GB2332278A - Electrochemical sensor - Google Patents

Abstract

The sensor comprises an ion-sensitive electrode ("ISE") 2, 3 and a reference electrode 4, 5, 6 in combination with a permeable barrier 8 enclosing the ISE - and preferably enclosing both electrodes - to interface with samples under examination so that the sample itself no longer provides the main bridging contact between the ISE and reference electrode to complete the measuring circuit. The permeable barrier controls diffusion of analyte and impurities and preferably may also be selective. Diffusion can be controlled to regulate flow of components in either direction through the barrier. Various forms are described which can facilitate more rapid identification of the analyte content in a sample.

Description

I 1 - TITLE: SENSOR DEVICES AND ANALYTICAL METHOD.

2332278 This invention relates to sensor devices and analytical methods using them.

Various types of electrodes are known f or use in the electrochemical analysis of samples, and one of these is the ion-sensitive electrode (conveniently referred to as an "ISE"), which functions on the basis of measuring the electrical potential of the ISE when in contact with the sample. This requires two electrodes - one being the ionsensitive electrode (ISE) and the other being a reference electrode assembly. Such electrodes are well-known. The reference electrode assembly usually employs a liquid junction between (a) the sample and (b) the reference electrode and its associated internal electrolyte. The liquid junction maintains electrical continuity in the electrochemical cell while restricting contamination of the inner electrolyte of the reference electrode assembly by the sample.

The known methods and devices for using an ISE for detection and/or measurement purposes are all based on the simple procedure of putting both the ISE and the liquid junction of the reference electrode assembly in contact with the sample, and then measuring the electrical potential between the ISE and the reference electrode. Appropriate analytical conclusions are drawn from the measurements of this potential, e.g. by comparison with the potential generated when standard solutions are used.

However, the known devices and systems have been found to suffer from disadvantages so that they are not entirely satisfactory in use, because the standard modes for using them require careful calibration against standards and also stabilisation before they can give accurate or reliable results.

We have now found that this difficulty can be overcome by covering the ISE with a permeable barrier of restricted permeability which then interfaces with the sample, so that 1 2 the sample itself no longer provides the sole bridging contact between the ISE and a reference electrode assembly to complete the measuring circuit. This permeable barrier allows the system to operate by diffusion of components, between the sample and the region within the permeable barrier, before the output signals from the electrodes are measured and such measurements are used as a basis for the determination of the composition of the sample. For this, the permeable barrier covers at least the ISE, and preferably covers both the ISE and the reference electrode assembly.

Thus according to our invention we provide a sensor system comprising an ion-sensitive electrode and a reference electrode in combination, characterised in that the ion sensitive electrode is enclosed within a permeable barrier adapted to interface with a sample under examination, so that the sample itself no longer provides the main bridging contact between the ion-sensitive electrode and the reference electrode to complete the measuring circuit.

Preferably, both the ISE and the reference electrode are enclosed within the same permeable barrier to separate them from the sample.

Thus according to our invention we also provide a sensor device comprising an ion-sensitive electrode and a reference electrode in combination, characterised in that these are both enclosed within a permeable barrier adapted to interface with a sample under examination, so that the sample itself no longer provides the main bridging contact between the ion-sensitive electrode and the reference electrode to complete the measuring circuit.

Our invention also provides an improved method for the determination of an ionic analyte in a sample, which comprises using a sensor device with an ion-sensitive electrode and a reference electrode in combination as described herein.

Thus according to our invention we also provide a method for the determination of an ionic analyte in a sample, which comprises using a sensor device incorporating an ion- sensitive electrode and a reference electrode in combination, characterised in that these are the ionsensitive electrode (and preferably also the reference electrode) is enclosed within a permeable barrier adapted to interface with a sample under examination, so that the sample itself no longer provides the main bridging contact between the ion-sensitive electrode and the reference electrode to complete the measuring circuit, measuring the potential between the ion-sensitive electrode and the reference electrode and using this measure for determining the content of the ionic analyte.

The two types of electrode used (the ISE and reference electrodes) are well-known and are amply described in the literature. Their precise form and construction are not critical but the following summary assists in describing them.

