Ion-Selective Electrode

Ion-selective electrodes (ISEs) are electrochemical ion sensors that convert the ac-
tivity of a target ion into an electrical potential as the measurable signal.

From: TrAC Trends in Analytical Chemistry, 2016

Related terms:

Biosensor, Fluorine Atom, Sodium Atom, Chloride, Fluoride, Ion, Ionophore, Be-
havior as Electrode, Reference Electrode, pH Value

View all Topics

Ion-Selective Electrodes | Overview

Eric Bakker, in Encyclopedia of Analytical Science (Third Edition), 2019

Selectivity of Ion-Selective Membranes

To assess whether ion-selective electrodes can reliably measure in the sample of
interest, one may benefit from an approximate knowledge of the anticipated con-
centrations of the analyte ion and that of potential interferences. Armed with this
information and a description of selectivity of the probe, the anticipated error in the
activity measurement can be predicted. The selectivity behavior of an ion-selective
electrode has traditionally been described by the Nikolskii equation,11 written as:

(10)

Here, I denotes the ion one aims to measure (also called primary ion) while j is any
other ion of the same charge that may interfere in the measurement. This equation
is a direct extension of the Nernst equation and incorporates an additional weighted
activity term that describes the selectivity. The selectivity coefficient is written in
the form KI, jpot, where the superscript “pot” indicates a selectivity coefficient for
a potentiometric probe and the subscript indicates in the first position the primary
ion and in the second position the interfering ion. For a potassium-selective elec-
trode with sodium as potential interference, one writes for example the selectivity
coefficient as KK, Napot. Smaller selectivity coefficients indicate better selectivity.
As their values can be very small in some cases, it is customary to write them as
logarithmic values, such as logKI, jpot. Large negative values indicate small selectivity
coefficients and excellent selectivity.

Eq. 10 is directly derived from ion-exchange equilibrium considerations and can

be considered thermodynamically correct. If the two ions that are compared have
different charges, the equation needs to be extended. Traditionally this has been
done by the so-called Nikolskii-Eisenman equation, a semiempirical equation that
is not strictly correct12:

(11)

In the absence of primary ions, Eq. (11) predicts correctly the appropriate Nernst
equation for the interfering ion, but it unfortunately fails if both ions substantially
contribute to the potential. Thermodynamically sound descriptions have been put
forward in the literature, but one may alternatively use the following general equa-
tion that is reasonably applicable for ions of any valency.13 For any two such ions,

(12)

The anticipated error of the measurement, pI,j(%), from the interfering ion is de-
scribed quite readily if one assumes less than about a 10% error12:

(13)

From this relationship, the required selectivity coefficient for a given tolerated error
up to about 10% is given as:

(14)

Selectivity coefficients are obtained experimentally by comparing the response of

the membrane to the primary ion to that of the interfering ion.14 This may often
be performed by recording calibration curves in separate primary or interfering ion
solutions, see Fig. 2. This is commonly called the separate solutions method and the
resulting selectivity coefficient is found from the two intercepts, or alternatively
two potentials EI and Ej on the Nernstian response curve with the associated ion
activities aI and aj as:
Fig. 2. The selectivity coefficient for ion-selective membrane relates to the relative
preference of two ions. It may be determined from the observed potential differences
for the separately measured ion responses in the Nernstian response regions, as
shown on the right. In ideal cases, the selectivity coefficient may also dictate the
thermodynamically expected detection limit for a calibration in a fixed electrolyte
background, as shown on the left.

(15)

For pH electrodes particularly, one varies the concentration of the primary ion in a
wide range to observe deviation from Nernst behavior at low ion concentrations.
This comprises the fixed interference method. As shown in Fig. 2, the selectivity
coefficient is obtained from extrapolating the Nernstian response range to the
potential of the background electrolyte, which gives the detection limit discussed
below, ai(LDL). Together with the knowledge of the background ion activity one gets:

(16)

Note that one should confirm a near-Nernstian response slope for each ion to avoid
experimental bias.14 For very selective membranes one strongly benefits from opti-
mized protocols to achieve this, for example using chelating agents or precipitation
reactions to reduce the primary ion concentration, or, especially with polymeric
membrane electrodes, reconditioning steps or the extrapolation of time dependent
selectivity coefficients.14

A more phenomenological characteristic of selectivity, independent of any theory

can alternatively be described by the so-called matched potential method.15 The
electrode is first subjected to a concentration change of primary ion in a solution of
interest. Subsequently, the interfering ion concentration is changed until an equiv-
alent potential change is observed, the potential changes are therefore “matched”
in this way. One should be careful not to use the same symbol for the resulting
selectivity coefficient, as it does not have the same meaning. We therefore write:

(17)

This method is particularly justified for potentiometric probes that function in un-
usual ways that are difficult to describe theoretically, as with kinetically responding
probes, some gas sensors or enzyme based potentiometric biosensors, or other
probes that rely on the combination of different recognition principles.

> Read full chapter

New trends in ion-selective electrodes

Sergey Makarychev-Mikhailov, ... Eric Bakker, in Electrochemical Sensors, Biosen-
sors and their Biomedical Applications, 2008

4.6 FUTURE PROSPECTS AND CONCLUSIONS

Ion-selective electrode research for biomedical analysis is no longer the relatively
narrow, focused field of identifying and synthesizing ionophores for improved
selectivity and the integration of ion-selective electrodes into clinical analyzers and
portable instruments. These efforts have matured now to such an extent that they
can teach valuable lessons to other chemical sensing fields that are just emerging
technologies.

