Funded by: the National Science Foundation, Division of Chemistry
Dr. Jason Dwyer and his lab at the University of Rhode Island are developing new nanofabricated sensors to enable better characterization of an important class of biomolecules known as polysaccharides, or glycans. Glycans play important roles as a source of energy, as markers in important biological processes, and can also serve therapeutic functions – for example, the anticoagulant heparin is the most prominent medically useful polysaccharide. Identification and characterization of glycans can be incredibly challenging, in part because they are made from more than 100 different sugar building blocks connected in a variety of different ways. Drug safety can require detection of subtle and often low-abundance variants; in 2008, failure to detect a toxic contaminant in heparin resulted in ~100 deaths in the U.S. The Dwyer group is developing a rapid and inexpensive tool for selective analysis/screening of glycan samples. Students involved in this multidisciplinary work learn about nanofabrication of chemical measurement devices that have the potential to be used easily where they are needed, not just in a specialized chemistry laboratory staffed by highly trained scientists. Thus, broader impacts derive not only from potential nanopore-based assays for targets like heparin, but also from student classroom and laboratory exposure to the principles and practice of microfluidics, 3D printing, and computer-aided design, as well as the nature of innovation and technology transfer.
The approach taken by the Dwyer group utilizes nanopores for single molecule sensors and manipulators. Specifically, representative polysaccharides are being targeted using thin-film silicon nitride nanopores of varying sizes and surface chemistries (e.g., charge-polarity). Covalent and noncovalent labelling of the glycans is used to tune sensitivity and selectivity. Interactions among polysaccharides are also being studied. More broadly, the work addresses the design and reproducibility of chemically functionalized nanopores for glycomics, genomics, and proteomics, ideally with the potential for low barriers to widespread adoption.