Single-Molecule Reaction Chemistry in Patterned Nanowells.
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.
Department of Chemistry, Columbia University , 3000 Broadway, New York, New York 10027 United States.
Delphine
D
Bouilly
Department of Chemistry, Columbia University , 3000 Broadway, New York, New York 10027 United States.
Jason
J
Hon
Department of Chemistry, Columbia University , 3000 Broadway, New York, New York 10027 United States.
Nathan S
NS
Daly
Department of Electrical Engineering, Columbia University , 500 W. 120th Street, New York, New York 10027 United States.
Scott
S
Trocchia
Department of Electrical Engineering, Columbia University , 500 W. 120th Street, New York, New York 10027 United States.
Sefi
S
Vernick
Department of Chemistry, Columbia University , 3000 Broadway, New York, New York 10027 United States.
Jaeeun
J
Yu
Department of Electrical Engineering, Columbia University , 500 W. 120th Street, New York, New York 10027 United States.
Steven
S
Warren
Department of Chemistry, Columbia University , 3000 Broadway, New York, New York 10027 United States.
Ying
Y
Wu
Department of Chemistry, Columbia University , 3000 Broadway, New York, New York 10027 United States.
Ruben L
RL
Gonzalez
Department of Electrical Engineering, Columbia University , 500 W. 120th Street, New York, New York 10027 United States.
Kenneth L
KL
Shepard
Department of Chemistry, Columbia University , 3000 Broadway, New York, New York 10027 United States.
Colin
C
Nuckolls
D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D007477:Ions; D037742:Nanotubes, Carbon; D009690:Nucleic Acid Conformation
D007477:Ions; D037742:Nanotubes, Carbon; D004247:DNA
Single-molecule; biofunctionalization; carbon nanotubes; electrical conductance; electronic devices; sensors