Ion-selective electrodes are now well understood in terms of the underlying theory,
and this has made it possible for new sensing principles to emerge that make
use of the thousands of chemical receptors originally developed for ion-selective
electrodes. One is the field of optical sensors, which has not been discussed here
because it is outside the focus of this chapter. Such so-called bulk optodes do
not require electrical connectivity between the sensing and detection unit and are
therefore more easily brought into various shapes and sizes, including particle
formats, which suit the need of modern chemical analysis.

Electrochemical sensors, however, currently share one key advantage: an excitation

signal may be imposed that can trigger a sensing reaction, and the energy required
for an otherwise thermodynamically unfavorable extraction and/or binding process
can be instrumentally imposed. While ion-selective electrodes historically have been
passive sensing devices where such control is not possible, much of current research
deals with non-classical response principles where concentration polarizations take
place at the sample–membrane interface. Galvanostatic and voltammetric control of
ion-selective membranes is now also possible and offers an exciting path to novel
approaches in extraction/complexation-based sensing. The key application discussed
above has been the development of reversible sensors for the anticoagulant heparin
and its antidote protamine, but many other important sensing principles may be
developed since the tools are now in place to fabricate reversible sensors on the basis
of otherwise irreversible reactions.

This field is therefore at an exciting stage. Ion-selective electrodes have a proven

track record in terms of clinical and biomedical analysis, with a well-developed
theory and a solid history of fundamental research and practical applications. With
novel directions in achieving extremely low detection limits and instrumental control
of the ion extraction process this field has the opportunity to give rise to many
new bioanalytical measurement tools that may be truly useful in practical chemical
analysis.

> Read full chapter

ANALYTICAL APPLICATION OF
MEMBRANES
K. Scott, in Handbook of Industrial Membranes (Second Edition), 1995

Ion-Selective Electrodes
Ion-selective electrodes have many applications in water analysis and environmental
analysis. Electrodes include those for the determination of pH, F−, CN−, NH3 and
total hardness (Ca2+ + Mg2+). The principle of operation of the electrode is shown
in Fig 10. The measurement of the potential between the ion-selective electrode
and the reference electrode allows the determination of the ion Mn+ between the
analysed solution and an internal standard solution. In most cases the ion-selective
electrode and reference electrode are mounted in a single (combination) probe (see
Fig 10).
FIGURE 10. Basic electrode principle for determination of a ion Mn+ with an ion-se-
lective electrode.

The analysis with an ion-selective electrode is almost completely dependent on the

membrane properties. The potential measured by the ion-selective electrode is a
function of the membrane potential

FIGURE 11. Common construction of ion-selective electrodes.

As, in principle, all factors associated with the use of the electrode, other than the
ion concentration to be measured, remain constant (eg Cs), the measurement of the
cell potential is directly proportional to the logarithm of the ion concentration.

In practice the response of the membrane should be independent of other species

in solution and reach a stable potential rapidly. In many cases this is difficult
to achieve and reflects the largely empirical way of selection and design of the
membrane. Overall a range of different types of membranes are used in ion-selective
electrodes; including glass, solid state, heterogeneous and liquid membranes. Table
X gives a selection of commercial ion-selective electrodes in which these four types
of membranes are used.

Glass membranes are generally based on Na2O-Al2O3-SiO2 mixtures. Membranes

selective to H+ ions are rich in SiO2, eg 72% SiO2 0% Al2O3 and low in Al2O3.
Membranes selective to alkaline metal ion have a higher content of Al2O3. In the
latter cases there are major interferences from other alkali metal ions.

A variety of different solid state membranes are used for different ion detection.
Many of these use a combination of Ag2S + Ag X (X = Cl−, Br− or SCN−) in the form
of a pressed disc and the electrode responds to X”. For the determination of cations
(M+) the membrane material is a mixture of Ag2S + Mn/2 S.

TABLE 17. Typical membranes and commercial ion-selective electrodes.

Ion electrode Membrane Concentration Major interferences

range/mol dm−3
h+ Glass 10−14–1 None
k+ Valinomycin 10−6–1 Cs+, NH4+
Na+ Glass 10−6–sat. Ag+, H+, Li+
F− LaF3 10−6–sat. OH−, H+
Cl− Ag2S/AgCl 10−5–1 Br−, I−, CN−, S2−
Br− Ag2S/AgBr 10−6–1 I−, CN−, S2−
I− Ag2S/AgI 10−7–1 CN−, S2−
CN− Ag2S/AgI 10−6–10−2 I−, S2-
S2− Ag2S 10−7–sat. Hg2+
Ag+ Ag2S 10−7–1 Hg2+
Cd2+ CdS/Ag2S 10−7–1 Ag+, Hg2+, Cu2+
Pb2+ PbS/Ag2S 10−7–1 Ag+, Hg2+, Cu2+
Cu2+ CuS/Ag2S 10−8–sat. Ag+, Hg2+, S2-
Ca2+ (RO)2PO-/(RO)3PO 10−5–10−1 Zn2+, Fe2+, Pb2+, Cu2+
Ca2++Mg2+ (hardness) (RO)2PO$/ROH 10−7–1 Cu2+ Zn2+ Fe2+, Ni2+-
, Pb2+
NO3− R4N+/ether 10−5–1 ClO4−, ClO4−, I−, Br−

FIGURE 12. A typical pH electrode.

