CA1233511A - Ion selective electrode - Google Patents
Ion selective electrodeInfo
- Publication number
- CA1233511A CA1233511A CA000490329A CA490329A CA1233511A CA 1233511 A CA1233511 A CA 1233511A CA 000490329 A CA000490329 A CA 000490329A CA 490329 A CA490329 A CA 490329A CA 1233511 A CA1233511 A CA 1233511A
- Authority
- CA
- Canada
- Prior art keywords
- electrode body
- electrode
- ion selective
- membrane
- moat
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/333—Ion-selective electrodes or membranes
- G01N27/3335—Ion-selective electrodes or membranes the membrane containing at least one organic component
Abstract
ION SELECTIVE ELECTRODE
ABSTRACT OF THE DISCLOSURE
An ion selective electrode includes a conductive electrode body which is supported by an insulating substrate. A convex dome-shaped membrane containing an electroactive species is deposited over and is directly in contact with the electrode body and a surface of the substrate surrounding the electrode body. The membrane has its greatest height above the electrode body and slopes down to meet the surface of the substrate . A moat formed in the insulating substrate surrounds and is spaced from the electrode body to define the outer boundary of the dome-shaped membrane .
ABSTRACT OF THE DISCLOSURE
An ion selective electrode includes a conductive electrode body which is supported by an insulating substrate. A convex dome-shaped membrane containing an electroactive species is deposited over and is directly in contact with the electrode body and a surface of the substrate surrounding the electrode body. The membrane has its greatest height above the electrode body and slopes down to meet the surface of the substrate . A moat formed in the insulating substrate surrounds and is spaced from the electrode body to define the outer boundary of the dome-shaped membrane .
Description
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The present lnventlon relates to devices for senslng the presence of speclfic ions ln fluids. In particular, the pre-sent invention relates to ion selective electrode (ISE) technol-ogy, and methods of making ion selective electrodes.
An ion-selective electrode (ISE) is an electrode which exhibits an electrical response which is a function of concentra-tion of a specl.~ic ion contained in a solution which is in con-tact with the ISE and a reference electrode. Ion selective elec-trodes operate on the basis of the Nernst princlple, which wasdiscovered by W.H. Nernst, a ~5 ~, -- 1 335~L~
German physicist, in the late 1800's. The Nernst equation defines a logarithmic relationship between the potential of a solution and its ionic concentration. When an ion selective elec-trode and a 05 reEerence electrode are exposed to a solution, a potentiometric measurement can be made between the two electrodes which indicate the concentration in the solution of the particular ion to which the ion selective electrode responds.
I'he Nernst equation can be written as:
Y = M lo~lOX ~ B
where X is ion concentration, Y is the output potential, M is the Nernstian slope, and B is a constant.
Most commercially available ion selective electrodes include an internal reference electrode, an electrolyte (in either liquid or gel form) which is in contact with the internal reference electrode, and a membrane which separates the internal reference electrode and the electrolyte from the solution. The membrane is commonly a glass or polymeric membrane in which an electroactive species is incorporated. The particular electroactive species differs depending upon the particular ion to be sensed~
Coated wire electrodes are a type of ion selective electrode in which an electroactive species is incorporated in a thin polymeric film coated directly -to a metallic conductor. Coated wire electrodes differ Erom other ion selective electrodes in -that they do not use an electrolyte as an internal reEerence solution. Although coated wire electrode~
oEfer simplified construction in contrast to other ion selective electrodes, they have not found significant use other than in experimental studies.
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Although ion selective electrode (ISE) technology has been known for several decades, its use generally has been limited to laboratories with highly trained technicians making the measurements 05 and interpreting the data. One of the deterrents to the use oE ISE systems outside the laboratory has been the necessity for calibration of electrodes to establish their Nernstian slopes (M) in terms of the millivolt output response (Y) of the electrode per clecade change in concentration (X). After this is done, a further measurement has to be made in the test solution to assess its concentration. From time to time, the ISE has to be recalibrated since the Nernstian slope can change by several millivolts and its intercept on the Y axis (i.e. the constant B) can shift.
Still another deterrent is that when ISE's are initially put into use or reused after storage, they need to be equilibrated in a suitable solution.
This I'preconditioning'l of an ISE is time-consuming and inconvenient.
In the past, ISE'~ have typically exhibited significant drift. One of -the major causes of this drift in ISE's is capacitive efEects which are uncontrolled and therefore "float". This floating or changing capacitance causes drift, error, and t`he need for standardization and restandardization. The capacitance effects are related to three significant deficiencies in the prior art ion selective electrodes.
First, the spatial relationship of the reference electrode to the sensing electrode is not fixed.
Second, the prior art ISE's typically are ~33~
constructed in multiple layers over a conductor, and eacll oE these layers have varying characteristics WiliCh give varying capacitances and thereEore uncontrollable changes in capacitance.
05 rrhird, in certain multilayer ISEs having a hydropllylic layer interposed between the sensing electrode and tlle conducting layer, the capacitance challc3es continuously with time as the dried hydrophylliLc layer changes its state of hydration during the test. There are still other type~ oE
electrodes whlch have variou~ layers are not fixed:
and t~e~c c.~n be physically deformed as well, causing additional uncontrollabl~ changes in capacitance.
The present invention is an improved ion selective electrode which provides an essentially instantaneous response with no need for initial equilibrium time, and which exhibits a fixed slope.
The electrode of the present invention has a simple structure which does away with the need for an internal electrolyte associated with an internal reference electrode.
The ion selective electrode of the present inverltion includes a conductive elactrode body which is supported by an insulating substrate. A convex dome-shaped membrane containing an electroactive species is deposited over and is directly in contact with the electrode body and a surface of the sub~trate surroundiny the electrode body. ~he membrane h~s its greatest height above the electrode body and slopes down to meet the surEace oE -the substrate.
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Thus according to the aspect thereof the present inven-tion provides an ion selective electrode comprising: a conductive electrode body having an essentially planar first surface Al with an outer edge; an insulating substrate supporting the elec-trode body and having an essentially planar first surface which sur-rounds and is essentially coplanar with the first surface of the electrode body; and a convex dome shaped ion selective membrane over the first surface of the electrode body and the insulating substrate; the membrane covering an area A2 which is greater than area of the first surface of the electrode body and the membrane having an outer edge which is spaced laterally from and which is essentially coplanar with the outer edge of the first surface of the electrode body. Suitably, the electrode body has a second surface spaced from the first surface; and wherein the ion selec-tive electrode further comprises means for making an electricalconnection to the second surface of the electrode body. Desir-ably, the substrate is a sheet having a second surface generally parallel to its first surface; and wherein the means for making an electrical connection comprises an electrical conductor which extends over a portion of the second surface of the substrate and contacts the second surface of the electrode body.
The electrode body has a surface area Al which is less than the area A2 of the membrane. In preferred embodiments, the ratio Al/A2 is preferably in a range of about 0.01 to about 0.25.
The height of the membrane over the electrode body is preferably greater than about 0.5 mm.
In preferred embodiments oE the present invention, the insulating substrate includes a moat which surrounds and is spaced from the electrode body. An inner edge of the moat defines an outer boundary of the dome-shaped membrane.
In another aspect thereof the present lnvention pro-vides an ion s01ective electrode comprising: a conductive elec-trode body having an essentially planar first surface; an insu-~335~1~
lating substrate supporting the electrode body, the substratehaving a first surface essentially coplanar with the first sur-face of the electrode body and having an annular moat depression surrounding and spaced from the electrode body; and a convex dome-shaped ion selective membrane deposited over and directly in contact with the electrode body and the first surface of the sub-strate located within an area defined by an inner edge of the moat depression, the membrane having an outer edge which is spaced from an outer edge of the electrode body and whlch is defined by the inner edge of the moat.
In a further aspect thereof the present invention pro-vides an ion selective electrode comprising: a conductive elec-trode having an essentially planar first surface with an area A1;
an insulating substrate supporting the electrode body and having an essentially planar first sur~ace which surrounds and is essen-tially coplanar with the first surface of the electrode body; and a convex dome-shaped ion selective membrane over the first sur-faces of the electrode body and the insulating substrate; the membrane having a maximum thickness at a position over the first surface of the electrode body which is between about 0.5 mm and about 0.88mm; and the membrane having an area A2 which is greater than area Al of the first surface of the electrode body and hav-ing an outer edge which is generally concentrically spaced from and coplanar with an outer edge of the first surface of the elec--trode body, wherein Al/A2 is between about 0.01 and about 0.25.
Suitably, the selective electrode comprises a moat depressi.on in the first surface of the substrate having an inner edge spaced laterally from and surrounding the outer edge of the first sur-face of the electrode body, and wherein the outer edge of themembrane is defined by an inner edge of the moat.
