WO2003023389A2 - Electrode - Google Patents

Electrode Download PDF

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Publication number
WO2003023389A2
WO2003023389A2 PCT/GB2002/004114 GB0204114W WO03023389A2 WO 2003023389 A2 WO2003023389 A2 WO 2003023389A2 GB 0204114 W GB0204114 W GB 0204114W WO 03023389 A2 WO03023389 A2 WO 03023389A2
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WO
WIPO (PCT)
Prior art keywords
solid state
sensor
electrode
sensor according
membrane
Prior art date
Application number
PCT/GB2002/004114
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English (en)
Other versions
WO2003023389A9 (fr
WO2003023389A3 (fr
Inventor
Simon Allan
Geoff King
Paul Treloar
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Hypoguard Limited
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Publication date
Application filed by Hypoguard Limited filed Critical Hypoguard Limited
Priority to AU2002331930A priority Critical patent/AU2002331930A1/en
Publication of WO2003023389A2 publication Critical patent/WO2003023389A2/fr
Publication of WO2003023389A3 publication Critical patent/WO2003023389A3/fr
Publication of WO2003023389A9 publication Critical patent/WO2003023389A9/fr

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    • 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
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • G01N33/5438—Electrodes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes
    • C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes
    • C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
    • C12Q1/006—Enzyme electrodes involving specific analytes or enzymes for glucose

Definitions

  • This invention relates to novel methods of analysis and to a novel form of electrode associated thereto.
  • biosensor constructs of the type which may be used in a clinical biochemistry analyser comprise a platinum working electrode mounted with a membrane laminate, the precise nature of the laminate being varied depending upon, for example, the analyte.
  • the laminate comprises an inner membrane, with selective properties, an outer diffusion limiting membrane and an enzyme layer sandwiched between the two membrane layers.
  • the enzyme layer typically comprises an oxidase enzyme appropriate to the analyte to be measured.
  • the analyte passes through the outer membrane, which may have a pore size around 30nm.
  • the analyte then contacts the oxidase layer and reacts to generate hydrogen peroxide, the peroxide then passes through the selective membrane and is detected by the platinum electrode.
  • Such biosensors when incorporated in a laboratory analyser may provide precise and accurate results, but they suffer from a number of disadvantages including relatively high cost and high maintenance requirements. In addition, as the sensor is reused, it must be calibrated frequently. Oxidase type biosensors, as described above, have also suffered from the particular disadvantage that the inner selective membrane, designed to permit the flow of hydrogen peroxide, may also permit the flow of interferents e.g. paracetamol, giving rise to inaccurate measurements.
  • biosensors may comprise a screen printed electrode track on an inert plastic substrate.
  • the sensor itself comprises glucose oxidase enzyme incorporated in a carbon based working electrode, being covered by hydrophilic mesh.
  • This, type of biosensor provides some advantages over the laboratory based laminate. In particular, as it is disposable and provides only one test, it requires no ongoing calibration by the user, thereby reducing the rurrning costs and complexity of test. Also, with devices of this type where hydrogen peroxide is replaced with an alternative electron transfer mediator, glucose can be detected using lower polarising voltages at the working electrode, thereby affording some improvement in selectivity.
  • this type of biosensor suffers from a number of disadvantages. Due to the absence of a selective membrane, they cannot provide the degree of selectivity against interferents possible with the best selective membranes incorporated in a laminate type biosensors (refi European Patent Application No. 0 225 094). In addition, due, inter alia, to the imprecision of the screen printing techniques often used in fabrication of the critical working electrode, this biosensor construct can only provide limited analytical precision. Thus, when configured as a disposable test, this ' biosensor provides inferior precision and accuracy against the conventional laminate system when incorporated in a laboratory analyser, hi addition, it maybe more vulnerable to matrix effects e.g. haematocrit.
  • a novel sensor which overcomes the problems of prior art sensors by the use of silicon die technology used in tandem with an inert, plastic strip substrate.
  • silicon we mean silicon or a compound of silicon, for example, silicon dioxide e.g. quartz.
  • a solid state electrochemical sensor comprising a non-conducting substrate supporting a plurality of electrode tracks, and at least a working electrode fabricated on a silicon die.
  • the substrate may additionally have a counter and/or reference electrode laid down on it.
  • the reference and/or counter electrodes may be separate to the die based strip electrode. It may also have more multiple dies mounted on it and or multiple reference and/or counter electrodes. These may be individually addressable, or may be addressed as one electrode or as combinations of electrodes.
