JPS584981B2 - ion selective electrode - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an electrode for analytical measurements, in particular for measuring ion concentration in a solution.

More specifically, the present invention relates to multilayer elements for use in potentiometrically determining ion concentrations in aqueous fluids, particularly body fluids such as serum.

Related technology includes a wide variety of electrodes of different types and constructions for measuring various ions in solution.

Instruments for such measurements typically include a reference electrode and a separate ion-selective electrode.

A reference cell is incorporated into the ion-selective electrode.

When a reference electrode and an ion-selective electrode are simultaneously immersed in the same test liquid, an electrochemical cell is constructed and a potential is developed.

This potential is proportional to the logarithm of the activity of a particular ion, which is a function of the concentration of that ion in the solution that the ion-selective electrode is sensitive to.

The relationship between this potential and the ion activity in the solution is ζ
It can be expressed using the well-known Nernst equation.

To measure the potential between the electrodes, an electrical measurement device is used, usually a direct readout circuit or a zero current potentiometric measurement circuit.

Conventional ion-selective electrodes include an electrode body (usually some type of glass container) containing a known reference solution in contact with a half cell of known potential, typically Ag/AgC1/"XMC1"; An ion-selective glass membrane is attached to the opening in the main body so that when the electrode is immersed in an unknown solution, the glass membrane comes into contact with both the reference solution inside the electrode body and the unknown solution. there were.

A suitable metal prolab coated with a layer of an insoluble salt of the metal was immersed in the reference solution in the electrode body and used for contacting the electrode.

The selectivity of the electrode is determined by the composition or components of the glass membrane.

In this specification, such an electrode will be referred to as a "barrel" electrode.

For this type of electrode, US Pat. No. 3,598,71
No. 3 and No. 3502560 have detailed explanations.

In recent years, synthetic polymeric ion-selective membranes have been developed as an alternative to ion-selective glass membranes, increasing the number of ions that can be measured potentiometrically using "barrel" electrodes.

Such membranes generally consist of a polymeric binder or support impregnated with a solution of an ion carrier.

This type of membrane can be designed to selectively transmit specific ions by carefully selecting the ion carrier, its solvent, etc., depending on the individual order.

This type of membrane and "barrel" electrodes using such a membrane in place of a glass membrane are described in detail in US Pat. No. 3,562,129, US Pat. No. 3,691,047 and US Pat.

The main advantage of the "barrel" electrode is that, in addition to its high selectivity, the electrode can be used repeatedly to measure the concentration of the same ion in different solutions, provided that some kind of rigorous adjustment operation is applied between measurements. It is possible to use it.

The main drawbacks of conventional ion-selective electrodes are as follows.

(1) Price.

Typically, a single electrode will cost several hundred dollars.

(2) Vulnerability.

The glass electrode body and membrane are fragile.

(3) Reproducibility.

Even if the preparation procedure is very careful, electrodes used to measure anion activity in unconditioned liquids such as body fluids have the potential for contamination by previous test liquids, so The exact composition of the coalescing) membrane is unknown, so the results are often questionable.

With the intention of solving these problems, Cattral, Rl.
W., and Freiser, H., Anal, Chem.
l, 431905 (1971) and James, ■0
, Carmack, Q., and Freiser, H.
, Anal, Cheml, 44856 (1972),
Calcium ion-selective "coated wire" electrodes have been proposed in which a platinum wire is coated with a layer of, for example, a polyvinyl chloride solution of calcium didodecyl phosphate (see also GB 1375785).

However, these authors say nothing about the use of internal standard reference electrodes or internal reference solutions, and exclude these components in their descriptions of specific examples.

An evaluation of such electrodes was made by Stworzewicz at a symposium on ion-selective electrodes held in Muttla Héred, Hungary in October 1972.
, To, Cyapkibwicz, J-.

5electivity of Coated Wir published by Lesko, M., et al.
e and Ion-3elective, Elect
Punger, E., ed. I
on-8elective Electrodes, 2
59-267, published in Budapest, 1973, in Proceedings), such electrodes have large electrical potential fluctuations and require frequent re-standardization. Difficult to commercially use.

Other known ion-selective electrodes include U.S. Pat.
There are reference electrodes and hydrogen ion selective electrodes described in No. 33495 and No. 3671414.

A reference solution of an ionic salt, e.g. KCI, thickened with a suitable "solvent medium" e.g. agar, carboxymethylcellulose, polyvinyl alcohol, etc. is placed into these retractable tube structures, one end of which is open to the test liquid. ,
A silver-silver halide reference electrode immersed in this is used.

In use, the reference solution is in direct contact with the test solution, with no ion-selective membrane in between.

The reference solution also contains a significant amount of water, as evidenced by the fact that the proposed electrode preparation procedure uses a syringe to inject the electrolyte into the tubing structure.

French Patent No. 2158905 contains appropriate salts (
For example, ion-selective electrodes have been described using solutions of KCI) in hydrated methylcellulose gels or in hydrophobic polystyrene ion exchange resins as internal reference electrolytes.

The gel or ion exchange resin is overcoated with an ion-selective membrane of organopolysiloxane or polycarbonate containing a suitable ion carrier, such as palinomycin, dissolved or dispersed therein.

The internal reference electrode described in that patent consists of a metal wire (eg Ag) with a coating of controlled salt (eg AgCl).

Regardless of which reference electrolyte material (ie, gel or ion exchange resin) is used, the reference electrolyte material is "hydrated" prior to application of the ion-selective membrane.

When the hydrophobic ion exchange resin material is prepared by the method of US Pat. No. 3,134,697, as described in that French patent, its water content is between 15 and 50%.

Those skilled in the art will appreciate that it is not easy to remove this water of hydration from such ion exchange resin materials.

US Pat. No. 3,730,868 describes a carbon dioxide sensitive electrode using a silver/silver halide internal reference electrode.

It also uses a quinhydrone electrode as a pH sensor to detect changes in pH caused by CO2 passing through an overcoated carbon dioxide permeable membrane.

However, there is no suggestion in this patent that a useful electrode would be obtained by directly overcoating the redox electrode with an ion-selective membrane.

Rather, CO2 from CO2 passing through a CO2-permeable membrane
An ion exchange resin is used as an electrolytic solution to quantify changes in concentration.

The electrode of this US patent is therefore similar to that of French Patent No. 2,158,905, except that it uses a solid quinhydrone electrode as the pH sensor.

No. 3,856,649 to GeHshaw et al. and Analytical Chemis by the same authors.
Miniatu published in try volume 45 pages 1782-84
rb 5olid 5tate Potassium
Electrode for Serum Analysis
The paper entitled ``Sis'' describes a solid-state ion-selective electrode for the detection of potassium ions.

This has on the wire an electrically conductive internal element (on its surface part there is a salt having the cationic form of the internal element as a cation and also an anion), in close contact with the salt and its It consists of a solid hydrophilic layer containing a water-soluble salt of an anion, and a hydrophobic layer in close contact with the hydrophilic layer, so that when the electrode is immersed in a liquid containing the analyte ion, the hydrophilic layer It is designed so that it does not come into contact with the test ion-containing liquid.

The patent states that it is important to maintain the electrode in a "hydrated" state during its manufacturing process, and states in column 3, section 2.
Lines 7-29 say, ``This state of hydration appears to be important for the proper functioning of the electrodes of this invention.

” is stated.

Although it is not specifically stated in the patent written by Genshaw, the invention is clearly stated in the above-mentioned paper and as shown in the examples below, and as found in the evaluation of this type of electrode, it is possible to achieve accurate reproducibility. In order to obtain certain results, this type of electrode should be kept dry (i.e. under atmospheric conditions of 40-50% relative humidity) for a long period of time after manufacture.
Must be hydrated before use.

Hydration requires that the electrode be stored in an aqueous solution or preconditioned in an aqueous solution before being used to measure ioglossia.

If this is not done, at least until the electrode is hydrated by the sample liquid, the result will be a violation of the Nernst equation and will exhibit substantially random fluctuations, as discussed below.

Furthermore, if the electrode is to be used in a "dry" state, i.e. without any preconditioning, to quantify ions in small volumes of sample liquid, on the order of about 100 μl or less, it is necessary to bring the wire electrode into equilibrium. Because so much water is absorbed, the actual ion concentration changes considerably before reproducible potential readings are obtained.

Therefore, although the "solid state" electrodes of Genshaw et al. have considerable advantages over their predecessors in terms of electrode size and the amount of sample required for measurements, they still require storage in a wet state. Alternatively, it has the disadvantage that it needs to be hydrated (ie, preconditioned) for a certain period of time before use.

Israeli Patent No. 3 entitled “Ion Specificity Measuring Electrode”
No. 5473 describes an ion-selective membrane having an ion-selective membrane in conductive contact with a "conductive solid material", i.e., graphite (granular or compact), and from which the electrode leads are taken out. Although electrodes are described, there is no mention or suggestion of reference solutions or redox caggles.

No. 3,649,506 and US Pat. No. 3,718,569, a conductor with a surface layer of an electrochemically active metal is coated with a first coating consisting of a mixture of glass and a halide of said active metal and then ion-selective. A "solid state" glass electrode coated with a second coating of glass is described.

These electrodes will also require similar preconditioning as conventional glass electrodes.

US Pat. No. 3,900,382 describes a miniature electrochemical electrode that acts as an oxygen or carbon dioxide electrode and as an ion-selective electrode.

There is a suggestion in column 2, lines 43-53 of this patent to the effect that each layer can be applied by dipping the metal wire core of the electrode into the respective organic solution and then evaporating the solvent; This does not apply to the "electrolyte layer" consisting of sodium bicarbonate, sodium chloride, and a thickener, which is shown in No. 17 in the same patent.

This is because this layer is not obtained from an "organic solution."

Furthermore, column 4, lines 49-58 of the same patent specifies that the electrolyte is an aqueous solution.

The invention provides a dry operable ion-selective electrode comprising (a) a dry internal reference electrode and (b) a hydrophobic ion-selective membrane in contact with the reference electrode.

