CA1250019A - Electrode for electrochemical sensors - Google Patents

Abstract

ELECTRODE FOR ELECTROCHEMICAL SENSORS Abstract of the Disclosure A disposable, inexpensive electrode for an electrochemical sensor includes a laminat-ed anode and a laminated cathode. The anode is a film substrate with anodic material such as platinum deposited on the substrate. The cathode is also a film substrate with cathodic material such as silver deposited on the substrate. The anode and cathode can be laminated with an inter-mediate layer of dielectric material. A working surface is provided on the electrode and defined, in part, by the anode and cathode. One pro-cedure for defining the working surface is to fabricate spaced openings in the cathode film and the layer of dielectric material. The openings in the cathode film and dielectrical layer are aligned and the exposed surfaces of the anode and cathode define the working area. An enzyme, such as glucose oxidase, is bonded to the exposed anode and a membrane is applied over the working area and enzyme. The membrane is preferably a silicone water-based elastomer. The laminated anode, cathode and dielectric layer are then severed to form individual electrodes each in-cluding a working area.

Description

ELECTRODE FOR ELECTROCHEMICAL SENSORS
Backqround of t:he Invention A. Field of the Invention The present invention relates to a new 5 and improved electrode for electrochemical sensors and to a new and improved method of fabricating electrodes for electrochemical sensors; and more specifically, to a new and improved disposable, inexpensive electrode for electrochemical sensors 10 and a method of fabricating the electrode.
B. Description of the Prior Art Products that measure fluctuations in a person's blood sugar, or glucose levels have become everyday necessities for many of the 15 nation's seven million diabetics. Because this disorder can cause dangerous anomalies in blood chemistry and is believed to be a contributor to vision loss and kidney failure, most diabetics need to test themselves periodically and adjust 20 their glucose count accordingly, usually with insulin injections. Patients who are insulin dependent - about 10% to 15% of diabetics - are instructed by doctors to check their blood-sugar levels as often as four times daily.
For years the solution for diabetics was one of several urinanaLysis kits that, despite repeated improvements, provided imprecise measure-ments of glucose in the blood. The first such kits used tablets. This early testing procedure 30 is described in United States Patent ,, .
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Nos. 2,387,244 and 3,164,534. Later, reagent strips for urine testing were developed. Testing using urine, however, is limited in accuracy.
The renal threshhold for glucose spillage is different Eor each individual. Moreover, sugar in urine is a sign that the sugar level i5 too high and has been too high for several hours.
This is due to the delay in sugar reaching the urine.
More accurate readings are possible by taking readings from bloocl. The advent of home blood tests is considered by some to be the most significant advance in the care of diabetics since the discovery of insulin in 1921. Home blood glucose testing was made available with the development of reagent strips for whole blood testing. Reagent strips of this type are describ-ed in United States Patent Nos. 3,164, 534 and 3,092,465. A breakthrough in self-care came in 1979, when the Ames division of Miles Laboratories brought out its Visidex home blood test. Visidex consists of chemically coated plastic strips. When blood drawn by pricking a finger is placed on one of these disposable strips, the resulting color change can be compared with a color-coded glucose scale included in the kits or a reflectometer can be used.
The advantage of the current technology available for home use, the reagent strip, is low cost (roughly fifty cents per use) and a one minute response time. There are significant problems with reagent strips, however. Test timing using reagent strips is very critical.
Exactly sixty seconds must elapse from the time a blood sample is placed on a strip to when it is removed by rinsing. The color on the strip must then be compared with a chart. This time constraint and the necessity to ascertain dif-ferences in shades of colors results in the tech-nique being very user sensitive.
; An alternative to reagent strips is a glucose sensor using an electrode. Electrodes are more costly and the technology is more com-plicated but the life of an electrode is weeks or months as compared to the single use of a reagent strip. The response time of electrodes is quick and electrodes are not user sensitive resulting in increased accuracy over reagent strips.
Electrodes in electrochemical glucose sensors utilize an enzyme to convert glucose to an electroactive product which is then analyzed electrochemically. The reactions for this elec-trode are given in the following equations.
C6H12O~ ~ 2 + H2O = C6H127 + ~22 H22 = 2 + 2H+ + 2e~

2 ~ 4H+ = 2H20 In the first equation glucose is oxidized by oxygen to form gluconolactone and hydrogen peroxide. This reaction is catalyzed by the enzyme glucose oxidase. The hydrogen peroxide may be detected either by oxidation as shown in the second equation or by measuring the decrease in oxygen partial pressure by the reaction shown in the third equation. In either case a current is obtained which is related to the glucose con-centration. The oxidation of the hydrogen per-oxide is done at a platinum electrode and the reduction may be done at either a platinum or a silver electrode.
In these electrodes~ diffusion of glu-cose through membranes and reactions of glucose ~S-1408 .

in memhranes is of concern. In known electrodes, glucose and oxygen from diluted blood as well as many interferents diffuse through a primary mem-brane. As glucose diffusing through this membrane reaches a second membrane, glucose oxidase catalyzes the conversion of the glucose to hydrogen peroxide and gluconolactone. The hydrogen peroxide may diffuse back through the primary membrane or it may further diffuse through the second membrane to the electrode where it can be oxidi2ed back to oxygen and produce a current used for analysis.
The secondary membrane prevents passage to the electrode of substantially everything except the hydrogen peroxide.
Glucose electrochemical sensors are essentially made up of two major components; a permanent or factory replaceable electrode and a user replaceable, disposable membrane assembly including a primary membrane and a secondary membrane. The electrode is based on a Clark electrode operating in the hydrogen peroxide mode. An electrode of this type is described in United States Patent No. 2,913,386. The Clark electrode includes a platinum anode and a silver cathode. A voltage of .7 volts is applied to the electrod~ and current between the cathode and anode is measured.
The primary membrane is used to separate high molecular and cellular components of the blood from the glucose. This membrane must be permeable to glucose but relatively impermeable to the larger molecular and cellular components of blood. The typical primary membrane is not whole blood compatible, since to do so requires a surface treatment. Due its this incompatibility, the primary membrane is quickly fouled by protein , ~.t '~ .

~9 deposits or blood clots requiring the membrane assembly to be replaced by the user.
Before electrochemical sensors can be made for use in the home, technology must be advanced to allow measurements using whole blood.
This has not been achievable in electrochemical sensors to date because primary membranes present-ly used are not whole blood compatible and are quickly fouled by contaminants in whole blood.
Many of the disadvantages of prior sensors could be eliminated if a longer lasting membrane could be provided. A membrane of this type is disclosed in copending Canadian Patent Application No.
507,190 filed April 21! 1986 and assigned to the assignee of the present in-vention. A membrane of this type, however, is bonded to the electrode. When the membrane fails, the membrane and electrode must be replaced rather than only the membrane, and it is desirable to provide an inexpensive electrode that can be disposed of after several uses.
Summary of the Invention An object of the present invention is to provide a new and improved electrode for an electrochemical sensor.
Another object o the present invention is to provide a disposable electrode for a glucose sensor.
A furth2r object of the present inven-tion is to provide a new and improved electrodefor a glucose sensor that has a life of several weeks and is cost competitive with present glucose testing devices.
A still further object of the present invention is to provide a new and improved ~ethod _ --6 of fabricating a disposable electrode for glucose sensors.
Another object of the present invention is to provide a new and improved laminated elec-trode for a glucose sensor.
Briefly~ tne present invention is direct~
ed to a new and improved electrode for an electro-chemical sensor and to a new and improved method for fabricating the electrode~ The electrode is inexpensive and easily replaced by a user of the sensor. The electrode is the result of the dis-covery that only a few molecular layers of the anode and cathode material of an electrode are actually required for the electrode to functionO
With this discovery it was determined lamination technology could be utilized. Using lamination technology, platinum or other anodic material is vapor deposited or sputtered onto a thin film to define the anode of the electrode. Similarly, the cathode is defined by depositing silver or similar cathodic material onto a film.
One electrode fabrication procedure involves laminating the cathode film onto the anode film with a layer of dielectric material between the two films. An opening is fabricated in the cathode and the dielectric layer, thus defining an anode working area~ Apertures or similar access structure are then fabricated in the electrode to allow connection to electrical contacts.
The electrode of the present invention is inexpensive allowing it to be disposable. By being disposable, the sensor described in copend-ing application Serial No. 507,190 filed April 21, 1986 which may use the electrode of the present is feasible for home use since the ~S-1408 , , ~ - ~.