Heterogeneous membranes use similar active components as solid state devices but
instead the active material is deposited into the pores of an inert support, eg silicone
rubber.

Ion-selective electrodes based on liquid membranes immobilise an active species, an

organic molecule (dissolved in a solvent), in the pores of an inert polymer. The typical
active species are phosphate diesters for calcium ion detection, metal complexes for
anion detection and neutral macrocyclic crown ethers for alkali metal detection.

New developments in ion-selective electrode are in the combination of ion-selective

membranes with metal oxide semi-conductor field-effect transistors (MOSFET).
The so-called ion-selective field-effect transistor (ISFET) is an electronic device to
measure a selected ion concentration in a solution using an exposed gate insulator or
membrane, the membrane use plasma polymerised materials, eg tetrafluorethylene,
chlorobenzene, doped with ions eg iodide.

TABLE 18. Construction and performance of gas sensing ion-selective electrodes.

Gas Ion-selective Electrolyte Membrane Concentra- Serious inter-

electrode tion ferences
range/mol
dm−3
H2S S2− Citrate buffer Polypropylene 10−6−10−2 None
pH 5
NH3 pH 0.1 mol dm−3 PTFE 10−1−1 Volatile amines
NH4Cl
CO2 PH 0.01 mol dm- PTFE 10−2−10−4 Volatile weak
−3 NaHCO- acids
3 +0.1 mol
dm−3 NaCl
NO2 PH 0.1 mol dm- PTFE or 10−6−10−2 Volatile weak
−3 NaNO- polypropylene acids
2 +0.1 mol
dm−3 NaCl
SO2 pH 0.1 mol dm- PTFE or sili- 10−6−10−2 Volatile weak
−3 K2S2O- cone rubber acids
5 +0.1 mol
dm−3 NaCl
HCN Ag+ 10−2 mol dm- Polypropylene 10−7−10−1 Sulphide
−3 KAg(CN)2

> Read full chapter

Updates and Bibliography

Pratima Bajpai, in Biermann's Handbook of Pulp and Paper (Third Edition), 2018

Ion-Selective Electrodes
Ion-selective electrodes (ISEs) are very similar in use to pH electrodes. They are used
for chloride, potassium, calcium, carbon dioxide/carbonate, oxygen, and a variety
of other ions. These methods are particularly suited for field analysis and online
measurements.
Lenz, B.L. and J.R. Mold, Ion—selective electrode method compared to
standard methods for sodium determination in mill liquors, Tappi J. 54(12):
2051–55(1971).Sodium ion can be quickly measured directly with ion-specific
electrodes, with about 1% error, over a wide range of concentrations. A small
sample is diluted with a small amount of ionic strength adjuster (ISA, an
ammonium buffer solution) and the solution measured as if for pH, but in
this case for p(Na+). This method would probably be useful for measuring
sodium loss in pulp by incubating the pulp with ISA until ammonium ion
has exchanged sodium ion. It could also measure sodium concentrations at
various stages of the recovery process.
Cooper, Jr., H.B.H., Continuous measurement of sodium sulfide in black
liquor, Tappi 58(6):59–62(1975).This is a general article on the subject.
Schwartz, J.L. and T.S. Light, Analysis of alkaline pulping liquor with sulfide
ion—selective electrode, Tappi J. 53(1):90–95(1970).New electrodes often use
a salicylate buffer with 1:3 sample:buffer dilution. This article has much exper-
imental detail.

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Surfactants☆
María C. Prieto-Blanco, ... Dario Prada-Rodríguez, in Encyclopedia of Analytical
Science (Third Edition), 2019

Electroanalytical Techniques
New ion-selective electrodes were applied for the end-point detection in poten-
tiometric titration of ionic surfactants in raw technical materials, formulations and
even wastewater of industrial plants. Different polyvinyl chloride (PVC) membrane
electrodes with different analytical properties were designed by modifying their
electroactive material. For the analysis of anionic surfactants, the electroactive ma-
terial can be formed by a cationic surfactant and tetraphenylborate, although ionic
liquids or cationic complexes of metals with organic reagents were also proposed.5
To meet the demand for miniaturized systems for an in situ surfactant analysis,
screen-printed carbon paste electrodes measured in small volumes can be carried
for field titration in portable devices. Major anionic surfactants found in cleansing
products, alkyl sulfates and alkylbenzenesulfonates, and CPC and BAK in phar-
maceutical formulations are the most common analytes titrated using surfactant
selective electrodes. Similarly to ionic surfactants, nonionic surfactants were also
analyzed by PVC membrane electrodes containing a complex of nonionic surfactants
with metal cations as electroactive material. Interferences between surfactants as
that detected in titration of SLS in presence of CAPB had to be controlled.

Electronic tongue accomplishes the determination of anionic surfactants (such as

AS and LAS) and nonionic surfactants (ethoxylates, nonylphenols) by processing
the analytical signal through mathematical techniques such as neural networks.
Likewise, an impedimetric sensor for residual concentration of ionic and nonionic
surfactants in washing machines was constructed.