In particular, the invention relates to: (a) a dry internal reference electrode comprising one of the following: (1) a conductive layer of a metal in contact with a layer of an insoluble salt of the metal; and (2) a redox couple comprising an electrically conductive layer and at least two types of water-soluble redox couple layers. a redox-coupled electrode comprising a layer comprising a water-soluble salt, the layer comprising a water-soluble salt formed from the dried residue of a solution of the salt and a hydrophilic polymeric binder in a solvent for the polymer and the salt; and (b) a hydrophobic ion-selective membrane in contact with said reference electrode and having a predetermined uniform thickness in the portion to be in contact with the test sample, wherein said membrane is in contact with said reference electrode. The membrane comprises a hydrophobic binder containing dispersed ion carriers dissolved in a carrier solvent.

The ion-selective electrode of the present invention does not need to be preconditioned before use for A-4th degree measurements.

The reference electrode may be a metal/metal salt reference half-cell or a dried single-layer or multi-layer redox-coupled reference electrode (wet as well when applying an aqueous sample as described below).
Even if it is, it's fine.

As used herein, the term "dried" is defined below.

Preferably, the hydrophobic membrane comprises a hydrophobic binder containing a dispersed inert ion carrier dissolved in a suitable carrier solvent.

The contact surface with the test sample is preferably substantially flat;
For this purpose, it is preferable to use a hydrophobic membrane that has a predetermined uniform thickness in the area where it should come into contact with the test sample.

The electrode may optionally have a support.

The novel ion-selective electrode of the present invention, designed for potentiometric analysis of liquids, is simple in construction, easy to manufacture at a reasonably low cost, and therefore disposable and economical for one-time use. Therefore, the ion-selective membrane remains intact for each measurement, and thus the results are highly accurate.

As will be explained in detail later, the electrodes of the present invention can be manufactured in a variety of ways, shapes, and sizes.

To fully understand this invention, one must understand the phenomenon of electrode drift.

Electrode drift is a change over time in the potential experienced by an ion-selective electrode in contact with an ion-containing solution.

Electrode drift is apparently caused by a number of factors, including the fact that the solvent (generally water) in the test solution passes through an ion-selective membrane over time, which causes the concentration of ions in the test solution to change in the vicinity of the electrode. Due to fluctuations, etc.

All ion-selective electrodes drift to a greater or lesser extent, but conventional electrodes minimize drift phenomena by preconditioning them to an equilibrium state close to that likely to be encountered under test conditions.

In this way, the person using the electrode reduces the factors that cause drift, thereby reducing drift under test conditions.

Therefore, the use of ion-selective electrodes without any preconditioning can lead to severe drift, and the measurement of ion concentrations is usually difficult before the equilibrium state achieved by preconditioning is reached under the test conditions. One would think that one would only obtain potential measurements that would be unusable.

According to the invention, it is possible to produce an ion-selective electrode that can be used without any kind of preconditioning, and the drift that the electrode exhibits, which can be considerable in some cases, can be corrected. It was found that the concentration of specific ions in the test liquid can be measured accurately and with good reproducibility.

In this specification, the term "dry operable" means "dry operable" before use.
The ion activity potential, which is a function of the ion concentration of the aqueous analyte, can be reproducibly adjusted without wet storage (i.e., kept in an aqueous solution) or preconditioning (i.e., immersed in a salt solution). Used to describe ion-selective electrodes that can be measured metrically.

What is meant by this term is that a "dry operable" electrode provides an accurate, reproducible, and detectable measurement of potential without having to pre-hydrate it or bring it into said equilibrium state; This means that by correcting this, it is possible to determine the ion activity and, ultimately, the ion concentration in the test aqueous solution.

Many of the electrodes of this invention are dry-operable, even when used immediately after storage at 20% RH.

The practical meaning of this term will become even clearer from the following description and specific examples.

With respect to the individual layers of the electrodes of this invention, the term "thin" or "thin layer" is used herein to describe a layer having a thickness of about 1.25 mm or less.

Such a thin layer has a thickness of about 0.25 mm or less, particularly about 0.25 mm or less.
Preferably, it is on the order of 0.05 mm or less.

In this specification, the term "predetermined and uniform" with respect to the thickness of the ion-selective membrane of a "dry operable" electrode describes the thickness tolerance of that layer at the point where it is to be in contact with the test sample. used for

This tolerance can be achieved if the drift exhibited by an electrode with such a layer can be corrected, i.e. without preconditioning the electrode or leaving it in the test solution for an extended period of time without adjusting it with the test solution. , is satisfied if a reproducible and detectable potential measurement value can be obtained, from which the concentration can be determined by correction within the tolerance range of the intended measurement.

Electrodes that do not have a "predetermined uniform" thickness will exhibit random drift and correction of potential measurements will not yield results that allow direct determination of ion concentration.

The uniformity of thickness required for dry operation is generally such that the maximum variation in film thickness is 20% or less in the portion of the film that is to be brought into contact with the test sample.

In this specification, "
The term "dried" means that such a layer is subjected to drying conditions, i.e., high temperature, low vapor pressure, etc. during manufacture, and a sufficient amount of solvent or dispersion medium is removed to form the layer and an overcoat layer thereon. refers to the physical state of such a layer obtained by rendering it non-tacky in the sense normally understood in the coatings industry before application.

Drying to remove this solvent or dispersion medium is one of the main factors that gives the electrode of the present invention the possibility of "dry operation."

Although the mechanism for why this occurs is not fully understood, and the electrode of the present invention is not limited by any theory of operation, the layer shrinks with loss of liquid during the drying process. This ensures intimate contact between the "dried" layer and the adjacent overcoated ion-selective membrane even under harsh storage conditions of extremely low relative humidity, i.e. 20% RH or less. It seems that it will.

In this regard, it is generally desirable to select the relative humidity of the drying conditions during manufacturing in relation to the anticipated conditions of use.

In so doing, an optimal hydration state for the ion-selective membrane would be achieved.

However, useful electrodes can be obtained without doing so.

More specific conditions and requirements for certain dry requirements of the electrodes of this invention are discussed below.

A typical example of the dried layer referred to herein is a layer obtained by forming the layer under the following conditions: (A) a solution containing about 5 to about 9% by weight gelatin; ? /m2 and dried under the following conditions:

(1) cold set at 4° C., 50% RH dew point for about 6 minutes, and (2) dry at 21° C., 50% RH for about 4 minutes.

(B) About 6% by weight of a solution containing about 5% to about 9% by weight of polyvinyl alcohol or 2-hydroxyethyl polyacrylate.
4? /m2 and dried under the following conditions:

That is, (1) heat set at 55° C., 50% RH for about 6 minutes, and (2) dry at 35° C., 50% RH for about 4 minutes.

These drying conditions are not absolute, but are representative of those that can be used to obtain dried layers of the type described herein using various polymeric matrices suitable as binders for the reference electrolyte layer. It is a condition.

The layer thus obtained has the "dryness" required for the reference electrode layer before application of the ion-selective membrane.

The electrodes of this invention generally provide concentration measurements with a coefficient of variation of less than about 10%.

For electrodes produced according to preferred embodiments, this coefficient of variation is less than about 3%, and according to particularly preferred embodiments, coefficients of variation of less than about 2% have been achieved.

The coefficient of variation is the standard deviation divided by the mean and multiplied by 100.

The average is the arithmetic mean value of a series of a large number of measured values, that is, the sum of the measured values divided by the number of measurements.

Standard deviation is calculated by finding the difference between each measurement value obtained in a series of measurements and the average value, squaring each layer, summing the squared values, dividing by the number of measurements, and then square-rooting the result. It is the number obtained by

As previously mentioned, what has traditionally been called a "solid state" electrode can contain either an aqueous solution of salt, a hydrated salt, or a salt-impregnated glass layer as the internal electrolyte for the measurement of ion concentrations. It was necessary to do this.

All of these known electrodes required preliminary conditioning before being used for ion concentration determination.

According to this invention, surprisingly, "dried"
Using an electrode with an internal reference electrolyte and an ion-selective membrane of predetermined uniform thickness, potentiometric measurements of ion concentrations can be made with a level of precision previously only achievable with preconditioned electrodes. It has been found that the process can be carried out under ambient conditions and without the need for substantial preconditioning or wet storage.

The ion-selective electrode of the present invention has a dry, solid appearance and can perform accurate measurements with as little as a single drop (ie, about 50 μl or less, preferably about 10 μl) of test liquid.

The electrodes of this invention do not require pre-conditioning before use, can generally perform measurements within 5 minutes, are inexpensive, can be disposed of after a single measurement, avoid contamination from use, and can be used for each new measurement. This ensures the integrity of the ion-selective membrane.

Furthermore, according to the new measurement method using the ion-selective membrane of the present invention, it is possible to quickly and accurately quantify ions.

Hereinafter, in this specification, one layer is referred to as "on top of another layer".
"coating,""applying," or "spreading" refers to the act of depositing or depositing one layer on top of another, as well as the actual application of each layer using conventional coating, dipping, or extrusion techniques. It goes without saying that the meaning includes the covering operation.

The dry-operable ion-selective electrode of this invention comprises (a)
(b) a hydrophobic, ion-selective membrane in contact with the reference electrode, the portion of which is to be contacted with the test liquid having a predetermined uniform thickness; and (e) Depending on the case, it further comprises a support.

As in any ion-selective electrode useful for measuring ion activity and thus ion concentration in a reference electrode solution, the electrode of the present invention also has an internal reference electrode.

The internal reference electrode shows a constant reference potential, and the potential generated at the interface between the ion-selective electrode and the test liquid is measured with respect to this reference potential.

According to the invention, there are two types of internal reference electrodes, each exhibiting a constant reference potential necessary to achieve useful results.

Useful reference electrodes are: (1) metal/metal salt electrodes (Figure 1) and (2) redox couple electrodes (Figure 2).

Metal/Metal Salt Electrodes A commonly used internal reference electrode consists of a metal in contact with an insoluble salt of the metal, which in turn is in contact with an electrolyte, a solution containing the anion of the metal salt.

An example of such an element that is very commonly used is Ag/
It can be represented by AgC1/XMCI-, where XMC1- indicates a solution of known C1- concentration, and consists of a silver wire coated with silver chloride.

This can be produced, for example, by immersing a silver wire in an aqueous solution with a known chloride ion concentration.

