Biological nanostructures: platforms for analytical chemistry at the sub-zeptomolar level

The analysis and manipulation of molecules at the sub-zeptomolar level (i.e., from 1 to 600 molecules) remains the unconquered frontier of analytical chemistry. While some techniques offer sensitivity to single molecules, there are no established tools for the manipulation of such small quantities of material. Scanning probe lithography has begun to provide practicable means to manipulate biological organisation on length scales of 100 nm and less, and three promising approaches (dip-pen nanolithography, nanoshaving, and scanning near-field photolithography) are reviewed. Each offers extraordinary spatial resolution combined with the capability for use under ambient and, in some cases, fluid conditions. These techniques offer a multitude of strategies that may at last make the manipulation of handfuls of molecules--and perhaps single molecules--a practical possibility for the analytical chemist.