Response Mechanism of Polymer Membrane-Based Potentiometric Polyion Sensors

Abstract

The potentiometric response mechanism of a previously reported polymer membrane-based electrode sensitive to the polyanion heparin is established. Based on transport and extraction studies, the heparin response is attributed to a nonequilibrium change in the phase boundary potential at the sample/membrane interface. While true equilibrium polyion response, obtained for low heparin concentrations only after very long equilibration times (> 20 h), yields the expected Nernstian response slope of < 1 mV/decade, the observed large and reproducible EMF response to clinically relevant heparin concentrations (approximately 10(-7) M) during typical measurement periods (2-5 min) is ascribed to a steady-state kinetic process defined by the flux of the polyion both to the surface and into the bulk of the polymer membrane. A model describing this nonequilibrium response is presented. With this model, the uniqueness of the polymer membrane composition (e.g., very low plasticizer content, strictly controlled cationic site concentration, etc.) required to achieve analytically useful heparin response becomes clear. Practical working conditions and limitations of the sensor are discussed. To support the generality of the steady-state model proposed, corresponding EMF response data for a newly developed membrane electrode sensitive to a polycationic protein (protamine) are also presented. It is shown that the protamine-responsive membrane electrode appears to operate via the exact same kinetic mechanism as the heparin sensing system.

Potentiometric flow injection sensing system for determination of heparin based on current-controlled release of protamine

“…However, the spontaneous release of protamine across the membrane to the sample solution cannot recover the membrane rapidly, thus inducing a large potential drift and a long recovery time. This effect may be due to the fact that the protamine molecules with high molecular weights need a rather long time to cross the membrane [13]. Recently, it has been found that the ion fluxes across the membrane can be modulated and controlled precisely by applying an external current [23,[30][31][32].…”

“…The ratio of membrane components, which determines the diffusion coefficient and the cation-exchanger sites of protamine in the membrane phase, play an important role in controlling the concentration of protamine released at the membrane surface [13,28]. It is known that higher plasticizer contents increase the diffusion coefficient of protamine, and more anionic sits promote the ion-exchange process in the membrane phase.…”

“…Unfortunately, these methods may not be suitable for whole blood analysis. In recent years, potentiometric sensors based on polyion-sensitive membranes have made significant contributions to heparin quantification, even in undiluted blood, via direct [12][13][14][15] or indirect [16][17][18][19][20] detection modes. Since the spontaneous extraction of polyions into membrane phase can form cooperative ion pairs with the lipophilic ion exchangers in the membranes, it is unfortunate that these electrodes are naturally irreversible [14,15,21].…”

Label-Free and Substrate-Free Potentiometric Aptasensing Using Polycation-Sensitive Membrane Electrodes

“…It should be noted that conventional polyionsensitive electrodes usually are conditioned with highly discriminated ions and avoid contact with primary ions before measurements to ensure the counterdiffusion of primary ions with discriminated ions. 23 In contrast, the proposed polycationsensitive electrode is conditioned with the primary ion (i.e., protamine) for generation of ion fluxes of protamine from the inner solution to the sample solution. The strong electrostatic binding interaction between aptamer and protamine facilitates the stripping of protamine out of the membrane surface by the ion-exchange process with discriminated ions from the sample solution.…”

“…19−22 The potentiometric response of such polyion sensors is governed by a nonequilibrium steady-state extraction of the polyion into the organic membrane phase of the electrodes via formation of cooperative ion pairs with lipophilic ion exchangers in the membrane phase. 23 This response is dependent on the charge density, lipophilicity, and molecular weight of the polyion species. 24 Aptamers are oligonucleic acid sequences which bind to target molecules with high affinity and specificity.…”