In a still further aspect thereof the present invention provides an i.on selective electrode comprising: a conductive electrode body having an essentially planar surface; an insulat-ing substrate supporting the electrode body, the substrate having - 5a -~ Z ~ 3 ~ ~
a surface essentially coplanar with and surrounding the planar surface of the electrode body and having an annular moat depres-sion generally concentrically positioned to surround the elec-trode body with an inner edge of the moat depression spaced from an outer edge; and a convex dome ion selective membrane deposited over and directly in co.ntact with the electrode body and a sur-face of the substrate within the moat.
The present inventlon further provides a method of mak-ing an ion selective electrode comprising: mounting a conductiveelectrode body in an insulating substrate so that the electrode body and the i:nsulating substrate form an essentially planar exposed surface surrounded generally concentrically by a moat depression; and depositing over the planar exposed surface a mix-ture of a polymer dispersed in plasticizer with an electroactivespecies dispersed therein to form, as a result of surface ten-sion, a convex dome-shaped membrane over the electrode body and the portion of the insulating substrate surrounding -the electrode body, the membrane having an outer edge defined by an inner edge of the moat depression.
The present invention further provides a method of mak-ing an ion selective electrode comprising: mounting a conductive electrode body in an insulating substrate so that the electrode body and the insulating substrate define an essentially planar surface with a moat depression in the insulating surface which surrounds and has an inner edge which is spaced laterally from an outer edge of the electrode body; and depositing over the essen-tially planar surface a mixture of a polymer dispersed in plasti-cizer with an electroactive species dispersed therein to form aconvex dome-shaped membrane over the essentially planar surface defined by the electrode body and a portion of the insulating substrate surrounding the electrode body, the membrane having an outer edge defined by the inner edge of the moat depression.
Suitably the ion selective electrode comprises polishing the exposed surface of the electrode body prior to depositing.
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The present invention does not include an electrolyte or a separate internal reference. This greatly simplifies both the structure and the fabrication of the elec-trode, and elimi-nates multiple layers which are a cause of drift in prior art ISE's. With the present invention, ISE's having Nernstian slopes which are highly reproducible can be manufactured on a large scale basis.
The present invention will be further illustrated by way of the accompanying drawings, in which:-Figures lA and lB are top and cross-sectional views of a preferred embodiment of the ion selective electrode of the pre-sent invention, Figure 2 is a graph showing the response of ISE's of the present invention having a valinomycin incorporated membrane to potassium in O.lN NaCl solution, Figure 3 is a graph showing the response of ISE's of the present invention having a monensin incorporated membrane to sodium in NaCl solution, Figure 4 is a graph showing the response of ISE's of the present invention having a methyl - 5c -:~2~
monensin incorporated membrane to ~a~ ions in the physioloyical range of blood.
Figure 5 is a graph showing the response oE
ISI~s oE the present invention having a sodium 05 ionophore incorporated membrane to Na ions in the pllysiological range of blood.
Figure 6 is a graph showing the response of IS~3s oE the present invention having a tridodecylamine incorporated membrane to H+ ions in the ph~siological range of blood.
Figure 7 is a graph showing the response of IS~s oE the present invention having an ~liquat 336 incorporated membrane to Cl- in the physiological range oE blood.
Figure 8 is a graph comparing the response as a funtion of time of IS~s of the present invention and prior art ISEs.
Figures 9~ and 9B show top and cross-sectional views of a preferred embodiment of the ISE of the present invention used as a part of a disposable sensing device.
In Figures lA and lB, a preferred embodiment oE tlle iOII ~elective electrode 10 oE the pre~ent invention i8 shown. In this embodiment, ISE 10 is Eormed by insulating substrate 12, conductive electrode body 14, species selective membrane 16, and conductive pin 18.
Substrate 12 is, in this preferred embodiment, an insulating plastic body having a top surace 12~ and a bottom surface 12B whicll are generally planar. ~xtending through substrate 12 is J
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hole 20, with an enlarged upper recess 22 at its upper end and an enlarged lower recess 24 at its lower end. Pin 18 has its head 18A positioned in upper recess 22 and extends downward throu~h hole 20 05 50 that lower end 18B is exposed below lower surface 12B.
Electrode body 14 is inserted in upper reces~ 22 so that top surEace 14A is coplanar with surEace 12A. Bottom surEace 14B i9 bonded to conducive pin 18 by conductive silver epoxy 26.
.~urrounding and spaced Erom electrode body 14 is annular moat 28, which is a groove Eormed in upper surface 12A oE substrate 12. In the embodiment shown in Figures lA and lB, moat 28 and electrode body 14 are concentrically arranged.
Membrane 16 is preferably formed by a mixture oE a polymer dispersed in plasticizer with an electroactive species dispersed therein. As shown in Figure lB, membrane 16 has a convex dome shape, with its greatest height over electrode body 14. Inner surface 16A of membrane 16 covers and is in direct contact with top surface 14A of electrode body 14, as well as the portions o~ top surEace 12A of substrate 12 which are located within moat 28. The outer periphery oE membrane 16 is deEined by the inner s`houlder of moat 28.
Conductive pin 18 provides an electrical conductive path by which electrode body 14 can be connected to electrical mea~urement equipment necessary to make a potentiometric measurement based upon the potential difEerence between ISE 10 and another electrode (e.g. a reference electrode) which `, ' ', . '~ ' : -~ ~3~
does not interact with th0 specific ion of interest in the samemanner as ISE 10.
ISE 10 of the presen-t invention exhibits ins-tantaneous response and a predictable Nernstian slope to within ~ 2 milli-volts (and usually within + 1 millivolt). This makes the present lnvention well suited for use in a disposable, single-use sensing device. ~s a result of the highly reproducible slope, and the instantaneous response without the need for preconditloning or for equilibration, ISE 10 permits the use of a one point calibra-tion technique such as described in applicant's copending Cana-dian applica-tion No. 478,745 filed April 10, 1985. In other words, with ISE 10 is it only necessary for a single calibration measurement to be made, with a known concentration, since slope M
is a single known value and the calibrant concentration Xl is known. By measuring the voltage output Yl, a value for constant B lS determined. A second measuremen-t with a sample of unknown concentration yields ou-tput Y2 from which the unknown concentra-tion value X2 can be calculated, since both slope M and constant B are knownO
The extreme simplicity of construction of the present invention contributes to its suitability for use in a disposable, single-use sensing device. Unlike prior art devices, the present inventlon does not utilize a complex geometry or multiple layers which increase manufacturing complexity and cost, and contribute to drift and unpredictable slope values.
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In preferred embodimen-ts of the present invention, substrate 12 is made of acetonitrile butadriene styrene (ABS), and electrode body 14 is a carbon cylinder cut from a carbon ~graphite) rod.
05 ~lthough other conductive materials (such as metals like platinum) have also been used as electrode body 1~, carbon is a preferred electrode body material becau e it works best with a wide range of difEerent electroactive compounds. This i 5 particularly important since membrane 16 is in direct contact with top surface 14A of electrode body 14.
Prior to the deposition of membrane 16, top suraces 14A and 12A are cleaned with methanol.
Polishing of top surfaces 14A prior to cleaning also appears to be advantageous, although not absolutely necessary. It has been found that the more uniform and finer grained the surface 14A of electrode body 14, the less variation in the value of constant B of the Mernst equation. Coarse sanding of the surface 14A results in variation o~ about + 100 millivolts in the value of constant B. With the use of finer grade abrasives, the variation is reduced to about ~ 40 millivolts.
The alignment of the crystalline ~tructure of electrode body 14 at surface 14A is believed to play a role in response characteristics of IS¢ 10.
The mobility of electrons is highest when the diamond structure of graphite, for example, is perpendicular to the direction of electron flow. ELectrode body 1~
is typically cut from an extended graphite rod, and most of the crystals of body 14 are aligned in the direction for optimum electron flow. Some polishing, therefore, appears to be of advantage in yiving a more uniEorm Gibbs free energy at the surface.
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Elowever, polishing which alters the crystalline structure at surface 14A appears to reduce electron transfer, ana therefore response, and also increases variation in the value of constant B.
05 The present invention lends itself to a simplified manufacturing process, since only a sinyle deposition is required for each ISE. Ater surEaces l~A and 12A have been cleaned, the membrane material, in liquid form, is deposited on surface 14A. The liquid n~turally Eorms the dome-shaped structure due to surface tension, which holds the liquid material within the boundaries defined by moat 28.
ISE 10 of the present invention is useful as an ion sensor for a wide range of different ions.
The structure remains the same, regardless of the particular electroactive species which is incorporated within membrane 16. For purposes of illustration, the following examples describe a number of different membrane compositions, all of which have been used successfully with the ISE
~; structure o the present invention.