The reference electrode may be any of those known or used in the art. The preferred and most convenient form of reference electrode assembly comprises a conventional cell containing a silver/silver chloride (Ag/AgCl) or calomel electrode system, with its conventional filling solution (usually an electrolyte), enclosed in a container which has a "liquid junction" to make contact with the sample. This "liquid junction" is commonly a porous membrane which serves to allow the necessary electrical conductivity to complete the electrical measuring circuit while restricting flow and/or diffusion of the sample or its components into the reference cell or any outward flow to contaminate the sample.

For ease of fabrication, forms having simple geometry, for example planar forms, are most convenient. Construction may also be simple. For example, a Ag/AgCl electrode may be overlaid with a membrane of material such as polyvinyl alcohol, which readily hydrates and (in terms of the electrode potential) the arrangement is satisfactorily stable, especially when the electrode is required for only a 4 short measurement duration.

The ISE for use in our invention may be any of those known or used in the art, for example a conventional ionsensitive electrode with an internal electrolyte and an internal reference (e.g. Ag/AgCl) or a coated wire electrode where a base metal wire is in direct contact with a covering ion-sensitive membrane.

The response of an ISE is based on an internal sensing electrode covered or enclosed by a coating or membrane of a material having ion-sensitive or ion-sensitive properties. This coating or membrane surface interacts with the ionic components from a sample to generate a measuring voltage (EMF) and may allow preferential passage of those ions which it is desired to measure. The sensing electrode may be a conventional one capable of use for measurement of electrochemical potentials such as Ag/AgCl but may also be, for example, metals such as platinum, gold, silver or copper as in coated wire electrodes. Examples of coatings include those containing additive components which are ion- sensitive in the sense of having powers for ion-exchange, ionadsorption, complex- forming neutral compounds or chelating ions, or the like, or combinations of such properties.

The potential forms at the membrane or across it the internal electrode is there simply to make a contact like the reference to measure potential between two points either side of the membrane.

Likewise, solid-state electrodes may be used without the need for an ionsensitive coating if they already themselves possess the necessary ionsensitive properties.

The ISE usually comprises a covering or layer (e.g. a membrane or a gel) over a core electrode and the components imparting ion-sensitivity may be in or on the core electrode and/or the said covering or layer. A common form of ISE may contain, when in use, an inner electrolyte and associated contacting electrodes.

Alternatively, it may be a solid-state electrode, for example any of those available commercially. One form of these can be used to detect chloride ions (Cl -). Examples of this type include ion selective field effect transistors (conveniently referred to as "ISFET11 devices).

The ISE can be in any convenient shape. It is easy and convenient to make them in planar form, f or example as a flat form of the coated wire.

It is possible also for the reference electrode to be another ISE which is under conditions which make it produce a stable EMF, in a manner comparable to a true conventional reference electrode. This can be an ISE with a dif f erent (and constant) inner, stable electrolyte within the porous liquid-junction membrane.

The permeable barrier surrounding the ISE and reference electrode may be of various materials and forms. Its main function is to enclose the ISE and reference electrode assembly and make contact with the sample, but also it may serve to hold the two electrode systems together as a single assembly, and even provide some protection for them against damage from contact with other bodies. Also, it usually contains an electrolyte medium enclosed within the permeable barrier.

The permeable barrier may be made of any material which can provide the desired degree of permeability towards the sample or its components in addition to a sufficient degree of cohesion, strength and durability to maintain its physical integrity while the device is in contact with the sample and in use.

Conveniently, it may be simply a membrane or a gel, but it may comprise any combination of these - using one or more of either type of material (which may be the same or different) if desired. As its principal purpose is only to regulate, by diffusion, access of the sample or its components to the ISE and the reference electrode assembly, its composition and form are not critically important. The range of suitable materials is therefore quite conveniently extensive, (and can be used to improve selectivity), which is one of the advantages of our invention. Also, it does 6 - not matter whether or not the barrier may produce a potential of its own (i.e. a "membrane potential") because such a potential, if generated, does not alter the potential difference which we wish to use -- i.e. the potential between the ISE and the reference electrode.

The diffusion is a function of the concentrations of the ion species on opposite sides of the permeable barrier, and in its simplest form that is all that is required of it, as it then functions only to regulate the access of the sample or its components to the ISE. This regulation can be very helpful in keeping the concentration of the components affecting the ISE potential within limits which allow ease of measurement or preventing excessive amounts contacting the ISE and distorting the output potential from it and distorting the accuracy of measurement.