The calomel electrode, Hg/Hg2C12/C1-, is another example of this type of electrode.

This type of internal reference electrode, in most barrel electrodes,
It is also used in known so-called "solid state" (as so called in the aforementioned US patents to Genshaw et al.) electrodes.

In known "solid state" electrodes, the electrolyte solution consists of a hydrated gel, hydrated PVA, a hydrophobic ion exchange resin, etc., as described above.

In contrast, the reference electrode of the present invention is dried during manufacture and, unexpectedly, does not require conditioning before use.

According to the invention, a metal/metal salt reference electrode comprises a conductive layer of a metal in contact with a layer of a salt of the metal as used in known electrodes; It has a dried electrolyte.

The conductive metal layer can be comprised of any suitable conductive metal of the known type conventionally used in such electrodes, unless inconsistent with the particular structure of the electrode described herein.

Particularly useful conductive metals include silver, nickel, platinum and appropriately thin layers of gold.

The salt layer in contact with the conductive layer can consist essentially of any insoluble salt of the metal of the conductive layer provided that it establishes a constant interfacial potential with the metal of the conductive layer.

Such layers are well known and described in detail in the aforementioned patents and other publications, but generally include salts of the metal that are oxidation products of the metal, such as AgCl, Hg2
It consists of c12 etc.

In a particularly preferred embodiment of this invention, the well-known Ag/A
The potential of the reference electrode is established using the interface gnX (where X is 5--1CI-1Br- or ■- and n is 1 or 2).

Electrode elements of this type can be manufactured using a variety of well-known techniques.

By way of example, a layer of silver can be produced as a wire, foil or supported thin layer by dipping it into molten silver halide.

In a preferred embodiment of the invention, silver is vacuum deposited on a suitable support of the type described below, preferably an insulating film, and then the surface layer of the silver layer is chemically converted to silver halide. The silver/silver halide couple described above is created.

Generally, the technique of chemically adding a metal to a metal halide involves placing the surface of the metal (silver in this case) in a solution of a salt containing the same anion as the halide desired to be formed, until the desired chemical reaction occurs. There is a method of contacting or exposing the material for a sufficient period of time and at a sufficient temperature.

Although typical conditions necessary for this type of chemical reaction are well known, a simple and preferred technique is illustrated in the Examples below.

Other useful techniques for manufacturing such electrodes include U.S. Pat.
No. 806439.

Although the techniques described in these patents are primarily intended for the production of wire electrodes, it is within the skill of those skilled in the art to transfer the techniques to the production of electrodes supported on thin layers of polymeric support film. would be easy.

Alternatively, a layer of silver halide islands may be applied over the silver layer.

Provided that proper contact is maintained between the silver and silver halide.

The ratio of the thickness of the metal layer to the metal salt layer at the metal/metal salt interface is virtually arbitrary, but in preferred embodiments to ensure a sufficiently dense metal salt layer, the thickness of the insoluble metal salt layer is The thickness is preferably 10% or more of the total thickness of the conductive metal layer.

In a preferred embodiment of the invention in which the surface layer of the vacuum deposited silver layer is converted to the appropriate salt, about 10 to about 20% of the thickness of the silver layer is converted to the silver salt by chemical conversion techniques.

The second component in the metal/metal salt reference electrode of this invention consists of an electrolyte layer.

In a preferred embodiment of this invention, the electrolyte layer is
This is a dried hydrophilic layer.

The dried electrolyte solution of this invention consists of a hydrophilic binder in solid solution with a salt.

According to a preferred embodiment, the anions of this salt are common to those of the salt of the metal salt layer and at least some of the cations of this salt are identical to the ions to be measured.

The "dried" hydrophilic electrolyte solution referred to in this specification is
This is distinctly different from the hydrated polyvinyl alcohol layer described in US Pat. No. 3,856,649.

The "dried" reference solution of this invention consists of the dried residue of a solution of salts and the appropriate hydrophilic polymeric binder in a solvent for the salts and polymers.

This distinction will become even clearer from the following description of how to make and use the electrodes of this invention. , the salt of the electrolyte layer and, if the layer is formed by coating, any hydrophilic material suitable to form a solvent system that is miscible with both the ionic salt and the polymeric binder.

Preferred materials of this type are hydrophilic natural and synthetic polymers such as polyvinyl alcohol, gelatin, agarose, deionized gelatin, polyacrylamide, polyvinylpyrrolidone, polyhydroxyethyl acrylate, polymethacrylic acid, hydroxyethyl polyacrylic acid, etc. It is a film-forming substance.

Particularly preferred among these materials are hydrophilic colloids such as gelatin (especially deionized gelatin), agarose, polyvinyl alcohol and hydroxyethyl polyacrylate.

Some residual solvent of the ionic salt must remain in the "dried solution" and contribute to the electrolytic conductivity within the polymer layer.

Therefore, the layer must not be completely photo-dried so that there is no residual solvent.

As a general rule, when water is the solvent, the residual water is
A significant amount of less than about 20%, preferably less than 20%, particularly preferably 1 to 2%, of the total weight of the "dried solution" and the "dried" electrolyte is non-stick.

Similar residual solvent levels are desirable for extra-Mercury solvents.

The ionic salt dissolved in the polymeric binder solution will be determined by the metal/metal salt moiety 6 composition of the electrode.

For example, in the case of a potassium-selective electrode using AgCl as the insoluble metal salt, sodium chloride or the like cannot be used, but potassium chloride should be selected theoretically.

Sodium chloride may be useful when measuring sodium ions with a device of the same construction.

That is, the salt generally has a cation selected from ammonium, alkali metals and alkaline earth metals, and any other suitable cation to which the electrode responds, and as an anion a water-soluble salt having a halogen or sulfur, depending on the composition of the metal salt layer. It must be sexual salt.

These anionic conductive metal salts are generally insoluble in water.

Suitable solvents for the polymeric binder and ionic groups include:
Mainly depending on the type of their polymers and salts.

In general, any polar solvent that dissolves the salts and polymers will be sufficient.

Thus, water is the preferred solvent for hydrophilic layers such as polyvinyl alcohol and gelatin.

Since the "dried" electrolyte layer thickness determines to some extent the response characteristics of the electrode, it is generally desirable for the "dried" layer to be relatively thin.

A dry layer thickness of about 0.0025 mm to about 0.013 mm has been found useful.

The preferred thickness is about 0.005 mm.

Of course, if the response characteristics of the electrode are not important, the thickness of the layer can vary widely, and the upper and lower limits will be determined by the common general knowledge of those skilled in the art and the conditions of use of the finished electrode.

The concentration of ionic salt in the "dried electrolyte layer" can also vary widely, depending on the amount of polymer used, among other things, such as the required response time.

Binder level is about 2.4P/m” or about lot/
m2, the salt concentration is about 1,4
0 to about 2.5? /m2.

If the salt concentration is below this level, electrode drift may become a problem, and if it is above this level, layer application becomes somewhat difficult.

Of course, salt concentrations outside the above ranges may be used if drift is less of a problem and substantially thicker layers are used, or if the layers are created by techniques other than coating.

Generally, a salt concentration of about 30 to about 50 percent by weight of total solids in the layer is preferred.

If the reference electrode is manufactured by coating one layer on top of another, it may be desirable to include a surfactant or coating aid in the coating solution during manufacture.

Such additives should generally be non-ionic and, whatever their composition, should not contain any ions that would alter the constant potential difference that exists at each electrode layer interface. , is preferably inert to potash potentiometric measurements.

Of course, if additives are used that alter the potential difference at each interface, two identical ion-selective electrodes can be used, one connected to a solution of known ion concentration and the other connected to an unknown test solution. By using differential measurements to compare the readings of those electrodes, the modification can correct for this.

Among the substances found to be useful for the above purpose are natural surfactants such as saponins, synthetic substances such as polyethylene glycol and Ofin Math.
Other useful materials of this type include octylphenoxypolyethoxyethanols such as TX-100, TX-405, etc., available from Rohm &Haas; There is.

According to another aspect, useful metals/metal salts, especially Ag/A
gX) The reference electrode element can be manufactured using techniques commonly used in the manufacture of photographic films.

According to such an operation, one or both of the metal (ie, silver) and the metal salt (ie, silver halide) can be produced by coating a suitable silver halide photographic emulsion and subjecting it to a prescribed treatment.

For example, useful silver halide layers include a vacuum deposited silver layer with a conventional fine-grain silver chloride-gelatin emulsion, and 0.5% gelatin.
054 to 0.54 P/m” and silver 1 as silver chloride
．． It can be manufactured by coating with a coverage of 16 to 1.83 g/m2.

When such an electrode was tested using a chloride ion standard solution, it showed a response that substantially matched the Nernst equation (
In other words, the slope is approximately 59 mV/1 digit).

A useful silver layer capable of overcoating the silver halide layer as described above was prepared as follows.

That is, a layer of fine-grain silver chloride-gelatin emulsion is deposited on a polyethylene terephthalate support using conventional photographic film manufacturing techniques to obtain a silver chloride concentration of 2.02? The silver chloride layer was coated with a coverage of 95/m2 gelatin and 95/m2 gelatin and then developed for 5 minutes at room temperature under conditions in a standard black and white developer known as Kodak Developer D-19.

After this layer was thoroughly washed with water and dried, it was overcoated with a silver chloride emulsion as described above.

The response of this electrode sample to the standard chloride ion solution was satisfactory.

Useful electrodes could also be obtained by coating silver chloride emulsions on deposited layers of gold, copper and nickel, and by using fine-grained silver bromide emulsions to create metal salt layers.

Redox Electrode A second type of internal reference electrode useful in the practice of this invention is a so-called redox electrode (hereinafter referred to as a redox electrode).

Redox electrodes are well known and generally consist of an inert metal wire immersed in a solution containing two different oxidation states of the same chemical species.

An example of such an electrode is one consisting of a platinum wire immersed in a solution containing ferrous and ferric ions.

This battery can be abbreviated as Pt/Fe+ or Fe++.

The electrode reaction is Fe10++e-=Fe+10.

Redox electrodes can also be created using organic molecules that exist in two different oxidation states.

The most widely used type of this type is the so-called Golden Quadrupole, in which case the redox system is , and the battery can be abbreviated as Pt/QH2,Q,H+.