In each example, substrate 12 was ABS
plastic, electrode body 14 was a carbon (graphite) disc of 2.032 mm diameter, and conductive pin 18 was copper. Moat 28 had an inner diameter of 3.048 mm.
Example No. 1 ~ potassium ion ISE in accordance with the present invention used a membrane which incorporated valinomycin as the electroactive species. The membrane composition was made up of 0.0088 grams of valinomycin in 0.0221 grams oE high molecular weight polyvinyl chloride tPvc~ with 0.1995 grams o didecylpthalate which acted as a plasticizer in approximately 0.35 milliliters of tetrahydrafuran.
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Example No. 2 -A sodium ion ISE was fabricated using the monocyclic antibiotic monensin as the electroactive ~pecies. The membrane composition was identical to 05 that used in the potassium i~n ISE described in Example ~o. 1, with the ionophore valinomycin 'being replaced weight-~or-weiyht by monensin.
Example No. 3 To eliminate the effect of pH dependence, the acid group in monensin was substituted with a methyl group, and the resulting methyl monensin was used as the electroactive spe~ies in the membrane.
The weight of the plasticizer in the membrane was reduced considerably to 0~09 grams. All other components were the same as in Example Nos. 1 and 2, with methyl monensin substituted for monensin weight-for-weight.
Exam le No 4 p _ .
Sodium ion ISEs using the sodium ionophore N-~ dibenzyl-~-N diphenyl 1-2 pheneLenedioxydi-acetamide were also studied. In this example, 0.005 grams of the ionophore was mixed with high molecular weight polyvinyl chloride of 0.0086 grams togsther with 0.0860 grams of didecylpthalate and made up in 0.350 milliliters of tetahydrafuran.
Exam le No 5 P
A hydrogen ion (p~l) selective electrode formed in accordance wit'h the present invention used tridodecylamine as the electroactive compound. The membrane mixture was similar to Example No. 1, with tridodecylamine replacing valinomycin weight-Eor-weig'ht.
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~xampLe No, 6 A chloride ion ISE used Aliquat 336 ~which consists mainl~ o~ triepryl-methylammonium chloride) as the electroactive compound. 0.6630 grams of 05 ~ uat 336 was dissolved in 0.5 milliliters of decyl alcohol. 0.08 grams oE cellulose acetate was dissolved in 1 milliliter oE cyclohexanone separately. When both of these mixtures had been homogenized, the cellulose ~cetate mixture was added -to the Aliquat mix-ture and the resulting mixture was then vortexed rapidly to form a uniform homogenous membrane mixture. This mixture was then depos;ted on the previously prepared electrode/substrate surface.
The electrode responses for the ISEs oE
Example Nos. 1-6 were monitored as a function of concentration by using the ISE together with a silver/silver chloride reference electrode (from Orion Research, Inc.) and measuring the signal between the two electrodes obtained in four dif~erent solutions using an Orion pH meter. The solutions were made up for testing in the physiological concentrate ranges found in whole blood, and the ionic strength of the solu-tions were maintained with suitable salts. Except as otherwise stated, the concentration oE the four solutions used to test the electrode response were multicomponent mi~tures with a Eixed ionic strength of 160. The ionic contents of the Eour solutions were as follows:
Solution Solution Solution Solution I II III IV
Na~ 0.75 100 125 160 K~ 1.5 3.0 6.0 10.0 Cl- 70 90 116 152 p~l 7.784 7.53 7.014 6.877 .. ~ ,. , . ... ,~.
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The ionic strength of these solutions is made up by adding appropriate amounts of MgCl and MgS04. The p~l was maintained by adding sodium TES and hydrogen TES in suitable porportions.
05 ~s shown in Figure 2, the response of valinomycin incorporated membrane ISE's (Example 1) was linear with a slope of about 54 millivolts per decade of concentration change. The standard deviation of slope observed was ~ 0.5 millivolts.
ISEs using a monensin incorporated membrane (Example 2) exhibited excellent linearity in response to sodium concentration, as shown in Figure 3.
Because of the known sensi-tivity of monen~in to potassium, the potassium level in the reference solutions used for testing were reduced to approximately 10 meq. The selectivity of sodium over potassium under those conditions was excellent. It was found, however, that the ISEs of Example 2 wera pH sensitive due to the acid group in monensin.
As shown in Figure 4, the ISEs using methyl monensin incorporated membranes (Example 3) exhibited a Nernstian slope with excellent linearity and reproducibility. The selectivity of the methyl monensin incorpora-ted membrane ISEs over potassium, magnesium and hydrogen ions was found to be excellent in the physiological range for blood.
The sodium ionophore incorporated membrane ISEs (Example ~) also exhibited excellent lirlearity and response in the physiological range of blood --see Figure 5.
As shown in Figure 6, -the response of pH
sensitive ISEs using a tridodecylamine incorporated membrane (Example 5) was found to be superivr for i :~33S~ ~
the physiological pH range oE blood (pH between about 6~5 and about 8.0). The cons~ant value B was found to fall within a very narrow range from one ISE to another.
05 The chloride ion ISEs (Example 6) also showed yood linearity over the range which was studied. See Figure 7.
The time responses of the ISE~ of Example Nos. 1, 4, 5 and 6 were monitored on an oscilloscope screen and compared to the response of commercially available potassium, sodium, p~ and chloride ISEs made by Orion Research, Inc. As shown in Figure 8, the sodium, potassium and pH ISEs of the examples (labelled "SenTech") exhibited comparable or faster response than the corresonding Orion ISEs. In the case of the chloride ISE, the response was slightly slower, but reached equilibrium in approximately one second.
It has been found that the shape of membrane 16, and the dimensional relationships between membrane 16 and electrode body 14 have a significant effect upon a response of ISE 10. In particular, it has been found that electrode body 14 must have an electrode surface area Al which is smaller than the surface area A2 covered by membrane 16. Particuarly good results are obtained when the ratio of Al/A2 i9 between about 0.01 and about 0.25. Preferably, the ratio i8 about 0.16.
The height (thic~ness) of membrane 16 at its point above electrode surEace 14A is also an important factor. IS~s having membrane heiyh-ts or thicknesses less than about 0.5 mm tend to exhibit low slopes and high variability in the slope values.
In addition, the failure rate of these ISEs tends to 10 I ~4 59721<
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be high when the height of membrane 16 is less than about 0.5 mm.
Membrane heights in the range of 0.5 mm to about o,9 mm are preferable, with a height of about 0.65 mrn has proved very advantageous in achieving high Nernstian slope values, repro-ducibility of those slopes without using an excessive amount of membrane material.
The convex shape of membrane 1~ allows for transport of the elec-troactive species to be more uniform across the active area of the electrode than other electrode con~igurations. For example, in e~periments, applicants form ISE structures in which the electrode body was located in a shallow well which had a greater diameter than the diameter of the electrode body.
Although the membrane covered a greater surface area than just the surface area of the electrode body, the shape of the membrane was convex rather than concave. These ISE's exhibited low slopes, with high variability in slope value, and a high failure rate.
A particular advantage of the ISE of the present inven-tion is its adaptability to a configuration useful in a dispos-able single-use device like the one described in the previously mentioned copending applications. Fig.s 9A and 9B show top and cross-sectional side views of ISE 110 which forms a part of a disposable single-use sensing card device. ISE 110 includes sub-strate 112, electrode body 114, species selec-tive membrane 116 and conductor 118. In this particular embodiment, substrate 112 is an ABS plastic sheet whlch has a thickness of about 1.6 mm.
Electrode body 114 is a solid graphite cylinder which has a diam-eter of 2.032 mm and which extends through hole 120 so that upper surfaces 112A and ll~A and lower surfaces 112B and ll~B are coplanar.
Conductor 118 runs over bottom surfaces 112B and makes contact with bottom surface ll~B of electrode body 114.
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Conductor 118 provides the conductive path between the electrode body 11~ and measurement circuitry of a clinical chemistry analyzer (not shown).
Moat 128 formed in upper surface 112 A is concentri-cally arranged around electrode body 114 and defines the outer edge of membrane 116. Moat 128 has an essentially vertical inner shoulder 128A, an essentially horizontal bottom 128B, and a sloped outer shoulder 128C. The dlameter of the inner edge of moat 128 is 3.556 mm, and the dep-th of moat 128 is about 0.381 mm. The inner diameter of sloped shoulder 128C is ~.064 mm, and the outer diameter of shoulder 128C is 4.826 mm. Shoulder 128C
is sloped to accommodate the flow of calibrant and sample fluids, as they are introduced into a test chamber in which ISE 110 is located.
In conclusion, the present invention is an improved ion selective electrode which provides accurate response (i.e. Nerns-tian slopes), linear and reproducible slope values, and an extremely simple and low cost structure to manufacture.