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cost per use is competitive with reagent strips.
The electrode is also easily replaceable by a user of the sensor. This allows a home user to conduct as many tests as needed and easily replace the electrode when it no longer functions.
The electrod is constructed so that the home user need not recalibrate the sensor or use a technician to replace the electrode.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and other objects and advan-tages and novel ~eatures of the present invention will become apparent from the following detailed description of the preferred embodiment of the invention illustrated in the accompanying drawings wherein:
FIG. 1 is a top plan view of a dielec-tric top sheet prior to being laminated to form the electrode of the present invention;
FIG. 2 is a top plan view of a silver foil or film prior to being laminated to form the electrode of the present invention;
FIG. 3 is a top plan view of a dielec-tric middle sheet prior to being laminated to form the electrode of the present invention;
FIG. 4 is a schematic illustration of the step of laminating the top dielectric sheet, the silv~r foil or film and the middle dielectric sheet to platinum foil or film;
FIG. 5 is an enlarged, vertical cross sectional view of a laminated electrode construct-ed in accordance with the principles of the pre-sent invention;
FIG. 6 is a top, plan view of an alter-native embodiment of an electrode constructed in accordance with the principles of the present inventiorl;
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; , FIG. 7 is a top, plan view of a second alternative embodiment of an electrode constructed in accordance with the principles of the present invention;
FIG. 8 is a view taken generally along line 8-8 in FIG. 7; and FIG. 9 is a view taken generally along line 9-9 in FIG. 7.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Prior art electrochemical sensors used for measuring glucose in whole blood include a disposable membrane assemb:Ly and a semipermanent electrode. Typicaily, the electrode is replace-able by a skilled service person. A new electro-chemical sensor for home use is disclosed in afoFesaid ,~pplication. Serial No.. 507,190.
The new sensor uses a whole blood compatible membrane integral}y bonded to the electrode. In the new sensor, the electrode, enzyme layer and membrane are an in-tegral unit increasing the efficiency and response time of the electrode; however, due to the limited life of the membrane, a disposable interface between ~he instrumental system of the sensor and the membrane is necessary. The disposable portion must be inexpensive in order to maintain the cost per use of the sensor competitive with current home testing devices, such as reagent strips. The disposable portion should also be easily replaceable allowing replacement by a home user.
In prior art sensors, the disposable portion is the membrane assembly. However, because the present electrode utilizes only a few molecular layers of the anode and cathode materials, a ~S-1408 .
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relatively inexpensive disposable electrode can be produced using vapor deposition and lamination technologies to provide a laminated electrode that requires little precious material. Such a disposable electrode was made possible by t~e discovery that only the top few molecular layers of the anode and cathode Gf an electrode are active.
Referring now to the drawings and par-ticularly to FIGS. 1-5, there is illustrated a laminated electrode 10 constructed in accordance with the principles and method o~ the present invention. Electrode 10, in one embodiment, includes an anode 12 which can be platinum foil or a film with a layer of platinum vapor deposited or otherwise deposited onto the ~ilm. The cathode 14 of electrode 10 is similarly fabricated from silver foil or silver vapor deposited onto a film. In accordance with the discovery of the surface phenomenum that only a few molecular layers of the anode and cathode are used, or are active, the thicknesses of the foils or the deposited metals utilized on the anode and cathode 12 and 14 are only a few molecular layers. It is to be understood that platinum and silver are described as the preferred metals for the anode 12 and cathode 14 r respectively, but other materials, well known in the art, can be used.
The anode 12 and cathode 14 of electrode 10 are electrically isolated by a layer of dielectric material 16 and the upper surface of cathode 14 can be protected by a top sheet of dielectric material 18.
To allow electrode 10 to function as an enzyme electrode in an electrochemical sensor, a working area 20 for the measurement of glucose ' , .

is defined. Working area 20 consists of aligned apertures 22, 24 and 26 in the dielectric layer 16, the cathode film 14 and the dielectric sheet 18, respectively, and the exposed anode 12 and cathode 14. Working area 20 allows the detection of hydrogen peroxide through a current related to glucose concentration. In the reaction to be measured, oxidation of hydrogen peroxide is done at the platinum anode 12. Hydrogen peroxide is produced through catalytic: reaction of glucose and oxygen with an enzyme such as glucose oxidase~
In the preferred electrode 10, a layer of enzyme ?8 (FIG. 5),such as glucose o~idase, is bonded or immobili2ed on anode 12 at the wor~ing area 20. To allow passage of glucose and oxygen to the enzyme 28 and to block passage of other contaminants, a glucose permeable membrane 30 is bonded over the enzyme layer 28 and to the work-ing area 20. Preferably, membrane 30 is a sili-cone water-based elastomer of the type described in the afoxesaid cop~din~ applicati~n Sexi~l No. 507,190.
In accordance with an important feature cf the present invention it has been found that a dispersion of a polymerizable silicon-contain-ing compound applied in an incompletely cured form as a silicon compound dispersed phase in a liquid carrier, the carrier being essentially insoluble in the dispersed phase and removable from the dispersion during curing, will dry and cure as a continuous layer, film or membrane having unexpectedly high glucose-permeability to function as a single membrane 30. The silicon-containing compound can be dispersed in the con-tinuous pbase as a monomer, oligomer, prepolymer,or incompletely cured polymer. The silicon com-pound is cured in place as a continuous polymeric coating or layer. The removable carrier removed during curing, such as by volatilization, should be included in an amount of at least 5% by weight of the dispersion, and preferably 10-90% by weight.
It has been found that the polymerizable silicon-containing compounds including monomers, oligomers, prepolymers, and incompletely cured polymers or mixtures thereof capable of polymeri-zation or further polymerization in dispersed form will form cured layers or membranes when cured or polymerized in a dispersed layer upon removal of the continuous phase during curing to provide a layer or membrane having unexpectedly good oxygen and glucose-permeability without allowing the passage of electrode-sensitive inter-ferents therethrough. The polymerizable silicon-. containing compounds, after dispersion in a con-tinuous phase, such as by including an emulsifier, can be cured in any known manner during removal of the continuous phase, such as by evaporation o water from a water-continuous phase silicon emulsion or dispersion, as disclosed in the Johnson et al Patent No. 4,221,688 or as disclosed in Elias Patent No. 4, 427, 811.
Further, the dispersion of the silicon-containing compound can include a suitable curing catalyst or can be heat cured so long as the dispersion of the polymerizable silicon-contain-ing compound is applied as a layer in the fcrm of an incompletely cured dispersion and at least a portion of the carrier or continuous phase is removed from the dispersion during final curing.
Without being limited to any oarticular mechanism, it is theorized that some alignment of the aggre-s~
-~.2-gating or polymerizing silicon-containing polymer molecules, during polymerization, occurs during final removal of the carrier to form micells such that the aggregating silicon-containing polymer molecules are bound upon curing in a manner capable of permitting the permeation of glucose and oxygen between molecules while exclud-ing electrode-sensitive interferants.
The silicon-containing compounds, useful in accordance with the invention are those which can be dispersed in an essentially insoluble liquid carrier, such as water, are polymerizable in the dispersed form, and result in a continuous film or layer upon curing In accordance with one embodiment of the present invention, the polymerizable silicon-containing compound is an organosiloxane, and particularly a diorganosiloxane comprising essen-tially a linear species of repeating diorgano-siloxane units which may include small numbers of monoorganosiloxane units up to a maximum of about one monoorganosiloxane unit for each 100 diorganosiloxane units wherein the polymer chain is terminated at each end with silicone-bonded hydroxyls, as disclosed in Johnson et al. U.S.
Patent No. 4,221,688.