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Potentiometric Ion-Selective Elec-

trodes
Shigeru Amemiya, in Handbook of Electrochemistry, 2007

7.1 INTRODUCTION
Potentiometric ion-selective electrodes (ISEs) are one of the most important groups
of chemical sensors. The application of ISEs has evolved to a well-established routine
analytical technique in many fields, including clinical and environmental analysis,
physiology, and process control. The essential part of ISEs is the ion-selective
membrane that is commonly placed between two aqueous phases, i.e., the sample
and inner solutions that contain an analyte ion. The membrane may be a glass, a
crystalline solid, or a liquid (1). The potential difference across the membrane is
measured with two reference electrodes positioned in the respective aqueous phases

reference electrode 2 || sample solution | membrane | inner solution || reference

electrode 1 (cell 1)

Under equilibrium conditions, the measured potential (or emf of the cell), E, can be
expressed as

(7.1.1)

where zI is the charge of the analyte ion, I, aIw is its activity in the sample solution,
and the constant term, E10, is unique for the analyte and also includes the sum
of the potential differences at all the interfaces other than the membrane/sample
solution interface. This well-known “Nernst” equation for ISEs represents their
unique response properties, i.e., Nernstian responses, where the sensor signal,E ,
is proportional to logarithm of the analyte activity rather than the activity itself. The
slope in an E versus lnaIw (or more commonly logaIw) plot is used for identification
of the analyte based on the charge. A wide range of the analyte activity can be
determined because of the logarithmic dependence of the potential on the analyte
activity. Moreover, a very low analyte activity can be determined only by measuring
the potential difference rather than detecting a very small signal. A well-known
example is a glass membrane pH electrode, which has a detection limit of down
to 10–12 M for H+.

How can we create such a membrane for a wider range of analytes? The most
successful approach is to use ion-selective liquid membranes (2, 3). The liquid mem-
branes are hydrophobic and immiscible with water, and most commonly made of
plasticized poly(vinyl chloride). The selectivity is achieved by doping the membranes
with a hydrophobic ion (ionic site) and a hydrophobic ligand (ionophore or carrier)
that selectively and reversibly forms complexes with the analyte (Figure 7.1). Whereas
the technique has been well established experimentally since the 1960s, it is only re-
cently that the response mechanisms are fully understood. In this chapter, principles
of liquid membrane ISEs will be introduced using simple concepts of ion-transfer
equilibrium at water/liquid membrane interfaces. Non-equilibrium effects on the
selectivity and detection limits will also be discussed. This information will enable
practitioners of ISEs to better optimize experimental conditions and also to interpret
data. Additionally, examples of ISEs based on commercially available ionophores
are listed. More comprehensive lists of ionophore-based ISEs developed so far are
available in recent IUPAC reports (4–6).

Figure 7.1. Schematic view of the equilibrium between sample, ion-selective mem-
brane, and inner filling solution (cell 1). The cation-selective membranes are based
on (A) cation exchanger (R−), (B) electrically neutral ionophore (L) and anionic sites
(R−), and (C) charged ionophore (L−) and cationic sites (R+). The aqueous solutions
contain an analyte cation (I+) and its counter anion (X−). Adapted from reference (2).

> Read full chapter

Ion-Selective Electrodes | Glass Elec-

trodes☆
S. Głąb, ... A. Hulanicki, in Reference Module in Chemistry, Molecular Sciences and
Chemical Engineering, 2013
Origin of Glass Electrodes
Glass electrodes are ion-selective electrodes, that belong to the group of electrodes
with a noncrystalline solid membrane. Typical glasses are supercooled liquids with
a network composed most commonly of silicon oxide; however other compositions
may have similar properties and can be used as sensors.

The formation of an electric potential difference on a thin glass membrane in

contact with solutions was observed by Cramer in 1906, and used for construction
of a device for measuring the acidity of solutions by Haber and Klemensiewicz in
1909. Due to the high resistance of the glass membrane, practical application in
routine measurements of acidity, and of course solution pH, was postponed until
the invention of the vacuum tube amplifiers, and later semiconductors. One of the
first types of glass used in manufacturing electrodes was introduced in 1928–1929
by Corning under the designation 015. The research devoted to the mechanism of
this electrode action was a stimulus that helped to develop and introduce other types
of ion-selective electrodes.

> Read full chapter

Magnesium Silicate
Iyad Rashid, ... Adnan A. Badwan, in Profiles of Drug Substances, Excipients and
Related Methodology, 2011

4.2.1.4 Potentiometric analysis by ion-selective electrode [39]

A series of ion-selective electrodes (ISEs) for Ca2+, Mg2+, NH4+, K+, Na+, Li+, and
H+ is used for the analysis of water samples from different sources. The selectivity
of the calcium and magnesium ISEs is not fully achieved as other cationic species
may interfere with the analysis. The proposed sensor array device can overcome this
drawback since it can take advantage of the cross-selectivities of cationic species
toward each ISE. Results obtained are in reasonable concordance with those attained
by the standard method based on complexometric analysis.

> Read full chapter

Molecularly Imprinted Polymer-Based

Potentiometric Sensors for the Deter-
mination of Drugs in Pharmaceutical,
Biological, and Environmental Samples
Mehran Javanbakht, Behrouz Akbari-Adergani, in Molecularly Imprinted Sensors,
2012

7 Analytical Performance
The properties of an ion-selective electrode are characterized by parameters such as
linearity, limit of detection (LOD), limit of quantification (LOQ), sensitivity, selectiv-
ity, reproducibility, accuracy, robustness, response time, and lifetime.