The present lnventlon relates to devices for senslng the presence of speclfic ions ln fluids. In particular, the pre-sent invention relates to ion selective electrode (ISE) technol-ogy, and methods of making ion selective electrodes.
An ion-selective electrode (ISE) is an electrode which exhibits an electrical response which is a function of concentra-tion of a specl.~ic ion contained in a solution which is in con-tact with the ISE and a reference electrode. Ion selective elec-trodes operate on the basis of the Nernst princlple, which wasdiscovered by W.H. Nernst, a ~5 ~, -- 1 335~L~
German physicist, in the late 1800's. The Nernst equation defines a logarithmic relationship between the potential of a solution and its ionic concentration. When an ion selective elec-trode and a 05 reEerence electrode are exposed to a solution, a potentiometric measurement can be made between the two electrodes which indicate the concentration in the solution of the particular ion to which the ion selective electrode responds.
I'he Nernst equation can be written as:
Y = M lo~lOX ~ B
where X is ion concentration, Y is the output potential, M is the Nernstian slope, and B is a constant.
Most commercially available ion selective electrodes include an internal reference electrode, an electrolyte (in either liquid or gel form) which is in contact with the internal reference electrode, and a membrane which separates the internal reference electrode and the electrolyte from the solution. The membrane is commonly a glass or polymeric membrane in which an electroactive species is incorporated. The particular electroactive species differs depending upon the particular ion to be sensed~
Coated wire electrodes are a type of ion selective electrode in which an electroactive species is incorporated in a thin polymeric film coated directly -to a metallic conductor. Coated wire electrodes differ Erom other ion selective electrodes in -that they do not use an electrolyte as an internal reEerence solution. Although coated wire electrode~
oEfer simplified construction in contrast to other ion selective electrodes, they have not found significant use other than in experimental studies.
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Although ion selective electrode (ISE) technology has been known for several decades, its use generally has been limited to laboratories with highly trained technicians making the measurements 05 and interpreting the data. One of the deterrents to the use oE ISE systems outside the laboratory has been the necessity for calibration of electrodes to establish their Nernstian slopes (M) in terms of the millivolt output response (Y) of the electrode per clecade change in concentration (X). After this is done, a further measurement has to be made in the test solution to assess its concentration. From time to time, the ISE has to be recalibrated since the Nernstian slope can change by several millivolts and its intercept on the Y axis (i.e. the constant B) can shift.
Still another deterrent is that when ISE's are initially put into use or reused after storage, they need to be equilibrated in a suitable solution.
This I'preconditioning'l of an ISE is time-consuming and inconvenient.
In the past, ISE'~ have typically exhibited significant drift. One of -the major causes of this drift in ISE's is capacitive efEects which are uncontrolled and therefore "float". This floating or changing capacitance causes drift, error, and t`he need for standardization and restandardization. The capacitance effects are related to three significant deficiencies in the prior art ion selective electrodes.
First, the spatial relationship of the reference electrode to the sensing electrode is not fixed.
Second, the prior art ISE's typically are ~33~
constructed in multiple layers over a conductor, and eacll oE these layers have varying characteristics WiliCh give varying capacitances and thereEore uncontrollable changes in capacitance.
05 rrhird, in certain multilayer ISEs having a hydropllylic layer interposed between the sensing electrode and tlle conducting layer, the capacitance challc3es continuously with time as the dried hydrophylliLc layer changes its state of hydration during the test. There are still other type~ oE
electrodes whlch have variou~ layers are not fixed:
and t~e~c c.~n be physically deformed as well, causing additional uncontrollabl~ changes in capacitance.
The present invention is an improved ion selective electrode which provides an essentially instantaneous response with no need for initial equilibrium time, and which exhibits a fixed slope.
The electrode of the present invention has a simple structure which does away with the need for an internal electrolyte associated with an internal reference electrode.
The ion selective electrode of the present inverltion includes a conductive elactrode body which is supported by an insulating substrate. A convex dome-shaped membrane containing an electroactive species is deposited over and is directly in contact with the electrode body and a surface of the sub~trate surroundiny the electrode body. ~he membrane h~s its greatest height above the electrode body and slopes down to meet the surEace oE -the substrate.
.
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Thus according to the aspect thereof the present inven-tion provides an ion selective electrode comprising: a conductive electrode body having an essentially planar first surface Al with an outer edge; an insulating substrate supporting the elec-trode body and having an essentially planar first surface which sur-rounds and is essentially coplanar with the first surface of the electrode body; and a convex dome shaped ion selective membrane over the first surface of the electrode body and the insulating substrate; the membrane covering an area A2 which is greater than area of the first surface of the electrode body and the membrane having an outer edge which is spaced laterally from and which is essentially coplanar with the outer edge of the first surface of the electrode body. Suitably, the electrode body has a second surface spaced from the first surface; and wherein the ion selec-tive electrode further comprises means for making an electricalconnection to the second surface of the electrode body. Desir-ably, the substrate is a sheet having a second surface generally parallel to its first surface; and wherein the means for making an electrical connection comprises an electrical conductor which extends over a portion of the second surface of the substrate and contacts the second surface of the electrode body.
The electrode body has a surface area Al which is less than the area A2 of the membrane. In preferred embodiments, the ratio Al/A2 is preferably in a range of about 0.01 to about 0.25.
The height of the membrane over the electrode body is preferably greater than about 0.5 mm.
In preferred embodiments oE the present invention, the insulating substrate includes a moat which surrounds and is spaced from the electrode body. An inner edge of the moat defines an outer boundary of the dome-shaped membrane.
In another aspect thereof the present lnvention pro-vides an ion s01ective electrode comprising: a conductive elec-trode body having an essentially planar first surface; an insu-~335~1~
lating substrate supporting the electrode body, the substratehaving a first surface essentially coplanar with the first sur-face of the electrode body and having an annular moat depression surrounding and spaced from the electrode body; and a convex dome-shaped ion selective membrane deposited over and directly in contact with the electrode body and the first surface of the sub-strate located within an area defined by an inner edge of the moat depression, the membrane having an outer edge which is spaced from an outer edge of the electrode body and whlch is defined by the inner edge of the moat.
In a further aspect thereof the present invention pro-vides an ion selective electrode comprising: a conductive elec-trode having an essentially planar first surface with an area A1;
an insulating substrate supporting the electrode body and having an essentially planar first sur~ace which surrounds and is essen-tially coplanar with the first surface of the electrode body; and a convex dome-shaped ion selective membrane over the first sur-faces of the electrode body and the insulating substrate; the membrane having a maximum thickness at a position over the first surface of the electrode body which is between about 0.5 mm and about 0.88mm; and the membrane having an area A2 which is greater than area Al of the first surface of the electrode body and hav-ing an outer edge which is generally concentrically spaced from and coplanar with an outer edge of the first surface of the elec--trode body, wherein Al/A2 is between about 0.01 and about 0.25.
Suitably, the selective electrode comprises a moat depressi.on in the first surface of the substrate having an inner edge spaced laterally from and surrounding the outer edge of the first sur-face of the electrode body, and wherein the outer edge of themembrane is defined by an inner edge of the moat.
In a still further aspect thereof the present invention provides an i.on selective electrode comprising: a conductive electrode body having an essentially planar surface; an insulat-ing substrate supporting the electrode body, the substrate having - 5a -~ Z ~ 3 ~ ~
a surface essentially coplanar with and surrounding the planar surface of the electrode body and having an annular moat depres-sion generally concentrically positioned to surround the elec-trode body with an inner edge of the moat depression spaced from an outer edge; and a convex dome ion selective membrane deposited over and directly in co.ntact with the electrode body and a sur-face of the substrate within the moat.
The present inventlon further provides a method of mak-ing an ion selective electrode comprising: mounting a conductiveelectrode body in an insulating substrate so that the electrode body and the i:nsulating substrate form an essentially planar exposed surface surrounded generally concentrically by a moat depression; and depositing over the planar exposed surface a mix-ture of a polymer dispersed in plasticizer with an electroactivespecies dispersed therein to form, as a result of surface ten-sion, a convex dome-shaped membrane over the electrode body and the portion of the insulating substrate surrounding -the electrode body, the membrane having an outer edge defined by an inner edge of the moat depression.
The present invention further provides a method of mak-ing an ion selective electrode comprising: mounting a conductive electrode body in an insulating substrate so that the electrode body and the insulating substrate define an essentially planar surface with a moat depression in the insulating surface which surrounds and has an inner edge which is spaced laterally from an outer edge of the electrode body; and depositing over the essen-tially planar surface a mixture of a polymer dispersed in plasti-cizer with an electroactive species dispersed therein to form aconvex dome-shaped membrane over the essentially planar surface defined by the electrode body and a portion of the insulating substrate surrounding the electrode body, the membrane having an outer edge defined by the inner edge of the moat depression.
