patricia J Database of electronically profiled cells and methods for generating and using same
GB0509919D0 (en) * 2005-05-16 2005-06-22 Ralph Ellerker 1795 Ltd Improvements to door closure system
US7955856B2 (en) * 2005-07-15 2011-06-07 Nipro Diagnostics, Inc. Method of making a diagnostic test strip having a coding system
US8999125B2 (en) 2005-07-15 2015-04-07 Nipro Diagnostics, Inc. Embedded strip lot autocalibration
GB0517773D0 (en) * 2005-09-01 2005-10-12 Palintest Ltd Electrochemical sensor
US8105469B2 (en) 2006-03-17 2012-01-31 Andrew John Whitehead Microelectrode array
US20080020452A1 (en) * 2006-07-18 2008-01-24 Natasha Popovich Diagnostic strip coding system with conductive layers
AU2012254906B2 (en) * 2006-11-09 2015-01-29 Trividia Health, Inc. Diagnostic strip test system and related methods of use
JP5405916B2 (en) * 2008-06-24 2014-02-05 パナソニック株式会社 Biosensor, method for manufacturing the same, and detection system including the same
US9523653B2 (en) 2013-05-09 2016-12-20 Changsha Sinocare Inc. Disposable test sensor with improved sampling entrance
US9518951B2 (en) 2013-12-06 2016-12-13 Changsha Sinocare Inc. Disposable test sensor with improved sampling entrance
US9897566B2 (en) 2014-01-13 2018-02-20 Changsha Sinocare Inc. Disposable test sensor
US9939401B2 (en) 2014-02-20 2018-04-10 Changsha Sinocare Inc. Test sensor with multiple sampling routes
CN103822961B (en) * 2014-03-13 2018-08-31 南京洁态环保科技有限公司 Electrochemical microfluidic chip and preparation method thereof
WO2015160905A1 (en) 2014-04-16 2015-10-22 Abbott Laboratories Droplet actuator fabrication apparatus, systems, and related methods
DE102014016903A1 (en) * 2014-11-17 2016-05-19 Rheinisch-Westfälische Technische Hochschule Aachen Process for producing an electrode
CN110935496A (en) 2014-12-31 2020-03-31 雅培制药有限公司 Digital microfluidic dilution apparatus, systems, and related methods
JP7469881B2 (en) * 2016-12-09 2024-04-17 デジタル センシング リミテッド Electrochemical sensors and methods of use thereof
CN111039520B (en) * 2020-01-07 2021-11-05 苏州他山石环保科技有限公司 Industrial sewage treatment system
CN113655102A (en) * 2021-08-25 2021-11-16 深圳市溢鑫科技研发有限公司 Electrochemical measurement microelectrode structure and manufacturing method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0206218A2 (en) * 1985-06-28 1986-12-30 Miles Inc. Electrode for electrochemical sensors
EP0305769B1 (en) * 1987-08-17 1991-09-11 BASF Aktiengesellschaft Redox electrode for the determination of nitrous acid and nitrosyl compounds

