New trends in ion-selective electrodes - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 103

anticoagulants such as heparin and the continuous release of biologically active mol-
ecules such as nitric oxide [99]. Polymers with better biocompatibility such as poly-
urethanes have been employed as well. An interesting approach was used by the group
of Bachas [100], who prepared a potassium-selective electrode coated with a copoly-
mer containing phosphorylcholine, which mimicked the polar groups on cell surfaces.
Decreased adhesion and activation of platelets was demonstrated after soaking the
PVC membranes in platelet-rich plasma. At the same time the biocompatible coating
did not affect the ISE sensing characteristics.
The second aspect of biocompatibility is a leaching problem. Ion-selective elec-
trode materials, especially components of solvent polymeric membranes, are subject
to leaching upon prolonged contact with physiological media. Membrane components
such as plasticizers, ion exchangers and ionophores may activate the clotting cas-
cade or stimulate an immune response. Moreover, they can be potentially toxic when
released to the blood stream in signifi cant concentrations.
There is a practical limit in the synthesis of ionophores and ion exchangers con-
taining longer alkyl chains that potentially improve component retention. Replacement
of solvent polymeric membranes with self-plasticized compositions with all sensing
components covalently attached to the polymeric backbone appears to be an elegant
solution to the leaching problem. Many self-plasticized polymers have been studied
as ion-selective membrane matrices, including polyurethanes, polysiloxanes, and poly-
acrylates [101]. Among them alkyl acrylate copolymers appear to be very promising,
combining several important advantages such as simplicity of variation of physical
properties and the possibility of attaching sensing components to the matrix via single-
step solution polymerization.
Several examples of ion-selective electrodes with ionophores covalently attached to
a self-plasticized polymeric matrix have been reported in the literature. For instance,
a Ca-selective electrode with the ionophore attached to a methylmethacrylate- co -
decyl methacrylate backbone was developed recently [91]. Ion exchangers such as the
dodecacarborane anion have been anchored to the polymeric backbone, with grafted
dodecarborane showing greatly improved retention in the polymeric phase [88].

4.5 MINIATURIZATION

4.5.1 Miniaturization
Miniaturization of polymeric ISEs has been the focus of efforts of many research
groups over decades [21] and still is of high relevance. Biology and medicine greatly
demand analytical techniques for intracellular measurements. They provide information
on the electrolyte concentration in living cells and give access to fundamental parame-
ters such as cell membrane potential and cellular ion transport and may enable a deeper
understanding of the connected physiological processes. Automated sample handling
and separation techniques such as various fl ow injection methods and micro total analy-
sis systems ( µ TAS) require miniature detectors. Microsensors compatible with existing