Conceptually, extending the premise of bioelectronic interfaces down to the
scale of single molecules is a straightforward goal. In practice, the
challenges are purely technological. Single-molecule bioelectronic devices
would have to involve features much smaller than state-of-the-art
semiconductor electronics, and successful design would have unique
requirements for sensitivity and stability.
These imposing specifications are balanced by the potential of enormous
rewards, because single-molecule bioelectronics would be a breakthrough
technology for biochemical research and applications. By peering past the
ensemble behaviors of traditional characterization, single-molecule
techniques aim to directly observe the stochastic fluctuations,
instantaneous dynamics, and non-equilibrium behaviors that make up a
molecule’s full functionality. Moreover, single-molecule measurements
can uncover the unusual reaction trajectories of a genetically mutated
protein or a receptor interacting with pharmacological inhibitors. Building
a better understanding of the precise roles of proteins in complex
biological processes is a grand challenge for biology, biochemistry, and
biophysics in the twenty-first century.
These potential benefits have spurred the development of a variety of
single-molecule techniques. Single-molecule fluorescence, specifically
Förster resonance energy transfer (FRET), has become a standard tool for
single-molecule biochemistry [1]. Meanwhile, single-molecule bioelectronics
has remained elusive, despite the wide-ranging capabilities of modern solid
state electronics.