Family Cites Families (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3655547A (en) * 1969-08-27 1972-04-11 Lockheed Aircraft Corp Electrochemical cell having a bipolar electrode
GB1382873A (en) * 1971-01-13 1975-02-05 Radiometer As Electrode for potentiometric measurements
US3855099A (en) * 1971-08-02 1974-12-17 Environmental Sciences Ass Inc Electrode for anodic stripping voltammetry
JPS4835893A (en) * 1971-08-02 1973-05-26
JPS5756163B2 (en) * 1971-12-27 1982-11-29
DE2451659A1 (en) * 1973-11-20 1975-05-28 Hercules Inc Mercury electrode for anodic and cathodic voltametry - using a substrate of pyrolytic graphite
US3914509A (en) * 1973-11-20 1975-10-21 Hercules Inc Chemical modification of the surface of pyrolytic graphite
FR2273276B1 (en) * 1974-05-27 1978-08-04 Radiotechnique Compelec
DE2436261B2 (en) * 1974-07-27 1976-11-25 Bayer Ag, 5090 Leverkusen ELECTROCHEMICAL GAS DETECTORS
US3904487A (en) * 1974-10-29 1975-09-09 Us Navy Anodic stripping volammetry and apparatus therefor
US4062750A (en) * 1974-12-18 1977-12-13 James Francis Butler Thin film electrochemical electrode and cell
GB1600146A (en) * 1978-01-11 1981-10-14 Environmental Sciences Ass Chemical reagent compositions for serum iron test
US4214968A (en) * 1978-04-05 1980-07-29 Eastman Kodak Company Ion-selective electrode
US4863873A (en) * 1980-01-14 1989-09-05 Esa, Inc. Method for biological testing and/or developing pharmaceuticals for treatment of disorders
US5104639A (en) * 1980-01-14 1992-04-14 Esa, Inc. Method for biological testing and/or developing pharmaceuticals for treatment of disorders using electrochromatography
US4450842A (en) * 1980-04-25 1984-05-29 Cordis Corporation Solid state reference electrode
JPS57118152A (en) * 1981-01-14 1982-07-22 Matsushita Electric Ind Co Ltd Enzyme electrode
US4442841A (en) * 1981-04-30 1984-04-17 Mitsubishi Rayon Company Limited Electrode for living bodies
US4414059A (en) * 1982-12-09 1983-11-08 International Business Machines Corporation Far UV patterning of resist materials
US4524114A (en) * 1983-07-05 1985-06-18 Allied Corporation Bifunctional air electrode
US4481230A (en) * 1983-10-27 1984-11-06 Rca Corporation Method of depositing a semiconductor layer from a glow discharge
US4508749A (en) * 1983-12-27 1985-04-02 International Business Machines Corporation Patterning of polyimide films with ultraviolet light
DE3423605A1 (en) * 1984-06-27 1986-01-09 W.C. Heraeus Gmbh, 6450 Hanau COMPOSITE ELECTRODE, METHOD FOR THEIR PRODUCTION AND THEIR USE
DE3585915T2 (en) * 1984-12-28 1993-04-15 Terumo Corp ION SENSOR.
JPS61187237A (en) * 1985-02-14 1986-08-20 Toshiba Corp Formation of pattern
EP0266432B1 (en) * 1986-04-22 1992-01-15 Toray Industries, Inc. Microelectrode for electrochemical analysis
GB8618022D0 (en) * 1986-07-23 1986-08-28 Unilever Plc Electrochemical measurements
NO873013L (en) * 1987-04-13 1988-10-14 Electrolyt Zinc Australasia PROCEDURE AND APPARATUS FOR DETERMINING ELECTROCHEMICALLY ACTIVE COMPONENTS.
US4874500A (en) * 1987-07-15 1989-10-17 Sri International Microelectrochemical sensor and sensor array
WO1989004479A1 (en) * 1987-11-02 1989-05-18 Biologix Inc. Electrode system for use in a portable blood chemistry measuring apparatus
US4933048A (en) * 1988-02-16 1990-06-12 I-Stat Corporation Reference electrode, method of making and method of using same
US4874499A (en) * 1988-05-23 1989-10-17 Massachusetts Institute Of Technology Electrochemical microsensors and method of making such sensors
GB8927377D0 (en) * 1989-12-04 1990-01-31 Univ Edinburgh Improvements in and relating to amperometric assays
US5183549A (en) * 1990-01-26 1993-02-02 Commtech International Management Corporation Multi-analyte sensing electrolytic cell
US5091339A (en) * 1990-07-23 1992-02-25 Microelectronics And Computer Technology Corporation Trenching techniques for forming vias and channels in multilayer electrical interconnects
US5281323A (en) * 1991-03-20 1994-01-25 Fujitsu Limited Electrolyte composition for screen printing and miniaturized oxygen electrode and production process thereof
US5192416A (en) * 1991-04-09 1993-03-09 New Mexico State University Technology Transfer Corporation Method and apparatus for batch injection analysis
US5292423A (en) * 1991-04-09 1994-03-08 New Mexico State University Technology Transfer Corp. Method and apparatus for trace metal testing
DE4115414C2 (en) * 1991-05-10 1995-07-06 Meinhard Prof Dr Knoll Process for the production of miniaturized chemo- and biosensor elements with an ion-selective membrane as well as carriers for these elements
GB9112086D0 (en) * 1991-06-05 1991-07-24 Capteur Sensors & Analysers Improvements relating to electrodes
DE69122383T2 (en) * 1991-08-22 1997-02-27 Secr Defence Brit Anodic strip voltammetry
EP0560137A1 (en) * 1992-03-12 1993-09-15 Firma Willi Möller Mercury containing complexing agents for anions (halogenides and pseudohalogenides) and method for the determination of halogenides and pseudohalogenides in aqueous media
US5290420A (en) * 1992-08-12 1994-03-01 Esa, Inc. Sampling system and analysis cell for stripping voltammetry
GB9223016D0 (en) * 1992-11-03 1992-12-16 Environmental And Medical Prod Electrochemical sensor
GB9311035D0 (en) * 1993-05-28 1993-07-14 Environmental Med Prod Electrochemical metal analysis
GB2297172A (en) * 1993-07-30 1996-07-24 Capteur Sensors & Analysers Analysis of liquid solutions