The diffusion is usually inward diffusion (i.e. through the permeable barrier from the sample towards the ISE) by the ionic analyte species to be determined. This results in the ISE being is uniformly exposed to the inwardly diffusing ions to be measured. It also has the advantage that the ISE is less likely to be exposed to any unsuitably high concentration of the ion analyte species (as could be the case if the sample contains a very high concentration and the ISE were exposed directly to the sample) before the measurement is completed. By the time concentration levels within the permeable barrier rise sufficiently to cause problems, the measurement would have been completed.

Furthermore, it causes the concentration of the ionic analyte in contact with the ISE to change progressively as diffusion proceeds, and this change - especially the rate of change of concentration - is an exceptionally useful basis for the determination of ion content which we wish to make.

Alternatively, as a variant, the contents of the permeable barrier may be provided with a concentration of the analyte ion which is higher than that in the sample to be examined, so that diffusion of the analyte ion will then be outwards - away f rom the ISE and into the sample - so resulting in a decrease of its concentration adjacent to the ISE. This mode also can be used, as the rate of change is more important for the measurement purposes than the absolute concentration itself.

In the simplest form of our invention no selectivity is necessary for the material of the permeable barrier but, if desired, the permeable barrier may have selective properties in the way it limits diffusion - as distinct from the ISE membrane selectivity phenomenon. This could be important in improving the apparent selectivity of the ISE, and improved usefulness of our invention may be secured by making the barrier of a material which provides some degree of selectivity. This may then enable the device to exclude any components which could compromise the selective functioning of the ISE, and so serve as a means for eliminating problematic interference with measurements being made. For this variant, a complete or high degree of selectivity may not be necessary, and even a partial discrimination again access by particular components may be sufficient to ensure satisfactorily reliable measurements - depending upon the particular application of the invention and the nature of the sample and/or the components sought to be determined.

It is usual for an electrolyte medium to be required between the ISE and the reference electrode within the permeable barrier, as a "filling," though some forms of ISE may be able to function without the need for any such filling electrolyte, This electrolyte medium may be provided in a variety of ways. For example:- (1) It may be provided in the device as made. This allows the device to be made in a form suitable for sale or storage but also for immediate use. For this form, the electrolyte can be in the form of a hydrated gel, which is both practicable and convenient.

(2) It may be added at the time it is to be used, for example by making the device in a form in which the ISE is surrounded by the permeable barrier material, and 8 - then soaking it in a suitable electrolyte solution to make it ready for use. An example of this mode is to use a thin permeable membrane (e.g. a dialysis membrane) around the electrodes. Such a membrane may comprise any conventional material, e.g. cellulose or cellulosic material as often used for dialysis membranes. if desired, the robustness of the construction or the degree of permeability can be obtained by using multiple layers of the membrane (which may be the same or different). Using four layers of dialysis membrane can provide a very convenient form of such a device.

(3) It may be provided by obtaining the necessary liquid from a sample itself, by permeation of water and diffusion of electrolyte ions from the sample through the barrier when the device and the sample are brought together.

our preference is for the last of these, (3) above, but the most readily practicable is that marked (2) above.

The permeable barrier is adapted to interface with a sample under examination by the fact that at least the ISE and preferably both the ISE and the reference electrode assembly - are enclosed within the permeable barrier. This enables all that is required of a sensor device to be included in a single unit, by carrying the ISE and the reference electrode assembly upon a support which serves to hold the assembly together while insulating the ISE and the reference electrode assembly from each other. Various forms of construction may employed. For example, if the ISE and the reference electrode assembly are assembled upon a substantially flat insulating support, the permeable barrier may take the form of a "bubble" or "envelope" over them. This allows the sample under study to be applied to the side of the insulating support on which the electrodes are exposed, and the electrical connections to the measuring circuit. The electrical connecting leads to the electrodes will need to be properly insulated, both chemically and electrically, from the media around them so as to avoid any 9 interference of loss of the electrode signals.

Alternatively, the electrical connections to the two electrodes can be made in the usual manner and all the leads and connections from them insulated and sealed to pass through the region within the permeable barrier. This allows the whole device to be made in a f orm in which the permeable barrier is more extensive and covers more than just the area required for sample to be applied and access the electrodes, so that the barrier can cover as much of the device as desired - even the whole of it - so making it easier to use by dipping into a sample.

The measuring circuit may be any of the conventional ones for electrochemical measurement, and use conventional apparatus (meters, recording devices, and the like) for detecting an EMF or potential differences, and the signals from the electrode system of our devices can be interpreted and converted to specific measurements of components by conventional methods.