  • the non-conducting substrate strip may also support an analyte target electrode wherein the electrode tracks and the target electrode area are connected by an interconnect comprising a globule of conducting material, for example, a silver globule.
  • the size of the silicon die may vary, thus the die may be from 100 to 500 ⁇ m thick, preferably about 250 ⁇ m thick, e.g. in the form of a silicon wafer.
  • the bare die may have a size in the region of 1.1mm x 2mm, although the specific dimensions may be varied.
  • the non-conducting substrate preferably is both electrically and chemically inert.
  • a substrate preferentially comprises a thin strip of material which may be e.g. a plastics material.
  • plastics material include, but are not limited to, polycarbonate, polyimide, polyvinylchloride, polyacetate.
  • An especially preferred plastics material is PE (polyester).
  • the senor of the invention may advantageously be provided with one or more connector pins or pads, preferentially a plurality of connector pins or pads.
  • Reference hereinafter to connector pins should be construed as including, optionally, connector pads.
  • the connector pins may comprise any conventionally known conducting material, such as silver, gold, platinum, copper, etc. or any combination thereof.
  • Preferred connector pins comprise a silver/resin system or a silver loaded ink, of the type used for screen printing inks.
  • the connector pins are integrated with the sensor trackwork which is used to connect up various components, e.g. the working and/or , reference and/or counter electrode(s) together if required with an identification resistor.
  • the sensor may be connected to the target instrumentation via the connector pins, either by directly inserting the sensor into a suitable sensor connector in the instrument casework, or by inserting the sensor into a sensor connector mounted in a separate probe, umbilically linked to the required instrumentation.
  • Suitable instrumentation may be designed for handheld use or for benchtop operation.
  • the identification resistor is preferably a resistor device coated on the substrate which can be connected via the sensor connecting pins.
  • the identification resistor is preferably a resistor device coated on the substrate which can be connected via the sensor connecting pins.
  • the identification resistor can confirm the interrogation regime required to initialise the sensor, specific to the sensor type. Furthermore, it may determine the specific instrument check sequence required. Addition of sample to the sensor can be detected automatically by deviation of the initialising baseline beyond normal limits e.g. +/- 3 standard deviations.
  • the sensor of the invention may be adapted disposable use, re-use or continuous use.
  • the trackwork is then typically coated with an insulating compound so as to expose on the proximal connector pins and distil electrodes and prevent fluid ingress to the interconnecting trackwork.
  • an insulating compound Any conventionally known insulating compound may be used.
  • a preferred insulating compound is a resin, for example, an epoxy resin, such as a UN curable epoxy resin.
  • the working or counter electrodes may comprise any electrically conductive material adhered to a portion of the substrate.
  • an electrode may comprise silver, copper, gold or platinum, or any combination thereof.
  • An especially preferred electrode is a silver or silver/silver chloride reference electrode and/or a silver counter electrode.
  • connection between the die fabricated working electrode and the electrode trackwork is the connection between the die fabricated working electrode and the electrode trackwork.
  • Such connections are conventionally wire bond connection.
  • the die based working electrode is connected to the electrode tracks by a globule of conducting material, known as a "glob top".
  • the conducting material of the interconnect is a metal, such as silver or gold, however silver is especially preferred to achieve high conductivity whilst minimising cost.
  • the metal is preferentially deposited in a metal/resin/solvent based ink system suitable for screen printing, e.g. a silver loaded ink. Alternatively, it may be deposited by electroplating or vapour phase sputtering.
  • a silver interconnect may be made by applying a silver loaded ink between a connection pad and a conducting leg and sealed using a globtop as hereinbefore described, dispensed over the area.
  • the silver interconnect is encapsulated by an inert, dielectric coating.
  • a variety of materials may be suitable, but it is preferable that the material be UN or thermally curable, is non-porous and is inert to the analyte and/or analyte solution.
  • the adhesive used to fix the silicon die should also be non-porous, particularly since the adhesive must also act to prevent ingress of solvents and analytes to the silver interconnect. Dielectric materials need to be water impermeable and stable when exposed to water.
  • the silver globule is preferentially applied as a liquid, for example, as silver flakes in a polymer/solvent carrier system.
  • the die based electrode may comprise an array of electrodes or a single elecfrode.
  • the electrode region of the die may comprise any conventionally known electrode materials e.g. platinum, palladium, gold or silver.
