Mechanistic studies of ion-selective electrodes

MECHANISTIC ELECTRODES

STUDIES OF ION-SELECTIVE

G.J. Moody ABSTRACT A knowledge of the chemical composition of blood urine and other body flvids is a daily requirement for departments of biochemistry. Electronic circuitry and computers to process the data are readily available, but satisfactory transducers to convert chemical composition into electrical signals are frequently the weakest link in the chain of measurement. This review is concerned with one group of transducers: ion-selective electrodes. Since the commercial success of the calcium and fluoride ions-selective electrodes in the mid-sixties, a range ofother electrodes has become available. Their use has already conferred considerable benefus upon medicine, e.g. rapid, low-cost, multiple assay of major blood components; diagnostic surveys of chloride sweat levels relating to cystic fibrosis; and momtoting blood fluorides during and after halothane administration Ttiir adoption for indirectly sensing enzymes and associated substrates is particularly noteworthy. Recent advances in electronics, coupled with flow injection schemes based on ion-selective electrodes, have facilitated the

Keywords:

Electrodes,

ions, medical

electronics,

ion-selective

electrodes

INTRODUCTION

MEMBRANES

Mechanistic studies on sensor membranes are relevant to the design of new and improved ionselective electrodes as well as to the transport of material in biological membranes. Techniques’ --98 designed to study the mechanistic aspects of these sensors relate mainly to the use of radiotracers and resistance/impedance measurements, but more recently some interesting surface analyses have been conducted. Many miscellaneous techniques, a selection of which is presented in Tables I and 2, have also been re orted, a recent example being a holographic inte K erometric study of potassium ion fluxes through a liquid membrane cornprizing a crown ether in chloroform95. From a practical standpoint such investigations have been based on the complete electrochemical cell or just the sensor membrane material. The sensor membrane of ionselective electrodes may be simply classified on the basis of their fured or mobile sites; this review is concerned chiefly with tracer and impedance work associated with a restricted number of ion-selective electrodes from each of the four types in Tables 1 and 2.

Department of Applied Chemistry, CF1 3XF, UK

0 1985 Buttetworth 0141-5425/85/030183-13

management of hundreds of samples daily. However, developments in the mechanistic knowledge of these sensors have not matched the increase in their application, although definite progress can be reported for example with regard to the origin of the potential signals induced by ion actimties in solution Numerous techniques have been devised to unravel mechanistic problems, among which radioisotope tracer and impedance measurements may be cited as especially valuable. Selectivity pe$ormance, particularly in complex biologual media, and undesirable features such as protan poisoning need further research Organic chemists are now better placed to synthesize new designs of acyclic and cyclic molecules as mobile site, ion-selective, sensor materials which with appropnate mediator solvents, provide improved sensor cocktails. This design feature is well illustrated by the continuing quest for a lithium ion-selective electrode compatible with the high levels of sodmm intelference in blood

UWIST, PO Box 13, Cardiff,

& Co (Publishers) $03.00

Glass membrane

WITH

FIXED

SITES

(Two types)

electrodes

Thomson’s proposal in 1875 that glass possessed ionic conductivity99 was verified some thirty years later by Cremer’ O”. Further research by Haber and Klemensiewicz”’ established that glass surfaces swelled in water and moreover these surfaces functioned as hydrogen electrodes in a nearNernstian fashion. The identity of the actual ions which are transported, partially or completely, across the width of a sensor membrane material, as well as those excluded, is of paramount importance; thus Burt’** managed to drive sodium ions across the soda glass walls of an incandescent lamp immersed in molten sodium nitrate at 312°C. Electrons emitted from the hot internal filament maintained at a negative potential relative to the melt, reduced the sodium ions. High yields of sodium ( - 300 mg/h) and excellent quality (K content < 2 p.p.b.) were produced despite the use of impure sodium nitrate. It is significant that potassium was not similarly transported when potassium nitrate was substituted for sodium nitrate, while sodium ions were no{ mobile in Pyrex glass.

Ltd J. Biomed. Eng.

985, Vol. 7, July

183

Ion-selective electrodes: G.J. Moody

Table 1

Selected mechanistic studies on sensor membranes with fxed sites

Membrane Type

Glass

CtystaI

Table 2

Technique

Sensor system

Reference No.

‘H,2’Na,‘zK tracer Titration Impedance Resistance Ion sputtering

Silicate and hydrated glasses Porous glasses/evaluation of pK sites Commercial glasses Ingold LOT glasses/acid, alkali and neutral media Leached glasses/ion concentration profiles

5,6 16 8,18,20,46,47 +11 14

Coulometry Impedance Conductance Auger spectrometry ESCA (XPS) XRF SEM X-ray and neutron diffraction a1Br tracer “F tracer

LaF, membrand99.2% current efficiency IaFs;AgCI;Ag,S;CuSAg,S LaF, membranes and electrodes Cu(I1) electrodes/interference films AgCkAg,S,Cu,bAg,S and PbS membranes Cl and CN sensor membranes Ag,S;AgBr and AgI (silicone rubber) membranes AgBr sensors AgCl electrodes/bromide interference

36 19,21-24,49 31 56 57,61,62 62,69 64,67,68 64 64 38

LaFs

Selected mechanistic studies on sensor membranes with mobile sites

Membrane

Technique

Sensor system

Reference No.

