Polymer membrane-based electrodes sensitive to low molecular weight heparin (LMWH) have been used to examine the binding between several preparations of LMWH and heparin-binding foldamers, which have recently been developed as potential inhibitors of the anticoagulant activity of LMWHs. It was found that the structure of the heparin-binding foldamer affects the equilibrium binding constant, K(eq), determined by analysis of the titration curves of the foldamers with LMWHs monitored with these electrodes, and further, the strength of binding depends on the specific LMWH preparation. Additionally, polymer membrane-based electrodes utilizing dinonylnaphthalene sulfonate as the ion-exchanger were developed to measure the heparin-binding foldamers directly in whole blood, and the response was found to depend on the lipophilicity and charge density of the foldamer.