In accordance with another important embodiment of the present invention, the polymeriz-able silicon-containing compound forming a glucose-permeable membrane is applied onto an electrode as an aqueous silicone emulsion comprising a continuous water phase and an anionically stabiliz-ed dispersed silicone phase wherein the silicone phase is a graft copolymer of a water soluble silicate and a hydroxyl endblocked polydiorgano-., ' , .. ..
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siloxane. As disclosed in the Saam Patent No.
4,244,849, such silicone emulsions having a pH
within the range of from 8.5 to 12, are stable upon extended storage and result in a cured elas-tomeric continuous layer upon removal o~ waterunder ambient conditions~ These silicone compounds are obtained from the interaction of hydroxyl end-blocked polydiorganosiloxanes and alkali metal silicates to ~orm graft copolymers anionically stablized in aqueous emulsions at a pH of, for example, 8.5 to 12. If stability is not important, however, the pH is not critical.
For example, the emulsion can be applied in layer form to manufacture the membrane as soon as the components are homogeneously dispersed.
~ he expression "hydroxyl endblocked polydi-organosiloxane" is understood to describe an essentially linear polymer of repeating diorgano-siloxane units containing no more than small impurities of monoorganosiloxane units. The hydroxyl endblocked diorganosiloxane will there-fore have essentially two silicon-bonded hydroxyl radicals per molecule. To impart elastomeric properties to the product obtained after removal of the water from the emulsio~, the polysiloxane should have a weight average molecular weight (Mw~ of at least 5,000. Polysiloxanes with weight average molecular weights below 5000, Eor example down to about 90, also are use~ul so long as the polymers form a continuous ~ilm or layer upon curing. Tensile strengths and elongations at break improve with increasing molecular weight with relatively high tensile strengths and elongations obtained above 50,000 Mw. However, since in a preferred embodiment of the invention, the cured polymers are bonded directly to an MS-1~08 ~s~

electrode and do not undergo any severe mechanical stress during use, high strength is not necessary for the polymer to be useful in the invention described herein. The maximum Mw is one which can be emulsified or otherwise dispersed in a li~uid carrier or continuous phase, such as water.
Weight average molecular weights up to about 1,000,000 for the incompletely cured dispersed polysiloxane are expected to be practial for this invention. Upon curing, there is no upper limit to the molecular weight of the membrane.
The preferred Mw for the polymerizable dispersed siloxane is in the range of 1,000 to 700,000.
Organic radicals on useful hydroxyl endblocked polydiorganosiloxanes can be, for example, monovalent hydrocarbon radicals containing less than seven carbon atoms per radical and 2-(perfluoroalkyl)ethyl radicals containing less than seven carbon atoms per radical. Examples of monovalent hydrocarbon radicals include methyl, ethyl, propyl, butyl, isopropyl, pentyl, hexyl, vinyl, cyclohexyl and phenyl and examples of 2-(perfluoroalkyl)ethyl radicals include 3,3,3-trifluoropropyl and 2-(perfluorobutylmethyl).
The hydroxyl endblocked polydiorganosiloxanes preferably contain organic radicals in which at least 50 percent are methyl. The preferred poly-diorganosiloxanes are the hydroxyl endblocked polydimethylsiloxanes.
In accordance with one important embodi-ment of the present invention, the hydroxyl end-blocked polydiorganosiloxane is employed as an anionically stabilized aqueous emulsion. For the purposes of this embodiment "anionically stabilized" means the polydiorganosiloxane is stabilized in emulsion with an anionic surfactant.

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The most preferred anionically stabilized aqueous emulsion of hydroxyl endblocked polydiorganosiloxane are those prepared by the method of anionic emul-sion polymerization described by Findlay et al.
in U.S. Patent No. 3,294,725 to showing the methods of polymerization and showing anionically stabilized emulsions of hydroxyl endblocked polydiorganosiloxanes. Another method of preparing hydroxyl endblocked polydi-organosiloxanes is described by Hyde et al inU.S. Patent No~ 2,891,920, to showing the hydroxyl endblocked polydiorganosilo~anes and their method of prepara-tion. These methods a~d others are known in the art.
An alkali metal silicate or colloidal silica can be included in the emulsified silicone composition for the preparation of extended storage stable emulsions used in the invention. The ?O alkali metal silicates preferred for use in the emulsions forming the glucose-permeable membranes of the present invention are water soluble sili-cates. The alkali metal silicate is preferably employed as an aqueous solution. Aqueous silicate solutions of any of the alkali metals can be employed such as lithium silicate, sodium silicate, potassium silicate, rubidium silicate and cesium sllicate.
The colloidal silicas are well known in the art and many are commercially available and can be included in the dispersion for increas-ed strength and storage stability. Although any of the colloidal silicas can be used including fumed colloidal silicas and precipitated colloidal silicas, the preferred colloidal silicas are those which are available in an aqueous medium.
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Colloidal silicas in an aqueous medium are usually available in a stabilized form, such as those stabilized with sodium ion, ammonia or an aluminum ion. Aqueous colloidal silicas which have been stabilized with sodium ion are particularly useful for forming an emulsion because the pH requirement can be met by using such a sodium ion stabilized colloidal silica without having to add additional ingredients to bring the pX within the range of, for example, 8.5 to 12. The term "colloidal silica" as used herein are those silicas which have particle diameters of from 0.00~1 to 0.1 micrometers. Preferably, the particle diameters of the colloidal silicas are from 0.001 to 0.05 micrometers.
The colloidal silica can be added to the anionically stabilized hydroxylated polydi-organosiloxane in the form of a dry powder or as an aqueous dispersionO The best method is to add the colloidal silica in the form of a sodium ion stabilized aqueous dispersion of colloidal silica. There are many such sodium ion stabilized aqueous dispersions of colloidal silica which are commercially available. These commercial colloidal silicas are usually available in aqueous dispersions having from 15 to 3~ weight percent colloidal silica and having a pH in the range of .5 to 10.5.
Aqueous solutions of sodium or potassium silicate are well known and are commercially available. The solutions generally do not contain any significant amount of discrete particles of amorphous silica and are commonly referred to as water glass. The ratio by weight of SiO~ t~
alkali metal oxide in the aqueous solutions of alkali metal silicates is not critical and can . ..