‘*C,‘*K and WI tracer Speciation Current-voltage plots Impedance Speciation IR spectroscopy Transport Current-voltage plots r5Ca,L”Ba and ‘“Cl tracer

WC-Valinomycin membranes/Transfer numbers measured Orion 92-19 potassium ISE Orion 92-19 potassium ISE K-valinomycin membranes Cation-crown complexes Nigericin and monensin complexes with Li,Na,K,Rb,Cs Monensin membrane/sodium PVC-calcium -braus PVC-bariurwAntarox CO880 membranes

78.85 76 79 46,87 77 86 75 84 91

XRF, g.1.c ‘H,‘Be,2’NqHCq*9Sr,‘3’Ba and ‘6CI tracer Impedance Bipolar pulse conductometry Zero current potentiometry

PVC-calcium electrodes/surfactant PVCcalcium electrodes Commercial and PVC ISEs Calcium electrodes Calcium electrodes

72 88.-9a.92 17,29,39 32 28

Type

Neutral carrier

Charged

carrier

However, these elegant experimentslo are unrealistic at high temperatures and in the absence of the usual aqueous medium. Later Haugaard44 demonstrated electrolytic conduction across the membranes of glass bulbs comprising Corning glass 015 (Na,O, 22%; Ca0,6%; SiO,,72%) filled with hydrochloric acid (0.02 M) while immersed in acid of the same strength. The decrease in acidity of both inner and outer solutions after lengthy electrolysis (561 h) at 220 V and 25°C matched the silver deposited in a silver voltameter connected in parallel. Haugaard concluded that sodium ions, but not hydrogen ions, were responsible for the quantitative transfer of charge through the glass. Schwabe and DahmsS employed similar electrolysis tactics with pH glass bulbs containing hydrochloric acid (0.01 M) plus tritium (1.3 - 3.1 mC cmP3), for

shorter times and at 72.2” - 80.5”C. The outer solutions were kept in contact with the glass electrodes for between one and five days when the /3 counts amounted to < lo-‘OC, i.e. -2 X log tritium atoms. The inner solutions were not counted. This series of experiments, designed to establish that hydrogen ions were not transported across the MacInnes glass membranes containing - 2% titanium dioxide, are therefore inconclusive.

184

J. Biomed. Eng. 1985, Vol. 7, July

interference

New glass electrodes are unsuitable sensors until properly soaked in water; during such soaking (conditioning) periods the surface becomes swollen, as found by interferomet$. Haugaard4 has shown that a glass electrode with a conditioned inner surface, i.e. soaked in hydrochloric acid (0.01 M) for a week but with a fresh outer membrane surface, (i.e. no soaking at all) exhibited potential drift. This drift was correlated with the ability of the glass to exchange its sodium ions for hydrogen ions for at least forty minutes after immersion in citrate buffer. Swollen surfaces are generally understood to be hydrolysed silica-rich regions in which a portion of the monovalent cations, e.g. sodium, has been exchanged for hydrogen: I Si-0-Na(glass)+

H+ &

ZSi-0-H(glass)

+ Na+ (I)

Glass can be viewed as a concentrated electrolyte which functions as a perfect cation exchanger and is susceptible to a spontaneous uptake of water until the osmotic pressure is balanced*. The equilibrium ion-exchange process at the very thin glass surfaces, and diffusion processes within the bulky and much thicker glass interior, were considered by Eisenman to contribute algebraically

Ion-selective electrodes: G.J. Moody

to the source of the observed potentials*7

to 60 h indicated a diffusional process. Finally the equilibrium ion-exchange constant was calculated from the amount of ‘*K diffusing into the hydrate< rl glass in its non-radioactive sodium form from a solution with a constant (high) sodium carbonate and variable (low) ‘*K level.

glass electrode

A simple equation has been derived which accounts for these exchange and diffusion potentials: E= Constant

+ n +

ln[ a?

+ (u$u*) (K ug)l’n] (2)

Here uA and a,., are the activities of the primary and any interfering ion, uA and uB their mobilities in the glass, while K, the ion-exchange equilibrium constant, and 12 depend on the pair of cations and glass composition’j. Since the mobility ratio is frequently unknown it is convenient to express this Eisenman equation as: E = Constant

+ 12

where the selectivity

(3) coefficient,

kr,

is:

k Eisenman and co-workers were the first to demonstrate that the composition of the glass relates to the selectivity coefficient and this concept led to very important developments in cation glass electrode,+. Thus the NAS 11-18 Corning sodium ion-selective electrode is one whose membrane contains aluminium oxide (Na,O, 11%; Al,03, 18%; SiO,,7 1%). The negative charges of the four oxygen atoms are offset by the three positive charges on the aluminium cation and not four on the silicon atom, as in the non-aluminium based Corning 015 glass electrode. The resultant negative sites on the oxygen atoms are thus relatively even more negative. This means that silicate sites are preferentially selective to hydrogen cations while aluminosilicate sites prefer cations6. Eisenman demonstrated a clear quantatitive relation between on the one hand the potentiometric selectivity coefficient, and on the other, the equilibrium ion-exchange constant, K, and the mobility ratio U,+/UB, for a glass electrode sensitive to potassium and also sodium6p7. Thus kGa was measured by the separate solution technique which should of course match the K(uNJuK) term in Equation 4. Next the relative contributions of uNJuK and K to the selectivity term were evaluated using z4Na and ‘*K tracers. Their self-diffusion coefficients were found by following the uptake of either ‘*K, or *‘Na, by glass electrodes thoroughly pre-equilibrated with their corresponding non-radioactive isotopes with respect to time. Their ratio was taken as the mobility ratio. This is based on two assumptions, one is that the ratio of tracer diffusion coefficients at a particular ion concentration in the glass is equal to uNa/uKand the other that the mobility ratio is independent of relative ionic concentrations in the glass. The uptake of either tracer which increased linearly with (time)% for periods from. 30 s

Results for one of the NAS 27-4 glass electrodes are illustrative of Eisenman’s elegant experiment?. The average values of uNaJuKand krda were 0.088 + 30% and 8.5 f 0.3 respectively and the ion-exchange equilibrium constant for the glass surface exchange reactions was calculated as 97 f 30% from Equation 4, compared with a value of 102 found by diffusion of ‘*K into the sodium loaded glass. The agreement was considered adequate to accept the concepts of the origin of the glass potential as endorsed in Equation 3. Eisenman concluded that the electrode potential for the potassium glass electrode cornprized a phase boundary (ion-exchange) potential contribution in the same direction as the total potential and a diffusion potential contribution in the opposite direction. Moreover, within the Nernstian range of the electrode any change in potential is due to changes in the phase boundary potentials alone since the diffusion potential is constant in such situation&. The low mobility of calcium ions in the hydrated surfaces of the glass membrane accords with that for other divalent cations in zeolites and glass and offers a sound reason for the poor selectivity parameters of such solid state exchangers6*7. The design of divalent glass sensors can thus be based on increasing the mobility of the particular cation in the hydrated layer and/or the ion-exchange constant. AC impedance research has provided valuable information about the electrochemical processes occuring both at membrane/solution interfaces and in the membrane bulk for all four types of ISE. In general, up to three zones can be recognized in the Cole-Cole plots of impedance data obtained for a complete BE-reference pair in solution, as the angular frequency W, of the excitation signal is varied (Figure I ). It is also convenient to consider each property of the electrode system as its electrical analogue and

*

Increasing w

Z real

Figure 1 membrane

Generalized system

Cole-Cole

sketch

J. Biomed.

Eng.

for an ion-selective

1985,

Vol.

