Moderator’s note: Make sure to read the forum intro" and the Nature Biotech review and commentary linked there!

The chief reason to explore synthetic nanopores is the ability to construct an arbitrary pore structure from the ground up, rather than rely on a pre-existing protein pore scaffold. Synthetic, generally solid-state, nanopores may also enable more sophisticated DNA readout schemes, but come with their own set of challenges.
To date, the most explored readout observable has been the “co-passing” ionic current through the pore, but this technique has yet to show more than weak resolution between bases of the same class (i.e., purines or pyrimidines). The transverse tunneling current across the pore may provide better recognition and resolution, although theoretical calculations suggest that such a measurement is only possible under restricted conditions.
In both conductance and tunneling approaches, the electrical characteristics will be a function of the DNA’s position and conformation relative to the pore, as well as its translocation dynamics through the pore, none of which are presently controlled. The tunneling current scheme provides an obvious decoupling of translocation dynamics from the readout technique. Where protein-based pores have fairly obvious means of modification and conjugation with, e.g., DNA processive enzymes, synthetic pores offer the possibility of directly embedding electronics in the pore itself.
Questions to get us started: There are two key issues for synthetic pores: how best to design them (what is the ideal readout?), and how to build them. Let’s start with the latter.

• For the designs that have been proposed, what will be the lithographic and assembly challenges?
• How much control over the pore size and shape do we really have?
• How small can we make the pore?
• Are there ways to achieve the same results with different geometries or materials?
• Are there techniques from protein pores that can be adapted to synthetic pores?