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be varied within the usual range of about 1~5 to

3.5 for the sodium silicates and 2.1 to 2.5 for the potassium silicates. The aqueous alkali metal silicate solutions are particularly useful in preparing the emulsions of the present inven-tion because the addition of the silicate solu-tion often brings the pH oi- the emulsion within the range of about 8.5 to about 12 so that addi-tional ingredients are not necessary to adjust the pH of the emulsion. O~ course, oth~r aqueous alkali metal silicate solutions such as those prepared by hydrolyzing si:Licon esters in aqueous alkali metal hydroxide solutions can also be employed in the present invention.
In accordance with one embodiment of the present invention, the polymerizable silicon-containing compound is dispersed by combining an aqueous solution of an alkali metal silicate and the polymerizable silicon-containing compound in an emulsion so that a graft copolymer is formed as dispersed particles. The preferred procedure for preparing silicone emulsions is to add the alkali metal silicate to an anionically stabilized aqueous emulsion of one or more hydroxyl endblocked polydiorganosiloxanes, adjust the pH o~ the emul-sion within the range of about 8.5 to 12 and then age the emulsion for a time period such that an elastomeric product is formed upon removal of the water under ambient conditions. In this embodiment, the pH of the emulsion containing dissolved silicate and dispersed hydroxyl end-blocked polydiorganosiloxane is important to the formation of the emulsion. A pH of 8.5 to 1~
maintains the alkali metal silicate dissolved so that sufficient graft copolymerization between the dissolved silicate and dispersed siloxane , -5~

occurs during removal of the carrier (e.g. ~ater) to produce an emulsion capable of providing poly-merization or further polymerization of the sili-con-containing compound when deposited as a layer to form a membrane~ If the pH is lower than the stated range, silicic acid is formed from the alkali metal silicate. Silicic acid is unstable and rapidly polymerizes by condensation which can gel the emulsion. Sinc:e silicic acid formation is almost completely suppressed at a pH of 10 to 12 and the reaction between dissolved alkali metal silicate and dispersed siloxanes occurs more rapidly within the pH range of 10-12, this pH range is preferred for emulsions containing an alkali metal silicate.
Silicone emulsions prepared by this silicate copolymerization embodiment are aged at a pH range of 8.5 to 12 ~or a time period suffi-cient to allow interaction between the dissolved silicate and the dispersed siloxane so that an elastomeric product is formed upon removal of the water under ambient conditions, as disclosed in Saam U.S. Pat. No. 4,244,849.
The aging period is effec-tively reduced when an organic tin salt is em-ployed in an amount of about 0.1 to 2 parts by weight for each 100 parts by weight of polydi-organosiloxane. The organic tin salts expected to be useful in the emulsions include mono-, di-and triorganotin salts. The anion of the tinsalt employed is not critical and can be either organic or inorganic although organic anions such as carboxylates are generally preferred.
Organic tin salts that can be employed include octyltin triacetate, dioctyltin dioctoate, di-decyltin diacetate, dibutyltin diacetate, di-butyltin dibromide, dioctyltin dilaurate and trioctyltin acetate. The preferred diorganotin dlcarboxylate is dioctyltin dilaurate.
The concentration of the polymerizable si]icon-containing compound, e.g. the hydroxyl endblocked polydiorganosiloxane in the stabilized emulsion is not critical particularly since the water or other continuous phase carrier is removed during curing of the Si phase during film, layer 10 or membrane formation.
The relative amounts of alkali metal silicates and hydroxyl endblocked polydiorgano-siloxane employed can vary over a considerable range. Preferred elastomer properties are obtain-15 ed when 0.3 to 30 parts by weight silicate is employed for each 100 parts by weight siloxane.
Other useful polymerizable silicon-containing compounds for forming the dispersions useful in forming a continuous silicon containing 20 polymer membrane having glucose-permeability in accordance with the present invention include the vinyl endblocked polydiorganosiloxanes dis-persed together with an organosilicone compound having silicone-bonded hydrogen atoms, as disclos-25 ed in the Willing Patent No. 4,248,751.
As disclosed in the Willing patent, these silicone compounds are generally dispersed by emulsifying the vinyl endblocked polydiorganosiloxane together with an 30 organosilicone compound having silicon-bonded hydrogen atoms using water and a surfactant to form an emulsion and thereafter adding a platinum catalyst and heating the emulsion to form a cross-linked silicone.
The vinyl endblocked polydiorganosiloxane can be any of the polydiorganosiloxanes endblocked ~2~

with diorganovinylsiloxy units and can be repre-sented by the formula (CH2=CH) R2SiO (R2Sio) XSiR2 (CH=CH2) where each R is a monovalent hydrocarbon radical or a monovalent halogenated hydrocarbon radical and x is a representation of the number of repeating diorganosiloxane units in the polymer. The mono-valent radicals can be any of those known in the art, but are preferably th~se with six carbon atoms or less. The preferred polydiorganosiloxanes are those wherein the monovalent organic radicals are methyl, ethyl, phenyl, 3,3,3,-trifluoropropyl and mixtures thereof wherein at least 50 percent of the radicals are methyl radicals. The poly-diorganosiloxane can be a single type polymer with the same kind of repeating diorganosiloxane units or with a combination of two or more kinds of repeating diorganosiloxane units, such as a combination of dimethylsiloxane units and methyl-phenylsiloxane units. A mixture of two or more polydiorganosiloxanes also is useful. The value of x is not critical since upon final curing in the dispersèd layer, the value of x increases rapidly. The upper limit of polydiorganosiloxane which is suitable for this invention is limited only to the extent that it cannot be dispersed to form a homogenous dispersion to achieve a homogenous layer capable of forming a continuous membrane upon complete curing.
In accordance with this vinyl-endblocked embodiment, the organosilicone compound or mixture of compounds dispersed with the polydiorgano-silvxane is one which contains silicon-bonded hydrogen atoms. The organosilicon compound can be any compound or combination of compounds con-taining silicon-bonded hydrogen atoms useful as ~:r ' ~

crosslinkers and providing an average of silicon-bonded hydrogen atoms per molecule of organo-siloxane compound of at least 2.1. Such organo-silicon compounds are known in the art as illus-trated in U.S. Pat. No. 3,697,473.
The preferred organo-silicon compounds are those which are siloxanes made up of units selected from XSiOl.s, R'HSiO, R'2HSiOo~s, R~Siol~s~ R'2SiO, R'3SiOo 5 and SiO2 such that there is at least: 2.1 silicon-bonded hydrogen atoms per molecule. Each R' is prefer-ably selected from an alkyl radical of 1 to 12 carbon atoms inclusive, phenyl and 3,3,3-trifluoro-propyl.
The amount of vinyl endblocked diorgano-siloxane and organosilicon compound can vary broadly in weight amounts because the unit of weight for each vinyl radical or silicon-bonded hydrogen atom will vary considerably. Such "units of weight" are determined by dividing the mole-cular weight by the number of vinyl radicals pes molecule or number of SiH per molecule. Because the cross-linked molecules in the membrane are formed by the reaction between the vinyl radical of the polydiorganosiloxane and the silicon-bonded hydrogen atom (SiH) of the organosilicon compound, the amounts of each will depend upon the ratio of Si~ to vinyl. The stoichiometry would suggest that about one SiH per vinyl is all that is neededr however, the reactivity of the SiH can vary significantly, as well as its availability for reaction. ~or this reason, the ratio of SiH to vinyl can vary beyond the stoichio-metric amounts and still provide products capahle of polymerizing in layer form to provide continu-ous glucose-permeable membranes. The vinyl end-blocked polydiorganosiloxane and organosilicon compound preferably are combined such that the ratio of SiH to vinyl can vary from 0.75/1 to