7, July

185

Ion-.qelective electrodes: GJ. Moody

Figure 2 system

Equivalent circuit of an ion-selective

membrane

to represent this as an equivalent circuit simplified in Figure 2. Here C, and Ci are the double-layer capacitances at the metal/solution interfaces, Zf and Z’r the corresponding faradaic impedances and R, and R; the solution resistancedO. The membrane/ solution interfaces are modelled as parallel doublelayer capacitances/charge transfer resistance combinations, Cdl/R~ and CA,/&, while the bulk membrane is modelled22-24 as a geometric capacitance/bulk resistance combination, C$R,. The model, however, does not account for the nonzero current/voltage curve intercepts and the membrane capacitances are thought to be more diffi.ts&6~47 than shown. Warburg impedances may also be included in some other models to simulate ion transport through the solution, the interfaces and the bulk membran@*24~46. The high frequency semi-circle I in Figure I is related to the RC time of Figure 2, while constant of the C R, combination ue to the C,,/R~ interfacial semi-circle II is CB processes. At very low frequencies a finite Warburg impedance arc (III) may sometimes be seen corresponding to ion transport through solutions and/or membranes. Normal RC behaviour follows a perfect semi-circle, i.e. where 9 = 0’ but in many cases it is depressed below the real impedance axis. This degree of lowering, 8, is measured from the vertical impedance axis to the line drawn from the centre of the circle to the high frequency intersection with Z, axis and can be quite large, e.g. 60” for a valinomycin membrane electrod@. This depressed feature is common and has been attributed to the diffuse nature of the capacitanceS46~47 and the nonequivalence of the two interfaces caused by different concentrations of ions in the internal and external solutions22-24. Considerable quantitative information can be obtained from such Cole-Cole profiles. Thus the resistances are found from the distances between the intercepts of a semi-circle on the real axis and capacitances from the radial frequency of maximum Z, and the expression, RCo,, = 1, which in turn gives the time constant. Current exchange densities can also be evaluated22~87. Sandifer and Buck? measured the impedances of Beckman GP hemisphere pH electrodes whose inner reference electrode nearly matched that of

186

J. Biomed. Eng. 1985, Vol. 7, July

the coupled external Ag/AgCl reference electrode. Two lowered semi-circles were obtained in the Cole-Cole plot, the first with 8 = 24”, relating to bulk properties. The second, lower-frequency semicircle (8 = 30”) was clearly shown to be dependent on the outer layer or surface properties of the GP electrode, but not their shapes (spherical or flat) or thickness. Replacing the outer potassium chloride bathing solution with mercury caused the lower frequency semi-circle to shrink but the higher frequency one was little changed. Etching in 10% hydrofluoric acid caused a further reduction in size of the lower frequency but not higher fre uency semi-circle; it is of interest that the lower 9 requency sector did not then completely disappear on leaching the inner surface of the GP electrode with hydrogen fluoride. The fact that only this lower frequency sector was affected by changing the external or internal surfaces clearly indicates their dependance on interfacial processes. In this work the predicted Warburg response lay beyond the low frequency range of the impedance device. The time constant for finite Warburg transport is of the order [thickness]*/diffusion constant, which meanS”j that months are required to transport ions through glass membranes; this relates closely to the longterm electrolysis studies undertaken by Haugaard4. Impedance measurements provide crucial information on electrochemical events at, and inside, membranes of glass electrodes. Crystal

membrane

electrodes

Commercial introduction of the remarkable Orion 94-09 fluoride ion-selective electrode in the midsixties heralded a much needed revolution in electrochemical sensors. Its sensor membrane comprised lanthanum fluoride plus a small amount of europium (II) fluoride. The requirement that the membrane of such a device be electrically conducting can be met in theory by ion transport, electron transport or a mixture of both mechanisms. The conductivity of one sample of lanthanum fluoride measured between 27” and 727°C was *lo-’ n-l cm-’ at the lowest temperature and the principal contribution to this conductivity was considered to be the migration of fluoride amor@. Coulometric experiments showed that fluoride was transported in the lanthanum fluoride membrane of an actual electrode with a 99.2% current efficienc)56. Stahr and Clad?* established that 18F accumulated to a depth of -300 A in such a sensor crystal after application of 7 V for 5 min. Van den Winkel and co-workersz4 have proposed heterogeneous fluoride exchange reactions of two types of lanthanum fluoride doped with europium (II), one involving electronic and the other ionic conduction:

(EW, + F-,FW, (LaF,), + [ 1-(LaF2): (LaF,)+

+ Fq -(LaF,),

+ e + p-1

(5) (6) (7)

Ion-selectwe clec?rodec GJ

Moody

frequency variable impedances in series, the second of which was attributed to a surface film of lanthanum hydroxidei9.