This type of redox electrode can also be made in the "solid state" and serve as the internal reference element of the ion-selective composite electrode of the present invention.

Such an electrode can also be used as an external reference electrode in place of a conventional external reference electrode, such as a standard calomel (ie, Hg/HgC12) electrode, in the measurement of total ion concentration in a solution.

Such a redox electrode is also described in US Pat. No. 3,730,868.

The redox electrode of this invention is (a) Solid conductive layer (b) Redox couple If it comes into contact with

The redox couple may be dissolved or dispersed in the conductive layer, or it may be dissolved or dispersed in a suitable binder to form a separate solid layer that is brought into conductive contact with the conductive layer. You may let them.

Conductive Layer The conductive layer of the redox reference electrode consists of an electrically conductive material or conductor (conductor in the sense commonly understood in the drawing industry).

Of course, the conductive material may not interact with the redox composition other than to react in the desired and controlled manner necessary for electrode operation, i.e. to establish a stable reference potential. Must not be.

Useful results have been obtained with inert conductors such as carbon, platinum, gold and nickel.

The conductor may be of any type so long as it is selected so as not to cause unstable electrochemical or other undesirable interactions with the redox couple.

A particularly useful conductor is carbon (particularly granular carbon), as detailed below and as seen from the examples.

When the inert conductor is in the form of discrete conductive particles, as in the case of carbon, it may be necessary to hold such particles in conductive contact in a solid phase by some kind of binder or matrix. be.

The binder can be any material that provides intimate particle-to-particle contact and conductive contact with the conductor and redox couple.

Such binders typically consist of relatively low concentrations of hydrophilic polymers such as gelatin, polyvinyl alcohol and polyvinylpyrrolidone.

However, it is also possible to use hydrophobic polymers as binders, such as silicone rubber.

Whatever binder is used, the ratio of conductor to binder must be high enough to ensure low resistance of the layer and proper conductivity.

This can be achieved by using a conductor to binder weight ratio of about 1:1 to about 3:2.

Redox Couple Compositions Redox couple compositions consist of soluble redox couples and require some means to hold the composition in solid form until such time that the electrode is wetted and at least a portion of the redox couple dissolves and comes into contact with the conductor. It is.

Other means for this generally consist of some kind of matrix or binder or other matrix or binder containing the redox couple as a solid solution or dispersion.

The redox cup of the present invention is composed of a pair of identical chemical species (usually ions) having different oxidation states, as described above.

The formal potential of the reference electrode of the present invention, that is, the electrical potential of a redox couple at equal concentrations of reducing and oxidizing components at a certain ionic strength is (1) a certain redox couple and (2) the activity of the oxidizing component and the activity of the reducing component. It is determined by the ratio of

According to a preferred embodiment of the invention, the ratio of oxidized to reduced components (ie, the molar ratio of material in one oxidation state to material in another oxidation state) is about 1.

Naturally, depending on the type of measurement performed using the electrodes described herein, this ratio can vary within a very wide range.

When the electrode is wetted with a sample solution, the redox scuffle must be able to form a stable interface with the conductive layer and establish a stable and reproducible potential.

That is, the redox couple must be able to exchange electrons with the conductive layer in a defined manner when the potentiometric circuit is closed.

The conductive layer and the redox coggle cooperate to create a redox chemical potential in a fast electrochemical exchange reaction between the redox couple and the conductor.

This ability to establish a certain potential can be explained by the ``compatibility'' between the redox couple and the conductive layer.
Reference is made in this specification as .lity)J.

A redox couple that easily establishes such a constant potential in a given conductor is termed "compatibl" with the conductor.
able) J.

According to a preferred embodiment, it should be understood that the oxidized and reduced forms of the couple must be stable for the desired storage time to provide a shelf-stable electrode.

Redox couples that have been found to be particularly useful in the successful practice of this invention include Fe(CN)6-3/Fe(CN)6-4.
/ferrous ion couple and Co (thylpyridyl)2+
3/Co (tylpyridyl) 2+2 (alpyridyl is 2.
6-di2'-pyridylpyridine)
/Part ■There is a cobalt caffle.

Redox couples that are capable of exchanging electrons with a compatible conductive layer and are sufficiently stable to air oxidation to provide useful storage properties are useful in the successful practice of this invention.

Although the redox couple can be applied directly to the conductive layer as a solid phase without the use of a matrix or binder, many useful redox couples have high solubility and this type of material can be applied in solid form (i.e. as a crystal, etc.) to the conductive layer. Because of the difficulties in applying redox couples, it is generally desirable to apply the redox couple as a dispersion or solution in a suitably porous or water-permeable binder or matrix.

Preferred water-permeable matrices for redox couples consist of hydrophilic colloids such as gelatin, polyvinyl alcohol, polyacrylamide, polyvinylpyrrolidone, and the like.

This colloid is particularly preferred if it is as shown in (a) and (b) below.

(a) sufficiently cured or cross-linked to prevent substantial dissolution thereof by water that is capable of contacting the colloid; and (b) sufficiently hydrophilic to permit electrolytic contact with the conductive metal layer. Being sexual.

As mentioned above, it is also possible to use highly porous layers of hydrophobic material that are wettable due to their porosity or that allow conductive contact between the particulate members of the redox couple due to their porosity.

Thus cellulose acetate or 8s/1015 poly(n-
Butyl methacrylate toko 2-acrylamide-2-
A water-permeable, highly porous layer of a hydrophobic material such as methylpropanesulfonic acid-io2-acetoacetoxyethyl methacrylate can be used as a binder or matrix for the redox couple.

Although redox reference electrodes are generally made in a two-layer arrangement (i.e., a solid layer of inert conductor is in conductive contact with an overlying solid dry redox couple layer), both the inert conductor and the redox couple are combined in a single layer. It has also been found that useful electrodes can be obtained by blending with

In the case of a single layer, it is preferred to use a hydrophilic matrix of the type described above in conjunction with the redox-coupled layer of the coalescing layer.

However, hydrophobic binders are also useful.

Embodiments of single layer reference electrodes are described in the examples below.

The techniques for their construction and use are the same as for the construction of bilayer or bilayer electrodes as described herein.

Ion-Selective Membrane When using any of the internal reference electrodes described above, the ion-selective membrane is laminated, coated or otherwise applied directly thereon.

In order to effectively carry out this invention, the ion-selective membrane must be applied during fabrication so that the ion-selective membrane and the surface of the adjacent reference electrode are closely and uniformly bonded (at least in the area in contact with the test solution). ``Dry operation possible'' with secure contact
It is important to obtain the electrodes.

Such intimate contact during fabrication of the ion-selective membrane and the dried internal reference electrode creates a reference electrode-ion-selective membrane interface that responds almost immediately upon contact between the ion-selective membrane and the test solution. do.

Among the patents and publications describing ion-selective membranes of the type useful in this invention are: U.S. Pat.
62129, 3753887, 3856649: British Patent No. 1375446: German Patent Publication No. 2251287: Morf, W. E., Kohr, G., and Simon
, Wo, “Reduction of the Ani”
on Interference in Neutra
l Carrier Liquid-Membrane
Electrodes Re5ponsive to
"Cations", Analytical Lett
ers, Vol, 7, No. 1, pp. 9-22 (1
974); Morfow, El, Ammann, Dl, Prets
Ch.

Eo, and Simon, W., “Carrier A.
ntibiotics and Model Comp
ounds as Components of Io
n-3ensistive Electrodes”, P
ure and Applied Chemistry
, Vol. 36, No. 4, pp. 421-39 (19
73); Amman, D., Pretsch, Eo, and Si
mon, W, “Sodium Ion-3electi
ve Electrodes Ba5edon Neu
tral Carrier”, Analytical
Letters Vol. 7, No. 1, pp.

23-32 (1974); Cattrall, RoWo, and Freiser
,H,,Anal,Chem,,Sat3,1905(19
71); and James, Hl, Carmack Go, and Fr.
eiser, H,, Anal, Chem,, 44.85
6 (1972).

This type of well-known membrane generally comprises an inert hydrophobic binder or matrix with ion carriers dispersed therein.

The ion carrier imparts selectivity to the membrane.

The carrier is dissolved in a carrier solvent to provide adequate ion mobility in the membrane.

The carrier solvent also acts as a plasticizer for the membrane binder.

The binder used in the ion-selective membrane of this invention includes:
Included are hydrophobic natural or synthetic polymers that are sufficiently permeable to form thin films with ionophores and ionophore solvents to produce apparent ion mobility across them.

In detail, polyvinyl chloride, polyvinylidene chloride, acrylonitrile, polyurethane (and aromatic polyurethane), copolymers of polyvinyl chloride and polyvinyl acetate, copolymers of polyvinyl chloride and polyvinylidene chloride,
Polyvinyl butyral, polyvinyl formal, polyvinyl acetate, silicone distomers, copolymers of polyvinyl alcohol, cellulose esters, polycarbonates, carboxylated polymers of vinyl chloride and mixtures and copolymers of such materials which have proven useful. It is a combination.

Films of such materials containing ion carriers and carrier solvents can be produced using conventional film coating or casting techniques and coated on an internal reference electrode or on some suitable intermediate layer, as shown in the examples. By coating and film forming directly on
Alternatively, it can be formed by forming them separately and laminating them.

The ion carrier used in ion-selective membranes is generally a substance that is capable of preferentially associating or binding itself with the particular alkali metal ion, alkaline earth metal ion, ammonium ion, or other ion desired.

The manner in which ions become associated with carriers is not completely understood, but is generally thought to be complexation, steric trapping phenomena by coordination or ion exchange.

What is a suitable ion carrier? This will be explained in more detail below.

Since the selectivity of an electrode for a particular ion depends on the chemical nature of the ion carrier, the use of different chemical components as uncharged ion carriers will result in different membranes for use in ion-selective electrodes that are specific for different ions. is obtained.

