Branton, D; Golovchenko, J

Nature, vol. 398, no. 6729, pp. 660-661, 22 Apr 1999

New strategies for detecting and characterizing single-molecule events are now emerging in the biochemical sciences. The latest example comes from Gu et al. on page 686 of this issue. This group, working in Hagan Bayley's laboratory, show how measurement of ionic transport through a single, atomic-scale pore in an insulating membrane can be used to detect organic molecules of relative molecular mass as low as 100. Coupled with highly sensitive semiconductor electronics, the membrane-pore system can amplify these currents on timescales commensurate with the interaction times between the molecule and the pore. The system thus reveals the presence, nature and interaction of single molecules with the pore. Remarkably, a single protein channel can be adapted for simultaneous analysis of a mixture of organic molecules. Gu et al. assemble the nanoscale chemical and mechanical building blocks of their detector from the toolbox of biochemistry; the key components are shown on the page 687. Seven alpha -haemolysin molecules (a bacteral toxin) self-assemble to form a channel with a 15-angstrom-diameter aqueous pore through a 50-angstrom-thick lipid bilayer membrane. The membrane separates two chambers filled with a conducting salt solution. Because the lipid bilayer is a nearly perfect insulator, the d.c. electrical conductance across the membrane is determined by the interaction between ions of the salt and the molecular pore in the alpha -haemolysin channel. When a bias is applied across the membrane, the current flow is tiny (at the picoampere level), but it can nonetheless be measured with modern room-temperature semiconductor electronics.