POLYMER MEMBRANE-BASED POLYION SENSORS - DEVELOPMENT, RESPONSE MECHANISM, AND BIOANALYTICAL APPLICATIONS

Polymer membrane type ion-selective electrodes (ISEs) are now used routinely to measure clinically important ions (e.g., Na+, K+, Ca2+) in undiluted blood. However, efforts to develop similar sensors suitable for the direct detection of larger biomolecules have been less successful owing to the difficulty in identifying appropriate membrane chemistries that yield a significant and selective response toward the desired macromolecular analytes. Recently, we have found that poorly plasticized polymer membranes (PVC) doped with lipophilic anion and cation exchangers exhibit unexpectedly large and reproducible potentiometric responses to low levels (< 1 mu M) of certain biomedically important macromolecular polyionic species (heparin and protamine). This article provides data demonstrating how the specific membrane formulation and electrode geometry used influence the magnitude of the polyion EMF responses observed. The results suggest a non-equilibrium/steady-state polyion extraction process is responsible for the potentiometric heparin and protamine responses exhibited by appropriately formulated membranes. The practical utility of these sensors for monitoring heparin levels in blood as well as heparin/protamine binding to other biologically important macromolecules will be described. Further, the prospects of adapting the same polyion extraction chemistry to devise optically sensitive thin polymer films for monitoring heparin will also be addressed.