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0206218A2 (en) * 1985-06-28 1986-12-30 Miles Inc. Electrode for electrochemical sensors
EP0305769B1 (en) * 1987-08-17 1991-09-11 BASF Aktiengesellschaft Redox electrode for the determination of nitrous acid and nitrosyl compounds

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Dechiema Monogr., vol. 117, 1989, J. Thielke et al.: "Microelectrode processes in a focused laser beam", pages 175-189 see summary; figure 1 *
Langmuir, vol. 4, no. 3, 1988, American Chemical Society, E.S. Kirkor et al.: "A simple method for the production of controlled electro-plated designs on a metal surface", pages 578-579 *

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU682188B2 (en) * 1989-12-30 1997-09-25 Rowett Research Institute, The Method to detect bone and other connective tissue disorders in humans and animals
US5246576A (en) * 1990-12-10 1993-09-21 Ppg Industries, Inc. Cathode in a layered circuit and electrochemical cell for a measurement of oxygen in fluids
US5611902A (en) * 1990-12-10 1997-03-18 Ppg Industries, Inc. Cathode in a layered circuit and electrochemical cell for measurement of oxygen in fluids
EP0494382A1 (en) * 1990-12-10 1992-07-15 Ppg Industries, Inc. Cathode in a layered circuit and electrochemical cell for measurement of oxygen in fluids
US5575930A (en) * 1992-10-07 1996-11-19 Tietje-Girault; Jordis Method of making gas permeable membranes for amperometric gas electrodes
WO1994008236A1 (en) * 1992-10-07 1994-04-14 Ecossensors Limited Gas permeable membranes for amperometric gas electrodes and uses thereof
GB2291714B (en) * 1993-04-07 1997-03-05 Ecossensors Ltd Biological species detection method and biosensor therefor
WO1995022052A1 (en) * 1994-02-11 1995-08-17 Ecossensors Limited Detection of lead in blood
US5814205A (en) * 1994-02-11 1998-09-29 Palintest Limited Detection of lead in blood
US5646863A (en) * 1994-03-22 1997-07-08 Morton; Stephen G. Method and apparatus for detecting and classifying contaminants in water
EP0685735A1 (en) * 1994-06-03 1995-12-06 Metrohm Ag Voltammetric apparaus, indicating electrode arrangement for such apparatus, especially as a part of a tape cassette, and voltammetric method for serial analysis
US5686829A (en) * 1994-06-03 1997-11-11 Metrohm Ag Voltammetric method and apparatus
US6020110A (en) * 1994-06-24 2000-02-01 Cambridge Sensors Ltd. Production of electrodes for electrochemical sensing
WO1996000385A1 (en) * 1994-06-24 1996-01-04 Environmental Sensors Ltd. The production of electrodes for electrochemical sensing
US5830343A (en) * 1994-07-11 1998-11-03 Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E.V. Electrochemical analysis process
WO1996001993A1 (en) * 1994-07-11 1996-01-25 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Electrochemical analysis process
WO1996010174A1 (en) * 1994-09-28 1996-04-04 Cranfield Biotechnology Ltd. Electrochemical oxygen sensor
AU688595B2 (en) * 1994-09-28 1998-03-12 Cranfield Biotechnology Ltd. Electrochemical oxygen sensor
US5942103A (en) * 1995-02-03 1999-08-24 New Mexico State University Technology Transfer Corporation Renewable-reagent electrochemical sensor
US5676820A (en) * 1995-02-03 1997-10-14 New Mexico State University Technology Transfer Corp. Remote electrochemical sensor
WO1996024840A1 (en) * 1995-02-10 1996-08-15 Ecossensors Limited Measuring metal ions in a solution
US5554268A (en) * 1995-02-22 1996-09-10 Priddy; Richard V. Disposable sensor for metal analysis
AU698852B2 (en) * 1995-04-19 1998-11-12 Microarray Limited Sensor
WO1996033403A1 (en) * 1995-04-19 1996-10-24 The Manchester Metropolitan University Sensor
US6083366A (en) * 1995-04-19 2000-07-04 The Manchester Metropolitan University Sensor
WO1998023957A1 (en) * 1996-11-27 1998-06-04 Ecole Polytechnique Federale De Lausanne (Laboratoire D'electrochimie) Surface patterning of affinity reagents using photoablation
EP0908725A1 (en) * 1997-09-30 1999-04-14 Seiko Epson Corporation Manufacture of a microsensor device
US6762050B2 (en) 1997-09-30 2004-07-13 Seiko Epson Corporation Manufacture of a microsensor device and a method for evaluating the function of a liquid by the use thereof
US7029841B2 (en) 1997-09-30 2006-04-18 Seiko Epson Corporation Manufacture of a microsensor device and a method for evaluating the function of a liquid by the use thereof
US7073246B2 (en) 1999-10-04 2006-07-11 Roche Diagnostics Operations, Inc. Method of making a biosensor
US8105478B2 (en) 2004-01-29 2012-01-31 Siemens Aktiengesellschaft Method for measuring the concentration or change in concentration of a redox-active substance and corresponding device
DE102005003911B4 (en) * 2004-01-29 2018-11-15 Boehringer Ingelheim Vetmedica Gmbh Method for measuring the concentration or concentration change of a redox-active substance and associated device