50

0

loo Z,kn)

Cole-Cole plot for an Orion 94-09 ion-selective Figure 3 electrode as a function of various reference electrodes

50 B = 1.3

0

100

50 z,Ml,

Influence of fluoride on the Cole-Cole Figure 4 Orion 94-09A ion-selective electrode

plot for an

where [ ] represents a lattice vacancy. The first reaction is interpreted as a semiconductor behaviour with a deep donor level of europium (II), i.e. 0.4i eV energy gap between donor and conduction 1evelP. The second reaction requires a crystal fluoride anion to jump into a lattice vacancy near the crystal surface followed by exchange with a fluoride anion in the aqueous solution. Buclc!O has proposed rapid reversible ion-exchange at the membrane interfaces and mobile defects within the membrane. Brand and Rechnitz19 measured the impedances of four different fluoride ion-selective electrodes. The bulk resistances varied from 6 k Sz for the black bodied Orion 94-09 model to 1.6 M n for the Beckman 39600 model, and the low frequency resistances from 5 k Sz to 2.2 M a, except that the latter parameter was absent in the case of the early white bodied Orion model. The equivalent circuit was considered unique in that it contained two

Subsequent impedance measurements were more extensive and revealed subtle differences between the two Orion models 22-24, model 94-09 containing a classical internal reference electrode element immersed in a chloride/fluoride solution. This has been completely replaced in later 94-09A models by a solid contact at the back of the sensor membrane. In fact this approach has been adopted in many commercial types of ion-selective electrodes. The effect of various parameters on the three impedance configurations, Zi, Z,, and Ztt,, in the Cole-Cole plot for the 94-09 model was studied (Figure 3). D’ff 1 erent types of reference electrodes seemed to have no significant influence on these configurations and the measured impedance was considered to be due solely to the fluoride electrode. For reasons of symmetry, in the remaining investigations an Ag/AgCl reference electrode was chosen, it is similar to the inner electrode of the fluoride model. The influence of external fluoride levels and stirring rates on the impedance profiles is interesting (Figure 4, Table 3). The resistance and capacitance components of Zi are independent of fluoride concentration. However, concentration exerted a considerable influence on the ohmic rather than capacitive parameters of Z,,. In another experiment with an equal concentration of internal and external fluoride the Z,, indicatrix was a perfect semi-circle, due to equalization of the double-layer capacitances and transfer resistors at both sides of the membrane. Convection exerted no influence on Zi or Zn or the slope, 8, of the linear section of the indicatrix Z,,i. The mean slope for /? is not unity which indicates that due to complex diffusion at the membrane surface the diffusion impedance cannot be represented by a pure Warburg impedance. The fact that the crystal surface of the older 94-09

Table 3 Influence of fluoride levels and stirring rates on data of AC impedance electrod22~*’ Fluoride’

Stirring

(M)

(r.p.m.)

101

10’

lo-

rate

;A-,

lO”C,IF

parameters

RI, (W

of an Orion 9449A

fluoride

106C,JF

B

0

38

105

35

0.7

250 500 1000

37 38 37

107 105 107

37 36 36

0.5 0.7 0.4

1.3 1.1 1.0 1.2

0 250 500 1000

38 38 38 41

105 105 105 97

43 41 43 46

0.5 0.5 0.4 0.7

1.1 1.0 1.1 1.5

0 250 500 1000

41 39 39 48

97 105 101 98

80 a5 89 110

2 2 2 1.5

1.6 1.2 1.1 1.4

a All fluoride samples constituted

in 0.33

M

s

1.2

1.2

1.3

NaCl

J. Biomed.

Eng. 1985, Vol. 7, July

187

Ion-selective electrodes: GJ. Moody

electrode was scratched and also that the newer 94-09A model carries a solid internal reference contact could account for their different ZllI profiles**. The resistance R, was associated with charge transfer through the bulk of the membrane and Ci with a subsurface distributed space-charge layer on both sides of the crystal. The exchange current density, i,, calculated*’ from (RTIF) (l/Rii) was 0.2 PAcm” compared with 10 PAcm-* reported by Camman and Rechnitz*$ in current-voltage plots for a Corning 476137 fluoride electrode. Finally the activation energy of the charge-transfer in the crystal was evaluated** from resistance measurements between 238 K and 330 K at 0.41 eV. The composition of these solid internal backings at the rear of sensor membranes is frequently proprietory information but one Orion 94-17A chloride electrode was shown, by X-ray fluorescent@*, to be silver and tungsten in about equal quantities. Fjeldy and Nagyn have examined the impedance behaviour of lanthanum fluoride membranes with a silver-silver fluoride backing. This electrode of the second kind, Ag 1AgF 1LaFs 11 I$@, has the overall reversible reaction: AgF + e +

Ag + F

(8)

Fluoride ions were proposed to exchange reversibly at the AgF/LaF, interface while electrons exchanged reversibly at the AglAgF interface. This interesting proposal should at least remove some of the controversy regarding the thermodynamics of sensors with such solid state internal backing contacts. Impedance studies on other solid state crystal membrane electrodes such as silver chloride showed just one semi-circleig. The bulk resistance for the respective Beckman, Corning and Orion models were 0.97, 10 and 22 M a; the equivalent circuits resembling that of lanthanum fluoride but without film impedancetg. Impedance studied6 on ultra pure silver chloride crystals (2 mm thick) also revealed one semi-circle. The resistance as measured from the real axis decreased by -30% on increasing the temperature from 24.7” to 34.8”C but 8 remained at 5”. In complete contrast to lanthanum fluoride and silver chloride, the complex impedance of membranes comprizing silver bromide, iodide or sulphide showed no tendency to intercept the real axis even at the lowest frequency employed, 10-j Hz. The bulk resistance was absent from their equivalent circuits and there was no net ion transport across the membrane. Mechanistic studies should also encompass the role of counterions on the behaviour of ion-selective electrodes. Eisenman’s classical tracer work6 clearly established the relationship between the

188

J. Bionled.

Eng. 1985. Vol. 7, July

potentiometric selectivity coefficient and two fundamental parameters; the ion-exchange equilibrium constant and the mobility ratio of primary and interfering ions. A common type of interference associated with crystal membranes involved metathesis of interfering ion with a component of the membrane as shown for a chloride ion-selective electrode: AgCl(s) +Br-

*

AgBr(s) +Cl-

(9)