4/1, with the most preferred range of 0.75/1 to 1.5/1.
The platinum catalyst can be any of the platinum catalysts known to catalyze the addition of silicon-bonded hydrogen atoms to silicon-bonded vinyl radicals. Platinum catalysts can be any of the known forms, ranging from plati-num as such or as deposited on carriers such as silica gel or powdered charcoal, to platinic chlorides, salts of platinum and chloroplatinic acid. The dispersibilty of the platinum catalysts in the siloxane can be increased by complexing it with vinyl-containing siloxanes such as describ-ed in U.S. Pat. No. 3,419,593.
The amount of platinum catalyst used should be such that there is at least 0.1 part by weight platinum per one million parts by weight of the combined weight of polydiorganosiloxane and organosilicon compound. Preferably, the amount of catalyst used is from 1 to 20 parts by weight platinum per million parts by weight of polydiorganosiloxane and organosilicon compound~
Larger amounts of platinum can be used if economic considerations are not important.
For those cases where a platinum catalyst is included in the dispersion and a platinum catalyst inhibitor is desired to prevent complete curing prior to layering the dispersion for forma-tion of the membranel there are many types of known inhibitors. These inhibitors retard or inhibit the activity of the platinum catalyst, but allow the platinum catalyst to become active at elevated temperatures, sucn as above 70 C.

~ ~5~1~i9 If the carrier in the dispersion is water, the selection of an inhibitor should be one which does not have its effectiveness destroyed by water or surfactants or it does not destroy the emulsion. Effective inhibitors include the acetylenic alcohols and other acetylenic compounds described in U.S. Pat. No. 3,445,420. Other platinum catalyst inhibitors are known as defin,ed in U.S. Pat. No.3,188,299, U.S. Pat. No.
3,188,300, U.S. Pat. No. 3,192,181, U.S. Pat.
No. 3,344,111, U.S. Pat. No. 3,383,356, U.S.
Pat. No. 3,453,233, U.S. Pat. No. 3,453,234 and U.S. Pat. No. 3,532,649. The dispersed compo-sition can be heated for a period of time to partially cross-link the Si-containing compounds to foxm a stable emulsion of cross-linked particles - dispersed in a carrier. After application in layer form on an electrode, the layer further cures to form a continuous, glucose permeable membrane.
Evaporation of the carrier may be assisted by a flow of dry air or other gas, either at ambient temperature or at an elevated tempera-ture, by infrared heating or a combination of the various means. Care should be taken when accelerated means are used to evaporate the car-rier, e.g. water, that the rapidly leaving water vapor does not produce undesirable discontinuities in the film.
Other reinforcing materials useful for increasing the structural integrity of the cured glucose-permeable membranes of the pr~sent inven-tion include the copolymers disclosed in the Huebner et al Patent No. 4,288,356. The copolymexs axe em,ulsion polymerized a~d comprise free radical pol~merized monomers selected from at least one unsaturated organic monomer and at least one unsaturated organosilicone monomer. The copolymers are made from 1 to 7 weight percent unsaturated organo-silicon monomer and from 93 to 99 weight percentorganic monomer. It is believed that any of the unsaturated organic monomers commonly used to form polymers through free radical polymerization can be used either by themselves or in combination;
for example, styrene, methylmethacrylate, and vinyl chloride. The unsaturated organosilicon monomer can be an unsaturated silane, siloxane !
or sila~ane that will copolymerize with the un-saturated organic monomer or mixture of unsaturat-ed organic monomers used and will form = SiOHunder the conditions of an emulsion polymerization method used to produce the copolymer.
The unsaturated organosilicon monomer can be a silane of the formula R'R''XSi(R''')3-x where R' is an olefinic unsaturated radical such as vinyl, allyl, acryloxypropyl, or methacryloxy-propyl, R" is an alkyl radical containing l to inclusive carbon atoms or a phenyl radical, and R' " is a hydrolyzable group such as -OR", -OCOR", or halogen, and x is 0, l or 2. The un-saturated organosilicon monomer can be a cyclic siloxane of the formula (R'R"SiO)a where R' and R" are as defined and a is from 3 to 6 inclusive.
The unsaturated organosilicon monomer can be a disilazane of the formula R'R"2Si-NH-SiR"2R' where R' and R" are as defined. The unsaturated organosilicon monomer can be a cyclic silazane of the formula (R'R"SiNH)3 where R' and R" are as defined. A preferred unsaturated organosilicon monomer is vinyltriethoxysilane ~S-1408 , :

- '`

Examples of unsaturated organosilicon monomers include silanes such as ViMeSiCl2, ViMe2SiOMe, ViMeSi(OEt)2, and ViSi(OEt)3, siloxanes such as (ViMe2Si)2)0, (ViMeSiO)3, and (ViMeSiO)a where a is 3 to 6 inclusive, and silazanes such as (ViMe2Si)2NH and (ViMeSiNH)3 where Me is methyl radical, E is an ethyl radical and Vi is vinyl radical.
The unsaturated organic monomer and the unsaturated organosilic:on monomer can be emulsion polymerized by the common methods of performing such copolymerizations. One such process is described by Blackderf in U.S. Pat. No.
3,706,697, showing a process ~or copolymeri~ing and acrylic ester and an acrylozyalkylalkox~silane by emulsion polymerization of the organic monomer through - a free radical generator.
For example, a mixture is prepared of 2G water and an anionic surfactant, and then a mixture of styrene and vinyltriethoxysilane is slowly added under a nitrogen blanket. A~monium persul-fate then is added as the polymerization catalyst.
Heating the mixture initiates the polymerization, but it is also necessary to control the reaction temperature so that the emulsion does not overheat due to the exothermic reaction. After polymeriza-tion, the emulsion is adjusted to a pH of greater than 7.
The copolymer is added in an amount of

5 to 100 parts by weight of the emulsion polymerized copolymer for each 100 parts by weight of poly-merizable Si-containing compound, e.g. polydi-organosiloxane2 The addition of tne copolymer serves ~o act as a reinforcement or filler for the polycliorganosiloxane. Amounts of from 5 to 25 parts of copolymer added per 100 parts of - ,............................... .

.

~2~

polymeriæable Si-containing compound yield a reinforced membrane having the desired glucose-permeability and strength without the addition of other fillers such as SiO2. When the amount of copolymer added is from 25 to 60 parts by weight, the final product obtained by drying the emulsion is a higher strength membrane. The more copolymer added, the harder and less elastic the final membrane becomes.
In accordance with one embodiment of - the invention, an alkyl tin salt is added to the dispersion to catalyze the curing of the final emulsion during the devolatilization or other removal of the carrier to yield the cured membrane.
Preferred salts are dialkyltin dicarboxylates such as dibutyltindiacetate, dibutyltindilaurate, and dioctyltindilaurate. Most preferred is dibutyl-tindilaurate. The emulsion of catalyst is used in an amount sufficient to yield from 0.1 to 2 parts by weight of the alkyl tin salt for each 100 parts by weight of the polymerizable Si-containing compound, e.g. polydiorganosiloxane~
Larger amounts could be used, but the larger amount would serve no useful purpose.
A silane cross-linking agent, of ~he general formula Am-Si(OR)4-m can be added to the dispersion to enhance the physical properties of the cured membrane. The radical A, in the silane cross-linking agent is a member seIected from the group consisting of a hydrogen atom, monovalent hydrocarbon radicals containing 1 to 6 inclusive carbon atoms, and monovalent halohydrocarbon radicals containing 1 to ~ inclusive carbon atoms.
Preferred radicals are methyl, ethyl, phenyl, and 3,3,3-trifluoropropyl with methyl being most preferred. The radical R is a hydrogen atom, . , .