7.1 Linearity and Detection Limits

Perhaps the most surprising and innovative research direction in potentiometric
sensors is the dramatic improvement of the lower detection limit. Each poten-
tiometric sensor has a lower and upper detection limit where the response starts
to distance significantly from a Nernstian electrode slope. Generally, they fall
into activity ranges where the electrode starts to lose sensitivity to the target ion.
According to the IUPAC recommendation, the detection limit is defined by the
cross-section of the two extrapolated linear calibration curves [54]. The linearity of
a potentiometric sensor is defined as the activity ratio of upper and lower detection
limit and approximately corresponds to the range where the electrode responds
according to the Nernst equation.

Figure 11.8 exhibits a Nernstian slope of 28.0 mV/decade in a cetirizine concentra-

tion range between 1.0 × 10−6 mol/L and 1.0 × 10−2 mol/L, with a lower detection
limit of 7.0 × 10−7 mol/L [31]. The carbon paste electrode with the nonimprinted
polymer presented a nonlinear potentiometric response, and the slope was very low
(approximately 9.2 mV/decade).

FIGURE 11.8. Calibration curve for a cetirizine potentiometric sensor.

Table 11.3 summarizes the MIP-based potentiometric sensors reported in the liter-
ature and includes the studies of their linearity and detection system.

TABLE 11.3. Construction, Recognition System, and Linear Range of Different

Potentiometric Electrodes Based on MIP

Analyte Sensor construc- Recognition sys- Linear range Ref.

tion tem (mol/L)
Dipicolinic acid Template and OTS ITO-coated glass 1.5 × 10−6 to 1.9 × 49
were co-adsorbed plate 10−2
on the polar solid
surface of the ITO
glass plate.
Atrazine A glassy mem- A glassy mem- 3 × 10−5 to 1 × 10−3 28
brane is ob- brane
tained from poly-
merization of a
reagent mixture
containing MAA,
EGDMA, tem-
plate, and AIBN.
Atrazine By dispersing A PVC membrane 1 × 10−7 to 1 × 10−2 39
the atrazine-im-
printed polymer
particles in the
DOP plasticizer
and, then, em-
bedding in the
PVC matrix.
Methylphosphonic By casting a A PVC membrane 5 × 10−8 to 1 × 40
acid membrane af-
ter dispersing 10−4and1 × 10−3
the MPA-imprint-
ed polymer parti- to 1 × 10−1
cles in NPOE and
embedding in the
PVC matrix.
Methylphosphonic By surface im- ITO-coated glass 1 × 10−2 to 1 × 10−1 30
acid printing tech- plate
nique coupled
with a nanoscale
transducer, ITO.
Pinacolyl By dispersing A PVC membrane 4 × 10−8 to 1 × 10−3 26
methylphospho- the PMP-imprint-
nate ed polymer mate-
rials and the sus-
pension in PVC.
Levamisole By dispersing A PVC membrane 2.5 × 10−6 to 1.0 × 41
the levamisol-im- 10−1
printed polymer
particles in the
DBS plasticizer
and, then, em-
bedding in the
PVC matrix.
cAMP The imprinted ISFET 5 × 10−6 to 1.2 × 50
polymer mem-
brane was coated 10−2
on the ISFET elec-
trode
Hydroxyzine A CPE is pre- Carbon paste 1.0 × 10−6 to 1.0 × 12
pared by mixing 10−1
graphite powder,
paraffin oil, and
 hydroxyzin- im-
printed polymer.

Abbreviations: OTS, octadecyltrichlorosilane; ODS, octadecylsiloxane; ITO, indium

tin oxide; DBS, sebacic acid dibutyl ester; PVC, polyvinylchloride; DOP, dioctyl
phthalate; o-NPPE, o-nitrophenyl octyl ether; PMP, pinacolyl methylphosphonate;
N-CBZ-Asp, N-cabobenzoxy-aspartic acid.

7.2 Sensitivity
Providing that some conditions are gotten together, the theoretical slope (sensitivity)
of the calibration curve of an ISE toward a given singly charged ion, at 25 °C, should
be 59.2/z mV/decade, as formulated by the Nernst equation. The ISE membranes
must have a sufficient perm-selectivity. For the following two situations, a
non-Nernstian may be seen:

1. Co-extraction of the counter ions, which leads to considerable ion pairing,

reduces slopes.
2. Non-Nernstian behaviors may also happen, if an ISE is exposed to ions that
complex by the ionophore.

Surfactants and proteins, and other species that may be present together with the
target ions in pharmaceuticals and biological fluids, can also interfere with the
normal ion-extraction process resulting in nontheoretical (non-Nerstian) behaviors.

It has been demonstrated that the membrane composition has a significant

effect on the sensitivity of potentiometric sensors. Table 11.4 displays the slopes,
linear ranges, and LODs of the resulting potentiometric calibration curves for the
hydroxyzine ion-selective electrodes, obtained in buffered solutions at the pH value
of 2.0 [12]. Clearly, an increase at the MIP level in the CPE caused a slope increase of
the calibration curve. The MIP-modified electrode with the graphite powder/paraffin
oil/MIP percentage ratio of 64%/21%/15% was selected as the one with the optimal
membrane ingredient composition. The MIP-modified electrodes exhibited Nerns-
tian response (29.4 ± 1.0 mV/decade) in the concentration range 1.0 × 10−6 to 1.0 ×
10−1 mol/L for hydroxyzine.