If an ISE suffers interference from unknown amounts of another ion, this interference can be reduced or eliminated by filling the enclosed region (around the ISE and within the permeable barrier) with an electrolyte containing a suitable high concentration of this other "interfering" ion. In this way, the concentration of the interfering ion can then be kept effectively constant with time - and the rate Qf potential chancre in the ISE output signal due to the desired analyte could thus be distinguishable.

The components of a sample which can be determined by the use of the present invention are those for which the conventional ion-sensitive electrodes are applicable. these include anions, e.g. sodium (Na+) and potassium (K+), and anions, e.g. nitrate (N03-) and fluoride (F-),but others may be determined if desired by appropriate ion-sensitive electrodes.

Selectivity can sometimes be improved by appropriate choice of the barrier membrane. For example, selectivity for organic anions (e.g. chloride Cl_) may be enhanced by use of an anionic barrier membrane.

The sample may be obtained and prepared in any conventional manner, but is preferably a liquid. If solids or samples which are not completely liquid are to examined, it may be necessary to add water or other aqueous solvent media to them to ensure that the components in them are put into a suitable state for measurement.

Usually, all that is required is that the ionic analyte to be detected and measured should be in solution in the sample so that it is able to diffuse through the permeable barrier. The ionic analyte may be present initially as such (and therefore can be determined directly), but if desired it may be generated in situ, for example by enzyme or chemical action, and this may enable measurements of some analytes to be made indirectly. Such indirect measurement can be useful as a means for making one analyte into another which is diffuses more readily through the permeable barrier or be detected at the ISE (for example by converting a nonionic analyte into an ionic one), but it can also be used to assist in reducing interference by components which could otherwise behave similarly to the ionic analyte be that it is to be measured.

The sensor devices of this invention may be used in substantially the same way as an ordinary ISE, by contacting the permeable barrier over the ISE with the sample (if, necessary, prepared for this in the manner described above). This may be done by applying it to the sensor device or, more conveniently, by dipping the sensor device into the sample. Of course, some forms of construction may be better adapted for particular modes of contacting with the sample, but the choice can easily be made to suit the particular situation and the user's preferences.

In use, advantages which can be secured by use of the sensor devices of the present invention include:- (1) the ISE and the reference electrode, being combined, make the device very much more easy and convenient to use.

(2) potential problems of contamination of the reference electrode are reduced or eliminated.

(3) the variety of analytes which can be measured is wide because a considerable range of standard ion-sensitive (e.g. ion-exchange) materials are available.

(4) selectivity of component measurement can be enhanced by use of a permselective layer in the permeable barrier.

(5) small sample volumes can be examined and their contents determined, particularly when using a flat form of device.

no calibration of the device is required to counteract for any baseline drift. This is a key advantage so far as practical use is concerned, as in "single shot" use.

(7) the device is simple enough to be made disposable, for a "use once, no rinsing" procedure.

(8) in its flat form, the device is of a very similar format to amperometric planar sensors, i.e. they can use different circuitry but the same fabrication and user presentation techniques, and so can offer opportunities for "mixed technique,, multi-analyte sensor strips.

(9) adaptable to use any ISE system.

(10) advantageous for the examination of samples containing the analyte at high concentrations which would not allow the ISE to function satisfactorily if brought into direct contact with the the ISE.

Applications for which the devices of the invention may be used include medical and clinical use, especially as a disposable electrolyte sensor which reduces risk of crosscontamination between sample or subjects; checks on levels of ionic fertiliser components in soils, rivers, plant materials and the like; checks on levels of ionic components (which may be considered to be desirable ones or may be any considered as contaminants or undesirable) in foods, waters, industrial liquid and effluents and the like.

The device is most advantageous for single use in a constant sample, and after that use can be discarded. After making a single measurement, i.e. not continuous monitoring, 12 - the device can be "reconditioned" to some extent so that it can be used again, but this can be slow and not worthwhile.

If it is to be re-used, the advantage of calibration avoidance is effectively lost.

The devices of our invention may be made in a variety of forms and shapes, to suit the particular needs of a user.

Thus, the device may be a single one - which can then be made conveniently small and inexpensively, and be most simple to use. Other forms include combinations or arrays containing more than one of our sensor devices, which may be constructed to obtain an enhanced output signal for easier measurement or for special uses.