Examples of such ingredients are numerous, and some of those known to be antibiotics include: (1) Valithumimin, potassium selective (over sodium), constructed in accordance with this invention; Ion carrier that gives the membrane selectivity for potassium ions of the order of 10-4 and selectivity for ammonium ions (over sodium) of the order of 10-2: (2) Makes the membrane selective for lithium, rubidium, potassium, cesium, or sodium. and (3) other substances with ion selectivity similar to palinomycin, such as other substances of the palinomycin group, tetralactones, macrolidoactin (monactin, nonactin, dinactin, trinactin). ), enninatine group (enninatin A.

B), cyclohexadepsipeptide, gramicidin, nigericin, dianemycin, nystatin, mononsin,
Antamanid and alamethicin (cyclic polypeptide)
.

It is also possible to use one or a mixture of substances of the following formula: R2ni(CH2)n-C0O-CH2-CH3n=1
to 10 ■ R'nee CH3 R2: (CH2)6-CHs ■ R1=R2nee CH2-CH2-CH3 ■ R'nee CH2-CH2-CH3 R2nie CH2-C-(CH3)3 Other useful ion carriers Examples are quaternary borates (especially tetraphenylboron) and quaternary ammonium salts.

Compounds such as trifluoroacetyl-p-alkylbenzene are described in US Pat. No. 3,723,281 for HCO3-.

Compounds of the following structural formula are also useful as ionophores: (where (a) R=CH2CON(CH2CH2CH3)2
11zzi, M., PretSch, E., Simon
W., Borowitz, 1. J., Weiss,
L,, He1v.

Chim, Acta, 58-1535 (1975).

Numerous other useful materials are described in the aforementioned publications and patents, as well as other literature on this subject.

The concentration of ion carriers in the membrane will, of course, vary with the particular ion carrier used, the analysis to be performed on the ions, the carrier solvent, etc.

However, in general, assuming the film thickness is preferred here, carrier concentrations below about 0.11 per square meter of film produce marginal and generally undesirable results.

Ion carrier concentrations of about 0.3 to about 0.5 y/m2 are preferred.

Ion carriers can be added at much higher levels, but the cost of many of these materials makes such levels economically disadvantageous.

The carrier solvent provides ion mobility within the membrane.

Although the mechanism of ion transport within such membranes is not completely understood, the presence of a carrier solvent is clearly necessary to obtain excellent ion transport.

The carrier solvent must, of course, be compatible with the membrane binder and be a solvent for the carrier.

Two other characteristics are most desirable in the structure of this invention.

One is that the carrier solvent is sufficiently hydrophilic to rapidly wet the membrane with an aqueous sample applied to it, allowing the movement of ions across the interface between the sample and the membrane.

Alternatively, the carrier must be made hydrophilic by the action of a suitable non-interfering surfactant which improves the contact between the membrane and the sample i carrier.

Another highly desirable advantage is that the carrier solvent be sufficiently insoluble in water that it will not migrate significantly into the aqueous sample in contact with the surface of the membrane, as discussed below.

Generally, the upper limit of solubility in water is about 4. o? /l, and the preferred limit is about 1? /l or less.

Within these limits, virtually any solvent for the ion carrier that is also compatible with the binder can be used.

As mentioned above, it is of course also preferred that the solvent is a plasticizer for the binder.

It is also desirable that the carrier solvent be substantially non-volatile to provide the electrode with an extended shelf life.

Among the useful solvents are phthalates, sebacates, aromatic and aliphatic ethers and adipates.

As shown in Example 8 below, examples of specific useful carrier solvents include bromophenyl phenyl ether, 3-methoxyphenylphenyl ether, 4-methoxyphenylphenyl ether, dimethyl phthalate, dibutyl phthalate, dioctyl phenyl phosphonate, bis( 2-ethylhexyl) phthalate, octyl diphenyl phosphate, tritolyl phosphate and dibutyl sebacate.

Particularly preferred within this class is sulbromo phenyl phenyl ether for potassium electrodes using palinomycin as the ion carrier.

Numerous other useful solvents are detailed in the reference books cited above;
These references describe the manufacture of ion-selective membranes, and any of these membranes that permit construction of electrodes of the type described herein can be effectively used in the practice of this invention.

Although the concentration of carrier solvent in the film will also vary widely with a given film component, a carrier solvent to binder weight ratio of about 1:1 to about 5:2 provides useful films.

The thickness of the membrane will affect the response of the electrode, as explained in more or less detail below.

The thickness of this layer is less than or equal to about 0.125 mm, preferably about 0.
．． It is preferable to maintain it at 0.025 mm or less.

As discussed in more detail below, the uniformity of the thickness of the ion-selective membrane plays an important role in the optimal utilization of electrodes of the type described herein.

Therefore, if maximum benefit is to be obtained in storability and short response times, the ion-selective membrane should be relatively uniform as defined above.

Support According to a preferred embodiment, the ion-selective electrode of the present invention comprises a support which can support any other necessary parts of the electrode as hereinafter detailed, either directly or by some intervening adhesion improving layer. It can be made of materials.

Thus, the support may consist of ceramic wood, glass, metal, paper, or cast, extruded or molded plastic or polymeric materials, and the like.

The support is capable of supporting the components of the electrode overlying it and is inert, i.e., unless it interferes with the observed indicating potential, for example by reacting with one of the overlying substances in an uncontrolled manner. Composition is not important.

In the case of porous materials, such as wood, paper or ceramics, it may be desirable to seal the pores before applying the overlying electrode component.

The means of creating such a seal are well known and need no further explanation here.

Although electrically insulating supports are preferred, as discussed below, versatile metallic conductive supports are equally useful and may in fact simplify the construction of the electrode.

According to a highly preferred embodiment of the invention, the support consists of a sheet or film of insulating polymeric material.

Various film-forming polymeric materials are well suited for this purpose, such as hacellulose acetate, poly(ethylene terephthalate), polycarbonate, and polystyrene.

The polymeric support may be of any suitable thickness, typically about 0.5 mm.
0.5 mm to about 0.5 mm.

Thin layers or surfaces of other aforementioned materials can be used as well.

Methods for forming such layers are well known in the art.

In some cases, it is not necessary to form a separate, distinct support.

Such cases occur when one or more layers of the electrode exhibit sufficient mechanical strength to support the rest of the electrode.

For example, when using a metal/inert metal salt electrode as the internal reference electrode, the metal layer can be in the form of a self-supporting foil.

This metal foil acts as a support, an integral part of the internal reference electrode as well as a contact point for the electrode.

Manufacturing of ElectrodesPrior art solid-state electrodes use a conductive wire as the starting material, and this conductor is successively immersed in a highly viscous solution of the components of the individual finishing electrode layers to form a bulbous multilayer. This is commonly achieved by constructing "solid-state" electrodes.

See, eg, US Pat. No. 3,856,649.

Alternatively, individual layers of ion-selective glass are applied to the tip of a conductive wire, as shown in US Pat. No. 3,649,506.

In both of these cases, the resulting ion-selective membrane has a relatively non-uniform thickness in the area that is to be brought into contact with the aqueous solution whose ion activity is to be measured.

U.S. Pat. No. 3,856,649 (column 2, lines 1-3) teaches that similar multilayer solid-state electrodes can be fabricated in sheet or web form, such as on a metallized film or metal foil on a non-conductive support. Although there are suggestions that such electrodes may not exist.

The structure of the wire electrode falls within the scope of this invention.

However, when manufacturing such electrodes, care should be taken to reduce (within the tolerances described here) such as layer thickness discrepancies, which may give undesirable results in the novel measurement method described below. have to pay.

The electrodes of the invention are manufactured by top coating, laminating or otherwise applying the various individual layers in a conventional manner.

Therefore, a typical method of manufacturing a metal/insoluble metal salt reference element electrode is to chemically apply a layer of an insoluble metal salt to a layer of a compatible conductive metal in the form of a coating on a non-conductive support or metal foil. the metal salt layer is overcoated with a layer of electrolyte solution, and the layer so applied is dried to remove the solvent. ) and subsequent overcoating with a solution of the components of the ion-selective membrane and drying to form the complete electrode.

Alternatively, the layers can be laminated as long as intimate contact between the layers is achieved and maintained and uniformity of the thickness of the ion-selective membrane is obtained.

The particular drying conditions that must be applied to the internal reference electrode in the manufacture of any particular ion-selective electrode depend on the composition of the electrode's layers, the particular binder used, and the solvent or dispersion medium used to form the layer. Of course, these will vary greatly depending on, and these will be readily determined by the skilled person.

Typical conditions are described in the Examples below for layers of the compositions described therein.

The various electrode layer coatings provide a uniquely simple and efficient method of fabricating the electrodes described herein.

Using well-known techniques to provide highly accurate layer composition, dryness and layer thickness, which are critical to the effective fabrication of the electrodes described here, Various layers can be deposited under carefully controlled conditions.

If the electrode is manufactured on a flexible support, once manufactured by coating, which is usually done in a flat or substantially flat shape, the electrode can be cut, bent, etc. into almost any shape. , which allows the ion-selective membrane to be contacted with the test solution.

As discussed below, a preferred technique for using the electrode is in a substantially flat configuration by applying a drop (less than about 50 μl) of the test solution to the ion-selective membrane.

In use, potentiometric analysis of liquids can be carried out by placing the two previously described electrodes in spaced relationship in a frame of the type depicted in FIG.

As shown, the frame 20 includes a flat member 22
shape, which facilitates stacking and storage when used with automated processing equipment.

Two rectangular cavities are formed in the bottom surface 23 of the flat bottom 22 to house and support in spaced relationship two similarly shaped electrodes 24, 26, shown in dashed lines.

The electrodes 24 and 26 have the same structure and are similar to those shown in FIG. 1 or 2.
It is of the type shown in either of the figures.

In FIG. 1, 1 is a support, 2 is a metal, 3 is an insoluble metal salt, 4 is a reference electrolyte, and 5 is an ion-selective membrane.
On the other hand, in FIG. 2, 11 is a support, 12 is a conductive layer, 1
3 indicates a redox couple layer and 15 indicates an ion-selective membrane.

The frame is made of a non-conductive material, preferably plastic, to electrically isolate the electrodes from each other.

Holes 32 and 34 are formed in the upper surface 30 of the flat member 22 to accommodate leads 36 and 3 of the electric meter 40.
8 can be in electrical contact with the conductive layers of electrodes 24 and 26, respectively.