The selectivity coefficient, @t)fg, , is simply given4’ by the quotient of the appropriate solubility products: KS, AgCl/K,, AgBr = 1.82 X lo-‘O/5.2 X lo-i3 = 350 Rhodes and Bucpg observed four distinct regions in the e.m.f. time response profiles of thin anodized silver-silver chloride electrodes after immersion in chloride-bromide interfering mixtures. Selectivity coefficients for these very thin electrodes also varied with time and surface coverage by the metathetic silver bromide, typical upper limiting values being 455 to 467. However, an Orion 94-17 chloride electrode with its thicker sensor membrane can completely scavenge low levels of bromide, e.g. < 10m3 M, when selectivity values of 5 to 10 were recorded“g. Selectivity coefficients measured for three 94-17 Orion chloride electrodes by the classical separate solution method and a multiple spiking mixed solution technique ranged from 111 to 325 and 259 to 332 respectively6*. The visual appearance of the sensor membranes after such interference runs in bromide and especially in iodide and thiocynate, varied enormously in colour, degree of surface coverage and adhesion; and the kg& and kg,: values were depressed. These facts strongly support the variable nature of the surfaces of such ionselective membranes. Sometimes the interference reaction extended beyond the sensor membrane itself so as to cover partially or totally, the surrounding black PTFE support ring and even the lower section of the vertical stem of the electrode body with yellow silver iodide. The extreme craterlike formations seen on membranes in some iodide and thiocyanate runs were even more dramatic?*. Any run where the sensor surface is only partially covered cannot be expected to produce the maximum interference e.m.f. and hence the maximum selectivity value. The incomplete coverage of the surface of a Philips IS 550 chloride electrod@ by silver iodide, as revealed by electron microscopy, resulted in a remarkable kc,\ value of 5 compared with that of - lo6 expected from Equation 9. Space restrictions in the sample holding chambers of some XRF and ESCA instruments preclude the examination of complete sensor electrodes. Mock discs cornprizing AgCl: Ag,S (1: 1 molar) were immersed in stirred potassium bromide solution (lo-‘M) for 1, 5 and 148 min respectively with the

h-selective

cleaned, shiny surface uppermost. XRF indicated that -50% of the total bromide detected in the disc surface after 148 min exposure was deposited in the first minute as a dull, even grey layer. The expected elements Ag, Cl and S were observed by ESCA for freshly polished mock discs. In particular both the 2p and 2s peaks for sulphur revealed two chemical species corresponding to sulphide and one whose relative area indicated about 45% of the surface to be sulphate62. Pungor and co-worker?’ have also detected sulphate as a monolayer on the surface of pressed copper sulphide discs by the ESCA technique. The new AgCl/Ag2S mock discs were then immersed in stirred 10-l M potassium chloride (100 cm3) and spiked with lo-‘M potassium bromide (5 cmj). Even after a 10 min spiking period the signals for sulphide and sulphate had disappeared, those for silver and chloride had decreased whereas those relating to bromide and potassium appeared62. The nature, depth of penetration and rate of formation of surface interference species are fundamental to the interference mechanisms of ion-selective electrodes. Preliminary results from surface techniques such as XRF, ESCA (XPS), Auger spectrometry and diffraction studies, reveal their considerable potential for future mechanistic studies. MEMBRANES

WITH

Neutral

complex

carrier

MOBILE

SITES

(Two types)

electrodes

Neutral carrier materials are exemplified by polyesters, polyethers (crown compounds) and cyclodepsipeptides. Functional ion-selective electrodes cannot be fabricated from neutral carriers alone: a mixture with an appropriate mediator solvent to promote the highest possible selectivity is essential, as is the need to plasticize the poly(viny1 chloride) matrix which is now used to house many mobile site sensor systems. Unlike other types of ion-selective membranes with fixed sites, or liquid ion-exchangers, charged ionexchange sites are absent. Instead, ‘sites’ are inherently present within the neutral carrier molecules where ion-dipole interactions with cations lead to complexation often on a 1: 1 basis after possible loss of ligando water as shown for the cyclodepsipeptide, valinomycin, V: V + [K(HsO),]+KYY+\

(10)

VK+ + nH,O

Eyal and Rechnitz76 demonstrated that the selectivity ratio K+/M+ for this type of electrode can be deduced, to a first approximation, from the quotient of the appropriate pair of formation constants. Thus the rubidium interference parameter for the valinomycin electrode can be expressed as:

KwJbzb+ =

2880 + 260 6040 * g50

=

0.47

+ 0.12

electrodes: G.J. Moady

which compared favourably with the experimental value of 0.4: The mobility of the VM+ species is likely to be independent of the small cation and thus z+~+/u~~~+would be about unity; the selectivity will therefore be dominated largely by equilibria events (see Equation 10). A similar correlation has been established with alkali metal cations and four crown compounds”; dicyclohexyk 18-crown6; dibenzol8-crown-6; dibenzo-80crown-10 and benzo-l5-crown-5. In these studies the selectivity values are expressed as reciprocals of the usual IUPAC selectivity coefficient format. Various theories have been advanced for the role of neutral carriers and ion transport in membranes, in which complexation is a central theme. According to one model, the valinomycin molecule facilitates the passage of ions into the membrane, wherein they move as free ions by a ‘pore’ mechanism. A second model explains the enhanced permeability on the basis of ‘canal’ formation involving the passage of ions through a canal, or ordered stack, of valinomycin molecules. A third mechanism involves initial complexation (Equation lo), followed by transport of the sameVM+ species through the membrane, i.e., one valinomycin functions as a ‘carrielJ for one potassium, a more elaborate version involves a ‘carrier-relay’. The ‘carrier’ mechanism is also supported by studies on the actin type antibioticsg7. In an attempt to differentiate between the four mechanisms Eyal and Rechnitz76 measured selectivities first with the membrane phase comprising phenylether/valinomycin solutions frozen (at -5” C) while the aqueous phases were still liquid, then at 25°C for the wholly liquid three-phase system in the body of an Orion 92series model electrode. It was reasoned that the ‘freezing should not alter the selectivities if the ‘canal model was the correct one, whereas it should change them significantly for the ‘carrier’ mechanism by decreasing the mobility of the bulky valinomycin molecules in the organic phase. The considerable deterioration in Rf;q= from rc~1O4 to -0.5 and kE&+, from - 0.02 to - 1 respectively was more consistent with the ‘carrier’ proposal in which the bulky complexes lost considerable mobility in the frozen membrane phase”j. More extensive research has been conducted with l4 C-labelled valinomycin, 42KC1 and K36Cl respectively 78. In the first experiment valinomycin current/time profiles were run on a stack of i4C-valinomycin/dioctyladipate/PVC membranes in contact with non-radioactive KC1 at 20 V. One hour after reaching a steady electrodialysis state, the five closely packed PVC membranes (each 40 pm thick) were independently counted. Identical experiments were then run but with non-Iabelled stacks of PVC/valinomycin/mediator membranes in contact with K3’j Cl in the cathode and 42KCl in the anode compartments. The tracer profiles indicated considerable buildup of l4 C-valinomycin and 36C1 towards the cathode stacks while those for

