New trends in ion-selective electrodes - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 85

60)
with the Nernstian slope (59.2/ z mV decade 1 ) were shown to be promising reference
electrode systems for measurements in physiological samples, especially in blood [33].
However, the limited selectivity of polyion sensors makes them inapplicable univer-
sally. While various setups based on unresponsive hydrophobic membranes or salt-
doped resins were evaluated as promising reference electrodes, all of them have both
advantages and shortcomings [34], and the universal solid contact reference electrode is
yet to be developed.

Polyion-selective electrodes (see below), responding to highly charged ions ( z

4.3 NEW TRANSDUCTION PRINCIPLES

4.3.1 Polyion-selective electrodes
The possibility of detecting polyionic macromolecules added a new thrust to the area
of ion-selective electrodes in the past decade. Professors Ma and Meyerhoff from the
University of Michigan described in their pioneering work [35] the fi rst polymeric
membrane electrodes that respond to the polyanion heparin.
Heparin is a highly sulfated polysaccharide (copolymer of uronic/iduronic acids
alternating with sulfated glucosamine residues) with an average charge of

70 and an
average molecular mass of 15 000 Da. It is the most commonly used anticoagulant dur-
ing cardiac or vascular surgery. A typical fragment of heparin molecule is depicted in
Fig. 4.8. The anticoagulant activity of heparin is attributed to its interaction with anti-
thrombin III, a serine protease inhibitor, causing the formation of heparin-antithrombin
complexes, which drastically increase the inhibition ability of antithrombin on enzymes
involved in the coagulation process.
More than 1 trillion units are administered annually to approximately 12 million
patients in the United States. Real-time monitoring of heparin concentration in blood
prevents the risk of possible bleeding and reduces postoperative complications. The
activated clotting time measurement (ACT) is a widespread method for the determi-
nation of the heparin concentration in whole blood. Although this method is fast and
simple, it is non-specifi c and indirect, and the results can be affected by many factors,
such as hemodilution and hypothermia [36]. Alternative methods such as chromogenic
heparin assays based on factor Xa inhibition, although widely used in clinical laborato-
ries, cannot be performed during the surgery with whole blood samples. In contrast to
other methods, the heparin-selective electrode was able to detect heparin concentration
directly in whole blood or plasma samples.
One may think that the idea of detecting ionic compounds such as heparin using
polymeric ion-selective electrodes seems very diffi cult due to the high charge of polyi-
onic molecules, which makes the slope of the electrode function negligibly small for
an analytical application. Indeed, for heparin-selective electrodes the theoretical slope
is less than 1 mV decade 1 and the potential practically does not depend on heparin
concentration, which means that this ISE can be useful as a reference electrode [33].
Nonetheless, Ma and Meyerhoff noticed that the potential of polymeric membrane