To facilitate electrical contact between the electricity meter leads 36 and 38 and the conductive or metallic layers of the electrodes 24 and 26, the upper layer of the electrode (i.e., the ion-selective membrane, reference electrolyte in the embodiment of FIG. and insoluble metal salts, or ion-selective membranes and redox couple layers in the embodiment of FIG. 2) are preferably not present in the electrode structure near holes 32 and 34.

Additionally, circular holes A and B are formed in the upper surface 30 of the member 22, which are located directly above each electrode;
Communicating with an ion-selective membrane.

Single drops of reference and test liquids are brought into contact with the electrodes through these holes.

To prevent droplet expansion across surface 30, holes A and B are widened to create a sloped surface at the edge of the boundary.

To enable the movement of ions between the liquid warms located on holes A and B, as required in potentiometric measurements,
A "bridge" is formed between holes A and B.

Such a bridge is in the form of a groove 42 formed in the surface 30 between holes A and B.

Preferably, grooves 42 are coated with a surfactant capable of promoting ion migration.

When the frame glass is hydrophobic, examples of suitable surfactants are Triton Nonylphenoxyethanol manufactured by 01in-Mathieson.

The drops will then flow together to create a junction due to capillary action.

Alternatively, grooves 42 can be coated with an ionic porous material.

The ionic porous material consists of, for example, a binder, a thickener and a material such as polycarbonate or polyamide, which material is mixed with atomized silica or glass powder.

Referring now to the cross-sectional view of FIG. 5, a drop of reference liquid 50 and a drop of test liquid 51 are deposited on holes A and B, respectively, and the drops tend to spread over electrodes 24, 260 and the ion-selective membrane. be.

If not reduced, liquid from these droplets will flow down the edges of the electrodes, thereby shorting out the various layers.

This would produce erroneous electricity meter readings.

To reduce this flow, endless annular grooves 5
2 is formed in the lower surface 23 of the flat member 22, such an annular groove surrounding the holes A and B and located within the electrode receiving cavity.

The platform 56 formed by the inner race 58 is somewhat recessed from the electrical surface (eg, a distance of 0.25 mm).

The effect of this structure is to create a meniscus between the platform 56 and the ion-selective surface of the electrode;
Such a meniscus acts to prevent the liquid from flowing further toward the edge of the electrode due to surface tension effects.

Preferably, the annular groove has a minimum width of at least 0.025 cm and the edges 59 of the inner race are sharp to provide effective convex flow constraint.

Alternatively, the annular groove can be replaced with an annular strip of adhesive.

For a droplet volume of about 10 microliters, the typical surface area of platform 56 is approximately 2.5 mm in diameter for holes A and B.
0 mm and the internal diameter of the annular groove is typically about 5.0 mm, which is approximately 20 square millimeters.

Other additives such as paints, plasticizers, etc. can be added to the layer as desired, provided they do not interfere with the function of the layer or components of the electrode.

Because the hydrophobic membrane layer described below is generally coated directly onto the hydrophilic reference electrode, it is not entirely anticipated that adhesion problems between these two layers will sometimes occur with certain embodiments of the electrodes discussed herein. There isn't.

In such cases, it may be useful to add a thin adhesion improving layer or subbing layer between the reference electrode and the hydrophobic membrane.

Care must, of course, be taken to ensure that such a layer does not interfere with the conductive contact between the membrane and the internal reference electrode and that no substances are introduced that could interfere with the fixation established on the reference electrode. Must.

It is important that the electrolyte layer is dried before applying the overlying ion-selective membrane if the electrode is dry operable.

When a hydrophobic ion-selective membrane is applied to a reference electrode element that is still wet or fully hydrated as suggested by the prior art, the ion-selective membrane present in the reference electrode when the electrode is stored at ambient conditions Water will migrate out of the electrode.

Since the electrolyte layer is hydrophilic, i.e. water-swellable, upon evaporation therefrom, the electrolyte layer clearly shrinks, whereas the overcoated hydrophobic layer does not shrink substantially.

Therefore, gaps or voids (i.e., reticular wrinkles) may occur between the reference electrode and the hydrophobic membrane;
These partially exclude the reference electrode and the hydrophobic membrane from electrolytic ground, and the hydrophilic electrolyte solution then rehydrates and swells once more to bring the internal reference electrode and membrane into contact again.

This phenomenon leads to the requirements in US Pat. No. 3,856,649.

This requirement is that the membrane be coated onto the electrolyte layer while it is still hydrated.

This US patent reveals that when a hydrophobic membrane is applied to a "dry" hydrophilic reference electrode and subsequently hydrated for use, the membrane blisters or tears.

Electrodes using redox reference elements are manufactured using techniques similar to those described above for metal/insoluble metal salt reference electrodes.

That is, coating an inert conductive layer, which can be a metal wire or foil, or a dispersion of particulate conductors, e.g. carbon, with a solution or dispersion of a layer containing redox species, drying this latter layer, This is coated with an ion-selective membrane as described above.

Alternatively, both the inert conductor and the redox species are incorporated into the matrix or binder composition and coated in a single layer to form the desired reference element.

Of course, the individual layers may be laminated in conductive contact relationship.
Similarly useful structures can be formed.

The ion selectivity of the membrane electrode used is determined by the steady state of the electrical potential between solution 1 and solution 2 (both usually aqueous solutions) in the cell arrangement shown schematically below. It can be observed by measuring the difference in states: Reference electrode l/solution l//membrane// solution 2/reference electrode 2 The calculations required to determine the ionic activity of solution 2 (generally a solution of unknown concentration) are: (Derived from the known Nernst equation, cited in the above-mentioned reference book edited by Pungor, Simon and Morf, “Cation 5e.
Lectivity of Liquid Member
ane, Electrodes Ba5ed upo
n New Organic Ligands”.

The electrode described herein has substantially all components necessary to perform potentiometric quantifications other than a second reference electrode, a potential indicator, and connecting wires incorporated into its structure, making it easy to use. The user merely needs to prepare the sample for contacting the ion-selective membrane, where preferably a small amount of the sample to be analyzed (50
(approximately μl) is applied to the ion-selective membrane, and an appropriate lead wire is connected.

Automated dispensers for applying controlled amounts of sample to the appropriate locations on the electrode are known, and any such dispenser or careful manual dispensing can be used to contact the sample with the electrode. be able to.

In particular, a dispenser of the type disclosed in US Pat. No. 3,572,400 is adapted to dispense small amounts (i.e., drops) onto the surface of the electrodes of this invention.

Other suitable dispensers include German Patent Application No. 255
No. 9090.

Alternatively, when the electrode is a structure consisting of a wire, cylinder, rod, etc., i.e. a surface other than a flat surface capable of spotting, the electrode is actually submerged in or in contact with the surface of the solution to be analyzed. can be done.

Second reference electrodes, such as saturated calomel electrodes, for use in combination with the integral electrode of this invention are also well known.

In addition to such electrodes, reference elements of the type described herein as internal reference electrodes can also be used as second or external reference electrodes.

Similarly, potentiometers that can read the potential developed in the ion-selective electrodes of this invention are well known and, when properly connected as described below, can give a sensory indication of the potential. From this instruction, the ion activity in the unknown solution can be calculated.

Of course, by incorporating computing power into the potentiometer, the zero-hold ion concentration in solution can be directly read as a function of ion activity.

As stated many times herein, it is in its use that the electrode of the present invention exhibits highly unexpected properties.

That is, many prior art electrodes are preconditioned before use;
Although requiring wet storage or equilibration, the electrodes of this invention
Apparently, because of the predetermined uniform thickness of the dried internal reference electrode and the ion-selective membrane, it can be used without the need for conventional preconditioning, wet storage or equilibration.

Now, in accordance with the present invention, electrodes of the type described herein can be stored under ambient conditions normally encountered in a laboratory environment (most commonly below about 65% RH) and subsequently When spotted or otherwise contacted with a sample of the aqueous ion-containing liquid described above under known conditions, the reproducible pattern of the potential exhibited by this electrode is
It was discovered that it defines a potential versus time diagram as shown in fig.

This phenomenon represented by a curved shape is "drift", which will be defined hereinafter.

The curve Q shape produced by any particular electrode is determined by its composition and shape.

As mentioned above, it is theorized that drift, particularly in the electrodes described herein, is primarily related to the thickness and composition of the ion refraction membrane, which adjusts the rate of water permeation of the electrode.

Therefore, composition and shape (eg, physical dimensions such as electrode thickness) play a very significant role in the shape defined by any electrode or set of electrodes.

Example 47 shows the specific results obtained by changing the thickness.
Shown below.

Therefore, when making precise measurements using a series of disposable, single-use electrodes, the thickness and composition of the ion-selective membrane must be carefully controlled to ensure that each electrode has a predetermined uniform thickness and It will be clear that it is important to maintain within the area of a single electrode that is intended to be in contact with the sample.

A lack of such scheduled and controlled thickness uniformity will exhibit irregular or random drift that cannot be calibrated as described herein.

Such drift would make it difficult, if not impossible, to calibrate a series of electrodes, since variations in film thickness from electrode to electrode have no significance on ion activity or concentration. This is because the method produces calibration curves of different shapes that are related.

Studying Figure 3 shows that after some moderate interval, generally about 10
After a few minutes, the potential exhibited by the various electrodes begins to stabilize (i.e.,
(the slope becomes constant), thus indicating that an initial stage of equilibrium within the electrode has been reached.

After wet storage or preconditioning, measurements of the potential are carried out using prior art electrodes and from this measurement the Nerns
It is at the limit of this stabilizing portion of the potentiometric curve that the ion concentration was calculated using the t equation.

When the electrodes of this invention are used after storage under ambient conditions, the drift can actually be calculated.

We have now discovered that, using ``calibrated drift,'' ion concentrations can be reproducibly and precisely quantified almost immediately after contact of the electrode surface with a test aqueous solution.

Such results are achieved without following any special storage procedures for the electrodes before use other than to prevent contamination as is done with common laboratory glassware and equipment.

The depth and width of the trough will vary somewhat depending on the ambient conditions of use (mainly humidity) and the thickness of the various layers (mainly hydrophobic membranes).