A form of interesting applicability is that in which several individual sensor devices of our invention are is mounted together and the internal electrolyte (within the permeable barrier) of each of these is contains (pre-loaded) different concentrations of the analyte to be measured. By contacting all the sensor devices with the sample, the flux of any interfering ions would be constant for all of them, but the fluxes of the desired analyte would be different and their differential behaviour would be a function of the concentration of the desired analyte in the sample and so enable interference effects to be reduced or eliminated.

Another variant of this is an array of a number of our sensor devices, each with its internal electrolyte loaded with different pre-determined (and known) concentrations of the analyte sought. When such an array is contacted with the sample, the different sensors will give different responses - but for the particular sensor in which the loaded concentration of analyte ion equals that in the sample there will be no diffusion through the permeable barrier and no potential change with time will be observed. This can reduce the need for detailed measurements to be made, as the sensor showing "no change" Pnil diffusion") can be distinguished easily and quickly and will indicate the analyte concentration immediately.

An especial feature in using our invention is in the 13 - way in which the measurements are made and interpreted. The ion to be determined diffuses through the permeable barrier and this progressive diffusion gives a continually changing response from the ISE/reference electrode combination. We have found that, using a sensor device of the present invention, the rate of change of response is most indicative of the analyte content, and that it is possible to obtain more reliable measures of the analyte concentration by determining this. When measurements (by observation and recording) of the output potential are made and plotted in terms of the rate of change of potential against the analyte concentration, the plot slope is independent of any baseline EMF and also of the particular reference electrode used.

The responses are usually and conveniently measured in mV/minute, and are plotted as the rate of change of potential against the concentration or, preferably, against the log concentration.

For this mode of using the measurements, the absolute value of the ISE/reference potential is not important so long as the reference keeps stable during the short time required for measurement, the problems previously caused by long term drift are minimised, and calibrations for use is not necessary. Though the baseline EMF of ISEs may drift about, this slope of the response plot is much more stable. This is in contrast to the usual way in which an ISE is used, which involves waiting long enough for the ISE to be at equilibrium.

Sometimes, during initial stages of setting up a sensor device of our invention for use, it may be found that there can be some initial abnormality (a "spike,, or surge) in the response, but this is only brief and can be allowed to pass prior to making measurements to determine the slope of the plot as indicated above.

The invention is illustrated but not limited by the following Example and accompanying drawings, which are schematic and not drawn to scale.

1 14 - EXAMPLE 1.

Figures 1 and represent illustrations of forms of sensor constructed according to the present invention, and are schematic drawings, in transverse section and not to scale.

In Figure 1, a planar sheet of ceramic material of approximately 0.5 mm thickness and 1.5 cm by 3.0 cm in area (1) serves as an insulating support and carries, upon one of its planar surfaces, two electrodes -- (A) an ion-sensitive electrode comprising a thick metallic film (2) of platinum deposited from a platinum-containing ink or paint and coated with an ion-sensitive material (3), and (B) a standard reference electrode (4) comprising a film of silver coated with silver chloride, surrounded by an aqueous solution (5) of potassium chloride (concentration in the range 0.5 to 3.5 M) and enclosed within a porous layer (6) to serve as the required liquid junction in use. 20 The two electrodes (A) and (B) are totally enclosed by a permeable barrier layer or membrane (8) which also makes sealing contact with the sheet of insulating support material (1) all around the area containing both electrodes.

The space between this enclosing membrane (8) and the two electrodes (A) and (B) is filled with an aqueous solution (7) of sodium chloride. This completes the electrolytefiled permeable barrier as the enclosure for the pair of electrodes.

On the other side of the planar support sheet (1), 30 remote from the two electrodes (A) and (B), electrical leads are fitted (10 and 11 respectively) to provide electrical connection to the electrodes (A) and (B) (more specifically, to the conducting f ilms (2) and (4). These leads (10 and 11) are sealed into the sheet (1) to prevent any leakage of liquid past them, and are insulated and provided with means for connection to a voltage measuring device V (not shown).

In use, a liquid sample to be examined (9) is put into contact with the surrounding membrane (8) Conveniently, this is done by simply dipping the assembly (constructed as described above) into the sample liquid (9). The insulation covering on the connecting leads (10 and 11) ensures that there is no electrical short-circuit occurring between them.

Alternatively, the assembly is laid horizontally, with the electrodes, membranes, etc. uppermost, and the sample is then applied on top of theouter membrane (8).