  • the electrode area comprises an array of electrodes preferentially an array of platinum electrodes.
  • the array may be varied depending upon, inter alia, the analyte and also the silicon die and/or processing requirements.
  • the platinum electrode array comprises an arrangement of 4 x 4 electrodes.
  • the silicon die is preferentially fixed to the subsfrate by a region of (die attach) adhesive. Any conventionally known adhesives may be used. However, it is important that the adhesive is resistant to both solvents and analytes which may be relevant to the steps required for further processing or the analytical use of the sensor. Thus, commonly, for example, the adhesive must be resistant to alcohols, such as ethanol.
  • the die attach adhesive, interconnecting silver/resin system and the dielectric encapsulant should be capable of being auto dispensed, permitting automated production of the biosensors of the invention.
  • a solid state electrochemical sensor comprising a non-conducting substrate supporting a plurality of elecfrode tracks and an analyte target area characterised in that one or more electrodes are in intimate contact with a selective membrane.
  • the use of a membrane may be advantageous with any conventionally known strip biosensor, particularly where the membrane is selective, and can minimise sample matrix effects.
  • the invention comprises a biosensor provided with a silicon die working electrode as hereinbefore described wherein at least the working electrode is in intimate contact with a hydrophilic, selective membrane.
  • the selective membrane is preferentially a permeable or a semi-permeable membrane.
  • a semi-permeable membrane such a membrane shall be described as a semi-permeable membrane.
  • the preferred semi-permeable membrane is one which is selective only to the indicator of choice.
  • This may be the analyte itself if it is directly suitably electrochemically active, or it may be an indicator produced by a suitable detection chemistry.
  • Detection chemistries may yield an indicator which may for example be a reaction product or co-substrate or co-factor generated by reaction of the analyte with an enzyme, or direct or indirect detection the reaction of analyte with and antibody or other affinity molecule.
  • Suitable membranes may include those mentioned in various of our earlier Patents, including, inter alia, European Patent Applications No. 92906395.6, 93917908.1, 95906425.4, 96938307.4 and International Patent application No. PCT/GB97/03005.
  • One especially preferred semi-permeable membrane may be that described in European Patent Application No. 0 225 094.
  • Such a semi-permeable membrane may be provided with hydrophilic groups and/or groups which have an affinity to polar molecules. Such groups include, for example, sulphonic acid groups.
  • the semi-permeable membrane may be formed from a material which comprises a sulphonated or unsulphonated polyarylsulphone or a sulphonated or unsulphonated polyarylketone as defined in European Patent Application No. 0 225 094.
  • the semi-permeable membrane is formed form a material which comprises a sulphonated polyarylsulphone or a sulphonated polyarylketone as defined in European Patent Application No. 0 225 094.
  • the most preferred membrane is one which is formed from a material comprising a sulphonated polyarylsulphone
  • a preferred material is a sulphonated polyarylsulphone of the type sulphonated polyether ether sulphone co-polymerised with polyether sulphone (SPEES/PES where the preferred sulphonation ratio is in the range 5-8.
  • SPEES/PES polyether sulphone
  • the membrane materials described in European Patent Application No. 0 225 094 are known to be especially useful in glucose determination as a selective barrier membrane permeable to hydrogen peroxide.
  • such membrane materials prevent the solid state electrochemical sensor of the invention from being attacked by alcohols, such as ethanol.
  • alcohols such as ethanol.
  • the protective membrane may either reduce the amount of solvent able to access the electrode construct or, alternatively, it may entrap components which may subsequently leach so preventing these from interfering with electrochemical detection at the electrode surface.
  • Materials which may be protected in this way with the construct cited here include dielectric coatings for insulation of tracking and interconnects, and die adhesive for mounting of dies on the required substrate.
  • the reference and/or counter electrodes are deposited on the base substrate, these too may benefit from membrane coating, particularly the reference electrode.
  • the working electrode may also, optionally, be membrane coated.
  • the- electrode surface/solution interface is provided with a measure of control via the permselective membrane which is not available if the reference elecfrode surface is directly exposed to sample.
  • membrane encapsulation of an electrolyte layer adjacent to the reference electrode is possible which may enable further improvement in the control of the reference electrode voltage stability on exposure to samples.
  • Liquid sample may be applied to the sensor by simply immersing the sensor in the solution to be analysed together with any addition reference and/or counter elecfrodes and temperature sensor.