-~7-and alkyl group containing 1 to 4 inclusive carbon atoms, O O
-~CH3, -CC2Hs, -CH2c~2O
-CH2CH2OCH3, or a -CH2C-H2OC2Hs group. The R
radicals on a silane molecule can be the same or different. The number of A radicals can be 0 or 1, meaning that a silane molecule can be either tri or tetra-functional in order to function as a cross-linker in the curing of the final membrane of this invention. The OR group on the silane is a hydrolyzable group that forms =SiOH during curing of the membranes of this invention. The preferred silane cross-linlcing agent is methyltri-methoxysilane. The silane crosslinking agent can be included in a sufficient amount to obtain - the desired degree of crosslinking. The amount to be used depends upon the hydroxyl content of the polymerizable Si-containing compound and the molecular weight of the crosslinking agent chosen.
The more crosslinking agent used, the harder and less elastic the membrane becomes. Useful amounts of the preferred methyltrimethoxysilane cross-linker vary from 1 to 7 parts by weight of silane per 100 parts hy weight of polydiorganosiloxane.
Other useful silicone containing com-pounds capable of polymerizing to form a membrane, film or layer that is glucose-permeable include the copolymers of diorganosiloxanes and any hydro-lyzable silane, as disclosed in the Sor~in Patent No. 3,624,017.
The diorganosiloxanes can be included in the dispersion as a monomer or a polymer.
The monomer can be partially polymerized in the dispersion or e-.nulsion and then silane added and copolymerized with the diorganosiloxane polymer.

The surfactant used to form an emulsion with the copolymers can be either anionic, cationic or nonionic and any catalyst useful to initiate the copolymerization can be used, such as a strong acid or a strong base. The starting diorgano-siloxane can be either a cyclic or a linear materi-al and the molecular weight: of the starting di-organosiloxane is not critical.
The dispersion of the polymerizable silicon-containing compouncl or compounds can contain the components in a broad range of con-centrations. The preferrecl concentration range will depend on the thickness of the membrane desired. For example, to provide a thick elasto-meric membrane (0.5 mm thick) that does not formcracks as the carrier or continuous phase evaporates, it is best to use a dispersion having a combined amount of silicate and polydiorganosiloxane in the range of 67 to 169 parts by weight for each 100 parts by weight of carrier, e~g. water. Pre-ferred membrane thicknesses are 0.073 to 0.64 mm (0.5 to 25 mils), for example 0.11 mm (4.5 mils).
If an emulsifying agent is incorporated into the composition to form the dispersion the amount of emulsifying agent can be less than 2 weight percent of the emulsion, and the emulsify-ing agent can result from neutralized sulfonic acid used in the emulsion polymerization method for the preparation of a hydroxyl endblocked polydiorganosiloxane.
Anionic surfactants are preferably the salt of the surface active sulfonic acids used in the emulsion polymerization to form the hydroxyl endblocked polydiorganosiloxane as shown in U.S.
Pat. No. 3,294~725 , show the su~ace ac~iye sulfonic acids ;~S-1408 :
~, , '`' '' ''`` ' `

~2~`J~

and salts thereof. The alkali metal salts of the sulfonic acids are preferred, particularly the sodium salts. The sulfonic acid can be illus-- trated by aliphatically substituted benzene-sulfonic acids, aliphatically substituted naphthalene sulfonic acids, aliphatic sulfonic - acids, silylalkylsulfonic acids and aliphatically substituted diphenylethersulfonic acids. Other anionic emulsifying agents can be used, for example, alkali metal sulforicinoleates, sulEonated glyceryl esters of fatty acids, salts of sulfonated mono-valent alcohol esters, amides of amino sulfonic acid such as the sodium salt of oleyl methyl-tauride, sulfonated aromatic hydrocarbon alkali salts such as sodium alpha-naphthalene monosul-fonate, condensation products of naphthalene sulfonic acids with formaldehyde, and sulfates such as ammonium lauryl sulfate, triethanol amine lauryl sulfate and sodium lauryl ether sulfate.
Nonionic emulsifying agents also can be included in the emulsion in addition to the anionic emulsifying agents. Such nonionic emul-sifying agents are, for example, saponins, con-densation products of fatty acids with ethylene oxide such as dodecyl ether of tetraethylene oxide, condensation products of ethylene oxide and sorbitan trioleate, condensation products of phenolic compounds having side chains with ethylene oxide such as condensation products of ethylene oxide with isododecylphenol, and imine deri-vatives such as polymerized ethylene imine.
The polymerizable silicon-compound dispersion used to form the glucose-permeable membranes of the present invention can contain additional ingredients to modify the properties of the dispersions or the cured polymeric m~mbrane ~S-1408 ~æ~

products obtained from the dispersion. For example, a thickener can be added to modify viscosity of the dispersion or to provide thixotropy for the dispersion. An antifoam agent can be added to the dispersion to reduce foaming during preparation, coating or curing in layer form.
Fillers can be added to the dipsersion to reinforce, extend or pigment the rnembrane.
Useful fillers include colloidal silica, carbon black, clay, alumina, calcium carbonate, quart2, zinc oxide, mica, titanium dioxide and others well known in the art. These fillers should be finely divided and it may be advantageous to use aqueous dispersions of such fillers i they are commercially available, such as aqueous dispersions of carbon black. The polymerizable Si-compound containing dispersions do not require a filler and such can be added in dry or aqueous forms to provide selected properties to the membrane.
The filler preferably has an average particle diameter of less than 10 micrometers.
Useful fillers have had average particle diameters ranging down to as low as 0.05 micrometers. When these silicone emulsions are spread out for final curing to form the glucose-permeable membranes of the present invention, the water or other nonsolvent carrier evaporates~ or is otherwise removed, to leave a cured glucose and oxygen-permeable membrane. Evaporation of the carrieris usually complete within a few hours to about one day depending on the dispersion film thickness and method of application. Another of the impor-tant advantages of the present invention is the excellent adhesion shown by these membranes for both po]ar and non-polar substrates.

