New trends in ion-selective electrodes - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 86

1. Heparin

CH 3 OSO 3

O O

CO 2

O

O

OSO 3

NHSO 3

NH 2 NH 2

2. Protamine

NH 2

NH

NH 2

NH

(CH 2 ) 3 (CH 2 ) 3

O

NH

NH NH

O

O

(CH 2 ) 3

NH

NH 2
NH 2

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

electrode doped with TDMACl (tridecylmethylammonium chloride) or Aliquat 336
(tricaprylmethylammonium chloride) exhibited signifi cant potentiometric anion
response when heparin was added to 0.15 M NaCl (Fig. 4.9a) [35, 37].
Soon after the initial development of the heparin sensor, an electrode for the detec-
tion 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).
In contrast to conventional ISEs the resulting polyion responses yielded non-lin-
ear S-shaped calibration curves. After prolonged exposure to the solutions containing
polyions both electrodes lost their response function demonstrating negligible slope
close to the calculated according Nernst equation (Fig. 4.9). In order to explain this
unusual non-classical response function a theoretical non-equilibrium model was pro-
posed [39]. Briefl y, the membrane initially acts as an ion exchanger-based sodium
electrode and a Nernstian response slope to sodium ions is expected when protamine
is absent. Once a low concentration (ca. 1

M) of protamine is present in the sample,
it is preferably extracted into the membrane owing to the ion exchanger, which sta-
bilizes the polyion charge not unlike that in a reverse micelle. This extraction forces
the sodium ions initially present in the membrane to be expelled by ion exchange.
The amount of sodium expelled depends directly on the mass transport kinetics of the

µ