  • it may be appropriate to add the sample to the sensor in a drop form or using lateral flow membrane techniques, wicks or sample absorbent pads.
  • the use of a hydrophilic mesh sample dispersent may be advantageous, alternative sample delivery may be provided using a capillary fill system or derivative of this approach.
  • Sample may be pretreated prior to application to the sensor (cite Bettix patent). This may be necessary for example to enable filtration, degassing or oxygenation. In addition, it may be desirable to perform modification of the sample e.g. by buffering, addition of reagents or indicators, or addition of e.g. enzyme or antibody indicator chemistries.
  • the sensor may be interrogated by any appropriate electrochemical technique. This may include amperometry, voltammetry (including pulse based interrogation techniques), potentiometry or conductimetric techniques. Electrode construct can be varied accordingly e.g. provision of counter elecfrode as well as a reference electrode in combination with the die based working electrode should a three electrode cell be required, alternatively provision of simply a combined counter/reference (pseudo reference) if this simplification is advantageous.
  • Sensors may be used to detect multiple analytes by varying the interrogation technique using the same sensor construct, and selecting the interrogation method required via the identification resistor.
  • multiple die fabricated elecfrode sensors may be incorporated onto a single substrate strip. These may be configured to detect the same analyte or different analytes.
  • Sensors constructed on the above type constructs may require correction of the resultant signals on sensor interrogation to allow for bias in the signals associated with batch to batch variation of sensor output for production sensors. This can be provided for using a sensor bias code to enable correction of the calibration intercept, the calibration slope, and any nonlinearity in the calibration. In addition correction for temperature sensitivity of the sensors can be made.
  • the semi-permeable membrane is preferentially permeable to the analyte, or a relevant analyte indicator, and impermeable or only partially permeable to other contaminants which may be present in the sample to be analysed.
  • a variety of semi-permeable membranes may be used depending upon, inter alia, the nature of the analyte. Therefore, according a yet further feature of the invention we especially provide an alcohol, e.g. ethanol, sensor which includes semi-permeable membrane formed from a material comprising a sulphonated or unsulphonated polyarylsulphone or a sulphonated or unsulphonated polyarylketone as hereinbefore described.
  • Ethanol is elecfrochemically reactive but requires relatively high polarising voltages and as the reaction product (aldehyde) also passivates the electrode, a more sophisticated interrogation than simple amperometry is required to achieve sensitive detection.
  • a suitable typical pulse regime is 0.65V for 0.7s, 1.1N for 0.3s, -0.4N for 0.6s vs a silver/silver chloride reference elecfrode.
  • hydrophilic character of the SPEES/RES membrane facilitates rapid wet- up of the sensor from a dry-state storage condition. Therefore, sensors fabricated using this membrane have a rapid response time with steady state currents achievable within 30s. We have also found that as no enzyme is required with this sensor, it has very good stability characteristics after fabrication. We have found no detectable shift in sensor calibration after more than 2 months storage of these sensors.
  • the inner selective membrane is provided by SPEES/PES which is a highly selective membrane, particularly valuable for screening out interferents in clinical type samples (e.g. blood, serum, plasma).
  • SPEES/PES which is a highly selective membrane, particularly valuable for screening out interferents in clinical type samples (e.g. blood, serum, plasma).
  • the membrane has to be cast and then manipulated in laminate fabrication as a pre-formed membrane, direct coating on the die mounted elecfrode provides a particularly convenient method of membrane fabrication avoiding handling of the delicate membrane post fabrication.
  • Direct coating of the die mounted electrode strip ensures intimate contact of membrane with the electrode surface which superior is to pre-formed laminate type biosensors where contact between the inner membrane and the elecfrode surface is enabled typically by mechanically clamping the laminate in place.
  • Enzyme type biosensors can be developed using a range of potential outer membranes (see earlier list) to provide diffusion limitation of subsfrate, protection from cells, colloids etc, encapsulation of the enzyme layer together with required chemistries/indicator systems.
  • a range of enzymes can be employed which can be oxidases e.g. glucose, pyruvate, lactate, alcohol or dehydrogenases e.g. malate, alcohol, glucose.
  • oxidases e.g. glucose, pyruvate, lactate, alcohol or dehydrogenases e.g. malate, alcohol, glucose.
  • This sensor type can be used to detect immunoassay, for example in the type of format previously described (plasticised PVC patent, or immunoassay patent). It may also be applicable to other ligand binding type detection systems.
