Nanopore sensing is an emerging analytical technique for measuring single molecules. Under an applied potential bias, analyte molecules are transported through the nanopore and cause ionic current... Show moreNanopore sensing is an emerging analytical technique for measuring single molecules. Under an applied potential bias, analyte molecules are transported through the nanopore and cause ionic current modulations. Accordingly, the fingerprint of the analyte is reflected in the signature of the current blockage events. Due to its advantages such as lable-free and multi-analyte detection, nanopore sensing technology has been utilized as an attractive versatile tool to study a variety of topics, including biosensing of different species, such as DNA, RNA, proteins, peptides, anions, and metal ions.Metal ions play a crucial role in human health and environmental safety. Although metal ions are essential for numerous biological processes, the presence of the wrong metal, or even the essential metals in the wrong concentration or location, can lead to undesirable results and serious health concerns, including antibiotic resistance, metabolic disorders, mental retardation, and even cancer. Therefore, it is still of prime importance to develop highly sensitive and selective sensors for metal ions.In this dissertation, various nanopore sensing strategies to detect metal ions will first be discussed. These include: a) construction of metal ion binding sites in the nanopore inner surface; b) utilization of a biomolecule as a ligand probe; and c) employing enzymatic reactions. Then, three projects will be summarized. Among them, two projects are involved with detection of non-essential metal ions: uranyl and thorium ions, while the other is targeted at essential element, zinc ion. To be more specific, uranyl and thorium ions are detected by taking advantage of peptide molecules as ligand probes. In this case, the event signatures of peptide molecules in the nanopore are significantly different in the absence and presence of metal ions, which might be attributed to the conformational change of the biomolecules induced by the metal ion-biomolecule interaction. On the other hand, zinc ion is detected based on enzymatic reaction: without Zn2+, ADAM17 (a zinc dependent protease) is inactive and cannot cleave peptide substrate molecules; in contrast, with Zn2+ ion in the solution, the enzyme was activated, and its cleavage of the peptide substrate produced new types of blockage events with smaller residence time and amplitude values than those the peptide substrate. Show less