Suitably the ion selective electrode comprises polishing the exposed surface of the electrode body prior to depositing.
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The present invention does not include an electrolyte or a separate internal reference. This greatly simplifies both the structure and the fabrication of the elec-trode, and elimi-nates multiple layers which are a cause of drift in prior art ISE's. With the present invention, ISE's having Nernstian slopes which are highly reproducible can be manufactured on a large scale basis.
The present invention will be further illustrated by way of the accompanying drawings, in which:-Figures lA and lB are top and cross-sectional views of a preferred embodiment of the ion selective electrode of the pre-sent invention, Figure 2 is a graph showing the response of ISE's of the present invention having a valinomycin incorporated membrane to potassium in O.lN NaCl solution, Figure 3 is a graph showing the response of ISE's of the present invention having a monensin incorporated membrane to sodium in NaCl solution, Figure 4 is a graph showing the response of ISE's of the present invention having a methyl - 5c -:~2~
monensin incorporated membrane to ~a~ ions in the physioloyical range of blood.
Figure 5 is a graph showing the response oE
ISI~s oE the present invention having a sodium 05 ionophore incorporated membrane to Na ions in the pllysiological range of blood.
Figure 6 is a graph showing the response of IS~3s oE the present invention having a tridodecylamine incorporated membrane to H+ ions in the ph~siological range of blood.
Figure 7 is a graph showing the response of IS~s oE the present invention having an ~liquat 336 incorporated membrane to Cl- in the physiological range oE blood.
Figure 8 is a graph comparing the response as a funtion of time of IS~s of the present invention and prior art ISEs.
Figures 9~ and 9B show top and cross-sectional views of a preferred embodiment of the ISE of the present invention used as a part of a disposable sensing device.
In Figures lA and lB, a preferred embodiment oE tlle iOII ~elective electrode 10 oE the pre~ent invention i8 shown. In this embodiment, ISE 10 is Eormed by insulating substrate 12, conductive electrode body 14, species selective membrane 16, and conductive pin 18.
Substrate 12 is, in this preferred embodiment, an insulating plastic body having a top surace 12~ and a bottom surface 12B whicll are generally planar. ~xtending through substrate 12 is J
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hole 20, with an enlarged upper recess 22 at its upper end and an enlarged lower recess 24 at its lower end. Pin 18 has its head 18A positioned in upper recess 22 and extends downward throu~h hole 20 05 50 that lower end 18B is exposed below lower surface 12B.
Electrode body 14 is inserted in upper reces~ 22 so that top surEace 14A is coplanar with surEace 12A. Bottom surEace 14B i9 bonded to conducive pin 18 by conductive silver epoxy 26.
.~urrounding and spaced Erom electrode body 14 is annular moat 28, which is a groove Eormed in upper surface 12A oE substrate 12. In the embodiment shown in Figures lA and lB, moat 28 and electrode body 14 are concentrically arranged.
Membrane 16 is preferably formed by a mixture oE a polymer dispersed in plasticizer with an electroactive species dispersed therein. As shown in Figure lB, membrane 16 has a convex dome shape, with its greatest height over electrode body 14. Inner surface 16A of membrane 16 covers and is in direct contact with top surface 14A of electrode body 14, as well as the portions o~ top surEace 12A of substrate 12 which are located within moat 28. The outer periphery oE membrane 16 is deEined by the inner s`houlder of moat 28.
Conductive pin 18 provides an electrical conductive path by which electrode body 14 can be connected to electrical mea~urement equipment necessary to make a potentiometric measurement based upon the potential difEerence between ISE 10 and another electrode (e.g. a reference electrode) which `, ' ', . '~ ' : -~ ~3~
does not interact with th0 specific ion of interest in the samemanner as ISE 10.
ISE 10 of the presen-t invention exhibits ins-tantaneous response and a predictable Nernstian slope to within ~ 2 milli-volts (and usually within + 1 millivolt). This makes the present lnvention well suited for use in a disposable, single-use sensing device. ~s a result of the highly reproducible slope, and the instantaneous response without the need for preconditloning or for equilibration, ISE 10 permits the use of a one point calibra-tion technique such as described in applicant's copending Cana-dian applica-tion No. 478,745 filed April 10, 1985. In other words, with ISE 10 is it only necessary for a single calibration measurement to be made, with a known concentration, since slope M
is a single known value and the calibrant concentration Xl is known. By measuring the voltage output Yl, a value for constant B lS determined. A second measuremen-t with a sample of unknown concentration yields ou-tput Y2 from which the unknown concentra-tion value X2 can be calculated, since both slope M and constant B are knownO
The extreme simplicity of construction of the present invention contributes to its suitability for use in a disposable, single-use sensing device. Unlike prior art devices, the present inventlon does not utilize a complex geometry or multiple layers which increase manufacturing complexity and cost, and contribute to drift and unpredictable slope values.
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In preferred embodimen-ts of the present invention, substrate 12 is made of acetonitrile butadriene styrene (ABS), and electrode body 14 is a carbon cylinder cut from a carbon ~graphite) rod.
05 ~lthough other conductive materials (such as metals like platinum) have also been used as electrode body 1~, carbon is a preferred electrode body material becau e it works best with a wide range of difEerent electroactive compounds. This i 5 particularly important since membrane 16 is in direct contact with top surface 14A of electrode body 14.
Prior to the deposition of membrane 16, top suraces 14A and 12A are cleaned with methanol.
Polishing of top surfaces 14A prior to cleaning also appears to be advantageous, although not absolutely necessary. It has been found that the more uniform and finer grained the surface 14A of electrode body 14, the less variation in the value of constant B of the Mernst equation. Coarse sanding of the surface 14A results in variation o~ about + 100 millivolts in the value of constant B. With the use of finer grade abrasives, the variation is reduced to about ~ 40 millivolts.
The alignment of the crystalline ~tructure of electrode body 14 at surface 14A is believed to play a role in response characteristics of IS¢ 10.
The mobility of electrons is highest when the diamond structure of graphite, for example, is perpendicular to the direction of electron flow. ELectrode body 1~
is typically cut from an extended graphite rod, and most of the crystals of body 14 are aligned in the direction for optimum electron flow. Some polishing, therefore, appears to be of advantage in yiving a more uniEorm Gibbs free energy at the surface.
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Elowever, polishing which alters the crystalline structure at surface 14A appears to reduce electron transfer, ana therefore response, and also increases variation in the value of constant B.
05 The present invention lends itself to a simplified manufacturing process, since only a sinyle deposition is required for each ISE. Ater surEaces l~A and 12A have been cleaned, the membrane material, in liquid form, is deposited on surface 14A. The liquid n~turally Eorms the dome-shaped structure due to surface tension, which holds the liquid material within the boundaries defined by moat 28.
ISE 10 of the present invention is useful as an ion sensor for a wide range of different ions.
The structure remains the same, regardless of the particular electroactive species which is incorporated within membrane 16. For purposes of illustration, the following examples describe a number of different membrane compositions, all of which have been used successfully with the ISE
~; structure o the present invention.
In each example, substrate 12 was ABS
plastic, electrode body 14 was a carbon (graphite) disc of 2.032 mm diameter, and conductive pin 18 was copper. Moat 28 had an inner diameter of 3.048 mm.
Example No. 1 ~ potassium ion ISE in accordance with the present invention used a membrane which incorporated valinomycin as the electroactive species. The membrane composition was made up of 0.0088 grams of valinomycin in 0.0221 grams oE high molecular weight polyvinyl chloride tPvc~ with 0.1995 grams o didecylpthalate which acted as a plasticizer in approximately 0.35 milliliters of tetrahydrafuran.
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Example No. 2 -A sodium ion ISE was fabricated using the monocyclic antibiotic monensin as the electroactive ~pecies. The membrane composition was identical to 05 that used in the potassium i~n ISE described in Example ~o. 1, with the ionophore valinomycin 'being replaced weight-~or-weiyht by monensin.
Example No. 3 To eliminate the effect of pH dependence, the acid group in monensin was substituted with a methyl group, and the resulting methyl monensin was used as the electroactive spe~ies in the membrane.
The weight of the plasticizer in the membrane was reduced considerably to 0~09 grams. All other components were the same as in Example Nos. 1 and 2, with methyl monensin substituted for monensin weight-for-weight.
Exam le No 4 p _ .
Sodium ion ISEs using the sodium ionophore N-~ dibenzyl-~-N diphenyl 1-2 pheneLenedioxydi-acetamide were also studied. In this example, 0.005 grams of the ionophore was mixed with high molecular weight polyvinyl chloride of 0.0086 grams togsther with 0.0860 grams of didecylpthalate and made up in 0.350 milliliters of tetahydrafuran.
