Renewable pH cross-sensitive potentiometric heparin sensors with incorporated electrically charged H+ ionophores

Polymer membrane-based potentiometric sensors have been developed earlier to provide a rapid and direct method of analysis for polyions such as heparin, a natural anticoagulant administered to prevent thrombus formation during cardiovascular surgery. These heparin sensors are irreversible, requiring a membrane renewal procedure between measurements which currently prevents the sensors from being used for continuous monitoring of blood heparin. A newly developed heparin sensor is shown here to allow an alternate and more practical method of membrane renewal. The electrically charged H+ ionophore 5-(octadecanoyloxy)-2-(4-nitrophenylazo)-phenol (ETH 2412) is incorporated as an additional ionophore into a heparin-sensing membrane. This membrane will respond to pH only at low H+ concentrations, while sample anions are coextracted with H+ ions into the membrane at physiological pH. In buffered samples at physiological pH, the sensors will therefore respond to heparin via an ion-exchange mechanism with chloride anions. The pH cross-sensitive heparin-sensing membranes are shown to give an excellent potentiometric response toward heparin in aqueous samples at physiological pH and Cl-levels as well as in undiluted whole blood with no loss of heparin response. The membrane renewal is accomplished by moderately increasing the pH of the sample, causing heparin to diffuse out of the membrane with H+ ions. Reproducibilities are, with less than 1 mV standard deviation, improved over the classical system. Unlike the high NaCl concentration used to strip heparin from the previously established heparin sensor, the pH change used here could ultimately be performed locally at the sample-membrane interface, allowing the sensor to be used for automated long-term monitoring of heparin in blood. A theoretical model is presented to explain the experimental results.