  • the die mounted strip sensor may have reference and counter electrodes incorporated on the strip. These may be fabricated on the die itself, using the preferred materials described above, thus the strip provides the addition requirements — trackwork for connecting electrodes, connector pins together with an identification resistor as may required. Alternatively, the die may only provide the working elecfrode or elecfrode array with the counter and reference elecfrodes be provided via fabrication on the strip. Combinations of the above two formats are possible. Alternatively, in a third format, reference and/or counter electrode are provided by additional electrodes which may be presented to the sample in conjunction with the die mounted strip electrode.
  • An especially preferable configuration to maximise analytical accuracy and precision is the use of a die mounted strip electrode to provide a die fabricated working electrode, a subsfrate fabricated counter electrode and a separate reference electrode presented to the sample in conjunction with the die mounted strip electrode.
  • This configuration may provide for the best possible reference elecfrode voltage accuracy and stability by enabling the use of a silver/silver chloride reference elecfrode in the presence of a suitable filling solution (e.g. silver chloride saturated 3M potassium chloride) protected from the sample using a ceramic frit (i.e. a conventional format reference elecfrode with liquid junction and filling solution.
  • a suitable filling solution e.g. silver chloride saturated 3M potassium chloride
  • a ceramic frit i.e. a conventional format reference elecfrode with liquid junction and filling solution.
  • other conventional reference electrode materials can be employed e.g. calomel in combination with other conventional reference elecfrode configurations and structures.
  • thermosensor An additional feature to maximise the precision and accuracy of measurements made with the die mounted strip electrode is the use of a temperature sensor. This has value as electrochemical reactions measured at the die-based working electrode are temperature dependent. Thus precision and accuracy of measurements is improved by compensating the sensor responses for temperature changes. This has particular value for measurement of samples which may be presented at a wide variation of ⁇ temperatures e.g. in the measurement of wine or beer where sample temperature may range between 4°C - 30°C.
  • the temperature sensor may be mounted on the die mounted strip electrode by fabricating on the electrode die itself, alternatively a temperature sensing device may be attached to the strip elecfrode in combination with the elecfrode die.
  • the temperature sensor may alternatively be presented as a device separate from the die mounted strip electrode and presented to the sample in conjunction with the die mounted strip electrode together with any additional counter and/or reference elecfrodes required.
  • a method of determination of an analyte comprises the use of a solid state elecfrochemical sensor in conjunction with a discrete reference elecfrode, said sensor comprising a non-conducting substrate supporting a plurality of tracks, the tracks providing interconnection to an identification resistor, a working elecfrode and a counter electrode.
  • the working electrode being fabricated on a silicone chip.
  • a solid state elecfrochemical sensor comprising a non-conducting substrate supporting a plurality of tracks, the tracks interconnecting an identification elecfrode, a counter electrode and a die fabricated working elecfrode characterised in that it is in intimate contact with a selective membrane.
  • the reference elecfrode may be integral to the solid state elecfrochemical sensor or alternatively it may comprise the use of a separate discrete reference electrode.
  • the method of the invention may be applied to the determination of a variety of analytes, however, specific analytes which may be mentioned are alcohols, such as ethanol and polysaccharides, such as glucose. According to one aspect of the invention we provide a method as hereinbefore described in which the analyte is glucose. According a to a preferred aspect of the invention we provide a method as hereinbefore described in which the analyte is ethanol.
  • any conventionally known reference elecfrode may be used, indeed, this may vary depending, inter alia, upon the nature of the analyte.
  • the external reference electrode may advantageously be a silver/silver chloride electrode immersed in a solution of 3M potassium chloride saturated with silver chloride and separated from the sample by means of a ceramic frit.
  • solid state elecfrochemical sensors conventionally comprise an integral reference electrode
  • the solid state elecfrochemical sensor used in the method of the invention as hereinbefore described is therefore novel er se. According to a further feature of the method of preparing a novel solid state sensor of the invention which comprises;
  • the process of the invention may include dicing and mounting the die onto a surf tape using machines which are conventionally known er se.
  • the bare die may be bonded onto a, e.g. screen printed substrate, using a screen printed adhesive, and an automatic pick and place machine.
  • the elecfrodes deposited on the base subsfrate can be prepared a number of techniques including screen printing of the elecfrode onto the subsfrate, plating electrodes or deposition of electrodes by sputtering of metals from a vapour phase.