J. Bwnwd.

Eng. 1985, Vol. 7, July

189

Ion-selective electrodes: GJ. Moody 4

Impedance

Membrane

composition

Table

data

for various

(mg)

WC

Valinomycin

MediatoP

67.5

2.9

121.9

59.7

69.0

2.9(0.8) 4.4(1.1)<

232.8 123.4

0 Selectivity coefficients R,,, pot for each (2-ethylhexyl)sebacic ester

PVC-valinomycin

membranes”*’

Contact solution 0.1 M

Resistance parameters (Imcm*) Charge transfer (R,,) Bulk (R,)

KC1 NaCl

139 487

1.5 21.5

14.3

17.2 1.2

KC1 NaCI

5.3 15

2.0 129.5

64.8

12.8 0.2

KC1 NaCl

28 56

10.5 85.5

8.1

2.4 0.3

electrode

= IO-s/10 +, * Sodium

tetraphenylborate,

c Potassium

tetraphenylborate,

d Bis

‘*K remained essentially the same in all five segments. The transport of ‘* K (tK = 1.02f0.04) accompanied by equivalent transport of “C-valinomycin was considered to be consistent with the formation and transport of a 1: I compIex. The uptake of ‘*K was a linear function of times. The same relationship has been reported by Eisenman for the respective uptake of 42K and 24Na by glass membrane.@. Thoma and co-workers concluded that a carrier-relay mechanism was operative in valinonomycin-potassium systems’*.

does not originate solely at the membrane/solution interface. If this were the case then the charge transfer ratio, which reflects the ease with which ions enter membranes, would also be around 103/104. Armstrong and co-workers8’ concluded that a contribution to the selectivity arises in parts of the membrane deeper than in the thickness (0.5 nm) of the electrical double layer. The upper value in a range of exchange current densities, 2.4-17.2 PA cme2, is much lower than reported -for a potassium/ valinomycin/diphenylether system79.

Useful AC impedance studies have been mad@’ on PVC-valinomycin potassium selective electrodes of different compositions over the frequency range 1O-3 Hz to 1 MHz at 25°C (Table 4). Two distinct semi-circles characterize their Cole-Cole profiles following immersion of the freshly cast membranes in 0.1 M potassium chloride for thirty minutes. Profiles for sodium chloride were not shown. The high and low frequency semi-circles were taken to represent the bulk resistance and charge-transfer resistance respectively. As mentioned previously the neutral carrier type membranes as first cast, are non-functional in the sense that the primary ion load is absent. A fresh membrane was exposed to five changes of fresh 0.1 M potassium chloride and after the first 30 min soak, the bulk resistance calculated from the Cole-Cole plot was - 100 k 51, which steadied to - 50 k Sz by the fifth cycle. The eventual steady bulk resistance value could thus reflect a PVC membrane in which a considerable fraction of the valinomycin is loaded with potassium. The bulk resistances listed in Table 4 may therefore relate to such conditioned valinomycin membranes, and in any event the bulk resistances were all higher after exposure to sodium. This feature was thought to reflect the greater mobility of potassium in the membrane; interesting in relation to the alternative mechanisms based on a ‘carrier’ or carrier-relay’, both of course invoke the bulky VM+ ions as mobile species.

An independent impedance study of a valinomycin potassium ion selective electrode with an unspecified solvent mediator showed a very depressed, high frequency semi-circle with 8 = 60’ and bulk resistance of -700 k a. The lower frequency values which did not extend far enough to reveal the expected semi-circle are not purely resistive and the possible onset of Warburg or kinetic behaviour is hinted at still lower frequenciesJ6.

The highest ratio of the charge transfer resistances N 65: 1, and the selectivity for all three membranes of 103/104, indicate that the selectivity* * It is regrettable that selectivities are still being quoted as the reciprocal of the recommended IUPAC format, i.e. as lO’/lO’ and not kSP = 10’/101 for example

190

J. Biomed. Eng. 1985, Vol. 7, July

Liquid

ion-exchange

electrodes

The first really viable calcium ion-selective electrode, namely the Orion 92-20 model, became commercially available in the mid-sixties. Its liquid ion-exchanger was listed as a calcium bis(alkyl)phosphate coupled with the water immiscible mediator solvent, di--n-octylphenylphosphate. However, t.1.c of one commercial batch of Orion exchangers revealed three additional components in considerable qua.ntityio3. Nonetheless the performance of the electrode was adequate for many analytical purposes although the pH, and especially @& characteristics were considerably improved on replacing the original calcium salt with a bis-di[4-(n-octyl)phenyl] phosphate preparationio4. The ingenious design of the three-channel plastic 92-20 body required a considerable charge ( - 0.4 cm3) of expensive 92-20-02 exchanger, and moreover, the placement of its inert supporting membrane caused assembly problems. This arrangement was greatly simplified by incorporating the liquid ion-exchanger in a thin poly(viny1 chloride) matrix and without loss of

Ion-selective electrodes: G.J. Moody

electrochemical functionto5. This matrix has been utilized subsequently for sensor purposes with a wide variety of liquid ion-exchangers as well as neutral carrier materials.

PVC-Orion 92-20-02 calcium ion-exchanger membranes into chlorides of magnesium (run S), strontium (run 4) and barium (run 5), compared with those for calcium (run l), match their low selectivity coefficients (Table 5). Correspondingly low fluxes for beryllium (run 2) are unexpected on

Virtually no attention has been given to the function of this polymer based membrane matrix but the molecular mass is critical and the average value of -70 000 for the Breon S125 (11) BP material is certainly very suitable. Membranes incorporating organophosphatesro6* lo’ and a phosphonaterO’ covalently linked to the copolymer VAGH (a part&y hydrolysed copoIymer of vinylchloride and vinylacetate with 6% OH groups) also provided variable, but not superior, calcium sensors, H

H ..

