New trends in ion-selective electrodes - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 72

and to be more stable and have improved biocompatibility [11]. A small number of the
most successful ionophores used in the polymeric ion-selective electrodes are depicted in
Fig. 4.1. Signifi cant progress has been achieved in the development of solid contact sen-
sors, especially on those based on conducting polymers [12]. Such sensors can be eas-
ily miniaturized, which signifi cantly simplifi es the sensor fabrication process, decreases
sample volume, enables in-vivo measurements and provides compatibility with microchip
technologies and other advances [13]. Microsensors can also be incorporated into sensor
arrays, capable of multianalyte detection and pattern recognition [14].
4.1.2 Most important biomedical applications of
ion-selective electrodes
Clinical chemistry, particularly the determination of the biologically relevant elec-
trolytes in physiological fl uids, remains the key area of ISEs application [15], as bil-
lions of routine measurements with ISEs are performed each year all over the world
[16]. The concentration ranges for the most important physiological ions detectable in
blood fl uids with polymeric ISEs are shown in Table 4.1. Sensors for pH and for ion-
ized calcium, potassium and sodium are approved by the International Federation of
Clinical Chemistry (IFCC) and implemented into commercially available clinical ana-
lyzers [17]. Moreover, magnesium, lithium, and chloride ions are also widely detected
by corresponding ISEs in blood liquids, urine, hemodialysis solutions, and elsewhere.
Sensors for the determination of physiologically relevant polyions (heparin and pro-
tamine), dissolved carbon dioxide, phosphates, and other blood analytes, intensively
studied over the years, are on their way to replace less reliable and/or awkward ana-
lytical procedures for blood analysis (see below).
In contrast to other analytical methods, ion-selective electrodes respond to an ion
activity, not concentration, which makes them especially attractive for clinical appli-
cations as health disorders are usually correlated to ion activity. While most ISEs
are used in vitro , the possibility to perform measurements in vivo and continuously
with implanted sensors could arm a physician with a valuable diagnostic tool. In-vivo
detection is still a challenge, as sensors must meet two strict requirements: fi rst, mini-
mally perturb the in-vivo environment, which could be problematic due to injuries and
infl ammation often created by an implanted sensor and also due to leaching of sensing
materials; second, the sensor must not be susceptible to this environment, and effects
of protein adsorption, cell adhesion, and extraction of lipophilic species on a sensor
response must be diminished [13]. Nevertheless, direct electrolyte measurements in
situ in rabbit muscles and in a porcine beating heart were successfully performed with
microfabricated sensor arrays [18].
The relative simplicity of the sensor setup allows them to be implemented into port-
able automated devices or bed-side analyzers (Fig. 4.2), which are easily installed at
patient beds, eliminating the time-consuming laboratory analyses. On the other hand,
modern high throughput clinical analyzers may process more than 1000 samples per
hour and simultaneously determine dozens of analytes, using a handful of analytical
methods. Blood electrolyte analysis, however, remains one of the most important in