Ion-Current Rectifying Nanopores in Aprotic Solvent: From Fundamentals to Applications

Ion current rectification (ICR) has long been studied in aqueous electrolyte, but remains virtually unexplored in aprotic organic solvent, where ion transport is highly sensitive to both the number and orientation of aprotic solvent molecules at the quartz interface. These particularities are favorable for sensing applications, exploiting changes to solvent ordering at the internal wall in the presence of analytes, as well as more “traditional” modulations of nanopore surface charge through analyte-probe interactions. In this thesis, ICR in confined acetonitrile (MeCN) is explored in detailed fundamental studies, and in an number of applications relevant to the pharmaceutical industry. First, a trace metal sensor capable of picomolar detection is described, which can be used in place of ICP-MS to determine residual metal concentration in organic products of Pd-catalyzed reactions. Additionally, a new detection paradigm based on changes to solvent ordering in the presence of solute is reported. This is based on the high degree of ordering exhibited by MeCN molecules at silica surfaces, which is disrupted in the presence of organic compounds possessing unique solvation shells. This is applied to the determination of enantiopurity in commercial and synthetic samples, with an ability to discriminate mixtures of enantiomers up to enantiomeric excess (ee) values of 99 %. Overall, this thesis demonstrates the remarkable potential of ICR in aprotic solvent as a sensing platform, facilitating a wider range of industrial applications than those for which aqueous nanopore sensors are currently developed, particularly in the pharmaceutical industry. The nanopore sensors developed are low-cost, miniaturizable, and simple to use, which is a far cry from the dedicated facilities and highly trained personnel currently required for quality control in the pharmaceutical industry.