Chen, Xin2024-01-052024-01-052019-08https://hdl.handle.net/11299/259698University of Minnesota Ph.D. dissertation. August 2019. Major: Chemistry. Advisor: Philippe Bühlmann. 1 computer file (PDF); xxii, 257 pages.The focus of this dissertation is on two main topics: the development of chemical sensors with reduced biofouling for applications in biological samples (Chapter I–II), and the development of chemical sensors with improved biocompatibility (Chapter III–V). Conventional polymeric membrane-based ion-selective electrodes (ISEs) rely on plasticized poly(vinyl chloride) (PVC) as sensor membranes. The plasticizers that solubilize PVC backbone—a prerequisite for PVC-phase ISEs—leach out gradually, resulting in a limited sensor lifetime. Polar groups in the plasticizer may also lower the sensor selectivity. To improve selectivity and expand working ranges, fluorous-phase ISEs relying on nonpolar perfluorinated compounds as sensing membrane were developed. A novel fluorophilic ionophore was synthesized and used to make ionophore-doped fluorous-phase ISEs with Nernstian responses and an optimal working range centered around neutral pH—suitable for most biological samples. The reproducibility of fluorous-phase ISEs was enhanced by a new electrode body design. Importantly, fluorous-phase ISEs maintained their excellent selectivity after prolonged exposure in serum whereas PVC-phase ISEs lost selectivity considerably. Insights were also obtained on the optimal ionophore-to-ionic site ratio. To improve biocompatibility, silicone-based reference and ion-selective electrodes were developed to eliminate plasticizers. Reference electrodes doped with several ionic liquids showed sample-independent and long-term stable potentials in artificial blood electrolytes and serum samples. Potassium-selective silicone-based ISEs developed with two ionophores and two silicones showed Nernstian responses and good selectivities. In an attempt to prevent leaching of ionophores from ISE membrane into samples, a well-known potassium ionophore was covalently attached to silicone membranes. Miniaturized microelectrodes suitable for implantable devices were also developed based on this platform. In a similar effort, plasticizer-free polymethacrylate-based ISEs exhibited Nernstian responses to pH and selectivities comparable to PVC-phase ISEs. To further improve biocompatibility for applications in the pharmaceutical and food industries, either an ionophore or ionic site or both were covalently attached to sensor membranes. Sensors with either ionophore or ionic site attached provided similar good characteristics whereas when both were attached, Nernstian responses were not found consistently. Furthermore, heating experiments showed that sensors exposed to 90 ˚C heating maintained good selectivity.enanti-biofoulingbiocompatibilityion-selective electrodespotentiometryreference electrodesensorThesis or Dissertation