Exam le No 5 P
A hydrogen ion (p~l) selective electrode formed in accordance wit'h the present invention used tridodecylamine as the electroactive compound. The membrane mixture was similar to Example No. 1, with tridodecylamine replacing valinomycin weight-Eor-weig'ht.
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~xampLe No, 6 A chloride ion ISE used Aliquat 336 ~which consists mainl~ o~ triepryl-methylammonium chloride) as the electroactive compound. 0.6630 grams of 05 ~ uat 336 was dissolved in 0.5 milliliters of decyl alcohol. 0.08 grams oE cellulose acetate was dissolved in 1 milliliter oE cyclohexanone separately. When both of these mixtures had been homogenized, the cellulose ~cetate mixture was added -to the Aliquat mix-ture and the resulting mixture was then vortexed rapidly to form a uniform homogenous membrane mixture. This mixture was then depos;ted on the previously prepared electrode/substrate surface.
The electrode responses for the ISEs oE
Example Nos. 1-6 were monitored as a function of concentration by using the ISE together with a silver/silver chloride reference electrode (from Orion Research, Inc.) and measuring the signal between the two electrodes obtained in four dif~erent solutions using an Orion pH meter. The solutions were made up for testing in the physiological concentrate ranges found in whole blood, and the ionic strength of the solu-tions were maintained with suitable salts. Except as otherwise stated, the concentration oE the four solutions used to test the electrode response were multicomponent mi~tures with a Eixed ionic strength of 160. The ionic contents of the Eour solutions were as follows:
Solution Solution Solution Solution I II III IV
Na~ 0.75 100 125 160 K~ 1.5 3.0 6.0 10.0 Cl- 70 90 116 152 p~l 7.784 7.53 7.014 6.877 .. ~ ,. , . ... ,~.
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The ionic strength of these solutions is made up by adding appropriate amounts of MgCl and MgS04. The p~l was maintained by adding sodium TES and hydrogen TES in suitable porportions.
05 ~s shown in Figure 2, the response of valinomycin incorporated membrane ISE's (Example 1) was linear with a slope of about 54 millivolts per decade of concentration change. The standard deviation of slope observed was ~ 0.5 millivolts.
ISEs using a monensin incorporated membrane (Example 2) exhibited excellent linearity in response to sodium concentration, as shown in Figure 3.
Because of the known sensi-tivity of monen~in to potassium, the potassium level in the reference solutions used for testing were reduced to approximately 10 meq. The selectivity of sodium over potassium under those conditions was excellent. It was found, however, that the ISEs of Example 2 wera pH sensitive due to the acid group in monensin.
As shown in Figure 4, the ISEs using methyl monensin incorporated membranes (Example 3) exhibited a Nernstian slope with excellent linearity and reproducibility. The selectivity of the methyl monensin incorpora-ted membrane ISEs over potassium, magnesium and hydrogen ions was found to be excellent in the physiological range for blood.
The sodium ionophore incorporated membrane ISEs (Example ~) also exhibited excellent lirlearity and response in the physiological range of blood --see Figure 5.
As shown in Figure 6, -the response of pH
sensitive ISEs using a tridodecylamine incorporated membrane (Example 5) was found to be superivr for i :~33S~ ~
the physiological pH range oE blood (pH between about 6~5 and about 8.0). The cons~ant value B was found to fall within a very narrow range from one ISE to another.
05 The chloride ion ISEs (Example 6) also showed yood linearity over the range which was studied. See Figure 7.
The time responses of the ISE~ of Example Nos. 1, 4, 5 and 6 were monitored on an oscilloscope screen and compared to the response of commercially available potassium, sodium, p~ and chloride ISEs made by Orion Research, Inc. As shown in Figure 8, the sodium, potassium and pH ISEs of the examples (labelled "SenTech") exhibited comparable or faster response than the corresonding Orion ISEs. In the case of the chloride ISE, the response was slightly slower, but reached equilibrium in approximately one second.
It has been found that the shape of membrane 16, and the dimensional relationships between membrane 16 and electrode body 14 have a significant effect upon a response of ISE 10. In particular, it has been found that electrode body 14 must have an electrode surface area Al which is smaller than the surface area A2 covered by membrane 16. Particuarly good results are obtained when the ratio of Al/A2 i9 between about 0.01 and about 0.25. Preferably, the ratio i8 about 0.16.
The height (thic~ness) of membrane 16 at its point above electrode surEace 14A is also an important factor. IS~s having membrane heiyh-ts or thicknesses less than about 0.5 mm tend to exhibit low slopes and high variability in the slope values.
In addition, the failure rate of these ISEs tends to 10 I ~4 59721<
~ 3 3 ~ ~
be high when the height of membrane 16 is less than about 0.5 mm.
Membrane heights in the range of 0.5 mm to about o,9 mm are preferable, with a height of about 0.65 mrn has proved very advantageous in achieving high Nernstian slope values, repro-ducibility of those slopes without using an excessive amount of membrane material.
The convex shape of membrane 1~ allows for transport of the elec-troactive species to be more uniform across the active area of the electrode than other electrode con~igurations. For example, in e~periments, applicants form ISE structures in which the electrode body was located in a shallow well which had a greater diameter than the diameter of the electrode body.
Although the membrane covered a greater surface area than just the surface area of the electrode body, the shape of the membrane was convex rather than concave. These ISE's exhibited low slopes, with high variability in slope value, and a high failure rate.
A particular advantage of the ISE of the present inven-tion is its adaptability to a configuration useful in a dispos-able single-use device like the one described in the previously mentioned copending applications. Fig.s 9A and 9B show top and cross-sectional side views of ISE 110 which forms a part of a disposable single-use sensing card device. ISE 110 includes sub-strate 112, electrode body 114, species selec-tive membrane 116 and conductor 118. In this particular embodiment, substrate 112 is an ABS plastic sheet whlch has a thickness of about 1.6 mm.
Electrode body 114 is a solid graphite cylinder which has a diam-eter of 2.032 mm and which extends through hole 120 so that upper surfaces 112A and ll~A and lower surfaces 112B and ll~B are coplanar.
Conductor 118 runs over bottom surfaces 112B and makes contact with bottom surface ll~B of electrode body 114.
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Conductor 118 provides the conductive path between the electrode body 11~ and measurement circuitry of a clinical chemistry analyzer (not shown).
Moat 128 formed in upper surface 112 A is concentri-cally arranged around electrode body 114 and defines the outer edge of membrane 116. Moat 128 has an essentially vertical inner shoulder 128A, an essentially horizontal bottom 128B, and a sloped outer shoulder 128C. The dlameter of the inner edge of moat 128 is 3.556 mm, and the dep-th of moat 128 is about 0.381 mm. The inner diameter of sloped shoulder 128C is ~.064 mm, and the outer diameter of shoulder 128C is 4.826 mm. Shoulder 128C
is sloped to accommodate the flow of calibrant and sample fluids, as they are introduced into a test chamber in which ISE 110 is located.
In conclusion, the present invention is an improved ion selective electrode which provides accurate response (i.e. Nerns-tian slopes), linear and reproducible slope values, and an extremely simple and low cost structure to manufacture.
Claims (22)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. An ion selective electrode comprising:
a conductive electrode body having an essentially planar first surface Al with an outer edge;
an insulating substrate supporting the electrode body and having an essentially planar first surface which surrounds and is essentially coplanar with the first surface of the electrode body; and a convex dome-shaped ion selective membrane over the first surfaces of the electrode body and the insulating substrate; the membrane covering an area A2 which is greater than area of the first surface of the electrode body and the membrane having an outer edge which is spaced laterally from and which is essentially coplanar with the outer edge of the first surface of the electrode body.
a conductive electrode body having an essentially planar first surface Al with an outer edge;
an insulating substrate supporting the electrode body and having an essentially planar first surface which surrounds and is essentially coplanar with the first surface of the electrode body; and a convex dome-shaped ion selective membrane over the first surfaces of the electrode body and the insulating substrate; the membrane covering an area A2 which is greater than area of the first surface of the electrode body and the membrane having an outer edge which is spaced laterally from and which is essentially coplanar with the outer edge of the first surface of the electrode body.
2. The ion selective electrode of claim 1 wherein a ratio of area A1 of the first surface of the electrode body and area A2 covered by the membrane is between about 0.01 and about 0.25.
3. The ion selective electrode of claim 2 wherein the ratio A1/A2 is about 0.16.
4. The ion selective electrode of claim wherein the membrane has a maximum thickness at a position over the first surface of the electrode body.
5. The ion selective electrode of claim 4 wherein the maximum thickness has a lower limit of about 0.5 mm.
6. The ion selective electrode of claim 5 wherein the maximum thickness has an upper limit of about 0.9 mm.
7. The ion selective electrode of claim 6 wherein the maximum thickness is about 0.65 mm.
8. The ion selective electrode of claim 1 wherein the electrode body has a second surface spaced from the first surface; and wherein the ion selective electrode further comprises means for making an electrical connection to the second surface of the electrode body.