TABLE 11.4. Composition of the MIP-Based Hydroxyzine CPEs and Their Poten-
tiometic Response Characteristics, Measured in Phosphate Buffer Solutions (pH 2.0)

Electrode Composition% Slope (mV Linear range (M) LOD (M)

decade−1)
MIP Graphite powder Paraffin oil
CPE1 0a 64 21 ~8 (±2.0) - 5.0 × 10−6
CPE2 5 71 24 10.7(±1.9) 1.0 × 10−5 to 7.0 × 10−6
1.0 × 10−1
CPE4 7 70 23 12.9(±1.8) 5.0 × 10−6 to 3.0 × 10−6
1.0 × 10−1
CPE5 10 68 22 21.8(±1.5) 1.0 × 10−5 to 7.0 × 10−6
5.0 × 10−2
CPE6 15 64 21 29.4(±1.0) 1.0 × 10−6 to 7.0 × 10−7
1.0 × 10−1

a Containing 15% NIP.

7.3 Selectivity
The potentiometric selectivity coefficients can be determined by different proce-
dures, namely, the so-called fixed interference method (FIM), the separate solution
method (SSM), and the matched potential method (MPM). The coefficients
describe the preference of the suggested electrode for an interfering ion, X, with
reference to the analyte ion. The IUPAC recommended the use of SSM and FIM,
two different procedures to determine the Nicolskii coefficients of ISEs [54]. The
SSM involves the measurement of two separate solutions, each containing a salt
of the determined ion only. The Nicolskii coefficient is then calculated from the
two observed emf values. In the FIM, an entire calibration curve is measured for
the analyte ion in a constant interfering ion background, aj(BG). The linear response
curve of the electrode as a function of the analyte ion activity is extrapolated until,
at the lower detection limit aI(DL), it intersects with the observed potential for the
background alone. The FIM coefficient is calculated from the resulting the lower
detection limit to the interfering ion activity ratio (Eq. 11.2):

(11.2)

The MPM was introduced in the mid-1980s by Gadzekpo and Christian to provide
a selectivity formalism that would give empirically more meaningful results [55].
According to the MPM method, the specified activity (concentration) of the primary
ions is added to a reference solution, and the potential is measured. In another
experiment, the interfering ions (X) are successively added to an identical reference
solution, until the measured potential matches that obtained before the addition of
the primary ions. The MPM selectivity coefficient, , is then given by the ratio of
resulting primary ion activity (concentration) to the interfering ion activity increases
in the two experiments (Eq. 11.3):

(11.3)

The MPM and FIM selectivity coefficients for the hydroxyzine ion-selective elec-
trode at the constant pH value of 2.0 are listed in Table 11.5 [12]. As is obvious from
this table, when the MIP sensor is applied to determine hydroxyzine, all the other
substances (except for cetirizine) hardly interfere with the determination. In most
cases, the selectivity coefficients are on the order of 5.0 × 10−4 and lower. The MPM
selectivity sequence of the employed MIP for different drugs and organic materials
(Fig. 11.9) approximately obeys the order: cetirizine > piperazine > pipyridine >
tri-ethyl ammonium chloride > promethazine > salbutamol ≈ metochlorpramide
> pyrrole ≈ aniline. As a result, the MIP molecular recognition is based both on
the template molecular structure (shape) and on the interactions between the print
molecule and the imprinted polymer. Cetirizine is of a similar chemical structure,
in which an acetic acid (-CH2-COOH) moiety presents instead of the ethanol (-CH2-
–CH2-OH) moiety in the aliphatic chain. This behavior confirmed that this molecule
could interfere in the hydroxyzine detection.

TABLE 11.5. Potentiometric Selectivity Coefficient Values, , for a Hydroxyzine

Potentiometric Sensor

Interfering, X Log Log Interfering, X Log Log

Cetrizine −1.8 −1.9 Pyrrole −4.2 −4.3
Promethazine −3.9 −4.1 Aniline −4.2 −4.2
Salbutamol −4.1 −4.2 KNO3 −3.3 −3.5
sulfate
Piperazine −3.3 −3.3 NaNO3 −4.8 −4.1
Metochlor- −4.1 −4.4 NaCl −4.8 −5.0
pramide
Pipyridine −3.4 −3.5 Ca(NO3)2 −3.5 −3.6
N(CH2CH3)3Cl −3.5 −3.7 Mg(NO3)2 −4.0 −4.2
Terazosine −4.5 −4.6

FIGURE 11.9. Structure of the investigated drugs and organic materials as interfer-
ences in MIP-based hydroxyzine sensor.

7.4 Response Time

In previous IUPAC recommendations, response time is the average time required for
the electrodes to reach a potential response within ±1 mV of the final equilibrium
value, or has reached 90% of the last value, after successive immersions in a series of
target solutions, each having a 10-fold concentration difference [54]. More recently,
it has been extended to be able to treat drifting systems as well. In this case, the
second time instant is defined as the one at which the emf/time slope (dE/dt)
becomes equal to a limiting value [56]. Fig. 11.10 shows the resulting potential-time
responses for the hydroxyzine potentiometric sensor, obtained upon changing the
hydroxyzine concentration from 1.0 × 10−3 mol/L to 1.0 × 10−2 mol/L and from 1.0
× 10−2 mol/L to 1.0 × 10−3 M. It is evident that the potentiometric response of the
electrode is rapid (approximately 15 s) and reversible, although the time needed
to reach the equilibrium value for the case of high-to-low sample concentration is
longer than that of the low-to-high sample concentration [12].

