A new approach to
synthetic chemistry is performed in ultraminiaturized, nanofabricated
reaction chambers. Using lithographically defined nanowells, we achieve
single-point covalent chemistry on hundreds of individual carbon nanotube
transistors, providing robust statistics and unprecedented spatial
resolution in adduct position. Each device acts as a sensor to detect,
in real-time and through quantized changes in conductance, single-point
functionalization of the nanotube as well as consecutive chemical
reactions, molecular interactions, and molecular conformational changes
occurring on the resulting single-molecule probe. In particular, we
use a set of sequential bioconjugation reactions to tether a single-strand
of DNA to the device and record its repeated, reversible folding into
a G-quadruplex structure. The stable covalent tether allows us to
measure the same molecule in different solutions, revealing the characteristic
increased stability of the G-quadruplex structure in the presence
of potassium ions (K+) versus sodium ions (Na+). Nanowell-confined reaction chemistry on carbon nanotube devices
offers a versatile method to isolate and monitor individual molecules
during successive chemical reactions over an extended period of time.