Also Published As

Publication number Publication date
DK0504196T3 (en) 1996-01-22
EP0653629A3 (en) 1995-08-02
DE69021888T2 (en) 1996-04-11
DE69021888D1 (en) 1995-09-28
ES2077213T3 (en) 1995-11-16
US5512489A (en) 1996-04-30
US5739039A (en) 1998-04-14
AU6880091A (en) 1991-06-26
US5635054A (en) 1997-06-03
ATE126888T1 (en) 1995-09-15
GB8927377D0 (en) 1990-01-31
EP0504196B1 (en) 1995-08-23
EP0653629A2 (en) 1995-05-17
EP0504196A1 (en) 1992-09-23

Similar Documents

Publication Publication Date Title
US5739039A (en) Microelectrodes and amperometric assays
US6020110A (en) Production of electrodes for electrochemical sensing
US8354012B2 (en) Electrochemical cell
JP4073969B2 (en) Electrodes for measuring analytes in small sample volumes
US5141868A (en) Device for use in chemical test procedures
AU588245B2 (en) Devices for use in chemical test procedures
US7625469B1 (en) Nanoelectrode array for electrochemical analysis
Seddon et al. Printed microelectrode array and amperometric sensor for environmental monitoring
CN101057136A (en) Microfluidic device with minimised ohmic resistance
Seddon et al. The application of excimer laser micromachining for the fabrication of disc microelectrodes
Feldman et al. Electrochemical determination of low blood lead concentrations with a disposable carbon microarray electrode
EP0215446A2 (en) Device and method for measuring ion activity
AU1585995A (en) Detection of lead in blood
EP0394990B1 (en) Dry-operative ion-selective electrode
WO1994023295A1 (en) Biological species detection method and biosensor therefor
JP2005083994A (en) Method of manufacturing electrode for electrochemical analysis
Sandison Micro-and nano-electrode arrays for electroanalytical sensing
Ansell et al. Electrochemical sensors
Suzuki et al. Evaporative concentration of analytes and sensing using a super hydrophobic surface
Petrovic Application of microelectrodes for the detection of metallic analytes using thin layer chromatography-square wave anodic stripping voltammetry (TLC-SWASV)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA FI JP KR NO US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LU NL SE

WWE Wipo information: entry into national phase

Ref document number: 1991900041

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1991900041

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: CA

WWG Wipo information: grant in national office

Ref document number: 1991900041

Country of ref document: EP