I

I

Table 5 Passive tracer fluxes (SYC) across PVC-Orion 92-20-02 calcium ion-exchanger Run No.

Active solution M)

(10’ Batch A of 92-20-02 1 2 3 4 5

Inactive solution (10’

liquid

membraness8

d(c”lc’)dt

G;

(10’

at 35°C

s-l)

M)

ion-exchanger

CaCl,

CaCl,

18(19)a

-

CaCl, CaCl, CaCl, CaCI,

BeCl,

2.5(2.2) 8.0(8.4) 8.5(9.1) 8.4(7.5)

14(5 x 0.05(4 0.09(4 0.01(4

MgCl, SrCl, BaCl,

10’)b x 10’) x 10’) x 10’)

WC-cc a Values in parentheses

for reverse set-up, i.e. with 45Ca radiotracer in the external solution. b Values in parentheses molarity of counterion B in mixed solution evaluation for selectivity coefficient

R-O-P

Table 6 Passive tracer fluxes (35’C) across PVC- Orion 92-2&02 calcium ion-exchanger

\OH

where R=n-CroH,, or CH,C( CH&C6H,. Alternative matrices such as poly(methylacrylate)108 and poly(vinylidene chloride)72 lie in the same category.

Run No.

Form

of

exchanger

The loss of sensor and/or mediator species from such mobile site based sensor membranes, which dictates the lifetimes of these devicesrW~*rO, has been established by tl.c.72~107~109,g.l.~.~~,‘~ and XRFr2 techniques. For a potassium sensitive glass electrode the selectivity parameter can be related to the balance between an ion-exchange process and the mobility ratio, u$uA. Eisenman in a discussion of the similarities and differences between solid and liquid ion-exchangers has emphasized that the mobility constraint* is removed in the latter case’. This is because the mobility of the undissociated species is likely to be independent of the particular (small) counterion bound. The mobility ratio of these undissociated species should therefore, be of the order of unity, which implies that the potential selectivity of liquid ion-exchangers will be dominated mainly by their equilibrium ionexchange selectivitied.

sensorsLM*“”

the concept

Active

Inactive

d(C”lC’)dt

solution

solution

(IO7 sl)

Final M in membrane

(3

liquid

ion-exchanger

6 7

Ca Be

CaCI, BeCl,

8 9 10 11 12

Sr Ba Ca Ca Ca

SrCI, BaCl, SrCl, BaCl, B&l,

Batch C of 92-2042

10.8

CaCl,

1.7

0 0.23 0 0 0 0

BeCl, SrCl, BaCl, SrCl, BaCI, B&I,

39,72 0.5 0.4 0.3 0.7 93,94

liquid ion-exchanger

13

Ca

CaCI,

CaCl,

22

3.5

14 15

Ba Sr

CaCI, CaCI,

CaCl, CaCl,

20 22

2.3 2.9

Table 7 Passive 45Ca-tracer fluxes (35°C) across PVC membranes containing calcium bis-di]&( 1,1,3,3-tetramethylbutyl)phenyl] phosphate with various solvent mediators (Doyle, Moody, Nassory and Thomas, unpublished work) Run No.

16

Solvent mediator

d(d’lc’)dt (lO’s1)

Batch

18

4.0

32

9.6

D of 92-20-02

Final ” Ca in membrane (%)

calcium liquid ionexchanger only

Migrations of ions from radioactive solutions across PVC-calcium and PVC-divalent ion-selective membranes into initially non-radioactive solutions have been extensively studied88+2. Results have been expressed in terms of d(C”lC’)dt where tracer fluxes between initially inactive (tracer concentration s C”) and active (tracer concentration G C’) solutions increase linearly with time (Tables 5- 7). The low calcium ion fluxes across * It is to be noted that in the case of grafted mobile sites needs modification

membranes89

W’PO,I,M Batch B of 92-20-02

for

of

17

d&n-octylphenylphosphonate

2.6

5.2

18

Tributylphosphate

19

Tripentylphosphate

59

12.0

20

Trioctylphosphate

37

6.0

21

Tri(l,1,3,3-tetramethylbutyl) phosphate

25

6.5

22

Orion liquid

32’

’ For

lo-)

92-32-02 divalent ion-exchanger only

on each side, as well as for IO-’ M CaCl, lo-’ M MgCl, on the otherPO

M CaCl,

one side and

J. Biomed.

Eng. 1985, Vol. 7, July

191

Ion-selective electrodm GJ. Moody

basis of the high selectivity coefficient However, beryllium ions may block the ionexchanger sites of the dialkyl phosphoric acid in the membrane; this is supported by the high extraction coefftcient of a similar liquid ionexchanger, bis(2-ethylhexyl) phosphoric acid for aqueous beryllium salts (log K = 4.3). Corresponding co-ion migration can probably be discounted since radioactive chloride did not diffuse from the Ca3‘jC1, side of the PVC-exchanger membrane. Similar exclusion of tritiated water indicated the loss of ligand water prior to calcium ion-transport.