FIGURE 11.10. Dynamic response of the MIP-based hydroxyzine sensor for

low-to-high (1.0 × 10−3 mol/L to 1.0 × 10−2 mol/L, left part) and high-to-low (1.0 ×
10−2 mol/L to 1.0 × 10−3 mol/L, right part) step concentrations.

Rafailovich et al. introduced a hemoglobin-imprinted thiol modified electrode with

the response time of 2–10 min [47].

7.5 Lifetime
The lifetime of the MIP-based electrode can be studied by periodically recalibrating
the potentiometric response to the target drug in the standard solutions. After the
conditioning step, the electrode was repeatedly calibrated three times every month,
and any change in the electrode performance was recorded.

The average lifetime for most of the reported PVC-plasticized membrane electrodes
is in the range of 1–2 months [39,40,42–46]. After this time, a slow deterioration
of selectivity and response will be observed. It is well established that the loss of
plasticizer or ionic site from the polymeric film due to leaching into the sample
is a primary reason for the limited lifetimes of ISEs [33]. From this point, the
chemically modified electrodes were found to have significant advantages over their
corresponding plasticized PVC membranes. Since these electrodes did not contain
any special plasticizer or membrane solvent, they were more durable and less toxic
than the plasticized PVC membranes to be applied to ion sensors.

MIP-modified electrodes for hydroxyzine and cetirizine demonstrated the successful

fabrication and durable lifetime, and so no significant change in the electrodes'
performance during 5 months was observed [12,31].

7.6 Accuracy and Precision

Usually, the accuracy of the measurements by means of the potentiometric sensors
is checked by calculating the recovery of a known analyte concentration.

The hydroxizine potentiometric sensor was applied to assay of hydroxizine in spiked

human serum and urine samples. The results of the recovery studies are listed in
Table 11.6. The recoveries of the methods are in the range of 95 to 110% and 96 to
109% for the spiked serum and urine samples, respectively [12].

TABLE 11.6. Recovery Results for the Hydroxyzine Potentiometric Sensor in Urine
and Serum Samples

Amount added (M) Urine Serum

Amount founda (M) Recovery% Amount founda (M) Recovery%
5.0 × 10−6 5.40(±0.34 ) × 10−6 109 5.51(±0.24) ×10−5 111
1.0 × 10−5 1.06(±0.06 ) × 10−5 104 − −
5.0 × 10−5 − − 5.06(±0.05 ) ×10−5 106
1.0 × 10−4 1.02(±0.09 ) × 10−4 103 1.4(±0.37 ) × 10−4 107
5.0 × 10−4 − − 4.83(±0.19 ) × 10−4 94

a Average of three determinations.

For the evaluation of reproducibility, the analytical method must be repeated several
times. The precision of the procedure can be reported in terms of relative standard
deviation. The analytical performance of the hydroxizine potentiometric sensor was
evaluated with five repeated potentiometric measurements of the 1.0 × 10−5 M hy-
droxizine solution in different laboratories. The precision of the described procedure
in terms of relative standard deviation was 6.5% [12].

7.7 Robustness/Ruggedness
Robustness is defined as the persistence of a system’s characteristic behavior under
perturbations or conditions of uncertainty. In other hands, robustness is a measure
of its capacity to remain unaffected by small but deliberate variations in the analytical
procedure parameters. A robust chemosensor capable of specifically sensing the
presence of chloropropanols in complex sample matrices with adequate sensitivity
was reported by K.P.L. Mitch and co-workers [57]. This MIP-based sensor showed
good selectivity for 3-chloro-1,2-propanediol (3-MCPD) since both 3-MCPD and
1,3-DCP often coexist as contaminants in epoxy resins used in the paper industry
and in food products.

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ION-SELECTIVE ELECTRODES | Food

Applications☆
M. Maj-Żurawska, A. Hulanicki, in Encyclopedia of Analytical Science (Third Edi-
tion), 2013

Characteristics of Potentiometric Sensors in Food Analysis

The analysis of foodstuffs by ion-selective electrodes must take into account the spe-
cial nature of the sample, the characteristics of ISEs, and the conditions of measure-
ments. In contrast to most analytical techniques, in potentiometric measurements
the analytical signal is directly correlated to the activity of the sensed species. This
could be of advantage in food analysis as the bioavailability of a species is closely
related to the activity of the ion. However, measuring of activity of analytes in real
samples requires the fulfillment of some special conditions that are rarely attained in
practical analysis. The activity of the analyte ion depends on the characteristics of the
medium, e.g., its electric permittivity, temperature and ionic composition, the latter
being expressed in dilute solutions by the value of the ionic strength. The presence
of non-aqueous solvents also influences the activity/concentration relationship.
Therefore only for samples that are dilute aqueous solutions alone a potentiometric
measurement may give a relatively reasonable evaluation of the activity. In the case
of real food samples, we rarely have such ideal situations. In most cases samples,
both liquid and solid, need pretreatment, such as dissolution, dilution, extraction of
the analyte, or separation of interferents. After such a treatment the only information
that may be gained from the potentiometric measurement is the concentration of
the analyte.