9. The ion selective electrode of claim 8 wherein the substrate is a sheet having a second surface generally parallel to its first surface; and wherein the means for making an electrical connection comprises an electrical conductor which extends over a portion of the second surface of the substrate and contacts the second surface of the electrode body.
10. The ion selective electrode of claim 1 and further comprising a moat depression in the first surface of the substrate spaced from and surrounding the outer edge of the first surface of the electrode body.
11. The ion selective electrode of claim 10 wherein the outer edge of the membrane is defined by an inner edge of the moat depression.
12. The ion selective electrode of claim 11 wherein the moat depression in the first surface has an inner shoulder which extends downward from the inner edge of the moat and an outer shoulder which extends upward and outward to an outer edge of the moat.
13. The ion selective electrode of claim 1 wherein the membrane is a mixture of a polymer and an electroactive species.
14. The ion selective electrode of claim 1 wherein the electrode body is carbon.
15. The ion selective electrode of claim 1 wherein the first surface of the electrode body is a polished surface.
16. An ion selective electrode comprising:
a conductive electrode body having an essentially planar first surface;
an insulating substrate supporting the electrode body, the substrate having a first surface essentially coplanar with the first surface of the electrode body and having an annular moat depression surrounding and spaced from the electrode body; and a convex dome-shaped ion selective membrane deposited over and directly in contact with the electrode body and the first surface of the substrate located within an area defined by an inner edge of the moat depression, the membrane having an outer edge which is spaced from an outer edge of the electrode body and which is defined by the inner edge of the moat.
a conductive electrode body having an essentially planar first surface;
an insulating substrate supporting the electrode body, the substrate having a first surface essentially coplanar with the first surface of the electrode body and having an annular moat depression surrounding and spaced from the electrode body; and a convex dome-shaped ion selective membrane deposited over and directly in contact with the electrode body and the first surface of the substrate located within an area defined by an inner edge of the moat depression, the membrane having an outer edge which is spaced from an outer edge of the electrode body and which is defined by the inner edge of the moat.
17. A method of making an ion selective electrode comprising:
mounting a conductive electrode body in an insulating substrate so that the electrode body and the insulating substrate define an essentially planar surface with a moat depression in the insulating surface which surrounds and has an inner edge which is spaced laterally from an outer edge of the electrode body; and depositing over the essentially planar surface a mixture of a polymer dispersed in plasticizer with an electroactive species dispersed therein to form a convex dome-shaped membrane over the essentially planar surface defined by the electrode body and a portion of the insulating substrate surrounding the electrode body, the membrane having an outer edge defined by the inner edge of the moat depression.
mounting a conductive electrode body in an insulating substrate so that the electrode body and the insulating substrate define an essentially planar surface with a moat depression in the insulating surface which surrounds and has an inner edge which is spaced laterally from an outer edge of the electrode body; and depositing over the essentially planar surface a mixture of a polymer dispersed in plasticizer with an electroactive species dispersed therein to form a convex dome-shaped membrane over the essentially planar surface defined by the electrode body and a portion of the insulating substrate surrounding the electrode body, the membrane having an outer edge defined by the inner edge of the moat depression.
18. The method of claim 17 and further comprising:
polishing the exposed surface of the electrode body prior to depositing.
polishing the exposed surface of the electrode body prior to depositing.
19. An ion selective electrode comprising:
a conductive electrode having an essentially planar first surface with an area A1;
an insulating substrate supporting the electrode body and having an essentially planar first surface which surrounds and is essentially coplanar with the first surface of the electrode body: and a convex dome-shaped ion selective membrane over the first surfaces of the electrode body and the insulating substrate; the membrane having a maximum thickness at a position over the first surface of the electrode body which is between about 0.5 mm and about 0.88 mm; and the membrane having an area A2 which is greater than area A1 of the first surface of the electrode body and having an outer edge which is generally concentrically spaced from and coplanar with an outer edge of the first surface of the electrode body, wherein A1/A2 is between about 0.01 and about 0.25.
a conductive electrode having an essentially planar first surface with an area A1;
an insulating substrate supporting the electrode body and having an essentially planar first surface which surrounds and is essentially coplanar with the first surface of the electrode body: and a convex dome-shaped ion selective membrane over the first surfaces of the electrode body and the insulating substrate; the membrane having a maximum thickness at a position over the first surface of the electrode body which is between about 0.5 mm and about 0.88 mm; and the membrane having an area A2 which is greater than area A1 of the first surface of the electrode body and having an outer edge which is generally concentrically spaced from and coplanar with an outer edge of the first surface of the electrode body, wherein A1/A2 is between about 0.01 and about 0.25.
20. The ion selective electrode of claim 19 and further comprising a moat depression in the first surface of the substrate having an inner edge spaced laterally from and surrounding the outer edge of the first surface of the electrode body, and wherein the outer edge of the membrane is defined by an inner edge of the moat.
21. An ion selective electrode comprising:
a conductive electrode body having an essentially planar surface;
an insulating substrate supporting the electrode body, the substrate having a surface essentially coplanar with and surrounding the planar surface of the electrode body and having an annular moat depression generally concentrically positioned to surround the electrode body with an inner edge of the moat depression spaced from an outer edge; and a convex dome ion selective membrane deposited over and directly in contact with the electrode body and a surface of the substrate within the moat.
a conductive electrode body having an essentially planar surface;
an insulating substrate supporting the electrode body, the substrate having a surface essentially coplanar with and surrounding the planar surface of the electrode body and having an annular moat depression generally concentrically positioned to surround the electrode body with an inner edge of the moat depression spaced from an outer edge; and a convex dome ion selective membrane deposited over and directly in contact with the electrode body and a surface of the substrate within the moat.
22. A method of making an ion selective electrode comprising:
mounting a conductive electrode body in an insulating substrate so that the electrode body and the insulating substrate form an essentially planar exposed surface surrounded generally concentrically by a moat depression; and depositing over the planar exposed surface a mixture of a polymer dispersed in plasticizer with an electroactive species dispersed therein to form, as a result of surface tension, a convex dome-shaped membrane over the electrode body and the portion of the insulating substrate surrounding the electrode body, the membrane having an outer edge defined by an inner edge of the moat depression.
