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

Polymer membrane-based potentiometric sensors have been developed earlier t o provide a rapid and direct method of analysis for polyions such as hepari n, a natural anticoagulant administered to prevent thrombus formation durin g 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+ ionophor e 5-(octadecanoyloxy) -2- (4-nitrophenylazo)-phenol (ETH 2412) is incorpora ted as an additional ionophore into a heparin-sensing membrane. This membra ne will respond to pH only at low H+ concentrations, while sample anions ar e coextracted with Ht ions into the membrane at physiological pH. In buffer ed samples at physiological pH, the sensors will therefore respond to hepar in via an ion-exchange mechanism with chloride anions. The pH cross-sensiti ve heparin-sensing membranes are shown to give an excellent potentiometric response toward heparin in aqueous samples at physiological pH and Cl- leve ls as well as in undiluted whole blood with no loss of heparin response. Th e membrane renewal is accomplished by moderately increasing the pH of the s ample, causing heparin to diffuse out of the membrane with H+ ions. Reprodu cibilities are, with less than 1 mV standard deviation, improved over the c lassical system. Unlike the high NaCl concentration used to strip heparin f rom the previously established heparin sensor, the pH change used here coul d ultimately be performed locally at the sample-membrane interface, allowin g the sensor to be used for automated long-term monitoring of heparin in bl ood. A theoretical model is presented to explain the experimental results.