Solid-contact potassium ion-selective electrodes with plasticizer-free silicone-based membranes for extended potassiumiIon monitoring in physiological samples

Abstract

In recent years, wearable potentiometric sensors have been used to monitor the real-time concentration of ions such as K+, pH, Na+ in sweat or interstitial fluid. However, a majority of ISEs reported to-date comprise a plasticized poly(vinyl chloride) (PVC) membrane, a mobile ionophore, and mobile ionic sites. Leaching of these species from the ISE into the sample can be toxic to the surrounding tissue and limits the lifetime of ISEs, especially for ISEs with thin sensing membranes, like those in wearable or implantable devices. Solid-contact ion-selective electrodes (SC-ISEs) in direct contact with physiological samples for long-term measurements must be biocompatible and resistant to biofouling.Silicone ISEs are a promising alternative to plasticized PVC because of their excellent biocompatibility, but little work has been done to study the relationship between silicone composition and ISE performance. In this thesis, we studied the influence of silicone composition on ISE performance in simple KCl solutions and blood plasma. SC-ISEs prepared with different silicone ion-selective membranes (ISMs) and colloid-imprinted mesoporous (CIM) carbon solid contacts have no differences in response slope, selectivity, or drift in simple aqueous salt solutions. However, substantial differences in emf drift were observed in porcine blood plasma in long-term experiments, even between silicones with very similar structure. Wearable and implantable SC-ISEs need to be sufficiently small to be comfortable for the patient. In the case of CIM carbon as the solid contact material, the particle size is very large, and as a result, the ISE must be quite thick. We show that the particle size of CIM carbon can be reduced to <15 µm and that SC-ISEs with a total CIM carbon + ion-selective membrane thickness below 100 µm can be prepared. We also discuss the theoretical lower limit of the geometric size of the electrode on how often the SC-ISEs need to be recalibrated to keep error below a defined limit. To improve biocompatibility and extend SC-ISE lifetime, we prevented ionophore leaching from the ion-selective membrane by covalently attaching it to the silicone membrane. To achieve this, we synthesized a modified version of the K+-ionophore BME-44 (a bis-crown ether) containing triethoxysilyl groups that react with condensation curing silicones during the curing process. Up to 96% of ionophore can be covalently bound to the silicone membrane polymer and ISEs prepared with this ionophore have excellent selectivity to K+ vs. Na+, making them suitable for use in physiological samples. Finally, I discuss some of the remaining challenges with silicone-based ISEs. I discuss the complexity associated with condensation curing silicones, which I suspect contributes to significant batch-to-batch variability in the behavior of the resulting ISEs, and I propose several methods to make ISEs with more reproducible silicones.