The correct interpretation of the relation between the activity and concentration
requires a proper choice of experimental conditions and a careful interpretation
of the results. The most common procedure involves the use of an ionic strength
adjustment solution (buffer). It consists of an inert salt at constant concentration,
that which does not interact with the analyte (e.g., KNO3), providing a solution of
constant ionic strength, not influenced by small changes of the composition of
the sample solution. Usually the other components have additional functions. For
example, in total fluoride determination, such as Al3 + or Fe3 +, which bind fluoride
ions, should be complexed with cyclohexane-1,2-diamine-N,N.N ,N -tetraacetic
acid to liberate fluoride ions. In determination of total calcium content, controlled
complexation of the analyte by addition of iminodiacetic acid eliminates the ef-
fects caused by the presence of other weaker complexants of various strength and
concentration. Usually such an ionic strength adjustment solution also contains a
pH-buffer, which provides optimal pH value for the ISE used. Under conditions
of constant ionic strength there exists an exact correlation between the potential
reading and the logarithm of concentration of the analyte ion according to the
Nernst equation.

A very special situation exists in the case of pH measurements based on mea-

surements made using glass electrodes or other membrane sensors selective to
hydrogen ions. By definition, the pH value is directly related to the activity of the
hydrogen ion in solution. This is determined by calibrating the meter with primary
(or secondary) pH standard buffers. However, aqueous standards may be usable
only under specific conditions. When measurements are carried under conditions
differing from these, as in the presence of ethanol, the result of the measurement
has only a relative value, e.g., indicating whether the samples differ from one
another. Good results, less dependent on the sample material, are obtained from
differential pH measurements. The possibility of measuring pH potentiometrically
with high precision, coupled with high specificity of enzymatic reactions, permits
the determination of a variety of analytes (urea, citric acid, reducing sugars, alkaline
phosphatase, pesticides etc.) in milk, wine, and other fluid samples, with no or little
sample pretreatment.

In principle the ion-selective electrodes are sensitive only to free (hydrated) ions of
the analyte and do not respond to various complexed species of the analyte. This
property could be exploited in the speciation analysis, distinguishing the free and
bound analyte species. However, it must be remembered that most procedures of
sample pretreatment: dilution, extraction, addition of reagents, change the initial
speciation, corresponding to the nontreated sample. Therefore, only when the
species are kinetically inert, and the sample pretreatment is carried out with special
caution is there a possibility of analyte speciation. For example, calcium in milk is
present as a free (hydrated) ion or in combination with proteins, lipids or larger
molecular mass species. The evaluation of each of the species is the aim of speciation
analysis. The task is relatively simple when the species investigated are inert, do not
dissociate, or otherwise undergo decompose during sample pretreatment. A similar
problem is common in analysis of other biological samples, e.g., in blood analysis,
where even 20-fold dilution results in nearly complete dissociation of the calcium
complexes with various ligands. Similarly the measurements with iodide selective
electrode does not respond to iodine bound to organic matrix.
Potentiometric (as well as other electrochemical) measurements have the important
advantage over optical measurements in that the color or opacity of the sample
solution do not obscure the proper determination of the analyte. It was found that
in many instances the ISE measurements give superior precision than spectropho-
tometric determinations. On the other hand, functioning of the electrodes in the
presence of colloids and suspensions may also produce erroneous results. This is
described as a suspension effect that is due to blocking the electrode surface or the
porous plug connecting the reference electrode. This requires frequent checking the
proper functioning of the electrode system, or even using special electrode systems
to avoid troubles. Measurements using flow systems often diminish such effects.

The main limitation of the use of ISEs in practical analysis is in the range of analyte
determination and the selectivity of the electrodes. Most commercially available
electrodes allow precise measurements of the analyte down to 10− 5–10− 6 mol l− 1
concentration. For some crystalline electrodes this may be shifted down by some
orders of magnitude, but only in the case when the species measured remain in
an labile equilibrium in an ion (e.g., metal ion) buffer. Obviously measurements in
the lowest concentration range suffer all the difficulties typical for trace analysis
(e.g., contamination), which may affect the determination. The concentration range
of analyte that may be measured using ISEs is usually between 10− 2 and 10− 4 mol l− 1,
and the sample size and subsequent dilution should be adjusted to those conditions.

Several electrodes of differing selectivity are commercially available at present for

measurements of most common ions. Preliminary information may be obtained on
the basis of tabulated values of the selectivity coefficients; nevertheless, it must
be remembered that their values depend on the method of determination, on the
manner in which the electrodes are maintained, and on the life of the electrode.
Therefore it is a good habit to check the selectivity under standard conditions of
planned application measurements. After long periods of use the selectivity of the
electrode may also change, giving rise to erratic results. For reliable measurements
the potentiometric selectivity coefficient should not be greater than 10− 2, for
ions of the same charge and for comparable concentration levels of the analyte and
interferent.

Quantification in measurements made using ISEs can be carried out in different

ways. The most common one is based on the calibration graph, prepared using
standard calibrating solutions adjusted to the expected concentration range of the
analyte, with similar addition of the ionic strength adjustment solution. Another
possibility is the known addition or analyte addition mode. These modes may often
help to eliminate possible interferences. For determination of larger concentrations,
ISEs are used as end point indicators in titrations. The acidity of foodstuffs is
determined routinely using acid-base titration with a pH sensitive electrode, glass
 electrodes being used most commonly as the indicator. It should be mentioned that
titration gives the concentration of the analyte directly.

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