the

Control experiments showed that radiocalcium did not migrate across PVC membranes alone or PVC membranes incor orating just the mediator solvent, din-octy Pphenylphosphonate. This mechanistic approach to calcium electrodes was later extendeda to the use of ‘Be, 89Sr and 133Ba, and where the original calcium ionexchanger material had been converted into its corresponding beryllium, strontium or barium form (Table 6). In addition, at the end of the runs, membranes were removed and. counted, and their activities expressed as the percentage of radio tracer in the membrane. Experiments 3-l 1 indicate little or no tendency for strontium or barium ions to migrate across the PVC membranes in their strontium or barium chlorides. This inhibition of migration by the low affinity of strontium and barium ions for sites in the phosphate liquid ion-exchanger is confirmed by the rather small tracer count in the membranes when removed at the end of the runs. The strong afftnity of beryllium for ion-exchange sites is indicated in runs 7 and 12, where a high proportion of the original tracer is resident in the membrane, but little or none in the original inactive solution. The low affinity of strontium and barium for ion-exchange sites is evident in runs 13-15. Calcium ions permeate through either barium or strontium forms of the exchanger (runs 15 and 16) at about the same rate as the calcium form (run 13). The different d(C”lC’)dt values for runs 1, 6 and 13 relate to the different amounts of calcium exchanger in batches A, B and C of the 92-20-02 products *lE9. Calcium ions are therefore free to exchange with calcium ions in an aqueous bathing medium. Shortly after membrane/aqueous phase contact, calcium ions are either gained or lost to the aqueous phase and so generate a space charge and an interfacial potential develops; this increases positively as the activity of the calcium in the aqueous phases increase?*. Viable electrodes cannot be fabricated from either the calcium salt or di-n-octylphenylphosphonate alone. The role of a solvent mediator in a liquid ion-exchanger cocktail is to promote high selectivity, while a high viscosity and low water solubility reduces leaching effects and so enhances operational lifetime. In the case of PVC

192

J. Biomed.

Eng. 198.5, Vol. 7, July

membranes function.

it should also have a plasticizer

PVC calcium ion-selective electrodes based on calcium bis-di-[4-( 1,1,3,3-tetramethylbutyl)phenyl] phosphate with variable amounts of decan-l-01 plus di-n-octylphenylphosphonate showed a continuous gradation in selectivity coefftcients on going from a high fraction of decan-l-01 to a high fraction of the second mediator. Thus RPzM, changed from 1.6 for an electrode base di exclusively on decan-l-01 to 4.9 X 1OA for one based completely on di-n-octylphenylphosphonate!O. The corresponding k&values were 7 .O X 10” and 1.1 X 10”. This dramatic influence of soTvent mediators on selectivity parameter is further illustrated by tracer studies (Table 7). With organophosphates and decan-l-01 in place of di-n-octylphenylphosphonate, there is little difference between magnesium and calcium ions in ion fluxes for calcium, as shown by the Orion 9232-02 divalent liquid-ion exchanger. Thus the migration profile of 45Ca between identical pairs of calcium chloride ( 10-3~) placed on either side of a PVC membrane containing the Orion 92-32-02 divalent cation exchanger matches that measured when the inactive calcium solution is replaced by inactive magnesium chloride ( 10e3 M) when d(C”lC’)dt = 32 x lo-’ s-r. The corresponding timeindependent values for identical experiments undertaken with calcium bis-di[4-( 1,1,3,3tetramethylbutyl)phenyl]phosphate and di-n-octylphenylphosphonate were 29 x lo-’ s-r and 4.3 x lo-’ s-l respectivelfO. This difference accords with a system for which k{F& 32.

Ion-selective electrodes: G.J. Moody

zmar = 520Kll

Z mar = 44.7

KQ.

Zmar = 42.9 KS-l

Figure 5 Normalized Cole-Cole plots for PVC-chloride ion-selective electrodes. a, fresh membrane with n-tetradecylakohol (TDA) mediator, b fresh membrane with 5-phenyl-I-pentanol (5PP) mediator, c, 5-PP membrane after two months immersion in sodium . , . chloride (0.1 M); d, 5-PP membrane after contact with a sekm

Brand and Rechnitz concluded from their impedance studies on several liquid ion-exchanger electrodes arranged in a non-PVC mode, i.e. in Orion 92-20 bodies, that transport of ions through the liquid membranes and across the membrane! solution interface, occurred by electromigration and a process for which there is no simple physical analogy”. A replot’ of their calcium data, this time using equal impedance axes, revealed a single depressed semi-circle with 6 = 3.3” and bulk resistance H 12 M a. A similar depressed semicircle was also obtained for the analagous PVC calcium ion-selective electrode model together with the suggestion of another arc at the lowest frequenyg. This was attributed to processes at the membrane surface. The bulk resistance was calculated as 10.54 f 0.05 M a with a time constant of 0.228 f 0.003 ms. The influence of the mediator is again demonstrated in the Cole-Cole plots for PVC chloride ion-selective electrodes based on methyltridodecylammonium chloride (Figure 5), the membrane plasticized by n-TDA exhibiting a collapsed pattern which recomposed into two semicircles (Fig-we 54. For the 5-PP based membrane two arcs were presented as well defined semi-circles by extrapolation (Figure 56). In both cases the high and low frequency semi-circles, each with different time constants, resistances and lowering, were related to the bulk transport and interfacial ion transport processes respectivelfg. Relatively little information is available on the most suitable amounts of sensor and mediator for PVC sensor membranes”‘. Maruizumi and co-workers3g

established that the minimum impedance and shortest time constant were related to a 5-PP content of -10 mass%. Then, as expected, an ionselective electrode with a membrane of this composition showed the optimum characteristics in terms of Nernstian slopes and response times. After immersion in sodium chloride (0.1 M) for two months the time constant for the bulk membrane process increased while the maximum absolute impedance about doubled. One sign of membrane deterioration lies in the ill-defined membrane/ solution interfacial process appearing in the lowest 5 Hz range of the Cole-Cole plot (Figure 5~). The loss of 5-PP mediator from the PVC membrane, as detected by g.1.c relates to this phenomenon3g. Even greater deterioration was evident after the two month old membranes had been contacted with serum when the sector relating to the solution/ membrane process was completely smeared out. (Figure 5d). CONCLUSION Research on the mechanistic aspects of ionselective electrodes has led to a better understanding of their performance. Yet a considerable effort is still needed regarding, for example, the effect of interference, particularly in clinical circumstances; and the intriguing facets of rapid time responses on a scale comparable with nervous impulses W-SW the relatively slow ion transport in thick sensor membranes. Clearly further progress will require the exploitation of the widest array of current techniques and a greater involvement of solid state physics.

J. Biomed. Eng. 1985. Vol. 7, July

19s

Ion-selective electrodes:G.J. Moody

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30 31 32 33 34 35 36 37 38 39 40 41

44 45 46

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195