" `'' ','' ` - . ' It should be understood that this inven-tion is not limited to removal of continuous liquid phase in ~he silica dispersion by evapora-tion, since other methods such as coagulation may be useful. Heating the polymerizable silicon-containing compound dispersions to more rapidly remove the carrier to produce more rapidly cured membranes also may be advantageous.
In accordance with the present invention, the glucose-permeable membranes 30 disclosed herein are use~ul in conjunction with any known method and apparatus for measuring the concentra-tion of glucose permeating the membrane. More specifically, glucose concentrations have been determined amperometrically using soluble glucose oxidase held between Cupropane membranes or physic-ally entrapped in a polyacrylamide gel coated onto an oxygen electrode. The decrease in oxygen pressure is equivalent to the glucose content in the biological fluid, such as blood or plasma, in accordance with the reaction:
glucose oxidase glucose + 2 + H2O ~ H2O2 + gluconic acid.
Instead of measuring the decrease in oxygen con-~5 tent, the hydrogen peroxide produced in the enzymatic reaction using a platinum electrode is an alternative use for the glucose-permeable membrane. Such a platinum eiectrode device for measuring the hydrogen peroxide is disclosed in the Clark U.S. Patent No. 3,539,455.
Some presently existing apparatus uses glucose oxidase held on a filter trap and utilizes two platinum electrodes, one to compensate for any electrooxidizable compounds in the sample, such as ascorbic acid, and the second to monitor the enzy~e reaction producing the hydrogen peroxide. Others also have used quinone as the hydrogen accepter in place of oxygen and measure the electro oxidation of quinone in accordance with the reaction:
Glucose oxidase glucose+quinone+H20 =D-gluconic acid+hydroquinone hydroquinone Pt ~, quinone + 2H~+2e~
~E = 0.4 V vs. standard calomel electrode) In such a quinone electrooxidation, glucose oxidase is trapped in a porous gelled layer and covered with a dialysis membrane over a platinum electrode.
Others have immobilized glucose oxidase onto a platinum-glass electrode held in place by cello-phane. The current produced is proportional to the glucose concentration. Others have measured the local decrease in iodide activity at an elec-- trode surface either in a flow stream or at a stationary electrode in accordance with the fol-lowing catalyzed reactions:
glucose oxidase glucose + 2--~a-gluconic acid ~ H22 peroxidase H22 + 2I- + 2H+ 2~20 ~ I2 While, in the prior art, such an electrode measure-ment of glucose required removal of interferring reducing agents~ such as ascorbic acid, the glucose-permeable membranes of the present inven-tion are very selective to permeation of glucose and oxygen while preventing the permeation of electrode sensitive reducing agents. Accordingly, the membranes of the present invention are also very well suited to such electrode measurement systems.

Ms-l4n~

~ .. , .:

~2'j~1g One o~ the more important advantages to the glucose-permeable membranes of the present invention, however, is the capability of these membranes to be bonded to an electrode activated with a bonded layer of a suitable catalyst, such as glucose oxidase, or glucose dehydrogenase to eliminate any necessity for any intermediate layer of ion-conducting buffer solution. In accordance with this embodiment of the present invention a compound capable of catalyzing the reaction of glucose with oxygen is bonded directly to the electrode 10, e.g. the anode 12, and the glucose-permeable membrane 30 of the present invention is coated over the catalyzed anode 12 to entrap the catalyst 28 between the membrane layer 30 and the anode 12 outer surface. The catalyst e.g. glucose oxidase 28, is immobilized on the outer surface of the electrode 10 in any suitable manner.
Immobilization of enzyme 28 directly on anode 12 can be accomplished in several ways known in the art. For example, im~obilization can be accomplished through a silane coupling agent such as N-beta-aminoethyl-g~mma-aminopro-pyltrimetho~y silane. An important characteristic of silane coupling agents is their ability to form covalent bonds with many metal oxides and hydroxylated metal surfaces at the Si(OR3) por-tion of the silane molecule. This is true with platinum. Upon normal exposure to ambient condi-tions, pl~tinum readily develops an hydroxy func-tional surface. An alkoxysilane rapidly reacts with this surface to form stable "Pt-O-Si" bonds.
The silane coupling agents also include an organo-functional, e.g. amino, group that reacts with the catalyst, such as glucose oxidase 28, via a . .

.

.

~rw~

suitable crosslinking agent, such as glutaraldehyde, to immobilize the oxidizing enzyme, e.g. glucose oxidase 28, directly onto the anode 12 and the bonded enzyme 28 remains active for several months.
To achieve the full advantage of the present invention, the catalyst 28 capable of catalyzing the reaction of glucose with oxygen is immobilized on the surface of the anode 12 using a silane coupling a~ent and a suitable crosslinking agent. Crosslinking agents suitable for immobilizing a protein catalyst such as glu-cose oxidase to a platinum surface of an electrode include glutaraldehyde, cyanogen bromide, hydrazine, benzoquinone, periodate, trichloro-s-triazine, tosyl chloride and diazonium. Each of these crosslinking agents is suitable for immobiliza-tion of proteins such as glucose oxidase by coupling to a primary amino functional silane coupling agent, with the exception of the diazonium which is co~plable to a phenol or aromatic amine functional silane coupling agent. Further, the trichloro-s~triazine cross-linking agent can crosslink the enzyme through a hydroxyl functional group of a silane coupling agent and tosyl chloride is couplable to a thiol functional group of a silane coupling a~ent. Some of the suitable silane coupling agents include 3-aminopropyltri-ethoxysilane; N-2-aminoethyl-3-aminopropyltri-methoxysilane; 4-aminobutyldimethylmethoxysilane;
(aminoethylaminomethyl)phemethyltrimethoxysilane;
4-aminobutyltriethoxysilane; N-(2-aminoethylj-3-aminomethyldimethoxysilane; and 3-aminopropyltris-(trimethylsiloxy)silane and the like.
Once the catalyst 28 has been bonded to the anode 12, the mem~rane 30 is applied over the enzy~e 28 in working area 20. The membrane materials described herein are very compatible with whole blood, have a durable surface and are highly selective to oxygen penetration so that a sufficient stoichiometric excess of oxygen per-meates the membrane 30 even from whole blood.
A surprising characteristic of the polymerized silicon-containing membrane 30 is glucose-permeability wllich is contrary to the teaching o~ the prior art.
Another surprising characteristic of the membrane 30 is its ability to prevent passage of abscorbic acid to electrode lO. ~bsorbic acid is a major interferent and is essentially prevented from reaching the electrode surface 1 by membrane 30. Further, the cured membrane 30 has a durable and resilient surface allowing the membrane 30 to be rinsed and wiped off after use to remove any contaminents that could build up and foul the membrane.
The preferred materials for membrane 30 a~e an anionically stabilized, water-based hydroxyl endblocked polydimethylsiloxane elastomer containing about 5 percent by weight colloidal silica sold by Dow ~orning as elastomer and manu-Eactured in accordance with Do~ Corning U.S.
Pat. No. 4,221,668 To show the new and unexpect-ed results using membranes 30 formed from a dis-persion of polymerizable silicon-containing com-pounds applied in layer form in an incompletely cured state dispersed in a removable liquid carrier, four membranes were made-three from silicone-water liquid dispersions and one from a silicone paste material having essentially no remo~able liquid phase. The mem~ranes were prepared by casting the elastomers onto a polyester film with a 0.25 mm (lQ mil). doctor blade and ,~
: . .
~:

curing at ambient conditions. The three composi-tions having a removable carrier ~water) were applied as neat polysiloxane emulsions. Curing was accomplished in 30-60 minutes but can be accelerated with heat. This process gave a final dry film (membrane) thickness of approximately .11 mm (4.5 mils).
The three carrier-removable silicone latex compositions from Dc,w Corning differ only slightly in material composition. Dow Corning 3-5024 is the base system containing hydroxyl endblocked dimethylpolysiloxane elastomer with 5 percent by weight SiO2, and an anionic emulsifier and may also include a suitable cross-linking agent such as a silane and catalyst, such as an alkyl tin salt. This material is the least viscous (1000 cps) of the thxee and cures to a thin clear film.
A second silicone water based elastomer, Dow Corning 3-5025, identical to Dow Corning 3-5024 with the addition of an organic, thixotropic additive, has a precured viscosity of 25000 cps.
This film is also clear on drying.
A third silicone water based elatomer, Dow Corning 3-5035, includes about 4~5 percent by weight Tio2 filler. These films are op~que and white in color.
A heat-curable silicone paste (Dow Corning 3-9595) having essentially no volatizable carrier was also tested for comparison purposes.
Dow Corning 3-9595 is a dimethylpolysiloxane elastomer containing 40 percent by weight silica and is supplied as a two-part putty~like material requiring the material to be spread into a layer using a doctor blade.

i LS

..... ... . .