  • the preferred technique used herein is screen printing which ability to produce the base substrate reference, counter and/or working elecfrodes with requisite tracking and identification resistor at low cost in high volume.
  • the process of the invention comprises applying the elecfrode to the die by a sputtering technique.
  • platinum sputtering is especially preferred when using photolithographic mask and etch techniques.
  • the method also comprises encapsulating the working elecfrode(s) and subsfrate deposited counter and/or reference electrodes in a selective membrane.
  • the senor as hereinbefore described as an alcohol, e.g. ethanol, sensor we especially provide the use wherein the sensor as hereinbefore described as an alcohol, e.g. ethanol, sensor.
  • the solid state elecfrochemical sensor can be utilised with a variety of analytes. Therefore, it is advantageous that identification means be included so any related software can identify the nature of the analyte.
  • the identification means is preferentially a register, generally referred to as an ID resistor.
  • a kit comprising at least a disposable solid state sensor and optionally a separate reference elecfrode.
  • Figure 1 shows the front, back and top views of the hand held instrument
  • Figure 2 shows a sensor of the invention
  • Figure 2a is a schematic representation of a plan view of the working elecfrode area of the solid state elecfrochemical sensor of Figure 2;
  • Figure 3 illustrates a reference electrode
  • Figure 4 illustrates a sample bottle
  • Figure 5 illustrates inserting a sleeve into the bottle of Figure 4.
  • Figure 6 illustrates inserting the sensor into the sensor contact slot
  • Figure 7 illustrates the probe
  • a sensor (1) comprises an inert subsfrate strip (2) provided with an analyte target area (3), a working elecfrode (4) and counter electrode (5). Further electrodes (6) and (7) are connected to an identification resistor (8).
  • the analyte target area (3) comprises a silicon wafer (9) mounted on the strip and provided with platinum electrodes (10).
  • the target area (3) comprises a silicon chip die (9), upon which is mounted an elecfrode area (110) comprising a plurality of, e.g. platinum elecfrodes (111) attached via a platinum connector (112) to a platinum terminal (113).
  • the terminal (113) is connected via a silver interconnect (114) to the electrode tracks (6 and 7).
  • the silicon chip die (9) is fixed to the surface of the strip (2) by the use of an adhesive layer (not shown).
  • the adhesive layer fixes the surface of the silicon chip die (9) to the strip (2).
  • the substrate (2), the electrode tracks (6 and 7) and the target area (3) are coated with a selective membrane, e.g. a SPEES/PES membrane.
  • a reference electrode (11) comprises a temperature probe (12) and an elecfrode (13) in an elecfrode support (14).
  • the support (14) is provided with an annular O'-ring (15).
  • Figures 4 and 5 illustrate a bottle as described in International Patent Application No. PCT/GB99/01820.
  • a probe (16) is fitted with a reference electrode (13) and a temperature probe (12).
  • the elecfrode support (14) is provided with a sensor contact slot (17) into which is inserted a sensor (1).
  • the sensor system is preferentially stored in the bottle of Figure 4, such that the reference electrode (13) and temperature probe (12) are placed in a storage solution (18).
  • the sensor may, preferentially, be provided with a protective film such as is described in our co-pending UK Patent application No. 011388.1
  • the electrodes of the invention are intended to be used with, for example, the hand held unit that connects to the sensor probe as illustrated by Figure 1.
  • the system can be used to prompt the user to the next action by instructions displayed on and LCD.
  • An external reference can be prepared by gently squeezing the end of the teat and pulling away from the body of the electrode.
  • the teat has a small amount of storage solution in it to keep the tip wet. Insert the reference elecfrode into the circular socket in the probe and blot dry before use.
  • the docking station in the stabilising base is then filled with the reference storage solution to a depth of 10mm.
  • the instrument should be calibrated. There are three levels of calibration available for the system. It is possible to improve the accuracy of the instrument by calibrating to the type of, for example, wine or beer to be analysed. To use the calibration function, samples with a known alcohol content must be available. The calibration levels are:
  • Level 1 is the default calibration supplied by the factory. The instrument has been calibrated using a wide range of different wines and beers and the default method should be adequate for most routine procedures.
  • Level 2 is the two-point calibration, which increases the accuracy of the system and analyses one sample at two different operating temperatures. This calibration will result in the most accurate alcohol measurement around the sample alcohol concentration used for calibration.
  • Level 3 the four-point calibration, analyses two samples with different alcohol content at two temperatures. This calibration will generate the most accurate results across the full alcohol concentration range -
  • Very gaseous samples such as sparkling white wine, may require the process to be repeated more times.
  • the sample should be allowed to settle for 20 seconds. Meanwhile, the probe is placed into the docking station - the probe should be stored in this way when not in use, or in between samples to ensure that the sensor contact slot is protected and remains dry. Refer to section titled Storing the system when not in use.
  • a sensor can be loaded into the contact slot on the probe (taking care not to push too hard).
  • the sensor is inserted with the sensor side facing the reference electrode and temperature probe (see Fig. 6).
  • the storage solution in the docking station should be changed approximately every 100 samples or more frequently if required.

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  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • Pathology (AREA)
  • Medicinal Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Emergency Medicine (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne un capteur électrochimique transistorisé, qui comprend une bande substrat non conductrice munie de plusieurs tracés métalliques reliant des broches d'interconnexion à au moins une électrode de travail caractérisée en ce qu'elle est réalisée sur un dé de silicium. L'invention concerne également un procédé de détermination d'un analyte, qui consiste à utiliser le capteur électrochimique transistorisé de l'invention en association avec une électrode de référence discrète.
PCT/GB2002/004114 2001-09-10 2002-09-10 Electrode WO2003023389A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002331930A AU2002331930A1 (en) 2001-09-10 2002-09-10 Solid electrochemical sensor

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GB0121669.6 2001-09-10
GB0121669A GB0121669D0 (en) 2001-09-10 2001-09-10 Electrode

Publications (3)

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WO2003023389A2 true WO2003023389A2 (fr) 2003-03-20
WO2003023389A3 WO2003023389A3 (fr) 2003-06-26
WO2003023389A9 WO2003023389A9 (fr) 2003-09-18

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US7648468B2 (en) 2002-04-19 2010-01-19 Pelikon Technologies, Inc. Method and apparatus for penetrating tissue
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7708701B2 (en) 2002-04-19 2010-05-04 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device
US7717863B2 (en) 2002-04-19 2010-05-18 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US9034639B2 (en) 2002-12-30 2015-05-19 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
US9072842B2 (en) 2002-04-19 2015-07-07 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9089294B2 (en) 2002-04-19 2015-07-28 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US9261476B2 (en) 2004-05-20 2016-02-16 Sanofi Sa Printable hydrogel for biosensors
WO2016049552A1 (fr) * 2014-09-26 2016-03-31 Abbott Point Of Care Inc. Identification de dispositif de cartouche pour analyses de coagulation dans des échantillons de fluide
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US9561000B2 (en) 2003-12-31 2017-02-07 Sanofi-Aventis Deutschland Gmbh Method and apparatus for improving fluidic flow and sample capture
US9560993B2 (en) 2001-11-21 2017-02-07 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US9694144B2 (en) 2001-06-12 2017-07-04 Sanofi-Aventis Deutschland Gmbh Sampling module device and method
CN106999931A (zh) * 2014-09-26 2017-08-01 雅培医护站股份有限公司 具有用于测定流体样本中的凝结的微环境传感器的微制造设备
US9724021B2 (en) 2002-04-19 2017-08-08 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
CN107078031A (zh) * 2014-07-28 2017-08-18 佳能安内华股份有限公司 成膜方法、真空处理装置、半导体发光元件的制造方法、半导体发光元件、半导体电子元件的制造方法、半导体电子元件、照明装置
US9795747B2 (en) 2010-06-02 2017-10-24 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US9820684B2 (en) 2004-06-03 2017-11-21 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
US9839386B2 (en) 2002-04-19 2017-12-12 Sanofi-Aventis Deustschland Gmbh Body fluid sampling device with capacitive sensor
US9903877B2 (en) 2014-09-26 2018-02-27 Abbott Point Of Care Inc. Sensors for assaying coagulation in fluid samples
US9921232B2 (en) 2014-09-26 2018-03-20 Abbott Point Of Care Inc. Ellagic acid formulations for use in coagulation assays
US10034628B2 (en) 2003-06-11 2018-07-31 Sanofi-Aventis Deutschland Gmbh Low pain penetrating member
US10048282B2 (en) 2014-09-26 2018-08-14 Abbott Point Of Care Inc. Cartridge device with fluidic junctions for coagulation assays in fluid samples
