Electrolysis: processes – compositions used therein – and methods – Electrolytic analysis or testing – Involving enzyme or micro-organism
Reexamination Certificate
1999-07-19
2001-10-30
Tung, T. (Department: 1743)
Electrolysis: processes, compositions used therein, and methods
Electrolytic analysis or testing
Involving enzyme or micro-organism
C205S794500, C204S403060, C204S294000
Reexamination Certificate
active
06309535
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to electrodes and their use in assays, and in particular to the detection and quantification of analytes that are present only at low levels.
BACKGROUND OF THE INVENTION
Electrodes have been produced by deposition of conductive ink materials onto solid substrates. Such devices may comprise a solid layer of a precious metal, e.g. gold or platinum, on a ceramic substrate. They may be produced by, for example, thick film deposition (TFD) of an ink material loaded with finely-divided particles of the metal; drying the ink layer at extreme temperatures (usually in excess of 500° C.) removes all ink components such as binders and solvents, and fuses together the particles of precious metal, to form a continuous film of metal on the substrate.
The performance of such devices as electrode materials very closely approximates to that of ideal materials, i.e. solid, machined pure metal electrodes of (say) gold and platinum characterised by high conductivity, high sensitivity to the analyte of interest, low noise levels, and a response to the analyte which is relatively independent of temperature. However, such devices are expensive to produce, since the ink materials must have extremely high metal loadings, and require expensive high temperature drying/curing facilities.
Alternative electrode materials have been described, which are fabricated by TFD of an ink material consisting of finely-divided noble metal particles, intimately mixed with or deposited on carbon, a resin binder material and, if required, a solvent. Such devices are considerably less expensive than those described above, since the ink materials contain much lower levels of noble metal and are fabricated by low temperature curing of the ink material; the carbon content of the ink is designed to compensate for the loss in conductivity that results from reduction of the noble metal content.
Such carbon-based devices are described in, for example, GB-A-2191003. They suffer from three major problems. Firstly, the noble metavcarbon mix is highly heterogeneous, so that products suffer from very poor precision due to the non-uniform dispersion of the noble metal in the ink material. Secondly, there are high background currents during analysis (cf noise), resulting from high surface areas of the carbon components; non-faradaic components, i.e. double layer charging currents. are a direct function of the carbon particle surface area. Thirdly, the temperature dependency of the background current increases with increasing temperature; this is usually a function of the flexible nature of the polymer binder, which essentially softens with increasing temperature, thus changing the surface topography of the electrode.
Diabetes is the most common endocrine disease, and has major deleterious health consequences for the sufferers. Disease morbidity may be decreased by a program of blood glucose monitoring in which patients use samples of blood to monitor their blood glucose levels and adjust diets, drugs and insulin therapy according to the level of blood glucose. In extreme cases, such monitoring may be used to avoid hypoglycemic attacks which may cause coma and subsequent death. However, blood for analysis is obtained either by a fingerstick or venous sample, which causes patient pain and discomfort. Sweat-collecting devices are known. These are usually skin patches made of a hydrogel containing permeation enhancers. The collected sweat or exudate is either placed in water to allow the glucose to diffuse out of the hydrogel and then be analysed or the skin patch is allowed to concentrate the sweat in the patch by driving off the collected water and a specific binding partner in the patch is used to present a visual indication of its presence in the patch. These methods are both qualitative. In addition, the patient has to carry out several manipulations which would be particularly difficult if the patient is ill or entering hypoglycemic coma.
GB-A-2191003 (see above) discloses that an enzyme such as glucose oxidase should be adsorbed or immobilised on the resin-bonded carbon or graphite particles of an electrode. For example, enzyme is held within the pores of the oxygen-permeable resin-bonded layer.
WO-A-97028 11 discloses a hydrogel patch containing glucose oxidase. This can be used with a standard electrode, as a glucose sensor.
SUMMARY OF THE INVENTION
According to the present invention, an electrode comprises a conductive layer, positioned by thick film printing, on a non-conducting plastic substrate. The conductive layer comprises graphite particles (size up to 20 &mgr;m; surface area 1-50 m
2
/g) uniformly coated with a noble metal such as platinum, and non-coated andlor platinum-coated carbon particles, held sufficiently close together to facilitate electrical contact between the particles, by a polymer binder.
Electrodes of the invention allow the amperometric detection of electroactive analyte species at low concentrations, with improved signal-to-noise ratios resulting from the use of low surface area graphitic supports. the improved homogeneity of the metal coating on the surface of the graphite particle leads to improved electrode-to-electrode precision, and the cross-linking of the polymer binder reduces the sensitivity of the electrode response to fluctuations in temperature.
DESCRIPTION OF THE INVENTION
In producing products of the invention, the essential components may be deposited as a single electrode, a micro-electrode or as a microelectrode array. The electrode may be used in conjunction with referencelcounter electrodes deposited on the same substrate. For example, an electrode device may be produced by depositing a noble metal-modified graphite, carbon and polymer binder-containing, conducting layer on a non-conducting substrate, and depositing a second conducting layer comprising silver/silver chloride, to function as a reference/counter electrode, adjacent to the first layer.
The non-conducting substrate material may be a polyester sheet material, or made of polycarbonate, polyvinyl chloride, high density polypropylene or low density polypropylene. In a preferred embodiment, a polyester sheet material is heat stabilised prior to application of the conducting layers, to confer dimensional stability.
For the conducting layer, the noble metal is, for example, platinum, rhodium, palladium, iridium, ruthenium or osmium. The graphite component has an average particle size of less than 20 &mgr;m and a typical surface area less than 50 m
2
/g, and is inherently conductive, it may be derived from either natural sources or produced synthetically. The noble metal is deposited uniformly onto the surface of the graphite material, or is uniformly dispersed in colloidal form within the graphite material. Preferably, the amount of the metal is 5-20% w/w with respect to the graphite.
The carbon component has an average particle size less than 1 &mgr;m, e.g. 5-70 nm, and a typical surface area of less than 150, e.g. 1-150, m
2
/g. Like the graphite component, it is also inherently conductive. The polymer binder may be derived from any of the diverse polymer families. It preferably contains chemical fiunctionalities which facilitate covalent cross-linking, such as carboxylate, hydroxyl, amine, thiol, ester, epoxide or amide groups.
The conducting electrode material may be deposited on the non-conducting substrate by a conventional printing process, e.g. thick film printing (also known as screen printing), lithography, letter press printing, vapour deposition, spray coating, ink jet printing, laser jet printing, roller coating or vacuum deposition.
Following deposition of the conductive electrode material, the polymer binder may be stabilised or cured by a number of conventional processes, such as forced air drying, forced air drying at elevated temperatures, infra-red irradiation, ultraviolet irradiation, ion beam irradiation or gamma irradiation. All of these processes result to varying degrees in the cross-linking of individual molecules of the polymer binder. The use of ultraviole
Blair Neil
Williams Stephen Charles
Yon-Hin Bernadette
Cambridge Sensors Limited
Noguerola Alex
Tung T.
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