However, these changes can be made by means of index measurements that compare the ion concentration of an unknown sample with the ion concentration of a similar sample of known ion concentration (i.e., a calibration material or standard) applied to the same electrode at the same time, or at a constant ambient temperature. First derive a calibration curve for the electrodes for a set of conditions,
The conditions of the individual measurements are then easily corrected by relating them to such a calibration curve.

No. 38,566, as described in the Examples below.
A somewhat similar drift was observed when electrodes prepared as described in No. 49 were stored in "dry" conditions, ie, at relative humidity below about 65%, and used as just described.

However, in these cases, the drift was random and varied substantially from electrode to electrode, generally giving ``no calibration curve'' results.

The reason for this is mostly due to the non-uniformity of the layer thickness of such electrodes and the fact that after hydrating or equilibrating the reference electrode a true and uniform contact between the internal reference electrode and the hydrophobic membrane occurs. This seems to be due to the necessity of

Quite obviously, it is difficult to produce electrodes with a predetermined and uniform layer thickness using dipping techniques, but such electrodes can be manufactured using coating solutions of highly controlled viscosity. It is believed that it can be produced by rotating the immersed workpiece in a manner that prevents the formation of bulbous structures of non-uniform thickness.

Since it is difficult to use such a technique, it is preferred in the present invention that the electrodes be made in planar form.

This not only simplifies the manufacturing technique, but also allows only a very small amount (i.e. about 5
Planar electrodes can be used by simply depositing micro-amounts (of the order of less than 0 μl) and then measuring.

The present invention will be explained in more detail with the following examples.

Example I Ag/AgX Electrode A sample of vacuum deposited metallic silver (~10 mgAg/da'') on a polyethylene terephthalate support was prepared.

This sample was treated with the following solution for 5 minutes. glacial acetic acid
0.45ml sodium hydroxide
0.202 Potassium ferricyanide o, so
y Potassium bromide 2.501 Distilled water
The sample was then washed in running distilled water for 5 minutes.

Upon visual inspection, the layer of metallic silver remained adjacent to the support, but some of the silver had become silver bromide.

To make electrical contacts, the edges of the samples were briefly immersed in a thiosulfate bath to expose the silver layer.

The electrochemical response was measured by applying small aqueous samples of different Br-activities to the silver bromide layer.

A linear response was observed that roughly matched the theoretical slope (Nernst's equation).

Example 2 Potassium chloride chromate 8.45? A half-cell was prepared as described in Example 1, except that it was treated for 30 seconds in a solution containing 0.25%.

When the electrochemical response was measured, the potential response to changes in C1- and Ag+ activities was linear.

Example 3 Ion-selective laminated electrode A silver-silver chloride film on polyethylene terephthalate was prepared as described in Example 2.

The total amount of silver is 7.6? /m2, and AgC1(1,1
The conversion rate to 6P/m2) was 15%.

Then 5% polyvinyl alcohol (PVA)-0.2M
KCI solution was applied.

(1,51KC1,5,0PPVA/m”). After drying the PVA layer by heating to 54°C for 10 minutes, palinomycin (VAL) 0.50f/m2, polyvinyl chloride (
A preformed ion-selective membrane consisting of 40.41 g/m2 of PVC) and 100.2 g/m2 of bromphenylphenyl ether as carrier solvent was hand laminated onto the film coating.

The resulting ion-selective electrode, designated as Ag/AgC1/PvA-KC1/ion-selective membrane, was tested according to (1) and (2) below.

(1) Connect the silver-silver chloride film to the high impedance input of the voltmeter and (2) KCI to be measured from the tip of the saturated NaNO3 salt bridge.
A drop of solution (25-50 μl) is applied and the drop is brought into contact with the electrode surface.

The salt bridge is connected to an external reference electrode (Hg/Hg2CI2), which is connected to the reference input side of the voltmeter.

The entire cell for potential difference measurement is expressed as follows.

Hg/HgCl2/KCI(XM) test solution/ion selective membrane/PVA-KCl/AgC1/Ag A semi-logarithmic linear response to potassium ions was observed.

In the range of pK0 from 1 to 4, the slope of the potential was 57 mV per digit of potassium ion concentration.

Example 4 Ion selective coated electrode VALO, 58? /m2, polyvinyl chloride 22.9? /
An electrode was prepared as described in Example 3, except that an ion-selective membrane consisting of m2 and BPPEll, 2 g/m2, was coated directly onto the KCl-PVA layer rather than laminated as described in Example 3.

This integrated electrode was tested as described in Example 3 and found that
A semi-logarithmic linear response to potassium ions was observed.

The slope of the curve was 50 mV per digit of potassium ion concentration.

Example 5 Changes in Reference Electrolyte Composition A series of electrodes were made by varying the surfactant in the reference electrolyte solution and the water-soluble polymer as the binder for KCI.

The polymers used were polyvinyl alcohol (PVA), deionized gelatin and polyacrylamide (PAM) (see Table 1).

KCI 1.5 for all electrodes unless otherwise noted
P/m” was included.

These electrodes were then laminated with a preformed ion-selective membrane of the composition described in Example 3.

The resulting electrode was evaluated as described in Example 3 and the results are shown in Table 1 below.

According to the data in Table 1, the electrodes prepared as described have slopes of 51 to 57 mv/mv for potassium ions.
It can be seen that a linear response is shown (at a single-digit potassium ion concentration).

Example 6-16 Composition of Ion-Selective Membrane A number of laminated and coated electrodes were prepared and the effect of changing the composition of the ion-selective membrane on electrode response was investigated.

The elements were evaluated as described in Example 3.

The results are shown in Table 2 below.

According to the data in Table 2, VAL, BPPE in the electrode formulation
It can be seen that changing PVC has the following effects.

A. Palinomycin in the membrane is 0.2? /m', there is little or no response to potassium ions.

B. When the BPPE/PVC ratio is less than 1:1, the film becomes dry and unresponsive.

Generally, the ratio of carrier solvent to polymer is between 1:1 and 5:1.
2, a useful film layer is obtained.

Examples 17-23 Composition of Ion Selective Membranes A number of laminated and coated electrodes were prepared to demonstrate the utility of other polymers in the ion selective membrane layers of electrodes.

Polymers tested included Butvar B76 (polyvinyl butyral sold by Monosanto Chemical Company), Estane 5107F1 (B, F, aromatic polyurethane sold by Gutdrich Company, VY
NS (PV sold by Union Carbide)
C/PVAc*-90/10 copolymer) and 5ilas
tic■ 731RTV (silicone rubber from Dow Corning, Midland, Michigan).

After fabrication, the electrodes were evaluated as described in Example 3.

The results are shown in Table 3 below.

*PVAc-Polyvinyl Acetate The data in Table 3 indicates that all polymers tested are useful in the electrode configuration of the present invention.

Examples 24-38 Composition of Ion Selective Membranes (Carrier Solvents) A series of electrodes were fabricated to compare bromophenyl phenyl ether (BPPE) with other possible carrier solvents for the membrane layer.

Other solvents tested included 3-methoxyphenylphenyl ether (3MPPE), l-methoxyphenylphenyl ether (4MPPE), dimethyl phthalate (
DMF), dibutyl phthalate (DBP), dioctyl phenylphosphonate (DOPP) and bis(2-ethylhexyl) phthalate (BEHP) and dibutyl sebacate (DBS).

The integrated electrode was evaluated as described in Example 3 (the results are shown in Table 4).

Phenyl ether, phthalate, as carrier solvent
The data in Table 4 shows that the use of sebacate provides an electrode that responds well to potassium ions.

Example 39 Electrodes were prepared and evaluated as described in Example 3 using various formulations of carrier solvent and coating solvent in the membrane layer.

The results are shown in Table 5. BEHP = bisethylhexyl phthalate THF - tetrahydrofuran MEK = methyl ethyl ketone DDP - didodecyl phthalate The composition of the film was as follows: 0,48? /m2 Palinomycin 9.76 g/m2 Polyvinyl chloride 0.15 g/m2 Carrier Solvent Example 40 Sensitivity of Electrode A coated electrode was prepared as described in Example 3 and subjected to selectivity testing as described below.

Is the normal amount of potassium ions in the evaluation serum approximately 4 ml? /l, while sodium is 30 to 40 times that amount.

It is therefore important that sodium ions do not interfere with potassium ion measurements.

To determine the extent to which sodium ions interfere with the response to potassium ions, the selectivity coefficient KK+/Na+, defined by the following equation, was determined for the coating.

Measurements on this coating using a certain disturbance method gave a value of 1.times.10@-3 in 0.15 M NaCl.

In a solution containing K+5mM and Na+150mM, this coating exhibits approximately 3% inhibition of the sodium response.

Thus, the clinical range (i.e. NaO, 12M to 0.16
For small variations in Na+ within a range over M, the disturbance variation is less than 1%.

Example 41 Deionized gelatin (9,7 P/m2), granular carbon (1
5,5? /m') and Triton A redox reference electrode with a double layer structure was prepared by coating a poly(ethylene terephthalate) film substrate with a redox layer consisting of potassium cyanide (54 meq/m2) and potassium ferrocyanide (5,4 meq/m2).

The resulting reference electrodes were laminated by hand and palinomycin (V
AL) (0,49P/m2), bis(2-ethylhexyl) phthalate (BEHP) (14,5?/m2) and polyvinyl chloride (PVC) (9,2f/m2). Molded.

The resulting composite ion-selective electrode was tested in the following cell.

Starting at 2 minutes shows a linear semi-logarithm depending on the potassium ion concentration.

The slope is 57 mv/one digit of potassium ion concentration.

The potential drifts over time after 50 μl of the test solution is spotted onto the element.

The magnitude of the reproducible drift is about 0.1 mv/min for 2 to 10 minutes.

Example 42 Deionized gelatin (4.3 g/m2) as ion-selective electrode binder using a single layer Fe(H)/Fe(■) reference electrode,
polyethylene with a layer consisting of granular carbon (6,9?/m2), octylphenoxypolyethoxyethanol (0,12?/m2), potassium ferricyanide (7,5 meq/m2), and potassium ferrocyanide (7,5 meq/m2). A reference electrode with a single layer structure was made by coating a terephthalate film support.