mounting a conductive electrode body in an insulating substrate so that the electrode body and the insulating substrate form an essentially planar exposed surface surrounded generally concentrically by a moat depression; and depositing over the planar exposed surface a mixture of a polymer dispersed in plasticizer with an electroactive species dispersed therein to form, as a result of surface tension, a convex dome-shaped membrane over the electrode body and the portion of the insulating substrate surrounding the electrode body, the membrane having an outer edge defined by an inner edge of the moat depression.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/649,434 US4549951A (en) | 1984-09-11 | 1984-09-11 | Ion selective electrode |
| US649,434 | 1984-09-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1233511A true CA1233511A (en) | 1988-03-01 |
Family
ID=24604764
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000490329A Expired CA1233511A (en) | 1984-09-11 | 1985-09-10 | Ion selective electrode |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US4549951A (en) |
| EP (1) | EP0192760B1 (en) |
| JP (1) | JPS62500197A (en) |
| CA (1) | CA1233511A (en) |
| DE (1) | DE3580981D1 (en) |
| WO (1) | WO1986001894A1 (en) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3585915T2 (en) * | 1984-12-28 | 1993-04-15 | Terumo Corp | ION SENSOR. |
| KR900008847B1 (en) * | 1985-05-27 | 1990-11-30 | 테루모가부시끼가이샤 | Ion senser and method of manufacturing same |
| US5139626A (en) * | 1985-10-02 | 1992-08-18 | Terumo Corporation | Ion concentration measurement method |
| DK626986A (en) * | 1985-12-25 | 1987-06-26 | Terumo Corp | ion sensor |
| JPS62169044A (en) * | 1986-01-22 | 1987-07-25 | Fuji Photo Film Co Ltd | Chlorine ion selection electrode |
| EP0235470B1 (en) * | 1986-01-24 | 1992-11-11 | TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION | Ion-sensitive fet sensor |
| JPS62180263A (en) * | 1986-02-04 | 1987-08-07 | Terumo Corp | Oxygen sensor |
| US5310473A (en) * | 1986-03-19 | 1994-05-10 | Horiba Ltd. | Removable sample testing member for use in measuring ion concentration |
| US5248403A (en) * | 1986-03-19 | 1993-09-28 | Horiba, Ltd. | Gelatinized member for use in electrodes measuring ion concentration |
| US4871442A (en) * | 1986-05-01 | 1989-10-03 | Terumo Corporation | Ion sensor |
| JPS62277547A (en) * | 1986-05-26 | 1987-12-02 | Terumo Corp | Gas sensor |
| US5011588A (en) * | 1986-09-17 | 1991-04-30 | Rao K Jagan M | Ion selective dip electrode assembly |
| JPS63131056A (en) * | 1986-11-20 | 1988-06-03 | Terumo Corp | Fet electrode |
| JPS63131057A (en) * | 1986-11-20 | 1988-06-03 | Terumo Corp | Enzyme sensor |
| EP0333862A4 (en) * | 1986-12-10 | 1992-01-02 | Terumo Kabushiki Kaisha | Ion carrier membrane and ion sensor provided with same |
| JPH0446205Y2 (en) * | 1986-12-11 | 1992-10-29 | ||
| US4762594A (en) * | 1987-01-29 | 1988-08-09 | Medtest Systems, Inc. | Apparatus and methods for sensing fluid components |
| US5004583A (en) * | 1987-01-29 | 1991-04-02 | Medtest Systems, Inc. | Universal sensor cartridge for use with a universal analyzer for sensing components in a multicomponent fluid |
| US4946562A (en) * | 1987-01-29 | 1990-08-07 | Medtest Systems, Inc. | Apparatus and methods for sensing fluid components |
| JPS63225164A (en) * | 1987-03-16 | 1988-09-20 | Horiba Ltd | Sheet like electrode for measuring ion |
| US4889612A (en) * | 1987-05-22 | 1989-12-26 | Abbott Laboratories | Ion-selective electrode having a non-metal sensing element |
| US4874500A (en) * | 1987-07-15 | 1989-10-17 | Sri International | Microelectrochemical sensor and sensor array |
| US5192417A (en) * | 1987-09-21 | 1993-03-09 | Terumo Kabushiki Kaisha | Lithium ion sensor |
| JPH021535A (en) * | 1987-10-05 | 1990-01-05 | Arden Medical Syst Inc | Sensor for measuring chemical seed allowing dehydrogenation from enzyme in aqueous solution |
| JPH01272957A (en) * | 1988-04-25 | 1989-10-31 | Terumo Corp | Ion sensitive film its production and ion sensor |
| GR880100664A (en) * | 1988-10-05 | 1994-03-31 | Arden Medical Systems Inc | Sensor for measurement of enzyme hydrogenetable/dehydrogenetable chemical species in aqueous solutions |
| US6306594B1 (en) * | 1988-11-14 | 2001-10-23 | I-Stat Corporation | Methods for microdispensing patterened layers |
| US5200051A (en) * | 1988-11-14 | 1993-04-06 | I-Stat Corporation | Wholly microfabricated biosensors and process for the manufacture and use thereof |
| US5221456A (en) * | 1991-10-22 | 1993-06-22 | Rosemount Inc. | Insulated core electrode for ph sensor |
| AU3274693A (en) * | 1991-12-31 | 1993-07-28 | Abbott Laboratories | Composite membrane |
| US5310469A (en) * | 1991-12-31 | 1994-05-10 | Abbott Laboratories | Biosensor with a membrane containing biologically active material |
| US5283186A (en) * | 1991-12-31 | 1994-02-01 | Abbott Laboratories | Preparation of a compressed membrane containing immobilized biologically acting material |
| US5286365A (en) * | 1992-01-15 | 1994-02-15 | Beckman Instruments, Inc. | Graphite-based solid state polymeric membrane ion-selective electrodes |
| GB9401356D0 (en) * | 1994-01-25 | 1994-03-23 | Univ Manchester | Sensor device |
| JP3441461B2 (en) * | 1994-03-25 | 2003-09-02 | ノバルティス アクチェンゲゼルシャフト | Optical sensor for ion measurement |
| US6146510A (en) * | 1996-05-16 | 2000-11-14 | Sendx Medical, Inc. | Sensor cartridge for a fluid analyte analyzer |
| US6022463A (en) * | 1996-05-16 | 2000-02-08 | Sendx Medical, Inc. | Sensors with subminiature through holes |
| US5916425A (en) * | 1996-05-16 | 1999-06-29 | Sendx Medical, Inc. | Electronic wiring substrate with subminiature thru-holes |
| US6398931B1 (en) | 2000-01-31 | 2002-06-04 | Phoenix Electrode Company | Combination ion-selective electrode with a replaceable sensing membrane |
| US6896778B2 (en) * | 2001-06-04 | 2005-05-24 | Epocal Inc. | Electrode module |
| US7101472B2 (en) * | 2002-03-13 | 2006-09-05 | The Charles Stark Draper Laboratory, Inc. | Microfluidic ion-selective electrode sensor system |
| US7407570B2 (en) * | 2002-03-13 | 2008-08-05 | The Charles Stark Draper Laboratory, Inc. | Disposable, self-administered electrolyte test |
| US20040249600A1 (en) * | 2003-06-03 | 2004-12-09 | Tiller William A. | Apparatus and methods of measuring a thermodynamic potential of a limited physical space characterized by a series of symmetry states |
| US20060042961A1 (en) * | 2004-08-30 | 2006-03-02 | Xihai Mu | Potentiometric measurement of chloride concentration in an acidic solution |
| EP3097181B1 (en) * | 2014-01-22 | 2020-07-01 | Molecular Devices, LLC | Replaceable ground electrode for electrophysiology |
| DE102018118792A1 (en) * | 2017-08-14 | 2019-02-14 | Endress+Hauser Conducta Gmbh+Co. Kg | Method for manufacturing an ISE half cell, ISE half cell, sensor and multiparameter sensor |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3406109A (en) * | 1964-07-20 | 1968-10-15 | Yellow Springs Instr | Polarographic sensor |
| CH479870A (en) * | 1966-08-09 | 1969-10-15 | Simon Wilhelm | Ion-specific electrode system |
| US3700576A (en) * | 1970-02-27 | 1972-10-24 | Hydronautics | Ion-activity measuring electrode |
| US3912614A (en) * | 1972-01-10 | 1975-10-14 | Int Biophysics Corp | Sensor |
| CH589096A5 (en) * | 1972-04-24 | 1977-06-30 | Moeller W Glasblaeserei | |
| CA1002271A (en) * | 1972-11-10 | 1976-12-28 | Masumi Hattori | Method of making an ion-selective electrode |
| US4182667A (en) * | 1974-09-04 | 1980-01-08 | National Research Development Corporation | Ion-sensitive electrodes |
| HU170325B (en) * | 1974-10-31 | 1977-05-28 | ||
| US4116796A (en) * | 1975-04-23 | 1978-09-26 | Radelkis Elektrokemiai Muszergyarto Szovetkezet | Selective halide and sulfide sensitive electrodes |
| US4133735A (en) * | 1977-09-27 | 1979-01-09 | The Board Of Regents Of The University Of Washington | Ion-sensitive electrode and processes for making the same |
| US4276141A (en) * | 1978-02-24 | 1981-06-30 | Beckman Instruments, Inc. | Solid state ion selective electrodes |
| US4214968A (en) * | 1978-04-05 | 1980-07-29 | Eastman Kodak Company | Ion-selective electrode |
| JPS5564759U (en) * | 1978-10-27 | 1980-05-02 | ||
| US4225410A (en) * | 1978-12-04 | 1980-09-30 | Technicon Instruments Corporation | Integrated array of electrochemical sensors |
| SU898314A1 (en) * | 1979-08-08 | 1982-01-15 | Предприятие П/Я М-5534 | Ion selective membrane electrode |
| US4340457A (en) * | 1980-01-28 | 1982-07-20 | Kater John A R | Ion selective electrodes |
| JPS5837555U (en) * | 1981-09-07 | 1983-03-11 | オリンパス光学工業株式会社 | ion selective electrode |
-
1984
- 1984-09-11 US US06/649,434 patent/US4549951A/en not_active Expired - Fee Related
-
1985
- 1985-09-09 EP EP85904710A patent/EP0192760B1/en not_active Expired - Lifetime
- 1985-09-09 WO PCT/US1985/001704 patent/WO1986001894A1/en active IP Right Grant
- 1985-09-09 DE DE8585904710T patent/DE3580981D1/en not_active Expired - Fee Related
- 1985-09-09 JP JP60504144A patent/JPS62500197A/en active Pending
- 1985-09-10 CA CA000490329A patent/CA1233511A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| EP0192760B1 (en) | 1990-12-19 |
| EP0192760A4 (en) | 1987-03-05 |
| JPS62500197A (en) | 1987-01-22 |
| US4549951A (en) | 1985-10-29 |
| EP0192760A1 (en) | 1986-09-03 |
| WO1986001894A1 (en) | 1986-03-27 |
| DE3580981D1 (en) | 1991-01-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |