Dwyer, Jason R.
glycomics, nanopores, polysaccharides
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Single-molecule sensing represents the ultimate in chemical sensitivity, but is tremendously challenging to achieve. Larger proteins have a diameter of 10 nm, which is 1/10,000th the size of a strand of hair, and 1/100,000th the size of a grain of sand. Because imaging at the nanoscale is difficult and expensive, developing techniques to measure single molecules requires ingenuity, and often relies on the interpretation of electrical signals. So how do nanopores help us measure at the single-molecule level?
A nanopore is simply a nano-sized hole in a membrane or material. In the early stages of nanopore science, biological nanopores were isolated from nature; cells have special proteins that are responsible for allowing single molecules to pass in and out of the cell body. These proteins self-assemble into cylinders, which are about 2 nm in diameter. The first and most commonly used biological nanopore was a protein called α-hemolysin.1 While biological nanopores have many applications, they rely on a lipid-bilayer support system, which is fragile and reliable only in certain pH ranges. Therefore, the field has turned to solid-state nanopores, which are manufactured in a man-made material.
In the Dwyer research group, we use an electric field to create nanopores in silicon nitride (SiNx) membranes. We adopted the technique of electrically “shocking” a nanopore into a SiNx membrane from Vincent Tabard-Cossa.2 Once the membrane has a hole, we mount it in a holder, so that it sits between two wells of electrolyte. We then monitor the electrical current to detect single molecules as they pass through the nanopore. In my honors project this semester, I explored how solid state nanopores can be used to detect and characterize sugar molecules. Sugars have complex branching structures, and significant molecule to molecule variability. However, sugars are easily absorbed by the body, and their potential to be used as a new drug delivery system depends on their characterization.
- Song, L. et al. Structure of staphylococcal a-hemolysin, a heptameric transmembrane pore. Science. 1996, 274, 1859–1865.
- Kwok, H., Briggs, K., Tabard-Cossa, V. Nanopore Fabrication by Controlled Dielectric Breakdown. PLOS ONE. 2014, 9, e92880.