This construction allows electrolyte contact at each of the membranes (3) and (8) and also the bridging part (7), to allow the completion of an electrical conducting circuit between electrode (A) and (B) which avoids direct exposure of electrode coverings (3) and (6) to the sample (9) itself.

Measurement of the potential between the two electrodes (A) and (B) is made by an appropriate meter, usually an ISE meter, typically a voltmeter with a single high impedance input for the ISE.

In Figure 2, which represents a transverse section of part of a long strip of a ceramic base (11) coated with a pair of metallic stripes (12)- and (13). Stripe (12) is of gold and serves as the conductor for the ISE part, and stripe (3) is of metallic silver coated with silver chloride and serves as the reference electrode. Over the base (11) is a layer of insulating material (14), made by casting a solution of unplasticised PVC in tetrahydrofuran over the stripe-coated ceramic base and allowing the solvent to evaporate off. A small "window" in the deposit of PVC is lef t so that the stripes (12) and (13) are exposed and not covered by the PVC (14). Then, the area over and around the 16 gold stripe (12) is coated with a solution of PVC, a plasticiser, and an ion-carrier to form a coating (15). Then finally the whole area which is not covered by the PVC (14) is covered with polyvinyl alcohol, which forms a permeable layer (16) which is sealed on to the surrounding PVC (14) and completely covers the electrodes. Electrical connections are made (by means not shown, but conveniently comprising the ends of stripes (12) and (13) protruding from under the PVC layer (14) beyond the "well" or "window,, filled by the layers (15) and (16). For use, the sample is then contacted with the of the polyvinyl alcohol layer (16), and the potential between electrodes (12) and (13) is measured. In this form of construction, basically electrolyte and membrane are combined.

For these electrodes, the unplasticised PVC used has a molecular weight of 100,000 to 200,000 and is dissolved in tetrahydrofuran. This is used to form the PVC layers.

To make the ISE coatings (3) and (15), the solution of unplasticised PVC in tetrahydrofuran is used, with addition of tri-caprylyl methyl ammonium chloride as plasticiser and as ion carrier for chloride or with di-octyl phthalate as plasticiser and valinomycin as ion-carrier for potassium.

The layers of metal are deposited from metal-containing paints, in conventional manner, and the various coatings of polymer-based material are applied by dip-coating the ceramic strip in the solutions, masking areas which are not to be coated and cutting out parts of the applied coatings where a "well" or "window" is to be formed.

In place of the gold, using platinum and copper as alternative metals gives substantially the same results.

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Claims (26)

WHAT WE CLAIM IS:-

1. Sensor system comprising an ion-sensitive electrode and a reference electrode in combination, characterised in that the ion sensitive electrode ("ISE") is enclosed within a permeable barrier adapted to interface with a sample under examination, so that the sample itself no longer provides the main bridging contact between the ISE and the reference electrode to complete the electrolytic measuring circuit.

2. Sensor system as claimed in Claim 1 wherein both the ISE and the reference electrode are enclosed within the same permeable barrier to separate them from the sample.

3. Sensor system as claimed in Claim 1 or Claim 2 wherein an electrolyte medium is enclosed within the permeable barrier.

4. Sensor system as claimed in any of Claims 1 to 3 wherein the permeable barrier is a membrane of material which readily hydrates, for example poly vinyl alcohol.

5. Sensor system as claimed in any of Claims 1 to 4 wherein the permeable barrier has selective properties in the way it limits diffusion, as distinct from any selectivity phenomenon due to a membrane in the ISE itself.

6. Sensor system as claimed in any of Claims 1 to 5 wherein the ISE has internal electrolyte and an internal reference (e.g. Ag/AgCl) or a coated wire electrode where a base metal wire is in direct contact with a covering ionselective membrane.

Sensor system as claimed in any of Claims 1 to 6 wherein the ISE comprises a covering or layer (e.g. a membrane or a gel) over a core electrode and the components imparting ion-sensitivity may be in or on the core electrode and/or the said covering or layer.

8. Sensor system as claimed in any of Claims 1 to 7 wherein the ISE contains, when in use, an inner electrolyte and associated contacting electrodes.

9. Sensor system as claimed in any of Claims 1 to 8 wherein the ISE is a solid-state electrode, for example an ion 7 1116- selective field effect transistor (conveniently referred to as an 11ISFET11 device).