US10048281B2 (en) 2014-09-26 2018-08-14 Abbott Point Of Care Inc. Cartridge device with segmented fluidics for assaying coagulation in fluid samples
US10114031B2 (en) 2014-09-26 2018-10-30 Abbott Point Of Care Inc. Single channel cartridge device for coagulation assays in fluid samples

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EP1671096A4 (fr) 2003-09-29 2009-09-16 Pelikan Technologies Inc Procede et appareil permettant d'obtenir un dispositif de capture d'echantillons ameliore
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US9802007B2 (en) 2001-06-12 2017-10-31 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US9694144B2 (en) 2001-06-12 2017-07-04 Sanofi-Aventis Deutschland Gmbh Sampling module device and method
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US9560993B2 (en) 2001-11-21 2017-02-07 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9795334B2 (en) 2002-04-19 2017-10-24 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9072842B2 (en) 2002-04-19 2015-07-07 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9089294B2 (en) 2002-04-19 2015-07-28 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US9089678B2 (en) 2002-04-19 2015-07-28 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9186468B2 (en) 2002-04-19 2015-11-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US7648468B2 (en) 2002-04-19 2010-01-19 Pelikon Technologies, Inc. Method and apparatus for penetrating tissue
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US7717863B2 (en) 2002-04-19 2010-05-18 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9498160B2 (en) 2002-04-19 2016-11-22 Sanofi-Aventis Deutschland Gmbh Method for penetrating tissue
US9907502B2 (en) 2002-04-19 2018-03-06 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7713214B2 (en) 2002-04-19 2010-05-11 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with optical analyte sensing
US7708701B2 (en) 2002-04-19 2010-05-04 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device
US9839386B2 (en) 2002-04-19 2017-12-12 Sanofi-Aventis Deustschland Gmbh Body fluid sampling device with capacitive sensor
US9724021B2 (en) 2002-04-19 2017-08-08 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9034639B2 (en) 2002-12-30 2015-05-19 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
US10034628B2 (en) 2003-06-11 2018-07-31 Sanofi-Aventis Deutschland Gmbh Low pain penetrating member
US9561000B2 (en) 2003-12-31 2017-02-07 Sanofi-Aventis Deutschland Gmbh Method and apparatus for improving fluidic flow and sample capture
US9261476B2 (en) 2004-05-20 2016-02-16 Sanofi Sa Printable hydrogel for biosensors
US9820684B2 (en) 2004-06-03 2017-11-21 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
US9795747B2 (en) 2010-06-02 2017-10-24 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
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CN107078031A (zh) * 2014-07-28 2017-08-18 佳能安内华股份有限公司 成膜方法、真空处理装置、半导体发光元件的制造方法、半导体发光元件、半导体电子元件的制造方法、半导体电子元件、照明装置
US10048282B2 (en) 2014-09-26 2018-08-14 Abbott Point Of Care Inc. Cartridge device with fluidic junctions for coagulation assays in fluid samples
US10473612B2 (en) 2014-09-26 2019-11-12 Abbott Point Of Care Inc. Cartridge device identification for coagulation assays in fluid samples
WO2016049552A1 (fr) * 2014-09-26 2016-03-31 Abbott Point Of Care Inc. Identification de dispositif de cartouche pour analyses de coagulation dans des échantillons de fluide
US9903877B2 (en) 2014-09-26 2018-02-27 Abbott Point Of Care Inc. Sensors for assaying coagulation in fluid samples
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US10048281B2 (en) 2014-09-26 2018-08-14 Abbott Point Of Care Inc. Cartridge device with segmented fluidics for assaying coagulation in fluid samples
US10114031B2 (en) 2014-09-26 2018-10-30 Abbott Point Of Care Inc. Single channel cartridge device for coagulation assays in fluid samples
US10247741B2 (en) 2014-09-26 2019-04-02 Abbott Point Of Care Inc. Microfabricated device with micro-environment sensors for assaying coagulation in fluid samples
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US10598675B2 (en) 2014-09-26 2020-03-24 Abbott Point Of Care Inc. Single channel cartridge device for coagulation assays in fluid samples
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US11156620B2 (en) 2014-09-26 2021-10-26 Abbott Point Of Care Inc. Microfabricated device with micro-environment sensors for assaying coagulation in fluid samples
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AU2002331930A1 (en) 2003-03-24
WO2003023389A9 (fr) 2003-09-18
WO2003023389A3 (fr) 2003-06-26
GB0121669D0 (en) 2001-10-31

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