12~J(~ 9 Results of the evaluation of membranes made from the above-identified four materials are summarized in the following table:

,: , . . . .

. ' o o o o _~ ~ ~ o o o o o X X X
X X X X X
~ o ~o O ~D 0~ ~1 a~ ~ ~ cn Lr~
~ m ~ c~
w m m P;
Z 'P O
O ~1 ~L~_~ ~ O ~1~ O
H O O t ~ ~) ~1 ~ O O O O O O
1--1 H ~1 _I~1 ~/ --1~I r-l X x X X X X X X
~ O ~: ~ ~r O ~) I~ o ~u:>cn u~ c~
U~
-E~
~ ~ O
m I I ~~,1 ~ I _~
o o II I I~c I
E3 ~ ~ oo o o o o ~i X X --' XX X X X X
C~ ~U~
H H ~r_I ~~ ~ 0 ~~ C~ . ^ Ul Z) ~¢ 1 I
t) C) ~,q _ ~ --1 I C
Ul o o OO O O O O
1~ a~ 4J
a x x xx x x x x XUl C~ ~ 1`~ ~8~~1 U~
~::) Or~ ~)~ N~r~r ~r O --~C~ . .. . . .
1~3 ,11` ~~ oo ~1--11 11ll11 11 v ~n n ~ ~ o ~ x o ~ o ~ u~ ~ ~1 a~
X U ~ X LO a~ X a~ ~ a ~: ~ V ~ a ~ ~ ~ 3 ~ a ;-., .:
: ' . .

~ .~

r.~ 9 Quite surprisingly, the glucose perme-ability of the silicone material in paste form having essentially no volatizable carrier is three orders of magnitude lower than Dow Corning 3-5025 and Dow Corning 3-5035 and two orders of magntidue lower than Dow C'orning 3-5024. The evaluation table also emphasizes the three latex materials are much more selective for glucose relative to ascorbic acid than the paste form silicone.
Since laminated electrode 10 requires only a few molecular layers of platinum and silver or similar materials and membrane 30 requires very little material, electrode 10 is inexpensive.
Further reducing the cost of electrode 10 is the method of fabrication. Referring to FIGS. 1-4, the method of fabricating electrode lO is illus-trated. The initial step involves fabricating apertures or holes 22, 24 and 26 in the dielectric layer 16 (FIG. 3), the cathode layer 14 (FIG.
2) and the dielectric sheet 18 (FIG~ 1), respec-tively. Each of the dielectric sheet 18, cathode layer 14 and the dielectric layer 16 may be backed with adhesive such as silicone based adhesive with paper backing. The paper backing is peeled off and dielectric sheet 16, cathode layer 14 and dielectric layer 18 are laminated together and to the anode layer 12 by rollers 32 and 34 or a similar procedure. The membrane 30 is then applied in liquid form to the working areas 20 and allowed to cure. The resultant laminated strip is then cut by blades 36 and 38 to form individual electrodes 10.
It has been determined the adhesive backing functions as a dielectric and the adhesive backing on cathode layer 14 can be used to replace .

g dielectric layer 16. This replacement ~urther reduces the cost of electrode 10 by eliminating material and one assembly step. This also reduces the thickness of electrode 10 making it more planar and easier to apply the membrane 30.
Electrodes 10 can be configured in several different ways to provide for connection of the anode 12 and cathocle 14 to electrical terminals or connectors that are couple~ to an 10 electronic readout in an electrochemical sensor.
One configuration is illustrated in FIG. 5.
Electrode 10 is configurecl in a stair step type of configuration with dielectric sheet 18 shorter than cathode 14. Cathode 14 is exposed and an 15 electrical connection can be made to the upper surface. Anode 12 is exposed on the upper side and an electrical connection can easily be made.
Another procedure for electrical connec-tion is to form slots in the electrode. Referring 20 to FIG. 6, an alternative electrode 100 is illus-trated. Electrode 100 is substantially the same as electrode 10 except the anode 112 and cathode 114 are formed in strips or ribbons and positioned side by side. Working area 120 is defined by an 25 aperture 140 extending through a top sheet 118 of dielectric material. To provide access for connection of terminals, slots 142 are formed in the top sheet 118 exposing anode 112 and cathode 114 allowing electrical connection. Slots 142 30 provide the advantage of allowing electrode 100 to be plugged into an electrochemical sensor with electrical contacts that slide onto the slots 142 making csntact.
Another procedure for electrical connec-35 tion is illustrated in FIG~ 7. A second alterna-tive electrode 200 is composed of the same elements ~S-1408 , ~

as electrode 10 and includes an anode film 212, a layer 216 of dielectric material, a cathode film 21~ and a top sheet 218 of dielectric material. Slots 242 can be formed in the top sheet 218 with a first hole 250 in top sheet 218 allowing access for an electrical contact pin to cathode 214. A second hole 252 can be fabricated in top sheet 218 and cathode 214 allowing access for a second electrical pin to the anode 212.
It is to be understood, several other configurations for electrical connection will connection be recognized by those skilled in the art and it is not intended to limit the present invention by the illustrated configurations.
In addition to vapor deposition, other procedures ~or forming the anode and cathode are contemplated. For example, the selected anode and cathode materials may be sputtered onto film or the materials may be silk screened onto a ceramic substrate. The examples mentioned are not intended to be limiting and other procedures known in the art are also contemplated.
By using vapor deposition and lamina-tion technologies, the cost of the electrode is significantly reduced since the amount of these expensive materials is minimized. Reduction of the amount o~ anode and cathode materials allows the~amount of enzyme material used in layer 28 to be increased without significantly changing 3~ the cost of the electrode. The incre sed enzyme provides a much larger signal from the electrode with a better response.
Many modifications and variations of the present invention are possible in light of the above teachings. Thus, it is to be under-stood that, within the scope of the appended %,~.J~ ~ ~9 claims, the invention may be practiced other than as specifically described.

Claims (9)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A laminated electrode, consisting essentially of:
a cathode consisting of an electrically conductive film having a molecular layer of metal deposited thereon;
a layer of dielectric material laminated to said cathode; and an anode consisting of an electrically conductive film having a molecular layer of metal deposited thereon, said anode being laminated to said dielectric material;
wherein an interactive area consisting of aligned apertures is present in said dielectric material, in said anode or in said cathode and wherein said interactive area contains a glucose permeable, silicone water-based elastomer bonded to said aligned apertures.

2. The laminated electrode of claim 1 in which the anode comprises an electrically conductive film with a layer of platinum vapor deposited thereon.

3. The laminated electrode of claim 1 in which the cathode comprises an electrically conductive film with silver vapor deposited thereon.

4. The laminated electrode of claim 1 containing glucose oxidase in said interactive area.

5. The laminated electrode of claim 1 in which glucose dehydrogenase is present in said interactive area.

6. The laminated electrode of claim 1 in which the glucose permeable, silicone water-based elastomer comprises a diorganosiloxane.

7. The laminated electrode of claim 1 wherein the glucose permeable, silicone water-based elastomer comprises an end-blocked diorganosiloxane.

8. The laminated electrode of claim 1 wherein the glucose permeable, silicone water-based elastomer comprises a vinyl or hydroxy end-blocked diorganosiloxane.

9. The laminated electrode of claim 1 in which the glucose permeable, silicone water-based elastomer comprises a dimethylsiloxane.