Date of Award
Master of Science in Chemistry
Jason R. Dwyer
In 2007-08 over 100 people died as a result of a contaminated batch of the polysaccharide heparin, an otherwise life-saving anticoagulant drug. After the contaminant was discovered, the development of assays that detect the contaminant, a structurally similar molecule, oversulfated chondroitin sulfate, became a necessity. Solid-state nanopores, which can, with appropriate experimental design, readily detect single molecules of analyte, may be able to help distinguish the two with greater ease than conventional assays, and with greater throughput even at concentrations well below that of USP assays. Polysaccharides, especially naturally occurring polysaccharides, have a vast range of structures characterized by widely varying molecular weights and charge distributions, and variability in linkage type. These polymers are challenging to analyze, and so studies using synthetic glycopolymers with known sizes and charge distributions, should be able to help one establish conditions to probe differences in molecular structure more easily. Under the right experimental conditions, solid-state nanopores were readily able to detect and distinguish between oversulfated chondroitin sulfate and heparin, and also synthetic glycopolymers of varying charge and length. This work may provide the necessary context to use nanopores for drug purity assays, to aid in understanding glycopolymer interactions, and also as a tool for characterizing polysaccharide structure and properties.
Nichols, Jonathan, "Detection and Discrimination of Natural and Synthetic Polysaccharides in a Solid-State Nanopore" (2018). Open Access Master's Theses. Paper 1187.