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 first polymeric membrane electrodes that respond to the polyanion heparin. 

One may think that the idea of detecting ionic compounds such as heparin using polymeric ion-selective electrodes seems very difficult due to the high charge of polyionic 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 ImV decade 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 

FIGURE 4.8 Structures of representative fragments of heparin (1) and protamine (2) molecules. 

Soon after the initial development of the heparin sensor, an electrode for the detection of the polycation protamine was proposed [38] based on a polymeric membrane doped with the cation exchanger tetrakis-(4-chlorophenyl)borate. Protamine is a polypeptide and usually administered as a heparin antidote. Protamine is a polycation with an average charge of +20 and is rich in arginine (Fig. 4.8). The response function of protamine-selective electrodes is similar to the heparin response function (Fig. 4.9b). 

Electrochemical Sensors, Biosensors and Their Biomedical Applications 

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Due to their response mechanism the polyion-selective electrodes are not sensitive to the small fragments of polyionic macromolecules. Thus, if an enzyme cleaves the polyionic molecule these sensors can be used for detection of enzyme activity. Polycation protamine is rich in arginine residues that make it a suitable substrate for protease-sensitive electrochemical assays. Real-time detection of trypsine activity was demonstrated with the protamine-selective electrode as a detector [38],... 

Non-equilibrium processes at the sample/membrane interface and across the bulk membrane bias the selectivity and detection limits of the electrodes. Elimination of these nonequilibrium effects by operating the electrodes under complete equilibrium conditions will be of both practical and fundamental significance. While non-equilibrium responses are useful for potentiometric polyion-selective electrodes, it is not obvious whether potentiometry based on mixed ion-transfer potentials is a better transduction mechanism than amperome-try/voltammetry based on selective polyion transfer (65, 66). Ion-transfer electrochemistry at polarized liquid/liquid interfaces is introduced in Chapter 17 of this handbook. 

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