The resulting reference electrode was then treated with palinomycin (0,49?
/m2), BEHP (14,5?/m”) and PVC (
9,21/m2) by hand onto a preformed ion-selective membrane.

The resulting integrated electrode was evaluated as described in Example 40 with the following results.

The electromotive force at 2 minutes shows a linear semi-logarithm depending on the potassium ion concentration.

The slope is S5. V/(potassium ion concentration, single digit).

The potential of this single layer type is approximately 1. Drift for 2 to 10 minutes at a speed of omv/min.

Example 43 Deionized gelatin (9,8 f/m2) as electrode binder using double layer Co(■)/Co(■) reference electrode,
Granular carbon (15,6 g/m2), saponin (0,2 g/m2)
m2) and Hibis(vinylsulfonyl methyl ether) (
A conductive layer consisting of deionized gelatin (io, 8?/m2), octylphenoxypolyethoxyethanol (0,22?/m2), bis(vinylsulfonylmethyl) ether (0, 8?/m2) and a conductive layer consisting of 22?/
A reference electrode with a double layer structure was prepared by coating a polyethylene terephthalate film substrate with a redox layer consisting of 2), co(thylpyridyl)2(BF4)2 (210 phycromol/m2).

The resulting coating was then immersed in 0.1 NKI for 30 minutes and
Dry in indoor atmosphere for 4 hours, and then VAL(0,4?/
m2), BEHP (14,5 g/m2) and PVC (9
, 2 g/m2) by hand onto a preformed ion-selective membrane.

In this example, the immersion step in the preparation process is incorporated as a method for absorbing calylum ions into the redox layer to maintain equilibrium of the membrane.

In Examples 40 and 41, this step was unnecessary because the ferro/ferricyanide buffer was prepared using a potassium salt.

Evaluation of the elements was performed as described in Example 40 with the following results.

The electromotive force at 2 minutes shows a linear semi-logarithm depending on the potassium ion concentration.

The slope is 57 mv/(potassium ion concentration in one digit).

The polarants drift for about 3 to 10 minutes at a rate of about 0.1 mv/min.

Example 44 An electrode was prepared as described in US Pat. No. 3,856,649.

The electrodes were maintained at 38° C. and 66% relative humidity during and after fabrication.

Immediately after fabrication, this electrode was evaluated, and as a result it showed a response with a slight drift and a linear slope of about 6 omv/(potassium ion concentration of one digit) over 10-4 to 10-IMKCI.

■ The same electrode was stored under laboratory ambient conditions of about 35-40% relative humidity for 15 days, then the electrode was immersed in a solution of known KCI concentration and measured as described in Example 3 above. A random drift of minutes was shown.

The drift rate decreased after about 10-14 minutes while the electrode exhibited a relatively stable positive drift of 1 mv/min.

Drift became smaller with subsequent use of the same electrode.

That is, in use, as the internal reference became hydrated, the electrode tended to equilibrate as expected, thus providing more accurate measurements as wetting continued.

Example 45 The preparation of an electrode according to the present invention was simulated using G
Wire electrodes having a generally bulbous shape were made using the immersion technique proposed by enshaw et al.

The hydrophilic layer was then dried before application of the ion-selective membrane without controlling the uniformity of the layer thickness.

By keeping these electrodes in room conditions (i.e. 35-40% relative humidity) and subsequent use, we observed an initial highly random drift of 16 to 57 mv/(4 orders of magnitude potassium ion concentration) for 2 to 10 minutes. The curve shown was obtained.

When immersed in 10-IMKCl, the phenomenon of oozing or tearing of the outer membrane was observed only 9 days after immersion, as described by Genshaw et al.

l-11-1O+ after the first few hours of soaking before bursting.
A linear Nernstian response was observed over the range of .

Example 46 A wire electrode was prepared as described in Example 45 except that the ion selective membrane was dried at 29°C instead of 57°C.

Relative humidity approximately 80% without preconditioning
When used after being kept under preselected indoor conditions of less than
These electrodes showed very random fluctuations up to about 15 to 16 minutes.

After that, the drift stabilized and a linear Nernstian response was observed.

It will be apparent from the foregoing that electrodes made according to the technique described by Gen3haw et al. exhibit a linear Nernstian response when properly preconditioned and hydrated.

However, without such preconditioning, the behavior of the electrode is random and erratic and cannot be corrected under normal indoor use conditions without an appropriate induction period.

Electrodes prepared as described in the technique used, in which the area of the electrode in contact with the sample for analysis consists of ion-selective membranes of varying thicknesses, exhibit uncorrectable drifts as shown in Examples 44-46 above. shows.

Example 47 A coated electrode was prepared as described in Example 4, in which the reference electrolyte layer and ion selective membrane compositions were as follows.

Reference electrolyte layer PVA 4.8P/m2
KCI ~2.4? /m2 Ion selective membrane PVC9,7? /m2 DDP 14.6 f/m” Palinomycin 0.5 g/m2 Figure 3 shows the time obtained by varying the thickness of said layer by doubling one or the other of the components of each composition. shows the curve of E for

It will be appreciated that these curves may take on a variety of shapes, each of which can be corrected and thereby provide accurate values of the potential for ion activity and concentration.

Example 48 A coated electrode was prepared as described in Example 4 with the following compositions of the reference electrolyte layer and ion selective membrane.

When a droplet-sized sample of an aqueous sodium ion solution was applied to this electrode, a Nernst slope of 57 mv/(single digit potassium ion concentration) was observed.

Example 49 A coated electrode was prepared as described in Example 48 in which the composition of the ion selective membrane was as follows.

When an aqueous sample containing CO3- was applied to the ion-selective membrane, this electrode exhibited a slope of 27 mv/(single digit potassium ion concentration).

Example 50 A coated electrode was prepared as described in Example 48 in which the composition of the ion selective membrane was as follows.

When in contact with an aqueous solution containing CI- ions, this electrode
The Nernst slope of smv/(single digit potassium ion concentration) is shown.

Although the layered electrode elements of the present invention have been primarily described in connection with potentiometric quantification of alkali metal and alkaline earth metal ions, the structures, compositions, and techniques described herein are also primarily applicable to ion-selective membranes. Other cations such as NH4+ and SO by choosing appropriate ion-specific carriers
It is applicable to electrode assemblies for analysis of anions such as 3-.

Such electrodes are clearly within the scope of the present invention.

Additionally, it is within the scope of the invention to incorporate a protective overlayer into the electrode.

This top layer simply helps protect the electrode surface or increases mechanical strength.

The upper layer may also be used for a number of other purposes, such as allowing selective penetration of specific ions or only certain gaseous components of the solution under test, such as oxygen or carbon dioxide. Helpful.

It may be useful to use electrodes of the type described herein in combination with an upper layer containing an enzyme that acts on the substrate to specifically and selectively release ions that can be quantified by the electrode.

Although the invention has been described in detail with reference to preferred embodiments thereof, it will be understood that modifications may be made thereto within the spirit of the invention.

[BRIEF DESCRIPTION OF THE DRAWINGS] FIG. 1 is a cross-sectional view of an example of the ion-selective electrode of the present invention, and FIG. 2 is a cross-sectional view of another example of the ion-selective electrode of the present invention. Figure 3 is a graph showing typical potential versus time obtained using the ion-selective electrode of the present invention as described in Example 47, and Figure 4 is a graph showing typical potential versus time obtained using the ion-selective electrode of the present invention as described in Example 47. 5 is a full-size view of an example of an apparatus that can be used in making measurements, and FIG. 5 is a sectional view taken along line V--■ of FIG. 4; In FIG. 1, 1 is a support, 2 is a metal, 3 is an insoluble metal salt, 4 is a reference electrolyte, and 5 is an ion-selective membrane.
On the other hand, in FIG. 2, 11 is a support, 12 is a conductive layer, 1
3 indicates a redox couple layer and 15 indicates an ion-selective membrane.

Claims (1)

Claims: 1(a) A dry internal reference electrode consisting of one of the following: (1) an electrically conductive layer of a metal in contact with a layer of an insoluble salt of the metal, and the metal salt as an anion; or (2) a redox couple electrode consisting of a conductive layer and a redox couple layer containing at least two types of water-soluble redox couple salts. , wherein said layer comprising said water-soluble salt consists of the dry residue of a solution of said salt and a hydrophilic polymeric binder in a solvent for said polymer and salt; and (b) a hydrophobic ion-selective membrane having a predetermined uniform thickness in the part to be contacted with the test sample in contact with said reference electrode, said membrane being in a carrier solvent; A dry operable ion selective electrode comprising: a hydrophobic binder containing dispersed ion carriers. 2 The hydrophobic binder is polyvinyl chloride, polyurethane, carboxylated polyvinyl chloride, copolymer of polyvinyl chloride and polyvinyl acetate, silicone elastomer, polycarbonate, cellulose ester, copolymer of polyvinyl chloride and polyvinylidene chloride. 2. The electrode of claim 1, wherein the electrode is a polymer selected from the group consisting of polyvinyl butyral, polyvinyl butyral, and polyvinyl formal. 3 The ion carrier is palinomycin, a cyclic lactone, a macrolide actin, a cyclic polypeptide, a quaternary ammonium salt, a compound of the following formula: (wherein, I R':CH3R2(CH2)n -C0O-CH2-CH3n=l
or 10 ■ R' knee CH3 R2 knee (CH2)6-CH3 ■ R' = R2 knee CH2-CH2-CH3 ■ R1 knee CH2-CH2-CH3 R2 knee CH2-C-(CH3)3 (However, in the formula (a )R-CH2CH2(CH2CH2CH3)2.4 The carrier solvent is an aromatic ether, an aliphatic ether, a phthalic ester, an adipate ester, and sebacin. The electrode according to claim 1, wherein the hydrophilic binder is selected from the group consisting of acid esters. 5. The hydrophilic binder is polyvinyl alcohol, gelatin, agarose, polyacrylamide, polyvinylpyrrolidone, polyhydroxyethyl methacrylate, polyacrylic acid. 6. The electrode of claim 1, which is a member selected from the group consisting of hydroxyethyl and polyacrylic acid. 6. The redox couple is a ferri/ferroferrocyanide ion pair or a primary/secondary cobalt terpyridyl ion. An electrode according to claim 1.