10. Sensor system as claimed in any of Claims 1 to 9 wherein the reference electrode assembly is a conventional silver/silver chloride (Ag/AgCl) or calomel electrode system, with its conventional filling solution (usually an electrolyte), enclosed in a container which has a "liquid junction" to make contact with the sample.

11. Sensor system as claimed in any of Claims 1 to 10 wherein the reference electrode is also an ISE which, under the conditions of use, produces a stable EMF.

12. Sensor system as claimed in any of Claims 1 to 11 wherein the electrolyte is provided in the device as made, for example in the form of a hydrated gel.

3. Sensor system as claimed in any of Claims 1 to 12 wherein the electrolyte is added at the time the sensor is to be used, for example by soaking in an appropriate electrolyte solution to make it ready for use.

14. Sensor system as claimed in any of Claims 1 to 13 wherein the electrolyte is provided by obtaining the necessary liquid from a sample itself, by permeation of water and diffusion of electrolyte ions from the sample through the permeable barrier when the device and a sample are brought together.

15. Sensor system as claimed in any of Claims I to 14 wherein the diffusion of ionic analyte to be determined is inward diffusion, i.e. through the permeable barrier from the sample towards the ISE.

16. Sensor system as claimed in any of Claims 1 to 15 wherein the electrolyte contents within the permeable barrier are provided with a concentration of analyte ion which is higher than that in the sample to be examined, so that diffusion of the analyte ion will be outwards - away from the ISE and into the sample - so resulting in a decrease of its concentration adjacent to the ISE.

17. Sensor system as claimed in any of Claims 1 to 16 which is in the form of a single unit, carrying the ISE and the )q- reference electrode assembly upon a support which serves to hold the assembly together while insulating the ISE and the reference electrode assembly from each other, for example by assembling the ISE and reference electrode assembly upon a substantially flat insulating support with the permeable barrier in the form of a "bubble,, or "envelope" over them.

18. Sensor system comprising an ion-sensitive electrode and a reference electrode, substantially as described.

19. Method for the determination of an ionic analyte in a sample, which comprises using a sensor device with an ionsensitive electrode and a reference electrode in combination as claimed in any of Claims 1 to 18.

20. Method for the determination of an ionic analyte in a sample, which comprises using a sensor device incorporating an ion-sensitive electrode and a reference electrode in combination, characterised in that these are the ion-sensitive electrode (and preferably also the reference electrode) is enclosed within a permeable barrier adapted to interface with a sample under examination, so that the sample itself no longer provides the main bridging contact between the ion-sensitive electrode and the reference electrode to complete the measuring circuit, measuring the potential between the ion-sensitive electrode and the reference electrode and using this measure for determining the content of the ionic analyte.

21. Method as claimed in Claim 19 or Claim 20 wherein the enclosed region around the ISE and within the permeable barrier is filled with an electrolyte containing an appropriately high concentration of an ion species liable to interfere with the desired measurements so that it can diffuse out through the permeable barrier and thereby reduce interference from that ion species if present in the sample.

22. Method as claimed in any of Claims 19 to 21 wherein several individual sensor devices of our invention are mounted together and the internal electrolyte (within the permeable barrier) of each of these is pre-loaded with different concentrations of the analyte to be measured so that, by contacting all the sensor devices with the sample, the flux of any interfering ions will be be constant for all of them, but the fluxes of the desired analyte will be different and their differential behaviour will then be a function of the concentration of the desired analyte in the sample and interference effects will be reduced.

23. Method as claimed in any of Claims 19 to 22 wherein the output potential measurements of the electrode system are made and plotted in terms of the rate of change of potential against the analyte concentration, and the plot slope is used as an indication of the analyte content.

24. Method as claimed in any of Claims 19 to 23 wherein the analyte sought is a sodium or potassium cation or a chloride, nitrate or fluoride anion.

25. Method as claimed in any of Claims 19 to 24 wherein an array of a number of sensor devices as claimed in any of Claims 1 to 18, each with its own internal electrolyte loaded with different pre-determined and known concentrations of the analyte sought, so that when the array is contacted with a sample, the different sensors will give different responses but for the sensor in which the loaded concentration of analyte ion equals that in the sample there will be no diffusion through the permeable barrier and no potential change with time will be observed, and the sensor showing "no change" ("nil diffusion") is easily and quickly distinguishable and will indicate the analyte concentration immediately.

26. Method for the electrolytic determination of an ionic analyte, substantially as described with reference to the foregoing example.